Boosting immune responses in lung tumor immune microenvironment: A comprehensive review of strategies and adjuvants.

The immune system has a substantial impact on the growth and expansion of lung malignancies. Immune cells are encompassed by a stroma comprising an extracellular matrix (ECM) and different cells like stromal cells, which are known as the tumor immune microenvironment (TIME). TME is marked by the presence of immunosuppressive factors, which inhibit the function of immune cells and expand tumor growth. In recent years, numerous strategies and adjuvants have been developed to extend immune responses in the TIME, to improve the efficacy of immunotherapy. In this comprehensive review, we outline the present knowledge of immune evasion mechanisms in lung TIME, explain the biology of immune cells and diverse effectors on these components, and discuss various approaches for overcoming suppressive barriers. We highlight the potential of novel adjuvants, including toll-like receptor (TLR) agonists, cytokines, phytochemicals, nanocarriers, and oncolytic viruses, for enhancing immune responses in the TME. Ultimately, we provide a summary of ongoing clinical trials investigating these strategies and adjuvants in lung cancer patients. This review also provides a broad overview of the current state-of-the-art in boosting immune responses in the TIME and highlights the potential of these approaches for improving outcomes in lung cancer patients.

Lung cancer remains a significant global health concern, and researchers are actively exploring innovative approaches to boost the immune system's ability to recognize and destroy cancer cells. Boosting the immune system responses against the lung tumor microenvironment is one of promising approaches for lung cancer therapy. The lung tumor microenvironment refers to the complex network of cells, proteins, and molecules that surround and support the growth of lung tumors. Unfortunately, this environment often hinders the body's immune response, allowing cancer cells to evade detection and destruction. By comprehending the cellular and molecular factors at play, researchers can devise novel strategies to tip the balance in favor of the immune system. Cancer cells often employ various mechanisms to suppress the immune system within the lung tumor microenvironment. One approach to combating this suppression is the use of adjuvants, substances that enhance the immune response. Adjuvants can be administered alongside cancer vaccines or other immunotherapies to strengthen the immune system's ability to recognize and attack tumor cells. The recent progresses have shown the potential of some products, adjuvants, immunotherapy drugs, vaccines, and nanoparticles. This article aims to discuss recent advancements in the field of cancer immunotherapy, specifically focusing on strategies to strengthen the body's immune response against lung tumors.

Effects of a new magnetostrictive ultrasonic scaler and a traditional piezoelectric ultrasonic scaler on root surfaces and patient complaints.

Tooth wear and pain are the primary concerns of patients undergoing periodontal scaling. The aims of this study were to compare the effects of a new magnetostrictive ultrasonic scaler and a traditional piezoelectric ultrasonic scaler on tooth surface roughness and calculus removal and to determine their impacts on patient discomfort during supragingival cleaning. This article had two parts: an in vitro study and a clinical study. In the in vitro study, thirty teeth with subgingival calculus were randomly assigned to two scaling treatment groups: magnetostrictive scalers (n = 15) and piezoelectric scalers (n = 15). Surface roughness measurements were taken at baseline and after scaling, and the root samples were visualised by SEM after scaling. Additionally, a single-centre randomised split-mouth clinical trial was conducted. Eighty-five participants diagnosed with chronic gingivitis or periodontitis were randomly assigned to receive supragingival scaling. The magnetostrictive scaler was used in half of the mouths (n = 85), and the piezoelectric scaler was used in the other half of the mouths (n = 85). Data on pain, noise, and vibration were collected using a VAS questionnaire, and the operating time was recorded. In both in vitro and clinical studies, magnetostrictive scalers were reported to be more effective than piezoelectric scalers in removing dental deposits (P < 0.05). Additionally, the root surface after scaling with the magnetostrictive scaler was smoother than that after scaling with the piezoelectric scaler in the in vitro study (P = 0.02). SEM examination also revealed that fewer dental materials were lost after instrumentation with the magnetostrictive scaler than after instrumentation with the piezoelectric scaler. Piezoelectric scalers caused less discomfort to patients in terms of pain, noise, and vibration than magnetostrictive scalers (P < 0.05). According to this clinical study, the magnetostrictive scaler caused more discomfort during supragingival scaling than the piezoelectric scaler. Moreover, the magnetostrictive scaler was also more efficient and produced a smoother root surface with less material loss after scaling than the piezoelectric scaler, as demonstrated in the in vitro study.

