High-Q integrated lithium tantalate microring resonators for on-chip comb generation.

Lithium tantalate on insulator (LTOI), taking advantage of high cost-effectiveness, ultra-low optical loss, and prominent electro-optic (EO) coefficient, shows great potential as an integrated waveguide-based optical platform for commercialization. Further research on monolithic nonlinear source generators with tunable features is crucial in its early stages. Here, we fabricate low-loss microring resonators (intrinsic Q value above 4 × 106) via universal subtractive manufacturing. Both Kerr and EO combs are realized based on X-cut LTOI high-Q resonators. Specifically, we elucidate the complicated synergy caused by a photorefractive (PR) effect and thermo-optic modulation, observing the soliton step using the facile laser scanning technique. Furthermore, the preliminary experimental result of the static EO comb is also exploited in a 20 GHz free spectral range (FSR) LTOI microring resonator, verifying the versatility of this unique photonic platform for on-chip microcomb generation.

Disturbance of mitochondrial dynamics led to spermatogenesis disorder in mice exposed to polystyrene micro- and nanoplastics.

The widespread presence of polystyrene micro- and nanoplastics (PS-MPs/NPs) in the environment poses a threat to the health of the population. Animal studies have shown PS-MPs/NPs had male reproductive toxicity, while its mechanisms are unclear. To investigate that, male Balb/c mice were randomized into 3 groups: the control, 1 µm PS-MPs and 70 nm PS-NPs group, and they were given PS-MPs/NPs by intratracheal instillation for 28 days. Results revealed that PS-MPs/NPs up-regulated the expression of mitochondrial fission related factors (p-DRP1/DRP1, FIS1) and down-regulated the level of mitochondrial fusion related factors (MFN1/2, OPA1), causing over mitochondrial fission, which activating mitochondrial apoptotic pathway (BAX, Cleaved-Caspase9, Cleaved-Caspase3), resulting in cell apoptosis. Moreover, the damaged structure of mitochondria and over mitochondrial fission caused mitochondrial DNA (mtDNA) to translocate from mitochondria to cytoplasm, which activated DNA sensing pathway (cGAS-STING) and induced cell pyroptosis in testis by raising the expression of inflammation factors (NLRP3, ASC, Caspase1 p20, IL-1ß). In vitro, by using the mitochondrial fission inhibitor Mdivi-1, it is found that PS-NPs-induced cell apoptosis and pyroptosis were associated with over mitochondrial fission. Taken together, we conclude that PS-MPs/NPs cause spermatogenesis disorder possibly through damaging mitochondrial structure and dynamic homeostasis, which on the one hand results in mitochondria-mediated apoptosis, and on the other hand leads to mtDNA mislocalization, activating cGAS-STING pathway and inflammation, ultimately resulting in pyroptosis. This study may provide a new reference to the potential mechanisms of male reproductive toxicity caused by PS-MPs/NPs.

Realizing Excellent Infrared Nonlinear Optical Performance in Eu-Based Chalcogenides via Rational Cross Substitution Strategy.

In recent years, rare-earth-based chalcogenides have gained attention promising materials in the field of infrared nonlinear optical (IR-NLO) applications owing to their exceptional physicochemical properties. However, they frequently encounter challenges such as adverse two-photon absorption and low laser-induced damage thresholds (LIDTs) caused by narrow optical band gaps (Eg), which limit their practical utility. In this study, we started with the centrosymmetric (CS) parent compound EuGa2S4 to develop two new noncentrosymmetric (NCS) Eu-based chalcogenides, namely, EuZnSiS4 and EuCdSiS4, employing a rational cross-substitution strategy. Despite having identical stoichiometry, both compounds crystallize in distinct NCS orthorhombic space groups [Fdd2 (no. 43) vs Ama2 (no. 40)], as confirmed by single-crystal structure analysis. Their crystal structures feature highly distorted tetrahedral motifs interconnected via corner-sharing, forming unique two-dimensional layers that host Eu2+ cations. Furthermore, both compounds exhibit robust phase-matching second-harmonic generation (SHG) intensities of 1.5 × AgGaS2 for EuZnSiS4 and 2.8 × AgGaS2 for EuCdSiS4 under 2050 nm excitation. They also demonstrate high LIDTs (approximately 14-17 × AgGaS2), wide Eg (>2.5 eV), and transparency windows extending up to 18.2 µm. Particularly noteworthy, EuCdSiS4 stands out as a pioneering example in the Eu-based IR-NLO system for successfully combining a broad Eg (>2.56 eV, equivalent to that of AgGaS2) with a significant SHG effect (>1.0 × AgGaS2) simultaneously. Structural analyses and theoretical insights underscore that the reasonable combination of asymmetric functional units plays a pivotal role in driving the CS-to-NCS structural transformation and enhancing the NLO and linear optical properties of these Eu-based chalcogenides. This study presents a promising chemical pathway for advancing rare-earth-based functional materials and suggests exciting opportunities for their future applications in IR-NLO technologies.

