Effect of industrial alkene ozonolysis on atmospheric H2SO4 formation.

This study has employed the master chemical mechanism (MCM) to investigate the influence of the ozone oxidation pathways in the atmospheric formation of H2SO4 from short-chain olefins in industrialized areas. In-situ H2SO4 formation data were obtained using a high-resolution chemical ionization time-of-flight mass spectrometer, and the simulated H2SO4 concentrations calculated using updated parameters for the MCM model exhibited good agreement with observations. In the simulation analysis of different reaction pathways involved in H2SO4 formation, hydroxyl radicals were found to dominate H2SO4 production during the daytime, while olefin ozone oxidation contributed up to 65% of total H2SO4 production during the night-time. A sensitivity analysis of the H2SO4 production parameters has revealed a high sensitivity to changes in sulfur dioxide, and a relatively high sensitivity to olefins with fast ozonolysis reaction rates and bimolecular reaction rates of resulting stabilized Criegee Intermediates. A high relative humidity promotes daytime H2SO4 formation, but has an inhibiting effect during the night-time due to the different dominant reaction pathways.

Small Molecule Hydrogels Loading Small Molecule Drugs from Chinese Medicine for the Enhanced Treatment of Traumatic Brain Injury.

Self-assembly of hydrogels for mechanical support and drug delivery has been extensively researched in traumatic brain injury (TBI), where treatment options are limited. The chief challenge is that most self-assembled hydrogels rely on high molecular carriers or the incorporation of exogenous inactive substances as mediators. It is difficult for these drug delivery systems to achieve clinical translation due to concerns regarding biological safety. Here we report a small molecule hydrogel (GBR-gel) loading small molecule drugs (glycyrrhizic acid, berberine, and rhein) that originated from popular Chinese medicines without additional drug loading or inactive components under physiological conditions. In the long run, GBR-gel possesses several advantages, including ease of preparation, cost-effectiveness, and high biocompatibility. As a proof-of-concept, GBR-gel allows for prompt administration at the site of brain injury to exert potent pharmacodynamic effects. Further single-cell RNA sequencing and experimental validation indicated that GBR-gel can effectively rescue the suppressed glutamatergic synapse pathway after TBI, thereby attenuating inflammatory responses and neural impairments. Our work provides an alternative strategy for timely intervention of TBI.

Ultrasound-responsive nanocarriers with siRNA and Fe3O4 regulate macrophage polarization and phagocytosis for augmented non-small cell lung cancer immunotherapy.

The immunosuppressive tumor microenvironment (TME) significantly inhibits the effective anti-tumor immune response, greatly affecting the efficacy of immunotherapy. Most tumor-associated macrophages (TAMs) belong to the M2 phenotype, which contributes significantly to the immunosuppressive effects in non-small cell lung cancer (NSCLC) TME. The interaction between signal regulatory protein α (SIRPα) expressed on macrophages and CD47, a transmembrane protein overexpressed on cancer cells, activates the "eat-me-not" signaling pathway, inhibiting phagocytosis. In this study, a folic acid (FA)-modified ultrasound responsive gene/drugs delivery system, named FA@ PFP @ Fe3O4 @LNB-SIRPα siRNA (FA-PFNB-SIRPα siRNA), was developed using 1,2-dioleoacyl-3-trimethylammonium-propane (DOTAP), FA-1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [amino (polyethylene glycol)2000] (DSPE-PEG2000-FA), cholesterol, and perfluoropentane (PFP), for the delivery of siRNA encoding SIRPα mRNA and immune adjuvant Fe3O4 nanoparticles. Under ultrasound conditions, the nanobubbles effectively transfected macrophages, inhibiting SIRPα mRNA and protein expression, promoting the phagocytosis of TAMs, and synergistically reversing M2 polarization. This system promotes the infiltration of T cells, enhances the proliferation and activation of cytotoxic T cells, and inhibits the infiltration of immunosuppressive cells in tumor tissues. Administration of FA-PFNB-SIRPα siRNA combined with ultrasound significantly inhibits NSCLC progression. The study highlights the potential of ultrasound nanotechnology-enabled delivery of SIRPα siRNA and Fe3O4 as an effective strategy for macrophage-based immunotherapy to reshape the immunosuppressive TME for cancer therapy.

