Severe anemia, severe leukopenia, and severe thrombocytopenia of amphotericin B deoxycholate-based induction therapy in patients with HIV-associated talaromycosis: a subgroup analysis of a prospective multicenter cohort study.

BACKGROUND: This study's objective was to investigate the predictors for severe anemia, severe leukopenia, and severe thrombocytopenia when amphotericin B deoxycholate-based induction therapy is used in HIV-infected patients with talaromycosis. METHODS: A total of 170 HIV-infected patients with talaromycosis were enrolled from January 1st, 2019, to September 30th, 2020. RESULTS: Approximately 42.9%, 20.6%, and 10.6% of the enrolled patients developed severe anemia, severe leukopenia, and severe thrombocytopenia, respectively. Baseline hemoglobin level < 100 g/L (OR = 5.846, 95% CI: 2.765 ~ 12.363), serum creatinine level > 73.4 µmol/L (OR = 2.573, 95% CI: 1.157 ~ 5.723), AST/ALT ratio > 1.6 (OR = 2.479, 95% CI: 1.167 ~ 5.266), sodium level ≤ 136 mmol/liter (OR = 4.342, 95% CI: 1.747 ~ 10.789), and a dose of amphotericin B deoxycholate > 0.58 mg/kg/d (OR = 2.504, 95% CI:1.066 ~ 5.882) were observed to be independent risk factors associated with the development of severe anemia. Co-infection with tuberculosis (OR = 3.307, 95% CI: 1.050 ~ 10.420), and platelet level (per 10 × 109 /L) (OR = 0.952, 95% CI: 0.911 ~ 0.996) were shown to be independent risk factors associated with the development of severe leukopenia. Platelet level < 100 × 109 /L (OR = 2.935, 95% CI: 1.075 ~ 8.016) was identified as the independent risk factor associated with the development of severe thrombocytopenia. There was no difference in progression to severe anemia, severe leukopenia, and severe thrombocytopenia between the patients with or without fungal clearance at 2 weeks. 10 mg on the first day of amphotericin B deoxycholate was calculated to be independent risk factors associated with the development of severe anemia (OR = 2.621, 95% CI: 1.107 ~ 6.206). The group receiving a starting amphotericin B dose (10 mg, 20 mg, daily) exhibited the highest fungal clearance rate at 96.3%, which was significantly better than the group receiving a starting amphotericin B dose (5 mg, 10 mg, 20 mg, daily) (60.9%) and the group receiving a starting amphotericin B dose (5 mg, 15 mg, and 25 mg, daily) (62.9%). CONCLUSION: The preceding findings reveal risk factors for severe anemia, severe leukopenia, and severe thrombocytopenia. After treatment with Amphotericin B, these severe adverse events are likely unrelated to fungal clearance at 2 weeks. Starting amphotericin B deoxycholate at a dose of 10 mg on the first day may increase the risk of severe anemia but can lead to earlier fungal clearance. TRIAL REGISTRATION: ChiCTR1900021195. Registered 1 February 2019.

Quantitative Analysis of Camellia oleifera Seed Saponins and Aqueous Two-Phase Extraction and Separation.

At present, the technology used for the extraction and purification of Camellia oleifera saponins generally has the problems of high cost and low purity, and the quantitative detection of Camellia oleifera saponins also has the problems of low sensitivity and easy interference from impurities. To solve these problems, this paper aimed to use liquid chromatography for the quantitative detection of Camellia oleifera saponins, and to adjust and optimize the related conditions. In our study, the average recovery of Camellia oleifera saponins obtained was 100.42%. The RSD of precision test was 0.41%. The RSD of the repeatability test was 0.22%. The detection limit of the liquid chromatography was 0.06 mg/L, and the quantification limit was 0.2 mg/L. In order to improve the yield and purity, the Camellia oleifera saponins were extracted from Camellia oleifera Abel. seed meal by methanol extraction. Then, the extracted Camellia oleifera saponins were extracted with an ammonium sulfate/propanol aqueous two-phase system. We optimized the purification process of formaldehyde extraction and aqueous two-phase extraction. Under the optimal purification process, the purity of Camellia oleifera saponins extracted by methanol was 36.15%, and the yield was 25.24%. The purity of Camellia oleifera saponins obtained by aqueous two-phase extraction was 83.72%. Thus, this study can provide a reference standard for rapid and efficient detection and analysis of Camellia oleifera saponins for industrial extraction and purification.

