Distribution and spatial variation of volatile methylsiloxanes in surface water and wastewater from the Yangtze River Basin, China.

Volatile methylsiloxanes (VMSs) earned serious concerns due to their detection and toxicities after their release to the environments. They were also detected in rivers around the globe, but their distribution remained to be explored in larger rivers with longer length, higher water volume and wider watershed. In the present study, 8 cyclic VMSs (cVMSs) and 7 linear ones (lVMSs) were investigated in 42 water samples (27 surface water (including 7 drinking source water) and 15 wastewater) from the Yangtze River Basin, China. Results showed that VMSs were detected in all sampling sites. In surface water, the concentrations of total cVMSs ranged from 17.3 to 4.57 × 103 ng/L, while those of lVMSs ranged from 1.72 to 81.6 ng/L. In wastewater, the total concentrations of cVMSs and lVMSs showed ranges of 17.6-1.66 × 103 ng/L and 2.59-252 ng/L, respectively. Apparently, cVMSs showed significantly higher concentrations than lVMSs. The concentrations of cVMSs followed an order of lower > upper > middle reaches, while those of lVMSs did not show clear distribution patterns. Among cVMSs, those with less Si numbers were dominant, while those with more Si numbers were dominant in lVMSs. Notably, the VMSs were also detected in 7 surface waters that served as drinking source waters, which earned them further concerns. In addition, the VMSs in surface water showed positive correlation with those in wastewater, which led to necessity in management on industrial emissions in the future.

Influence of dietary status on the obesogenic effects of erythromycin antibiotic on Caenorhabditis elegans.

As emerging pollutants, antibiotics were widely detected in water bodies and dietary sources. Recently, their obesogenic effects raised serious concerns. So far, it remained unclear whether their obesogenic effects would be influenced by water- and diet-borne exposure routes. In present study, Caenorhabditis elegans, nematodes free-living in air-water interface and feeding on bacteria, were exposed to water- and diet-borne erythromycin antibiotic (ERY). The statuses of the bacterial food, inactivated or alive, were also considered to explore their influences on the effects. Results showed that both water- and diet-borne ERY significantly stimulated body width and triglyceride contents. Moreover, diet-borne ERY's stimulation on the triglyceride levels was greater with alive bacteria than with inactivated bacteria. Biochemical analysis showed that water-borne ERY inhibited the activities of enzymes like adipose triglyceride lipase (ATGL) in fatty acid ß-oxidation. Meanwhile, diet-borne ERY inhibited the activities of acyl-CoA synthetase (ACS) and carnitine palmitoyl transferase (CPT) in lipolysis, while it stimulated the activities of fatty acid synthase (FAS) in lipogenesis. Gene expression analysis demonstrated that water-borne ERY with alive bacteria significantly upregulated the expressions of daf-2, daf-16 and nhr-49, without significant influences in other settings. Further investigation demonstrated that ERY interfered with bacterial colonization in the intestine and the permeability of the intestinal barrier. Moreover, ERY decreased total long-chained fatty acids (LCFAs) in bacteria and nematodes, while it decreased total short-chained fatty acids (SCFAs) in bacteria but increased them in nematodes. Collectively, the present study demonstrated the differences between water- and diet-borne ERY's obesogenic effects, and highlighted the involvement of insulin and nhr-49 signaling pathways, SCFAs metabolism and also the interaction between intestinal bacteria and the host.

Obesogenic potentials of environmental artificial sweeteners with disturbances on both lipid metabolism and neural responses.

