An engineered multidomain fungicidal peptide against plant fungal pathogens.

Fungal pathogens represent major problems for human health and agriculture. As eukaryotic organisms, fungi share some important features with mammalian cells. Therefore, current anti-fungal antibiotics often can not distinguish between fungi and mammalian cells, resulting in serious side effects in mammalian cells. Accordingly, there is strong impetus to develop antifungal alternatives that are both safe and effective. The E1 family of colicin are channel-forming bacteriocins produced by Escherichia coli, which are bactericidal only to E. coli and related species. To target the channel-forming domain of colicin to fungal cell membrane, we engineered a sexual mating pheromone of Candida albicans, α-factor pheromone to colicin Ia. A peptide was constructed consisting of an α mating pheromone of C. albicans fused to the channel-forming domain of colicin Ia to create a new fusion protein, pheromonicin-CA (PMC-CA). Indirect immunolabeling showed that the PMC-CA bound to fungal cells and inhibited growth in the laboratory and field. In the field, the protective activity of pheromonicin against rice blast disease was significantly greater, on a molar basis, than that of triazoles, tricyclazole or isoprothiolane. These results suggest that fusion peptides may be of value as fungicidal agents under agricultural conditions.

A case of West syndrome and global developmental delay in a child with a heterozygous mutation in the TBL1XR1 gene: A case report.

BACKGROUND: TBL1XR1, also known as IRA1 or TBLR1, encodes a protein that is localized in the nucleus and is expressed in most tissues. TBL1XR1 binds to histones H2B and H4 in vitro and functions in nuclear receptor-mediated transcription. TBL1XR1 is also involved in the regulation of the Wnt-ß-catenin signaling pathway. Mutations in the TBL1XR1 gene impair the Wnt-ß-catenin signaling pathway's ability to recruit Wnt-responsive element chromatin, affecting brain development. Mutations in this gene cause various clinical phenotypes, including Pierpont syndrome, autism spectrum disorder, speech and motor delays, mental retardation, facial dysmorphism, hypotonia, microcephaly, and hearing impairment. CASE SUMMARY: A 5-month-old female child was admitted with "episodic limb tremors for more than 1 month." At the time of admission, the child had recurrent episodes of limb tremors with motor retardation and a partially atypical and hypsarrhythmic video electroencephalogram. It was determined that a heterozygous mutation in the TBL1XR1 gene caused West syndrome and global developmental delay. Recurrent episodes persisted for 6 months following oral treatment with topiramate; the addition of oral treatment with vigabatrin did not show any significant improvement, and the disease continued to recur. The child continued to have recurrent episodes of limb tremors at follow-up until 1 year and 3 months of age. Additionally, she developed poor eye contact and a poor response to name-calling. CONCLUSION: We report the case of a child with West syndrome and a global developmental delay caused by a heterozygous mutation in the TBL1XR1 gene. This study adds to our understanding of the clinical phenotype of TBL1XR1 mutations and provides a realistic and reliable basis for clinicians.

Development and validation of the thyroid cancer self-perceived discrimination scale to identify patients at high risk for psychological problems.

Objective: To develop a Thyroid Cancer Self-Perceived Discrimination Scale (TCSPDS) to identify patients at high risk for psychological problems and to test its reliability, validity and acceptability. Methods: Using classical test theory, a total of 176 thyroid cancer patients from November 2021 to October 2022 were recruited to develop the TCSPDS. Item analysis was used to improve the preliminary TCSPDS. Exploratory factor analysis (EFA), confirmatory factor analysis (CFA) and structural equation model (SEM) were used to test the construct validity of the final TCSPDS. Pearson correlation coefficient was used to analyze the validity coefficient between TCSPDS and EORTC QLQ-C30 to test the criterion-related validity (CRV) of the final TCSPDS. The internal consistency coefficient (Cronbach's alpha coefficient), split half reliability (Spearman-Brown coefficient) and test-retest reliability were used to verify the reliability of the final TCSPDS. The questionnaire completion time and effective response rate were used to validate the acceptability of the final TCSPDS. Results: The TCSPDS consisted of 20 items and was divided into 3 subscales: 8 items for stigma, 6 items for self-deprecation, and 6 items for social avoidance. The TCSPDS had good validity (χ2/df=1.971, RMSEA=0.074, GFI=0.921, CFI= 0.930, IFI=0.932, TLI=0.901, Validity coefficient=0.767), reliability (Cronbach's alpha=0.867, Spearman-Brown coefficient=0.828, test-retest reliability coefficient=0.981) and acceptability [average completion time (15.01 ± 1.348 minutes) and an effective response rate of 95.14%]. Patients with higher TCSPDS scores reported a lower quality of life (P<0.05). Conclusion: The TCSPDS could be used for early identification and assessment of the level of self-perceived discrimination in patients with thyroid cancer, which may provide a scientific basis for health education, social support and psychosocial oncology services in the future, especially in Southwest China.

