An Ultrasensitive and Efficient microRNA Nanosensor Empowered by the CRISPR/Cas Confined in a Nanopore.

This work presents a clustered regularly interspaced short palindromic repeat (CRISPR)/Cas-nanopipette nano-electrochemistry (Cas = CRISPR-associated proteins) capable of ultrasensitive microRNA detection. Nanoconfinement of the CRISPR/Cas13a within a nanopipette leads to a high catalytic efficacy of ca. 169 times higher than that in bulk electrolyte, contributing to the amplified electrochemical responses. CRISPR/Cas13a-enabled detection of representative microRNA-25 achieves a low limit of detection down to 10 aM. Practical application of this method is further demonstrated for single-cell and real human serum detection. Its general applicability is validated by addressing microRNA-141 and the SARS-CoV-2 RNA gene fragment. This work introduces a new CRISPR/Cas-empowered nanotechnology for ultrasensitive nano-electrochemistry and bioanalysis.

Single-Cell Caspase-3 Measurement Using a Biomimetic Nanochannel.

Direct single-cell caspase-3 (Casp-3) analysis has remained challenging. A study of single-cell Casp-3 could contribute to revealing the fundamental pathogenic mechanisms in Casp-3-associated diseases. Here, a biomimetic nanochannel capable of single-cell sampling and ionic detection of intracellular Casp-3 is devised, which is established upon the installment of target-specific organic molecules (luc-DEVD) within the orifice of a glass nanopipette. The specific cleavage of luc-DEVD by Casp-3 could induce changes of inner-surface chemical groups and charge properties, thus altering the ionic response of the biomimetic nanochannel for direct Casp-3 detection. The practical applicability of this biomimetic nanochannel is confirmed by probing intracellular Casp-3 fluctuation upon drug stimulation and quantifying the Casp-3 evolution during induced apoptosis. This work realizes ionic single-cell Casp-3 analysis and provides a different perspective for single-cell protein analysis.

DeepLncPro: an interpretable convolutional neural network model for identifying long non-coding RNA promoters.

Long non-coding RNA (lncRNA) plays important roles in a series of biological processes. The transcription of lncRNA is regulated by its promoter. Hence, accurate identification of lncRNA promoter will be helpful to understand its regulatory mechanisms. Since experimental techniques remain time consuming for gnome-wide promoter identification, developing computational tools to identify promoters are necessary. However, only few computational methods have been proposed for lncRNA promoter prediction and their performances still have room to be improved. In the present work, a convolutional neural network based model, called DeepLncPro, was proposed to identify lncRNA promoters in human and mouse. Comparative results demonstrated that DeepLncPro was superior to both state-of-the-art machine learning methods and existing models for identifying lncRNA promoters. Furthermore, DeepLncPro has the ability to extract and analyze transcription factor binding motifs from lncRNAs, which made it become an interpretable model. These results indicate that the DeepLncPro can server as a powerful tool for identifying lncRNA promoters. An open-source tool for DeepLncPro was provided at https://github.com/zhangtian-yang/DeepLncPro.

Identification and characterization of a fungal cutinase-like enzyme CpCut1 from Cladosporium sp. P7 for polyurethane degradation.

Plastic degradation by biological systems emerges as a prospective avenue for addressing the pressing global concern of plastic waste accumulation. The intricate chemical compositions and diverse structural facets inherent to polyurethanes (PU) substantially increase the complexity associated with PU waste management. Despite the extensive research endeavors spanning over decades, most known enzymes exhibit a propensity for hydrolyzing waterborne PU dispersion (i.e., the commercial Impranil DLN-SD), with only a limited capacity for the degradation of bulky PU materials. Here, we report a novel cutinase (CpCut1) derived from Cladosporium sp. P7, which demonstrates remarkable efficiency in the degrading of various polyester-PU materials. After 12-h incubation at 55°C, CpCut1 was capable of degrading 40.5% and 20.6% of thermoplastic PU film and post-consumer foam, respectively, while achieving complete depolymerization of Impranil DLN-SD. Further analysis of the degradation intermediates suggested that the activity of CpCut1 primarily targeted the ester bonds within the PU soft segments. The versatile performance of CpCut1 against a spectrum of polyester-PU materials positions it as a promising candidate for the bio-recycling of waste plastics.IMPORTANCEPolyurethane (PU) has a complex chemical composition that frequently incorporates a variety of additives, which poses significant obstacles to biodegradability and recyclability. Recent advances have unveiled microbial degradation and enzymatic depolymerization as promising waste PU disposal strategies. In this study, we identified a gene encoding a cutinase from the PU-degrading fungus Cladosporium sp. P7, which allowed the expression, purification, and characterization of the recombinant enzyme CpCut1. Furthermore, this study identified the products derived from the CpCut1 catalyzed PU degradation and proposed its underlying mechanism. These findings highlight the potential of this newly discovered fungal cutinase as a remarkably efficient tool in the degradation of PU materials.

