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Objective Both belimumab and telitacicept are recognised blockers for B lymphocyte activation, both of which have been approved as add-on therapies for SLE in China. The aim of this study is to compare the efficacy of rituximab (RTX) followed by belimumab or telitacicept in a real-world cohort.Methods A total of 49 refractory lupus nephritis patients were enrolled from four independent centres, subsequently categorised into two treatment groups: belimumab group (n=35) and telitacicept group (n=14) based on their treatment following RTX. The outcomes of renal response rates were evaluated.Results In this study cohort, 63.3% presented with anti-dsDNA antibody positivity and 79.6% exhibited hypocomplementemia, with a mean Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Score of 13±6, estimated glomerular filtration rate (eGFR) of 76.2 (30.2, 113.7) mL/min and urinary protein creatinine ratio (uPCR) of 2.45 (0.77, 5.19) g/g. There was no significant differences between groups. After a follow-up duration of 26±12 months, renal objective remission rate was 80.0% (28 patients) in belimumab group and 85.7% (12 patients) in telitacicept group (difference, 5.7 percentage points, 95% CI, −25.8 to 26.8, p=1.000). Renal complete response was 54.3% (19 patients) in belimumab group and 78.6% (11 patients) in telitacicept group (difference, 24.3 percentage points, 95% CI, 9.7 to 47.8, p=0.194). The anti-dsDNA antibody, complement, eGFR, uPCR and SLEDAI-2K Score were improved in both groups with a significant reduction in prednisone dose. Major adverse effects included immunoglobulin deficiency, respiratory tract infection and urinary tract infection. No death occurred.Conclusions The sequential treatment of belimumab or telitacicept following RTX may represent a promising therapeutic approach in the management of refractory lupus nephritis. Further investigation is necessary to establish optimal protocols and long-term benefits.

ABSTRACTEpstein-Barr virus (EBV) infection in humans is ubiquitous and associated with various diseases. Remodeling of the immune microenvironment is the primary cause of EBV infection and pathogenesis; however, the underlying mechanism has not been fully elucidated. In this study, we used whole-transcriptome RNA-Seq to detect mRNAs, long non-coding RNAs (lncRNA), and microRNA (miRNA) profiles in the control group, 3 days, and 28 days after EBV infection, based on the tree shrew model that we reported previously. First, we estimated the proportion of 22 cell types in each sample using CIBERSORT software and identified 18 high-confidence DElncRNAs related to immune microenvironment regulation after EBV infection. Functional enrichment analysis of these differentially expressed lncRNAs primarily focused on the autophagy, endocytosis, and ferroptosis signalling pathways. Moreover, EBV infection affects miRNA expression patterns, and many miRNAs are silenced. Finally, three competing endogenous RNA regulatory networks were built using lncRNAs that significantly correlated with immune cell types, miRNAs that responded to EBV infection, and potentially targeted the mRNA of the miRNAs. Among them, MRPL42-AS-5 might act as an hsa-miR-296-5p “sponge” and compete with target mRNAs, thus increasing mRNA expression level, which could induce immune cell infiltration through the cellular senescence signalling pathway against EBV infection. Overall, we conducted a complete transcriptomic analysis of EBV infection in vivo for the first time and provided a novel perspective for further investigation of EBV-host interactions.

BackgroundTertiary hospitals in China are confronted with significant challenges due to limited spatial capacity and workforce constraints, leading to saturated allocation of medical resources and restricted growth in medical service provision. The incorporation of digital health into medical service process reengineering (MSPR) marks a pivotal transformation and restructuring of conventional health service delivery models. Specifically, the application of MSPR to blood sampling services processes reengineering (BSSPR) holds promise for substantially enhancing the efficiency and quality of medical services through streamlining and optimizing these procedures. However, the comprehensive impact of BSSPR has been infrequently quantified in existing research. ObjectiveThis study aims to investigate the influence of BSSPR on the efficiency and quality of medical services and to elucidate the key informative technological support points underpinning BSSPR. MethodsData were collected from both the new and old laboratory information systems from August 1, 2019, to December 31, 2021. A combination of statistical description, chi-square test, and t test was used to compare check-in time and waiting time of outpatients before and after the implementation of BSSPR. An interrupted time-series design was used to analyze the impact of BSSPR on medical service efficiency and quality, enabling the control of confounding variables, including changes in medical human resources and both long- and short-term temporal trends. ResultsBSSPR had an impact on the efficiency and quality of medical services. Notably, there was a significant increase in the number of patients receiving blood sampling services, with a daily service volume increase of ~150 individuals (P=.04). The average waiting time for patients decreased substantially from 29 (SD 36) to 11 (SD 11) minutes, indicating a marked improvement in patient experience. During the peak period, the number of patients receiving blood sampling services per working hour statistically increased from 9.56 to 16.77 (P

Abstract Stretching elastic materials containing nanoparticle lattices is common in research and industrial settings, yet our knowledge of the deformation process remains limited. Understanding how such lattices reconfigure is critically important, as changes in microstructure lead to significant alterations in their performance. This understanding has been extremely difficult to achieve due to a lack of fundamental rules governing the rearrangements. Our study elucidates the physical processes and underlying mechanisms of three-dimensional lattice transformations in a polymeric photonic crystal from 0% to over 200% strain during uniaxial stretching. Corroborated by comprehensive experimental characterizations, we present analytical models that precisely predict both the three-dimensional lattice structures and the macroscale deformations throughout the stretching process. These models reveal how the nanoparticle lattice and matrix polymer jointly determine the resultant structures, which breaks the original structural symmetry and profoundly changes the dispersion of photonic bandgaps. Stretching induces shifting of the main pseudogap structure out from the 1st Brillouin zone and the merging of different symmetry points. Evolutions of multiple photonic bandgaps reveal potential optical singularities shifting with strain. This work sets a new benchmark for the reconfiguration of soft material structures and may lay the groundwork for the study of stretchable three-dimensional topological photonic crystals.

The conventional droop method for load sharing control in DC microgrid suffers from poor power sharing and voltage regulation, which affects the State of Charge (SoC) balance of distributed Battery Energy Units (BEUs). In this paper, an adaptive droop method based on superimposed frequency is proposed to balance the SoC among distributed BEUs. Accurate current sharing is achieved by using the introduced AC reactive power to adjust the reference voltage according to differences in line resistance. With the proposed SoC balance control method, the SoC balance among BEUs can be guaranteed by the accurate current sharing regardless of the different line resistances in the DC microgrid. In addition, voltage restoration is performed to maintain the average output voltage of the BEU at the nominal value. The effectiveness of the proposed control system is verified by simulation and HIT experimental tests.

