Interferon Gamma Inducible Protein 30: from biological functions to potential therapeutic target in cancers.

Interferon Gamma Inducible Protein 30 (IFI30), also known as Gamma-Interferon-Inducible Lysosomal Thiol Reductase (GILT), is predominantly found in lysosomes and the cytoplasm. As the sole enzyme identified to catalyze disulfide bond reduction in the endocytic pathway, IFI30 contributes to both major histocompatibility complex (MHC) class I-restricted antigen cross-presentation and MHC class II-restricted antigen processing by decreasing the disulfide bonds of endocytosed proteins. Remarkably, emerging research has revealed that IFI30 is involved in tumorigenesis, tumor development, and the tumor immune response. Targeting IFI30 may provide new strategies for cancer therapy and improve the prognosis of patients. This review provided a comprehensive overview of the research progress on IFI30 in tumor progression, cellular redox status, autophagy, tumor immune response, and drug sensitivity, with a view to providing the theoretical basis for pharmacological intervention of IFI30 in tumor therapy, particularly in immunotherapy.

Association between severe premenstrual disorders and change of romantic relationship: A prospective cohort of 15,606 women in Sweden.

BACKGROUND: Premenstrual disorders (PMDs) affect women's quality of life, yet the impact on romantic relationships remains unclear. This study aimed to examine the association between severe PMDs and relationship disruption and initiation. METHODS: We conducted a prospective cohort study of 15,606 women during 2009-2021 in Sweden. PMDs were assessed with the modified Premenstrual Symptom Screening Tool at baseline (one-time retrospective self-report), while relationship status was obtained from national population registers during follow-up. Poisson regression was employed to assess the risk of relationship change. RESULTS: At baseline (mean age 33.5 years), 1666 (10.6 %) women met the criteria for severe PMDs. All women were followed for 9.1 years on average for any change of relationship status. Among married/cohabiting women, PMDs were positively associated with relationship disruption (Incidence risk ratio, IRR =1.21, 95 % CI: 1.01-1.43, p = 0.03). A more pronounced association was suggested for premenstrual dysphoric disorder (IRR = 1.22, 95 % CI: 1.01-1.45, p = 0.03) than severe premenstrual syndrome (IRR = 1.01, 95 % CI: 0.43-1.96, p = 0.98) and among women without depression/anxiety (IRR = 1.21, 95 % CI: 1.00-1.47, p < 0.05) than among those with (IRR = 0.99, 95 % CI: 0.61-1.54 p = 0.96) and IRR = 1.01, 95 % CI: 0.57-1.72, p = 0.97). Among single women, a null association was found between PMDs and relationship initiation (IRR = 1.05, 95 % CI: 0.95-1.15, p = 0.32). LIMITATIONS: PMDs were not assessed using prospective symptom charting. CONCLUSIONS: Married/cohabiting women with probable severe PMDs have an increased risk of relationship disruption. PMDs were not associated with relationship initiation in single women. Healthcare professionals should recognize relationship challenges in women with severe PMDs, and they may require support to maintain healthy relationships.

Blastic plasmacytoid dendritic cell neoplasm in Jinhua, China: Two case reports.

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and clinically aggressive hematologic malignancy originating from the precursors of plasmacytoid dendritic cells. BPDCN often involves the skin, lymph nodes, and bone marrow, with rapid clinical progression and a poor prognosis. The BPDCN diagnosis is mainly based on the immunophenotype. CASE SUMMARY: In this paper, we retrospectively analyzed 2 cases of BPDCN. Both patients were elderly males. The lesions manifested as skin masses. Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues. Immunohistochemistry staining showed that cluster of differentiation CD4, CD56, CD43, and CD123 were positive. CONCLUSION: In this paper, we retrospectively analyzed 2 cases of BPDCN. Both patients were elderly males. The lesions manifested as skin masses. Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues. Immunohistochemistry staining showed that cluster of differentiation CD4, CD56, CD43, and CD123 were positive.

