Functions of Epimedin C in a zebrafish model of glucocorticoid-induced osteoporosis.

Epimedium is thought to enhance the integrity of tendons and bones, ease joint discomfort and rigidity and enhance kidney function. Although glucocorticoids are commonly used in clinical practice, the mechanism by which the active compound Epimedin C (EC) alleviates glucocorticoid-induced osteoporosis (GIOP) is not well understood. The therapeutic potential of EC in treating GIOP was evaluated using alizarin red S staining, calcein immersion and fluorescence imaging, and bone mineralization, bone mass accumulation and bone density in zebrafish larvae were determined. Using the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the key signalling pathways related to bone development were identified. A protein-protein interaction network (PPIN) was constructed to identify osteoclast characteristic genes and the findings were verified using real-time quantitative PCR (RT-qPCR). The bone tissue damage caused by prednisolone was reduced by EC. It also altered physiological processes, improved bone density, boosted mineralization and increased bone mass and activity. Subsequent empirical investigations showed that EC impacted the major signalling pathways involved in bone development, such as osteoclast differentiation, oestrogen, MAPK, insulin resistance, PPAR and AMPK signalling pathways. It also decreased the expression of genes typical of osteoclasts. The results of our study uncover a previously unknown function of EC in controlling bone formation and emphasize the potential of EC as a therapeutic target. The osteoprotective effect of EC indicates its potential as a cost-effective strategy for treating GIOP.

Diagnostic performance of the thyroid imaging reporting and data system improved by color-coded acoustic radiation force pulse imaging.

OBJECTIVE: To explore the value of color-coded virtual touch tissue imaging (CCV) using acoustic radiation force pulse technology (ARFI) in diagnosing malignant thyroid nodules. METHODS: Images including 189 thyroid nodules were collected as training samples and a binary logistic regression analysis was used to calculate regression coefficients for Thyroid Imaging Reporting and Data System (TI-RADS) and CCV. An integrated prediction model (TI-RADS+CCV) was then developed based on the regression coefficients. Another testing dataset involving 40 thyroid nodules was used to validate and compare the diagnostic performance of TI-RADS, CCV, and the integrated predictive models using the receiver operating characteristic (ROC) curves. RESULTS: Both TI-RADS and CCV are independent predictors. The diagnostic performance advantage of CCV is insignificant compared to TI-RADS (P = 0.61). However, the diagnostic performance of the integrated prediction model is significantly higher than that of TI-RADS or CCV (all P < 0.05). Applying to the validation image dateset, the integrated predictive model yields an area under the curve (AUC) of 0.880. CONCLUSIONS: Developing a new predictive model that integrates the regression coefficients calculated from TI-RADS and CCV enables to achieve the superior performance of thyroid nodule diagnosis to that of using TI-RADS or CCV alone.

A rare case of bladder cancer that metastasized to brain, heart, and lung lymph nodes benefited from immunotherapy.

Bladder cancer is a common malignant tumor of the genitourinary system, with the primary cause of death being metastasis. The most common metastatic sites are the lymph nodes, liver, lung, bone, peritoneum, pleura, kidney, adrenal gland, and the intestine. Brain and heart metastases are rare. In this report, we describe a patient who had pulmonary lymph node metastases more than a year after being diagnosed with bladder cancer, followed by brain and cardiac metastases more than two years later. Following the failure of standard first-line chemotherapy, the patient accepted 6 cycles of tislelizumab immunotherapy. The re-examination revealed that the bilateral frontal brain metastases had vanished, the right temporal lobe metastases had been greatly decreased, the neurological symptoms had been alleviated, and the cardiac metastases had disappeared. This is a rare clinical case with encouraging effects of tislelizumab and can serve as a model for the treatment of similar patients.

Multidisciplinary management of pediatric malignant rhabdoid tumor based on 5 years of experience at a tertiary care center.

