The mTORC1-eIF4F axis controls paused pluripotency.

Mouse embryonic stem cells (mESCs) can self-renew indefinitely and maintain pluripotency. Inhibition of mechanistic target of rapamycin (mTOR) by the kinase inhibitor INK128 is known to induce paused pluripotency in mESCs cultured with traditional serum/LIF medium (SL), but the underlying mechanisms remain unclear. In this study, we demonstrate that mTOR complex 1 (mTORC1) but not complex 2 (mTORC2) mediates mTOR inhibition-induced paused pluripotency in cells grown in both SL and 2iL medium (GSK3 and MEK inhibitors and LIF). We also show that mTORC1 regulates self-renewal in both conditions mainly through eIF4F-mediated translation initiation that targets mRNAs of both cytosolic and mitochondrial ribosome subunits. Moreover, inhibition of mitochondrial translation is sufficient to induce paused pluripotency. Interestingly, eIF4F also regulates maintenance of pluripotency in an mTORC1-independent but MEK/ERK-dependent manner in SL, indicating that translation of pluripotency genes is controlled differently in SL and 2iL. Our study reveals a detailed picture of how mTOR governs self-renewal in mESCs and uncovers a context-dependent function of eIF4F in pluripotency regulation.

Genome-wide identification and characterization of greenbug-inducible NAC transcription factors in sorghum.

BACKGROUND: Sorghum (Sorghum bicolor) is an important cereal crop grown worldwide because of its multipurpose uses such as food, forage, and bioenergy feedstock and its wide range of adaption even in marginal environments. Greenbug can cause severe damage to sorghum plants and yield loss. Plant NAC transcription factors (TFs) have been reported to have diverse functions in plant development and plant defense but has not been studied in sorghum yet. METHODS AND RESULTS: In this study, a comprehensive analysis of the sorghum NAC (SbNAC) gene family was conducted through genome-wide analysis. A total of 112 NAC genes has been identified in the sorghum genome. These SbNAC genes are phylogenetically clustered into 15 distinct subfamilies and unevenly distribute in clusters at the telomeric ends of each chromosome. Twelve pairs of SbNAC genes are possibly involved in the segmental duplication among nine chromosomes except chromosome 10. Structure analysis showed the diverse structures with a highly variable number of exons in the SbNAC genes. Furthermore, most of the SbNAC genes showed specific temporal and spatial expression patterns according to the results of RNA-seq analysis, suggesting their diverse functions during sorghum growth and development. We have also identified nine greenbug-inducible SbNAC genes by comparing the expression profiles between two sorghum genotypes (susceptible BTx623 and resistant PI607900) in response to greenbug infestation. CONCLUSIONS: Our systematic analysis of the NAC gene expression profiles provides both a preliminary survey into their roles in plant defense against insect pests and a useful reference for in-depth characterization of the SbNAC genes and the regulatory network that contributes genetic resistance to aphids.

Interrelationships among growth hormone, thyroid function, and endocrine-disrupting chemicals on the susceptibility to attention-deficit/hyperactivity disorder.

Abnormal growth hormones and thyroid function may be linked to pathophysiology of attention-deficit/hyperactivity disorder (ADHD). Phthalates and bisphenol-A (BPA), two endocrine-disrupting chemicals (EDCs), may affect the human endocrine system. In this study, we aimed to perform a comprehensive investigation of whether growth hormone, thyroid function, and EDCs exhibited differential levels between ADHD patients and healthy controls. In total, 144 children with ADHD and 70 healthy control subjects were enrolled. Their endocrine systems were evaluated using the serum levels of insulin-like growth factor-1 (IGF-1), IGF-binding protein-3 (IGFBP-3), thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), and Free T4. The urinary levels of EDCs, including monoethyl phthalate (MEP), mono-methyl phthalate (MMP), monoethylhexyl phthalate (MEHP), mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), and BPA, were also examined. Patients with ADHD had lower IGF-1 levels than healthy controls (p = 0.003), but we observed no significant difference in IGFBP-3, TSH, T3, T4, or Free T4. Compared to the control group, patients with ADHD demonstrated higher MEHP levels (p = 0.043), MnBP (p = 0.033), and MBzP (p = 0.040). Furthermore, MEHP levels (p < 0.001) and BPA levels (p = 0.041) were negatively correlated with IGF-1 levels, while IGF-1 levels were negatively correlated with principal components consisting of ADHD clinical symptoms and neuropsychological performance variables. We suggest that MEHP exposure may be associated with decreased serum levels of IGF-1 and increased risk of ADHD. The mechanism underlying this association may be important for protecting children from environmental chemicals that adversely affect neurodevelopment.

