Combined Application Research Articles

Enhanced bacteriostatic effects of phage vB_C4 and cell wall-targeting antibiotic combinations against drug-resistant Aeromonas veronii.

Aeromonas veronii is a vital zoonotic pathogen known for its extensive drug resistance and ability to form biofilms, which contribute to its antibiotic resistance. In this study, the phage vB_C4, specifically targeting A. veronii, was isolated and subjected to bioinformatic analysis and bacteriostatic activity assays. The combination of phage vB_C4 with antibiotics such as cephalothin and cefoxitin, which target the bacterial cell wall, resulted in a significantly enhanced bacteriostatic effect compared to either the phage or antibiotics alone. Furthermore, the phage dosage was critical in optimizing the antimicrobial effect when used in conjunction with antibiotics. This combined treatment exhibited a more distinct effect in removing mature biofilms and inhibiting biofilm formation, leading to a considerable decrease in bacterial density within the biofilm. Overall, the synergistic use of phage and antibiotics offers a novel attitude for treating pathogenic bacteria and holds significant potential in preventing the emergence of drug-resistant strains.IMPORTANCEThe combined application of phages and antibiotics not only effectively inhibits the emergence of phage-resistant bacteria but also reduces the required effective concentration of antibiotics. Additionally, this combination therapy demonstrates significant therapeutic effects on clinical infections mediated by biofilms. Consequently, this study establishes a basis for evaluating the parameters essential for utilizing phage-antibiotic combination therapy in the treatment of biofilm-associated infections, thereby offering a novel selection for the clinical management of multidrug-resistant bacterial infections.

Kill two birds with one stone: Biochar immobilised polydopamine coated compound bacterial agent for remediation of dibutyl phthalate contaminated soil.

The severe contamination of the plasticiser dibutyl phthalate (DBP) in agriculture soils is often accompanied by a decrease in nutrient utilisation. Though the combined application of a variety of microorganisms can simultaneously address the problems of soil contamination and nutrient deprivation, the activity and function of microorganisms can be severely inhibited by DBP, and studies on their protection under DBP contamination are almost non-existent. In this study, a compound bacterial agent KPSB was prepared by optimising with Fe3O4-modified biochar loaded with DBP-degrading bacterium Enterobacterium sp. DNB-S2 and polydopamine (PDA)-coated potassium-solubilizing bacterium Paenibacillus sp. KT. The results showed that KPSB was able to simultaneously remove DBP and increase the soil available potassium (K) content. PDA has good biocompatibility and shielding effect, and the strain KT coated by it has more complete cell membrane and stronger ability to secrete low molecular weight organic acids to promote K solubilisation. The Fe3O4-modified biochar with suitable pore structure, large specific surface area and abundant functional groups could provide a good growth microenvironment for functional microorganisms and support the growth of strains while promoting the degradation of DBP. The expression of DBP-degradation-related genes was significantly increased in KPSB, which promoted the removal of DBP. In addition, KPSB has good acid and alkali resistance and a wide range of temperature adaptability, and is able to remove DBP and increase the available K content better under different environmental conditions. These results will provide new perspectives for the research of in situ soil remediation technology.

The Application of Building Information Modeling in Large Scale Railway Integrated Transportation Hubs

In recent years, as the traditional construction industry has been upgraded, smart construction has emerged as a new direction for its development, and there has been a gradual increase in global attention to related technologies. BIM, as a bridge for the transformation and upgrading of the construction industry, and an indispensable tool in the construction process, its importance is self-evident. This article elaborates on the application of BIM in the constructing-scale railway comprehensive hubs from two aspects: basic application and combined application with related technologies (GIS, AI) through a literature review and case analysis. Regarding basic applications, BIM mainly participates in construction from four aspects: design, construction, maintenance, and management. In terms of combined applications, BIM primarily concentrates on integrating its advantages with other technologies, compensating for its shortcomings, and aiming to double its impact. In the future, BIM will increasingly focus on research that combines applications such as BIM+Internet of Things, BIM+green building, etc., providing technical support for future research in the smart construction industry related to BIM

Strategic Selenium Application Methods and Timing Enhance Grain Yield, Minimize Cadmium Bioaccumulation, and Optimize Selenium Fortification in Triticum aestivum L.