Characterising and differentiating cognitive and motor speed in older adults: structural equation modelling on a UK longitudinal birth cohort.

OBJECTIVES: Information processing speed (IPS) has been proposed to be a key component in healthy ageing and cognitive functioning. Yet, current studies lack a consistent definition and specific influential characteristics. This study aimed to investigate IPS as a multifaceted concept by differentiating cognitive and motor IPS. DESIGN, SETTING AND PARTICIPANTS: A retrospective data analysis using data from the Medical Research Council National Survey of Health and Development (a population-based cohort of UK adults born in 1946) at childhood (ages 8, 11 and 15) and adulthood (ages 60-64 and 68-70). Using structural equation modelling, we constructed two models of IPS with 2124 and 1776 participants, respectively. OUTCOME MEASURES: Measures of interest included IPS (ie, letter cancellation, simple and choice reaction time), intelligence (ie, childhood intelligence and National Adult Reading Test), verbal memory, socioeconomic status (SES) and cognitive functions measured by the Addenbrooke's Cognitive Examination III, as well as a variety of health indexes. RESULTS: We found distinct predictors for cognitive and motor IPS and how they relate to other cognitive functions in old age. In our first model, SES and antipsychotic medication usage emerged as significant predictors for cognitive IPS, intelligence and smoking as predictors for motor IPS while both share sex, memory and antiepileptic medication usage as common predictors. Notably, all differences between both IPS types ran in the same direction except for sex differences, with women performing better than men in cognitive IPS and vice versa in motor IPS. The second model showed that both IPS measures, as well as intelligence, memory, antipsychotic and sedative medication usage, explain cognitive functions later in life. CONCLUSION: Taken together, these results shed further light on IPS as a whole by showing there are distinct types and that these measures directly relate to other cognitive functions.

Screening Strategy Identifies an Overlooked Deep-Ultraviolet Transparent Nonlinear Optical Crystal.

In the deep-ultraviolet (DUV) region, nonlinear optical (NLO) crystals must meet stringent requirements, including a large optical band gap and sufficient second harmonic generation (SHG) response. Typically, these criteria are fulfilled by borates, carbonates and nitrates containing π-conjugated groups. In contrast, sulfates and phosphates, with polarizabilities significantly smaller than those of π-conjugated groups, struggle to achieve similar performance. Here, we present the discovery of Mg2PO4Cl, a magnesium-based phosphate, identified from over 10,000 phosphates based on a polar-axial-symmetry screening strategy, which exhibits the highest SHG response (5.2×KH2PO4 (KDP)) with phase-matching ability among non-π-conjugated DUV transparent NLO crystals. This compound belongs to the Pna21 space group, with [PO4] units consistently aligned along the 21 screw axis and glide planes throughout its crystal structure. Theoretical calculations attribute its remarkable SHG effect to the orderly arrangement of heteroanionic [MgO5Cl] and [MgO4Cl2] polyhedra alongside isolated [PO4] tetrahedra, supported by Berry phase analysis. Furthermore, a crystallographic structure analysis of phosphates and sulfates with significant SHG effects validates the effectiveness of our screening strategy. These findings offer valuable insights into the origins of NLO effects in non-π-conjugated compounds from both a material design and structural chemistry perspective, inspiring future efforts to revitalize DUV phosphates.

