Significant Synergistic Effect Research Articles

The enhanced photocatalytic peroxymonosulfate activation for 2, 4-dichlorophenoxyacetic acid degradation over Z-scheme PTCDA/MIL-88A(Fe) under visible light

To attain significant synergy between adsorption and peroxymonosulfate (PMS) activation for the 2, 4-dichlorophenoxyacetic acid (2, 4-D) elimination, 3, 4, 9, 10-perylenetetracarboxylic dianhydride (PTCDA)/MIL-88A(Fe) (PTxMy) composites were constructed by the facile ball-milling. The adsorption capacity of PT25M175 toward 2, 4-D was calculated as 76.0 mg/g at 308 K based on the Langmuir models. The decomposition of 2, 4-D in PT25M175/Vis/PMS system was investigated through a synergic action of adsorption and photocatalytic PMS activation, in which the optimum PT25M175 composite exhibited the 2, 4-D elimination efficiency up to 98.4 % within 10.0 min. The 2, 4-D degradation was mostly contributed by singlet oxygen (1O2) and superoxide radicals (O2•−), in which non-radical 1O2 accounts for a preponderant oxidation contribution (90.6 %). Based on LC-MS analysis, DFT computation, ecotoxicity analysis, and phytotoxicity evaluation, the 2, 4-D breakdown routes and the toxicity assessment of the degradation products were suggested. The elimination efficiency could be maintained at 97.9 % after five rounds of catalytic experiments. This study provided some guidance for compositing semiconductors with MOFs and utilizing a significant synergistic effect between adsorption and photocatalytic PMS activation to degrade organic pollutants.

Use of integrated multi-omics analysis to determine antitumor efficacy of donafenib in combination with FADS2 inhibition in hepatocellular carcinoma.

e15083 Background: Pharmacotherapy remains a pivotal treatment strategy for patients with advanced hepatocellular carcinoma (HCC). Donafenib, globally the first targeted therapy proven to offer superior survival benefits and safety over sorafenib in a large-scale phase III clinical trial with head-to-head comparison, has been adopted for first-line treatment of advanced HCC. Given the limited basic research on Donafenib both domestically and internationally, and its constrained clinical efficacy, this study aims to explore combination drug therapy for HCC in an attempt to achieve further breakthroughs and enhance the anticancer activity of Donafenib. Methods: A xenograft tumor model in nude mice was established to observe the in vivo antitumor effects of Donafenib. Transcriptomics and proteomics were employed to characterize the gene expression changes in HCC cell lines after Donafenib intervention and to screen for key molecules. A series of assays, including the Cell Counting Kit-8 (CCK8), flow cytometry, scratch assays, Transwell assays, Western blotting, and in vivo tumorigenicity in nude mice, were conducted to determine the impact of the hub gene on the malignant behavior of HCC and to evaluate the combined antitumor effects of the molecular inhibition and Donafenib treatment in HCC. Results: Treatment with Donafenib significantly slowed tumor growth in a nude mouse xenograft model, resulting in a marked reduction in final tumor volumes compared to control subjects. Proteomic analyses post-Donafenib treatment identified FADS2 as the protein with the highest absolute log2 fold change among all differentially expressed proteins in HCC cells. This finding was corroborated by transcriptomic data, which indicated a concurrent downregulation of FADS2 at the mRNA level. Subsequent in vitro and in vivo assays validated the inhibitory effect of FADS2 blockade on the malignant biological behaviors of HCC cells. Importantly, the concomitant administration of Donafenib and the FADS2 inhibitor SC-26196 exhibited a synergistic antitumor action, significantly enhancing therapeutic efficacy in both HCC cell lines and xenografted tumors in nude mice. Conclusions: Combination therapy, a prevalent approach in clinical oncology, has the potential to augment treatment efficacy while simultaneously diminishing toxicity. This study employed an extensive multi-omics approach complemented by a range of both in vitro and in vivo experiments. It revealed that the synergistic use of Donafenib and SC-26196 markedly enhances Donafenib-induced the inhibition of cancer cell growth and metastasis, demonstrating a significant synergistic antitumor effect. These findings from our preclinical investigations may offer a promising new combinational drug regimen for the therapeutic management of HCC patients.

