Clinical features and genetic spectrum of a multicenter Chinese cohort with myotonic dystrophy type 1.

BACKGROUND: As the most common subtype of adult muscular dystrophy worldwide, large cohort reports on myotonic dystrophy type I (DM1) in China are still lacking. This study aims to analyze the genetic and clinical characteristics of Chinese Han DM1 patients. METHODS: Based on the multicenter collaborating effort of the Pan-Yangtze River Delta Alliance for Neuromuscular Disorders, patients with suspected clinical diagnoses of DM1 were genetically confirmed from January 2020 to April 2023. Peak CTG repeats in the DMPK gene were analyzed using triplet repeat-primed PCR (TP-PCR) and flanking PCR. Time-to-event analysis of onset age in females and males was performed. Additionally, detailed clinical features and longitudinal changes from the disease onset in 64 DM1 patients were retrospectively collected and analyzed. The Epworth Sleepiness Scale and Fatigue Severity Scale were used to quantify the severity of daytime sleepiness and fatigue. RESULTS: Among the 211 genetically confirmed DM1 patients, the mean age at diagnosis was 40.9 ± 12.2 (range: 12-74) with a male-to-female ratio of 124:87. The average size of CTG repeats was 511.3 (range: 92-1945). Among the DM1 patients with comprehensive clinical data (n = 64, mean age 41.0 ± 12.0), the age at onset was significantly earlier in males than in females (4.8 years earlier, p = 0.026). Muscle weakness (92.2%), myotonia (85.9%), and fatigue (73.4%) were the most prevalent clinical features. The predominant involved muscles at onset are hands (weakness or myotonia) (52.6%) and legs (walking disability) (42.1%). Of them, 70.3% of patients had daytime sleepiness, 14.1% had cataract surgery, 7.8% used wheelchairs, 4.7% required ventilatory support, and 1.6% required gastric tubes. Regarding the comorbidities, 4.7% of patients had tumors, 17.2% had diabetes, 23.4% had dyspnea, 28.1% had intermittent insomnia, 43.8% experienced dysphagia, and 25% exhibited cognitive impairment. Chinese patients exhibited smaller size of CTG repeats (468 ± 139) than those reported in Italy (613 ± 623), the US (629 ± 386), and Japan (625 [302, 1047]), and milder phenotypes with less multisystem involvement. CONCLUSION: The Chinese Han DM1 patients presented milder phenotypes compared to their Caucasian and Japanese counterparts. A male predominance and an early age of onset were identified in male Chinese Han DM1 patients.

High triglyceride-glucose index at admission is a predictor of post-stroke cognitive impairment in patients with acute ischemic stroke.

BACKGROUND: Post-stroke cognitive impairment (PSCI) is a very common complication of ischemic stroke (IS). Triglyceride-glucose (TyG) index was an effective alternative marker of insulin resistance (IR). This prospective study was designed to explore the correlation between TyG index and PSCI. METHODS: Between January 1 2021 to June 30 2022, consecutive patients with first onset IS were enrolled prospectively. Baseline information was collected at admission and fasting blood was drawn the next morning. Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive function at three months after stroke. Multiple regression analysis was used to explore the correlation between PSCI and TyG. Receiver operating characteristic (ROC) was performed to evaluate the predictive ability. RESULTS: Ultimately, 313 patients were enrolled in this study. The TyG index was higher in patients with PSCI than those without PSCI (8.99 (8.55, 9.54) vs. 8.61(8.25, 8.87), P<0.001). The spearman correlation analysis indicated that TyG index was negatively correlated with MoCA score (r=-0.272, P<0.001). The multivariate logistic regression analysis demonstrated that TyG index was correlated with PSCI independently (P<0.001) regardless of whether the patients had diabetes or not. The area under curve (AUC) of the ROC was 0.684 (95%CI=0.635-0.768, P<0.001). The optimal cutoff value of TyG index for predicting PSCI was 8.81, with a sensitivity of 61.7% and a specificity of 73.6%. CONCLUSION: A higher TyG index level at admission was independently correlated with increased risk of PSCI three months later and could be used as a predictor.

