Fetal Hyperthyroidism with Maternal Hypothyroidism: Two Cases of Intrauterine Therapy.

Fetal hyperthyroidism can occur secondary to maternal autoimmune hyperthyroidism. The thyroid-stimulating hormone receptor antibody (TRAb) transferred from the mother to the fetus stimulates the fetal thyroid and causes fetal thyrotoxicosis. Fetuses with this condition are difficult to detect, especially after maternal Graves disease therapy. Here, we present two cases of fetal hyperthyroidism with maternal hypothyroidism and review the assessment and intrauterine therapy for fetal hyperthyroidism. Both women were referred at 22+ and 23+ weeks of gestation with abnormal ultrasound findings, including fetal heart enlargement, pericardial effusion, and fetal tachycardia. Both women had a history of Graves disease while in a state of hypothyroidism with a high titer of TRAb. A sonographic examination showed a diffusely enlarged fetal thyroid with abundant blood flow. Invasive prenatal testing revealed no significant chromosomal aberration. Low fetal serum TSH and high TRAb levels were detected in the cord blood. Fetal hyperthyroidism was considered, and maternal oral methimazole (MMI) was administered as intrauterine therapy, with the slowing of fetal tachycardia, a reduction in fetal heart enlargement, and thyroid hyperemia. During therapy, maternal thyroid function was monitored, and the dosage of maternal levothyroxine was adjusted accordingly. Both women delivered spontaneously at 36+ weeks of gestation, and neonatal hyperthyroidism was confirmed in both newborns. After methimazole and propranolol drug treatment with levothyroxine for 8 and 12 months, both babies became euthyroid with normal growth and development.

Doxorubicin-Loaded Liposome with the Function of "Killing Two Birds with One Stone" against Glioma.

The blood-brain barrier (BBB) continues to be one of the main clinical obstacles in the treatment of glioma. Current chemotherapies always bring many different side effects, some even permanent. To date, nanomaterial-based vehicles have shown great potential in treating glioma. Herein, we developed a dual targeting liposomal delivery vector loaded with the anticancer drug doxorubicin (DOX) to treat glioma. SS31, a small peptide, has shown dual targeting effects of penetrating the BBB and specifically targeting mitochondria. In this study, a new liposomal delivery system, LS-DOX, was prepared by modifying DOX-loaded liposomes with SS31 for the treatment of in situ glioma. The liposomes demonstrated a high drug encapsulation rate and drug-loading capacity, satisfactory biocompatibility, high glioma accumulation ability, and good stability in vitro. Experimental results showed that the liposomes could effectively cross the BBB and target gliomas, and mitochondria-targeting of SS31 enhances cell uptake. In addition, the liposomes showed a good therapeutic effect on nude mice with glioma in situ with no obvious toxicity and side effects. Therefore, the present research will provide a novel alternative and reference for the effective treatment of glioma.

Latent characteristics and influencing factors of stigma in rheumatoid arthritis: A latent class analysis.

To explore the latent classes of stigma in patients with rheumatoid arthritis, we analyzed the characteristics of the different categories. Adopting a convenient sampling method, socio-demographic and disease-related information from the outpatient clinics and wards of 3 tertiary care hospitals in China was collected. The Chinese version of the Internalized Stigma of Mental Illness scale-Rheumatoid Arthritis was used in this survey. Rheumatoid arthritis stigma was divided into 3 potential categories: Low Stigma-Strong Resistance (83, 41.5%), Medium Stigma-Strong Alienation (78, 39.0%), and High Stigma-Weak Resistance (39, 19.5%). Unordered multinomial logistic regression analysis showed that pain (OR = 1.540, P = .005; OR = 1.797, P < .001), elementary school education and below (OR = 4.051, P = .037), and duration of morning stiffness (OR = 0.267, P = .032) were risk factors for stigma, whereas family history was a protective factor against stigma (OR = 0.321, P = .046). Patients with longer morning stiffness, more severe pain, and less education have a greater risk of heavier stigma. Strong alienation is an early warning of heavy stigma. Resistance to stigma and family support can help patients overcome their psychological obstacles. More attention should be paid to constructing family centered support systems to help resist stigma.

DNA methylation and gene transcription act cooperatively in driving the adaptation of a marine diatom to global change.

