Opioid-induced fragile-like regulatory T cells contribute to withdrawal.

Dysregulation of the immune system is a cardinal feature of opioid addiction. Here, we characterize the landscape of peripheral immune cells from patients with opioid use disorder and from healthy controls. Opioid-associated blood exhibited an abnormal distribution of immune cells characterized by a significant expansion of fragile-like regulatory T cells (Tregs), which was positively correlated with the withdrawal score. Analogously, opioid-treated mice also showed enhanced Treg-derived interferon-γ (IFN-γ) expression. IFN-γ signaling reshaped synaptic morphology in nucleus accumbens (NAc) neurons, modulating subsequent withdrawal symptoms. We demonstrate that opioids increase the expression of neuron-derived C-C motif chemokine ligand 2 (Ccl2) and disrupted blood-brain barrier (BBB) integrity through the downregulation of astrocyte-derived fatty-acid-binding protein 7 (Fabp7), which both triggered peripheral Treg infiltration into NAc. Our study demonstrates that opioids drive the expansion of fragile-like Tregs and favor peripheral Treg diapedesis across the BBB, which leads to IFN-γ-mediated synaptic instability and subsequent withdrawal symptoms.

Rigid CuInS2/ZnS Core/Shell Quantum Dots for High Performance Infrared Light-Emitting Diodes.

CuInS2 (CIS) quantum dots (QDs) represent an important class of colloidal materials with broad application potential, owing to their low toxicity and unique optical properties. Although coating with a ZnS shell has been identified as a crucial method to enhance optical performance, the occurrence of cation exchange has historically resulted in the unintended formation of Cu-In-Zn-S alloyed QDs, causing detrimental blueshifts in both absorption and photoluminescence (PL) spectral profiles. In this study, we present a facile one-pot synthetic strategy aimed at impeding the cation exchange process and promoting ZnS shell growth on CIS core QDs. The suppression of both electron-phonon interaction and Auger recombination by the rigid ZnS shell results in CIS/ZnS core/shell QDs that exhibit a wide near-infrared (NIR) emission coverage and a remarkable PL quantum yield of 92.1%. This effect boosts the fabrication of high-performance, QD-based NIR light-emitting diodes with the best stability of such materials so far.

Environmentally Relevant Levels of Antiepileptic Carbamazepine Altered Intestinal Microbial Composition and Metabolites in Amphibian Larvae.

There is growing concern about the potential ecological risks posed by pharmaceutical residues in the aquatic environment. However, our understanding of the toxic effects of antiepileptic pharmaceuticals, such as carbamazepine (CBZ), on aquatic animal larvae is still limited. In this study, the tadpoles of the black-spotted pond frog (Pelophylax nigromaculatus) were exposed to environmentally relevant concentrations of CBZ (0.3 and 3.0 µg/L) for 30 days, and their growth, intestinal microbial composition, and metabolites were investigated to assess the potential toxic effects of CBZ in non-targeted aquatic organisms. Some tadpoles died during exposure, but there was no significant among-group difference in the survival and growth rates. CBZ exposure significantly altered the composition of tadpole intestinal microbiota. Relative abundances of some bacterial genera (e.g., Blautia, Prevotella, Bacillus, Microbacterium, etc.) decreased, while others (e.g., Paucibacter, etc.) increased in CBZ-exposed tadpoles. Interestingly, CBZ-induced alterations in some bacteria might not necessarily lead to adverse outcomes for animals. Meanwhile, small molecular intestinal metabolites related to energy metabolism, and antioxidant and anti-inflammatory activities were also altered after exposure. Taken together, environmentally relevant levels of CBZ might alter the metabolic and immune performances of amphibian larvae by modifying the abundance of some specific bacteria and the level of metabolites in their intestines, thereby potentially causing a long-term effect on their fitness.

Exogenous c-di-GMP inhibited the biofilm formation of Vibrio splendidus.

