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Chlorine-containing disinfectants have been widely used all over the world to prevent COVID-19. However, little is known about the potential risk of chlorine-containing disinfectants in the marine environment. Phaeodactylum tricornutum (P. tricornutum) is a typical marine economic diatom, often used as an effective biomarker in ecotoxicology research. Here, the present study has investigated the effect of different effective chlorine concentrations on photosynthesis of P. tricornutum by chlorophyll fluorescence spectroscopy. Results have demonstrated that chlorine exposure promoted the chlorophyll fluorescence intensity at initial stage (24 h), suggesting that a large amount of energy is emitted in the form of fluorescence. However, the chlorophyll fluorescence intensity could not be detected under the high effective chlorine concentrations (6.7 × 10−3, 1.0 × 10−2, 1.3 × 10−2 and 1.7 × 10−2 mg L−1) after 48 h, indicating that the chlorine had high toxicity leading to the death of microalgae. In addition, the emission spectra of P. tricornutum were determined to contain two distinct fluorescence peaks representing the core antenna of photosystem II (685 nm) and the photosystem I complexes (710 nm) in the control group. The fluorescence emission peak value at 685 nm is significantly lower than the peak value at 710 nm in the control group, whereas chlorine treatments were opposite. It can be concluded that microalgae can regulate the distribution of excitation energy between the two photosystems to ensure that algae can utilize light energy. The result also found that the peak position of fluorescence emission spectra has a blue shift in all of NaClO treatments. The fluorescence intensity of microalgae excited at 467 nm was lower than that at 439 nm in chlorine treatments, illustrating chlorophyll b antenna was more easily damaged than chlorophyll a antenna. Our findings are providing new insights into the changing mechanism of chlorophyll fluorescence on P. tricornutum under chlorine stress and valuable data for risk assessment of marine environments.

Abstract Background SYN1 encodes synapsin I, which is a neuronal phosphoprotein involving in regulating axonogenesis and synaptogenesis. Variants in the gene have been associated with X-linked neurodevelopmental disorders in recent years. Methods In the study, we reported two male patients with familial SYN1 variants related neurodevelopmental disorders from Asian population. Previously published cases with significant SYN1 variants from the literature were also included to analyze the phenotype and genotype of the disorder. Results Two maternally inherited SYN1 variants, including c.C1076A, p.T359K in proband A and c.C1444T, p. Q482X in proband B (NM_133499) were found, which have never been described in detail. Combining with our research, all reported probands were male in the condition, whose significant SYN1 variants were inherited from their asymptomatic or mild affected mother. Although the disorder encompasses three main clinical presentations: mental deficiency, easily controlled reflex seizure and behavior problems, patients’ clinical manifestations vary in genders and individuals, even in the same pedigree. Conclusion We firstly reported two familial SYN1-related neurodevelopmental disorders in Asian pediatric patients. Gender and phenotype differences should be highly valued in the disorder.

ObjectiveAlthough many unexplained intellectual disability/global developmental delay (ID/GDD) individuals have benefited from the excellent detection yield of copy number variations and next-generation sequencing testing, many individuals still who suffer from ID/GDD of unexplained etiology. In this study, we investigated the applicability of fragile X syndrome (FXS) testing in unexplained ID/GDD individuals with negative or absent genetic testing.MethodsIn this study, we used the triplet repeat primed polymerase chain reaction to evaluate the value and application of fragile X testing in unexplained ID/GDD individuals with negative or absent genetic testing (n = 681) from three hospitals.ResultsOf the 681 ID/GDD individuals with negative or absent genetic testing results detected by FXS testing, 12 men and one woman were positive. This corresponded to a diagnostic yield of 1.9% for FXS testing in our cohort. All FXS individuals had either a family history of ID/GDD or suggestive clinical features. The detection yield of FXS testing in ID/GDD individuals who completed genetic testing (2.70%, 12/438) was significantly higher than in individuals without any genetic testing (0.40%, 1/243).ConclusionsThis is the first report of FXS testing in ID/GDD individuals who lacked previous genetic testing, which promotes standardization of the FXS diagnostic process. These results highlight the utility of FXS testing of unexplained ID/GDD individuals with negative results from standard genetic testing. In the era of next-generation sequencing, FXS testing is more suitable as a second-tier choice and provides clinicians and geneticists with auxiliary references for tracing the etiology of ID/GDD.

