Minisci-Type Dehydrogenative Coupling of N-Heteroaromatic Rings with Inert C(sp3)-H Enabled by a Visible-Light-Catalyzed Intermolecular Hydrogen Atom Transfer Process.

The Minisci-type dehydrogenative coupling of N-heteroaromatic rings with inert C-H or Si-H partners via visible-light-catalyzed hydrogen atom transfer has been reported. This methodology allows the coupling reactions to be carried out in water as a solvent under air atmospheric conditions with visible-light illumination. A wide range of inert C-H and Si-H partners could be directly coupled with various N-aromatic heterocycles to deliver products in good to excellent yields.

Reading Braille by Touch Recruits Posterior Parietal Cortex.

Blind readers use a tactile reading system consisting of raised dot arrays: braille/⠃⠗⠇. How do human brains implement reading by touch? The current study looked for signatures of reading-specific orthographic processes in braille, separate from low-level somatosensory responses and semantic processes. Of specific interest were responses in posterior parietal cortices (PPCs), because of their role in high-level tactile perception. Congenitally blind, proficient braille readers read real words and pseudowords by touch while undergoing fMRI. We leveraged the system of contractions in English braille, where one braille cell can represent multiple English print letters (e.g., "ing" ⠬, "one" ⠐⠕), making it possible to separate physical and orthographic word length. All words in the study consisted of four braille cells, but their corresponding Roman letter spellings varied from four to seven letters (e.g., "con-c-er-t" ⠒⠉⠻⠞. contracted: four cells; uncontracted: seven letters). We found that the bilateral supramarginal gyrus in the PPC increased its activity as the uncontracted word length increased. By contrast, in the hand region of primary somatosensory cortex (S1), activity increased as a function of a low-level somatosensory feature: dot-number per word. The PPC also showed greater response to pseudowords than real words and distinguished between real and pseudowords in multivariate-pattern analysis. Parieto-occipital, early visual and ventral occipito-temporal, as well as prefrontal cortices also showed sensitivity to the real-versus-pseudoword distinction. We conclude that PPC is involved in orthographic processing for braille, that is, braille character and word recognition, possibly because of braille's tactile modality.

Heterochromatin protects retinal pigment epithelium cells from oxidative damage by silencing p53 target genes.

Oxidative stress (OS)-induced retinal pigment epithelium (RPE) cell apoptosis is critically implicated in the pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness in the elderly. Heterochromatin, a compact and transcriptional inert chromatin structure, has been recently shown to be dynamically regulated in response to stress stimuli. The functional mechanism of heterochromatin on OS exposure is unclear, however. Here we show that OS increases heterochromatin formation both in vivo and in vitro, which is essential for protecting RPE cells from oxidative damage. Mechanistically, OS-induced heterochromatin selectively accumulates at p53-regulated proapoptotic target promoters and inhibits their transcription. Furthermore, OS-induced desumoylation of p53 promotes p53-heterochromatin interaction and regulates p53 promoter selection, resulting in the locus-specific recruitment of heterochromatin and transcription repression. Together, our findings demonstrate a protective function of OS-induced heterochromatin formation in which p53 desumoylation-guided promoter selection and subsequent heterochromatin recruitment play a critical role. We propose that targeting heterochromatin provides a plausible therapeutic strategy for the treatment of AMD.

Leveraging shared connectivity to aggregate heterogeneous datasets into a common response space.

Connectivity hyperalignment can be used to estimate a single shared response space across disjoint datasets. We develop a connectivity-based shared response model that factorizes aggregated fMRI datasets into a single reduced-dimension shared connectivity space and subject-specific topographic transformations. These transformations resolve idiosyncratic functional topographies and can be used to project response time series into shared space. We evaluate this algorithm on a large collection of heterogeneous, naturalistic fMRI datasets acquired while subjects listened to spoken stories. Projecting subject data into shared space dramatically improves between-subject story time-segment classification and increases the dimensionality of shared information across subjects. This improvement generalizes to subjects and stories excluded when estimating the shared space. We demonstrate that estimating a simple semantic encoding model in shared space improves between-subject forward encoding and inverted encoding model performance. The shared space estimated across all datasets is distinct from the shared space derived from any particular constituent dataset; the algorithm leverages shared connectivity to yield a consensus shared space conjoining diverse story stimuli.