First-in-human study of ZGGS15, a dual specific antibody targeting LAG-3 and TIGIT, as monotherapy in patients with advanced solid tumors.

e14678 Background: ZGGS15 is a recombinant humanized bispecific antibody composed of a monoclonal antibody against LAG-3 and TIGIT. It can specifically bind LAG-3 and TIGIT. It reverses LAG-3 and TIGIT immune suppression to T and NK cells, relieves suppression of Treg to T and NK cells, promotes the activation and proliferation of T and NK cells, and cytokines release. ZGGS15 restores T and NK cell functions to kill tumor cells. In non-clinical studies, we found that ZGGS15 had significant anti-tumor effects and synergistic anti-tumor effects with Anti-PD-1 antibody. Therefore, we conducted a Phase 1 clinical study to assess the tolerability, safety, and preliminary efficacy of this drug as monotherapy in patients with advanced solid tumors. Methods: During the dose escalation stage, an accelerated titration design (ATD) in the first dose (1 subject if ≤Grade 2 treatment-related adverse event occurred) and the standard "3+3" design in the rest doses were used. Subjects were patients with advanced solid tumors who failed to the available standard treatments. The dose groups were set from 0.3 to 30 (0.3, 1, 3, 10, 20, 30) mg/kg, intravenous infusion, once every 3 weeks. The first 21-day period was defined as the dose-limiting toxicity (DLT) observation period. Subjects could continue to receive ZGGS15 until treatment discontinuation criteria were met. Tumor response was assessed by RECIST1.1 and iRECIST. Pharmacokinetics (PK) and receptor occupancy (RO) profiles were also assessed in this study. Results: A total of 12 patients (4 males and 8 females) completed the DLT observation in the first four dose groups (0.3 to 10 mg), with a median age of 57 years. Eight (66.7%) of them received at least 3 lines of antineoplastic therapies, and five (41.7%) have been exposed to PD-1 or PD-L1 inhibitors. There was no DLT event observed. Thirty-eight treatment-related adverse events (TRAEs) occurred. Up to now, TRAEs were all grade 1 ~ 2. The most frequent TRAEs were proteinuria (33.3%, 4/12), hypokalemia (25%, 3/12), hypoalbuminemia (25%, 3/12), and hypertriglyceridemia (25%, 3/12). The Cmax and AUC increased from 0.3-1 mg/kg approximately in dose proportion. Nearly complete and sustained RO of T and NK cells in PBMCs was observed at 1 mg/kg dose of ZGGS15 for at least 3 weeks. Conclusions: The first four dose levels of ZGGS15 were very well tolerated. A good PK profile, and a long-lasting RO were observed in this escalation study. It is anticipated that this product could provide an additional benefit only when use in combination with an anti-PD-1 antibody. Clinical trial information: NCT05864573 .

Apatinib potentiates doxorubicin with cRGD-functionalized pH-senstive micelles against glioma

Glioma is a severe malignant brain tumor marked by an exceedingly dire prognosis and elevated incidence of recurrence. The resilience of such tumors to chemotherapeutic agents, coupled with the formidable obstacle the blood-brain barrier (BBB) presents to most pharmacological interventions are major challenges in anti-glioma therapy. In an endeavor to surmount these impediments, we have synergized pH-sensitive nanoparticles carrying doxorubicin and apatinib to amplify the anti-neoplastic efficacy with cyclic arginine–glycine–aspartate acid (cRGD) modification. In this study, we found that the combination of doxorubicin (DOX) and apatinib (AP) showed a significant synergistic effect, achieved through cytotoxicity and induction of apoptosis, which might be due to the increased intracellular uptake of DOX following AP treatment. Besides, polycaprolactone-polyethylene glycol-cRGD (PCL-PEG-cRGD) drug carrier could cross the BBB by its targeting ability, and then deliver the drug to the glioma site via pH-responsive release, increasing the concentration of the drugs in the tumor. Meanwhile, DOX/AP-loaded PCL-PEG-cRGD nanoparticles effectively inhibited cell proliferation, enhanced glioma cell apoptosis, and retarded tumor growth in vivo. These results collectively identified DOX/AP-loaded PCL-PEG-cRGD nanoparticles as a promising therapeutic candidate for the treatment of glioma.