CSNK2B has recently been identified as the causative gene for Poirier–Bienvenu neurodevelopmental syndrome (POBINDS). POBINDS is a rare neurodevelopmental disorder characterized by early-onset epilepsy, developmental delay, hypotonia, and dysmorphism. Limited by the scarcity of patients, the genotype–phenotype correlations in POBINDS are still unclear. In the present study, we describe the clinical and genetic characteristics of eight individuals with POBINDS, most of whom suffered developmental delay, generalized epilepsy, and hypotonia. Minigene experiments confirmed that two intron variants (c.367+5G>A and c.367+6T>C) resulted in the skipping of exon 5, leading to a premature termination of mRNA transcription. Combining our data with the available literature, the types of POBINDS-causing variants included missense, nonsense, frameshift, and splicing, but the variant types do not reflect the clinical severity. Reduced casein kinase 2 holoenzyme activity may represent a unifying pathogenesis. We also found that individuals with missense variants in the zinc finger domain had manageable seizures (p = 0.009) and milder intellectual disability (p = 0.003) than those with missense variants in other domains of CSNK2B. This is the first study of genotype–phenotype correlations in POBINDS, drawing attention to the pathogenicity of intron variants and expanding the understanding of neurodevelopmental disorders.

Glutamate-induced excitotoxicity is a pathological basis of many acute/chronic neurodegenerative diseases. Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2b) is a membrane-embedded P-type ATPase pump that manages the translocation of calcium ions (Ca2+) from cytosol into the lumen of the endoplasmic reticulum (ER) calcium stores. It participates in a wide range of biological functions in the central nervous system (CNS). However, the role of SERCA2b in glutamate-induced excitotoxicity and its mechanism must be elucidated. Herein, we demonstrate that SERCA2b mutants exacerbate the excitotoxicity of hypo-glutamate stimulation on HT22 cells. In this study, SERCA2b mutants accelerated Ca2+ depletion through loss-of-function (reduced pumping capacity) or gain-of-function (acquired leakage), resulting in ER stress. In addition, the occurrence of ER Ca2+ depletion increased mitochondria-associated membrane formation, which led to mitochondrial Ca2+ overload and dysfunction. Moreover, the enhancement of SERCA2b pumping capacity or inhibition of Ca2+ leakage attenuated Ca2+ depletion and impeded excitotoxicity in response to hypo-glutamate stimulation. In conclusion, SERCA2b mutants exacerbate ER Ca2+-depletion-mediated excitotoxicity in glutamate-sensitive HT22 cells. The mechanism of disruption is mainly related to the heterogeneity of SERCA2b mutation sites. Stabilization of SRECA2b function is a critical therapeutic approach against glutamate-induced excitotoxicity. These data will expand understanding of organelle regulatory networks and facilitate the discovery and creation of drugs against excitatory/inhibitory imbalance in the CNS.

Objective:Vitro functional analyses of KCNB1 variants have been done to disclose possible pathogenic mechanisms in KCNB1-related neurodevelopmental disorder. “Complete or partial loss of function (LoF),” “dominant-negative (DN) effect” are applied to describe KCNB1 variant's molecular phenotypes. The study here aimed to investigate clinical presentations and variant effects associations in the disorder.Methods: We reported 10 Chinese pediatric patients with KCNB1-related neurodevelopmental disorder here. Functional experiments on newly reported variants, including electrophysiology and protein expression, were performed in vitro. Phenotypic, functional, and genetic data in the cohort and published literature were collected. According to their variants' molecular phenotypes, patients were grouped into complete or partial LoF, and DN effect or non-dominant-negative (non-DN) effect to compare their clinical features.Results: Nine causative KCNB1 variants in 10 patients were identified in the cohort, including eight novel and one reported. Epilepsy (9/10), global developmental delay (10/10), and behavior issues (7/10) were common clinical features in our patients. Functional analyses of 8 novel variants indicated three partial and five complete LoF variants, five DN and three non-DN effect variants. Patient 1 in our series with truncated variants, whose functional results supported haploinsufficiency, had the best prognosis. Cases in complete LoF group had earlier seizure onset age (64.3 vs. 16.7%, p = 0.01) and worse seizure outcomes (18.8 vs. 66.7%, p = 0.03), and patients in DN effect subgroup had multiple seizure types compared to those in non-DN effect subgroup (65.5 vs. 30.8%, p = 0.039).Conclusion: Patients with KCNB1 variants in the Asian cohort have similar clinical manifestations to those of other races. Truncated KCNB1 variants exhibiting with haploinsufficiency molecular phenotype are linked to milder phenotypes. Individuals with complete LoF and DN effect KCNB1 variants have more severe seizure attacks than the other two subgroups.