Characterization and genomic analysis of a novel bacteriophage BUCT_49532 lysing Klebsiella pneumoniae.

Bacteriophages are a type of virus widely distributed in nature that demonstrates a remarkable aptitude for selectively recognizing and infecting bacteria. In particular, Klebsiella pneumoniae is acknowledged as a clinical pathogen responsible for nosocomial infections and frequently develops multidrug resistance. Considering the increasing prevalence of antibiotic-resistant bacteria, bacteriophages have emerged as a compelling alternative therapeutic approach. In this study, a novel phage named BUCT_49532 was isolated from sewage using K. pneumoniae K1119 as the host. Electron microscopy revealed that BUCT_49532 belongs to the Caudoviricetes class. Further analysis through whole genome sequencing demonstrated that BUCT_49532 is a Jedunavirus comprised of linear double-stranded DNA with a length of 49,532 bp. Comparative genomics analysis based on average nucleotide identity (ANI) values revealed that BUCT_49532 should be identified as a novel species. Characterized by a good safety profile, high environmental stability, and strong lytic performance, phage BUCT_49532 presents an interesting case for consideration. Although its host range is relatively narrow, its application potential can be expanded by utilizing phage cocktails, making it a promising candidate for biocontrol approaches.

Distribution pattern of iron deposition in the basal ganglia of different motor subtypes of Parkinson's disease.

OBJECTIVE: The quantitative susceptibility mapping (QSM) technique was used to analyze the distribution pattern of iron deposition in the basal ganglia region of patients with motor subtypes of Parkinson's disease (PD) and to explore the difference in iron content in the basal ganglia region of PD motor subtypes on the major motor symptomatic side. METHODS: The study included 76 patients with PD and 37 healthy controls (HC). Patients with PD were divided into two groups: postural instability/gait disorder (PIGD)(n = 48), and tremor dominance (TD)(n = 28). We classified patients with PD according to the side of the major motor symptoms as left PIGD (n = 23), left TD (n = 14), right PIGD (n = 25), and right TD (n = 14). All subjects underwent brain magnetic resonance scanning to obtain QSM and susceptibility values in the corresponding regions of interest (ROI). RESULTS: (1) Compared with the HC, the bilateral SN in the PD-PIGD and TD group showed greater susceptibility values. The susceptibility values in the left CN, bilateral PUT were also greater in the PD-PIGD group than the HC. (2) Compared with the TD, the left PUT susceptibility values were greater in the PIGD group, especially in patients whose major symptomatic side were on the right limb. (3) Correlation analysis showed that in the PD group, bilateral SN was positively correlated with the unified Parkinson's disease rating scale III part scores of the Movement Disorder Society (MDS-UPDRS III) and the Hoehn-Yahr stage. Bilateral dentate nucleus (DN) susceptibility values were significantly positively correlated with TD scores, and left PUT susceptibility values were positively correlated with PIGD scores. The left SN within the PIGD group was positively correlated with the PIGD score. CONCLUSION: There were different iron deposition patterns in the basal ganglia between the PD-PIGD and TD groups. There also seems to be a difference in iron deposition in PD motor subtypes on different major motor symptom sides.

High-risk screening of late-onset Pompe disease: A different early portrait in China.

Introduction: The lack of knowledge regarding the differences between Chinese and other ethnicities in the early manifestation of late-onset Pompe disease (LOPD) prohibits the development of an effective screening strategy. We conducted a multicenter screening study to determine LOPD prevalence in high-risk populations and define the early manifestation of LOPD in China. Methods: Between August 2020 and April 2021, the participants were prospectively identified through medical examination at 20 centers from inpatient departments and outpatient neuromuscular clinics in China. The inclusion criteria were as follows: (1) age ≥ 1 year and (2) either one of the following conditions: (a) persistent hyperCKemia, (b) muscle weakness of the axial and/or limb-girdle muscles, or (c) unexplained restrictive respiratory insufficiency (RI). Enzymatic activity of acid α-glucosidase (GAA) was measured in a dried blood spot (DBS) using a tandem mass spectrometry (MS/MS) assay. Next-generation sequencing (NGS) was used to evaluate all samples with decreased GAA activity, searching for GAA mutations and pseudodeficiency alleles. Results: Among the 492 cases, 26 positive samples (5.3%) were detected in the DBS test. Molecular studies confirmed a diagnosis of LOPD in eight cases (1.6%). Using MS/MS assay, GAA activities in individuals with pseudodeficiency could be distinguished from those in patients with LOPD. The median interval from the onset of symptoms to diagnosis was 5 years. All patients also showed RI, with a mean forced vital capacity (FVC) of 48%, in addition to axial/proximal muscle weakness. The creatine kinase (CK) level ranged from normal to no more than 5-fold the upper normal limit (UNL). LOPD with isolated hyperCKemia was not identified. Conclusion: Less frequent hyperCKemia and predominant RI depict a different early portrait of adult Chinese patients with LOPD. A modified high-risk screening strategy should be proposed for the early diagnosis of Chinese patients with LOPD.