Study on morphological traits, nutrient compositions and comparative metabolomics of diploid and tetraploid Tartary buckwheat sprouts during sprouting.

Tartary buckwheat (TB) sprout is a kind of novel nutritional vegetable, but its consumption was limited by low biomass and thin hypocotyl. The tetraploid TB sprouts was considered to be able to solve this issue. However, the nutritional quality of tetraploid TB sprouts and differences between conventional (diploid) and tetraploid TB sprouts remain unclear. In this study, the morphological traits, nutrient compositions and metabolome changes of diploid and tetraploid TB sprouts were analyzed. The water, pigments and minerals contents of TB sprouts increased during sprouting, while the contents of total soluble protein, reducing sugar, cellulose, and total phenol decreased. Compared with diploid sprouts, tetraploid sprouts had higher biomass and thicker hypocotyl. Tetraploid sprouts had higher ash and carotenoid contents, but had lower phenol and flavonoid accumulation. 677 metabolites were identified in TB sprouts by UPLC-MS analysis, including 62 diseases-resistance metabolites and 43 key active ingredients. Some key bioactive metabolites, such as rimonabant, quinapril, 1-deoxynojirimycin and miglitol, were identified. 562 differential expressed metabolites (DEMs) were identified during sprouting with seven accumulation patterns, and five hormones were found to be involved in sprout development. Additionally, 209 DEMs between diploid and tetraploid sprouts were found, and some key bioactive metabolites were induced by chromosome doubling such as mesoridazine, amaralin, atractyloside A, rhamnetin and Qing Hau Sau. This work lays a basis for the development and utilization of TB sprouts and provides evidence for the selection of tetraploid varieties to produce sprouts with high biomass and quality.

Effects of Iron Addition on the Collision of Polycyclic Aromatic Hydrocarbon Clusters: A Molecular Dynamics Study.

In this work, soot particle size distributions in iron-doped premixed ethylene flames are examined using scanning mobility particle sizer measurements. It is found that iron addition promotes the growth in soot particle size, and the enhanced particle coagulation is inferred to be an important reason. To support that, the influence of iron addition on the coagulation of polycyclic aromatic hydrocarbon (PAH) clusters, the analogue of incipient soot particles, is further investigated using molecular dynamics simulations. Based on the results of hundreds of binary head-on collision simulations, the collision between two coronene-Fe-coronene dimers is found to have a significantly higher coagulation efficiency than that between two coronene dimers. However, this enhancement effect weakens as the size of the PAH monomer increases. Although the coagulation efficiency can be increased by iron addition, the collision frequency is almost unaffected, as revealed from the binary off-central collision simulations. Moreover, the simulation results of coronene cluster growth via coagulation show that iron addition promotes coronene cluster growth, leading to larger cluster size, which may explain the larger soot particle size observed in iron-doped flames.

Theoretical studies on Lennard-Jones parameters of benzene and polycyclic aromatic hydrocarbons.

Lennard-Jones (L-J) parameters, i.e. collision diameter and well depth, of benzene and polycyclic aromatic hydrocarbons (PAHs) interacting with bath gases helium and nitrogen are studied theoretically in this work. The results of three different computing methods, called SA, σ-ε, η-ξ methods respectively, are compared with literature data. The SA method determines effective L-J parameters from the spherically averaged intermolecular potentials; the σ-ε method averages L-J parameters obtained from different relative orientations of interacting partners; and the η-ξ method uses an orientation-averaging rule on the basis of two characteristic variables η and ξ representing repulsive and attractive energy scales respectively. The σ-ε and η-ξ methods require much less computational time than the SA method due to the use of an iterative search algorithm. For validation of the L-J parameters, binary diffusion coefficients computed using L-J parameters by these three methods and those by empirical estimations are compared with experimental data from literature. Results show that while the SA method is reliable and the σ-ε method is efficient, the η-ξ method is both reliable and efficient for computing L-J parameters for benzene and PAHs, and captures the anisotropic effects of molecular structure on L-J parameters better than empirical methods.