Based on previous research, we hypothesized that an SeVI and SeMet combined application at different growth stages could increase the yield and Se concentration and decrease Cd concentration in wheat grains. To verify this hypothesis, we designed a pot experiment throughout the wheat growth period and investigated the effects of SeIV, SeVI, and SeMet applied individually or in combination at different growth stages on yield traits; Cd absorption and transport; and Se content under Cd stress. The results indicated that grain yield was the highest under the SeVI individual application treatment and the SeVI (at the seedling, jointing, and heading stages) and SeMet (at the filling stage) combined application treatment (3 + 1 treatment), showing a more than 42% increase compared with the Cd-only control treatment (CK). Under the 5 mg/kg Cd stress, the grain Cd content in the 3 + 1 treatment was 34.1% lower than that in CK and over 14.1% lower than those in Se individual treatments. Furthermore, grain Se content was the highest under the 3 + 1 treatment, being 160.8%, 99.7%, and 39.5% higher than those in the SeIV, SeVI, and SeMet individual treatments under 5 mg/kg Cd stress. This may be attributed to early SeVI application in the 3 + 1 treatment, which enhanced yield traits and effectively promoted the retention of Cd in the middle and lower organs, reducing its transport to the grains. Furthermore, the SeMet application enhanced Se translocation to the grains, further reducing Cd content and increasing the Se concentration. In conclusion, the combined application of SeVI (at the seedling, jointing, and heading stages) and SeMet (at the filling stage) helped achieve the desired outcomes of high grain yield, low Cd content, and Se enrichment under Cd stress.

Optimizing Sustainable Community Spatial Layouts and Public Service Facility Accessibility: A GIS and Machine Learning Approach

This paper discusses the integration of Geographic Information Systems (GIS) and machine learning (ML) to enhance community performance based on sustainable urban planning by optimising community layouts and providing better access to public services. GIS is a technology that provides spatial data on the land use and the risks, which can support urban planners to understand the existing urban settlement. On the other hand, ML can predict the future needs of the public services such as transport, education and health care, which can help the planners to allocate the resources. The combined application of GIS and ML can assist urban planners to create resilient, climate-adaptive and socially equitable communities, and can also address the rapid urbanisation issues that can efficiently meet the future community demands. It is a framework that can enhance the accessibility to the public service and develops a socially equitable, environmentally sustainable and optimised community wellbeing, which can provide an all-sided strategy for the city facing the climatic change and demographic change.

Agonists Targeting the cGAS-STING Signaling Pathway and Their Applications in Cancer Therapy

The cyclic GMP-AMP synthase (cGAS) serves as a pivotal component of the immune system, playing a crucial role in regulating the innate immune response elicited by both exogenous and endogenous DNA. This enzyme recognizes the aberrant presence of DNA in the cytoplasm, subsequently activating the signaling pathway mediated by the stimulator of interferon genes (STING) and thereby fulfilling a critical role in immune response mechanisms. This review delineates the mechanisms of the cGAS-STING pathway and elucidates the small-molecule agonists targeting STING, along with their combined applications in various tumor treatment strategies. The aim of this review is to provide a valuable reference framework and insights for ongoing research in related fields.

Mixed radiation with different doses induces CCL17 to recruit CD8+T cell to exert anti-tumor effects in non-small cell lung cancer

