Diagnostic and evaluative efficiency of 68Ga-FAPI-04 in skeletal muscle injury.

BACKGROUND: Skeletal muscles are vital for daily function, yet assessing their injuries remain challenging. We aimed to elucidate the effectiveness of 68Ga-FAPI-04 in evaluating skeletal muscle remodeling. RESULTS: C2C12 cells were subjected to graded H2O2 stimulation in vitro, revealing an initial rise and subsequent decline in fibroblast activation protein (FAP) expression as H2O2 concentration increased. In vivo, a murine triceps surae injury model was created using various solutions to simulate normal repair, mild repair failure, and severe repair failure. Assessments were conducted on days 1, 3, 7, and 14 using PET, MRI, and ultrasound. With 68Ga-FAPI-04, the normal and mild repair failure groups showed significantly higher SUVmax and T/B ratios on day 1 compared to the severe repair failure group. These values gradually decreased in the normal repair group, becoming negligible after day 7. MRI results for the normal repair group showed low to moderate signal intensity by day 7. A clinical study retrospectively evaluated post-hip arthroplasty patient images at intervals of 1 month, 2-3 months, 5-6 months, and over 7 months. In these patients, 18F-FDG SUVmax and volume remained relatively stable over time, while 68Ga-FAPI-04 SUVmax initially increased, then decreased, with a consistent reduction in volume. CONCLUSION: In skeletal muscle injuries, FAP demonstrates a distinctive mechanism of action, and 68Ga-FAPI-04, in comparison to other tests, more precisely captures alterations in lesion site uptake intensity and volume. TRIAL REGISTRATION: Trial registration: ChiCTR2000041204. Registered 22 December 2020, https://www.chictr.org.cn/showproj.html?proj=66211.

Overall survival prediction of gastric cancer using the gene signature of CT-detected extramural venous invasion combined with M2 macrophages infiltration.

BACKGROUND: CT-detected Extramural venous invasion (EMVI) is known as an independent risk factor for distant metastasis in patients with advanced gastric cancer (GC). However, the molecular basis is not clear. In colorectal cancer, M2 macrophages plays a vital role in determining EMVI. This study aimed to investigate the relationship between CT-detected EMVI and the M2 macrophages as well as prognosis predictionusing a radiogenomic approach. METHOD: We utilized EMVI-related genes (from mRNA sequencing of 13 GC samples correlated with EMVI score by spearman analysis, P < 0.01) to overlap the co-expression genes of WGCNA module and M2 macrophages related genes (from mRNA data of 371 GC patients in TCGA database), generating a total of 136 genes. An EMVI-M2-prognosis-related hub gene signature was constructed by COX and least absolute shrinkage and selection operator (LASSO) analysis from a training cohort TCGA database (n = 371) and validated it in a validation cohort from GEO database (n = 357). High- and low-risk groups were divided by hub gene (EGFLAM and GNG11) signature-derived risk scores. We assessed its predictive ability through Kaplan-Meier (K-M) curve and COX analysis. Furthermore, we utilized ESTIMATE to detect tumor mutation burden (TMB) and evaluate sensitivity to immune checkpoint inhibitors (ICIs). Expression of hub genes was tested using western blotting and immunohistochemistry (IHC) analysis. RESULTS: The overall survival (OS) was significantly reduced in the high-risk group (Training/Validation: AUC = 0.701/0.620; P < 0.001/0.003). Furthermore, the risk score was identified as an independent predictor of OS in multivariate COX regression analyses (Training/Validation: HR = 1.909/1.928; 95% CI: 1.225-2.974/1.308-2.844). The low-risk group exhibited significantly higher TMB levels (P = 1.6e- 07) and greater sensitivity to ICIs. Significant higher expression of hub-genes was identified on multiple GC cell lines and original samples. Hub-genes knockdown in gastric cancer cell lines inhibited their proliferation, metastatic and invasive capacity to varying degrees. In vivo experiments indicate that EGFLAM, as one of the hub genes, its high expression can serve as a biomarker for low response to immunotherapy. CONCLUSION: Our study demonstrated EMVI-M2 gene signature could effectively predict the prognosis of GC tissue, reflecting the relationship between EMVI and M2 macrophages.