Artificial sweeteners (ASs) entered the environments after application and emissions. Recent studies showed that some ASs had obesogenic risks. However, it remained unclear whether such risks are common and how they provoke such effects. Presently, the effects of 8 widely used ASs on lipid accumulation were measured in Caenorhabditis elegans. Potential mechanisms were explored with feeding and locomotion behavior, lipid metabolism and neural regulation. Results showed that acesulfame (ACE), aspartame (ASP), saccharin sodium (SOD), sucralose (SUC) and cyclamate (CYC) stimulated lipid accumulation at µg/L levels, showing obesogenic potentials. Behavior investigation showed that ACE, ASP, SOD, SUC and CYC biased more feeding in the energy intake aspect against the locomotion in the energy consumption one. Neotame (NEO), saccharin (SAC) and alitame (ALT) reduced the lipid accumulation without significant obesogenic potentials in the present study. However, all 8 ASs commonly disturbed enzymes (e.g., acetyl-CoA carboxylase) in lipogenesis and those (e.g., carnitine palmitoyl transferase) in lipolysis. In addition, ASs disturbed PPARγ (via expressions of nhr-49), TGF-ß/DAF-7 (daf-7) and SREBP (sbp-1) pathways. Moreover, they also interfered neurotransmitters including serotonin (5-HT), dopamine (DA) and acetylcholine (ACh), with influences in Gsα (e.g., via expressions of gsα-1, ser-7), glutamate (e.g., mgl-1), and cGMP-dependent signaling pathways (e.g., egl-4). In summary, environmental ASs commonly disturbed neural regulation connecting behavior and lipid metabolism, and 5 out of 8 showed clear obesogenic potentials. ENVIRONMENTAL IMPLICATION: Artificial sweeteners (ASs) are become emerging pollutants after wide application and continuous emission. Recent studies showed that some environmental ASs had obesogenic risks. The present study employed Caenorhabditis elegans to explore the influences of 8 commonly used ASs on lipid metabolisms and also the underlying mechanisms. Five out of 8 ASs stimulated lipid accumulation at µg/L levels, and they biased energy intake against energy consumption. The other three ASs reduced the lipid accumulation. ASs commonly disturbed lipogenesis and lipolysis via PPARγ, TGF-ß and SREBP pathways, and also influenced neurotransmitters with Gsα, glutamate and cGMP-dependent signaling pathways.

Metastatic effects of perfluorooctanoic acid (PFOA) on Drosophila melanogaster with metabolic reprogramming and dysrhythmia in a multigenerational exposure scenario.

Perfluorooctanoic acid (PFOA) exposure correlated with various cancers and their mortality. Its persistence in the environment made its long-term multigenerational influences of significant concerns. However, it remained unanswered whether its multigenerational exposure could influence metastasis which contributes ~90 % to cancer mortality. In the present study, long-term effects of PFOA were measured in Drosophila melanogaster over 3 consecutive generations. In the morning-eclosed (AM) adult flies, PFOA significantly promoted tumor invasion rates and distances which increased over generations. Regarding metabolic reprogramming, PFOA disturbed the expressions of Glut1 and Pdk1, activities and contents of FASN1 (fatty acid synthase), ACC (acetyl-CoA carboxylase) and SREBP1 (sterol regulatory element binding protein). Regarding antioxidant responses, PFOA exposure generated provoked oxidative stress via H2O2 and stimulated antioxidants including glutathione (GSH), catalase (CAT), melatonin, serotonin and cortisol, with downregulations on PI3K/AKT pathways and upregulations on MAPK ones. The biochemical and molecular effects altered over generations. In the afternoon-eclosed (PM) adult flies, the metastasis of PFOA was more deteriorated than in AM adults. The significant influences of dysrhythmia were also observed in the multigenerational effects of PFOA on the metabolism reprogramming and antioxidant responses. The effects on rhythm-regulating gene expressions and protein levels explained the dysrhythmia and also indicated close interactions among metabolism reprogramming, antioxidant responses and rhythm regulation. ENVIRONMENTAL IMPLICATION: Numerous emerging per- and polyfluoroalkyl substances (PFASs) are being detected. Meanwhile, the toxicities of the emerging PFASs still depend on the progress of legacy PFASs for the continuity of scientific studies. As one legacy PFAS, perfluorooctanoic acid (PFOA) exposure correlated with various cancers and their mortality. Its persistence in the environment made its long-term multigenerational influences of significant concerns. However, it remained unanswered whether its multigenerational exposure could influence metastasis which contributes ~90 % to cancer mortality. The present study performed PFOA exposure for 3 consecutive generations. Results showed that the metastasis by PFOA increased over generations, and it was further deteriorated by dysrhythmia. Further analysis demonstrated the interactive involvement of metabolism reprogramming, antioxidant responses and rhythm regulation. The findings of the present study would highlight considerate points for studying the toxicities of emerging PFASs.