Prediction Model of Photodegradation for PBAT/PLA Mulch Films: Strategy to Fast Evaluate Service Life.

Eco-friendly biodegradable PBAT/PLA mulch films are attracting increasing interest in sustainable agricultural production. However, currently, little is known about the service life for the PBAT/PLA mulch films. Herein, PBAT/PLA mulch films are subjected to indoor UV-accelerated degradation (UAD) experiments and field cultivation environment degradation (CED) experiments to systematically investigate the relationship between UAD and CED processes. Results demonstrate that 10 days of indoor UAD treatment corresponds to around 120 days aging under outdoor CED conditions. Using eight PBAT/PLA evaluation indicators (haze, elongation at break, tensile strength, gel content, light transmittance, polydispersity index, Mn, Mw), we established a service life prediction model for PBAT/PLA mulch films based on short-term indoor UAD experiments, which could accurately estimate the long-term service life of the mulch films in the field. In particular, using the haze value, near-perfect correlation (R2 = 0.995 for eq. 1 and R2 = 0.993 for eq. 2) was found between CED days and UAD days. The establishment of these reliable predictive models for the service lifetime of PBAT/PLA mulch films will avoid the undesirable premature breakdown during crop growth, thus fostering end-user confidence in eco-friendly biodegradable mulch films.

On the determination of Lennard-Jones parameters for polyatomic molecules.

Characterizing the key length and energy scales of intermolecular interactions, Lennard-Jones parameters, i.e., collision diameter and well depth, are prerequisites for predicting transport properties and rate constants of chemical species in dilute gases. Due to anisotropy in molecular structures, Lennard-Jones parameters of many polyatomic molecules are only empirically estimated or even undetermined. This study focuses on determining the effective Lennard-Jones parameters between a polyatomic molecule and a bath gas molecule from interatomic interactions. An iterative search algorithm is developed to find orientation-dependent collision diameters and well depths on intermolecular potential energy surfaces. An orientation-averaging rule based on characteristic variables is proposed to derive the effective parameters. Cross-interaction parameters for twelve hydrocarbons with varying molecular shapes, including long-chain and planar ones, interacting with four bath gases He, Ar, N2, and O2 are predicted and reported. Three-dimensional parametric surfaces are constructed to quantitatively depict molecular anisotropy. Algorithmic complexity analysis and numerical experiments demonstrate that the iterative search algorithm is robust and efficient. By using the latest experimental diffusion data, it is found that the proposed orientation-averaging rule improves the prediction of cross-interaction Lennard-Jones parameters for polyatomic molecules, including for long-chain molecules that challenge the consistency of previous methods. By introducing characteristic variables, the present study shows a new route to determining effective Lennard-Jones parameters for polyatomic molecules.

Molecular Dynamics Study on the Condensation of PAH Molecules on Quasi Soot Surfaces.

In this paper, the condensation efficiency of polycyclic aromatic hydrocarbon (PAH) molecules up to coronene, from 500 to 2000 K, is calculated based on hundreds of collisions between a PAH molecule and the quasi soot surface, which is composed of stacked coronene molecules with periodic boundary conditions, using molecular dynamics simulations. The results show that the condensation efficiency increases with the PAH molecular mass but decreases as the temperature increases, following a Gaussian function. Meanwhile, when the presence of aliphatic chains on soot particle surfaces is considered, the condensation efficiency can be lowered by up to 40%, being affected more significantly at higher temperatures. A condensation efficiency model is thus proposed from the molecular trajectories. Finally, when this newly proposed PAH condensation efficiency model is adopted, better agreement with the experiments is achieved in predicting soot volume fractions of an ethylene/oxygen/nitrogen mixture in a tandem jet-stirred reactor and a plug-flow reactor.

Integrating transcriptome and physiological analyses to elucidate the molecular responses of buckwheat to graphene oxide.