[CiteSpace knowledge map of research hotspots and frontiers of traditional Chinese medicine intervention in psoriasis in recent ten years].

This study aimed to investigate the development status of traditional Chinese medicine(TCM) intervention in psoriasis in recent ten years, analyze the research hotspots, and summarize the development trends to provide reference materials for scholars in this field. Taking the available literature related to the field of TCM intervention in psoriasis as the research object, the trends, contents, and source publications were statistically analyzed based on bibliometrics. The research cooperation and co-occurrence of keywords in this field were studied by the knowledge map analysis method based on CiteSpace. The total number of Chinese papers was 2 993 and English papers 285. In terms of publication trend, the annual publication of English papers was low but showed an obvious upward trend, while the increase in Chinese papers fluctuated and tended to be flat. In terms of the content of Chinese papers published, TCM ranked first according to the discipline(2 415). In English papers, the number of publications in pharmacology and pharmaceutical science was the highest(87). Literature source analysis showed that the Chinese and English journals with the most publications were China Journal of Traditional Chinese Medicine and Pharmacy and Evidence Based Complementary and Alternative Medicine, respectively. Beijing University of Chinese Medicine published the most dissertations in China(99). The authors with the most publications in Chinese and English were LI Bin(Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine) and LU Chuan-jian(Guangdong Hospital of Traditional Chinese Medicine). As revealed by the CiteSpace analysis of the research cooperation network, there were four mature and stable core teams in this field, but the cooperation intensity between different teams was weak. According to the keywords co-occurrence knowledge graph constructed by CiteSpace, the current hot keywords in this field are as follows: psoriasis, blood-heat syndrome, blood-stasis syndrome, fire needle, blood-dryness type, imiquimod, TCM bath, etiology and pathogenesis, cytokines, cupping therapy, etc. In summary, Chinese scholars have conducted active exploration and research in the field of TCM intervention in psoriasis in recent ten years. The overall development trend is good, and the breadth and depth of the research are constantly extending. It is suggested that relevant research should be free from discipline restrictions and strive for interdisciplinary integration.

Exonuclease combinations reduce noises in 3D genomics technologies.

Chromosome conformation-capture technologies are widely used in 3D genomics; however, experimentally, such methods have high-noise limitations and, therefore, require significant bioinformatics efforts to extract reliable distal interactions. Miscellaneous undesired linear DNAs, present during proximity-ligation, represent a main noise source, which needs to be minimized or eliminated. In this study, different exonuclease combinations were tested to remove linear DNA fragments from a circularized DNA preparation. This method efficiently removed linear DNAs, raised the proportion of annulation and increased the valid-pairs ratio from ∼40% to ∼80% for enhanced interaction detection in standard Hi-C. This strategy is applicable for development of various 3D genomics technologies, or optimization of Hi-C sequencing efficiency.

An Optimization Method for the Station Layout of a Microseismic Monitoring System in Underground Mine Engineering.

The layout of microseismic monitoring (MSM) station networks is very important to ensure the effectiveness of source location inversion; however, it is difficult to meet the complexity and mobility requirements of the technology in this new era. This paper proposes a network optimization method based on the geometric parameters of the proposed sensor-point database. First, according to the monitoring requirements and mine-working conditions, the overall proposed point database and model are built. Second, through the developed model, the proposed coverage area, envelope volume, effective coverage radius, and minimum energy level induction value are comprehensively calculated, and the evaluation reference index is constructed. Third, the effective maximum envelope volume is determined by taking the analyzed limit of monitoring induction energy level as the limit. Finally, the optimal design method is identified and applied to provide a sensor station layout network with the maximum energy efficiency. The method, defined as the S-V-E-R-V model, is verified by a comparison with the existing layout scheme and numerical simulation. The results show that the optimization method has strong practicability and efficiency, compared with the mine's layout following the current method. Simulation experiments show that the optimization effect of this method meets the mine's engineering requirements for the variability, intelligence, and high efficiency of the microseismic monitoring station network layout, and satisfies the needs of event identification and location dependent on the station network.

