Exploring Dynamic Changes in HIV-1 Molecular Transmission Networks and Key Influencing Factors: Cross-Sectional Study.

BACKGROUND: The HIV-1 molecular network is an innovative tool, using gene sequences to understand transmission attributes and complementing social and sexual network studies. While previous research focused on static network characteristics, recent studies' emphasis on dynamic features enhances our understanding of real-time changes, offering insights for targeted interventions and efficient allocation of public health resources. OBJECTIVE: This study aims to identify the dynamic changes occurring in HIV-1 molecular transmission networks and analyze the primary influencing factors driving the dynamics of HIV-1 molecular networks. METHODS: We analyzed and compared the dynamic changes in the molecular network over a specific time period between the baseline and observed end point. The primary factors influencing the dynamic changes in the HIV-1 molecular network were identified through univariate analysis and multivariate analysis. RESULTS: A total of 955 HIV-1 polymerase fragments were successfully amplified from 1013 specimens; CRF01_AE and CRF07_BC were the predominant subtypes, accounting for 40.8% (n=390) and 33.6% (n=321) of the specimens, respectively. Through the analysis and comparison of the basic and terminal molecular networks, it was discovered that 144 sequences constituted static molecular networks, and 487 sequences contributed to the formation of dynamic molecular networks. The findings of the multivariate analysis indicated that the factors occupation as a student, floating population, Han ethnicity, engagement in occasional or multiple sexual partnerships, participation in anal sex, and being single were independent risk factors for the dynamic changes observed in the HIV-1 molecular network, and the odds ratio (OR; 95% CIs) values were 2.63 (1.54-4.47), 1.83 (1.17-2.84), 2.91 (1.09-7.79), 1.75 (1.06-2.90), 4.12 (2.48-6.87), 5.58 (2.43-12.80), and 2.10 (1.25-3.54), respectively. Heterosexuality and homosexuality seem to exhibit protective effects when compared to bisexuality, with OR values of 0.12 (95% CI 0.05-0.32) and 0.26 (95% CI 0.11-0.64), respectively. Additionally, the National Eight-Item score and sex education experience were also identified as protective factors against dynamic changes in the HIV-1 molecular network, with OR values of 0.12 (95% CI 0.05-0.32) and 0.26 (95% CI 0.11-0.64), respectively. CONCLUSIONS: The HIV-1 molecular network analysis showed 144 sequences in static networks and 487 in dynamic networks. Multivariate analysis revealed that occupation as a student, floating population, Han ethnicity, and risky sexual behavior were independent risk factors for dynamic changes, while heterosexuality and homosexuality were protective compared to bisexuality. A higher National Eight-Item score and sex education experience were also protective factors. The identification of HIV dynamic molecular networks has provided valuable insights into the characteristics of individuals undergoing dynamic alterations. These findings contribute to a better understanding of HIV-1 transmission dynamics and could inform targeted prevention strategies.

Gap-free genome assembly of Salangid icefish Neosalanx taihuensis.

Neosalanx taihuensis is widely distributed in freshwater and brackish water areas in China. Due to its high commercial value, it has been artificially introduced into many lakes and reservoirs, showing strong ecological adaptability. Here, a gap-free chromosome-level reference genome was constructed by combining short reads, PacBio HiFi long reads, Nanopore ultralong reads and Hi-C data. The reference genome of N. taihuensis was 397.29 Mb with a contig N50 of 15.61 Mb. The assembled sequences were anchored to 28 chromosomes. Furthermore, 20,024 protein-coding genes and 98.16% of the predicted genes were annotated in publicly available biological databases. This high-quality gap-free assembled genome will provide an essential reference for studying the evolution and ecological adaptability of N. taihuensis.

Fluoride passivation of ZnO electron transport layers for efficient PbSe colloidal quantum dot photovoltaics.