Comparison of HIV DNA decay and immune recovery between early and chronic HIV-infected individuals 96 weeks after ART.

OBJECTIVES: Although antiretroviral therapy (ART) has prolonged the lives of HIV-infected individuals, HIV reservoir remains the main stumbling block to HIV cure. Presently, early ART initiation is one of the effective measures to reduce the HIV reservoir. The effects of ART in Chinese individuals with acute and early HIV infection (AEHI) and chronic HIV infection (CHI) were analyzed in this study. METHODS: We performed virological and immunological parameter analysis in 29 AEHI and 19 CHI individuals who were initiated into ART in Beijing, China. The HIV DNA, CD4+ T-cell and CD8+ T-cell counts, and CD4/CD8 ratios between the two groups were compared using statistical analyses. RESULTS: At weeks 48 and 96, the total HIV DNA was significantly lower in the AEHI group than that the CHI group (2.48 [2.26-2.66] vs. 3.06 [2.79-3.33] log10 copies/106 peripheral blood mononuclear cells (PBMCs), p < 0.01 at week 48 and 2.17 [1.85-2.45] vs. 2.92 [2.73-3.24] log10 copies/106  PBMCs, p < 0.01 at week 96, respectively). The CD4/CD8 T-cell ratio in the AHI group at week 24 was significantly higher than that in the CHI group (0.71 [0.50-0.99] vs. 0.45 [0.34-0.65], p = 0.08). After 48 weeks of ART, there was still a negative correlation between the CD4/CD8 ratio and the HIV DNA level in the CHI group rather than the AEHI group. CONCLUSIONS: Early ART initiation could enhance an earlier immunological recovery in AEHI. Immunological normalization after ART initiation could provide important protection against the viral reservoir seeded in AEHI individuals.

Novel sequential therapy with metformin enhances the effects of cisplatin in testicular germ cell tumours via YAP1 signalling.

BACKGROUND: Testicular germ cell tumours (TGCTs) are the most commonly diagnosed malignancy in young men. Although cisplatin has been shown to be effective to treat TGCT patients, long-term follow-up has shown that TGCT survivors who accepted cisplatin treatment suffered from a greater number of adverse reactions than patients who underwent orchiectomy alone. As metformin has shown an anticancer effect in various cancers, we investigated whether metformin could enhance the effects of cisplatin to treat TGCTs. METHODS: The anticancer effects of different treatment strategies consisting of metformin and cisplatin in TCam-2 and NTERA-2 cells were assessed in vitro and in vivo. First, we used a colony formation assay, CCK-8 and MTT assays to explore the viability of TGCT cells. Flow cytometry was used to assess the cell cycle and apoptosis of TGCTs. Then, Western blotting was used to detect the protein expression of TGCTs cells after different treatments. In addition, a xenograft model was used to investigate the effects of the different treatments on the proliferation of TGCT cells. Immunohistochemistry assays were performed to analyse the expression of related proteins in the tissues from the xenograft model. RESULTS: Metformin inhibited the proliferation of TCam-2 and NTERA-2 cells by arresting them in G1 phase, while metformin did not induce apoptosis in TGCT cells. Compared with cisplatin monotherapy, the CCK-8, MTT assay and colony formation assay showed that sequential treatment with metformin and cisplatin produced enhanced anticancer effects. Further study showed that metformin blocked the cells in G1 phase by inducing phosphorylated YAP1 and reducing the expression of cyclin D1, CDK6, CDK4 and RB, which enhanced the chemosensitivity of cisplatin and activated the expression of cleaved caspase 3 in TGCTs. CONCLUSIONS: Our study discovers the important role of YAP1 in TGCTs and reports a new treatment strategy that employs the sequential administration of metformin and cisplatin, which can reduce the required cisplatin dose and enhance the sensitivity of TGCT cells to cisplatin. Therefore, this sequential treatment strategy may facilitate the development of basic and clinical research for anticancer therapies to treat TGCTs.

