Artificial Intelligence-Assisted Optimization of Antipigmentation Tyrosinase Inhibitors: De Novo Molecular Generation Based on a Low Activity Lead Compound.

Artificial intelligence (AI) de novo molecular generation is a highly promising strategy in the drug discovery, with deep reinforcement learning (RL) models emerging as powerful tools. This study introduces a fragment-by-fragment growth RL forward molecular generation and optimization strategy based on a low activity lead compound. This process integrates fragment growth-based reaction templates, while target docking and drug-likeness prediction were simultaneously performed. This comprehensive approach considers molecular similarity, internal diversity, synthesizability, and effectiveness, thereby enhancing the quality and efficiency of molecular generation. Finally, a series of tyrosinase inhibitors were generated and synthesized. Most compounds exhibited more improved activity than lead, with an optimal candidate compound surpassing the effects of kojic acid and demonstrating significant antipigmentation activity in a zebrafish model. Furthermore, metabolic stability studies indicated susceptibility to hepatic metabolism. The proposed AI structural optimization strategies will play a promising role in accelerating the drug discovery and improving traditional efficiency.

Molecular regulatory mechanisms of staminate strobilus development and dehiscence in Torreya grandis.

Gymnosperms are mostly dioecious, and their staminate strobili undergo a longer developmental period than those of angiosperms. However, the underlying molecular mechanisms remain unclear. This study aimed to identify key genes and pathways involved in staminate strobilus development and dehiscence in Torreya grandis. Through weighted gene co-expression network analysis (WGCNA), we identified fast elongation-related genes enriched in carbon metabolism and auxin signal transduction, whereas dehiscence-related genes were abundant in alpha-linolenic acid metabolism and the phenylpropanoid pathway. Based on WGCNA, we also identified PHYTOCHROME-INTERACTING FACTOR4 (TgPIF4) as a potential regulator for fast elongation of staminate strobilus and 2 WRKY proteins (TgWRKY3 and TgWRKY31) as potential regulators for staminate strobilus dehiscence. Multiple protein-DNA interaction analyses showed that TgPIF4 directly activates the expression of TRANSPORT INHIBITOR RESPONSE2 (TgTIR2) and NADP-MALIC ENZYME (TgNADP-ME). Overexpression of TgPIF4 significantly promoted staminate strobilus elongation by elevating auxin signal transduction and pyruvate content. TgWRKY3 and TgWRKY31 bind to the promoters of the lignin biosynthesis gene PHENYLALANINE AMMONIA-LYASE (TgPAL) and jasmonic acid metabolism gene JASMONATE O-METHYLTRANSFERASE (TgJMT), respectively, and directly activate their transcription. Overexpression of TgWRKY3 and TgWRKY31 in the staminate strobilus led to early dehiscence, accompanied by increased lignin and methyl jasmonate levels, respectively. Collectively, our findings offer a perspective for understanding the growth of staminate strobili in gymnosperms.

Steep-slope vertical-transport transistors built from sub-5 nm Thin van der Waals heterostructures.

Two-dimensional (2D) semiconductor-based vertical-transport field-effect transistors (VTFETs) - in which the current flows perpendicularly to the substrate surface direction - are in the drive to surmount the stringent downscaling constraints faced by the conventional planar FETs. However, low-power device operation with a sub-60 mV/dec subthreshold swing (SS) at room temperature along with an ultra-scaled channel length remains challenging for 2D semiconductor-based VTFETs. Here, we report steep-slope VTFETs that combine a gate-controllable van der Waals heterojunction and a metal-filamentary threshold switch (TS), featuring a vertical transport channel thinner than 5 nm and sub-thermionic turn-on characteristics. The integrated TS-VTFETs were realised with efficient current switching behaviours, exhibiting a current modulation ratio exceeding 1 × 108 and an average sub-60 mV/dec SS over 6 decades of drain current. The proposed TS-VTFETs with excellent area- and energy-efficiency could help to tackle the performance degradation-device downscaling dilemma faced by logic transistor technologies.