Retinitis pigmentosa with or without skeletal abnormalities due to homozygous mutations in the CWC27 gene: A case report.

RATIONALE: Retinitis pigmentosa with or without skeletal abnormalities (RPSKA) is an autosomal recessive disorder caused by mutations in the CWC27 gene. Skeletal dysplasia and non-syndromic retinitis pigmentosa are typical manifestations, and most patients present with retinopathy such as retinitis pigmentosa and limited visual field. Its clinical manifestations are complex and diverse, often involving multiple systems. Examples include short finger deformities, peculiar facial features, short stature, and neurodevelopmental abnormalities, and it is easy to misdiagnose clinically, and early diagnosis is crucial for prognosis. PATIENT CONCERNS: A 2-year and 2-month-old female child was admitted to the hospital due to "unsteady walking alone and slow reaction for more than half a year." After admission, the child was found to have delayed motor development, accompanied by special face, abnormal physical examination of the nervous system, cranial MRI Dandy-Walker malformation, considering developmental delay. DIAGNOSES: Whole exome sequencing of the family line revealed the presence of a c.617(exon7)C>A pure mutation in the CWC27 gene in the affected child (this locus has been reported in the clinical literature); the final diagnosis is RPSKA. INTERVENTIONS: Unfortunately, there is no specific drug for the disease; we give children rehabilitation training treatment. OUTCOMES: During follow-up process we found that children's condition is better than before. LESSONS SUBSECTIONS AS PER STYLE: We reported a case of RPSKA caused by mutations in the CWC27 gene. This study adds to our understanding of the clinical phenotype of TBL1XR1 mutations and provides a realistic and reliable basis for clinicians.

Children with infectious pneumonia caused by Ralstonia insidiosa: A case report.

BACKGROUND: Ralstonia is a Gram-negative non-fermentative bacterium widespread in nature, and includes four species, Ralstonia pickettii, Ralstonia solanacearum, Ralstonia mannitolilytica, and Ralstonia insidiosa, which were proposed in 2003. Ralstonia is mainly found in the external water environment, including municipal and medical water purification systems. This bacterium has low toxicity and is a conditional pathogen. It has been reported in recent years that infections due to Ralstonia are increasing. Previous studies have shown that most cases of infection are caused by Ralstonia pickettii, a few by Ralstonia mannitolilytica, and infections caused by Ralstonia insidiosa are rare. CASE SUMMARY: A 2-year-old Chinese child suffered from intermittent fever and cough for 20 d and was admitted to hospital with bronchial pneumonia. Bronchoscopy and alveolar lavage fluid culture confirmed Ralstonia insidiosa pneumonia. The infection was well controlled after treatment with meropenem and azithromycin. CONCLUSION: Ralstonia infections are increasing, and we report a rare case of Ralstonia insidiosa infection in a child. Clinicians should be vigilant about Ralstonia infections.

Clinical manifestations and gene analysis of Hutchinson-Gilford progeria syndrome: A case report.

BACKGROUND: This case report describes a child with Hutchinson-Gilford progeria syndrome (HGPS, OMIM: 176670) caused by LMNA (OMIM: 150330) gene mutation, and we have previously analyzed the clinical manifestations and imaging characteristics of this case. After 1-year treatment and follow-up, we focus on analyzing the changes in the clinical manifestations and genetic diagnosis of the patient. CASE SUMMARY: In April 2020, a 2-year-old boy with HGPS was found to have an abnormal appearance, and growth and development lagged behind those of children of the same age. The child's weight did not increase normally, the veins of the head were clearly visible, and he had shallow skin color and sparse yellow hair. Peripheral blood DNA samples obtained from the patient and his parents were sequenced using high-throughput whole-exosome sequencing, which was verified by Sanger sequencing. The results showed that there was a synonymous heterozygous mutation of C.1824 C>T (P. G608G) in the LMNA gene. CONCLUSION: Mutation of the LMNA gene provides a molecular basis for diagnosis of HGPS and genetic counseling of the family.

Novel compound heterozygous variants in the TAF6 gene in a patient with Alazami-Yuan syndrome: A case report.

