Metabolome and Transcriptome Association Analysis Reveals Mechanism of Synthesis of Nutrient Composition in Quinoa (Chenopodium quinoa Willd.) Seeds.

Quinoa (Chenopodium quinoa Willd.) seeds are rich in nutrition, superior to other grains, and have a high market value. However, the biosynthesis mechanisms of protein, starch, and lipid in quinoa grain are still unclear. The objective of this study was to ascertain the nutritional constituents of white, yellow, red, and black quinoa seeds and to employ a multi-omics approach to analyze the synthesis mechanisms of these nutrients. The findings are intended to furnish a theoretical foundation and technical support for the biological breeding of quinoa in China. In this study, the nutritional analysis of white, yellow, red, and black quinoa seeds from the same area showed that the nutritional contents of the quinoa seeds were significantly different, and the protein content increased with the deepening of color. The protein content of black quinoa was the highest (16.1 g/100 g) and the lipid content was the lowest (2.7 g/100 g), among which, linoleic acid was the main fatty acid. A combined transcriptome and metabolome analysis exhibited that differentially expressed genes were enriched in "linoleic acid metabolism", "unsaturated fatty acid biosynthesis", and "amino acid biosynthesis". We mainly identified seven genes involved in starch synthesis (LOC110716805, LOC110722789, LOC110738785, LOC110720405, LOC110730081, LOC110692055, and LOC110732328); five genes involved in lipid synthesis (LOC110701563, LOC110699636, LOC110709273, LOC110715590, and LOC110728838); and nine genes involved in protein synthesis (LOC110710842, LOC110720003, LOC110687170, LOC110716004, LOC110702086, LOC110724454 LOC110724577, LOC110704171, and LOC110686607). The data presented in this study based on nutrient, transcriptome, and metabolome analyses contribute to an enhanced understanding of the genetic regulation of seed quality traits in quinoa, and provide candidate genes for further genetic improvements to improve the nutritional value of quinoa seeds.

Dural arteriovenous fistula and sinus thrombosis presenting as parkinsonism and dementia: a case report with literature review.

Introduction: Dural arteriovenous fistula (DAVF) is an uncommon malformation involving an abnormal connection between dural arteries, or the pachymeningeal branches of cerebral arteries, and dural veins. Its exact pathogenesis remains elusive. Known potential triggers for DAVF include cerebral venous sinus thrombosis (CVST), trauma, ear infections, and cranial surgeries. Due to its rarity and diverse clinical presentations, diagnosing DAVF can be a challenge. Case description: We present a case of DAVF associated with CVST, manifesting as rapidly advancing parkinsonism accompanied by dementia over a month. Brain magnetic resonance imaging (MRI) revealed bilateral symmetric T2 hyperintensities in the basal ganglia and brain stem. Cerebral angiography further confirmed a fistula between the torcular herophili and the transverse-sigmoid sinuses. Despite strong recommendations for transvenous embolization of the fistula, the patient declined the procedure. The anticoagulant therapy and symptomatic treatments administered did not yield any improvement in the patient's condition. Additionally, we reviewed 27 DAVF-derived parkinsonism and dementia cases. Conclusion: DAVF must be considered in the differential diagnosis of cases of rapidly progressive parkinsonism with concurrent dementia. Given its potential for treatment and reversibility, timely diagnosis and intervention for DAVF are paramount.

Metagenomic next-generation sequencing for diagnosis of fatal Balamuthia amoebic encephalitis.

INTRODUCTION: Balamuthia amoebic encephalitis (BAE), caused by Balamuthia mandrillaris, is a rare and life-threatening infectious disease with no specific and effective treatments available. The diagnosis of BAE at an early stage is difficult because of the non-specific clinical manifestations and neuroimaging. CASE DESCRIPTION: A 52-year-old male patient, who had no previous history of skin lesions, presented to the emergency department with an acute headache, walking difficulties, and disturbance of consciousness. The patient underwent a series of examinations, including regular cerebrospinal fluid (CSF) studies and magnetic resonance imaging, and tuberculous meningoencephalitis was suspected. Despite being treated with anti-TB drugs, no clinical improvement was observed in the patient. Following corticosteroid therapy, the patient developed a rapid deterioration in consciousness with dilated pupils. Metagenomic next-generation sequencing (mNGS) revealed an unexpected central nervous system (CNS) amoebic infection, and the patient died soon after the confirmed diagnosis. CONCLUSION: This study highlights the application of mNGS for the diagnosis of patients with suspected encephalitis or meningitis, especially those caused by rare opportunistic infections.