Initiating antiretroviral therapy within 2 weeks of anti-Pneumocystis treatment does not increase mortality or AIDS-defining events in patients with HIV-associated moderate to severe Pneumocystis pneumonia: results of a prospective observational multicenter study.

BACKGROUND: The mortality rate remains high among patients with coinfection with Pneumocystis pneumonia (PCP) and HIV. The timing for initiation of antiretroviral therapy (ART) after a diagnosis of moderate to severe PCP remains controversial, however. We therefore designed the present study to determine the optimal timing for ART initiation in AIDS-associated PCP (AIDS/PCP) patients. METHODS: This was a multicenter, observational, prospective clinical trial. Eligible participants were recruited from 14 hospitals in mainland China, and assigned to an Early ART arm (initiation of ART ≤ 14 days after PCP diagnosis) and a Deferred ART arm (initiation of ART > 14 days after PCP diagnosis). The primary outcomes were death and the incidence of AIDS-defining events at week 48. The secondary outcomes were the changes in CD4+ T-cell counts from baseline values at weeks 12, 24, and 48, the virological suppression rate at week 24 and week 48, the rate of development of PCP-associated immune reconstitution inflammatory syndrome (PCP/IRIS), and the rate of adverse events over 48 weeks. RESULTS: The present study was performed using the data of 363 participants, with 169 participants in the Early ART arm, and 194 participants in the Deferred ART arm. Immunological and virological outcomes were found to be similar in both treatment arms. At week 48, there were no significant differences for the incidence of mortality (20 vs. 26, p = 0.860), and AIDS-defining events (17 vs. 26, p = 0.412). Over 48 weeks, the rates of PCP/IRIS (2 vs. 3, p = 1.000), adverse events (70 vs. 72, p = 0.465), and grade 3 or 4 adverse events (28 vs. 34, p = 0.919) did not reach statistical significance. A significant difference observed between two study arms was that 11 participants (55.0%) in the Early ART arm compared to 23 participants (88.5%) in the Deferred ART arm (p = 0.026) succumbed before ART had ever been started. CONCLUSIONS: Early ART initiation results in no increase in mortality, AIDS-defining events, IRIS, adverse events, and immunological or virological outcomes. These results support the early initiation of ART in patients with moderate to severe AIDS/PCP. Clinical trial registration The present trial was registered at Chinese Clinical Trial Registry (ChiCTR1900021195). Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362 .

Multicentre derivation and validation of a prognostic scoring system for mortality assessment in HIV-infected patients with talaromycosis.

BACKGROUND: Although the widespread use of modern antiretroviral therapy (ART) has reduced the incidence of talaromycosis in people living with HIV, mortality remains as high as 20% in this population, even after appropriate antifungal treatment. OBJECTIVES: The objective of our study was to develop a risk assessment system for HIV-infected patients with comorbid talaromycosis, in order to provide these patients with appropriate, effective and potentially life-saving interventions at an early stage of their illness. PATIENTS/METHODS: This was a multicentre, retrospective cohort study conducted in China. We built a predictive model based on data from 11 hospitals, and a validated model using the data of 1 hospital located in an endemic area. RESULTS: Forward stepwise multivariate statistical calculations indicated that age, aspartate aminotransferase/alanine transaminase ratio and albumin levels, and BUN levels were valid, independent predictors of the risk of death in HIV-infected patients with talaromycosis. Our developed and validated risk scoring system is effective for the identification of HIV-infected patients with talaromycosis at high risk of death at hospital admission (p < .001; AUC = 0.860). In our study, our risk prediction model provided functional and robust discrimination in the validation cohort (p < .001; AUC = 0.793). CONCLUSION: The prognostic scoring system for mortality assessment developed in the present study is an easy-to-use clinical tool designed to accurately assist clinicians in identifying high-risk patients with talaromycosis.

Dual antivascular function of human fibulin-3 variant, a potential new drug discovery strategy for glioblastoma.