Extraction and Structural Analysis of Sweet Potato Pectin and Characterization of Its Gel.

Pectin is widely used in the food and pharmaceutical industries. However, data on sweet potato pectin extraction and structural property analyses are lacking. Here, for the high-value utilization of agricultural processing waste, sweet potato residue, a byproduct of sweet potato starch processing, was used as raw material. Ammonium oxalate, trisodium citrate, disodium hydrogen phosphate, hydrochloric acid and citric acid were used as extractants for the pectin constituents, among which ammonium oxalate had a high extraction rate of sweet potato pectin, low ash content and high molecular weight. Structural and gelation analyses were conducted on ammonium oxalate-extracted purified sweet potato pectin (AMOP). Analyses showed that AMOP is a rhamnogalacturonan-I-type pectin, with a molecular weight of 192.5 kg/mol. Chemical titration and infrared spectroscopy analysis confirmed that AMOP is a low-ester pectin, and scanning electron and atomic force microscopy demonstrated its linear molecular structure. Gelation studies have revealed that Ca2+ is the key factor for gel formation, and that sucrose significantly enhanced gel hardness. The highest AMOP gel hardness was observed at pH 4, with a Ca2+ concentration of 30 mg/g, pectin concentration of 2%, and sucrose concentration of 40%, reaching 128.87 g. These results provide a foundation for sweet potato pectin production and applications.

Wavelength-tunable high-fidelity entangled photon sources enabled by dual Stark effects.

The construction of a large-scale quantum internet requires quantum repeaters containing multiple entangled photon sources with identical wavelengths. Semiconductor quantum dots can generate entangled photon pairs deterministically with high fidelity. However, realizing wavelength-matched quantum-dot entangled photon sources faces two difficulties: the non-uniformity of emission wavelength and exciton fine-structure splitting induced fidelity reduction. Typically, these two factors are not independently tunable, making it challenging to achieve simultaneous improvement. In this work, we demonstrate wavelength-tunable entangled photon sources based on droplet-etched GaAs quantum dots through the combined use of AC and quantum-confined Stark effects. The emission wavelength can be tuned by ~1 meV while preserving an entanglement fidelity f exceeding 0.955(1) in the entire tuning range. Based on this hybrid tuning scheme, we finally demonstrate multiple wavelength-matched entangled photon sources with f > 0.919(3), paving the way towards robust and scalable on-demand entangled photon sources for quantum internet and integrated quantum optical circuits.

Alterations and associations between lung microbiota and metabolite profiles in silica-induced lung injury.

Silicosis, caused by silica exposure, is the most widespread and deadliest occupational disease. However, effective treatments are lacking. Therefore, it is crucial to elucidate the mechanisms and targets involved in the development of silicosis. We investigated the basic processes of silicosis development and onset at different exposure durations (2 or 4 weeks) using various techniques such as histopathology, immunohistochemistry, Enzyme linked immunosorbent assay(ELISA),16 S rRNA, and untargeted metabolomics.These results indicate that exposure to silica leads to progressive damage to lung tissue with significant deterioration observed over time. Time-dependent cytokines such as the IL-4, IL-13, and IL-6 are detected in lung lavage fluid, the model group consistently exhibited elevated levels of these cytokines, indicating a persistent and worsening inflammatory response in the lungs. Meanwhile, HE and Masson results show that 4-week exposure to silica causes more obvious lung injury and pulmonary fibrosis. Besides, the model group consistently exhibited a distinct lung bacterial population, known as the Lachnospiraceae_NK4A136_group, regardless of exposure duration. However, with increasing exposure duration, specific temporal changes were observed in lung bacterial populations, including Haliangium, Allobaculum, and Sandaracinus (at 4 weeks; p < 0.05). Furthermore, our study revealed a strong correlation between the mechanism of silica-induced lung injury and three factors: oxidative stress, impaired lipid metabolism, and imbalanced amino acid metabolism. We observed a close correlation between cytokine levels, changes in lung microbiota, and metabolic disturbances during various exposure periods. These findings propose that a possible mechanism of silica-induced lung injury involves the interplay of cytokines, lung microbiota, and metabolites.