Multi- and trans-generational effects of di-n-octyl phthalate on behavior, lifespan and reproduction of Caenorhabditis elegans through neural regulation and lipid metabolism.

Di-n-octyl phthalate (DOP) is one important phthalate analog whose toxicities need comprehensive investigation to fully demonstrate phthalates health risks. In the present study, apical effects of DOP on behavior, lifespan and reproduction and the underlying mechanisms were explored in Caenorhabditis elegans for four consecutive generations (F1 to F4) and the trans-generational effects were also measured in the great-grand-children (T4 and T4') of F1 and F4. Multi-generational results showed that DOP caused both stimulation and inhibition on head swing, body bending, reverse, Omega steering, pharyngeal pump and satiety quiescence. The stimulation and inhibition altered over concentrations and across generations, and the alteration was the greatest in reverse locomotion which showed both concentration-dependent hormesis and trans-hormesis. DOP stimulated lifespan and inhibited reproduction, showing trade-off relationships. Significant trans-generational residual effects were found in T4 and T4' where the exposure was completed eliminated. Moreover, both similar and different effects were found in comparisons between F1 and F4, between F1 and T4, between F4 and T4' and also between T4 and T4'. Further analysis showed close connections between effects of DOP on neurotransmitters (including dopamine, acetylcholine, γ-aminobutyric acid and serotonin) and enzymes in lipid metabolism (including lipase, acetyl CoA carboxylase, fatty acid synthetase, carnitine palmitoyl-transferase, glycerol phosphate acyltransferase and acetyl CoA synthetase). Moreover, the close connections were also found between biochemical and apical effects. Notably, the connections were different in multi- and trans-generational effects, which urged further studies to reveal the response strategies underlying the exposure scenarios.

18 F-FDG PET/CT predicts the role of neoadjuvant immunochemotherapy in the pathological response of esophageal squamous cell carcinoma.

BACKGROUND: This study aimed to investigate the predictive value of 18 F-FDG PET/CT for pathological response after neoadjuvant immunochemotherapy (NICT) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: The clinical data of 54 patients with ESCC who underwent two cycles of NICT followed by surgery were retrospectively analyzed. NICT consisted of PD-1 blockade therapy combined with chemotherapy. 18 F-FDG PET/CT scans were performed before and after NICT. The pathological results after surgery were used to assess the degree of pathological response. The scan parameters of 18 F-FDG PET/CT and their changes before and after NICT were compared with the pathological response. RESULTS: Among the 54 patients, 10 (18.5%) achieved complete pathological response (pCR) and 21 (38.9%) achieved major pathological response (MPR). The post-NICT scan parameters and their changes were significantly associated with the pathological response. In addition, the values of the changes in the scanned parameters before and after treatment can further predict the pathological response of the patient. CONCLUSION: 18 F-FDG PET/CT is a useful tool to evaluate the efficacy of NICT and predict pathological response in patients with ESCC. The post-NICT scan parameters and their changes can help identify patients who are likely to achieve pCR or MPR.

SARS-CoV-2 N protein enhances the anti-apoptotic activity of MCL-1 to promote viral replication.

