Major depressive disorder (MDD) is a ubiquitous mental illness with heterogeneous symptoms, however, the pathophysiology mechanisms are still not fully understood. Clinical and preclinical studies ...suggested that depression could cause disturbances in sensory perception systems, disruptions in auditory and visual functions may serve as an essential clinical features underlying MDD.
The current study investigated the abnormal intrinsic connectivity within and between visual and auditory networks in 95 MDD patients and 97 age-, gender-, education level-matched healthy controls (HCs) by using resting-state functional magnetic resonance imaging (fMRI). One auditory network (AN) and three visual components including visual component 1 (VC1), VC2, and VC3 were identified by using independent component analysis method based on the fMRI networks during the resting state with the largest spatial correlations, combining with brain regions and specific network templates.
We found that MDD could be characterized by the following disrupted network model relative to HCs: (i) reduced within-network connectivity in the AN, VC2, and VC3; (ii) reduced between-network connectivity between the AN and the VC3. Furthermore, aberrant functional connectivity (FC) within the visual network was linked to the clinical symptoms.
Overall, our results demonstrated that abnormalities of FC in perception systems including intrinsic visual and auditory networks may explain neurobiological mechanisms underlying MDD and could serve as a potential effective biomarker.
•MDD showed decreased FCs within and between the auditory network and the visual network relative to HCs.•The decreased FC of right middle occipital gyrus within the VC3 was positively related with the course of illness in MDD group.•The hypoconnectivity in visual and auditory networks may serve as an effective biomarker.
Porcine reproductive and respiratory syndrome virus (PRRSV), a highly infectious virus, causes severe losses in the swine industry by regulating the inflammatory response, inducing tissue damage, ...suppressing the innate immune response, and promoting persistent infection in hosts. Interleukin-13 (IL-13) is a cytokine that plays a critical role in regulating immune responses and inflammation, particularly in immune-related disorders, certain types of cancer, and numerous bacterial and viral infections; however, the underlying mechanisms of IL-13 regulation during PRRSV infection are not well understood. In this study, we demonstrated that PRRSV infection elevates IL-13 levels in porcine alveolar macrophages. PRRSV enhances m6A-methylated RNA levels while reducing the expression of fat mass and obesity associated protein (FTO, an m6A demethylase), thereby augmenting IL-13 production. PRRSV nonstructural protein 9 (nsp9) was a key factor for this modulation. Furthermore, we found that the residues Asp567, Tyr586, Leu593, and Asp595 were essential for nsp9 to induce IL-13 production via attenuation of FTO expression. These insights delineate PRRSV nsp9’s role in FTO-mediated IL-13 release, advancing our understanding of PRRSV's impact on host immune and inflammatory responses.
Most current researches focus solely on reducing soil chromium availability. It is difficult to reduce soil Cr(VI) concentration below 5.0 mg kg-1 using single remediation technology. This study ...introduced a sustainable soil Cr(VI) reduction and stabilization system, Penicillium oxalicum SL2–nanoscale zero-valent iron (nZVI), and investigated its effect on Cr(VI) reduction efficiency and microbial ecology. Results showed that P. oxalicum SL2–nZVI effectively reduced soil total Cr(VI) concentration from 187.1 to 3.4 mg kg–1 within 180 d, and remained relatively stable at 360 d. The growth curve of P. oxalicum SL2 and microbial community results indicated that γ-ray irradiation shortened the adaptation time of P. oxalicum SL2 and facilitated its colonization in soil. P. oxalicum SL2 colonization activated nZVI and its derivatives, and increased soil iron bioavailability. After restoration, the negative effect of Cr(VI) on soil microorganisms was markedly alleviated. Cr(VI), Fe(II), bioavailable Cr/Fe, Eh, EC and urease (SUE) were the key environmental factors of soil microbiota. Notably, Penicillium significantly stimulated the growth of urease-positive bacteria, Arthrobacter, Pseudarthrobacter, and Microvirga, synergistically reducing soil chromium availability. The combination of P. oxalicum SL2 and nZVI is expected to form a green, economical and long-lasting Cr(VI) reduction stabilization strategy.
