Enhancing microbial superoxide generation and conversion to hydroxyl radicals for enhanced bioremediation using iron-binding ligands.

Harnessing bacteria for superoxide production in bioremediation holds immense promise, yet its practical application is hindered by slow production rates and the relatively weak redox potential of superoxide. This study delves into a cost-effective approach to amplify superoxide production using an Arthrobacter strain, a prevalent soil bacterial genus. Our research reveals that introducing a carbon source along with specific iron-binding ligands, including deferoxamine (DFO), diethylenetriamine pentaacetate (DTPA), citrate, and oxalate, robustly augments microbial superoxide generation. Moreover, our findings suggest that these iron-binding ligands play a pivotal role in converting superoxide into hydroxyl radicals by modulating the electron transfer rate between Fe(III)/Fe(II) and superoxide. Remarkably, among the tested ligands, only DTPA emerges as a potent promoter of this conversion process when complexed with Fe(III). We identify an optimal Fe(III) to DTPA ratio of approximately 1:1 for enhancing hydroxyl radical production within the Arthrobacter culture. This research underscores the efficacy of simultaneously introducing carbon sources and DTPA in facilitating superoxide production and its subsequent conversion to hydroxyl radicals, significantly elevating bioremediation performance. Furthermore, our study reveals that DTPA augments superoxide production in cultures of diverse soils, with various soil microorganisms beyond Arthrobacter identified as contributors to superoxide generation. This emphasizes the universal applicability of DTPA across multiple bacterial genera. In conclusion, our study introduces a promising methodology for enhancing microbial superoxide production and its conversion into hydroxyl radicals. These findings hold substantial implications for the deployment of microbial reactive oxygen species in bioremediation, offering innovative solutions for addressing environmental contamination challenges.

Serum BAFF levels are associated with the prognosis of idiopathic membranous nephropathy.

OBJECTIVE: High serum levels of B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) have been observed in patients with idiopathic membranous nephropathy (iMN); however, their relationships with disease severity and progression remain unclear. METHODS: Patients with iMN diagnosed via renal biopsy were enrolled in this study. The concentrations of BAFF and APRIL were determined using ELISA kits. Proteinuria remission, including complete remission (CR) and partial remission (PR), and renal function deterioration were defined as clinical events. The Cox proportional hazards method was used to analyze the relationship between cytokine levels and disease progression. RESULTS: Seventy iMN patients were enrolled in this study, with a median follow-up time of 24 months (range 6-72 months). The serum levels of BAFF and APRIL were higher in iMN patients than in healthy controls but lower than those in minimal change disease (MCD) patients. The serum BAFF level was positively correlated with the serum APRIL level, serum anti-phospholipase A2 receptor (anti-PLA2R) antibody level, and 24-h proteinuria and negatively correlated with the serum albumin (ALB) level. However, no significant correlation was observed between the serum APRIL level and clinical parameters. According to the multivariate Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure (SBP), estimated glomerular filtration rate (eGFR), immunosuppressive agent use, 24-h proteinuria, APRIL level, and anti-PLA2R antibody, only the serum BAFF level was identified as an independent predictor of PR (HR, 0.613; 95% CI, 0.405-0.927; p = 0.021) and CR of proteinuria (HR, 0.362; 95% CI, 0.202-0.648; p < 0.001). CONCLUSIONS: A high serum BAFF level is associated with severe clinical manifestations and poor disease progression in patients with iMN.

Enhanced Enantioselective Discrimination Regulated by Achiral Ligands in Chiral Metal-Organic Frameworks.

