Progressive Optimization of Lanthanide Nanoparticle Scintillators for Enhanced Triple-Activated Radioluminescence Imaging.

Lanthanide nanoparticle (LnNP) scintillators exhibit huge potential in achieving radionuclide-activated luminescence (radioluminescence, RL). However, their structure-activity relationship remains largely unexplored. Herein, progressive optimization of LnNP scintillators is presented to unveil their structure-dependent RL property and enhance their RL output efficiency. Benefiting from the favorable host matrix and the luminescence-protective effect of core-shell engineering, NaGdF4 : 15 %Eu@NaLuF4 nanoparticle scintillators with tailored structures emerged as the top candidates. Living imaging experiments based on optimal LnNP scintillators validated the feasibility of laser-free continuous RL activated by clinical radiopharmaceuticals for tumor multiplex visualization. This research provides unprecedented insights into the rational design of LnNP scintillators, which would enable efficient energy conversion from Cerenkov luminescence, γ-radiation, and ß-electrons into visible photon signals, thus establishing a robust nanotechnology-aided approach for tumor-directed radio-phototheranostics.

Role of intracranial bone marrow mesenchymal stem cells in stroke recovery: A focus on post-stroke inflammation and mitochondrial transfer.

Stem cell therapy has become a hot research topic in the medical field in recent years, with enormous potential for treating a variety of diseases. In particular, bone marrow mesenchymal stem cells (BMSCs) have wide-ranging applications in the treatment of ischemic stroke, autoimmune diseases, tissue repair, and difficult-to-treat diseases. BMSCs can differentiate into multiple cell types and exhibit strong immunomodulatory properties. Although BMSCs can regulate the inflammatory response activated after stroke, the mechanism by which BMSCs regulate inflammation remains unclear and requires further study. Recently, stem cell therapy has emerged as a potentially effective approach for enhancing the recovery process following an ischemic stroke. For example, by regulating post-stroke inflammation and by transferring mitochondria to exert therapeutic effects. Therefore, this article reviews the therapeutic effects of intracranial BMSCs in regulating post-stroke inflammation and mitochondrial transfer in the treatment of stroke, providing a basis for further research.

Electroacupuncture attenuates nociceptive behaviors in a mouse model of cancer pain.

Pain is a major symptom in cancer patients, and cancer-induced bone pain (CIBP) is the most common type of moderate and severe cancer-related pain. The current available analgesic treatments for CIBP have adverse effects as well as limited therapeutic effects. Acupuncture is proved effective in pain management as a safe alternative therapy. We evaluated the analgesic effect of acupuncture in treatment of cancer pain and try to explore the underlying analgesic mechanisms. Nude mice were inoculated with cancer cells into the left distal femur to establish cancer pain model. Electroacupuncture (EA) treatment was applied for the xenograft animals. Pain behaviors of mice were evaluated, followed by the detections of neuropeptide-related and inflammation-related indicators in peripheral and central levels. EA treatment alleviated cancer-induced pain behaviors covering mechanical allodynia, thermal hyperalgesia and spontaneous pain, and also down-regulated immunofluorescence expressions of neuropeptide CGRP and p75 in the skin of affected plantar area in xenograft mice, and inhibited expressions of overexpressed neuropeptide-related and inflammation-related protein in the lumbar spinal cord of xenograft mice. Overall, our findings suggest that EA treatment ameliorated cancer-induced pain behaviors in the mouse xenograft model of cancer pain, possibly through inhibiting the expressions of neuropeptide-related and inflammation-related protein in central level following tumor cell xenografts.

Eugenol Possesses Colitis Protective Effects: Impacts on the TLR4/MyD88/NF-[Formula: see text]B Pathway, Intestinal Epithelial Barrier, and Macrophage Polarization.