In order to support diverse service demands of communication scenarios, 5G adopts the mixed-numerology system based on orthogonal frequency division multiplexing (OFDM).The mixed-numerology systems still have the problem of high peak-to-average power ratio (PAPR).Furthermore, its design structure makes it difficult to apply traditional PAPR suppression methods straight forwardly, in which mixed signals are generated by superimposing multiple sub-signals with different parameters.An optimization model for minimizing PAPR in mixed-numerology systems was established based on tone reservation method.Utilizing the characteristic of single-peak of time-domain kernel, the multiple copies were generated in different numerologies based on the peak position of the mixed signal.The mixed time-domain kernel was then superimposed to reduce the peaks of the mixed signal.Since the proposed algorithm didn’t require inverse fast Fourier transform (IFFT)/ fast Fourier transform (FFT) operations during iteration, it had relatively low computational complexity.Simulation results show that the proposed algorithm effectively reduces the PAPR of mixed signals.

The SO2/NOX pollution in the flue gas of non-ferrous smelting is increasingly serious. At the same time, the accumulation of red mud (RM) in the aluminum industry and phosphorus sludge (PS) in the yellow phosphorus industry has caused serious harm to the environment. To remove SO2 and NOX from the non-ferrous smelting flue gas and realize the resource utilization of the above two solid wastes, an ultrasonic field was used in this study to strengthen the PS excited O3 process and RM wet desulfurization and denitrification process. In the process of O3 excitation, the response surface method (RSM) is used to obtain the optimal O3 excitation concentration, and the optimal reaction conditions are designed based on the response surface optimization model: T is 53.226 °C, power density is 0.4 W/cm2, PS concentration is 51.433 g/L, O3 formation concentration up to 250 ppm or more, which provides a theoretical basis for subsequent desulfurization and denitrification steps. It is proved that this study can replace the expensive traditional O3 generator and provide a basis for NOX removal in the following process. In addition, the optimum experimental conditions of ultrasonic enhanced RM desulfurization and denitrification process were also explored. Under ultrasonic frequency of 28 kHz, ultrasonic power density of 0.4 W/cm2, T of 50 °C, RM concentration of 15 g/L, and stirring intensity of 1000 rpm, the desulfurization efficiency of the reaction system can be maintained above 95 % within 250 min, and the denitrification efficiency can be maintained above 90 % within 250 min. The effect of desulfurization and denitrification in this study is much better than that of traditional methods. Finally, the reaction mechanism of ultrasonic enhanced O3 excitation and RM wet desulfurization and nitrogen removal was discussed by combining adsorption thermodynamics, isotherm, and kinetics. The results showed that the OH· free radicals generated by ultrasonic cavitation and the physical effects brought by emulsification had significant promoting effects.

Abstract Background Epstein-Barr virus (EBV) infection is a major global threat; its manifestations range from the absence of symptoms to multiorgan malignancies and various gastrointestinal diseases. Analyzing the composition and metabolomic profile of gut microbiota during acute EBV infection might be instrumental in understanding and controlling EBV. Methods Six tree shrews were inoculated with EBV by intravenous injection. Blood was collected at regular intervals thereafter from the femoral vein to detect EBV and inflammatory biomarker. At the same time, tree shrew faeces were collected for 16 S rRNA gene sequencing and Non-targeted metabolomics analysis. Results 16 S rRNA gene characterization along with β diversity analysis exhibited remarkable alterations in gut microflora structure with a peak at 7 days post-infection(dpi). Some alterations in the relative richness of bacterial taxon were linked to infectious indicators. Of note, Butyricicoccus relative richness was positively linked to EBV presence in the blood and plasma, the opposite correlation was seen with Variovorax and Paramuribaculum. Non-targeted metabolomics indicated the fecal metabolome profile altered during EBV infection, particularly 7 dpi. The relative abundance of geranic acid and undecylenic acid in stool samples was positively linked to systemic inflammatory biomarkers, and an inverse relationship was reported with the estrone glucuronide, linoleic acid, protoporphyrin IX and tyramine. Conclusion Collectively, EBV infection in this model correlated with changes in the composition and metabolome profile of the gut microbiota.

Four pigment-producing rhizobial strains nodulating Sesbania cannabina (Retz.) Poir. formed a unique group in genus Microvirga in the phylogeny of a 16S rRNA gene and five housekeeping genes (gyrB, recA, dnaK, glnA, and atpD) in a genome analysis, phenotypic characteristics analysis, and chemotaxonomic analysis. These four strains shared as high as 99.3% similarity with Microvirga tunisiensis LmiM8T in the 16S rRNA gene sequence and, in an MLSA, were subdivided into two clusters, ANI (genome average nucleotide) and dDDH (digital DNA–DNA hybridization) which shared sequence similarities lower than the species thresholds with each other and with the reference strains for related Microvirga species. The polar lipids elucidated that phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin were the main components for strain SWF67558T and for strain HBU65207T, with the exception of PC. SWF67558T and HBU65207T strains had similar predominant cellular fatty acids, including C16:0, C18:0, summed feature 2, and summed feature8, but with different contents. In addition, all the four novel strains produced pink-pigment, and the main coloring material extract from strain SWF67558T was identified as zeaxanthin, which presented antioxidant ability and reduction power. With all the phylogenetic and phenotypic divergency, we proposed these pink-pigmented symbiotic bacteria as two novel species, named Microvirga sesbaniae sp. nov. and Microvirga yunnanensis sp. nov., with SWF67558T (=KCTC82331T=GDMCC1.2024T) and HBU65207T (=KCTC92125T=GDMCC1.2023T) as the type strains, respectively.

BackgroundSystemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple systems. Patients with SLE are prone to a variety of malignancies, especially neoplasms of the female reproductive tract. Synchronous tumors, considered to involve multiple sites, are rare in the female reproductive tract. There are hardly any reports of SLE with synchronous reproductive tract tumors.Case presentationWe report the occurrence of two to three reproductive tract tumors in two women with SLE. A 52-year-old woman was diagnosed with vulvar cancer and cervical cancer. Another woman, aged 67, was diagnosed with concurrent vulvar cancer, vaginal cancer, and cervical cancer and also presented with a suspected lung cancer.ConclusionThe presence of synchronous tumors of the reproductive tract in patients with SLE is uncommon and can be easily disregarded. It is crucial to highlight that SLE patients with multiple primary malignancies exhibit notable late-stage presentation at the time of diagnosis, inadequate disease-free survival, poor overall survival, rapid progression rates, and mortality. Consequently, greater awareness must be raised regarding synchronous reproductive tract tumors in patients with SLE. Regular comprehensive cancer screening and management should be implemented for individuals diagnosed with SLE.