Overlooked Role of Fungi in Drinking Water Taste and Odor Issues.

Taste and odor (T&O) are among the most frequently encountered aesthetic issues in drinking water. While fungi have been reported to produce offensive odors, their contribution to T&O in drinking water remains understudied and often overlooked. In this study, the profiles of fungal community and odorants produced by 10 native fungal isolates were investigated in 36 samples collected from two drinking water treatment plants and a premise plumbing system. A total of 17 odorants were identified with Penicillium, Aspergillus, Paecilomyces, and Alternaria genera exhibiting the highest odorant yields. Significant concentrations of musty/earthy compounds were produced by these fungal isolates, such as 2-methylisoborneol (2-MIB) (26-256 ng/L), geosmin (10-13 ng/L), and 2-isobutyl-3-methoxy-pyrazine (IBMP) (3-13 ng/L). The high odor activity value of the odorants primarily occurred within 4 d, while toxicity continued to increase during the 8 d incubation. UV treatment in premise plumbing significantly (p < 0.05) reduced the gene read counts of Ascomycota phylum, Aspergillus spp., Fusarium spp., Rhizopus spp., and Trichoderma spp., by 2.3-4.0 times. These findings underscore the previously underestimated role of fungi in contributing to T&O issues in drinking water and corresponding risks to consumers and indicate UV as a promising strategy for fungal control in drinking water.

Maternal suicide attempts and deaths in the first year after cesarean delivery.

BACKGROUND: Cesarean delivery (CD) has been associated with postpartum psychiatric disorders, but less is known about the risk of suicidal behaviors. We estimated the incidence and risk of suicide attempts and deaths during the first postpartum year in mothers who delivered via CD v. vaginally. METHOD: All deliveries in Sweden between 1973 and 2012 were identified. The mothers were followed since delivery for 12 months or until the date of one of the outcomes (i.e. suicide attempt or death by suicide), death by other causes or emigration. Associations were estimated using Cox proportional hazards regression models. RESULTS: Of 4 016 789 identified deliveries, 514 113 (12.8%) were CDs and 3 502 676 (87.2%) were vaginal deliveries. During the 12-month follow-up, 504 (0.098%) suicide attempts were observed in the CD group and 2240 (0.064%) in the vaginal delivery group (risk difference: 0.034%), while 11 (0.0037%) deaths by suicide were registered in the CD group and 109 (0.0029%) in the vaginal delivery group (risk difference: 0.008%). Compared to vaginal delivery, CD was associated with an increased risk of suicide attempts [hazard ratio (HR) 1.46; 95% CI 1.32-1.60], but not of deaths by suicide (HR 1.44; 95% CI 0.88-2.36). CONCLUSIONS: Maternal suicidal behaviors during the first postpartum year were uncommon in Sweden. Compared to vaginal delivery, CD was associated with a small increased risk of suicide attempts, but not death by suicide. Improved understanding of the association between CD and maternal suicidal behaviors may promote more appropriate measures to improve maternal mental well-being and further reduce suicidal risks.

Complete mitochondrial genome and its phylogenetic implications of Rhinogobio nasutus, an endemic species from the Yellow River.