Eugenol (EU) has been shown to ameliorate experimental colitis due to its anti-oxidant and anti-inflammatory bioactivities. In this study, DSS-induced acute colitis was established and applied to clarify the regulation efficacy of EU on intestinal barrier impairment and macrophage polarization imbalance along with the inflammatory response. Besides, the adjusting effect of EU on macrophages was further investigated in vitro. The results confirmed that EU intervention alleviated DSS-induced colitis through methods such as restraining weight loss and colonic shortening and decreasing DAI scores. Microscopic observation manifested that EU maintained the intestinal barrier integrity in line with the mucus barrier and tight junction protection. Furthermore, EU intervention significantly suppressed the activation of TLR4/MyD88/NF-[Formula: see text]B signaling pathways and pro-inflammatory cytokines gene expressions, while enhancing the expressions of anti-inflammatory cytokines. Simultaneously, WB and FCM analyses of the CD86 and CD206 showed that EU could regulate the DSS-induced macrophage polarization imbalance. Overall, our data further elucidated the mechanism of EU's defensive effect on experimental colitis, which is relevant to the protective efficacy of intestinal barriers, inhibition of oxidative stress and excessive inflammatory response, and reprogramming of macrophage polarization. Hence, this study may facilitate a better understanding of the protective action of the EU against UC.

NIR-II imaging-guided precise photodynamic therapy for augmenting tumor-starvation therapy by glucose metabolism reprogramming interference.

Metabolic reprogramming is a mechanism by which cancer cells alter their metabolic patterns to promote cell proliferation and growth, thereby enabling their resistance to external stress. 2-Deoxy-D-glucose (2DG) can eliminate their energy source by inhibiting glucose glycolysis, leading to cancer cell death through starvation. However, a compensatory increase in mitochondrial metabolism inhibits its efficacy. Herein, we propose a synergistic approach that combines photodynamic therapy (PDT) with starvation therapy to address this challenge. To monitor the nanodrugs and determine the optimal triggering time for precise tumor therapy, a multifunctional nano-platform comprising lanthanide-doped nanoparticle (LnNP) cores was constructed and combined with mesoporous silicon shells loaded with 2DG and photosensitizer chlorin e6 (Ce6) in the mesopore channels. Under 980 nm near-infrared light excitation, the downshifted 1550 nm fluorescence signal in the second near-infrared (NIR-II, 1000-1700 nm) window from the LnNPs was used to monitor the accumulation of nanomaterials in tumors. Furthermore, upconverted 650 nm light excited the Ce6 to generate singlet oxygen for PDT, which damaged mitochondrial function and enhanced the efficacy of 2DG by inhibiting hexokinase 2 and lactate dehydrogenase A expressions. As a result, glucose metabolism reprogramming was inhibited and the efficiency of starvation therapy was significantly enhanced. Overall, the proposed NIR-II bioimaging-guided PDT-augmented starvation therapy, which simultaneously inhibited glycolysis and mitochondria, facilitated the effects of a cancer theranostic system.

A continuously efficient O2-supplying strategy for long-term modulation of hypoxic tumor microenvironment to enhance long-acting radionuclides internal therapy.

Radionuclides internal radiotherapy (RIT) is a clinically powerful method for cancer treatment, but still poses unsatisfactory therapeutic outcomes due to the hypoxic characteristic of tumor microenvironment (TME). Catalase (CAT) or CAT-like nanomaterials can be used to enzymatically decompose TME endogenous H2O2 to boost TME oxygenation and thus alleviate the hypoxic level within tumors, but their effectiveness is still hindered by the short-lasting of hypoxia relief owing to their poor stability or degradability, thereby failing to match the long therapeutic duration of RIT. Herein, we proposed an innovative strategy of using facet-dependent CAT-like Pd-based two-dimensional (2D) nanoplatforms to continuously enhance RIT. Specifically, rationally designed 2D Pd@Au nanosheets (NSs) enable consistent enzymatic conversion of endogenous H2O2 into O2 to overcome hypoxia-induced RIT resistance. Furthermore, partially coated Au layer afford NIR-II responsiveness and moderate photothermal treatment that augmenting their enzymatic functionality. This approach with dual-effect paves the way for reshaping TME and consequently facilitating the brachytherapy ablation of cancer. Our work offers a significant advancement in the integration of catalytic nanomedicine and nuclear medicine, with the overarching goal of amplifying the clinical benefits of RIT-treated patients.

