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Abstract. Schizophrenia is a life-long, complex mental illness that still lacks satisfactory treatments. In recent years, increasing numbers of candidate biomarkers of schizophrenia occurrences and drug responses to schizophrenia therapies have been successfully identified by many omics studies. This review discusses the latest discoveries regarding effective drug targets and relevant drug classifications in schizophrenia. It also assesses our understanding of biomarkers for drug efficacy and adverse drug reactions in current schizophrenia treatments using omics technologies. Future applications in clinical practice have been proposed based on these new findings, and are now considered highly promising strategies to better treat schizophrenia. Finally, we explore several novel approaches that aim to reveal additional genetic signatures of schizophrenia using multi-omics data, which are hoped to improve the diagnosis and treatment of this illness in the future.

Abstract. Navigation and recognition of disease lesions remain challenging during colorectal cancer diagnosis and treatment, given that the precision and capacity of using specific surface antigens as recognition sites are relatively lacking. Moreover, the low penetration rate of noninvasive detection methods has delayed disease diagnosis in developing countries. We developed a bacterial device targeting the Thomsen–Friedenreich antigen, which is abundant on lesion tissue, and produced vesicles that serve as markers for ultrasonic detection. The device uses a bacterial cell surface display system and acoustic reporter gene to function as a screening device for colorectal cancer detection. The diagnostic efficiency of this device was determined by flow cytometry, immunohistochemistry, microfluidic chip-based assay, and ultrasonic examinations on both cellular and tissue scales. In all scales and experiments, our device showed great feasibility upon differentiating disease lesion and normal tissue, while foundation of the usage of vesicle reporter system as noninvasive method has also been laid. The application of this device provides insight into the practicability and prospect of bacterial detecting agents in the field of diagnostics. All animal studies were approved by the Institutional Animal Care and Use Committee of Shanghai Jiao Tong University, China (approval No. 201801015) on February 23, 2018.

Beta3-adrenergic receptor (b3-AR) signaling in response to cold activates adipose tissue thermogenesis. Here the authors identify the transcription factor FoxP1 as a direct negative regulator of b3-AR expression and show that loss of FoxP1 leads to enhanced development of thermogenic adipose tissue.

Objectives To evaluate the diagnostic yield and safety of brainstem stereotactic biopsy for brainstem lesions. Methods We performed a meta-analysis of English articles retrieved from the PubMed, Web of Science, Cochrane Library, and APA psycInfo databases up to May 12, 2021. A binary fixed-effect model, the inverse variance method, or a binary random-effect model, the Dersimonian Laird method, were utilized for pooling the data. This meta-analysis was registered with INPLASY, INPLASY202190034. Findings A total of 41 eligible studies with 2792 participants were included. The weighted average diagnostic yield was 97.0% (95% confidential interval [CI], 96.0-97.9%). The weighted average proportions of temporary complications, permanent deficits, and deaths were 6.2% (95% CI, 4.5–7.9%), .5% (95% CI, .2–.8%), and .3% (95% CI, .1–.5%), respectively. The subgroup analysis indicated a nearly identical weighted average diagnostic yield between MRI-guided stereotactic biopsy and CT-guided stereotactic biopsy (95.9% vs 95.8%) but slightly increased proportions of temporary complications (7.9% vs 6.0%), permanent deficits (1.9% vs .2%), and deaths (1.1% vs .4%) in the former compared to the latter. Moreover, a greater weighted average diagnostic yield (99.2% vs 97.6%) and lower proportions of temporary complications (5.1% vs 6.8%) and deaths (.7% vs 1.5%) were shown in the pediatric patient population than in the adult patient population. Conclusions Brainstem stereotactic biopsy demonstrates striking accuracy plus satisfying safety in the diagnosis of brainstem lesions. The diagnostic yield, morbidity, and mortality mildly vary based on the diversity of assistant techniques and subject populations.

1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH), as an emerging pollutant, was often detected in the aquatic environments, but the chemical behavior and potential eco-toxicity of each stereoisomer are poorly understood. Here, the chemical behavior of TBECH stereoisomers under the oxidation of ROS (OH· and HO2·) in the aqueous phase was investigated by computational chemistry. Besides, the eco-toxicity effects of TBECH and representative transformation products were obtained by computational toxicology. In the natural environments, TBECH stereoisomers could be transformed under the initiation of ROS, and the key oxidation species is OH· rather than HO2· in this process. DOM could indirectly promote the transformation of TBECH stereoisomers, resulting in the half-life (t1/2) of TBECH stereoisomers in less than 180 days, thus no longer maintaining environmental persistence. Although TBECH stereoisomers may show environmental persistence in natural waters, AOPs based on OH· could bring about their rapid transformation, which predicts the effectiveness of OH-based AOPs for the treatment of TBECH wastewater. The results of the eco-toxicity assessment showed that the transformation of TBECH stereoisomers is beneficial to the reduction of toxicity, but the transformation products are not completely harmless. Thus, it is urgent to clarify the environmental behaviors and risks of these transformation products that remain toxic in the aquatic environments.

Abstract Nanomaterials having hetero‐metallic junctions are being explored for sensing, catalytic, and biomedical applications. Insight into the bimetallic junction at nanoscale is important from both fundamental and application perspectives. In this study, we synthesized segmented Au–Ag wire by sequentially electroplating Au and Ag in cylindrical pores in anodic alumina membrane filters. We probed the one photon, two photon, and second harmonic signal in Au–Ag wire at single particle level by focusing laser beam to a diffraction limited spot using a home‐built sample scanning type micro‐spectrometer. When exciting the Au–Ag junctions into the mid‐UV range using two‐photon excitation, we observed two luminescence peaks at 455 and 520 nm, respectively, possibly because of the surface plasmon resonances supported by the sharp boundary and granular nanostructures on the Au–Ag interface. Interestingly, we also observed intense second harmonic generation (SHG) signal from the junction with a yield more than two orders of magnitude higher than that from the Au tips. The SHG intensity as a function of excitation wavelength showed a similar trend to the two‐photon excited luminescence emission spectrum, indicating that the SHG signal was enhanced in the presence of optical resonances. The observation of enhanced radiative properties of the bimetallic junction in the suggested that the Au–Ag wire may serve as an excellent imaging probe or single particle sensors.

