Combined Treatment Research Articles

Novel insights into vancomycin-loaded calcium sulfate and negative pressure wound therapy in preventing infections in open fractures.

Open fractures are challenging due to susceptibility to Staphylococcus aureus infections. This study examines the impact of Vancomycin-Loaded Calcium Sulfate (VLCS) and negative pressure wound therapy (NPWT) on macrophage behavior in enhancing healing and infection resistance. Both VLCS and NPWT were evaluated individually and in combination to determine their effects on macrophage polarization and infection resistance in open fractures. Through single-cell RNA sequencing, genomic expressions in macrophages from open fracture patients treated with VLCS and NPWT were compared to a control group. The analysis focused on MBD2 gene changes related to macrophage polarization. Remarkable modifications in MBD2 expression in the treatment group indicate a shift towards M2 macrophage polarization. Additionally, the combined treatment group exhibited greater improvements in infection resistance and healing compared to the individual treatments. This shift suggests a healing-promoting atmosphere with improved infection resilience. VLCS and NPWT demonstrate the ability to alter macrophage behavior toward M2 polarization, which is crucial for infection prevention in open fractures. The synergistic effect of their combined use shows even greater promise in enhancing outcomes in orthopedic trauma care.

Beetroot (Beta vulgaris L.) Extract Gives Superior Effect than Beetroot Juice on Increasing HDL and Decreasing LDL and IL-6 in Dyslipidemic Rats Model

BACKGROUND: Dyslipidemia derives from disturbances in lipid metabolism as an interaction between genetic and environmental factors, characterized by increased levels of cholesterol, triglycerides, low-density lipoprotein (LDL) and decreased levels of high-density lipoprotein (HDL). Continuous dyslipidemia will increase the risk of atherosclerosis. In dyslipidemia, macrophages release inflammatory cytokines such as interleukin (IL)-1, IL-6, IL-12, IL-15, IL-18, and then induce T-cell infiltration formed atherosclerotic plaques. Beet (Beta vulgaris L.) which contains active compounds and antioxidant, such as flavonoids and betacyanin, has the ability to reduce dyslipidemia. This study evaluated effect of beetroot juice and beetroot extract on dyslipidemic rat models by evaluating the level of HDL, LDL and IL-6.METHODS: Fourty-two male Sprague Dawley rats were divided into seven groups. Rats were fed either with standard food or high fat diet (HFD) for 28 days, then different interventions using either single combination of simvastatin, beetroot juice, or beetroot extract were given alongside the standard food or HFD diet for another 28 days. LDL and HDL were measured pre- and post-intervention, while IL-6 was measured only post-treatment.RESULTS: Daily administration of a single beetroot juice or beetroot extract or in combination with simvastatin reduced LDL significantly compared to pre-intervention. The interventions also increased HDL significantly and lower IL-6 concentrations compared to group that received no intervention.CONCLUSION: Administration of beetroot juice and beetroot extract can lower LDL, increase HDL, and decrease IL-6 either alone or in combination treatment with simvastatin, it is indicated beetroot have a potential benefit for prevention and therapeutic in dyslipidemia.KEYWORDS: beetroot juice, beetroot extract, LDL, HDL, IL-6

Low impact of Carpobrotus edulis on soil microbiome after manual removal from a climate change field experiment

