Integrated sentence-level speech perception evokes strengthened language networks and facilitates early speech development.

Natural poetic speeches (i.e., proverbs, nursery rhymes, and commercial ads) with strong prosodic regularities are easily memorized by children and the harmonious acoustic patterns are suggested to facilitate their integrated sentence processing. Do children have specific neural pathways for perceiving such poetic utterances, and does their speech development benefit from it? We recorded the task-induced hemodynamic changes of 94 children aged 2 to 12 years using functional near-infrared spectroscopy (fNIRS) while they listened to poetic and non-poetic natural sentences. Seventy-three adult as controls were recruited to investigate the developmental specificity of children group. The results indicated that poetic sentences perceiving is a highly integrated process featured by a lower brain workload in both groups. However, an early activated large-scale network was induced only in the child group, coordinated by hubs for connectivity diversity. Additionally, poetic speeches evoked activation in the phonological encoding regions in the children's group rather than adult controls which decreases with children's ages. The neural responses to poetic speeches were positively linked to children's speech communication performance, especially the fluency and semantic aspects. These results reveal children's neural sensitivity to integrated speech perception which facilitate early speech development by strengthening more sophisticated language networks and the perception-production circuit.

Design of Refined Quaternary Electrolyte LiF-LiCl-LiBr-LiI Used for the Liquid Metal Battery.

The advanced electrolyte of liquid metal battery should have low melting point, low ionic solubility, low viscosity, high electric and thermal conductivities, and a suitable density between anode and cathode for declining the operating temperature and realizing the goal of saving-energy. In this study, an excellent quaternary LiF-LiCl-LiBr-LiI (9.1 : 30.0 : 21.7 : 39.2) electrolyte is refined by using thermodynamic models to balance various properties of LiX (X=F, Cl, Br, I) and meet the requirement of advanced electrolyte of liquid metal battery. The refined properties of electrolyte correspond to 2.398 g/cm3 for density, 0.286 mol% for solubility, 4.486 Ohm-1 cm-1 for ionic conductivity, and 0.609 W m-1 for thermal conductivity. The measured melting point is 609.1 K, which is lower than the current operating temperature of 723 K for the lithium-based liquid metal battery. The refined electrolyte consisted by quaternary halide molten-salt provides important references for preparing the advanced liquid metal battery.

Analysis of abdominal adhesion using the ileostomy model.

Abdominal adhesion occurs commonly in clinical practice, causing unfavorable symptoms and readmission. The ileostomy operation is a common surgical procedure and we utilized this model to evaluate abdominal adhesion. Adhesion grade score was calculated in 35 patients (Cohort 1) and subjected to correlation and receiver operating characteristic analysis. Then 98 consecutive patients (Cohort 2) who underwent ileostomy and ileostomy closure were included into a retrospective study. Logistic regression analysis was performed, and the risk of small bowel obstruction was also assessed. The time of ileostomy closure correlated with adhesion grade score in Cohort 1, justifying its use as an indicator of abdominal adhesion. All patients in Cohort 2 were then divided into the high- and low-adhesion group. A multi-variable logistic regression analysis indicated that type of surgery and peritoneum suture during ileostomy were significant factors affecting the risk of abdominal adhesion. Abdominal adhesion had the trend to prolong the length of stay postoperatively without increasing the risk of bowel obstruction. Nine patients suffered bowel obstruction, and age older than 65 significantly increased the risk. We proposed the ileostomy procedure to be a model of abdominal adhesion, and the operative time of ileostomy closure could be used as an alternative of adhesion score. Type of surgery and peritoneum suture may be risk factors of abdominal adhesion. Older age increased the risk of small bowel obstruction after ileostomy surgery.

Early Visual Deprivation Impairs Functional Development of the Visual Ventral Stream.