Non-invasive estimation of the powder size distribution from a single speckle image.

Non-invasive characterization of powders may take one of two approaches: imaging and counting individual particles; or relying on scattered light to estimate the particle size distribution (PSD) of the ensemble. The former approach runs into practical difficulties, as the system must conform to the working distance and other restrictions of the imaging optics. The latter approach requires an inverse map from the speckle autocorrelation to the particle sizes. The principle relies on the pupil function determining the basic sidelobe shape, whereas the particle size spread modulates the sidelobe intensity. We recently showed that it is feasible to invert the speckle autocorrelation and obtain the PSD using a neural network, trained efficiently through a physics-informed semi-generative approach. In this work, we eliminate one of the most time-consuming steps of our previous method by engineering the pupil function. By judiciously blocking portions of the pupil, we sacrifice some photons but in return we achieve much enhanced sidelobes and, hence, higher sensitivity to the change of the size distribution. The result is a 60 × reduction in total acquisition and processing time, or 0.25 seconds per frame in our implementation. Almost real-time operation in our system is not only more appealing toward rapid industrial adoption, it also paves the way for quantitative characterization of complex spatial or temporal dynamics in drying, blending, and other chemical and pharmaceutical manufacturing processes.

Survival Analysis of Antiretroviral Treatment for PLWH in Sichuan Province, China, 2003-2022: A Large Retrospective Cohort Study.

Background: Sichuan Province was severely affected by the HIV, and there was a scarcity of data regarding the survival time and influencing factors for People Living with HIV/AIDS (PLWH) in Sichuan Province who have received Antiretroviral Therapy (ART). Therefore, it is necessary to conduct a survival analysis for PLWH receiving ART. Methods: A retrospective cohort study was conducted on PLWH who had received ART≥6 months in Sichuan Province from January 1, 2003, to December 31, 2022. The Kaplan-Meier method was used to calculate median survival time and plot survival curves, while a Cox proportional hazards regression model was applied to analyze factors affecting survival time. Bilateral tests were performed, with P≤0.05 considered statistically significant. Results: The cumulative survival rates at 1, 3, 5, and 10 years for the 223,386 subjects were 94.54%, 89.07%, 84.82%, and 76.44%, respectively. Multivariate analysis using the Cox regression model indicated lower mortality risks for females (HR=0.59, 95% CI: 0.54-0.65), homosexual transmission (HR=0.43, 95% CI: 0.33-0.55), and baseline BMI≥24 (HR=0.81, 95% CI: 0.72-0.90). Higher mortality risks were associated with age≥50 years at diagnosis (HR=3.21, 95% CI: 2.94-3.50), being unmarried or divorced (HR=1.23, 95% CI: 1.11-1.37), living separately (HR=1.32, 95% CI: 1.22-1.43), baseline BMI <18.5 (HR=1.27, 95% CI: 1.13-1.41), presence of single-drug resistance (HR=1.25, 95% CI: 1.15-1.36), baseline WHO stage IV (HR=1.27, 95% CI: 1.09-1.47), and a diagnosis-to-treatment interval >12 months (HR=1.27, 95% CI: 1.15-1.41). Compared to those with CD4(+) T cell count of 200-350cells/µL, 350-500cells/µL, and >500cells/µL at baseline, individuals with <200cells/µL had higher mortality risks (HR=0.73, 95% CI: 0.67-0.79; HR=0.57, 95% CI: 0.51-0.64; and HR=0.58, 95% CI: 0.51-0.66, respectively). Conclusion: The survival rate for PLWH receiving ART in Sichuan Province was relatively high. Male gender, age over 50 at diagnosis, being unmarried, divorced, or living separately, presence of single-drug resistance, low baseline BMI, baseline CD4+ T cell <200cells/µL, baseline WHO stage IV, and a diagnosis-to-treatment interval >12 months were risk factors for the survival of PLWH.

Multi-layered carbon accommodation of MnO2 enabling fast kinetics for highly stable zinc ion batteries.