Mitochondrial Transplantation and Immune Response of Human Bone Marrow Mesenchymal Stem Cells for the Therapeutic of Ischemic Stroke.

Ischemic stroke is the leading cause of death and disability worldwide, with increasing incidence and mortality, imposing a significant social and economic burden on patients and their families. However, cerebral vascular occlusion leads to acute loss of neurons and destruction of synaptic structures. The limited treatment options cannot adequately address intra-neuronal mitochondrial dysfunction due to stroke. Therefore, stem cell-derived mitochondria transplantation plays an important role in neuronal protection and recovery after stroke, when combined with the intracranial and extracranial immunoregulatory effects of stem cell therapy, revealing the mechanism of transferred mitochondria in stem cells in protecting neurological function among chronic-phase ischemic stroke by affecting the endogenous apoptotic pathway of neuronal cells. This research elaborated on the mitochondrial dysfunction in neurons after ischemic stroke, followed by human bone marrow mesenchymal stem cells (hBMSC) rescued damaged neurons by mitochondrial transfer through tunneling nanotubes (TNTs), and the immunomodulatory effect of the preferential transfer of stem cells to the spleen when transplanted into the body.which created an immune environment for nerve repair, as well as improved neurological recovery after the chronic phase of stroke. This review is expected to provide a novel idea for applying intracranial stem cell transplantation in chronic-phase ischemic stroke treatment.

An Extended NIR-II Superior Imaging Window from 1500 to 1900†nm for High-Resolution In Vivo Multiplexed Imaging Based on Lanthanide Nanocrystals.

High-resolution in vivo optical multiplexing in second near-infrared window (NIR-II, 1000-1700 nm) is vital to biomedical research. Presently, limited by bio-tissue scattering, only luminescent probes located at NIR-IIb (1500-1700 nm) window can provide high-resolution in vivo multiplexed imaging. However, the number of available luminescent probes in this narrow NIR-IIb region is limited, which hampers the available multiplexed channels of in vivo imaging. To overcome the above challenges, through theoretical simulation we expanded the conventional NIR-IIb window to NIR-II long-wavelength (NIR-II-L, 1500-1900 nm) window on the basis of photon-scattering and water-absorption. We developed a series of novel lanthanide luminescent nanoprobes with emission wavelengths from 1852 nm to 2842 nm. NIR-II-L nanoprobes enabled high-resolution in vivo dynamic multiplexed imaging on blood vessels and intestines, and provided multi-channels imaging on lymph tubes, tumors and intestines. The proposed NIR-II-L probes without mutual interference are powerful tools for high-contrast in vivo multiplexed detection, which holds promise for revealing physiological process in living body.

Breeding of ZhongKeFaZaoGeng1 by molecular design.

Double-cropping early-season rice is one important part of staple crop rice. In recent years, great progress has been made in breeding the double-cropping early-season japonica rice variety, ZhongKeFaZaoGeng1 (ZKFZG1), with high yield, good quality, and high resistance. The breeding of ZKFZG1 aimed at the severe problems of low quality, low income and pre-harvest sprouting in double-cropping early-season rice production, and was achieved through molecular design by selecting three parents with different beneficial genes, KongYu131, NanFangChangLiGeng, and JiGeng88 and screening for key agronomic genes in cross-breeding. ZKFZG1 has a compact plant architecture, a plant height of ~90 cm, a number of ~120 grains per panicle, a setting rate of ~85%, a 1000-grain weight of 26 grams, a yield of 8.25 t/ha, and especially good grain quality. The successful breeding of ZKFZG1 provides a new direction for double-cropping early-season rice production.

Preparation of eicosavalent triazolylsialoside-conjugated human serum albumin as a dual hemagglutinin/neuraminidase inhibitor and virion adsorbent for the prevention of influenza infection.