Lead selenide (PbSe) colloidal quantum dots (CQDs) are suitable for the development of the next-generation of photovoltaics (PVs) because of efficient multiple-exciton generation and strong charge coupling ability. To date, the reported high-efficient PbSe CQD PVs use spin-coated zinc oxide (ZnO) as the electron transport layer (ETL). However, it is found that the surface defects of ZnO present a difficulty in completion of passivation, and this impedes the continuous progress of devices. To address this disadvantage, fluoride (F) anions are employed for the surface passivation of ZnO through a chemical bath deposition method (CBD). The F-passivated ZnO ETL possesses decreased densities of oxygen vacancy and a favorable band alignment. Benefiting from these improvements, PbSe CQD PVs report an efficiency of 10.04%, comparatively 9.4% higher than that of devices using sol-gel (SG) ZnO as ETL. We are optimistic that this interface passivation strategy has great potential in the development of solution-processed CQD optoelectronic devices.

Omics techniques reveal the toxicity mechanisms of three antiepileptic drugs to juvenile zebrafish (Danio rerio) brain and liver.

Epilepsy, a neurological disorder, is characterized by seizures that are an appearance of excessive brain activity and is symptomatically treated with antiepileptic drugs (AEDs). Oxcarbazepine (OCBZ), lamotrigine (LTG), and carbamazepine (CBZ) are widely used AEDs in clinics and are very often detected in aquatic environments. However, neither the sub-lethal effects nor the specific mechanisms of these AEDs' action on the fish are well understood. In this study, juvenile zebrafish were exposed to a sub-lethal concentration (100 µg/L) of OCBZ, LTG, and CBZ for 28 d, after which indicators of oxidative stress (i.e. superoxide dismutase (SOD) activity, catalase (CAT) activity, and malondialdehyde (MDA) level) and neurotoxicity (i.e. acetylcholinesterase (AChE) activity, γ-aminobutyric acid (GABA) level, and glutamic acid (Glu) level) were measured. Brain SOD activity was significantly increased by three AEDs, while brain CAT activity was significantly inhibited by LTG and CBZ. Liver SOD activity was significantly enhanced by CBZ, and liver CAT activity was significantly induced by OCBZ and LTG. Liver MDA level was significantly increased by three AEDs. Brain AChE activity was significantly increased by LTG and CBZ, and brain GABA level was significantly enhanced by three AEDs. However, there were no significant alterations in the levels of MDA and Glu in zebrafish brain. To ascertain mechanisms of AEDs-induced toxicity, brain transcriptomics and liver metabolomics were conducted in zebrafish. The brain transcriptomics results showed that lots of differentially expressed genes (DEGs) were enriched in the sensory system, the immune system, the digestive system, the metabolic processes, and others in three AEDs treated groups. The metabolomics data indicated dysregulation of glycerophospholipid signaling and lipid homeostasis in zebrafish liver after three AEDs exposure. The overall results of this study improve understanding of the sub-lethal effects and potential molecular mechanisms of action of AEDs in fish.

Development and testing of a planktonic index of biotic integrity (P-IBI) for Lake Fuxian, China.

Lake Fuxian has the largest reserves of high-quality water resources in China, and understanding its ecological health status is the basis of its environmental protection. Based on a seasonal field investigation of the plankton community, we established a planktonic index of biotic integrity (P-IBI) evaluation system to assess the lake's ecosystem health. The biological integrity of Lake Fuxian was relatively good during winter and spring, but gradually deteriorated from summer to autumn. Areas with poor biological integrity were mainly distributed near tourist attractions along the lake's west coast. Redundancy analysis (RDA) was performed to explore the relationships between the P-IBI, its selected indicators, and the environmental variables. Water temperature (WT), pH, ammonia nitrogen (NH3-N), and dissolved oxygen (DO) significantly influenced the P-IBI and its selected indicators. NH3-N and DO were significantly positively correlated with the P-IBI, indicating that it could be used as a water quality indicator to indirectly reflect lake biological integrity. We demonstrated that the P-IBI can effectively reflect temporal and spatial variations of biological integrity and could be used as a potential tool to evaluate Lake Fuxian ecosystem health.

Flexible Axial Shielding Strategy for Improving Ethylene (Co)polymerization with 8-Cycloalkylnaphthyl α-Diimine Catalysts.