Viral infection in respiratory tract usually leads to cell death, impairing respiratory function to cause severe disease. However, the diversity of clinical manifestations of SARS-CoV-2 infection increases the complexity and difficulty of viral infection prevention, and especially the high-frequency asymptomatic infection increases the risk of virus transmission. Studying how SARS-CoV-2 affects apoptotic pathway may help to understand the pathological process of its infection. Here, we uncovered SARS-CoV-2 imployed a distinct anti-apoptotic mechanism via its N protein. We found SARS-CoV-2 virus-like particles (trVLP) suppressed cell apoptosis, but the trVLP lacking N protein didn't. Further study verified that N protein repressed cell apoptosis in cultured cells, human lung organoids and mice. Mechanistically, N protein specifically interacted with anti-apoptotic protein MCL-1, and recruited a deubiquitinating enzyme USP15 to remove the K63-linked ubiquitination of MCL-1, which stabilized this protein and promoted it to hijack Bak in mitochondria. Importantly, N protein promoted the replications of IAV, DENV and ZIKV, and exacerbated death of IAV-infected mice, all of which could be blocked by a MCL-1 specific inhibitor, S63845. Altogether, we identifed a distinct anti-apoptotic function of the N protein, through which it promoted viral replication. These may explain how SARS-CoV-2 effectively replicates in asymptomatic individuals without cuasing respiratory dysfunction, and indicate a risk of enhanced coinfection with other viruses. We anticipate that abrogating the N/MCL-1-dominated apoptosis repression is conducive to the treatments of SARS-CoV-2 infection as well as coinfections with other viruses.

Photocatalyzed regioselective hydrosilylation for the divergent synthesis of geminal and vicinal borosilanes.

Geminal and vicinal borosilanes are useful building blocks in synthetic chemistry and material science. Hydrosilylation/hydroborylation of unsaturated systems offer expedient access to these motifs. In contrast to the well-established transition-metal-catalyzed methods, radical approaches are rarely explored. Herein we report the synthesis of geminal borosilanes from α-selective hydrosilylation of alkenyl boronates via photoinduced hydrogen atom transfer (HAT) catalysis. Mechanistic studies implicate that the α-selectivity originates from a kinetically favored radical addition and an energetically favored HAT process. We further demonstrate selective synthesis of vicinal borosilanes through hydrosilylation of allyl boronates via 1,2-boron radical migration. These strategies exhibit broad scopes across primary, secondary, and tertiary silanes and various boron compounds. The synthetic utility is evidenced by access to multi-borosilanes in a diverse fashion and scaling up by continuous-flow synthesis.

Age-dependent neurovascular coupling characteristics in children and adults during general anesthesia.

General anesthesia is an indispensable procedure in clinical practice. Anesthetic drugs induce dramatic changes in neuronal activity and cerebral metabolism. However, the age-related changes in neurophysiology and hemodynamics during general anesthesia remain unclear. Therefore, the objective of this study was to explore the neurovascular coupling between neurophysiology and hemodynamics in children and adults during general anesthesia. We analyzed frontal electroencephalogram (EEG) and functional near-infrared spectroscopy (fNIRS) signals recorded from children (6-12 years old, n = 17) and adults (18-60 years old, n = 25) during propofol-induced and sevoflurane-maintained general anesthesia. The neurovascular coupling was evaluated in wakefulness, maintenance of a surgical state of anesthesia (MOSSA), and recovery by using correlation, coherence and Granger-causality (GC) between the EEG indices [EEG power in different bands and permutation entropy (PE)], and hemodynamic responses the oxyhemoglobin (Δ[HbO]) and deoxy-hemoglobin (Δ[Hb]) from fNIRS in the frequency band in 0.01-0.1 Hz. The PE and Δ[Hb] performed well in distinguishing the anesthesia state (p > 0.001). The correlation between PE and Δ[Hb] was higher than those of other indices in the two age groups. The coherence significantly increased during MOSSA (p < 0.05) compared with wakefulness, and the coherences between theta, alpha and gamma, and hemodynamic activities of children are significantly stronger than that of adults' bands. The GC from neuronal activities to hemodynamic responses decreased during MOSSA, and can better distinguish anesthesia state in adults. Propofol-induced and sevoflurane-maintained combination exhibited age-dependent neuronal activities, hemodynamics, and neurovascular coupling, which suggests the need for separate rules for children's and adults' brain states monitoring during general anesthesia.