Identification of avian flapping motion from non-volant winged dinosaurs based on modal effective mass analysis.

The origin of avian flight is one of the most controversial debates in Paleontology. This paper investigates the wing performance of Caudipteryx, the most basal non-volant dinosaur with pennaceous feathered forelimbs by using modal effective mass theory. From a mechanical standpoint, the forced vibrations excited by hindlimb locomotion stimulate the movement of wings, creating a flapping-like motion in response. This shows that the origin of the avian flight stroke should lie in a completely natural process of active locomotion on the ground. In this regard, flapping in the history of evolution of avian flight should have already occurred when the dinosaurs were equipped with pennaceous remiges and rectrices. The forced vibrations provided the initial training for flapping the feathered wings of theropods similar to Caudipteryx.

[Research on THz and Raman Spectra of RNA Nucleobases].

The Infrared and Raman spectra of RNA nucleobases in terahertz (THz) band (1~10 THz) were detected with Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy. The position of all the characteristic peaks and corresponding vibration modes of RNA nucleobase crystals were obtained with Guassian09 software and energy-based fragmentation approach under periodic boundary conditions (PBC-GEBF) method. The computational results were verified to be in accordance with experimental data, which indicated that the powder of RNA nucleobases is amorphous crystal structure. The infrared spectra demonstrated that adenine, guanine and cytosine all have 6 infrared active vibrational modes, while uracil only has 3. Comparing to experimental results, the position and intensity of the absorption peaks were nicely corroborated by the predicted spectrum, except that one weak vibrational frequency at 6.35 THz is missing and two peaks (4.83 and 5.39 THz) merge in the predicted spectrum of guanine; two peaks in 4.3 and 4.79 THz merge into a single one in the calculated spectrum of cytosine; the peaks of thymine in 3.32 and 3.82 THz merged. The computational results of Raman spectra were also verified to be in line with the experimental data. The position and intensity of the characteristics peaks were exactly simulated except that two peaks of guanine in 3.52 and 4.48 THz merged; two peaks in 7.26 and 8.03 THz merge and five peaks (3.57, 4.02, 4.49, 4.89, 5.98 THz) merge in the calculated spectrum of guanine. Through the analysis and identification of the characteristic peaks, it is indicated that the vibration modes of DNA nucleobases in 1~10 THz were derived from collective vibration of molecules in the lattice. The intermolecular hydrogen bond and the weak interaction force contribute greatly to the vibration modes. In addition, as the frequency increases to over 5.5 THz, the vibration modes will change from the atoms collective vibration to some atoms vibration. This research has important theoretical and practical reference value to reveal the effect of RNA nucleobases in the areas of RNA molecular structure constitution, biological macromolecules identification and terahertz spectra formation mechanism and biological inheritance.

Terahertz Spectroscopy of Biotin and Pyridoxine.

Terahertz (THz) absorption spectra of the biotin and pyridoxine were studied using Fourier transform infrared spectroscopy (FTIR) at room temperature. These spectra exhibit enhanced absorption in THz range because of strong intramolecular and intermolecular vibration modes. In the experiment, the samples were mixed with high density polyethylene powder, which was used as spectrophotometric grid. The absorption spectra show worse consistency at higher frequencies for the high ratio of the samples to polyethylene. It indicates that the absorbance of the biotin and pyridoxine increased with frequency. Molecular vibrational spectral calculations based on density functional theory (DFT) show strong correlation with the experiment. We investigated the absorption spectra of isolated molecules (single molecule, two molecules, three molecules) and unit cell of crystal to clarify the mechanism of the spectra change due to intramolecular and intermolecular vibration and rotation.