Autoimmune encephalitis related to LGI1 antibodies with negative MRI study: Description of two cases / Encefalitis autoinmune relacionada con anticuerpos LGI1 con estudio de RM negativo: descripción de dos casos

Background Leucine-rich glioma inactivated 1 (LGI1) antibody-related autoimmune encephalitis is easily misdiagnosed clinically because of its complex and diverse clinical manifestations. We present two cases of LGI1 antibody-related encephalitis with negative imaging findings and perform a literature review on this disease entity. Case description The first case was that of a 60-year-old man who presented with involuntary movement of the paroxysmal right limb. The second case was that of a 66-year-old man who presented with hearing hallucinations, involuntary shaking of the right limb, and progressive cognitive impairment. Both patients in this study showed negative magnetic resonance imaging (MRI) results. Routine cerebrospinal fluid (CSF) and biochemical examinations showed no significant abnormalities, and positive LGI1 antibodies were detected in both the CSF and serum. Conclusion Based on our experience and the literature review, we recommend that LGI1 antibody-related encephalitis should be considered when faciobrachial dystonic seizures, acute and subacute-onset seizures, low serum sodium (possibly with low CSF chloride), and cognitive-psychiatric disorders are encountered, even in the absence of specific radiographic and altered CSF findings (AU)

Antecedentes La encefalitis autoinmunitaria relacionada con anticuerpos LGI1 puede ser fácilmente mal diagnosticada clínicamente debido a sus manifestaciones clínicas complejas y diversas. Presentamos dos casos de encefalitis relacionada con anticuerpos LGI1 con hallazgos de imágenes negativas y realizamos una revisión de la literatura sobre esta entidad patológica. Descripción de casos El primer caso fue el de un hombre de 60años que presentó movimientos involuntarios del miembro derecho paroxístico. El segundo caso fue el de un hombre de 66años que presentó alucinaciones auditivas, temblores involuntarios del miembro derecho y un deterioro cognitivo progresivo. Ambos pacientes en este estudio mostraron resultados negativos de imágenes por resonancia magnética (RM). Los exámenes rutinarios de líquido cefalorraquídeo (LCR) y bioquímicos no mostraron anomalías significativas, pero se detectaron anticuerpos LGI1 positivos en ambos: LCR y suero. Conclusión Basándonos en nuestra experiencia y en la revisión de la literatura, recomendamos considerar la posibilidad de encefalitis relacionada con anticuerpos LGI1 cuando aparezcan crisis distónicas faciobraquiales, convulsiones de inicio agudo o subagudo, hiponatremia (posiblemente con hipoclorhidria del LCR) y trastornos cognitivo-psiquiátricos, incluso en ausencia de hallazgos radiográficos específicos o modificaciones en el LCR (AU)

Hyper-production of porcine contagious pleuropneumonia subunit vaccine proteins in Escherichia coli by developing a bicistronic T7 expression system.

The ApxII toxin and the outer membrane lipoprotein (Oml) of Actinobacillus pleuropneumoniae are important vaccine antigens against porcine contagious pleuropneumonia (PCP), a prevalent infectious disease affecting the swine industry worldwide. Previous studies have reported the recombinant expression of ApxII and Oml in Escherichia coli; however, their yields were not satisfactory. Here, we aimed to enhance the production of ApxII and Oml by constructing a bicistronic expression system based on the widely used T7 promoter. To create efficient T7 bicistronic expression cassettes, 16 different fore-cistron sequences were introduced downstream of the T7 promoter. The expression of three vaccine antigens Oml1, Oml7, and ApxII in the four strongest bicistronic vectors were enhanced compared to the monocistronic control. Further optimization of the fermentation conditions in micro-well plates (MWP) led to improved production. Finally, the production yields reached unprecedented levels of 2.43 g L-1 of Oml1, 2.59 g L-1 of Oml7, and 1.21 g L-1 of ApxII, in a 5 L bioreactor. These three antigens also demonstrated well-protective immunity against A. pleuropneumoniae infection. In conclusion, this study establishes an efficient bicistronic T7 expression system that can be used to express recombinant proteins in E. coli and achieves the hyper-production of PCP vaccine proteins.

Discovery of matrix metalloproteinase inhibitors as anti-skin photoaging agents.

