Recent Progress in Thermally Activated Delayed Fluorescence Photosensitizers for Photodynamic Therapy.

Photodynamic therapy (PDT) is a rapidly growing discipline that is expected to become an encouraging noninvasive therapeutic strategy for cancer treatment. In the PDT process, an efficient intersystem crossing (ISC) process for photosensitizers from the singlet excited state (S1) to the triplet excited state (T1) is critical for the formation of cytotoxic reactive oxygen species and improvement of PDT performance. Thermally activated delayed fluorescence (TADF) molecules featuring an extremely small singlet-triplet energy gap and an efficient ISC process represent an enormous breakthrough for the PDT process. Consequently, the development of advanced TADF photosensitizers has become increasingly crucial and pressing. The most recent developments in TADF photosensitizers aimed at enhancing PDT efficiency for bio-applications are presented in this review. TADF photosensitizers with water dispersibility, targeting ability, activatable ability, and two-photon excitation properties are highlighted. Furthermore, the future challenges and perspectives of TADF photosensitizers in PDT are proposed.

Mitochondria-associated endoplasmic reticulum membranes involve in oxidative stress-induced intestinal barrier injury and mitochondrial dysfunction under diquat exposing.

Many factors induced by environmental toxicants have made oxidative stress a risk factor for the intestinal barrier injury and growth restriction, which is serious health threat for human and livestock and induces significant economic loss. It is well-known that diquat-induced oxidative stress is implicated in the intestinal barrier injury. Although some studies have shown that mitochondria are the primary target organelle of diquat, the underlying mechanism remains incompletely understood. Recently, mitochondria-associated endoplasmic reticulum membranes (MAMs) have aroused increasing concerns among scholars, which participate in mitochondrial dynamics and signal transduction. In this study, we investigated whether MAMs involved in intestinal barrier injury and mitochondrial dysfunction induced by diquat-induced oxidative stress in piglets and porcine intestinal epithelial cells (IPEC-J2 cells). The results showed that diquat induced growth restriction and impaired intestinal barrier. The mitochondrial reactive oxygen species (ROS) was increased and mitochondrial membrane potential was decreased following diquat exposure. The ultrastructure of mitochondria and MAMs was also disturbed. Meanwhile, diquat upregulated endoplasmic reticulum stress marker protein and activated PERK pathway. Furthermore, loosening MAMs alleviated intestinal barrier injury, decrease of antioxidant enzyme activity and mitochondrial dysfunction induced by diquat in IPEC-J2 cells, while tightening MAMs exacerbated diquat-induced mitochondrial dysfunction. These results suggested that MAMs may be associated with the intestinal barrier injury and mitochondrial dysfunction induced by diquat in the jejunum of piglets.

Significance of non-motor symptoms and development of a screening tool for osteoporosis in Parkinson's disease.

BACKGROUND AND PURPOSE: Parkinson's disease (PD) patients have a higher likelihood of having osteoporosis compared to controls, therefore deserving special attention. This study was to 1) investigate the association of non-motor symptoms with osteoporosis amongst PD patients, and 2) develop screening tools for osteoporosis. MATERIALS AND METHODS: PD Patients were included (n = 109). The factors/variables were obtained from clinical records due to the retrospective nature of this study. The bone mineral density (BMD) of the lumbar spine and femoral neck was examined using a dual-energy X-ray absorptiometry machine, according to which they were categorized as either having (T-score ≤ -2.5) or not having osteoporosis (T-score>-2.5) at the two sites. The non-motor symptoms were assessed using clinical scales, including non-motor experiences of daily living, depression, anxiety, cognitive function, and autonomic function. The potential covariates included demographic and clinical factors/variables, such as age and sex. Logistic regression was used to investigate the associations and establish the screening tools. RESULTS: Patients with autonomic dysfunction had significantly (p = 0.011) higher odds of having femoral neck osteoporosis compared to those with no/minimal dysfunction after adjusting for sex, disease duration, and body mass index, demonstrating a strong association (odds ratio=12.81). Based on the four factors/variables, a screening tool with a good accuracy was established (C-statistic = 0.85). CONCLUSION: PD patients with autonomic dysfunction had greater odds of having femoral neck osteoporosis compared to those with no/minimal dysfunction. The screening tool may lay a foundation for developing screening models with higher accuracy to identify which PD patients may require a BMD test.