Contribution of the language network to the comprehension of Python programming code.

Does the perisylvian language network contribute to comprehension of programming languages, like Python? Univariate neuroimaging studies find high responses to code in fronto-parietal executive areas but not in fronto-temporal language areas, suggesting the language network does little. We used multivariate-pattern-analysis to test whether the language network encodes Python functions. Python programmers read functions while undergoing fMRI. A linear SVM decoded for-loops from if-conditionals based on activity in lateral temporal (LT) language cortex. In searchlight analysis, decoding accuracy was higher in LT language cortex than anywhere else. Follow up analysis showed that decoding was not driven by presence of different words across functions, "for" vs "if," but by compositional program properties. Finally, univariate responses to code peaked earlier in LT language-cortex than in the fronto-parietal network. We propose that the language system forms initial "surface meaning" representations of programs, which input to the reasoning network for processing of algorithms.

A comparison of computed tomography imaging with histopathology in the sensitivity and correlation of evaluating coronary arterial calcification.

Background: The sensitivity and correlation of coronary computed tomography angiography (CTA) as compared with histopathology are unknown in evaluating coronary arterial calcification. In this study, we retrospectively evaluated qualitatively and quantitatively the sensitivity and correlation of coronary CTA compared with histopathology in assessing coronary arterial calcification. Methods: This study was conducted on 12 randomly selected cadavers aged over 40 years at the time of death, and 53 segments of coronary arteries from these 12 cadavers were obtained from the Human Anatomy Laboratory of Tianjin Medical University. The artery segments were scanned using contrasted-enhanced dual-source computed tomography (DSCT) with an axial slice thickness of 0.6 mm. Coronary artery calcification in a coronary segment was defined as the presence of 1 or more voxels with a CT density >130 Hounsfield units. According to the arc of calcification in the cross section of the coronary artery wall, calcified plaques were divided into three categories: mild, moderate, and severe calcification. The coronary artery stenosis caused by calcified plaque was observed and calculated with multiplanar reconstruction (MPR), maximum density projection, volume rendering (VR), and cross-sectional reconstruction. After CT enhancement scanning, the coronary artery specimens were cut into 4-mm long segments and embedded in paraffin for pathological staining. Pathological classification and coronary artery stenosis measured with pathological analysis were used as comparison criteria. Results: Histopathology detected 69 Vb-type plaques, while DSCT detected 57 calcified plaques. The sensitivity of CT for detecting mild, moderate, and severe calcified plaques were 88.3% [95% confidence interval (CI): 74.1-95.6%], 100% (95% CI: 69.8-100%), and 100% (95% CI: 73.2-100%), respectively. DSCT had a significant (P<0.001) correlation with histopathology in quantifying coronary artery stenosis caused by mild, moderate, and severe calcified plaques (R2=0.9278, R2=0.9158, R2=0.7923, respectively). Compared with histopathology, DSCT overestimated coronary artery stenosis caused by mild, moderate, and severe calcified plaques (3.2%±2.0%, 4.9%±4.7%, and 14.7%±8.2%, respectively; P<0.05). Conclusions: DSCT contrast enhancement scanning can detect and characterize coronary artery calcification with a good correlation with histopathologic quantification of coronary artery stenosis caused by different types of calcified plaques, even though coronary CTA may overestimate the stenosis.

Altered fear engram encoding underlying conditioned versus unconditioned stimulus-initiated memory updating.