Synergistic effects and interactions among components in the surimi/κ-carrageenan/soybean oil system

When κ-carrageenan (KC), soybean oil, and surimi are mixed in appropriate proportions, they demonstrate significant synergistic effects. This study established a ternary system composed of surimi, KC, and soybean oil, exploring the synergistic effects and interactions among surimi, KC, and oil from multiple dimensions, including gel properties, rheological behavior, Raman spectroscopy, and microstructure. Gel strength analysis revealed that when the KC concentration was 4.0% (w/w), the surimi gel exhibited the highest gel strength. Moreover, the addition of an extra 5.0% oil further enhanced the gel strength. Rheological analysis indicated that the highest storage modulus (G′) exhibited by the ternary system containing 5.0% oil is the result of synergistic effects among surimi, KC, and oil. Raman spectroscopy further uncovered the hydrogen bonding and electrostatic interactions between surimi proteins and KC, the hydrophobic interactions between surimi proteins and oil, and the hydrogen bonding between KC and oil. The results from scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) indicated that, compared to the pure surimi gel, the Surimi/KC/Oil ternary gel containing 5.0% oil exhibits a more compact and uniform network structure, attributable to the filling effect of KC and oil on the gel network. These results indicate that the synergistic effects and physicochemical interactions among surimi, KC, and oil in appropriate proportions can promote the formation of a stable and compact gel network structure.

The impact of different hydrocolloids on gluten-free bazlama bread quality

The growing global interest in healthy and clean ingredients has prompted a shift in the composition of gluten-free products. This study specifically directed its focus towards Bazlama bread due to its simple ingredient list. The aim of this study was to investigate if clean label hydrocolloids can replace xanthan gum to produce high-quality gluten-free bread. The functional ingredients evaluated were psyllium husk gum (P5), xanthan gum (X5), and fenugreek gum (F5), each at 5.0 g addition level (on 100 g rice/chickpea flour base), as well as a mixture of xanthan and fenugreek gums in a 50:50 wt ratio, used at 3.0 (XF3), 5.0 (XF5), and 6.0 (XF6) g addition levels. The pasting properties of hydrocolloid-flour slurries, the rheological behavior of the gluten-free batters, and the overall quality of the gluten-free bazlama bread (GFBB) were investigated. Results showed that adding P5 increased RVA slurry viscosities and bread thickness comparable to the X5 recipe. However, no significant synergistic effect was observed when combining xanthan and fenugreek gum in any of the tests. GFBB with P5 and X5 stood out for their desirable characteristics such as high thickness and springiness values, while GFBB with F5 and XF3 distinguished themselves from other GFBBs in terms of their higher spread ratio, hardness, diameter, and chewiness. Principle Component Analysis revealed negative correlations between bread thickness and pasting temperature, while the viscoelastic modulus of the batter samples correlated positively with bread thickness. The inclusion of hydrocolloids did not significantly alter the starch digestibility of the GFBB.

Bisphenol AF exposure synergistically increases the risk for suicidality among early adolescents with child maltreatment: A prospective cohort study

BackgroundChild maltreatment (CM) is correlated with suicidality risk among adolescents. Additionally, exposure to bisphenol AF (BPAF) may increase this risk. However, the combined effect of CM and BPAF exposure remains unknown and should be further investigated. MethodsIn this study, 1,475 early adolescents (mean age = 12.48 years) from the Chinese Early Adolescents Cohort were enrolled. Data were collected at three time points with an interval of 12 months between 2019 and 2021. Participants’ history of CM and suicidality (including suicidal ideation and suicidal attempts) were evaluated using a self-report questionnaire. Blood samples were obtained from participants to measure serum BPAF concentrations at baseline. Group-based trajectory modeling was employed to identify different developmental trajectories of suicidality across the three waves. After adjusting for potential confounders, the association between CM and BPAF exposure on suicidal ideation and suicidal attempts was assessed using logistic regression and Poisson regression analyses. ResultsParticipants with CM were associated with a risk of one- and two-year incident suicidality (all ps < 0.05), and BPAF levels were positively associated with two-year incident suicidal ideation (adjusted OR = 1.68, 95% CI: 1.13–2.50). Additionally, middle and high levels of BPAF exposure synergistically increase the risk for one- and two-year incident suicidal ideation among participants with CM (adjusted ORs = 2.00–3.83). Similarly, participants exposed to high-level BPAF as well as CM were at a greater risk of one- and two-year incident suicidal attempts than those with low-level BPAF exposure and no CM (adjusted incidence rate ratio [IRRs] = 2.82–4.34). Moreover, compared with participants with a low developmental trajectory of suicidality across the three waves, high BPAF exposure exhibited a significant synergistic effect on participants with CM in the persistently high suicidal ideation trajectory and the increasing suicidal attempts trajectory (all ps < 0.05). Sex subgroup analysis revealed that females were more susceptible to the synergistic effect of BPAF and CM exposure on suicidality than males. ConclusionsEnvironmental factors and the psychological status of individuals may synergistically increase their susceptibility to suicidality. These results offer novel insights into enhancing our understanding of suicidality among adolescents.