Photodamage is the result of prolonged exposure of the skin to sunlight. This exposure causes an overexpression of matrix metalloproteinases (MMPs), leading to the abnormal degradation of collagen in the skin tissue and resulting in skin aging and damage. This review presents a detailed overview of MMPs as a potential target for addressing skin aging. Specifically, we elucidated the precise mechanisms by which MMP inhibitors exert their anti-photoaging effects. Furthermore, we comprehensively analyzed the current research progress on MMP inhibitors that demonstrate significant inhibitory activity against MMPs and anti-skin photoaging effects. The review also provides insights into the structure-activity relationships of these inhibitors. Our objective in conducting this review is to provide valuable practical information to researchers engaged in investigations on anti-skin photoaging.

OCT1 regulates the migration of colorectal cancer cells by acting on LDHA.

Colorectal cancer is one of the most common cancers with high morbidity and mortality. Effective treatments to improve the prognosis are still lacking. The results of online analysis tools showed that OCT1 and LDHA were highly expressed in colorectal cancer, and the high expression of OCT1 was associated with poor prognosis. Immunofluorescence demonstrated that OCT1 and LDHA co-localized in colorectal cancer cells. In colorectal cancer cells, OCT1 and LDHA were upregulated by OCT1 overexpression, but downregulated by OCT1 knockdown. OCT1 overexpression promoted cell migration. OCT1 or LDHA knockdown inhibited the migration, and the downregulation of LDHA restored the promoting effect of OCT1 overexpression. OCT1 upregulation increased the levels of HK2, GLUT1 and LDHA proteins in colorectal cancer cells. Consequently, OCT1 promoted the migration of colorectal cancer cells by upregulating LDHA.

Autoimmune encephalitis related to LGI1 antibodies with negative MRI study: Description of two cases.

BACKGROUND: Leucine-rich glioma inactivated 1 (LGI1) antibody-related autoimmune encephalitis is easily misdiagnosed clinically because of its complex and diverse clinical manifestations. We present two cases of LGI1 antibody-related encephalitis with negative imaging findings and perform a literature review on this disease entity. CASE DESCRIPTION: The first case was that of a 60-year-old man who presented with involuntary movement of the paroxysmal right limb. The second case was that of a 66-year-old man who presented with hearing hallucinations, involuntary shaking of the right limb, and progressive cognitive impairment. Both patients in this study showed negative magnetic resonance imaging (MRI) results. Routine cerebrospinal fluid (CSF) and biochemical examinations showed no significant abnormalities, and positive LGI1 antibodies were detected in both the CSF and serum. CONCLUSION: Based on our experience and the literature review, we recommend that LGI1 antibody-related encephalitis should be considered when faciobrachial dystonic seizures, acute and subacute-onset seizures, low serum sodium (possibly with low CSF chloride), and cognitive-psychiatric disorders are encountered, even in the absence of specific radiographic and altered CSF findings.

Dexmedetomidine mitigates neuroinflammation in an Alzheimer's disease mouse model via the miR-204-3p/FBXL7 signaling axis.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by neuroinflammation. Dexmedetomidine (Dex) is known for its neuroprotective properties in clinical settings. In this study, we investigated the potential of Dex in protecting against neuroinflammation in an AD mouse model induced by amyloid-beta (Aß) injection. First, in the AD mouse model, Aß injection were administered, and the model was confirmed through behavioral tests, including the Morris water maze and Y-maze. Neuroinflammatory states in Aß-injected mice were assessed using hematoxylin and eosin staining and enzyme-linked immunosorbent assay. Expression levels of microRNA (miR)-204-3p and F-box/LRR-repeat protein 7 (FBXL7) in mouse tissues were determined through real-time quantitative polymerase chain reaction and Western blot. The binding interaction between miR-204-3p and FBXL7 was elucidated using dual-luciferase analysis. Aß-injected mice exhibited cognitive impairment, neuroinflammation, and downregulated miR-204-3p. Upregulation of miR-204-3p reduced inflammatory infiltration and mitigated neuroinflammation in Aß-injected mice. Dex treatment reduced inflammation in hippocampal tissues of Aß-injected mice. Dex treatment upregulated miR-204-3p, leading to suppressed FBXL7 expression in tissues. Inhibition of miR-204-3p or overexpression of FBXL7 reversed the alleviating effect of Dex on neuroinflammation in Aß-injected mice. Overall, Dex increased miR-204-3p expression, resulting in the inhibition of FBXL7, and subsequently alleviated neuroinflammation in Aß-injected mice.