Enantioselective recognition is a fundamental property of chiral linkers in chiral metal-organic frameworks (CMOFs). However, clarifying the efficient enantioselective discrimination tailored by achiral linkers remains challenging to explain the chiral recognition mechanism and efficiency. Here, two CMOFs ([Zn2(l-Phe)2(bpa)2]n and [Zn2(l-Phe)2(bpe)2]n) with the completely different enantioselective recognition are synthesized from different nonchiral ligands and the same chiral ligands. The enantioselective recognition of CMOF is undoubtedly related to l-Phe, which differs in the hydrogen bonding to the Trp enantiomer. However, the electrochemical signals are weak and undifferentiated. [Zn2(l-Phe)2(bpe)2]n produces a flattened coplanar conformation with the -C═C- tether in the achiral ligand. The flattened achiral bpee ligand and its surrounding chiral phenylalanine molecules interact through multiple π-π stacking and hydrogen bonding, which together create a chiral sensor that facilitates the recognition of l-Trp. However, [Zn2(l-Phe)2(bpa)2]n produces a stepped conformation due to the -C-C- tether in the achiral ligand; despite the recognition effect of bpea, the recognition is unsatisfactory. Therefore, the chiral recognition of the two CMOFs stems from the synergistic effect between chiral and achiral ligands. This work shows that nonchiral ligands are also crucial in determining enantiomeric discrimination and opens up a new avenue for designing chiral materials.

Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1.

BACKGROUND: Bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, inhibits angiogenesis and reduces tumor growth. Serum VEGF-C, lactate dehydrogenase, and inflammatory markers have been reported as predictive markers related to bevacizumab treatment. Programmed cell death ligand 1 (PD-L1) could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis. AIM: To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer (CRC) according to the expression of PD-L1. METHODS: This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24, 2014 and February 28, 2022, at Samsung Medical Center (Seoul, South Korea). Analysis of patient data included evaluation of PD-L1 expression by the combined positive score (CPS). We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC. RESULTS: A total of 124 patients was included in this analysis. Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy. While 77% of patients received FOLFOX, 23% received FOLFIRI as backbone first-line chemotherapy. The numbers of patients with a PD-L1 CPS of 1 or more, 5 or more, or 10 or more were 105 (85%), 64 (52%), and 32 (26%), respectively. The results showed no significant difference in progression-free survival (PFS) and overall survival (OS) with bevacizumab treatment between patients with PD-L1 CPS less than 1 and those with PD-L1 CPS of 1 or more (PD-L1 < 1% vs PD-L1 ≥ 1%; PFS: P = 0.93, OS: P = 0.33), between patients with PD-L1 CPS less than 5 and of 5 or more (PD-L1 < 5% vs PD-L1 ≥ 5%; PFS: P = 0.409, OS: P = 0.746), and between patients with PD-L1 CPS less than 10 and of 10 or more (PD-L1 < 10% vs PD-L1 ≥ 10%; PFS: P = 0.529, OS: P = 0.568). CONCLUSION: Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

Synthesis and biological evaluation of novel aminoquinolines with an n-octyl linker: Impact of halogen substituents on C(7) or a terminal amino group on anticholinesterase and BACE1 activity.

Alzheimer's disease is age-related multifactorial neurodegenerative disease manifested by gradual loss of memory, cognitive decline and changes in personality. Due to rapid and continuous growth of its prevalence, the treatment of Alzheimer's disease calls for development of new and efficacies drugs, especially those that could be able to simultaneously act on more than one of possible targets of action. Aminoquinolines have proven to be a highly promising structural scaffold in the design of such a drug as cholinesterases and ß-secretase 1 inhibitors. In this study, we synthesised twenty-two new 4-aminoquinolines with different halogen atom and its position in the terminal N-benzyl group or with a trifluoromethyl or a chlorine as C(7)-substituents on the quinoline moiety. All compounds were evaluated as multi-target-directedligands by determining their inhibition potency towards human acetylcholinesterase, butyrylcholinesterase and ß-secretase 1. All of the tested derivatives were very potent inhibitors of human acetylcholinesterase and butyrylcholinesterase with inhibition constants (Ki) in the nM to low µM range. Most were estimated to be able to cross the blood-brain barrier by passive transport and were nontoxic toward cells that represented the main models of individual organs.

Surface Structure of Lecithin-Capped Cesium Lead Halide Perovskite Nanocrystals Using Solid-State and Dynamic Nuclear Polarization NMR Spectroscopy.