8-aryl or alkyl-naphthyl substituents are widely used as an effective axial shielding strategy for the suppression of chain transfer in late-transition metal-catalyzed ethylene (co)polymerization to yield high molecular weight polyethylene and copolymers. In this study, two 8-cycloalkylnaphthyl acenaphthene-based α-diimine ligands and the corresponding four nickel and palladium complexes were designed and synthesized to explore the effect of axial flexible shielding on ethylene (co)polymerization. In ethylene polymerization, the nickel complexes displayed high activities (up to 1.99 × 106 g mol-1 h-1) and generated lightly branched (34-54/1000 C) polyethylenes with high molecular weights (up to Mn = 1075 kg/mol), whereas the corresponding palladium complexes exhibited moderate activities (level of 104 g mol-1 h-1), producing highly branched (111-125/1000 C) polyethylenes with high molecular weights (up to Mn = 37.6 kg/mol). Highly branched (110-123/1000 C) E-MA copolymers with moderate insertion ratios (1.97-5.56 mol %) were produced by these palladium complexes in ethylene/methyl acrylate (MA) copolymerization. In addition, the size of the 8-cycloalkyl ring in these α-diimine catalysts strongly influences the ethylene (co)polymerization. Compared to cyclopentyl groups, cyclohexyl groups are more effective in suppressing chain transfer reactions in the polymerization of ethylene and the copolymerization of ethylene and MA, leading to higher molecular weight polyethylene and E-MA copolymers. Most interestingly, compared to the reported rigid planar 8-arylnaphthyl catalysts, the flexible 8-cyclohexylnaphthyl catalysts exhibited higher activity and produced higher molecular weight polyethylene in ethylene polymerization. Moreover, in nickel-catalyzed ethylene polymerization, the cyclohexyl catalyst produced significantly reduced branched polyethylene, while in palladium-catalyzed ethylene (co)polymerization, the cyclohexyl catalyst produced more highly branched polyethylene and copolymers. In contrast to the previously reported flexible 8-butylnaphthyl nickel catalysts, the 8-cycloalkylnaphthyl catalysts reported in this work yielded polyethylene with narrow unimodal molecular weight distributions.

Serum vitamin D levels and Sjogren's syndrome: bi-directional Mendelian randomization analysis.

BACKGROUND: Based on the results of existing observational studies, it can be found that the association between serum vitamin D levels and the risk of Sjogren's syndrome (SS) in humans is still controversial. Based on this situation, this study aimed to assess the causal relationship between serum vitamin D levels and SS by using the Mendelian randomization (MR) approach. METHODS: In this study, genome-wide association studies (GWAS) summary statistics on serum vitamin D levels [sample size = 417,580 (UK Biobank)] and SS [sample size = 416,757 (cases = 2495, controls = 414,262) (FinnGen)] were used. The bi-directional MR analysis was then used to assess possible causal relationships. The major analysis method of MR was performed using inverse-variance weighted (IVW), supplemented by MR-Egger and the weighted median approaches. In addition, sensitivity analyses were used to ensure the stability of the results, including Cochran's Q test, MR-PRESSO, MR-Egger intercept test, and the leave-one-out test. RESULTS: The MR suggested that no significant causal effects of serum 25(OH)D levels on SS risks were observed [odds ratio (OR) = 0.9824; 95% confidence interval (CI) = 0.7130 to 1.3538; P = 0.9137]. Similarly, no evidence supported the causal effects of SS on serum vitamin D levels (ß: 0.0076, 95% CI: - 0.0031 to 0.0183; P = 0.1640). CONCLUSION: This study found no obvious evidence that serum vitamin D level is causally associated with SS risks or vice versa. We call for larger sample size studies to further unravel the potential causal relationship and the exact mechanism.

Immune reconstitution efficacy after combination antiretroviral therapy in male HIV-1 infected patients with homosexual and heterosexual transmission.