It is known that post-retrieval extinction but not extinction alone could erase fear memory. However, whether the coding pattern of original fear engrams is remodeled or inhibited remains largely unclear. We found increased reactivation of engram cells in the prelimbic cortex and basolateral amygdala during memory updating. Moreover, conditioned stimulus- and unconditioned stimulus-initiated memory updating depends on the engram cell reactivation in the prelimbic cortex and basolateral amygdala, respectively. Last, we found that memory updating causes increased overlapping between fear and extinction cells, and the original fear engram encoding was altered during memory updating. Our data provide the first evidence to show the overlapping ensembles between fear and extinction cells and the functional reorganization of original engrams underlying conditioned stimulus- and unconditioned stimulus-initiated memory updating.

Secular trends and urban-rural disparities in the median age at menarche among Chinese han girls from 1985 to 2019.

BACKGROUND: Menarche is a substantial milestone of female puberty. Timing of age at menarche is considered the key to understanding the potential linkages with women's health outcomes later in life. This study aimed to explore the secular trends and urban‒rural disparities in the median age at menarche among Chinese Han girls from 1985 to 2019. METHODS: Data were extracted from the 1985, 1995, 2005, 2014, and 2019 Chinese National Surveys on Students' Constitution and Health, which were nationally representative cross-sectional studies, and a total of 173,535 Han girls aged 9-18 years were examined. Girls were asked whether menarche had occurred. The median age at menarche was estimated by probit analysis. Z tests were used to compare the differences between survey years and between urban and rural areas. RESULTS: The median age at menarche among Chinese Han girls decreased from 13.37 years in 1985 to 12.00 years in 2019, and the overall decrease was more significant in rural areas (1.77 years) than in urban areas (0.99 years). The average five-year change in the decrease in the median age at menarche showed an accelerating and then slowing pace; and it was observed similarly in both urban and rural areas. The urban‒rural disparities shrank from 0.64 years in 1985 to 0.44 years in 1995, then to 0.27 years in 2005, 0.24 years in 2014, and finally to - 0.14 years in 2019. CONCLUSIONS: The median age at menarche among Chinese Han girls continued to decline from 1985 to 2019 but at a slowing pace in the last five years. Urban‒rural disparities gradually narrowed. Sexual and reproductive health education and interventions to prevent the decline in the age of menarche are needed, especially in rural areas.

Evaluation of the potential of ultrasound-mediated drug delivery for the treatment of ovarian cancer through preclinical studies.

Ovarian cancer (OC) has the greatest mortality rate among gynecological cancers, with a five-year survival rate of <50%. Contemporary adjuvant chemotherapy mostly fails in the case of OCs that are refractory, metastatic, recurrent, and drug-resistant. Emerging ultrasound (US)-mediated technologies show remarkable promise in overcoming these challenges. Absorption of US waves by the tissue results in the generation of heat due to its thermal effect causing increased diffusion of drugs from the carriers and triggering sonoporation by increasing the permeability of the cancer cells. Certain frequencies of US waves could also produce a cavitation effect on drug-filled microbubbles (MBs, phospholipid bilayers) thereby generating shear force and acoustic streaming that could assist drug release from the MBs, and promote the permeability of the cell membrane. A new class of nanoparticles that carry therapeutic agents and are guided by US contrast agents for precision delivery to the site of the ovarian tumor has been developed. Phase-shifting of nanoparticles by US sonication has also been engineered to enhance the drug delivery to the ovarian tumor site. These technologies have been used for targeting the ovarian cancer stem cells and protein moieties that are particularly elevated in OCs including luteinizing hormone-releasing hormone, folic acid receptor, and vascular endothelial growth factor. When compared to healthy ovarian tissue, the homeostatic parameters at the tissue microenvironment including pH, oxygen levels, and glucose metabolism differ significantly in ovarian tumors. US-based technologies have been developed to take advantage of these tumor-specific alterations for precision drug delivery. Preclinical efficacy of US-based targeting of currently used clinical chemotherapies presented in this review has the potential for rapid human translation, especially for formulations that use all substances that are deemed to be generally safe by the U.S. Food and Drug Administration.

MYPT1/PP1-Mediated EZH2 Dephosphorylation at S21 Promotes Epithelial-Mesenchymal Transition in Fibrosis through Control of Multiple Families of Genes.