BACKGROUND: This case report describes a novel genotypic and phenotypic presentation of Alazami-Yuan syndrome, and contributes to the current knowledge on the condition. CASE SUMMARY: We report an 11-year-old boy with Alazami-Yuan syndrome. The main clinical manifestations were rapid development of puberty, typical facial features of Cornelia de Lange syndrome, and normal intelligence. Peripheral blood DNA samples obtained from the patient and his parents were sequenced using high-throughput whole-exosome sequencing, which was verified by Sanger sequencing. The results showed that there was a compound heterozygous mutation of c.1052delT and c.76A>T in the TATA-Box Binding Protein Associated Factor 6 (TAF6) gene. The mutation of c.1052delT was from his mother and the mutation of c.76A>T was from his father. CONCLUSION: This study extends the mutation spectrum of the TAF6 gene, and provides a molecular basis for the etiological diagnosis of Alazami-Yuan syndrome and genetic consultation for the family.

Two novel mutations in the VPS33B gene in a Chinese patient with arthrogryposis, renal dysfunction and cholestasis syndrome 1: A case report.

BACKGROUND: The VPS33B (OMIM: 608552) gene is located on chromosome 15q26.1. We found a female infant with autosomal recessive arthrogryposis, renal dysfunction and cholestasis syndrome 1 (ARCS1) caused by mutation in VPS33B. The child was diagnosed with ARCS1 (OMIM: 208085) after the whole exome sequencing revealed two heterozygous mutations (c.96+1G>C, c.242delT) in the VPS33B gene. CASE SUMMARY: We report a Chinese female infant with neonatal cholestasis disorder, who was eventually diagnosed with ARCS1 by genetic analysis. Genetic testing revealed two new mutations (c.96+1G>C and c.242delT) in VPS33B, which is the causal gene. The patient was compound heterozygous, and her parents were both heterozygous. CONCLUSION: This study extends the mutational spectrum of the VPS33B gene to provide a molecular basis for the etiological diagnosis of ARCS1 and for genetic counseling of the family.

VARS2 gene mutation leading to overall developmental delay in a child with epilepsy: A case report.

BACKGROUND: The mitochondrial respiratory chain defects have become the most common cause of neurometabolic disorders in children and adults, which can occur at any time in life, often associated with neurological dysfunction, and lead to chronic disability and premature death. Approximately one-third of patients with mitochondrial disease have biochemical defects involving multiple respiratory chain complexes, suggesting defects in protein synthesis within the mitochondria. We here report a child with VARS2 gene mutations causing mitochondrial disease. CASE SUMMARY: A girl, aged 3 years and 4 mo, had been unable to sit and crawl alone since birth, with obvious seizures and microcephaly. Brain magnetic resonance imaging showed symmetrical, flaky, long T1-weighted and low T2-weighted signals in the posterior part of the bilateral putamen with a high signal shadow. T2 fluid-attenuated inversion recovery imaging showed a slightly high signal and diffusion-weighted imaging showed an obvious high signal. Whole-exome gene sequencing revealed a compound heterozygous mutation in the VARS2 gene, c.1163(exon11)C>T and c.1940(exon20)C>T, which was derived from the parents. The child was diagnosed with combined oxidative phosphorylation deficiency type 20. CONCLUSION: In this patient, mitochondrial disorders including Leigh syndrome and MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) were ruled out, and combined oxidative phosphorylation deficiency type 20 was diagnosed, expanding the phenotypic spectrum of the disease.

Novel frameshift mutation in the AHDC1 gene in a Chinese global developmental delay patient: A case report.

BACKGROUND: Xia-Gibbs syndrome (XGS, OMIM: 615829), caused by mutations within the AT-Hook DNA-binding motif-containing protein 1 (AHDC1) gene (OMIM: 615790), located on the short arm of chromosome 1 within the cytogenetic band 1p36.11, contains five noncoding 5 exons, a single 4.9-kb coding exon, and a noncoding 3 exon. CASE SUMMARY: In this case report, we diagnosed and treated a 6-mo-old girl with XGS. The primary clinical symptoms included global developmental delay, hypotonia, and mild dysmorphic features. Using high-throughput whole-exosome sequencing to sequence the patient and her parents, and the results showed a novel frameshift mutation of c.1155dupG (p.Arg386Alafs*3) in the AHDC1 gene. The paternal gene was wild type. CONCLUSION: This report extends the mutation spectrum of the AHDC1 gene to provide the diagnostic basis for genetic counseling in families with XGS.