Prognostic characteristics of a six-gene signature based on ssGSEA in sarcoma.

BACKGROUND: Sarcoma is a rare malignant tumor originating of the interstitial or connective tissue with a poor prognosis. Next-generation sequencing technology offers new opportunities for accurate diagnosis and treatment of sarcomas. There is an urgent need for new gene signature to predict prognosis and evaluate treatment outcomes. METHODS: We used transcriptome data from the Cancer Genome Atlas (TCGA) database and single sample gene set enrichment analysis (ssGSEA) to explore the cancer hallmarks most associated with prognosis in sarcoma patients. Then, weighted gene coexpression network analysis, univariate COX regression analysis and random forest algorithm were used to construct prognostic gene characteristics. Finally, the prognostic value of gene markers was validated in the TCGA and Integrated Gene Expression (GEO) (GSE17118) datasets, respectively. RESULTS: MYC targets V1 and V2 are the main cancer hallmarks affecting the overall survival (OS) of sarcoma patients. A six-gene signature including VEGFA, HMGB3, FASN, RCC1, NETO2 and BIRC5 were constructed. Kaplan-Meier analysis suggested that higher risk scores based on the six-gene signature associated with poorer OS (P < 0.001). The receiver Operating characteristic curve showed that the risk score based on the six-gene signature was a good predictor of sarcoma, with an area under the curve (AUC) greater than 0.73. In addition, the prognostic value of the six-gene signature was validated in GSE17118 with an AUC greater than 0.72. CONCLUSION: This six-gene signature is an independent prognostic factor in patients with sarcoma and is expected to be a potential therapeutic target for sarcoma.

Maintaining Drosha expression with Cdk5 inhibitors as a potential therapeutic strategy for early intervention after TBI.

Traumatic brain injury (TBI) is a major cause of death and disability in adults. The pathological process of TBI involves a multifactorial cascade in which kinases have been proven contribute to interactions between relevant factors and amplification of signaling cascades. Cyclin-dependent kinase 5 (Cdk5) is a promising kinase that has been implicated in various brain disorders, including TBI. However, the mechanism by which Cdk5 induces neuronal damage remains unclear. Here, we show for the first time that Drosha, a key enzyme in microRNA biogenesis, is a pivotal substrate of abnormally activated Cdk5. Cdk5-mediated phosphorylation decreases Drosha expression and exacerbates nerve injury in TBI. We proved that maintaining Drosha expression via the administration of repurposed Cdk5 inhibitors that were previously studied in clinical trials is a promising approach for the early treatment of TBI. Together, our work identifies Drosha as a novel target for neuroprotective strategies after TBI and suggests Cdk5-mediated regulation of Drosha expression as a potential therapeutic strategy for early TBI intervention.

Risperidone plasma level, and its correlation with CYP2D6 gene polymorphism, clinical response and side effects in chronic schizophrenia patients.