Inorganic colloidal cesium lead halide perovskite nanocrystals (NCs) encapsulated by surface capping ligands exhibit tremendous potential in optoelectronic applications, with their surface structure playing a pivotal role in enhancing their photophysical properties. Soy lecithin, a tightly binding zwitterionic surface-capping ligand, has recently facilitated the high-yield synthesis of stable ultraconcentrated and ultradilute colloids of CsPbX3 NCs, unlocking a myriad of potential device applications. However, the atomic-level understanding of the ligand-terminated surface structure remains uncertain. Herein, we use a versatile solid-state nuclear magnetic resonance (NMR) spectroscopic approach, in combination with dynamic nuclear polarization (DNP) and atomistic molecular dynamics (MD) simulations, to explore the effect of lecithin on the core-to-surface structures of CsPbX3 (X = Cl or Br) perovskites, sized from micron to nanoscale. Surface-selective (cross-polarization, CP) solid-state and DNP NMR (133Cs and 207Pb) methods were used to differentiate the unique surface and core chemical environments, while the head-groups {trimethylammonium [-N(CH3)3+] and phosphate (-PO4-)} of lecithin were assigned via 1H, 13C, and 31P NMR spectroscopy. A direct approach to determining the surface structure by capitalizing on the unique heteronuclear dipolar couplings between the lecithin ligand (1H and 31P) and the surface of the CsPbCl3 NCs (133Cs and 207Pb) is demonstrated. The 1H-133Cs heteronuclear correlation (HETCOR) DNP NMR indicates an abundance of Cs on the NC surface and an intimate proximity of the -N(CH3)3+ groups to the surface and subsurface 133Cs atoms, supported by 1H{133Cs} rotational-echo double-resonance (REDOR) NMR spectroscopy. Moreover, the 1H-31P{207Pb} CP REDOR dephasing curve provides average internuclear distance information that allows assessment of -PO4- groups binding to the subsurface Pb atoms. Atomistic MD simulations of ligand-capped CsPbCl3 surfaces aid in the interpretation of this information and suggest that ligand -N(CH3)3+ and -PO4- head-groups substitute Cs+ and Cl- ions, respectively, at the CsCl-terminated surface of the NCs. These detailed atomistic insights into surface structures can further guide the engineering of various relevant surface-capping zwitterionic ligands for diverse metal halide perovskite NCs.

Insights into the Photochemical Mechanism of Goethite: Roles of Different Types of Surface Hydroxyl Groups in Reactive Oxygen Species Generation and Fe(III) Reduction.

The surface photochemical activity of goethite, which occurs widely in surface soils and sediments, plays a crucial role in the environmental transformation of various pollutants and natural organic matter. This study systemically investigated the mechanism of different types of surface hydroxyl groups on goethite in generating reactive oxygen species (ROSs) and Fe(III) reduction under sunlight irradiation. Surface hydroxyl groups were found to induce photoreductive dissolution of Fe(III) at the goethite-water interface to produce Fe2+(aq), while promoting the production of ROSs. Substitution of the surface hydroxyl groups on goethite by fluoride significantly inhibited the photochemical activity of goethite, demonstrating their important role in photochemical activation of goethite. The results showed that the surface hydroxyl groups (especially the terminating hydroxyl groups, ≡FeOH) led to the formation of Fe(III)-hydroxyl complexes via ligand-metal charge transfer on the goethite surface upon photoexcitation, facilitating the production of Fe2+(aq) and •OH. The bridging hydroxyl groups (≡Fe2OH) were shown to mainly catalyze the production of H2O2, leading to the subsequent light-driven Fenton reaction to produce •OH. These findings provide important insights into the activation of molecular oxygen on the goethite surface driven by sunlight in the environment, and the corresponding degradation of anthropogenic and natural organic compounds caused by the generated ROSs.

Binding characterization of odorant-binding protein BhorOBP29 in Batocera horsfieldi (Hope) with host-plant volatiles.

