Combined Treatment Research Articles

The rate of change in clinical indicators can predict the progression of hepatitis B virus-related acute-on-chronic preliver failure.

The objective of this study was to investigate the predictors and predictive model construction of the progression of HBV-Pre.Acute-on-chronic liver failure (ACLF), a total of 133 patients with HBV-Pre.ACLF was divided into the progressive group (52 patients) and the recovery group (81 patients) according to whether they progressed to ACLF or not. The clinical parameters N%, L%, PLT, ALT, TBiL, ALB, Cre, Na, NH3, CRP, AFP, prothrombin time (PT), international normalized ratio (INR), FIB, and their rate of change at baseline were analyzed in the 2 groups. The independent risk factors for HBV-Pre.ACLF progression was found by univariate and multivariate analyses, and a predictive model was constructed. The clinical parameters ALB, FIB, Na, combined alprostadil treatment and MELD, and MELD-Na scores at baseline were significantly different between the 2 groups (P <.05), while ALT, TBiL, Cre, CHE, NH3, N%, L%, PLT, INR, and PT were not significantly different (P >.05). The change rates of Na, CHE, PT, FIB, CRP, Cre, PLT, and the ratio after to before of N% were significantly different between the 2 groups (P <.05), while the change rates of ALT, TBIL, NH3, AFP, L%, and the ratio after to before of INR were not significantly different between the 2 groups (P >.05). Univariate and multivariate analyses showed that baseline ALB, Na, FIB, combined alprostadil therapy and the rate of change of Na and PLT were protective factors for disease progression, and the rate of change of PT, CRP, and the ratio after to before of N% were independent risk factors for disease progression. The novel model was LogitP = -6.051 + 4.049×ΔPT + 0.626×ΔCRP + 4.527×the ratio after to before N% and its area under the curve was 0.944 (95% confidence interval: 0.900-0.988) predicting progression of HBV-Pre.ACLF, and the best cutoff value was -0.22. The patients with a higher logitP score (> -0.22) had an increased risk for progression to ACLF (P <.05). The novel model logitP shows good predictive value for the disease progression of HBV-Pre.ACLF.

Novel Porous Starch Granules Fabricated Using Controlled Lipase-Amylase Treatments: Application as Delivery Systems and Resistant Starches.

Porous starch granules (PSGs) are promising biomaterials for the encapsulation, protection, and delivery of bioactive ingredients. In this study, a lipase treatment was first used to generate pores in native starch granules, and then α-amylase was used to enlarge these pores. Electron and fluorescence microscopy analysis showed that the lipase treatment exposed the starch molecules located below the lipid-rich regions on the starch granule surfaces, which increased the swelling of the granules in aqueous solutions. Moreover, lipase treatment caused the surrounding areas to become more loosely packed, which facilitated subsequent starch hydrolysis and the formation of large internal cavities. Fourier transform infrared spectroscopy, X-ray diffraction, and thermogravimetric analyses provided further insights, these methods showed that the short-range order, long-range order, and thermal stability of the PSGs was enhanced by the sequential lipase-amylase modification. PSGs were highly resistant to amylase digestion and had strong adsorption capacity to hydrophobic and hydrophilic substances. This study shows that a combined lipase-amylase treatment can be used to fabricate PSGs, which may have health benefits due to their low digestibility and ability to encapsulate bioactive agents. These PSGs may therefore be suitable for application in the functional food, supplement, personal care, and pharmaceutical industries.

