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Biology subjects

Li, H.-J.

Publications and source records attributed to Li, H.-J..

8 recordsLinked to original sources

The Unity/Diversity Framework of Executive Functions in Older Adults

Executive functions (EFs), encompassing inhibition, shifting, and updating as three fundamental subdomains, are typically characterized by a unity/diversity construct. However, given the dedifferentiation trend observed in aging, it remains controversial whether the construct of EFs in older adults becomes unidimensional or maintains unity/diversity. This study aims to explore and validate the construct of EFs in older adults. At the behavioral level, we conducted confirmatory factor analysis on data from 222 older adults who completed six tasks specifically targeting inhibition, shifting, and updating. One unidimensional model and six unity/diversity models of EFs were evaluated. Our results indicated that the EFs of older adults demonstrated greater congruence with the unity/diversity construct. At neural level, thirty older adults completed three thematically consistent fMRI tasks, targeting three subdomains of EFs respectively. Multivariate pattern analysis showed that rostromedia prefrontal cortex robustly showed similar neural representation across different tasks (unity). Meanwhile, the three EF domains were encoded by distinct global neural representation and the lateral prefrontal cortex play a crucial role in classification (diversity). These findings underscore the unity/diversity framework of EFs in older adults and offer important insights for designing interventions aimed at improving EFs in this population.

neuroscience↗

Calneuron 1 reveals the pivotal roles in schizophrenia via perturbing human forebrain development and causing hallucination-like behavior in mice

Schizophrenia is a highly heritable neurodevelopmental disorder with unknown genetic pathogenic mechanisms. Here, we selected 11 schizophrenia risk genes and generated single-gene-knockout-precise-dorsal/ventral-forebrain-organoids (SKOPOS) via CRISPR-Cas9 system. 90 bulk and 249,430 single-cell RNA-sequencing of SKOPOS revealed that knockout of 11 risk genes lead to different levels of deficits in dorsal/ventral forebrain organoids. Among them, calneuron 1 (CALN1) acts as a pivotal pathogenic gene of schizophrenia via severe disruption of gene expression network, interaction with about 32% (34/106) known schizophrenia risk genes, delayed maturation and impaired spontaneous neural circuit in human developing forebrain. Furtherly, including the spontaneous abrupt burst spiking in cortical neurons and the defects of spatial memory, cognition and social ability, Caln1 KO mice surprisingly displayed spontaneous startle behavior and head-twitch response correlated with hallucination-like behavior, which could be inhibited by antipsychotic drug SEP-363856. In summary, CALN1 is identified as a pivotal pathogenic gene of schizophrenia in forebrain development.

neuroscience↗

Reconstructing fresh green leaf spectra in the SWIR-2 region (2001-2500 nm) collected in a humid environment by referring to publicly available green leaf spectral databases