BackgroundDifferent doses of radiotherapy (RT) exert diverse effects on tumor immunity, although the precise irradiation method remains unknown. This study sought to elucidate the influence of combining different doses of RT with immune checkpoint inhibitors (ICIs) on the infiltration of CD8+T cells within tumors, thereby augmenting the anti-tumor response.MethodsConstructing a mouse model featuring bilateral lung cancer tumors subjected to high and low dose irradiation, the analysis of RNA transcriptome sequencing data and immunohistochemical validation for tumors exposed to various dosages guided the selection of the optimal low-dose irradiation scheme. Subsequently, upon the integration of immune checkpoint inhibitors (ICIs) therapy, the infiltration of immune cells within the tumor was ascertained via immunohistochemistry (IHC) and flow cytometry (FCM). Finally, through bioinformatics analysis and experimental verification, potential strategies to bolster the anti-tumor immune response were investigated.ResultsIn comparison to the administration of 20Gy alone to the primary tumor, supplementing with 6Gy directed at the abscopal tumor produces a more pronounced abscopal response. The synergy of 20Gy, 6Gy, and ICIs markedly boosts the efficiency of ICIs. According to the findings from IHC and FCM studies, the triple therapy group exhibits a heightened infiltration of immune cells into the tumor, largely attributable to the augmented expression of CCL17 within the tumor under these irradiation regimens, which subsequently draws CD8+ T cells to infiltrate the tumor site, exerting cytotoxic effects.ConclusionOur study shows that the combined application of 20Gy and 6Gy can enhance the infiltration of tumor CD8+T cells in mice and improve the effectiveness of immunotherapy.

A Peptide Nanoregulator Enriched at the Endoplasmic Reticulum for Boosting Fractionated Radiotherapy‐Mediated Antitumor Immune Response

AbstractFractionated radiotherapy (FRT), typically delivering low‐dose radiation of 2 Gy per fraction, has been used as the main clinical treatment regimen for various tumors. However, its therapeutic efficacy is severely hindered by inadequate pro‐immunogenic effect and ionizing radiation‐induced immunosuppression. Herein, a peptide nanoregulator (SPER‐NO‐Ind) is constructed from self‐assembling peptides that can enrich nitric oxide (NO) at the endoplasmic reticulum (ER) and inhibit indoleamine 2,3‐dioxygenase (IDO) to enhance FRT‐mediated antitumor immunity and reinforce treatment outcomes. SPER‐NO‐Ind triggered S‐nitrosylation of the ryanodine receptor by ER‐specific enrichment of NO, triggering the release of Ca2+ within ER and induction of robust ER stress. The combination of 2 Gy γ‐radiation with SPER‐NO‐Ind induced intense immunogenic cell death (ICD) in ER‐stressed 4T1 cells. Furthermore, this nanoregulator inhibited IDO and decreased kynurenine production, reversing FRT‐induced immunosuppressive effects. The combined application of FRT and SPER‐NO‐Ind demonstrated superior efficacy in suppressing breast tumor growth, amplifying abscopal effects, and inhibiting metastasis in mice. The SPER‐NO‐Ind treatment achieved a 40% decrease in the total radiation dose while securing equivalent tumor suppression efficacy. Collectively, the work presents a facile approach to augment the efficacy of fractionated radiotherapy for tumors, opening up a new way to enhance the antitumor immune response of radiotherapy.

Seed pretreatment with cloquintocet-mexyl protects wheat seedlings from fomesafen injury by promoting photosynthesis and decreasing oxidative stress.

Fomesafen is a selective herbicide widely used to control post-emergent broad-leaf weeds in soybean and peanut fields. Because of its persistent nature in soil, it can suppress subsequent crops, including wheat. There is limited information focusing on methods of protecting wheat from fomesafen injury by soil residue. Bioassay results showed slight variations in tolerance to fomesafen among 31 wheat cultivars. Soil-applied biochar (200 g m-2) could alleviate fomesafen injury at 2 mg L-1, and partially alleviate fomesafen injury at 4 mg L-1. Seed soaking in safeners cloquintocet-mexyl and mefenpyr-diethyl was more effective in protecting seedlings from fomesafen injury at 4 mg L-1 compared with 1,8-naphthalic anhydride, fenclorim or dichlormid. Indoor tests suggested that the combined application of biochar and cloquintocet-mexyl or mefenpyr-diethyl had a synergistic alleviating effect on wheat injury caused by fomesafen, which was further confirmed in a field trial. Wheat seeds treated with cloquintocet-mexyl increased expression of the fomesafen target protoporphyrinogen IX oxidase and light-harvesting chlorophyll a/b binding protein, leading to an increase in chlorophyll content and a decrease in oxidative stress of wheat exposed to fomesafen. Cloquintocet-mexyl treatment had no influence on the expression of P450 genes, toxic transport genes, most glutathione S-transferase (GST) genes, the enzyme activity of P450 or GSTs, and the metabolism rate of fomesafen. These results suggested that cloquintocet-mexyl acted by increasing photosynthesis and decreasing oxidative stress to alleviate injury to wheat exposed to fomesafen stress, showing no influence on fomesafen metabolism in wheat. This study provided valuable information for fomesafen injury management in wheat. © 2025 Society of Chemical Industry.

