Mechanical biomimetic silk nano fiber-magnesium ion complex/hydroxyethylcellulose/glycerol hydrogel dressing with angiogenic capacity for accelerating scarless diabetic wound healing.

Quick scarless healing remains a key issue for diabetic wounds. Here, a stretchable elastomeric hydrogel dressing composed of hydroxyethylcellulose (HEC), silk nano fiber-magnesium ion complex (Mg2+-SNF) and glycerol (Gly) was developed to optimize mechanical niche, anti-inflammatory and angiogenic behavior simultaneously. The composite hydrogel dressing exhibited skin-like elasticity (175.1 ± 23.9 %) and modulus (156.7 ± 2.5 KPa) while Mg2+-SNF complex endowed the dressing with angiogenesis, both favoring quick scarless skin regeneration. In vitro cell studies revealed that the hydrogel dressing stimulated fibroblast proliferation, endothelial cell migration and vessel-like tube formation, and also induced anti-inflammatory behavior of macrophages. In vivo results revealed accelerated healing of diabetic wounds. The improved granulation ingrowth and collagen deposition suggested high quality repair. Both thinner epidermal layer and low collagen I/III ratio of the regenerated skin confirmed scarless tissue formation. This bioactive hydrogel dressing has promising potential to address the multifaceted challenges of diabetic wound management.

Cryo-EM Structure of human HCN3 channel and its regulation by cAMP.

HCN channels are important for regulating heart rhythm and nerve activity and have been studied as potential drug targets for treating depression, arrhythmia, nerve pain and epilepsy.Despite possessing unique pharmacological properties, HCN channels share common characteristics in that they are activated by hyperpolarization and modulated by cAMP and other membrane lipids. However, the mechanisms of how these ligands bind and modulate HCN channels are unclear. In this study, we solved structures of full-length human HCN3 using cryo-EM and captured two different states, including a state without any ligand bound and a state with cAMP bound. Our structures reveal the novel binding sites for cholesteryl hemisuccinate in apo-state and show how cholesteryl hemisuccinate and cAMP binding cause conformational changes in different states. These findings explain how these small modulators are sensed in mammals at the molecular level.The results of our study could help design more potent and specific compounds to influence HCN channel activity and offer new therapeutic possibilities for diseases that lack effective treatment.

Prediction of Junior High School Students' Problematic Internet Use: The Comparison of Neural Network Models and Linear Mixed Models in Longitudinal Study.

Purpose: With the rise of big data, deep learning neural networks have garnered attention from psychology researchers due to their ability to process vast amounts of data and achieve superior model fitting. We aim to explore the predictive accuracy of neural network models and linear mixed models in tracking data when subjective variables are predominant in the field of psychology. We separately analyzed the predictive accuracy of both models and conduct a comparative study to further investigate. Simultaneously, we utilized the neural network model to examine the influencing factors of problematic internet usage and its temporal changes, attempting to provide insights for early interventions in problematic internet use. Patients and Methods: This study compared longitudinal data of junior high school students using both a linear mixed model and a neural network model to ascertain the efficacy of these two methods in processing psychological longitudinal data. Results: The neural network model exhibited significantly smaller errors compared to the linear mixed model. Furthermore, the outcomes from the neural network model revealed that, when analyzing data from a single time point, the influences of seventh grade better predicted Problematic Internet Use in ninth grade. And when analyzing data from multiple time points, the influences of sixth, seventh, and eighth grades more accurately predicted Problematic Internet Use in ninth grade. Conclusion: Neural network models surpass linear mixed models in precision when predicting and analyzing longitudinal data. Furthermore, the influencing factors in lower grades provide more accurate predictions of Problematic Internet Use in higher grades. The highest prediction accuracy is attained through the utilization of data from multiple time points.

Total syntheses of Tetrodotoxin and 9-epiTetrodotoxin.