Multiple sclerosis (MS) is an autoimmune disease that leads to the demyelination of nerve axons. An increasing number of studies suggest that patients with MS exhibit altered metabolic profiles, which might contribute to the course of MS. However, the alteration of metabolic profiles in Chinese patients with MS and their potential roles in regulating the immune system remain elusive. In this study, we performed a global untargeted metabolomics approach in plasma samples from 22 MS-affected Chinese patients and 21 healthy subjects. A total of 42 differentially abundant metabolites (DAMs) belonging to amino acids, lipids, and carbohydrates were identified in the plasma of MS patients and compared with those in healthy controls. We observed an evident reduction in the levels of amino acids, such as L-tyrosine, L-isoleucine, and L-tryptophan, whereas there was a great increase in the levels of L-glutamic acid and L-valine in MS-affected patients. The levels of lipid and carbohydrate metabolites, such as sphingosine 1-phosphate and myo-inositol, were also reduced in patients with MS. In addition, the concentrations of proinflammatory cytokines, such as IL-17 and TNF-α, were significantly increased, whereas those of several anti-inflammatory cytokines and chemokines, such as IL-1ra, IL-7, and MIP-1α, were distinctly reduced in the plasma of MS patients compared with those in healthy subjects. Interestingly, some DAMs, such as L-tryptophan and sphingosine 1-phosphate, showed an evident negative correlation with changes in the level of TNF-α and IL-17, while tightly positively correlating with altered concentrations of anti-inflammatory cytokines and chemokines, such as MIP-1α and RANTES. Our results revealed that altered metabolomic profiles might contribute to the pathogenesis and course of MS disease by modulating immuno-inflammatory responses in the peripheral system, which is essential for eliciting autoimmune responses in the central nervous system, thus resulting in the progression of MS. This study provides potential clues for developing therapeutic strategies for MS in the near future.

BackgroundIntraoperative radiotherapy (IORT) and whole-breast irradiation (WBI) are both effective radiotherapeutic interventions for early breast cancer patients undergoing breast-conserving surgery; however, an issue on whether which one can entail the better prognosis is still controversial. Our study aimed to investigate the 5-year oncological efficacy of the IORT cohort and the WBI cohort, respectively, and compare the oncological efficacy between the cohorts.Materials and MethodsWe conducted a computerized retrieval to identify English published articles between 2000 and 2021 in the PubMed, the Web of Science, the Cochrane Library, and APA PsycInfo databases. Screening, data extraction, and quality assessment were performed in duplicate.ResultsA total of 38 studies were eligible, with 30,225 analyzed participants. A non-comparative binary meta-analysis was performed to calculate the weighted average 5-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) in the two cohorts, respectively. The LRFS, DMFS, and OS (without restriction on the 5-year outcomes) between the two cohorts were further investigated by a comparative binary meta-analysis. The weighted average 5-year LRFS, DMFS, and OS in the IORT cohort were 96.3, 96.6, and 94.1%, respectively, and in the WBI cohort were 98.0, 94.9, and 94.9%, respectively. Our pooled results indicated that the LRFS in the IORT cohort was significantly lower than that in the WBI cohort (pooled odds ratio [OR] = 2.36; 95% confidential interval [CI], 1.66–3.36). Nevertheless, the comparisons of DMFS (pooled OR = 1.00; 95% CI, 0.76–1.31), and OS (pooled OR = 0.95; 95% CI, 0.79–1.14) between the IORT cohort with the WBI cohort were both not statistically significant.ConclusionsDespite the drastically high 5-year oncological efficacy in both cohorts, the LRFS in the IORT cohort is significantly poorer than that in the WBI cohort, and DMFS and OS do not differ between cohorts.

Approximately 40% of rectal cancers during initial diagnosis are identified as locally advanced rectal cancers (LARCs), for which the standardized treatment scenario is total mesorectal excision following neoadjuvant chemoradiotherapy (nCRT). nCRT can lead to discernible reductions in local relapse rate and distant metastasis rate in LARC patients, in whom previously inoperable tumors may potentially be surgically removed. However, only 4% to 20% cases can attain pathological complete response, and the remaining patients who are unresponsive to nCRT have to suffer from the side effects plus toxicities and may encounter poor survival outcomes due to the late surgical intervention. As such, employing potential biomarkers to differentiate responders from nonresponders before nCRT implementation appears to be the overarching goal. Well-defined competing endogenous RNA (ceRNA) networks include long noncoding RNA (lncRNA)-microRNA (miRNA)-mRNA and circRNA-miRNA-mRNA networks. As ceRNAs, lncRNAs, and circRNAs sponge miRNAs to indirectly suppress miRNAs downstream of oncogenic mRNAs or tumor-suppressive mRNAs. The abnormal expression of mRNAs regulates the nCRT-induced DNA damage repair process through pluralistic carcinogenic signaling pathways, thereby bringing about alterations in the nCRT resistance/sensitivity of tumors. Moreover, many molecular mechanisms relevant to cell proliferation, metastasis, or apoptosis of cancers (eg, epithelial-mesenchymal transition and caspase-9-caspase-3 pathway) are influenced by ceRNA networks. Herein, we reviewed a large group of abnormally expressed mRNAs and noncoding RNAs that are associated with nCRT resistance/sensitivity in LARC patients and ultimately pinpointed the backbone role of ceRNA networks in the molecular mechanisms of nCRT resistance/sensitivity.

Objective: This pilot study aimed to investigate the immediate effects of single-session intermittent theta-burst stimulation (iTBS) on the cerebellar vermis during a balance task, which could unveil the changes of cerebral cortical excitability in healthy individuals.Subjects: A total of seven right-handed healthy subjects (26.86 ± 5.30 years) were included in this study.Interventions: Each subject received single-session iTBS on cerebellar vermis in a sitting position.Main Measures: Before and after the intervention, all subjects were asked to repeat the balance task of standing on the left leg three times. Each task consisted of 15 s of standing and 20 s of resting. Real-time changes in cerebral cortex oxygen concentrations were monitored with functional near-infrared spectroscopy (fNIRS). During the task, changes in blood oxygen concentration were recorded and converted into the mean HbO2 for statistical analysis.Results: After stimulation, the mean HbO2 in the left SMA (P = 0.029) and right SMA (P = 0.043) significantly increased compared with baseline. However, no significant changes of mean HbO2 were found in the bilateral dorsolateral prefrontal lobe (P > 0.05).Conclusion: Single-session iTBS on the cerebellar vermis in healthy adults can increase the excitability of the cerebral cortex in the bilateral supplementary motor areas during balance tasks.Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [ChiCTR2100048915].

Palladium (Pd)‐based materials have attracted increasing attentions as a kind of novel candidate catalysts for many electrocatalytic reactions to replace classic platinum (Pt) catalysts, especially in the fuel cell‐related electrocatalysis. However, the requirement of high activity and stability toward further practical applications makes the development of Pd‐based catalysts cease to advance. Combining alloying and structure‐controlled strategies has well addressed this challenge by optimizing the adsorption/desorption behaviors toward reaction intermediates. Herein, the recent advances of rational structural designs in terms of tuning the dimensionalities of Pd‐based nanoalloys are overviewed. To further enhance the intrinsic electrocatalytic activity, several advanced strategies, including intermetallics, doping, defects, surface, and interface engineering, are presented to engineer the electronic and/or physical properties of Pd‐based electrocatalysts. Using typical electrocatalytic reactions as probes, the significance of structural regulation of Pd‐based nanocrystals on the enhanced electrocatalysis is demonstrated. Finally, several possible trends and challenges for future advanced research directions are presented. It is anticipated that the rational structural regulation can make promising Pd‐based catalysts touch the ceiling of electrocatalytic activity and stability.