Exploring interactive effect of nitrogen and zinc for enhancing cotton productivity in arid climate

Nutrients imbalance particularly nitrogen (N) and zinc (Zn) is a major constraint for sustainable cotton production. Thus, we hypothesized that the combined application of N and Zn may increase N and Zn availability and enhance cotton productivity due to the synergistic effect between these nutrients. Therefore, the present field study was carried out for two consecutive years to explore the interactive effects of different N rates (N0 = 0, N1 = 120, N2 = 160, and N3 = 200 kg ha−1) and Zn rates (Zn0 = 0, Zn1 = 5 and Zn2 = 10 kg ha−1) on soil available N and Zn, and growth and yield traits of the cotton crop. The results indicated a linear increase in the soil available N and Zn and all the studied traits of the cotton crop with the progressive increase in N and Zn rates until 160 kg ha−1 N and 10 kg ha−1 Zn. The cotton crop showed the maximum seed cotton yield (3337–3368 kg ha−1) and total dry matter (9916–9988 kg ha−1) with the simultaneous application of 160 kg ha−1 N and 10 kg ha−1 Zn, which was attributed to higher growth, morphophysiological and yield traits in this treatment during both years. The findings of the study suggest that the application of 160 kg ha−1 N in combination with 10 kg ha−1 Zn is the best fertilizer management for increasing N and Zn availability and achieving higher seed cotton yield of cotton crop.

Clinical Practice Guidelines for Topical NSAIDs in the Treatment of Sports Injuries.

Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat sports injuries, but evidence-based medical guidance for their standardized and rational use is lacking. This guideline working group identified clinically important issues, obtained the full opinions of patients and clinical staff, and discussed them with the expert group. Based on evidence from the literature, the "clinical practice guidelines for topical NSAIDs in the treatment of sports injuries" were formulated following the methods and principles of international guidelines. According to these guidelines, 7 clinical concerns were ultimately selected, and 22 recommendations were formed. These included the status, indications, contraindications, efficacy, combined application, use in special populations, adverse reactions, and countermeasures of topical NSAIDs in the treatment of sports injuries. The purpose of these guidelines is to provide evidence-based recommendations for practitioners in the fields of orthopedics, sports medicine, rehabilitation medicine, and sports science, as well as other fields, in the treatment of sports injuries to promote more standardized and rational use of topical NSAIDs.