Leaf spectra (reflectance and transmittance) are key parameters for land surface physical and biogeochemical modeling and are commonly measured using a portable spectroradiometer and an integrating sphere or contact probe with an artificial light source. However, spectral data may be obscured mainly because of water vapor and low signal-to-noise ratios, especially in the shortwave infrared-2 region (SWIR-2, 2001-2500 nm). This erroneous pattern is particularly pronounced in humid conditions, such as in many tropical and subtropical regions, making data unusable in SWIR-2. In this study, we proposed a statistical/mathematical spectral reconstruction approach to retrieve noise-free SWIR-2 fresh green leaf spectra by referring to the available previously published quality-controlled fresh green leaf reflectance and transmittance reference databases. We processed 896 pairs of fresh tea (Camellia sinensis var. sinensis) leaf reflectance and transmittance data from Alishan in central Taiwan. The spectral data were acquired by a field spectroradiometer with an integrating sphere. We selected a subset (500-1900 nm) of the spectra in the visible, near-infrared, and SWIR-1 regions (VNS-1) that was relatively insensitive to atmospheric conditions. Then, we applied a Gaussian fitting function to smooth the spectral profile. We matched those spectra with publicly available, quality-controlled, and Gaussian fitting function smoothed reference green leaf spectral databases obtained from Italy (LOPEX), Panama (SLZ), and Puerto Rico (G-LiHT) (1694 reflectance and 997 transmittance samples) and selected the one that was most similar (yielding the highest correlation coefficient) to each smoothed Alishan VNS-1 spectrum. We then used multivariable linear regression, linear parameter multiplication, and spectral reversion to reconstruct SWIR-2 spectra based on VNS-1 spectra. To assess the validity of the proposed SWIR-2 reconstruction method, we acquired an independent set of green leaf spectral databases from France (Angers) with SWIR-2 of 2001- 2450 nm. We found that the performance of the SWIR-2 reconstruction approach was satisfactory, with mean ({+/-} standard deviation) root-mean-square errors (RMSEs) of 0.0041 {+/-} 0.0019 (reflectance, 3.0% of the mean SWIR-2 of the test data) and 0.0054 {+/-} 0.0027 (transmittance, 2.5%) for each spectrum and RMSEs of 0.0058 {+/-} 0.0027 (reflectance, 4.2%) and 0.0055 {+/-} 0.0043 (transmittance, 2.5%) for each SWIR-2 band. The proposed approach successfully modeled SWIR-2 of the test spectra, which could be further improved with the availability of a more comprehensive set of green leaf reference spectral databases.

biochemistry↗

A longitudinal resource for population neuroscience of school-age children and adolescents in China

During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), a ten-year pilot stage of the lifespan CCNP (2013-2032), is an ongoing project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community (https://www.scidb.cn/en/c/ccnp) at the Science Data Bank. Design TypesO_LIAccelerated longitudinal design C_LIO_LIBrain-mind development C_LIO_LIPopulation imaging C_LIO_LIBrain chart C_LIO_LIRepeated measure C_LI MeasurementsO_LIPsychological behaviours C_LIO_LIBiophysical and physical measures C_LIO_LIIntelligence quotient measure C_LIO_LINeuroimaging C_LI Sample Characteristic - OrganismO_LIHomo sapiens C_LI Sample Characteristic - EnvironmentO_LISchool- and community-based sample C_LI Sample Characteristic - LocationO_LIChongqing and Beijing, China C_LI DurationO_LI10 years (2013-2022) C_LI

neuroscience↗

Identification of a female determinant gene for the sexual determination of a hemipteran insect, the brown planthopper

The sex determination mechanism for hemipteran species remains poorly understood. During the sex determination of the brown planthopper (BPH), Nilaparvata lugens, one species of Hemiptera, the functions of doublesex (Nldsx) and NlTra-2 (NlTra-2) genes were identified in our previous studies. Here, we identify an upstream gene for Nldsx in the sex determination cascade, NlFmd, which acts as female determinant gene for N. lugens. The sex-specific transcript of NlFmd (NlFmd-F) encodes an arginine/serine-, and proline-rich protein that is essential for female development. The knockdown of NlFmd resulted in the development of pseudomales, with sex-specific alternative Nldsx processing, and maternal RNA interference (RNAi) against NlFmd generates male-only progeny. Moreover, homologous genes for NlFmd have also been identified in two rice planthopper species, the white-backed planthopper (WBPH, Sogotalla furcifera) and the small brown planthopper (SBPH, Laodelphax striatellus), and these genes appear to be involved in the sex determination cascades for these species. Our data suggest that the sex determination cascade in Delphacidae is conserved.

molecular biology↗

Long-Term Outcomes of Pediatric Graves Disease Patients Treated with Anti-Thyroid Drugs: Experience from a Taiwan Medical Center