Alteration of white matter microstructure in patients with sleep disorders after COVID-19 infection.

BACKGROUND: The pathophysiology of coronasomnia remains unclear. This study aimed to investigate changes in white matter (WM) microstructure and inflammatory factors in patients with sleep disorders (SD) characterized by poor sleep quantity, quality, or timing following coronavirus disease 2019 (COVID-19) infection in the acute phase (within one month) and whether these changes could be recovered at 3-month follow-up. METHODS: 29 acute COVID-19 patients with SD (COVID_SD) and 27 acute COVID-19 patients without SD (COVID_NonSD) underwent diffusion tensor imaging (DTI), tested peripheral blood inflammatory cytokines level, and measured Pittsburgh Sleep Quality Index (PSQI), and matched 30 uninfected healthy controls. Analyzed WM abnormalities between groups in acute phase and explored its changes in COVID_SD at 3-month follow-up by using tract-based spatial statistics (TBSS). Correlations between DTI and clinical data were examined using Spearman partial correlation analysis. RESULTS: Both COVID_SD and COVID_NonSD exhibited widespread WM microstructure abnormalities. The COVID_SD group showed specific WM microstructure changes in right inferior fronto-occipital fasciculus (IFOF) (lower fractional anisotropy [FA]/axial diffusivity [AD] and higher radial diffusivity [RD]) and left corticospinal tract (CST) (higher FA and lower RD) and higher interleukin-1ß (IL-1ß) compared with COVID_NonSD group. These WM abnormalities and IL-1ß levels were correlated PSQI score. After 3 months, the IFOF integrity and IL-1ß levels tended to return to normal accompanied by symptom improvement in the COVID_SD relative to baseline. CONCLUSION: Abnormalities in right IFOF and left CST and elevated IL-1ß levels were important neurophenotypes correlated with COVID_SD, which might provide new insights into the pathogenesis of neuroinflammation in SD patients induced by COVID-19.

Genetic analysis of transcription factors in dopaminergic neuronal development in Parkinson's disease.

BACKGROUND: Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson's disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD. METHODS: Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls. RESULTS: We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. CONCLUSIONS: Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

Case report: A case of primary angiitis of the central nervous system: misdiagnosed for 3.5 years.

Introduction: Primary angiitis of the central nervous system (PACNS) is an uncommon inflammatory condition that exclusively affects blood vessels within the brain parenchyma, leptomeninges, and spinal cord. Due to its infrequency and the variability in its clinical presentation and imaging findings, diagnosing PACNS can be challenging. Case description: In this study, we present the case of a teenager who initially presented with headaches and epilepsy. Comprehensive laboratory tests yield normal results. A series of brain magnetic resonance imaging (MRI) revealed a progression of changes, starting from localized cerebral atrophy and culminating in the development of a contrast-enhanced mass with vasogenic edema. Immune-associated encephalitis and mitochondrial encephalopathy were suspected, but immunologic investigations, mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) sequencing using biopsied muscle, and muscle pathologies were all negative. Ultimately, a diagnosis of PACNS was confirmed through a stereotactic brain biopsy, which took place 3.5 years after the onset of symptoms. The patient responded favorably to treatment with glucocorticoids and cyclophosphamide. Conclusion: In summary, we have described a case of PACNS characterized by localized cerebral atrophy and tumor-like MRI findings, who was misdiagnosed as immune-associated encephalitis or mitochondrial encephalopathy for 3.5 years. We emphasize the importance of dynamic observation of MRI changes, as well as brain biopsy.

Rapid Sample Enrichment, Novel Derivatization, and High Sensitivity for Determination of 3-Chloropropane-1,2-diol in Soy Sauce via High-Performance Liquid Chromatography-Tandem Mass Spectrometry.