The Role of miRNA in Hyperthyroidism Induced by Excessive Iodine in Drinking Water.

In recent years, iodine deficiency-related diseases have been effectively controlled; the prevalence of excessive iodine-induced thyroid diseases has increased, such as hyperthyroidism. However, there are still several controversial outcomes regarding the relationship between excessive iodine intakes and hyperthyroidism. MicroRNAs (miRNAs) extensively participate in the progression of thyroid diseases; nevertheless, the relationship and mechanism between iodine exposure and miRNAs have not been explored in hyperthyroidism patients. In this study, a total of 308 pairs of hyperthyroidism patients and healthy controls were enrolled in. Logistic regression analysis showed that level of water iodine >100 µg/L was an independent risk factor for hyperthyroidism. Compared with the healthy control, the serum thyroglobulin (Tg) content and levels of interferon-γ (IFN-γ), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were significantly elevated in hyperthyroidism patients. Further, high-throughput miRNA sequencing was applied to find crucial miRNAs involved in the occurrence of hyperthyroidism related to excessive water iodine. Based on the fold change and Q value, miR-144-3p, miR-204-5p, miR-346, miR-23b-5p, and miR-193b-3p were selected for validation by qRT-PCR. Our results showed that miR-346 and miR-204-5p in the case group were significantly lower than those of the control group, and the similar results found under the level of water iodine >300 µg/L. Nonetheless, no significant difference was found at 10-100 µg/L level of water iodine. Furthermore, the ROC curve indicated that miR-346 and miR-204-5p had the ability to diagnose hyperthyroidism patients. Taken together, excessive water iodine may decrease the expression of miR-346 and miR-204-5p, which mediate the elevation of Tg and cytokines, ultimately making contribution to the development of hyperthyroidism.

Effects and Mechanisms of Lutein on Aging and Age-Related Diseases.

Aging and age-related diseases are serious public health issues that are receiving growing attention from researchers. Lutein has a critical function in the prevention and management of these issues. Possible mechanisms mainly include suppressing inflammation and oxidative stress, regulating cell activity, and modulating the levels of toxic substances. In this narrative review paper, we sum up the most current developments in the study of the effects of lutein on aging and five age-related diseases (age-related macular degeneration, cataracts, Alzheimer's disease, Parkinson's disease, and osteoporosis), and fundamental mechanisms are reviewed. The bioavailability of lutein and the strategies to improve its bioavailability are discussed. This piece of work can bring a clearer comprehension of the protective effects of lutein against aging and age-related diseases and can be also helpful for developing lutein as functional food and dietary supplements for these age-related diseases.

Fabrication of versatile and durable superhydrophobic cotton fabrics using PTA-Ala adhesive.

In recent years, the preparation of functional textiles based on polyphenols adhesion has received extensive attention and research. However, polyphenols are prone to peroxidation during oxidative polymerization, which can compromise the interfacial adhesion of their monomers. Reintroducing reactive functional groups after oxidative polymerization of polyphenols may potentially compensate for the lost interfacial adhesion while increasing cohesion. In this paper, L-alanine (Ala) is introduced into poly (tannic acid) (PTA) solution to generate the PTA-Ala via Michael addition and Schiff base reaction. Original cotton fabrics are modified with PTA-Ala solution to enhance adhesion strength between the fabrics and subsequent functional modifiers. A silver nanowire network is then incorporated to increase the surface roughness through tannic acid reduction. Finally, polydimethylsiloxane is applied to reduce fabric surface energy, resulting in superhydrophobic multifunctional OH-PDMS/Ag/PTA-Ala/cotton fabrics. The finished cotton fabric exhibits a water contact angle of 166.7 ± 1.9° and a rolling angle of 5 ± 0.5°. Moreover, the fabric features diverse functionalities such as oil-water separation, photothermal conversion, antimicrobial properties, water collection, and anti-icing capabilities, alongside excellent durability and self-healing properties that extend its service life. This finished cotton fabric demonstrates promising applications in oil pollution control, outdoor clothing and medical protection, highlighting its broad across various industries.

CT assessed morphological features can predict higher mitotic index in gastric gastrointestinal stromal tumors.

