Molecular Epidemiology and Clinical Characteristics of Hand, Foot and Mouth Disease in North Sichuan Region, China, 2018-2023: A Descriptive Study

Background: Hand, foot and mouth disease (HFMD) remains an important public health problem in China. Many studies on the epidemiological characteristics of HFMD have been reported, but studies in North Sichuan region have been neglected. Methods: HFMD-related enterovirus infected cases were clinically confirmed and underwent real-time RT-PCR (rRT-PCR) from May 2018 to October 2023 in Guangyuan Central Hospital. Results: During 2018-2023, other EV (437 cases, 81.08%) was the most predominant serotype followed by CV-A16 (94 cases, 17.44%), EV-A71 (8 cases, 1.48%) was the least predominant serotype. Peak infections occurred in July and October. There were no significant differences in gender, age and serotypes. HFMD was concentrated in children under 47 months of age, with the highest incidence in children aged 12 - 23 months and the highest proportion of other EV infections in the whole age group. COVID-19 did not cause significant changes in gender, age and serotype. Overall, there was a significant increase in the proportion of children aged 12 - 23 months infected with CV-A16, and an increase in the proportion of children aged over 36 months infected with other EVs. Conclusions: The incidence of HFMD caused by EV-A71 has decreased significantly, and other EVs have become the main pathogens of HFMD in North Sichuan region in recent years. In the prevention and control of CV-A16, more attention should be paid to children aged 12 - 23 months and the dominant serotype should be closely monitored. Our study highlights the importance of developing of new diagnostic reagents and vaccines for the prevention and control of enterovirus infection. This study for the first time provides insights into district interventions to local conditions.

Assessment of pathogenicity and functional characterization of APPL1 gene mutations in diabetic patients

BACKGROUND Adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 1(APPL1)plays a crucial role in regulating insulin signaling and glucose metabolism.Mutations in the APPL1 gene have been associated with the development of maturity-onset diabetes of the young type 14(MODY14).Currently,only two mutations[c.1655T>A(p.Leu552*)and c.281G>A p.(Asp94Asn)]have been identified in association with this disease.Given the limited understanding of MODY14,it is imperative to identify additional cases and carry out comprehensive research on MODY14 and APPL1 mutations.AIM To assess the pathogenicity of APPL1 gene mutations in diabetic patients and to characterize the functional role of the APPL1 domain.METHODS Patients exhibiting clinical signs and a medical history suggestive of MODY were screened for the study.Whole exome sequencing was performed on the patients as well as their family members.The pathogenicity of the identified APPL1 variants was predicted on the basis of bioinformatics analysis.In addition,the pathogenicity of the novel APPL1 variant was preliminarily evaluated through in vitro functional experiments.Finally,the impact of these variants on APPL1 protein expression and the insulin pathway were assessed,and the potential mechanism underlying the interaction between the APPL1 protein and the insulin receptor was further explored.RESULTS A total of five novel mutations were identified,including four missense mutations(Asp632Tyr,Arg633His,Arg532Gln,and Ile642Met)and one intronic mutation(1153-16A>T).Pathogenicity prediction analysis revealed that the Arg532Gln was pathogenic across all predictions.The Asp632Tyr and Arg633His variants also had pathogenicity based on MutationTaster.In addition,multiple alignment of amino acid sequences showed that the Arg532Gln,Asp632Tyr,and Arg633His variants were conserved across different species.Moreover,in in vitro functional experiments,both the c.1894G>T(at Asp632Tyr)and c.1595G>A(at Arg532Gln)mutations were found to downregulate the expression of APPL1 on both protein and mRNA levels,indicating their pathogenic nature.Therefore,based on the patient’s clinical and family history,combined with the results from bioinformatics analysis and functional experiment,the c.1894G>T(at Asp632Tyr)and c.1595G>A(at Arg532Gln)mutations were classified as pathogenic mutations.Importantly,all these mutations were located within the phosphotyrosinebinding domain of APPL1,which plays a critical role in the insulin sensitization effect.CONCLUSION This study provided new insights into the pathogenicity of APPL1 gene mutations in diabetes and revealed a potential target for the diagnosis and treatment of the disease.