BACKGROUND: To explore the influence of CYP2D6 genetic polymorphism on risperidone metabolism, thereby affecting risperidone's effects and safeties in patients with chronic schizophrenia. METHODS: Sixty-nine subjects with chronic schizophrenia treated with risperidone were recruited. CYP2D6 genotypes was determined using targeted sequencing and translated into phenotype using activity system. Risperidone plasma concentrations were measured using HPLC. Positive and Negative Symptom Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) were used to evaluate the existence and severity of psychiatric symptoms, Barnes Akathisia Scale (BAS) and Extrapyramidal Symptom Rating Scale (ESRS) for neurological side effects. Metabolic and endocrine status assess were also included. RESULTS: The plasma drug concentrations varied hugely among individuals. Intermediate metabolizer (IM) group had higher plasma levels of RIP and dose corrected RIP concentration, RIP/9-OH-RIP ratio and C/D ratio than normal metabolizer (NM) group (p < 0.01). There was no statistic difference between responders and non-responders in dose-adjusted plasma concentrations and ratios of RIP/9-OH-RIP and C/D. The occurrence of EPS was related to active moiety levels in 4th week (p < 0.05). The prolactin (PRL) levels in two follow-ups were both significantly higher than baseline (p < 0.01). PRL change from baseline to week 4 and week 8 were both positively associated with active moiety concentration detected in week 4 (p < 0.05). CONCLUSIONS: The risperidone plasma levels have great inter- and intraindividual variations, and are associated with the CYP2D6 phenotypes, as well as the changes in serum prolactin in patients diagnosed with chronic schizophrenia.

High-sensitivity profiling of dipeptides in sauce-flavor Baijiu Daqu by chemical derivatization and ultrahigh-performance liquid chromatography coupled with high-resolution mass spectrometry.

Dipeptides in sauce-flavor Baijiu Daqu are protein degradation products during the fermentation of Daqu, which are believed to play a crucial role in the flavor and quality of Baijiu. Herein, we integrated dansyl chloride derivatization with ultrahigh-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS) for comprehensively profiling dipeptides in Daqu. The derivatization efficiency was higher than 99.1 % for all 17 dipeptide standards under the optimized derivatization conditions. In total, 118 dipeptides were detected in Daqu. The method was validated and the analytical characteristics including the linearity (spanned across 2-4 orders of magnitude), precision (1.2-19.9 %), limit of detection (varied from 1.1 to 53.4 pmol/mL) and the stability (3.6-15.8 %) are satisfactory. The usefulness of the method was examined by studying the distribution characteristics of dipeptides in Daqu under different production conditions. The present method provides an effective and robust strategy for comprehensively analyzing dipeptide compounds in complex biological samples.

Direct regulation of FNIP1 and FNIP2 by MEF2 sustains MTORC1 activation and tumor progression in pancreatic cancer.

MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1) orchestrates diverse environmental signals to facilitate cell growth and is frequently activated in cancer. Translocation of MTORC1 from the cytosol to the lysosomal surface by the RRAG GTPases is the key step in MTORC1 activation. Here, we demonstrated that transcription factors MEF2A and MEF2D synergistically regulated MTORC1 activation via modulating its cyto-lysosome shutting. Mechanically, MEF2A and MEF2D controlled the transcription of FNIP1 and FNIP2, the components of the FLCN-FNIP1 or FNIP2 complex that acts as a RRAGC-RRAGD GTPase-activating element to promote the recruitment of MTORC1 to lysosome and its activation. Furthermore, we determined that the pro-oncogenic protein kinase SRC/c-Src directly phosphorylated MEF2D at three conserved tyrosine residues. The tyrosine phosphorylation enhanced MEF2D transcriptional activity and was indispensable for MTORC1 activation. Finally, both the protein and tyrosine phosphorylation levels of MEF2D are elevated in human pancreatic cancers, positively correlating with MTORC1 activity. Depletion of both MEF2A and MEF2D or expressing the unphosphorylatable MEF2D mutant suppressed tumor cell growth. Thus, our study revealed a transcriptional regulatory mechanism of MTORC1 that promoted cell anabolism and proliferation and uncovered its critical role in pancreatic cancer progression.Abbreviation: ACTB: actin beta; ChIP: chromatin immunoprecipitation; EGF: epidermal growth factor; EIF4EBP1: eukaryotic translation initiation factor 4E binding protein 1; FLCN: folliculin; FNIP1: folliculin interacting protein 1; FNIP2: folliculin interacting protein 2; GAP: GTPase activator protein; GEF: guanine nucleotide exchange factors; GTPase: guanosine triphosphatase; LAMP2: lysosomal associated membrane protein 2; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MEF2: myocyte enhancer factor 2; MEF2A: myocyte enhancer factor 2A; MEF2D: myocyte enhancer factor 2D; MEF2D-3YF: Y131F, Y333F, Y337F mutant; MTOR: mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; NR4A1: nuclear receptor subfamily 4 group A member 1; RPTOR: regulatory associated protein of MTOR complex 1; RHEB: Ras homolog, mTORC1 binding; RPS6KB1: ribosomal protein S6 kinase B1; RRAG: Ras related GTP binding; RT-qPCR: real time-quantitative PCR; SRC: SRC proto-oncogene, non-receptor tyrosine kinase; TMEM192: transmembrane protein 192; WT: wild-type.