The Wolf Spider Tigrosa helluo Uses Visual Associative and Beacon Landmarks During Water Maze Navigation Tasks

ABSTRACTWolf spiders can learn simple spatial navigation tasks. Previous studies have shown that the wolf spider Tigrosa helluo can use environmental edge features (reference frame landmarks) to learn the location of a dry target in flooded T‐mazes; however, the relative importance of different types or numbers of landmark cues to spatial learning remains unknown. We used a modified open arena water maze and recorded the ability of adult female T. helluo to find a target reward (a dark and dry cup) among cups that were identical to the target but flooded. We measured variation in spatial learning by measuring time to target with no landmark (control), with a beacon (a landmark that is part of the target), with an associative cue (a landmark associated with a specific navigational action), and with both a beacon and an associative cue (N = 92 subjects, n = 23 per landmark cue treatment). For each treatment, we tested females for five trials each on four consecutive days, with the last trial on the fourth day having an altered target location, totaling 19 training trials and one reversal trial (1840 trials). We found that spiders took significantly less time to find the target over subsequent trials within a day and learned more quickly when landmark cues were present, but we found no difference in the type or number of landmark features in the meantime to target entrance. After learning a target location, moving the landmark significantly increased the mean time to target entrance in the combined beacon and associative cue treatment relative to other treatments. Our results indicate that wolf spiders use visual beacons and associative cue landmarks alone or in combination and that performance improves across trials when landmarks are present and deteriorates more when multiple landmarks are moved.

Synergizing Bacillus halotolerans, Pseudomonas sihuiensis and Bacillus atrophaeus with folic acid for enhanced drought resistance in wheat by metabolites and antioxidants

Drought stress imposes a serious challenge to cultivate wheat, restricting its growth. Drought reduces the capability of plant to uptake essential nutrients. This causes stunted growth, development and yield. Traditional ways to increase wheat growth under drought stress have shortcomings. Using plant-growth-promoting rhizobacteria (PGPR) has proved feasible and eco-friendly way to enhance wheat growth even under the drought stress. Combining PGPR in consortiums further boosts up their effects. In this study, we have checked the efficacy of drought-tolerant Bacillus halotolerans, Pseudomonas sihuiensis and Bacillus atrophaeus in combination. These strains were allowed to grow on PEG 6000 with concentrations (-0.15, -0.49, -0.73 and − 1.2) Mega Pascal (MPa) alone and in combination. Furthermore, Fourier transmission infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) were used. Their biochemical traits such as solubilization of K, P and Zn and the synthesis of siderophore, indole acetic acid (IAA), protease, amylase, hydrogen cyanide (HCN) and 1-aminocyclopropane-1-carboxylate (ACC) deaminase were done. In addition to this, we investigated the optimum folic acid concentration i.e 150 ppm for wheat against drought stress. We conducted a pot experiment to check the growth-enhancing and drought-mitigating effects of consortium and folic acid alone and in combination. As a result, we found a significantly increased wheat biomass, relative water content (RWC), chlorophyll content, antioxidants including glutathione reductase and total soluble sugars and protein content under all treatments. However, the combined treatment of bacterial consortium and folic acid showed maximum potential to boost wheat growth and survival even under drought. We also investigated the minerals uptake by wheat after the treatments and found maximum nutrient uptake under the co-effect of folic acid and bacterial consortium We believe this is the first study that has investigated the optimal dose of folic acid for wheat. Our research is also novel in that we seek to investigate the effects of folic acid along with a bacterial consortium comprising Bacillus halotolerans, Pseudomonas sihuiensis and Bacillus atrophaeus on wheat grown under the drought stress.

Effect of ultrahigh frequency ozone therapy on oxidative metabolism in the blood of rats with ischemic skin flaps: A preclinical experimental randomized study