Differences between total amount of heavy metals and their occurrence form contents in the wastelands of a molybdenum mine area

In a single sample plot,the total amount of heavy metals in the soil could not necessarily reflect the contents of their effective states.This must be considered when attempting to determine the degree of soil heavy-metal pollution in an area.In the present study,the soil around the molybdenum mining area in Huludao,China,was surveyed and sampled to evaluate soil heavy-metal pollution using the Nemerow multifactor pollution index method.The Tessier continuous extraction method was used to analyze the distribution of heavy-metal forms'and their content changes in the soil of this area.Thus,the bioactivity of heavy metals in the soil,the absorption of heavy metals by plants,and the distribution of heavy metals in plants were explored to provide data supporting the use of phytoremediation technology to treat the heavy-metal pollution in the molybdenum mining area and develop ecological restoration strategies for the area's wastelands.The pollution index results indicate that heavy-metal pollution in the soil around the tailings pond is severe,mainly due to Pb and Zn heavy metals.Heavy-metal pollution in the surrounding land is mainly due to Cd and Zn.Content analysis of the heavy-metal forms/states in soils shows that exchangeable forms,which are most effective and toxic to plants,of the following metals are highest in the following areas:Cd,Cu,and Zn in the mountains around the stope;Zn,Mo,and Cu in the cultivated land around the dump;and Cd,Zn,and Mo in the cultivated land around the tailings pond.The pollution index analysis provides a basic overview of soil heavy-metal pollution across the entire mining area.However,content analysis of heavy-metal forms/states better reflects the relationship between the availability of heavy metals in the soil and the effectiveness of plants.Thus,the latter analysis can help ensure that phytoremediation strategies are adequately targeted,science-based,and effective.

Interplanting Patterns of Cash Crops under Forest

At the same time of tending forests,it is necessary to explore the under-forest economic development mode,bring into play production function of economic plants,establish cultivation mode of edible fungus,wild vegetables and medicinal plants under forest,to obtain certain economic benefit in short period. This paper made a preliminary study on significance and existing problems of the under-forest economy,and came up with several interplanting patterns,in the hope of providing a comprehensive operation and cultivation approach for developing the under-forest economy.

Effects of Different Types of Verbal Activities on Heart Rate Variability

In the present study, the effects of different types of verbal activities on heart rate variability (HRV) were investigated. ECG signals were recorded in ten volunteers during resting (R), reading silently (RS), reading aloud (RA) and talking freely (TF). Time domain, frequency domain and Poincaré plot measures of HRV were calculated for analyzing. Time domain parameter of pNN50, frequency domain parameter of LF (n.u.) and Poincaré plot parameter of SD1/SD2 were found statistically difference in RA and TF compared to R and RS. The results in this study show that HRV decreased while subjects were reading aloud and talking freely. The results also indicated that verbal activities of reading aloud and talking freely improve the sympathetic nervous activity.

Three-Tier Knowledge Management System Based on .NET

Three-tier knowledge management system based on .NET architecture is designed according to requirement specification, characteristics of and relationship between enterprise electronic archives and knowledge management. This system using three-tier design based on factory pattern has good encapsulation and portability, with clearer and more concise structure. It degrades the costs of system development and maintenance and upgrades system’s high reusability and development efficiency.

Antibacterial and antioxidant bifunctional hydrogel based on hyaluronic acid complex MoS_(2)-dithiothreitol nanozyme for treatment of infected wounds

Wound repair is a complex physiological process that often leads to bacterial infections,which significantly threaten human health.Therefore,developing wound-healing materials that promote healing and prevent bacterial infections is crucial.In this study,the coordination interaction between sulfhydryl groups on dithiothreitol(DTT)and MoS_(2)nanosheets is investigated to synthesize a MoS_(2)-DTT nanozyme with photothermal properties and an improved free-radical scavenging ability.Double-bond-modified hyaluronic acid is used as a monomer and is cross-linked with a PF127-DA agent.PHMoD is prepared in coordination with MoS_(2)-DTT as the functional component.This hydrogel exhibits antioxidant and antibacterial properties,attributed to the catalytic activity of catalase-like enzymes and photothermal effects.Under the near-infrared(NIR),it exhibits potent antibacterial effects against gram-positive(Staphylococcus aureus)and gram-negative bacteria(Escherichia coli),achieving bactericidal rates of 99.76%and 99.42%,respectively.Furthermore,the hydrogel exhibits remarkable reactive oxygen species scavenging and antioxidant capabilities,effectively countering oxidative stress in L929 cells.Remarkably,in an animal model,wounds treated with the PHMoD(2.0)and NIR laser heal the fastest,sealing completely within 10 days.These results indicate the unique biocompatibility and bifunctionality of the PHMoD,which make it a promising material for wound-healing applications.

Chemical composition and pharmacological properties of Flos sophorae immaturus, Flos sophorae and Fructus sophorae: a review

The flower buds and fruits of Sophora japonica are known as Flos sophorae immaturus(Chinese Huaimi,FSI),Flos sophorae(Chinese Huaihua,FLS)and Fructus sophorae(Chinese Huaijiao,FRS)due to their different physiological forms.FSI and FLS are precious resources of homology of medicine and food,while FRS is a valuable Chinese herb,and all of which have been used for thousands of years.There are great differences in the active ingredients,functions and toxicological properties of FSI,FLS and FRS.However,they are often confused and assumed to have fairly similar validity,which is detrimental to their precision development of resources of homology of medicine and food.This review summarized the active constituents,analytical techniques and pharmacological properties of FSI,FLS and FRS,then systematically compared their differences.The article will help people better understand and distinguish the differences and characteristics of FSI,FLS and FRS in bioactive constituents,content of functional components and pharmacological properties,which can contribute to their highly efficient targeted applications in the future food and medical fields.