OBJECTIVE: Malignant rhabdoid tumor (MRT) is a highly aggressive tumor that occurs mostly in young children with extremely poor prognosis. Standardized and effective treatment strategies for MRT have yet to be established because of its rarity. Here, we report our single-institutional experience involving MRT treatment. METHODS: Patients with newly diagnosed MRT between March 2016 and October 2021 were included. The clinical characteristic, treatment-related toxicities, clinical outcomes, and prognostic factor were retrospectively analyzed. RESULTS: A total of 18 patients with MRT were enrolled during the 5 years. The median age was 42.8 months (range 10 to 82 years). Among the 18 patients, 9 patients died after a median of follow-up 26 months (range 3 to 42 months). The 1-year event-free survival (EFS) and 3-year overall survival (OS) rates of the entire cohort were 63% (95% CI 46% to 74%) and 67% (95% CI 49% to 82%), respectively. Univariate analysis of patients who underwent gross or total resection followed by adjuvant chemotherapy and radiotherapy demonstrated an improvement in 1-year EFS. However, only gross resection and total resection predicted a better 3-year OS. CONCLUSIONS: Surgical excision is still the mainstream treatment for MRT. Postoperative adjuvant treatments including chemotherapy and radiotherapy contribute to improved disease control rate. Our single-institute experience may provide insights into the multimodal treatment of MRT.

Color-map virtual touch tissue imaging (CMV) combined with BI-RADS for the diagnosis of breast lesions.

OBJECTIVE: To investigate the importance of color-map virtual touch tissue imaging (CMV) in assisting Breast Imaging Reporting and Data Systems (BI-RADS) in diagnosing malignant breast lesions. METHODS: A dataset included 134 patients and 146 breast lesions was assembled. All patients underwent biopsy or surgical excision of breast lesions, and pathological results were obtained. All patients with breast lesions also underwent conventional ultrasound (US) and CMV. Each lesion was assigned a CMV score based on the color pattern of the lesion and surrounding breast tissue and a BI-RADS classification rating based on US characteristics. We compared the diagnostic performance of using BI-RADS and CMV separately and their combination. RESULTS: BI-RADS (odds ratio [OR]: 3.665; 95% confidence interval [CI]: 2.147, 6.258) and CMV (OR: 6.616; 95% CI: 2.272, 19.270) were independent predictors of breast malignancy (all P < 0.05). The area under the receiver operating characteristic curves (AUC) for either CMV or BI-RADS alone was inferior to that of the combination (0.877 vs. 0.962; 0.938 vs. 0.962; all P < 0.05). CONCLUSIONS: The performance of BI-RADS in diagnosing breast lesions is significantly improved by combining CMV. Therefore, we recommend CMV as an adjunct to BI-RADS.

Analysis of the Relationship Between Modic Change and Spinopelvic Parameters in the Sagittal Plane.

BACKGROUND This study explored relationship between Modic change and spinopelvic parameters in the sagittal plane. MATERIAL AND METHODS We divided 80 patients into 4 groups: 60 subjects diagnosed with Modic changes (MC) were enrolled in the MC groups (MC1, MC2, and MC3) with each MC type consisting of 20 subjects, and 60 healthy subjects were enrolled in the control group. Spinopelvic parameters in the sagittal plane were calculated to assess their associations with MC. Multivariate logistic regression was used to explore possible risk factors for MC. RESULTS PI and LL in the MC groups were significant smaller than in the control group (p<0.05). PI, SS, and PT were significantly correlated with LL with a correlation coefficient of 0.75PI, 0.71SS and 0.69PT (p<0.05). Multivariate logistic regression of the significant variables showed that PI (less than 43.2°) is an independent significant risk factor for MC. ROC analysis showed that moderate diagnostic value was obtained for the significant variable, with an area under the curve (AUC) of 0.80 (p>0.05). CONCLUSIONS We concluded that PI is risk factor for MC, and smaller PI is associated with higher incidence of MC.

Genetic Diversity of Listeria monocytogenes Isolates from Invasive Listeriosis in China.

