A single photoreceptor splits perception and entrainment by cotransmission.

Vision enables both image-forming perception, driven by a contrast-based pathway, and unconscious non-image-forming circadian photoentrainment, driven by an irradiance-based pathway1,2. Although two distinct photoreceptor populations are specialized for each visual task3-6, image-forming photoreceptors can additionally contribute to photoentrainment of the circadian clock in different species7-15. However, it is unknown how the image-forming photoreceptor pathway can functionally implement the segregation of irradiance signals required for circadian photoentrainment from contrast signals required for image perception. Here we report that the Drosophila R8 photoreceptor separates image-forming and irradiance signals by co-transmitting two neurotransmitters, histamine and acetylcholine. This segregation is further established postsynaptically by histamine-receptor-expressing unicolumnar retinotopic neurons and acetylcholine-receptor-expressing multicolumnar integration neurons. The acetylcholine transmission from R8 photoreceptors is sustained by an autocrine negative feedback of the cotransmitted histamine during the light phase of light-dark cycles. At the behavioural level, elimination of histamine and acetylcholine transmission impairs R8-driven motion detection and circadian photoentrainment, respectively. Thus, a single type of photoreceptor can achieve the dichotomy of visual perception and circadian photoentrainment as early as the first visual synapses, revealing a simple yet robust mechanism to segregate and translate distinct sensory features into different animal behaviours.

Structural and Functional Characterization of a Fish Type I Subgroup d IFN Reveals Its Binding to Receptors.

Teleost fish type I IFNs and the associated receptors from the cytokine receptor family B (CRFB) are characterized by remarkable diversity and complexity. How the fish type I IFNs bind to their receptors is still not fully understood. In this study, we demonstrate that CRFB1 and CRFB5 constitute the receptor pair through which type I subgroup d IFN (IFNd) from large yellow croaker, Larimichthys crocea, activates the conserved JAK-STAT signaling pathway as a part of the antiviral response. Our data suggest that L. crocea IFNd (LcIFNd) has a higher binding affinity with L. crocea CRFB5 (LcCRFB5) than with LcCRFB1. Furthermore, we report the crystal structure of LcIFNd at a 1.49-Å resolution and construct structural models of LcIFNd in binary complexes with predicted structures of extracellular regions of LcCRFB1 and LcCRFB5, respectively. Despite striking similarities in overall architectures of LcIFNd and its ortholog human IFN-ω, the receptor binding patterns between LcIFNd and its receptors show that teleost and mammalian type I IFNs may have differentially selected helices that bind to their homologous receptors. Correspondingly, key residues mediating binding of LcIFNd to LcCRFB1 and LcCRFB5 are largely distinct from the receptor-interacting residues in other fish and mammalian type I IFNs. Our findings reveal a ligand/receptor complex binding mechanism of IFNd in teleost fish, thus providing new insights into the function and evolution of type I IFNs.

Structural transitions upon guide RNA binding and their importance in Cas12g-mediated RNA cleavage.

Cas12g is an endonuclease belonging to the type V RNA-guided CRISPR-Cas family. It is known for its ability to cleave RNA substrates using a conserved endonuclease active site located in the RuvC domain. In this study, we determined the crystal structure of apo-Cas12g, the cryo-EM structure of the Cas12g-sgRNA binary complex and investigated conformational changes that occur during the transition from the apo state to the Cas12g-sgRNA binary complex. The conserved zinc finger motifs in Cas12g undergo an ordered-to-disordered transition from the apo to the sgRNA-bound state and their mutations negatively impact on target RNA cleavage. Moreover, we identified a lid motif in the RuvC domain that undergoes transformation from a helix to loop to regulate the access to the RuvC active site and subsequent cleavage of the RNA substrate. Overall, our study provides valuable insights into the mechanisms by which Cas12g recognizes sgRNA and the conformational changes it undergoes from sgRNA binding to the activation of the RNase active site, thereby laying a foundation for the potential repurposing of Cas12g as a tool for RNA-editing.

Three-dimensional ranging system based on Fresnel incoherent correlation holography.