Hydrographic field investigations in the Northern South China Sea by open cruises during 2004-2013

In the past 10 years （2004-2013）, annual open cruise during late summer provided new opportunities for comprehensive studies in the Northern South China Sea （NSCS）. The 10-year field investigation program was carried out by the South China Sea Institute of Oceanology, Chinese Academy of Sciences （SCSIO, CAS）. Measurements inclu- ded water mass property, ocean circulation, atmospheric structure, and chemical and biological elements. The observation data collected during these open cruises have been intensively used in the studies of marine oceanographic, meteorological, chemical, and biological processes in the NSCS. In this study, comprehensive assessment of data application in oceanographic and meteorological studies is provided： （1） the property and variability of water masses in different layers; （2） the distribution of main currents and three-dimensional structure of mesoscale eddies; and （3） atmospheric structure and its feedback to the ocean. With the continuance of open cruises, it is feasible to construct high- quality, gridded climatological marine meteorological datasets in the NSCS in the near future.

Photocaged prodrug under NIR light-triggering with dual-channel fluorescence: in vivo real-time tracking for precise drug delivery

Light-triggered drug delivery system is an effective strategy for precise diagnosis and therapy in cancer treatment. However, it suffers from difficultly balancing the dosimetry of drug with light dose and a lack of in vivo models for validating their clinical benefits. Here we report an unprecedented near-infrared(NIR) light photocaged cyanine-based prodrug Cy-CPT-Biotin with dual-channel fluorescence mode, enabling NIR light to precisely regulate where, when and how the intact and active prodrugs are delivered. The synergy of photochemical reaction and modulation in π-conjugated polyene backbone of cyanine can fully perform distinct dual-channel fluorescence changes in a NIR light-mediated manner. The prodrug has striking characteristics of excellent tumor-targeting ability, real-time monitoring of the in vivo behaviors by dual-channel mode and NIR-light triggering,especially for achieving fine regulation and on-demand drug release in the precise dosimetry of drug with light dose in living animals. This optical orthogonality strategy that conjuncts with NIR light-triggered and dual-channel fluorescence in vivo imaging provides a powerful tool for in vivo real-time tracking and finely tuning the prodrug release for precise drug delivery.

Uniaxial tensile deformation behavior of a sandwich-like structural TiNb-NiTi composite for biomedical applications

The uniaxial tensile deformation behavior of a sandwich-like structural TiNb-NiTi composite was investigated by uniaxial tensile test and in situ high-energy synchrotron X-ray diffraction(SXRD).It is found that below 1.2%macroscopic strains,the elastic deformations of the B2,β,B19'andα"phases take place in the TiNbNiTi composite.During the subsequent loading,theβ→α"and B2→B19'stress-induced martensitic transformations(SIMTs)occur within the macroscopic strains of 0.5%-4.2%and the macroscopic strains of 0.7%-6.2%,respectively.At the macroscopic strain of about 4.2%,the outer TiNb layer of the TiNb-NiTi composite experiences a partial fracture,as proved by the disappearance of(040)_(α")and a sudden jump in the(110)_(B19')d-spacing caused by load transfer.With further uniaxial tensile deformation,the TiNbNiTi composite finally fractures at a strain of~6.2%.Our results might provide some valuable information for understanding the deformation behavior of novel sandwich-like structural shape memory composites in more depth.

Synthesis of one-dimensional GaN nanorods by Tb intermediate layer with different thicknesses

GaN nanorods were synthesized by magnetron sputtering and ammonification system, and the thickness of Tb intermediate layer was changed to study the effect on GaN nanorods. The resultant was tested by scanning electron microscopy （SEM）, X-ray diffraction （XRD）, transmission electron microscopy （TEM）, high-resolution transmission electron microscopy （HRTEM）, and photo- luminescence （PL） spectra. The results show that the thickness of Tb layer has an evident effect on the modality, quality, and luminescence properties of GaN nanorods. PL spectra at room temperature show a very strong emission peak at 368 nm and a weak emission peak at 387 nm, and the intensities of the peak for the produced samples reach the maximum when Tb layer is 20 nm. Finally, the optimal thickness of 20 nm of Tb intermediate layer for synthe- sizing GaN nanostructures is achieved.