BIOMETRIC INDICATORS AND POTATO YIELD FOR GROWING IN SHORT-ROTATION CROP ROTATIONS AND MONOCULTURE

Objective. Establishing the growth, development, and yield formation characteristics of potatoes in short-rotation crop rotations and continuous monoculture, as well as developing measures to reduce the negative impact of crop saturation in crop rotations. Methods – general scientific and specialized: field stationary experiment; measurement weight method; laboratory field; statistical mathematical. Results. The article presents the results of research on the peculiarities of crop growth, development and formation in crop rotations and monocultures, depending on their saturation with culture, fertilizer and the use of planting material of various categories. The research established that potato plants formed the largest vegetative mass during the flowering phase. The fertilization system significantly affected the growth of the tops. It was noted that the maximum leaf area was achieved during the flowering phase, ranging from 19,600 to 36,100 m²/ha, influenced by weather conditions. No significant impact of crop rotation saturation with potatoes on the formation of the photosynthetic apparatus was found. It was determined that the photosynthesis net productivity (PNP) of potatoes increased with plant growth, reaching a peak during the budding – flowering period at 3.7–5.0 g/m² per day, affected by weather conditions. As the degree of crop rotation saturation with potatoes increased, yield decreased. On average, over the years of research, the yield was 22.8 t/ha with 20% potato saturation in crop rotation, 20.8 t/ha with 50% saturation, and the lowest yield of 18.4 t/ha with 100% saturation. Yield in monoculture was significantly affected by the combined application of organic and mineral fertilizers and annual replacement of seed material. Conclusions. The highest photosynthesis net productivity (3.7–5.0 g/m² per day) was observed during the budding and flowering stages, but later, as natural leaf dieback began, it decreased to 1.4–1.7 g/m² per day. The research also shows that with increasing potato saturation in crop rotation, yield gradually decreased: at 20% saturation, the yield was 22.8 t/ha, at 50% saturation – 20.8 t/ha, and at 100% saturation – 18.4 t/ha. The application of organic fertilizers in two-field crop rotations did not lead to significant yield changes (16.9–20.8 t/ha). However, the highest yield (23.6 t/ha) was achieved in monoculture with the application of 40 t/ha of manure and mineral fertilizers (N90P60K90), as well as the annual replacement of seed material. These results are important for optimizing agrotechnical practices and improving potato yield.

Inhibition of macrophage polarization and pyroptosis in collagen-induced arthritis through MSC-exo and ginsenoside Rh2

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, tissue damage, and fibrosis, significantly affecting the quality of life. While there are currently some effective treatments available, they often come with side effects. There is an urgent need to find new treatments that can further improve therapeutic outcomes and reduce side effects.MethodsOur study investigates the role of Mesenchymal Stem Cell exosomes (MSC-exo) combined with Ginsenoside Rh2 (Rh2) in the treatment of RA. We specifically focus on how this combined strategy influences macrophage polarization and pyroptosis. This research utilized a collagen-induced rat arthritis model.ResultsThe study findings reveal that the combination of MSC-exo combined with Rh2 can inhibit the polarization of M1 macrophages, increase the proportion of M2-like macrophages, and suppress M1-like macrophage pyroptosis via the NLRP3/Caspase11/GSDMD-N pathway. In the rat arthritis model, the combination of MSC-exo and Rh2 showed synergistic therapeutic effects.ConclusionThis research contributes to a deeper understanding of RA’s pathogenesis and presents new potential targeted therapeutic interventions. The combined application of MSC-exo and Rh2 offers promising insights for future innovative strategies in RA treatment, paving the way for more effective management of this autoimmune disease.

Effect of pelvic floor muscle training combined with electrical stimulation therapy on stress urinary incontinence: a Meta-analysis.

Introduction SUI is a common pelvic floor dysfunction in middle-aged and elderly women, which has a serious negative impact on the patient's quality of Life (QoL), pelvic floor muscle training (PFMT) and electrical stimulation (ES), as common non-surgical treatment modalities, have been widely used in the management of SUI. However, there is controversy about the effectiveness of the combined application of these two interventions. For this reason, this study evaluated the efficacy of PFMT combined with ES in the treatment of SUI by Meta-analysis. To systematically evaluate the efficacy of PFMT combined with ES in improving urinary incontinence symptoms, increasing pelvic floor muscle strength, enhancing QoL, and improving clinical symptoms, with the aim of providing more adequate evidence to support clinical treatment. Methods A literature search was conducted in PubMed, Embase, Web of Science, and Cochrane Library databases from database construction to October 2024 to include RCTs and case-control studies evaluating PFMT combined with ES for the treatment of SUI. The Cochrane Risk Assessment Tool and NOS were used to assess the quality of the included literature, and effect sizes were calculated by random-effects model and fixed-effects model, and the main outcome indicators included incontinence symptoms, pelvic floor muscle strength, QoL and clinical symptoms. Results Eight studies were ultimately included, with a total sample size of 885 cases. Meta-analysis showed that PFMT combined with ES was significantly better than the control group on all outcome measures. The combined effect size for improvement in urinary incontinence symptoms was OR = 1.42 (95% CI: 1.10, 1.85, P < 0.05), that for pelvic floor muscle strength was OR = 1.55 (95% CI: 1.20, 2.05, P < 0.01), that for QoL improvement was OR = 4.29 (95% CI: 3.68, 4.99, P < 0.0001), and the combined effect size for clinical symptom improvement was OR = 1.35 (95% CI: 1.05, 1.70, P < 0.05). Heterogeneity between studies was low (I² values were less than 40%), indicating a high degree of consistency in the effect of the combination treatment. Conclusion PFMT combined with ES showed significant benefits in improving incontinence symptoms, enhancing pelvic floor muscle strength, boosting QoL and improving clinical symptoms. Future studies should further standardize the intervention parameters and extend the follow-up period to fully assess the long-term effects of the combined treatment.