We aimed to explore the impact of sexual transmission modes on immune reconstitution after combined antiretroviral therapy (cART). We have retrospectively analyzed longitudinal samples from 1557 treated male patients with virological suppression (HIV-1 RNA < 50 copies/ml) for at least 2 years. Both heterosexuals (HET) and men who have sex with men (MSM) patients showed an increasing annual trend in CD4+ T cell counts after receiving cART (HET, ß: 23.51 (cell/µl)/year, 95% CI: 16.70-30.31; MSM, ß: 40.21 (cell/µl)/year, 95% CI: 35.82-44.61). However, the CD4+ T cell recovery rate was much lower in HET patients than MSM patients, determined by both the generalized additive mixed model (P < 0.001) and generalized estimating equations (P = 0.026). Besides HIV-1 subtypes, baseline CD4+ T cell counts and age at cART initiation, HET was an independent risk factor for immunological non-responders (adjusted OR: 1.73; 95% CI: 1.28-2.33). HET was also associated with lower probability of achieving conventional immune recovery (adjusted HR: 1.37; 95%CI: 1.22-1.67) and optimal immune recovery (adjusted HR: 1.48, 95%CI: 1.04-2.11). Male HET patients might have poorer immune reconstitution ability even after effective cART. Early initiation of cART after diagnosis and clinical monitoring for male HET patients should be highly emphasized.

In-silico target prediction by ensemble chemogenomic model based on multi-scale information of chemical structures and protein sequences.

Identification and validation of bioactive small-molecule targets is a significant challenge in drug discovery. In recent years, various in-silico approaches have been proposed to expedite time- and resource-consuming experiments for target detection. Herein, we developed several chemogenomic models for target prediction based on multi-scale information of chemical structures and protein sequences. By combining the information of a compound with multiple protein targets together and putting these compound-target pairs into a well-established model, the scores to indicate whether there are interactions between compounds and targets can be derived, and thus a target prediction task can be completed by sorting the outputted scores. To improve the prediction performance, we constructed several chemogenomic models using multi-scale information of chemical structures and protein sequences, and the ensemble model with the best performance was used as our final model. The model was validated by various strategies and external datasets and the promising target prediction capability of the model, i.e., the fraction of known targets identified in the top-k (1 to 10) list of the potential target candidates suggested by the model, was confirmed. Compared with multiple state-of-art target prediction methods, our model showed equivalent or better predictive ability in terms of the top-k predictions. It is expected that our method can be utilized as a powerful computational tool to narrow down the potential targets for experimental testing.

Macrophage Migration Inhibitory Factor in Psoroptes ovis: Molecular Characterization and Potential Role in Eosinophil Accumulation of Skin in Rabbit and Its Implication in the Host-Parasite Interaction.

Psoroptes ovis, a common surface-living mite of domestic and wild animals worldwide, results in huge economic losses and serious welfare issues in the animal industry. P. ovis infestation rapidly causes massive eosinophil infiltration in skin lesions, and increasing research revealed that eosinophils might play an important role in the pathogenesis of P. ovis infestation. Intradermal injection of P. ovis antigen invoked massive eosinophil infiltration, suggesting that this mite should contain some relative molecules involved in eosinophil accumulation in the skin. However, these active molecules have not yet been identified. Herein, we identified macrophage migration inhibitor factor (MIF) in P. ovis (PsoMIF) using bioinformatics and molecular biology methods. Sequence analyses revealed that PsoMIF appeared with high similarity to the topology of monomer and trimer formation with host MIF (RMSD = 0.28 angstroms and 2.826 angstroms, respectively) but with differences in tautomerase and thiol-protein oxidoreductase active sites. Reverse transcription PCR analysis (qRT-PCR) results showed that PsoMIF was expressed throughout all the developmental stages of P. ovis, particularly with the highest expression in female mites. Immunolocalization revealed that MIF protein located in the ovary and oviduct of female mites and also localized throughout the stratum spinosum, stratum granulosum, and even basal layers of the epidermis in skin lesions caused by P. ovis. rPsoMIF significantly upregulated eosinophil-related gene expression both in vitro (PBMC: CCL5, CCL11; HaCaT: IL-3, IL-4, IL-5, CCL5, CCL11) and in vivo (rabbit: IL-5, CCL5, CCL11, P-selectin, ICAM-1). Moreover, rPsoMIF could induce cutaneous eosinophil accumulation in a rabbit model and increased the vascular permeability in a mouse model. Our findings indicated that PsoMIF served as one of the key molecules contributing to skin eosinophil accumulation in P. ovis infection of rabbits.