CuS@MoS2 p[sbnd]n heterojunction photocatalyst integrating photothermal and piezoelectric enhancement effects for tetracycline degradation

Photocatalysis is an environmentally friendly and low-cost technology for the degradation of pollutants. In addition to the construction of heterojunction which may decrease the recombination of charge carriers and extend the photo-response range, the utilization of piezoelectricity and photothermal conversion also provides the promising routes to improve the photocatalytic performance. Herein, a CuS@MoS2 heterostructure was developed to simultaneously meet the needs of these enhancement mechanisms. The formation of pn heterojunction was confirmed and the associated energy band diagram was constructed with band gaps of CuS and MoS2 as 1.56 and 1.80 eV, respectively. For the degradation of tetracycline, it was demonstrated that the inherent piezoelectric property of MoS2 surface enhanced the piezocatalytic activity by inducing an electric field to aid charge separation. The heat generated by illumination raised the photocatalytic reaction rate by supplying extra energy to carriers. The CuS@MoS2 heterostructure exhibited significantly better catalytic performance than the individual CuS or MoS2 due to the formation of pn heterojunction. Furthermore, the combination of piezoelectricity and photothermal conversion also led to a significant synergistic effect, achieving a degradation efficiency of over 95% within 30 min. As compared to the conditions under ultrasonic vibration, visible light irradiation and visiblenearinfrared light irradiation alone, the combination of visiblenearinfrared irradiation and ultrasonic vibration could lead to 96, 205 and 81% enhancement. This work provides valuable insights into the design of novel heterojunction photocatalysts integrating the piezoelectric and photothermal enhancement effects.

Synergistic effects of silver nanoparticles in combination with ineffective antibiotics against multidrug resistant Salmonella typhi.

To determine the antimicrobial activity of silver nano-particles(AgNPs) with tetracycline and ampicillin against multi-drug resistance (MDR) and extensively-drug resistance (XDR) Salmonella typhi. Cross sectional non-probability purposive study was conducted from September, 2021 to May, 2022 at Microbiology department PNS Shifa, Hospital Karachi. Blood cultures of patients suspicious of typhoid fever were collected and incubated in automated Bact/Alert system. Positive cultures were identified on blood and MacConkey and processed by API-10S, confirmed by serotyping (O9 antisera) (SSI Diagnostica's Salmonella). Antibiotic resistance was done by Kirby-Bauer disk diffusion (Sigma and Rich). MDR and XDR isolates were preserved in Brain Heart Infusion in a volume of 2ml in screw capped bottles at -70°C. Antimicrobial powders (ampicillin and tetracycline (Alfa Aesar) weighed by an electrical weighing balance (OHAUS) to take 1mg of antimicrobial drug. Absorbance spectra of serial concentrations of antibiotics (UV-Vis spectrophotometer (Mole-Qule-) AgNPs (10nm) (nanocomposix) + Antibiotic in (1:1 volume ratio). Conjugation of silver nanoparticles with tetracycline and ampicillin was done by FTIR (thermos scientificThermos ScientificNicolet 50). Out of 77 isolates, 54 were resistant to ceftriaxone (XDR) and 23 sensitive to ceftriaxone (MDR). All isolates were susceptible to azithromycin and meropenem. Comparison of zone of inhibitions of ampicillin and Amp-AgNPsas and tetracycline with Tet-AgNPs was done. Minimal inhibitory concentration was also done to determine antimicrobial activity. Significant synergistic inhibitory effects against Salmonella Typhi isolates were obtained by combination of tetracycline with silver nano-particles even at low concentration.