The methyltransferase EZH2 plays an important role in regulating chromatin conformation and gene transcription. Phosphorylation of EZH2 at S21 by AKT kinase suppresses its function. However, protein phosphatases responsible for the dephosphorylation of EZH2-S21 remain elusive. Here, it is demonstrated that EZH2 is highly expressed in the ocular lens, and AKT-EZH2 axis is important in TGFß-induced epithelial-mesenchymal transition (EMT). More importantly, it is identified that MYPT1/PP1 dephosphorylates EZH2-S21 and thus modulates its functions. MYPT1 knockout accelerates EMT, but expression of the EZH2-S21A mutant suppresses EMT through control of multiple families of genes. Furthermore, the phosphorylation status and gene expression modulation of EZH2 are implicated in control of anterior subcapsular cataracts (ASC) in human and mouse eyes. Together, the results identify the specific phosphatase for EZH2-S21 and reveal EZH2 dephosphorylation control of several families of genes implicated in lens EMT and ASC pathogenesis. These results provide important novel information in EZH2 function and regulation.

A case of gynandromorphy in Ducetia japonica (Thunberg, 1815) (Orthoptera: Tettigoniidae: Phaneropterinae).

In this paper, we described an example of gynandromorphy in a katydid, Ducetia japonica. Its color is brown, while normal individuals are green. Its left maxilla is smaller, and left maxillary palpus is shorter. Left forewing as male is shorter than right one as female. Hindwing is also shorter in left. Cercus, epiproct and subgenital plate are left in male and right in female.

PVT1 Knockdown Inhibits Autophagy and Improves Gemcitabine Sensitivity by Regulating the MiR-143/HIF-1α/VMP1 Axis in Pancreatic Cancer.

OBJECTIVES: Elucidation of the regulatory mechanisms of gemcitabine sensitivity is needed to improve the therapeutic effects of this drug in pancreatic cancer. METHODS: PANC-1 cells were transfected with small hairpin RNA against PVT1 or microRNA (miR)-143 mimics or inhibitor. The gemcitabine sensitivity of pancreatic cancer was evaluated. Autophagosomes were analyzed with an immunofluorescence assay. Cell viability and proliferation were examined with MTT assays. Quantitative reverse transcription-polymerase chain reaction and Western blotting were used to analyze the expression of PVT1, miR-143, HIF-1α, VMP1, LC3I/II, p62, and Beclin-1. The interactions of PVT1/miR-143 and miR-143/HIF-1α were assessed by dual-luciferase reporter assays. RESULTS: PVT1 was upregulated while miR-143 was downregulated in pancreatic cancer. Both PVT1 knockdown and miR-143 overexpression suppressed autophagy and improved gemcitabine sensitivity in pancreatic cancer. PVT1 directly sponged miR-143 to regulate HIF-1α expression. MiR-143 inhibitor reversed the effect of PVT1 knockdown on autophagy and gemcitabine sensitivity. CONCLUSIONS: PVT1 knockdown inhibited autophagy and improved gemcitabine sensitivity via the miR-143/HIF-1α/VMP1 axis in pancreatic cancer. Our investigation elucidated a novel regulatory mechanism of gemcitabine sensitivity and may contribute to improve the therapeutic effects of chemotherapy drugs on pancreatic cancer.

Neural alignment predicts learning outcomes in students taking an introduction to computer science course.

Despite major advances in measuring human brain activity during and after educational experiences, it is unclear how learners internalize new content, especially in real-life and online settings. In this work, we introduce a neural approach to predicting and assessing learning outcomes in a real-life setting. Our approach hinges on the idea that successful learning involves forming the right set of neural representations, which are captured in canonical activity patterns shared across individuals. Specifically, we hypothesized that learning is mirrored in neural alignment: the degree to which an individual learner's neural representations match those of experts, as well as those of other learners. We tested this hypothesis in a longitudinal functional MRI study that regularly scanned college students enrolled in an introduction to computer science course. We additionally scanned graduate student experts in computer science. We show that alignment among students successfully predicts overall performance in a final exam. Furthermore, within individual students, we find better learning outcomes for concepts that evoke better alignment with experts and with other students, revealing neural patterns associated with specific learned concepts in individuals.