Multi-omics analysis reveals PUS1 triggered malignancy and correlated with immune infiltrates in NSCLC.

Non-small cell lung cancer (NSCLC) is the main pathological type of lung cancer. In this study, multi-omics analysis revealed a significant increase of pseudouridine synthase 1 (PUS1) in NSCLC and the high expression of PUS1 was associated with shorter OS (Overall Survival), PFS (Progression Free Survival), and PPS (Post Progression Survival) of NSCLC patients. Clinical subgroup analysis showed that PUS1 may be involved in the occurrence and development of NSCLC. Besides, TIMER, ESTIMATE, and IPS analysis suggested that PUS1 expression was associated with immune cell infiltration, and the expression of PUS1 was significantly negatively correlated with DC cell infiltration. GESA analysis also indicated PUS1 may involve in DNA_REPAIR, E2F_TARGETS, MYC_TARGETS_V2, G2M_CHECKPOINT and MYC_TARGETS_V1 pathways and triggered NSCLC malignancy through MCM5 or XPO1. Furthermore, PUS1 may be a potential target for NSCLC therapy.

Mechanistic insight into homogeneous catalytic crosslinking behavior between cellulose and epoxide by explicit solvent models.

Inspired by recent advances on functional modification of cellulosic materials, the crosslinking behaviors of epoxide with cellulose under the catalysis of different homogeneous catalysts including H2O, Brønsted acid, Brønsted base, Lewis acid and neutral salt were systematically investigated using density functional theory (DFT) methods with hybrid micro-solvation-continuum approach. The results showed that catalytic activity, reaction mechanism and regioselectivity are determined by the combined effect of catalyst type, electronic effect and steric hindrance. All the homogeneous catalysts have catalytic activity for the crosslinking reaction, which decreases in the order of NaOH > HCl > NCl3 > MCl2 > CH3COOH > NaCl (N = Fe3+, Al3+; M = Zn2+, Ca2+). Upon the catalysis of NaOH, hydroxyl group of cellulose is firstly deprotonated to form a carbanion-like intermediate which will further attack the less sterically hindered C atom of epoxide showing excellent regioselectivity. Acidic catalysts readily cause epoxide protonated, which suffers from nucleophilic attack of cellulose and forms the carbocation-like intermediate. Brønsted acid exhibits poor regioselectivity, however, Lewis acid shows an interesting balance between catalytic activity and regioselectivity for the crosslinking reaction, which may be attributed to the unique catalysis and stabilization effects of its coordinated H2O on the transition state structure.

Combined transcriptome and proteome analysis revealed the molecular regulation mechanisms of zinc homeostasis and antioxidant machinery in tobacco in response to different zinc supplies.

