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Multi-modal information retrieval is among the prevailing forms of daily human–computer interaction. The recent deep cross-modal hashing methods have received increasing attention because of their superior search performance and efficiency capability. However, effectively exploring the high-ranking semantic correlation and preserving representation consistency are still challengeable due to the heterogeneity property of different modalities. In this paper, a Self-Attention and Adversary Learning Hashing Network (SAALDH) is designed for large scale cross-modal retrieval. Specifically, the hash representations across different layers of the deep network are integrated and then the significance of each position in the integrated hash representation is enhanced by employing a novel self-attention mechanism. Meanwhile, an adversarial learning mechanism is adopted to further preserve the consistency of hash representations during hash functions learning. Moreover, a novel batch semi-hard selection is designed for triplet loss to solve the issue of local optimum during the optimization of SAALDH. Experimental results evaluated on two large scale image-text modality datasets show the effectiveness and efficiency of the proposed SAALDH. And SAALDH achieves better performances by comparing with several state-of-the-art methods. The source code URL of our SAALDH is: http://github.com/SWU-CS-MediaLab/SAALDH. [ABSTRACT FROM AUTHOR]

Thick nanoporous electrode design with pore size in several nanometers can substantially improve the active sites to achieve high energy density. However, the sluggish ion/charge kinetics and mechanical instability limit their rate and long-term cycling capability. To address these obstacles, herein, a thick vacancy-riched nanoporous NiCoMn@oxides (V o -3DNCM@oxides) core-shell structure as pseudocapacitive electrode in alkaline electrolyte was prepared by polarizing a nanoporous NiCoMn alloy and subsequently mild annealing in Ar atmosphere. As a result, a large number of coordination unsaturated sites can be exposed on active oxide layer by mild annealing. Meanwhile, the nanopores can be coarsened to tens of nanometers. The coordination unsaturated sites synergy with coarsened nanopores can not only endow high-efficient ion/electrons transport channels but also hold the structure stable during fast charge/discharge process. Electrochemical performance characterization illustrates that the 4V o -3DNCM@oxides electrode annealed at 400 °C shows high capacity retention of about 69.7% at current rates from 1 A cm−3 to upward of 10 A cm−3 (1464 C cm−3 at 1 A cm−3 and 908 C cm−3 at 10 A cm−3) and high energy density of 90.7 mWh cm−3, demonstrating a potential application in pseudocapacitors. More importantly, the novel structural design exhibits promising prospects toward the practical application of integrated thick electrodes. [ABSTRACT FROM AUTHOR]

In response to the severe blocks of the large volume change and sluggish capacity decay originating from the Lithium ion insertion/extraction in the anodes of Lithium ion batteries, transition metal oxides with high cycle stability are desirable yet extremely challenging for achieving high energy density anodes. Here, we report that a double-shelled NiO nanocrystal-doped MnO layer with robust defects, epitaxially grown on a nanoporous Ni network by simultaneously dealloying and oxidising NiMn alloy, can overcome these challenges to deliver a large capacity with excellent cycle stability. The interconnected core-shell nanoporous structure with robust defects possesses ultrahigh efficient electron/ion transport and a volume buffer. Consequently, the free-standing electrode as a whole delivers a highly reversible capacity of 1172 mAh cm−3 (960 mAh g−1) with a remarkable cycle life (105% retention after 200 cycles at 100 mA g−1). Furthermore, the electrode achieves a high capacity of 831.5 mAh cm−3 (681 mAh g−1) even at 1000 mA g−1, demonstrating a high rate capability. The proposed synthetic strategy can be further explored for the construction of other three-dimensional metal@metal oxide electrodes for application in next-generation energy storage systems. [ABSTRACT FROM AUTHOR]

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 × 10 3  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 × 10 3  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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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-β/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-β and SREBP pathways, and also influenced neurotransmitters with Gsα, glutamate and cGMP-dependent signaling pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

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 β-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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 H 2 O 2 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

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., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

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., Competing Interests: The authors declare no conflicts of interest., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

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 ([C 2 mim]PF 6 ) 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 [C 2 mim]PF 6 and histidine showed similar modes of actions despite some differences, implying the contribution of their shared imidazole structure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors did not report any conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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.

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., (Copyright © 2021. Published by Elsevier B.V.)

