Age-related differences in auditory spatial processing revealed by acoustic change complex.

Objectives: The auditory spatial processing abilities mature throughout childhood and degenerate in older adults. This study aimed to compare the differences in onset cortical auditory evoked potentials (CAEPs) and location-evoked acoustic change complex (ACC) responses among children, adults, and the elderly and to investigate the impact of aging and development on ACC responses. Design: One hundred and seventeen people were recruited in the study, including 57 typically-developed children, 30 adults, and 30 elderlies. The onset-CAEP evoked by white noise and ACC by sequential changes in azimuths were recorded. Latencies and amplitudes as a function of azimuths were analyzed using the analysis of variance, Pearson correlation analysis, and multiple linear regression model. Results: The ACC N1'-P2' amplitudes and latencies in adults, P1'-N1' amplitudes in children, and N1' amplitudes and latencies in the elderly were correlated with angles of shifts. The N1'-P2' and P2' amplitudes decreased in the elderly compared to adults. In Children, the ACC P1'-N1' responses gradually differentiated into the P1'-N1'-P2' complex. Multiple regression analysis showed that N1'-P2' amplitudes (R2 = 0.33) and P2' latencies (R2 = 0.18) were the two most variable predictors in adults, while in the elderly, N1' latencies (R2 = 0.26) explained most variances. Although the amplitudes of onset-CAEP differed at some angles, it could not predict angle changes as effectively as ACC responses. Conclusion: The location-evoked ACC responses varied among children, adults, and the elderly. The N1'-P2' amplitudes and P2' latencies in adults and N1' latencies in the elderly explained most variances of changes in spatial position. The differentiation of the N1' waveform was observed in children. Further research should be conducted across all age groups, along with behavioral assessments, to confirm the relationship between aging and immaturity in objective ACC responses and poorer subjective spatial performance. Significance: ACCs evoked by location changes were assessed in adults, children, and the elderly to explore the impact of aging and development on these differences.

Core fucosylation of maternal milk N-glycans imparts early-life immune tolerance through gut microbiota-dependent regulation in RORγt+ Treg cells.

Milk glycans play key roles in shaping and maintaining a healthy infant gut microbiota. Core fucosylation catalyzed by fucosyltransferase (Fut8) is the major glycosylation pattern on human milk N-glycan, which was crucial for promoting the colonization and dominant growth of Bifidobacterium and Lactobacillus spp. in neonates. However, the influence of core-fucose in breast milk on the establishment of early-life immune tolerance remains poorly characterized. In this study, we found that the deficiency of core-fucose in the milk of maternal mice caused by Fut8 gene heterozygosity (Fut8+/-) resulted in poor immune tolerance towards the ovalbumin (OVA) challenge, accompanied by a reduced proportion of intestinal RORγt+ Treg cells and the abundance of Lactobacillus spp., especially L. reuteri and L. johnsonii, in their breast-fed neonates. The administration of the L. reuteri and L. johnsonii mixture to neonatal mice compromised the OVA-induced allergy and up-regulated the intestinal RORγt+ Treg cell proportions. However, Lactobacillus mixture supplementation did not alleviate allergic responses in RORγt+ Treg cell-deficient mice caused by Rorc gene heterozygosity (Rorc+/-) post OVA challenge, indicating that the intervention effects depend on the RORγt+ Treg cells. Interestingly, instead of L. reuteri and L. johnsonii, we found that the relative abundance of another Lactobacillus spp., L. murinus, in the gut of the offspring mice was significantly promoted by intervention, which showed enhancing effects on the proliferation of splenic and intestinal RORγt+ Treg cells in in vitro studies. The above results indicate that core fucosylation of breast milk N-glycans is beneficial for the establishment of RORγt+ Treg cell mediated early-life immune tolerance through the manipulation of symbiotic bacteria in mice.

Identification of mitophagy-related hub genes during the progression of spinal cord injury by integrated multinomial bioinformatics analysis.