Vibrio splendidus, a gram-negative bacterium that is ubiquitously present in marine environments, has been increasingly deemed an important opportunistic pathogen of marine animals. In this study, the biofilm formation of V. splendidus was quantitatively determined and morphologically characterized. Three stages of biofilm formation, including adhesion, aggregation and maturation were observed in the biofilm formed by V. splendidus. The inhibitory effect of exogenous bis (3',5')-cyclic dimeric guanosine monophosphate (c-di-GMP) on the biofilm formation from the scratch and preformed established biofilms of V. splendidus was determined. When 200 µmol/L c-di-GMP was added, the quantity of biofilm decreased by 88.1% or 66.7% under the two conditions. To explore the preliminary mechanism of exogenous c-di-GMP on the biofilm formed by V. splendidus, proteomic analysis was performed. GO enrichment analysis showed that exogenous c-di-GMP upregulated biological processes, including the tricarboxylic acid cycle, oxidation‒reduction reactions and organonitrogen compound catabolism and significantly downregulated tRNA threonylcarbamoyladenosine modification, protein dephosphorylation, and lactate transmembrane transporter activity. Sequence-specific DNA binding activity was the most markedly downregulated molecular function. KEGG analysis showed that the valine, leucine and isoleucine degradation pathway was the most enriched pathway, followed by nitrogen metabolism, among the 20 upregulated pathways. Among the downregulated pathways, a nonribosomal peptide structure pathway and the streptomycine, polyketide sugar unit, acarbose and validamycin biosynthesis pathways were significantly enriched. Our present study provides basic data for the biofilm formation of V. splendidus and the preliminary inhibitory mechanism of exogenous c-di-GMP on the biofilm formation of V. splendidus.

Nickel-Catalyzed Sodium Hypophosphite-Participated Direct Hydrophosphonylation of Alkyne toward H-Phosphinates.

The traditional methods for the synthesis of phosphinate esters use phosphorus trichloride (PCl3) as the phosphorous source, resulting in procedures that are often highly polluting and energy intensive. The search for an alternative approach that is both mild and environmentally friendly is a challenging, yet highly rewarding task in modern chemistry. Herein, we use an inorganic phosphorous-containing species, NaH2PO2, to serve as the source of phosphorous that participates directly in the nickel-catalyzed selective alkyne hydrophosphonylation reaction. The transformation was achieved in a multicomponent fashion and at room temperature, and most importantly, the H-phosphinate product generated is an advanced intermediate which can be readily converted into diverse phosphinate derivatives, including those bearing new P-C, P-S, P-N, P-Se, and P-O bonds, thus providing a complimentary method to classic phosphinate ester synthesis techniques.

Relationship between gut microbiota dysbiosis and immune indicator in children with sepsis.

Sepsis is a life-threatening multiple-organ injury caused by disordered host immune response to microbial infection. However, the correlation between gut microbiota dysbiosis and immune indicators remains unexplored. To address this gap in knowledge, we carried out 16 S rDNA sequencing, analyzed clinical fecal samples from children with sepsis (n = 30) and control children (n = 25), and obtained immune indicators, including T cell subtypes (CD3+, CD3+CD4+, CD3+CD8+, and CD4/CD8), NK cells, cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ), and immunoglobulin indices (IgA, IgE, IgM and IgG). In addition, we analyzed the correlation between gut microbiota dysbiosis and immune indicators, and evaluated the clinical discriminatory power of discovered bacterial biomarkers. We found that children with sepsis exhibited gut bacterial dysbiosis and low alpha diversity. The Spearman's rank correlation coefficient suggested that Rhodococcus erythropolis had a significantly positive correlation with IFN-γ and CD3+ T cells. Klebsiella pneumoniae and Streptococcus mitis were significantly correlated with NK cells. Bacteroides uniformis was significantly positively correlated with IgM and erythrocyte sedimentation rate, and Eubacterium eligens was significantly positively correlated with IL-4 and CD3+CD8+ T cells. The biomarkers discovered in this study had strong discriminatory power. These changes in the gut microbiome may be closely related to immunologic dysfunction and to the development or exacerbation of sepsis. However, a large sample size is required for verification.

Metformin exposure altered intestinal microbiota composition and metabolites in amphibian larvae.

