Tuning vibration-induced emission through macrocyclization and catenation.

In order to investigate the effect of macrocyclization and catenation on the regulation of vibration-induced emission (VIE), the typical VIE luminogen 9,14-diphenyl-9,14-dihydrodibenzo[a, c]phenazine (DPAC) was introduced into the skeleton of a macrocycle and corresponding [2]catenane to evaluate their dynamic relaxation processes. As investigated in detail by femtosecond transient absorption (TA) spectra, the resultant VIE systems revealed precisely tunable emissions upon changing the solvent viscosity, highlighting the key effect of the formation of [2]catenane. Notably, the introduction of an additional pillar[5]arene macrocycle featuring unique planar chirality endows the resultant chiral VIE-active [2]catenane with attractive circularly polarized luminescence in different states. This work not only develops a new strategy for the design of new luminescent systems with tunable vibration induced emission, but also provides a promising platform for the construction of smart chiral luminescent materials for practical applications.

Gas explosion characteristics and spray control mechanism in underground square.

The spray system mechanism during a gas explosion in an underground square pipeline is complex. In this paper, the underground square of Fuxin City is selected as the research object. FLACS numerical simulation software is used to analyze the spatial and temporal distribution characteristics of a gas explosion in an underground square pipeline with an unopened spray system using combustion and combustion rate models. Different spray pressures were compared and analyzed to determine the optimal spray control pressure, and the spray system mechanism was clarified. The results revealed that the gas explosion overpressure is divided into the overpressure gentle, overpressure rising, and overpressure decay stages, corresponding to a trend of rapid growth and slow decline. The influence of spray pressure on the gas explosion exhibits a promotion-inhibition-promotion trend, corresponding to 0-0.2 MPa, 0.2-0.6 MPa, and 0.6-1.6 Mpa, respectively. The peak overpressure and overpressure propagation rates are the lowest at 0.6 MPa, and the explosion suppression effect is the most pronounced. The spray system mechanism varies with the explosion overpressure stages. Generally, the time to peak value, that is, the peak time, the overall duration of the explosion, and the duration of the explosion stage decrease, whereas the peak explosion overpressure decreases.

A Carbon-Caged Rhodamine Generating Nitrosoperoxycarbonate for Photoimmunotherapy.

Photoimmunotherapy is a promising cancer treatment modality. While potent 1-e- oxidative species are known to induce immunogenic cell death (ICD), they are also associated with unspecific oxidation and collateral tissue damage. This difficulty may be addressed by post-generation radical reinforcement. Namely, non-oxidative radicals are first generated and subsequently activated into powerful oxidative radicals to induce ICD. Here, we developed a photo-triggered molecular donor (NPCD565) of nitrosoperoxycarbonate (ONOOCO2 -), the first of its class to our knowledge, and further evaluated its feasibility for immunotherapy. Upon irradiation of NPCD565 by light within a broad spectral region from ultraviolet to red, ONOOCO2 - is released along with a bright rhodamine dye (RD565), whose fluorescence is a reliable and convenient build-in reporter for the localization, kinetics, and dose of ONOOCO2 - generation. Upon photolysis of NPCD565 in 4T1 cells, damage-associated molecular patterns (DAMPs) indicative of ICD were observed and confirmed to exhibit immunogenicity by induced maturation of dendritic cells. In vivo studies with a bilateral tumor-bearing mouse model showcased the potent tumor-killing capability of NPCD565 of the primary tumors and growth suppression of the distant tumors. This work unveils the potent immunogenicity of ONOOCO2 -, and its donor (NPCD565) has broad potential for photo-immunotherapy of cancer.

Ultrafast and Multichannel Generation of the Triplet State in DNA-Intercalated Gilvocarcin V for an Enhanced Photoaddition Reaction.