Study of the Effect of Cell Prestress on the Cell Membrane Penetration Behavior by Atomic Force Microscopy.

In recent years, atomic force microscopes have been used for cell transfection because of their high-precision micro-indentation mode; however, the insertion efficiency of the tip of AFM into cells is extremely low. In this study, NIH3T3 mouse fibroblast cells cultured on a flexible dish with micro-groove patterns were subjected to various substrate strains at 5%, 10%, 15%, and 20%. It was found that the cell stiffness depends on the prestress of the cell membrane, and that the insertion rate of AFM tips into the cell membrane is proportional to the stiffness through the AFM indentation experiment. The finite element analysis proves that prestress increases the bending stiffness of the cytoskeleton, allowing it to better support the cell membrane, which realizes the stress concentration in the contact area between the AFM tip and the cell membrane. The results indicate that the prestress contributes to the mechanical properties of the cell and suggest that the insertion efficiency could be greatly improved with an increase of the prestress of the cell membrane.

Hormone-mediated multi- and trans-generational reproductive toxicities of 1-ethyl-3-methylimidazolium hexafluorophosphate on Caenorhabditis elegans.

Ionic liquids (ILs) are emergent pollutants and their reproductive toxicities show hormesis, earning attentions on their environmental risk. Yet, their reproductive effects over generations and the mechanisms were seldom explored. In the present study, the reproductive effects of 1-ethyl-3-methylimidazolium hexafluorophosphate ([C2mim]PF6) on Caenorhabditis elegans were measured in 11 continuously exposed generations (F1 to F11) to explore the multi-generational effects, and also in the non-exposed generations of F1 and F11 (i.e., their great-grand-daughters, T4 and T4') to explore the trans-generational effects. In multi-generational reproductive effects, there were concentration-dependent hormetic effects with hazard-benefit alteration between low and high concentrations (e.g., in F3). There were also generation-dependent hormetic effects with hazard-benefit alterations over generations (e.g., between F4 and F5, between F8 and F9, and between F10 and F11). Meanwhile, the results also showed benefit-hazard alteration between F2 and F3, between F6 and F7, and between F9 and F10. Trans-generational effects showed common inhibitions in T4 and T4' at both low and high concentrations. In the biochemical analysis, hormones and hormone-like substances including progesterone (P), estradiol (E2), prostaglandin (PG) and testosterone (T) showed multi- and trans-generational changes with inhibition and stimulation, which contributed to the reproductive outcomes in each generation. Such contribution was also observed in the hormones' precursor cholesterol and the proteins that are essential for reproduction including vitellogenin (Vn) and major sperm protein (MSP). Moreover, the biochemicals showed significant involvement in the connection among generations. Furthermore, the multi- and trans-generational effects of [C2mim]PF6 and histidine showed similar modes of actions despite some differences, implying the contribution of their shared imidazole structure.

Nontargeted metabolomic evidence for antagonism between tetracycline and its resistance bacteria underlying their obesogenic effects on Caenorhabditis elegans.

Environmental antibiotics raise serious health concerns due to their contribution to the obesity prevalence. Moreover, antibiotics promote antibiotic-resistance bacteria (ARB) which represent another emerging pollutant. However, the interaction between antibiotic and ARB in the obesogenic effects remained unexplored. In the present study, the obesogenic effects of tetracycline antibiotic (TCH) and ARB containing tetA were studied on C. elegans, and E. coli OP50 (OP50) was referred as a normal bacterial food. Results showed that TCH stimulated nematode triglyceride contents, while ARB alone had no significant influences. The combination of TCH and ARB showed less obesogenic effects than TCH alone, showing antagonism. Biochemical assays showed that the combination of TCH and ARB showed similar effects to ARB alone, and had less increases in lipid metabolism enzymes or metabolites than those of TCH or ARB alone, supporting the antagonism. In the nontargeted metabolomic analysis, TCH with ARB showed less significantly changed metabolites (SCMs) in the nematodes than TCH or ARB alone, partially explaining the antagonism. The metabolomic results also pointed out the significant involvement of amino acids, the carboxylic acids and derivatives, and also the benzene and substituted derivatives in the obesogenic effects of TCH and ARB. The findings of the present study provided a direct support for interaction between antibiotics and ARB underlying their health risks.