Efficacy and Safety of Specific Immunotherapy Combined with Biologics in Allergic Rhinitis and Asthma: A Systematic Review and Network Meta-Analysis.

Allergic diseases are common clinical diseases. Although allergen-specific immunotherapy (AIT) and biologics have been widely recognized, the clinical efficacy, safety, advantages and disadvantages of the combined application have not yet been sufficiently recognized. We aimed to investigate the efficacy and safety of AIT combined with biologics in patients with allergic rhinitis and asthma. PubMed, EMBASE, the Cochrane Library, and Web of Science were systematically searched to identify RCTs investigating AIT combined with biologics for treating allergic rhinitis and asthma. The relevant outcome indicators, including incidences of emergency drugs use, severe nasal symptoms, severe adverse effects (AEs), local reactions at the site of administration, headache, and general AEs, were collected and extracted. Routine and network meta-analyses were conducted using RevMan-5.4 and STATA-MP-14 to assess efficacy and safety. Eight RCTs and a retrospective study involving 1494 patients aged 5 to 65 years with allergic rhinitis and asthma were included in this review. ① Routine meta-analysis revealed that AIT combined with biologics was significantly better than control treatment (placebo, AIT or biologics) in terms of the incidence of emergency drugs use, severe nasal symptoms, and severe AEs (P=0.0002; P=0.01; P=0.02). However, the differences in the incidence of local reactions at the site of administration, headache and general AEs were not significant. ② In the network meta-analysis, compared with AIT or placebo alone, AIT combined with biologics observably reduced the incidence of emergency drugs use and severe nasal symptoms (OR=0.32, 95% CI 0.14-0.73; OR=0.41, 95% CI 0.26-0.63). Furthermore, AIT combined with biologics yielded an evidently lower incidence of serious adverse reactions than AIT alone (OR=0.42, 95% CI 0.23-0.74). The combined application of AIT and biologics has promising prospects in the clinical treatment of allergic rhinitis and asthma due to the improvement of both clinical efficacy and safety. SYSTEMATIC REVIEW REGISTRATION (PROSPERO #CRD42024496277).