Ultrasound-Responsive Nanocarriers Delivering siRNA and Fe3O4 Nanoparticles Reprogram Macrophages and Inhibit M2 Polarization for Enhanced NSCLC Immunotherapy.

Lung cancer has emerged as the second most common type of malignant tumor worldwide, and it has the highest mortality rate. The overall 5-year survival rate stands at less than 20%, which is primarily related to the limited therapeutic options and the complexity of the tumor immune microenvironment. In the tumor microenvironment, M1 macrophages are known for their tumor-killing capabilities. Although they are less numerous, they play an important role in tumor immunity. Therefore, increasing M1 macrophages' presence is considered a strategy to enhance targeted phagocytosis and antitumor efficacy in nonsmall cell lung cancer (NSCLC). This study introduces the development of folic acid (FA)-conjugated liposomal nanobubbles for precise delivery of PFH, STAT3 siRNA, and Fe3O4 to the tumor microenvironment. These encapsulated PFH liposomal nanobubbles exhibit significant visualization potential and underwent phase transition when exposed to low-intensity focused ultrasound (LIFU). The release of Fe3O4 activates the IRF5 signaling pathway, converting M2-like macrophages to M1. In addition, STAT3 siRNA effectively interrupts the JAK-STAT3 pathway, inhibiting the polarization of M2-like macrophages in tumor-associated macrophages (TAMs). This dual-action therapy facilitates T-cell activation and proliferation, thereby enhancing the immune response against NSCLC.

Two Thiophene-Functionalized Co-MOFs as Green Heterogeneous Catalysts for the Biginelli Reaction.

Two Co(II) metal-organic frameworks (Co-MOFs), namely, [Co(DMTDC)(bimb)]n (Co-MOF-1) and {[Co(DPTDC)(bimb)(H2O)]·2DMF}n (Co-MOF-2) (H2DMTDC = 3,4-dimethylthieno[2,3-b]thiophene-2,5-dicarboxylic acid, H2DPTDC = 3,4-diphenylthieno[2,3-b]thiophene-2,5-dicarboxylic acid, bimb = 1,4-bis((1H-imidazol-1-yl)methyl)benzene), were obtained by the reaction of flexible N-containing ligand bimb and two structurally related thiophene-containing ligands H2DMTDC and H2DPTDC, respectively. These Co-MOFs displayed a 3D framework and porous structure, respectively. Co-MOF-1 and the activated sample Co-MOF-2' could act as green heterogeneous catalysts for the one-pot multicomponent Biginelli reaction, specifically the dehydration condensation process involving aldehydes, acetoacetates, and urea to yield dihydropyrimidin-2(1H)-ones. The reaction has advantages such as solvent-free conditions, water as only byproduct, readily accessible starting materials, excellent functional group compatibility, and simple operation. Both catalysts exhibited a wide substrate scope and maintained significant catalytic activity over five cycles. The special catalytic performance may be ascribed to functional groups within the ligand.

Formation of atmospheric molecular clusters containing nitric acid with ammonia, methylamine, and dimethylamine.

This study investigates the formation of atmospheric molecular clusters containing ammonia (NH3, A), methylamine (CH3NH2, MA), or dimethylamine (CH3NHCH3, DMA) with nitric acid (HNO3, NA) using quantum mechanics. The Atmospheric Cluster Dynamic Code (ACDC) was employed to simulate the total evaporation rate, formation rate, and growth pathways of three types of clusters under dry and hydrated conditions. This study evaluates the enhancing potential of A/MA/DMA for NA-based new particle formation (NPF) at parts per trillion (ppt) levels. The results indicate that A/MA/DMA can enhance NA-based NPF at high nitric acid concentrations and low temperatures in the atmosphere. The enhancing potential of MA is weaker than that of DMA but stronger than that of A. Cluster growth predominantly follows the lowest free energy pathways on the acid-base grid, with the formation of initial acid-base dimers (NA)(A), (NA)(MA), and (NA)(DMA) being crucial. Hydration influences the evaporation rate and formation rate of clusters, especially for initial clusters. When the humidity is at 100%, the formation rate for NA-A, NA-MA, and NA-DMA clusters can increase by approximately 109, 107, and 104-fold compared to the corresponding unhydrated clusters, respectively. These results highlight the significance of nitric acid nucleation in NPF events in low-temperature, high-humidity atmospheres, particularly in regions like China with significant automobile exhaust pollution.