Metastatic effects of environmental carcinogens mediated by MAPK and UPR pathways with an in vivo Drosophila Model.

Metastasis includes tumor invasion and migration and underlies over 90% of cancer mortality. The metastatic effects of environmental carcinogens raised serious health concerns. However, the underlying mechanisms remained poorly studied. In the present study, an in vivo RasV12/lgl-/- model of the fruitfly, Drosophila melanogaster, with an 8-day exposure was employed to explore the metastatic effects of 3,3',4,4',5-pentachlorobiphenyl (PCB126), perfluorooctanoic acid (PFOA) and cadmium chloride (CdCl2). At 1.0 mg/L, PCB126, PFOA, and CdCl2 significantly increased tumor invasion rates by 1.32-, 1.33-, and 1.29-fold of the control, respectively. They also decreased the larval body weight and locomotion behavior. Moreover, they commonly disturbed the expression levels of target genes in MAPK and UPR pathways, and their metastatic effects were significantly abolished by the addition of p38 inhibitor (SB203580), JNK inhibitor (SP600125) and IRE1 inhibitor (KIRA6). Notably, the addition of the IRE inhibitor significantly influenced sna/E-cad pathway which is essential in both p38 and JNK regulations. The results demonstrated an essential role of sna/E-cad in connecting the effects of carcinogens on UPR and MAPK regulations and the resultant metastasis.

Sex-dependent obesogenic effect of tetracycline on Drosophila melanogaster deteriorated by dysrhythmia.

Antibiotics have been identified as obesogens contributing to the prevalence of obesity. Moreover, their environmental toxicity shows sex dependence, which might also explain the sex-dependent obesity observed. Yet, the direct evidence for such a connection and the underlying mechanisms remain to be explored. In this study, the effects of tetracycline, which is a representative antibiotic found in both environmental and food samples, on Drosophila melanogaster were studied with consideration of both sex and circadian rhythms (represented by the eclosion rhythm). Results showed that in morning-eclosed adults, tetracycline significantly stimulated the body weight of females (AM females) at 0.1, 1.0, 10.0 and 100.0 µg/L, while tetracycline only stimulated the body weight of males (AM males) at 1.0 µg/L. In the afternoon-eclosed adults, tetracycline significantly stimulated the body weight of females (PM females) at 0.1, 1.0 and 100.0 µg/L, while it showed more significant stimulation in males (PM males) at all concentrations. Notably, the stimulation levels were the greatest in PM males among all the adults. The results showed the clear sex dependence of the obesogenic effects, which was diminished by dysrhythmia. Further biochemical assays and clustering analysis suggested that the sex- and rhythm-dependent obesogenic effects resulted from the bias toward lipogenesis against lipolysis. Moreover, they were closely related to the preference for the energy storage forms of lactate and glucose and also to the presence of excessive insulin, with the involvement of glucolipid metabolism. Such relationships indicated potential bridges between the obesogenic effects of pollutants and other diseases, e.g., cancer and diabetes.

Metabolic modeling of single bronchoalveolar macrophages reveals regulators of hyperinflammation in COVID-19.