Unveiling the role of mtDNA in Liver-Kidney Crosstalk: Insights from trichloroethylene hypersensitivity syndrome.

In specific pathological conditions, addressing liver injury may yield favorable effects on renal function through the phenomenon of liver-kidney crosstalk. Mitochondrial DNA (mtDNA) possesses the capability to trigger downstream pathways of inflammatory cytokines, ultimately leading to immune-mediated organ damage. Consequently, understanding the intricate molecular mechanisms governing mtDNA involvement in diseases characterized by liver-kidney crosstalk is of paramount significance. This study seeks to elucidate the role of mtDNA in conditions marked by liver-kidney crosstalk. In previous clinical cases, it has been observed that patients with Trichloroethylene Hypersensitivity Syndrome (TCE-HS) who experience severe liver injury often also exhibit renal injury. In this study, patients diagnosed with trichloroethylene hypersensitivity syndrome were recruited from Shenzhen Occupational Disease Control Center. And Balb/c mice were treated with trichloroethylene. The correlation between liver and kidney injuries in patients with TCE-HS was assessed using Enzyme-Linked Immunosorbent Assay (ELISA). Alterations in mtDNA levels were examined in mouse hepatocytes, red blood cells (RBCs), and renal tubular epithelial cells utilizing immunofluorescence and PCR techniques. TCE-sensitized mice exhibited a significant increase in reactive oxygen species (ROS) and the opening of the mitochondrial permeability transition pore in hepatocytes, resulting in the release of mtDNA. Furthermore, heightened levels of mtDNA and Toll-like Receptor 9 (TLR9) expression were observed in RBCs. Additional experiments demonstrated elevated expression of TLR9 and its downstream mediator MyD88 in renal tubule epithelial cells of TCE-sensitized mice. In vitro investigations confirmed that mtDNA activates the TLR9 pathway in TCMK-1 cells. Collectively, these results suggest that mtDNA released from mitochondrial damage in hepatocytes is carried by RBCs to renal tubular epithelial cells and mediates inflammatory injury in renal tubular epithelial cells through activation of the TLR9 receptor.

Trichloroethylene exposure, multi-organ injury, and potential mechanisms: A narrative review.

Trichloroethylene (TCE) is a common environmental pollutant and industrial chemical that has been associated with adverse health effects, especially on organ systems. The purpose of this review is to summarize the current findings on organ system damage caused by TCE exposure and the underlying mechanisms involved. Numerous studies have shown that TCE exposure may cause damage to multiple organ systems, mainly the skin, liver, kidney, and circulatory system. The mechanisms leading to TCE-induced organ system damage are complex and diverse. TCE is metabolized in vivo to reactive intermediates, through which TCE can induce oxidative stress, interfere with cell signaling pathways, and promote inflammatory responses. In addition, studies have shown that TCE interferes with DNA repair mechanisms, leading to genotoxicity and potentially carcinogenic effects. This review highlights the importance of understanding the deleterious effects of TCE exposure on organ systems and provides insights into the underlying mechanisms involved. Further research is needed to elucidate the full range of organ system damage caused by TCE and to develop effective prevention and treatment strategies.

Cinnamaldehyde alleviates aspirin-induced gastric mucosal injury by regulating pi3k/akt pathway-mediated apoptosis, autophagy and ferroptosis.