The "Narratives" fMRI dataset for evaluating models of naturalistic language comprehension.

The "Narratives" collection aggregates a variety of functional MRI datasets collected while human subjects listened to naturalistic spoken stories. The current release includes 345 subjects, 891 functional scans, and 27 diverse stories of varying duration totaling ~4.6 hours of unique stimuli (~43,000 words). This data collection is well-suited for naturalistic neuroimaging analysis, and is intended to serve as a benchmark for models of language and narrative comprehension. We provide standardized MRI data accompanied by rich metadata, preprocessed versions of the data ready for immediate use, and the spoken story stimuli with time-stamped phoneme- and word-level transcripts. All code and data are publicly available with full provenance in keeping with current best practices in transparent and reproducible neuroimaging.

Computer code comprehension shares neural resources with formal logical inference in the fronto-parietal network.

Despite the importance of programming to modern society, the cognitive and neural bases of code comprehension are largely unknown. Programming languages might 'recycle' neurocognitive mechanisms originally developed for natural languages. Alternatively, comprehension of code could depend on fronto-parietal networks shared with other culturally-invented symbol systems, such as formal logic and symbolic math such as algebra. Expert programmers (average 11 years of programming experience) performed code comprehension and memory control tasks while undergoing fMRI. The same participants also performed formal logic, symbolic math, executive control, and language localizer tasks. A left-lateralized fronto-parietal network was recruited for code comprehension. Patterns of activity within this network distinguish between 'for' loops and 'if' conditional code functions. In terms of the underlying neural basis, code comprehension overlapped extensively with formal logic and to a lesser degree math. Overlap with executive processes and language was low, but laterality of language and code covaried across individuals. Cultural symbol systems, including code, depend on a distinctive fronto-parietal cortical network.

A new species of Goniurosaurus from Hainan Island, China based on molecular and morphological data (Squamata: Sauria: Eublepharidae).

Three species of geckos in the genus Goniurosaurus have been recorded from Hainan Island in China. We describe a new species, Goniurosaurus kwanghua sp. nov. Zhu He, bringing the number of this genus in Hainan Island to four. We conducted phylogenetic analyses with two mitochondrial genes (16S Cytb) and two nuclear genes (RAG1 C-MOS) to validate this new species. The new species is similar to G. hainanensis, but differs in the following characters: (1) middle section of the nuchal loop wide and posteriorly protracted, (2) wider body bands with dark markings, (3) yellow stripes on posterior side of humerus and femur, linked to the first and third body bands, respectively. The type specimens are deposited in the Museum of Biology, East China Normal University (ECNU).

Thermo-Electro-Mechanical Vibrations of Porous Functionally Graded Piezoelectric Nanoshells.

In this work, we aim to study free vibration of functionally graded piezoelectric material (FGPM) cylindrical nanoshells with nano-voids. The present model incorporates the small scale effect and thermo-electro-mechanical loading. Two types of porosity distribution, namely, even and uneven distributions, are considered. Based on Love's shell theory and the nonlocal elasticity theory, governing equations and corresponding boundary conditions are established through Hamilton's principle. Then, natural frequencies of FGPM nanoshells with nano-voids under different boundary conditions are analyzed by employing the Navier method and the Galerkin method. The present results are verified by the comparison with the published ones. Finally, an extensive parametric study is conducted to examine the effects of the external electric potential, the nonlocal parameter, the volume fraction of nano-voids, the temperature rise on the vibration of porous FGPM cylindrical nanoshells.