Functional Study of cAMP-Dependent Protein Kinase A in Penicillium oxalicum.

Signaling pathways play a crucial role in regulating cellulase production. The pathway mediated by signaling proteins plays a crucial role in understanding how cellulase expression is regulated. In this study, using affinity purification of ClrB, we have identified sixteen proteins that potentially interact with ClrB. One of the proteins, the catalytic subunit of cAMP-dependent protein kinase A (PoPKA-C), is an important component of the cAMP/PKA signaling pathway. Knocking out PoPKA-C resulted in significant decreases in the growth, glucose utilization, and cellulose hydrolysis ability of the mutant strain. Furthermore, the cellulase activity and gene transcription levels were significantly reduced in the ΔPoPKA-C mutant, while the expression activity of CreA, a transcriptional regulator of carbon metabolism repression, was notably increased. Additionally, deletion of PoPKA-C also led to earlier timing of conidia production. The expression levels of key transcription factor genes stuA and brlA, which are involved in the production of the conidia, showed significant enhancement in the ΔPoPKA-C mutant. These findings highlight the involvement of PoPKA-C in mycelial development, conidiation, and the regulation of cellulase expression. The functional analysis of PoPKA-C provides insights into the mechanism of the cAMP/PKA signaling pathway in cellulase expression in filamentous fungi and has significant implications for the development of high-yielding cellulase strains.

SNHG3/WISP2 Axis Promotes Hela Cell Migration and Invasion via Activating Wnt/ß-Catenin Signaling.

BACKGROUND/AIM: Cervical cancer (CC) poses a significant threat to women's health and has a relatively poor prognosis due to local invasion and metastasis. It is, therefore, crucial to elucidate the molecular mechanisms of CC metastasis. SNHG3 has been implicated in various tumor metastasis processes, but its involvement in CC has not been thoroughly studied. Our study aimed to investigate the role of SNHG3 in metastasis and elucidate its underlying mechanisms in CC. MATERIALS AND METHODS: LncRNA SNHG3 expression in CC tissues was analyzed using TCGA and GSE27469 databases. Normal cervical epithelial cells and CC cell lines were used to detect mRNA expression of SNHG3 via quantitative reverse transcription polymerase chain reaction (qRT-PCR). With RNA interference (RNAi) technology, antisense oligonucleotides (ASO) can act on HeLa cells to knockdown target gene expression. The influence of SNHG3 on cell migration and invasion were determined by wound healing and transwell assays. Transcriptome sequencing (RNA-seq) was used to seek abnormally expressed genes between SNHG3 knockdown cells and control cells. The expressions of epithelial-mesenchymal transition (EMT) and Wnt/ß-catenin signaling related proteins were detected using western blot. RESULTS: SNHG3 was obviously up-regulated in CC tissues and cell lines, and ectopic expression of SNHG3 was associated with lymph node metastasis of CC. Knockdown of SNHG3 significantly inhibited cell migration and invasion in CC. Further molecular mechanism studies showed that SNHG3 knockdown could down-regulate the expression of WNT1 Inducible Signaling Pathway Protein 2 (WISP2) so as to inhibit the activation of the Wnt/ß-catenin signaling pathway, and regulated the expression of EMT-related markers, that promoted the protein expression of E-cadherin, as well as decreased the expression of N-cadherin and vimentin. CONCLUSION: SNHG3 appears to exert a pro-metastatic effect in CC, as evidenced by inhibition of cell migration and invasion upon SNHG3 knockdown. EMT also appears to be attenuated. Of interest is the down-regulation of WISP2 following SNHG3 knockdown leads to the inactivation of the Wnt/ß-catenin signaling pathway.

Enantioselective Synthesis of 2,3,3a,8a-Tetrahydrofuro[2,3-b]benzofuran Scaffolds Enabled by Cu(II)/SPDO-Catalyzed [3+2] Cycloaddition of 2,3-Dihydrofuran and Quinone Esters.