Serum TG/HDL-C level at the acute phase of ischemic stroke is associated with post-stroke cognitive impairment.

BACKGROUND: The ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) bears a relation with poor outcomes of acute ischemic stroke (AIS), but the impact of serum TG/HDL-C level on post-stroke cognitive impairment (PSCI) remains unknown. We conducted this prospective study to explore the association between TG/HDL-C and PSCI. METHODS: Consecutive AIS patients from the Stroke Units of our hospital were prospectively enrolled between July 1, 2020, and June 30, 2021. Blood samples were collected within 24 h after admission. Cognition function was evaluated by the Montreal Cognitive Assessment (MoCA) at 3 months after stroke. We used logistic regression analyses to explore the relationship between TG/HDL-C and PSCI, and then used a receiver operating characteristic (ROC) analysis to assess the ability of acute TG/HDL-C for predicting PSCI. RESULTS: A total of 227 AIS patients were recruited. Compared with patients without PSCI, those with PSCI had a higher level of TG/HDL-C at admission (P < 0.01). The multivariate logistic regression analyses showed that TG/HDL-C level was independently associated with PSCI (P < 0.01). The area under the curve of the ROC for TG/HDL-C as predictor of PSCI was 0.701 (95%CI 0.635-0.768). The optimal cutoff value of TG/HDL-C to indicate PSCI was 1.564, which gave a sensitivity of 55.2% and specificity of 80.6%. CONCLUSIONS: Our study demonstrated that a higher level of TG/HDL-C at the acute phase of ischemic stroke predicted the presence of PSCI at 3 months after stroke.

A simple electrochemiluminesecence aptasenor using a GCE/NCQDs/aptamers for detection of Pb.

An electrochemiluminescence (ECL) aptasensor was prepared to detect Pb2+ with nitrogen-doped carbon quantum dots (NCQDs) as ECL materials. To prepare the working electrode, NCQDs with carboxyl groups were loaded on a glassy carbon electrode (GCE) and then Pb2+ aptamers were covalently bound to the NCQDs to form a stable GCE/NCQDs/aptamers. On addition of Pb2+, the chain aptamers change to a pb2+ G-quadruplex conformation, which lead to a large decrease in the ECL intensity. The variation of intensity and the logarithm of the Pb2+ concentration had a good linear relationship (R2 = 0.998). The detection range was wide (50 pM to 387.9 nM) with a low detection limit (18.9 pM). In interference experiments, the ECL Pb2+ aptasensor did not suffer from interference and it had good stability. The NCQDs ECL aptasensor can detect Pb2+ quickly and accurately, and provides a fast and efficient method for detection of Pb2+. Compared with literatures, the Pb2+ aptasensor has simpler preparation process, lower cost; furthermore, it is more environmentally friendly.

Highly Selective Entrapment of His-Tagged Enzymes on Superparamagnetic Zirconium-Based MOFs with Robust Renewability to Enhance pH and Thermal Stability.