Development and validation of a combined ferroptosis and immune prognostic signature for lung adenocarcinoma.

Background: Studies have shown that the regulation of ferroptosis could be a new approach to cancer treatment and abnormal ferroptosis is closely associated with a dysregulated immune response. However, a combined signature with ferroptosis-related genes (FRGs) and immune-related genes (IRGs) is necessary to be constructed for predicting prognoses and guiding individualized precision therapy of lung adenocarcinoma (LUAD) patients. Methods: In this study, based on the Cancer Genome Atlas (TCGA) cohort, prognosis-related FRGs and IRGs were first identified and incorporated into the Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression model to generate a combined signature of ferroptosis- and immune-related genes (CSFI) values to predict the overall survivals (OSs) of LUAD patients. And patients with LUAD from the Gene Expression Omnibus (GEO) database were applied for the validation set. Nomogram was constructed based on multivariate Cox regression analysis. Subsequently, ferroptosis, immunity, and gene mutation status of patients between the CSFI-high and -low groups were compared. Additionally, the enrichment pathways in CSFI-high and -low groups were explored by Gene Ontology (GO), Kyoto Gene and Genome Encyclopedia (KEGG) and Gene Set Enrichment Analysis (GSEA) analyses. Results: As a result, the CSFI-low group showed a good prognosis instead of the CSFI-high group. CSFI was identified to be an independent prognosis factor for LUAD. In general, there were ferroptosis- and immune-suppressive states in CSFI-high patients. Notably, the mutation frequencies of TP53 were higher in CSFI-high patients. Conclusions: In LUAD, CSFI which served as a novel classifier was offered for predicting the prognoses of patients and contributing to guiding personalized targeted therapy of patients. Therefore, based on these findings, it was believed that a synergistic treatment of ferroptosis and immunity would be more effective on LUAD patients with low CSFI values.

Association of ATRX mutations with immunologically active characteristics in patients with MSI-prone tumors.

OBJECTIVES: The role of DNA damage repair deficiency in improving immune checkpoint inhibitors (ICIs) efficacy has been widely recognized. Studies have confirmed the association of gene mutations in homologous recombination (HR) with an immune-activated microenvironment. Given the crucial role of the tumor microenvironment in ICIs response, our study aimed to identify specific HR gene mutations that influence the tumor microenvironment and thus serve as potential biomarkers for ICIs in tumors that are prone to occur with microsatellite instability (MSI) events (MSI-prone tumors). METHODS: The multi-omics and clinical data of MSI-prone tumors were extracted from ICIs-treated and non-ICIs-treated cohorts. We depicted the mutation landscape of HR genes in MSI-prone tumors and identified the prognosis related HR gene mutations. We integrated multiple immunotherapy-related indicators by bioinformatics methods to characterize the anti-tumor immunity and tumor microenvironment. RESULTS: ATRX, ARID1A, BRCA2 and ATM were the common top four frequently mutated HR genes in MSI-prone tumors, among which ATRX mutations were identified to have prognostic value for ICIs treatment. The bioinformatics analyses suggested that patients with ATRX mutilations (ATRX-mt) have enhanced anti-tumor immunity and inflamed tumor microenvironment in MSI-prone tumors. MSI-stratified analyses revealed the immunologically active features in both microsatellite instability-high (MSI-H) and non-MSI-H populations. There may exist a synergistic effect between ATRX mutations and MSI-H status in immune activation. CONCLUSIONS: Our work found the association of ATRX mutations with immunologically active characteristics in MSI-prone tumors. The combined use of ATRX mutations and MSI-H status might have potential clinical utility for ICIs selection in MSI-prone tumors.

Identification and validation of a genomic mutation signature as a predictor for immunotherapy in NSCLC.