ANALYSIS OF THE USE OF NON-RECEPTION ANTI-FEVER MEDICINES IN CHILDREN

The aim of the work was to analyze the use of over-the-counter antipyretic drugs in young children. Methods and materials. Marketing, analytical, comparative analysis and generalization of information were chosen as research methods. The study of the analysis of the needs of fever patients in the improvement of pharmaceutical care was conducted based on three pharmacies of the Podorozhnyk pharmacy chain, which were in the city of Ivano-Frankivsk. We conducted sociological research using questionnaires. The survey was conducted from October 1 to 31, 2023. To ensure representativeness, according to the calculations, 50 respondents (visitors of pharmacies) were involved in the survey, who approached the pharmacy employee with the aim of purchasing an antipyretic drug for a younger child. The results of the analysis were processed using computer programs. The results. As of November 2023, the market of Ukraine is dominated by Ukrainian-made medical devices (66.7%). Among the dosage forms, tablets prevail - a total of 41 names and capsules (36 names), the least oral solutions and solutions for injections - 1 name each. Taking into account that the greater number of drugs refers to over-the-counter drugs, an important aspect of responsible self-medication by the patient and pharmaceutical care by the pharmacist is the clinical and pharmaceutical characteristics of the medicinal product in view of the API or its combination, its dose, dosage form, possibility and features application in separate groups of patients, in particular children, was the study and analysis of instructions for the medical use of drugs regarding the possibility of taking these drugs in children. According to the analysis of the instructions for pharmaceuticals, it was found that 28% of drugs are allowed for use in children from birth to 1 year, from 1 year - 2.29%, from 3 years - 0.7%, from 5 years - 6.8%, from 6 years - 35.6%, from 10 years - 0.7%, from 12 years - 12.9%, more than 7 kg - 4.6%, more than 20 kg - 3.1%, more than 33 kg - 3.79%, as prescribed by a doctor taking into account the benefits/risks - 1.5%. To ensure representativeness, according to the calculations, 50 visitors to the pharmacy (representatives of the child) who came to the pharmacy to purchase an antipyretic drug for the treatment of a child's fever were involved in the survey. Conclusions. The conducted clinical and pharmaceutical analysis showed that the treatment of hyperthermia in children must be approached very carefully, because the assortment of over-the-counter drugs in Ukraine is large, there is a synonymy of the names of drugs of individual companies, which contain different compositions of active substances of different concentrations, which are indicated for use in individual groups of patients. Considering that many pharmaceuticals are over the counter, an important aspect is the responsible attitude of the pharmaceutical worker to inform and warn the buyer of the pharmacy, as well as responsible self-medication on the part of the patient. The effectiveness of antipyretic therapy will be higher when the pediatrician works together with the child's parents to improve medical literacy. From an ethical and deontological point of view, only close contact between the pediatrician and the patients' parents will allow to effectively eliminate febrile syndrome and prevent its dangerous and sometimes fatal consequences.

SMAC mimetic BV6 acts in synergy with mTOR inhibitor to increase cisplatin sensitivity in ovarian cancer.

The objective of this study is to observe the antitumor efficacy of the second mitochondria-derived activator of caspases (SMAC) mimetic bivalent smac mimetic (BV6) in combination with target of rapamycin (mTOR) inhibitor on DDP (cisplatin) sensitivity. Ovarian cancer cells were exposed to cisplatin, BV6, DDP + BV6, and DDP + BV6 + mTOR inhibitor Rapamycin. Using proteomics and bioinformatics, protein expression profiles in ovarian cancer were determined. Bagg Albino color nude mice were treated with DDP or BV6 alone or in combination, or BV6 + DDP + Rapamycin. The effects of different treatments on ovarian cancer cells and tumor growth were evaluated in vivo and in vitro . Proteomics and bioinformatics analysis revealed significant changes of protein kinase (AKT)/mTOR pathway. Consistently, western blot data indicated that AKT/mTOR axis was gradually activated in BV6-treated ovarian cancer cells and attenuated the cytotoxic effect of BV6. Functional assays showed that DDP or BV6 treatment alone significantly enhanced the sensitivity and inhibited the migration of ovarian cancer cells, but without any synergistic effects. In addition, combination with BV6 and mTOR inhibitor Rapamycin significantly decreased cell viability and inhibited migration of ovarian cancer cells exposed to DDP. Consistently, the xenograft model showed that co-treatment with Rapamycin with BV6 had significantly suppressed tumor growth and metastasis. Our study demonstrated that SMAC analogue BV6 exhibits a strong anticancer effect on ovarian cancer in vitro and in vivo . Combination with Rapamycin overcomes the activation of mTOR pathway by BV6 and increases the chemosensitivity to DDP. These data suggest a potential application of triple combination with DDP + BV6 + Rapamycin in clinical management of ovarian cancer.

New insights into autochthonous fungal bioaugmentation mechanisms for recalcitrant petroleum hydrocarbon components using stable isotope probing.