SARS-CoV-2 infection induces imbalanced immune response such as hyperinflammation in patients with severe COVID-19. Here, we studied the immunometabolic regulatory mechanisms for the pathogenesis of COVID-19. We depicted the metabolic landscape of immune cells, especially macrophages, from bronchoalveolar lavage fluid of patients with COVID-19 at single-cell level. We found that most metabolic processes were upregulated in macrophages from lungs of patients with mild COVID-19 compared to cells from healthy controls, whereas macrophages from severe COVID-19 showed downregulation of most of the core metabolic pathways including glutamate metabolism, fatty acid oxidation, citrate cycle, and oxidative phosphorylation, and upregulation of a few pathways such as glycolysis. Rewiring cellular metabolism by amino acid supplementation, glycolysis inhibition, or PPARγ stimulation reduces inflammation in macrophages stimulated with SARS-CoV-2. Altogether, this study demonstrates that metabolic imbalance of bronchoalveolar macrophages may contribute to hyperinflammation in patients with severe COVID-19 and provides insights into treating COVID-19 by immunometabolic modulation.

Hazard of polystyrene micro-and nanospheres to selected aquatic and terrestrial organisms.

Plastics contamination in the environment is a major concern. Risk assessment of micro- and nanoplastics (MPL and NPL) poses significant challenges due to MPL and NPL heterogeneity regarding compositional polymers, particle sizes and morphologies in the environment. Yet, there exists considerable toxicological literature on commercial polystyrene (PS) micro- and nanospheres. Although such particles do not directly represent the environmental MPL and NPL, their toxicity data should be used to advance the hazard assessment of plastics. Here, toxicity data of PS micro- and nanospheres for microorganisms, aquatic and terrestrial invertebrates, fish, and higher plants was collected and analyzed. The evaluation of 294 papers revealed that aquatic invertebrates were the most studied organisms, nanosized PS was studied more often than microsized PS, acute exposures prevailed over chronic exposures, the toxicity of PS suspension additives was rarely addressed, and ∼40 % of data indicated no organismal effects of PS. Toxicity mechanisms were mainly studied in fish and nematode Caenorhabditis elegans, providing guidance for relevant studies in higher organisms. Future studies should focus on environmentally relevant plastics concentrations, wide range of organisms, co-exposures with other pollutants, and method development for plastics identification and quantification to fill the gap of bioaccumulation assessment of plastics.

Reproductive toxicities of ofloxacin and norfloxacin on Caenorhabditis elegans with multi-generational oscillatory effects and trans-generational residual influences.

The reproductive toxicities over generations are essential to assess the long-term impacts environmental fluoroquinolone antibiotics (FQs). In the present study, the multi-generational effects of ofloxacin (OFL) and norfloxacin (NOR) on reproduction were studied on Caenorhabditis elegans from 9 successive generations (F1-F9). Results showed that OFL showed no effects in F1, stimulation in F2 to F4, and inhibition F5 to F9. The effects of NOR also showed oscillation between stimulation and inhibition across generations. Further biochemical analysis demonstrated that the reproductive toxicities of OFL and NOR were more closely connected with total cholesterol (TCHO), progesterone (P) and testosterone (T), than major sperm protein (MSP) and vitellogenin (Vn). Moreover, OFL and NOR also showed significant trans-generational reproductive toxicities in T4 and T4', the great-grand-daughter of F1 and F9. Differences between T4 and T4' and between OFL and NOR, indicated influences of multi-generational exposure and urged more exploration on different mechanisms between FQs.

Balances among reproduction, antioxidant responses and lipid metabolism underlying the multi-generational effects of N-butylpyridinium bromide on Caenorhabditis elegans.