Currently, the benefits of immune checkpoint inhibitor (ICI) therapy prediction via emerging biomarkers have been identified, and the association between genomic mutation signatures (GMS) and immunotherapy benefits has been widely recognized as well. However, the evidence about non-small cell lung cancer (NSCLC) remains limited. We analyzed 310 immunotherapy patients with NSCLC from the Memorial Sloan Kettering Cancer Center (MSKCC) cohort. Lasso Cox regression was used to construct a GMS, and the prognostic value of GMS could be able to verify in the Rizvi cohort (N=240) and Hellmann cohort (N=75). We further conducted immunotherapy-related characteristics analysis in The Cancer Genome Atlas (TCGA) cohort (N=1052). A total of seven genes (ZFHX3, NTRK3, EPHA7, MGA, STK11, EPHA5, TP53) were identified for GMS model construction. Compared with GMS-high patients, patients with GMS-low had longer overall survival (OS; P<0.001) in the MSKCC cohort and progression-free survival (PFS; P<0.001) in the validation cohort. Multivariate Cox analysis revealed that GMS was an independent predictive factor for NSCLC patients in both the MSKCC and validation cohort. Meanwhile, we found that GMS-low patients reflected enhanced antitumor immunity in TCGA cohort. The results indicated that GMS had not only potential predictive value for the benefit of immunotherapy but also may serve as a potential biomarker to guide clinical ICI treatment decisions for NSCLC.

Neurotransmitter release cycle-related genes predict the prognosis of lung adenocarcinoma.

Because of the limitations of therapeutic approaches, patients suffering from lung adenocarcinoma (LUAD) have unsatisfactory prognoses. Studies have shown that neurotransmitters participated in tumorigenesis and development. In LUAD, the expression of neurotransmitter release cycle-related genes (NRCRGs) has been reported to be disordered. This study aimed to study the correlation between NRCRGs and LUAD. In this study, based on the Cancer Genome Atlas cohort, consensus clustering analyses were performed on ten neurotransmitter release cycle-related (NRCR) differentially expressed genes. Neurotransmitter release cycle (NRC) scores were derived by the Least Absolute Shrinkage and Selection Operator-Cox regression model constituted by 3 NRCRGs. Univariate and multivariate Cox regression analyses were performed to evaluate the prognosis value of the NRC score. In addition, single-Sample Gene Set Enrichment Analysis and CIBERSORT were conducted in the Cancer Genome Atlas cohort. Finally, gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were also performed. As a result, the NRC-low group showed a good prognosis instead of the NRC-high group. NRC score was identified to be an independent prognosis factor for LUAD. In general, the NRC score based on the prognostic model was found to be closely correlated with immunotherapy-related anti-cancer immunity and inflamed tumor microenvironment. Functional enrichment results demonstrated that differentially expressed genes between 2 NRC groups were closely correlated with DNA replication, cell-substrate adhesion, Golgi vesicle transport, MAPK signal pathway, and many others. Novel biomarkers were offered for predicting the prognoses of LUAD patients. The NRC score might contribute to guiding LUAD patients with immunotherapy selection.

The Molecular Epidemiological and Immunological Characteristics of HIV-1 CRF01_AE/B Recombinants in Nanjing, China.