Zinc (Zn) is an essential micronutrient for plants. Adequate regulation of Zn uptake, transport and distribution, and adaptation to Zn-deficiency stress or Zn-excess toxicity are crucial for plant growth and development. However, little has been done to understand the molecular responses of plants toward different Zn supply levels. In the present study, we investigated the growth and physiological responses of tobacco seedlings grown under Zn-completely deficient, Zn-limiting, Zn-normal, and Zn-4-fold sufficient conditions, respectively, and demonstrated that Zn deficiency/limitation caused oxidative stress and impaired growth of tobacco plants. Combined transcriptome and proteome analysis revealed up-regulation of genes/proteins associated with Zn uptake and distribution, including ZIPs, NAS3s, and HMA1s, and up-regulation of genes/proteins involved in regulation of oxidative stress, including SODs, APX1s, GPX6, and GSTs in tobacco seedlings in response to Zn deficiency/limitation, suggesting that tobacco possessed mechanisms to regulate Zn homeostasis primarily through up-regulation of the ZIPs-NAS3s module, and to alleviate Zn deficiency/limitation-induced oxidative stress through activation of the antioxidant machinery. Our results provide novel insights into the adaptive mechanisms of tobacco in response to different Zn supplies, and would lay a theoretical foundation for development of varieties of tobacco or its relatives with high tolerance to Zn-deficiency.

Higher expression of pseudouridine synthase 7 promotes non-small cell lung cancer progression and suggests a poor prognosis.

BACKGROUND: Lung cancer is currently the second most common cancer, and non-small cell lung cancer accounts for about 85% of cases. NSCLC has not been studied for pseudouridine synthase 7 (PUS), a member of the PUS family that is associated with cancer development. Here, we focused on the role and clinical significance of PUS7 in non-small cell lung cancer. AIM: To explore the role of PUS7 in NSCLC and its clinical significance. METHODS: We downloaded datasets from the TCGA database and CPTAC database. In normal bronchial epithelial cells as well as NSCLC cell lines, RT-PCR and Western blot were used to quantify PUS7 expression. The role of PUS7 in NSCLC has been investigated by CCK8, migration assay, migration assay, and flow cytometry. PUS7 expression in tumor tissues was detected by immunohistochemical staining, and we evaluated the influence of PUS7 expression on the prognosis of NSCLC patients after surgery using Cox regression analysis, both univariate and multivariate. RESULTS: NSCLC cell lines and tissues expressed high levels of PUS7, and PUS7 was found to influence the proliferation, migration, and invasion of cancer cells without affecting their apoptosis. There was a worse prognosis for NSCLC patients who have higher PUS7 expression, suggesting that PUS7 was an independent indicator of prognosis (P = .05).

Profiling and annotation of carbonyl compounds in Baijiu Daqu by chlorine isotope labeling-assisted ultrahigh-performance liquid chromatography-high resolution mass spectrometry.

Carbonyl compounds are among the most important flavor substances that affect the taste of Baijiu. However, high coverage analysis of carbonyl compounds is obstructed due to the poor ionization efficiency of these compounds. Here we report a chlorine isotope labeling-assisted ultrahigh-performance liquid chromatography-high resolution mass spectrometry-based method (CIL-UHPLCHRMS) for profiling and annotation of carbonyl compounds in sauce flavored-Baijiu Daqu. 4-Chloro-2-hydrazinylpyridine was demonstrated to be a good labeling reagent that could achieve highly sensitive profiling and high-coverage screening of carbonyl compounds in the absence of heavy isotope labeling reagents. In the analysis of eight carbonyl standards representing different carbonyl categories, l-(-)-fucose, 2-carboxybenzaldehyde, 2-hydroxyacetophenone and heptan-2-one could be ionized only after labeling and MS signals were significantly increased for other 4 standards with an enhancement factor ranging from 181-fold for 3-methoxysalicylaldehyde to 3141-fold for tridecan-2-one. The annotation was achieved based on multidimensional information including MS1, predicted tR, in silico MS/MS and manually annotated fragments. In total, 487 carbonyl compounds were detected in Baijiu Daqu, among which, 314 (64.5%) of them were positively or putatively identified. The outcome of the linearity (with a linear range of 2, 3 orders of magnitude), precision (less than 10%), and limit of detection (varied from 0.07 to 0.10 nM) indicated that the method was adequate for profiling carbonyl compounds in complex biological samples. The established method was successfully applied to study carbonyl compounds in Baijiu Daqu with different colors and different seasons. Taken collectively, the present work provides an effective, simple and economic strategy for comprehensive analysis of carbonyl compounds in complex matrix samples.