Genetic changes together with epigenetic modifications such as DNA methylation have been demonstrated to regulate many biological processes and thereby govern the response of organisms to environmental changes. However, how DNA methylation might act cooperatively with gene transcription and thereby mediate the long-term adaptive responses of marine microalgae to global change is virtually unknown. Here we performed a transcriptomic analysis, and a whole-genome bisulfite sequencing, along with phenotypic analysis of a model marine diatom Phaeodactylum tricornutum adapted for 2 years to high CO2 and/or warming conditions. Our results show that the methylated islands (peaks of methylation) mCHH were positively correlated with expression of genes in the subregion of the gene body when the populations were grown under high CO2 or its combination with warming for ~2 years. We further identified the differentially expressed genes (DEGs), and hence the metabolic pathways in which they function, at the transcriptomics level in differentially methylated regions (DMRs). Although DEGs in DMRs contributed only 18-24% of the total DEGs, we found that those DEGs acted cooperatively with DNA methylation and then regulated key processes such as central carbon metabolism, amino acid metabolism, ribosome biogenesis, terpenoid backbone biosynthesis, and degradation of misfolded proteins. Taken together, by integrating transcriptomic, epigenetic, and phenotypic analysis, our study provides evidence for DNA methylation acting cooperatively with gene transcription to contribute to the adaptation of microalgae to global changes.

Multi-trait analysis reveals large interspecific differences for phytoplankton in response to thermal change.

Understanding the responses of multiple traits in phytoplankton, and identifying interspecific variabilities to thermal changes is crucial for predicting the impacts of ocean warming on phytoplankton distributions and community structures in future scenarios. Here, we applied a trait-based approach by examining the patterns in multi-traits variations (eight traits) and interspecific variabilities in five phytoplankton species (two diatoms, three dinoflagellates) in response to a wide range of ecologically relevant temperatures (14-30 °C). Our results show large inter-traits and interspecific variabilities of thermal reaction norms in all of the tested traits. We also found that the interspecific variability exceeded the variations induced by thermal changes. Constrained variations and trade-offs between traits both revealed substantial interspecific differences and shifted as the temperature changed. Our study helps to understand the species-specific response patterns of multiple traits to ocean warming and to investigate the implications of these responses in the context of global change.

Long-term adaptation to elevated temperature but not CO2 alleviates the negative effects of ultraviolet-B radiation in a marine diatom.

Multifaceted changes in marine environments as a result of anthropogenic activities are likely to have a compounding impact on the physiology of marine phytoplankton. Most studies on the combined effects of rising pCO2, sea surface temperature, and UVB radiation on marine phytoplankton were only conducted in the short-term, which does not allow to test the adaptive capacity of phytoplankton and associated potential trade-offs. Here, we investigated populations of the diatom Phaeodactylum tricornutum that were long-term (∼3.5 years, ∼3000 generations) adapted to elevated CO2 and/or elevated temperatures, and their physiological responses to short-term (∼2 weeks) exposure of two levels of ultraviolet-B (UVB) radiation. Our results showed that while elevated UVB radiation showed predominantly negative effects on the physiological performance of P. tricornutum regardless of adaptation regimes. Elevated temperature alleviated these effects on most of the measured physiological parameters (e.g., photosynthesis). We also found that elevated CO2 can modulate these antagonistic interactions, and conclude that long-term adaptation to sea surface warming and rising CO2 may alter this diatom's sensitivity to elevated UVB radiation in the environment. Our study provides new insights into marine phytoplankton's long-term responses to the interplay of multiple environmental changes driven by climate change.

Chromosome-level genome assembly and resequencing of camphor tree (Cinnamomum camphora) provides insight into phylogeny and diversification of terpenoid and triglyceride biosynthesis of Cinnamomum.