A novel, simplified derivatization method and a rapid sample preparation process using carbon yarn as a sorbent for the determination of 3-chloropropane-1,2-diol (3-MCPD) in soy sauce via high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed. 3-MCPD was first enriched and purified with carbon yarn and then eluted with a methanol-water solution. Subsequently, the analyte underwent derivatization with p-(dimethylamino)-phenol for sensitive detection via HPLC-MS/MS. The limit of detection and the limit of quantitation for 3-MCPD were validated to be 0.5 and 1.0 µg/kg, respectively. Spiking experiments showed recoveries between 83 and 94%, with a relative standard deviation of ≤10%. The method was further validated with a certified reference material. Furthermore, 11 real soy sauce samples from local markets were tested by using this method. These results reveal the widespread 3-MCPD contamination. Consequently, this study offers a preferable alternative for the sensitive, accurate, and precise determination of 3-MCPD in soy sauce.

Case report: Desquamating dermatitis, bilateral cerebellar lesions in a late-onset methylmalonic acidemia patient.

Introduction: Cobalamin C (cblC) deficiency is a rare hereditary disorder affecting intracellular cobalamin metabolism, primarily caused by mutations in MMACHC. This condition is characterized by combined methylmalonic acidemia and hyperhomocysteinemia, displaying a wide range of clinical manifestations involving multiple organs. Owing to its uncommon occurrence and diverse clinical phenotypes, diagnosing cblC deficiency is challenging and often leads to delayed or missed diagnoses. Case description: In this report, we present a case of late-onset cblC deficiency with brown desquamating dermatitis on the buttocks. Magnetic resonance imaging (MRI) of the brain revealed bilateral cerebellar abnormalities. The suspicion of an inherited metabolic disorder was raised by abnormal serum amino acid and acylcarnitine levels, along with increased urine methylmalonic acid and serum homocysteine levels. Whole-exome sequencing helped identify a homozygous variant (c.482G>A) in MMACHC, confirming the diagnosis of cblC deficiency. However, despite receiving treatment with hydroxocobalamin and betaine, the patient did not experience clinical improvement, which may be attributed to the delayed diagnosis as indicated by the declining homocysteine and methylmalonic acid levels. Conclusion: Collectively, we emphasize the significance of recognizing the skin lesions and observing serial MRI changes in patients with cblC deficiency. Our case underscores the importance of early diagnosis and timely therapeutic intervention for this severe yet frequently manageable condition.

Selective surface enhanced Raman detection and effective photocatalytic degradation of sulfonamides antibiotic based on a flexible three-dimensional chitosan/carbon nitride/silver substrate.

The prevalence of sulfonamide residues in aquatic environments poses serious environmental risks, and the sensitive detection and effective degradation of sulfonamides have attracted widespread attention. Here, the environmentally friendly chitosan (CS)/carbon nitride (CN) with three-dimensional porous structure is fabricated by freeze-drying method, and subsequently a new bifunctional flexible substrate (CS/CN/Ag) is prepared by anchoring of small sized AgNPs (6 ∼ 12 nm) on CS/CN. Importantly, the CS/CN/Ag substrate shows high adsorption capacity (∼ 83.06%) for sulfamethoxazole (SMX) solution within 20 mins and the limit of detection can be as low as 7.46 × 10-9 mol·L-1 with an enhancement factor of 3.3 × 105. Also, the CS/CN/Ag substrate displays highly selective for surface-enhanced Raman spectroscopy (SERS) detection of sulfonamides and also shows excellent SERS response for SMX in hospital wastewater samples. In addition, the photocatalytic degradation efficiency of SMX could reach as high as 99.22% within 20 mins of irradiation and the CS/CN/Ag still maintains outstanding photocatalytic performance after six cycles. Moreover, the Ag content in the CS/CN/Ag substrate is only 2.35%, and also the CS/CN/Ag exhibits good uniformity, repeatability, recyclability and stability. Therefore, this flexible and cost-effectively substrate of CS/CN/Ag shows great potential for the simultaneous SERS detection and photocatalytic degradation of pollutants in actual wastewater samples.

Case report: Reversible encephalopathy caused by dyskinesia-hyperpyrexia syndrome.