The Buxue Tongluo pill (BTP) is a self-made pill with the functions of nourishing blood, promoting blood circulation, dredging collaterals, and relieving pain. It consists of Angelica sinensis (Oliv.) Diels, Pheretima aspergillum (E.Perrier), Panax notoginseng (Burk.) F. H. Chen, Astragalus membranaceus (Fisch.) Bge, and Glycyrrhiza uralensis Fisch. Various clinical practices have confirmed the therapeutic effect of BTP on osteonecrosis of the femoral head (ONFH), but little attention has been paid to the study of its bioactive ingredients and related mechanisms of action. In this study, UPLC/MS-MS combined with GEO data mining was used to construct a bioactive ingredient library of BTP and a differentially expressed gene (DEG) library for ONFH. Subsequently, Cytoscape (3.7.2) software was used to analyze the protein–protein interaction between BTP and DEGs of ONFH to screen the key targets, and functional annotation analysis and pathway enrichment analysis were carried out. Finally, 34 bioactive compounds were screened, which acted on 1,232 targets. A total of 178 DEGs were collected, and 17 key genes were obtained after two screenings. By bioinformatics annotation on these key genes, a total of 354 gene ontology (GO) functional annotation analyses and 42 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were obtained. The present study found that GO and KEGG enrichment were mainly related to apoptosis, suggesting that BTP may exert an anti-ONFH effect by promoting osteoclast apoptosis. Experiments in vitro demonstrated that BTP could increase the mitochondrial membrane potential (MMP) and induce remarkable apoptosis in osteoclasts. Furthermore, we determined the apoptosis marker of cleaved(C)-caspase-3, bcl-2, and bax and found that BTP could upregulate the C-caspase-3 and bax expression in osteoclasts and decrease the expression of bcl-2, p-Akt, and p-PI3K in a dose-dependent manner, indicating that BTP could induce PI3K/Akt-mediated apoptosis in osteoclasts to treat ONFH. This study explored the pharmacodynamic basis and mechanism of BTP against ONFH from the perspective of systemic pharmacology, laying a foundation for further elucidating the therapeutic effects of BTP against ONFH.

With the advancement of technology and the rise of the unmanned aerial vehicle industry, the use of drones has grown tremendously. For drones performing near-ground delivery missions, the problem of 3D space-based path planning is particularly important in the autonomous navigation of drones in complex spaces. Therefore, an improved butterfly optimization (BOA-TSAR) algorithm is proposed in this paper to achieve the autonomous pathfinding of drones in 3D space. First, this paper improves the randomness strategy of the initial population generation in the butterfly optimization algorithm (BOA) via the Tent chaotic mapping method, by means of the removal of the short-period property, which balances the equilibrium of the initial solutions generated by the BOA algorithm in the solution space. Secondly, this paper improves the shortcomings of the BOA algorithm in terms of slower convergence, lower accuracy, and the existence of local optimal stagnation when dealing with high-dimensional complex functions via adaptive nonlinear inertia weights, a simulated annealing strategy, and stochasticity mutation with global adaptive features. Finally, this paper proposes an initial population generation strategy, based on the 3D line of sight (LOS) detection method, to further reduce the generation of path interruption points while ensuring the diversity of feasible solutions generated by the BOA algorithm for paths. In this paper, we verify the superior performance of BOA-TSAR by means of simulation experiments. The simulation results show that BOA-TSAR is very competitive among swarm intelligence (SI) algorithms of the same type. At the same time, the BOA-TSAR algorithm achieves the optimal path length measure and smoothness measure in the path-planning experiment.

Dazomet (DZ) is a soil fumigant that has been used for decades at many countries, however it was reported to have caused phytotoxicity and reduced crop yield in many countries. In this experiment, in order to clarify whether the diameter of DZ is related to phytotoxicity, this research investigated the degradation rate of DZ with different diameter ranges under three soil types held at 15, 20 or 30% soil water content at 4, 15, 25 or 37 °C, and monitored concentrations of methyl isothiocyanate (MITC) produced when Shunyi soil was fumigated with DZ using the different particle sizes ranges. When the soil water content and temperature increased, the degradation rate of DZ with different particle sizes accelerated. However, the degradation rate of DZ with large particle sizes was still lower than small particle sizes. NO3−-N, available phosphorus (AP), available potassium (AK), pH and silt content in the soil were all significantly positively correlated with 400 μm DZ. However, organic matter (OM) and sand content produced the opposite result. The maximum concentration of MITC produced by 100–300 μm of DZ in 25 °C Shunyi soil at 30% water content were 102.2 mg/kg at 24 h. DZ produced peaks significantly higher and earlier at 30% than at 20% soil water content. We recommend selecting DZ manufactured with particle in the range of 100 to 300 μm, fumigating at about 25 °C and ensuring that about 30% soil water content is present in the soil immediately after fumigation.

Background: Schizophrenia (SCZ) is a severe psychiatric disorder that affects approximately 0.75% of the global population. Both genetic and environmental factors contribute to development of SCZ. SCZ tends to run in family while both genetic and environmental factor contribute to its etiology. Much evidence suggested that alterations in DNA methylations occurred in SCZ patients. Methods: To investigate potential inheritable pattern of DNA methylation in SCZ family, we performed a genome-wide analysis of DNA methylation of peripheral blood samples from 106 Chinese SCZ family trios. Genome-wide DNA methylations were quantified by Agilent 1 × 244 k Human Methylation Microarray. Findings: In this study, we proposed a loci inheritance frequency model that allows characterization of differential methylated regions as SCZ biomarkers. Based on this model, 112 hypermethylated and 125 hypomethylated regions were identified. Additionally, 121 hypermethylated and 139 hypomethylated genes were annotated. The results of functional enrichment analysis indicated that multiple differentially methylated genes (DMGs) involved in Notch/HH/Wnt signaling, MAPK signaling, GPCR signaling, immune response signaling. Notably, a number of hypomethylated genes were significantly enriched in cerebral cortex and functionally enriched in nervous system development. Interpretation: Our findings not only validated previously discovered risk genes of SCZ but also identified novel candidate DMGs in SCZ. These results may further the understanding of altered DNA methylations in SCZ. Funding: None.

Mammalian female fertility is defined by a successful and strictly periodic ovarian cycle, which is under the control of gonadotropins and steroid hormones, particularly progesterone and estrogen. The latter two are produced by the ovaries that are engaged in controlled follicular growth, maturation, and release of the eggs, i.e., ovulation. The steroid hormones regulate ovarian cycles via genomic signaling, by altering gene transcription and protein synthesis. However, despite this well-studied mechanism, steroid hormones can also signal via direct, non-genomic action, by binding to their membrane receptors. Here we show, that the recently discovered membrane progesterone receptor α/β hydrolase domain-containing protein 2 (ABHD2) is highly expressed in mammalian ovaries where the protein plays a novel regulatory role in follicle maturation and the sexual cycle of females. Ablation of Abhd2 caused a dysregulation of the estrous cycle rhythm with females showing shortened luteal stages while remaining in the estrus stage for a longer time. Interestingly, the ovaries of Abhd2 knockout (KO) females resemble polycystic ovary morphology (PCOM) with a high number of atretic antral follicles that could be rescued with injection of gonadotropins. Such a procedure also allowed Abhd2 KO females to ovulate a significantly increased number of mature and fertile eggs in comparison with their wild-type littermates. These results suggest a novel regulatory role of ABHD2 as an important factor in non-genomic steroid regulation of the female reproductive cycle.