Odorant binding proteins (OBPs) are involved in odorant discrimination and act as the first filter in the peripheral olfactory system. Previous studies have shown that BhorOBP29 is potentially involved in olfactory perception in an important wood-boring pest Batocera horsfieldi (Hope) (Coleoptera: Cerambycidae), however, its function remains unclear. Here, we investigated the ligand-binding profiles of recombinant BhorOBP29 with 22 compounds from its host plant using fluorescence competitive binding assays and fluorescence quenching assays. The results showed that BhorOBP29 could bind to five ligands relying mainly on hydrophobic interactions. Molecular docking analysis indicated that residues Ile48, Leu51, Met52, Trp57, Asn105, and Val119 were extensively involved in the interactions between BhorOBP29 and the five ligands. Furthermore, the site-directed mutagenesis analysis revealed that Leu51 and Met52 residues were indispensable for BhorOBP29-ligands binding. Finally, electroantennogram (EAG) assays confirmed that hexanal, (-)-limonene, and 2-methylbutyraldehyde elicited a concentration-dependent EAG response with a maximum at the concentration of 1/10 v/v. These findings suggest that BhorOBP29 may play a significant role in the perception of host plant volatiles by B. horsfieldi. This study may help to discover novel behavioral regulation and environmentally friendly strategies for controlling B. horsfieldi in the future.

Strong PD-L1 affect clinical outcomes in advanced NSCLC treated with third-generation EGFR-TKIs.

Background: In first/second generation EGFR-TKIs, strong PD-L1 expression contributes to primary resistance, significantly affecting patient prognosis. The relationship between PD-L1 expression levels and third-generation TKIs remains unclear.Methods: This study analyzed advanced NSCLC who received third-generation EGFR-TKIs as first-line systemic therapy from March 2019 to June 2022. The EGFR and PD-L1 status of the patients was also assessed.Results: Overall, 150 patients were included in this study. PD-L1 expression was negative (PD-L1 tumor proportion score <1%) in 89 cases, weak (1-49%) in 42 cases, and strong (≥50%) in 19 cases. mPFS for patients with negative, weak and strong PD-L1 expressions was 23.60, 26.12 and 16.60 months, respectively. The mPFS for strong PD-L1 expression was significantly shorter than that for with weak PD-L1 expression but was not associated with negativity. The same conclusions were shown in subgroup analyses of mutation types and TKI kinds. In addition, Relative to PD-L1-negative patients, resistance to TKIs may be associated with early progression for patients with strong PD-L1 expression.Conclusion: PD-L1 expression in tumor cells influenced the clinical outcomes of patients with advanced NSCLC treated with third-generation EGFR-TKIs. Stronger PD-L1 expression in TKIs-treated patients with advanced first-line EGFR-mutated NSCLC was associated with worse PFS.

[Box: see text].

Selective Detection of Chromate and Permanganate Ions Using Gallic Acid Capped CaF2:Tb3+ Nanocrystals.

In this study, we have developed ligand-sensitized Ln3+-doped nanocrystals (NCs) for the selective sensing of Cr2O72- and MnO4- ions in nanomolar concentrations. This is accomplished with the gallic acid capped-CaF2:Tb3+ NCs. These NCs display bright green emission through an efficient energy transfer from surface functionalized gallic acid molecules to Tb3+ ions upon UV light excitation. The luminescence emissions from Tb3+ ions are selectively quenched by the addition of Cr2O72- and MnO4- anions. The reduction in the luminescence intensity is found to be quite selective, as the addition of other strong oxidizing species (I-, F-, Br-, Cl-, PO32-, SO42-, VO3-, WO42-, IO3-, ClO4-,) had minimal impact on the luminescence intensity of Tb3+ ions. The calculated limit of detection from the experimental results (for the 3/slope criterion) is 77 nM and 55 nM for K2Cr2O7 and KMnO4, respectively. The findings show that tuning the resonance energy transfer (RET) between analytes and Tb3+ inside the NCs serves as a tool for the detection of dichromate and permanganate ions selectively.