Parkinson's disease (PD) is a common neurodegenerative disorder. Some patients with advanced-stage disease are accompanied by emergencies and critical issues such as dyskinesia-hyperpyrexia syndrome (DHS), parkinsonism-hyperpyrexia syndrome (PHS), and serotonin syndrome (SS). In this study, we report a patient with reversible encephalopathy caused by DHS who presented with an acute onset of fidgetiness, dyskinesia, and hyperpyrexia after antiparkinsonian drug abuse. In the present case, brain magnetic resonance imaging (MRI) showed multiple abnormal signals in the cortex and subcortex of the bilateral parietal and occipital lobes that resolved within weeks, which coincided with the characteristic MRI findings in posterior reversible encephalopathy (PRES). Our report expands on the neuroimaging features of DHS and highlights the importance of early identification, diagnosis, and treatment to improve patient prognosis.

Integrated transcriptome and metabonomic analysis of key metabolic pathways in response to cadmium stress in novel buckwheat and cultivated species.

Introduction: Buckwheat (Fagopyrum tataricum), an important food crop, also has medicinal uses. It is widely planted in Southwest China, overlapping with planting areas remarkably polluted by cadmium (Cd). Therefore, it is of great significance to study the response mechanism of buckwheat under Cd stress and further develop varieties with excellent Cd tolerance. Methods: In this study, two critical periods of Cd stress treatment (days 7 and 14 after Cd treatment) of cultivated buckwheat (Pinku-1, named K33) and perennial species (F. tatari-cymosum Q.F. Chen) (duoku, named DK19) were analyzed using transcriptome and metabolomics. Results: The results showed that Cd stress led to changes in reactive oxygen species (ROS) and the chlorophyll system. Moreover, Cd-response genes related to stress response, amino acid metabolism, and ROS scavenging were enriched or activated in DK19. Transcriptome and metabolomic analyses highlighted the important role of galactose, lipid (glycerophosphatide metabolism and glycerophosphatide metabolism), and glutathione metabolism in response to Cd stress in buckwheat, which are significantly enriched at the gene and metabolic levels in DK19. Discussion: The results of the present study provide valuable information for a better understanding of the molecular mechanisms underlying Cd tolerance in buckwheat and useful clues for the genetic improvement of drought tolerance in buckwheat.

Analysis of histomorphometric and proteome dynamics inside the silk gland lumen of Bombyx mori revealed the dynamic change of silk protein during the molt stage.

Silkworms spin different silks at different growth stages for specific purposes. The silk spun before the end of each instar is stronger than that at the beginning of each instar and cocoon silk. However, the compositional changes in silk proteins during this process are unknown. Consequently, we performed histomorphological and proteomic analyses of the silk gland to characterize changes from the instar end to the next instar beginning. The silk glands were collected on day 3 of third- and fourth-instar larvae (III-3 and IV-3) and the beginning of fourth-instar larvae (IV-0). Proteomic analysis identified 2961 proteins from all silk glands. Silk proteins P25 and Ser5 were significantly more abundant in III-3 and IV-3 than in IV-0, and many cuticular proteins and protease inhibitors increased significantly in IV-0 compared with III-3 and IV-3. This shift may cause mechanical property differences between the instar end and beginning silk. Using section staining, qPCR, and western blotting, we found for the first time that silk proteins were degraded first and then resynthesized during the molting stage. Furthermore, we revealed that fibroinase mediated the changes of silk proteins during molting. Our results provide insights into the molecular mechanisms of silk proteins dynamic regulation during molting.

A portable architectonics of Al/carbon nitride/metal-organic frameworks anchored Ag nanoparticles for SERS detection and photocatalytic degradation of fungicide.

In recent years, it is urgent to develop bi-functional materials for highly sensitive SERS detection and photocatalytic degradation of contaminants in water of fish pond. Herein, using 5-mercapto-1-methyltetrazole as the ligand, the tree-trunk like zeolitic imidazolate framework (ZIF-8) is induced and in-situ grown on the surface of aluminum/flower carbon nitride (Al/f-C3N4). Then, AgNPs are tightly anchored in ZIF-8 of Al/f-C3N4/ZIF-8 by strong Ag-N and Ag-S bonds, and a portable architecture of Al/f-C3N4/ZIF-8/Ag is successfully prepared. Results indicate that the Al/f-C3N4/ZIF-8/Ag architecture exhibits excellent SERS activity and the detection limit can as low as 2.15 × 10-11 mol⋅L-1 for crystal violet (CV, a typical fungicide). Also, the Al/f-C3N4/ZIF-8/Ag substrate presents good photocatalytic activity for CV molecule, and the degradation efficiency reaches 98.58% after illumination for 90 min. This is mainly due to the good adsorption capacity of ZIF-8 which can enrich more CV molecules and pull them to "hot spots" generated by Ag in Al/f-C3N4/ZIF-8/Ag, and thus SERS response are enhanced significantly. Besides, the strong synergistic effect of f-C3N4, ZIF-8 and AgNPs is also important which facilitates the separation of photogenerated electrons and holes. Thus, the designed portable and bi-functional substrate could be used as a potential material for the detection and removal of CV in practical application.

