NEXMIF Combined with KIDINS220 Gene Mutation Caused Neurodevelopmental Disorder and Epilepsy: One Case Report.

of Medical History: A male infant, 8 months old, was admitted to hospital with cough and fever. The clinical symptoms were found to be mental retardation, obesity, dystonia, movement limitation, and visual retardation. Early development was normal, but after 6 months, the child developed upright head instability, difficulty grasping, and seizures. Symptoms and Signs: The child presents with mental retardation, obesity, increased muscle tone, motor dysfunction, visual impairment, and seizures. DIAGNOSIS: A whole exon test was performed to detect a neurite extension and migration factor (NEXMIF) gene mutation (NM_001008537.2: c.1042C > T (p. Arg348*)), which is known to be associated with intellectual disability and neurological symptoms. In addition, the test revealed a mutation in the Kinase D interacting substrate of 220 kDa (KIDINS220) gene (NM_020738.2: c.3242_3243insC (p. Leu1082AIafs*5)) with a heterozygous mutation in the father and wild type in the mother. TREATMENT: The patient was treated with anti-infection, aerosol inhalation, calcium supplement, and anti-epileptic drugs (levetiracetam), and the disease was controlled. Home and hospital rehabilitation is also underway. CLINICAL OUTCOME: The condition of the child improved after treatment and no seizures occurred again. The patient needs continuous rehabilitation treatment and follow-up observation. CONCLUSION: For male children with unexplained neurodevelopmental disorders and comorbidities such as obesity, dystonia, and seizures, mutations in related genes such as NEXMIF should be considered. Clinical practice should improve genetic testing as early as possible to provide a basis for genetic counseling.

H2O2-activated in situ polymerization of aniline derivative in hydrogel for real-time monitoring and inhibition of wound bacterial infection.

Wound is highly susceptible to bacterial infection, which can cause chronic wound and serial complications. However, timely treatment is hampered by the lack of real-time monitoring of wound status and effective therapeutic systems. Herein, in situ biosynthesis of functional conjugated polymer in artificial hydrogel was developed via the utilization of biological microenvironment to realize monitoring in real time of wound infection and inhibition of bacteria for the first time. Specially, an easily polymerizable aniline dimer derivative (N-(3-sulfopropyl) p-aminodiphenylamine, SPA) was artfully in situ polymerized into polySPA (PSPA) in calcium alginate hydrogel, which was initiated via the catalysis of hydrogen peroxide (H2O2) overexpressed in infected wound to produce hydroxyl radical (•OH) by preloaded horseradish peroxidase (HRP). Benefitting from outstanding near infrared (NIR) absorption of PSPA, such polymerization can be ingeniously used for real-time monitoring of H2O2 via naked-eye and photoacoustic signal, as well as NIR light-mediated photothermal inhibition of bacteria. Furthermore, combining the persistent chemodynamic activity of •OH, the in vivo experimental data proved that the wound healing rate was 99.03% on the 11th day after treatment. Therefore, the present work opens the way to manipulate in situ biosynthesis of functional conjugated polymer in artificial hydrogels for overcoming the issues on wound theranostics.

An Extremely Streamlined Macronuclear Genome in the Free-Living Protozoan Fabrea salina.

Ciliated protists are among the oldest unicellular organisms with a heterotrophic lifestyle and share a common ancestor with Plantae. Unlike any other eukaryotes, there are two distinct nuclei in ciliates with separate germline and somatic cell functions. Here, we assembled a near-complete macronuclear genome of Fabrea salina, which belongs to one of the oldest clades of ciliates. Its extremely minimized genome (18.35 Mb) is the smallest among all free-living heterotrophic eukaryotes and exhibits typical streamlined genomic features, including high gene density, tiny introns, and shrinkage of gene paralogs. Gene families involved in hypersaline stress resistance, DNA replication proteins, and mitochondrial biogenesis are expanded, and the accumulation of phosphatidic acid may play an important role in resistance to high osmotic pressure. We further investigated the morphological and transcriptomic changes in the macronucleus during sexual reproduction and highlighted the potential contribution of macronuclear residuals to this process. We believe that the minimized genome generated in this study provides novel insights into the genome streamlining theory and will be an ideal model to study the evolution of eukaryotic heterotrophs.