Ionic liquids (ILs) are difficult to degrade and even accumulate in the environment. Accordingly, their long-term toxicities are particularly important to demonstrate their accurate risk assessment. However, their long-term toxicities over generations and the toxicity mechanisms lacked thorough investigation. Presently, N-butylpyridinium bromide ([bpyr]Br), a representative IL, was chosen to measure its long-term effects on Caenorhabditis elegans for seven consecutive generations at 0.0225 and 22.5 mg/L. Toxicity mechanisms were explored in F1, F3, F5 and F7 by combining both antioxidant responses and lipid metabolism. Results showed that [bpyr]Br at low concentration provoked oscillatory effects on the reproduction over 7 generations, with inhibition in F1 and F7 and stimulation in F2, F4 and F5. At high concentration, [bpyr]Br showed similar multi-generational oscillation with greater inhibition in F1 and greater stimulation in F5. The effects of [bpyr]Br on the antioxidant responses to oxidative stress also showed oscillation over generations. The integrated biomarker response (IBR) values showed that [bpyr]Br at low concentration did not provoke significant influences on the overall antioxidant homeostasis in F1 and F3, but significantly stimulated it in F5 and F7. Meanwhile, [bpyr]Br at high concentration stimulated the antioxidant homeostasis in F1 and F7 with non-significant influences in F3 and F5. The IBR values regarding indicators in lipid metabolism showed that [bpyr]Br significantly and commonly stimulated the overall metabolism without concentration-dependent differences. Further analysis implied that [bpyr]Br provoked different mechanisms underlying the responses at low and high concentrations.

Bioinformatics approach reveals the critical role of the NOD-like receptor signaling pathway in COVID-19-associated multiple sclerosis syndrome.

Multiple sclerosis (MS) is a kind of central nervous system (CNS) autoimmune disease, which mainly damages nerves, the brain, and the spinal cord. Recently, several clinical cases reported the relativity between Coronavirus Disease 2019 (COVID-19) and the development of MS, but the mechanism of how COVID-19 affects the occurrence of MS was still not clear. It is bioinformatics technology that we use to explore the potential association at the gene level. The genetic information related to the two diseases was collected from the DisGNET platform for functional protein network analysis and used STRING to identify the complete gene set. The protein-protein interaction (PPI) network was analyzed by STRING. Finally, in the GEO database, we selected peripheral blood mononuclear cell (PBMC) RNA sequencing data (GSE164805, GSE21942) from COVID-19 patients and MS patients to verify the potential cross mechanism between the two diseases. The similar gene set of immune or inflammation existed between the patients with COVID-19 and ones with MS, including L2RA, IFNG, IL1B, NLRP3, and TNF. Interaction network analysis among proteins revealed that IL1B, P2RX7, IFNB1, IFNB1, TNF, and CASP1 enhanced the network connectivity between the combined gene set of COVID-19 and MS associated with NOD-like receptor (NLR) signaling. The involvement of NLR signaling in both diseases was further confirmed by comparing peripheral blood monocyte samples from COVID-19 and MS patients. Activation of NLR signaling was found in both COVID-19 and MS. The PBMC samples analyses also indicated the involvement of the NLR signaling pathway. Taken together, our data analyses revealed that the NLR signaling pathway might play a critical role in the COVID-19-related MS.

Architecting Braided Porous Carbon Fibers Based on High-Density Catalytic Crystal Planes to Achieve Highly Reversible Sodium-Ion Storage.

Carbonaceous materials are considered strong candidates as anode materials for sodium-ion batteries (SIBs), which are expected to play an indispensable role in the carbon-neutral era. Herein, novel braided porous carbon fibres (BPCFs) are prepared using the chemical vapour deposition (CVD) method. The BPCFs possess interwoven porous structures and abundant vacancies. The growth mechanism of the BPCFs can be attributed to the polycrystalline transformation of the nanoporous copper catalyst in the early stage of CVD process. Density functional theory calculations suggest that the Na+ adsorption energies of the mono-vacancy edges of the BPCFs (-1.22 and -1.09 eV) are lower than that of an ideal graphene layer (-0.68 eV), clarifying in detail the adsorption-dominated sodium storage mechanism. Hence, the BPCFs as an anode material present an outstanding discharge capacity of 401 mAh g-1 at 0.1 A g-1 after 500 cycles. Remarkably, this BPCFs anode, under high-mass-loading of 5 mg cm-2, shows excellent long-term cycling ability with a reversible capacity of 201 mAh g-1 at 10 A g-1 over 1000 cycles. This study provided a novel strategy for the development of high-performance carbonaceous materials for SIBs.