The ECM protein EFEMP1 (fibulin-3) is associated with all types of solid tumor through its cell context-dependent dual function. A variant of fibulin-3 was engineered by truncation and mutation to alleviate its oncogenic function, specifically the proinvasive role in glioblastoma multiforme (GBM) cells at stem-like state. ZR30 is an in vitro synthesized 39-kDa protein of human fibulin-3 variant. It has a therapeutic effect in intracranial xenograft models of human GBM, through suppression of epidermal growth factor receptor/AKT and NOTCH1/AKT signaling in GBM cells and extracellular MMP2 activation. Glioblastoma multiforme is highly vascular, with leaky blood vessels formed by tumor cells expressing endothelial cell markers, including CD31. Here we studied GBM intracranial xenografts, 2 weeks after intratumoral injection of ZR30 or PBS, by CD31 immunohistochemistry. We found a 70% reduction of blood vessel density in ZR30-treated xenografts compared with that of PBS-treated ones. Matrigel plug assays showed the effect of ZR30 on suppressing angiogenesis. We further studied the effect of ZR30 on genes involved in endothelial transdifferentiation (ETD), in 7 primary cultures derived from 3 GBMs under different culture conditions. Two GBM cultures formed mesh structures with upregulation of ETD genes shortly after culture in Matrigel Matrix, and ZR30 suppressed both. ZR30 also downregulated ETD genes in two GBM cultures with high expression of these genes. In conclusion, multifaceted tumor suppression effects of human fibulin-3 variant include both suppression of angiogenesis and vasculogenic mimicry in GBM.

JC Polyomavirus, progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome: a review.

The human neurotropic virus JC Polyomavirus, a member of the Polyomaviridae family, is the opportunistic infectious agent causing progressive multifocal leukoencephalopathy, typically in immunocompromised individuals. The spectrum of underlying reasons for the systemic immunosuppression that permits JCV infection in the central nervous system has evolved over the past 2 decades, and therapeutic immunosuppression arousing JCV infection in the brain has become increasingly prominent as a trigger for PML. Effective immune restoration subsequent to human immunodeficiency virus-related suppression is now recognized as a cause for unexpected deterioration of symptoms in patients with PML, secondary to a rebound inflammatory phenomenon called immune reconstitution inflammatory syndrome, resulting in significantly increased morbidity and mortality in a disease already infamous for its lethality. This review addresses current knowledge regarding JC Polyomavirus, progressive multifocal leukoencephalopathy, progressive multifocal leukoencephalopathy-related immune reconstitution inflammatory syndrome, and the immunocompromised states that incite JC Polyomavirus central nervous system infection, and discusses prospects for the future management of these conditions.

MRS1754 inhibits proliferation and migration of bladder urothelial carcinoma by regulating mitogen-activated protein kinase pathway.

Bladder urothelial carcinoma (BUC) is one of the most common urological malignancies. Our previous study found that adenosine A2b receptor (A2bR) was upregulated in BUC tissues and cells. In the present study, we investigated the effect of MRS1754 (a selective A2bR antagonist) on cell proliferation and migration in two well-studied invasive urothelial cell carcinoma lines EJ and T24. Our results showed that MRS1754 reduced BUC cell proliferation and induced a G0/G1 phase cell-cycle arrest. Next, MRS1754 inhibited cell migration and Bay60-6583 (a selective A2bR agonist) treatment could reverse the inhibitory effect of MRS1754 on BUC cells migration. Furthermore, our results showed MRS1754 treatment downregulated the protein levels of p-P38, p-JNK, and phospho-extracellular signal-regulated kinase (p-ERK). These findings suggest that MRS1754 can inhibit progression of BUC via mitogen-activated protein kinase (MAPK) pathway and indicate the therapeutic potential of A2B antagonists in BUC.

The Adenosine A1 Receptor Antagonist DPCPX Inhibits Tumor Progression via the ERK/JNK Pathway in Renal Cell Carcinoma.