Discovery of new genetic loci for male sexual orientation in Han population.

Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB, Pmeta = 8.36 × 10-8, OR = 1.29; rs7259428, 19q12, ZNF536, Pmeta = 7.58 × 10-8, OR = 0.75) showing consistent association with male sexual orientation. A fixed-effect meta-analysis including individuals of Han Chinese (n = 4791) and European ancestries (n = 408,995) revealed 3 genome-wide significant loci of same-sex sexual behavior (rs9677294, 2p22.1, SLC8A1, Pmeta = 1.95 × 10-8; rs2414487, 15q21.3, LOC145783, Pmeta = 4.53 × 10-9; rs2106525, 7q31.1, MDFIC, Pmeta = 6.24 × 10-9). These findings may provide new insights into the genetic basis of male sexual orientation from a wider population scope. Furthermore, we defined the average ZNF536-immunoreactivity (ZNF536-ir) concentration in the suprachiasmatic nucleus (SCN) as lower in homosexual individuals than in heterosexual individuals (0.011 ± 0.001 vs 0.021 ± 0.004, P = 0.013) in a postmortem study. In addition, compared with heterosexuals, the percentage of ZNF536 stained area in the SCN was also smaller in the homosexuals (0.075 ± 0.040 vs 0.137 ± 0.103, P = 0.043). More homosexual preference was observed in FMR1NB-knockout mice and we also found significant differences in the expression of serotonin, dopamine, and inflammation pathways that were reported to be related to sexual orientation when comparing CRISPR-mediated FMR1NB knockout mice to matched wild-type target C57 male mice.

Phenotypic and genomic characterization of a Vibrio parahaemolyticus strain causing disease in Penaeus vannamei provides insights into its niche adaptation and pathogenic mechanism.

The virulence of Vibrio parahaemolyticus is variable depending on its virulence determinants. A V. parahaemolyticus strain, in which the virulence is governed by the pirA and pirB genes, can cause acute hepatopancreatic necrosis disease (AHPND) in shrimps. Some V. parahaemolyticus that are non-AHPND strains also cause shrimp diseases and result in huge economic losses, while their pathogenicity and pathogenesis remain unclear. In this study, a non-AHPND V. parahaemolyticus, TJA114, was isolated from diseased Penaeus vannamei associated with a high mortality. To understand its virulence and adaptation to the external environment, whole-genome sequencing of this isolate was conducted, and its phenotypic profiles including pathogenicity, growth characteristics and nutritional requirements were investigated. Shrimps following artificial infection with this isolate presented similar clinical symptoms to the naturally diseased ones and generated obvious pathological lesions. The growth characteristics indicated that the isolate TJA114 could grow well under different salinity (10-55 p.p.t.), temperature (23-37 °C) and pH (6-10) conditions. Phenotype MicroArray results showed that this isolate could utilize a variety of carbon sources, amino acids and a range of substrates to help itself adapt to the high hyperosmotic and alkaline environments. Antimicrobial-susceptibility test showed that it was a multidrug-resistant bacterium. The whole-genomic analysis showed that this V. parahaemolyticus possessed many important functional genes associated with multidrug resistance, stress response, adhesions, haemolysis, putative secreted proteases, dedicated protein secretion systems and a variety of nutritional metabolic mechanisms. These annotated functional genes were confirmed by the phenotypic profiles. The results in this study indicated that this V. parahaemolyticus isolate possesses a high pathogenicity and strong environmental adaptability.

Myc is involved in Genistein protecting against LPS-induced myocarditis in vitro through mediating MAPK/JNK signaling pathway.