Spinal cord injury (SCI) is a disturbance of peripheral and central nerve conduction that causes disability in sensory and motor function. Currently, there is no effective treatment for SCI. Mitophagy plays a vital role in mitochondrial quality control during various physiological and pathological processes. The study aimed to elucidate the role of mitophagy and identify potential mitophagy-related hub genes in SCI pathophysiology. Two datasets (GSE15878 and GSE138637) were analyzed. Firstly, the differentially expressed genes (DEGs) were identified and mitophagy-related genes were obtained from GeneCards, then the intersection between SCI and mitophagy-related genes was determined. Next, we performed gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), protein-protein interaction network (PPI network), least absolute shrinkage and selection operator (LASSO), and cluster analysis to identify and define the hub genes in SCI. Finally, the link between hub genes and infiltrating immune cells was investigated and the potential transcriptional regulation/small molecular compounds to target hub genes were predicted. In total, SKP1 and BAP1 were identified as hub genes of mitophagy-related DEGs during SCI development and regulatory T cells (Tregs)/resting NK cells/activated mast cells may play an essential role in the progression of SCI. LINC00324 and SNHG16 may regulate SKP1 and BAP1, respectively, through miRNAs. Eleven and eight transcriptional factors (TFs) regulate SKP1 and BAP1, respectively, and six small molecular compounds target BAP1. Then, the mRNA expression levels of BAP1 and SKP1 were detected in the injured sites of spinal cord of SD rats at 6 h and 72 h after injury using RT-qPCR, and found that the level were decreased. Therefore, the pathways of mitophagy are downregulated during the pathophysiology of SCI, and SKP1 and BAP1 could be accessible targets for diagnosing and treating SCI.

Dual output feature fusion networks for femoral segmentation and quantitative analysis of the knee joint.

BACKGROUND: Magnetic resonance imaging (MRI) is the preferred imaging modality for diagnosing knee disease. Segmentation of the knee MRI images is essential for subsequent quantification of clinical parameters and treatment planning for knee prosthesis replacement. However, the segmentation remains difficult due to individual differences in anatomy, the difficulty of obtaining accurate edges at lower resolutions, and the presence of speckle noise and artifacts in the images. In addition, radiologists must manually measure the knee's parameters which is a laborious and time-consuming process. PURPOSE: Automatic quantification of femoral morphological parameters can be of fundamental help in the design of prosthetic implants for the repair of the knee and the femur. Knowledge of knee femoral parameters can provide a basis for femoral repair of the knee, the design of fixation materials for femoral prostheses, and the replacement of prostheses. METHODS: This paper proposes a new deep network architecture to comprehensively address these challenges. A dual output model structure is proposed, with a high and low layer fusion extraction feature module designed to extract rich features through the cross-fusion mechanism. A multi-scale edge information extraction spatial feature module is also developed to address the boundary-blurring problem. RESULTS: Based on the precise automated segmentation results, 10 key clinical parameters were automatically measured for a knee femoral prosthesis replacement program. The correlation coefficients of the quantitative results of these parameters compared to manual results all achieved at least 0.92. The proposed method was extensively evaluated with MRIs of 78 patients' knees, and it consistently outperformed other methods used for segmentation. CONCLUSIONS: The automated quantization process produced comparable measurements to those manually obtained by radiologists. This paper demonstrates the viability of automatic knee MRI image segmentation and quantitative analysis with the proposed method. This provides data to support the accuracy of assessing the progression and biomechanical changes of osteoarthritis of the knee using an automated process, thus saving valuable time for the radiologists and surgeons.

Optical fiber-integrated achromatic metalens based on catenary metasurfaces.