The antidiabetic pharmaceutical metformin (MET) is largely unmetabolized by the human body. Its residues are readily detectable in various aquatic environments and may have adverse impacts on the growth and survival of aquatic species. To date, its toxicological effects have scarcely been explored in non-fish species. Here, we exposed the tadpoles of black-spotted pond frog (Pelophylax nigromaculatus) to different concentrations (0, 1, 10 and 100 µg/L) of MET for 30 days and measured the body size, intestinal microbiota and metabolites to evaluate potential effects of MET exposure in amphibian larvae. MET exposure did not affect the growth and intestinal microbial diversity of tadpoles. However, intestinal microbial composition changed significantly, with some pathogenic bacteria (e.g., bacterial genera Salmonella, Comamonas, Stenotrophomonas, Trichococcus) increasing and some beneficial bacteria (e.g., Blautia, Prevotella) decreasing in MET-exposed tadpoles. The levels of some intestinal metabolites associated with growth and immune performance also changed significantly following MET exposure. Overall, our results indicated that exposure to MET, even at environmentally relevant concentrations, would cause intestinal microbiota dysbiosis and metabolite alteration, thereby influencing the health status of non-target aquatic organisms, such as amphibians.

Proteomic analysis of the initial wake up of vibrio splendidus persister cells.

Vibrio splendidus is a ubiquitous pathogen that causes various diseases in aquaculture with a wide range of hosts. In our previous studies, we showed that L-glutamic acid was the optimal carbon source that could revive V. splendidus persister cells. In our present study, single cell observation under microscopy showed that V. splendidus could revive using L-glutamic acid as carbon source. A proteomic analysis was carried out to further illustrate the initial wake up of persister cells with L-glutamic acid. To collect the initially revived cells, SDS-PAGE was used to determine the revived time. The total proteins from the persister cells and the revived cells were analyzed using LC‒MS/MS. A total of 106 proteins, including 42 downregulated proteins and 64 upregulated proteins, were identified. GO analysis of the differentially expressed proteins (DEPs) showed that biological processes, including protein complex assembly, protein oligomerization, and arginine metabolism; cellular components, including extracellular membrane, plasma membrane and ribosome; and molecular functions, including the activities of arginine binding and structural constituent of ribosome, were enriched. KEGG analysis showed that lipopolysaccharide biosynthesis, porphyrin and chlorophyll metabolism, and peptidoglycan biosynthesis were upregulated, while the ribosome was downregulated. This is the first time to study the initial wake up of persister cells based on proteomic analysis, and the results revealed the main pathways involved in the early resuscitation of V. splendidus persister cells.

Correlation between salivary cytokine profiles and white spot lesions in adolescent patients receiving clear aligner orthodontic treatment.

BACKGROUND: To explore the relationship between changes in salivary cytokine levels and the occurrence of white spot lesions in adolescents receiving clear aligner orthodontic treatment and investigate the predictive value of various factors for lesion occurrence. METHODS: We retrospectively analyzed sixthy eight adolescent in the permanent dentition period, who received clear aligner orthodontics in our hospital were randomly divided into two groups according to the occurrence or aggravation of white spot lesions after treatment. The general condition of the oral cavity was analyzed, saliva was collected, and inflammation-related cytokines with varying transcription levels between groups were screened by transcriptome analysis. The expression levels of inflammatory cytokines in the saliva of the patients in the two groups were measured, and the risk factors for white spot lesions were screened by correlation analysis and binary logistic regression analysis. The value of the independent and combined application of risk factors for predicting the occurrence of white spot lesions in adolescent patients after invisible orthodontic treatment was analyzed by receiver operating characteristic (ROC) curve analysis. RESULTS: Transcriptome and GO and KEGG pathway analyses showed that there were differences in the transcription levels of inflammatory cytokines such as CXCL1, CXCL2, CXCL8, CCL3, CCL4, IL-1ß and IL-2 between groups. The levels of CXCL8, CCL3, CCL4, IL-1ß and IL-2 in the saliva of patients with white spot lesions were significantly higher in patients after invisible orthodontic treatment (P < 0.05). Correlation analysis and binary logistic regression analysis showed that elevated levels of CXCL8, IL-1ß and IL-2 were independent risk factors for the occurrence of white spot lesions (P < 0.05). CXCL8 had the highest independent predictive value for the occurrence of white spot lesions (AUC = 0.773, P < 0.05), and the combination of IL-1ß and IL-2 was also of high value in predicting the occurrence of white spot lesions. CONCLUSION: After invisible orthodontic treatment, the oral microenvironment, including inflammatory cytokine levels, in adolescent patients changes; in particular, the levels of inflammatory cytokines such as CXCLs and ILs change. CXCL8 expression is significantly associated with the occurrence of white spot lesions and is an important potential target for the prevention and treatment of white spot lesions in the future.