Listeria monocytogenes is a deadly foodborne pathogen, and infections can result in meningoencephalitis and sepsis with mortality rates of up to 30%. In this study, we performed comparative whole-genome analysis of 30 clinical isolates sequenced together with 32 previously sequenced clinical and food isolates from China. The data indicate that L. monocytogenes isolates belonging to the clonal complexes (CC) -1, -8, -9, -87, -121, and -155 are present in human clinical cases. The majority of isolates are from CC-87, 9, and 8 and overlap with those CCs previously reported on the basis of multilocus sequence typing for isolates from Chinese food products. Detailed genome analysis of isolates, representative of CCs in clinical and food products, revealed strong similarities both in their core- and accessory genomes indicating that they are highly related. When compared to genome sequences of isolates of a given CC worldwide, clinical isolates of China were distinct and clustered in unified clades. Our data indicate that epidemic clones of L. monocytogenes (CC-87, 9, and 8) with unusually high occurrence of plasmids are unique to China and suggest that common populations of L. monocytogenes clones are present in both clinical and food products in China.

[Effect of ferulic acid on cholesterol efflux in macrophage foam cell formation and potential mechanism].

The formation of macrophage-derived foam cells is a typical feature of atherosclerosis (AS). Reverse cholesterol efflux (RCT) is one of important factors for the formation of macrophage foam cells. In this study, macrophage form cells were induced by oxidized low density lipoprotein (ox-LDL) and then treated with different concentrations of ferulic acid, so as to observe the effect of ferulic acid on the intracellular lipid metabolism in the ox-LDL-induced macrophage foam cell formation, the cholesterol efflux and the mRNA expression and protein levels of ATP binding cassette transporter A1 (ABCA1) and ATP binding cassette transporter G1 (ABCG1) that mediate cholesterol efflux, and discuss the potential mechanism of ferulic acid in resisting AS. According to the findings, compared with the control group, the ox-LDL-treated group showed significant increase in intracellular lipid content, especially for the cholesterol content; whereas the intracellular lipid accumulation markedly decreased, after the treatment with ferulic acid. The data also demonstrated that the mRNA and protein expressions of ABCA1 and ABCG1 significantly increased after macrophage foam cells were treated with different concentrations of ferulic acid. In summary, ferulic acid may show the anti-atherosclerosis effect by increasing the surface ABCA1 and ABCG1 expressions of macrophage form cells and promoting cholesterol efflux.

[Prokaryotic expression and immunological characteristics of Mycobacterium tuberculosis Rv1886c].

OBJECTIVE: Ag85B (Rv1886c) is secreted during the early stages of infection by Mycobacterium tuberculosis. The purpose of this study was probed into the immune response against Ag85B in vivo. METHODS: Ag85B was prokaryotic expressed and identified, its immunological characteristics were evaluated with indirect-ELSIA, Sandwich-ELISA and RESULTS: Ag85B was mainly expressed in form of inclusion body enzyme-linked immunospot assay (ELISPOT). confirmed by SDS-PAGE. Western blot analysis shows that the fusion protein had good specific reaction with serum of tuberculosis patient and serum of mice immunized with LM-Ag85B. C57BL/6 mice were subcutaneously immunized with Ag85B, the production of IFN-gamma and IL-4 in the spleen cells was determined by Sandwich ELISA, the level of IFN-gamma was significantly higher than that of IL-4 (P < 0.001) in the Ag85B immunization group, it indicated the protein induced Th1-tendency immune responses. Furthermore, purified protein derivative (PPD) used as coating antigen, antibody titer against Ag85B in murine serum reached 1:6400, it was demonstrated that Ag85B could also induce humoral immune responses. Additionally, C57BL/6 mice were intravenously immunized with M. tb H37Rv and bacillus Calmette-Guérin (BCG) respectively for 42 days, M. tb H37Rv group intended to induce Ag85B specific Th1 type immune response, and its ability of eliciting cellular immunity was significantly stronger than BCG group (P < 0.001). CONCLUSION: Ag85B can affectively induce strongly Th1-tendency immune response and humoral response. Whereas, BCG prime vaccination only can elicit low levels of Ag85B(240-259) specific immune response. The study laid foundation for probing the pathogenic mechanism, the development of novel vaccine and the establishment of clinical diagnostic method.

Structural characteristics, biomechanics and clinical significance of calcar femorale: A review.