Quinoline yellow acts as a novel amyloid fibrillation probe by using surface-enhanced Raman spectroscopy.

Protein amyloid fibrillation is linked to a wide range of neurodegenerative diseases. Protein oligomer is an intermediate substance in the process of fibrillation, which is neurotoxic and formed by the aggregation of protein molecules under physiological stress. Early detection of protein oligomers could make timely intervention of protein fibrillation related diseases. Therefore, it is crucial to develop efficient inhibitors and probes for monitoring amyloid fibril formation. In this study, we developed a novel amyloid inhibitor quinoline yellow (QY), which was proved to be effective in inhibiting insulin protein fibrillation as demonstrated by fluorescence, morphology characterization and circular dichroism. When QY binds to insulin, it exerts inhibitory effects on the nucleation process and effectively impedes the formation of fibrillar fibrils. In addition, we present the application of surface-enhanced Raman spectroscopy (SERS) as an extremely sensitive technique for identifying amyloid oligomers. The investigation employed the probe QY, which demonstrated a linear reaction for identifying oligomers in the concentration range of 1.0-58.0 µM. Impressively, it showcased an exceptionally sensitive detection threshold of 0.2 µM. And also illustrating the binding sites and interaction mechanisms between small molecules of QY and insulin by SERS. The aforementioned methodology was also employed for the identification of insulin oligomers in human serum samples. Thereby, the proposed approach presenting a promising avenue with extensive implications in the realms of pharmaceutical exploration and disease diagnosis.

Anti-PD-1/PD-L1 inhibitor therapy for melanoma brain metastases: a systematic review and meta-analysis.

Melanoma brain metastases present a major challenge in cancer treatment and reduce overall survival despite advances in managing primary melanoma. Immune checkpoint inhibitors (ICIs) that target PD-1/PD-L1 pathways have shown promise in treating advanced melanoma, but their efficacy for melanoma brain metastases is debated. This systematic review and meta-analysis summarize evidence on anti-PD-1/PD-L1 inhibitors for melanoma brain metastases. This systematic review and meta-analysis followed PRISMA guidelines. PICO criteria targeted melanoma brain metastasis patients treated with PD-1/PD-L1 inhibitors, assessing overall survival, progression-free survival, and complications. Inclusion criteria were English studies on humans using PD-1/PD-L1 inhibitors for melanoma brain metastases with > 10 patients. A total of 22 trials involving 1523 melanoma brain metastase patients treated with anti-PD-1/PD-L1 inhibitors were thoroughly analyzed. Our findings show the 6-month OS rate of 0.75 [95%CI:0.67-0.84], the 6-months PFS rate of 0.42 [95%CI:0.31-0.52], the 1-year OS rate of 0.63 [95%CI:0.52-0.74], the 1-year PFS rate was 0.45 [95%CI:0.32-0.58], the 18-months OS rate of 0.52 [95%CI:0.37-0.67], the 2-year OS rate of 50% [95% CI: (34%-65%)], the 2 year PFS rate of 0.36 (95%CI:0.23-0.50), the 3-year OS rate of 0.42 (95%CI:0.17-0.67), the 4-year PFS rate of 0.35 [95%CI:0.08-0.61], the 4-year OS rate of 0.29 [95%CI:0.01-0.56], the 5-year OS rate of 0.29 (95%CI:0.09-0.50), and the 5-year PFS rate of 0.11 (95%CI:0.03-0.19). The combined disease stability rate was 0.13 [95%CI:0.05-0.20], the progressive disease rate was 0.49 [95%CI:0.37-0.62], the partial response rate was 0.14 [95%CI:0.07-0.20], the object response rate was 0.35 [95%CI:0.24-0.46], and the complete response rate was 0.22 [95%CI:0.12-0.32]. In conclusion, our meta-analysis provides compelling evidence supporting the efficacy of PD-1/PD-L1 inhibitors in patients with melanoma brain tumors, as evidenced by favorable survival outcomes and disease control rates.