Effects of Basal Selenium Fertilizer Application on Agronomic Traits, Yield, Quality, and Se Content of Dryland Maize.

To explore the efficiency of selenium (Se) fertilizer application in dryland maize, we tested five Se fertilizer application treatments: 0 g ha-1 (Se0), 75 g ha-1 (Se1), 150 g ha-1 (Se2), 225 g ha-1 (Se3), and 300 g ha-1 (Se4). Compared with Se0, Se2 increased the leaf area, chlorophyll content, internode length, plant height, and ear height by 7.95%, 3.20%, 13.19%, 1.89%, and 7.98%, respectively. Se2 and Se3 significantly affected the stem internode diameter, cortex thickness, and cellulose content, which were positively correlated with lodging resistance. Compared with Se0, Se3 promoted the contents of soluble sugar, crude protein, crude fat, and starch in grains, which increased by 9.48%, 6.59%, 1.56%, and 4.82%, respectively. It implies that maize grain application of Se significantly improves their Se content. Se1 did not observably influence the growth of maize, and the promoting effect of Se4 on maize decreased. The lodging resistance of maize as analyzed by Pearson correlation analysis correlated with the application of Se fertilizer. It proved that higher yield, grain quality, grain Se content, and lodging resistance of stems were concerned with Se fertilizer application in the range of 150-225 g ha-1. The results provide useful information for Se fertilizer treatment in dryland maize.

Insights into the structure and composition of mineralized hard cocoons constructed by the oriental moth, Monema (Cnidocampa) flavescens Walker.

Animals widely use minerals and organic components to construct biomaterials with excellent properties, such as teeth, bones, molluscan shells and eggshells. The larvae of the oriental moth, Monema (Cnidocampa) flavescens Walker, secrete silk proteins that combine closely with calcareous minerals to construct a hard cocoon, which is completely different from the mineral-free Bombyx mori cocoon. The cocoons of oriental moths are likely to be the hardest among the cocoons constructed by insect species. The cocoons of oriental moths were found to be mainly composed of calcium oxalates and Asx/Ser/Gly-rich cocoon proteins, but the types of calcium oxalates and cocoon proteins remain to be elucidated. In this study, we provide an in-depth explanation of the inorganic and organic components in the oriental moth cocoon. Microscopy and imaging technologies revealed that the cocoon is composed of mineral crystals, silk fibers and other organic matter. X-ray diffraction and infrared spectral analyses showed that the mineral crystals in the oriental moth cocoon were mainly CaC2H2O4·H2O. ICP-OES analysis suggested that the mineral crystals in the cocoons were mainly CaC2H2O4·H2O. LC-MS/MS-based proteomics allowed us to identify 467 proteins from the oriental moth cocoon, including 252 uncharacterized proteins, 87 enzymes, 36 small molecule binding proteins, and 5 silk proteins. Among the uncharacterized proteins, 25 of which were Asn-rich proteins because they contained a high proportion of Asn residues (19.1%-41.4%). Among the top 20 cocoon proteins with the highest abundance, 9 of which were Asn-rich proteins. The qPCR was used to investigate the expression patterns of the major cocoon protein-coding genes. Three fibroins and three Asn-rich proteins were expressed only in the silk gland but not in other tissues. The expression of Asn-rich proteins in the silk gland gradually increased from the anterior silk gland to the posterior silk gland. These findings provide important references for understanding the formation mechanism and mechanical properties of mineralized hard cocoons constructed by oriental moths.

Associated factors and abnormal dorsal raphe nucleus connectivity patterns of freezing of gait in Parkinson's disease.