Cinnamomum species attract attentions owing to their scents, medicinal properties, and ambiguous relationship in the phylogenetic tree. Here, we report a high-quality genome assembly of Cinnamomum camphora, based on which two whole-genome duplication (WGD) events were detected in the C. camphora genome: one was shared with Magnoliales, and the other was unique to Lauraceae. Phylogenetic analyses illustrated that Lauraceae species formed a compact sister clade to the eudicots. We then performed whole-genome resequencing on 24 Cinnamomum species native to China, and the results showed that the topology of Cinnamomum species was not entirely consistent with morphological classification. The rise and molecular basis of chemodiversity in Cinnamomum were also fascinating issues. In this study, six chemotypes were classified and six main terpenoids were identified as major contributors of chemodiversity in C. camphora by the principal component analysis. Through in vitro assays and subcellular localization analyses, we identified two key terpene synthase (TPS) genes (CcTPS16 and CcTPS54), the products of which were characterized to catalyze the biosynthesis of two uppermost volatiles (i.e. 1,8-cineole and (iso)nerolidol), respectively, and meditate the generation of two chemotypes by transcriptional regulation and compartmentalization. Additionally, the pathway of medium-chain triglyceride (MCT) biosynthesis in Lauraceae was investigated for the first time. Synteny analysis suggested that the divergent synthesis of MCT and long-chain triglyceride (LCT) in Lauraceae kernels was probably controlled by specific medium-chain fatty acyl-ACP thioesterase (FatB), type-B lysophosphatidic acid acyltransferase (type-B LPAAT), and diacylglycerol acyltransferase 2b (DGAT 2b) isoforms during co-evolution with retentions or deletions in the genome.

Temporal and Spatial Cluster Analysis of 2019 Novel Coronavirus Pneumonia in Chongqing, 2020.1∼2020.2.

In order to explore the spatial and temporal distribution characteristics of COVID-19 in Chongqing from January 22 to February 25, 2010, and provide a series of suggestions for scientific prevention and control of epidemic situation, we will mainly analyze the epidemic situation data of Chongqing Municipal Health Committee members and improve the descriptive analysis. Regional distribution and spatiotemporal scans were analyzed for COVID-19 outbreaks using ArcGIS10.2 and SaTScan9. 5 software. After the analysis, a total of 576 novel coronavirus pneumonia patients were confirmed in Chongqing. The incidence trend increased rapidly from January 22 to January 31, then decreased gradually, and there were no new cases until February 25. The purely spatial scanning results were consistent with spatiotemporal scanning, and a first-level accumulation area was detected by spatiotemporal scanning in the east and northeast of Chongqing from January 22 to February 10. From January 22 to February 25, 2020,COVID-19 occurred in the eastern and northeast regions of Chongqing. It is recommended to strengthen the detection of cluster areas to prevent another outbreak of COVID-19 risk.

Adaptation of a marine diatom to ocean acidification increases its sensitivity to toxic metal exposure.

Most previous studies investigating the interplay of ocean acidification (OA) and heavy metal on marine phytoplankton were only conducted in short-term, which may provide conservative estimates of the adaptive capacity of them. Here, we examined the physiological responses of long-term (~900 generations) OA-adapted and non-adapted populations of the diatom Phaeodactylum tricornutum to different concentrations of the two heavy metals Cd and Cu. Our results showed that long-term OA selected populations exhibited significantly lower growth and reduced photosynthetic activity than ambient CO2 selected populations at relatively high heavy metal levels. Those findings suggest that the adaptations to high CO2 results in an increased sensitivity of the marine diatom to toxic metal exposure. This study provides evidence for the costs and the cascading consequences associated with the adaptation of phytoplankton to elevated CO2 conditions, and improves our understanding of the complex interactions of future OA and heavy metal pollution in marine waters.

Abnormal Y chromosome detection in infertile males using multiplex ligation-dependent probe amplification.

Y chromosome abnormalities are the leading cause of male infertility. The clinical detection of abnormalities is necessary for appropriate genetic counselling. This study describes the prevalence, distribution and characteristics of Y chromosome abnormalities, which should be considered in the clinical management of infertile males. A total of 121 patients with oligozoospermia, 120 with azoospermia and 88 normal individuals were recruited between June 2019 and July 2021. Y chromosome microdeletions were assessed using multiplex ligation-dependent probe amplification (MLPA). The abnormal Y chromosome prevalence was 30.70%, and it was most common in patients aged 26-40 years. The frequencies of azoospermia factor (AZF) deletion, duplication and deletions/duplications were 19.76%, 9.42% and 1.52% respectively. The most common abnormalities were AZFc deletion (19.80%), AZFc partial deletion (40.59%) and AZFc partial duplication (17.82%). Oligozoospermia was associated with an increased incidence of AZF deletion. In the subgroup analysis, patients <30 years old with azoospermia exhibited elevated follicle-stimulating hormone levels and oestradiol. Moreover, the incidence of AZF deletion was higher in those with azoospermia (OR: 2.12; 95% CI: 1.05-5.28; p = 0.023) or oligozoospermia (OR: 2.54; 95% CI: 1.13-5.79; p = 0.008) than in normal individuals for ages ≥30 years.