Tetrodotoxin and congeners are specific voltage-gated sodium channel blockers that exhibit remarkable anesthetic and analgesic effects. Here, we present a scalable asymmetric syntheses of Tetrodotoxin and 9-epiTetrodotoxin from the abundant chemical feedstock furfuryl alcohol. The optically pure cyclohexane skeleton is assembled via a stereoselective Diels-Alder reaction. The dense heteroatom substituents are established sequentially by a series of functional group interconversions on highly oxygenated cyclohexane frameworks, including a chemoselective cyclic anhydride opening, and a decarboxylative hydroxylation. An innovative SmI2-mediated concurrent fragmentation, an oxo-bridge ring opening and ester reduction followed by an Upjohn dihydroxylation deliver the highly oxidized skeleton. Ruthenium-catalyzed oxidative alkyne cleavage and formation of the hemiaminal and orthoester under acidic conditions enable the rapid assembly of Tetrodotoxin, anhydro-Tetrodotoxin, 9-epiTetrodotoxin, and 9-epi lactone-Tetrodotoxin.

The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer.

This study aimed to explore the value of color Doppler ultrasonography combined with carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in differential diagnosis of gastric stromal tumor (GST) and gastric cancer (GC). An analysis of the clinical data of 180 patients with clinically suspected gastric space occupying lesions. According to the postoperative pathological results, 180 suspected gastric space-occupying lesion patients were divided into GST group (n = 83) and GC group (n = 97). Color Doppler ultrasonography, serum tumor markers CEA and CA19-9 were compared. The research results showed that serum CEA and CA19-9 levels were lower in patients with GST group than those with GC group (both P < 0.001). With postoperative pathology as the gold standard, detection rates of GST and GC by combination of color Doppler ultrasound (CDUS), serum CEA, and CA19-9 were higher than those of each index alone (both P < 0.001). There was no difference between detection rates of GST and GC by combination of CDUS, serum CEA, and CA19-9 (P = 0.058). Color Doppler ultrasonography combined with serum tumor markers CEA and CA19-9 tests has a certain differential diagnostic value for GST and GC, which may provide a reliable reference basis for clinical diagnosis and treatment.

[Spatial Distribution of Aerobic Bacteria, Sources and Risks of Nitrogen and Phosphorus in Taihu Lake Sediments].

The release of nitrogen and phosphorus from sediments into lake water will exacerbate the eutrophication of lakes and endanger ecological safety and human health. Microorganisms are indispensable in nitrogen and phosphorus conversion, and accurate analysis of the distribution characteristics and sources of nitrogen and phosphorus in sediments as well as their relationship with microorganisms is an important prerequisite for lake eutrophication control. Taking Taihu Lake as the study area, 30 surface sediment samples were collected, and the grain size, pH, organic matter (OM), dissolved organic carbon (DOC), total phosphorus (TP), total nitrogen (TN), nitrate nitrogen (NO3--N), and dissolved organic nitrogen (DON) along with some other index contents were measured and analyzed; accordingly, spatial distribution characteristics were analyzed. While using nutrient agar (NA), the number of aerobic bacteria (AB) was determined by plate counting in the medium. Combined with principal component analysis (PCA) and Pearson correlation analysis, the spatial distribution characteristics and sources of sediments and AB in Taihu Lake were explored. The characteristics of sediment pollution in Taihu Lake were studied using the comprehensive pollution index and the organic pollution index methods. The results revealed that the average sediment indicators of the surface layer of Taihu Lake were as follows:AB was 9.25×104 CFU·g-1, average particle size (MZ) was 17.59 µm, pH was 7.62, ω(OM) was 15.05 g·kg-1, ω(DOC) was 71.60 mg·kg-1, ω(TP) was 598.13 mg·kg-1, ω(TN) was 1113.92 mg·kg-1, ω(NO3--N) was 3.22 mg·kg-1, and ω(DON) was 22.60 mg·kg-1. The comprehensive pollution index (FF) showed that 13% of the Taihu Lake was moderately polluted, while 87% was heavily polluted. Excluding the area in the center of the lake, the southern lake area, and some lakes in the western part of the East Taihu Lake, TN in the rest of the area was moderately and severely polluted. In addition to the heavy pollution of Zhushan Bay, the TP in Taihu Lake was generally at light and moderate pollution. The organic pollution index (OI) showed that the organic pollution of the sediments of Taihu Lake was relatively light, majorly caused by organic nitrogen (ON) pollution. DOC, DON, TN, and OM in Taihu Lake were primarily derived from the influence of aquatic plants, and TP And AB were primarily derived from the influence of the external input of rivers. This research will provide theoretical support for lake eutrophication treatment and also provide new ideas for further analysis of AB to remove nitrogen and phosphorus pollution from sediments.