Gilvocarcin V (GV) is a natural antibiotic exhibiting excellent antitumor activities and remarkably low toxicity in near-ultraviolet or visible light-dependent treatment. Notwithstanding, the [2 + 2] cycloaddition reaction between GV and thymine has been proven to be the key for its function in photodynamic therapy, and crucial mechanistic details about such a reaction are poorly understood. In this study, the electronic relaxation pathways and photoaddition reaction are characterized by femto- to nanosecond time-resolved spectroscopy combined with quantum chemical calculation. Our results reveal that ultrafast intersystem crossing (<3 ps) leads to the population of a local triplet excited state in DNA-intercalated GV. Such a state can further induce the formation of a biradical state, which is identified as the important reactive precursor for photoaddition between GV and thymine. The overall photoaddition quantum efficiency is determined to be 11.57 ± 1.0%. These results are essential to the elucidation of the DNA photoaddition mechanism of C-aryl glycoside-based artificial photocytotoxic agents and could help further development of those medicines.

Ultrafast spectroscopy study of DNA photophysics after proflavine intercalation.

Proflavine (PF), an acridine DNA intercalating agent, has been widespread applied as an anti-microbial and topical antiseptic agent due to its ability to suppress DNA replication. On the other hand, various studies show that PF intercalation to DNA can increase photogenotoxicity and has potential chances to induce carcinomas of skin appendages. However, the effects of PF intercalation on the photophysical and photochemical properties of DNA have not been sufficiently explored. In this study, the excited state dynamics of the PF intercalated d(GC)9 • d(GC)9 and d(AT)9 • d(AT)9 DNA duplex are investigated in an aqueous buffer solution. Under 267 nm excitation, we observed ultrafast charge transfer (CT) between PF and d(GC)9 • d(GC)9 duplex, generating a CT state with an order of magnitude longer lifetime compared to that of the intrinsic excited state reported for the d(GC)9 • d(GC)9 duplex. In contrast, no excited state interaction was detected between PF and d(AT)9 • d(AT)9. Nevertheless, a localized triplet state with a lifetime over 5 µs was identified in the PF-d(AT)9 • d(AT)9 duplex.

The identification of signature genes and their relationship with immune cell infiltration in age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is a prevalent source of visual impairment among the elderly population, and its incidence has risen in tandem with the increasing longevity of humans. Despite the progress made with anti-VEGF therapy, clinical outcomes have proven to be unsatisfactory. METHOD: We obtained differentially expressed genes (DEGs) of AMD patients and healthy controls from the GEO database. GO and KEGG analyses were used to enrich the DEGs. Weighted gene coexpression network analysis (WGCNA) was used to identify modules related to AMD. SVM, random forest, and least absolute shrinkage and selection operator (LASSO) were employed to screen hub genes. Gene set enrichment analysis (GSEA) was used to explore the pathways in which these hub genes were enriched. CIBERSORT was utilized to analyze the relationship between the hub genes and immune cell infiltration. Finally, Western blotting and RT‒PCR were used to explore the expression of hub genes in AMD mice. RESULTS: We screened 1084 DEGs in GSE29801, of which 496 genes were upregulated. These 1084 DEGs were introduced into the WGCNA, and 94 genes related to AMD were obtained. Seventy-nine overlapping genes were obtained by the Venn plot. These 79 genes were introduced into three machine-learning methods to screen the hub genes, and the genes identified by the three methods were TNC, FAP, SREBF1, and TGF-ß2. We verified their diagnostic function in the GSE29801 and GSE103060 datasets. Then, the hub gene co-enrichment pathways were obtained by GO and KEGG analyses. CIBERSORT analysis showed that these hub genes were associated with immune cell infiltration. Finally, we found increased expression of TNC, FAP, SREBF1, and TGF-ß2 mRNA and protein in the retinas of AMD mice. CONCLUSION: We found that four hub genes, namely, FAP, TGF-ß2, SREBF1, and TNC, have diagnostic significance in patients with AMD and are related to immune cell infiltration. Finally, we determined that the mRNA and protein expression of these hub genes was upregulated in the retinas of AMD mice.

Non-Faradaic optoelectrodes for safe electrical neuromodulation.