BACKGROUND/AIMS: The adenosine A1 receptor (A1R) has been reported to be involved in the pathogenesis of various cancers, and the effects of A1R on different cancers are pleiotropic. However, the role of A1R in renal cell carcinoma (RCC) remains not well-known. METHODS: The expression of A1R in RCC cells was detected by quantitative real-time PCR and Western blotting analysis. Cell proliferation was detected using an MTT assay and a colony formation assay. Tumor growth was also evaluated in nude mice. Cell invasion and migration were evaluated using a wound healing assay and a transwell assay. Cell cycle distribution and apoptosis rates were analyzed by flow cytometry. RESULTS: A1R was the main subtype of ARs and was up-regulated in 786-O and ACHN cells. Functionally, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), an A1R antagonist, inhibited RCC cell proliferation in vitro and tumor growth in vivo. Furthermore, DPCPX inhibited RCC cell migration, while N6-Cyclopentyladenosine (CPA), a selective A1 agonist, was able to rescue RCC cell migration. In addition, DPCPX promoted 786-O and ACHN cell apoptosis and induced an S phase cell cycle arrest. Finally, we demonstrated that DPCPX inhibited tumor progression in part via the ERK/JNK pathway. CONCLUSION: These findings suggest the potentially important role of DPCPX in the control of RCC cell proliferation and migration by regulating the ERK/JNK signaling pathway.

Effects of temperature and fatigue on the metabolism and swimming capacity of juvenile Chinese sturgeon (Acipenser sinensis).

Chinese sturgeon (Acipenser sinensis) is a critically endangered species. A flume-type respirometer, with video, was used to conduct two consecutive stepped velocity tests at 10, 15, 20, and 25 °C. Extent of recovery was measured after the 60-min recovery period between trials, and the recovery ratio for critical swimming speed (U crit) averaged 91.88% across temperatures. Temperature (T) effects were determined by comparing U crit, oxygen consumption rate (MO 2), and tail beat frequency (TBF) for each temperature. Results from the two trials were compared to determine the effect of exercise. The U crit occurring at 15 °C in both trials was significantly higher than that at 10 and 25 °C (p < 0.05). The U crit was plotted as a function of T and curve-fitting allowed calculation of the optimal swimming temperature 3.28 BL/s at 15.96 °C (trial 1) and 2.98 BL/s at 15.85 °C (trial 2). In trial 1, MO 2 increased rapidly with U, but then declined sharply as swimming speed approached U crit. In trial 2, MO 2 increased more slowly, but continuously, to U crit. TBF was directly proportional to U and the slope (dTBF/dU) for trial 2 was significantly lower than that for trial 1. The inverse slope (tail beats per body length, TB/BL) is a measure of swimming efficiency and the significant difference in slopes implies that the exercise training provided by trial 1 led to a significant increase in swimming efficiency in trial 2.

Discovery of imidazopyridazines as potent Pim-1/2 kinase inhibitors.

High levels of Pim expression have been implicated in several hematopoietic and solid tumor cancers, suggesting that inhibition of Pim signaling could provide patients with therapeutic benefit. Herein, we describe our progress towards this goal using a screening hit (rac-1) as a starting point. Modification of the indazole ring resulted in the discovery of a series of imidazopyridazine-based Pim inhibitors exemplified by compound 22m, which was found to be a subnanomolar inhibitor of the Pim-1 and Pim-2 isoforms (IC50 values of 0.024nM and 0.095nM, respectively) and to potently inhibit the phosphorylation of BAD in a cell line that expresses high levels of all Pim isoforms, KMS-12-BM (IC50=28nM). Profiling of Pim-1 and Pim-2 expression levels in a panel of multiple myeloma cell lines and correlation of these data with the potency of compound 22m in a proliferation assay suggests that Pim-2 inhibition would be advantageous for this indication.

The discovery of novel 3-(pyrazin-2-yl)-1H-indazoles as potent pan-Pim kinase inhibitors.

The three Pim kinases are a small family of serine/threonine kinases regulating several signaling pathways that are fundamental to tumorigenesis. As such, the Pim kinases are a very attractive target for pharmacological inhibition in cancer therapy. Herein, we describe our efforts toward the development of a potent, pan-Pim inhibitor. The synthesis and hit-to-lead SAR development from a 3-(pyrazin-2-yl)-1H-indazole derived hit 2 to the identification of a series of potent, pan-Pim inhibitors such as 13o are described.

The discovery and optimization of aminooxadiazoles as potent Pim kinase inhibitors.