Objective and Impact Statement: The microspheres were widely utilized in the field of life sciences, and we have developed an innovative microelectromechanical system (MEMS)-based bioprinting technology (MBT) system for the preparation of the microspheres. The microspheres can be automatically and high-throughput produced with this cutting-edge system. Introduction and Methods: This paper mainly introduced a novel, efficient, and cost-effective approach for the microsphere fabrication with the MBT system. In this work, the whole microsphere production equipment was built and the optimal conditions (like concentration, drying temperature, frequency, and voltage) for generating uniform hydroxypropyl cellulose–cyclosporine A (HPC-CsA) and poly-l-lactic acid (PLLA) microspheres were explored. Results: Results demonstrated that the optimal uniformity of HPC-CsA microspheres was achieved at 2% (w/v) HPC-CsA mixture, 45 °C (drying temperature), 1,000 Hz (frequency), and 25 V (voltage amplitude). CsA microspheres [coefficient of variation (CV): ~9%] are successfully synthesized, and the drug encapsulation rate was 84.8%. The methodology was further used to produce PLLA microspheres with a diameter of ~2.55 μm, and the best CV value achieved 6.84%. Conclusion: This investigation fully highlighted the integration of MEMS and bioprinting as a promising tool for the microsphere fabrication, and this MBT system had huge potential applications in pharmaceutical formulations and medical aesthetics.

ABSTRACT: Objectives: Inappropriate antimicrobial use (AMU) and healthcare-associated infections (HAIs) are important drivers of antimicrobial resistance, but data from the developing world are scarce. We conducted the first point prevalence survey (PPS) to determine the prevalence of AMU and HAIs and the suggested targeted interventions for appropriate AMU and HAI prevention in Shanxi Province, China. Methods: A multicentre PPS was performed in 18 hospitals in Shanxi. Detailed data on AMU and HAI were collected using the Global-PPS method developed by the University of Antwerp and the methodology developed by the European Centre for Disease Prevention and Control, respectively. Results: There were 2171 (28.2%) of the 7707 inpatients receiving at least one antimicrobial. The most commonly prescribed antimicrobials were levofloxacin (11.9%), ceftazidime (11.2%), and cefoperazone and beta-lactamase inhibitor (10.3%). Out of the total indications, 89.2% of antibiotics were prescribed for therapeutic, 8.0% for prophylaxis, and 2.8% for either unknown or other. Of the total surgical prophylaxis, 96.0% of antibiotics were given for more than one day. In general, antimicrobials were given mainly parenterally (95.4%) and empirically (83.3%). A total of 264 active HAIs were identified in 239 patients (3.1%), of which 139 (52.3%) were culture positive. The most common HAI was pneumonia (41.3%). Conclusions: This survey indicated the relatively low prevalence of AMU and HAIs in Shanxi Province. However, this study has also highlighted several priority areas and targets for quality improvement, and repeated PPSs in the future will be useful to gauge progress at controlling AMU and HAIs.

Abstract Numerous researches have evaluated the prevalence and clinical outcome of vitamin D deficiency in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). But the quantitative vitamin D status in acute kidney injury (AKI) patients and its relationship with prognosis remains controversial. We conducted this systemic review and meta-analysis to assess the quantitative difference of vitamin D status, including serum 25(OH) D and 1,25(OH)2D levels, between AKI patients and non-AKI controls, and further explore whether vitamin D status can be clearly correlated with the mortality of AKI. Major databases, including PubMed, Web of Science and EBSCO, were searched until 1st September 2021. All published observational studies related to vitamin D and AKI According to predefined inclusion and exclusion criteria were extracted. Meta-analyses were performed using Review Manager 5.3.5. Four studies including five cohorts were included with a total of 413 patients. The serum 25(OH)D levels showed no statistically significant difference in AKI patients and non-AKI controls. On the other hand, the serum 1,25(OH)2D levels were significant lower in AKI patients than in non-AKI controls (MD = − 17.79, 95% CI = − 32.73 to − 2.85, P = 0.02). As for the relationship between serum vitamin D status and AKI patients’ mortality, we were unable to give a consistent conclusion based on current limited and conflict study results. Our meta-analysis suggested that serum 1,25(OH)2D levels, rather than 25(OH)D, is significantly lower in AKI patients. The relationship between vitamin D status and clinical outcome of AKI remains controversial based on current evidence. Future comprehensive studies are required to confirm these relations and to elucidate potential mechanisms.

Background: Although it has been reported that miRNA carried by M2 microglial exosomes protects neurons from ischemia–reperfusion brain injury, the mechanism of action remains poorly understood. This study aimed to explore the miRNA signaling pathway by which M2-type microglia-derived exosomes (M2-exosomes) ameliorate oxygen–glucose deprivation/reoxygenation (OGD/R)-induced cytotoxicity in HT22 cells. Methods: BV2 microglia were induced by M2 polarization. Then, M2-exosomes were identified via transmission electron microscopy and special biomarker detection and co-cultured with HT22 cells. Cell proliferation was evaluated using the Cell Counting Kit-8 (CCK-8) assay. Intracellular concentrations of reactive oxygen species (ROS), Fe2+, glutathione (GSH), and malondialdehyde (MDA) were determined using dichlorofluorescein fluorescence and biochemical determination. miR-124-3p levels were determined using qRT-PCR, and protein expressions were examined via western blotting. Results: OGD/R suppressed the proliferation and induced the accumulation of Fe2+, ROS, and MDA and reduction of GSH in mouse HT22 cells, suggesting ferroptosis of HT22 cells. OGD/R-induced changes in the above mentioned indexes was ameliorated by M2-exosomes but restored by the exosome inhibitor GW4869. M2-exosomes with (mimic-exo) or without miR-124-3p (inhibitor-exo) promoted and suppressed proliferation and ferroptosis-associated indexes of HT22 cells, respectively. Moreover, mimic-exo and inhibitor-exo inhibited and enhanced NCOA4 expression in HT22 cells, respectively. NCOA4 overexpression reversed the protective effects of miR-124-3p mimic-exo in OGD/R-conditioned cells. NCOA4 was targeted and regulated by miR-124-3p. Conclusions: M2-exosome protects HT22 cells against OGD/R-induced ferroptosis injury by transferring miR-124-3p and NCOA4 into HT22 cells, with the latter being a target gene for miR-124-3p.