We proposed a three-dimensional (3D) ranging system based on Fresnel incoherent correlation holography (FINCH). Distinct from the displacement measurement based on coherent digital holography (DH), our system simultaneously achieves a 3D range measurement using incoherent illumination. The observation range is obtained by the holographic reconstruction, while the in-plane range is determined using the two-dimensional digital imaging correlation (2D-DIC) technique. Experimental results on the resolution target demonstrate precise 3D ranging determination and improved measurement accuracy.

Development of D-π-A organic dyes for discriminating HSA from BSA and study on dye-HSA interaction.

HSA (human serum albumin), a most abundant protein in blood serum, plays a key role in maintaining human health. Abnormal HSA level is correlated with many diseases, and thus has been used as an essential biomarker for therapeutic monitoring and biomedical diagnosis. Development of small-molecule fluorescent probes allowing the selective and sensitive recognition of HSA in in vitro and in vivo is of fundamental importance in basic biological research as well as medical diagnosis. Herein, we reported a series of new synthesized fluorescent dyes containing D-π-A constitution, which exhibited different optical properties in solution and solid state. Among them, dye M-H-SO3 with a hydrophilic sulfonate group at electron-acceptor part displayed selectivity for discrimination of HSA from BSA and other enzymes. Upon binding of dye M-H-SO3 with HSA, a significant fluorescence enhancement with a turn-on ratio about 96-fold was triggered. The detection limit was estimated to be âˆ¼ 40 nM. Studies on the interaction mechanism revealed that dye M-H-SO3 could bind to site III of HSA with a 1:1 binding stoichiometry. Furthermore, dye M-H-SO3 has been applied to determine HSA in real urine samples with good recoveries, which provided a useful method for HSA analysis in biological fluids.

Structural basis for the dual catalytic activity of the Legionella pneumophila ovarian tumor (OTU) domain deubiquitinase LotA.

Legionella pneumophila, a bacterial pathogen that causes a severe pneumonia known as Legionnaires' disease, extensively exploits the ubiquitin (Ub) pathway in the infected host cells through certain virulence effectors excreted by the Dot/Icm system. To date, several Dot/Icm effectors have been found to act as Ub ligases, and four effectors, including LotA, LotB, LotC, and Ceg7, have been identified as deubiquitinases (DUBs) from the ovarian tumor (OTU) domain family. LotA is unique among other OTU DUBs because it possesses two distinct DUB domains and exclusively exhibits catalytic activity against K6-linked diUb and polyUb chains. However, the structure of LotA and the molecular mechanism for the dual DUB activity remains elusive. In this study, we solved the structure of LotA in complex with proximally bound Ub and distal covalently bound Ub. Both Ub molecules are bound to the DUB1 domain and mimic a K6-linked diUb. Structural analysis reveals that the DUB1 domain utilizes a distinct mechanism for recognition of the K6-linked diUb within a large S1' binding site that is uncommon to OTU DUBs. Structural fold of the LotA DUB2 domain closely resembles LotB and LotC, similarly containing an extra α-helix lobe that has been demonstrated to play an important role in Ub binding. Collectively, our study uncovers the structural basis for the dual catalytic activity of the unique OTU family DUB LotA.

Structural basis for the shared neutralization mechanism of three classes of human papillomavirus type 58 antibodies with disparate modes of binding.

Human papillomavirus type 58 (HPV58) is associated with cervical cancer and poses a significant health burden worldwide. Although the commercial 9-valent HPV vaccine covers HPV58, the structural and molecular-level neutralization sites of the HPV58 complete virion are not fully understood. Here, we report the high-resolution (∼3.5 Å) structure of the complete HPV58 pseudovirus (PsV58) using cryo-electron microscopy (cryo-EM). Three representative neutralizing monoclonal antibodies (nAbs 5G9, 2H3 and A4B4) were selected through clustering from a nAb panel against HPV58. Bypassing the steric hindrance and symmetry-mismatch in the HPV Fab-capsid immune-complex, we present three different neutralizing epitopes in the PsV58, and show that, despite differences in binding, these nAbs share a common neutralization mechanism. These results offer insight into HPV58 genotype specificity and broaden our understanding of HPV58 neutralization sites for antiviral research.IMPORTANCE Cervical cancer primarily results from persistent infection with high-risk types of human papillomavirus (HPV). HPV type 58 (HPV58) is an important causative agent, especially within Asia. Despite this, we still have limited data pertaining to the structural and neutralizing epitopes of HPV58, and this encumbers our in-depth understanding of the virus mode of infection. Here, we show that representative nAbs (5G9, 10B11, 2H3, 5H2 and A4B4) from three different groups share a common neutralization mechanism that appears to prohibit the virus from associating with the extracellular matrix and cell surface. Furthermore, we identify that the nAbs engage via three different binding patterns: top-center binding (5G9 and 10B11), top-fringe binding (2H3 and 5H2), and fringe binding (A4B4). Our work shows that, despite differences in the pattern in binding, nAbs against HPV58 share a common neutralization mechanism. These results provide new insight into the understanding of HPV58 infection.