Autochthonous fungal bioaugmentation (AFB) is a promising strategy for the microbial remediation of petroleum hydrocarbon (PH)-contaminated soils. However, the mechanisms underlying AFB, particularly for degrading recalcitrant PH components, are not fully understood. This study employed stable isotope probing (SIP) and high-throughput sequencing to investigate the AFB mechanisms of two hydrocarbon-degrading fungi, Fusarium solani LJD-11 and Aspergillus fumigatus LJD-29, focusing on three challenging PH components: n-Hexadecane (n-Hex), Benzo[a]pyrene (BaP), and Dibenzothiophene (DBT). Our findings indicate that both fungal strains significantly enhanced pollutant removal rates, with combined application yielding optimal results. AFB treatment reduced the microbial diversity index and altered the soil microbial community, especially affecting fungal populations. A significant correlation between the microbial diversity index and degradation efficiency suggests that greater diversity enhances pollutant removal. SIP analysis showed that LJD-11 and LJD-29 could directly assimilate n-Hex and DBT, but not BaP. Correlation analyses between functional microorganisms and other biological indicators suggest that the removal of pollutants is also attributable to indigenous functional bacteria. Additionally, non-inoculated functional fungi present in the soil play a crucial role in BaP degradation. These findings reveal distinct degradation pathways for the three pollutants. The addition of carrier substrate reduced the complexity of the network, while AFB treatment restored it. In addition, the combined fungal treatment resulted in higher network parameters, leading to a more complex and stable network structure. These results provide insights into the mechanisms of AFB for degrading recalcitrant PH components, underscoring its potential for in situ bioremediation of petroleum-contaminated soils.

Stability and bifurcation analysis of simply supported rectangular nanoplate embedded on visco-Pasternak foundation based on first-order shear deformation theory

Vibrations of simply supported nanoplates embedded on visco-Pasternak foundation and stressed by in-plane periodic forces are investigated. The governing size-dependent equations employ the first-order shear deformation theory, nonlinear von Kármán strains, and the nonlocal elasticity theory. Reducing the governing system is carried out by the Bubnov-Galerkin method, which is based on two-mode model, thus the resulting system contains two ordinary differential equations with size- and time-dependent coefficients. Analysing the linearized system, the stability of the nanoplate structure is studied depending on the foundation parameters, force parameters and small-scale parameter. Nonlinear dynamics approaches are employed to determine the nature of vibration after the loss of stability. Time history, Poincare section, Lyapunov exponent are analysed for chosen values of excitation parameters, visco-Pasternak foundation parameters to indicate small-scale effects and nonlinear effects. The novelty of the work consists of the combined application of the nonlocal theory, first-order shear deformation theory, Floquet theory, methods of nonlinear dynamics and obtaining new results by a numerical experiment.

Moving Toward Metaproteogenomics: A Computational Perspective on Analyzing Microbial Samples via Proteogenomics.

Microbial sample analysis has received growing attention within the last decade, driven by important findings in microbiome research and promising applications in the biotechnological field. Modern mass spectrometry-based methodology has been established in this context, providing sufficient sensitivity, resolution, dynamic range, and throughput to analyze the so-called metaproteome of complex microbial mixtures from clinical or environmental samples. While proteomic analyses were previously restricted to common model organisms, next-generation sequencing technologies nowadays allow for the rapid and cost-efficient characterization of whole metagenomes of microbial consortia and specific genomes from non-model organisms to which microbes contribute by significant amounts. This proteogenomic approach, meaning the combined application of genomic and proteomic methods, enables researchers to create a protein database that presents a tailored blueprint of the microbial sample under investigation. This contribution provides an overview of the computational challenges and opportunities in proteogenomics and metaproteomics as of January 2018. For practical application, we first showcase an integrative proteogenomic method that circumvents existing reference databases by creating sample-specific transcripts. The underlying algorithm uses a graph network approach that combines RNA-Seq and peptide information. As a second example, we provide a tutorial for a simulation tool that estimates the computational limits of detecting microbial non-model organisms. This method evaluates the potential influence of error-tolerant searches and proteogenomic approaches on databases of interest. Finally, we discuss recommendations for developing future strategies that may help overcome present limitations by combining the strengths of genome- and proteome-based methods and moving toward an integrated metaproteogenomics approach.