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•P. oxalicum SL2–nZVI effectively reduced soil total Cr(VI) and available chromium.•Gamma-ray irradiation pretreatment facilitated P. oxalicum SL2 colonization in soil.•The negative effect of Cr(VI) on soil microorganisms was mitigated after remediation.•Cr- and Fe- related indicators, Eh, EC and SUE were the key environmental factors.•Penicillium colonization significantly stimulated the growth of urease-positive bacteria.
The protein phosphatase PP2C plays an important role in plant responses to stress. Therefore, the identification of maize
genes that respond to drought stress is particularly important for the ...improvement and creation of new drought-resistant assortments of maize. In this study, we identified 102
genes in maize at the genome-wide level. We analyzed the physicochemical properties of 102
and constructed a phylogenetic tree with
. By analyzing the gene structure, conserved protein motifs, and synteny, the
were found to be strongly conserved during evolution. Sixteen core genes involved in drought stress and rewatering were screened using gene co-expression network mapping and expression profiling. The qRT-PCR results showed 16 genes were induced by abscisic acid (ABA), drought, and NaCl treatments. Notably,
exhibited a substantial expression difference. Through genetic transformation, we overexpressed
and generated the CRISPR/Cas9 knockout maize mutant
. Overexpressing
in
under drought stress enhanced growth and survival compared with WT plants. The leaves exhibited heightened superoxide dismutase (SOD), peroxidase (POD), ascorbate peroxidase (APX), and catalase (CAT) activities, elevated proline (Pro) content, and reduced malondialdehyde (MDA) content. Conversely,
mutant plants displayed severe leaf dryness, curling, and wilting under drought stress. Their leaf activities of SOD, POD, APX, and CAT were lower than those in B104, while MDA was higher. This suggests that
positively regulates drought tolerance in maize by affecting the antioxidant enzyme activity and osmoregulatory substance content. Subcellular localization revealed that
was localized in the nucleus and cytoplasm. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) experiments demonstrated
's interaction with ZmWIN1, ZmADT2, ZmsodC, Zmcab, and ZmLHC2. These findings establish a foundation for understanding maize
gene functions, offering genetic resources and insights for molecular design breeding for drought tolerance.
Ankylosing spondylitis (AS) is a common chronic progressive inflammatory autoimmune disease. T helper 17 (Th17) cells are the major effector cells mediating AS inflammation. Histone 3 Lys 27 ...trimethylation (H3K27me3) is an inhibitory histone modification that silences gene transcription and plays an important role in Th17 differentiation. The objective of this study was to investigate the expression of H3K27me3 in patients with AS and to explore its epigenetic regulation mechanism of Th17 differentiation during AS inflammation. We collected serum samples from 45 patients with AS at various stages and 10 healthy controls to measure their Interleukin-17 (IL-17) levels using ELISA. A quantitative polymerase chain reaction was used to quantify the mRNA levels of RORc and the signaling molecules of the JAK2/STAT3 pathway, JMJD3, and EZH2. Additionally, Western blot analysis was performed to quantify the protein levels of H3K27me3, RORγt, JAK2, STAT3, JMJD3, and EZH2 in cell protein extracts. The results showed that H3K27me3 expression in peripheral blood mononuclear cells (PBMCs) was significantly lower in patients with active AS compared to both the normal control groups and those with stable AS. Moreover, a significant negative correlation was observed between H3K27me3 expression and the characteristic transcription factor of Th17 differentiation, RORγt. We also discovered that patients with active AS exhibited significantly higher levels of JMJD3, an inhibitor of H3K27 demethylase, compared to the normal control group and patients with stable AS, while the expression of H3K27 methyltransferase (EZH2) was significantly lower. These findings suggest that H3K27me3 may be a dynamic and important epigenetic modification in AS inflammation, and JMJD3/EZH2 regulates the methylation level of H3K27me3, which may be one of the key regulatory factors in the pathogenesis of AS. These findings contribute to our understanding of the role of epigenetics in AS and may have implications for the development of novel therapeutic strategies for AS.