Background. Maintaining and restoring skin microcirculation in surgical flaps, as well as accelerating rehabilitation after skin flap transplantation, in order to mitigate the consequences of burns and injuries, remain a pressing issue. In addition to various timings and techniques for plastic surgery, physiotherapeutic approaches prove to be efficient and include low-intensity electromagnetic radiation in millimeter waves as their prominent techniques. In recent years, experts have paid an increasing attention to the application of low-intensity electromagnetic radiation across different frequency ranges for the enhancement of microcirculation in patients after surgical correction of burn consequences. However, this approach is yet to be further validated. Objective. To investigate the effect of different combinations of ultrahigh frequency electromagnetic radiation with ozone therapy on the oxidative metabolism of blood in rats using a model of ischemic skin flaps. Methods. A preclinical experimental randomized study was conducted on 100 adult male Wistar rats weighing between 200 and 250 grams. Five equal-sized groups of animals were formed in the study: Group 1: intact (no interventions), and Groups 2, 3, 4, and 5: after surgical intervention (modeling of ischemic skin flaps). Animals in Group 2 (control group) received no therapeutic procedures. Rats in Groups 3 and 5 underwent a 10-minute course of electromagnetic radiation exposure with a dose of 0.06 mJ for seven days. Animals in Group 3 were exposed to electromagnetic radiation of ultrahigh frequency with a range of 53–78 GHz. Animals in Group 4 received injections of ozonized saline solution (with a saturating ozone concentration in the ozonized oxygen mixture of 3000 µg/L) daily for 7 days, administered intraperitoneally at a volume of 1 mL. Group 5 underwent a combined treatment: daily exposure to ultrahigh frequency electromagnetic radiation along with intraperitoneal ozone therapy (the application modalities of these treatments were similar to those used in Groups 3 and 4, respectively). The intensity of lipid peroxidation, peroxide resistance in erythrocytes, and overall antioxidant system activity were assessed in order to investigate the balance of pro- and antioxidant systems in plasma and erythrocytes. Additionally, the study involved determination of the level of malondialdehyde content and evaluation of the activity of superoxide dismutase and catalase in erythrocytes. The obtained date were analyzed, using MS Office 2013 (Microsoft Corporation, USA) and Statistica 10 (StatSoft, USA). Results. The conducted analysis revealed an antioxidant effect from ultrahigh frequency electromagnetic radiation, with this effect being enhanced by ozone therapy. In addition, the study detected the inhibition of free radical oxidation under the ultrahigh frequency electromagnetic radiation and ozone therapy. Conclusion. Thus, the positive effects of the studied therapeutic factors manifest at the systemic level, as evidenced by the optimization of biochemical parameters and indicators of oxidative metabolism in the plasma of animal blood. It has been established that ultrahigh frequency electromagnetic radiation, administered in a noise mode, exerts a regulatory effect on pro- and antioxidant systems in the body, as demonstrated in a model of transplanted skin flap. This intervention leads to a reduction in the severity of oxidative stress and an enhancement of antioxidant reserves in the blood. The observed effect is further amplified with the additional application of ozone therapy.

Enhancing Proton Radiosensitivity of Chondrosarcoma Using Nanoparticle-Based Drug Delivery Approaches: A Comparative Study of High- and Low-Energy Protons

To overcome chondrosarcoma’s (CHS) high chemo- and radioresistance, we used polyethylene glycol-encapsulated iron oxide nanoparticles (IONPs) for the controlled delivery of the chemotherapeutic doxorubicin (IONPDOX) to amplify the cytotoxicity of proton radiation therapy. Human 2D CHS SW1353 cells were treated with protons (linear energy transfer (LET): 1.6 and 12.6 keV/µm) with and without IONPDOX. Cell survival was assayed using a clonogenic test, and genotoxicity was tested through the formation of micronuclei (MN) and γH2AX foci, respectively. Morphology together with spectral fingerprints of nuclei were measured using enhanced dark-field microscopy (EDFM) assembled with a hyperspectral imaging (HI) module and an axial scanning fluorescence module, as well as scanning electron microscopy (SEM) coupled with energy-dispersive X-Ray spectroscopy (EDX). Cell survival was also determined in 3D SW3153 spheroids following treatment with low-LET protons with/without the IONPDOX compound. IONPDOX increased radiosensitivity following proton irradiation at both LETs in correlation with DNA damage expressed as MN or γH2AX. The IONPDOX–low-LET proton combination caused a more lethal effect compared to IONPDOX–high-LET protons. CHS cell biological alterations were reflected by the modifications in the hyperspectral images and spectral profiles, emphasizing new possible spectroscopic markers of cancer therapy effects. Our findings show that the proposed treatment combination has the potential to improve the management of CHS.