Synergic effects between climate change and invasive species may alter soil microbial diversity and functioning, as well as cause major shifts in physicochemical properties. Moreover, some of these ecological impacts may manifest even after the removal of the invasive species. We have conducted a field experiment to assess such effects on soil microbial communities (fungi and bacteria) and physicochemical properties seven months after the removal of Carpobrotus edulis (L.), an invasive plant of coastal dune ecosystems. C. edulis grew on the experimental plots for 14 months under current (“invasive species treatment”) and increased warming and drought conditions (“combined treatment”). Then, all plant parts (above and belowground biomass) were removed with a non-aggressive eradication method and soil samples were collected seven months later in the experimental and control plots (no invasive species and current climatic conditions). We predicted a general compositional shift in microbial communities in response to the presence of the invasive species. Moreover, given that water is the most limiting factor in this type of ecosystem, we also predicted a more pronounced compositional shift in the treatment combining invader presence and climate change. While species richness was similar amongst treatments, we observed some taxonomic and functional variation in soil microbial communities. Notably, fungal and bacterial communities exhibited contrasting responses. The species composition of bacteria differed significantly between the “invasive species” and “control” treatments, while, in the case of fungi, the most substantial difference occurred between the “invasive species” treatment and the combined treatment of “invasive species and climate change”. Some chemical properties, such as carbon and nitrogen content or pH, strongly differed amongst treatments, with the “invasive species” showing a different response compared to the other two treatments. Overall, our study suggests smaller short-term effects on the microbial community compared to soil chemical properties. Furthermore and contrary to our initial expectations, the potential impact on the soil microbiome seemed to be weaker in the face of rising temperatures and drought conditions predicted by climate change. This outcome highlights the remarkable complexity of the impact of invasive species and climate change on belowground microbial communities.

Efficacy of Recombinant Human Parathyroid Hormone 1-34 and Vitamin K2 Combination Therapy in Postmenopausal Osteoporosis.

This study aimed to assess the efficacy and safety of a combined recombinant human parathyroid hormone 1-34 [rhPTH (1-34)] and vitamin K2 therapy versus vitamin K2 alone in the treatment of postmenopausal osteoporosis. A total of 77 postmenopausal osteoporosis patients were randomly divided into two groups. Patients in one group received vitamin K2 alone, while patients in the other group received a combination of rhPTH (1-34) and vitamin K2. Bone mineral density (BMD), electrolyte levels, pain scores, bone metabolism levels, and adverse drug reactions were compared pre- and post-treatment. Both two treatments improved BMD, blood calcium concentrations, pain scores, and increased osteocalcin and osteoprotegerin levels. Notably, the combined rhPTH (1-34) and vitamin K2 treatment demonstrated superior efficacy in improving BMD and bone metabolism markers. Furthermore, there was no significant difference in the incidence of adverse reactions between the two groups, indicating the safety of the combined treatment. In summary, the combined therapy of rhPTH (1-34) and vitamin K2 exhibited more potent efficacy in the treatment of postmenopausal osteoporosis, more effectively enhancing BMD and bone metabolism markers than vitamin K2 alone, without a significant increase in adverse reactions.

Treatments Technology and Mechanisms of East Asia Black Cotton Soil

The East Asia black cotton soil (BCS) cannot be used as embankment filling directly due to its high clay content, liquid limit, plasticity index, and low CBR strength (CBR < 3%). This study evaluates the effects of treating East Asia BCS with lime, volcanic ash, or a combination of both on its engineering properties. Experiments were conducted to analyze the basic physical properties, swelling characteristics, and mechanical properties of the treated soil. Results indicate that lime addition significantly reduces the free swelling rate, improves limit moisture content, increases optimum moisture content, decreases maximum dry density, and enhances CBR value. Although volcanic ash also improves BCS performance, its effects are less pronounced than those of lime. The combined treatment with lime and volcanic ash exhibits superior performance, greatly reducing expansion potential and significantly increasing soil strength. Specifically, a mixture of 3% lime and 15% volcanic ash optimizes the liquid limit, plasticity index, and CBR value to 49.2%, 23.8, and 24.7%, respectively, meeting the JTG D30-2015 requirements and reducing construction costs. The treatment mechanisms involve hydration exothermic reactions, volcanic ash reactions, and semipermeable membrane effects, which collectively enhance the soil’s properties by producing dense, high-strength compounds.

S-p-bromobenzyl-glutathione cyclopentyl diester (BBGC) as novel therapeutic strategy to enhance trabectedin anti-tumor effect in soft tissue sarcoma preclinical models.