BACKGROUND: Rhinogobio nasutus, an endemic species from the Yellow River, is listed under the second class of the National Key Protected Wildlife List in China due to its dramatically decreased population. Despite its important status, the mitochondrial genes and phylogenetic relationships of R. nasutus are unknown. METHODS AND RESULTS: The complete mitochondrial genome of R. nasutus was sequenced, assembled, and annotated for the first time. The mitochondrial genome was 16,609 bp in length, consisting of 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, and 1 non-coding control region. The gene order in the mitochondrial genome of R. nasutus was identical to that of other Rhinogobios species. Analysis of synonymous and non-synonymous nucleotide substitutions showed that the Ka/Ks ratio in all tested protein-coding genes was less than 1, indicating that these genes were evolving under purifying selection. Further phylogenetic analysis showed that R. nasutus was first clustered with R. typus, then grouped with the other two Rhinogobio species, indicating the phylogenetically close relationship between R. nasutus and R. typus. CONCLUSIONS: This was the first genomic resource developed for R. nasutus, which could not only improve our understanding of its phylogenetic status, but also serve as a genomic tool for the development of genetic markers that will be used in conservation and evolutionary genetics studies.

The evolution of N6-methyladenosine regulators in plants.

As a reversible modification, N6-methyladenosine (m6A) plays key roles in series of biological processes. Although it has been found that m6A modification is regulated by writers, erasers and readers, their evolutionary processes are still not clearly and systematically described. In the present work, we identified 1592 m6A modification regulators from 65 representative plant species and performed the phylogenetic relationships, sequence structure, selection pressure, and codon usage analysis across species. The regulators from different species or subfamilies were distinguishable based on the phylogenetic trees. Although the gene structure was structurally and functionally conserved for each kind of regulators, the unique exon/intron structures and motif organizations were observed among different families. The selection pressure analysis demonstrated that the regulators experienced purifying selection. Interestingly, the selection pressure for the regulators in higher plants was more relaxed, indicating that they might have acquired new functions during evolution. In addition, the different codon usage preferences were observed for the different kinds of m6A modification regulators. These results will not only facilitate our understanding of the evolution of m6A regulators, but also shed light on how the evolutionary differences affect their functional divergence.

Electrophysiological evidence of crossmodal correspondence between auditory pitch and visual elevation affecting inhibition of return.

Inhibition of return (IOR) has proved to be weakened by audiovisual integration because of the increased perceptual salience of targets. Although other audiovisual interactions, such as crossmodal correspondence, have also been shown to facilitate attentional processes, to the best of our knowledge, no study has investigated the interaction between crossmodal correspondence and IOR. The present study employed Posner's spatial cueing paradigm and manipulated the cue validity, crossmodal correspondence congruency and time interval of auditory and visual stimuli (AV interval) to explore the effect of crossmodal correspondence on the IOR effect. The behavioral results showed a reduced IOR effect under the correspondence congruency condition in contrast to the correspondence incongruency condition at the AV interval of 200 ms, whereas at an AV interval of 80 ms, the decreased IOR effect under crossmodal correspondence congruency was eliminated. The electrophysiological results showed a reduced amplitude difference in P2 between valid and invalid cue conditions when the crossmodal correspondence effect decreased the IOR effect. The present study provided the first evidence of the weakened effect of the crossmodal correspondence effect on the IOR effect, which could be eliminated by audiovisual integration.

Sleep quality as a mediator of the relationship between screen time and negative emotions among Chinese college freshmen.

College freshmen are special populations facing great challenges in adapting to the brand new environment, and their lifestyle and emotional states are worthy of attention. Especially during the COVID-19 pandemic, their screen time and prevalence of negative emotions were significantly increased, but few studies have focused on such situation of college freshmen and illustrated relevant mechanisms. Thus, based on a sample of Chinese college freshmen during the COVID-19 pandemic, the current study aimed to investigate the association between their screen time and negative emotions (depression, anxiety and stress), and further explore the mediating effects of sleep quality. Data from 2,014 college freshmen was analyzed. The screen time was self-reported by participants using predesigned questionnaires. The Pittsburgh Sleep Quality Index (PSQI) and Chinese Version of Depression Anxiety and Stress Scale-21 (DASS-21) were used to assess sleep quality and emotional states, respectively. The mediation analysis was conducted to examine the meditation effect. Results indicated that participants with negative emotions tended to have longer daily screen time and worse sleep quality, sleep quality partially mediated the association between screen time and negative emotions.The critical role of sleep quality and related intervention measures should be recognized and implemented.

