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Elevated interstitial fluid pressure (IFP) within pathological tissues (e.g., tumors, obstructed kidneys, and cirrhotic livers) creates a significant hindrance to the transport of nanomedicine, ultimately impairing the therapeutic efficiency. Among these tissues, solid tumors present the most challenging scenario. While several strategies through reducing tumor IFP have been devised to enhance nanoparticle delivery, few approaches focus on modulating the intrinsic properties of nanoparticles to effectively counteract IFP during extravasation and penetration, which are precisely the stages obstructed by elevated IFP. Herein, we propose an innovative solution by engineering nanoparticles with a fusiform shape of high curvature, enabling efficient surmounting of IFP barriers during extravasation and penetration within tumor tissues. Through experimental and theoretical analyses, we demonstrate that the elongated nanoparticles with the highest mean curvature outperform spherical and rod-shaped counterparts against elevated IFP, leading to superior intratumoral accumulation and antitumor efficacy. Super-resolution microscopy and molecular dynamics simulations uncover the underlying mechanisms in which the high curvature contributes to diminished drag force in surmounting high-pressure differentials during extravasation. Simultaneously, the facilitated rotational movement augments the hopping frequency during penetration. This study effectively addresses the limitations posed by high-pressure impediments, uncovers the mutual interactions between the physical properties of NPs and their environment, and presents a promising avenue for advancing cancer treatment through nanomedicine. [ABSTRACT FROM AUTHOR]

Background: Diabetic osteoporosis exhibits heterogeneity at the molecular level. Ferroptosis, a controlled form of cell death brought on by a buildup of lipid peroxidation, contributes to the onset and development of several illnesses. The aim was to explore the molecular subtypes associated with ferroptosis in diabetic osteoporosis at the molecular level and to further elucidate the potential molecular mechanisms. Methods: Integrating the CTD, GeneCards, FerrDb databases, and the microarray data of GSE35958, we identified ferroptosis-related genes (FRGs) associated with diabetic osteoporosis. We applied unsupervised cluster analysis to divide the 42 osteoporosis samples from the GSE56814 microarray data into different subclusters based on FRGs. Subsequently, FRGs associated with two ferroptosis subclusters were obtained by combining database genes, module-related genes of WGCNA, and differentially expressed genes (DEGs). Eventually, the key genes from FRGs associated with diabetic osteoporosis were identified using the least absolute shrinkage and selection operator (LASSO), Boruta, support vector machine recursive feature elimination (SVM RFE), and extreme gradient boosting (XGBoost) machine learning algorithms. Based on ROC curves of external datasets (GSE56815), the model's efficiency was examined. Results: We identified 15 differentially expressed FRGs associated with diabetic osteoporosis. In osteoporosis, two distinct molecular clusters related to ferroptosis were found. The expression results and GSVA analysis indicated that 15 FRGs exhibited significantly different biological functions and pathway activities in the two ferroptosis subclusters. Therefore, we further identified 17 FRGs associated with diabetic osteoporosis between the two subclusters. The results of the comprehensive analysis of 17 FRGs demonstrated that these genes were heterogeneous and had a specific interaction between the two subclusters. Ultimately, the prediction model had a strong foundation and excellent AUC values (0.84 for LASSO, 0.84 for SVM RFE, 0.82 for Boruta, and 0.81 for XGBoost). IDH1 is a common gene to all four algorithms thus being identified as a key gene with a high AUC value (AUC = 0.698). Conclusions: As a ferroptosis regulator, IDH1 is able to distinguish between distinct molecular subtypes of diabetic osteoporosis, which may offer fresh perspectives on the pathogenesis of the disease's clinical symptoms and prognostic heterogeneity. [ABSTRACT FROM AUTHOR]