Fermented Bamboo Fiber Improves Productive Performance by Regulating Gut Microbiota and Inhibiting Chronic Inflammation of Sows and Piglets during Late Gestation and Lactation.

Sows exhibit metabolic syndrome and significant changes in intestinal microbiota during late gestation and lactation, affecting sow performance and piglet health. Dietary fiber (DF) is widely applied to improve sow performance by modulating gut microbiota and their by-products. Here, 60 sows were randomly allocated to groups, including CON (8% wheat bran), FBF-1 (1% fermented bamboo fiber), FBF-2 (2.5% fermented bamboo fiber), and FBF-3 (4% fermented bamboo fiber) from day 80 of gestation (G80d) to the end of lactation (L21d). Compared with CON, the FBF-3 diet decreased lactation backfat loss, increased average daily feed intake (ADFI) during lactation, and the weight gain of piglets, while supplementation of FBF increased fecal water content and reduced the rate of constipation in sows. Further, the yield and quality of milk of sows in FBF groups were improved. The FBF-3 diet significantly reduced markers of intestinal permeability (diamine oxidase and endotoxin) and systemic inflammation (interleukin-6 [IL-6] and tumor necrosis factor alpha) in sow serum during lactation, while it increased the anti-inflammatory marker (IL-10). Similarly, the piglets in the FBF-2 and FBF-3 groups had lower levels of IL-6 and higher levels of IgG, IgM, and insulin-like growth factor in serum. In addition, sows fed the 4% FBF diet had higher levels of acetate, propionate, butyrate, and total short-chain fatty acids (SCFAs) in feces than CON, and total SCFAs were promoted in piglets from the FBF-3 group. Spearman correlation analysis showed that immunity, inflammation, and intestinal microbiota are closely related to sow performance, which can affect piglet growth. The potential mechanism could be that FBF promoted the enrichment of beneficial genera such as Lachnospira, Lachnospiracea_XPB1014_Group, and Roseburia and the production of SCFAs in the sow's intestine, and reduced the relative abundance of harmful bacteria such as Fusobacterium, Sutterellaceae, and Sutterella. Meanwhile, the intake of FBF by sows affected the gut microbial composition of their offspring piglets, significantly increasing the relative abundance of beneficial bacteria Alistipes and Lachnoclostridium and decreasing the relative abundance of pathogenic bacteria Trueperella among colonic microorganisms. IMPORTANCE Dietary fiber is widely applied in the nutrition of sows due to its potential value in improving performance and intestinal health. Fermented bamboo fiber, rich in dietary fiber, has not been fully evaluated to be used in sow diets. Sows mobilize body reserves during gestation and lactation due to nutrients being prioritized for lactation purposes while feeding piglets, which generally leads to metabolism and immunity undergoing drastic changes. The main manifestations are increased inflammation and intestinal permeability and disturbed intestinal flora, which ultimately reduces the ADFI and milk quality, thus affecting the growth of piglets. The study described here is the first attempt to provide FBF for sows in late gestation and lactation can reverse this process. The 4% FBF was initially explored to have the most significantly beneficial effect. It provides a potentially effective method for dietary modification to control the gut microbiota and its metabolites to improve sow and piglet health. Moreover, the sow-piglet model offers a reference for investigating the impact of dietary fiber on the intestinal health of human mothers and infants.

Performance assessment of medical service for organ transplant department based on diagnosis-related groups: A programme incorporating ischemia-free liver transplantation in China.