Revealing Differential Expression of Phytohormones in Sorghum in Response to Aphid Attack Using the Metabolomics Approach.

Sorghum (Sorghum bicolor) is an important multipurpose crop grown worldwide, but like many other crops, it is often threatened by insect pests. Sugarcane aphid (SCA, Melanaphis sacchari Zehntner), for example, is one of the most severe pests in sorghum, which causes plant damage and yield loss. The main objective of this study was to assess the effect of phytohormones on host plant resistance to aphid attack. Two sorghum genotypes, BTx623 (susceptible) and Tx2783 (resistant), were selected for a comparative analysis of differential expression of a group of phytohormones in response to aphid infestation. The quantification of phytohormones through LC-MS demonstrated higher levels of jasmonic acid (JA), salicylic acid (SA), abscisic acid (ABA), and auxins in the resistant genotype infested with SCA. The PCA plot supports the strong differential responses between resistant and susceptible genotypes, indicating a positive correlation between JA and ABA and a negative correlation between SA and auxins. Similarly, RT-PCR results of the phytohormones-related marker genes showed higher expression in the resistant genotype compared to the susceptible one. Furthermore, to corroborate the role of phytohormones in plant defense, the susceptible genotype was treated with SA, JA, and ABA. The exogenous application of SA and JA + ABA significantly reduced plant mortality, aphid number, and damage in the susceptible genotype, suggesting a strong correlation between phytohormones and plant survival. Our findings indicate that phytohormones play positive roles in plant defense against aphids and provide new insights into the molecular mechanisms operating in plants for self-protection. These findings could also stimulate further research into the mystery about the regulation of phytohormone production during plant interaction with aphids.

Maternal Supplementation of Probiotics, Prebiotics or Postbiotics to Prevent Offspring Metabolic Syndrome: The Gap between Preclinical Results and Clinical Translation.

Metabolic syndrome (MetS) is an extremely prevalent complex trait and it can originate in early life. This concept is now being termed the developmental origins of health and disease (DOHaD). Increasing evidence supports that disturbance of gut microbiota influences various risk factors of MetS. The DOHaD theory provides an innovative strategy to prevent MetS through early intervention (i.e., reprogramming). In this review, we summarize the existing literature that supports how environmental cues induced MetS of developmental origins and the interplay between gut microbiota and other fundamental underlying mechanisms. We also present an overview of experimental animal models addressing implementation of gut microbiota-targeted reprogramming interventions to avert the programming of MetS. Even with growing evidence from animal studies supporting the uses of gut microbiota-targeted therapies start before birth to protect against MetS of developmental origins, their effects on pregnant women are still unknown and these results require further clinical translation.

Genome-wide identification and classification of Lipoxygenase gene family and their roles in sorghum-aphid interaction.