Predictive Value of Lymphocyte-to-Neutrophil Ratio and Platelet-to-Neutrophil Ratio on PD-L1 Expression in Lung Cancer.

OBJECTIVE: This study aimed to examine the predictive effect of the lymphocyte-to-neutrophil ratio (LNR) and the platelet-to-neutrophil ratio (PNR) on the expression of programmed death receptor ligand 1 (PD-L1) in patients diagnosed with lung cancer. METHODS: The clinical records of 86 patients diagnosed with lung cancer between January 2020 and February 2022 at Fu Yang People's Hospital were retrospectively analyzed. The records included information on age, gender, smoking history, hematological indices at the time of admission, staging of the lung malignancy, histopathological subtype, comorbidities, and the expression levels of PD-L1. Patients were stratified into two distinct cohorts based on their PD-L1 expression levels: Those with an expression level greater than or equal to 1% were classified into the PD-L1 positive expression group, while the remainder were categorized as the PD-L1 negative expression group. Univariate analysis and multivariate logistic regression analysis were used to identify the influencing factors of PD-L1, and the diagnostic efficacy was calculated using the receiver operating characteristic (ROC) curve. RESULTS: Upon analysis, the PD-L1 positive expression group manifested notably lower values as compared to their counterparts in the PD-L1 negative expression group (LNR: 0.262 ± 0.105 vs. 0.390 ± 0.201; PNR: 41.03 [29.64, 50.11] vs. 49.50 [37.38, 73.83]), and these differences were statistically significant. There was a notable disparity in PD-L1 expression based on gender, with males exhibiting a statistically significant higher positivity rate compared to females. Furthermore, patients in Stages I-III of the disease demonstrated a markedly elevated PD-L1 positivity rate compared to those in Stage IV (p < 0.05). Incorporating univariates with statistical differences into multivariate logistic regression analysis suggests that stage and LNR are independent risk factors for PD-L1 negative expression. ROC curve analyses revealed that the area under the ROC curve (AUC) for LNR as an indicator for PD-L1 positive expression stood at 0.706, while the AUC for PNR was calculated at 0.687. CONCLUSION: PD-L1 expression is correlated with gender and lung cancer staging, and LNR and PNR have a predictive value for PD-L1 expression.

Correlations of PSGL-1 VNTR polymorphism with the susceptibility to severe HFMD associated with EV-71 and the immune status after infection.

Enterovirus 71 (EV-71) has strong neurotropism, and it is the main pathogen causing severe hand, foot, and mouth disease (HFMD). In clinical observations, significant differences were observed in the severity and prognosis of HFMD among children who were also infected with EV-71. Genetic differences among individuals could be one of the important causes of differences in susceptibility to EV-71-induced HFMD. As P-selectin glycoprotein ligand-1 (PSGL-1) is an important receptor of EV-71, the correlation between single-nucleotide polymorphisms (SNPs) in PSGL-1 and the susceptibility to severe HFMD following EV-71 infection is worth studying. Given the role of PSGL-1 in immunity, the correlations between PSGL-1 SNPs and the immune status after EV-71 infection are also worth studying. Meanwhile, PSGL-1 variable number of tandem repeats (VNTR) represents a research hotspot in cardiovascular and cerebrovascular diseases, but PSGL-1 VNTR polymorphism has not been investigated in HFMD caused by EV-71 infection. In this study, specific gene fragments were amplified by polymerase chain reaction, and PSGL-1 VNTR sequences were genotyped using an automatic nucleic acid analyzer. The correlations of PSGL-1 VNTR polymorphism with the susceptibility to EV-71-associated severe HFMD and the post-infection immune status were analyzed. The PSGL-1 VNTR A allele was identified as a susceptible SNP for severe HFMD. The risk of severe HFMD was higher for AA + AB genotype carriers than for BB genotype carriers. The counts of peripheral blood lymphocyte subsets were lower in AA + AB genotype carries than in BB genotype carries. In conclusion, PSGL-1 VNTR polymorphism is associated with the susceptibility to EV-71-induced severe HFMD and the immune status after infection. PSGL-1 VNTR might play a certain role in the pathogenesis of severe cases.