The calcar femorale, first identified by Merkel in 1874, plays a pivotal role in the weight-bearing capacity of the proximal femur, and its structural integrity is crucial for the efficient distribution of mechanical loads. Originating at the vertical ridge where the pubofemoral ligament anchors, this bony prominence extends laterally behind the neutral axis from the medial to lateral aspects. Its presence is not merely an anatomical curiosity but significantly influences the biomechanics of the hip joint by providing additional strength and support against compressive forces encountered during activities such as walking or jumping. Despite its clear description in orthopedic texts, misconceptions persist about its exact function and importance. This article delves into the nuanced anatomy and biomechanical properties of the calcar femorale, offering a detailed literature-based examination that demonstrates its relevance in clinical practice. The review highlights how the robustness of the calcar femorale contributes to the prevention of femoral neck fractures as well as the stabilization of hip prostheses. Furthermore, the indispensable role of the calcar femorale in surgical outcomes is discussed, especially in the context of fracture repair and joint replacement, thus illustrating its enduring significance in contemporary medical applications.

Development and validation of a pyroptosis-related prognostic signature associated with osteosarcoma metastasis and immune infiltration.

Pyroptosis is a programmed cell death, which has garnered increasing attention because it relates to the immune and therapy response. However, few studies focus on the application of pyroptosis-related genes (PRGs) in predicting osteosarcoma (OS) patients' prognoses. In this study, the gene expression and clinical information of OS patients were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Based on these PRGs and unsupervised clustering analysis, all OS samples can be classified into 2 clusters. The 8 key differential expressions for PRGs (LAG3, ITGAM, CCL2, TLR4, IL2RA, PTPRC, FCGR2B, and CD5) were established through the univariate Cox regression and utilized to calculate the risk score of all samples. According to the 8-gene signature, OS samples can be divided into high and low-risk groups and correlation analysis can be performed using immune cell infiltration and immune checkpoints. Finally, we developed a nomogram to improve the PRG-predictive model in clinical application. We verified the predictive performance using receiver operating characteristic (ROC) and calibration curves. There were significant differences in survival, immune cell infiltration and immune checkpoints between the low and high-risk groups. A nomogram was developed with clinical indicators and the risk scores were effective in predicting the prognosis of patients with OS. In this study, a prognostic model was constructed based on 8 PRGs were proved to be independent prognostic factors of OS and associated with tumor immune microenvironment. These 8 prognostic genes were involved in OS development and may serve as new targets for developing therapeutic drugs.

CAR-NK cells in combination therapy against cancer: A potential paradigm.

Various preclinical and a limited number of clinical studies of CAR-NK cells have shown promising results: efficient elimination of target cells without side effects similar to CAR-T therapy. However, the homing and infiltration abilities of CAR-NK cells are poor due to the inhibitory tumor microenvironment. From the perspective of clinical treatment strategies, combined with the biological and tumor microenvironment characteristics of NK cells, CAR-NK combination therapy strategies with anti-PD-1/PD-L1, radiotherapy and chemotherapy, kinase inhibitors, proteasome inhibitors, STING agonist, oncolytic virus, photothermal therapy, can greatly promote the proliferation, migration and cytotoxicity of the NK cells. In this review, we will summarize the targets selection, structure constructions and combinational therapies of CAR-NK cells for tumors to provide feasible combination strategies for overcoming the inhibitory tumor microenvironment and improving the efficacy of CAR-NK cells.

High-Efficiency Blue-Emitting Mn-Ligand passivated CsPbBr3 nanoplatelets.

Perovskite nanoplatelets (NPLs), as a promising material to achieve pure blue emission, have attracted significant attention in high gamut displays. However, the high surface-to-volume ratio and the loosely connected ligands of NPLs make them susceptible to degradation from light, air and heat. As a result, NPLs often exhibit low photoluminescence (PL) intensity and instability. Here, an Mn-ligand passivation strategy is proposed, in which Mn-doped DMAPbBr3 is used as a precursor. During the perovskite transformation, Mn2+ ions migrate from the lattice of DMAPbBr3 to the surface of CsPbBr3 NPLs, which have strong binding forces with ligands. The final products Mn-CsPbBr3 (M-CPB) NPLs are then acquired by the ligand-induced ripening growth process, which not only exhibit pure blue emission with narrow full width at half maximum (FWHM), but also possess near-unity PL quantum yields (QYs). Besides, M-CPB NPLs show excellent stability due to the strong Mn-ligand passivation layer. Based on the new growth mechanism discovery, the reaction time can be shortened to several minutes by heating. The innovative growth model proposed in this work will provide a paradigm for designing and optimizing future synthesis schemes.