Different gain modulations of selective attention at short and long cue-target delays.

Previous studies have tested attentional gain patterns, for example, within the normalization model of attention (NMoA), by altering the relative sizes of the attention field and stimuli. Existing studies have not investigated whether the gain patterns of altering the relative exogenous cue size as compared with the target stimuli matches the prediction of NMoA and whether these gain patterns exist in the late stage of attentional processing. To resolve these questions, the present study maintained the target grating size and changed the exogenous cue size in both short and long cue-target onset asynchronies (CTOAs) conditions. The results revealed response gain for small cue/large target size conditions and contrast gain for large cue/small target size conditions, which was consistent with the NMoA. However, we observed the decrease in the contrast gain factor only with long CTOAs, regardless of whether the cue size was relatively small or large. This indicated that NMoA-related effects based on the relative attentional field dominated in the early stage and that the contrast gain dominated in the late stage.

Association between screen time and depressive symptoms in a sample of Chinese medical students: Mediator role of empathy.

Medical students are at high risk of psychological subhealth under heavy stress with increasing screen time. This study aimed to explore the association between screen time and depressive symptoms and determine empathy as a mediating factor. In this cross-sectional study, a total of 945 medical students were surveyed, and 924 medical students were ultimately included after standard exclusion criteria. They reported their daily screen time and completed the Chinese version of the Jefferson Scale of Empathy-Student Version (JSE-S) and the Self-Rating Depression Scale (SDS). t tests and analysis of variance showed a significant difference in empathy and depressive symptoms by sex, stage, and screen time. The correlation analysis revealed that both affective and cognitive empathy have inverse associations with depressive symptoms. The mediation model confirmed that cognitive empathy played a positive mediating role between screen time and depressive symptoms, reducing the impact of screen time on depressive symptoms. Our study may add empirical evidence to prevent and intervene in depressive symptoms. These findings call for considering controlling screen time and enhancing cognitive empathy as interventions for medical students' depressive symptoms.

Reward Weakened Inhibition of Return (IOR) in the Near Depth Plane.

In attentional orienting, researchers have proposed that reward history is a component of attentional control, as the reward value might enhance the spatial attention process to achieve more efficient goal-directed behavior and to improve target-detection performance. Although the effect of reward-induced motivation on attentional orienting has been studied in two-dimensional (2-D) space, the specific mechanisms underlying the influence of reward on inhibition of return (IOR) of attentional orienting in three-dimensional space (3-D) remain unclear. In the present study, by incorporating the Posner spatial-cueing paradigm into a virtual 3-D environment, we aimed to investigate the influence of reward on IOR in 3-D space. The results showed the following: (1) IOR size in the rewarded conditions was smaller than IOR size in the unrewarded condition in the near depth plane, resulting in an IOR difference with or without reward. (2) Reward weakened IOR in the near depth plane because the response to the uncued location was delayed, not because the response to the cued location was accelerated. The present study indicated that the different depth planes of the target location in 3-D space could influence the interaction between reward and IOR, and reward weakened IOR in the near depth plane.

Parental care and depressive symptoms among Chinese medical students: roles of empathy and gender.