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 Ras V12 /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 (CdCl 2 ). At 1.0 mg/L, PCB126, PFOA, and CdCl 2 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

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., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Although the polyether ether ketone (PEEK) has excellent comprehensive properties, its non-antibacterial and low wear-resistant limit the wide application in the field of artificial joint materials. In this paper, Nano-ZnO was generated in situ on the surface of PEEK powder by one-step hydrothermal method, which improved the binding force of Nano-ZnO and PEEK matrix. Then the PEEK-based nanocomposites were prepared by melt blending with the synthesized Nano-ZnO-PEEK powders and PEEK powders. The microstructure, mechanical, biological and tribological properties of PEEK-based nanocomposites were studied. The results showed that the compressive strength of PEEK-based nanocomposites can reach up to 319.2 ± 2.4 MPa. Both PEEK and PEEK-based nanocomposites were non-toxic to cells. Meanwhile, PEEK-based nanocomposites showed good antibacterial activity against E.coli and Staphylococcus aureus, and the antibacterial activity was better with the increase of Nano-ZnO content. In addition, when the Nano-ZnO content was 5%, the wear rate of PEEK-based nanocomposites was about 68% lower than that of pure PEEK materials. Thus, PEEK-based nanocomposites has a dual function of good antibacterial property and excellent wear resistance., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A metal-free sulfenylation/spirocyclization of indolyl-ynones realized by organosulfenyl chloride, generated in situ from the reaction of disulfides and PhICl 2 , is presented. This cascade one-pot process enables a chemoselective synthesis of diverse sulfenylated spiroindolenines depending on the substituent pattern at the two-position of indolyl-ynones.

Brain endothelial cells (ECs) are an important component of the blood-brain barrier (BBB) and play key roles in restricting entrance of possible toxic components and pathogens into the brain. However, identifying endothelial genes that regulate BBB homeostasis remains a time-consuming process. Although somatic genome editing has emerged as a powerful tool for discovery of essential genes regulating tissue homeostasis, its application in brain ECs is yet to be demonstrated in vivo. Here, we used an adeno-associated virus targeting brain endothelium (AAV-BR1) combined with the CRISPR/Cas9 system (AAV-BR1-CRISPR) to specifically knock out genes of interest in brain ECs of adult mice. We first generated a mouse model expressing Cas9 in ECs ( Tie2 Cas9 ). We selected endothelial β-catenin ( Ctnnb1 ) gene, which is essential for maintaining adult BBB integrity, as the target gene. After intravenous injection of AAV-BR1-sg Ctnnb1 -tdTomato in 4-week-old Tie2 Cas9 transgenic mice resulted in mutation of 36.1% of the Ctnnb1 alleles, thereby leading to a dramatic decrease in the level of CTNNB1 in brain ECs. Consequently, Ctnnb1 gene editing in brain ECs resulted in BBB breakdown. Taken together, these results demonstrate that the AAV-BR1-CRISPR system is a useful tool for rapid identification of endothelial genes that regulate BBB integrity in vivo ., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

[Figure: see text].

Short-chained perfluorobutane sulfonate (PFBS, four-carbon) and perfluorohexane sulfonate (PFHxS, six-carbon) are widely employed to substitute long-chained per- and poly-fluoroalkyl substances (PFASs). Recent studies showed the potential persistence of PFBS and PFHxS, and also reported their correlation with obesity. However, the long-term outcome and underlying mechanisms remained poorly understood. Presently, the effects of PFBS and PFHxS were studied on C. elegans with multi- and trans-generational experiments. The multi-generational effects were measured in continuous four generational exposure (i.e., F1 to F4). Results showed that PFBS did not stimulate the fat content in F1 but in F4 with continuous but different disturbances on the lipid metabolism and the insulin and insulin-like (IIS) pathway. PFHxS stimulated the fat content in F1 and F4 with similar disturbances on the lipid metabolism and IIS pathway. The trans-generational results showed that the effects of PFBS and PFHxS on the lipid metabolism and IIS pathway were not totally recovered in the offspring of F1 (i.e., T1-T3) and F4 (i.e., T1'-T3') which were not continuously exposed. PFHxS showed a common pattern to up-regulate daf-7 in both multi- and trans-generational effects. The long-term consequences of the short-chained PFASs substitutes should be concerned and epigenetic regulations should be considered in future mechanism studies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Excessive inflammatory responses induced upon SARS-CoV-2 infection are associated with severe symptoms of COVID-19. Inflammasomes activated in response to SARS-CoV-2 infection are also associated with COVID-19 severity. Here, we show a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. N protein facilitates maturation of proinflammatory cytokines and induces proinflammatory responses in cultured cells and mice. Mechanistically, N protein interacts directly with NLRP3 protein, promotes the binding of NLRP3 with ASC, and facilitates NLRP3 inflammasome assembly. More importantly, N protein aggravates lung injury, accelerates death in sepsis and acute inflammation mouse models, and promotes IL-1β and IL-6 activation in mice. Notably, N-induced lung injury and cytokine production are blocked by MCC950 (a specific inhibitor of NLRP3) and Ac-YVAD-cmk (an inhibitor of caspase-1). Therefore, this study reveals a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation and induces excessive inflammatory responses., (© 2021. The Author(s).)