Trabectedin, approved for the treatment of soft tissue sarcoma (STS), interferes with cell division and genetic transcription processes. Due to its strong anti-tumor activity in only certain histotypes, several studies on trabectedin combinations are currently ongoing to improve its efficacy. In this study, we aimed to investigate novel potential therapeutic strategies to enhance the anti-tumor effect of trabectedin using integrated in silico, in vitro, and in vivo approaches. For in silico analysis, we screened two public datasets, GSEA M5190 and TCGA SARC. Fibrosarcoma, leiomyosarcoma, dedifferentiated, and myxoid liposarcoma cell lines were used for in vitro studies. For in vivo experiments, fibrosarcoma orthotopic murine model was developed. In silico analysis identified Glo1 as the only druggable target upregulated after trabectedin treatment and correlated with poor prognosis. The specific Glo1 inhibitor, S-p-bromobenzylglutathione cyclopentyl diester (BBGC), increased trabectedin cytotoxicity in STS cells, and restored drug sensitivity in myxoid liposarcoma cells resistant to trabectedin. Moreover, the combined treatment with BBGC and trabectedin had a synergistic antitumor effect in vivo without any additional toxicity to mice. Based on these results, we believe that BBGC warrants further investigation to evaluate its potential clinical use in combination with trabectedin.

Impact of Organic Manures and Liquid Formulations on Garlic Growth, Yield and Quality in Uttarakhand, India

The field study was carried out to VCSG, UUHF, Pauri Garhwal in 2022-2023 to investigate the integrated effect of organic manures and organic liquid formulations on the growth and yield of garlic. The main objective of this study was to determine the benefits of using organic manures and liquid formulations over conventional farming because the abundant use of nitrogenous fertilizers causes excessive vegetative growth at the expense of bulb formation. Among fourteen different treatment combinations that consist of various combinations of organic manures (FYM and Vermicompost) and organic liquid formulations (Panchgavya and Jeevamrit) treatment T3 i.e., FYM (10t/ha) + Panchgavya (2%) emerged as the best treatment concerning growth and yield of garlic. The findings showed that the maximum plant height (69.080 cm), number of leaves (8.400), leaf length (47.880 cm) and breadth (3.207 cm), and leaf area index (1.023) at all the 30 days intervals after sowing of garlic has been observed with the application of Treatment T3. The fundamental reason for the increased growth might be due to growth-promoting substances like auxins and gibberellins in panchgavya and high nitrogen and phosphorus in FYM. Concerning yield and quality attributes, the bulb diameter (5.657 cm), fresh weight of bulb (64.643 cm), length of the bulb (5.853 cm), number of cloves per bulb (12.200), bulb yield (120.833 q), total chlorophyll content (2.127 mg/g) and ascorbic acid content (15.333 mg/100g) was obtained maximum with the application of same treatment T3 i.e., FYM (10t/ha) + Panchgavya (2%) with yield increases up to 30% compared to control. However, the harvest index percent was found to be maximum (89.243 %) in treatment T13 i.e., Vermicompost (5t/ha) + Jeevamrit (6%). These findings suggest that organic farming practices can effectively enhance garlic production, offering a sustainable alternative to chemical fertilizers. Moreover, this study provides practical insights for farmers and contributes to the growing body of research on sustainable agriculture.