Improving CO2 adsorption efficiency of an amine-modified MOF-808 through the synthesis of its graphene oxide composites.

This research developed a novel composite of MOF-NH2 and graphene oxide (GO) for enhanced CO2 capture. Employing the response surface methodology-central composite design (RSM-CCD) for experiments design, various MOF-NH2/GO samples with GO loadings from 0 to 30 wt% were synthesized. The results of SEM, XRD, EDS, and BET analysis revealed that the materials maintained their MOF crystal structure, confirmed by X-ray diffraction, and exhibited unique texture, high porosity, and oxygen-enriched surface chemistry. The influence of temperature (25-65 °C) and pressure (1-9 bar) on CO2 adsorption capacity was assessed using a volumetric adsorption system. Optimum conditions were obtained at weight percent of 22.6 wt% GO, temperature of 25 °C, and pressure of 9 bar with maximum adsorption capacity of 303.61 mg/g. The incorporation of amino groups enhanced the CO2 adsorption capacity. Isotherm and kinetic analyses indicated that Freundlich and Fractional-order models best described CO2 adsorption behavior. Thermodynamic analysis showed the process was exothermic, spontaneous, and physical, with enthalpy changes of - 16.905 kJ/mol, entropy changes of - 0.030 kJ/mol K, and Gibs changes energy of - 7.904 kJ/mol. Mass transfer diffusion coefficients increased with higher GO loadings. Regenerability tests demonstrated high performance and resilience, with only a 5.79% decrease in efficiency after fifteen cycles. These findings suggest significant potential for these composites in CO2 capture technologies.

Rh(I)/Sulfoxide-Imine-Olefin Complex Catalyzed Enantioselective Allylic Alkylation of 2-Fluoromalonate: Synthesis of Chiral α-Fluorolactone Bearing Vicinal Stereogenic Centers.

Highly enantioselective Rh-catalyzed allylic substitution of the racemic branched allylic substrates with 2-fluoromalonate was realized enabled by a novel chiral sulfoxide-imine-olefin ligand under mild reaction conditions. The utilization of CuSO4 is beneficial for improving the enantioselectivity. Notably, the chiral fluoro-containing allyl products can be employed in a selective cyclic esterification to form chiral α-fluorolactone bearing vicinal stereogenic centers.

Preparation of double-loaded bitter ginseng derivative B21-DOX liposomes co-modified with SP94 and BR2 ligand and its in vitro anti-hepatocarcinogenic effect.

AIM: To construct a novel liposomal drug delivery system co-modified with SP94 and BR2 ligands, encapsulating both the bitter ginseng derivative B21 and doxorubicin (DOX), to achieve superior anti-tumour efficacy and reduced toxic side effects. METHODS: Liposomes were prepared using an organic phase reaction method, with B21 encapsulated in the lipid phase and DOX in the aqueous phase. The liposomes were further modified with SP94 and BR2 peptides. The characterisations, cytotoxicity, and in vitro targeting effects were assessed through various methods including ultraviolet spectrophotometry, high-performance liquid chromatography, nano-size analysis, ultrafiltration centrifugation, dialysis, transmission electron microscopy, flow cytometry, Methylthiazolyldiphenyl-tetrazolium bromide assay, confocal laser scanning microscopy, transwell assay, and tumorsphere assay. RESULTS: SP94/BR2-B21/DOX-LP liposomes were spherical with an average diameter of 120.87 ± 1.00 nm, a polydispersity index (PDI) of 0.223 ± 0.006, and a surface charge of -23.1 ± 1.27 mV. The encapsulation efficiencies for B21 and DOX were greater than 85% and 97% (mg/mg), respectively. The results indicated that SP94/BR2-B21/DOX-LP exhibited enhanced targeting and cytotoxicity compared to single-ligand modified and unmodified liposomes, with the combined encapsulation of B21 and DOX showing synergistic anti-hepatocarcinogenic effects. CONCLUSION: SP94/BR2-B21/DOX-LP liposomes represent a promising targeted drug delivery system for hepatocellular carcinoma, offering improved membrane penetration, enhanced therapeutic efficacy, and reduced systemic toxicity.