BACKGROUND: Gastric mucosal injury is a chronic and progressive stomach disease that can be caused by nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, there is an urgent need to find safe and effective drugs to prevent gastric mucosal injury due to NSAIDs. Cinnamaldehyde (CA) is a bioactive compound extracted from the rhizome of cinnamon and has various pharmacological functions, including anti-inflammatory, analgesic, antiapoptotic, and antioxidant activities. However, the potential pharmacological effect of CA on gastric mucosal injury remains unknown. PURPOSE: The aim of this study was to investigate the protective effects of CA on aspirin-induced gastric mucosal injury and to explore its mechanism of action METHODS: The effect of CA on gastric mucosal injury was investigated in vitro and in vivo, in vitro mouse model of gastric mucosal injury induced by aspirin, in vitro model of GES-1 cell injury by aspirin and Erastin. The mechanism of action of CA was determined using Transcriptomics and bioinformatics. RESULTS: CA exerted its protective effects against gastric mucosal injury by modulating the downstream targets, including mTOR, GSK3ß, and NRF2, via the PI3K/AKT signaling pathway to inhibit autophagy, apoptosis, and ferroptosis in the gastric epithelial cells. Further cellular experiments confirmed that the PI3K/AKT pathway was a key target for CA against gastric mucosal injury. CONCLUSION: This study provides the first evidence of CA, an active compound in cinnamon, possessing therapeutic potential in preventing and treating gastric mucosal injury, with its mechanism involving the regulation of apoptosis, autophagy, and ferroptosis in gastric epithelial cells mediated by the PI3K/AKT signaling pathway.

The role of mitochondrial dysfunction in kidney injury and disease.

Mitochondria are the main sites of aerobic respiration in the cell and mainly provide energy for the organism, and play key roles in adenosine triphosphate (ATP) synthesis, metabolic regulation, and cell differentiation and death. Mitochondrial dysfunction has been identified as a contributing factor to a variety of diseases. The kidney is rich in mitochondria to meet energy needs, and stable mitochondrial structure and function are essential for normal kidney function. Recently, many studies have shown a link between mitochondrial dysfunction and kidney disease, maintaining mitochondrial homeostasis has become an important target for kidney therapy. In this review, we integrate the role of mitochondrial dysfunction in different kidney diseases, and specifically elaborate the mechanism of mitochondrial reactive oxygen species (mtROS), autophagy and ferroptosis involved in the occurrence and development of kidney diseases, providing insights for improved treatment of kidney diseases.

Predictive value of pre-operative prognostic nutritional index and systemic immune-inflammation index for efficacy and survival in patients with non-small cell lung cancer undergoing neoadjuvant chemotherapy.

OBJECTIVE: To explore the predictive value of preoperative prognostic nutritional index (PNI) and systemic immune inflammation index (SII) in relation to the efficacy and prognosis in patients with non-small cell lung cancer (NSCLC) undergoing neoadjuvant chemotherapy (NACT). METHODS: Data of patients with stage IIIA-N2 NSCLC who received NACT in the 910th Hospital of Chinese People's Liberation Army from January 2017 to April 2020 were retrospectively analysed. Patients undergoing NACT were divided into the pCR group (80 cases with complete remission or partial remission) and the non-pCR group (46 cases with stable disease or progressive disease) in accordance with their treatment outcome. The pathologic and clinical data of the patients were collected and analysed to identify the factors affecting efficacy of NACT for stage IIIa-N2 NSCLC, and to evaluate the predictive value of PNI and SII in determining the efficacy of NACT. The patients were followed up for 3 years to observe the overall survival, and Cox regression analysis was employed to identify the risk factors affecting patient survival. Furthermore, the effect of PNI and SII on the survival time was analysed. RESULTS: Multivariate regression analysis showed that tumor diameter, PNI, and SII were influencing factors for poor efficacy of NACT in patients with stage IIIa-N2 NSCLC. The non-pCR group exhibited a higher mortality within 3 years, thus a lower 3-year overall survival rate than the pCR group (P<0.05). Cox regression analysis revealed that both PNI and SII were risk factors for poor prognosis in patients with stage IIIa-N2 NSCLC undergoing NACT. Further analysis found a lower 3-year survival rate in patients with low PNI and high SII than in counterparts (P<0.05). CONCLUSION: Tumor diameter, PNI and SII are risk factors for poor efficacy in patients with stage IIIa-N2 NSCLC undergoing NACT. Low PNI and high SII can indicate a poor prognosis in these patients.

Histone demethylase KDM4A mediating macrophage polarization: A potential mechanism of trichloroethylene induced liver injury.