Assessing bioenergy prospects of algal biomass and yard waste using an integrated hydrothermal carbonization and pyrolysis (HTC–PY): A detailed emission–to–ash characterization via diverse hyphenated analytical techniques and modelling strategies

Hydrothermal carbonization (HTC) presents a promising method for converting carbonaceous waste into renewable fuels, facilitating energy recovery. This study focuses on the HTC pretreatment of microalgae (Chlorella sorokiniana) and yard waste, examining their physicochemical structural changes, component migration, and potential for valorization via integrated HTC and pyrolysis processes. HTC notably enhances the carbon content while reducing oxygen and nitrogen levels in these feedstocks, producing a clean solid fuel with high energy density. The study investigates the pyrolytic behavior of hydrochars and their blends using different analytical techniques, kinetic modeling, and fixed–bed reactor experiments. The blends with 90% and 70% of microalgae hydrochar (CSH) exhibited the most significant synergistic effects during co–pyrolysis, evident in its devolatilization behaviors and reduced activation energies. Integrating artificial neural networks and response surface methodology models facilitated optimization of pyrolysis parameters and accurate prediction of bio–oil, biochar, and gas yields. The analytical techniques enabled characterization of pyrolysis products, revealing notable changes in bio–oil and biochar compositions, suggesting potential enhancements. The study comprehensively evaluates the HTC–pyrolysis approach’s potential for converting microalgae and lignocellulosic biomass into eco–friendly biofuels for industrial applications.

Competitive Inhibition and Synergistic Effects of Nutraceutical and Metabolite Molecules on Anti-Acetylcholinesterase Activity

The rapidly increasing prevalence of Alzheimer's disease (AD) poses a significant global public health threat. While medications such as Donepezil, Galantamine, and Rivastigmine are used, their serious side effects and limited healing fail to provide a definite cure. Consequently, combination therapies are being explored to enhance the efficacy of existing drugs. This study aims to evaluate the anti-acetylcholinesterase activities of previously identified nutraceutical and metabolite compounds, namely Queuine, Etoperidone, and Thiamine. Combined use of Queuine with Donepezil, Etoperidone, and Thiamine on acetylcholinesterase enzyme inhibition is also evaluated. The effects of the drug combinations on cell viability and acetylcholinesterase inhibition were investigated by using safe doses determined for each drug. The cytotoxic effect of drug combinations was investigated on the SH-SY5Y cell line using the RTCA method. All the individual or drug combinations were non-toxic to neuronal cells. Anti-acetylcholinesterase activities were estimated by Ellman’s method yielding the inhibition percentages as 70%, 61%, 45%, and 51% for Donepezil, Etoperidone, Queuine, and Thiamine, respectively. When drug combinations were analyzed, competitive inhibition resulted for Queuine+Donepezil and Queuine+Thiamine, the enzyme inhibition percentages being diminished to 47% and 21%, respectively. A significant synergistic effect was observed for Queuine+Etoperidone with the highest inhibition of 74%. This study provides the first evidence of the nutraceutical molecule Queuine's impact on acetylcholinesterase inhibition and the synergistic effect of Queuine and Etoperidone as a potent drug combination surpassing the effectiveness of Donepezil. Queuine and Etoperidone synergism may serve as a potential AD treatment by further in vivo validations.

Effects of the interaction between cold spells and fine particulate matter on mortality risk in Xining: a case-crossover study at high altitude.

With global climate change, the health impacts of cold spells and air pollution caused by PM2.5 are increasingly aggravated, especially in high-altitude areas, which are particularly sensitive. Exploring their interactions is crucial for public health. We collected time-series data on meteorology, air pollution, and various causes of death in Xining. This study employed a time-stratified case-crossover design and conditional logistic regression models to explore the association between cold spells, PM2.5 exposure, and various causes of death, and to assess their interaction. We quantitatively analyzed the interaction using the relative excess odds due to interaction (REOI), attributable proportion due to interaction (AP), and synergy index (S). Moreover, we conducted stratified analyses by average altitude, sex, age, and educational level to identify potential vulnerable groups. We found significant associations between cold spells, PM2.5, and various causes of death, with noticeable effects on respiratory disease mortality and COPD mortality. We identified significant synergistic effects (REOI>0, AP > 0, S > 1) between cold spells and PM2.5 on various causes of death, which generally weakened with a stricter definition of cold spells and longer duration. It was estimated that up to 9.56% of non-accidental deaths could be attributed to concurrent exposure to cold spells and high-level PM2.5. High-altitude areas, males, the older adults, and individuals with lower educational levels were more sensitive. The interaction mainly varied among age groups, indicating significant impacts and a synergistic action that increased mortality risk. Our study found that in high-altitude areas, exposure to cold spells and PM2.5 significantly increased the mortality risk from specific diseases among the older adults, males, and those with lower educational levels, and there was an interaction between cold spells and PM2.5. The results underscore the importance of reducing these exposures to protect public health.