Polyamine Derived Photosensitizer: A Novel Approach for Photodynamic Therapy of Cancer.

Polyamines play a pivotal role in cancer cell proliferation. The excessive polyamine requirement of these malignancies is satisfied through heightened biosynthesis and augmented extracellular uptake via the polyamine transport system (PTS) present on the cell membrane. Meanwhile, photodynamic therapy (PDT) emerges as an effective anti-cancer treatment devoid of drug resistance. Recognizing these intricacies, our study devised a novel polyamine-derived photosensitizer (PS) for targeted photodynamic treatment, focusing predominantly on pancreatic cancer cells. We synthesized and evaluated novel spermine-derived fluorescent probes (N2) and PS (N3), exhibiting selectivity towards pancreatic cancer cells via PTS. N3 showed minimal dark toxicity but significant phototoxicity upon irradiation, effectively causing cell death in vitro. A significant reduction in tumor volume was observed post-treatment with no pronounced dark toxicity using the pancreatic cancer CDX mouse model, affirming the therapeutic potential of N3. Overall, our findings introduce a promising new strategy for cancer treatment, highlighting the potential of polyamine-derived PSs in PDT.

Selective Synthesis of Mono- and Bis-Phosphorylated (Dihydro)pyrans via TMSCl-Mediated Cascade Phosphorylation Cycloisomerization of Enynones.

A chlorotrimethylsilane (TMSCl)-mediated cascade phosphorylation and cycloisomerization of enynones with diphenylphosphine oxides is presented. This methodology enables the highly selective synthesis of monophosphorylated 2H-pyrans and bisphosphorylated dihydropyrans through precise solvent-reagent stoichiometry control. The strategy demonstrated excellent functional group compatibility and high yields (up to 96%), providing facile access to structurally diverse phosphorylated heterocycles with potential applications in medicinal chemistry and materials science.

Palladium-Catalyzed Four-Component Radical Cascade Carbonylation Access to 2,3-Disubstituted Benzofuran Derivatives.

Multicomponent radical tandem reactions have emerged as a crucial technique for synthesizing complex molecules in organic chemistry. In this study, we report a palladium-catalyzed four-component difluoroalkylative carbonylation of enynes and ethyl difluoroiodoacetate. This transformation proceeds through a multistep sequential reaction that introduces reactive difluoro and carbonyl groups while constructing the benzofuran skeleton. Moreover, a variety of valuable 2,3-disubstituted benzofuran derivatives were obtained in respectable yields with excellent functional group compatibility.

Nickel-Catalyzed Narasaka-Heck Cyclization Carbonylation of Unsaturated Oxime Esters with Arylboronic Acids.

The Narasaka-Heck reaction is one of the most straightforward methods for constructing pyrroline derivatives. Herein, we report a novel nickel-catalyzed three-component carbonylation reaction, which cleverly realizes the continuous construction of C(sp3)-N bonds and C(sp3)-C(sp2) bonds and effectively promotes the synthesis of acyl-substituted pyrroline derivatives. Furthermore, this strategy not only expands the conversion pathway of γ,δ-unsaturated oxime esters but also provides a new method for the synthesis of nitrogen-containing heterocyclic compounds.

Do Confidence Ratings Reactively Modify Children's Academic Assessment Performance? Negative Answer from a Three-Year Longitudinal Study.

The reactivity effect of metacognitive judgments on first-order task performance has received increased research attention. Previous studies showed that soliciting retrospective confidence ratings (CRs) reactively enhances task performance itself, such as performance in decision making and reasoning tasks, especially for those with high self-confidence. It remains unknown whether CRs can improve students' academic assessment performance in real educational settings. The current study recruited 795 fourth-grade elementary school children to explore if making CRs reactively affects students' academic assessment performance in two main subjects (i.e., Chinese Language and Mathematics). The data were collected across six waves with half-year intervals. From Wave 2, children either provided (CR group) or did not provide CRs (no-CR group) when completing standardized academic assessments. The results showed Bayesian evidence supporting the claim that making CRs does not influence children's academic assessment performance (both the average performance across waves 2-6 and the performance in each wave) in both subjects. Furthermore, children's self-confidence did not moderate the reactive influence of CRs. The results from multilevel regression analyses re-confirmed the above conclusions. Possible explanations for the absence of the reactivity effect of CRs on children's academic assessment performance are discussed.