This paper proposes the step-by-step design procedure for obtaining independent dual band-notch performance, which provides a valuable method for designing tunable dual band-notched UWB antenna. The proposed antenna consists of the semicircle ring-like radiating patch with an elliptical-shaped slot and double split ring resonators on the top surface of the substrate and defected ground structure (DGS) on the bottom surface of the substrate. The operating frequencies ranged from 1.3 to 11.6 GHz (S11 < − 10 dB). By loading varactor diodes at the gap of the resonators structure and changing the varactor diode's reverse bias voltage(0–30 V), a wider band-notched tuning range from 2.47–4.19 to 4.32–5.96 GHz can be achieved, which covers the whole WiMAX band and WLAN band. The experimental results agree well with the simulated results. The notched gain at notched frequency points is about − 5.3 dBi and − 5 dBi, demonstrating that the narrow-band interference signal could be efficiently suppressed. The security of UWB communication systems can be further enhanced. Meanwhile, the selection of varactor diode and DC bias circuit are fully considered. Hence, the accuracy of the experiment results and antenna operating performance have been improved. Furthermore, the proposed antenna only has an electrical size of 0.26λ*0.19λ at 1.3 GHz. Compared to the related reported antennas, the proposed antenna has achieved a simpler structure, low profile, compact size, tunable dual band-notched characteristics, extensive independent tunable range, and good band-notched performance simultaneously, to the best of our knowledge. The proposed antenna is believed to have a valuable prospect in UWB communication, Wireless Body Area Network, Industry Science Medicine, mobile communication applications, etc. [ABSTRACT FROM AUTHOR]

Background: Globally, among all women, the most frequently detected and diagnosed and the most lethal type of cancer is breast cancer (BC). In particular, bone is one of the most frequent distant metastases 24in breast cancer patients and bone metastasis arises in approximately 80% of advanced patients. Thus, we need to identify and validate early detection markers that can differentiate metastasis from non-metastasis breast cancers. Methods: GSE55715, GSE103357, and GSE146661 gene expression profiling data were downloaded from the GEO database. There was 14 breast cancer with bone metastasis samples and 8 breast cancer tissue samples. GEO2R was used to screen for differentially expressed genes (DEGs). The volcano plots, Venn diagrams, and annular heatmap were generated by using the ggplot2 package. By using the cluster Profiler R package, KEGG and GO enrichment analyses of DEGs were conducted. Through PPI network construction using the STRING database, key hub genes were identified by cytoHubba. Finally, K-M survival and ROC curves were generated to validate hub gene expression. Results: By GO enrichment analysis, 143 DEGs were enriched in the following GO terms: extracellular structure organization, extracellular matrix organization, leukocyte migration class II protein complex, collagen tridermic protein complex, extracellular matrix structural constituent, growth factor binding, and platelet-derived growth factor binding. In the KEGG pathway enrichment analysis, DEGs were enriched in Staphylococcus aureus infection, Complement and coagulation cascades, and Asthma. By PPI network analysis, we selected the top 10 genes, including SLCO2B1, STAB1, SERPING1, HLADOA, AIF1, GIMAP4, C1orf162, HLA-DMB, ADAP2, and HAVCR2. By using TCGA and THPA databases, we validated 2 genes, SERPING1 and GIMAP4, that were related to the early detection of bone metastasis in BC. Conclusions: 2 abnormally expressed hub genes could play a pivotal role in the breast cancer with bone metastasis by affecting bone homeostasis imbalance in the bone microenvironment. [ABSTRACT FROM AUTHOR]

Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder without a recognized cause. Aquaporins (AQPs) are transmembrane channels that carry water through cell membranes and are critical for cerebrospinal fluid circulation and cerebral water balance. The function of AQPs in developing and maintaining hydrocephalus should be studied in greater detail as a possible diagnostic and therapeutic tool. Recent research indicates that patients with iNPH exhibited high levels of aquaporin 1 and low levels of aquaporin 4 expression, suggesting that these AQPs are essential in iNPH pathogenesis. To determine the source of iNPH and diagnose and treat it, it is necessary to examine and appreciate their function in the genesis and maintenance of hydrocephalus. The expression, function, and regulation of AQPs in iNPH are reviewed in this article, in order to provide fresh targets and suggestions for future research. [ABSTRACT FROM AUTHOR]