A triazolylsialoside-human serum albumin conjugate was prepared as a multivalent hemagglutinin and neuraminidase inhibitor using a di-(N-succinimidyl) adipate strategy. Matrix-Assisted Laser Desorption/Ionization-Time of Flight-Mass Spectrometry (MALDI-TOF-MS) indicated that five tetravalent sialyl galactosides were grafted onto the protein backbone resulting in an eicosavalent triazolylsialoside-protein complex. Compared with monomeric sialic acid, molecular interaction studies showed that the synthetic pseudo-glycoprotein bound tightly not only to hemagglutinin (HA)/neuraminidase (NA) but also to mutated drug-resistant NA on the surface of the influenza virus with a dissociation constant (KD) in the 1 µM range, attributed to the cluster effect. Moreover, this glycoconjugate exhibited potent antiviral activity against a broad spectrum of virus strains and showed no cytotoxicity towards Human Umbilical Vein Endothelial Cells (HUVECs) and Madin-Darby canine kidney (MDCK) cells at high concentrations. Further mechanistic studies demonstrated this multivalent sialyl conjugate showed strong capture and trapping of influenza virions, thus disrupting the ability of the influenza virus to infect host cells. This research lays the experimental foundation for the development of new antiviral agents based on multivalent sialic acid-protein conjugates.

Effects of short-term extreme temperature treatment on the development and reproductive capacity of Encarsia formosa.

Encarsia formosa is a natural enemy of the invasive pest Bemisia tabaci and is known to be a dominant parasitic. The frequency and magnitude of climate extremes, particularly temperature extremes, have increased, which has put insect populations at risk. However, the effects of temperature extremes on E. formosa are not well understood. To examine the impact of short-term extreme temperature exposure on the development and reproduction of E. formosa, eggs, larvae, pupae, and adults were exposed to high/low temperature treatments (HLT25, HLT50, LLT25, and LLT50). Our findings indicate that the pupal stage of E. formosa exhibited the strongest tolerance to both heat and cold, while adults exhibited a weaker tolerance. The shortest egg-to-adult development period of 12.65 days was observed in E. formosa exposed to HLT50 treatment during the egg-larval stage. The parasitism peak of the adult stage was delayed by 1-6 days after exposure to extreme temperatures during the egg-larval stage. Conversely, the parasitism peak was advanced by 1-3 days after exposure to extreme temperatures during the pupal and adult stages. The eclosion rate, total parasitism, eclosion rate of the F1 generation, and adult longevity of the F1 generation were lower in the treatment groups than in the control groups. The F1 generation's development period was prolonged to 15.49 and 15.19 days after exposure to HLT25 and HLT50 treatments, respectively, during the egg-larval stage. The F1 generation's development period was shortened to 13.33 days after exposure to LLT50 treatment during the pupal stage. Male individuals appeared in the F1 generation after exposure to HLT50 treatment during the pupal stage, with females accounting for only 56.38%. Our results demonstrate that short-term exposure to extreme temperatures has detrimental effects on the growth and reproduction of E. formosa. In field biocontrol against E. formosa, the release of E. formosa should be avoided as much as possible when the ambient temperature is higher than 35°C or lower than 0°C. During extreme temperature conditions, timely supplementation and release of E. formosa population, along with ventilation and cooling in greenhouse facilities during summer, are necessary for better pest control efficacy.

Effects of long-term regular oral aspirin combined with atorvastatin to prevent ischemic stroke on human gut microbiota.