Highly efficient and stable Cs3Mn0.93Zn0.07Br5@SiO2 for wide color gamut backlight displays.

Mn-based perovskites have become a new candidate material for backlight display applications. However, low efficiency and poor stability are the key problems limiting the application of Mn-based perovskites. In this work, Zn-doped and SiO2-encapsulated Cs3MnBr5, denoted as Cs3Mn0.93Zn0.07Br5@SiO2 (CMZBS), was successfully synthesized to improve the photoluminescence quantum yield (PLQY) and stability. After Zn doping, the PLQY increased from 51% to 72% due to the reduction in the energy transfer between [MnBr4]2-. The PLQY can be further improved to 80% after coating SiO2. Compared with Cs3MnBr5 (CMB), CMZBS showed better stability against thermal, air, light, and polar solvents (ethanol and isopropanol). In addition, a white LED (WLED) device with a CIE of (0.323, 0.325) was fabricated by integrating CMZBS and the red phosphor K2SiF6:Mn4+ on a 465 nm blue GaN chip, which exhibited a high luminous efficiency of 92 lm W-1 and excellent stability, demonstrating its great potential application in wide color gamut displays.

Synergetic spin crossover and fluorescence in a mononuclear iron(III) complex.

Two mononuclear iron(III) complexes (XEA)[Fe(azp)2]·H2O (H2azp = 2,2'-azodiphenol, XEA = 2-fluoroethylammonium and 2-chloroethylammonium) are synthesized, which exhibit the counterion dependence of magnetic and fluorescent properties. The synergetic effect between abrupt spin crossover and fluorescence is observed in an iron(III) complex for the first time.

Efficient Homojunction/Heterojunction Photocatalyst via Integrating CsPbBr3 Quantum Dot Homojunction with TiO2 for Degradation of Organic Dyes.

A novel TiO2-CsPbBr3(Q) photocatalyst is proposed and rationally constructed, where CsPbBr3 perovskite quantum dots (QDs) of various sizes inside mesopore TiO2 (M-TiO2) are integrated. These perovskite QDs, generated in situ within M-TiO2, establish a type-II homojunction. Interestingly, a Z-scheme heterojunction is simultaneously formed at the interface between CsPbBr3 and TiO2. Due to the coexistence of the type-II homojunction and the Z-scheme heterojunction, photogenerated electrons are effectively transferred from TiO2 to CsPbBr3, thereby suppressing carrier recombination and thus enhancing the degradation of rhodamine B (RhB). Compared with pure CsPbBr3 and TiO2, TiO2-CsPbBr3(Q) shows significantly enhanced photocatalytic performance for RhB degradation. The degradation efficiency of RhB in the presence of the TiO2-CsPbBr3(Q) attains 97.7% in 5 min under light illumination, representing the highest efficiency observed among photocatalysts based on TiO2. This study will facilitate the development of superior semiconductor catalysts for photocatalytic applications.

Polystyrene microplastics alleviate the developmental toxicity of silver nanoparticles in embryo-larval zebrafish (Danio rerio) at the transcriptomic level.

Since silver nanoparticles (AgNPs) and polystyrene microplastics (PS-MP) share common environmental niches, their interactions can modulate their hazard impacts. Herein, we assessed the developmental toxicity of 1 mg/L PS-MP, 0.5 mg/L AgNPs and the mixtures of AgNPs and PS-MP on embryo-larval zebrafish. We found that AgNPs co-exposure with PS-MP remarkably decreased mortality rates, malformation rates, heart rates and yolk sac area, while it increased hatching rates and eye size compared to the AgNPs group. These phenomena revealed that the cell cycle, oxidative stress, apoptosis, lipid metabolism, ferroptosis and p53 signalling pathway were obviously affected by single AgNPs exposure at 96 hpf (hours post fertilization). Interestingly, all these effects were effectively ameliorated by co-exposure with PS-MP. The combination of transcriptomic and metabolomic analyses showed that the imbalance of DEGs (differentially expressed genes) and DEMs (differentially expressed metabolites) (PI, phosphatidylinositol and TAG-FA, triacylglycerol-fatty acid) disturbed both the cell cycle and lipid metabolism following single AgNPs exposure and co-exposure with PS-MP. These findings suggest that PS-MP attenuates the developmental toxicity of AgNPs on embryo-larval zebrafish. Overall, this study provides important insight into understanding the transcriptional responses and mechanisms of AgNPs alone or in combination with PS-MPs on embryo-larval zebrafish, providing a reference for ecological risk assessment of combined exposure to PS-MP and metal nanoparticles.