KEY MESSAGE: This report shows detailed characterization of LOX gene family in sorghum and provides new insight of sorghum LOX genes in genetic structure and their roles in plant response to infestation by sugarcane aphids. Lipoxygenases (LOXs) are monomeric, nonheme iron-containing dioxygenases that initiate the fatty acid oxidation pathway creating oxylipins and plant hormone jasmonate both have a key role in plant development and defense. To date, a comprehensive and systematic analysis of sorghum LOXs is still deficient. Thus, we performed a genome-wide analysis of the sorghum LOXs genome and identified nine LOXs genes. Detailed examination of protein sequences and phylogenetic analysis categorized the sorghum LOXs into two subclasses, 9-LOXs (SbLOX1, SbLOX3, SbLOX4, SbLOXm, and SbLOXo), 13-LOXs (SbLOX9, SbLOX5, and SbLOX2), and the unclassified SbLOX8. This classification was further supported by sequence similarity/identity matrix and subcellular localization analysis. The lipoxygenase domains, motifs, and vital amino acids were highly conserved in all sorghum LOX genes. In silico analysis of the promoter region of SbLOXs identified different hormones responsive cis-elements. Furthermore, to explore the roles of sorghum LOXs during sugarcane aphid feeding and exogenous MeJA application, expression analysis was conducted for all the eight LOXs in resistant (Tx2783) and susceptible (Tx7000) sorghum lines, respectively. As detailed in this report, the data generated from both genome-wide identification and expression analysis of lipoxygenase genes suggest the putative functions of two 13-LOXs (SbLOX9 and SbLOX5) and three 9-LOXs (SbLOX1, SbLOX3, and SbLOXo) in biosynthesis of jasmonic acid, green leaf volatiles and death acids, and all of them are involved in defense-related functions in plants. Furthermore, this report represents the first genome-wide analysis of the LOX gene family in sorghum, which will facilitate future studies to characterize the roles of each individual LOXs gene in aphid resistance and defense responses to other stresses.

Individuals at ultra-high risk of psychosis and first-degree relatives of patients with schizophreniaexperience impaired family functionality and social support deficit in comparison to healthy controls.

AIM: The present study was designed to assess the role of family function and social support in the context of different phases of schizophrenia. METHODS: First-episode patients with experiences of schizophrenia (FEP), ultra-high risk for psychosis (UHR), first-degree relatives (FDR) of patients with experiences of schizophrenia, and healthy controls (HC) (40 per group) were subjected to in-person clinical interviews. The results of these interviews were then used to gauge social support and family function using the Perceived Social Support Scale (PSSS) and the Family Adaptability and Cohesion Scales (FACESII-CV). Data were analyzed through ANCOVA, correlation analysis and logistic regression analyses. RESULTS: We found that family function and social support showed a approximately gradual downward trend through the HC, FDR, UHR, and FEP groups but no significant differences were found in the family function of the FDR, UHR and FDR group. Logistic regression analyses indicated that UHR group patients exhibited decreased family support and family cohesion relative to members of the HC group, but had greater perceived social support than did members of the FEP group. Results for members of the FDR group were in line with those of members of the UHR group. CONCLUSIONS: These findings suggested that both UHR and FDR individuals experience impaired family functionality and social support which expanded the understanding of the psychological characteristics of the prodromal period of schizophrenia. Further explorations are warranted to develop optimal psychosocial interventions.

Montelukast does not increase the risk of attention-deficit/hyperactivity disorder in pediatric asthma patients: A nationwide population-based matched cohort study.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) has been linked to pediatric asthma patients treated with montelukast. This study is the first to use a nationwide health insurance research database (NHIRD) to study whether asthmatic children using montelukast are at an increased risk of ADHD. METHODS: We used data from the Taiwan NHIRD, which is a longitudinal database of one million randomly selected subjects. The enrolled patients were followed up until 2013. Patients younger than and equal to 12 years old with new-onset asthma (ICD-9 CM code 493.X) diagnosed between 1997 and 2013 were enrolled. A multivariate Cox regression analysis was conducted to evaluate the association between montelukast treatment and the risk of ADHD (ICD-9-CM code 314.X). RESULTS: We enrolled a total of 54,487 asthmatic children younger than and equal to 12 years old who had at least one claim of inpatient admission or at least three claims of an ambulatory visit. Montelukast users and match controls were identified by matching age, gender, residence, the comorbidities including allergic rhinitis and atopic dermatitis, admission or emergency department visits due to asthma attack, and index date of starting montelukast in a 1:1 ratio, with 12,806 in the montelukast group and 12,806 in the non-montelukast group. The montelukast group had a similar risk of ADHD (n = 632, 4.94%) as the non-montelukast group (n = 610, 4.76%) [adjusted hazard ratio 1.04; 95% confidence interval, 0.93 to 1.17]. In children treated with montelukast, high cumulative days of montelukast use did not increase the risk of ADHD. CONCLUSION: This nationwide population-based cohort study reveals that asthma children treated with montelukast were not at an increased risk of developing ADHD. Nevertheless, validation of our retrospective survey requires further prospective study.