Metal-organic frameworks (MOFs), as a kind of poriferous nanoparticle, are promising candidates for enzyme immobilization to enhance their stability and reusability. However, most MOFs could not specifically immobilize enzymes and regenerate easily, which inevitably leads to serious high consumption and environmental pollution. In this study, renewable and magnetic MOFs were first constructed to specially immobilize His-tagged enzymes from the cell lysates without purification. The immobilized ß-glucuronidase exhibited wider pH adaptability and temperature stability. The relative activity of immobilized ß-glucuronidase was still maintained at ∼80% after eight cycles. Importantly, after simple treatment, the immobilization capacity of regenerated MOFs after simple treatment was restored to more than 90% in the first three times. The specific magnetic MOFs were proven to be an efficient and renewable platform for one-step immobilization and purification of His-tagged enzymes, showing great potential in industrial applications of nanotechnology and biocatalysis.

Multiple chiroptical switches and logic circuit based on salicyl‒ imine‒chitosan hydrogel.

A chitosan-based chiral hydrogel was fabricated by grafting achiral salicylaldehyde (SA) on chitosan chains, followed by supramolecular assembly (CS-SA hydrogel hereafter). The structures and properties of the CS-SA hydrogel were characterized and investigated. The results indicated that the swelling ability of the CS-SA hydrogel depended on the medium pH and crosslinking degree. Circular dichroism measurements revealed that the chiral information of the chitosan was successfully transcribed to the achiral salicylic chromophores through imine bonds. Chiroptical switches based on acid-base responses of the imine bond and the OH fragment of SA and the swelling properties of the CS-SA hydrogel were fabricated, which is first reported for a chitosan-based hydrogel. In addition, a gel film showed good fatigue resistance under external stimuli. IMPLICATION, INHIBIT, and PASS logic gates and a logic circuit based on the chiroptical switches were successfully designed. This study suggests a new method of constructing biobased chiral functional materials.

The correlation of clinical evaluation with life quality and mental status in a Chinese cohort with dysferlinopathy.

INTRODUCTION: Impaired mood and quality of life was common in muscular dystrophies and play an important role in long-term management. Previous studies in dysferlinopathies mainly focused on the genotype-phenotypes correlations. Currently there are very few reports regarding the mental status, life quality and the correlated factors. METHODS: A total of 22 patients with dysferlinopathy was recruited and evaluated by 6-minute walking test (6MWT) and adapted-North Star Ambulatory Assessment (a-NSAA). Chinese version of SF-36, PHQ-9, and GAD-7 scale were used to evaluate the Quality of Life (QoL), depression and anxiety. Statistical analysis was applied to investigate the correlation between clinical variables and life quality or mental status. RESULTS: SF-36 evaluation revealed multiple dimensional impairment in dysferlinopathy patients. Declined score in body pain (78.00 vs. 91.23, p = 0.0129) and mental health (56.00 vs.72.88, p = 0.0493) were of note in female patients. Some patients suffered from depression (23%) and anxiety (23%) with a high score in PHQ-9/GAD-7. The 6MWT was well-correlated with the severity of depression and most scores in QoL except Body Pain and Role emotion. CONCLUSION: The cross-sectional study revealed impaired mental status and life quality in dysferlinopathy, particularly in female patients. The life quality impairment is correlated with the clinical severity.

Water inversed helicity of nanostructures from ionic self-assembly of a chiral gelator and an achiral component.

The ionic self-assemblies (ISAs) formed by a cationic chiral organogelator (l-glutamide amphiphile, abbreviated as PULG) and anionic dyes exhibited helical nanostructures. And the formed helical structures can be tuned by water amount in the ethanol/water solvent. In pure ethanol, the chirality of the gelator was successfully transferred to the achiral components, which was confirmed by the appearance of an induced CD signal in the achiral components. Meanwhile, the electrostatic interaction between the gelator and achiral dyes contributed to the chirality amplification, causing the nanofibrous structures of the gelator to be transformed to uniform left-handed helices. Upon adding water to ethanol, the induced CD signal exhibited inversion from positive to negative. Interestingly, the left-handed helices formed by ISA of PULG/anionic dyes in ethanol were inverted to right-handed helices with the addition of water. Based on detailed investigations of the XRD patterns, CD and UV/Vis spectra, the mechanism of helicity inversion was proposed: left-handed helices were dominated by hydrogen bonding and right-handed helices were dominated by π-π stacking. This work exemplifies a feasible method to invert the helicity of chiral nanostructures in co-assembly and gives an insight into the conformation change of biomacromolecules in a biological system.