Viral neutralization by antibody-imposed physical disruption.

In adaptive immunity, organisms produce neutralizing antibodies (nAbs) to eliminate invading pathogens. Here, we explored whether viral neutralization could be attained through the physical disruption of a virus upon nAb binding. We report the neutralization mechanism of a potent nAb 8C11 against the hepatitis E virus (HEV), a nonenveloped positive-sense single-stranded RNA virus associated with abundant acute hepatitis. The 8C11 binding flanks the protrusion spike of the HEV viruslike particles (VLPs) and leads to tremendous physical collision between the antibody and the capsid, dissociating the VLPs into homodimer species within 2 h. Cryo-electron microscopy reconstruction of the dissociation intermediates at an earlier (15-min) stage revealed smeared protrusion spikes and a loss of icosahedral symmetry with the capsid core remaining unchanged. This structural disruption leads to the presence of only a few native HEV virions in the ultracentrifugation pellet and exposes the viral genome. Conceptually, we propose a strategy to raise collision-inducing nAbs against single spike moieties that feature in the context of the entire pathogen at positions where the neighboring space cannot afford to accommodate an antibody. This rationale may facilitate unique vaccine development and antimicrobial antibody design.

Enhanced PAHs-contaminated site soils remediation by mixed persulfate and calcium peroxide.

Polycyclic aromatic hydrocarbons (PAHs) remain in the site soils after relocated coking plants and oil refineries pose huge constraints to the subsequent land utilization. However, single persulfate (PS) or calcium peroxide (CP) remediation strategies can only inefficiently oxidize some PAHs in soil. This work sought to optimize PS/CP oxidation remediation strategy and verify its practical application effect in soil samples spiked with PAHs. The results showed that the mixed PS/CP oxidation remediation was better than the single oxidants strategies; it had high remediation performance in different particles and pollution loads of PAHs-contaminated soils. Simultaneously, reactive radicals (SO4·- and ·OH) were detected, and one side-product (CaSO4) was characterized. This work optimized the mixed PS/CP system (0.3 mol/L PS, and 8 g/kg CP, together with 0.18 mol/L Fe2+ and 0.11 mol/L C2O42-), and the corresponding Total-PAHs removal rate was 85.41%. Compared to the cost based on benzopyrene (BaP) removal, the study provided a cost-effective mixed PS/CP oxidation remediation technique (1.22 $/ton), widely applicable in soils polluted with various organic contaminants represented such as PAHs.

Capillary Nylon 6 polymer material produced by femtosecond laser processing.

A wicking Nylon 6 polymer material was produced through surface structuring by a direct femtosecond laser nano/microstructuring approach. The produced wicking structure is an array of parallel microgrooves, the surface of which is textured with irregular nanostructures and fine microstructures. High-speed imaging of water spreading vertically uphill against the gravity discloses a series of capillary flow regimes with h ∝ t, h ∝ t1/2, and h ∝ t1/3 scaling laws, where h is the height of capillary rise and t is the time. In the initial stage, the capillary flow occurs with a single front, from which at a certain time a precursor front forms and advances ahead of the main one. Our study shows that the onset of the precursor front occurs in h ∝ t flow regime. The created material exhibits excellent wicking properties and may find applications in various technologically important areas.

The career success scale in nursing: psychometric evidence to support the Chinese version.