Human immunodeficiency virus-type 1 (HIV-1) CRF01_AE/B recombinants are newly emerging strains that are spreading rapidly in Southern and Eastern China. This study aimed to elucidate the molecular epidemiological characteristics of HIV-1 CRF01_AE/B recombinants in Nanjing and to explore the impact of these novel strains on the immunological status. A total of 1,013 blood samples from newly diagnosed HIV-1-infected patients were collected in Nanjing from 2015 to 2019, among which 958 partial Pol sequences were sequenced successfully. We depicted the molecular epidemiological characteristics of CRF01_AE/B recombinants by the molecular evolutionary analysis, Bayesian system evolution analysis, and transmission network analysis. The generalized additive mixed model was applied to evaluate the CD4+ T-cell count change of CRF01_AE/B recombinants. The Kaplan-Meier analysis was performed to assess the time from combined antiretroviral therapy (cART) initiation to immune reconstruction. We have identified 102 CRF01_AE/B recombinants (102/958, 10.65%) in Nanjing, including CRF67_01B (45/102, 44.12%), CRF68_01B (35/102, 34.31%), and CRF55_01B (22/102, 12.57%). According to the Bayesian phylogenetic inference, CRF55_01B had a rapid decline stage during 2017-2019, while CRF67_01B and CRF68_01B have experienced a fast growth phase during 2014-2015 and then remained stable. We have constructed 83 transmission networks, in which three larger clusters were composed of CRF67_01B and CRF68_01B. CRF01_AE/B recombinants manifested a faster decrease rate of CD4+ T-cell count than CRF_07BC but similar to CRF01_AE. The probability of achieving immune reconstruction in CRF01_AE/B recombinants was lower than CRF07_BC in the subgroup of baseline CD4+ T-cell count at cART initiation <300 cells/µl. In summary, CRF67_01B and CRF68_01B were the major strains of CRF01_AE/B recombinants in Nanjing, which have formed large transmission clusters between Nanjing and other provinces. CRF01_AE/B recombinants might be associated with rapid disease progression and poor immune reconstruction. The continuous epidemiological monitoring of CRF01_AE/B recombinants should be highly emphasized.

Transcriptome profiling reveals toxicity mechanisms following sertraline exposure in the brain of juvenile zebrafish (Danio rerio).

Sertraline (SER) is one of the most commonly detected antidepressants in the aquatic environment that can negatively affect aquatic organisms at low concentrations. Despite some knowledge on its acute toxicity to fish, the effects of chronic SER exposure remain poorly understood along with any underlying mechanisms of SER-induced toxicity. To address this knowledge gap, the effects of chronic exposure to three SER concentrations from low to high were investigated in zebrafish. Juvenile zebrafish were exposed to three concentrations of 1, 10, or 100 µg/L of SER for 28 d, after which indicators of oxidative stress and neurotoxicity in the brain were measured. Superoxide dismutase (SOD) activity was significantly enhanced by SER at 1 up to 100 µg/L, and catalase (CAT) activity was significantly induced by SER at 1 or 10 µg/L. The activity of acetylcholinesterase (AChE) was significantly induced by 10 and 100 µg/L of SER, and the serotonin (5-HT) level was significantly increased by all three concentrations of SER. To ascertain mechanisms of SER-induced toxicity, transcriptomics was conducted in the brain of zebrafish following 100 µg/L SER exposure. The molecular signaling pathways connected with circadian system and the immune system were significantly altered in the zebrafish brain. Based on transcriptomic data, the expression levels of six circadian clock genes were measured, and three genes were significantly altered in relative abundance in fish from all experimental treatments with SER, including cryptochrome circadian regulator 2 (cry2), period circadian clock 2 (per2), and period circadian clock 3 (per3). We hypothesize that the circadian system may be related to SER-induced neurotoxicity and oxidative stress in the central nervous system. This study reveals potential mechanisms and key events (i.e., oxidative stress and neurotoxicity) associated with SER-induced toxicity, and improves understanding of the molecular and biochemical pathways putatively perturbed by SER.

Synthesis of High-Molecular-Weight Branched Polyethylene Using a Hybrid "Sandwich" Pyridine-Imine Ni(II) Catalyst.

Most pyridine-imine Ni(II) and Pd(II) catalysts tend to yield low-molecular-weight polyethylene and ethylene-based copolymers in olefin insertion polymerization, as the unilateral axial steric structure of such complexes often cannot provide effective shielding of the metal center. In this study, we synthesized a series of hybrid "semi-sandwich" and "sandwich" type pyridine-imine Ni(II) complexes by incorporating diarylmethyl or dibenzosuberyl groups onto 8-aryl-naphthyl motif. The as-prepared Ni(II) complexes afforded highly branched polyethylene with high molecular weights (level of 105 g/mol), and moderate activities (level of 105 g/(molh)) in ethylene polymerization. Most interestingly, compared to "semi-sandwich" Ni(II) complexes bearing (2-diarylmethyl-8-aryl)naphthyl units, the "full-sandwich" counterpart containing (2-dibenzosuberyl-8-aryl)naphthyl motif was able to produce higher-molecular-weight polyethylene with higher branching density. In addition, the effect of remote non-conjugated electronic substituents in diarylmethyl groups of the Ni(II) system was also observed in ethylene polymerization.