Microbial production of glycolate from acetate by metabolically engineered Escherichia coli.

Escherichia coli was metabolically engineered to synthesize glycolate using acetate as the carbon source. The native glyoxylate bypass pathway was reinforced by the overexpression of isocitrate lyase and isocitrate dehydrogenase kinase/phosphatase. Glyoxylate/hydroxypyruvate reductase was overexpressed to convert glyoxylate to glycolate. Meanwhile, side reactions were eliminated by inactivating genes encoding malate synthase, glyoxylate carboligase, and glycolate oxidase to prevent loss of glyoxylate and glycolate. The engineered E. coli produced 1.78 g/L glycolate from 3.23 g/L acetate after 48 h shake flask cultivation using minimal medium supplemented with 1 g/L yeast extract. When citrate synthase, phosphotransacetylase, and acetate kinase were co-overexpressed to strengthen the tricarboxylic acid cycle and acetate utilization, glycolate production titer was improved to 2.75 g/L with pH control in shake flasks. The results of this work offer an approach for producing glycolate using acetate as the carbon source.

Fermentation scale up for α-arbutin production by Xanthomonas BT-112.

α-Arbutin is a glycosylated hydroquinone that has an inhibitory function against tyrosinase. The aim of the present study is to develop an efficient and inexpensive method for large-scale production of α-arbutin by using Xanthomonas BT-112 as biocatalyst. To accomplish this goal, various surfactants were tested to enhance the α-arbutin production, and the optimal operational conditions for 30L jar fermenter were scaled up for a production level of 3000L with using a constant volumetric oxygen transfer coefficient (KLa) and the volumetric aeration rate per volume unit (Q/V) as scale-up criteria. Under the optimized conditions, the α-arbutin produced in the presence of 0.4% (w/v) Tween-80 was 124.8% higher than that of the control, and the yield of α-arbutin in 3000L fermenter was 38.2g/L with a molar conversion ratio of 93.7% based on the amount of hydroquinone supplied. This result is comparable to the results from laboratory-scale fermenter. Hence, 100-fold scale-up was successfully achieved.

Controlled synthesis and photocatalysis of sea urchin-like Fe3O4@TiO2@Ag nanocomposites.

Based on the synergistic photocatalytic activities of nano-sized TiO2 and Ag, as well as the magnetic properties of Fe3O4, a sea urchin-like Fe3O4@TiO2@Ag nanocomposite (Fe3O4@TiO2@Ag NCs) is controllably synthesized with tunable cavity size, adjustable shell layer of TiO2 nanofiber, higher structural stability and larger specific surface area. Here, Fe3O4@TiO2@Ag NCs are obtained with Fe3O4 as the core and nanofiber TiO2/Fe3O4/Ag nanoheterojunctions as the shell; and Ag nanoparticles with diameter of approximately 4 nm are loaded both on TiO2 nanofibers and inside the cavities of sea urchin-like Fe3O4@TiO2 nanocomposites uniformly. Ag nanoparticles lead to the production of more photogenerated charges in the TiO2/Fe3O4/Ag heterojunction via LSPR absorption, and enhance the band-gap absorption of TiO2, while the Fe3O4 cocatalyst provides the active sites for oxygen reduction by the effective transfer of photogenerated electrons to oxygen. So the photocatalytic performance is improved due to the synergistic effect of TiO2/Fe3O4/Ag nanoheterojunctions. As photocatalysts under UV and visible irradiation, the as-synthesized nanocomposites display enhanced photocatalytic and recycling properties for the degradation of ampicillin. Moreover, they present better broad-spectrum antibiosis under visible irradiation. The enhanced photocatalytic activity and excellent chemical stability, in combination with the magnetic recyclability, makes this multifunctional nanostructure a promising candidate for antibiosis and remediation in aquatic environmental contamination in the future.

Biodiesel production using lipase immobilized on epoxychloropropane-modified Fe3O4 sub-microspheres.