BACKGROUND: Genistein is widely used as a pharmacological compound as well as a food additive. However, the pharmaceutical effects of Genistein on myocarditis and its potential mechanisms have not been studied in detail. METHODS: H9c2 cells were continuously stimulated by lipopolysaccharide (LPS) for 12 h to simulate the in vitro model of myocarditis injury. DrugBank, String, and GEO dataset were used to investigate specific genes that interacting with Genistein. KEGG and GO enrichment analysis were employed to explore Myc-related signaling pathways. Biological behaviors of H9c2 cells were observed with the support of cell counting kit-8, MTT and flow cytometry. Expression levels of cytokines including TNF-α and ILs were evaluated by enzyme-linked immunosorbent assay. Western blot was applied to detect the expression of Myc and MAPK pathway related proteins. RESULTS: Genistein alleviated the damage of H9c2 cells subjected to LPS from the perspective of elevating cells growth ability, and inhibiting cells apoptosis and inflammatory response. Through bioinformatics analysis, we identified Myc as the potential target of Genistein in myocarditis, and MAPK as the signaling pathway. Significantly, Myc was highly up-regulated in myocarditis samples. More importantly, by performing biological experiments, we discovered that Genistein relieved H9c2 cells apoptosis and inflammatory reaction which caused by LPS stimulation through inhibiting Myc expression. Additionally, the marked augmentation of p-P38 MAPK and p-JNK expression in LPS-induced cardiomyocyte model were blocked by Genistein and si-Myc. CONCLUSIONS: Our research revealed that Myc mediated the protective effects of Genistein on H9c2 cells damage caused by LPS partly through modulation of MAPK/JNK signaling pathway.

Freshwater snail Parafossarulus striatulus estrogen receptor: Characteristics and expression profiles under lab and field exposure.

The modes of action by which putative endocrine disrupting chemicals (EDCs) elicit toxicity in mollusks remains unclear due to our limited understanding of the molluscan endocrine system. We identified and partially characterised the estrogen receptor (ER) of the mollusk Parafossarulus striatulus. The full-length cDNA of the ER of P. striatulus (psER) was isolated and found to have an ORF of 1386 bp which corresponded to 461 amino acids. Phylogenetic analysis revealed that psER is an orthologue of ER of other mollusks. Moreover, the DNA-binding domain, ligand-binding domain, P-box, D-box, and AF2 domain were also identified in psER. Exposure of females and males to 17ß-estradiol (E2, 100 ng/L) for 24 h and 72 h did not alter psER transcription, but exposure to 17α-methyltestosterone (MT, 100 µg/L) for 72 h significantly decreased ER transcription in females only (p < 0.05). psER transcription was surveyed in males and females seeded in different regions in Taihu Lake, China. psER transcription were elevated among females and males maintained at site ML. This elevation was statistically significant (p < 0.05) among male snails as compared to snails held at the more pristine site of SZ. This was different to the results from lab, implying that some unknown chemicals or other environmental factors in field could affect psER transcription level in snails. Furthermore, females and males held at site ML also exhibited a significant elevation in vitellogenin transcription as compared to snails held at site SZ, suggesting that vitellogenin production may be directly regulated by psER or co-regulated with psER in this species.

Morphology, morphogenesis and molecular phylogeny of a new brackish water subspecies, Neourostylopsis flava paraflava nov. subsp. (Ciliophora, Hypotrichia, Urostylidae), with redefinition of the genus Neourostylopsis.

The morphology, morphogenesis and small subunit (SSU) rRNA gene-based phylogeny of Neourostylopsis flava paraflava nov. subsp. were investigated. Neourostylopsis flava paraflava nov. subsp. was separated from N. flava flava nov. stat. by habitat (brackish water vs. fresh water), pretransverse cirri (absent in all specimens vs. present in 15% of specimens), the numbers of frontal cirri (8-15 vs. 6-8) and left marginal cirral rows (6-9 vs. 4-5). The main morphogenetic features of N. flava paraflava nov. subsp. are as follows: (1) streaks I-VI (or I-VIII, deduced from morphological data) produce the bicorona; (2) the oral primordium and frontoventral-transverse cirral anlagen in the opisthe are formed de novo on the cell surface; (3) the numerous macronuclear nodules fuse into a branch-like mass; (4) two pretransverse ventral cirri are formed initially but disappear in the later stages; and (5) some of the frontoventral-transverse cirral anlagen develop in a primary mode. Based on SSU rDNA sequence data, phylogenetic analyses show a close relationship between N. flava paraflava nov. subsp., N. flava flava nov. stat. and other Neourostylopsis species. An improved diagnosis for Neourostylopsis is provided: Urostylidae with five or more frontal cirri which form an indistinct or distinct bicorona; pretransverse cirri present or absent; transverse cirri present; buccal cirri present; two frontoterminal cirri; midventral complex composed of midventral pairs only; more than one row of marginal cirri on each side which derive from individual anlagen within each parental row; caudal cirri lacking; three dorsal kineties; endoral and paroral rather long, endoral straight, paroral distinctly curved anteriorly.