Co-occurrence of multiple cyanotoxins and taste-and-odor compounds in the large eutrophic Lake Taihu, China: Dynamics, driving factors, and challenges for risk assessment.

Cyanobacterial blooms producing toxic metabolites occur frequently in freshwater, yet the environmental behaviors of complex cyanobacterial metabolites remain largely unknown. In this study, the seasonal and spatial variations of several classes of cyanotoxins (microcystins, cylindrospermopsins, saxitoxins) and taste-and-odor (T&O) compounds (ß-cyclocitral, ß-ionone, geosmin, 2-methylisoborneol) in Lake Taihu were simultaneously investigated for the first time. The total cyanotoxins were dominated by microcystins with concentrations highest in November (mean 2209 ng/L) and lowest in February (mean 48.7 ng/L). Cylindrospermopsins were abundant in May with the highest content of 622.8 ng/L. Saxitoxins only occurred in May (mean 19.2 ng/L) and November (mean 198.5 ng/L). Extracellular T&O compounds were most concentrated in August, the highest being extracellular ß-cyclocitral (mean 240.6 ng/L) followed by 2-methylisoborneol (mean 146.6 ng/L). Environment variables play conflicting roles in modulating the dynamics of different groups of cyanotoxins and T&O compounds. Total phosphorus (TP), total nitrogen (TN), chlorophyll-a and cyanobacteria density were important factors affecting the variation of total microcystins, ß-cyclocitral and ß-ionone concentrations. In contrast, total cylindrospermopsins, 2-methylisoborneol and geosmin concentrations were significantly influenced by water temperature and TP. There was a significant and linear relationship between microcystins and ß-cyclocitral/ß-ionone, while cylindrospermopsins were positively correlated with 2-methylisoborneol and geosmin. The perceptible odors may be good indicators for the existence of cyanotoxins. Hazard quotients revealed that potential human health risks from microcystins were high in August and November. Meanwhile, the risks from cylindrospermopsins were at moderate levels. Cylindrospermopsins and saxitoxins were first identified in this lake, suggesting that diverse cyanotoxins might co-occur more commonly than previously thought. Hence, the risks from other cyanotoxins beyond microcystins shouldn't be ignored. This study also highlights that the necessity for further assessing the combination effects of these complex metabolites.

Flexible "Sandwich" (8-Alkylnaphthyl α-Diimine) Catalysts in Insertion Polymerization.

8-Arylnaphthyl substituents are privileged motifs frequently integrated into late-transition-metal catalysts, endowing them with an ability to retard chain transfer in ethylene polymerization. In this contribution, we disclose a sort of novel α-diiminenickel and -palladium complexes containing flexible 8-alkylnaphthyl in lieu of rigid 8-arylnaphthyl and their catalytic performance in ethylene polymerization. An interesting feature of these 8-alkylnaphthyl-substituted α-(diimine)PdMeCl complexes is that they present as a mixture of syn and anti isomers (syn:anti = ca. 1:1 ratio, determined by 1H and 13C NMR spectroscopy). In ethylene polymerization, these nickel complexes displayed high activity (up to 3.37 × 106 g mol-1 h-1) and generated branched polyethylenes with broad or bimodal molecular weight distributions (4.6-29.3), while the corresponding palladium complexes exhibited moderate activity, producing highly branched polyethylenes with unimodal and narrow molecular weight distributions (<1.8). In ethylene (E)/methyl acrylate (MA) copolymerization, highly branched E-MA copolymers with considerable MA incorporations were achieved by these palladium complexes. Most interestingly, compared to rigid 8-arylnaphthyl-substituted α-diiminenickel and -palladium complexes, the flexible 8-alkylnaphthyl ones showed significantly improved activity and generated lower or comparable molecular weight polyethylenes or E-MA copolymers.