A challenge in all-fiber-integrated metasurface devices is to efficiently control dispersion in the limited fiber end area to build metasurfaces, therefore, the design of metasurfaces with a special structure becomes crucial to meet the demands of dispersion control. A unique phase response of circularly polarized light in catenary metasurfaces can offer new opportunities for polarization-sensitive arbitrary chromatic dispersion control. Herein, we proposed an optical achromatic metalens based on equal width catenary metasurfaces integrated on the large-mode optical fiber (LMF) end. To reduce phase distortions, the LMF is designed to generate quasi-plane waves (QPW), and then QPW converts from catenary metasurfaces to realize achromatic focusing. A notable feature of this device is its axial focal length shift as low as 0.09% across the working wavelength range from 1.33 µm to 1.55 µm, commonly used in optical fiber communication, demonstrating its excellent dispersion control capability. Furthermore, the device exhibits exceptional capabilities to break through the diffraction limit of the output field. This research has potential applications in the fields of achromatic devices, chromatic aberration correction, fiber lasers, and optical communication and modulation.

The development of cancers research based on mitochondrial heat shock protein 90.

Mitochondrial heat shock protein 90 (mtHsp90), including Tumor necrosis factor receptor-associated protein 1 (TRAP1) and Hsp90 translocated from cytoplasm, modulating cellular metabolism and signaling pathways by altering the conformation, activity, and stability of numerous client proteins, and is highly expressed in tumors. mtHsp90 inhibition results in the destabilization and eventual degradation of its client proteins, leading to interference with various tumor-related pathways and efficient control of cancer cell development. Among these compounds, gamitrinib, a specific mtHsp90 inhibitor, has demonstrated its safety and efficacy in several preclinical investigations and is currently undergoing evaluation in clinical trials. This review aims to provide a comprehensive overview of the present knowledge pertaining to mtHsp90, encompassing its structure and function. Moreover, our main emphasis is on the development of mtHsp90 inhibitors for various cancer therapies, to present a thorough overview of the recent pre-clinical and clinical advancements in this field.

The Development of Immunotherapy for the Treatment of Recurrent Glioblastoma.

Recurrent glioblastoma (rGBM) is a highly aggressive form of brain cancer that poses a significant challenge for treatment in neuro-oncology, and the survival status of patients after relapse usually means rapid deterioration, thus becoming the leading cause of death among patients. In recent years, immunotherapy has emerged as a promising strategy for the treatment of recurrent glioblastoma by stimulating the body's immune system to recognize and attack cancer cells, which could be used in combination with other treatments such as surgery, radiation, and chemotherapy to improve outcomes for patients with recurrent glioblastoma. This therapy combines several key methods such as the use of monoclonal antibodies, chimeric antigen receptor T cell (CAR-T) therapy, checkpoint inhibitors, oncolytic viral therapy cancer vaccines, and combination strategies. In this review, we mainly document the latest immunotherapies for the treatment of glioblastoma and especially focus on rGBM.

A novel structural design of cellulose-based conductive composite fibers for wearable e-textiles.

Cellulose-based conductive composite fibers hold great promise in smart wearable applications, given cellulose's desirable properties for textiles. Blending conductive fillers with cellulose is the most common means of fiber production. Incorporating a high content of conductive fillers is demanded to achieve desirable conductivity. However, a high filler load deteriorates the processability and mechanical properties of the fibers. Here, developing wet-spun cellulose-based fibers with a unique side-by-side (SBS) structure via sustainable processing is reported. Sustainable sources (cotton linter and post-consumer cotton waste) and a biocompatible intrinsically conductive polymer (i.e., polyaniline, PANI) were engineered into fibers containing two co-continuous phases arranged side-by-side. One phase was neat cellulose serving as the substrate and providing good mechanical properties; another phase was a PANI-rich cellulose blend (50 wt%) affording electrical conductivity. Additionally, an eco-friendly LiOH/urea solvent system was adopted for the fiber spinning process. With the proper control of processing parameters, the SBS fibers demonstrated high conductivity and improved mechanical properties compared to single-phase cellulose and PANI blended fibers. The SBS fibers demonstrated great potential for wearable e-textile applications.

Core-Shell-Structured Electrorheological Fluid with a Polarizability-Tunable Nanocarbon Shell for Enhanced Stimuli-Responsive Activity.