Large-scale durable aqueous zinc ion batteries for stationary storage are realized by spray-coating conductive PEDOT(Poly(3,4-ethylenedioxythiophene)) wrapping MnO2/carbon microspheres hybrid cathode in this work. The porous carbon microspheres with multiple layers deriving from sucrose provide suitable accommodation for MnO2 active materials, exposing more redox active sites and enhancing the contact surface between electrolyte and active materials. As a result, MnO2/microspheres are adhered to the current collector by a conductive PEDOT coating without any binder. The ternary design retards the structural degradation during cycling and shortens the electron and ion transport path, rendering the full batteries high capacity and long cycle stability. The resulting batteries perform the capacity of 277, 227, 110, 85 and 50 mAh/g at 0.2, 0.5, 1, 2 and 5 A/g, respectively. After 3000 cycles the initial capacity retains 86%, and 80% after 5000 cycles. GITT indicates PEDOT wrapping MnO2/microspheres cathode enables better ion intercalating kinetics than conventional MnO2. The work could represent a novel and significant step forward in the studies on the large-scale application of zinc ion batteries.

Clinicopathological Analysis of Epstein-Barr Virus-Positive Inflammatory Follicular Dendritic Cell Sarcoma of the Spleen: A Case Report.

OBJECTIVE: The present study aims to explore the clinicopathological characteristics of Epstein-Barr virus (EBV)-positive inflammatory follicular dendritic cell sarcoma (IFDCS; EBV+ IFDCS). CASE REPORT: The case involved a 32-year-old woman who underwent surgical resection of a splenic nodule. Histological examination and immunohistochemistry were performed using cluster of differentiation (CD) markers, and in-situ hybridization was conducted to detect EBV-encoded RNA (EBER). RESULTS: A microscopic analysis revealed neoplastic cells with various morphologies, including round, ovoid, or spindled shapes, dispersed within a prominent lymphoplasmacytic infiltrate. The tumor cells exhibited nuclear atypia, with some resembling Reed-Sternberg cells. The immunohistochemistry demonstrated focal positivity for follicular dendritic cell markers, such as CD21, CD23 and CD35, and focal negativity for other markers, including CD3, CD34, CD20, CD79a, myeloperoxidase and HMB45. Additionally, the EBER staining showed strongly positive results. The patient showed no local recurrence or metastasis during the 13-month follow-up. CONCLUSION: A comprehensive understanding of EBV+IFDCS, including its clinicopathological features and immunohistochemical characteristics, is crucial for accurate diagnosis and differential diagnosis of this rare tumor.

A new tetracyclic triterpenoid from endophytic fungus Fusarium sporotrichioides.

Objective: To isolate bioactive compounds from the endophytic fungus Fusarium sporotrichioides isolated from Rauwolfia yunnanensis, and investigate their pharmacological activities. Methods: The chemical constituents were isolated and purified by combining with ODS column chromatography, silica gel column chromatography and by performing semipreparative HPLC. Their structures were established on the basis of 1D NMR (1H-NMR and 13C-NMR) and 2D NMR (1H-1H COSY, HSQC, HMBC and NOESY), as well as HRESIMS and comparison with literature data. In addition, the absolute configuration of compound 1 was determined by calculated ECD data. Results: One previously undescribed tetracyclic triterpenoid derivative, named as integracide L (1), 12α-acetoxy-4,4-dimethyl-24-methylene-5α-cholesta-8,14-diene-2α,3ß,11ß-triol (2), 12α-acetoxy-4,4-dimethyl-24-methylene-5α-cholesta-8-momoene-2α,3ß,11ß-triol (3), 12α-acetoxy-4,4-dimethyl-24-methylene-5α-cholesta-8,14-diene-3ß,11ß-triol (4), and 12α-acetoxy-4,4-dimethyl-24-methylene-5α-cholesta-8-momoene-3ß,11ß-triol (5) were isolated from F. sporotrichioide. Moreover, compound 1 was rare tetracyclic triterpenoid with single methyl replacement at C-4 position. Conclusion: Compound 1 was a new tetracyclic triterpenoid isolated from the endophytic fungus F. sporotrichioides. In addition, compound 2 could inhibit the growth of three different human cancer cells significantly. Compounds 3 and 5 were found to possess better cytotoxic activities on HepG-2 cells than the other compounds, with IC50 values of (2.8 ± 0.1) and (6.3 ± 0.3) µmol/L respectively.

