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Scientific Reports May 2024Numerous heat transfer applications, such as heat exchangers, solar trough collectors, and fields including food processing, material research, and aerospace...
Numerous heat transfer applications, such as heat exchangers, solar trough collectors, and fields including food processing, material research, and aerospace engineering, utilize hybrid nanofluids. Compared to conventional fluids, hybrid nanofluids exhibit significantly enhanced thermal conductivity. The aim of this work is to explore flow and heat transmission features under of magneto-hydrodynamic bioconvective flow of carbon nanotubes over the stretched surface with Dufour and Soret effects. Additionally, comparative dynamics of the carbon nanotubes (SWCMT - MWCNT/CHO with SWCMT - MWCNT/CHO - HO) flow using the Prandtl fluid model in the presence of thermal radiation and motile microorganisms has been investigated. Novel feature Additionally, the focus is also to examine the presence of microorganisms in mixture base hybrid nanofluid. To examine heat transfer features of Prandtl hybrid nanofluid over the stretched surface convective heating is taken into consideration while modeling the boundary conditions. Suitable similarity transform has been employed to convert dimensional flow governing equations into dimensionless equations and solution of the problem has been obtained using effective, accurate and time saving bvp-4c technique in MATLAB. Velocity, temperature, concentration and microorganisms profiles have been demonstrated graphically under varying impact of various dimensionless parameters such as inclined magnetization, mixed convection, Dufour effect, Soret effect, thermal radiation effect, and bioconvection lewis number. It has been observed that raising values of magnetization (0.5 ≤ M ≤ 4), mixed convection (0.01 ≤ λ ≤ 0.05) and inclination angle (0° ≤ α ≤ 180°) enhance fluid motion rapidly in Ethylene glycol based Prandtl hybrid nanofluid (SWCMT - MWCNT/CHO) when compared with mixture base working fluid of carbon nanotubes SWCMT - MWCNT/CHO - HO). Raising thermal radiation (0.1 ≤ Rd ≤ 1.7) and Dufour number (0.1 ≤ Du ≤ 0.19) values improves temperature profile. Moreover, a good agreement has been found between the current outcome and existing literature for skin friction outcomes.
PubMed: 38796613
DOI: 10.1038/s41598-024-62647-2 -
BMC Cancer May 2024The proposed trial is to examine the feasibility of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-guided...
Protocol for CHAMPION study: a prospective study of maximal-cytoreductive therapies for patients with de novo metastatic hormone-sensitive prostate cancer who achieve oligopersistent metastases during systemic treatment with apalutamide plus androgen deprivation therapy.
BACKGROUND
The proposed trial is to examine the feasibility of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-guided cytoreduction plus apalutamide and androgen deprivation therapy (ADT) for newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) at oligometastatic state.
METHODS
CHAMPION (NCT05717582) is an open-label, single-arm, phase II trial, planning to enroll newly diagnosed mHSPC cases with oligometastases (≤ 10 distant metastatic sites in conventional imaging). Patients will receive 6 cycles of apalutamide plus ADT. Patients with oligometastatic disease at PSMA PET/CT after 3 treatment cycles will receive cytoreductive radical prostatectomy. PSMA PET/CT-guided metastasis-directed external radiation therapy will be determined by the investigators. Apalutamide plus ADT will be continued for 2 weeks postoperatively. The primary endpoint is the proportion of patients with undetectable prostate-specific antigen (PSA), no disease progression, and no symptom deterioration after 6 cycles of apalutamide plus ADT. Secondary endpoints include the percentage of patients with PSA ≤ 0.2 ng/mL and oligometastases by the end of 3 treatment cycles, PSA response rate, and safety. Fleming's two-stage group sequential design will be adopted in the study, where the null hypothesis is that the rate of patients with an undetectable PSA is ≤ 40% after 6 cycles of treatment, while the alternate hypothesis is an undetectable PSA of > 60%; with one-sided α = 0.05, power = 0.80, and an assumed dropout rate of 10%, the required number of patients for an effective analysis is 47. Enrolment in the study commenced in May 2023.
DISCUSSION
The multi-modal therapy based on treatment response may improve the prognosis of newly diagnosed mHSPC patients with oligometastases.
TRIAL REGISTRATION
The study is registered with Clinical Trials.Gov (NCT05717582). Registered on 8th February 2023.