Exploring the effect of fertilizer application on yield and decoding CO2 flux under flooded paddy conditions towards sustainable agriculture

The impact of organic and inorganic nutrient management on the emission of carbon dioxide (CO2), soil properties such as available nutrients, microbial population and soil organic carbon (SOC) were investigated in paddy (Oryza sativa L.) field (at 8o 46’ N Latitude and 77o 42?’ E Longitude) under flooded condition during late pishanam season in 2023-2024. The treatments were designed to observe the effects of applying fertilizer based on the soil test crop response (100 % STCR-based NPK) that had been modified by organic amendments, which include absolute control (unfertilized), inorganic fertilizers, sole application of organic amendments (Farm yard manure, Green leaf manure, Vermicompost and Poultry manure) and combined these organic amendments with inorganic fertilizers. The main objective of this study is to understand the intricate relationship between fertilizers and carbon flux in paddy soils, which is crucial for developing sustainable agricultural practices that minimize environmental harm while ensuring food security. The observation of the experimental field study reported that the combined application of poultry manure at the rate of 5 tonnes per hectare with 100% STCR-based inorganic fertilizer recorded maximum yield and yield attributes. The treatment combination of poultry manure + inorganic fertilizer enhanced in sequestrating the soil organic carbon (0.67%) resulted in higher grain yield (5972 kg ha-1) and also observed that this combination will limit the emission of CO2 to the atmosphere. Therefore, it could be a better choice for carbon storage and higher productivity in a sustainable rice cropping system.

Mifepristone and misoprostol versus misoprostol alone for induction of labor in women with intrauterine fetal death: Ameta-analysis and systematic review.

Misoprostol is largely used in labor induction in cases of intrauterine fetal death. However, recent randomized clinical trials (RCTs) showed that the combination of mifepristone and misoprostol might have better effects than the use of misoprostol alone. To compare mifepristone and misoprostol lines of treatment. Pubmed, Embase, Cochrane and Web of Science databases were systematically searched until April 9, 2024. The eligibility criteria were (1) RCT, (2) comparing misoprostol alone versus the combined treatment, (3) patients undergoing labor induction due to intrauterine fetal death and (4) reporting at least one relevant outcome. Data were examined using the Mantel-Haenszel method and 95% CIs. Heterogeneity was assessed using I2 statics. R, version 4.2.3 was used for statistical analysis. The analyzed outcomes were delivery time interval, adverse effects (fever, vomiting, diarrhea and nausea) and the preinduction Bishop score. Other important outcomes, such as uterus rupture, could not be included due to lack of data from the included studies. A total of seven RCTs comprising 599 patients with intrauterine fetal death were randomized to misoprostol or combined treatment to induce labor. Compared to the misoprostol only group, combined treatment presented lower delivery time interval (MD -6.86 h; 95% CI: -10.32 to -3.4; P = 0.0001; I2 = 87%). However, in terms of adverse effects, the combined treatment group presented lower occurrence of fever (2.25% vs 12.12%; RR 0.26; 95% CI: 0.09-0.74; P = 0.01; I2 = 0%) and vomiting (7.64% vs 14.45%; RR 0.54; 95% CI: 0.29-1.01; P = 0.05; I2 = 0%). No statistically significant differences were observed when comparing the preinduction Bishop score of the two groups (MD -0.09; 95% CI: -0.28-0.10; P = 0.35; I2 = 0%). Additionally, the mean of the preinduction Bishop score of the combined treatment was 2 versus 2.1 of the control group. In this updated meta-analysis, consistent results suggest that the combined treatment is associated with more beneficial outcomes than the misoprostol alone treatment in patients undergoing labor induction in intrauterine fetal death.

Antiviral combination treatment strategies for SARS-CoV-2 infection in immunocompromised patients.