Summary: TENM4, encoding a member of the teneurin protein family, is a risk gene shared by many types of mental diseases and is implicated in neuronal plasticity and signaling. However, the role and the mechanisms of TENM4 in schizophrenia (SCZ) remain unclear. We identified possible pathogenic mutations in the TENM4 gene through target sequencing of TENM4 in 68 SCZ families. We further demonstrated that aberrant expression of Ten-m leads to lower learning ability, sleep reduction, and increased aggressiveness in animal models. RNA sequencing showed that aberrant expression of Ten-m was related to stimulus perception and metabolic process, and Gene Ontology enrichment terms were neurogenesis and ATPase activity. This study provides strong evidence that TENM4 contributes to SCZ, and its functional mutations might be responsible for the impaired neural circuits and behaviors observed in SCZ.

Acupuncture treatment is based on acupoint stimulation; however, the biological basis is not understood. We stimulated one acupoint with catgut embedding for 8 weeks and then used isobaric tags for relative and absolute quantitation to screen proteins with altered expression in adjacent acupoints of Sprague Dawley rats. We found that kininogen expression was significantly upregulated in the stimulated and the nonstimulated adjacent acupoints along the same meridian. The enhanced kininogen expression was meridian dependent and was most apparent among small vessels in the subcutaneous layer. Enhanced signals of nitric oxide synthases, cGMP-dependent protein kinase, and myosin light chain were also observed at the nonstimulated adjacent acupoints along the same meridian. These findings uncover biological changes at acupoints and suggest the critical role of the kininogen–nitric oxide signaling pathway in acupoint activation.

The transmission property of acoustic wave in a waveguide composed of index-near-zero (INZ) and reciprocal-modulus-near-zero (RMNZ) has been investigated. As long as the connectivity of the INZ is not broken, the transmittance of acoustic wave in the waveguide is kept close to 100%, which is unaffected by the shape, the size as well as the number of these RMNZ components. In the waveguide, acoustic wave can go around these acoustic RMNZ components and transmits through the INZ spontaneously. The phenomenon of “percolation” of acoustic wave has been observed. Our work overcomes the limitation of such “percolation” of wave occurring only in the system of the vector waves. A new method of manipulating the acoustic wave in acoustic INZ medium is proposed. Further, we find that the RMNZ components can mainly eliminate the influence of impurities made up of soft medium or regular acoustic mediums on the transmission performance of the INZ waveguide effectively.

Summary: Schizophrenia (SCZ) is a severe neuropsychiatric disorder that affects 1% of the global population. Copy number variations (CNVs) have been shown to play a critical role in its pathophysiology; however, only case-control studies on SCZ susceptibility CNVs have been conducted in Han Chinese. Here, we performed an array comparative genomic hybridization-based genome-wide CNV analysis in 100 Chinese family trios with SCZ. Burden test suggested that the SCZ probands carried more duplications than their healthy parents and unrelated healthy controls. Besides, five CNV loci were firstly reported to be associated with SCZ here, including both unbalanced transmitted CNVs and enriched de novo CNVs. Moreover, two genes (CTDSPL and MGAM) in these CNVs showed significant SCZ relevance in the expression level. Our findings support the crucial role of CNVs in the etiology of SCZ and provide new insights into the underlying mechanism of SCZ pathogenesis.

The razor clam, Sinonovacula constricta is a commercially important bivalve in the western Pacific Ocean, yet little is known about the mechanisms of sex determination/differentiation and gametogenesis. In the present study, the comparative transcriptome analysis of adult gonads (female gonads and male gonads) was conducted to identify potential sex-related genes in S. constricta. The number of reads generated for each target library (three females and three males) ranged from 31,853,422 to 37,750,848, and 20,489,472 to 26,152,448 could be mapped to the reference genome of S. constricta (the map percentage ranging from 63.71 to 71.48%). A total of 8,497 genes were identified to be differentially expressed between the female and male gonads, of which 4,253 were female-biased (upregulated in females), and 4,244 were male-biased. Forty-five genes were identified as potential sex-related genes, including DmrtA2, Sox9, Fem-1b, and Fem-1c involved in sex determination/differentiation and Vg, CYP17A1, SOHLH2, and TSSK involved in gametogenesis. The expression profiles of 12 genes were validated by qRT-PCR, which further confirmed the reliability and accuracy of the RNA-Seq results. Our results provide basic information about the genes involved in sex determination/differentiation and gametogenesis, and pave the way for further studies on reproduction and breeding in S. constricta and other marine bivalves.

An experimental investigation was performed on the wake flow field of an isolated roughness element of a flat plate at Mach 6 by employing the nanoparticle-based planar laser scattering (NPLS) approach. The three-dimensional features and causes of the flow field structure were scrutinized by transient flow field images of roughness elements on various planes. The time-resolved NPLS technique was implemented to examine the time evolution characteristics of the wake flow field of roughness elements. In the following, the process of dynamic evolution of large-scale vortex structures in the wake flow field was methodically assessed. Additionally, the influences of roughness element heights on the wake vortex structure were evaluated and the obtained results were compared.

Psychiatric disorders are a class of complex disorders characterized by brain dysfunction with varying degrees of impairment in cognition, emotion, consciousness and behavior, which has become a serious public health issue. The NGFR gene encodes the p75 neurotrophin receptor, which regulates neuronal growth, survival and plasticity, and was reported to be associated with depression, schizophrenia and antidepressant efficacy in human patient and animal studies. In this study, we investigated its association with schizophrenia and major depression and its role in the behavioral phenotype of adult mice. Four NGFR SNPs were detected based on a study among 1010 schizophrenia patients, 610 patients with major depressive disorders (MDD) and 1034 normal controls, respectively. We then knocked down the expression of NGFR protein in the hippocampal dentate gyrus of the mouse brain by injection of shRNA lentivirus to further investigate its behavioral effect in mice. We found significant associations of s2072446 and rs11466162 for schizophrenia. Ngfr knockdown mice showed social and behavioral abnormalities, suggesting that it is linked to the etiology of neuropsychiatric disorders. We found significant associations between NGFR and schizophrenia and that Ngfr may contribute to the social behavior of adult mice in the functional study, which provided meaningful clues to the pathogenesis of psychiatric disorders.

For optical remote sensing images with high spatial resolution and low spectral number, the complexity of ground objects poses great challenges to cloud detection algorithms, such as the differentiation of clouds from objects with similar features as clouds and the identification of thin clouds. In this paper, a novel cloud detection method is proposed for Gaofen-2 remote sensing imagery. The radiation transmittance is estimated based on the dark channel prior, and the overestimated radiation transmittance is corrected using spectral features. A three-step post-processing strategy is adopted to eliminate misidentification introduced by the highlighted surfaces based on object geometric, textural, and boundary features. In the experiments, Gaofen-2 multispectral images with different cloud categories and cloud thicknesses are involved to evaluate the performance of the proposed method. The results show that the proposed method can obtain an average cloud detection accuracy of 0.9573 on six different clouds. The proposed algorithm can also effectively detect both thick and thin clouds with an average accuracy of more than 0.9517. The advantages of the method for thin cloud detection are further demonstrated by comparison with existing algorithms.