Nanoscale optoelectrodes hold the potential to stimulate optically individual neurons and intracellular organelles, a challenge that demands both a high-density of photoelectron storage and significant charge injection. Here, we report that zinc porphyrin, commonly used in dye-sensitized solar cells, can be self-assembled into nanorods and then coated by TiO2. The J-aggregated zinc porphyrin array enables long-range exciton diffusion and allows for fast electron transfer into TiO2. The formation of TiO2(e-) attracts positive charges around the neuron membrane, contributing to the induction of action potentials. Far-field cranial irradiation of the motor cortex using a 670 nm laser or an 850 nm femtosecond laser can modulate local neuronal firing and trigger motor responses in the hind limb of mice. The pulsed photoelectrical stimulation of neurons in the subthalamic nucleus alleviates parkinsonian symptoms in mice, improving abnormal stepping and enhancing the activity of dopaminergic neurons. Our results suggest injectable nanoscopic optoelectrodes for optical neuromodulation with high efficiency and negligible side effects.

Ultrafast Formation of a Delocalized Triplet-Excited State in an Epigenetically Modified DNA Duplex under Direct UV Excitation.

Epigenetic modifications impart important functionality to nucleic acids during gene expression but may increase the risk of photoinduced gene mutations. Thus, it is crucial to understand how these modifications affect the photostability of duplex DNA. In this work, the ultrafast formation (<20 ps) of a delocalized triplet charge transfer (CT) state spreading over two stacked neighboring nucleobases after direct UV excitation is demonstrated in a DNA duplex, d(G5fC)9•d(G5fC)9, made of alternating guanine (G) and 5-formylcytosine (5fC) nucleobases. The triplet yield is estimated to be 8 ± 3%, and the lifetime of the triplet CT state is 256 ± 22 ns, indicating that epigenetic modifications dramatically alter the excited state dynamics of duplex DNA and may enhance triplet state-induced photochemistry.

Dual Stimuli-Responsive [2]Rotaxanes with Tunable Vibration-Induced Emission and Switchable Circularly Polarized Luminescence.

Aiming at the construction of novel stimuli-responsive fluorescent system with precisely tunable emissions, the typical 9,14-diphenyl-9,14-dihydrodibenzo[a, c]phenazine (DPAC) luminogen with attractive vibration-induced emission (VIE) behavior has been introduced into [2]rotaxane as a stopper. Taking advantage of their unique dual stimuli-responsiveness towards solvent and anion, the resultant [2]rotaxanes reveal both tunable VIE and switchable circularly polarized luminescence (CPL). Attributed to the formation of mechanical bonds, DPAC-functionalized [2]rotaxanes display interesting VIE behaviors including white-light emission upon the addition of viscous solvent, as evaluated in detail by femtosecond transient absorption (TA) spectra. In addition, ascribed to the regulation of chirality information transmission through anion-induced motions of chiral wheel, the resolved chiral [2]rotaxanes reveal unique switchable CPL upon the addition of anion, leading to significant increase in the dissymmetry factors (glum ) values with excellent reversibility. Interestingly, upon doping the chiral [2]rotaxanes in stretchable polymer, the blend films reveal remarkable emission change from white light to light blue with significant 6.5-fold increase in glum values up to -0.035 under external tensile stresses. This work provides not only a new design strategy for developing molecular systems with fluorescent tunability but also a novel platform for the construction of smart chiral luminescent materials for practical use.

Bacteria-loaded biochar for the immobilization of cadmium in an alkaline-polluted soil.

The combination of biochar and bacteria is a promising strategy for the remediation of Cd-polluted soils. However, the synergistic mechanisms of biochar and bacteria for Cd immobilization remain unclear. In this study, the experiments were conducted to evaluate the effects of the combination of biochar and Pseudomonas sp. AN-B15, on Cd immobilization, soil enzyme activity, and soil microbiome. The results showed that biochar could directly reduce the motility of Cd through adsorption and formation of CdCO3 precipitates, thereby protecting bacteria from Cd toxicity in the solution. In addition, bacterial growth further induces the formation of CdCO3 and CdS and enhances Cd adsorption by bacterial cells, resulting in a higher Cd removal rate. Thus, bacterial inoculation significantly enhances Cd removal in the presence of biochar in the solution. Moreover, soil incubation experiments showed that bacteria-loaded biochar significantly reduced soil exchangeable Cd in comparison with other treatments by impacting soil microbiome. In particular, bacteria-loaded biochar increased the relative abundance of Bacillus, Lysobacter, and Pontibacter, causing an increase in pH, urease, and arylsulfatase, thereby passivating soil exchangeable Cd and improving soil environmental quality in the natural alkaline Cd-contaminated soil. Overall, this study provides a systematic understanding of the synergistic mechanisms of biochar and bacteria for Cd immobilization in soil and new insights into the selection of functional strain for the efficient remediation of the contaminated environments by bacterial biochar composite.