A Frequent Diagnostic Pitfall: Dermatological Clinical Features and Pathological Results in Diagnosing Pagetoid Squamous Cell Carcinoma in situ (Case Series).

Squamous cell carcinoma (SCC) in situ can occur on any skin or mucus surface and is more commonly found in elderly patients on areas of skin that have been sunburnt. Most previous case reports are from dermatologists, with few published reports from pathologists. In this study, three patients underwent pathological routine and auxiliary immunohistochemical (IHC) examination and were ultimately diagnosed with pagetoid SCC in situ - a different diagnosis from the initial clinical assessment. All three patients received a complete resection of the skin mass. After follow-up, as of June 2023, the patients had no tumour recurrence or metastasis. Pagetoid SCC in situ is a particular type of SCC in situ that has no specific features in clinical manifestations, gross diagnosis or histopathological sections. The final diagnosis depends on IHC staining. Pagetoid SCC in situ expresses EMA, CK5/6 and p63 but not CEA, CK8 or S-100, which are expressed in extramammary Paget's disease. Pagetoid SCC in situ is usually only locally invasive, and the main treatment is complete surgical resection. The prognosis is related to human papillomavirus infection, surgical margin closure, disease location, tumour thickness and other factors.

Honokiol and magnolol: A review of structure-activity relationships of their derivatives.

Honokiol (HK) and magnolol (MAG) are typical representatives of neolignans possessing a wide range of biological activities and are employed as traditional medicines in Asia. In the past few decades, HK and MAG have been proven to be promising chemical scaffolds for the development of novel neolignan drugs. This review focuses on recent advances in the medicinal chemistry of HK and MAG derivatives, especially their structure-activity relationships. In addition, it also presents a comprehensive summary of the pharmacology, biosynthetic pathways, and metabolic characteristics of HK and MAG. This review can provide pharmaceutical chemists deeper insights into medicinal research on HK and MAG, and a reference for the rational design of HK and MAG derivatives.

Elevated circulating BMP9 aggravates pulmonary angiogenesis in hepatopulmonary syndrome rats through ALK1-Endoglin-Smad1/5/9 signalling.

BACKGROUND: Bone morphogenetic protein 9 (BMP9) is a hepatokine that plays a pivotal role in the progression of liver diseases. Moreover, an increasing number of studies have shown that BMP9 is associated with hepatopulmonary syndrome (HPS), but its role in HPS is unclear. Here, we evaluated the influence of CBDL on BMP9 expression and investigated potential mechanisms of BMP9 signalling in HPS. METHODS: We profiled the circulating BMP9 levels in common bile duct ligation-induced HPS rat model, and then investigated the effects and mechanisms of HPS rat serum on pulmonary vascular endothelial dysfunction in rat model, as well as in primarily cultured rat pulmonary microvascular endothelial cells. RESULTS: Our data revealed that circulating BMP9 levels were significantly increased in the HPS rats compared to control group. Besides, the elevated BMP9 in HPS rat serum was not only crucial for promoting endothelial cell proliferation and tube formation through the activin receptor-like kinase1 (ALK1)-Endoglin-Smad1/5/9 pathway, but also important for accumulation of monocytes. Treatments with ALK1-Fc or silencing ALK1 expression to inhibit the BMP9 signalling pathway effectively eliminated these effects. In agreement with these observations, increased circulating BMP9 was associated with an increase in lung vessel density and accumulation of pro-angiogenic monocytes in the microvasculature in HPS rats. CONCLUSIONS: This study provided evidence that elevated circulating BMP9, secreted from the liver, promote pulmonary angiogenesis in HPS rats via ALK1-Endoglin-Smad1/5/9 pathway. In addition, BMP9-regulated pathways are also involved in accumulation of pro-angiogenic monocytes in the pulmonary microvasculature in HPS rats.