Quantitative Trait Loci Mapping of Heading Date in Wheat under Phosphorus Stress Conditions.

Wheat (Triticum aestivum L.) is a crucial cereal crop, contributing around 20% of global caloric intake. However, challenges such as diminishing arable land, water shortages, and climate change threaten wheat production, making yield enhancement crucial for global food security. The heading date (HD) is a critical factor influencing wheat's growth cycle, harvest timing, climate adaptability, and yield. Understanding the genetic determinants of HD is essential for developing high-yield and stable wheat varieties. This study used a doubled haploid (DH) population from a cross between Jinmai 47 and Jinmai 84. QTL analysis of HD was performed under three phosphorus (P) treatments (low, medium, and normal) across six environments, using Wheat15K high-density SNP technology. The study identified 39 QTLs for HD, distributed across ten chromosomes, accounting for 2.39% to 29.52% of the phenotypic variance. Notably, five stable and major QTLs (Qhd.saw-3A.7, Qhd.saw-3A.8, Qhd.saw-3A.9, Qhd.saw-4A.4, and Qhd.saw-4D.3) were consistently detected across varying P conditions. The additive effects of these major QTLs showed that favorable alleles significantly delayed HD. There was a clear trend of increasing HD delay as the number of favorable alleles increased. Among them, Qhd.saw-3A.8, Qhd.saw-3A.9, and Qhd.saw-4D.3 were identified as novel QTLs with no prior reports of HD QTLs/genes in their respective intervals. Candidate gene analysis highlighted seven highly expressed genes related to Ca2+ transport, hormone signaling, glycosylation, and zinc finger proteins, likely involved in HD regulation. This research elucidates the genetic basis of wheat HD under P stress, providing critical insights for breeding high-yield, stable wheat varieties suited to low-P environments.

Effects of inactivated Lactobacillus rhamnosus on growth performance, serum indicators, and colonic microbiota and metabolism of weaned piglets.

BACKGROUND: To assess the effects of inactivated Lactobacillus rhamnosus (ILR) on growth performance, serum biochemical indices, colonic microbiota, and metabolomics in weaned piglets, 120 piglets were randomly divided into five groups. Samples in the control group were fed a basal diet, while the experimental ILR1, ILR2, ILR3, and ILR4 groups were fed basal diets supplemented with 0.1%, 0.2%, 0.3%, and 0.4% ILR, respectively. The prefeeding period lasted for 5 days and was followed by a formal period of 28 days. RESULTS: Compared to the control, the average daily gain increased by 4.38%, 7.98%, 19.32%, and 18.80% for ILR1, ILR2, ILR3, and ILR4, respectively, and the ratio of feed to gain decreased by 0.63%, 3.80%, 12.66%, and 10.76%, respectively. Serum IgA, IgG, IgM, total antioxidant capacity, and glutathione peroxidase levels increased significantly in weaned piglets in the treatment groups. Addition of 0.3% ILR significantly increased the Shannon and Simpson indices of the colonic microbiota in weaned piglets and altered the microbiota composition. Changes in metabolic profiles were observed and were primarily related to the urea cycle, amino acid metabolism, and lipid metabolism. CONCLUSION: ILR improved growth performance and serum immunological and biochemical indices and optimized the colonic microbiota structure and metabolism of weaned piglets.

Targeting the phosphatidylglycerol lipid: An amphiphilic dendrimer as a promising antibacterial candidate.