A randomized, 13-week study assessing the efficacy and metabolic effects of paliperidone palmitate injection and olanzapine in first-episode schizophrenia patients.

BACKGROUND: This study was conducted to evaluate the efficacy and metabolic effects of paliperidone palmitate (PP) injections against oral olanzapine in first-episode schizophrenia (FES) patients. METHODS: Eligible patients were randomized to receive PP or olanzapine. Efficacy assessments and weight-related parameters were assessed at baseline, weeks 1, 5, 9, and endpoint or at early withdrawal. Lipid, glucose, insulin and prolactin were evaluated at baseline and endpoint or at early withdrawal. RESULTS: The Positive And Negative Syndrome Scale (PANSS) scores declined significantly after treatment in both groups. Significant increases in weight-related parameters from baseline to endpoint were shown in both groups. Although there was no significant difference in PANSS scores and weight-related parameters between the two groups through the whole 13-week study. The increased level of triglyceride and HOMA-IR at endpoint from baseline in the olanzapine group was higher than the PP group. There was a stronger elevation of prolactin level in the PP group. CONCLUSIONS: In summary, PP and olanzapine showed similar improvement in the treatment of FES patients. This study also reinforced the necessity for regular monitoring of metabolic parameters in schizophrenia patients prescribed atypical antipsychotics. Clinical trial registration numbers: ChiCTR-IOR-14005304. Date of registration: 2014-10-11.

Effects of storage temperature and time of antimony release from PET bottles into drinking water in China.

Antimony (Sb) concentrations were measured in 10 brands of PET bottled drinking water available in supermarkets in China. To simulate general storage habits based on market research, these PET bottles with drinking water were stored for 4 weeks in a lab or a car trunk during the summer. Although the PET package material of brand A had the lowest Sb level (142.71 ± 29.81 µg/g), it showed a significant increase in Sb concentrations when stored in both the car trunk and the lab. There was significant release of Sb from the PET bottles into the water following 24 h of incubation at ≥ 40 °C (40, 50, 60, and 70 °C), especially at 70 °C. The potential health risk of Sb release from PET bottles was calculated based on daily intake values and determined to be acceptable for consumers under normal storage conditions.

Transcriptomic responses of the freshwater snail (Parafossarulus striatulus) following dietary exposure to cyanobacteria.

Freshwater snails are promising bioindicators that can be used in ecotoxicological testing and ecological risk assessments. To screen molecular responses following mollusk exposure to algal blooms, whole transcriptome sequencing was performed with the freshwater snail (Parafossarulus striatulus) fed with blue algae (Microcystis aeruginosa). A total of 86,848 unigenes were assembled, and 10,413 unigenes were annotated in the TrEMBL, Pfam, KEGG, and SwissProt databases. In snails fed with both green and blue algae, a total of 276 differentially expressed unigenes were identified, though there were limited differences in snails fed with only green algae. In addition, ten randomly selected differentially expressed unigenes were analyzed in snails collected from Taihu Lake, China. The expression of four unigenes exhibited a trend consistent with that observed in transcriptome profiling of laboratory snails. The results of this study provide an invaluable resource for enhancing our understanding of ecotoxicology following the occurrence of algal blooms in lakes.

Microplastics releasing from personal care and cosmetic products in China.

Microplastics (MPs) have become a major global issue; their release from various products affects the aquatic environment, especially marine ecosystems. As a primary source of MPs, personal care and cosmetics products (PCCPs) containing MPs contribute to this environmental risk. We visited several supermarket chains in Beijing, China to identify PCCPs containing MPs. Overall, 7.1% of facial cleansers contained MPs, with an average weight of 25.04±10.69mgMP/g and average size of 313±130µm; whereas, 2.2% of shower gel products contained an average weight of 17.80±7.50mgMPs/g with an average size of 422±185µm. The majority of MPs were made of polyethylene, based on Raman and Fourier transform-infrared spectra analyses, while only a few were made of walnut shells and carbon particles. Finally, estimated 39tons MPs were released into the environment based on PCCPs use in China based on available data.