Effects of chronic exposure to the fungicide vinclozolin on gut microbiota community in an aquatic turtle.

Environmental issues associated with the widespread use of agricultural chemicals are being seriously concerned. Of them, toxicological impacts of fungicides in aquatic organisms are often overlooked. Here, soft-shelled turtle (Pelodiscus sinensis) hatchlings were exposed to different concentrations of vinclozolin (0, 5, 50, 500 and 5000 µg/L) for 60 days to investigate the impact of fungicide exposure on their gut microbial composition and diversity. Vinclozolin exposure significantly affected the composition of the gut microbiota in hatchling turtles. Unexpectedly, gut bacterial diversity and richness of vinclozolin-exposed turtles (but not for the 5000 µg/L-exposed group) were relatively higher than control ones. At the phylum level, the abundance of Firmicutes was decreased, while that of Proteobacteria was increased in high-concentration groups. At the genus level, some bacterial genera including Cellulosilyticum, Romboutsia and Clostridium_sensu_stricto, were significantly changed after vinclozolin exposure; and some uniquely observed in high-concentration groups. Gene function predictions showed that genes related to amino acid metabolism were less abundant, while those related to energy metabolism more abundant in high-concentration groups. The prevalence of some pathogens inevitably affected gut health status of vinclozolin-exposed turtles. Such gut microbiota dysbiosis might be potentially linked with hepatic metabolite changes induced by vinclozolin exposure.

Lewis acid-catalyzed Pudovik reaction-phospha-Brook rearrangement sequence to access phosphoric esters.

Herein, we report a Lewis acid-catalyzed Pudovik reaction-phospha-Brook rearrangement sequence between diarylphosphonates or -phosphinates and α-pyridinealdehydes to access valuable phosphoric ester compounds. This transformation provides an extended substrate scope that is complementary to similar previously reported base-catalyzed transformations.

Angle-resolved polarized Raman spectra of the basal and edge plane of MoS2.

Angle-resolved polarized (ARP) Raman spectroscopy can be utilized to characterize the Raman modes of two-dimensional layered materials based on crystal symmetry or crystal orientation. In this paper, the polarization properties of E 1 2g and A1g modes on the basal plane and edge plane of high purity 2H-MoS2 bulk crystal grown by chemical vapor transport (CVT) method were investigated by ARP Raman spectroscopy. The I and II type ARP Raman spectroscopy with four kinds of polarization configurations: αY, αX, ßY, and ßX were used to explore the intensity dependence of E 1 2g and A1g modes at different planes on the polarization direction of incident/scattered light. The results show that the E 1 2g and A1g modes exhibit different polarization properties dependent on the polarization of the incident laser and the in-plane rotation of the sample at different planes. The experimental results were confirmed and analyzed through theoretical calculation. Our work sheds light on the intriguing effect of the subtle atomic structure in stacked MoS2 layers on the resulting ARP Raman properties. This provides a reference for the study of other two-dimensional layered crystalline materials by ARP Raman spectroscopy.

Dual-specificity phosphatase 15 (DUSP15) in the nucleus accumbens is a novel negative regulator of morphine-associated contextual memory.

Drug relapse among addicts often occurs due to the learned association between drug-paired cues and the rewarding effects of these drugs, such as morphine. Contextual memory associated with morphine has a central role in maintenance and relapse. We showed that morphine-conditioned place preference (CPP) activates extracellular-regulated protein kinase (ERK) in the nucleus accumbens (NAc). The main enzymes that mediate ERK dephosphorylation are members of the dual-specificity phosphatase (DUSP) superfamily. It is unclear which members regulate the morphine CPP-induced activation of ERK. After screening, DUSP15 was found to be decreased during both morphine CPP expression and the reinstatement period. Intra-NAc infusions of AAV-DUSP15 (overexpression) not only prevented the expression of morphine-induced CPP but also facilitated extinction, inhibited reinstatement, and abolished ERK activation. However, after repeated morphine exposure and withdrawal in mice, there was no change in the expression of p-ERK and DUSP15, and the overexpression of DUSP15 in the NAc did not improve the impaired spatial memory or anxiety-like behaviour induced by morphine. Together, these findings indicate that DUSP15 not only prevents the expression of drug-paired contextual memory but also promotes the extinction of existing addiction memories, thus providing a novel therapeutic target for the treatment of drug addiction.