Problematic Internet Use in Early Adolescents: Gender and Loneliness Differences in a Latent Growth Model.

Purpose: Based on the Cognitive-Behavioral model and the Interaction of Person-Affect-Cognition-Execution model, this study examined the developmental trajectory of problematic Internet use (PIU) in early adolescents and explored whether there were gender differences in the onset level and rate of development of this developmental trajectory, and tested whether developmental changes in loneliness could have an impact on the developmental trajectory of problematic Internet use. Participants and Methods: This longitudinal study collected data on PIU and loneliness from 296 early adolescents (Mage=11.65, SD=0.58) in four waves. The development of PIU in adolescents and the effects of gender and loneliness development on PIU development were examined using a latent growth model. Results: The results revealed that individuals' PIU development showed a nonlinear latent growth model, with PIU significantly higher than 0 in grade 6 and its growth rate slowing down as PIU increased. Individuals' PIU at low starting levels developed more rapidly later. Boys had higher initial levels of PIU but their PIU developed and increased at the same rate as girls'. Both the initial value and slope of loneliness had a significant effect on the initial value and slope of boys' and girls' PIU. Conclusion: Interventions for PIU in early adolescents also need to consider loneliness at the same time, and intervention groups can focus on individuals with low initial levels of PIU, boys, and individuals with high levels of loneliness.

[Occurrence Characteristics of Microplastics in Baiyangdian Lake Water and Sediments].

In order to explore the occurrence characteristics of microplastics in the freshwater environment of Baiyangdian Lake in China, ten overlying water samples and ten sediment samples were collected in Baiyangdian Lake of Hebei Province in October 2021, and the abundance distribution, shape, particle size, and polymer type of microplastics in the samples were identified using laboratory pretreatment, microscope observation, and laser infrared spectroscopy. The sedimentation law of microplastics at the overlying water-sediment interface was studied using the Stokes sedimentation formula, and their pollution characteristics and potential sources were analyzed. The abundances of microplastics in the overlying water and sediments in Baiyangdian Lake ranged from 474-19382 n·m-3 and 95.3-29542.5 n·kg-1, respectively, with an average value of 6255.4 n·m-3 and 11088 n·kg-1. The main polymer of the microplastics in the overlying water was polyethylene terephthalate[PET, (17.20±0.26)%], and the microplastics in the sediments were mainly chlorinated polyethylene[CPE, (46.11±1.30)%]. The sedimentation velocities of microplastics in the sedimentation zone ranged from 0.0793-111.7547 mm·s-1. The particles with larger particle size had higher sedimentation velocity and easily settled and remained in the sediments. The main sources of microplastic pollution in the study area were the discharge of textile fibers from washing wastewater and the wear and tear of ship paint, ship rubber, and building materials.

MD-SGT: Multi-dilation spherical graph transformer for unsupervised medical image registration.

Deformable medical image registration is an essential preprocess step for several clinical applications. Even though the existing convolutional neural network and transformer based methods achieved the promising results, the limited long-range spatial dependence and non-uniform attention span of these models prohibit further improving the registration performance. To deal with this issue, we proposed a multi-dilation spherical graph transformer (MD-SGT), in which the encoder combined the advantages of convolutional and graph transformer blocks to distinguish effectively the differences between the reference and the template images at various scales. Specifically, the features of each voxel were obtained by aggregating the information from its neighbors sampled from different spherical regions with different dilation rates. The implicit convolution inductive bias and long-range uniform attention span induced by such information aggregation manner made the features more representative for registration. Through the qualitative and quantitative comparisons with state-of-the-art methods on two datasets, we demonstrated that combining long-range uniform attention span and inductive bias are beneficial for promoting the image registration performance, with the Dice score, ASD and HD95 being improved at least by 0.5%, 2.2% and 1.1%, respectively.

Tumor-associated myeloid cells in cancer immunotherapy.