Frequency and correlates of violence against patients with schizophrenia living in rural China.

BACKGROUND: Violence against patients with schizophrenia is very common, however it is rarely studied in China, especially in primary health care institutions of rural areas. Therefore, we investigated the frequency of violence against patients with community-living schizophrenia in rural China and examined its associated factors and impact on quality of life (QoL) and social function. METHOD: A survey was conducted among 487 patients with schizophrenia living in rural communities. Data about violent victimization experiences in the past 6 months, demographic information, and clinical characteristics were collected by questionnaires. RESULTS: We found that 92 (18.9%) of 487 subjects experienced at least one type of violent event in the past 6 months. Logistic regression analysis suggested that a history of conducting dangerous behaviors(OR = 1.702, P = 0.02, 95%CI: 1.05-2.73), higher Brief Psychiatric Rating Scale (anxiety domain) score (OR = 1.15, P = 0.02, 95%CI: 1.01-1.304) and lower hospitalization rates (OR = 0.89, P = 0.04, 95%CI: 0.81-0.99) were significantly associated with violent victimization in patients with schizophrenia. Analysis of covariance showed the victims of violence tended to have worse social function in patients with schizophrenia living in rural communities of China (P = 0.04). CONCLUSIONS: Individuals with schizophrenia living in rural China had a high risk of being exposed to violence and violent victimization of patients with schizophrenia had adverse consequences for social function. More attention is needed for those patients experiencing violent events, because they are simultaneously possible to conduct dangerous behaviors.

Sexual dysfunction in Chinese rural patients with schizophrenia.

BACKGROUND: Sexual dysfunction is common in patients with schizophrenia, however it is poorly studied in China, especially in primary health care institutions in rural areas. We investigated the prevalence of sexual dysfunction and its correlates including quality of life (QoL), in schizophrenia patients treated in primary care in a rural area in China. METHOD: By using a random numbers table, 21 small town primary care service centers (from 63 totally) were selected in the study. Data of 720 community-dwelling patients with schizophrenia in rural area with diagnoses according to DSM -IV or ICD-10 were collected by interviews. Data on socio-demographic and clinical characteristics including sexual dysfunction and quality of life (QoL) were collected using a standardized protocol and data collection procedure. Data were analyzed using chi-square tests, t-tests, U-tests, ANCOVA and multiple logistic regression as appropriate by SPSS 21.0.The level of significance was set at 0.05 (two-tailed). RESULTS: In this sample, sexual dysfunction was found in 71.3% of the whole sample, 82.7% of female patients and 64.5% of male patients. Multiple logistic regression analysis showed that older age (OR = 1.06, P<0.001, 95%CI: 1.04-1.09) and higher Brief Psychotic Rating Scale (negative domain) score (OR = 1.16, P = 0.01, 95%CI: 1.02-1.31) were significantly associated with sexual dysfunction. Contrary to previous findings, sexual dysfunction was not associated with quality of life after controlling for confounding variables. CONCLUSIONS: More than 2/3 of schizophrenia patients living in a rural area complained of sexual dysfunction, which was associated with older age and more negative psychotic symptoms. Primary care physicians should pay attention to sexual dysfunction during the assessment and treatment of patients with schizophrenia in rural areas in China.

Integrated transcriptomic and pathway analyses of sorghum plants revealed the molecular mechanisms of host defense against aphids.