PURPOSE: Every year, there is a large number of people take aspirin and atorvastatin to prevent ischemic stroke, but the effect of these drugs on gut microbiota remains unknown. We aimed to examine the effects of long-term regular oral aspirin with atorvastatin to prevent ischemic stroke on human gut microbiota. METHODS: A cross-sectional study of 20 participants with the drugs over one year and the other 20 gender- and age-matching participants without medication were recruited from the Affiliated Hospital of Guizhou Medical University. The medication habits and dietary information were obtained using a questionnaire. Fecal samples collected from all participants were subjected to 16S rRNA sequencing of the microbiome. The datasets were analyzed using bioinformatics approaches. RESULTS: The Alpha diversity showed that compared with controls, medication participants had lower ACE and Chao1 index, while no difference in the Shannon index and Simpson index. The Beta diversity analysis revealed significant shifts in the taxonomic compositions of the two groups. Linear discriminant analysis effect size (LEfSe) analysis combined with receiver operating characteristic (ROC) curves revealed the marker bacteria associated with taking medication were g_Parabacteroides（AUC = 0.855）, g_Bifidobacterium（AUC = 0.815）, s_Bifidobacterium_longum_subsp（AUC = 0.8075）, and with no taking medication was g_Prevotella_9（AUC = 0.76）. CONCLUSIONS: Our findings indicated that long-term regular oral aspirin and atorvastatin modulate the human gut microbiota. Taking these drugs may affect the preventive effect of ischemic stroke by changing the abundance of specific gut microbiota.

A self-charging salt water battery for antitumor therapy.

Implantable devices on the tumor tissue as a local treatment are able to work in situ, which minimizes systemic toxicities and adverse effects. Here, we demonstrated an implantable self-charging battery that can regulate tumor microenvironment persistently by the well-designed electrode redox reaction. The battery consists of biocompatible polyimide electrode and zinc electrode, which can consume oxygen sustainably during battery discharge/self-charge cycle, thus modulating hypoxia level in tumor microenvironment. The oxygen reduction in battery leads to the formation of reactive oxygen species, showing 100% prevention on tumor formation. Sustainable consumption of oxygen causes adequate intratumoral hypoxic conditions over the course of 14 days, which is helpful for the hypoxia-activated prodrugs (HAPs) to kill tumor cells. The synergistic effect of the battery/HAPs can deliver more than 90% antitumor rate. Using redox reactions in electrochemical battery provides a potential approach for the tumor inhibition and regulation of tumor microenvironment.

Marked shifts of harmful algal blooms in the Bohai Sea linked with combined impacts of environmental changes.

The Bohai Sea, a semi-enclosed inland sea in China and an important mariculture region, has experienced extensive harmful algal blooms (HABs) and their negative impacts for several decades. To investigate the changes of HABs and their potential drivers over time and space, a dataset of 230 HAB events (1952-2017), along with corresponding environmental data (1990-2017) was compiled. The frequency of HAB events in the Bohai Sea has increased over time but plateaued in the last decade, and our analysis showed that history of HABs in the Bohai Sea could be categorized into three periods based on their frequency, scale, and HAB-forming species. The seasonal window of HAB events has started earlier and lasted longer, and the main hotspot has moved from Bohai Bay to coastal waters of Qinhuangdao over time. There were marked shifts in the representative HAB-forming microalgae, from dinoflagellates in the first period (before 2000) to haptophytes in the second period (2000-2009), and pelagophytes in the third period (2009 onwards). These community changes are accompanied by a trend toward diversification of HAB-forming microalgae, decrease in cell-size, and increase in negative impacts. Statistical analyses indicate that long-term changes in HABs in the Bohai Sea are linked with the combined effects of climate change, eutrophication and mariculture development. The results of the present study require to refine future monitoring programs, develop adaptive management strategies and predictive models for HABs in the Bohai Sea.

[Myrislignan Induces Apoptosis in Gastric Cancer Cell Line Through PI3K/AKT Signaling Pathway].