In vitro propagation of triploid Toxicodendron vernicifluum (Stokes) F. A. Barkl

AbstractTriploid lacquer trees have a higher yield of raw lacquer and greater stress resistance; however, it is challenging to develop efficient and rapid seedling culture techniques because of the influence of metabolites with raw lacquer. In this study, the stem segments of a triploid lacquer tree were used to investigate the effects of explant sterilization treatment, different combinations of exogenous hormone concentrations on the induction of axillary buds, seedling development, and rooting, as well as transplanting substrate ratios. The results showed that the optimal combination of disinfection treatment for triploid Toxicodendron vernicifluum (Stokes) F. A. Barkl explants involves 75% alcohol immersion for 10 s, followed by 2.0% benzalkonium chloride treatment for 1 min and 0.1% HgCl2 treatment for 4 min. The suitable medium for axillary bud induction was Murashige and Skoog (MS) containing 0.1 mg•L−1 zeatin (ZT) and 0.1 mg•L−1 6-benzylaminopurine (6-BA), resulting in a high induction rate of 95.0%. Use of 1/2 MS supplemented with 0.5 mg•L−1 6-BA and 0.3 mg•L−1 2,4-dichlorophenoxyacetic acid (2,4-D) was the most effective for axillary bud proliferation. The combination of 1/2 MS containing 0.1 mg•L−1 6-BA, 0.5 mg•L−1 2,4-D, 0.5 mg•L−1 indole-3-butyric acid (IBA), and 0.2% activated carbon (AC) was an optimum for hardening-off. With woody plant medium (WPM) supplemented with 0.5 mg•L−1 naphthaleneacetic acid (NAA) and 0.5 mg•L−1 2,4-D and 0.5 g•L−1 AC as a rooting medium, the rooting rate was 67.8%. Also, the appropriate transplanting substrate ratio for triploid Toxicodendron vernicifluum (Stokes) F. A. Barkl was grass charcoal:laterite:humus = 1:1:1. Collectively, the results provided the technical assurance for seedling scale multiplication and propagation, facilitating its application in production.

Shifts in Structure and Assembly Processes of Root Endophytic Community Caused by Climate Warming and Precipitation Increase in Alpine Grassland

Climate change poses great challenges to the survival of plants. Plant endophytes play important roles in improving plant adaptability. However, our knowledge of the effects of climate change on endophytic community structures is limited. Relying on a field experimental platform simulating climate warming, precipitation increases, and their combination in an alpine grassland, the root endophytic bacterial community structures and assembly processes of three coexisting plant species (Elymus nutans, Kobresia humilis, and Melissilus ruthenicus) were measured. The results indicated that Proteobacteria was the dominant phylum, with a relative abundance ranging from 50% to 80%, followed by Actinobacteria and Bacteroidetes. Bacterial diversity decreased significantly under the combined treatment for all three plant species, with the largest reduction observed in E. nutans. The climate manipulation treatments had a minimal effect on the endophytic bacterial community structures. The relative abundance of Burkholderiaceae increased significantly under the combined treatment for the three plant species. Moreover, the endophytic community assembly processes changed from stochastic dominated under control plots to deterministic dominated under the combined plots for E. nutans, while this shift was reversed for M. ruthenicus. The root endophytic bacterial community was affected by the soil’s available nitrogen and stoichiometric ratio. These results revealed that the sensitivity of endophyte community structures to climate change varies with host plant species, which has implications for plant fitness differences.

A real-world analysis of adherence, biochemical outcomes and healthcare costs in patients treated with rosuvastatin/ezetimibe as single-pill combination vs free combination in Italy

Abstract Aims To compare medication adherence, lipid goal attainment and healthcare costs between patients receiving a single-pill combination (SPC) vs a free combination treatment (FCT) of rosuvastatin/ezetimibe (ROS/EZE) in Italy. Methods and results Administrative databases of healthcare entities covering ∼7 million individuals were used to identify adults prescribed with ROS/EZE as SPC or FCT between Jan-2018 and Jun-2020. Adherence was calculated as proportion of days covered (PDC) after cohort balancing by propensity score matching. Patients with available LDL cholesterol testing were assessed for the proportion of those who at baseline were above lipid targets recommended by ESC/EAS guidelines for their cardiovascular risk category and reached the target during follow-up. Among 25,886 patients on SPC and 7,309 on FCT, adherent patients were more represented in SPC than FCT cohort (56.8% vs 44.5%, p<0.001), and this difference remained significant (p<0.001) after stratification by cardiovascular risk (very-high, high and other). The proportion of patients reaching LDL cholesterol target at one-year follow-up was significantly (p<0.001) higher in SPC vs FCT cohort: 35.4% vs 23.8% for very-high cardiovascular risk, 46.9% vs 23.1% for high-risk and 71.6% vs 49.5% for other risk. Total healthcare costs per patient at one-year follow-up were lower in SPC vs FCT users (2,337€ vs 1,890€, p<0.001). In both cohorts, costs were mainly driven by drug expenses and hospitalizations. Conclusions This real-world analysis in dyslipidemic patients found that treatment with ROS/EZE as SPC resulted in better adherence, higher chances of reaching lipid goals and cost savings over FCT, in all cardiovascular risk categories.