Sugarcane aphid has emerged as a major pest of sorghum recently, and a few sorghum accessions were identified for resistance to this aphid so far. However, the molecular and genetic mechanisms underlying this resistance are still unclear. To understand these mechanisms, transcriptomics was conducted in resistant Tx2783 and susceptible BTx623 sorghum genotypes infested with sugarcane aphids. A principal component analysis revealed differences in the transcriptomic profiles of the two genotypes. The pathway analysis of the differentially expressed genes (DEGs) indicated the upregulation of a set of genes related to signal perception (nucleotide-binding, leucine-rich repeat proteins), signal transduction [mitogen-activated protein kinases signaling, salicylic acid (SA), and jasmonic acid (JA)], and plant defense (transcription factors, flavonoids, and terpenoids). The upregulation of the selected DEGs was verified by real-time quantitative PCR data analysis, performed on the resistant and susceptible genotypes. A phytohormone bioassay experiment showed a decrease in aphid population, plant mortality, and damage in the susceptible genotype when treated with JA and SA. Together, the results indicate that the set of genes, pathways, and defense compounds is involved in host plant resistance to aphids. These findings shed light on the specific role of each DEG, thus advancing our understanding of the genetic and molecular mechanisms of host plant resistance to aphids.

Analysis of the effects of early screening combined with blood lactate on the severity of patients with sepsis.

This work aimed to investigate the adoption value of blood lactic acid (BLA) combined with the National Early Warning Score (NEWS) in the early screening of sepsis patients and assessing their severity. The data and materials utilized in this work were obtained from the electronic medical record system of 537 anonymized sepsis patients who received emergency rescue in the emergency rescue area of Liuzhou People's Hospital, Guangxi, from July 1, 2020, to December 26, 2020. Based on the 28-day outcomes of sepsis patients, the medical records were rolled into Group S (407 survival cases) and Group D (130 dead cases). Basic information such as the mode of hospital admission, initial management, use of emergency ventilator within 24 h of admission, NEWS score, arterial oxygen pressure/alveolar oxygen pressure ratio (PaO2/PAO2), alveolar-arterial oxygen difference (A-aDO2), serum creatinine (SCr), blood urea nitrogen (BUN), oxygenation index (OI), Glasgow Coma Scale (GCS), D-dimer, use of vasoactive drugs within 24 h of admission, C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), N-terminal pro-B-type natriuretic peptide (NT-proBNP), quick Sequential Organ Failure Assessment (qSOFA) score, SOFA score, BLA level, NEWS with lactate (NEWS-L) score, SOFA score including lactate level (SOFA-L) score, Intensive Care Unit (ICU) length of stay, total hospital stay, ICU stay/total hospital stay, and septic shock condition were compared between groups. Logistic regression analysis was performed to assess the impact of various predictive factors on prognosis and to plot the receiver operating characteristic (ROC) curve. The results suggested marked differences between Group S and Group D in terms of mean age (t = -5.620; OR = -9.96, 95 % CI: -13.44∼-6.47; P < 0.001). Group S showed drastic differences in terms of mode of hospital admission (χ2 = 9.618, P < 0.01), method of initial management (χ2 = 51.766, P < 0.001), use of emergency ventilator within 24 h of admission (χ2 = 98.564, P < 0.001), incidence of septic shock (χ2 = 77.545, P < 0.001), use of vasoactive drugs within 24 h of admission (χ2 = 102.453, P < 0.001), heart rate (t = -4.063, P < 0.001), respiratory rate (t = -4.758, P < 0.001), oxygenation status (χ2 = 20.547, P < 0.001), NEWS score (t = -6.120, P < 0.001), PaO2/PAO2 ratio (t = 2.625, P < 0.01), A-aDO2 value (Z = -3.581, P < 0.001), OI value (Z = -3.106, P < 0.01), PLT value (Z = -2.305, P < 0.05), SCr value (Z = -3.510, P < 0.001), BUN value (Z = -3.170, P < 0.01), D-dimer (Z = -4.621, P < 0.001), CRP level (Z = -4.057, P < 0.001), PCT value (Z = -2.783, P < 0.01), IL-6 level (Z = -2.904, P < 0.001), length of hospital stay (Z = -4.138, P < 0.001), total hospital stay (Z = -8.488, P < 0.001), CCU/total hospital stay (Z = -9.118, P < 0.001), NEWS score (t = -6.120, P < 0.001), SOFA score (t = -6.961, P < 0.001), SOFA-L score (Z = -4.609, P < 0.001), NEWS-L score (Z = -5.845, P < 0.001), BLA level (Z = -6.557, P < 0.001), and GCS score (Z = 6.909, P < 0.001) when compared to Group D. The use of ventilators, septic shock, PCT, NEWS score, GCS score, SOFA score, SOFA-L score, NEWS-L score, and BLA level were identified as independent risk factors for predicting the prognosis of sepsis patients (P < 0.001). The areas under ROC curve (AUC) of blood lactic acid, PCT, NEWS, NEWS-L, GCS, SOFA, and SOFA-L were 0.695, 0.665, 0.692, 0.698, 0.477, 0.700, and 0.653, respectively. These findings indicate that the combination of BLA with NEWS (NEWS-L) score and SOFA score has certain advantages in assessing the prognosis of sepsis.