OBJECTIVES: To investigate the correlation of the mitotic index (MI) of 1-5 cm gastric gastrointestinal stromal tumors (gGISTs) with CT-identified morphological and first-order radiomics features, incorporating subgroup analysis based on tumor size. METHODS: We enrolled 344 patients across four institutions, each pathologically diagnosed with 1-5 cm gGISTs and undergoing preoperative contrast-enhanced CT scans. Univariate and multivariate analyses were performed to investigate the independent CT morphological high-risk features of MI. Lesions were categorized into four subgroups based on their pathological LD: 1-2 cm (n = 69), 2-3 cm (n = 96), 3-4 cm (n = 107), and 4-5 cm (n = 72). CT morphological high-risk features of MI were evaluated in each subgroup. In addition, first-order radiomics features were extracted on CT images of the venous phase, and the association between these features and MI was investigated. RESULTS: Tumor size (p = 0.04, odds ratio, 1.41; 95% confidence interval: 1.01-1.96) and invasive margin (p < 0.01, odds ratio, 4.55; 95% confidence interval: 1.77-11.73) emerged as independent high-risk features for MI > 5 of 1-5 cm gGISTs from multivariate analysis. In the subgroup analysis, the invasive margin was correlated with MI > 5 in 3-4 cm and 4-5 cm gGISTs (p = 0.02, p = 0.03), and potentially correlated with MI > 5 in 2-3 cm gGISTs (p = 0.07). The energy was the sole first-order radiomics feature significantly correlated with gGISTs of MI > 5, displaying a strong correlation with CT-detected tumor size (Pearson's ρ = 0.85, p < 0.01). CONCLUSIONS: The invasive margin stands out as the sole independent CT morphological high-risk feature for 1-5 cm gGISTs after tumor size-based subgroup analysis, overshadowing intratumoral morphological characteristics and first-order radiomics features. KEY POINTS: Question How can accurate preoperative risk stratification of gGISTs be achieved to support treatment decision-making? Findings Invasive margins may serve as a reliable marker for risk prediction in gGISTs up to 5 cm, rather than surface ulceration, irregular shape, necrosis, or heterogeneous enhancement. Clinical relevance For gGISTs measuring up to 5 cm, preoperative prediction of the metastatic risk could help select patients who could be treated by endoscopic resection, thereby avoiding overtreatment.

Effects and Mechanisms of Polyunsaturated Fatty Acids on Age-Related Musculoskeletal Diseases: Sarcopenia, Osteoporosis, and Osteoarthritis-A Narrative Review.

Background: The process of the globally aging population has been accelerating, leading to an increasing social burden. As people age, the musculoskeletal system will gradually go through a series of degenerative and loss of function and eventually develop age-related musculoskeletal diseases, like sarcopenia, osteoporosis, and osteoarthritis. On the other hand, several studies have shown that polyunsaturated fatty acids (PUFAs) possess various important physiological functions on the health of muscles, bones, and joints. Objective: This narrative review paper provides a summary of the literature about the effects and mechanisms of PUFAs on age-related musculoskeletal diseases for the prevention and management of these diseases. Methods: Web of Science, PubMed, Science Direct, and Scopus databases have been searched to select the relevant literature on epidemiological, cellular, and animal experiments and clinical evidence in recent decades with keywords "polyunsaturated fatty acids", "PUFAs", "omega-3", "omega-6", "musculoskeletal diseases", "sarcopenia", "osteoporosis", "osteoarthritis", and so on. Results: PUFAs could prevent and treat age-related musculoskeletal diseases (sarcopenia, osteoporosis, and osteoarthritis) by reducing oxidative stress and inflammation and controlling the growth, differentiation, apoptosis, and autophagy of cells. This review paper provides comprehensive evidence of PUFAs on age-related musculoskeletal diseases, which will be helpful for exploitation into functional foods and drugs for their prevention and treatment. Conclusions: PUFAs could play an important role in the prevention and treatment of sarcopenia, osteoporosis, and osteoarthritis.

Metal-Carbon Bond Heterolysis Energy Scale for Model Palladium Catalysts.