•Multifunctional nanoplatform boosts allicin's bioavailability and duration.•Controlled release with pH-dependent and ROS-scavenging antibacterial properties.•Enhances collagen and new vessel growth, ...accelerates healing of infected wounds.
The development of non-antibiotic strategies for combating bacterial infections, particularly through reactive oxygen species (ROS) accumulation accompanying inflammation, has attracted much attention. Despite Allicin (Ac) emerges as a promising antimicrobial agent with wide and remarkable bioactivity, it still displays quite limited ROS scavenging and anti-inflammation capacity due to uncontrolled and poor bioavailability. Herein, a multifunctional nanoplatform with pH-dependent and ROS-scavenging antibacterial, anti-inflammatory and proangiogenic properties is introduced to promote infected wound healing by integrating Ac into silver nanoparticles (AgNPs)-loaded zeolite imidazole framework (ZIF-8), namely Ac@ZIF-8/AgNPs. Primarily, the nanoplatform is activated and controlled release in the infection microenvironment, with disrupting biofilms, scavenging ROS and antibacterial capacitys, outperforming conventional Ac. Moreover, in the mouse models induced by bacterial infection, Ac@ZIF-8/AgNPs can alleviate the inflammatory condition, scavenge ROS, facilitate the regeneration of collagen fiber and enhance vascular formation, collectively accelerating wound healing. Overall, this biocompatible nanoplatform is provided as a reliable approach to solve the long-standing problem of infected wound healing.
Stretchable electronics are of great significance for the development of the next-generation smart interactive systems. Here, we propose an intrinsically stretchable organic tribotronic transistor ...(SOTT) without a top gate electrode, which is composed of a stretchable substrate, silver nanowire electrodes, semiconductor blends, and a nonpolar elastomer dielectric. The drain-source current of the SOTT can be modulated by external contact electrification with the dielectric layer. Under 0-50% stretching both parallel and perpendicular to the channel directions, the SOTT retains great output performance. After being stretched to 50% for thousands of cycles, the SOTT can survive with excellent stability. Moreover, the SOTT can be conformably attached to the human hand, which can be used for tactile signal perception in human-machine interaction and for controlling smart home devices and robots. This work has realized a stretchable tribotronic transistor as the tactile sensor for smart interaction, which has extended the application of tribotronics in the human-machine interface, wearable electronics, and robotics.
Long-chain acyl-CoA synthetase 1 (ACSL1) plays an important role in fatty acid metabolism and fat deposition. The transcription of the
gene is regulated specifically among cells and physiological ...processes, and transcriptional regulation of
in adipogenesis remains elusive. Here, we characterize transcription factors (TFs) associated with adipogenesis in the porcine
gene. CCAAT-enhancer binding protein (C/EBP)α, a well-known adipogenic marker, was found to enhance the expression of the
gene via binding two tandem motifs in the promoter. Further, we demonstrate that ACSL1 mediates C/EBPα effects on adipogenesis in preadipocytes cultured from subcutaneous fat tissue of pigs via gain- and loss-of-function analyses. The cAMP-response element binding protein, another TF involved in adipogenesis, was also identified in the regulation of
gene expression. Additionally, single nucleotide polymorphisms (SNPs) were screened in the promoter of
among four breeds including the Chinese indigenous Min, and Duroc, Berkshire, and Yorkshire pigs through sequencing of PCR products. Two tightly linked SNPs, -517G>T and -311T>G, were found exclusively in Min pigs. The haplotype mutation decreases promoter activity in PK-15 and ST cells, and in vivo the expression of
, illustrating a possible role in adipogenesis regulated by C/EBPα/ACSL1 axis. Additionally, a total of 24 alternative splicing transcripts were identified, indicating the complexity of alternative splicing in the
gene. The results will contribute to further revealing the regulatory mechanisms of
during adipogenesis and to the characterization of molecular markers for selection of fat deposition in pigs.