Sulfate radical (SO 4 ·- )-based advanced oxidation processes (AOPs) attract increasing attention in the control of micropollutants. However, SO 4 ·- can react with other chemicals present in water and result in undesired oxidation by-products (OBPs) generation. The formation and degradation mechanisms of CX 3 R-type OBPs during cobalt catalyzed peroxymonosulfate (Co 2+ /PMS) oxidation were investigated. In the formation of CX 3 R-type OBPs, both Co 3+ and SO 4 ·- could convert chloride to free chlorine that then reacted with natural organic matter, leading to the formation of CX 3 R-type OBPs. The concentrations of trichloromethane, chloral hydrate, dichloroacetonitrile, dichloroacetamide and trichloroacetamide after 15 min reaction were 9.8, 3.9, 1.2, 5.9 and 22.3 nM, respectively. Compared to SO 4 ·- , Co 3+ played a more significant role in the CX 3 R-type OBP formation and calculated toxicity values of CX 3 R-type OBPs. CX 3 R-type OBPs could not only be formed but also be degraded at the same time during Co 2+ /PMS oxidation. As for the degradation of CX 3 R-type OBPs, both Co 3+ and SO 4 ·- could transform CX 3 R-type OBPs to chloride. Compared to Co 3+ , SO 4 ·- played a more important role in the degradation of CX 3 R-type OBPs and the conversion from chloride to final by-product chlorate. The adverse effects that results from Co 3+ need more attention in SO 4 ·- -based AOPs application., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Increasing concerns are earned on the multigenerational hazards of antibiotics due to the connection between their mother-children transfer via cord blood and breast milk and obesity in the children. Currently, Caenorhabditis elegans was exposed to sulfamethoxazole (SMX) over 11 generations (F0-F10). Indicators of obesogenic effects and gene expressions were measured in each generation and also in T11 to T13 that were the offspring of F10. Biochemical analysis results showed that SMX stimulated fatty acids in most generations including T13. The stimulation was resulted from the balance between enzymes for fatty acid synthesis (e.g., fatty acid synthetase) and those for its consumption (e.g., fatty acid transport protein). Gene expression analysis demonstrated that the obesogenic effects of SMX involved peroxisome proliferator activated receptors (PPARs, e.g., nhr-49) and insulin/insulin-like signaling (IIS) pathways (e.g., ins-1, daf-2 and daf-16). Further epigenetic analysis demonstrated that SMX caused 3-fold more H3K4me3 binding genes than the control in F10 and T13. In F10, the most significantly activated genes were in metabolic and biosynthetic processes of various lipids, nervous system and development. The different gene expressions in T13 from those in F10 involved development, growth, reproduction and responses to chemicals in addition to metabolic processes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Rationale: Organs of the body require vascular networks to supply oxygen and nutrients and maintain physiological function. The blood vessels of different organs are structurally and functionally heterogeneous in nature. To more precisely dissect their distinct in vivo function in individual organs, without potential interference from off-site targets, it is necessary to genetically target them in an organ-specific manner., Objective: The objective of this study was to generate a genetic system that targets vascular endothelial cells in an organ- or tissue-specific manner and to exemplify the potential application of intersectional genetics for precise, target-specific gene manipulation in vivo., Methods and Results: We took advantage of 2 orthogonal recombination systems, Dre-rox and Cre-loxP, to create a genetic targeting system based on intersectional genetics. Using this approach, Cre activity was only detectable in cells that had expressed both Dre and Cre. Applying this new system, we generated a coronary endothelial cell-specific Cre ( CoEC-Cre ) and a brain endothelial cell-specific Cre ( BEC-Cre ). Through lineage tracing, gene knockout and overexpression experiments, we demonstrated that CoEC-Cre and BEC-Cre efficiently and specifically target blood vessels in the heart and brain, respectively. By deletion of vascular endothelial growth factor receptor 2 using BEC-Cre , we showed that vascular endothelial growth factor signaling regulates angiogenesis in the central nervous system and also controls the integrity of the blood-brain barrier., Conclusions: We provide 2 examples to illustrate the use of intersectional genetics for more precise gene targeting in vivo, namely manipulation of genes in blood vessels of the heart and brain. More broadly, this system provides a valuable strategy for tissue-specific gene manipulation that can be widely applied to other fields of biomedical research., (© 2018 American Heart Association, Inc.)