Thermodynamic studies of transition-metal intermediates are crucial for understanding of metal-catalyzed transformations. Herein, a series of arylpalladium cyanomethanides were synthesized and characterized. Their palladium-carbon bond heterolysis energies (ΔGhet(Pd-C)) were determined in DMSO for the first time by equilibrium methods. ΔGhet(Pd-C) values of 7.9-19.1 kcal/mol, located between the ΔGhet(Pd-O) and ΔGhet(Pd-N) scales previously established, are much smaller than the corresponding ΔGhet(C-H)s of phenylacetonitrile (30.0 kcal/mol). Linear free energy relationship (LEFR) analysis reveals insights into the structure-property relationship and the factor dictating the thermodynamics of metalation. These ΔGhet(Pd-X)s in combination with ΔGhet(X-H)s are successfully used to diagnose the reaction feasibility and selectivity of X-H bond activation.

Nitrogen mustard induces dynamic nuclear protein spectrum change and DNA-protein crosslinking, with p97 mediating repair.

Nitrogen mustard (NM) is a chemotherapeutic agent capable of alkylating nucleophilic proteins and DNA, causing severe cell damage. However, no reports have been on the dynamic changes in proteomics induced by NM. In this study, we established a model of acute exposure to NM for 1 h and a continuous cultured model for 24 h after NM removal (repair stage) using 16HBE cells. The nuclear protein spectrum and nuclear proteins crosslinked with DNA were analyzed, and the function of p97 during NM damage was examined. An hour of NM exposure resulted in severe changes in the nuclear protein spectrum and protein into the cell nucleus, which is mainly involved in nuclear acid-related issues. After 24 h, the return to normal process of the types and amounts of differentially expressed proteins was inhibited by si-p97. The main processes involved in si-p97 intervention were nucleocytoplasmic transport, processing in the endoplasmic reticulum, metabolic abnormalities, and DNA-response; however. An hour of exposure to NM increased DNA-protein crosslinking (DPC), total-H2AX, and p-H2AX. In contrast, si-p97 only further increased or maintained their levels at 24 h yet not at 1 h. The effect of the proteasome inhibitor, MG132, was similar to that of si-p97. The siRNA of DVC1, a partner of p97, also increased the DPC content. Both si-p97 and si-DVC1 increased the cytoplasmic levels of the proteasome (PSMD2). These results suggest acute NM exposure induces severe nuclear protein spectral changes, rapid protein influx into the nucleus, DPC formation, and DNA double-strand breaks. Furthermore, our data indicated that p97 is involved in normal protein spectrum maintenance and DPC removal after NM withdrawal, requiring the participation of DVC1 and the proteasome.

Towards Sustainable and Dynamic Modeling Analysis in Korean Pine Nuts: An Online Learning Approach with NIRS.

Due to its advantages such as speed and noninvasive nature, near-infrared spectroscopy (NIRS) technology has been widely used in detecting the nutritional content of nut food. This study aims to address the problem of offline quantitative analysis models producing unsatisfactory results for different batches of samples due to complex and unquantifiable factors such as storage conditions and origin differences of Korean pine nuts. Based on the offline model, an online learning model was proposed using recursive partial least squares (RPLS) regression with online multiplicative scatter correction (OMSC) preprocessing. This approach enables online updates of the original detection model using a small amount of sample data, thereby improving its generalization ability. The OMSC algorithm reduces the prediction error caused by the inability to perform effective scatter correction on the updated dataset. The uninformative variable elimination (UVE) algorithm appropriately increases the number of selected feature bands during the model updating process to expand the range of potentially relevant features. The final model is iteratively obtained by combining new sample feature data with RPLS. The results show that, after OMSC preprocessing, with the number of features increased to 100, the new online model's R2 value for the prediction set is 0.8945. The root mean square error of prediction (RMSEP) is 3.5964, significantly outperforming the offline model, which yields values of 0.4525 and 24.6543, respectively. This indicates that the online model has dynamic and sustainable characteristics that closely approximate practical detection, and it provides technical references and methodologies for the design and development of detection systems. It also offers an environmentally friendly tool for rapid on-site analysis for nut food regulatory agencies and production enterprises.

Near-Infrared-Light-Induced Iron(I) Dimer-Enabled Radical Cascade Reactions of Fluoroalkyl Bromides for the Synthesis of Ring-Fused Quinazolinones.