Purpose: To probe the dynamic alternations of neural networks in real-time visual processing after visual deprivation (VD) removal. Methods: A prospective cross-sectional study was conducted. Twenty children with a history of early binocular VD caused by congenital cataracts and 20 matched typically developing (TD) children were enrolled. The event-related potential (ERP) data were obtained via high-density electroencephalography. ERP data were analyzed based on three components (P1, N170, and P2), three test conditions (objects, human faces, and Chinese characters), and peak time and region of interest (ROI) chosen on a grand average head map collapsed from the averaged waveform of each group. Source localization and alpha power spectrum density were applied to define the functional pattern of brain areas and evaluate the attention function. Results: The VD group showed significantly lower P1 amplitudes than the TD group under all conditions in peak ROIs, which were situated in the left occipito-temporal region. For both VD and TD groups, there were strong N170 effects in the character and human face conditions in the component's peak ROIs. Furthermore, source mapping indicated that the VD group generally showed significantly lower activation in the visual cortex and ventral stream, whereas the beyond network areas (mostly frontal areas) intensively participated in functional compensation in the VD group. The VD group showed significant poststimulus alpha desynchronization in object recognition. Conclusions: Our research described the mechanisms of visual networks after early binocular VD removal. Our findings may provide a new basis for the poor visual recovery after early binocular VD removal and offer clues for visual recovery strategies.

DNA-encoded chemical libraries yield non-covalent and non-peptidic SARS-CoV-2 main protease inhibitors.

The development of SARS-CoV-2 main protease (Mpro) inhibitors for the treatment of COVID-19 has mostly benefitted from X-ray structures and preexisting knowledge of inhibitors; however, an efficient method to generate Mpro inhibitors, which circumvents such information would be advantageous. As an alternative approach, we show here that DNA-encoded chemistry technology (DEC-Tec) can be used to discover inhibitors of Mpro. An affinity selection of a 4-billion-membered DNA-encoded chemical library (DECL) using Mpro as bait produces novel non-covalent and non-peptide-based small molecule inhibitors of Mpro with low nanomolar Ki values. Furthermore, these compounds demonstrate efficacy against mutant forms of Mpro that have shown resistance to the standard-of-care drug nirmatrelvir. Overall, this work demonstrates that DEC-Tec can efficiently generate novel and potent inhibitors without preliminary chemical or structural information.

Cerebral blood flow measured by diffuse correlation spectroscopy in children with autism spectrum disorder.

Diffuse correlation spectroscopy (DCS) was used to measure resting-state cerebral blood flow (CBF) in temporal lobes of children with autism spectrum disorder (ASD) and typically developing (TD) children. Twenty-two children with ASD and 34 age-matched TD children were recruited to participate in the experiment. DCS signals were recorded with 3 long source-detector (SD) channels (SD distance = 22.0 mm) and 1 short SD channel (SD distance = 10.5 mm) from each side of the temporal lobe. Significant difference in CBF between left and right hemispheres was observed in ASD group, but not in TD group. With the degree of CBF lateralization as a discrimination feature, a leave-one-out ROC curve was plotted with the area-under-curve (AUC) value of 0.731 ± 0.010, indicating children with ASD could be discriminated from TD children. This suggested CBF lateralization in temporal lobes measured with DCS might serve as a discriminative feature for ASD.

Ca2+ efflux facilitated by co-transport of inorganic phosphate anion in the H+/Ca2+ antiporter YfkE.

Ca2+ is an important signaling messenger. In microorganisms, fungi, and plants, H+/Ca2+ antiporters (CAX) are known to play key roles in the homeostasis of intracellular Ca2+ by catalyzing its efflux across the cell membrane. Here, we reveal that the bacterial CAX homolog YfkE transports Ca2+ in two distinct modes: a low-flux H+/Ca2+ exchange mode and a high-flux mode in which Ca2+ and phosphate ions are co-transported (1:1) in exchange for H+. Coupling with phosphate greatly accelerates the Ca2+ efflux activity of YfkE. Our studies reveal that Ca2+ and phosphate bind to adjacent sites in a central translocation pathway and lead to mechanistic insights that explain how this CAX alters its conserved alpha-repeat motifs to adopt phosphate as a specific "transport chaperon" for Ca2+ translocation. This finding uncovers a co-transport mechanism within the CAX family that indicates this class of proteins contributes to the cellular homeostasis of both Ca2+ and phosphate.