The incorporation of nanocarbon-based materials into electrorheological fluids has been shown to be an effective means of improving the electrorheological (ER) response. However, the mechanism of the sp2/sp3-hybridized carbon structure and high ER response is still under investigation. Herein, barium titanate@nanocarbon shell (BTO@NCs) composites are proposed and prepared by introducing carbonized polydopamine (C-PDA) into a shell. When the polymerization time of dopamine is tuned, the shell thickness, surface polar functional groups, and sp2/sp3-hybridized carbon can be effectively controlled. The maximum yield stress of the BTO@NCs-24 h ER fluid reaches 2.5 kPa under an electric field of 4 kV mm-1, which is attributed to the increased content of sp3 C-OH and oxygenous functional groups within the shell, resulting in a rapidly achievable polarization. Furthermore, the SiO2@NCs and TiO2@NCs ER fluids are also prepared with enhanced ER behavior in these phenomena, confirming an approach to high-performance ER fluids based on nanocarbon composites.

Connection between health risk and heavy metals in agricultural soils of China: a study based on current field investigations.

Heavy metal pollution in agricultural soil is a threat to people's health and sustainable development. However, there is currently no nationwide health risk assessment in China. In this study, we performed a preliminary assessment of heavy metals in agricultural soils of the Chinese mainland, and found obvious carcinogenic risks (total lifetime carcinogenic risk (TLCR) > 1 × 10-5). A similar spatial distribution pattern was found in soil heavy metal and the mortality of esophagus and stomach cancers. Combining the potential carcinogenic risk assessed by LCR for individual heavy metal with Pearson correlation, Geographical Detector (q statistic > 0.75 for TLCR, p < 0.05), and redundancy analysis (RDA), it was found that long-term exposure and intake route of heavy metals exceeding the maximum safety threshold (Health Canada standard) may induce digestive system (esophagus, stomach, liver, and colorectum) cancers in rural populations. Through Partial Least Squares Path Model (PLS-PM), it was also revealed that the LCR of heavy metals was closely related to the soil environmental background (path coefficients = 0.82), which in turn was affected by factors such as economic development and pollution discharge. The current research results highlight the potential carcinogenic risk to the digestive system associated with low-dose and long-term exposure to heavy metals in agricultural soils, and policymakers should propose countermeasures and solutions according to the local conditions.

Rapid extraction of osimertinib and its active metabolite in urine by miniaturized centrifugal spin-column extraction using ionic liquid hybrid hierarchical porous adsorbent.

Osimertinib (OSIM) is widely used as a mainstream drug for the treatment of non-small cell lung cancer (NSCLC). However, the lack of a rapid extraction and detection method for OSIM and its metabolite, AZ-5104, has limited clinical drug metabolism and drug resistance research because the drug is unstable. In this study, a new ionic liquid hybrid hierarchical porous material (IL-HHPM) was synthesized with hierarchical porous structures, including micropores (1.6-2.0 nm), mesopores (2.0-50.0 nm), macropores (50.0-148.7 nm), and multiple functional groups via a one-step hydrothermal method using silanized ionic liquids (IL) as functionalized hybrid monomer. The IL-HHPM has the advantages of a high specific surface area (437.4 ± 4.6 m2 g-1), sizable pore volume (0.74 cm3 g-1), and fast mass transfer, additionally, the IL-HHPM adsorbed OSIM and AZ-5104 via π-π interactions and hydrogen bonding. OSIM and AZ-5104 were rapidly extracted and measured in human urine using rapid and miniaturized centrifugal spin-column extraction (MCSCE), which was based on the IL-HHPM. The optimized factors for the extraction recoveries of OSIM and AZ-5104 were adsorbent dosage (8.0 mg), sample volume (0.5 mL), and operation time (9.0 min), and markedly reduced the adsorbent dosage and operation time. The IL-HHPM-MCSCE-HPLC method displayed good linearity (0.02-5.00 µg mL-1, r ≥ 0.9997), satisfying accuracy (spiked recoveries of 87.7%-100.0%), and good precision (RSDs ≤ 7.0%). The developed method is rapid, sensitive, and reproducible for the simultaneous determination of trace level of OSIM and AZ-5104 in human urine.