The use of an earth-abundant and inexpensive iron complex as a catalyst, coupled with near-infrared (NIR) light as the energy source, for radical reactions with alkyl halides has been far less developed. In this study, we report NIR light-mediated iron(I) dimer-catalyzed radical cascade reactions of fluoroalkyl bromides for the synthesis of ring-fused quinazolinones bearing a difluoromethyl group. In this process, the 3-bromo-1,10-phenanthroline ligand facilitates the reactivity of [CpFe(CO)2]2, thereby improving the efficiency of the reaction.

Exercise Induced Endothelial Mesenchymal Transition (EndMT) Facilitates Meniscal Fibrocartilage Regeneration.

The meniscus is a semilunar wedge-shaped fibrocartilage tissue within the knee joint that is important for withstanding mechanical shock during joint motion. The intrinsic healing capacity of meniscus tissue is very limited, which makes meniscectomy the primary treatment method in the clinic. An effective translational strategy for regenerating the meniscus after total or subtotal meniscectomy, particularly for extensive meniscal lesions or degeneration, is yet to be developed. The present study demonstrates that the endothelial mesenchymal transition (EndMT) contributes to meniscal regeneration. The mechanical stimulus facilitated EndMT by activating TGF-ß2 signaling. A handheld bioprinter system to intraoperatively fabricate a porous meniscus scaffold according to the resected meniscus tissue is developed; this can simplify the scaffold fabrication procedure and period. The transplantation of a porous meniscus scaffold combined with a postoperative regular exercise stimulus facilitated the regeneration of anisotropic meniscal fibrocartilaginous tissue and protected the joint cartilage from degeneration in an ovine subtotal meniscectomy model. Single-cell RNA sequencing and immunofluorescence co-staining analyses further confirmed the occurrence of EndMT during meniscal regeneration. EndMT-transformed cells gave rise to fibrochondrocytes, subsequently contributing to meniscal fibrocartilage regeneration. Thus, an efficient translational strategy to facilitate meniscal regeneration is developed.

Superconductivity under pressure in a chromium-based kagome metal.

Superconductivity in a highly correlated kagome system has been theoretically proposed for years (refs. 1-5), yet the experimental realization is hard to achieve6,7. The recently discovered vanadium-based kagome materials8, which exhibit both superconductivity9-11 and charge-density-wave orders12-14, are nonmagnetic8,9 and weakly correlated15,16. Thus these materials are unlikely to host the exotic superconductivity theoretically proposed. Here we report the discovery of a chromium-based kagome metal, CsCr3Sb5, which is contrastingly featured with strong electron correlations, frustrated magnetism and characteristic flat bands close to the Fermi level. Under ambient pressure, this kagome metal undergoes a concurrent structural and magnetic phase transition at 55 K, with a stripe-like 4a0 structural modulation. At high pressure, the phase transition evolves into two transitions, possibly associated with charge-density-wave and antiferromagnetic spin-density-wave orderings. These density-wave-like orders are gradually suppressed with pressure and, remarkably, a superconducting dome emerges at 3.65-8.0 GPa. The maximum of the superconducting transition temperature, Tcmax = 6.4 K, appears when the density-wave-like orders are completely suppressed at 4.2 GPa, and the normal state exhibits a non-Fermi-liquid behaviour, reminiscent of unconventional superconductivity and quantum criticality in iron-based superconductors17,18. Our work offers an unprecedented platform for investigating superconductivity in correlated kagome systems.

Effects of Fermentation with Kombucha Symbiotic Culture of Bacteria and Yeasts on Antioxidant Activities, Bioactive Compounds and Sensory Indicators of Rhodiola rosea and Salvia miltiorrhiza Beverages.