BACKGROUND: Freezing of gait (FOG) is a common, disabling symptom of Parkinson's disease (PD), and its exact pathophysiological mechanism is still poorly understood. The control of gait is a complex process that may be influenced by emotions modulated by serotonergic networks. Therefore, this study aimed to determine factors associated with FOG in PD patients and to evaluate the importance of the dorsal raphe nucleus (DRN; central node in the serotoninergic system) in FOG pathophysiology. METHODS: We combined cross-sectional survey data from 453 PD patients. According to the Freezing of Gait Questionnaire (FOGQ), patients were divided into two groups: the "PD with frozen gait (PD-FOG)" and "PD without frozen gait (PD-nFOG)" groups. Demographic characteristics, clinical features, and motor and nonmotor symptoms (NMS) assessments of PD patients were recorded. Univariate statistical analysis was performed between the two groups, and then regression analysis was performed on related factors. We also acquired resting-state functional MRI (rs-fMRI) data from 20 PD-FOG, 21 PD-nFOG, and 22 healthy controls (HCs) who were randomly chosen. We defined seeds in the DRN to evaluate functional connectivity (FC) patterns. RESULTS: The overall frequency of FOG was 11.9% patients in the PD-FOG group were older, had a longer disease duration, had a higher levodopa equivalent daily dose, had more severe motor symptoms and worse quality of life, had a higher proportion of dyskinesia, wearing-off and postural instability/gait difficulty (PIGD) clinical phenotype, and experienced more depression and impaired sleep function than those in the PD-nFOG group. Logistic regression analysis showed that H&Ystage ≥ 3, UPDRS-III scores, PIGD clinical phenotype and excessive daytime sleepiness were associated with FOG. In addition, there was significantly lower FC between the DRN and some cortical structures, including the supplementary motor area (SMA), left superior frontal gyrus (SFG), and left median cingulated cortex (MCC) in PD-FOG patients than HCs and PD-nFOG patients. CONCLUSIONS: These results demonstrate that the severity of PD and PIGD clinical phenotype are associated factors for freezing and that DRN dysfunction may play a key role in PD-related NMS and FOG. An abnormal cortical and brainstem networks may contribute to the mechanisms underlying FOG.

Identification and characterization of sericin5 reveals non-cocoon silk sericin components with high ß-sheet content and adhesive strength.

Sericins are glue proteins on the surface of silk fibers. Four sericins have been characterized in silkworm, namely sericin1 (Ser1), sericin2 (Ser2), sericin3 (Ser3), and sericin4 (Ser4). In this study, we report a novel sericin, sericin5 (Ser5), which exists only in non-cocoon silk. We describe the sequence, exon-intron structure, and translation products of Ser5 in Bombyx mori. The Ser5 gene is approximately 22-kb long and comprises 16 exons. Ser5 protein has a size of 260 kDa, as determined by SDS-PAGE, western blot, and LC-MS/MS. Immunofluorescence analysis revealed that Ser5 co-localizes with Ser1 in the sericin layer. The expression pattern of Ser5 was detected at the transcriptional and translational levels. We systematically analyzed and compared the amino acid composition, repeat regions, and hydrophilicity of silkworm sericins. Morphological observations showed that non-cocoon silk had more sericin than cocoon silk. Circular dichroism spectra revealed that non-cocoon silk sericin contained more ß-sheet structures than cocoon silk sericin. In addition, we found that the hydrophilicity and adhesive strength of native sericin increases gradually from the inner layer to the outer layer. This research enhances our understanding of various sericins from cocoon silk and non-cocoon silk with regard to their expression patterns, hydrophilicity, secondary structure and adhesive performances. STATEMENT OF SIGNIFICANCE: Sericin is a natural biomaterial with diverse biological properties, which has long been used as tissue engineering and biomedical applications. However, the composition and distribution of sericins in different kinds of silk are still uncertain, and the properties difference between sericins have not yet been reported. Our study makes a significant contribution to the literature as it identifies the sequence, composition, hydrophilicity and adhesive property of sericins. Moreover, it provides key insights into the structure-function and function-distribution relationships associated with sericins. We believe that this study will arouse the interest to the readership of your journal as it identifies the new complete sequence of sericin and revealed the composition and properties of sericin, thus highlighting their future potentials applications in both the biomaterial and technical fields.