An asymmetric [3+2] cycloaddition of quinone esters with 2,3-dihydrofuran has been realized via a newly developed Cu(II)/SPDO complex. It provides straightforward access to 2,3,3a,8a-tetrahydrofuro[2,3-b]benzofurans (TFB) with high enantioselectivity (up to 97.5:2.5 er) and diastereoselectivity (all >20:1 dr). The resulting adducts contain two adjacent stereocenters and a continuously functionalized benzene ring. Additionally, this transformation could be easily performed on a gram scale, allowing for expedient synthesis of natural dihydroaflatoxin D2 and aflatoxin B2.

Molecular characterization and transcriptional regulation analysis of the Torreya grandis squalene synthase gene involved in sitosterol biosynthesis and drought response.

The kernel of Torreya grandis cv. 'Merrillii' (Cephalotaxaceae) is a rare nut with a variety of bioactive compounds and a high economic value. ß-sitosterol is not only the most abundant plant sterol but also has various biological effects, such as antimicrobial, anticancer, anti-inflammatory, lipid-lowering, antioxidant, and antidiabetic activities. In this study, a squalene synthase gene from T. grandis, TgSQS, was identified and functionally characterized. TgSQS encodes a deduced protein of 410 amino acids. Prokaryotic expression of the TgSQS protein could catalyze farnesyl diphosphate to produce squalene. Transgenic Arabidopsis plants overexpressing TgSQS showed a significant increase in the content of both squalene and ß-sitosterol; moreover, their drought tolerance was also stronger than that of the wild type. Transcriptome data from T. grandis seedlings showed that the expression levels of sterol biosynthesis pathway-related genes, such as HMGS, HMGR, MK, DXS, IPPI, FPPS, SQS, and DWF1, increased significantly after drought treatment. We also demonstrated that TgWRKY3 directly bound to the TgSQS promoter region and regulated its expression through a yeast one-hybrid experiment and a dual luciferase experiment. Together, these findings demonstrate that TgSQS has a positive role in ß-sitosterol biosynthesis and in protecting against drought stress, emphasizing its importance as a metabolic engineering tool for the simultaneous improvement of ß-sitosterol biosynthesis and drought tolerance.

Coherent control of a high-orbital hole in a semiconductor quantum dot.

Coherently driven semiconductor quantum dots are one of the most promising platforms for non-classical light sources and quantum logic gates which form the foundation of photonic quantum technologies. However, to date, coherent manipulation of single charge carriers in quantum dots is limited mainly to their lowest orbital states. Ultrafast coherent control of high-orbital states is obstructed by the demand for tunable terahertz pulses. To break this constraint, we demonstrate an all-optical method to control high-orbital states of a hole via a stimulated Auger process. The coherent nature of the Auger process is proved by Rabi oscillation and Ramsey interference. Harnessing this coherence further enables the investigation of the single-hole relaxation mechanism. A hole relaxation time of 161 ps is observed and attributed to the phonon bottleneck effect. Our work opens new possibilities for understanding the fundamental properties of high-orbital states in quantum emitters and for developing new types of orbital-based quantum photonic devices.

The role of lncRNAs and exosomal lncRNAs in cancer metastasis.

Tumor metastasis is the main reason for cancer-related death, but there is still a lack of effective therapeutic to inhibit tumor metastasis. Therefore, the discovery and study of new tumor metastasis regulators is a prominent measure for cancer diagnosis and treatment. Long non-coding RNA (lncRNA) is a type of non-coding RNAs over 200 bp in length. It has been shown that the abnormally expressed lncRNAs promote tumor metastasis by participating in the epithelial-to-mesenchymal transition (EMT) process, altering the metastatic tumor microenvironment, or changing the extracellular matrix. It is,thus, critical to explore the regulation of lncRNAs expression in cells and the molecular mechanism of lncRNA-mediated cancer metastasis. Simultaneously, it has been shown that lncRNA is one kind of the main components of exosomes, which protects lncRNAs from being rapidly degraded. Meanwhile, the components of exosomes are parent-specific, making exosomal lncRNAs to be potential tumor metastasis markers and therapeutic targets. In view of this, we also summarized the aberrant enrichment of lncRNAs in exosomes and their role in metastatic cancer. The aberrant lncRNAs and exosomal lncRNAs gradually become biomarkers and therapeutic targets for tumor metastatic, and the potential of lncRNAs in therapeutics are studied here. Besides, the lncRNA-related databases, which could greatly facilitate in the study of lncRNAs and exosomal lncRNAs in metastatic of cancer are included in this review.