Kombucha is a well-known fermented beverage traditionally made from black tea infusion. Recent studies have focused on finding alternative materials to create novel kombucha beverages with various health benefits. In this study, we prepared and evaluated two novel kombucha beverages using Rhodiola rosea and Salvia miltiorrhiza as materials. The effects of fermentation with the residue of these plants on the kombucha were also investigated. The antioxidant activities, total phenolic contents, and concentrations of the bioactive compounds of the kombucha beverages were determined by the Trolox equivalent antioxidant capacity test, ferric-reducing antioxidant power test, Folin-Ciocalteu method, and high-performance liquid chromatography, respectively. The results revealed that the kombucha beverages made with Rhodiola rosea and Salvia miltiorrhiza had strong antioxidant capacities and abundant phenolic contents. Additionally, the kombucha fermented with Rhodiola rosea residue had higher FRAP, TEAC and TPC values than that fermented without residue. On the other hand, the Salvia miltiorrhiza kombucha fermented with residue had similar FRAP and TEAC values but lower TPC values compared to that fermented without residue. The correlation analysis showed that gallic acid, salidroside, and tyrosol were responsible for the antioxidant abilities and total phenolic contents of the Rhodiola rosea kombucha, and salvianolic acid A and salvianolic acid B contributed to the antioxidant abilities of the Salvia miltiorrhiza kombucha. Furthermore, the kombucha fermented with Rhodiola rosea residue had the highest sensory scores among the kombucha beverages studied. These findings suggest that Rhodiola rosea and Salvia miltiorrhiza are suitable for making novel kombucha beverages with strong antioxidant abilities and abundant phenolic contents, which can be used in preventing and managing oxidative stress-related diseases.

Molecular interactions of the chaperone CcmS and carboxysome shell protein CcmK1 that mediate ß-carboxysome assembly.

The carboxysome is a natural proteinaceous organelle for carbon fixation in cyanobacteria and chemoautotrophs. It comprises hundreds of protein homologs that self-assemble to form a polyhedral shell structure to sequester cargo enzymes, ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) and carbonic anhydrases. How these protein components assemble to construct a functional carboxysome is a central question in not only understanding carboxysome structure and function but also synthetic engineering of carboxysomes for biotechnological applications. Here, we determined the structure of the chaperone protein CcmS, which has recently been identified to be involved in ß-carboxysome assembly, and its interactions with ß-carboxysome proteins. The crystal structure at 1.99 Å resolution reveals CcmS from Nostoc sp. PCC 7120 forms a homodimer, and each CcmS monomer consists of five α-helices and four ß-sheets. Biochemical assays indicate that CcmS specifically interacts with the C-terminal extension of the carboxysome shell protein CcmK1, but not the shell protein homolog CcmK2 or the carboxysome scaffolding protein CcmM. Moreover, we solved the structure of a stable complex of CcmS and the C-terminus of CcmK1 at 1.67 Å resolution and unveiled how the CcmS dimer interacts with the C-terminus of CcmK1. These findings allowed us to propose a model to illustrate CcmS-mediated ß-carboxysome assembly by interacting with CcmK1 at the outer shell surface. Collectively, our study provides detailed insights into the accessory factors that drive and regulate carboxysome assembly, thereby improving our knowledge of carboxysome structure, function, and bioengineering.

Bone Marrow Disseminated Tumor Cell Detection Is Beneficial for the Early Finding of Bone Metastasis and Prognosis.

BACKGROUND: Disseminated tumor cells (DTCs) are thought to be the initiators of tumor recurrence and metastasis. However, based on the current imaging examination methods, early detection of DTCs is extremely difficult due to their small number and dormant state. METHODS: We used the SE-iFISH approach to detect bone marrow DTCs (mDTCs) in patients with breast or prostate cancer, and compared it with various imaging examination methods to explore its role in predicting metastasis and prognosis. RESULTS: Fifteen patients were enrolled in this study. Among them, 11 patients showed imaging-confirmed bone metastases in different sites of the body, of which seven patients had iliac mDTCs and signs of iliac bone metastases on imaging. For the remaining four patients, imaging confirmed that the bone metastatic foci were far from the ilium, but in one patient, mDTCs were detected in the ilium. Interestedly, iliac mDTCs were also detected in two out of four patients who had no sign of bone metastases on imaging. Furthermore, the epithelial marker, CK18, was ubiquitously expressed in mDTCs, but its expression was very low in peripheral circulating tumor cells (pCTCs). The Kaplan-Meier plot suggested that CK18+ mDTCs ≥ 5 was related to poor overall survival (OS) compared with that of CK18+ mDTCs < 5 in breast cancer patients (median OS: 22.1 vs. 46.9 months; log-rank, p = 0.035). CONCLUSIONS: SE-iFISH examination for mDTCs is more sensitive than the conventional methods used for detecting bone metastases. mDTC detection facilitated the early finding of tumor cells in the bone marrow and ≥5 CK18+ mDTCs was associated with a poor prognosis in breast cancer patients.