Spectrum of PHEX Mutations and FGF23 Profiles in a Taiwanese Cohort With X-Linked Hypophosphatemia Including 102 Patients.

BACKGROUND/AIM: X-linked hypophosphatemia (XLH), the most common form of hereditary rickets, results from loss-of-function mutations in the phosphate-regulating PHEX gene. Elevated fibroblast growth factor 23 (FGF23) contributes to hypophosphatemia in XLH. This study aimed to characterize PHEX variants and serum FGF23 profiles in Taiwanese patients with XLH. PATIENTS AND METHODS: We retrospectively reviewed the records of 102 patients clinically suspected of having hypophosphatemic rickets from 2006 to 2022. Serum intact Fibroblast growth factor-23 (iFGF23) levels were measured on clinic visit days. PHEX mutations were identified using Sanger sequencing, and negative cases were analyzed using whole-exome sequencing. RESULTS: The majority (92.1%) of patients exhibited elevated FGF23 compared with normal individuals. Among 102 patients, 44 distinct PHEX mutations were identified. Several mutations recurred in multiple unrelated Taiwanese families. We discovered a high frequency of novel PHEX mutations and identified variants associated with extreme FGF23 elevation and tumorigenesis. CONCLUSION: Our findings revealed the PHEX genotypic variants and FGF23 levels in Taiwanese patients with XLH. These results are crucial given the recent approval of burosumab, a monoclonal FGF23 antibody, for XLH therapy. This study provides key insights into the clinical management of XLH in Taiwan.

Analysis of plant expression profiles revealed that aphid attack triggered dynamic defense responses in sorghum plant.

Sorghum [Sorghum bicolor (L.) Moench] is one of the most important cereal crops grown worldwide but is often attacked by greenbug (aphid). In response to aphid attack, host plant initiates a large transcriptional reorganization, leading to activation of the host defense genes in aphid-attacked plants. In this study, our objective was to analyze defensive responses of sorghum against aphid and identify aphid resistance genes in sorghum. For the experiments, seedlings developed from an aphid resistant germplasm line (PI 550607) were divided into two groups, then, one group was infested with greenbug ((Schizaphis graminum Rondani) and the other group was used as control (un-infested). In addition, seedlings of sorghum cultivar Tx 7000, a susceptible genotype, prepared under the same conditions, were used as a genetic control. Those plant samples were used to develop transcriptional profiles using the microarray method, from which 26.1% of the 1,761 cDNA sequences spotted on the microarray showed altered expression between two treatments at 4 days after infestation. Sequence annotation and molecular analysis revealed that many differentially expressed genes (DEGs) were related to direct host defense or signal transduction pathways, which regulate host defense. In addition to common responsive genes, unique transcripts were identified in response to greenbug infestation specifically. Later, a similar transcriptional profiling was conducted using the RNA-seq method, resulted in the identification of 2,856 DEGs in the resistant line with a comparison between infested and non-infested at 4 days and 4,354 DEGs in the resistant genotype compared to the susceptible genotype at 4 days. Based on the comparative analysis, the data of RNA-seq provided a support for the results from the microarray study as it was noticed that many of the DEGs are common in both platforms. Analysis of the two differential expression profiles indicate that aphid triggered dynamic defense responses in sorghum plants and sorghum plant defense against aphid is a complex process involving both general defense systems and specific resistance mechanisms. Finally, the results of the study provide new insights into the mechanisms underlying host plant defense against aphids and will help us design better strategies for effectively controlling aphid pest.