With the increasing application of nanomaterials, evaluation of the phytotoxicity of nanoparticles has attracted considerable interest. Buckwheat is an economically pseudocereal crop, which is a potential model for investigating the response of plants to hazardous materials. In this study, the response of buckwheat to graphene oxide (GO) was investigated by integrating physiological and transcriptome analysis. GO can penetrate into buckwheat root and stem, and high concentrations of GO inhibited seedlings growth. High concentration of GO improved ROS production and regulated the activities and gene expression of oxidative enzymes, which implying GO may affect plant growth via regulating ROS detoxification. Root and stem exhibit distinct transcriptomic responses to GO, and the GO-responsive genes in stem are more enriched in cell cycle and epigenetic regulation. GO inhibited plant hormone biosynthesis and signaling by analyzing the expression data. Additionally, 97 small secreted peptides (SSPs) encoding genes were found to be involved in GO response. The gene expression of 111 transcription factor (TFs) and 43 receptor-like protein kinases (RLKs) were regulated by GO, and their expression showed high correlation with SSPs. Finally, the TFs-SSPs-RLKs signaling networks in regulating GO response were proposed. This study provides insights into the molecular responses of plants to GO.

Nitrate dose-responsive transcriptome analysis identifies transcription factors and small secreted peptides involved in nitrogen response in Tartary buckwheat.

Tartary buckwheat (Fagopyrum tataricum Gaertn.) is an economically important pseudocereal crop, which can adapt well to extreme environments, including low nitrogen (LN) stress. However, little is known regarding the associated molecular mechanisms. In this study, the molecular mechanism of Tartary buckwheat roots in response to different doses of nitrate was investigated by combining physiological changes with transcriptional regulatory network. LN improved elongation and branching of lateral roots, indicating that the plasticity of lateral roots drives the adaption of Tartary buckwheat under LN condition. The roots of the seedlings that were cultivated under four N conditions were selected for RNA-Seq analysis. In total 1686 nitrate dose-responsive genes were identified. Of these genes, 16 genes encoding N transporters showed response to N availability, and they may play important roles in N transport and root system architecture in Tartary buckwheat roots. 108 transcription factors (TFs) showed dose-response to N availability, and they may regulate N response and root growth under varied N conditions by modulating the expression of N transporters. A NIN-like protein, FtNLP7, was identified and it may contribute to the transcriptional regulation of N transporters. Furthermore, 81 N-responsive genes were identified as the small secreted peptides (SSPs). 48 N-responsive SSPs were annotated as hypothetical proteins and they may be the species-specific proteins of Tartary buckwheat. This paper provides useful information for further investigation of the mechanisms underlying the adaptation of Tartary buckwheat under N-deficient condition.

Flame synthesized nanoscale catalyst (CuCeWTi) with excellent Hg0 oxidation activity and hydrothermal resistance.

In view of poor hydrothermal resistance of impregnation prepared catalysts (Cu5Ce5W9Ti-I), this paper aims to enhance thermal and hydrothermal resistance of Cu/Ce based catalysts for Hg0 oxidation via flame synthesis technology. The result found that the flame synthesis method could form nanoscale Cu10Ce10W9Ti-F particles with smaller lattice size (8-25 nm), more stable carrier structure and more oxygen vacancies. The inter-doping and inter-substitution of Ce, Cu and Ti oxides created more oxygen vacancies (Ce3+) and L-sites (O2-). Furthermore, the carrier TiO2 of Cu10Ce10W9Ti-F existed in form of highly thermostable rutile rather than anatase. High Hg0 oxidation efficiency (MOE) of 83.9-99.7% at 100-450 °C proved excellent oxidation activity of Cu10Ce10W9Ti-F catalyst. Moreover, the thermal and hydrothermal treatment (700 °C) only decreased MOE by less than 5% since L-sites kept fine thermostability of Cu10Ce10W9Ti-F. The flame synthesis was proven to be a promising catalyst preparation method to enhance thermal and hydrothermal resistance.

ERRα inhibitor acts as a potential agonist of PPARγ to induce cell apoptosis and inhibit cell proliferation in endometrial cancer.