Topics: Humans; Male; Thiohydantoins; Androgen Antagonists; Prostatic Neoplasms; Prospective Studies; Neoplasm Metastasis; Positron Emission Tomography Computed Tomography; Antineoplastic Combined Chemotherapy Protocols; Aged; Prostate-Specific Antigen; Middle Aged; Clinical Trials, Phase II as Topic; Prostatectomy
PubMed: 38796422
DOI: 10.1186/s12885-024-12395-3 -
Materials (Basel, Switzerland) May 2024In this study, the rolling process of the warm-rolled duplex-phase Mg-8.3Li-3.1Al-1.09Si alloy and the strengthening mechanism of as-rolled Mg-Li alloy were...
In this study, the rolling process of the warm-rolled duplex-phase Mg-8.3Li-3.1Al-1.09Si alloy and the strengthening mechanism of as-rolled Mg-Li alloy were investigated. The highest ultimate tensile strength (UTS, 323.66 ± 19.89 MPa) could be obtained using a three-pass rolling process with a 30% thickness reduction for each pass at 553 K. The strength of the as-rolled LAS831 alloy is determined by a combination of second-phase strengthening, grain refinement strengthening, dislocation strengthening, and load-transfer reinforcement. Of these factors, dislocation strengthening, which is caused by strain hardening of the α-Mg phase, can produce a good strengthening effect but also cause a decrease in plasticity. The MgSi phase is broken up into particles or strips during the rolling process. After three passes, the AlLi particles were transformed into an AlLi phase, and the MgSi particles and nanosized AlLi particles strengthened the second phase to form a hard phase. The average size of the DRXed β-Li grains decreased with each successive rolling pass, and the average size of recrystallized grains in the three-pass-rolled LAS831 alloy became as low as 0.27 μm. The interface between the strip-like MgSi phase and the α-Mg phase is characterized by semicoherent bonding, which can promote the transfer of tensile and shear forces from the matrix to the strip-like MgSi phase, thereby improving the strength of the matrix and thus strengthening the LAS831 alloy.
PubMed: 38793388
DOI: 10.3390/ma17102321 -
Microorganisms May 2024Along with the standard therapies for glioblastoma, patients are commonly prescribed trimethoprim-sulfamethoxazole (TMP-SMX) and dexamethasone for preventing infections...
Along with the standard therapies for glioblastoma, patients are commonly prescribed trimethoprim-sulfamethoxazole (TMP-SMX) and dexamethasone for preventing infections and reducing cerebral edema, respectively. Because the gut microbiota impacts the efficacy of cancer therapies, it is important to understand how these medications impact the gut microbiota of patients. Using mice that have been colonized with human microbiota, this study sought to examine how TMP-SMX and dexamethasone affect the gut microbiome. Two lines of humanized microbiota (HuM) Rag1 mice, HuM1Rag and HuM2Rag, were treated with either TMP-SMX or dexamethasone via oral gavage once a day for a week. Fecal samples were collected pre-treatment (pre-txt), one week after treatment initiation (1 wk post txt), and three weeks post-treatment (3 wk post txt), and bacterial DNA was analyzed using 16S rRNA-sequencing. The HuM1Rag mice treated with TMP-SMX had significant shifts in alpha diversity, beta diversity, and functional pathways at all time points, whereas in the HuM2Rag mice, it resulted in minimal changes in the microbiome. Likewise, dexamethasone treatment resulted in significant changes in the microbiome of the HuM1Rag mice, whereas the microbiome of the HuM2Rag mice was mostly unaffected. The results of our study show that routine medications used during glioblastoma treatment can perturb gut microbiota, with some microbiome compositions being more sensitive than others, and these treatments could potentially affect the overall efficacy of standard-of-care therapy.
PubMed: 38792844
DOI: 10.3390/microorganisms12051015 -
Microorganisms May 2024Fungi are ubiquitous and metabolically versatile. Their dispersion has important scientific, environmental, health, and economic implications. They can be dispersed...