Preliminary evidence for snail deformation from a Eutrophic lake.

The incidence of deformities in snails Bellamya aeruginosa was investigated in a typical eutrophicated lake - Taihu Lake. A total of 15 105 specimens were collected, and 0.18-0.93% of the snails exhibited abnormal tentacle bifurcations. Abnormally developed snails were all female and were found in regions with relatively high Chlorophyll a levels (12.40±7.23µg/L). As tentacles are sexually dimorphic in B. aeruginosa, we postulated that factors associated with eutrophication might be responsible for the partial masculinization of tentacles in females. Differential gene expression analyses revealed that a number of unigenes were significantly up-regulated or down-regulated in snails sampled from three locations having high Chlorophyll a levels compared with snails sampled from the region with lower Chlorophyll a level (2.95µg/L). Thus, transcriptomic profiling revealed potential molecular signal of eutrophication that can lead to developmental abnormalities in this species.

Relationships between dorsolateral prefrontal cortex metabolic change and cognitive impairment in first-episode neuroleptic-naive schizophrenia patients.

The present study aimed to explore the possible associations between the dorsolateral prefrontal cortex (DLPFC) metabolites and the cognitive function in first-episode schizophrenia (FES).This study included 58 patients with FES (29 males and 29 females; mean age, 22.66 ±â€Š7.64 years) recruited from the First Affiliated Hospital, College of Medicine, Zhejiang University, and 43 locally recruited healthy controls (16 males and 27 females; mean age, 23.07 ±â€Š7.49 years). The single-voxel proton magnetic resonance spectroscopy was used to measure the levels of N-acetylaspartate (NAA); complex of glutamate, glutamine, and γ-aminobutyric acid (Glx); choline-containing compounds; and myo-inositol in the DLPFC. The ratios of metabolites to creatine (Cr) were calculated. The cognitive function was assessed by Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). Correlation analysis was used to assess the relationships between the DLPFC metabolites and the cognitive function.Compared with the healthy controls, the patients with FES showed significantly reduced scores in each part of the MCCB, significantly reduced NAA/Cr, and significantly increased Glx/Cr in the left DLPFC. Poor performance in verbal learning and visual learning was correlated to the reduced NAA/Cr ratio in the left DLPFC.These findings suggest that a lower NAA/Cr ratio in the left DLPFC is associated with the cognitive deficits in patients with FES, and may be an early biochemical marker for the cognitive impairment in schizophrenia.

Circulating T lymphocyte subsets, cytokines, and immune checkpoint inhibitors in patients with bipolar II or major depression: a preliminary study.

This study aimed to investigate the less known activation pattern of T lymphocyte populations and immune checkpoint inhibitors on immunocytes in patients with bipolar II disorder depression (BD) or major depression (MD). A total of 23 patients with BD, 22 patients with MD, and 20 healthy controls (HCs) were recruited. The blood cell count of T lymphocyte subsets and the plasma level of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were selectively investigated. The expression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), programmed cell death protein 1 (PD-1) and its ligands, PD-L1 and PD-L2, on T lymphocytes and monocytes, was detected. In results, blood proportion of cytotoxic T cells significantly decreased in BD patients than in either MD patients or HCs. The plasma level of IL-6 increased in patients with BD and MD. The expression of TIM-3 on cytotoxic T cells significantly increased, whereas the expression of PD-L2 on monocytes significantly decreased in patients with BD than in HCs. These findings extended our knowledge of the immune dysfunction in patients with affective disorders.

Relationship between negative symptoms and neurocognitive functions in adolescent and adult patients with first-episode schizophrenia.