Two transcriptional factors, peroxisome proliferator-activated receptor-γ (PPARγ) and estrogen-related receptor-α (ERRα), have been reported to be key regulators of cellular energy metabolism. However, the relationship between ERRα and PPARγ in the development of endometrial cancer (EC) is still unclear. The expression levels of PPARγ and ERRα in EC were evaluated by quantitative real-time PCR, western blot, tissue array and immunohistochemistry. A significant negative correlation was identified between PPARγ and ERRα expression in women with EC (ρ=-0.509, P<0.001). Bioinformatics analyses showed that PPARγ and ERRα can activate or inhibit the same genes involved in cell proliferation and apoptosis through a similar ModFit. ERRα activation or PPARγ inhibition could promote proliferation and inhibit apoptosis through the Bcl-2/Caspase3 pathways. Both PPARγ and ERRα can serve as serum tumor markers. Surprisingly, as evaluated by receiver operating characteristic (ROC) curves and a logistic model, a PPARγ/ERRα ratio≤1.86 (area under the ROC curve (AUC)=0.915, Youden index=0.6633, P<0.001) was an independent risk factor for endometrial carcinogenesis (OR=14.847, 95% CI= 1.6-137.748, P=0.018). EC patients with PPARγ(-)/ERRα(+) had the worst overall survival and disease-free survival rates (both P<0.001). Thus, a dynamic imbalance between PPARγ and ERRα leads to endometrial carcinogenesis and predicts the EC prognosis.

Recipient-specific T-cell repertoire reconstitution in the gut following murine hematopoietic cell transplant.

Graft-versus-host disease (GVHD) is a complication of hematopoietic cell transplantation (HCT) caused by alloreactive T cells. Murine models of HCT are used to understand GVHD and T-cell reconstitution in GVHD target organs, most notably the gastrointestinal (GI) tract where the disease contributes most to patient mortality. T-cell receptor (TCR) repertoire sequencing was used to measure T-cell reconstitution from the same donor graft (C57BL/6 H-2b) in the GI tract of different recipients across a spectrum of matching, from syngeneic (C57BL/6), to minor histocompatibility (MHC) antigen mismatch BALB.B (H-2b), to major MHC mismatched B10.BR (H-2k) and BALB/c (H-2d). Although the donor T-cell pools had highly similar TCR, the TCR repertoire after HCT was very specific to recipients in each experiment independent of geography. A single invariant natural killer T clone was identifiable in every recipient group and was enriched in syngeneic recipients according to clonal count and confirmatory flow cytometry. Using a novel cluster analysis of the TCR repertoire, we could classify recipient groups based only on their CDR3 size distribution or TCR repertoire relatedness. Using a method for evaluating the contribution of common TCR motifs to relatedness, we found that reproducible sets of clones were associated with specific recipient groups within each experiment and that relatedness did not necessarily depend on the most common clones in allogeneic recipients. This finding suggests that TCR reconstitution is highly stochastic and likely does not depend on the evaluation of the most expanded TCR clones in any individual recipient but instead depends on a complex polyclonal architecture.

NUDT21 knockdown inhibits proliferation and promotes apoptosis of pancreatic ductal adenocarcinoma through EIF2 signaling.

The NUDT family is thought to play an important role in cancer growth and progression. However, the clinicopathologic significance and potential role of nucleotide diphosphate-linked X-component motif 21, NM_007006 (NUDT21) in pancreatic ductal adenocarcinoma (PDAC) remains largely unknown. In this study, we observed that NUDT21 was frequently up-expressed in PDAC. Clinical data revealed that its level positively correlated with poor survival of patients with PDAC. We found that knockdown of NUDT21 significantly inhibited cell proliferation and promoted apoptosis both in vitro and in vivo. Screening by microarray analysis and verifying by Western blot, we found that the EIF2 signaling pathway represented the main molecular mechanism underlying the effects of NUDT21 knockdown in PANC-1 cells, and PKR, HSPA5, EIF4E and DDIT3 may be its target genes. Thus, our results revealed for the first time that NUDT21, a valuable marker of PDAC prognosis, promotes tumor proliferation, inhibits cells apoptosis and might represent a potential target for gene-based therapy.

Reaction kinetics of hydrogen addition reactions to methyl butenoate.