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Elucidating the interannual variation of soil organic nitrogen fractions and its response to straw returning is of great significance for rational regulation of soil organic nitrogen pool and sustainable soil utilization. We conducted a field microcosm experiment with typic hapludoll soil at the National Field Observation and Research Station of Shenyang Agroecosystems. Three treatments were set, including nitrogen fertilizer addition (200 kg N·hm-2, the same in other treatments), nitrogen fertilizer addition with 50% straw return, and nitrogen fertilizer addition with 100% straw return. We classified soil organic nitrogen fractions in the 1st, 3rd, 6th, and 9th years of the experiment by using the Bremner acid hydrolysis method. The results showed that the content of amino acid nitrogen increased with the tillage years, with an increase rate of 39.8% compared with 1st year. The content of hydrolyzable unknown nitrogen increased by 10.8% compared with 1st year, which reached the highest in the 3rd year. The content of total soil nitrogen and other organic nitrogen fractions showed limited variation with tillage years. The proportion of hydrolyzable total nitrogen that is relatively easy to mineralize in the total soil nitrogen gradually increased with the tillage years, and that of relatively stable acid insoluble nitrogen to total soil nitrogen gradually decreased, indicating that soil nitrogen availability increased with the tillage years, which would facilitate the soil nitrogen supply capacity. Compared with the treatment without straw returning, adding straw improved soil total nitrogen and each hydrolyzable nitrogen contents, with such positive effect be stronger under the treatment with heavier straw returning. The effect of straw returning on hydrolyzable nitrogen fractions mainly occurred in the 6th and 9th years. The components of soil total nitrogen that have been increased were mainly the amino acid nitrogen and hydrolyzed unknown nitrogen, resulting in increased proportion of hydrolyzable nitrogen. Straw returning could increase soil nitrogen pool and improve soil nitrogen conservation and supply capacity.

Novel compound heterozygous variants in the LHX3 gene caused combined pituitary hormone deficiency: A case report.

BACKGROUND: Combined pituitary hormone deficiency 3 (CPHD3; OMIM: 221750) is caused by mutations within the LHX3 gene (OMIM: 600577), which located on the subtelomeric region of chromosome 9 at band 9q34.3, has seven coding exons and six introns. LIM homeobox (LHX) 3 protein is the key regulator of pituitary development in fetal life. CASE SUMMARY: We have diagnosed and treate an 11-year-old boy with combined pituitary hormone deficiency (CPHD). The main clinical manifestations were pituitary hormone deficiency, hydrocele of the tunica vaginalis, pituitary dwarfism, gonadal dysplasia, micropenis, clonic convulsion, and mild facial dysmorphic features. We collected peripheral blood from the patient, the patient's older brother, as well as their parents, and sequenced them by using high-throughput whole-exosome sequencing, which was verified by Sanger sequencing. The results showed that there were two compound heterozygous variants of c.613G>C (p.V205L) and c.220T>C (p.C74R) in the LHX3 gene. c.613G>C (p.V205L) was inherited from his mother and c.220T>C (p.C74R) from his father. His brother also has both variants and symptoms. CONCLUSION: This study reported ununreported genetic mutations of LHX3, and recorded the treatment process of the patients, providing data for the diagnosis and treatment of CPHD.

Retroperitoneal leiomyoma located in the broad ligament: A case report.

BACKGROUND: Retroperitoneal leiomyoma is a rare benign tumor. Retroperitoneal leiomyomas located in the latissimus uterine ligament are even rarer. Retroperitoneal leiomyomas have similar characteristics to uterine leiomyomas in terms of tissue, which results in confusion during diagnosis. CASE SUMMARY: A 47-year-old female with 3 years of pain in the right lower quadrant and discovery of a pelvic mass 13 d ago underwent open abdominal exploration. In the right broad ligament, a solid mass with well circumscribed boundaries, approximately 15 cm × 10 cm × 10 cm in size was bluntly peeled off. The pathological result was a spindle cell tumor, morphologically considered to originate from smooth muscle. Immunohistochemical results supported a deep soft tissue leiomyoma. CONCLUSION: Retroperitoneal leiomyoma is a rare benign tumor, and surgical treatment can have a good therapeutic effect.

Autism with dysphasia accompanied by mental retardation caused by FOXP1 exon deletion: A case report.