Atrial fibrillation (AF) is the most common arrhythmia with significant morbidity and mortality. Exacerbated by the aging population, the prevalence of AF is gradually increasing. Accurate evaluation of structure and function of left atrium (LA) has important prognostic significance in patients with AF. Echocardiography is the imaging technique of first choice to assess LA structure and function due to its better availability, accessibility and safety over cardiac computed tomography and cardiac magnetic resonance. Therefore, the aim of this review is to summarize the recent research progress of evaluating LA size by three-dimensional echocardiography and LA function by speckle tracking echocardiography (STE) in predicting the occurrence and recurrence of AF and determining the risk of stroke in AF. In addition, we summarized the role of traditional echocardiography in detecting AF patients that are at high risk of heart failure or cardiovascular death.

Many carcinomas feature hypoxia, a condition has long been associated with tumor progression and poor prognosis, as well as resistance to chemoradiotherapy. Here, we report that the F-box protein JFK promotes mammary tumor initiation and progression in MMTV-PyMT murine model of spontaneous breast cancer. We find that JFK is inducible under hypoxic conditions, in which hypoxia-inducible factor HIF-1α binds to and transcriptionally activates JFK in breast cancer cells. Consistently, analysis of public clinical datasets reveals that the mRNA level of JFK is positively correlated with that of HIF-1α in breast cancer. We show that JFK deficiency leads to a decrease in HIF-1α-induced glycolysis in breast cancer and sensitizes hypoxic breast cancer cells to ionizing radiation and chemotherapeutic treatment. These results indicate that JFK is an important player in hypoxic response, supporting the pursuit of JFK as a potential therapeutic target for breast cancer intervention.

The outbreak of the COVID-19 epidemic continues to unfold globally, and its negative impact on the public's mental health is starting to reveal. Serving as reserve talents for the healthcare system, medical students are not yet professionally matured enough to face one of the worst global public health crises. This may exert increased mental stress and loneliness feelings, which in turn negatively influence medical students' future career choice. To address the issue, we conducted three online survey studies investigating how the epidemic affects the mental health as well as career attitude of medical students in China during the COVID-19 pandemic outbreak. The results revealed preliminary evidence showing that the perceived stress induced by the COVID-19 epidemic might negatively affect medical students' future career choice, and the feeling of loneliness may play a mediating role. This study invites more attention to medical students' mental health during severe public health crisis such as the COVID-19 pandemic.

We describe and illustrate Sedum lipingense (Crassulaceae), a new species of stonecrop found in the limestone areas of SE Guizhou, China. Based on the presence of adaxially gibbous carpels and follicles, this taxon belongs to sect. Sedum S.H. Fu. The new species superficially resembles S. subtile Miquel and S. bulbiferum Makino but differs from these two taxa in its development of a basal leaf rosette during florescence. The nrDNA internal transcribed spacer (ITS) sequences also support the claim that this plant is a new species in the Sedum genus.

Abstract. Flow has been widely studied in the field of positive psychology. However, little is known regarding its biological mechanism. This study aimed to ascertain flow-related gene loci. We investigated the association between flow and five single nucleotide polymorphisms associated with common mental disorders among a sample of 870 healthy 1st year students of Jining Medical University, Shandong Province, China. This study was approved by the Ethics Committee of Jining Medical University (approval No. JNMC-2016-KY-001) on June 1, 2016. rs11191454 demonstrated significant statistical association with flow after adjusting for age and gender (P = 0.004). The allele carriers achieved higher scores in all four dimensions of flow: merging of action and awareness, challenge-skill balance, sense of control, and clear goals. This biological research article indicates that rs11191454 in the arsenite methyltransferase (AS3MT) gene might be associated with flow in a Chinese Han population, and that might result from altered arsenic metabolism.

Presence of nano-bubbles within an atomically thin material generates potentially large pseudo-magnetic fields. Here, the authors report an innovative technique to induce nano-bubbles in graphene with desirable features and high precision through energized AFM tips, and experimentally measure three-fold symmetric pseudo-magnetic fields up to 120 T.

Plants glycerol-3-phosphate dehydrogenase (GPDH) catalyzes the formation of glycerol-3-phosphate, and plays an essential role in glycerolipid metabolism and stress responses. In the present study, the knock-out mutants of cytosolic GPDH (AtGPDHc2) and wild-type Arabidopsis plants were treated with 0, 50, 100, and 150 mmol L−1 NaCl to reveal the effects of AtGPDHc2 deficiency on salinity stress responses. The fluctuation in redox status, reactive oxygen species (ROS) and antioxidant enzymes as well as the transcripts of genes involved in the relevant processes were measured. In the presence of 100 and 150 mmol L−1 NaCl treatments, AtGPDHc2-deficient plants exhibited a pronounced reduction in germination rate, fresh weight, root length, and overall biomass. Furthermore, loss of AtGPDHc2 resulted in a significant perturbation in cellular redox state (NADH/NAD+ and AsA/DHA) and consequent elevation of ROS and thiobarbituric acid-reactive substances (TBARS) content. The elevated ROS level triggered substantial increases in ROS-scavenging enzymes activities, and the up-regulated transcripts of the genes (CSD1, sAPX and PER33) encoding the antioxidant enzymes were also observed. In addition, the transcript levels of COX15, AOX1A and GLDH in gpdhc2 mutants decreased in comparison to wild-type plants, which demonstrated that the deficiency of AtGPDHc2 might also has impact on mitochondrial respiration under salt stress. Together, this work provides some new evidences on illustrating the roles of AtGPDHc2 playing in response to salinity stress by regulating cellular redox homeostasis, ROS metabolism and mitochondrial respiration.

Abstract Background At present, the schizophrenia diagnoses are based on the clinical symptoms and behaviors neglecting the laboratory test indicators. Results To better investigate the diagnostic potential of miRNAs for schizophrenia, we selected 14 candidate miRNAs and examined their expressions in the serums of 40 schizophrenia patients and 40 healthy controls by qRT-PCR. Ultimately three abnormally expressed microRNAs were identified, i.e., miR-34a-5p, miR-432-5p and miR-449a. Then, binary regression analysis was employed to combine 3 dysregulated miRNAs. ROC analysis revealed that the AUC of the combination of miR-432-5p + miR-449a in serums was 0.841 (95% CI: 0.791~0.887) with 90% sensitivity and 80% specificity. The AUC of the combination of miR-34a-5p + miR-432-5p + miR-449a in serums was 0.843 (95% CI: 0.791~0.887) with 90% sensitivity and 77.5% specificity. The results indicated that the combined model of miR-432-5p + miR-449a and miR-34a-5p + miR-432-5p + miR-449a have better prediction performances. Conclusions The study concludes that the two miRNAs combinations have the potential to be used as biomarkers for schizophrenia diagnoses. The finding may be conducive to overcoming the dilemmas faced by current schizophrenia diagnosis.