Background
With the advancements in the dental health care industry, the demand for dental technicians has increased. Dental technicians should be thoroughly assessed and trained in practical skills ...and pass professional certification examinations to ensure that they are competent to work closely with dentists. Unfortunately, such training courses and tests are in short supply worldwide. The use of virtual simulation technology can help solve these problems.
Objective
This study presents a new strategic framework design for a certified dental technician practical examination called as the certified Objective Manipulative Skill Examination of Dental Technicians (OMEDT), which is based on the Objective Structured Clinical Examination (OSCE). We present the development and validation of the OMEDT system, a new virtual simulated training system, to meet the demands of the OMEDT framework. The combination of OMEDT and the OMEDT system can solve the complex problems encountered in the certified dental technician practical examination with excellent efficiency, high quality, and low cost.
Methods
The OMEDT framework design was constructed according to the OSCE guide and the Chinese vocational skill standards for dental technicians. To develop the OMEDT system, we organized a new framework based on the virtual learning network platform, the haptic feedback system, and the real-time dental training and evaluation system. The effectiveness evaluation of the OMEDT system was divided into 2 phases: in the first phase, 36 students were recruited to use the test module to finish the task and their performance data were collected and analyzed; and in the second phase, a questionnaire was administered to 30 students who used the system for their studies and graduation exams.
Results
The OMEDT and the corresponding skill training virtual simulation OMEDT system were developed, and preliminary user evaluation was performed to assess their effectiveness and usefulness. The OMEDT system was found to improve students’ practical skills by training with the evaluation results. In addition, several key research topics were explored, including the effects of positive feedback of the knowledge of results on the improvement of the students’ skill level and the common sense transformation of educators in the virtual simulation technology environment.
Conclusions
The development of OMEDT and the OMEDT system has been completed and their effectiveness has been verified.
Background:
Left bundle branch area pacing (LBBAP) is a novel pacing modality with stable pacing parameters and a narrow-paced QRS duration. We compared heart failure (HF) hospitalization events and ...echocardiographic measures between LBBAP and right ventricular pacing (RVP) in patients with atrioventricular block (AVB).
Methods and Results:
This multicenter observational study prospectively recruited consecutive AVB patients requiring ventricular pacing in five centers if they received LBBAP or RVP and had left ventricular ejection fraction (LVEF) >50%. Data on electrocardiogram, pacing parameters, echocardiographic measurements, device complications, and clinical outcomes were collected at baseline and during follow-up. The primary outcome was first episode hospitalization for HF or upgrade to biventricular pacing. LBBAP was successful in 235 of 246 patients (95.5%), while 120 patients received RVP. During a mean of 11.4 ± 2.7 months of follow-up, the ventricular pacing burden was comparable (83.9 ± 35.1 vs. 85.7 ± 30.0%), while the mean LVEF differed significantly (62.6 ± 4.6 vs. 57.8 ± 11.4%) between the LBBAP and RVP groups. Patients with LBBAP had significantly lower occurrences of HF hospitalization and upgrading to biventricular pacing than patients with RVP (2.6 vs. 10.8%,
P
<0.001), and differences in primary outcome between LBBAP and RVP were mainly observed in patients with ventricular pacing >40% or with baseline LVEF <60%. The primary outcome was independently associated with LBBAP (adjusted HR 0.14, 95% CI: 0.04–0.55), previous myocardial infarction (adjusted HR 6.82, 95% CI: 1.23–37.5), and baseline LVEF (adjusted HR 0.91, 95% CI: 0.86–0.96).
Conclusion:
Permanent LBBAP might reduce the risk of HF hospitalization or upgrade to biventricular pacing compared with RVP in AVB patients requiring a high burden of ventricular pacing.
Clinical Trial Registration:
URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03851315; URL:
http://www.chictr.org.cn
; Unique Identifier: ChiCTR2100043296.