Abstract Background It is worrisome that several pollutants can enhance the abundance of antibiotic resistance genes (ARGs) in the environment, including agricultural fungicides. As an important bioindicator for environmental risk assessment, earthworm is still a neglected focus that the effects of the fungicide carbendazim (CBD) residues on the gut microbiome and resistome are largely unknown. In this study, Eisenia fetida was selected to investigate the effects of CBD in the soil-earthworm systems using shotgun metagenomics and qPCR methods. Results CBD could significantly perturb bacterial community and enrich specific bacteria mainly belonging to the phylum Actinobacteria. More importantly, CBD could serve as a co-selective agent to elevate the abundance and diversity of ARGs, particularly for some specific types (e.g., multidrug, glycopeptide, tetracycline, and rifamycin resistance genes) in the earthworm gut. Additionally, host tracking analysis suggested that ARGs were mainly carried in some genera of the phyla Actinobacteria and Proteobacteria. Meanwhile, the level of ARGs was positively relevant to the abundance of mobile genetic elements (MGEs) and some representative co-occurrence patterns of ARGs and MGEs (e.g., cmx-transposase and sul1-integrase) were further found on the metagenome-assembled contigs in the CBD treatments. Conclusions It can be concluded that the enhancement effect of CBD on the resistome in the earthworm gut may be attributed to its stress on the gut microbiome and facilitation on the ARGs dissemination mediated by MGEs, which may provide a novel insight into the neglected ecotoxicological risk of the widely used agrochemicals on the gut resistome of earthworm dwelling in soil. Video abstract Graphical Abstract

[INLINE:1] An enriched environment is used as a behavioral intervention therapy that applies sensory, motor, and social stimulation, and has been used in basic and clinical research of various neurological diseases. In this study, we established mouse models of photothrombotic stroke and, 24 hours later, raised them in a standard, enriched, or isolated environment for 4 weeks. Compared with the mice raised in a standard environment, the cognitive function of mice raised in an enriched environment was better and the pathological damage in the hippocampal CA1 region was remarkably alleviated. Furthermore, protein expression levels of tumor necrosis factor receptor-associated factor 6, nuclear factor κB p65, interleukin-6, and tumor necrosis factor α, and the mRNA expression level of tumor necrosis factor receptor-associated factor 6 were greatly lower, while the expression level of miR-146a-5p was higher. Compared with the mice raised in a standard environment, changes in these indices in mice raised in an isolated environment were opposite to mice raised in an enriched environment. These findings suggest that different living environments affect the hippocampal inflammatory response and cognitive function in a mouse model of stroke. An enriched environment can improve cognitive function following stroke through up-regulation of miR-146a-5p expression and a reduction in the inflammatory response.

The ‘Huangguan’ pear disease spot detection and grading is the key to fruit processing automation. Due to the variety of individual shapes and disease spot types of ‘Huangguan’ pear. The traditional computer vision technology and pattern recognition methods have some limitations in the detection of ‘Huangguan’ pear diseases. In recent years, with the development of deep learning technology and convolutional neural network provides a new solution for the fast and accurate detection of ‘Huangguan’ pear diseases. To achieve automatic grading of ‘Huangguan’ pear appearance quality in a complex context, this study proposes an integrated framework combining instance segmentation, semantic segmentation and grading models. In the first stage, Mask R-CNN and Mask R-CNN with the introduction of the preprocessing module are used to segment ‘Huangguan’ pears from complex backgrounds. In the second stage, DeepLabV3+, UNet and PSPNet are used to segment the ‘Huangguan’ pear spots to get the spots, and the ratio of the spot pixel area to the ‘Huangguan’ pear pixel area is calculated and classified into three grades. In the third stage, the grades of ‘Huangguan’ pear are obtained using ResNet50, VGG16 and MobileNetV3. The experimental results show that the model proposed in this paper can segment the ‘Huangguan’ pear and disease spots in complex background in steps, and complete the grading of ‘Huangguan’ pear fruit disease severity. According to the experimental results. The Mask R-CNN that introduced the CLAHE preprocessing module in the first-stage instance segmentation model is the most accurate. The resulting pixel accuracy (PA) is 97.38% and the Dice coefficient is 68.08%. DeepLabV3+ is the most accurate in the second-stage semantic segmentation model. The pixel accuracy is 94.03% and the Dice coefficient is 67.25%. ResNet50 is the most accurate among the third-stage classification models. The average precision (AP) was 97.41% and the F1 (harmonic average assessment) was 95.43%.In short, it not only provides a new framework for the detection and identification of ‘Huangguan’ pear fruit diseases in complex backgrounds, but also lays a theoretical foundation for the assessment and grading of ‘Huangguan’ pear diseases.

Background: Melanin can be used in biomedical nanomaterials, but its solubility in water and bioavailability are low. Aim: Melanin nanoparticles were prepared and then PEG-natural melanin nanoparticles (NMNP-PEG) were obtained with good performance and optimize their (water solubility, dispersion stability, chelating metal ions, photothermal stability, drug delivery, and biocompatibility), therefore improve the water solubility of melanin and broaden its application scope in biology, medicine, food, and other fields. Methods: MFAK (melanin from apricot kernels) and NMNP-PEG were prepared and characterized using ultraviolet-visible spectrophotometry (UV-Vis), high-performance liquid chromatography (HPLC), Fourier-transform infrared spectroscopy (FTIR), 1H nuclear magnetic resonance (NMR), and electron microscopy. The chelation rate of metal ions, photothermal effect, doxorubicin loading, and cytotoxicity (MCF-7 cells) were examined. Results: UV-Vis, HPLC, FTIR, and NMR indicated that NMNPs contained melanin. NMNPs could be successfully modified using PEG. Under physiological pH conditions (pH 7.4), the metal ion chelation rate of NMNP-PEG increased with time and peaked at 12 h. The photothermal assay showed a temperature enhancement of 26.3°C with 1 mg/mL NMNP-PEG, compared with 1.9℃ with water. The NMNP-PEGs had a typical peak for doxorubicin in the FTIR spectrum, and the peak intensity was proportional to the drug loading. The release of doxorubicin in an acidic buffer was 40.8% at 24 h, almost threefold that in a neutral buffer (11.9%). There was no obvious cytotoxicity from NMNP-PEG. Conclusion: NMNP-PEG displays good stability, high metal ion chelation ability, efficient photothermal conversion potential, drug-retaining capability, sustained controlled drug release, and biocompatibility. This study provides a theoretical basis for NMNP-PEG applications in medicine (targeting specific sites to diagnose and treat diseases), food (extending the shelf life of food), and biology (as metal ion chelating agents to remove heavy metals from wastewater).

Indocyanine green (ICG) is an important kind of near infrared (NIR) photosensitive molecules for PTT/PDT therapy as well as imaging. When exposed to NIR light, ICG can produce reactive oxygen species (ROS), which can kill cancer cells and pathogenic bacteria. Moreover, the absorbed light can also be converted into heat by ICG molecules to eliminate cancer cells. In addition, it performs exceptionally well in optical imaging-guided tumor therapy and antimicrobial therapy due to its deeper tissue penetration and low photobleaching properties in the near-infrared region compared to other dyes. In order to solve the problems of water and optical stability and multi-function problem of ICG molecules, composite nanomaterials based on ICG have been designed and widely used, especially in the fields of tumors and sterilization. So far, ICG molecules and their composite materials have become one of the most famous infrared sensitive materials. However, there have been no corresponding review articles focused on ICG molecules. In this review, the molecular structure and properties of ICG, composite material design, and near-infrared light- triggered anti-tumor, and antibacterial, and clinical applications are reviewed in detail, which of great significance for related research.