The expression of PD-L1 on tumor-derived exosomes enhances infiltration and anti-tumor activity of αCD3 × αPD-L1 bispecific antibody-armed T cells.

Anti-cluster of differentiation (CD) 3 × α programmed death-ligand 1 (PD-L1) bispecific T-cell engager (BsTE)-bound T-cells (BsTE:T) are a promising new cancer treatment agent. However, the mechanisms of action of bispecific antibody-armed activated T-cells are poorly understood. Therefore, this study aimed to investigate the anti-tumor mechanism and efficacy of BsTE:T. The BsTE:T migration was assessed in vivo and in vitro using syngeneic and xenogeneic tumor models, flow cytometry, immunofluorescence staining, transwell migration assays, microfluidic chips, Exo View R100, western blotting, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 technology. In murine B16 melanoma, MC38 colon cancer, and human multiple myeloma cells, BsTE:T exhibited superior tumor elimination relative to that of T-cells or BsTE alone. Moreover, BsTE:T migration into tumors was significantly enhanced owing to the presence of PD-L1 in tumor cells and secretion of PD-L1-containing exosomes. Furthermore, increased infiltration of CD44highCD62Llow effector memory CD8+ T-cells into tumors was closely associated with the anti-tumor effect of BsTE:T. Therefore, BsTE:T is an innovative potential anti-tumor therapy, and exosomal PD-L1 plays a crucial role both in vitro and in vivo in the anti-tumor activity of BsTE:T.

Transarterial Embolization Enhances Programmed Cell Death Ligand 1 Expression and Influences CD8+T Lymphocytes Cytotoxicity in an Orthotopic Hepatocellular Carcinoma Rat Model.

PURPOSE: To investigate the influence of transarterial embolization (TAE) on programmed cell death-ligand 1(PD-L1) expression and CD8+T tumour infiltrative lymphocyte cytotoxicity in the Sprague-Dawley (SD) rat model of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: An orthotopic HCC model was established in twenty SD rats treated with TAE (lipiodol, n = 10) or sham (normal saline, n = 10) using homologous N1S1 hepatoma cells. Rats were euthanized 1 week after embolization. Flow cytometry was used to assess the proportion of CD4+T, CD8+T and programmed cell death-1+(PD-1+) CD8+T lymphocytes in the spleens and tumours. Distribution of CD8+T, granzyme-B+CD8+T lymphocytes and PD-L1+ cells was assessed by immunohistochemistry (IHC) or multiplex IHC. p value < 0.05 was considered statistically significant. RESULTS: The CD4/CD8 ratio and PD-1+CD8+ T lymphocytes exhibited higher values in TAE-treated tumours compared to sham-treated tumours (p = 0.021 and p = 0.071, respectively). Conversely, the number of CD8+T lymphocytes was decreased in TAE-treated tumours (p = 0.043), especially in the central region (p = 0.045). However, more CD8+T lymphocytes were found infiltrating the marginal region than central region in TAE-treated tumours (p = 0.046). The proportion of granzyme-B+CD8+T lymphocytes and the PD-L1 positive areas was elevated in tumours that treated with TAE (p all < 0.05). There was a negative correlation between PD-L1 expression and the number of infiltration of CD8+ T lymphocytes (p = 0.036). CONCLUSIONS: Immune cells are distributed unevenly in the tumours after TAE. The intrinsic induction state of the tumour after embolization may be insufficient to elicit a maximal response to PD-1/PD-L1 inhibitors.