Gradual transformation of anionic/zwitterionic wormlike micelles from viscous to elastic domains: Unravelling the effect of anionic surfactant chain length.

HYPOTHESIS: Ultra-long tailed zwitterionic surfactants often form aqueous wormlike elastic micelles, whereas the shorter ones mainly exhibit spherical viscous micelles. Anionic surfactants are widely used to tune the micellar morphology from spherical into wormlike. Systematic investigations in the molecular level are insightful to understand the viscoelasticity regulative mechanism. EXPERIMENTS: Anionic/zwitterionic hybrid wormlike micelles are composed of sodium alkylsulfate (SAS) homologues and dodecyl dimethyl amidopropyl hydroxyl sulfobetaine (DHSB). The formation of wormlike micelles was studied by employing rheometer, cryogenic transmission electron microscopy (cryo-TEM) and small angle X-ray scattering (SAXS) techniques. The effects of surfactant concentration, molar ratio, anionic surfactant chain length and temperature were investigated systematically. FINDINGS: SAS promoted the formation of SAS/DHSB hybrid wormlike micelles. The increase in both chain length and molar ratio (xSAS) of SAS are advantageous in the enhancement of viscosity. Interestingly, sodium hexadecylsulfate (SHS) endowed elastic wormlike micelles with thermally insensitive viscosity below its Krafft temperature (Tk), which was distinguished from the viscous ones formed by sodium octylsulfate (SOS). SAXS results showed that the size of SAS/DHSB wormlike micelles was primarily determinate by surfactants with longer hydrophobic tails.

Mutagenesis and structural analysis reveal the CTX-M ß-lactamase active site is optimized for cephalosporin catalysis and drug resistance.

CTX-M ß-lactamases are a widespread source of resistance to ß-lactam antibiotics in Gram-negative bacteria. These enzymes readily hydrolyze penicillins and cephalosporins, including oxyimino-cephalosporins such as cefotaxime. To investigate the preference of CTX-M enzymes for cephalosporins, we examined eleven active-site residues in the CTX-M-14 ß-lactamase model system by alanine mutagenesis to assess the contribution of the residues to catalysis and specificity for the hydrolysis of the penicillin, ampicillin, and the cephalosporins cephalothin and cefotaxime. Key active site residues for class A ß-lactamases, including Lys73, Ser130, Asn132, Lys234, Thr216, and Thr235, contribute significantly to substrate binding and catalysis of penicillin and cephalosporin substrates in that alanine substitutions decrease both kcat and kcat/KM. A second group of residues, including Asn104, Tyr105, Asn106, Thr215, and Thr216, contribute only to substrate binding, with the substitutions decreasing only kcat/KM. Importantly, calculating the average effect of a substitution across the 11 active-site residues shows that the most significant impact is on cefotaxime hydrolysis while ampicillin hydrolysis is least affected, suggesting the active site is highly optimized for cefotaxime catalysis. Furthermore, we determined X-ray crystal structures for the apo-enzymes of the mutants N106A, S130A, N132A, N170A, T215A, and T235A. Surprisingly, in the structures of some mutants, particularly N106A and T235A, the changes in structure propagate from the site of substitution to other regions of the active site, suggesting that the impact of substitutions is due to more widespread changes in structure and illustrating the interconnected nature of the active site.

An active site loop toggles between conformations to control antibiotic hydrolysis and inhibition potency for CTX-M ß-lactamase drug-resistance enzymes.