Additive impacts of ocean acidification and ambient ultraviolet radiation threaten calcifying marine primary producers.

Ocean acidification (OA) represents a threat to marine organisms and ecosystems. However, OA rarely exists in isolation but occurs concomitantly with other stressors such as ultraviolet radiation (UVR), whose effects have been neglected in oceanographical observations. Here, we perform a quantitative meta-analysis based on 373 published experimental assessments from 26 studies to examine the combined effects of OA and UVR on marine primary producers. The results reveal predominantly additive stressor interactions (69-84% depending on the UV waveband), with synergistic and antagonistic interactions being rare but significantly different between micro- and macro-algae. In microalgae, variations in interaction type frequencies are related to cell volume, with antagonistic interactions accounting for a higher proportion in larger sized species. Despite additive interactions being most frequent, the small proportion of antagonistic interactions appears to have a stronger power, leading to neutral effects of OA in combination with UVR. High levels of UVR at near in situ conditions in combination with OA showed additive inhibition of calcification, but not when UVR was low. The results also reveal that the magnitude of responses is strongly dependent on experimental duration, with the negative effects of OA on calcification and pigmentation being buffered and amplified by increasing durations, respectively. Tropical primary producers were more vulnerable to OA or UVR alone compared to conspecifics from other climatic regions. Our analysis highlights that further multi-stressor long-term adaptation experiments with marine organisms of different cell volumes (especially microalgae) from different climatic regions are needed to fully disclose future impacts of OA and UVR.

The complete chloroplast genome sequence of Machilus robusta W. W. Smith (Lauraceae) from Jiangxi Province, China.

Machilus robusta W. W. Smith is an evergreen plant distributed in the Yangtze River Basin and the south regions of China. Here we analyzed the complete chloroplast (cp) genome sequence of M. robusta to determine its structure and evolutionary relationship to other Lauraceae. The cp genome is 152,737 bp in length and has an overall GC content of 39.2% The genome includes a large single-copy (LSC) region of 93,706 bp and a small single-copy (SSC) region of 18,885 bp, and these are separated by a pair of inverted repeats (IRs) of 20,073 bp. The cp genome contains 128 genes, including 83 protein-coding, 37 tRNAs, and 8 rRNAs. Phylogenetic analysis based on complete cp genome sequences fully resolved M. robusta in a clade with M. balansae. This work provides new molecular data for evolutionary studies of the Lauraceae.

Correction: Neural correlates of creative insight: Amplitude of low-frequency fluctuation of resting-state brain activity predicts creative insight.

[This corrects the article DOI: 10.1371/journal.pone.0203071.].

Interhemispheric functional connectivity and its relationships with creative problem solving.

Creative problem solving (CPS) is a particular mental process when people solve problems. Findings from previous research, which used functional MRI, showed that CPS could involve specific neural mechanisms. However, few studies have directly explored the changes of interhemispheric resting-state functional connectivity during CPS. Recently, a validated voxel-mirrored homotopic connectivity (VMHC) method has been widely used to calculate the interhemispheric resting-state functional connectivity. In this study, we recruited 60 participants and used a revised chunk decomposing task to estimate participants' individual differences during CPS. Then, the VMHC method was used to explore neural correlates underlying individual differences of CPS. Results showed that altered VMHC in the bilateral middle frontal gyrus/precentral gyrus, bilateral hippocampus/insula/amygdala, and bilateral fusiform gyrus/cerebellum/middle occipital gyrus was related to individual differences of CPS. These brain regions reflect the information integration of both hemispheres might be critical for CPS. Therefore, our results may shed light on the neural correlates of CPS.

Neural correlates of creative insight: Amplitude of low-frequency fluctuation of resting-state brain activity predicts creative insight.

Creative insight has attracted much attention across cultures. Although previous studies have explored the neural correlates of creative insight by functional magnetic resonance imaging (fMRI), little is known about intrinsic resting-state brain activity associated with creative insight. In the present study, we used amplitude of low-frequency fluctuation (ALFF) as an index in resting-state fMRI (rs-fMRI) to identify brain regions involved in individual differences in creative insight, which was measured by the response time of creative Chinese character chunk decomposition. Our results showed that ALFF in the superior frontal gyrus (SFG) positively predicted creative insight, while ALFF in the middle cingulate cortex/insula cortex (MCC/IC), superior temporal gyrus/angular gyrus (STG/AG), anterior cingulate cortex/caudate nucleus (ACC/CN), and culmen/declive (CU/DC) negatively predicted creative insight. Moreover, these findings indicate that spontaneous brain activity in multiple regions related to breaking mental sets, solutions exploring, evaluation of novel solutions, forming task-related associations, and emotion experience contributes to creative insight. In conclusion, the present study provides new evidence to further understand the cognitive processing and neural correlates of creative insight.