Hierarchical Attention Master-Slave for heterogeneous multi-agent reinforcement learning.

Most multi-agent reinforcement learning (MARL) approaches optimize strategy by improving itself, while ignoring the limitations of homogeneous agents that may have single function. However, in reality, the complex tasks tend to coordinate various types of agents and leverage advantages from one another. Therefore, it is a vital research issue how to establish appropriate communication among them and optimize decision. To this end, we propose a Hierarchical Attention Master-Slave (HAMS) MARL, where the Hierarchical Attention balances the weight allocation within and among clusters, and the Master-Slave architecture endows agents independent reasoning and individual guidance. By the offered design, information fusion, especially among clusters, is implemented effectively, and excessive communication is avoided, moreover, selective composed action optimizes decision. We evaluate the HAMS on both small and large scale heterogeneous StarCraft II micromanagement tasks. The proposed algorithm achieves the exceptional performance with more than 80% win rates in all evaluation scenarios, which obtains an impressive win rate of over 90% in the largest map. The experiments demonstrate a maximum improvement in win rate of 47% over the best known algorithm. The results show that our proposal outperforms recent state-of-the-art approaches, which provides a novel idea for heterogeneous multi-agent policy optimization.

Genomic Island-Encoded Histidine Kinase and Response Regulator Coordinate Mannose Utilization with Virulence in Enterohemorrhagic Escherichia coli.

Enterohemorrhagic Escherichia coli (EHEC) is a highly adaptive pathogen and has acquired diverse genetic elements, such as genomic islands and prophages, via horizontal gene transfer to promote fitness in vivo. Two-component signaling systems (TCSs) allow bacteria to sense, respond to, and adapt to various environments. This study identified a putative two-component signaling system composed of the histidine kinase EDL5436 (renamed LmvK) and the response regulator EDL5428 (renamed LmvR) in EHEC. lmvK and lmvR along with EDL5429 to EDL5434 (EDL5429-5434) between them constitute the OI167 genomic island and are highly associated with the EHEC pathotype. EDL5429-5434 encode transporters and metabolic enzymes that contribute to growth on mannose and are directly upregulated by LmvK/LmvR in the presence of mannose, as revealed by quantitative PCR (qPCR) and DNase I footprint assays. Moreover, LmvR directly activates the expression of the type III secretion system in response to mannose and promotes the formation of attaching and effacing lesions on HeLa cells. Using human colonoid and mouse infection models, we show that lmvK and lmvR contributed greatly to adherence and microcolony (MC) formation ex vivo and colonization in vivo. Finally, RNA sequencing and chromatin immunoprecipitation coupled with sequencing analyses identified additional direct targets of LmvR, most of which are involved in metabolism. Given that mannose is a mucus-derived sugar that induces virulence and is preferentially used by EHEC during infection, our data revealed a previously unknown mechanism by which EHEC recognizes the host metabolic landscape and regulates virulence expression accordingly. Our findings provide insights into how pathogenic bacteria evolve by acquiring genetic elements horizontally to adapt to host environments. IMPORTANCE The gastrointestinal tract represents a complex and challenging environment for enterohemorrhagic Escherichia coli (EHEC). However, EHEC is a highly adaptable pathogen, requiring only 10 to 100 CFUs to cause infection. This ability was achieved partially by acquiring mobile genetic elements, such as genomic islands, that promote overall fitness. Mannose is an intestinal mucus-derived sugar that stimulates virulence and is preferentially used by EHEC during infection. Here, we characterize the OI167 genomic island of EHEC, which encodes a novel two-component signaling system (TCS) and transporters and metabolic enzymes (EDL5429-5434) involved in mannose utilization. The TCS directly upregulates EDL5429-5434 and genes encoding the type III secretion system in the presence of mannose. Moreover, the TCS contributes greatly to EHEC virulence ex vivo and in vivo. Our data demonstrate an elegant example in which EHEC strains evolve by acquiring genetic elements horizontally to recognize the host metabolic landscape and regulate virulence expression accordingly, leading to successful infections.