To investigate the kinetics of hydrogen addition reactions of unsaturated methyl esters, we selected two representative molecules that are isomers with C[double bond, length as m-dash]C double bonds at different locations, i.e. methyl 2-butenoate and methyl 3-butenoate for study. An appropriate quantum chemical method was determined to compute the potential energy surfaces. The high-pressure limit rate constants were computed by applying multi-structural canonical variational transition state theory including tunneling by the multi-dimensional small-curvature tunneling approximation. The master equation analysis was followed to study the pressure-dependence of the rate constants of H addition and the subsequent dissociation reactions. The results show that it is easier for the H atom to add to the C[double bond, length as m-dash]C than to the C[double bond, length as m-dash]O bond because of the lower barrier heights, and the hydrogen addition reactions are faster for both methyl 2-butenoate and methyl 3-butenoate, except that the hydrogen abstraction is dominant at above 1700 K for methyl 2-butenoate. Using our computed rate constants, the prediction for methyl propanoate mole fraction agreed better with experimental data of methyl 2-butenoate combustion.

Promoting SO2 Resistance of a CeO2(5)-WO3(9)/TiO2 Catalyst for Hg0 Oxidation via Adjusting the Basicity and Acidity Sites Using a CuO Doping Method.

The competition between SO2 and elemental mercury (Hg0) for active sites was an important factor for suppressing the Hg0 oxidation properties of catalysts. There were obvious differences in properties of basicity and acidity between SO2 and Hg0. Raising the SO2 resistance via adjusting the basicity and acidity sites of catalysts was promising for reducing the competition between SO2 and Hg0. This study aimed to form multiple active sites with different basicities via Cu, Fe, Mn, and Sn doping. The results indicated that Cu doping had the best modification performance. Five percent CuO doping could significantly improve the SO2 resistance of CuO(5)-CeO2(5)-WO3(9)/TiO2 and increase the mercury oxidation efficiency (MOE) from 54.7 to 85.5% in the condition (6% O2, 100 ppm NO, 100 ppm NH3, and 100 ppm SO2). CO2 temperature-programmed desorption analysis showed that CuO(5)-CeO2(5)-WO3(9)/TiO2 exhibited weak basic sites (CeO2), medium-strong basic sites (Cu-O-Ce), and strong basic sites (CuO). Therefore, the CuO in the Ce-O-Cu structure was prioritized for the reaction with acid gas SO2 and protected CeO2 from SO2 poisoning. This study prepared a highly SO2-resistant catalyst for Hg0 oxidation. This research and development will be conducive for use in Hg0 oxidation in actual coal-fired flue gases.

Peroxide-mediated site-specific C-H methylation of imidazo[1,2-a]pyridines and quinoxalin-2(1H)-ones under metal-free conditions.

An effective approach to realize the direct methylation of imidazo[1,2-a]pyridines and quinoxalin-2(1H)-ones with peroxides under metal-free conditions is described. In this protocol, peroxides serve as both the radical initiator and methyl source. Methylated imidazopyridines and quinoxalin-2(1H)-ones were smoothly synthesized in moderate to good yields. A free radical reaction mechanism was proposed to describe the methylation process.

On the Prediction of Standard Enthalpy of Formation of C2-C4 Oxygenated Species.

In this study, to determine an efficient and accurate method for predicting standard enthalpy of formation (ΔfHo) of oxygenated species, we calculated ΔfHo for several typical C2-C4 oxygenated species using atomization and isodesmic reactions in combination with various quantum chemical methods, including six density functional theory methods, three compound methods, and CCSD(T)/CBS. Compared with experimental values, at the same quantum chemical level, ΔfHo values predicted by using isodesmic reactions are more accurate than those using atomization reactions. Comparing various quantum chemical methods when isodesmic reactions are used, the performance of G4 is the best with a mean unsigned deviation (MUE) of 0.3 kcal/mol and a standard deviation (SD) of 0.3 kcal/mol, while M06-2X can predict ΔfHo efficiently and accurately with an MUE of 0.6 kcal/mol and SD of 0.5 kcal/mol. Using the best methods we have found, we calculated the enthalpies of formation and other thermodynamic properties for dimethyl carbonate (DMC) and its associated species and then applied them in a DMC combustion model for predicting ignition delay times. Better agreement with the experiments is achieved when the newly computed thermodynamic properties are adopted.