Superparamagnetic Fe3O4 sub-microspheres with diameters of approximately 200 nm were prepared via a solvothermal method, and then modified with epoxychloropropane. Lipase was immobilized on the modified sub-microspheres. The immobilized lipase was used in the production of biodiesel fatty acid methyl esters (FAMEs) from acidified waste cooking oil (AWCO). The effects of the reaction conditions on the biodiesel yield were investigated using a combination of response surface methodology and three-level/three-factor Box-Behnken design (BBD). The optimum synthetic conditions, which were identified using Ridge max analysis, were as follows: immobilized lipase:AWCO mass ratio 0.02:1, fatty acid:methanol molar ratio 1:1.10, hexane:AWCO ratio 1.33:1 (mL/g), and temperature 40 °C. A 97.11% yield was obtained under these conditions. The BBD and experimental data showed that the immobilized lipase could generate biodiesel over a wide temperature range, from 0 to 40 °C. Consistently high FAME yields, in excess of 80%, were obtained when the immobilized lipase was reused in six replicate trials at 10 and 20 °C.

A Chiroptical Logic Circuit Based on Self-Assembled Soft Materials Containing Amphiphilic Spiropyran.

A chiral logic circuit is proposed based on the multiple chiroptical responsiveness of a supramolecular gel material. The gel is fabricated by mixing a chiral gelator and a spiropyran derivative. Chiral responsiveness including the chiral switch and the logic gate is realized through the combined chirality transfer, photochromism, and acidichromism of the system.

Separation of capsaicin from capsaicinoids by macroporous resin adsorption chromatography.

The aim of present study is to develop an efficient and low-cost method for capsaicin production isolated from capsaicinoids by macroporous resin adsorption chromatography. HZ816 resin has shown the best adsorption and desorption capacities for capsaicin among other resins. To optimize the operating parameters for separation, initial concentration, diameter-to-height ratio, mobile phase ratio, and crystallization method were investigated. When capsaicinoids solution (5 g/L) was loaded onto the column (diameter-to-height ratio = 1:12) with ethanol/1% w/w NaOH (4:6, v/v) as the mobile phase, capsaicin was purified most effectively. By using acid neutralization as the crystallization method, the purity of capsaicin improved from 90.3 to 99.5% with 82.3% yield. In conclusion, this study provides a simple and low-cost method for the industrial-scale production of high-purity capsaicin.

Visualized discrimination of ATP from ADP and AMP through collapse of supramolecular gels.

A supramolecular gel was fabricated through mixing of a cationic gelator with methyl orange. The addition of ATP into the gel caused a distinct gel-collapse, whereas ADP and AMP preserved the gel formation. This observation provided a simple visualized way to discriminate ATP from AMP and ADP.

Water tuned the helical nanostructures and supramolecular chirality in organogels.

Water was found to tune the self-assembled nanostructures of a cationic amphiphile in organic solvents from nanofibers to helical tapes, helical tubes and chiral nanotwists with various pitch lengths depending on water content. Inversion of CD spectra was observed in the water-triggered polar and non-polar solvent gels.

[Physical and chemical properties of throughfall in main forest types of secondary forest ecosystem in montane regions of eastern Liaoning Province, China].

From July to September 2008, a measurement was made on the physical and chemical properties of bulk precipitation and throughfall in five main forest types, i.e., larch plantation (LP), Fraxinus rhynchophylla stand (FR), mixed forest stand (MF), Korean pine plantation (KP), and Mongolian oak stand (MO), of secondary forest ecosystem in montane regions of eastern Liaoning Province, China. Comparing with bulk precipitation, the throughfall in the five forest types was significantly acidified (P < 0.05), and the acidification degree was in the order of KP > LP > MF > MO > FR. The conductivity and total dissolved solids of the throughfall increased significantly (P < 0.05), and were in the sequence of MO > FR > LP > MF > KP. The dissolved oxygen concentration of the throughfall lowered significantly (P < 0.05), with the rank of KP > MF > FR > MO > LP, while the Cl- concentration increased significantly, ranked as LP > MO > MF > FR > KP. The NO3-concentrations of the throughfall in FR, MO and MF were higher, while those in LP and KP were lower than that of the bulk precipitation.