Honeycomb resin-based spin-column solid-phase extraction for efficient determination of alectinib and its metabolite in human urine.

Alectinib and its metabolite, M4, have demonstrated a satisfactory clinical therapeutic effect in the treatment of anaplastic lymphoma kinase-positive advanced non-small-cell lung cancer. Due to individual differences among patients, therapeutic drug monitoring (TDM) is critical for guaranteeing appropriate clinical drug use. To realize TDM for alectinib and its metabolite, M4, a honeycomb phenol-formaldehyde resin (PFR) with excellent hydrophilic properties, abundant adsorption force, and a stable porous structure was synthesized by modifying the porogens F127 and P123. The prepared PFR was employed as an adsorbent in a simple and efficient spin-column solid-phase extraction (SPE) process. A rapid method for detecting alectinib and its metabolite M4 in urine was thereby established. The established method showed a linear range of 0.0200 µg mL-1-5.00 µg mL-1 and the recovery range of 98.8-103% for spiked urine samples, with relative standard deviations of ≤ 4.87% (n = 3). Our results proved the practicability of the proposed honeycomb-PFR spin-column SPE method in TDM for alectinib and its metabolite, M4.

Anomalous wrinkle propagation in polycrystalline graphene with tilt grain boundaries.

Understanding the propagation of dynamic wrinkles in polycrystalline graphene with grain boundaries (GBs) is critical to the practical application of graphene-based nanodevices. Although wrinkle propagation behavior in pristine graphene (PG) and some defect-containing graphene samples have been investigated, there are no studies on the dynamic behavior of graphene with tilt GBs. Here, nine tilt GBs are constructed in graphene, and molecular dynamics (MD) simulations are performed to investigate anomalous wrinkle propagation. The MD simulation results show that a larger misorientation angle α first enhances the shielding effect of tilt GBs on wrinkle propagation before it weakens. The maximum Δz root mean square (RMS) shows that a greater misorientation angle α first increases the maximum RMS of the GB region (RGB) before it then decreases, while the maximum RMS of R80 exhibits the opposite trend. Moreover, approximately 96% of the C60 kinetic energy is converted into kinetic and potential energies in graphene, and the potential energy in graphene presents two evolution modes. Phase diagrams are plotted to study the effect of the distance d1 and rotation angle ß on the wrinkle propagation and sensitivity of the maximum RMS value to d1. It is expected that our results can provide a fundamental understanding of defect engineering and guidelines to design protectors, energy absorbers, and defect detectors in nanodevices.

Pig farm biogas slurry can effectively reduce the pH of saline-alkali soils.

Pig farm biogas slurry is being increasingly used as a potent organic fertilizer for sustainable agriculture under circular economy. However, the effect of biogas slurry on soil pH is currently controversial, and the underlying mechanisms especially in saline-alkali soils are not well understood. A saline-alkali soil (pH = 9.2, EC = 2.0 ms/cm) was selected for soil column (0-50 cm) experiments with (BS) and without (CK) addition of pig farm biogas slurry to investigate the soil pH change and its driving factors. Our results show that the soil pH under CK ranged between 9.1 and 9.5 across different soil depths. Compared to CK, the BS-treated soil had lower pH at 0-20 cm depth and higher pH at 20-30 cm depth (P < 0.01). The soil NH4+-N concentrations were negatively correlated with pH values under BS (P < 0.01), indicating that the oxidation of ammonium mainly contributed to the decrease of soil pH. Interestingly, the anions, such as Cl-, SO42- and NO3-, were accumulated in the topsoil (0-20 cm) under BS, resulting in the changed correlations of these anions with Na+ when compared to the control. FT-IR and 13C-NMR spectra uncovered that carboxyl, amide C, and total alkyl C groups may be responsible for reducing pH of the saline-alkali soil tested. The soil surface morphology confirmed a much tighter granular aggregate microstructure when mixing the biogas slurry with the soil. Overall, we concluded that from the perspective of soil pH, the utilization of biogas slurry for improving saline-alkali soil is feasible and sustainable.