Elephantopus scaber Linn. Leaf Extract Sensitizes Doxorubicin in Inducing Apoptosis in HSC-3 Tongue Cancer Cells through Inhibiting Survivin Activity at Thr34

BACKGROUND: Previous research has demonstrated the effect of Elephantopus scaber Linn. leaf extract (ESLE) on various cancer cell lines. However, research on the effects of ESLE on oral squamous cell carcinoma (OSCC), especially tongue cancer, is still lacking. Moreover, the apoptotic mechanisms induced by ESLE are not well understood and require further exploration. Therefore, this study was conducted to investigate the effects of ESLE on cell viability and apoptosis in human squamous cell carcinoma (HSC)-3 tongue cancer cells.METHODS: HSC-3 cells were treated with varying concentrations of ESLE, doxorubicin, and a combination of both. Cell viability and apoptosis were assessed using MTT and Sub-G1 assays. The expression levels of survivin and its phosphorylated form at threonine (Thr)34 were evaluated using Western blot analysis.RESULTS: ESLE exhibited a concentration-dependent cytotoxic effect on HSC-3 cells in decreasing cell viability (Kruskal Wallis, p=0.001) and increasing apoptotic cells (ANOVA, p=0.001) significantly. When combined with doxorubicin, ESLE further enhanced the induction of apoptosis compared with doxorubicin alone. The combined treatment resulted in a decrease in the levels of phosphorylated survivin (p-Surv) Thr34, indicating the inhibition of survivin's anti-apoptotic function.CONCLUSION: ESLE significantly enhances the efficacy of doxorubicin, thereby sensitizing its ability to induce apoptosis in HSC-3 tongue cancer cells. This sensitization occurs through the inhibition of survivin activity, particularly at the Thr34 phosphorylation site. These findings suggest that ESLE could serve as a potential adjuvant to improve the effectiveness of doxorubicin in inducing apoptosis in tongue cancer cells.KEYWORDS: Elephantopus scaber, doxorubicin, tongue cancer, HSC-3 cells, apoptosis, Survivin, Thr34 phosphorylation

Mesenchymal stem cell therapy for liver fibrosis need "partner": Results based on a meta-analysis of preclinical studies.

The efficacy of mesenchymal stem cells (MSCs) in treating liver fibrosis has been demonstrated in several clinical studies. However, their low survival and liver implantation rates remain problematic. In recent years, a large number of studies in animal models of liver fibrosis have shown that MSCs combined with drugs can improve the efficacy of MSCs in the treatment of liver fibrosis alone and inhibit its progression to end-stage liver disease. This has inspired new ways of thinking about treating liver fibrosis. To investigate the effectiveness and mechanisms of MSCs combined with drugs in treating liver fibrosis. Data sources included four electronic databases and were constructed until January 2024. The subjects, interventions, comparators, outcomes, and study design principle were used to screen the literature, and the quality of the literature was evaluated to assess the risk of bias. Relevant randomised controlled trials were selected, and the final 13 studies were included in the final study. A total of 13 studies were included after screening. Pooled analysis showed that MSCs combined with drug therapy significantly improved liver function, promoted the repair of damaged liver tissues, reduced the level of liver fibrosis-related indexes, and effectively ameliorated hepatic fibrosis by modulating the hepatic inflammatory microenvironment, promoting the homing of MSCs, and regulating the relevant signaling pathways, and the treatment efficacy was superior to MSCs alone. However, the combined treatment statistics showed no ame-lioration in serum albumin levels (standardized mean difference = 0.77, 95% confidence interval: -0.13 to 1.68, P = 0.09). In conclusion, MSCs combined with drugs for treating liver fibrosis effectively make up for the shortcomings of MSCs in their therapeutic effects. However, due to the different drugs, the treatment mechanism and effect also differ. Therefore, more randomized controlled trials are needed to compare the therapeutic efficacy of different drugs in combination with MSCs, aiming to select the "best companion" of MSCs in treating hepatic fibrosis.