Background: In July 2017, the first affiliated hospital of Sun Yat-sen university carried out the world's first case of ischemia-free liver transplantation (IFLT). This study aimed to evaluate the performance of medical services pre- and post-IFLT implementation in the organ transplant department of this hospital based on diagnosis-related groups, so as to provide a data basis for the clinical practice of the organ transplant specialty. Methods: The first pages of medical records of inpatients in the organ transplant department from 2016 to 2019 were collected. The China version Diagnosis-related groups (DRGs) were used as a risk adjustment tool to compare the income structure, service availability, service efficiency and service safety of the organ transplant department between the pre- and post-IFLT implementation periods. Results: Income structure of the organ transplant department was more optimized in the post-IFLT period compared with that in the pre-IFLT period. Medical service performance parameters of the organ transplant department in the post-IFLT period were better than those in the pre-IFLT period. Specifically, case mix index values were 2.65 and 2.89 in the pre- and post-IFLT periods, respectively (p = 0.173). Proportions of organ transplantation cases were 14.16 and 18.27%, respectively (p < 0.001). Compared with that in the pre-IFLT period, the average postoperative hospital stay of liver transplants decreased by 11.40% (30.17 vs. 26.73 days, p = 0.006), and the average postoperative hospital stay of renal transplants decreased by 7.61% (25.23 vs.23.31 days, p = 0.092). Cost efficiency index decreased significantly compared with that in the pre-IFLT period (p < 0.001), while time efficiency index fluctuated around 0.83 in the pre- and post-IFLT periods (p = 0.725). Moreover, the average postoperative hospital stay of IFLT cases was significantly shorter than that of conventional liver transplant cases (p = 0.001). Conclusion: The application of IFLT technology could contribute to improving the medical service performance of the organ transplant department. Meanwhile, the DRGs tool may help transplant departments to coordinate the future delivery planning of medical service.

Genome-Wide Identification and Expression Pattern of Cytochrome P450 Genes in the Social Aphid Pseudoregma bambucicola.

Cytochrome P450 monooxygenases (P450s) have a variety of functions, including involvement in the metabolism of exogenous substances and the synthesis and degradation of endogenous substances, which are important for the growth and development of insects. Pseudoregma bambucicola is a social aphid that produces genetically identical but morphologically and behaviorally distinct first-instar soldiers and normal nymphs within colonies. In this study, we identified 43 P450 genes based on P. bambucicola genome data. Phylogenetic analysis showed that these genes were classified into 4 clans, 13 families, and 23 subfamilies. The CYP3 and CYP4 clans had a somewhat decreased number of genes. In addition, differential gene expression analysis based on transcriptome data showed that several P450 genes, including CYP18A1, CYP4G332, and CYP4G333, showed higher expression levels in soldiers compared to normal nymphs and adult aphids. These genes may be candidates for causing epidermal hardening and developmental arrest in soldiers. This study provides valuable data and lays the foundation for the study of functions of P450 genes in the social aphid P. bambucicola.

The wild allotetraploid sesame genome provides novel insights into evolution and lignan biosynthesis.

INTRODUCTION: The wild tetraploid sesame (Sesamum schinzianum), an ancestral relative of diploid cultivated sesame, grows in the tropical desert of the African Plateau. As a valuable seed resource, wild sesame has several advantageous traits, such as strong environmental adaptability and an extremely high content of sesamolin in its seeds. High-quality genome assembly is essential for a detailed understanding of genome structure, genome evolution and crop improvement. OBJECTIVES: Here, we generated two high-quality chromosome-scale genomes from S. schinzianum and a cultivated diploid elite sesame (Sesamum indicum L.) to investigate the potential genetic basis underlying these traits of wild sesame. METHODS: The long-read data from PacBio Sequel II platform and high-throughput chromosome conformation capture (Hi-C) data were used to construct high-quality sesame genome. Then dissecting the molecular mechanisms of sesame evolution and lignan biosynthesis through comparative genomics and transcriptomics. RESULTS: We found evidence of divergent evolution that involved differences in the number, sequence and expression level of homologous genes between the two sets of subgenomes from allotetraploids in S. schinzianum, all of which might be driven by subfunctionalization after polyploidization. Furthermore, it was found that a great number of genes involved in the stress response have undergone positive selection and resulted from gene family expansion in the wild sesame genome compared with the cultivated sesame genome, which, overall, is associated with adaptative evolution to the environment. We hypothesized that the sole functional member CYP92B14 (SscC22g35272) could be associated with high content of sesamolin in wild sesame seeds. CONCLUSION: This study provides high-quality wild allotetraploid sesame and cultivated sesame genomes, reveals evolutionary features of the allotetraploid genome and provides novel insights into lignan synthesis pathways. Meanwhile, the wild sesame genome will be an important resource to conduct comparative genomic and evolutionary studies and plant improvement programmes.