Low complexity (LC) domains can drive the formation of both amyloid fibrils and protein droplets. Here, the authors identify reversible amyloid cores from the LC of hnRNPA1, based on which they elucidate the structural basis of reversible fibrillation and its interplay with hnRNPA1 droplet formation.

Personality and subjective well-being (SWB) have been suggested to be strongly related in previous studies. This study was intended to confirm the relationship between personality and SWB and tried to seek out the genetic variants which underlie both personality and SWB. The subjects were 890 participants from Chinese Han population. We evaluated their personality using the Big Five Inventory (BFI) and used the Satisfaction With Life Scale (SWLS) to reflect their SWB. Five single nucleotide polymorphisms (SNPs) were selected from the literature (rs1426371, rs2164273, rs322931, rs3756290, rs490647) and genotyped for genetic association study. We found negative correlations between neuroticism and SWB. On the contrary, extraversion and agreeableness were positively associated with SWB. Three SNPs (rs2164273, rs3756290, rs490647) out of the five were found to connect with personality (extraversion, neuroticism, conscientiousness and openness to experience) and rs490647 variants of GRIK3 was also associated with SWB. Individuals carrying G allele at this site were predisposed to have lower risk to be neuroticism and greater chance to be extraverted, open and satisfied with their life. In summary, our study revealed that rs490647 might be a good candidate genetic variant for personality and SWB in Chinese Han population.

Abstract Based on the weighted and shifted Grünwald formula, a fully discrete finite element scheme is derived for the variable coefficient time-fractional subdiffusion equation. Firstly, the unconditional stable and convergent of the fully discrete scheme in L1(H1) $L^{1}(H^{1})$-norm is proved. Secondly, through a new estimate approach, the superclose properties are obtained. The global superconvergence order O(τ2+hm+1) $\mathcal{O}(\tau ^{2}+h^{m+1})$ is deduced with the help of interpolation postprocessing technique. Finally, some numerical results are provided to verify the theoretical analysis.

Abstract Background Autoimmune factor was regarded as one of the risk factors in the pathogenesis of chronic pancreatitis (CP), especially for autoimmune pancreatitis (AIP). However, whether autoimmune factor plays a role in non-AIP CP or not was unknown. Methods Hospitalized patients with non-AIP CP from January 2010 to October 2016 were detected for 22 autoantibodies at the time of hospital admission. Autoantibodies with frequency > 0.5% were enrolled to calculate the frequency in historial healthy controls through literature search in PubMed. Differentially expressed autoantibodies were determined between patients and historial healthy controls, and related factors were identified by multivariate logistic regression analysis. Results In a total of 557 patients, 113 cases were detected with 19 kinds of positive autoantibodies, among them anti-β2-glycoprotein I (β2-GPI) antibody was most frequent (9.16%). Compared with historial healthy controls, the frequencies of serum β2-GPI and anti SS-B antibody in patients were significantly higher, while frequencies of anti-smooth muscle antibody and anticardiolipin antibody were significantly lower (all P

Abstract Background Brachydactyly type A1 (BDA1, OMIM 112500) is a rare inherited malformation characterized primarily by shortness or absence of middle bones of fingers and toes. It is the first recorded disorder of the autosomal dominant Mendelian trait. Indian hedgehog (IHH) gene is closely associated with BDA1, which was firstly mapped and identified in Chinese families in 2000. Previous studies have demonstrated that BDA1-related mutant IHH proteins affected interactions with its receptors and impaired IHH signaling. However, how the altered signaling pathway affects downstream transcriptional regulation remains unclear. Results Based on the mouse C3H10T1/2 cell model for IHH signaling activation, two recombinant human IHH-N proteins, including a wild type protein (WT, amino acid residues 28–202) and a mutant protein (MT, p.E95k), were analyzed. We identified 347, 47 and 4 Gli1 binding sites in the corresponding WT, MT and control group by chromatin immunoprecipitation and the overlapping of these three sets was poor. The putative cis regulated genes in WT group were enriched in sensory perception and G-protein coupled receptor-signaling pathway. On the other hand, putative cis regulated genes were enriched in Runx2-related pathways in MT group. Differentially expressed genes in WT and MT groups indicated that the alteration of mutant IHH signaling involved cell-cell signaling and cellular migration. Cellular assay of migration and proliferation validated that the mutant IHH signaling impaired these two cellular functions. Conclusions In this study, we performed integrated genome-wide analyses to characterize differences of IHH/Gli1 downstream regulation between wild type IHH signaling and the E95K mutant signaling. Based on the cell model, our results demonstrated that the E95K mutant signaling altered Gli1-DNA binding pattern, impaired downstream gene expressions, and leaded to weakened cellular proliferation and migration. This study may help to deepen the understanding of pathogenesis of BDA1 and the role of IHH signaling in chondrogenesis.

Abstract Background Plant glycerol-3-phosphate dehydrogenase (GPDH) catalyzes the reduction of dihydroxyacetone phosphate (DHAP) to produce glycerol-3-phosphate (G-3-P), and plays a key role in glycerolipid metabolism as well as stress responses. Results In this study, we report the cloning, enzymatic and physiological characterization of a cytosolic NAD+-dependent GPDH from maize. The prokaryotic expression of ZmGPDH1 in E.coli showed that the enzyme encoded by ZmGPDH1 was capable of catalyzing the reduction of DHAP in the presence of NADH. The functional complementation analysis revealed that ZmGPDH1 was able to restore the production of glycerol-3-phosphate and glycerol in AtGPDHc-deficient mutants. Furthermore, overexpression of ZmGPDH1 remarkably enhanced the tolerance of Arabidopsis to salinity/osmotic stress by enhancing the glycerol production, the antioxidant enzymes activities (SOD, CAT, APX) and by maintaining the cellular redox homeostasis (NADH/NAD+, ASA/DHA, GSH/GSSG). ZmGPDH1 OE Arabidopsis plants also exhibited reduced leaf water loss and stomatal aperture under salt and osmotic stresses. Quantitative real-time RT-PCR analyses revealed that overexpression of ZmGPDH1 promoted the transcripts accumulation of genes involved in cellular redox homeostasis and ROS-scavenging system. Conclusions Together, these data suggested that ZmGPDH1 is involved in conferring salinity and osmotic tolerance in Arabidopsis through modulation of glycerol synthesis, stomatal closure, cellular redox and ROS homeostasis.