Trichloroethylene (TCE) is a commonly used organic solvent in industry. Our previous studies have found that TCE can cause liver injury accompanied by macrophage polarization, but the specific mechanism is unclear. The epigenetic regulation of macrophage polarization is mainly focused on histone modification. Histone lysine demethylase 4A (KDM4A) is involved in the activation of macrophages. In this study, we used a mouse model we investigated the role of KDM4A in the livers of TCE-drinking mice and found that the expression of KDM4A, M1-type polarization indicators, and related inflammatory factors in the livers of TCE-drinking mice. In the study, BALB/c mice were randomly divided into four groups: 2.5 mg/mL TCE dose group and 5.0 mg/mL TCE dose group, the vehicle control group, and the blank control group. We found that TCE triggered M1 polarization of mouse macrophages, characterized by the expression of CD11c and robust production of inflammatory cytokines. Notably, exposure to TCE resulted in markedly increased expression of KDM4A in macrophages. Functionally, the increased expression of KDM4A significantly impaired the expression of H3K9me3 and H3K9me2 and increased the expression of H3K9me1. In addition, KDM4A potentially represents a novel epigenetic modulator, with its upregulation connected to ß-catenin activation, a signal critical for the pro-inflammatory activation of macrophages. Furthermore, KDM4A inhibitor JIB-04 treatment resulted in a decrease in ß-catenin expression and prevented TCE-induced M1 polarization and the expression of the pro-inflammatory cytokines TNF-α and IL-1ß. These results suggest that the association of KDM4A and Wnt/ß-catenin cooperatively establishes the activation and polarization of macrophages and global changes in H3K9me3/me2/me1. Our findings identify KDM4A as an essential regulator of the polarization of macrophages and the expression of inflammatory cytokines, which might serve as a potential target for preventing and treating liver injury caused by TCE.

Resin screening and process optimization for erythritol mother liquor chromatographic separation.

In order to improve the utilization value of the erythritol mother liquor, the separation and purification of the erythritol mother liquor was selected in this study. The selected chromatographic separation programme for erythritol crystallizing mother liquor is as follows: Firstly, erythritol is resolved from mannitol and arabitol with DTF-01Ca (Suqing Group) resin and then mannitol is resolved from arabitol with 99Ca/320 (Dowex) resin. At the same time, the chromatographic conditions of the DTF-01Ca (Suqing Group) and 99Ca/320 (Dowex) resins were optimized, resulting in an optimal separation temperature and mobile phase flow rate of 70 °C, 10 ml/min. On this basis, a single-column chromatographic model was used to calculate the TD model parameter (N) and the mass transfer coefficient (km ) of the separation of erythritol mother liquor by DTF-01Ca (Suqing Group) and 99Ca/320 (Dowex) resins. The adsorption isotherms, TD model parameter (N) and the mass transfer coefficient (km ) provides data references for the design and operation of the simulated moving beds (SMB) separation system for the industrial-scale separation of erythritol crystallizing mother liquor.

The role of PANoptosis in renal vascular endothelial cells: Implications for trichloroethylene-induced kidney injury.

Trichloroethylene (TCE), a widely distributed environmental chemical contaminant, is extensively dispersed throughout the environment. Individuals who are exposed to TCE may manifest occupational medicamentose-like dermatitis due to trichloroethylene (OMDT). Renal impairment typically manifests in the initial phase of OMDT and is intricately linked to the disease progression and patient outcomes. Although recombinant human tumor necrosis factor-α receptor II fusion protein (rh TNFR:Fc) has been employed in the clinical management of OMDT, there was no substantial improvement in renal function observed in patients following one week of treatment. This study primarily examined the mechanism of TNFα- and IFNγ-induced endothelial cells (ECs) PANoptosis in TCE-induced kidney injury and hypothesized that the synergistic effect of TNFα and IFNγ could be the key factor affecting the efficacy of rh TNFR:Fc therapy in OMDT patients. A TCE-sensitized mouse model was utilized in this study to investigate the effects of TNFα and IFNγ neutralizing antibodies on renal vascular endothelial cell PANoptosis. The gene of interferon regulatory factor 1 (IRF1) in human umbilical vein endothelial cells (HUVEC) was silenced by using small interfering RNA (siRNA), and the cells were then treated with TNFα and IFNγ recombinant protein to investigate the mechanism of TNFα combined with IFNγ-induced PANoptosis in HUVEC. The findings indicated that mice sensitized to TCE exhibited increased levels of PANoptosis-related markers in renal endothelial cells, and treatment with TNFα and IFNγ neutralizing antibodies resulted in a significant reduction in PANoptosis and improvement in renal function. In vitro experiments demonstrated that silencing IRF1 could reverse TNFα and IFNγ-induced PANoptosis in endothelial cells. These results suggest that the efficacy of rh TNFR:Fc may be influenced by TNFα and IFNγ-mediated PANoptosis in kidney vascular endothelial cells. The joint application of TNFα and IFNγ neutralizing antibody represented a solid alternative to existing therapeutics.