AIM: The purpose of this study was to examine the psychometric properties of the 11-item Chinese version of the Career Success Scale. BACKGROUND: Nurses play an important role in the healthcare system. Opportunities to achieve success and satisfaction from one's career affect the retention and stability of the nursing workforce. The Career Success Scale was originally developed in English and has been translated into Chinese. Psychometric testing of the Chinese Career Success Scale for measuring career success in nurses has not been performed. DESIGN: A cross-sectional survey was conducted. METHOD: A convenience sample of 1148 clinical nurses were recruited from 10 level-3 hospitals in Guangdong Province, mainland China, from December 2010-December 2011. RESULTS: Results indicated that the Chinese Career Success Scale demonstrated good internal consistency and test-retest reliability. Principal component analysis supported the three-factor structure of the original instrument: Career Satisfaction, Perceived within Organization Competitiveness and Perceived External Organization Competitiveness. There were significant correlations among the three factors, which demonstrated the good construct validity of the Chinese version of this scale. CONCLUSION: The Chinese Career Success Scale appears to be a reliable and valid instrument. It has the potential to be used to measure nurses' career success in mainland China. The findings will be useful for nurse leaders and policymakers in the evaluation of nurses' self-perceived career success and to develop strategies to promote nurse retention and career development.

The impact of information presentation on self-other risk decision-making.

To explore the impact of social distance and information presentation types on self-other risk preferences in monetary tasks. Risk preferences were examined in decision-making tasks and experiential information tasks within different frameworks when participants made decisions for themselves and others. Experiment 1 employed experiential decision tasks and revealed individual differences in decision-making for oneself and others. In gain situations, participants exhibited more risk aversion when deciding for others compared to themselves. Experiment 2 presented both types of information simultaneously to investigate whether risk decisions for oneself and others are influenced by information types. Results indicated that experiential information led participants to make more conservative choices for others, while descriptive information eliminated this effect. This study discovered the influence of social distance on self-other risk decisions and the role of information presentation types in self and other risk decision-making. Future research could further explore self-other decision-making from the perspectives of decision-makers' traits and culture.

Type-III-A structure of mycobacteria CRISPR-Csm complexes involving atypical crRNAs.

Tuberculosis (TB), a leading cause of mortality globally, is a chronic infectious disease caused by Mycobacterium tuberculosis that primarily infiltrates the lung. The mature crRNAs in M. tuberculosis transcribed from the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) locus exhibit an atypical structure featured with 5' and 3' repeat tags at both ends of the intact crRNA, in contrast to typical Type-III-A crRNAs that possess 5' repeat tags and partial crRNA sequences. However, this structural peculiarity particularly concerning the specific binding characteristics of the 3' repeat end within the mature crRNA within the Csm complex, has not been comprehensively elucidated. Here, our Mycobacteria CRISPR-Csm complexes structure represents the largest Csm complex reported to date. It incorporates an atypical Type-III-A CRISPR RNA (crRNA) (46 nt) with 5' 8-nt and 3' 4-nt repeat sequences in the stoichiometry of Mycobacteria Csm1125364151. The PAM-independent single-stranded RNAs (ssRNAs) are the most suitable substrate for the Csm complex. The 3'-repeat end trimming of mature crRNA was not necessary for its cleavage activity in Type-III-A Csm complex. Our work broadens our understanding of the Type-III-A Csm complex and identifies another mature crRNA processing mechanism in the Type-III-A CRISPR-Cas system based on structural biology.

The redevelopment mode selection framework for Third Front Brownfields in China.

Unlike most brownfields located in the urban center, there is a kind of special brownfields produced in the Third Front Construction (TFC) period of China, and in turn they are named the Third Front Brownfield (TFB) in this paper. In addition to commercial value, other values should also be considered when TFBs are redeveloped, which makes they may need a specific protective reuse way and their revitalization process is relatively slower. Therefore, it is of great significance to study the redevelopment mode of TFBs. Accordingly, this paper presents a redevelopment mode selection framework to support stakeholders' investment decision-making and facilitate the reuse of TFBs. First, a previous case base including two sets is developed to conduct experience mining. In specific, an attribute set and a TFB redevelopment mode set of previous successful cases are established through literatures and expert interviews. Second, the weights of abovementioned attributes are determined by using the G1 method. Third, a concept of matching rate is defined based on the Attribute Similarity Model (ASM) to search the similarity between the new TFB and previous cases so that stakeholders can get advice on the redevelopment of the new TFB. A case study is conducted to show the effectiveness of the proposed framework and some policy suggestions are made according to the study process.