Research progress on applications and mechanisms of osteogenesis effect of magnetic fields in oral field / 口腔疾病防治

@#Magnetic fields are safe and used in noninvasive physical therapies. Numerous studies have confirmed that magnetic fields have good osteogenic effects and certain value for clinical application in accelerating orthodontic tooth movement, promoting bone-implant integration, promoting fracture healing and improving the effects of distraction osteogenesis. Magnetic fields are expected to become applied as effective auxiliary methods for treating oral diseases. To support the clinical application of magnetic fields, this article reviews the applications of magnetic fields in the oral cavity, the biological effects on bone cells and the molecular mechanisms through which magnetic fields regulate bone metabolism. The biological effects of magnetic fields on bone cells include promoting osteogenesis by osteoblasts and mesenchymal stem cells and inhibiting bone resorption by osteoclasts. At the molecular level, bone cells sense and respond to magnetic stimulation, and through various mechanisms, such as displacement currents, Lorentz forces, and free radical pair effects, stimuli are transformed into biologically recognizable electrical signals that activate complex downstream signaling pathways, such as the P2 purinergic receptor signaling pathway, adenosine receptor signaling pathway, transforming growth factor-β receptor signaling pathway, mammalian target of rapamycin (mTOR) pathway, and Notch pathway. In addition, magnetic parameters, which are the factors affecting the osteogenic effects of magnetic fields, are discussed. However, the mechanisms of the osteogenic effects of magnetic fields are unclear, and further studies of these mechanisms could provide effective strategies for bone regeneration and periodontal tissue regeneration. In addition, considering the target of magnetic field therapies, combination with other drugs could lead to new strategies for the treatment of oral diseases.

Development of a ferroptosis-based molecular markers for predicting RFS in prostate cancer patients.

The goal of this study was to develop a ferroptosis-based molecular signature that can predict recurrence-free survival (RFS) in patients with prostate cancer (PCa). In this study, we obtained ferroptosis-related genes (FRGs) in FerrDb database and clinical transcriptome data in TCGA database and GEO database. Consensus cluster analysis was used to identify three molecular markers of ferroptosis in PCa with differential expression of 40 FRGs, including PD-L1 expression levels. We conducted a new ferroptosis-related signature for PCa RFS using four FRGs identified through univariate and multivariate Cox regression analyses. The signature was validated in the training, testing, and validation cohorts, and it demonstrated remarkable results in the area under the time-dependent receiver operating characteristic (ROC) curve of 0.757, 0.715, and 0.732, respectively. Additionally, we observed that younger patients, those with stage T III and stage T IV, stage N0, cluster 1, and cluster 2 PCa were more accurately predicted by the signature as independent predictors of RFS. DU-145 and RWPE-1 cells were successfully analyzed by qRT-PCR and Western blot for ASNS, GPT2, RRM2, and NFE2L2. In summary, we developed a novel ferroptosis-based signature for RFS in PC, utilizing four FRGs identified through univariate and multivariate Cox regression analyses. This signature was rigorously validated across training, testing, and validation cohorts, demonstrating exceptional performance as evidenced by its ROC curves. Notably, our findings indicate that this signature is particularly effective as an independent predictor of RFS in younger patients or those with stage T III and T IV, stage N0, and in clusters 1 and 2. Finally, we confirmed the expression of these four FRGs in DU-145 and RWPE-1 cell lines.

Acyl-caged rhodamines: photo-controlled and self-calibrated generation of acetyl radicals for neural function recovery in early AD mice.