This document is an editorial published in Frontiers in Pharmacology titled "Natural products, medicinal foods, herbal medicines, bone metabolism diseases, bone-related tumor diseases." The editorial discusses the importance of studying natural products, medicinal foods, and herbal medicines in the context of bone metabolism diseases and bone-related tumor diseases. These diseases, such as osteoporosis and bone tumors, are prevalent worldwide and pose significant challenges in terms of diagnosis and treatment. The editorial emphasizes the need for research on natural remedies and their bioactive metabolites, which have shown potential in promoting bone health and inhibiting tumor growth. The document also provides a summary of four articles included in the research topic, which explore the antibacterial properties of Tea-Seed Oil, the impact of Korean Red Ginseng extract on the gut-bone axis, the combined therapeutic effect of herbal medicine and Western medicine for osteoporosis in patients with rheumatoid arthritis, and the pharmacological properties of Hypericum sampsonii. The editorial concludes by highlighting the importance of further research on the molecular mechanisms and clinical translation of natural products for the treatment of bone-related diseases. [Extracted from the article]

Background. The increased risk and poor survival outcome of cervical adenocarcinoma (CAC) demand for effective early diagnostic biomarkers that can predict the disease progression and outcome. The purpose of this study was to investigate the value of methylation status of SOX1 and PAX1 in the detection and prognosis of CAC. Methods. We performed a quantitative methylation-specific polymerase chain reaction in 205 cervical paraffin-embedded specimens (175 CACs, 30 noncancer cervical tissues). Overall and progression-free survival (OS and PFS, respectively) rates were calculated and compared using the Kaplan-Meier method. The prognostic value of SOX1m and PAX1m on CAC patients was assessed by the Cox regression model. A mathematical formula combining SOX1m, PAX1m, and age was constructed for survival prediction. Results. The methylation status of SOX1 and PAX1 was higher in CAC tissues than in noncancer cervical tissues. In addition, SOX1m-positive CAC patients showed a higher 5-year OS rate than SOX1m-negative patients. In CAC patients with smaller tumor size (<4 cm), the PAX1m-positive group showed a higher 5-year PFS rate than the PAX1m-negative group. In the algorithm combining SOX1m, PAX1m, and age, the low-risk group showed a better 5-year OS and PFS rate than the high-risk group. Conclusion. SOX1 and PAX1 methylation levels are higher in CAC than in normal cervical tissues and are potential biomarkers for monitoring CAC prognosis. [ABSTRACT FROM AUTHOR]

In order to explore the scientific basis for the application of oil bodies (OBs) from different peanut varieties in food, the effect of NaCl (0-100 mM), thermal processing (25-45℃, 1 h) and pH (3.0, 7.4, and 9.0) on their zeta potentials was analyzed in this study. The zeta potentials of OB suspensions (in 10 mM phosphate buffer) prepared from five peanut varieties in different salt concentrations (0-100 mM) were positive at pH 3.0, while they remained negative at pH 7.4 and 9.0. The absolute values of zeta potentials were over 20 mV at a lower salt concentration (< 10 mM NaCl) at pH 3.0 and 7.4. Particularly, the values of zeta potentials of Yuhua27 and Yuhua9830 were as high as 40 mV in the absence of NaCl at pH 7.4. The OBs exhibited diverse change trends between the five peanut varieties in the temperatures from 25 to 45℃ (0 mM NaCl, pH 7.4). The OBs from Yuhua9830 exhibited the best thermal adaptability at the different temperatures tested than the other four peanut varieties. These outcomes suggested that OBs extracted from different varieties possess diverse properties and may provide a new insight into choosing a suitable peanut variety for the food industry. [ABSTRACT FROM AUTHOR]