ß-lactamases inactivate ß-lactam antibiotics leading to drug resistance. Consequently, inhibitors of ß-lactamases can combat this resistance, and the ß-lactamase inhibitory protein (BLIP) is a naturally occurring inhibitor. The widespread CTX-M-14 and CTX-M-15 ß-lactamases have an 83% sequence identity. In this study, we show that BLIP weakly inhibits CTX-M-14 but potently inhibits CTX-M-15. The structure of the BLIP/CTX-M-15 complex reveals that binding is associated with a conformational change of an active site loop of ß-lactamase. Surprisingly, the loop structure in the complex is similar to that in a drug-resistant variant (N106S) of CTX-M-14. We hypothesized that the pre-established favorable loop conformation of the N106S mutant would facilitate binding. The N106S substitution results in a ~100- and 10-fold increase in BLIP inhibition potency for CTX-M-14 and CTX-M-15, respectively. Thus, this indicates that an active site loop in ß-lactamase toggles between conformations that control antibiotic hydrolysis and inhibitor susceptibility. These findings highlight the role of accessible active site conformations in controlling enzyme activity and inhibitor susceptibility as well as the influence of mutations in selectively stabilizing discrete conformations.

Corrigendum: Children's neural sensitivity to prosodic features of natural speech and its significance to speech development in cochlear implanted children.

[This corrects the article DOI: 10.3389/fnins.2022.892894.].

Identification of PLAUR-related ceRNA and immune prognostic signature for kidney renal clear cell carcinoma.

Kidney renal clear cell carcinoma (KIRC) represents one of the most fatal cancers, usually showing malignant progression and a high tumor recurrence rate. The urokinase-type plasminogen activator receptor (PLAUR) plays a critical role in the initiation and progression of several cancers, including KIRC. However, the function and mechanism of PLAUR in patients with KIRC are still unclear and require further investigation. In the present study, we first explored the expression profile and prognostic values of PLAUR in pan-cancer based on The Cancer Genome Atlas and Genotype-Tissue Expression databases. PLAUR was upregulated in multiple cancers and was significantly associated with poor overall survival and disease-free survival only in patients with KIRC. Subsequently, the PVT1/SNHG15-hsa-miR-532-3p axis was identified as the most potential upstream regulatory network of PLAUR in KIRC. In addition, PLAUR expression was closely associated with tumor-infiltrating immune cells, tumor immunity biomarkers, and immunomodulator expression. Furthermore, we constructed a multiple-gene risk prediction signature according to the PLAUR-related immunomodulators (PRIs). A prognostic nomogram was then developed to predict the 1-, 3-, and 5-year survival probabilities of individuals. In conclusion, our study identified the PVT1/SNHG15-hsa-miR-532-3p-PLAUR axis and a prognostic signature of PRIs, which could be a reference for future clinical research.

Verification of cell cycle-associated cyclin-dependent kinases facilitated prostate cancer progression by integrated bioinformatic analysis and experimental validation.

Introduction: Cell cycle-associated cyclin-dependent kinases (ccCDKs) are essential regulators known to control cell division and facilitate tumorigenesis and progression. However, there is currently no comprehensive study of distinct ccCDKs in prostate cancer (PCa). The purpose of this study was to determine the value of ccCDK expression in predicting the prognosis of patients with PCa and to identify the gene functions of ccCDK in PCa. Methods: The UALCAN databases were analyzed to examine the expression of CDKs in prostate cancer. The Human Protein Atlas was used to verify the expression of CDKs online. Then, we assessed the prognostic values of CDKs using GEPIA. GeneMANIA and Metascape analyses were used to predict biological functions. We analyzed the mutation of CDKs by cBioPortal. The TIMER database was used to evaluate the correlation of CDKs and immune infiltration. The expression of CDKs in tissue was examined through quantitative real-time polymerase chain reaction. After that, we focused on CDK3 and identified the expression of CDK3 by immunohistochemistry and western blot. The functions of CDK3 in C4-2 cell proliferation were determined by CCK-8 assays. C4-2 cells were tested for their ability to invade and migrate through transwell and wound healing assays. Results: The results showed that CDK1/3/4/5/6/16 was expressed at relatively higher levels in PCa tissues than in normal tissues. Patients with low expression of CDK1/3/5/16 exhibited significantly better disease-free survival than those with high expression. ccCDKs were enriched in the IL-18 signaling pathway and correlated with the infiltration of immune cells in PCa. Moreover, our cohort study data verified that there were significantly higher expression of CDK1/3/5/16 in PCa tissues compared to benign prostate hyperplasia tissues, and CDK3 was remarkably associated with a shorter progression-free survival for biochemical recurrence in PCa patients. CDK3 was positively expressed in PCa cells and tissues, and functional experiments demonstrated that silencing CDK3 inhibited PCa cell proliferation, migration, and invasion. Conclusions: Our study provides new evidence of ccCDKS in promoting PCa progression and implies that CDK3 may serve as an oncogene in PCa and may be valuable in the prognosis of biochemical recurrence in PCa patients.