Plants must reprogram gene expression to adapt constantly changing environmental temperatures. With the increased occurrence of extremely low temperatures, the negative effects on plants, especially on growth and development, from cold stress are becoming more and more serious. In this research, strand-specific RNA sequencing (ssRNA-seq) was used to explore the dynamic changes in the transcriptome landscape of Arabidopsis thaliana exposed to cold temperatures (4°C) at different times. In total, 7,623 differentially expressed genes (DEGs) exhibited dynamic temporal changes during the cold treatments. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the DEGs were enriched in cold response, secondary metabolic processes, photosynthesis, glucosinolate biosynthesis, and plant hormone signal transduction pathways. Meanwhile, long non-coding RNAs (lncRNAs) were identified after the assembly of the transcripts, from which 247 differentially expressed lncRNAs (DElncRNAs) and their potential target genes were predicted. 3,621 differentially alternatively spliced (DAS) genes related to RNA splicing and spliceosome were identified, indicating enhanced transcriptome complexity due to the alternative splicing (AS) in the cold. In addition, 739 cold-regulated transcription factors (TFs) belonging to 52 gene families were identified as well. This research analyzed the dynamic changes of the transcriptome landscape in response to cold stress, which reveals more complete transcriptional patterns during short- and long-term cold treatment and provides new insights into functional studies of that how plants are affected by cold stress.

Based on the essence of satellite internet, the development status of satellite internet industry from three aspects of evolution path, global deployment and industrial chain was introduced. The operation mode of foreign satellite internet companies. was analyzed On this basis, combined with the network characteristics of the space-integrated-ground information network, and aimed at its basic business, the operation mode of the space-integrated-ground information network was proposed. Finally, the development suggestions of the application and operation of the space-integrated-ground information network were given.

This paper points out the significance of cooling in injection molding and briefly reviews the development of cooling systems. The focus of this survey is on the physical model, development, and optimization of conformal cooling systems which have curved cooling circuits following the shape of mold cavity. Compared with traditional cooling systems, conformal cooling can greatly reduce the warpage defect and shorten the cooling cycle time. The computational design methods and additive manufacturing techniques that prompt the development of conformal cooling are deeply investigated. At the end of this survey, the future perspectives for conformal cooling design and manufacturing are discussed.

Abstract Background There are conflicting research results about the survival differences between hemodialysis(HD) and peritoneal dialysis (PD). The present study estimated the survival and the relative mortality hazard for incident HD and PD patients with end stage renal disease (ESRD) in eastern China. Methods This study examined a cohort of patients with ESRD who initiated dialysis therapy in Zhejiang province between Jan of 2010 and Dec of 2014, followed up until the end of 2015. PD patients were matched in a 1:1 fashion with HD patients, and Kaplan–Meier analysis was used to explore the survival of them. The Cox proportional hazard regression model was applied to identify the factors that predict survival by treatment modality. Subgroup analyses were conducted by stratifying patients according to gender, age, causes of ESRD and comorbidities. Results Among a total of 22,379 enrolled patients (17,029 HD patients and 5350 PD patients), 5350 matched pairs were identified, and followed for a median of 29 months (3 ~ 72 months). Kaplan-Meier survival curve revealed that overall mortality rate was significantly higher in HD patients than in PD patients (log-rank test, P

Microfluidics attracts much attention due to its multiple advantages such as high throughput, rapid analysis, low sample volume, and high sensitivity. Microfluidics has profoundly influenced many fields including chemistry, biology, medicine, information technology, and other disciplines. However, some stumbling stones (miniaturization, integration, and intelligence) strain the development of industrialization and commercialization of microchips. The miniaturization of microfluidics means fewer samples and reagents, shorter times to results, and less footprint space consumption, enabling a high throughput and parallelism of sample analysis. Additionally, micro-size channels tend to produce laminar flow, which probably permits some creative applications that are not accessible to traditional fluid-processing platforms. The reasonable integration of biomedical/physical biosensors, semiconductor microelectronics, communications, and other cutting-edge technologies should greatly expand the applications of current microfluidic devices and help develop the next generation of lab-on-a-chip (LOC). At the same time, the evolution of artificial intelligence also gives another strong impetus to the rapid development of microfluidics. Biomedical applications based on microfluidics normally bring a large amount of complex data, so it is a big challenge for researchers and technicians to analyze those huge and complicated data accurately and quickly. To address this problem, machine learning is viewed as an indispensable and powerful tool in processing the data collected from micro-devices. In this review, we mainly focus on discussing the integration, miniaturization, portability, and intelligence of microfluidics technology.

The advantageous thermal stability and construction workability of gussasphalt, a type of asphalt concrete, has drawn increasing attention. To prepare a type of superior gussasphalt concrete using Qingchuan rock asphalt (QRA), a modified gussasphalt binder was prepared with modifiers made up by different dose of styrene-butadiene-styrene, terpene resin, furfural extraction oil and SAW. Then, the rheological properties, microstructure, and thermal stability of gussasphalt binder were studied. The results indicated that the modifier #1 had significant effects on the other indexes but for the ductility, it was less effective in improving the low-temperature performance of the asphalt binder. The low-temperature performance of the binder with modifier #2 was superior compared with that of binder with modifier #1. The binder with 12.5% QRA and 5% modifier #2 can be regarded as an optimal collocation, which had a superior compatibility, high-temperature performance, and comprehensive temperature susceptibility.

Epstein-Barr virus (EBV) is a human herpesvirus that latently infects approximately 95% of adults and is associated with a spectrum of human diseases including Infectious Mononucleosis and a variety of malignancies. However, understanding the pathogenesis, vaccines and antiviral drugs for EBV-associated disease has been hampered by the lack of suitable animal models. Tree shrew is a novel laboratory animal with a close phylogenetic relationship to primates, which is a critical advantage for many animal models for human disease, especially viral infections. Herein, we first identified the key residues in the CR2 receptor that bind the gp350 protein and facilitate viral entry. We found that tree shrew shares 100% sequence identity with humans in these residues, which is much higher than rabbits (50%) and rats (25%). In vitro analysis showed that B lymphocytes of tree shrews are susceptible to EBV infection and replication, as well as EBV-enhanced cell proliferation. Moreover, results of in vivo experiments show that EBV infection in tree shrews resembles EBV infection in humans. The infected animals exhibited transient fever and loss of weight accompanied by neutropenia and high viremia levels during the acute phase of the viral infection. Thereafter, tree shrews acted as asymptomatic carriers of the virus in most cases that EBV-related protein could be detected in blood and tissues. However, a resurgence of EBV infection occurred at 49 dpi. Nanopore transcriptomic sequencing of peripheral blood in EBV-infected animals revealed the dynamic changes in biological processes occurring during EBV primary infection. Importantly, we find that neutrophil function was impaired in tree shrew model as well as human Infectious Mononucleosis datasets (GSE85599 and GSE45918). In addition, retrospective case reviews suggested that neutropenia may play an important role in EBV escaping host innate immune response, leading to long-term latent infection. Our findings demonstrated that tree shrew is a suitable animal model to evaluate the mechanisms of EBV infection, and for developing vaccines and therapeutic drugs against EBV.