As an endoplasmic reticulum (ER)-anchored phospholipase, neuropathy target esterase (NTE) catalyzes the deacylation of lysophosphatidylcholine (LPC) and phosphatidylcholine (PC). The catalytic domain of NTE (NEST) exhibits comparable activity to NTE and binds to lipid droplets (LD). In the current study, the nucleotide monophosphate (cNMP)-binding domains (CBDs) were firstly demonstrated not to be essential for the ER-targeting of NTE, but to be involved in the normal ER distribution and localization to LD. NEST was associated with LD surface and influenced LD formation in human neuroblastoma cells. Overexpression of NEST enhances triacylglycerol (TG) accumulation upon oleic acid loading. Quantitative targeted lipidomic analysis shows that overexpression of NEST does not alter diacylglycerol levels but reduces free fatty acids content. NEST not only lowered levels of LPC and acyl-LPC, but not PC or alkyl-PC, but also widely altered levels of other lipid metabolites. Qualitative PCR indicates that the increase in levels of TG is due to the expression of diacylglycerol acyltransferase 1 gene by NEST overexpression. Thus, NTE may broadly regulate lipid metabolism to play roles in LD biogenesis in cells.

The continuing impact between the Eurasia Plate and India results in the thickening and shortening of the N-S Tibetan Plateau. There has been strong tectonic movement along the boundary of the zones of deformation of the NE corner of the Tibetan plateau (NET) since the new tectonic period, with its dynamic mechanisms remaining controversial. Here, we use observations of 39 Continuous Global Positioning System (CGPS) gauges and 451 Crustal Movement Observation Network of China (CMONOC) campaign-mode stations to detect the three-dimensional deformation of the crust in the NET. Improved processing procedures are implemented to strengthen the patterns of strain throughout the NET. The principal component analysis (PCA) technique is introduced to decompose the time series into spatial eigenvectors and principal components (PCs), and the first three PCs are used to estimate and rectify common mode errors (CMEs). In addition, GRACE observations are used to detect deformation changes that account for non-tidal oceanic mass loading, hydrological loading, and surface pressure. The rectified deformation of the crust indicates the anisotropic nature of both the subsidence and uplift, and that the highest uplift rate of the Longmen Shan fault uplift reaches 7.13 ± 0.53 mm/yr. Finally, the horizontal velocity is further used to enumerate the strain rates throughout the NET. The results show that the shear band retained property in line with the strike-slip fault along the Altyn Tagh fault, the Qilian Shan faults, the Haiyuan fault, the West Qinling fault, the East Kunlun fault, and the Longmen Shan fault. In addition, the results further indicate that the whole NET shows a strong relationship with the mean principal rates of horizontal shortening strain. Extension and compression of the crust reasonably describe its sinking and uplifting.

Abstract Background Pediatric patients always suffer from chronic pancreatitis (CP), especially those with steatorrhea. This study aimed to identify the incidence of and risk factors for steatorrhea in pediatric CP. To our best knowledge, there is no pediatric study to document the natural history of steatorrhea in CP. Methods CP patients admitted to our center from January 2000 to December 2013 were enrolled. Patients were assigned to the pediatric (

Low temperature is one of the major abiotic stresses that restrict the growth and development of maize seedlings. Membrane lipid metabolism and remodeling are key strategies for plants to cope with temperature stresses. In this study, an integrated lipidomic and transcriptomic analysis was performed to explore the metabolic changes of membrane lipids in the roots of maize seedlings under cold stress (5°C). The results revealed that major extraplastidic phospholipids [phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA), and phosphatidylinositol (PI)] were dominant membrane lipids in maize root tissues, accounting for more than 70% of the total lipids. In the transcriptome data of maize roots under cold stress, a total of 189 lipid-related differentially expressed genes (DEGs) were annotated and classified into various lipid metabolism pathways, and most of the DEGs were enriched in the “Eukaryotic phospholipid synthesis” (12%), “Fatty acid elongation” (12%), and “Phospholipid signaling” (13%) pathways. Under low temperature stress, the molar percentage of the most abundant phospholipid PC decreased around 10%. The significantly up-regulated expression of genes encoding phospholipase [phospholipase D (PLD)] and phosphatase PAP/LPP genes implied that PC turnover was triggered by cold stress mainly via the PLD pathway. Consequently, as the central product of PC turnover, the level of PA increased drastically (63.2%) compared with the control. The gene-metabolite network and co-expression network were constructed with the prominent lipid-related DEGs to illustrate the modular regulation of metabolic changes of membrane lipids. This study will help to explicate membrane lipid remodeling and the molecular regulation mechanism in field crops encountering low temperature stress.

Epilepsy is a chronic disease that can cause temporary brain dysfunction as a result of sudden abnormal discharge of the brain neurons. The seizure mechanism of epilepsy is closely related to the neurotransmitter imbalance, synaptic recombination, and glial cell proliferation. In addition, epileptic seizures can lead to mitochondrial damage, oxidative stress, and the disorder of sugar degradation. Although the mechanism of epilepsy research has reached up to the genetic level, the presently available treatment and recovery records of epilepsy does not seem promising. Recently, natural medicines have attracted more researches owing to their low toxicity and side-effects as well as the excellent efficacy, especially in chronic diseases. In this study, the antiepileptic mechanism of the bioactive components of natural drugs was reviewed so as to provide a reference for the development of potential antiepileptic drugs. Based on the different treatment mechanisms of natural drugs considered in this review, it is possible to select drugs clinically. Improving the accuracy of medication and the cure rate is expected to compensate for the shortage of the conventional epilepsy treatment drugs.

Summary: Exploitation of naturally occurring genetic mutations could empower the discovery of novel aspects of established cancer genes. We report here that TRPS1, a gene linked to the tricho-rhino-phalangeal syndrome (TRPS) and recently identified as a potential breast cancer driver, promotes breast carcinogenesis through regulating replication. Epigenomic decomposition of TRPS1 landscape reveals nearly half of H3K9me3-marked heterochromatic origins are occupied by TRPS1, where it encourages the chromatin loading of APC/C, resulting in uncontrolled origin refiring. TRPS1 binds to the genome through its atypical H3K9me3 reading via GATA and IKAROS domains, while TRPS-related mutations affect its chromatin binding, replication boosting, and tumorigenicity. Concordantly, overexpression of wild-type but not TRPS-associated mutants of TRPS1 is sufficient to drive cancer genome amplifications, which experience an extrachromosomal route and dynamically evolve to confer therapeutic resistance. Together, these results uncover a critical function of TRPS1 in driving heterochromatin origin firing and breast cancer genome evolution.

Background: The cardiac manifestations of coronavirus disease 2019 (COVID-19) patients with cardiovascular disease (CVD) remain unclear. We aimed to investigate the prognostic value of echocardiographic parameters in patients with COVID-19 infection and underlying CVD.Methods: One hundred fifty-seven consecutive hospitalized COVID-19 patients were enrolled. The left ventricular (LV) and right ventricular (RV) structure and function were assessed using bedside echocardiography.Results: Eighty-nine of the 157 patients (56.7%) had underlying CVD. Compared with patients without CVD, those with CVD had a higher mortality (22.5 vs. 4.4%, p = 0.002) and experienced more clinical events including acute respiratory distress syndrome, acute heart injury, or deep vein thrombosis. CVD patients presented with poorer LV diastolic and RV systolic function compared to those without CVD. RV dysfunction (30.3%) was the most frequent, followed by LV diastolic dysfunction (9.0%) and LV systolic dysfunction (5.6%) in CVD patients. CVD patients with high-sensitivity troponin I (hs-TNI) elevation or requiring mechanical ventilation therapy demonstrated worsening RV function compared with those with normal hs-TNI or non-intubated patients, whereas LV systolic or diastolic function was similar. Impaired RV function was associated with elevated hs-TNI level. RV function and elevated hs-TNI level were independent predictors of higher mortality in COVID-19 patients with CVD.Conclusions: Patients with COVID-19 infection and underlying CVD displayed impaired LV diastolic and RV function, whereas LV systolic function was normal in most patients. Importantly, RV function parameters are predictive of higher mortality.