The biological function of radicals is a broad continuum from signaling to killing. Yet, biomedical exploitation of radicals is largely restricted to the theme of healing-by-killing. To explore their potential in healing-by-signaling, robust radical generation methods are warranted. Acyl radicals are endogenous, exhibit facile chemistry and elicit matrix-dependent biological outcomes. Their implications in health and disease remain untapped, primarily due to the lack of a robust generation method with spatiotemporal specificity. Fusing the Norrish chemistry into the xanthene scaffold, we developed a novel general and modular molecular design strategy for photo-triggered generation of acyl radicals, i.e., acyl-caged rhodamine (ACR). A notable feature of ACR is the simultaneous release of a fluorescent probe for cell redox homeostasis allowing real-time monitoring of the biological outcome of acyl radicals. With a donor of the endogenous acetyl radical (ACR575a), we showcased its capability in precise and continuous modulation of the cell redox homeostasis from signaling to stress, and induction of a local oxidative burst to promote differentiation of neural stem cells (NSCs). Upon intracerebral-injection of ACR575a and subsequent fiber-optical activation, early AD mice exhibited enhanced differentiation of NSCs toward neurons, reduced formation of Aß plaques, and significantly improved cognitive abilities, including learning and memory.

Research on escalators used as evacuation stairs under fire scenarios.

Shopping malls are crowded areas which makes the evacuation routes unable to meet personnel evacuation needs. Therefore, this paper proposes the idea of using escalators evacuation to increasing evacuation routes. In addition, the effects of escalator fire shutters on the use of escalator evacuation paths, and the efficiency of mall personnel evacuation under different conditions were simulated. The results show that the different states of fire shutters have different effects on the emergency evacuation. When the fire shutter is not lowered, it will result in 1 person not being evacuated to complete. However, when the fire shutter is lowered to 1.8 m from the ground or sprinklers are set, escalators can be used for evacuation routes are verified. And compared to the normal descent of the fire shutter (only the staircase evacuation, 2 people not evacuate completed), the evacuation of people is completed and the efficiency of evacuation is improved. This result can improve the new evacuation model for emergency evacuation plans of shopping malls with escalators.

Mechanisms involved in the sequestration and resistance of cadmium for a plant-associated Pseudomonas strain.

Understanding Cd-resistant bacterial cadmium (Cd) resistance systems is crucial for improving microremediation in Cd-contaminated environments. However, these mechanisms are not fully understood in plant-associated bacteria. In the present study, we investigated the mechanisms underlying Cd sequestration and resistance in the strain AN-B15. These results showed that extracellular Cd sequestration by complexation in strain AN-B15 was primarily responsible for the removal of Cd from the solution. Transcriptome analyses have shown that the mechanisms of Cd resistance at the transcriptional level involve collaborative processes involving multiple metabolic pathways. The AN-B15 strain upregulated the expression of genes related to exopolymeric substance synthesis, metal transport, Fe-S cluster biogenesis, iron recruitment, reactive oxygen species oxidative stress defense, and DNA and protein repair to resist Cd-induced stress. Furthermore, inoculation with AN-B15 alleviated Cd-induced toxicity and reduced Cd uptake in the shoots of wheat seedlings, indicating its potential for remediation. Overall, the results improve our understanding of the mechanisms involved in Cd resistance in bacteria and thus have important implications for improving microremediation.

Catalytic enantioselective reductive alkynylation of amides enables one-pot syntheses of pyrrolidine, piperidine and indolizidine alkaloids.

The primary objective in synthetic organic chemistry is to develop highly efficient, selective, and versatile synthetic methodologies, which are essential for discovering new drug candidates and agrochemicals. In this study, we present a unified strategy for a one-pot, catalytic enantioselective synthesis of α-alkyl and α,α'-dialkyl pyrrolidine, piperidine, and indolizidine alkaloids using readily available amides and alkynes. This synthesis is enabled by the identification and development of an Ir/Cu/N-PINAP catalyzed highly enantioselective and chemoselective reductive alkynylation of α-unbranched aliphatic amides, which serves as the key reaction. This reaction is combined with Pd-catalyzed tandem reactions in a one-pot approach, enabling the collective, catalytic enantioselective total syntheses of eight alkaloids and an anticancer antipode with 90-98% ee. The methodology's enantio-divergence is exemplified by the one-step access to either enantiomer of alkaloid bgugaine.

Excitation localization/delocalization induced intramolecular singlet fission in cyclopentadithiophene-based quinoidal derivatives.