Earlier reports studied the time-dependent effects of imidazolium-based ionic liquids ([amim]X) in the aspect of biochemical explanation and that of key contributor in mixture effects. Presently, the effects of N-alkylpyridinium-based ILs ([apyr]BF4) were studied combining the above two aspects, i.e., the time-dependent effects of [bpyr]BF4, [hpyr]BF4 and [opyr]BF4 on luminescence and biochemical indicators in Vibrio qinghaiensis sp.-Q67, and those of the mixtures. In individual results, the inhibition on luminescence increased over concentrations and the side chain length, showing concentration- and side chain-dependence. Moreover, the inhibition of [apyr]BF4 decreased from 0.25 to 24h, showing a time-dependence. Notably, [hpyr]BF4 stimulated the luminescence at 24h. The biochemical effects, including inhibition and stimulation, were well correlated to those on luminescence. In mixture results, the inhibition on luminescence was lower than the predicted effects by concentration addition model which was based on individual results. Moreover, the mixture stimulation on luminescence was significantly higher than individual ones, and the mixture stimulation on biochemical indicators was even greater than that on luminescence. In mixture effects, [bpyr]BF4 was the positive contributor, and [hpyr]BF4 was the negative contributor. Similarities and differences between [amim]X and [apyr]BF4 indicated underlying mechanisms of the commonly observed hormetic effects of ionic liquids., (Copyright © 2016. Published by Elsevier B.V.)

Applications of 1-alkyl-3-methylimidazolium salts ([amim]X) in pharmaceuticals call for studies on the biological effects. Previously, [amim]Cl and [amim]Br caused time-dependent stimulatory effects on Vibrio qinghaiensis sp.-Q67 (Q67). Further studies are still needed to answer the question whether [amim]X with other anions have similar effects, and to explain such stimulatory effects. Here, effects of four [amim]BF4 with different alkyl side chains on Q67 were investigated. At the apical level, they inhibited luminescence at high concentrations and the toxicities decreased with time increasing from 0.25 to 12h. Meanwhile, they stimulated luminescence at low concentrations, and the stimulations increased over time. The maximum stimulations followed an order of [emim]BF4>[bmim]BF4>[hmim]BF4>[omim]BF4. Compared with [emim]BF4, imidazole caused lower stimulations, while NaBF4 caused significantly higher ones. Overview on effects of [amim]BF4, imidazole and NaBF4 indicated significant anionic contributions. At biochemical and molecular levels, favin mono-nucleotide (FMN) and nicotinamide adenine dinucleotide (NADH) increased over time, and expressions of luxA and luxB (encoding luciferase that catalyzes FMN:NADH reaction) in Q67 showed up-regulations, suggesting an overall enhancement of the bioactivities. Moreover, superoxide dismutase and catalase showed inductions with up-regulations on their encoding genes, indicating improved antioxidant responses., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Sulfonamides are one typical antibiotic which is an emerging hazardous material to the ecological stability due to their continuously application and biological effects to non-target organisms. The parent-progeny transgenerational effects need investigations to indicate their long-term consequences. Currently, we tested the transgenerational effects of sulfadiazine (SD), sulfapyridine (SP) and sulfamethazine (SMZ) on L3 larva of Caenorhabditis elegans. The nematodes were exposed to aqueous sulfonamides at micromolar concentrations for 96 h, and then the effects on the behavior and growth in the exposed parent and unexposed progeny were measured. Results showed that SD, SP and SMZ inhibited three behavior indicators including body bending frequency (BBF), reversal movement (RM) and Omega turn (OT), and the growth indicator (body length, BL). Behavior indicators showed higher sensitivities than the growth indicator, and BBF had the highest sensitivity among the behavior indicators. Moreover, the effects of sulfonamides were also observed in the unexposed progeny with partially rescued or more severe inhibitions on the indicators. The behavior also showed higher sensitivity than the growth in the progeny. The transgenerational effects of sulfonamides indicated that parental exposure can multiply the harmful effects of antibiotic pollution in following generations and their potential ecological risks at environmental concentrations were further raised., (Copyright © 2013 Elsevier B.V. All rights reserved.)