Sono-assisted photocatalytic degradation of ciprofloxacin in aquatic media using g-C3N4/MOF-based nanocomposite under visible light irradiation.

This research study is centered on the sono-assisted photocatalytic degradation of a well-known antibiotic (ciprofloxacin; CIP) in aquatic media using a g-C3N4/NH2-UiO-66 (Zr) catalyst under visible light irradiation. Initially, the catalyst was prepared by a simple method, and its physiochemical features were thoroughly analyzed by XRD, FT-IR, FE-SEM, EDX, EDS-Dot-Mapping, and UV-Vis analytical techniques. After that, the impact of several influential factors affecting the performance of the applied sono-assisted photocatalytic process such as the initial concentration of CIP, solution pH, catalyst dosage, light intensity, and ultrasound power was fully assessed, and the optimal conditions were established. After 75min of the sono-assisted photocatalytic treatment, the complete degradation of CIP (10mg/L) was accomplished under the condition as follows: g-C3N4/NH2-UiO-66 (Zr), 0.6g/L; pH, 5.0, and ultrasound power, light intensity 75 mw/cm2, 200 W/m2. Meanwhile, the photocatalytic degradation of CIP followed the pseudo-first-order kinetic model. In addition, the scavenger experiments demonstrated that OH˚ and O2°- radicals played a key role in the sono-assisted photocatalytic degradation process. It is also acknowledged that the applied catalyst was reused for five consecutive runs with a minor loss observed in its degradation efficiency. In a further experiment, a significant synergistic effect with regard to the degradation of CIP was observed once all three major parameters (visible light, ultrasound waves, and catalyst) were used in combination compared to each used alone. To sum up, it is thought that the integration of g-C3N4/MOF-based catalyst, ultrasound waves, and visible light irradiation could be potentially applied as a promising strategy for the degradation of various pharmaceuticals on account of high degradation performance, simple operation, excellent reusability, and eco-friendly approach.

Long-term combination therapy with metformin and oxymetholone in a Fanconi anemia mouse model.

Fanconi anemia (FA) is a disease caused by defective deoxyribonucleic acid (DNA) repair that manifests as bone marrow failure, cancer predisposition, and developmental defects. We previously reported that monotherapy with either metformin (MET) or oxymetholone (OXM) improved peripheral blood (PB) counts and the number and functionality of bone marrow hematopoietic stem progenitor cells (HSPCs) number in Fancd2-/- mice. To evaluate whether the combination treatment of these drugs has a synergistic effect to prevent bone marrow failure in FA, we treated cohorts of Fancd2-/- mice and wildtype controls with either MET alone, OXM alone, MET+OXM, or placebo diet from age 3weeks to 18months. The OXM treated animals showed modest improvements in blood parameters including platelet count (p=.01) and hemoglobin levels (p<.05). In addition, the percentage of quiescent hematopoietic stem cell (HSC) (LSK [Lin-Sca+c-Kit+]) was significantly increased (p=.001) by long-term treatment with MET alone. The combination of metformin and oxymetholone did not result in a significant synergistic effect in any hematopoietic parameter. Gene expression analysis of liver tissue from these animals showed that some of the expression changes caused by Fancd2 deletion were partially normalized by metformin treatment. Importantly, no adverse effects of the individual or combination therapies were observed, despite the long-term administration. We conclude that androgen therapy is not a contraindication to concurrent metformin administration in clinical trials. HIGHLIGHTS: Long-term coadministration of metformin in combination with oxymetholone is well tolerated by Fancd2-/- mice. Hematopoietic stem cell quiescence in mutant mice was enhanced by treatment with metformin alone. Metformin treatment caused a partial normalization of gene expression in the livers of mutant mice.