Regional Homogeneity Predicts Creative Insight: A Resting-State fMRI Study.

Creative insight plays an important role in our daily life. Previous studies have investigated the neural correlates of creative insight by functional magnetic resonance imaging (fMRI), however, the intrinsic resting-state brain activity associated with creative insight is still unclear. In the present study, we used regional homogeneity (ReHo) as an index in resting-state fMRI (rs-fMRI) to identify brain regions involved in individual differences in creative insight, which was compued by the response time (RT) of creative Chinese character chunk decomposition. The findings indicated that ReHo in the anterior cingulate cortex (ACC)/caudate nucleus (CN) and angular gyrus (AG)/superior temporal gyrus (STG)/inferior parietal lobe (IPL) negatively predicted creative insight. Furthermore, these findings suggested that spontaneous brain activity in multiple regions related to breaking and establishing mental sets, goal-directed solutions exploring, shifting attention, forming new associations and emotion experience contributes to creative insight. In conclusion, the present study provides new evidence to further understand the cognitive processing and neural correlates of creative insight.

A Novel Case of 15q24 Microdeletion Syndrome Detected by MLPA in a Chinese Family.

BACKGROUND: Chromosome 15q24 microdeletion syndrome is a rare disease. To date, only 40 cases have been reported. Here, we also confirmed a 15q24 microdeletion syndrome in a chorionic villus of miscarriage. METHODS: The microdeletion was screened by multiplex ligation-dependent probe amplification (MLPA) and then identified by chromosomal microarray analysis (CMA). RESULTS: A 15q24 microdeletion syndrome was screened by MLPA in the chorionic villus of miscarriage in a Chinese family and was confirmed to be a de novo 3.143 Mb 15q24.1q24.2 deletion (chr15:72930195-76073450) by chromosomal microarray analysis (CMA). CONCLUSIONS: We first reported the 15q24 microdeletion syndrome screened by MLPA in Chinese population, and we also considered that the technique of MLPA with a suitable kit and probe could screen such a rare microdeletion quickly, economically, and efficiently.

Acute Penicillium marneffei infection stimulates host M1/M2a macrophages polarization in BALB/C mice.

BACKGROUND: Penicillium marneffei (P. marneffei) is a thermally dimorphic fungus pathogen that causes fatal infection. Alveolar macrophages are innate immune cells that have critical roles in protection against pulmonary fungal pathogens and the macrophage polarization state has the potential to be a deciding factor in disease progression or resolution. The aim of this study was to investigate mouse alveolar macrophage polarization states during P. marneffei infection. RESULTS: We used enzyme-linked immunosorbent (ELISA) assays, quantitative real-time PCR (qRT-PCR), and Griess, arginase activity to evaluate the phenotypic markers of alveolar macrophages from BALB/C mice infected with P. marneffei. We then treated alveolar macrophages from infected mice with P. marneffei cytoplasmic yeast antigen (CYA) and investigated alveolar macrophage phenotypic markers in order to identify macrophage polarization in response to P. marneffei antigens. Our results showed: i) P. marneffei infection significantly enhanced the expression of classically activated macrophage (M1)-phenotypic markers (inducible nitric oxide synthase [iNOS] mRNA, nitric oxide [NO], interleukin-12 [IL-12], tumor necrosis factor-alpha [TNF-α]) and alternatively activated macrophage (M2a)-phenotypic markers (arginase1 [Arg1] mRNA, urea) during the second week post-infection. This significantly decreased during the fourth week post-infection. ii) During P. marneffei infection, CYA stimulation also significantly enhanced the expression of M1 and M2a-phenotypic markers, consistent with the results for P. marneffei infection and CYA stimulation preferentially induced M1 subtype. CONCLUSIONS: The data from the current study demonstrated that alveolar macrophage M1/M2a subtypes were present in host defense against acute P. marneffei infection and that CYA could mimic P. marneffei to induce a host immune response with enhanced M1 subtype. This could be useful for investigating the enhancement of host anti-P. marneffei immune responses and to provide novel ideas for prevention of P. marneffei-infection.