The rapid emergence and spread of multidrug-resistant bacterial pathogens require the development of antibacterial agents that are robustly effective while inducing no toxicity or resistance development. In this context, we designed and synthesized amphiphilic dendrimers as antibacterial candidates. We report the promising potent antibacterial activity shown by the amphiphilic dendrimer AD1b, composed of a long hydrophobic alkyl chain and a tertiary amine-terminated poly(amidoamine) dendron, against a panel of Gram-negative bacteria, including multidrug-resistant Escherichia coli and Acinetobacter baumannii. AD1b exhibited effective activity against drug-resistant bacterial infections in vivo. Mechanistic studies revealed that AD1b targeted the membrane phospholipids phosphatidylglycerol (PG) and cardiolipin (CL), leading to the disruption of the bacterial membrane and proton motive force, metabolic disturbance, leakage of cellular components, and, ultimately, cell death. Together, AD1b that specifically interacts with PG/CL in bacterial membranes supports the use of small amphiphilic dendrimers as a promising strategy to target drug-resistant bacterial pathogens and addresses the global antibiotic crisis.

Blood Plasma Film Multifractal Scanning in COVID-19 Consequences Diagnostics.

A 3D phase scanning method was applied to study blood plasma facies, generating layered polarization maps of the object field. The most sensitive parameters to changes in birefringence distribution were identified. Multifractal analysis using wavelet transforms and fractal dimension spectra provided specific insights into the scale self-similarity of the polarization maps. The multifractal spectra of ellipticity distributions were algorithmically derived, revealing that the third- and fourth-order statistical moments were most sensitive to changes in the supramolecular networks of the facies. These findings were successfully applied to differentiate post-COVID-19 effects with high accuracy.

A self-fused peptide-loaded hydrogel with injectability and tissue-adhesiveness for preventing postoperative peritoneal adhesions.

Peritoneal adhesions commonly occur following abdominal or pelvic surgery and can cause serious complications. Currently, physical barriers are the primary approach used in clinical practice to prevent adhesion, although their effectiveness is frequently inadequate. In this study, we developed an injectable peptide-loaded hydrogel with multiple functions, including self-fusion, tissue-adhesiveness, anti-inflammation, anti-cell adhesion and anti-angiogenesis. To assess the effectiveness of these hydrogels, which are stabilized by dynamic imine bonds and acetal connections, in preventing postoperative abdominal adhesions, we utilized both a rat abdominal adhesion model and a rat model simulating repeated-injury adhesions. In comparison to the commercially available HA hydrogel, as-prepared hydrogels exhibited significant reductions in inflammation, fibrosis, and angiogenesis, leading to an obvious decrease in peritoneal adhesions. Moreover, this peptide-loaded hydrogel demonstrated an ideal degradation time, maintaining an in vivo viability for about 10 days. We believe this peptide-loaded hydrogel presents a promising solution for the challenging clinical issue of postoperative abdominal adhesions.

Risk factors and clinical significance of posterior slip of the proximal vertebral body after lower lumbar fusion.

BACKGROUND: Adjacent segment disease (ASD) after fusion surgery is frequently manifests as a cranial segment instability, disc herniation, spinal canal stenosis, spondylolisthesis or retrolisthesis. The risk factors and mechanisms of ASD have been widely discussed but never clearly defined. AIM: To investigate the risk factors and clinical significance of retrograde movement of the proximal vertebral body after lower lumbar fusion. METHODS: This was a retrospective analysis of the clinical data of patients who underwent transforaminal lumbar interbody fusion surgery between September 2015 and July 2021 and who were followed up for more than 2 years. Ninety-one patients with degenerative lumbar diseases were included (22 males and 69 females), with an average age of 52.3 years (40-73 years). According to whether there was retrograde movement of the adjacent vertebral body on postoperative X-rays, the patients were divided into retrograde and nonretrograde groups. The sagittal parameters of the spine and pelvis were evaluated before surgery, after surgery, and at the final follow-up. At the same time, the Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) were used to evaluate the patients' quality of life. RESULTS: Nineteen patients (20.9%) who experienced retrograde movement of proximal adjacent segments were included in this study. The pelvic incidence (PI) of the patients in the retrograde group were significantly higher than those of the patients in the nonretrograde group before surgery, after surgery and at the final follow-up (P < 0.05). There was no significant difference in lumbar lordosis (LL) between the two groups before the operation, but LL in the retrograde group was significantly greater than that in the nonretrograde group postoperatively and at the final follow-up. No significant differences were detected in terms of the |PI-LL|, and there was no significant difference in the preoperative lordosis distribution index (LDI) between the two groups. The LDIs of the retrograde group were 68.1% ± 11.5% and 67.2% ± 11.9%, respectively, which were significantly lower than those of the nonretrograde group (75.7% ± 10.4% and 74.3% ± 9.4%, respectively) (P < 0.05). Moreover, the patients in the retrograde group had a greater incidence of a LDI < 50% than those in the nonretrograde group (P < 0.05). There were no significant differences in the ODI or VAS scores between the two groups before the operation, but the ODI and VAS scores in the retrograde group were significantly worse than those in the nonretrograde group after the operation and at the last follow-up, (P < 0.05). CONCLUSION: The incidence of posterior slippage after lower lumbar fusion was approximately 20.9%. The risk factors are related to a higher PI and distribution of lumbar lordosis. When a patient has a high PI and insufficient reconstruction of the lower lumbar spine, adjacent segment compensation via posterior vertebral body slippage is one of the factors that significantly affects surgical outcomes.