[Improving effect of selenium on spermatogenesis in mice with cyclophosphamide-induced spermatogenic impairment and its underlying mechanism].

OBJECTIVE: To investigate the effect of selenium on cyclophosphamide (CTX)-induced spermatogenic impairment (SI) in mice and its underlying mechanism. METHODS: We equally randomized 36 male KM mice into 3 SI model and 3 control groups, the first 3 treated by intraperitoneal injection of CTX at 100 mg/kg (the SI model control group), CTX plus SI model control group, selenium deficient model group (－Se SI), selenium supplemented model group (+Se SI), while latter 3 by intraperitoneal injection of normal saline (the normal control), selenium deficiency control group (－Se control), selenium addition control group (+Se control), respectively, all once a week for 6 successive weeks. Then we observed the histopathological changes in the testes of all the mice by HE staining, obtained the sperm count in the epididymides, determined the expressions of glutathione peroxidase 4 (GPx4) and SLC7A11 proteins by Western blot and ferroptosis-related genes by RT-qPCR, and examined the changes in the expressions of ferroptosis-related proteins and genes in the GC2-spd cells treated with ferroptosis inhibitors and inducers in combination with different concentrations of inorganic sodium selenite (SeS) and organic selenomethionine (SeM). RESULTS: Compared with the normal controls, the SI model mice showed significantly decreased testicular and prostatic organ coefficients, reduced spermatogenic layers, increased voids, decreased serum ferritin concentration (P<0.05), and elevated transferrin concentration (P<0.05). The organ coefficients were significantly higher in the +Se SI and +Se control than in the －Se SI and －Se control groups (P<0.05, P<0.01), with evident pathological improvement of the testis tissue in the +Se controls. The expressions of the GPx4 and solute carrier family 7 members 11（SLC7A11） genes in the testis were dramatically down-regulated in the SI model controls (P<0.01), but up-regulated in the +Se SI and +Se control compared with those in the －Se SI and －Se control group (P<0.01 and P<0.05), but there were no statistically significant differences between their protein expressions. The results of in vitro GC2 spd cell experiments indicated that the GPx4 gene and GPx4 protein levels in the - Se group were significantly lower than those in the normal control group (P<0.05), while the SLC7A11 gene level decreased (P<0.01). Different doses of SeS and SeM significantly increased the GPx4 protein expression compared to the average Se group. Low doses of SeM promoted a significant increase in GPx4 gene levels, while high doses of SeS increased the expression levels of SLC7A11 gene and SLC7A11 protein (P<0.05, P<0.01). The Se group showed a significant decrease in the levels of acsl4 and ptgs2 genes compared to the normal control group. SeM promoted the expression of acsl4, while SeS promoted the expression of ptgs2 and fth1 (P<0.01, P<0.05). The intervention results of GC2 spd showed that the Erastin group had a decrease in ptgs2 compared to the normal control group, while the SeS+Erastin and SeM+Erastin groups had an increase in ptgs2 gene expression compared to the Erastin group. However, the ptgs2 expression of Fer-1 was lower than that of the normal control group, and the ptgs2 gene level of SeS+Fer-1 and SeM+Fer-1 groups was lower than that of Fer-1 group (P<0.05); The gene quantity of GPx4 in the SeM+Erastin and SeM+Fer-1 groups increased compared to the Erastin and Fer-1 groups (P<0.01, P<0.05); SeM+Erastin and SeS+Erastin showed a decrease in SLC7A11 compared to the Erastin group, as well as SeM+Fer-1 and SeS+Fer-1 groups compared to the Fer-1 group, accompanied by an increase in acsl4 and fth1 (P<0.01). CONCLUSION: Selenium deficiency causes the reduction of the SLC7A11 and GPx4 gene levels, disorder of ferroptosis-related genes and down-regulation of the GPx4 protein expression in the mouse testis and spermatocytes. Selenium can promote the expression of GPx4, up-regulate the level of SLC7A11, and improve spermatogenesis in the testis of the mouse with SI. There are differences between organic SeM and inorganic SeS in regulating the ferroptosis pathway-related genes.