BACKGROUND: Medical students in China who face the dual pressure of study and employment tend to experience subclinical depressive symptoms. Parental care plays an important direct and indirect role in the psychological development of medical students, and the extent and mechanism of this role urgently need to be studied and discussed. METHODS: After simple random sampling and screening of valid questionnaires, data from a total of 924 people were used. The participants completed the parental bonding instrument, self-rating depression scale, Chinese version of the Jefferson empathy scale-medical student edition and self-rating anxiety scale to evaluate parental care, empathy, depressive symptoms and anxiety. The data were statistically processed using a descriptive analysis, correlation analysis and test of moderated mediation. RESULTS: Maternal care had a significant negative predictive effect on depressive symptoms among medical students. Strong maternal care can reduce the occurrence of depressive symptoms in medical students. Empathy played a positive mediating role such that both types of empathy could alleviate the effect of weak maternal care on the depressive symptoms of medical students. However, neither cognitive empathy nor affective empathy played a mediating role in the relationship between paternal care and depressive symptoms. Nevertheless, the relationship between maternal care and empathy was moderated by the medical students' gender. CONCLUSIONS: The effect of this relationship on female medical students deserves special attention. The results of this study provide a reference and basis for the adjustment of medical education. This study could also help in the design of effective psychological intervention measures to reduce the degree of depressive symptoms and enhance personal empathy.

Insight into the formation of iodinated trihalomethanes during chlorination, monochloramination, and dichloramination of iodide-containing water.

In this study, the formation of iodinated trihalomethanes (I-THMs) was systematically evaluated and compared for three treatment processes - (i) chlorination, (ii) monochloramine, and (iii) dichloramination - under different pH conditions. The results demonstrated that I-THM formation decreased in the order of monochloramination > dichloramination > chlorination in acidic and neutral pH. However, the generation of I-THMs increased in the dichloramination < chlorination < monochloramination order in alkaline condition. Specifically, the formation of I-THMs increased as pH increased from 5 to 9 during chlorination and monochloramination processes, while the maximum I-THM formation occurred at pH 7 during dichloramination. The discrepancy could be mainly related to the stability of the three chlor (am) ine disinfectants at different pH conditions. Moreover, in order to gain a thorough insight into the mechanisms of I-THM formation during dichloramination, further investigation was conducted on the influencing factors of DOC concentration and Br-/I- molar ratio. I-THM formation exhibited an increasing and then decreasing trend as the concentration of DOC increased from 1 to 7 mg-C/L, while the yield of I-THMs increased with increasing Br-/I- molar ratio from 5:0 to 5:10. During the three processes mentioned above, similar I-THM formation results were also obtained in real water, which indicates that the excessive generation of I-THMs should be paid special attention during the disinfection of iodide-containing water.

Micropollutant removal and disinfection byproduct control by sequential peroxymonosulfate-UV treatment in water: A case study with sulfamethoxazole.

UV/peroxymonosulfate (UV/PMS) advanced oxidation process has attracted significant attention for removal of micropollutants in water. However, during practical water treatment applications, the PMS treatment must be performed before the UV treatment to achieve full contact. In this study, sulfamethoxazole (SMX) was selected as the target micropollutant. Four different operational approaches, including UV alone, PMS alone, simultaneous UV/PMS and sequential PMS-UV, were compared for their differences in SMX removal and disinfection by-product (DBP) formation potentials during chlorine-driven disinfection. Among the four approaches, UV/PMS and PMS-UV achieved over 90% removal efficiencies for SMX without substantial differences. For raw water, the trichloronitromethane (TCNM) formation potential after treatment with PMS-UV was lower than that after UV/PMS treatment. The time interval over which the PMS-UV process was conducted had little effect on the final removal efficiency for SMX. However, a brief (5 min) pre-PMS treatment significantly reduced the TCNM formation potential and the genotoxicity from DBPs. The formation risk for TCNM during chlorination increased markedly with increasing PMS dosages, and the appropriate dosage under these experimental conditions was suggested to be 0.5-1.0 mmol/L. Under alkaline conditions, PMS-UV treatment can enhance SMX degradation as well as dramatically reduced the formation potentials for haloketones, haloacetonitriles and halonitromethanes. This study suggests that proper optimization of UV/PMS processes can remove SMX and reduce its DBP formation.

Rational Utilization of Photoelectrochemistry of Photosystem II for Self-Powered Photocathodic Detection of MicroRNA in Cells.