Dietary sodium acetate and sodium butyrate improve high-carbohydrate diet utilization by regulating gut microbiota, liver lipid metabolism, oxidative stress, and inflammation in largemouth bass (Micropterus salmoides).

BACKGROUND: Adequate level of carbohydrates in aquafeeds help to conserve protein and reduce cost. However, studies have indicated that high-carbohydrate (HC) diet disrupt the homeostasis of the gut-liver axis in largemouth bass, resulting in decreased intestinal acetate and butyrate level. METHOD: Herein, we had concepted a set of feeding experiment to assess the effects of dietary sodium acetate (SA) and sodium butyrate (SB) on liver health and the intestinal microbiota in largemouth bass fed an HC diet. The experimental design comprised 5 isonitrogenous and isolipidic diets, including LC (9% starch), HC (18% starch), HCSA (18% starch; 2 g/kg SA), HCSB (18% starch; 2 g/kg SB), and HCSASB (18% starch; 1 g/kg SA + 1 g/kg SB). Juvenile largemouth bass with an initial body weight of 7.00 ± 0.20 g were fed on these diets for 56 d. RESULTS: We found that dietary SA and SB reduced hepatic triglyceride accumulation by activating autophagy (ATG101, LC3B and TFEB), promoting lipolysis (CPT1α, HSL and AMPKα), and inhibiting adipogenesis (FAS, ACCA, SCD1 and PPARγ). In addition, SA and SB decreased oxidative stress in the liver (CAT, GPX1α and SOD1) by activating the Keap1-Nrf2 pathway. Meanwhile, SA and SB alleviated HC-induced inflammation by downregulating the expression of pro-inflammatory factors (IL-1ß, COX2 and Hepcidin1) through the NF-κB pathway. Importantly, SA and SB increased the abundance of bacteria that produced acetic acid and butyrate (Clostridium_sensu_stricto_1). Combined with the KEGG analysis, the results showed that SA and SB enriched carbohydrate metabolism and amino acid metabolism pathways, thereby improving the utilization of carbohydrates. Pearson correlation analysis indicated that growth performance was closely related to hepatic lipid deposition, autophagy, antioxidant capacity, inflammation, and intestinal microbial composition. CONCLUSIONS: In conclusion, dietary SA and SB can reduce hepatic lipid deposition; and alleviate oxidative stress and inflammation in largemouth bass fed on HC diet. These beneficial effects may be due to the altered composition of the gut microbiota caused by SA and SB. The improvement effects of SB were stronger than those associated with SA.

Dietary sodium acetate and sodium butyrate attenuate intestinal damage and improve lipid metabolism in juvenile largemouth bass (Micropterus salmoides) fed a high carbohydrate diet by reducing endoplasmic reticulum stress.