Fungi are ubiquitous and metabolically versatile. Their dispersion has important scientific, environmental, health, and economic implications. They can be dispersed through the air by the aerosolization of near surfaces or transported from distant sources. Here, we tested the contribution of local (scale of meters) versus regional (kilometers) sources by analyzing an airborne fungal community by ITS sequencing around a copper mine in the North of Chile. The mine was the regional source, whereas the soil and vegetal detritus were the local sources at each point. The airborne community was highly homogeneous at ca. 2000 km, impeding the detection of regional or local contributions. Ascomycota was the dominant phylum in the three communities. Soil and vegetal detritus communities had lower alpha diversity, but some taxa had abundance patterns related to the distance from the mine and altitude. On the contrary, the air was compositionally even and unrelated to environmental or spatial factors, except for altitude. The presence of plant pathogens in the air suggests that other distant sources contribute to this region's airborne fungal community and reinforces the complexity of tracking the sources of air microbial communities in a real world where several natural and human activities coexist.
PubMed: 38792765
DOI: 10.3390/microorganisms12050934 -
Journal of Clinical Medicine May 2024The survival rate among pediatric cancer patients has reached 80%; however, these childhood cancer survivors (CCSs) are at a heightened risk of developing chronic...
The survival rate among pediatric cancer patients has reached 80%; however, these childhood cancer survivors (CCSs) are at a heightened risk of developing chronic conditions in adulthood, particularly kidney and cardiovascular diseases. The aims of this study were to assess the serum α-Klotho and FGF23 levels in CCSs and to determine their association with nephro- and cardiotoxicity. This study evaluated a cohort of 66 CCSs who remained in continuous remission, with a mean follow-up of 8.41 ± 3.76 years. The results of this study revealed that CCSs exhibited significantly higher levels of soluble α-Klotho compared to healthy peers (1331.4 ± 735.5 pg/mL vs. 566.43 ± 157.7 pg/mL, < 0.0001), while no significant difference was observed in their FGF23 levels. Within the participant cohort, eight individuals (12%) demonstrated a reduced estimated glomerular filtration rate (eGFR) below 90 mL/min/1.73 m. The relationship between treatment with abdominal radiotherapy and reduced eGFR was confirmed ( < 0.05). No correlations were found between potential treatment-related risk factors, such as chemotherapy or radiation therapy, serum levels of α-Klotho and FGF23, and nephro- and cardiotoxicity. In conclusion, this preliminary cross-sectional study revealed elevated levels of α-Klotho among childhood cancer survivors but did not establish a direct association with anticancer treatment. The significance of elevated α-Klotho protein levels among CCSs warrants further investigation.
PubMed: 38792509
DOI: 10.3390/jcm13102968 -
Genes Apr 2024P53 overexpression plays a critical role in cancer pathogenesis by disrupting the intricate regulation of cellular proliferation. Despite its firmly established function...
P53 overexpression plays a critical role in cancer pathogenesis by disrupting the intricate regulation of cellular proliferation. Despite its firmly established function as a tumor suppressor, elevated p53 levels can paradoxically contribute to tumorigenesis, influenced by factors such as exposure to carcinogens, genetic mutations, and viral infections. This phenomenon is observed across a spectrum of cancer types, including bladder (BLCA), ovarian (OV), cervical (CESC), cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), diffuse large B-cell lymphoma (DLBC), esophageal carcinoma (ESCA), head and neck squamous cell carcinoma (HNSC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and uterine corpus endometrial carcinoma (UCEC). This broad spectrum of cancers is often associated with increased aggressiveness and recurrence risk. Effective therapeutic strategies targeting tumors with p53 overexpression require a comprehensive approach, integrating targeted interventions aimed at the p53 gene with conventional modalities such as chemotherapy, radiation therapy, and targeted drugs. In this extensive study, we present a detailed analysis shedding light on the multifaceted role of TP53 across various cancers, with a specific emphasis on its impact on disease-free survival (DFS). Leveraging data from the TCGA database and the GTEx dataset, along with GEPIA, UALCAN, and STRING, we identify TP53 overexpression as a significant prognostic indicator, notably pronounced in prostate adenocarcinoma (PRAD). Supported by compelling statistical significance ( < 0.05), our analysis reveals the distinct influence of TP53 overexpression on DFS outcomes in PRAD. Additionally, graphical representations of overall survival (OS) underscore the notable disparity in OS duration between tumors exhibiting elevated TP53 expression (depicted by the red line) and those with lower TP53 levels (indicated by the blue line). The hazard ratio (HR) further emphasizes the profound impact of TP53 on overall survival. Moreover, our investigation delves into the intricate TP53 protein network, unveiling genes exhibiting robust positive correlations with TP53 expression across 13 out of 27 cancers. Remarkably, negative correlations emerge with pivotal tumor suppressor genes. This network analysis elucidates critical proteins, including SIRT1, CBP, p300, ATM, DAXX, HSP 90-alpha, Mdm2, RPA70, 14-3-3 protein sigma, p53, and ASPP2, pivotal in regulating cell cycle dynamics, DNA damage response, and transcriptional regulation. Our study underscores the paramount importance of deciphering TP53 dynamics in cancer, providing invaluable insights into tumor behavior, disease-free survival, and potential therapeutic avenues.