Effects of Several Tea-like Plants on Liver Injury Induced by Alcohol via Their Antioxidation, Anti-Inflammation, and Regulation of Gut Microbiota.

Liver injury induced by alcohol is a serious global health problem. Several tea-like plants are widely used as beverages, which are drunk like tea. In this study, the hepatoprotective effects of eight tea-like plant extracts with the intake of 200 mg/kg.bw/day were investigated and compared using a C57BL/6J mouse model of acute alcohol exposure, including sweet tea, vine tea, Rabdosia serra kudo, broadleaf holly leaf, mulberry leaf, bamboo leaf, Camellia nitidissima, and Akebia trifoliata peels. The results showed that the eight tea-like plants had hepatoprotective effects to different degrees against acute alcohol exposure via enhancing the activities of alcoholic metabolism enzymes, ameliorating oxidative stress and inflammation in the liver, as well as regulating gut microbiota. In particular, sweet tea, bamboo leaf, mulberry leaf, and Camellia nitidissima increased the activities of alcohol dehydrogenase or aldehyde dehydrogenase. Among these tea-like plants, sweet tea and Camellia nitidissima had the greatest hepatoprotective effects, and their bioactive compounds were determined by high-performance liquid chromatography. Chlorogenic acid, rutin, and ellagic acid were identified in sweet tea, and epicatechin, rutin, and ellagic acid were identified in Camellia nitidissima, which could contribute to their hepatoprotective action. These tea-like plants could be drunk or developed into functional food against alcoholic liver injury, especially sweet tea and Camellia nitidissima. In the future, the effects of sweet tea and Camellia nitidissima on chronic alcoholic liver diseases should be further investigated.

Second-harmonic generation of 2D materials excited by the Laguerre-Gaussian beam.

We theoretically study the second-harmonic generation (SHG) of two-dimensional (2D) materials excited by a Laguerre-Gaussian (LG) beam at normal incidence and provide a method to distinguish SHG induced by the electric dipole (ED) interaction and SHG induced by the electric quadrupole and magnetic dipole (EQ-MD) interaction by their different dependence on the LG beam parameters, including the effective spot area v02 and the order of orbital angular momentum (OAM) m. In an approximation of neglecting reflection and taking a beam radius to infinity, the intensity of the ED induced SHG is proportional to F m/v02 with Fm = 2-2|m|(2|m|)!/(π(|m|!)2), while the EQ-MD induced one is proportional to (4|m|+2)F m/v04. An in-plane isotropic substrate can strongly affect the signal amplitude but slightly change the v0 and m dependence. Our results provide an all-optical way to detect the OAM by SHG, as well as a theoretical basis for studying the EQ-MD induced SHG by the LG beams.

Anti-Ceramide ScFv Prophylaxis for First Responders to a Limited Nuclear Attack.

BACKGROUND/AIMS: After 9/11, multiple government agencies instituted programs aimed at developing medical radiation countermeasures (MRCs) for two syndromes lethal within weeks of a limited nuclear attack; the hematopoietic-acute radiation syndrome (H-ARS) and the higher-dose gastrointestinal-acute radiation syndrome (GI-ARS). While re-purposing drugs that enhance marrow repopulation treats H-ARS, no mitigator protects GI tract. METHODS: We recently reported anti-ceramide 6B5 single-chain variable fragment (scFv) pre-treatment abrogates ongoing small intestinal endothelial apoptosis to rescue Lgr5+ stem cells, preventing GI-ARS lethality in C57B/L6J mice. Here, with US Department of Defense support, we provide evidence that humanized anti-ceramide scFv (CX-01) is a promising prophylactic MRC for first responders, who risk exposure upon entering a radiation-contaminated site. RESULTS: CX-01, when delivered up to 90 min before irradiation, is highly-effective in preventing small intestinal endothelial apoptosis in mice and lethality in both sexes. Unexpectedly, females require an ~2-fold higher CX-01 dose than males for full protection. CX-01 is effective subcutaneously and intramuscularly, a property critical for battlefield use. Increasing the maximally-effective dose 5-fold does not extend duration of bioeffectiveness. CONCLUSION: While CX-01 prevents GI-ARS lethality, structural modification to extend half-life may be necessary to optimize first responder prophylaxis.