The chlorophyll fluorescence parameter Fv/Fm plays a significant role in indicating the photosynthetic function of plants. The existing technical methods used to measure Fv/Fm are often inefficient and cumbersome. To realize fast and non-destructive monitoring of Fv/Fm, this study took rice under different fertilizer treatments and measured the hyperspectral reflectance information and Fv/Fm data of rice leaves during the whole growth period. Five spectral transformation methods were used to pre-process the spectral data. Then, spectral characteristic wavelengths were extracted by the correlation coefficient method (CC) combined with the competitive adaptative reweighted sampling (CARS) algorithm. Finally, based on the combination of characteristic wavelengths extracted from different spectral transformations, back propagation neural network (BPNN) models were constructed and evaluated. The results showed that: (1) first derivative transform (FD), multiplicative scatter correction (MSC) and standardized normal variation (SNV) methods could effectively highlight the correlation between spectral data and Fv/Fm. The most sensitive bands with high correlation coefficients were concentrated in the range of 650–850 nm, and the absolute values of the highest correlation coefficients were 0.84, 0.73, and 0.72, respectively. (2) The CC-CARS algorithm could effectively screen the characteristic wavelengths sensitive to Fv/Fm. The number of sensitive bands extracted by FD, MSC, and SNV pre-treatment methods were 14, 13, and 16 which only accounted for 2.33%, 2.16%, and 2.66% of the total spectral wavelength (the number of full spectral bands is 601), respectively. (3) The BPNN models were established based on the above sensitive wavelengths, and it was found that MSC-CC-CARS-BPNN had the highest prediction accuracy, and its testing set R2, RMSE and RPD were 0.74, 1.88% and 2.46, respectively. The results can provide technical references for hyperspectral data pre-processing and rapid and non-destructive monitoring of chlorophyll fluorescence parameters.

JET experiments using the fuel mixture envisaged for fusion power plants, deuterium and tritium (D–T), provide a unique opportunity to validate existing D–T fusion power prediction capabilities in support of future device design and operation preparation. The 2021 JET D–T experimental campaign has achieved D–T fusion powers sustained over 5 s in ITER-relevant conditions i.e. operation with the baseline or hybrid scenario in the full metallic wall. In preparation of the 2021 JET D–T experimental campaign, extensive D–T predictive modelling was carried out with several assumptions based on D discharges. To improve the validity of ITER D–T predictive modelling in the future, it is important to use the input data measured from 2021 JET D–T discharges in the present core predictive modelling, and to specify the accuracy of the D–T fusion power prediction in comparison with the experiments. This paper reports on the validation of the core integrated modelling with TRANSP, JINTRAC, and ETS coupled with a quasilinear turbulent transport model (Trapped Gyro Landau Fluid or QualLiKiz) against the measured data in 2021 JET D–T discharges. Detailed simulation settings and the heating and transport models used are described. The D–T fusion power calculated with the interpretive TRANSP runs for 38 D–T discharges (12 baseline and 26 hybrid discharges) reproduced the measured values within 20 $\%$ . This indicates the additional uncertainties, that could result from the measurement error bars in kinetic profiles, impurity contents and neutron rates, and also from the beam-thermal fusion reaction modelling, are less than $20\%$ in total. The good statistical agreement confirms that we have the capability to accurately calculate the D–T fusion power if correct kinetic profiles are predicted, and indicates that any larger deviation of the D–T fusion power prediction from the measured fusion power could be attributed to the deviation of the predicted kinetic profiles from the measured kinetic profiles in these plasma scenarios. Without any posterior adjustment of the simulation settings, the ratio of predicted D–T fusion power to the measured fusion power was found as 65%–96% for the D–T baseline and 81%–97% for D–T hybrid discharge. Possible reasons for the lower D–T prediction are discussed and future works to improve the fusion power prediction capability are suggested. The D–T predictive modelling results have also been compared to the predictive modelling of the counterpart D discharges, where the key engineering parameters are similar. Features in the predicted kinetic profiles of D–T discharges such as underprediction of n _e are also found in the prediction results of the counterpart D discharges, and it leads to similar levels of the normalized neutron rate prediction between the modelling results of D–T and the counterpart D discharges. This implies that the credibility of D–T fusion power prediction could be a priori estimated by the prediction quality of the preparatory D discharges, which will be attempted before actual D–T experiments.

Currently, many microchips must rely on an external force (such as syringe pump, electro-hydrodynamic pump, and peristaltic pump, etc.) to control the solution in the microchannels, which probably adds manual operating errors, affects the accuracy of fluid manipulation, and enlarges the noise of signal. In addition, the reasonable integration of micropump and microchip remain the stumbling block for the commercialization of microfluidic technique. To solve those two problems, we designed and fabricated a thermal bubble micropump based on MEMS (micro-electro-mechanical systems) technique. Many parameters (voltage, pulse time, cycle delay time, etc.) affecting the performance of this micropump were explored in this work. The experimental results showed the flow rate of solution with the assistance of a micropump reached more than 15 μL/min in the optimal condition. Finally, a method about measuring total aflatoxin in Chinese herbs was successfully developed based on the integrated platform contained competitive immunoassay and our micropump-based microfluidics. Additionally, the limit of detection in quantifying total aflatoxin (AF) was 0.0615 pg/mL in this platform. The data indicate this combined technique of biochemical assays and micropump based microchip have huge potential in automatically, rapidly, and sensitively measuring other low concentration of biochemical samples with small volume.