Background: RVEF (right ventricular ejection fraction) measured by three-dimensional echocardiography (3DE) has been used in evaluating right ventricular (RV) function and can provide useful prognostic information in other various cardiovascular diseases. However, the prognostic value of 3D-RVEF in coronavirus disease 2019 (COVID-19) remains unknown. We aimed to investigate whether 3D-RVEF can predict the mortality of COVID-19 patients.Methods: A cohort of 128 COVID-19-confirmed patients who had undergone echocardiography were studied. Thirty-one healthy volunteers were also enrolled as controls. COVID-19 patients were divided into three subgroups (general, severe, and critical) according to COVID-19 severity-of-illness. Conventional RV structure and function parameters, RV free wall longitudinal strain (FWLS) and 3D-RVEF were acquired. RVFWLS was measured by two-dimensional speckle tracking echocardiography. RVEF was acquired by 3DE.Results: Compared with controls, 2D-RVFWLS and 3D-RVEF were both significantly decreased in COVID-19 patients (−27.2 ± 4.4% vs. −22.9 ± 4.8%, P < 0.001; 53.7 ± 4.5% vs. 48.5 ± 5.8%, P < 0.001). Critical patients were more likely to have a higher incidence of acute cardiac injury and acute respiratory distress syndrome (ARDS), and worse prognosis than general and severe patients. The critical patients exhibited larger right-heart chambers, worse RV fractional area change (RVFAC), 2D-RVFWLS, and 3D-RVEF and higher proportion of pulmonary hypertension than general and severe patients. Eighteen patients died during a median follow-up of 91 days. The multivariate Cox regression analysis revealed the acute cardiac injury, ARDS, RVFAC, RVFWLS, and 3D-RVEF were independent predictors of death. 3D-RVEF (chi-square to improve 18.3; P < 0.001), RVFAC (chi-square to improve 4.5; P = 0.034) and 2D-RVFWLS (chi-square to improve 5.1; P = 0.024) all provided additional prognostic value of higher mortality over clinical risk factors. Moreover, the incremental predictive value of 3D-RVEF was significantly (P < 0.05) higher than RVFAC and RVFWLS.Conclusion: 3D-RVEF was the most robust independent predictor of mortality in COVID-19 patients and provided a higher predictive value over conventional RV function parameters and RVFWLS, which may be helpful to identify COVID-19 patients at a higher risk of death.

Odorant binding proteins (OBPs) play a key role in the olfactory recognition of insects, whose functions have been extensively studied in adult insects but rarely in larvae. In this study, one OBP (SlitOBP11) with high expression in larval antenna but low expression in adult antenna of Spodoptera litura was screened by RNA-seq and verified by quantitative real-time PCR. Furthermore, the function of SlitOBP11 was explored by analysis of the expression patterns and prokaryotic expression of proteins as well as assays of competitive binding. Competitive binding assay demonstrated that SlitOBP11 had high binding affinity to all four female sex pheromone components, but exhibited almost no binding affinity to plant volatiles except for a low affinity to Phenylacetaldehyde and Phenethyl acetate. Homology modeling and molecular docking implied that the shape of these four sex pheromones were linear, which were appropriate for the binding channel of SlitOBP11 and the amino acid residue Asn99 of SlitOBP11 might play an important role in binding. Taken together, our results indicate that SlitOBP11 may be involved in the perception of female sex pheromones by S. litura larvae, and OBPs in the larvae of S. litura play an important role in the olfactory perception process.

Background: Biventricular longitudinal strain has been recently demonstrated to be predictive of poor outcomes in various cardiovascular settings. Therefore, this study sought to investigate the prognostic implications of biventricular longitudinal strain in patients with coronavirus disease 2019 (COVID-19).Methods: We enrolled 132 consecutive patients with COVID-19. Left ventricular global longitudinal strain from the apical four-chamber views (LV GLS4CH) and right ventricular free wall longitudinal strain (RV FWLS) were obtained using two-dimensional speckle-tracking echocardiography.Results: Compared with patients without cardiac injury, those with cardiac injury had higher levels of coagulopathy and inflammatory biomarkers, higher incidence of complications, more mechanical ventilation therapy, and higher mortality. Patients with cardiac injury displayed decreased LV GLS4CH and RV FWLS, elevated pulmonary artery systolic pressure, and higher proportion of pericardial effusion. Higher biomarkers levels of inflammation and cardiac injury, and the presence of pericardial effusion were correlated with decreases in LV GLS4CH and RV FWLS. During hospitalization, 19 patients died. Compared with survivors, LV GLS4CH and RV FWLS were impaired in non-survivors. At a 3-month follow-up after discharge, significant improvements were observed in LV GLS4CH and RV FWLS. Multivariate Cox analysis revealed that LV GLS4CH [hazard ratio: 1.41; 95% confidence interval [CI]: 1.08 to 1.84; P = 0.011] and RV FWLS (HR: 1.29; 95% CI: 1.09–1.52; P = 0.003) were independent predictors of higher mortality in patients with COVID-19.Conclusions: LV GLS4CH and RV FWLS are independent and strong predictors of higher mortality in COVID-19 patients and can track improvement during the convalescent phase of their illness. Therefore, biventricular longitudinal strain may be crucial for risk stratification and serial follow-up in patients with COVID-19.

The striped flea beetle, Phyllotreta striolata (Fabricius), damages crops in the Brassicaceae. The genetic data for this pest are insufficient to reveal its insecticide resistance mechanisms or to develop molecular markers for resistance monitoring. We used PacBio Iso-Seq technology to sequence the full-length transcriptome of P. striolata. After isoform sequence clustering and removal of redundant transcripts, a total of 41,293 transcripts were obtained, and 35,640 of these were annotated in the database of gene products. Structure analysis uncovered 4,307 alternative splicing events, and 3,836 sequences were recognized as lncRNAs. Transcripts with the complete coding region of important detoxification enzymes were further classified. There were 57 transcripts of P450s distributed in CYP2, CYP3, CYP4, and Mito CYP clades, 29 transcripts of ESTs from 4 functional groups, 17 transcripts of GSTs classified into 5 families, 51 transcripts of ABCs distributed in 6 families, and 19 transcripts of UGTs. Twenty-five lncRNAs were predicted to be regulators of these detoxification genes. Full-length transcriptome sequencing is an efficient method for molecular study of P. striolata and it is also useful for gene function analysis.