Children's Neural Sensitivity to Prosodic Features of Natural Speech and Its Significance to Speech Development in Cochlear Implanted Children.

Catchy utterances, such as proverbs, verses, and nursery rhymes (i.e., "No pain, no gain" in English), contain strong-prosodic (SP) features and are child-friendly in repeating and memorizing; yet the way those prosodic features encoded by neural activity and their influence on speech development in children are still largely unknown. Using functional near-infrared spectroscopy (fNIRS), this study investigated the cortical responses to the perception of natural speech sentences with strong/weak-prosodic (SP/WP) features and evaluated the speech communication ability in 21 pre-lingually deaf children with cochlear implantation (CI) and 25 normal hearing (NH) children. A comprehensive evaluation of speech communication ability was conducted on all the participants to explore the potential correlations between neural activities and children's speech development. The SP information evoked right-lateralized cortical responses across a broad brain network in NH children and facilitated the early integration of linguistic information, highlighting children's neural sensitivity to natural SP sentences. In contrast, children with CI showed significantly weaker cortical activation and characteristic deficits in speech perception with SP features, suggesting hearing loss at the early age of life, causing significantly impaired sensitivity to prosodic features of sentences. Importantly, the level of neural sensitivity to SP sentences was significantly related to the speech behaviors of all children participants. These findings demonstrate the significance of speech prosodic features in children's speech development.

Retraction Notice to: LINC00355 Promotes Tumor Progression in HNSCC by Hindering MicroRNA-195-Mediated Suppression of HOXA10 Expression.

[This retracts the article DOI: 10.1016/j.omtn.2019.11.002.].

Diversification of Aryl Sulfonyl Compounds through Ligand-Controlled meta- and para-C-H Borylation.

Aryl sulfones and aryl sulfonamides are of great importance in organic synthesis and medicinal chemistry. Although ortho-C-H functionalization of aryl sulfonyl compounds has been extensively explored, the functionalization of remote meta- and para-C-H bonds is very rare. Herein, we report a tunable meta- and para-selective C-H borylation of aryl sulfonyl compounds enabled by computationally designed ligands and iridium catalyst. This method is capable of accommodating a broad range of substrates under mild reaction conditions. Gram-scale preparation can be achieved with iridium catalyst loading as low as 0.1 mol%. As the introduced boronate group can be easily converted into many other groups, our method provides a general solution to installing functional groups at either meta- or para-position of aryl sulfones and aryl sulfonamides with good to excellent selectivity.

Seasonal changes in the recent decline of combined high PM2.5 and O3 pollution and associated chemical and meteorological drivers in the Beijing-Tianjin-Hebei region, China.

China suffers from combined air pollution (CAP) comprising dual high O3 and PM2.5, particularly in the Beijing-Tianjin-Hebei (BTH) region, which is an urban agglomeration in the North China Plain. To characterize the seasonal changes in regional CAP, 82 CAP days were identified during the study period from 2015 to 2019 with the co-occurring pollution of O3 and PM2.5 in the BTH. It is found that CAP seasonality has undergone distinct changes with a declining trend in the interannual variations in CAP over recent years. It is also revealed that the monthly CAP peaks have recently shifted from summer to early spring (March and April), indicating seasonal changes in CAP in the BTH. Furthermore, the of chemical and meteorological roles in CAP changes was investigated using environmental and meteorological observation data. The recent reduction in PM2.5 and O3 concentrations had enhanced O3 production and atmospheric oxidizability, thereby causing increments in secondary PM2.5 proportion. The interaction between O3 and PM2.5 was responsible for changing the CAP of dual high O3 and PM2.5 to the transition/spring season in the context of mitigation of air pollutant emissions. Furthermore, principal component analysis in the T-mode (T-PCA) was applied to identify four synoptic circulation patterns that regulate CAP occurrence. The results show that the CAP occurrence was regulated by the dominant patterns of synoptic circulation in the BTH. Warm temperature and strong downward ultraviolet radiation anomalies were observed in the BTH, indicating the importance of meteorological drivers in O3 photochemical production on the CAP. The frequency of key synoptic circulation patterns during the spring season increased annually, thereby inducing seasonal changes in the atmospheric environment with CAP in the BTH in recent years.