The purpose of this review is to report the available evidence regarding the use of combination regimens of antivirals and/or antibody-based therapy in the treatment of SARS-CoV-2 in immunocompromised patients. Literature search identified 24 articles, excluding single case reports, which included mainly patients with hematological malignancies and/or B-cell depletion. Data were divided based on the timing and reason for administration of combination treatment, that is, early treatment to prevent progression to severe COVID-19 and treatment of prolonged or relapsed infection. We described the treated populations, treatment duration and composition of combination treatment. We briefly addressed new treatment options and we proposed an algorithm for the management of COVID-19 infection in patients affected by hematological malignancies. Combination treatment seems an effective (73-100%) and well tolerated (<5% reported bradycardia, hepatotoxicity, neutropenia) strategy for treating prolonged/relapsed SARS-CoV-2 infections in the immunocompromised host, although its optimal composition and duration cannot be defined based on the currently available evidence. The role of combination treatment as an early treatment strategy for immunocompromised patients at a high risk of progression to severe disease/persistent shedding requires further evidence from comparison with monotherapy, even though high efficacy was reported for combinations of antivirals plus mAbs in case of previous viral variants.

Abietic acid antagonizes the anti-inflammatory effects of celecoxib and ketoprofen: Preclinical assessment and molecular dynamic simulations

The present work is designed to explore the anti-inflammatory properties of AA and its modulatory effects on celecoxib (CEL) and ketoprofen (KET) through in vitro, ex vivo, in vivo, and in silico approaches. Different concentrations of AA were utilized to evaluate the membrane-stabilizing potential via egg albumin and the Human Red Blood Cell (HRBC) denaturation model. In the animal model, formalin (50 μL) was injected into the right hind paw of young chicks to induce inflammation. AA was administered at 20 and 40 mg/kg (p.o.) to the experimental animals. We used CEL and KET as positive controls. The vehicle was provided as a control group. Two combinations of AA with CEL and KET were also investigated in all tests to assess the modulatory activity of AA. In addition, in silico investigation was used for predictions about drug-likeness, pharmacokinetics, and toxicity of the selected chemical compounds, and the study also evaluated the binding affinity, visualization, and stability of ligand-receptor interactions through molecular dynamic (MD) simulation. Results manifested that AA concentration-dependently significantly inhibited the egg albumin denaturation (IC50: 27.53 ± 0.88 μg/ml) and breakdown of HRBC (IC50: 15.69 ± 0.75 μg/ml), indicating the membrane stabilizing potential compared to the control group. AA also significantly (p < 0.05) lessened the frequency of licking and alleviated the paw edema in a dose-dependent manner in an in vivo test. However, AA reduced the activity of CEL and KET in combination treatment. AA showed good pharmacokinetic characteristics to be considered as a therapeutic candidate. Additionally, the in silico study displayed that AA demonstrated a relatively higher docking score of −9.1 kcal/mol with the cyclooxygenase-2 (COX-2) enzyme and stable binding in MD simulation. Whereas the standard ligand (CEL) expressed the highest binding value of −9.2 kcal/mol to the COX-2.

Inhibition of PIM kinase in tumor associated macrophages suppresses inflammasome activation and sensitizes prostate cancer to immunotherapy.

Immunotherapy has changed the treatment paradigm for many types of cancer, but immune checkpoint inhibitors (ICIs) have not shown benefit in prostate cancer (PCa). Chronic inflammation contributes to the immunosuppressive prostate tumor microenvironment (TME) and is associated with poor response to ICIs. The primary source of inflammatory cytokine production is the inflammasome. Here, we identify PIM kinases as important regulators of inflammasome activation in tumor associated macrophages (TAMs). Analysis of clinical data from a cohort of treatment naïve, hormone responsive PCa patients revealed that tumors from patients with high PIM1/2/3 display an immunosuppressive TME characterized by high inflammation (IL-1β and TNFα) and a high density of repressive immune cells, most notably TAMs. Strikingly, macrophage-specific knockout of PIM reduced tumor growth in syngeneic models of prostate cancer. Transcriptional analyses indicate that eliminating PIM from macrophages enhanced the adaptive immune response and increased cytotoxic immune cells. Combined treatment with PIM inhibitors and ICIs synergistically reduced tumor growth. Immune profiling revealed that PIM inhibitors sensitized PCa tumors to ICIs by increasing tumor suppressive TAMs and increasing the activation of cytotoxic T cells. Collectively, our data implicate macrophage PIM as a driver of inflammation that limits the potency of ICIs and provides preclinical evidence that PIM inhibitors are an effective strategy to improve the efficacy of immunotherapy in prostate cancer.