α-Pheromone Precursor Protein Foc4-PP1 Is Essential for the Full Virulence of Fusarium oxysporum f. sp. cubense Tropical Race 4.

Fusarium oxysporum f. sp. cubense (Foc), which causes Fusarium wilt of bananas, is considered one of the most destructive fungal pathogens of banana crops worldwide. During infection, Foc secretes many different proteins which promote its colonization of plant tissues. Although F. oxysporum has no sexual cycle, it has been reported to secrete an α-pheromone, which acts as a growth regulator, chemoattractant, and quorum-sensing signaling molecule; and to encode a putative protein with the hallmarks of fungal α-pheromone precursors. In this study, we identified an ortholog of the α-pheromone precursor gene, Foc4-PP1, in Foc tropical race 4 (TR4), and showed that it was necessary for the growth and virulence of Foc TR4. Foc4-PP1 deletion from the Foc TR4 genome resulted in decreased fungal growth, increased sensitivity to oxidative stress and cell-wall-damaging agents, and attenuation of pathogen virulence towards banana plantlets. Subcellular localization analysis revealed that Foc4-PP1 was concentrated in the nuclei and cytoplasm of Nicotiana benthamiana cells, where it could suppress BAX-induced programmed cell death. In conclusion, these findings suggest that Foc4-PP1 contributes to Foc TR4 virulence by promoting hyphal growth and abiotic stress resistance and inhibiting the immune defense responses of host plants.

Effects of Glycogen Synthase Kinase-3 Beta Gene Polymorphisms on the Plasma Concentration of Aripiprazole in Chinese Patients with Schizophrenia: A Preliminary Study.

This study explored the differences in glycogen synthase kinase-3 beta (GSK3ß) gene polymorphisms between patients with schizophrenia and healthy controls and investigated the association between gene polymorphisms and plasma concentration of aripiprazole. We enrolled 127 patients with schizophrenia and 125 healthy controls from southern Fujian. The genotypes of the rs6438552, rs12630592, and rs3732361 loci of GSK3ß were evaluated by sequencing with amplified polymerase chain reaction, and the plasma concentration of aripiprazole was determined by high-performance liquid chromatography-tandem mass spectrometry. All three loci of GSK3ß had three genotypes each. The genotype distribution in each locus was not significantly different, but there was a significant difference in the allele frequency between the schizophrenia and control groups within each locus. Linkage disequilibrium analyses of the three single-nucleotide polymorphisms (SNPs) revealed strong linkage. The haplotype analysis results showed two haplotypes in the three SNPs of GSK3ß. The plasma concentrations, dose-corrected concentrations, and normalized concentrations of aripiprazole were significantly different among the different genotypes of the three SNPs. In conclusion, the rs6438552, rs12630592, and rs3732361 loci of GSK3ß may be involved in schizophrenia, and GSK3ß gene polymorphism may be correlated with the plasma concentration of aripiprazole.

Moral decision-making in pettism: The influence of animal type, pet ownership status, and social distance.

Speciesism prioritizes humans over animals and pets. Nevertheless, pet owners have a strong attachment bond with their pets, which makes their hierarchical view of pets less clear. Aiming to examine this issue, we present a dilemma involving animals and humans that allowed us to investigate whether animal type, social distance, and pet ownership status can affect moral decision-making related to pets. Save-willingness results showed that in the moral dilemmas of pets versus livestock versus wild animals (Studies 1a and 2a) and their own pets versus strangers (Studies 1b and 2b), pet owners prioritize pets whereas non-owners prioritize pets (Studies 1a and 2a) and strangers (Studies 1b and 2b). Pet owners prefer to save pets more than do non-owners (Study 1a), and this effect was only observed in females (Study 2a). Save-decision results showed that in the moral dilemmas of pets versus livestock versus wild animals (Study 2a), pet owners prioritize pets whereas in the dilemmas of pets versus strangers (Study 2b), pet owners prioritize strangers. The same result was found in non-owners. Pet owners prefer more than do non-owners to save pets (Study 2). Overall, the separation of save-willingness and save-decision results revealed that pet owners show special speciesism (i.e., pettism).