A Study on the Effect of New Surfactant Proportions on the Recovery Improvement of Carbonate Reservoir

The strategy of integrating water injection and chemical additives in combining secondary and tertiary oil recovery techniques has been widely investigated in enhancing oil recovery efficiency. Nevertheless, there is a lack of sufficient evidence on the effectiveness of a mixture of cationic and nonionic surfactants combined with water injection techniques in enhancing recovery in the application of carbonate reservoirs. Therefore, it is particularly critical to explore the impact of this combination strategy in enhancing recovery in fractured carbonate reservoirs. The recovery enhancement effect can be assessed by conducting phase behavior experiments and determining interfacial tension and contact angle. Further, the effectiveness of specific surfactant ration solutions in enhancing recovery can be verified by performing drive-off experiments. The results show that low mineralization water and surfactants have a significant synergistic effect in enhancing the recovery efficiency of carbonate reservoirs, with the optimal ratio of cationic to non-ionic surfactants being 2.5:1. The optimized surfactant ratio is able to increase the recovery of carbonate reservoirs by 20% compared to the original recovery rate.

Biological impact and therapeutic potential of a novel camptothecin derivative (FLQY2) in pancreatic cancer through inactivation of the PDK1/AKT/mTOR pathway

BackgroundCamptothecin (CPT), a pentacyclic alkaloid with antitumor properties, is derived from the Camptotheca acuminata. Topotecan and irinotecan (CPT derivatives) were first approved by the Food and Drug Administration for cancer treatment over 25 years ago and remain key anticancer drugs today. However, their use is often limited by clinical toxicity. Despite extensive development efforts, many of these derivatives have not succeeded clinically, particularly in their effectiveness against pancreatic cancer which remains modest. Aim of the studyThis study aimed to evaluate the therapeutic activity of FLQY2, a CPT derivative synthesized in our laboratory, against pancreatic cancer, comparing its efficacy and mechanism of action with those of established clinical drugs. MethodsThe cytotoxic effects of FLQY2 on cancer cells were assessed using an MTT assay. Patient-derived organoid (PDO) models were employed to compare the sensitivity of FLQY2 to existing clinical drugs across various cancers. The impact of FLQY2 on apoptosis and cell cycle arrest in Mia Paca-2 pancreatic cancer cells was examined through flow cytometry. Transcriptomic and proteomic analyses were conducted to explore the underlying mechanisms of FLQY2′s antitumor activity. Western blotting was used to determine the levels of proteins regulated by FLQY2. Additionally, the antitumor efficacy of FLQY2 in vivo was evaluated in a pancreatic cancer xenograft model. ResultsFLQY2 demonstrated (1) potent cytotoxicity; (2) superior tumor-suppressive activity in PDO models compared to current clinical drugs such as gemcitabine, 5-fluorouracil, cisplatin, paclitaxel, ivosidenib, infinitinib, and lenvatinib; (3) significantly greater tumor inhibition than paclitaxel liposomes in a pancreatic cancer xenograft model; (4) robust antitumor effects, closely associated with the inhibition of the TOP I and PDK1/AKT/mTOR signaling pathways. In vitro studies revealed that FLQY2 inhibited cell proliferation, colony formation, induced apoptosis, and caused cell cycle arrest at nanomolar concentrations. Furthermore, the combination of FLQY2 and gemcitabine exhibited significant inhibitory and synergistic effects. ConclusionThe study confirmed the involvement of topoisomerase I and the PDK1/AKT/mTOR pathways in mediating the antitumor activity of FLQY2 in treating Mia Paca-2 pancreatic cancer. Therefore, FLQY2 has potential as a novel therapeutic option for patients with pancreatic cancer.

A sensitive NH3 chemiresistive sensor with wide detection range: Employing a MOF-derived mesoporous carbon composite with polyaniline

Designing sensing materials with effective porous structure and compositions is a crucial strategy for constructing high-performance gas-sensitive devices. Herein, a dodecahedral mesoporous carbon derived from metal-organic frameworks (CMOF), e.g. Zeolitic Imidazolate Framework-8 (ZIF-8) derived porous carbon (ZIF-8-C) was prepared, and subsequently, three-dimensional (3D) hollow dodecahedral ZIF-derived carbon-polyaniline (PANI) based (ZCPx, x representing the mass fraction of ZIF-derived carbon) hierarchical hybrid materials were constructed by introducing protonated polyaniline on the surface of MOF carbon via in-situ oxidative polymerization. The MOF-derived structure provides a substantial interface surface area for the hybrid material, enabling rapid adsorption and charge transfer, along with essential structural stability. The 3D hollow ZCP50 hybrid material prepared exhibits a wide detection range (0.1–500 ppm), repeatability, acceptable long-term stability, and an 8.3 times response enhancement versus PANI. The above performance is attributed to the significant synergistic effect between ZIF-8-C and PANI. The unique design of this 3D framework holds promising potential for the commercial application of room-temperature gas sensors.