BACKGROUND: Forkhead box protein 1 (FOXP1) (OMIM: 605515) at chromosomal region 3p14.1 plays an important regulatory role in cell development and functions by regulating genetic expression. Earlier studies have suggested that FOXP1, an oncogene, is capable of initiating tumorigenicity depending on the cell type. FOXP1 also plays an important role in regulating the cell development and functions of the immune system, e.g., regulating B-cell maturation and mononuclear phagocyte differentiation, and in the occurrence and development of various immune diseases. The mRNA of this gene is widely expressed in humans, and its differential expression is related to numerous diseases. CASE SUMMARY: A 5-year-old boy mainly presented with attention deficit and hyperactivity disorder and developmental retardation accompanied by gait instability and abnormal facial features (low-set ears). DNA samples were extracted from the child's and his parents' peripheral blood to detect whole-exome sequences and whole-genome copy number variations. Results revealed heterozygous deletions of exon 6-21 of FOXP1 gene in the child. Physical examination upon admission showed that the child was generally in good condition, had a moderate nutritional status, a slightly slow response to external stimuli, equally large and equally round bilateral pupils, was sensitive to light reflection, and had poor eye contact and joint attention. He had no meaningful utterance and could not pronounce words properly. He was able to use gestures to simply express his thoughts, to perform simple actions, and to listen to instructions. He had no rash, cafe-au-lait macules, or depigmentation spots. He had thick black hair and low-set ears. He had highly sensitive skin, especially on his face and palms. He had no abnormal palm fingerprint. Cardiopulmonary and abdominal examinations revealed no abnormalities. He had normal limb muscle strength and tension. He showed normal tendon reflexes of both knees. His bilateral Babinski and meningeal irritation signs were negative. He had a normal male vulva. CONCLUSION: We report the characteristic features of autism with dysphasia accompanied by mental retardation caused by FOXP1 exon deletion. This study provides a molecular basis for etiological diagnosis and treatment of the child, as well as for genetic counseling for the pedigree.

Dynamically loading IFC models on a web browser based on spatial semantic partitioning.

Industry foundation classes (IFC) is an open and neutral data format specification for building information modeling (BIM) that plays a crucial role in facilitating interoperability. With increases in web-based BIM applications, there is an urgent need for fast loading large IFC models on a web browser. However, the task of fully loading large IFC models typically consumes a large amount of memory of a web browser or even crashes the browser, and this significantly limits further BIM applications. In order to address the issue, a method is proposed for dynamically loading IFC models based on spatial semantic partitioning (SSP). First, the spatial semantic structure of an input IFC model is partitioned via the extraction of story information and establishing a component space index table on the server. Subsequently, based on user interaction, only the model data that a user is interested in is transmitted, loaded, and displayed on the client. The presented method is implemented via Web Graphics Library, and this enables large IFC models to be fast loaded on the web browser without requiring any plug-ins. When compared with conventional methods that load all IFC model data for display purposes, the proposed method significantly reduces memory consumption in a web browser, thereby allowing the loading of large IFC models. When compared with the existing method of spatial partitioning for 3D data, the proposed SSP entirely uses semantic information in the IFC file itself, and thereby provides a better interactive experience for users.

Exploratory analysis of early treatment discontinuation and clinical outcomes of patients with attention-deficit/hyperactivity disorder.

INTRODUCTION: This post-hoc analysis was to investigate the impact of treatment discontinuation on clinical outcomes in patients with attention-deficit/hyperactivity disorder (ADHD). METHODS: Data are from a 12-month, observational, multinational study that included outpatients aged 6-17 years who were diagnosed with ADHD and treated with atomoxetine, methylphenidate, or nootropic agents. Treatment effectiveness and proportions of patients who discontinued treatment were compared between China and the other non-Western countries/regions combined. Propensity score matching was used to further estimate the association between treatment discontinuation and effectiveness. RESULTS: Of the 546 patients who entered the study, 337 patients had complete data and were included in the analyses. Compared with the other countries/regions, China subgroup had a higher treatment discontinuation rate (odds ratio = 25.80; P < 0.0001) and poorer treatment effectiveness: least-squares (LS) mean changes were 5.74 versus 8.56 (P = 0.0225) for the Child Health and Illness Profile-Child Edition (CHIP-CE) Achievement domain and -1.87 versus -2.13 (P = 0.0401) for Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S). Further analyses of matched discontinuer-maintainer pairs showed that discontinuers demonstrated poorer effectiveness: LS mean changes for the CHIP-CE Achievement domain and CGI-ADHD-S (discontinuer versus maintainer) were 5.36 versus 9.10 (P = 0.0255) and -1.32 versus -1.96 (P = 0.0179) for overall population, respectively, and 4.40 versus 10.17 (P = 0.0065) and -1.48 versus -2.45 (P = 0.0089), respectively, for China subgroup. DISCUSSION: This analysis found that early treatment discontinuation was associated with worse clinical outcomes for patients with ADHD. China subgroup had substantially higher discontinuation rates and poorer effectiveness outcomes. Strategies to improve medication persistence have the potential to improve outcomes for ADHD patients in China.