para-Selective C-H Borylation of Aromatic Quaternary Ammonium and Phosphonium Salts.

Aromatic ammonium and phosphonium salts are important synthetic intermediates and multifunctional materials, but para-selective functionalization of the aromatic salts remains a challenge. Here we develop an ionic ligand based on our newly designed "biphenyl-phenanthroline" skeleton and realize the Ir-catalyzed para-selective C-H borylation of seven types of aromatic quaternary ammonium and phosphonium salts. Gram-scale transformation, late-stage elaboration for drug molecule, and diversification of borylated products demonstrate the potential utility of this reaction. The mechanistic studies and computational analysis elucidate the origin of para-selectivity.

Within and beyond the visual cortex: brain tumors induce highly sensitive plasticity of visual processing in whole-brain neural functional networks.

Vision is a key source of information input for humans, which involves various cognitive functions and a great range of neural networks inside and beyond the visual cortex. There has been increasing observation that the cognitive outcomes after a brain lesion cannot be well predicted by the attributes of the lesion itself but are influenced by the functional network plasticity. However, the mechanisms of impaired or preserved visual cognition have not been probed from direct function-execution conditions and few works have observed it on whole-brain dynamic networks. We used high-resolution electroencephalogram recordings from 25 patients with brain tumors to track the dynamical patterns of functional reorganization in visual processing tasks with multilevel complexity. By comparing with 24 healthy controls, increased cortical responsiveness as functional compensation was identified in the early phase of processing, which was highly localized to the visual cortex and functional networks and less relevant to the tumor position. Besides, a spreading wide enhancement in whole-brain functional connectivity was elicited by the visual word-recognition task. Enhanced early rapid-onset cortical compensation in the local functional networks may contribute to largely preserved basic vision functions, and higher-cognitive tasks are vulnerable to impairment but with high sensitivity of functional plasticity being elicited.

Cryo-TEM and rheological study on shear-thickening wormlike micelles of zwitterionic/anionic (AHSB/SDS) surfactants.

HYPOTHESIS: Shear-thickening micelles were mostly made of cationic surfactants, but shear-thickening was rarely reported in the zwitterionic/anionic surfactants. Since wormlike micelles were essential in shear-thickening systems, it should be common for the hybrid wormlike micelles formed by zwitterionic/anionic surfactants, and their fundamental features need to be clarified. EXPERIMENTS: The micellization of zwitterionic surfactant homologies alkyl dimethyl amidopropyl hydroxyl sulfobetaine (AHSB) and sodium dodecyl sulfate (SDS) in brine was studied, and various environmental factors were considered systematically. Light scattering, rheology, zeta potential, 1H NMR and cryo-TEM techniques were employed to characterize the AHSB/SDS wormlike micelles. FINDINGS: AHSB/SDS hybrid wormlike micelles were formed in a wide xSDS region to endow them with apparent viscosities, in which the electrostatic and hydrophobic interactions between AHSB and SDS molecules were critical. AHSB with the longer tail, the higher cAHSB and cNaCl were advantageous to enhance the viscosity because of the longitudinal growth of wormlike micelles. The shear-thickening AHSB/SDS samples were commonly composed of unbranched wormlike micelles with various length, and the shear-induced alignment of wormlike micelles was the major cause as verified by cryo-TEM. Moreover, the quantitative relationships on the critical shear rate ɣ̇c were established, and the activation energies were obtained from the temperature-dependent ɣ̇c.