Hepatocyte mitochondrial DNA mediates macrophage immune response in liver injury induced by trichloroethylene.

We have previously shown that excessive activation of macrophage proinflammatory activity plays a key role in TCE-induced immune liver injury, but the mechanism of polarization is unclear. Recent studies have shown that TLR9 activation plays an important regulatory role in macrophage polarization. In the present study, we demonstrated that elevated levels of oxidative stress in hepatocytes mediate the release of mtDNA into the bloodstream, leading to the activation of TLR9 in macrophages to regulate macrophage polarization. In vivo experiments revealed that pretreatment with SS-31, a mitochondria-targeting antioxidant peptide, reduced the level of oxidative stress in hepatocytes, leading to a decrease in mtDNA release. Importantly, SS-31 pretreatment inhibited TLR9 activation in macrophages, suggesting that hepatocyte mtDNA may activate TLR9 in macrophages. Further studies revealed that pharmacological inhibition of TLR9 by ODN2088 partially blocked macrophage activation, suggesting that the level of macrophage activation is dependent on TLR9 activation. In vitro experiments involving the extraction of mtDNA from TCE-sensitized mice treated with RAW264.7 cells further confirmed that hepatocyte mtDNA can activate TLR9 in mouse peritoneal macrophages, leading to macrophage polarization. In summary, our study comprehensively confirmed that TLR9 activation in macrophages is dependent on mtDNA released by elevated levels of oxidative stress in hepatocytes and that TLR9 activation in macrophages plays a key role in regulating macrophage polarization. These findings reveal the mechanism of macrophage activation in TCE-induced immune liver injury and provide new perspectives and therapeutic targets for the treatment of OMDT-induced immune liver injury.

Rare-earth-based chalcogenides and their derivatives: an encouraging IR nonlinear optical material candidate.

With the continuous development of laser technology and the increasing demand for lasers of different frequencies in the infrared (IR) spectrum, research on infrared nonlinear optical (NLO) crystals has garnered growing attention. Currently, the three main commercially available types of borate materials each have their drawbacks, which limit their applications in various areas. Rare-earth (RE)-based chalcogenide compounds, characterized by the unique f-electron configuration, strong positive charges, and high coordination numbers of RE cations, often exhibit distinctive optical responses. In the field of IR-NLO crystals, they have a research history spanning several decades, with increasing interest. However, there is currently no comprehensive review summarizing and analyzing these promising compounds. In this review, we categorize 85 representative examples out of more than 400 non-centrosymmetric (NCS) compounds into four classes based on the connection of different asymmetric building motifs: (1) RE-based chalcogenides containing tetrahedral motifs; (2) RE-based chalcogenides containing lone-pair-electron motifs; (3) RE-based chalcogenides containing [BS3] and [P2Q6] motifs; and (4) RE-based chalcohalides and oxychalcogenides. We provide detailed discussions on their synthesis methods, structures, optical properties, and structure-performance relationships. Finally, we present several favorable suggestions to further explore RE-based chalcogenide compounds. These suggestions aim to approach these compounds from a new perspective in the field of structural chemistry and potentially uncover hidden treasures within the extensive accumulation of previous research.