In situ observations of tungsten speciation and partitioning behavior during fluid exsolution from granitic melt.

Most economically important tungsten (W) deposits are of magmatic-hydrothermal origin. The species and partitioning of W during fluid exsolution, considered to be the controlling factors for the formation of ore deposits, are thus of great significance to investigate. However, this issue has not been well addressed mainly due to the significant difference in reported partition coefficients (e.g., from strongly incompatible to strongly compatible) between fluid and melt (DWfluid/melt). Here, we used an in situ Raman spectroscopic approach to describe the W speciation, and to quantitatively determine the Dfluid/melt of individual and total W species in granite melts and coexisting Na2WO4 solutions at elevated temperatures (T; 700-800 °C) and pressures (P; 0.35-1.08 GPa). Results show that WO42- and HWO4- are predominant W species, and the fractions of these two species are similar in melt and coexisting fluid. The partitioning behaviors of WO42- and HWO4- are comparable, exhibiting strong enrichment in the fluid. The total DWfluid/melt ranges from 8.6 to 37.1. Specifically, DWfluid/melt decreases with rising T-P, indicating that shallow exsolution favors enrichment of W in evolved fluids. Furthermore, Rayleigh fractionation modeling based on the obtained DWfluid/melt data was used to describe the fluid exsolution processes. Our results strongly support that fluid exsolution can serve as an important mechanism to generate W-rich ore-forming fluids. This study also indicates that in situ approach can be used to further investigate the geochemical behavior of ore-forming elements during the magmatic-hydrothermal transition, especially for rare metals associated with granite and pegmatite.

Clinical features and genetic analysis of SGCE myoclonus-dystonia: A case report.

Myoclonus-dystonia caused by mutations in the SGCE gene is clinically characterized by early onset, myoclonus, and dystonia. Here we describe a family in which several members exhibit varying degrees of myoclonus and dystonia, caused by a novel heterozygous mutation in the SGCE gene.

Recognition of Freezing of Gait in Parkinson's Disease Based on Machine Vision.

Background: Freezing of gait (FOG) is a common clinical manifestation of Parkinson's disease (PD), mostly occurring in the intermediate and advanced stages. FOG is likely to cause patients to fall, resulting in fractures, disabilities and even death. Currently, the pathogenesis of FOG is unclear, and FOG detection and screening methods have various defects, including subjectivity, inconvenience, and high cost. Due to limited public healthcare and transportation resources during the COVID-19 pandemic, there are greater inconveniences for PD patients who need diagnosis and treatment. Objective: A method was established to automatically recognize FOG in PD patients through videos taken by mobile phone, which is time-saving, labor-saving, and low-cost for daily use, which may overcome the above defects. In the future, PD patients can undergo FOG assessment at any time in the home rather than in the hospital. Methods: In this study, motion features were extracted from timed up and go (TUG) test and the narrow TUG (Narrow) test videos of 50 FOG-PD subjects through a machine learning method; then a motion recognition model to distinguish between walking and turning stages and a model to recognize FOG in these stages were constructed using the XGBoost algorithm. Finally, we combined these three models to form a multi-stage FOG recognition model. Results: We adopted the leave-one-subject-out (LOSO) method to evaluate model performance, and the multi-stage FOG recognition model achieved a sensitivity of 87.5% sensitivity and a specificity of 79.82%. Conclusion: A method to realize remote PD patient FOG recognition based on mobile phone video is presented in this paper. This method is convenient with high recognition accuracy and can be used to rapidly evaluate FOG in the home environment and remotely manage FOG-PD, or screen patients in large-scale communities.