Monotropein Protects against Inflammatory Bone Loss and Suppresses Osteoclast Formation and Bone Resorption by Inhibiting NFATc1 via NF-κB and Akt/GSK-3ß Pathway.

Monotropein (Mon) is a kind of iridoid glycoside plant secondary metabolite primarily present in some edible and medicinal plants. The aim of this study was to investigate the effect of Mon on lipopolysaccharide (LPS)-induced inflammatory bone loss in mice and osteoclasts (OCs) derived from bone marrow-derived macrophages (BMMs), and explore the mechanisms underlying the effect of Mon on LPS-induced osteoclastogenesis. It was found that Mon markedly attenuated deterioration of the bone micro-architecture, enhanced tissue mineral content (TMC) and bone volume/total volume (BV/TV), reduced structure model index (SMI) and trabecular separation/spacing (Tb.Sp) in the bone tissue and decreased the activities of tartrate resistant acid phosphatase-5b (TRACP-5b), receptor activator NF-κB (RANK), and receptor activator NF-κB ligand (RANKL) as well as the serum levels of interleukin 6 (IL-6) and interleukin 1ß (IL-1ß) in LPS-treated mice. In addition, Mon treatment reduced the number of TRAP positive OCs in the bone tissue of LPS-treated mice and also exerted a stronger inhibitory effect on formation, differentiation, and F-actin ring construction of OCs derived from BMMs. Mon significantly inhibited the expression of the nuclear factor of activated T-cells c1 (NFATc1) and the immediate early gene (C-Fos) and nuclear translocation of NFATc1 in LPS-treated OCs, thereby inhibiting the expression of matrix metalloproteinase-9 (MMP-9), cathepsin K (CtsK), and TRAP. Mon significantly inhibited the expression of TRAF6, phosphorylation of P65, and degradation of IKBα, thus inhibiting the activation of NF-κB pathway in LPS-induced inflammatory mice and OCs derived from BMMs, and also inhibited LPS-induced phosphorylation of protein kinase B (Akt) and Glycogen synthase kinase 3ß (GSK-3ß) in OCs derived from BMMs. In conclusion, these results suggested that Mon could effectively inhibit osteoclastogenesis both in vitro and in vivo and therefore may prove to be potential option for prevention and treatment of osteoclastic bone resorption-related diseases.

Knowledge, Attitudes, and Practices Toward COVID-19 Among Rural Residents of Hebei Province: A Cross-Sectional Survey.

OBJECTIVE: Coronavirus disease (COVID-19) has spread worldwide due to high infectivity. The social sexual environment in rural areas of China and the weak basic medical facilities may affect the treatment and transmission of the disease. The aim of this study was to understand the knowledge, attitudes, and practices (KAP) related to COVID-19 among residents in rural areas experiencing the epidemic and the factors, to provide a basis for further epidemic prevention and control. METHODS: The COVID-19 KAP of rural residents in Hebei Province was collected by the snowball sampling method. The COVID-19 KAP questionnaire was distributed on social platforms such as WeChat and QQ through a network questionnaire. RESULTS: The overall level of COVID-19 KAP in rural residents was good, but in terms of knowledge, the correct rate of isolation was 73.2%, the correct rates of 2 disinfection items were 72.3% and 77.4%, and the correct rate of hand-washing was 70.7%; 54.5% residents felt panic; 81.0% disinfected household items; and 84.9% washed their hands correctly. Residents still needed to strengthen these aspects. A binary logistic analysis showed that age, education, and participation in training were factors affecting the level of COVID-19 KAP. CONCLUSIONS: This study found that rural residents had good levels of COVID-19 KAP, but there were gaps in specific issues that warrant attention. We advocate training on COVID-19 for rural residents.