Mesoporous polydopamine delivery system for intelligent drug release and photothermal-enhanced chemodynamic therapy using MnO2 as gatekeeper.

The non-specific leakage of drugs from nanocarriers seriously weakened the safety and efficacy of chemotherapy, and it was very critical of constructing tumor microenvironment (TME)-responsive delivery nanocarriers, achieving the modulation release of drugs. Herein, using manganese dioxide (MnO2) as gatekeeper, an intelligent nanoplatform based on mesoporous polydopamine (MPDA) was developed to deliver doxorubicin (DOX), by which the DOX release was precisely controlled, and simultaneously the photothermal therapy (PTT) and chemodynamic therapy (CDT) were realized. In normal physiological environment, the stable MnO2 shell effectively avoided the leakage of DOX. However, in TME, the overexpressed glutathione (GSH) degraded MnO2 shell, which caused the DOX release. Moreover, the photothermal effect of MPDA and the Fenton-like reaction of the generated Mn2+ further accelerated the cell death. Thus, the developed MPDA-DOX@MnO2 nanoplatform can intelligently modulate the release of DOX, and the combined CDT/PTT/chemotherapy possessed high-safety and high-efficacy against tumors.

Health risks posed by environmental benzophenone-type ultraviolet filters (BP-UVFs): An investigation into the binding of BP-UVFs to trypsin and their adverse effects.

Benzophenone-type ultraviolet filters (BP-UVFs) are ubiquitous in the environment, and people frequently ingest them via food chain and drinking water. However, there is no clear information about whether BP-UVFs are detrimental to human health. Herein, experiments using multi-spectroscopy revealed typical BP-UVFs, i.e., benzophenone (BP), 2-hydroxybenzophenone (2-OHBP), 4-hydroxybenzophenone (4-OHBP), 2,2'-dihydroxybenzophenone (2,2'-OHBP), 2,4-dihydroxybenzophenone (2,4-OHBP), 4,4'-dihydroxybenzophenone (4,4'-OHBP), 2,4,4'-trihydroxybenzophenone (2,4,4'-OHBP), 2,2',4,4'-tetraphydroxybenzophenone (2,2',4,4'-OHBP), 2-hydroxy-4-methoxybenzophenone (2-OH-4-MeOBP) and 2,2'-dihydroxy-4-methoxybenzophenone (2,2'-OH-4-MeOBP), could bind to the active site of trypsin with different binding constants (2.69 × 104-1.07 × 106 L/mol), cause structural abnormalities and inhibit the enzymatic activity in varying degrees, indicating that the BP-UVFs ingestion poses a risk to human health. In contrast to previous research, this study systematically analysed the binding mechanism using an innovative combination of molecular docking and advanced quantum chemistry calculations, including molecular dynamics simulations, energy calculations, etc. The results revealed that most amino acids that make up trypsin have a greater positive electrostatic surface potential (ESP). Therefore, the greater the area and distribution of negative ESP in a particular BP-UVFs, the more easily it will bind to trypsin. This provides new insight into the binding of pollutants to proteins. This study suggests a need for better monitoring and control of environmental BP-UVFs.

Conflict Experience Regulates the Neural Encoding of Cognitive Conflict.

Cognitive control is adaptive in that it rapidly adjusts attention in response to changing contexts and shifting goals. Research provides evidence that cognitive control can rapidly adjust attention to focus on task-relevant information based on prior conflict experience. Neural encoding of goal-related information is critical for goal-directed behaviour; however, the empirical evidence on how conflict experience affects the encoding of cognitive conflict in the brain is rather weak. In the present fMRI study, a Stroop task with different proportions of incongruent trial was used to investigate the neural encoding of cognitive conflict in the environment with changing conflict experience. The results showed that the anterior cingulate cortex, dorsolateral prefrontal cortex, and intraparietal sulcus played a pivotal role in the neural encoding of cognitive conflict. The classification in anterior cingulate cortex was significantly above chance in the high-proportion, moderate-proportion, and low-proportion conflict conditions conducted separately, suggesting that neural encoding of cognitive conflict in this region was not altered based on proportion of conflict. The dorsolateral prefrontal cortex and intraparietal sulcus showed significant above-chance classification in the moderate-proportion and low-proportion conflict conditions, but not in the high-proportion conflict condition. These findings provide direct evidence that conflict experience modulates the neural encoding of cognitive conflict.