Objective: The purpose of this study was to search for differential metabolites in urine organic acids, and to characterize metabolic features that can be used to identify metabolites for exploration of global developmental delay (GDD)/intellectual disability (ID) etiology and pathogenesis.Methods: We screened positive test results that could explain GDD/ID from 1,253 cases, and the major differential metabolites in 132 urine organic acids from the 1,230 cases with negative results (863 GDD cases, 367 ID cases), and 100 typically developing children (TD). Non-supervisory principal component analysis and orthogonal partial least squares discriminant analysis were used to develop models to distinguish GDD/ID from TD children, and to detect major differential metabolites.Results: We get 23 positive results that could identify the cause of GDD/ID from 1253 cases diagnosed with GDD/ID. Among 1,230 negative results, we get the differential metabolites of the GDD group and the ID group had the same trend compared with the TD group. Twenty four differential metabolites were obtained from the GDD group, and 25 from the ID group (VIP > 1.0, p < 0.01). These differential metabolites were mainly related to the following pathways: the synthesis and degradation of ketone bodies, citrate cycle, alanine, aspartate and glutamate metabolism, pyrimidine metabolism, butanoate metabolism, pyruvate metabolism, fatty acid biosynthesis, valine, leucine and isoleucine degradation.Conclusion: The use of metabolomics research methods to detect urine organic acids of children with GDD/ID can discover differential metabolites, which might be valuable for future research on the etiology, pathogenesis, prognosis and possible interventions of GDD/ID. The significantly altered differential metabolites indicators could therefore be potential diagnostic biomarkers for GDD/ID.

Real-time monitoring of large marine structures’ health, including drilling platforms, submarine pipelines, dams, and ship hulls, is greatly needed. Among the various kinds of monitoring methods, optical fiber sensors (OFS) have gained a lot of concerns and showed several distinct advantages, such as small size, high flexibility and durability, anti-electromagnetic interference, and high transmission rate. In this paper, three types of OFS used for marine structural health monitoring (SHM), including point sensing, quasi-distributed sensing, and distributed sensing, are reviewed. Emphases are given to the applicability of each type of the sensors by analyzing the operating principles and characteristics of the OFSs. The merits and demerits of different sensing schemes are discussed, as well as the challenges and future developments in OFSs for the marine SHM field.

A fiber-optic biosensing platform based on ultra-narrowband cladding mode resonances was developed on a high-reflectivity fiber Bragg grating (FBG) for targeting biomolecular detection. The multiple cladding modes with a high sensitivity to the refractive index (RI) were excited in the FBG by coupling between the forward-propagating guided core mode of the multimode fiber and the backward-propagating guided cladding mode of the FBG without any damage to the fiber structure or any change to the standard FBG manufacturing process. The full width at half maximum and the Q-factor of the typical cladding mode resonance operation of the proposed sensor are 80 pm and 19,270, respectively, which are better than those of most fiber-optic biosensors reported to date. In addition, the FBG sensor demonstrated a high sensitivity in protein detection and a high selectivity in serum sample assays. The sensitivity of this sensor was further increased simply by coating it with graphene oxide (GO) sheets on the sensing surface without using a signal amplification strategy. Furthermore, an ultra-low limit of detection (LOD) of 32 pM was obtained by the GO-coated FBG sensor for IgG detection. The proposed FBG sensor provides a competitive fiber-optic platform for biomolecular detection. It has a great potential for applications in label-free biosensing.

The coronavirus disease (COVID-19) is the most severe public health problem facing the world currently. Social distancing and avoidance of unnecessary movements are preventive strategies that are being advocated to prevent the spread of the causative virus [severe acute respiratory syndrome (SARS)-CoV2]. It is known that epileptic children need long term treatments (antiepileptic drugs and/or immunosuppressive agents) as well as close follow up due to the nature of the disease. In addition, it is clear that epilepsy can concur with other chronic illnesses which can lower body immunity. As a result, epileptic children have high risk of acquiring this novel disease due to weak/immature immune system. Of concern, the management of children with epilepsy has become more challenging during this outbreak due to the prevention measures that are being taken. Although children with controlled seizures can be managed at home, it is challenging for pediatricians when it comes to cases with uncontrolled seizures/severe cases. To this end, we provide recommendations for the management of epileptic children at home, outpatient and inpatient settings.

In this paper, we demonstrate a fiber-optic surface plasmon resonance (FO-SPR) biosensor based on image processing and back propagation (BP) neural network. The transmitted light of the FO-SPR sensor was captured by using visible (VIS) and near-infrared (NIR) CMOS sensors. The optical information related to the SPR effect was extracted from images based on grayscale conversion and an edge detection algorithm. To achieve accurate monitoring of refractive index (RI) changes, the grayscale means of the VIS and NIR images and the RGB summation of the edge-detected images were used as training and test inputs for the BP neural network. We verified the effectiveness and superiority of this sensing system by experiments on sodium chloride solution identification and protein binding detection. This work is promising for practical applications in standardized biochemical sensing.