Acoustic Change Complex Evoked by Horizontal Sound Location Change in Young Adults With Normal Hearing.

Acoustic change complex (ACC) is a cortical auditory-evoked potential induced by a change of continuous sound stimulation. This study aimed to explore: (1) whether the change of horizontal sound location can elicit ACC; (2) the relationship between the change of sound location and the amplitude or latency of ACC; (3) the relationship between the behavioral measure of localization, minimum audible angle (MAA), and ACC. A total of 36 normal-hearing adults participated in this study. A 180° horizontal arc-shaped bracket with a 1.2 m radius was set in a sound field where participants sat at the center. MAA was measured in a two-alternative forced-choice setting. The objective electroencephalography recording of ACC was conducted with the location changed at four sets of positions, ±45°, ±15°, ±5°, and ±2°. The test stimulus was a 125-6,000 Hz broadband noise of 1 s at 60 ± 2 dB SPL with a 2 s interval. The N1'-P2' amplitudes, N1' latencies, and P2' latencies of ACC under four positions were evaluated. The influence of electrode sites and the direction of sound position change on ACC waveform was analyzed with analysis of variance. Results suggested that (1) ACC can be elicited successfully by changing the horizontal sound location position. The elicitation rate of ACC increased with the increase of location change. (2) N1'-P2' amplitude increased and N1' and P2' latencies decreased as the change of sound location increased. The effects of test angles on N1'-P2' amplitude [F(1.91,238.1) = 97.172, p < 0.001], N1' latency [F(1.78,221.90) = 96.96, p < 0.001], and P2' latency [F(1.87,233.11) = 79.97, p < 0.001] showed a statistical significance. (3) The direction of sound location change had no significant effect on any of the ACC peak amplitudes or latencies. (4) Sound location discrimination threshold by the ACC test (97.0% elicitation rate at ±5°) was higher than MAA threshold (2.08 ± 0.5°). The current study results show that though the ACC thresholds are higher than the behavioral thresholds on MAA task, ACC can be used as an objective method to evaluate sound localization ability. This article discusses the implications of this research for clinical practice and evaluation of localization skills, especially for children.

Selenium Deficiency Leads to Changes in Renal Fibrosis Marker Proteins and Wnt/ß-Catenin Signaling Pathway Components.

Renal fibrosis is the final result of the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). Earlier studies confirmed that selenium (Se) displays a close association with kidney diseases. However, the correlation between Se and fibrosis has rarely been explored. Thus, this article mainly aimed to investigate the effect of Se deficiency on renal fibrosis and the Wnt/ß-catenin signaling pathway. Twenty BALB/c mice were fed a diet containing 0.02-mg/kg Se (Se-deficient diet) or 0.18-mg/kg Se (standard diet) for 20 weeks. A human glomerular mesangial cell (HMC) cell line was transfected with lentiviral TRNAU1AP-shRNA vector to establish a stable Se deficiency model in vitro. As indicated in this study, the glutathione (GSH) content in the Se-deficient group displayed an obvious decline compared with that in the control group, whereas the content of malondialdehyde (MDA) was obviously elevated. The results of Masson staining showed fibrosis around the renal tubules, and the results of immunohistochemistry showed that the area of positive fibronectin expression increased. In the Se-deficient group, the levels of collagen I, collagen III, matrix metalloproteinase 9 (MMP9), and other fibrosis-related proteins changed significantly in vivo and in vitro. Compared with the control group, the TRNAU1AP-shRNA group showed markedly reduced cell proliferation and migration abilities. Our data indicate that Se deficiency can cause kidney damage and renal fibrosis. Furthermore, the Wnt pathway is critical for the development of tissue and organ fibrosis. The data of this study demonstrated that the expression of Wnt5a, ß-catenin, and dishevelled 1 (Dvl-1) was significantly upregulated in the Se-deficient group. Therefore, the Wnt/ß-catenin pathway may play an important role in renal fibrosis caused by Se deficiency.