Long-term outcomes of LT4/LT3 combination treatment for persistent hypothyroid symptoms

Long-term outcomes of LT4/LT3 combination treatment for persistent hypothyroid symptoms

Quality Test of Hybrid Corn Seeds Based on the Position of the Seeds on the Cob with a Comparison of the Parental Ratios that Have Been Applied with Trichoderma sp.

Seeds are a means of production whose quality must be guaranteed and maintained. The seed production, quality testing is an important part. This research aims to determine the effect of seed position on the cob, ratio comparison, and application of Trichoderma sp. on the quality of hybrid corn seeds. This research was carried out in BALITSEREAL, Maros Regency from September to October 2018. This research used a 3-factor factorial design method with a Completely Randomized Basic Design with each treatment combination consisting of 3 replications. The results showed that the position of the base seed had an effect on PK 11.63cm, JAS 4.51. The position of the middle seed has an effect on BKKN 12.31g, DHL 8.19 (cm-2). A ratio of 1:2 has an effect on a JAS of 4.47. A ratio of 1:3 has an effect on a PAP of 16.84cm. Trichoderma sp. 108 has an effect on DHL 9.56 (cm-2). The interaction of the position of the middle seed with a ratio of 1:2 has an effect on BKKN 12.85g. The interaction of base seed position with a ratio of 1:2 has an effect on JAS 4.77. The interaction of base seed position with a ratio of 1:3 had an effect on DB of 99.33%. The interaction between middle seed position and Trichoderma sp. 104 has an effect on BKKN 12.89g. The interaction between seed base position and Trichoderma sp. 104 had an effect on JAS 4.83, PK 12.29cm. The interaction ratio of 1:3 with Trichoderma sp. 10 4 has an effect on BKKN 12.39g. The interaction ratio of 1:3 with Trichoderma sp.10 8 has an effect on PK 11.82cm. The interaction ratio of 1:2 with Trichoderma sp.10 8 has an effect on JAS I4.86, DHL 8.97 (cm-2). Interaction of seed base position, ratio 1:2 and Trichoderma sp. 108 has an effect on JAS 5.60. The interaction of base seed position, ratio 1:3 and Trichoderma sp.10 8 has an effect on PK 13.15cm. Interaction of middle seed position, ratio 1:3 and Trichoderma sp. 10 4 has an effect on BKKN 13.80g on the quality of hybrid corn seeds.

Improved survival of patients with stage III small-cell lung cancer with primary resection: A SEER-based analysis

Introduction: Small cell lung cancer (SCLC) is mostly diagnosed in stage III-IV patients and associated with poor prognosis. To date, surgery is no gold-standard treatment for any SCLC stage and evidence is lacking whether it is beneficial. Here we investigate the impact of surgery, with special attention to stage III SCLC patients, sub-stages and treatment combinations. Methods: The overall survival (OS) and cancer-specific survival (CSS) of 33,198 SCLC patients (SEER database) were analyzed retrospectively, using various statistical analyses, including propensity score matching (PSM), recursive partitioning, and sequential landmark analyses. Results: Independent of stage, the OS of patients with surgery-including treatments was almost always better than without surgery. This holds true for stage I-II patients, even after PMS analysis (p < 0.017). The same was found for stage IV patients that underwent surgery plus chemotherapy vs. chemotherapy alone (p = 0.013 after PSM). Stage III patients showed a robust improvement in OS and CSS after surgery (OS: 18 vs.13 months) or surgery plus chemotherapy (OS: 20 vs.15 months) as confirmed by well-balanced PSM and sequential landmark analyses of long-term survivors. More detailed analyses using two independent approaches showed prolonged OS in T3–4/N0–1 and T1–2/N2 stage III patients after surgery or surgery plus chemotherapy. Importantly, primary site surgery had a major survival advantage over surgery at regional sites (p < 0.003). Conclusion: Our study demonstrates that selected patients of all stages, including stage III T3–4/N0–1 and T1–2/N2, can benefit greatly from surgery-including treatments. Thus, surgery should be included into hospital treatment recommendations for specifically selected SCLC patients.Condensed abstractPrimary resection in patients with stage III SCLC needs re-evaluation. Selected patients with stage III SCLC benefit significantly from surgery. Patients with T3–4/N0–1 and T1–2/N2 stage III SCLC should be considered for surgery.