Tumor-associated myeloid cells (TAMCs) are among the most important immune cell populations in the tumor microenvironment, and play a significant role on the efficacy of immune checkpoint blockade. Understanding the origin of TAMCs was found to be the essential to determining their functional heterogeneity and, developing cancer immunotherapy strategies. While myeloid-biased differentiation in the bone marrow has been traditionally considered as the primary source of TAMCs, the abnormal differentiation of splenic hematopoietic stem and progenitor cells, erythroid progenitor cells, and B precursor cells in the spleen, as well as embryo-derived TAMCs, have been depicted as important origins of TAMCs. This review article provides an overview of the literature with a focus on the recent research progress evaluating the heterogeneity of TAMCs origins. Moreover, this review summarizes the major therapeutic strategies targeting TAMCs with heterogeneous sources, shedding light on their implications for cancer antitumor immunotherapies.

Quantitative Proteomics-Based Substrate Screening Revealed Cyclophilin Stabilization Regulated by Deubiquitinase Ubp7.

Quantitative proteomics has emerged as a crucial approach to identifying ubiquitinated substrates to investigate the functions of ubiquitination in cells. In this regard, although the substrate screening of certain enzymes in the ubiquitin system has been based on proteome or ubiquitinome level measurements, the direct comparison of these two approaches has not been determined to date. To quantitatively compare the efficiency and effectiveness of substrate screening from the entire proteomics to the ubiquitinomics filter, we used yeast deubiquitinating enzyme, Ubp7, as an example to evaluate it in this study. A total of 112 potential ubiquitinated substrates were identified from the ubiquitinomics level, whereas only 27 regulated substrates were identified from the entire proteomic screening, demonstrating the increased efficiency of ubiquitinomics quantitative analysis. Subsequently, we selected cyclophilin A (Cpr1) protein as an example, which was filtered out at the proteomics level but was a promising candidate according to the ubiquitinomics filter. Additional investigations revealed that Cpr1 possessed a K48-linked ubiquitin chain regulated by Ubp7, which may affect its homeostasis and, consequently, sensitivity to the therapeutic drug cyclosporine (CsA).

Quantitative proteomics revealed the transition of ergosterol biosynthesis and drug transporters processes during the development of fungal fluconazole resistance.

Fungal infections and antifungal resistance are the increasing global public health concerns. Mechanisms of fungal resistance include alterations in drug-target interactions, detoxification by high expression of drug efflux transporters, and permeability barriers associated with biofilms. However, the systematic panorama and dynamic changes of the relevant biological processes of fungal drug resistance acquisition remain limited. In this study, we developed a yeast model of resistance to prolonged fluconazole treatment and utilized the isobaric labels TMT (tandem mass tag)-based quantitative proteomics to analyze the proteome composition and changes in native, short-time fluconazole stimulated and drug-resistant strains. The proteome exhibited significant dynamic range at the beginning of treatment but returned to normal condition upon acquisition drug resistance. The sterol pathway responded strongly under a short time of fluconazole treatment, with increased transcript levels of most enzymes facilitating greater protein expression. With the drug resistance acquisition, the sterol pathway returned to normal state, while the expression of efflux pump proteins increased obviously on the transcription level. Finally, multiple efflux pump proteins showed high expression in drug-resistant strain. Thus, families of sterol pathway and efflux pump proteins, which are closely associated with drug resistance mechanisms, may play different roles at different nodes in the process of drug resistance acquisition. Our findings uncover the relatively important role of efflux pump proteins in the acquisition of fluconazole resistance and highlight its potential as the vital antifungal targets.

Construction of Probiotic Double-Layered Multinucleated Microcapsules Based on Sulfhydryl-Modified Carboxymethyl Cellulose Sodium for Increased Intestinal Adhesion of Probiotics and Therapy for Intestinal Inflammation Induced by Escherichia coli O157:H7.