Objective: To investigate the effect of myrislignan (MYR) on the apoptosis of gastric cancer cell line and its relationship with phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Methods: The gastric cells (SGC-7901) were treated with MYR at different concentrations, i.e., 0, 25, 50, 100, and 200 µmol/L, for 48 h and 72 h and the effect of MYR on the proliferation of SGC-7901 cells was measured by CCK-8 assay. Then, SGC-7901 cells were treated with different concentrations of MYR at 50, 100, and 200 µmol/L for 48 h. Meanwhile, a normal control group and a dimethyl sulfoxide (DMSO) solvent control group (0.1% DMSO) were established. Flow cytometry was used to determine the apoptosis rate of SGC-7901 cells. The protein expression levels of PI3K, AKT, Bcl-2-associated X protein (BAX), cysteine-dependent aspartate-specifc protease-3 (Caspase-3), and Caspase-9 were determined by Western blot. Then, PI3K activator (20 µmol/mL) was used to treat SGC-7901 cells for 48 h in 4 groups, the control group, 0.1% DMSO group, MYR group, and MYR+PI3K activator group, and the effect on MYR's induction of apoptosis and regulation of the protein expression levels of PI3K, AKT, BAX, Caspase-3, and Caspase-9 in SGC-7901 cells. Results: Compared with the control group, MYR at 50, 100 and 200 µmol/L inhibited the proliferation of gastric cancer cells, increased the apoptosis rate, down-regulated the protein expression levels of PI3K and AKT, and up-regulated the protein expression levels of BAX, Caspase-3, and Caspase-9 in a dose-dependent manner ( P<0.05). However, PI3K activator attenuated MYR-induced apoptosis in gastric cancer cells and MYR's regulation of PI3K, AKT, BAX, Caspase-3, and Caspase-9 protein expression ( P<0.05). Conclusion: MYR induces the expression of BAX, Caspase-3, and Caspase-9 proteins by inhibiting the PI3K/AKT signaling pathway, thereby promoting the apoptosis of gastric cancer cells.

Light-acquisition traits link aboveground biomass and environment in inner saline-alkaline herbaceous marshes.

A functional response-effect approach could predict how environmental changes affect ecosystem functioning. However, few studies have applied this approach to inner saline-alkaline marsh ecosystems where soil saline-alkaline, flooding/drought and nutrients stresses threat ecological functioning. To disentangle the relationships between environmental conditions and ecosystem functioning, a total of 81 plots were investigated across 22 marsh sites dominated by Phragmites australis and Bolboschoenus planiculmis in Western Songnen Plain wetlands, China. For both plant communities combined, deep flooding supported communities with higher specific leaf area (SLA), plant height and leaf nitrogen (N) content but lower leaf thickness. On the contrary, high soil salt content induced low leaf N and phosphorus (P) content, SLA and plant height. Only light acquisition-related trait, plant height and SLA, was the key traits which determined the relationships between ecosystem functioning (aboveground biomass) and saline-alkaline wetland environment. Yet indirect key traits related nutrient and water acquisition such as leaf thickness, N and P content were also found, and mediated the response of aboveground biomass through the allometric relationships with plant height or SLA. For the individual species community, only plant height was the key trait shared by P. australis and B. planiculmis, indicating the universality of plant height as a key trait for grass and sedge plants to explain how ecosystem functioning responds to abiotic factors. Hence, our findings suggest that saltmarsh plants are more inclined to alter light-acquisition traits to mediate the response of ecosystem functioning to environmental changes and that plant height is a particularly useful trait to predict plant productivity in earth system models under future environmental changes in inner saline-alkaline wetlands.

Real-World clinical features and survival outcomes associated with primary gastrointestinal natural killer/T-cell lymphoma from 1999 to 2020.