Biomimetic Modification of siRNA/Chemo Drug Nanoassemblies for Targeted Combination Therapy in Breast Cancer.

The development and progression of tumors are characterized by intricate biological processes. Monotherapy not only struggles to achieve effective treatment but also tends to precipitate a series of issues, including multidrug resistance and limited antitumor effect. Consequently, it is imperative to adopt a synergistic multitherapy approach to enhance the efficacy of tumor treatment. The integration of chemotherapy drug with oligonucleotide drug for combinational treatment has shown significant promise in improving tumor therapeutic efficiency. However, the effective in vivo codelivery of oligonucleotide drugs and chemotherapy drugs faces substantial challenges such as poor stability of oligonucleotide drugs during the circulation time, limited tumor accumulation, and uncertain delivery ratios of different payloads. To overcome these obstacles, we have engineered cyclic Arg-Gly-Asp (cRGD)-modified red blood cell membrane (RBCm)-coated multidrug nanocomplexes, which were self-assembled from the Polo-like kinase 1 siRNA (siPlk1) and an irreversible tyrosine kinase inhibitor neratinib targeted to human epidermal growth factor receptor 2 (HER2) overexpressed in breast cancer. Through electrostatic and amphiphilic interactions between the positively charged neratinib and negatively charged siPlk1, we have successfully fabricated uniform multidrug nanoparticles. The cRGD-modified red blood cell membranes coated on the surface of the multidrug nanoparticles could enhance drug stability in circulation and tumor accumulation. This targeted combinational therapy significantly enhanced the antitumor efficiency in HER2-positive breast cancer in vitro and in vivo.

Inactivation of Escherichia coli O157:H7 in tomato juice by combined treatment of ethanolic clove extract and mild heat

The combination of plant extracts with mild heat treatment is a promising strategy for obtaining microbiologically and chemically safe food products. In this study, we evaluated the antimicrobial activity of ethanolic clove extract against Escherichia coli O157: H7 in nutrient broth, buffer, and tomato juice. Clove extract at 0.4% concentration showed significant E. coli O157: H7 population reduction in all media tested. E. coli O157: H7 was most sensitive to the ethanolic clove extract in nutrient-deficient media but demonstrated relative resistance in nutrient-rich media and tomato juice. Moreover, we evaluated the potential of clove extract as a preservative in tomato juice stored at cold storage temperatures of 4 °C and 15 °C. The clove extract exhibited stronger inhibitory effects against the pathogen in tomato juice stored at 15 °C than at 4 °C. Additionally, we assessed the antimicrobial efficacy of clove extract in combination with mild heat treatment against E. coli O157: H7 in tomato juice. The combined treatment of 0.05% clove extract with mild heat at 60 °C for 30 min achieved a 5-log reduction in the E. coli population in tomato juice. Our findings present a potential hurdle technology against E. coli O157: H7 in tomato juice processing by employing a combination of naturally sourced antimicrobial agents from clove and mild heat treatment. This approach can be effectively adopted by large-scale industries and small-scale local juice vendors to ensure the safety of tomato juice products.

Inhibition of Chk1 with Prexasertib Enhances the Anticancer Activity of Ciclopirox in Non-Small Cell Lung Cancer Cells