Background: Heterotopic pancreas most commonly occurs in the upper gastrointestinal tract of adults, usually as an incidental finding. It seldom occurs at the umbilicus, and even rarely in the pediatric age group. Case presentation: Here we present a case of heterotopic pancreatic tissue in the omphalomesenteric duct remnant of a 9-month-old baby girl. She presented with redness at the base of the umbilicus associated with occasional mild wetness. A urachal fistula was suspected by ultrasound. Histology from subsequent resection revealed fibrous tissue with heterotopic pancreatic tissue and accompanying small bowel mucosa. The patient's umbilical redness resolved after the surgery. Conclusions: Upon literature search, we found only 17 other cases of heterotopic pancreas reported in the umbilicus. They described a high male to female ratio, frequent association with omphalomesenteric duct remnant and presentation of umbilical discharge. The Heinrich system is frequently used to classify heterotopic pancreas into 3 types, based on the presence of acini, islets and ducts. Several mechanisms have been proposed on the pathogenesis of heterotopic pancreas, including misplacement, metaplasia and totipotent cell theories. Heterotopic pancreas can manifest clinically with diseases of the pancreas, including malignant transformation, reported as high as 12.7% in a series. Awareness of this finding in the biopsy aids the suitable treatment decisions for the patient. [ABSTRACT FROM AUTHOR]

We report a case of pseudotuberculous granulomatous pyelitis in an elderly female patient with hydronephrotic right kidney secondary to obstructing urinary stone. Pseudotuberculous granulomatous pyelitis is a rarely reported entity, characterized by severe granulomatous inflammation limited predominantly to the renal pelvis. It is associated with urinary (pelvicalyceal) obstruction, urolithiasis well as non-Mycobacterial urinary tract infection. [ABSTRACT FROM AUTHOR]

The significant improvements in siRNA therapy have been achieved, which have great potential applications in humans. The kidney is a comparatively easy target organ of siRNA therapy due to its unique structural and functional characteristics. Here, we reviewed recent achievements in siRNA design, delivery and application with focuses on kidney diseases, in particular kidney transplant-related injuries. In addition, the strategy for increasing serum stability and immune tolerance of siRNA was also discussed. At last, the future challenges of siRNA therapy including organ/tissue/cell-specific delivery and time-controlled silence, as well as selecting therapeutic targets, were addressed as well. [ABSTRACT FROM AUTHOR]

The characterization of CD4+ T-cell subsets reflects the immune status and is important in the maintenance of tumorigenesis and homeostasis. To identify changes in the balance of T helper (Th)1, Th2, Th17 and regulatory T cells (Treg) in individuals with renal cell carcinoma (RCC), the present study investigated a total of 131 patients with RCC and 36 healthy volunteers. The number of CD4+ T-bet+ cells, CD4+ GATA binding protein 3+ cells, CD4+ RAR-related orphan receptor γt+ cells, CD4+ CD25hi CD127lo CD45RA- cells and CD4+ CD25hi CD127lo CD45RA+ cells, defined as Th1, Th2, Th17, activated and naïve Treg cells, respectively, were detected in the peripheral blood using flow cytometric analysis. In addition, tumor-infiltrating forkhead box P3 (Foxp3)+ cells were examined using immunohistochemistry. Compared with healthy volunteers, a significant decrease in the peripheral percentages of Th1, activated and naïve Treg cells was observed in patients with RCC, while those of the Th2 and Th17 cells were increased. In particular, as the tumor stage and grade progressed, the levels of Th1, activated and naïve Treg cells in the peripheral blood decreased; however, the levels of Th2 and Th17 cells increased. Furthermore, the number of tumor-infiltrating Foxp3+ cells increased with increasing tumor stage. These results demonstrated that the balance of Th1 and Th2 cells was skewed towards the Th2 profile and the balance of Th17 and Treg cells was skewed towards the Th17 profile in the peripheral blood of patients with renal cell carcinoma (RCC) and Treg cells were recruited to the tumor sites. Therefore, dysfunctional host anti-tumor immunity was observed in patients with RCC, with a skewed Th1/Th2 and Th17/Treg balance. [ABSTRACT FROM AUTHOR]