BACKGROUND: Primary gastrointestinal natural killer (NK)/T-cell lymphoma (PGINKTL) is a rare T-/NK-cell lymphoma subtype, and the clinical features and survival outcomes remain largely unknown. METHODS: To summarize the clinical features and survival outcomes of PGINKTL, PGINKTL cases diagnosed at our hospital from May 1999 to December 2020 were reviewed; and the clinical data, information on treatment strategies, and survival were collected. Survival analysis was performed using the Kaplan-Meier method and multivariable Cox proportional hazards regression. We constructed a nomogram to visualize the survival prediction of PGINKTL. The discriminative ability and calibration of the nomogram for prediction were tested using the concordance index (C-index) and calibration plots. RESULTS: The cohort included 81 cases, the median age was 36 years (range, 7-80 years), and the male-to-female ratio was 1.7:1. The most common clinical symptom at the time of diagnosis was abdominal pain (71.6%). The most common lesion site was the colon (59.3%). During a median follow-up period of 37.7 months, the median overall survival (OS) time of 81 patients was 4.0 months (95% confidence interval [CI], 3.1-4.9 months), and the 2-year OS rate was 30.7% (95% CI, 20.3%-40.1%). The multivariate analyses indicated that patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score ≥2, serum lactic dehydrogenase (LDH) level ≥ the upper limit normal (ULN), and perforation had worse OS. We used these data to establish a nomogram to predict survival for PGINKTL. The nomogram displayed good accuracy, with a C-index of 0.726. CONCLUSION: The clinical features and poor outcomes of PGINKTL, which is a rare and fatal lymphoma type, are presented. The proposed nomogram provides an individualized estimate of survival for these patients. In the future, the study focused on exploring a better treatment strategy to improve survival is required in PGINKTL.

Hierarchically Organized Cocrystal of Tetra-Anionic Porphyrin and Di-Cationic Viologen: Ion Conformations, Supramolecule Interactions, and Porphyrin Arrays.

Ionic co-assembly of tetra-anionic porphyrins has been extensively researched in the construction of hierarchically organized architectures with potential application value in organic semiconductors, sunlight catalysts and supramolecular chirality systems. However, such architectures are difficult to grow to a size suitable for single-crystal X-ray diffraction (SCXRD); the lack of single-crystal structures of these architectures leads to challenges in gaining deeper comprehension about that. This study reports a hierarchically organized cocrystal of meso-tetra(4-sulfonato-phenyl)-porphyrin (TSPP4- ) and N, N'-diethyl-viologen (DEV2+ ), wherein wave-like and saddle-like TSPP4- ions co-aggregate at a stoichiometric ratio of 1 : 2 to form unique porphyrin arrays; the spectrum characteristics and calculated coulombic exciton coupling energy show that these porphyrin arrays are J-aggregates. We prove that the distortion of porphyrin ring of TSPP4- strongly correlates with the deflection of its phenyl groups. The crystal comprises six different ionic conformations, and the multiplicity of ionic conformation leads to intricate supramolecular interactions.

Ethanol and its Nonoxidative Metabolites Promote Acute Liver Injury by Inducing ER Stress, Adipocyte Death, and Lipolysis.

BACKGROUND & AIMS: Binge drinking in patients with metabolic syndrome accelerates the development of alcohol-associated liver disease. However, the underlying mechanisms remain elusive. We investigated if oxidative and nonoxidative alcohol metabolism pathways, diet-induced obesity, and adipose tissues influenced the development of acute liver injury in a single ethanol binge model. METHODS: A single ethanol binge was administered to chow-fed or high-fat diet (HFD)-fed wild-type and genetically modified mice. RESULTS: Oral administration of a single dose of ethanol induced acute liver injury and hepatic endoplasmic reticulum (ER) stress in chow- or HFD-fed mice. Disruption of the Adh1 gene increased blood ethanol concentration and exacerbated acute ethanol-induced ER stress and liver injury in both chow-fed and HFD-fed mice, while disruption of the Aldh2 gene did not affect such hepatic injury despite high blood acetaldehyde levels. Mechanistic studies showed that alcohol, not acetaldehyde, promoted hepatic ER stress, fatty acid synthesis, and increased adipocyte death and lipolysis, contributing to acute liver injury. Increased serum fatty acid ethyl esters (FAEEs), which are formed by an enzyme-mediated esterification of ethanol with fatty acids, were detected in mice after ethanol gavage, with higher levels in Adh1 knockout mice than in wild-type mice. Deletion of the Ces1d gene in mice markedly reduced the acute ethanol-induced increase of blood FAEE levels with a slight but significant reduction of serum aminotransferase levels. CONCLUSIONS: Ethanol and its nonoxidative metabolites, FAEEs, not acetaldehyde, promoted acute alcohol-induced liver injury by inducing ER stress, adipocyte death, and lipolysis.