High-entropy-rate broadband chaos generation by using short-resonant-cavity DFB semiconductor laser with optical feedback.

Semiconductor lasers with delayed optical feedback are a promising source of optical chaos for practical applications, owing to simple configurations that are easy to integrate and synchronize. However, for traditional semiconductor lasers, the chaos bandwidth is limited by the relaxation frequency to several gigahertz. Here, we propose and experimentally demonstrate that a short-resonant-cavity distributed-feedback (SC-DFB) laser can generate broadband chaos only with simple feedback from an external mirror. The short distributed-feedback resonant cavity not only enhances laser relaxation frequency but also makes the laser mode more susceptible to external feedback. Experiments obtained a laser chaos with 33.6 GHz bandwidth and a spectral flatness of 4.5 dB. The corresponding entropy rate is estimated as more than 33.3 Gbit/s. It is believed that the SC-DFB lasers will promote development of chaos-based secure communication and physical key distribution.

Phosducin-like protein PoPlp1 impacts cellulase and amylase expression and development in Penicillium oxalicum via the G protein-cAMP signaling pathway.

In this study, a phosducin-like protein, PoPlp1, was identified and functionally studied in the cellulase-producing strain Penicillium oxalicum 114-2. PoPlp1 was proven to participate in several biological processes, including mycelium development, conidiation, and expression of cellulases and amylases. With deletion of Poplp1, morphology and development varied significantly in ΔPoplp1. Colony growth, glucose utilization, and the hydrolysis capability of starch and cellulose were limited, whereas conidiation was enhanced. Based on detection of the levels of expression of transcription factors involved in asexual development, we conjectured that PoPlp1 is involved in conidiation via the major factor BrlA. We explored the effect of PoPlp1 on cellulase and amylase expression and observed that cellulase and amylase activity and major gene transcription levels were all dramatically reduced in ΔPoplp1. Deletion of PoPlp1 caused a decrease in intracellular cAMP levels, and the cellulase gene expression level of ΔPoplp1 was restored to a certain extent through external addition of cAMP. These findings demonstrate that PoPlp1 may affect cellulase and amylase expression by regulating cAMP concentration. To comprehensively explore the mechanism of PoPlp1 in regulating multiple biological processes, we performed a comparative transcriptomic analysis between strains P. oxalicum 114-2 and ΔPoplp1. The major cellulase and amylase genes were all downregulated, congrent with the results of real-time quantitative polymerase chain reaction analysis. The genes involved in the G protein-cAMP signaling pathway, including several G-protein-coupled receptors, one regulator of G protein signaling, and two cAMP phosphodiesterases, were disrupted by deletion of PoPlp1. These results confirm the positive function of PoPlp1 in the G protein-cAMP signaling pathway. This functional analysis of PoPlp1 will be very beneficial for further study of the regulatory mechanisms of cellulase expression and other biological processes in P. oxalicum 114-2 via the G protein-cAMP signaling pathway.

A LncRNA gene polymorphism (rs1814343) is associated with the risk of coronary artery lesions in southern Chinese Kawasaki disease patients.

BACKGROUND: Kawasaki disease (KD) is a multisystemic angiitis, and its most disastrous complication is coronary artery lesions (CALs). Recently, the role of long non-coding RNAs (lncRNAs) in KD has been reported. rs1814343 is a lncRNA, but the relationship between the lncRNA rs1814343 polymorphism and KD risk remains elusive. METHODS: We enrolled 1625 Kawasaki disease patients (583 patients with CAL and 1042 without CAL) and 1000 healthy controls from a southern Chinese population. We genotyped the rs1814343 C > T polymorphism in KD and control patients using the TaqMan method. The odds ratio (OR) and 95% confidence interval (CI) were used to estimate the strength of the association. RESULTS: There was no significant association between the lncRNA rs1814343 C > T polymorphism and KD susceptibility. However, we stratified patients in this study by CAL and sex. First, compared with the control groups, we found that the rs1814343 genotype increased risk for KD patients with CAL (TT vs. CC + CT: OR = 1.36, 95% CI = 1.08-1.71, p = 0.009). Moreover, when KD patients were stratified by CAL, the TT genotypes of this lncRNA polymorphism contributed to a relatively higher occurrence of KD with CAL than that was found in the CC/CT genotype patients (TT vs. CC + CT: OR = 1.35, 95% CI = 1.07-1.69, p = 0.011). In addition, our research suggested that the TT variant genotype in the lncRNA rs1814343 had an obvious risk of KD with CAL susceptibility in male children. CONCLUSION: The lncRNA rs1814343 C > T polymorphism was related to higher susceptibility of KD with CAL.