The decreased number of viable bacteria and the ability of Bifidobacterium to adhere to and colonize the gut in the gastrointestinal environment greatly limit their efficacy. To solve this problem, thiolated carboxymethyl cellulose sodium (CMC) probiotic double-layered multinucleated microcapsules with Bifidobacterium adolescentis FS2-3 in the inner layer and Bacillus subtilis SN15-2 embedded in the outer layers were designed. First, the viable counts and release rates of microcapsules were examined by in vitro simulated digestion assays, and it was found that microcapsules were better protected from gastrointestinal digestion than the controls. Compared with free Bifidobacterium strains, double-layered multinucleated microcapsules have higher viable bacterial survival rates and storage stability. Second, through in vitro rheology, tensile tests, isotherm titration calorimetry, and adhesion tests, it was observed that thiolated CMC could enhance the strong interaction of Bifidobacterium with intestinal mucus and significantly promote the proliferation and growth of probiotics. Finally, double-layered multinucleated microcapsules containing B. adolescentis FS2-3 and B. subtilis SN15-2 modified with sulfhydryl-modified CMC were studied in the intestine. Alleviation of Escherichia coli O157:H7 induced intestinal inflammation. The results showed that microencapsulation could significantly increase the colon content of Bifidobacterium, relieve intestinal inflammation symptoms in mice with bacterial enteritis, and repair the intestinal microbiota disorder caused by inflammation. The probiotic double-layered multinucleated microcapsules prepared in this study can improve the survival rate of probiotics and promote proliferation, adhesion, and colonization of probiotics.

Establishment of Transgenic Mouse Leukemia Cell Lines Expressing Human CD4/CCR5/CyclinT1 Infected with HIV-1.

PURPOSE: Establishing a cross-species animal model of human immunodeficiency virus (HIV) infection is crucial for the study of HIV/acquired immunodeficiency syndrome (AIDS). However, due to the species-specific characteristics of HIV-1, the virus can only infect directly humans and a small number of non-human primates. It cannot directly infect mouse cells across species. METHODS: A mouse leukemia cell line with high CD4 (clusters of differentiation 4)/CCR5 (CC-chemokine receptor 5)/CyclinT1 expression was constructed in this study. First, CD4/CCR5/CyclinT1 lentiviral vector was used to infect a murine leukemia cell line L1210 to express the receptor CD4, co-receptor CCR5 and tat protein driving factor CyclinT1, which are required to infect L1210 cells with HIV-1. RESULTS: The results of sequencing identification and fluorescence expression showed that the plasmid expressing CD4, CCR5, and CyclinT1 vector was successfully constructed and wrapped as the lentiviral vector. Moreover, it was observed that CD4, CCR5, and CyclinT1 proteins were highly expressed in mouse leukemia cells L1210 compared to empty lentiviral vector-transfected cells. Next, viral entry and replication were demonstrated when HIV-1 RNA was detected in body cells and cultured supernatants. Transgenic mice cells L1210 showed significantly greater content of HIV-1 RNA compared to control L1210 cells. Finally, CEMx174 was infected with cell culture supernatants to clarify that the progeny virus is an active virus with infection ability. HIV-1 RNA was highly expressed in CEMx174 cells. CONCLUSIONS: This study made the foundation for future studies evaluating HIV-1 cross-species infection in a murine animal model. The results provided new direction for studies investigating the development of vaccines, antiviral drugs screening, and HIV/AIDS pathogenesis.

Promotion of Wound Healing Using Nanoporous Silk Fibroin Sponges.

Wound dressings are important for wound repair. The morphology of the biomaterials used in these dressings, and in particular, the pore structure affects tissue regeneration by facilitating attachment and proliferation of cells due to the hierarchical multiscale, water absorbance, and nutrient transport. In the present study, silk fibroin (SF) sponges with walls containing nanopores (SFNS) were prepared from SF nanoparticles generated during the autoclaving of SF solutions, followed by leaching the SF nanoparticles from the freeze-dried sponges of SF. The nano/microporous structure, biofluid absorbance, and porosity of the SF sponges with and without nanopores were characterized. In vitro cell proliferation, in vivo biocompatibility, and wound healing were evaluated with the sponges. The results demonstrated that SFNS had significantly increased porosity and water permeability, as well as cell attachment and proliferation when compared with SF sponges without the nanopores (SFS). Wound dressings were assessed in a rat skin wound model, and SFNS was superior to SFS in accelerating wound healing, supported by vascularization, deposition of collagen, and increased epidermal thickness over 21 days. Hence, such a dressing material with a hierarchical multiscale pore structure could promote cell migration, vascularization, and tissue regeneration independently without adding any growth factor, which would offer a new strategy to design and engineer better-performed wound dressing.