Altered hydroxymethylome in the substantia nigra of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, and aging and genetic and environmental exposure can contribute to its pathogenesis. DNA methylation has been suggested to play a pivotal role in neurodevelopment and neurodegenerative diseases. 5-hydroxymethylcytosine (5hmC) is generated through 5-methylcytosine (5mC) oxidization by ten-eleven translocation proteins and is particularly enriched in the brain. Although 5hmC has been linked to multiple neurological disorders, little is known about 5hmC alterations in the substantia nigra of patients with PD. To determine the specific alterations in DNA methylation and hydroxymethylation in PD brain samples, we examined the genome-wide profiles of 5mC and 5hmC in the substantia nigra of patients with PD and Alzheimer's disease (ad). We identified 4119 differentially hydroxymethylated regions (DhMRs) and no differentially methylated regions (DMRs) in the postmortem brains of patients with PD compared with those of controls. These DhMRs were PD-specific when compared with the results of AD. Gene ontology analysis revealed that several signaling pathways, such as neurogenesis and neuronal differentiation, were significantly enriched in PD DhMRs. KEGG enrichment analysis revealed substantial alterations in multiple signaling pathways, including phospholipase D (PLD), cAMP and Rap1. In addition, using a PD Drosophila model, we found that one of the 5hmC-modulated genes, PLD1, modulated α-synuclein toxicity. Our analysis suggested that 5hmC may act as an independent epigenetic marker and contribute to the pathogenesis of PD.

Augmented Renal Clearance in Severe Infections-An Important Consideration in Vancomycin Dosing: A Narrative Review.

Vancomycin is a hydrophilic antibiotic widely used in severe infections, including bacteremia and central nervous system (CNS) infections caused by Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci and enterococci. Appropriate antimicrobial dosage regimens can help achieve the target exposure and improve clinical outcomes. However, vancomycin exposure in serum and cerebrospinal fluid (CSF) is challenging to predict due to rapidly changing pathophysiological processes and patient-specific factors. Vancomycin concentrations may be decreased for peripheral infections due to augmented renal clearance (ARC) and increased distribution caused by systemic inflammatory response syndrome (SIRS), increased capillary permeability, and aggressive fluid resuscitation. Additionally, few studies on vancomycin's pharmacokinetics (PK) in CSF for CNS infections. The relationship between exposure and clinical response is unclear, challenging for adequate antimicrobial therapy. Accurate prediction of vancomycin pharmacokinetics/pharmacodynamics (PK/PD) in patients with high interindividual variation is critical to increase the likelihood of achieving therapeutic targets. In this review, we describe the interaction between ARC and vancomycin PK/PD, patient-specific factors that influence the achievement of target exposure, and recent advances in optimizing vancomycin dosing schedules for severe infective patients with ARC.

A wearable screen-printed SERS array sensor on fire-retardant fibre gloves for on-site environmental emergency monitoring.

Glove-based wearable sensors can offer the potential ability to a fast and on-site environmental threat assessment, which is crucial for timely and informed incident management. In this study, an on-demand surface-enhanced Raman scattering (SERS) array sensor has been patterned on fire-retardant fibre gloves via the screen-printing technique in large batches. The screen-printed ink contains one-pot synthesized silver nanoparticle and molybdenum disulfide nanocomposite (Ag/MoS2), and polyanionic cellulose (PAC) as a new adhesive agent. Rhodamine 6G (R6G) was employed as an initial probe molecule to systematically evaluate the performance of the resulting sensor. The results suggest that the fabricated fire-retardant screen-printed SERS array sensor displays high reproducibility and stability at 250 °C, with the lower detection limit of 10-13 M for R6G. The spot-to-spot SERS signals show that the intensity variation was less than 10%. Besides, the SERS signals can be maintained over 7 weeks. Further investigation was then successfully carried out to detect polycyclic aromatic hydrocarbons (PAHs), which are commonly used as flammable chemicals. In our perception, this wearable fire-retardant screen-printed SERS array sensor would be an ideal candidate for practical on-site environmental emergency monitoring due to its fire-retardant capability and timely measurement on a portable carrier.