Insights into the enzymatic degradation of DNA expedited by typical perfluoroalkyl acids.

Perfluoroalkyl acids (PFAAs) are considered forever chemicals, gaining increasing attention for their hazardous impacts. However, the ecological effects of PFAAs remain unclear. Environmental DNA (eDNA), as the environmental gene pool, is often collected for evaluating the ecotoxicological effects of pollutants. In this study, we found that all PFAAs investigated, including perfluorohexanoic acid, perfluorooctanoic acid, perfluorononanoic acid, and perfluorooctane sulfonate, even at low concentrations (0.02 and 0.05 mg/L), expedited the enzymatic degradation of DNA in a nonlinear dose-effect relationship, with DNA degradation fragment sizes being lower than 1,000 bp and 200 bp after 15 and 30 min of degradation, respectively. This phenomenon was attributed to the binding interaction between PFAAs and AT bases in DNA via groove binding. van der Waals force (especially dispersion force) and hydrogen bonding are the main binding forces. DNA binding with PFAAs led to decreased base stacking and right-handed helicity, resulting in loose DNA structure exposing more digestion sites for degrading enzymes, and accelerating the enzymatic degradation of DNA. The global ecological risk evaluation results indicated that PFAA contamination could cause medium and high molecular ecological risk in 497 samples from 11 contamination-hot countries (such as the USA, Canada, and China). The findings of this study show new insights into the influence of PFAAs on the environmental fates of biomacromolecules and reveal the hidden molecular ecological effects of PFAAs in the environment.

Current and Future Use of Long Axial Field-of-View Positron Emission Tomography/Computed Tomography Scanners in Clinical Oncology.

The latest technical development in the field of positron emission tomography/computed tomography (PET/CT) imaging has been the extension of the PET axial field-of-view. As a result of the increased number of detectors, the long axial field-of-view (LAFOV) PET systems are not only characterized by a larger anatomical coverage but also by a substantially improved sensitivity, compared with conventional short axial field-of-view PET systems. In clinical practice, this innovation has led to the following optimization: (1) improved overall image quality, (2) decreased duration of PET examinations, (3) decreased amount of radioactivity administered to the patient, or (4) a combination of any of the above. In this review, novel applications of LAFOV PET in oncology are highlighted and future directions are discussed.

Novel Gene Rearrangements in the Mitochondrial Genomes of Cynipoid Wasps (Hymenoptera: Cynipoidea).

Cynipoidea is a medium-sized superfamily of Hymenoptera with diverse lifestyles. In this study, 16 mitochondrial genomes were newly sequenced, 11 of which were the first obtained mitochondrial genomes in the family Liopteridae and four subfamilies (Anacharitinae, Aspicerinae, Figitinae, and Parnipinae) of Figitidae. All of the newly sequenced mitogenomes have unique rearrangement types within Cynipoidea, whereas some gene patterns are conserved in several groups. nad5-nad4-nad4L-nad6-cytb was remotely inverted and two rRNA genes were translocated to nad3 downstream in Ibaliidae and three subfamilies (Anacharitinae, Eucoilinae, and Parnipinae within Figitidae); two rRNA genes in Aspicerinae, Figitinae, and Liopteridae were remotely inverted to the cytb-nad1 junction; rrnL-rrnS was translocated to the cytb-nad1 junction in Cynipidae. Phylogenetic inference suggested that Figitidae was a polyphyletic group, while the Ibaliidae nested deep within Cynipoidea and was a sister-group to the Figitidae. These results will improve our understanding of the gene rearrangement of the mitogenomes and the phylogenetic relationships in the Cynipoidea.