Autism spectrum disorder (ASD) is frequently comorbid with other neurological disorders such as intellectual disability (ID) or global development delay (GDD) and epilepsy. The pathogenesis of ASD is complex. So far, studies have identified more than 1000 ASD risk genes. Most of them were also reported to relate with other neurological diseases, and only several of them have been confirmed as pathogenic genes for autism. Little is known about the roles of these risk genes in neurological diseases with ASD. In the present study, we recruited a cohort of 158 neurological disorder probands with 163 variants of 48 ASD risk genes. Of these, 50 individuals (31.6%) were diagnosed with ASD. In the ASD patient subset, we identified several rarely reported candidate genes including DOLK, USH2A, and HUWE1. In a comparison of patients with neurological disorders with and without ASD, we found that ID/GDD was frequently comorbid with ASD whereas epilepsy was more common in the non-ASD group. Statistical analyses of all possible risk factors implicated that variants in synaptic genes, especially non-voltage-gated ion channel genes and in transcriptional and chromosome genes were related to ASD, but none of the investigated environmental factors was. Our results are useful for the future diagnosis and prognosis of patients with neurological disorders and emphasize the utility of genetic screening.

There are many potential applications for biosensors that can provide real-time analysis, such as environmental monitoring and disease prevention. In this study, we investigated a simple strategy for real-time protein detection, which had the advantages of affordability, fast response, portability, and ease of use. A robust quantification of protein interaction was achieved by combining capillary localized surface plasmon resonance (LSPR) sensors and complementary metal−oxide−semiconductor (CMOS) image sensors. Gold nanoparticles were modified on the inner wall of the capillary, which was used as a microfluidic channel and sensing surface. We functionalized one of the LSPR sensors using ligand bound to gold nanoparticle. Our proposed biosensing platform could be easily multiplexed to achieve high throughput screening of biomolecular interactions, and it has the potential for use in disposable sensors. Moreover, the sensing signal was enhanced by the extinction effect of gold nanoparticles. The experimental results showed that our device could achieve qualitative identification and quantitative measurement of transferrin and immunoglobulin G (IgG). As a field-portable and low-cost optical platform, the proposed LSPR biosensing device is broadly applicable to various protein binding tests via a similar self-assembly of organic ultrathin films.

A miniaturization and integration dual-channel fiber optic surface plasmon resonance (SPR) system was proposed and demonstrated in this paper. We used a yellow light-emitting diode (LED, peak wavelength 595 nm) and built-in web camera as a light source and detector, respectively. Except for the detection channel, one of the sensors was used as a reference channel to compensate nonspecific binding and physical absorption. We packaged the LED and surface plasmon resonance (SPR) sensors together, which are flexible enough to be applied to mobile devices as a compact and portable system. Experimental results show that the normalized intensity shift and refractive index (RI) of the sample have a good linear relationship in the RI range from 1.328 to 1.348. We used this sensor to monitor the reversible, specific interaction between lectin concanavalin A (Con A) and glycoprotein ribonuclease B (RNase B), which demonstrate its capabilities of specific identification and biochemical samples concentration detection. This sensor system has potential applications in various fields, such as medical diagnosis, public health, food safety, and environment monitoring.

GNB2L1 and its O-GlcNAcylation has been reported to play roles in gastric cancer metastasis. However, the roles of GNB2L1 in chemoresistance of gastric cancer has never been determined. In the present study, we found that GNB2L1 was downregulated in chemoresistant patients of gastric cancer, and observed the decrease of GNB2L1 in protein levels instead of mRNA levels in different chemoresistant gastric cancer cell lines. Further we proved that this downregulation of GNB2L1 was resulted from its elevated O-GlcNAcylation catalyzed by OGT in both cell lines and patients. Next, we investigate the function of GNB2L1 and its O-GlcNAcylation on gastric cancer metastasis during chemoresistance, and confirmed Ser124 as the major O-GlcNAcylation site on GNB2L1 that regulated its function on metastasis. Furthermore, our data demonstrated that GNB2L1 modulated EMT via regulating the translation of EMT-related proteins in the process of chemoresistance. In summary, this study indicated that GNB2L1 and its O-GlcNAcylation regulated metastasis via modulating the translation of EMT-related proteins in the chemoresistance of gastric cancer.