In this study, we investigated how printed sowing machine transplanting impacts the yield of single-season rice by increasing the planting density and decreasing the amount of fertilizer needed. The study was aimed at exploring the relationships between the amount of fertilizer, transplanting density, and rice yield. During the rice growing season from 2019 to 2020 in the middle and lower reaches of the Yangtze River, six different field trials were conducted: low density and high fertilizer (LDHF), low density and low fertilizer (LDLF), middle density and high fertilizer (MDHF), middle density and low fertilizer (MDLF), high density and high fertilizer (HDHF), and high density and low fertilizer (HDLF). It turns out that compared to the LDHF, the thousand seed weight, the spikelets per panicle, the seed-setting rate, and the SPAD value at the filling stage decreased by 0.17% and 0.60%, 5.36% and 10.59%, 5.70% and 4.66%, and 17.52% and 4.93% in 2019 and 2020, respectively. However, compared to the LDHF, the panicles increased by 15.31% and 17.18%, respectively, the LAI at the filling stage increased by 1.92% and 0.48%, respectively, and the accumulation of dry matter above ground at the maturity stage also increased by 3.74% and 16.79% in 2019 and 2020, respectively. Therefore, compared to the yield of rice in the LDHF, the yield of rice in the HDLF increased by 5.06% and 6.64%. The yields of rice in the LDLF, MDHF, MDLF, and HDHF were lower than that in the LDHF and HDLF. The partial least squares path model (PLSPM) analysis showed that the fertilizer, density, and aboveground dry matter had positive effects on the yield, while the SPAD value and LAI had negative effects on the yield. This research shows that increasing the transplanting density can compensate for the yield loss caused by reducing the fertilizer amount. However, no combination of the transplanting density and fertilization amount can achieve the purpose of increasing the yield.

The chlorophyll fluorescence parameter Fv/Fm (maximum photosynthetic efficiency of optical system II) is an intrinsic index for exploring plant photosynthesis. Hyperspectral remote sensing technology can be used for rapid nondestructive detection of chlorophyll fluorescence parameters. Existing studies show that there is a good correlation between the vegetation index and Fv/Fm. However, due to the limited hyperspectral information reflected by the vegetation index, the established model often cannot reach the ideal accuracy. Therefore, this study took rice as the research object and explored the internal relationship between chlorophyll fluorescence parameters and spectral reflectance by setting different fertilization treatments. Spectral sensitive information was extracted by vegetation index and continuous wavelet transform (CWT) to explore a more suitable method for Fv/Fm hyperspectral estimation at the rice leaf scale. Then a monitoring model of Fv/Fm in rice leaves was established by the back propagation neural network (BPNN) algorithm. The results showed that: (1) the accuracy of univariate models constructed by Fv/Fm inversion based on 10 commonly used vegetation indices constructed by traditional methods was low; (2) The correlation between leaf hyperspectral reflectance and Fv/Fm could be effectively improved by using CWT, and the accuracy of the univariate model constructed by using the best wavelet coefficients could reach the level of rough evaluation of Fv/Fm; (3) The effect of wavelet transform using different mother wavelet functions as the basis function was different, and bior3.3 function was the best; R2, RMSE and RPD of the BPNN model constructed by using the first 10 best wavelet coefficients decomposed by the bior3.3 was 0.823 6, 0.013 2 and 2.304 3. In conclusion, this study proves that CWT can effectively extract sensitive bands of rice leaves for Fv/Fm monitoring, providing a reference for the follow-up rapid and nondestructive monitoring of chlorophyll fluorescence.

Objectives: In China, there are two major medical insurance models: the Urban Basic Medical Insurance (UBMI) and the New Cooperative Medical Scheme (NCMS). The aim of the present study was to evaluate the association of the medical insurance type of patients undergoing hemodialysis (HD) with their survival. Methods: We retrospectively analyzed the end-stage renal disease adult patients initiating HD between January 2010 and December 2014 in Zhejiang province, followed up through 31 December 2015. Patients who had received HD for over 3 months were separated into two groups, based on different medical insurance type. Demographic, clinical data, and clinical outcomes were analyzed. The survival rates were calculated by using the Kaplan–Meier method. Results: A total of 6779 patients (59 ± 16 years old, 4331 males (63.9%)) with UBMI and 7177 (59 ± 16 years old, 3778 males (52.8%)) with NCMS enrolled from 226 hemodialysis units. Compared with UBMI group, patients with NCMS had a smaller percentage of hypertensive nephropathy, diabetes mellitus and arteriovenous fistula, faced with more problems in anemia, hypoalbuminemia and metabolism of calcium and phosphorous. The 1-, 3- and 5-year survival rates were 95.4, 84.4, and 74.1% in UBMI group, 93.1, 79.7, and 67.7% in NCMS group, respectively. Patients with NCMS showed higher all-cause mortality compared with UBMI (p

We, the Editor and Publishers of Renal Failure, have retracted the following article: Xi Yao, Shaohua Chen, Wenhua Lei, Nan Shi, Weiqiang Lin, Xiaoying Du, Ping Zhang & Jianghua Chen, The relationship between hemodialysis mortality and the Chinese medical insurance type, Renal Failure, 41:1, 2019, 742–749, https://doi.org/10.1080/0886022X.2019.1652648. The above article has been retracted due to Publisher error as it is an earlier version of an article that was ultimately accepted and published in Renal Failure. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Based on a successive convex programming method, an alternating iteration algorithm is proposed for solving a parameter-dependent distributionally robust optimization. Under the Slater-type condition, the convergence analysis of the algorithm is obtained. When the objective function is convex, a modified algorithm is proposed and a less-conservative solution is obtained. Lastly, some numerical tests results are illustrated to show the efficiency of the algorithm.

Abstract Background Drugs that inhibit the MEK/ERK pathway have therapeutic benefit in bladder cancer treatment but responses vary with patients, for reasons that are still not very clear. Interferon-α (IFN-α) is also used as a therapeutic agent for bladder cancer treatment but the response rate is low. It was found that IFN-α could enhance the cytotoxic effect of MEK inhibition. However, the potential mechanisms of that are still unclear. Understanding of the cross-talk between the IFN-α and MEK/ERK pathway will help enhance the efficacy of IFN-α or MEK inhibitors on bladder cancer. Methods Immunoprecipitation and pull-down assay were used to reveal the formation of signaling complex. The protein expressions were detected by western blot and immunohistochemistry. The cAMP level, Phosphodiesterase 4D (PDE4D) activity and Prostaglandin E2 (PGE2) concentration in cells, serum and tissues were detected by enzyme-linked immunosorbent assay. The role of PDE4D in bladder tumorigenesis in vivo was examined by the xenograft model. Tissue microarray chips were used to investigate the prognostic roles of PDE4D and tumor progression locus 2 (TPL2) in bladder cancer patients. Results IFN-α down-regulated the cyclooxygenase-2 (COX-2) expression in bladder cancer cells through the inhibition of TPL2/NF-κB pathway; IFN-α also inhibited COX-2 expression by suppressing cAMP signaling through TPL2-ERK mediated PDE4D activity. Reduction of the intracellular cAMP level by PDE4D potentiated the antitumor effect of IFN-α against bladder cancer in vitro and in vivo. Further analysis of clinical samples indicated that low PDE4D expression and high level of TPL2 phosphorylation were correlated to the development and poor prognosis in bladder cancer patients. Conclusions Our data reveal that IFN-α can exert its antitumor effect through a non-canonical JAK-STAT pathway in the bladder cancer cells with low activity of IFN pathway, and the TPL2 inhibition is another function of IFN-α in the context of bladder cancer therapy. The antitumor effects of IFN-α and MEK inhibition also depend on the PDE4D-mediated cAMP level in bladder cancer cells. Suppression of the TPL2 phosphorylation and intracellular cAMP level may be possible therapeutic strategies for enhancing the effectiveness of IFN-α and MEK inhibitors in bladder cancer treatment.