[Immunobiologic characteristics of a recombinant Listeria monocytogenes expressing Mycobacterium tuberculosis antigens].

OBJECTIVE: Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis complex. Hence, novel vaccines against TB are urgently needed and important to the public health. METHODS: Immunobiologic characteristics of a recombinant attenuated Listeria monocytogenes strain LMdeltahly: :Ag85b-esat-6 was evaluated. RESULTS: LMdeltahly: :Ag85b-esat-6 had lost the hemolytic activity. It was completely cleared from the livers and spleens of mice 5 days after inoculation via intravenous route. Furthermore, the LD50 of the recombinant strain increased by 4 Logs comparing to that of the parent strain. Histopathology reveals no obvious pathological changes following administration of the recombinant strain to mice, indicating its safety. In addition, the potential protective immune response was evaluated on C57BL/6 mice via intravenous immunization route. The results indicate that the antigen delivered by the recombination LM could induce Th1 type immune response and elicit strong cytotoxic lymphocyte effect against Ag85B-ESAT-6. CONCLUSION: Thus, LMdeltahly::Ag85b-esat-6 had high safety to mice, and could be used as a novel vaccines candidate for preventing tuberculosis.

Virtual touch tissue imaging for differential diagnosis in ACR TI-RADS category 3-4 thyroid nodules: Conservative and aggressive methods.

PURPOSE: Many Thyroid Imaging Reporting and Data System (TI-RADS) category 3-4 nodules are benign. Our study aimed to add virtual touch tissue imaging (VTI) to TI-RADS using two methods, namely conservative and aggressive, and to explore which method had better diagnostic performance and which method avoided more unnecessary biopsies. METHODS: From January 2016 to December 2021, we included 121 thyroid nodules classified as TI-RADS category 3-4 in 115 consecutive patients in this retrospective study. This study used the reference standard for pathological diagnosis by surgical resection or biopsy. The diagnostic performance of the different methods was evaluated and compared by receiver operating characteristic (ROC) and area under the ROC curve (AUC). RESULTS: In this study, the aggressive approach had the best diagnostic performance among TI-RADS alone, the conservative approach, and the aggressive approach (AUC: 0.863 versus 0.598, P = 0.0007; 0.863 versus 0.755, P = 0.0067). When we used an aggressive approach, 75.44% (43/57) of the 57 false-positive nodes diagnosed by TI-RADS were appropriately downgraded from TI-RADS category 4 to category 3, avoiding unnecessary biopsies. CONCLUSION: VTI improves the diagnostic performance of TI-RADS. The aggressive approach of combining the TI-RADS with VTI would help reduce unnecessary biopsies.

Highly efficient and robust multi-color afterglow of ZnO nanoparticles.

Room temperature phosphorescence (RTP) materials are widely used in various fields. However, the realization of multicolor RTP via facile approaches still remains a great challenge. In this study, we propose an in situ hydrolysis method using different solvents to synthesize blue, green, and yellow phosphorescence ZnO/SiO2 composites. By investigating the photoluminescence (PL) and phosphorescence mechanisms of ZnO/SiO2 composites, it is discovered that the solvents not only introduce impurities to ZnO but also affect the position of defect energy levels, leading to the variation in luminescent performance. Meanwhile, the as-synthesized ZnO/SiO2 composites exhibit stable PL and phosphorescence under extreme conditions. Specifically, the PL and phosphorescence properties of the composites are well maintained at high temperature (523 K) or underwater. Owing to the multicolor phosphorescence properties of these ZnO/SiO2 products, herein, we demonstrate that ZnO/SiO2 composites can act as new smart materials for information encryption, fingerprint identification, and white light-emitting diodes (WLEDs).