Biorefining of rapeseed meal: A new and sustainable strategy for improving Cr(VI) biosorption on residual wastes from agricultural byproducts after phenolic extraction.

Phenolic recovery from agricultural byproducts has been highlighted due to their health-promoting bioactivities. However, uncontrolled discard of residues after extraction process would induce environmental pollution and bioresource waste. In this study, biorefining of phenolic-rich rapeseed meal (RSM) and its defatted sample (dRSM) was attempted by holistic utilization of phenolic extract and residue separately. Phenolic removal could significantly improve residues' Cr(VI) adsorption capacities by about 21%, which presented extended physical surface and more released functional groups. Moreover, simulating raw material by remixing 3% separated phenolic extracts or main component sinapic acid therein with corresponding residues further improved about 12% adsorption efficiencies. These indicated that the different present forms of phenolics had opposite effects on Cr(VI) removal. While natural conjugational form inhibited hosts' biosorption, free form had enhanced functions for either extract or residue. Four optimal adsorption parameters (pH, adsorbent dosage, contact time and initial Cr(VI) concentration), three kinetic (pseudo-first order, pseudo-second order and intra-particle diffusion) models and two isotherms (Langmuir and Freundlich) were used to reveal the adsorption process. The maximum Cr(VI) adsorption capacity on residues could reach about 100 mg/g, which was superior to that of most biosorbents derived from agricultural byproducts, even some biochar. Together with the residues' advantages with everlasting capacity after 3 adsorption-desorption cycles and excellent abilities for adsorbing multiple co-existed metal ions (Cr(VI), Cd(II), Cu(II), Pb(II), Ni(II) and Zn(II)), phenolic recovery was first proved to be a new and sustainable strategy for modifying biosorbents from agricultural byproducts with zero waste.

Transcriptome-referenced association study provides insights into the regulation of oil and fatty acid biosynthesis in Torreya grandis kernel.

INTRODUCTION: Torreya grandis is a gymnosperm belonging to Taxodiaceae. As an economically important tree, its kernels are edible and rich in oil with high unsaturated fatty acids, such as sciadonic acid. However, the kernels from different T. grandis landraces exhibit fatty acid and oil content variations. OBJECTIVES: As a gymnosperm, does T. grandis have special regulation mechanisms for oil biosynthesis? The aim of this study was to dissect the genetic architecture of fatty acid and oil content and the underlying mechanism in T. grandis. METHODS: We constructed a high integrity reference sequence of expressed regions of the genome in T. grandis and performed transcriptome-referenced association study (TRAS) for 10 fatty acid and oil traits of kernels in the 170 diverse T. grandis landraces. To confirm the TRAS result, we performed functional validation and molecular biology experiments for oil significantly associated genes. RESULTS: We identified 41 SNPs from 34 transcripts significantly associated with 7 traits by TRAS (-log10 (P) greater than 6.0). Results showed that LOB domain-containing protein 40 (LBD40) and surfeit locus protein 1 (SURF1) may be indirectly involved in the regulation of oil and sciadonic acid biosynthesis, respectively. Moreover, overexpression of TgLBD40 significantly increased seed oil content. The nonsynonymous variant in the TgLBD40 coding region discovered by TRAS could alter the oil content in plants. Pearson's correlation analysis and dual-luciferase assay indicated that TgLBD40 positively enhanced oil accumulation by affecting oil biosynthesis pathway genes, such as TgDGAT1. CONCLUSION: Our study provides new insights into the genetic basis of oil biosynthesis in T. grandis and demonstrates that integrating RNA sequencing and TRAS is a powerful strategy to perform association study independent of a reference genome for dissecting important traits in T. grandis.