While droplet-based microfluidics is a powerful technique with transformative applications, most devices are passively operated and thus have limited real-time control over droplet contents. In this report, an automated droplet-based microfluidic device with pneumatic pumps and salt water electrodes was developed to generate and coalesce up to six aqueous-in-oil droplets (2.77 nL each). Custom control software combined six droplets drawn from any of four inlet reservoirs. Using our μChopper method for lock-in fluorescence detection, we first accomplished continuous linear calibration and quantified an unknown sample. Analyte-independent signal drifts and even an abrupt decrease in excitation light intensity were corrected in real-time. The system was then validated with homogeneous insulin immunoassays that showed a nonlinear response. On-chip droplet merging with antibody-oligonucleotide (Ab-oligo) probes, insulin standards, and buffer permitted the real-time calibration and correction of large signal drifts. Full calibrations (LODconc = 2 ng mL−1 = 300 pM; LODamt = 5 amol) required

The tail-sitter Vertical Takeoff and Landing (VTOL) Unmanned Aerial Vehicle(UAV), flying in a fixed-wing model, overcomes many shortcomings of traditional fixed-wing UAVs, and inherits the advantage of high overall efficiency, which means it has great development potential and very broad application prospects. The attitude of tail-sitter VTOL UAV shows a wide change range in its takeoff and landing stages, and when the attitude sensor changes more than 90 degrees in pitch direction, the Euler angles converted by the Quaternions will have singular points, which means gimbal deadlock appears. From the solution algorithm, this paper provides a method of changing the order of rotation to avoid the appearance of singular points. The results show that this method can be well applied to the attitude solution of the VTOL UAV.

Our previous findings have demonstrated that autophagy regulation can alleviate the decline of learning and memory by eliminating deposition of extracellular beta-amyloid peptide (Aβ) in the brain after stroke, but the exact mechanism is unclear. It is presumed that the regulation of beta-site APP-cleaving enzyme 1 (BACE1), the rate-limiting enzyme in metabolism of Aβ, would be a key site. Neuro-2a/amyloid precursor protein 695 (APP695) cell models of cerebral ischemia were established by oxygen-glucose deprivation to investigate the effects of Rapamycin (an autophagy inducer) or 3-methyladenine (an autophagy inhibitor) on the expression of BACE1. Either oxygen-glucose deprivation or Rapamycin down-regulated the expression of BACE1 while 3-methyladenine up-regulated BACE1 expression. These results confirm that oxygen-glucose deprivation down-regulates BACE1 expression in Neuro-2a/APP695 cells through the introduction of autophagy.

OBJECTIVE:We examined the demographic and clinical profiles of Parkinson's disease in Shanghai, China, to assist in disease management and provide comparative data on Parkinson's disease prevalence, phenotype, and progression among different regions and ethnic groups.METHODS:A door-to-door survey and follow-up clinical examinations identified 180 community-dwelling Han-Chinese Parkinson's disease patients (104 males, 76 females).RESULTS:The average age at onset was 65.16±9.60 years. The most common initial symptom was tremor (112 patients, 62.22%), followed by rigidity (38, 21.11%), bradykinesia (28, 15.56%) and tremor plus rigidity (2, 1.11%). Tremor as the initial symptom usually began in a single limb (83.04% of patients). The average duration from onset to mild Parkinson's disease (Hoehn-Yahr phase 1-2) was 52.74±45.64 months. Progression from mild to moderate/severe Parkinson's disease (phase≥3) was significantly slower (87.07±58.72 months; p

Two medium-low temperature coal tars (MLCTs) derived from the pyrolysis of low-grade bituminous coal were separated into 11 narrow fractions by true boiling distillation. The primary property and chemical composition analysis of MLCTs and their distillate narrow fractions were investigated at the macroscopic and molecular level by gas chromatography-mass spectrometer (GC-MS) and proton nuclear magnetic resonance (1H NMR). The two MLCTs show obvious characteristics of medium-low temperature coal tar, including a high H/C, high-oxygen and nitrogen, low-sulfur, low-density, and low viscosity. As the boiling point increases, the molecular weight of each distillate fraction increases continuously. Meanwhile, the yield of each distillate fraction increases gradually, except for the 270−300 °C distillate fractions. The oxygen content in the 170−230 °C distillate fractions is much higher than that of the other distillate fractions. The dominant groups of compounds in the MLCTs were saturates, aromatics, and resins, and the resin content was above 24.5 wt%. The molecular composition of the below 170 °C fractions mainly consists of benzene, toluene, and xylene, and the main phenolic compounds in the 170−230 °C distillate fraction are low-rank phenols, such as phenol, cresol, and xylenol. Although the macroscopic properties of the MLCT-Z and MLCT-S were quite similar, the molecular composition, the group composition and hydrogen distribution in each MLCT and its narrow distillate fractions are still different. The present work has contributed to our present understanding of the composition of MLCTs and to the guiding of the efficient processing of MLCTs.

Arsenic (III) methyltransferase (AS3MT) is a cysteine (Cys)-rich enzyme that catalyzes the biomethylation of arsenic. To investigate how these crucial Cys residues promote catalysis, we used matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) to analyze Cys residues in recombinant human arsenic (III) methyltransferase (hAS3MT). We detected two disulfide bonds, Cys250-Cys32 and Cys368-Cys369, in hAS3MT. The Cys250-Cys32 disulfide bond was reduced by glutathione (GSH) or other disulfide bond reductants before the enzymatic methylation of arsenite (iAs3+). In addition to exposing residues around the active sites, cleavage of the Cys250-Cys32 pair modulated the conformation of hAS3MT. This adjustment may stabilize the binding of S-Adenosyl-L-methionine (AdoMet) and favor iAs3+ binding to hAS3MT. Additionally, we observed the intermediate of Cys250-S-adenosylhomocysteine (AdoHcy), suggesting that Cys250 is involved in the transmethylation. In recovery experiments, we confirmed that trivalent arsenicals were substrates for hAS3MT, methylation of arsenic occurred on the enzyme, and an intramolecular disulfide bond might be formed after iAs3+ was methylated to dimethylarsinous acid (DMA3+). In this work, we clarified both the functional roles of GSH and the crucial Cys residues in iAs3+ methylation catalyzed by hAS3MT.