Lung cancer is a leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) is the most prevalent lung cancer subtype. Ciclopirox olamine (CPX), an off-patent fungicide, has been identified as a new anticancer agent. Prexasertib (PRE), a Chk1 inhibitor, is in phase 1/2 clinical trials in various tumors. The anticancer effect of the combination of CPX with PRE on NSCLC cells is unknown. Here, we show that CPX is synergistic with PRE in inhibiting cell proliferation and inducing apoptosis of NSCLC (A549 and A427) cells. Combined treatment with CPX and PRE significantly increased the cell population in the G1/G0 and sub-G1 phases, compared to the single treatment with CPX or PRE. Concurrently, the combined treatment downregulated the protein levels of cyclins (A, B1), cyclin-dependent kinases 4, 6, 2 (CDK4, CDK6, CDK2), cell division cycle 25 B, C (Cdc25B, Cdc25C), and upregulated the protein levels of the CDK inhibitors p21 and p27, leading to decreased phosphorylation of Rb. In addition, the combined treatment increased DNA damage, evidenced by increased expression of γH2AX. In line with this, the combined treatment induced more apoptosis than either single treatment. This was associated with increased expression of DR4, DR5, Fas, and FADD and decreased expression of survivin, resulting in activation of caspase 8 and caspase 3 as well as cleavage of poly (ADP ribose) polymerase (PARP). Taken together, the results suggest that inhibition of Chk1 with PRE can enhance the anticancer activity of CPX at least partly by decreasing cell proliferation and increasing apoptosis in NSCLC cells.

Astragaloside IV augments anti-PD-1 therapy to suppress tumor growth in lung cancer by remodeling the tumor microenvironment.

Programmed cell death protein-1 (PD-1) inhibitors are increasingly utilized in the treatment of lung cancer (LC). Combination therapy has recently gained popularity in treating LC. This study aimed to assess the efficacy of combining Astragaloside IV (AS-IV) and anti-PD-1 in LC. C57BL/6J mice were subcutaneously injected with Lewis lung carcinoma (LLC) cells. After 3 weeks, the animals were sacrificed, and the tumors were harvested for analysis. Ki-67 immuno-labeling and TUNEL assay were used for evaluating cell proliferation and apoptosis in tumor tissues. In addition, anti-cleaved caspase 3 was used for immunolabelling of apoptotic cells. Immune cell infiltration (macrophages and T cells) and gene expression in tumor tissues were also investigated by using immunofluorescence staining. Compared to treatment with anti-PD-1 or AS-IV, the combination of AS-IV and anti-PD-1 notably reduced tumor volume and weight of LLC-bearing mice. Additionally, the combination treatment strongly induced the apoptosis and suppressed the proliferation in tumor tissues through inactivating PI3K/Akt and ERK signaling pathways, compared to single treatment group. Moreover, the combination treatment elevated levels of the M1 macrophage marker mCD86, reduced levels of the M2 macrophage marker mCD206, as well as upregulated levels of the T cell activation marker mCD69 in tumor tissues. Collectively, the combination treatment effectively inhibited tumor growth in LLC mice through promoting M1 macrophage polarization and T cell activation. These findings showed that combining AS-IV with anti-PD-1 therapy could be a promising therapeutic approach for LC.

Effects of Different LED Spectra on the Antioxidant Capacity and Nitrogen Metabolism of Chinese Cabbage (Brassica rapa L. ssp. Pekinensis)

Light quality optimization is a cost-effective method for increasing leafy vegetable quality in plant factories. Light-emitting diodes (LEDs) that enable the precise modulation of light quality were used in this study to examine the effects of red-blue (RB), red-blue-green (RBG), red-blue-purple (RBP), and red-blue-far-red (RBF) lights on the growth, antioxidant capacity, and nitrogen metabolism of Chinese cabbage leaves, while white light served as the control (CK). Results showed that the chlorophyll, carotenoid, vitamin C, amino acid, total flavonoid, and antioxidant levels of Chinese cabbage were all significantly increased under RBP combined light treatment. Meanwhile, RBG combined light treatment significantly increased the levels of amino acids but decreased the nitrite content of Chinese cabbage. In addition, RBF combined light treatment remarkably increased the amino acid levels but decreased the antioxidant capacity of Chinese cabbage. In conclusion, the addition of purple light to red-blue light was effective in improving the nutritional value and antioxidant capacity of Chinese cabbage. This light condition can be used as a model for a supplemental lighting strategy for leafy vegetables in plant factory production.