High levels of Pim expression have been implicated in several hematopoietic and solid tumor cancers. These findings suggest that inhibition of Pim signaling by a small molecule Pim-1,2 inhibitor could provide patients with therapeutic benefit. Herein, we describe our progress towards this goal starting from the highly Pim-selective indole-thiadiazole compound (1), which was derived from a nonselective hit identified in a high throughput screening campaign. Optimization of this compound's potency and its pharmacokinetic properties resulted in the discovery of compound 29. Cyclopropane 29 was found to exhibit excellent enzymatic potency on the Pim-1 and Pim-2 isoforms (Ki values of 0.55nM and 0.28nM, respectively), and found to inhibit the phosphorylation of BAD in the Pim-overexpressing KMS-12 cell line (IC50=150nM). This compound had moderate clearance and bioavailability in rat (CL=2.42L/kg/h; %F=24) and exhibited a dose-dependent inhibition of p-BAD in KMS-12 tumor pharmacodynamic (PD) model with an EC50 value of 6.74µM (18µg/mL) when dosed at 10, 30, 100 and 200mg/kg po in mice.

Datasets of Great Britain primary substations integrated with household heating information.

The growing demand for electrified heating, electrified transportation, and power-intensive data centres challenge distribution networks. If electrification projects are carried out without considering electrical distribution infrastructure, there could be unexpected blackouts and financial losses. Datasets containing real-world distribution network information are required to address this. However, the existing dataset at NERC that covers the whole of Great Britain (GB) does not provide information about demand and capacity, which is insufficient for evaluating the connection feasibility. Although each distribution network operator (DNO) has detailed network information for their supply area, the information is scattered in separate files and different formats even within the same DNO, which limits usability. On the other hand, studying the coupling between energy systems and societal attributes such as household heating is important in promoting social welfare, which calls for more comprehensive datasets that integrate the social data and the energy network data. However, social datasets are usually provided on a regional basis, and the link to energy networks is not straightforward, which explains the lack of the comprehensive datasets. To fill these gaps, this paper introduces two datasets. The first is the main dataset for the GB distribution networks, collecting information on firm capacity, peak demands, locations, and parent transmission nodes (grid supply points, namely GSPs) for all primary substations (PSs). PSs are a crucial part of UK distribution networks and are at the lowest voltage level (11 kV) with publicly available data. Substation firm capacity and peak demand facilitate an understanding of the remaining room in the existing network. The parent GSP information helps link the released datasets to transmission networks. These datasets are collected, standardised, and merged from various files with different formats published by the six DNOs in GB, using a Python script and manual validation. The second dataset extends the main network dataset, linking each PS to the number of households that use different types of central heating recorded in census data (Census in year 2021 for England and Wales, and Census 2011 for Scotland as the up-to-date Census 2022 data is not fully released). The derivation of the second dataset is based on the locations of PSs collected in the main dataset with appropriate assumptions. The derivation process may be replicated to integrate other social datasets. The datasets have the following reuse potentials: 1) Given the PS demand, capacity, and locations in our datasets, users can estimate the connection feasibility and evaluate the optimal deployment locations for different energy technologies, including electric vehicles, heat pumps, and the growing data centres, under different scenarios and at a national scale. These evaluations are beneficial not only for academic research, but also for industrial planning and policy making. 2) Our extended dataset links household information to distribution networks. The integrated information facilitates cross-disciplinary research and analysis across social science, energy policy, and power systems. 3) The network demand and capacity information provided by the datasets can also help with realistic parameter settings to improve the accuracy of case studies in broader power system research.

Evaluating the social benefits and network costs of heat pumps as an energy crisis intervention.

Fuel poverty, a pressing issue affecting social prosperity, has been exacerbated during the energy crisis triggered by the Russia-Ukraine conflict. This problem can be more severe for off-gas regions. Our study investigates heat pumps (HPs) as a cost-effective alternative to off-gas heating to alleviate fuel poverty in England and Scotland. We analyze regional fuel poverty rates and the associated greenhouse gas emission reduction by replacing all off-gas heating with HPs, observing positive effects under pre-crisis and crisis conditions, with existing government support for HP upfront costs. HP rollout can burden distribution networks especially for certain regions, but our correlation analysis shows that high benefits do not always come with network costs at the regional level, and we identify "priority" regions with low costs and high benefits. These findings provide valuable insights for policymakers to address fuel poverty and reach decarbonization. The methodology is adaptable to other countries with appropriate datasets.

Research Progress on the Pathogenesis of Aortic Aneurysm and Dissection in Metabolism.