Topics: Humans; Tumor Suppressor Protein p53; Neoplasms; Computational Biology; Gene Expression Regulation, Neoplastic; Biomarkers, Tumor
PubMed: 38790205
DOI: 10.3390/genes15050577 -
European Journal of Pharmaceutical... Aug 2024Myocardial fibrosis can induce cardiac dysfunction and remodeling. Great attention has been paid to traditional chinese medicine (TCM) 's effectiveness in treating MF....
Elucidating the mechanism of action of Radix Angelica sinensis (Oliv.) Diels and Radix Astragalus mongholicus Bunge ultrafiltration extract on radiation-induced myocardial fibrosis based on network pharmacology and experimental research.
Myocardial fibrosis can induce cardiac dysfunction and remodeling. Great attention has been paid to traditional chinese medicine (TCM) 's effectiveness in treating MF. Radix Angelica sinensis (Oliv.) Diels and Radix Astragalus mongholicus Bunge ultrafiltration extract (RAS-RA), which is a key TCM compound preparation, have high efficacy in regulating inflammation. However, studies on its therapeutic effect on radiation-induced myocardial fibrosis (RIMF) are rare. In this study, RAS-RA had therapeutic efficacy in RIMF and elucidated its mechanism of action. First, we formulated the prediction network that described the relation of RAS-RA with RIMF according to data obtained in different databases. Then, we conducted functional enrichment to investigate the functions and pathways associated with potential RIMF targets for RAS-RA. In vivo experiments were also performed to verify these functions and pathways. Second, small animal ultrasound examinations, H&E staining, Masson staining, transmission electron microscopy, Enzyme-linked immunosorbent assay (ELISA), Western-blotting, Immunohistochemical method and biochemical assays were conducted to investigate the possible key anti-RIMF pathway in RAS-RA. In total, 440 targets were detected in those 21 effective components of RAS-RA; meanwhile, 1,646 RIMF-related disease targets were also discovered. After that, PPI network analysis was conducted to identify 20 key targets based on 215 overlap gene targets. As indicated by the gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis results, inflammation and PI3K/AKT/mTOR pathways might have important effects on the therapeutic effects on RIMF. Molecular docking analysis revealed high binding of effective components to targets (affinity < -6 kcal/mol). Based on experimental verification results, RAS-RA greatly mitigated myocardial fibrosis while recovering the cardiac activity of rats caused by X-rays. According to relevant protein expression profiles, the PI3K/AKT/mTOR pathway was important for anti-fibrosis effect of RAS-RA. Experimental studies showed that RAS-RA improved cardiac function, decreased pathological damage and collagen fiber deposition in cardiac tissues, and improved the mitochondrial structure of the heart of rats. RAS-RA also downregulated TNF-α, IL-6, and IL-1β levels. Additionally, RAS-RA improved the liver and kidney functions and pathological injury of rat kidney and liver tissues, enhanced liver and kidney functions, and protected the liver and kidneys. RAS-RA also increased PI3K, AKT and mTOR protein levels within cardiac tissues and downregulated α-SMA, Collagen I, and Collagen III. The findings of this study suggested that RAS-RA decreased RIMF by suppressing collagen deposition and inflammatory response by inhibiting the PI3K/AKT/mTOR pathway. Thus, RAS-RA was the potential therapeutic agent used to alleviate RIMF.