Alum-anchored IL-12 combined with cytotoxic chemotherapy and immune checkpoint blockade enhanced antitumor immune responses in head and neck cancer models

BackgroundFirst-line treatment with pembrolizumab plus chemotherapy in recurrent and metastatic head and neck squamous cell carcinomas (HNSCC) has improved survival. However, the overall response rate with this standard of care...

Simultaneous degradation of pharmaceuticals and personal care products in hospital wastewater using ozone under ultraviolet irradiation

The discharge of Pharmaceuticals and personal care products (PPCPs) from industries and hospitals are responsible for the contamination of water body with slow or non-degradable toxic compounds. The removal of these contaminants required advanced treatment process because of unable to treat by conventional wastewater treatment process. In this study, the degradation of PPCP compounds, including caffeine (CAF), atenolol (ATL), carbamazepine (CBZ), sulfamethoxazole (SMX), trimethoprim (TMP), and acetaminophen (ACT) was evaluated under exposure to 1.0 and 1.5 mg/L dissolved ozone (O3), both with and without ultraviolet (UV) irradiation (254 nm). Using liquid chromatography with tandem mass spectrometry, we determined that the removal efficiency for the targeted contaminants exceeded 95 % within just 20 min of exposure to both 1.0 and 1.5 mg/L O3. However, when treated with UV light alone, the removal efficiency was limited at 3 %–11 %. A combination treatment involving dissolved 1.5 mg/L O3 and UV light led to over 97 % removal within 7 min. This outcome was attributed to hydroxylation reactions, aromatic ring opening, oxidation, and mineralization facilitated by the HO and peroxide generated through the photolysis of O3. The degradation rate of PPCP compounds followed pseudo-first-order kinetics and showed a decrease in the presence of humic acid and hospital wastewater further decreased it. Moreover, O3/UV treatment generated lower-weight degradation products. The toxicity analysis revealed that these transformation products exhibited environmental benignity and minimal health risks which O3/UV treatment potentially minimizes the presence of harmful byproducts. These findings provide a foundation for developing combined hybrid systems for PPCP containing wastewater, containing membrane filtration with ozonation system.

Corrigendum: Transcranial magnetic stimulation and ketamine: implications for combined treatment in depression

Corrigendum: Transcranial magnetic stimulation and ketamine: implications for combined treatment in depression

Synergistic bioremediation of petroleum-contaminated soil using immobilized consortium of Rhodococcus rhodochrous and Bacillus subtilis laccase

Petroleum-contaminated soil represents a significant environmental and public health challenge on a global scale. Microbial bioremediation has shown potential, yet the role of enzymes in enhancing petroleum degradation remains underexplored. In this study, the synergistic effects of Rhodococcus rhodochrous (R.rh) and Bacillus subtilis-derived laccase (BsLac) was investigated in the remediation of petroleum-contaminated soil. Immobilized R.rh (PSIMRH) and BsLac (ADIMLac) exhibited higher petroleum degradation rates than their free state, achieving 78.3% and 56.3% degradation in liquid systems, respectively. The combined treatment of PSIMRH and ADIMLac demonstrated a synergistic effect on petroleum degradation, achieving 43.6% with a maximum degradation constant of 0.0335 d−1, representing a 202.7% improvement over untreated soil. PSIMRH enhanced petroleum degradation through microbial metabolism, while ADIMLac accelerated the initial breakdown of complex hydrocarbons into simpler, more bioavailable ones via enzymatic oxidation, providing growth substrates for microbes and significantly improving petroleum degradation rates. The microbial analysis revealed an increase abundance of known petroleum-degrading bacterial genera, including Rhodococcus, Lysobacter, Micromonospora, and Streptomyces. However, the presence of BsLac appeared to reduce the competitive advantage of Rhodococcus, promoting the proliferation of indigenous strains like Lysobacter and Streptomyces. These results suggest that enzyme-microbe synergy can enhance the bioremediation process by altering microbial community dynamics and accelerating petroleum degradation. This study attempts to remediate petroleum-contaminated pollution with the combined use of strains and enzymes, providing a new approach for the remediation of other pollution problems.