Circular RNA MKLN1 promotes epithelial-mesenchymal transition in pulmonary fibrosis by regulating the miR-26a/b-5p/CDK8 axis in human alveolar epithelial cells and mice models.

Pulmonary fibrosis involves destruction of the lung parenchyma and extracellular matrix deposition. Effective treatments for pulmonary fibrosis are lacking and its pathogenesis is still unclear. Studies have found that epithelial-mesenchymal transition (EMT) of alveolar epithelial cells (AECs) plays an important role in progression of pulmonary fibrosis. Thus, an in-depth exploration of its mechanism might identify new therapeutic targets. In this study, we revealed that a novel circular RNA, MKLN1 (circMKLN1), was significantly elevated in two pulmonary fibrosis models (intraperitoneally with PQ, 50 mg/kg for 7 days, and intratracheally with BLM, 5 mg/kg for 28 days). Additionally, circMKLN1 was positively correlated with the severity of pulmonary fibrosis. Inhibition of circMKLN1 expression significantly reduced collagen deposition and inhibited EMT in AECs. EMT was aggravated after circMKLN1 overexpression in AECs. MiR-26a-5p/miR-26b-5p (miR-26a/b), the targets of circMKLN1, were confirmed by luciferase reporter assays. CircMKLN1 inhibition elevated miR-26a/b expression. Significantly decreased expression of CDK8 (one of the miR-26a/b targets) was observed after inhibition of circMKLN1. EMT was exacerbated again, and CDK8 expression was significantly increased after circMKLN1 inhibition and cotransfection of miR-26a/b inhibitors in AECs. Our research indicated that circMKLN1 promoted CDK8 expression through sponge adsorption of miR-26a/b, which regulates EMT and pulmonary fibrosis. This study provides a theoretical basis for finding new targets or biomarkers in pulmonary fibrosis.

IL-12-Overexpressed Nanoparticles Suppress the Proliferation of Melanoma Through Inducing ICD and Activating DC, CD8+ T, and CD4+ T Cells.

Purpose: The drug resistance and low response rates of immunotherapy limit its application. This study aimed to construct a new nanoparticle (CaCO3-polydopamine-polyethylenimine, CPP) to effectively deliver interleukin-12 (IL-12) and suppress cancer progress through immunotherapy. Methods: The size distribution of CPP and its zeta potential were measured using a Malvern Zetasizer Nano-ZS90. The morphology and electrophoresis tentative delay of CPP were analyzed using a JEM-1400 transmission electron microscope and an ultraviolet spectrophotometer, respectively. Cell proliferation was analyzed by MTT assay. Proteins were analyzed by Western blot. IL-12 and HMGB1 levels were estimated by ELISA kits. Live/dead staining assay was performed using a Calcein-AM/PI kit. ATP production was detected using an ATP assay kit. The xenografts in vivo were estimated in C57BL/6 mice. The levels of CD80+/CD86+, CD3+/CD4+ and CD3+/CD8+ were analyzed by flow cytometry. Results: CPP could effectively express EGFP or IL-12 and increase ROS levels. Laser treatment promoted CPP-IL-12 induced the number of dead or apoptotic cell. CPP-IL-12 and laser could further enhance CALR levels and extracellular HMGB1 levels and decrease intracellular HMGB1 and ATP levels, indicating that it may induce immunogenic cell death (ICD). The tumors and weights of xenografts in CPP-IL-12 or laser-treated mice were significantly reduced than in controls. The IL-12 expression, the CD80+/CD86+ expression of DC from lymph glands, and the number of CD3+/CD8+T or CD3+/CD4+T cells from the spleen increased in CPP-IL-12-treated or laser-treated xenografts compared with controls. The levels of granzyme B, IFN-γ, and TNF-α in the serum of CPP-IL-12-treated mice increased. Interestingly, CPP-IL-12 treatment in local xenografts in the back of mice could effectively inhibit the growth of the distant untreated tumor. Conclusion: The novel CPP-IL-12 could overexpress IL-12 in melanoma cells and achieve immunotherapy to melanoma through inducing ICD, activating CD4+ T cell, and enhancing the function of tumor-reactive CD8+ T cells.