Divergent incubation temperature effects on thermal sensitivity of hatchling performance in two different latitudinal populations of an invasive turtle.

The incubation temperature for embryonic development affects several aspects of hatchling performance, but its impact on the thermal sensitivity of performance attributes remains poorly investigated. In the present study, Trachemys scripta elegans hatchlings from two different latitudinal populations were collected to assess the effects of different incubation temperatures on the locomotor (swimming speed) and physiological (heart rate) performances, and the thermal sensitivity of these two attributes. The incubation temperature significantly affected the examined physiological traits. Hatchling turtles produced at low incubation temperature exhibited relatively higher cold tolerance (lower body temperatures at which the animals lose the ability to escape from the lethal conditions), and reduced heart rate and swimming speed. Furthermore, the effect of incubation temperature on the thermal sensitivity of swimming speed differed between the low- and high-latitude populations. At relatively high incubation temperatures, the high-latitude hatchling turtles exhibited reduced thermal sensitivities of swimming speed than those of the low-latitude ones. Reduced thermal sensitivity of locomotor performance together with high cold tolerance, exhibited by the high-latitude hatchling turtles potentially reflected local adaptation to relatively colder and more thermally-variable environments.

Evaluation and Prediction on the Effect of Ionic Properties of Solvent Extraction Performance of Oily Sludge Using Machine Learning.

Oily sludge produced in the process of petroleum exploitation and utilization is a kind of hazardous waste that needs to be urgently dealt with in the petrochemical industry. The oil content of oily sludge is generally between 15-50% and has a great potential for oil resource utilization. However, its composition is complex, in which asphaltene is of high viscosity and difficult to separate. In this study, The oily sludge was extracted with toluene as solvent, supplemented by three kinds of ionic liquids (1-ethyl-3-methylimidazole tetrafluoroborate ([EMIM] [BF4]), 1-ethyl-3-methylimidazole trifluoro-acetate ([EMIM] [TA]), 1-ethyl-3-methylimidazole Dicyandiamide ([EMIM] [N(CN)2])) and three kinds of deep eutectic solutions (choline chloride/urea (ChCl/U), choline chloride / ethylene glycol (ChCl/EG), and choline chloride/malonic acid (ChCl/MA)). This experiment investigates the effect of physicochemical properties of the solvents on oil recovery and three machine learning methods (ridge regression, multilayer perceptron, and support vector regression) are used to predict the association between them. Depending on the linear correlation of variables, it is found that the conductivity of ionic liquid is the key characteristic affecting the extraction treatment in this system.

CCL8 secreted by tumor-associated macrophages promotes invasion and stemness of glioblastoma cells via ERK1/2 signaling.

Tumor-associated macrophages (TAMs) constitute a large population of glioblastoma and facilitate tumor growth and invasion of tumor cells, but the underlying mechanism remains undefined. In this study, we demonstrate that chemokine (C-C motif) ligand 8 (CCL8) is highly expressed by TAMs and contributes to pseudopodia formation by GBM cells. The presence of CCL8 in the glioma microenvironment promotes progression of tumor cells. Moreover, CCL8 induces invasion and stem-like traits of GBM cells, and CCR1 and CCR5 are the main receptors that mediate CCL8-induced biological behavior. Finally, CCL8 dramatically activates ERK1/2 phosphorylation in GBM cells, and blocking TAM-secreted CCL8 by neutralized antibody significantly decreases invasion of glioma cells. Taken together, our data reveal that CCL8 is a TAM-associated factor to mediate invasion and stemness of GBM, and targeting CCL8 may provide an insight strategy for GBM treatment.

Anthrax toxin receptor 1/tumor endothelial marker 8 promotes gastric cancer progression through activation of the PI3K/AKT/mTOR signaling pathway.