Graves disease (GD) is the most common cause of thyrotoxicosis in children and adolescents, accounting for 15% of all thyroid diseases during childhood. Anti-thyroid drugs (ATD) are recommended as the first-line treatment in children and adolescents. However, the remission rate is lower in children than in adults, and the optimal treatment duration and favorite factors associated with remission remain unknown. We aimed to investigate long-term outcomes of pediatric GD patients receiving ATD. We retrospectively reviewed medical charts of 300 pediatric GD subjects, who were initially treated with ATD and followed up for more than one year, from 1985 to 2017 at MacKay Childrens Hospital. The 300 patients comprised 257 (85.7%) females and 43 (14.3%) males, median age at diagnosis was 11.6 (range 2.7-17.8) years, and median follow-up period was 4.7 (range 1.1-23.9) years. Overall, 122 patients achieved the criteria for discontinuing ATD treatment, seventy-nine (39.9%) patients achieved remission, with a median follow-up period of 5.3 (range 1.5-20.1) years. Patients in the remission group were more likely to be aged < 5 years (remission vs. relapse vs. ongoing ATD; 11.4 vs. 0 vs. 2.6%, P=0.02), less likely to have a family history of thyroid disease (24.1 vs. 42.1 vs. 52.6 %, P=0.001), and had lower TRAb levels (42.8 vs. 53.6 vs. 65.1 %, P=0.02).\n\nConclusionLong-term ATD remains an effective treatment option for GD in children and adolescents. Pediatric GD patients aged < 5 years, having no family history of thyroid disease and having lower TRAb levels were more likely to achieve remission.

physiology↗

Anti-HIV activity prediction and enrichment identify novel human targets for Anti-HIV therapy

Human immunodeficiency virus (HIV) relies heavily on the host proteins to facilitate its entry and replication. Currently, more than 4000 human proteins are recorded to be involved in the HIV-1 life cycle. Identifying appropriate anti-HIV targets from so many host proteins is crucial to anti-HIV drug development, but a challenging work. Here we combined anti-HIV activity prediction and enrichment analysis to identify novel human targets for anti-HIV therapy. We firstly developed an accurate prediction tool named Anti-HIV-Predictor (AUC>0.96) to predict the anti-HIV activity of given compounds. Using this tool, we predicted 10488 anti-HIV compounds from ChEMBLdb. Then, based on this result and relationships of targets and compounds, we inferred 73 anti-HIV targets that enriched with anti-HIV compounds. The functional annotation and network analysis revealed that they directly or indirectly interact with 20 HIV proteins through neuropeptide signaling, GPCR signaling, cell surface signaling pathway, and so on. Nearly half of these targets overlap with the NCBI HIV dataset. However, the percentage of known therapeutic targets in these targets is significantly higher than that in the NCBI HIV dataset. After a series of feature analysis, we identified 13 novel human targets with high potential as anti-HIV targets, the inhibitors of which have experimentally confirmed anti-HIV activity. It is noteworthy that the inhibitors of REN and CALCA have better anti-HIV activity than CCR5 inhibitors. Taken together, our findings provide novel human targets for the host-oriented anti-HIV drug development and should significantly advance current anti-HIV research.

bioinformatics↗

Efficient repositioning of approved drugs as anti-HIV agents using Anti-HIV-Predictor

Development of new, effective and affordable drugs against HIV is urgently needed. In this study, we developed a worlds first web server called Anti-HIV-Predictor (http://bsb.kiz.ac.cn:70/hivpre) for predicting anti-HIV activity of given compounds. This server is rapid and accurate (accuracy >93% and AUC > 0.958). We applied the server to screen 1835 approved drugs for anti-HIV therapy. Totally 67 drugs were predicted to have anti-HIV activity, 25 of which are anti-HIV drugs. Then we experimentally evaluated 35 predicted new anti-HIV compounds by assays of syncytia formation, p24 quantification, cytotoxicity. Finally, we repurposed 7 approved drugs (cetrorelix, dalbavancin, daunorubicin, doxorubicin, epirubicin, idarubicin and valrubicin) as new anti-HIV agents. The original indication of these drugs is involved in a variety of diseases such as female infertility and cancer. Anti-HIV-Predictor and the 7 repurposed anti-HIV agents provided here demonstrate the efficacy of this strategy for discovery of new anti-HIV agents.

bioinformatics↗