BACKGROUND: This study aimed to explore differences in links between negative symptoms and neurocognitive deficits in adolescent and adult patients with first-episode schizophrenia. Schizophrenia is a mental disorder often characterized by positive and negative symptoms, reduced emotional expression, excitatory status, and poor cognitive ability. The severity of negative symptoms in patients with schizophrenia was reported to be more related to poor quality of life, weak functional ability, and heavy burden from families than with the severity of positive symptoms. Previous studies suggested correlations between the severity of negative symptoms in patients with schizophrenia and neurocognitive deficits. METHODS: This study included 92 patients (33 adolescents and 59 adults) with first-episode schizophrenia and 57 healthy people matched by age and education level. Neurocognitive functions and clinical symptoms were assessed using a standardized questionnaire. RESULTS: Patients with first-episode schizophrenia showed neurocognitive deficits in most neuropsychological assessments compared with healthy people. With the variable of education level controlled, the negative factor score of adolescent patients with first-episode schizophrenia was strongly correlated with more time spent in part 1 (r = .646) and part 2 (r = .663) of the trail making test, and moderately correlated to more perseverative errors (r = .425) of the Wisconsin card sorting test and fewer correct trials 2 (r = -.425) of the continuous performance test. However, no such correlations were found in adult patients. CONCLUSIONS: This study indicated significant correlations between negative symptoms and most neurocognitive functions in patients with first-episode schizophrenia, with a stronger correlation in adolescent patients. TRIAL REGISTRATION: The trial registration number is ChiCTR-COC-14005302 , while retrospectively registered on January 5, 2014.

Efficacy of repetitive transcranial magnetic stimulation with quetiapine in treating bipolar II depression: a randomized, double-blinded, control study.

The clinical and cognitive responses to repetitive transcranial magnetic stimulation (rTMS) in bipolar II depressed patients remain unclear. In this study, thirty-eight bipolar II depressed patients were randomly assigned into three groups: (i) left high-frequency (n = 12), (ii) right low-frequency (n = 13), (iii) sham stimulation (n = 13), and underwent four-week rTMS with quetiapine concomitantly. Clinical efficacy was evaluated at baseline and weekly intervals using the 17-item Hamilton Depression Rating Scale (HDRS-17) and Montgomery-Asberg Depression Rating Scale (MADRS). Cognitive functioning was assessed before and after the study with the Wisconsin Card Sorting Test (WCST), Stroop Word-Color Interference Test (Stroop), and Trail Making Test (TMT). Thirty-five patients were included in the final analysis. Overall, the mean scores of both the HDRS-17 and the MADRS significantly decreased over the 4-week trial, which did not differ among the three groups. Exploratory analyses revealed no differences in factor scores of HDRS-17s, or in response or remission rates. Scores of WCST, Stroop, or TMT did not differ across the three groups. These findings indicated active rTMS combined with quetiapine was not superior to quetiapine monotherapy in improving depressive symptoms or cognitive performance in patients with bipolar II depression.

A wireless demodulation system for passive surface acoustic wave torque sensor.

Surface acoustic wave (SAW) resonators are utilized as torque sensors for their passive and wireless features. However, the response of a SAW torque sensor is difficult to detect because of the transient response duration and interruption of channel noise, which limit the application of SAW torque sensors. The sensitive mechanism and response function of a passive wireless SAW torque sensor are analyzed in this study. A novel demodulation system involving both hardware and software is developed for the SAW torque sensor. A clipping amplifier is utilized in the hardware to widen the dynamic response range and increase the length of the valid signal. Correlation extension and centroid algorithms are designed to lengthen the received signal and improve the estimation accuracy of the center frequency of the response signal, respectively. Meanwhile, a fast binary search algorithm is proposed to accelerate the scanning cycle according to the developed response function. Finally, the SAW torque sensor demodulation system is set up and SAW resonators with high sensitivity are fabricated on a quartz substrate. The presented demodulation system is tested, and a standard deviation of 0.28 kHz is achieved. This value is much smaller than that of classic and modern spectrum estimation methods. The sensitivity of resonance frequency shift versus torque on the shaft of the assembled senor is 2.03 kHz/Nm; the coefficient of determination is 0.999, and the linearity is 0.87%. Experimental results verify the validity and feasibility of the proposed SAW torque sensor demodulation system.