Two triplet excitons are generated through an ultrafast photophysical process, namely singlet fission (SF), providing a solution for efficient solar energy usage. In this work, we provide an effective guideline for designing SF materials by adjusting the planarity in cyclopentadithiophene (CPDT) derivatives. A practical strategy is proposed for tuning the quinoidal-biradical resonance structures by varying the electron push-pull groups of CPDTs for SF. The localized, delocalized, and intermediate charge-transfer excited configurations are predicted in the singlet excited state via computational simulations, which is further confirmed by ultrafast spectroscopy. Deduced from the potential energy surfaces in the low-lying excited states and transient absorption, the delocalized excited state is formed in 2.1 ps via postulated intramolecular SF in a polar solvent, followed by the ultrafast formation of the free triplet state with a lifetime of 6.8 ps. In comparison with different cross-conjugated chromophores, it is found that the increase in the charge separation could enhance the triplet-pair generation for iSF. We expect that by introducing symmetry-breaking modifications in the electronic configurations and adjusting the separation between the push-pull groups of CPDTs, it should be possible to prolong the duration of the free triplet state by preventing recombination within the triplet-pair excited configuration.

IL-8 Triggers Neutrophil Extracellular Trap Formation Through an Nicotinamide Adenine Dinucleotide Phosphate Oxidase- and Mitogen-Activated Protein Kinase Pathway-Dependent Mechanism in Uveitis.

Purpose: To explore the mechanism underlying IL-8-induced neutrophil extracellular trap (NET) formation in patients with ocular-active Behçet's disease (BD) and the effect of inhibiting NET formation on the severity of inflammation in experimental autoimmune uveitis (EAU) mice. Methods: The serum extracellular DNA and neutrophil elastase (NE) and IL-8 levels in patients with ocular-active BD, the expression of myeloperoxidase, NE, and histone H3Cit in IL-8-induced neutrophils isolated from healthy controls, and the effects of NETs on HMC3 cells were detected. Female C57BL/6J mice were immunized with IRBP651-670 to induce EAU and EAU mice received intravitreal injection of the CXCR2 (IL-8 receptor) antagonist SB225002 or PBS. The serum levels of extracellular DNA, NE, and keratinocyte-derived chemokine (the mouse ortholog of human IL-8) and expression of myeloperoxidase, NE, and histone H3Cit in mouse retinas were detected. Disease severity was evaluated by clinical and histopathological scores. Results: Serum keratinocyte-derived chemokine expression levels in EAU mice and IL-8 expression levels in patients with ocular-active BD increased. IL-8 notably increased NET formation in a dose-dependent manner through an nicotinamide adenine dinucleotide phosphate oxidase and mitogen-activated protein kinase pathway dependent mechanism. IL-8-induced NET formation damaged HMC3 cells in vitro. Pretreatment with SB225002 notably ameliorated the production of NETs in EAU mice. Conclusions: Our data confirm that NET formation is induced by IL-8. IL-8-induced NET formation was found to be related to mitogen-activated protein kinase and nicotinamide adenine dinucleotide phosphate pathways. Pretreatment with the CXCR2 antagonist SB225002 alleviated neutrophil infiltration and suppressed NET formation in EAU mice.

Plasmon-Induced Charge Transfer-Enhanced Raman Scattering on a Semiconductor: Toward Amplification-Free Quantification of SARS-CoV-2.

Semiconductors demonstrate great potentials as chemical mechanism-based surface-enhanced Raman scattering (SERS) substrates in determination of biological species in complex living systems with high selectivity. However, low sensitivity is the bottleneck for their practical applications, compared with that of noble metal-based Raman enhancement ascribed to electromagnetic mechanism. Herein, a novel Cu2 O nanoarray with free carrier density of 1.78×1021  cm-3 comparable to that of noble metals was self-assembled, creating a record in enhancement factor (EF) of 3.19×1010 among semiconductor substrates. The significant EF was mainly attributed to plasmon-induced hot electron transfer (PIHET) in semiconductor which was never reported before. This Cu2 O nanoarray was subsequently developed as a highly sensitive and selective SERS chip for non-enzyme and amplification-free SARS-CoV-2 RNA quantification with a detection limit down to 60 copies/mL within 5 min. This unique Cu2 O nanoarray demonstrated the significant Raman enhancement through PIHET process, enabling rapid and sensitive point-of-care testing of emerging virus variants.