High-carbohydrate (HC) diets decrease the intestinal levels of sodium acetate (SA) and sodium butyrate (SB) and impair the gut health of largemouth bass; however, SA and SB have been shown to enhance immunity and improve intestinal health in farmed animals. Thus, the present study was to investigate the effects of dietary SA and SB on HC diet-induced intestinal injury and the potential mechanisms in juvenile largemouth bass. The experiment set five isonitrogenous and isolipidic diets, including a low-carbohydrate diet (9% starch) (LC), a high carbohydrate diet (18% starch) (HC), and the HC diet supplemented with 2 g/kg SA (HCSA), 2 g/kg SB (HCSB) or a combination of 1 g/kg SA and 1 g/kg SB (HCSASB). The feeding experiment was conducted for 8 weeks. A total of 525 juvenile largemouth bass with an initial body weight of 7.00 ± 0.20 g were used. The results showed that dietary SA and SB improved the weight gain rate and specific growth rate (P < 0.05) and ameliorated serum parameters (alkaline phosphatase, acid phosphatase, glutamate transaminase, and glutamic oxaloacetic transaminase) (P < 0.05). And, importantly, dietary SA and SB repaired the intestinal barrier by increasing the expression levels of zonula occludens-1, occludin, and claudin-7 (P < 0.05), reduced HC-induced intestinal damage, and alleviated intestinal inflammation and cell apoptosis by attenuating HC-induced intestinal endoplasmic reticulum stress (P < 0.05). Further results revealed that dietary SA and SB reduced HC-induced intestinal fat deposition by inhibiting adipogenesis and promoting lipolysis (P < 0.05). In summary, this study demonstrated that dietary SA and SB attenuated HC-induced intestinal damage and reduced excessive intestinal fat deposition in largemouth bass.

AAA237, an SKP2 inhibitor, suppresses glioblastoma by inducing BNIP3-dependent autophagy through the mTOR pathway.

BACKGROUND: Glioblastoma (GBM) is the most common brain tumor with the worst prognosis. Temozolomide is the only first-line drug for GBM. Unfortunately, the resistance issue is a classic problem. Therefore, it is essential to develop new drugs to treat GBM. As an oncogene, Skp2 is involved in the pathogenesis of various cancers including GBM. In this study, we investigated the anticancer effect of AAA237 on human glioblastoma cells and its underlying mechanism. METHODS: CCK-8 assay was conducted to evaluate IC50 values of AAA237 at 48, and 72 h, respectively. The Cellular Thermal Shift Assay (CETSA) was employed to ascertain the status of Skp2 as an intrinsic target of AAA237 inside the cellular milieu. The EdU-DNA synthesis test, Soft-Agar assay and Matrigel assay were performed to check the suppressive effects of AAA237 on cell growth. To identify the migration and invasion ability of GBM cells, transwell assay was conducted. RT-qPCR and Western Blot were employed to verify the level of BNIP3. The mRFP-GFP-LC3 indicator system was utilized to assess alterations in autophagy flux and investigate the impact of AAA237 on the dynamic fusion process between autophagosomes and lysosomes. To investigate the effect of compound AAA237 on tumor growth in vivo, LN229 cells were injected into the brains of mice in an orthotopic model. RESULTS: AAA237 could inhibit the growth of GBM cells in vitro. AAA237 could bind to Skp2 and inhibit Skp2 expression and the degradation of p21 and p27. In a dose-dependent manner, AAA237 demonstrated the ability to inhibit colony formation, migration, and invasion of GBM cells. AAA237 treatment could upregulate BNIP3 as the hub gene and therefore induce BNIP3-dependent autophagy through the mTOR pathway whereas 3-MA can somewhat reverse this process. In vivo, the administration of AAA237 effectively suppressed the development of glioma tumors with no side effects. CONCLUSION: Compound AAA237, a novel Skp2 inhibitor, inhibited colony formation, migration and invasion of GBM cells in a dose-dependent manner and time-dependent manner through upregulating BNIP3 as the hub gene and induced BNIP3-dependent autophagy through the mTOR pathway therefore it might be a viable therapeutic drug for the management of GBM.

Progress of studies on natural products for glioblastoma therapy.

Glioblastoma (GBM) is the most common, malignant, and lethal primary brain tumor in adults. Up to now, the chemotherapy approaches for GBM are limited. Therefore, more studies on identifying and exploring new chemotherapy drugs or strategies overcome the GBM are essential. Natural products are an important source of drugs against various human diseases including cancers. With the better understanding of the molecular etiology of GBM, the development of new anti-GBM drugs has been increasing. Here, we summarized recent researches of natural products for the GBM therapy and their potential mechanisms in details, which will provide new ideas for the research on natural products and promote developing drugs from nature products for GBM therapy.