A combined method for human health risk area identification of heavy metals in urban environments.

Multi-medium heavy metals pollution is a crucial pathway to destroy the urban environmental resources cycle. In this study, Nanjing of China, a typical mega city, was taken as the study area. Compared with other cities or countries, Cr, Cu and Zn in human nails and hair in the study area have higher concentration characteristics, while Cd and Pb have lower concentration characteristics. By combining the health risk status of heavy metals in soil and dustfall, the spatial clustering characteristics of heavy metals in soil dustfall and the concentration information of heavy metals in humans in the study area, a potential toxic risk area identification method based on soil-dustfall-human (SDB-HR) was established. Through Monte Carlo analysis, it's found that the risk of Zn and Cr in soil-dustfall to human health is relatively high, with the probability of carcinogenesis reaching 51.2 % and 50.2 %, respectively. By the proposed method, different levels of heavy metal risk areas in urban environments can be more reasonably and effectively identified, which will provide important technical and theoretical support for the precise management of heavy metals in urban environments.

Source-oriented ecological risk assessment of heavy metals in sediments of West Taihu Lake, China.

The geographical location of West Taihu Lake determines that it is the entrance of the whole Taihu Lake, and the intensive industries around it pose a great threat to the ecology of Taihu Lake. We innovatively combined Pb isotope ratio analysis with ecological risk assessment index to quantify the source-oriented ecological risk of heavy metals (HMs) in the sediments of West Taihu Lake. In this study, the representative HMs Zn, Pb, Cr, and Cd in the surface (0-2 cm) sediments of West Tai Lake were determined, and the ecological risk assessment of HM sources was carried out based on the Pb isotope ratio and ecological risk index. The results showed that HMs were significantly enriched in the south and the west of the study area. The average geo-accumulation index (Igeo) of Pb was unpolluted, Cr and Zn were between unpolluted and moderately polluted, and Cd was moderately polluted. The average ecological risk index (Ei) of Pb, Cr, and Zn was low, and only Cd reached a considerable risk (ECd = 120.7), which accounted for 89.8% of the comprehensive ecological risk index (RI). However, the RI in the whole study area (RI = 134.4) still indicated low risk. There was a significant correlation between Pb and other HMs (P < 0.05). The IsoSource analysis showed that the order of contribution rate was fossil fuels (48.0%) > industrial sources (35.8%) > natural sources (14.9%) > agricultural sources (1.3%). The HM pollution caused by fossil fuel combustion and industrial activities reaches a moderate ecological risk, whereas natural sources and agricultural sources pose a low risk. Overall, the main sources of HM pollution are anthropogenic, which pose moderate ecological risk to the study area and should be paid more attention to.

Surface Hydrophobization Provides Hygroscopic Supramolecular Plastics Based on Polysaccharides with Damage-Specific Healability and Room-Temperature Recyclability.

Supramolecular materials with room-temperature healability and recyclability are highly desired because they can extend materials lifetimes and reduce resources consumption. Most approaches toward healing and recycling rely on the dynamically reversible supramolecular interactions, such as hydrogen, ionic and coordinate bonds, which are hygroscopic and vulnerable to water. The general water-induced plasticization facilitates the healing and reprocessing process but cause a troubling problem of random self-adhesion. To address this issue, here it is reported that by modifying the hygroscopic surfaces with hydrophobic alkyl chains of dodecyltrimethoxysilane (DTMS), supramolecular plastic films based on commercial raw materials of sodium alginate (SA) and cetyltrimethylammonium bromide (CTAB) display extraordinary damage-specific healability. Owing to the hydrophobic surfaces, random self-adhesion is eliminated even under humid environment. When damage occurs, the fresh surfaces with ionic groups and hydroxyl groups expose exclusively at the damaged site. Thus, damage-specific healing can be readily facilitated by water-induced plasticization. Moreover, the films display excellent room-temperature recyclability. After multiple times of reprocessing and re-modifying with DTMS, the rejuvenated films exhibit fatigueless mechanical properties. It is anticipated that this approach to damage-specific healing and room-temperature recycling based on surface hydrophobization can be applied to design various of supramolecular plastic polysaccharides materials for building sustainable societies.