Differential regulation of xylem and phloem differentiation in grape berries by GA3 and CPPU

Fruit vascular bundles play a critical role in transporting water and nutrients within fruit, ultimately impacting fruit size and quality. Gibberellic acid (GA) and the synthetic cytokinin forchlorfenuron (CPPU) are commonly used to enhance grape berry size. Understanding their effects on the structure and function of berry vascular bundles could provide new information on the regulatory mechanism of these hormones on grapevine expansion and quality. In this study, the fruitlets of ‘Pinot Noir’ and ‘Einset Seedless’ grape varieties were treated by GA3, CPPU, and a combination of both at two weeks after full bloom. The samples were collected at 20, 40 and 70 days post-treatment. The results showed that all treatments led to an increase in berry size, xylem area, phloem area, the relative abundance of large-diameter grade vessels (>6 μm), the corresponding xylem area-specific hydraulic conductivity, and water absorption in both grape varieties. Specifically, CPPU favored an increase in phloem area, while GA3 primarily increased the xylem area. The combined application had a strong effect on both xylem and phloem area. RNA-seq analysis revealed that all treatments induced variations in the expression levels of multiple hormone signal components and genes related to vascular development. GA3 treatment mainly influenced some specific transcription factors involved in xylem differentiation, while CPPU and the combination treatment induced a wide range of genes related to vascular cambium initiation, proliferation, and differentiation of phloem and xylem vessels. Overall, our findings suggest that GA3 played a significant role in xylem differentiation, whereas CPPU had a major impact on both phloem and xylem differentiation in grape berries. These results lay the groundwork for further research the precise regulation of fruit vascular development under GA3 and CPPU treatments.

Soy proteins modified using cavitation jet technology

Soy proteins are seen as a promising alternative food source for meat with environmentally friendly properties. The problem is that the functional properties of soy proteins do not meet the needs of the food industry, and some existing modification technologies have adverse effects. Recently, cavitation jet technology (CJT) has been studied because it generates high heat, high pressure, strong shear and strong shock waves. This review summarizes the history and mechanism of cavitation jets. The energy generated during the cavitation jet process can open molecular structures, and the shock waves and microjets generated can pulverize the materials by erosion. The impact of the CJT on the morphology, structure, and functionality of soy proteins is discussed. The impact of combining CJT with other techniques on the production of soy proteins was also reviewed. The modification of proteins using two or more methods with complementary strengths, avoiding the disadvantages of certain techniques, makes the modification of proteins more effective. One of the most prominent effects is the combined treatment of cavitation jets with physical techniques. Finally, the review provides a comprehensive analysis of the application of modified soy proteins in the food industry and highlights promising avenues for future research.

Preliminary treatment of landfill leachate by hydrodynamic cavitation supported by Fenton process