Tackling Event-Based Lip-Reading by Exploring Multigrained Spatiotemporal Clues.

Automatic lip-reading (ALR) is the task of recognizing words based on visual information obtained from the speaker's lip movements. In this study, we introduce event cameras, a novel type of sensing device, for ALR. Event cameras offer both technical and application advantages over conventional cameras for ALR due to their higher temporal resolution, less redundant visual information, and lower power consumption. To recognize words from the event data, we propose a novel multigrained spatiotemporal features learning framework, which is capable of perceiving fine-grained spatiotemporal features from microsecond time-resolved event data. Specifically, we first convert the event data into event frames of multiple temporal resolutions to avoid losing too much visual information at the event representation stage. Then, they are fed into a multibranch subnetwork where the branch operating on low-rate frames can perceive spatially complete but temporally coarse features, while the branch operating on high frame rate can perceive spatially coarse but temporally fine features. Thus, fine-grained spatial and temporal features can be simultaneously learned by integrating the features perceived by different branches. Furthermore, to model the temporal relationships in the event stream, we design a temporal aggregation subnetwork to aggregate the features perceived by the multibranch subnetwork. In addition, we collect two event-based lip-reading datasets (DVS-Lip and DVS-LRW100) for the study of the event-based lip-reading task. Experimental results demonstrate the superiority of the proposed model over the state-of-the-art event-based action recognition models and video-based lip-reading models.

The effect of different potency glucocorticosteroids treatments on tear inflammatory factors and corneal optical density after femtosecond-assisted laser in situ keratomileusis.

To assess the impact of glucocorticosteroids with varying potencies on inflammatory mediators in tears and corneal optical density after femtosecond-assisted laser in situ keratomileusis (FS-LASIK). In a prospective study, 110 patients (220 eyes) who underwent FS-LASIK were divided into 2 groups: 55 patients (110 eyes) received dexamethasone, and another 55 patients (110 eyes) received fluorometholone. Visual acuity, intraocular pressure, and corneal optical density were measured before, 1 week, and 1 month after surgery. Tear fluid samples were also collected to assess expression levels of TNF-α, IL-1α, IL-6, and TGF-ß1. One week after the procedure, the dexamethasone group exhibited elevated intraocular pressure (IOP) levels (P > .05) and a decreased expression of TNF-α in tears (P < .001) compared to the fluorometholone group. Within the 0 to 2 mm range from the corneal apex, the anterior corneal layer's optical density in the fluorometholone group surpassed that of the dexamethasone group (P < .05). At 1 month post-surgery, the IOP in the fluorometholone group was higher than that in the dexamethasone group (P < .05). In both the 0 to 2 mm and 2 to 6 mm intervals from the corneal apex, the optical density of the anterior corneal layer was significantly higher in the fluorometholone group compared to the dexamethasone group (P < .05). There was no statistically significant difference in visual acuity between the 2 groups at any postoperative time point. Short-term use of potent corticosteroids after FS-LASIK can swiftly address ocular surface inflammation, enhance corneal wound healing, reduce corneal edema, and accelerate the restoration of corneal transparency, in contrast to prolonged use of milder corticosteroids post-surgery.