Topics: Animals; Angelica sinensis; Drugs, Chinese Herbal; Male; Fibrosis; Network Pharmacology; Rats, Sprague-Dawley; Rats; Astragalus Plant; Myocardium; Ultrafiltration; Signal Transduction; Cardiomyopathies; TOR Serine-Threonine Kinases
PubMed: 38788908
DOI: 10.1016/j.ejps.2024.106794 -
Journal of Functional Biomaterials Apr 2024Cargo encapsulation through emulsion-based methods has been pondered over the years. Although several microemulsification techniques have been employed for the...
Cargo encapsulation through emulsion-based methods has been pondered over the years. Although several microemulsification techniques have been employed for the microcapsule's synthesis, there are still no clear guidelines regarding the suitability of one technique over the others or the impacts on the morphological and physicochemical stability of the final particles. Therefore, in this systematic study, we investigated the influence of synthesis parameters on the fabrication of emulsion-based microcapsules concerning morphological and physicochemical properties. Using poly(urea-formaldehyde) (PUF) microcapsules as a model system, and after determining the optimal core/shell ratio, we tested three different microemulsification techniques (magnetic stirring, ultrasonication, and mechanical stirring) and two different cargo types (100% TEGDMA (Triethylene glycol dimethacrylate) and 80% TEGDMA + 20% DMAM (N,N-Dimethylacrylamide)). The resulting microcapsules were characterized via optical and scanning electron microscopies, followed by size distribution analysis. The encapsulation efficiency was obtained through the extraction method, and the percentage reaction yield was calculated. Physicochemical properties were assessed by incubating the microcapsules under different osmotic pressures for 1 day and 1, 2, or 4 weeks. The data were analyzed statistically with one-way ANOVA and Tukey's tests (α = 0.05). Overall, the mechanical stirring resulted in the most homogeneous and stable microcapsules, with an increased reaction yield from 100% to 50% in comparison with ultrasonication and magnetic methods, respectively. The average microcapsule diameter ranged from 5 to 450 µm, with the smallest ones in the ultrasonication and the largest ones in the magnetic stirring groups. The water affinities of the encapsulated cargo influenced the microcapsule formation and stability, with the incorporation of DMAM leading to more homogeneous and stable microcapsules. Environmental osmotic pressure led to cargo loss or the selective swelling of the shells. In summary, this systematic investigation provides insights and highlights commonly overlooked factors that can influence microcapsule fabrication and guide the choice based on a diligent analysis of therapeutic niche requirements.
PubMed: 38786629
DOI: 10.3390/jfb15050117 -
Gels (Basel, Switzerland) May 2024Sacran is a supergiant cyanobacterial polysaccharide that forms mesogenic supercoil rods that exhibit liquid crystalline (LC) gels at deficient concentrations of around...
Structural Analyses of Polysaccharides Extracted from Cyanobacterial Extracellular Gels and Oriented Liquid Crystalline Microfiber Processing by Poly(vinyl alcohol)-Assisted Electrospinning.
Sacran is a supergiant cyanobacterial polysaccharide that forms mesogenic supercoil rods that exhibit liquid crystalline (LC) gels at deficient concentrations of around 0.5 wt%, and has several bioactive stimuli-responsive functions. Here, we attempted to form oriented microfibers of sacran by electrospinning, following structural analyses of the sacran rods. A heterogeneous acid-hydrolysis method using a protonated cation-exchange resin was adopted to examine the short-time exposition of concentrated acid to sacran rods. From the supernatant, the oligomeric fraction that was soluble in water and methanol was isolated. The oligomeric fraction had a main sugar ratio of -Glc:-Glc:-Xyl:-Xyl:-Rha of 2:5:1.5:1.5:4 (Glc:Xyl:Rha = 7 (=4 + 3):3:4), and it was speculated that the sacran structure includes rhamnoglucan and xyloglucan (4:3), which are generally rigid enough to exhibit LC. To make oriented microfibers of LC sacran, solubility testing was performed on sacran to find good new solvents of polyhydroxy alcohols such as ethylene glycol, 1,2-propanediol, and glycerol. The oriented film was prepared from a sacran aqueous solution where calcium compound particles deposited on the film are different from polyhydroxy alcohol solutions. Although sacran could not form microfibers by itself, polymer composite microfibers of sacran with poly(vinyl alcohol) were prepared by electrospinning. Cross-polarizing microscopy revealed the molecular orientation of the microfibers.
PubMed: 38786237
DOI: 10.3390/gels10050321