Revealing the tribological mechanism of synergistic effect between MoDTC and P-containing additives in aluminum-based grease

Purpose This study aims to reveal the tribological mechanism of synergistic effect between MoDTC and P-containing additives in aluminum-based grease. Design/methodology/approach The authors prepared a molybdenum dialkyl dithiocarbamate (MoDTC) and revealed the tribological mechanism of synergistic effect between MoDTC and P-containing additives in aluminum-based grease by combining with ZDDP and P-containing and S-free additives. Findings The MoDTC the authors prepared has good friction-reducing and anti-wear properties in aluminum-based grease and has an obvious synergistic effect with ZDDP. MoDTC and ZDDP have a significant synergistic effect on the tribological properties in aluminum-based grease, mainly because of the formation of phosphates and metaphosphates as well as more MoS2 in the friction film. P element plays a facilitating role in the chemical conversion of MoDTC to MoS2. Originality/value The experiments of MoDTC with tributyl phosphate and trimethylphenyl phosphate confirm that the P element plays a facilitating role in the chemical conversion of MoDTC into MoS2. Peer review The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-12-2023-0410

New synergistic combination therapy approaches with HDAC inhibitor quisinostat, cisplatin or PARP inhibitor talazoparib for urothelial carcinoma.

Urothelial carcinoma (UC) urgently requires new therapeutic options. Histone deacetylases (HDAC) are frequently dysregulated in UC and constitute interesting targets for the development of alternative therapy options. Thus, we investigated the effect of the second generation HDAC inhibitor (HDACi) quisinostat in five UC cell lines (UCC) and two normal control cell lines in comparison to romidepsin, a well characterized HDACi which was previously shown to induce cell death and cell cycle arrest. In UCC, quisinostat led to cell cycle alterations, cell death induction and DNA damage, but was well tolerated by normal cells. Combinations of quisinostat with cisplatin or the PARP inhibitor talazoparib led to decrease in cell viability and significant synergistic effect in five UCCs and platinum-resistant sublines allowing dose reduction. Further analyses in UM-UC-3 and J82 at low dose ratio revealed that the mechanisms included cell cycle disturbance, apoptosis induction and DNA damage. These combinations appeared to be well tolerated in normal cells. In conclusion, our results suggest new promising combination regimes for treatment of UC, also in the cisplatin-resistant setting.

Real-time monitoring of charcoal layer resistance for investigating the synergistic flame retardant mechanism of zinc oxide and intumescent flame retardants in SBS

Metal oxides as synergists of intumescent flame retardant (IFR) lead to an extremely complex formation process of intumescent char layers. The lack of means to detect the evolution of the char layer in real time makes it challenging to investigate the synergistic flame retardant mechanism between metal oxides and IFR. Herein, an innovative method of detecting real-time changes in the resistance of the char layer under flame ablation is used to investigate its changes in morphology, thus assisting in revealing the synergistic flame retardant mechanism of zinc oxide (ZnO) in IFR/SBS. ZnO showed a significant synergistic flame retardant effect with IFR without MEL and no synergistic effect with MEL-containing IFR. The analysis of the char layer structure revealed that ZnO played a role in promoting gas release and char layer formation and increasing the viscosity of the molten char layer regardless of the presence or absence of MEL.The difference in the morphology of the char layer could not reveal the experimental phenomenon that there is no synergistic flame retardant effect between ZnO and MEL-containing IFR. The analysis of the real-time resistance of the charcoal layer reveals that ZnO achieves its synergistic flame retardation with the MEL-free IFR by increasing the expansion of the charcoal layer at the initial stage of its formation. For MEL-containing IFR, 0.5% ZnO inhibits the rupture of the char layer by promoting its formation in the early stages of ablation, and 1% ZnO leads to the rupture of the char layer instead, due to the promotion of gas release. Excess ZnO (2%) caused pyrolysis gases to escape from the voids of the char layer rather than allowing it to expand. The analysis of the real-time resistance of the charcoal layer can help to accurately reveal the flame retardant mechanism.