Anthrax toxin receptor 1 (ANTXR1), a type I transmembrane protein, is one of the receptors that facilitates the entrance of anthrax toxin into cells. Previous studies have confirmed the pivotal role of ANTXR1 in progression and tumorigenesis of diverse cancer types. However, the biological function of ANTXR1 in gastric cancer (GC) is still unknown. The present study aimed to investigate the role of ANTXR1 in GC and illuminate the potential molecular mechanisms. Bioinformatics analysis found that ANTXR1 expression was significantly upregulated in GC tissue and its overexpression was associated with poor prognosis of GC patients. Moreover, we confirmed the upregulation of ANTXR1 in GC cell lines and GC tissue by quantitative PCR, western blot analysis, and immunohistochemical analysis. Additionally, high protein expression level of ANTXR1 was positively associated with several clinicopathological parameters in GC patients. In our study, a series of in vitro and in vivo assays were undertaken through strategies of loss/gain-of-function and rescue assays. Consequently, our results indicated that ANTXR1 induced proliferation, cell cycle progression, invasion and migration, and tumorigenicity and induced suppressed apoptosis in GC. Mechanistic investigation indicated that ANTXR1 exerted its promoting effects on GC through activation of the PI3K/AKT/mTOR signaling pathway. In conclusion, our findings suggested that ANTXR1 plays a crucial role in the development and progression of GC and could serve as a novel prognostic biomarker and potential therapeutic target for GC.

Long noncoding RNAs involvement in Epstein-Barr virus infection and tumorigenesis.

The Epstein-Barr virus (EBV) is a ubiquitous γ-herpesvirus related to various types of cancers, including epithelial nasopharyngeal carcinoma, gastric carcinoma, and lymphoma. Long noncoding RNAs (lncRNAs) are expressed extensively in mammalian cells and play crucial roles in regulating various cellular processes and multiple cancers. Cellular lncRNAs can be differentially expressed induced by EBV infection. The dysregulated lncRNAs probably modulate the host immune response and other biological functions. At present, lncRNAs have been found to be significantly increased or decreased in EBV-infected cells, exosomes and EBV-associated cancers, suggesting their potential function and clinical application as biomarkers. In addition, EBV-encoded lncRNAs, BART and BHLF1 lncRNAs, may play roles in the viral oncogenesis. Analysis of the specific lncRNAs involved in interactions with the EBV machinery will provide information on their potential mechanism of action during multiple steps of EBV tumorigenesis. Here, we review the current knowledge regarding EBV-related lncRNAs and their possible roles in the pathogenesis of EBV-associated cancers.

An Insight into the Excitation States of Small Molecular Semiconductor Y6.

Y6 is a new type of non-fullerene acceptor, which has led to power conversion efficiencies of single-junction polymer solar cells over 17% when combined with a careful choice of polymeric donors. However, the excited state characteristics of Y6, which is closely correlated with its opto-electronic applications, are not clear yet. In this work, we studied the excited state properties of the Y6 solution and Y6 film, by using steady-state and time-resolved spectroscopies as well as time-dependent density functional theory (TD-DFT) calculations. UV-Vis absorption and fluorescence simulation, natural transition orbitals (NTOs) and hole-electron distribution analysis of Y6 solution were performed for understanding the excitation properties of Y6 by using TD-DFT calculations. The lifetimes of the lowest singlet excited state in Y6 solution and film were estimated to be 0.98 and 0.8 ns, respectively. Combining the exciton lifetime and photoluminescence (PL) quantum yield, the intrinsic radiative decay lifetimes of Y6 in the solution and film were estimated, which were 1.3 and 10.5 ns for the Y6 solution and film, respectively. Long exciton lifetime (~0.8 ns) and intrinsic radiative decay lifetime (~10.5 ns) of Y6 film enable Y6 to be a good acceptor material for the application of polymer solar cells.

The role of exosomal noncoding RNAs in cancer.

Extracellular vesicles (EVs) membranes enclose nanosized vesicles with a size range of 30-150 nm and are plentiful in our body in both physiological and pathological conditions. Exosomes, a type of EV, are important mediators of intracellular communication among tumor cells, immune cells, and stromal cells. They can shuttle bioactive molecules, such as proteins, lipids, RNA, and DNA; however, the precise function of EVs remains largely unknown. In recent years, tumor-associated cargo in exosomes has been a hot topic in research, especially with respect to noncoding RNAs (ncRNAs). Herein, we review the role of exosomal ncRNAs, including miRNAs and long noncoding RNAs, in tumor biological processes. Clinically, exosomal ncRNAs may eventually become novel biomarkers and therapeutic targets in cancer progression.