The photoanode, photosystem II (PSII)/hierarchical inverse opal (IO) TiO2, is coupled to the complementary photocathode, PbS quantum dots (QDs)/DNA probes, which is then integrated into a two-compartment photoelectrochemical (PEC) cell to achieve a self-powered system to enable photocathodic detection of microRNA-10b from HeLa cells. In such a system, all of the PSII catalytic products, i.e., electrons, protons, and O2, were rationally utilized and could overcome the general issue of varied O2 levels in photocathodic detection. The correlation between the target-triggered formation of the DNA complexes and the catalytic reduction of the dissolved O2 makes possible the steady microRNA-10b detection with good sensitivity and selectivity. This work has unveiled the ability of PSII to construct self-powered detecting devices and shed light on its application in new arenas.

Twin Nanopipettes for Real-Time Electrochemical Monitoring of Cytoplasmic Microviscosity at a Single-Cell Level.

Cytoplasmic microviscosity (CPMV) plays essential roles in governing the diffusion-mediated cellular processes and has been recognized as a reliable indicator of the cellular response of many diseases and malfunctions. Current CPMV studies are exclusively established by probe-assisted optical methods, which nevertheless necessitate the complicated synthesis and delivery of optical probes into cells and thus the issues of biocompatibility and bio-orthogonality. Using twin nanopipettes integrated with a patch-clamp system, a practical electrochemical single-cell measurement is presented, which is capable of real-time and long-term CPMV detection without cell disruption. Specifically, upon the operation of the twin nanopipettes, the cellular CPMV status, which is correlated to cytoplasmic ionic mobility, could be sensibly transduced via the ionic current passing through the nanosystem. The average CPMV value of HeLa cells was detected as ca. 86 cP. Notably, the correlation between chemotherapy and CPMV alterations makes this approach possible for the real-time and long-term assessment of the evolution of external stimuli, as exemplified by the two natural products taxol and colchicine. Integrated with the patch-clamp setup, this study features the first use of twin nanopipettes for electrochemical CPMV monitoring of single living cells, and it is expected to inspire more interest in the exploitation of dual- and multiple nanopipettes for advanced single-cell analysis.

Repetition Suppression in Visual and Auditory Modalities Affects the Sound-Induced Flash Illusion.

Sound-induced flash illusion (SiFI) refers to the illusion that the number of visual flashes is equal to the number of auditory sounds when the visual flashes are accompanied by an unequal number of auditory sounds presented within 100 ms. The effect of repetition suppression (RS), an adaptive effect caused by stimulus repetition, upon the SiFI has not been investigated. Based on the classic SiFI paradigm, the present study investigated whether RS would affect the SiFI differently by adding preceding stimuli in visual and auditory modalities prior to the appearance of audiovisual stimuli. The results showed the auditory RS effect on the SiFI varied with the number of preceding auditory stimuli. The hit rate was higher with two preceding auditory stimuli than one preceding auditory stimulus in fission illusion, but it did not affect the size of the fusion illusion. However, the visual RS had no effect on the size of the fission and fusion illusions. The present study suggested that RS could affect the SiFI, indicating that the RS effect in different modalities would differentially affect the magnitude of the SiFI. In the process of multisensory integration, the visual and auditory modalities had asymmetrical RS effects.

Association between relational trauma and empathy among male offenders in China.

BACKGROUND: Offenders are more likely than the general population to have experienced relationship trauma. They are also more likely to have lower empathy. To date, relationships between historical trauma and later empathic states have not been examined among offenders. AIMS: To explore the association between history of trauma in close personal relationships and empathy among offenders. Our research question is: Is such relational trauma associated with self-rated impairments in empathy? METHODS: All men with a primary school education and above at a single all-male prison in Jiangsu Province in China were invited to participate. The self-reported Interpersonal Reactivity Index was used to evaluate empathy, and the Brief Betrayal Trauma Survey was to explore interpersonal trauma and classify such experiences. RESULTS: Interpersonal trauma was associated with higher personal distress and lower empathic concern among men reporting relational trauma in adulthood, but only higher personal distress when the trauma reported was in childhood. Non-relational trauma was associated with higher empathic concern. Cognitive aspects of empathy varied little between groups. CONCLUSIONS: Our findings add to the existing literature by making distinctions between the types of trauma and the age of key experience in its relationship to self-reported empathy. The differences found suggest that it may be helpful to consider planning any trauma-related interventions differently according to the type and age of trauma experiences.