Hydrodynamic cavitation as an effective and environmentally friendly method of treating wastewater. Massive amounts of energy may be released into the surrounding liquid during hydrodynamic cavitation, resulting in mechanical , chemical and thermal impacts. Bacteria and organic materials in sewage can be broken down by these circumstances. Furthermore, a coupling effect may be created by combining hydrodynamic cavitation with other water treatment techniques. In this study it is aim to investigate and improve the hydrodynamic cavitation (HDC) process supported by Fenton process for the pretreatment of landfill leachate. In the second phase of the study, the effectiveness of the hydrodynamic cavitation process was investigated in conjunction with the Fenton process. The parameters such as the number of cavitation events, pH, and temperature were evaluated. The effluent was characterized and monitored for COD measurements. The consequences of operational variables such H2O2, Fe+2 , and pH values were investigated to determine the optimal Fenton oxidation process parameters. The findings of the experiment showed that pH values were ideal for Fenton oxidation of 3.5-4.5, 30 mM H2O2, and 5 mM Fe+2. A combined treatment process of Fe+2+H2O2, HDC + Fenton, and Cavitation alone were conducted for the treatment of landfill leachate. The results showed that the removal rates of chemical oxygen demand (COD) for the combined processes were 32.85%, 44.28%, and 7%, respectively. Temperature, pH, and the number of cavitation events were among the parameters that were assessed. The effluent was measured for COD and was characterized.

Factors associated with the long-term use of benzodiazepine receptor agonists as hypnotics among patients with major depressive disorder and comorbid insomnia

BackgroundPatients with major depressive disorder (MDD) and comorbid insomnia are often co-prescribed benzodiazepines (BZDs) or Z-drugs as hypnotics with antidepressants to manage persistent insomnia. However, factors associated with their long-term use remain unclear among MDD patients. MethodsWe retrospectively analyzed data from 351 MDD patients who started antidepressants with co-prescribed hypnotics (BZDs/Z-drugs) and investigated the prevalence of and factors associated with their long-term use at 12 months. We conducted logistic regression analyses of their long-term use, and compared insomnia severities between the continued and discontinued groups of hypnotics in 32 patients whose insomnia severities had been longitudinally assessed. Results66.1% of patients had continued hypnotics for 12 months. Multiple logistic regression analysis revealed that the diazepam-equivalent dose of hypnotics at the start of the combined treatment (>5 mg), the presence of chronic insomnia prior to MDD, and hospitalization correlated with their long-term use (all p < 0.01). We also found the relationship between the insufficient amelioration of insomnia severities and their long-term use. However, confidence in these results is tempered by various factors, including the dependence on hypnotics, the patient's attitude about hypnotic treatment, and the exclusion of subjects treated with other drugs such as sedative antidepressants or antipsychotics. ConclusionsThese clinical indicators may facilitate the selection of treatment strategies for MDD with comorbid insomnia. To avoid the long-term use of hypnotics, their dose at the start of the combined treatment needs to be adequate (≤5 mg) and alternative treatments to BZDs/Z-drugs are required for refractory insomnia.

MEST promotes immune escape in gastric cancer by downregulating MHCI expression via SHP2

BackgroundImmune escape is a major obstacle to T-cell-based immunotherapy for cancers such as gastric cancer (GC). Mesoderm-specific transcript (MEST) is a tumor-promoting factor that regulates multiple oncogenic signaling pathways. However, the role of MEST-mediated immune escape is unclear. MethodsBioinformatics analysis of MEST expression and enrichment pathways were performed Quantitative reverse transcription PCR (qPCR) or western blot was used to detect the expression of MEST, Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2), Major histocompatibility class I (MHCI)-related genes. Cell function was assessed by Cell Counting Kit (CCK)-8, Transwell, Lactate dehydrogenase (LDH) kit, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry (IHC). Xenograft nude mice and immune-reconstructed mice were used to test the effects of different treatments on tumor growth and immune escape in vivo. ResultsMEST was upregulated in GC and promoted tumor proliferation, migration, and invasion. Rescue experiments revealed that TNO155 treatment or knockdown of SHP2 promoted the killing ability of CD8+ T cells and the expression of granzyme B (GZMB) and interferon-gamma (IFN-γ), and MEST overexpression reversed the effect. In vivo experiments confirmed that MEST promoted tumor growth, knockdown of MEST inhibited immune escape in GC, and that combination treatment with anti-PD-1 improved anti-tumor activity. ConclusionIn this study, we demonstrated that MEST inhibited IFN-γ secretion from CD8+ T cells by up-regulating SHP2, thereby downregulating MHCI expression in GC cells to promote immune escape and providing a new T cell-based therapeutic potential for GC.