Aortic aneurysm and dissection are complicated diseases having both high prevalence and mortality. It is usually diagnosed at advanced stages and posing diagnostic and therapeutic challenges due to the limitations of current detecting methods for aortic dissection used in clinics. Metabonomics demonstrated its great potential capability in the early diagnosis and personalized treatment of several diseases. Emerging evidence suggests that metabolic disorders including amino acid metabolism, glycometabolism, and lipid metabolism disturbance are involved in the pathogenesis of aortic aneurysm and dissection by affecting multiple functional aortic cells. The purpose of this review is to provide new insights into the metabolism alterations and their related regulatory mechanisms with a focus on recent advances and findings and provide a theoretical basis for the diagnosis, prevention, and drug development for aortic aneurysm and dissection.

Experimental Investigation of Reflectarray Antennas for High-Power Microwave Applications.

The power capacity of reflectarray antennas (RAs) is investigated through full-wave simulations and high-power microwave (HPM) experiments in this paper. In order to illustrate the results in detail, two RA elements are designed. The simulated power handling capacity of two RA elements are 7.17 MW/m2 and 2.3 GW/m2, respectively. To further study the HPM RA, two RA prototypes operating at 2.8 GHz are constructed with the aperture size of 1 m × 1 m. Simulations and experimental measurements are conducted for the two prototypes. The experimental results demonstrate that, even when subjected to 1 GW of power, the radiation beam of the RA with the second elements can still propagate in the intended direction. This research will establish a basis for advancing the practicality of RAs in HPM applications.

Artificial cavernosa-like tissue based on multibubble Matrigel and a human corpus cavernous fibroblast scaffold.

Ex vivo tissue culture of the human corpus cavernosum (CC) can be used to explore the tissue structural changes and complex signaling networks. At present, artificial CC-like tissues based on acellular or three-dimensional (3D)-printed scaffolds are used to solve the scarcity of primary penis tissue samples. However, inconvenience and high costs limit the wide application of such methods. Here, we describe a simple, fast, and economical method of constructing artificial CC-like tissue. Human CC fibroblasts (FBs), endothelial cells (ECs), and smooth muscle cells (SMCs) were expanded in vitro and mixed with Matrigel in specific proportions. A large number of bubbles were formed in the mixture by vortexing combined with pipette blowing, creating a porous, spongy, and spatial structure. The CC FBs produced a variety of signaling factors, showed multidirectional differentiation potential, and grew in a 3D grid in Matrigel, which is necessary for CC-like tissue to maintain a porous structure as a cell scaffold. Within the CC-like tissue, ECs covered the surface of the lumen, and SMCs were located inside the trabeculae, similar to the structure of the primary CC. Various cell components remained stable for 3 days in vitro, but the EC content decreased on the 7th day. Wingless/integrated (WNT) signaling activation led to lumen atrophy and increased tissue fibrosis in CC-like tissue, inducing the same changes in characteristics as in the primary CC. This study describes a preparation method for human artificial CC-like tissue that may provide an improved experimental platform for exploring the function and structure of the CC and conducting drug screening for erectile dysfunction therapy.

Microstructure and Mechanical Properties of Ni-20Cr-Eu2O3 Composites Prepared by Vacuum Hot Pressing.

Ni-20Cr-Eu2O3 composites were designed as new control rod materials and were synthesized from Ni, Cr, and Eu2O3 mixture powders via ball milling and vacuum hot pressing. During ball milling, Eu2O3 was fined, nano-crystallized, amorphized, and then dissolved into matrix. The effect of Eu2O3 content on the microstructure and mechanics was researched, and the corresponding mechanism was discussed. The relative densities, grain sizes, and microhardness increased when Eu2O3 content increased. According to the TEM observations, Eu2O3 particles showed a semi-coherent relationship with the matrix. The results of mechanical property testing showed that the ultimate tensile strength, yield strength, and elongation decreased with the Eu2O3 content increased. The maximum ultimate tensile strength, yield strength, and elongation were 741 MPa, 662 MPa, and 4%, respectively, with a 5 wt.% Eu2O3 addition. The experimental strengths were well matched with the theoretical values calculated by the strengthening mechanisms indicating that this method was highly effective for predicting the mechanical properties of Ni-20Cr-Eu2O3 composites.