The significant improvements in siRNA therapy have been achieved, which have great potential applications in humans. The kidney is a comparatively easy target organ of siRNA therapy due to its unique structural and functional characteristics. Here, we reviewed recent achievements in siRNA design, delivery and application with focuses on kidney diseases, in particular kidney transplant-related injuries. In addition, the strategy for increasing serum stability and immune tolerance of siRNA was also discussed. At last, the future challenges of siRNA therapy including organ/tissue/cell-specific delivery and time-controlled silence, as well as selecting therapeutic targets, were addressed as well. [ABSTRACT FROM AUTHOR]

Background Regulatory T cells (Treg) protect kidney against ischemia reperfusion (IR) injury via suppressing innate immunity, but the mechanism has not been fully clarified. Soluble fibrinogen-like protein 2 (sFGL2), a novel effector of Treg, may affect apoptosis and inflammation. This study investigated the role of sFGL2 in renal IR injury in a porcine kidney auto-transplantation model. Materials and methods The left kidney was retrieved from mini pigs and infused by University of Wisconsin solution into the renal artery with the renal artery and vein clamped for 24-h cold storage. After the right nephrectomy, the left kidney was auto-transplanted into the right for 2 weeks. 3 pigs were sacrificed at day 2, 5, 7, 10 and 14 post-transplantation respectively. Collected renal tissues and daily blood samples were stored for further analyses. Results Both serum creatinine and blood urea nitrogen were maximized during day 2 to 5 and followed by a gradual recovery over 2 weeks. The similar pattern were showed in histological damage, myeloperoxidase + cells and apoptosis in the kidney, as well as circulating TNF-α and IFN-γ. Serum sFGL2 presented a fluctuating increase and reached a peak at day 10. The expression of sFGL2 and its receptor FcγRIIB as well as Foxp3 and IL-10 in the kidney was notably increased from day 5 to 10. Conclusion The increased sFGL2 together with FcγRIIB during renal recovery after IR injury suggested that sFGL2 might be a potential renoprotective mediator involved in the renal self-repairing and remodeling in this 2-week porcine auto-transplantation model. [ABSTRACT FROM AUTHOR]

Background: The naked caspase-3 small interfering RNA (siRNA) infused into the renal artery during cold preservation was effective, but did not protect auto-transplant porcine kidneys with increased inflammation and apoptosis in our previous study. The mechanisms involved, in particular, whether siRNA or complementary systemic feedback eliciting innate immune responses are worthy to be further investigated. Methods: The protein and mRNA expression of innate immunity-related molecules were detected by western blotting and quantitative PCR in the tissues previously collected from 48 h auto-transplant kidneys. The donor kidneys were retrieved from mini pigs and cold preserved by University of Wisconsin solution with/without 0.3 mg caspase-3 siRNA for 24 h. Results: The protein level of Toll like receptor (TLR) 3, TLR7, and their main adapters, TRIF and MyD88, was up-regulated in the siRNA preserved auto-transplant kidneys. The mRNA level of NF-κB and c-Jun was increased, as well as pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α and interferon (IFN)-α, β and γ. In addition, the non-TLR RNA sensor PKR protein, but not RIG1, was also increased in the siRNA preserved auto-transplant kidneys. Conclusions: The activation of innate immunity with amplified inflammatory responses in the caspase-3 siRNA preserved auto-transplant kidneys are associated with increased TLR3, TLR7 and PKR, which might be due to complementary systemic feedback, although persistent actions initiated by short-acting caspase-3 siRNA cannot be completely ruled out. These results provided valuable evidence to guide future siRNA design and pre-clinic studies. [ABSTRACT FROM AUTHOR]