Identification and Validation of Genes Exhibiting Dynamic Alterations in Response to Bleomycin-Induced Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) carries a high mortality rate and has a poor prognosis. The pathogenesis of pulmonary fibrosis (PF) is highly related to dysregulation of multiple RNAs. This study aims to identify and validate dysregulated RNAs that exhibited dynamic alterations in response to bleomycin (BLM)-induced PF. The results will provide therapeutic targets for patients suffering from IPF. Whole transcriptomic profiles of BLM-induced PF were obtained through high-throughput RNA sequencing. miRNA profiling was downloaded from GSE45789 database in the Gene Expression Omnibus (GEO). We identified the differentially expressed RNAs (DERNAs) that exhibited dynamic alterations in response to BLM-induced PF. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis were conducted to discovery regulatory processes of PF. Weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) analysis, and co-expression analysis were performed to identify key genes and pathogenic pattern during the progression of PF. MiRanda, miRcode, and TargetScan were utilized to predict target relationships in the potential competing endogenous RNA (ceRNA) network. The results were verified by qRT-PCR analysis. In the context of BLM-induced PF, this study identified a total of 167 differentially expressed messenger RNAs (DEmRNAs), 115 differentially expressed long non-coding RNAs (DElncRNAs), 45 differentially expressed circular RNAs (DEcircRNAs), and 87 differentially expressed microRNAs (DEmiRNAs). These RNA molecules showed dynamic alterations in response to BLM-induced PF. These DEmRNAs exhibited a predominant association with the biological processes pertaining to the organization of extracellular matrix. A regulatory network was built in PF, encompassing 31 DEmRNAs, 18 DE lncRNAs, 13 DEcircRNAs, and 13 DEmiRNAs. Several DERNA molecules were subjected to validate using additional BLM-induced PF model. The outcomes of this validation process shown a strong correlation with the results obtained from RNA sequencing analysis. The GSE213001 dataset was utilized to validate the expression levels and diagnostic efficacy of four specific hub mRNAs (CCDC80, CLU, COL5A1, and COL6A3) in individuals diagnosed with PF. In this study, we identified and validated several RNA molecules that exhibited dynamic alternations in response to BLM-induced PF. These dysregulated RNAs participated in the pathogenesis of PF and can be used as therapeutic targets for early-stage IPF. Although more work must be done to confirm the results, our study may provide directions for future studies.

Feasibility, safety, and efficacy of task-oriented mirrored robotic training on upper-limb functions and activities of daily living in subacute poststroke patients: a pilot study.

BACKGROUND: Robotic training with high repetitions facilitates upper-limb movements but provides fewer benefits for activities of daily living. Integrating activities of daily living training tasks and mirror therapy into a robot may enhance the functional gains of robotic training. AIM: The aim of this study was to investigate the feasibility, safety, and efficacy of the task-oriented mirrored upper-limb robotic training on the upper-limb functions and activities of daily living of subacute poststroke patients. DESIGN: This study is a single-blinded, active-controlled pilot study. SETTING: The study was carried out at rehabilitation outpatient clinic and ward. POPULATION: A total of 32 subacute poststroke patients were enrolled in the study. METHODS: The enrolled patients were allocated into two groups in a ratio of 1:1. The experimental group received 4 weeks of task-oriented mirrored upper-limb robotic training, consisting of five sessions of 30-minute duration, along with 30 minutes of conventional training. The control group only received 60 minutes of conventional training. The outcome measures were the Fugl-Meyer Assessment Scale for Upper Extremity, Modified Barthel Index, Stroke Self-Efficacy Scale, System Usability Scale, and Quebec User Evaluation with Assistive Technology. RESULTS: All patients completed the full training sessions without significant adverse events related to robotic training. The task-oriented mirrored upper-limb robotic training led to increased Fugl-Meyer Assessment Scale for Upper Extremity (difference: 10.38 points, P<0.001) and Modified Barthel Index (difference: 18.38 points, P<0.001) scores, both of which exceeded the minimal clinically important difference. Intergroup analysis showed significantly higher improvements in the Fugl-Meyer Assessment Scale for Upper Extremity total scores, shoulder, wrist, and hand scores; and Modified Barthel Index scores in the experimental group than in conventional training (all P<0.05). Both groups showed significant improvements in Stroke Self-Efficacy Scale scores after the intervention (both P<0.001), but without a statistically significant intergroup difference (P>0.05). Participants in the experimental group scored an average usability perception score of 74.74 (good) and an average satisfaction score of four or more out of five. CONCLUSIONS: In general, task-oriented mirrored upper-limb robotic training appears feasible and safe for subacute poststroke rehabilitation, facilitating the recovery of upper-limb functions and activities of daily living. CLINICAL REHABILITATION IMPACT: Task-oriented mirrored upper-limb robotic training shows promise for future clinical rehabilitation and clinical trials involving subacute poststroke patients.

Effect of Tai Chi on Young Adults with Subthreshold Depression via a Stress-Reward Complex: A Randomized Controlled Trial.

BACKGROUND: Subthreshold depression is a highly prevalent mood disorder in young adults. Mind-body exercises, such as Tai Chi, have been adopted as interventions for clinical depressive symptoms. However, the possible effect and underlying mechanism of Tai Chi on subthreshold depression of young individuals remain unclear. This randomized controlled study aimed to evaluate the effects of Tai Chi training and tested the combined stress and reward circuitry model for subthreshold depression. RESULTS: A total of 103 participants completed this trial, with 49 in the 12-week 24-style Tai Chi group and 54 participants in control group. Our results showed significantly lower scores on depressive symptoms (P = 0.002) and anxiety symptoms (P = 0.009) and higher scores on quality of life (P = 0.002) after Tai Chi training. There were significant reductions in salivary cortisol levels (P = 0.007) and putamen gray matter volume (P < 0.001) in the Tai Chi group. The changes in cortisol levels and putamen gray matter volume had direct (bootstrapping confidence interval [- 0.91, - 0.11]) and indirect effects (bootstrapping confidence interval [- 0.65, - 0.19]) on the changes induced by Tai Chi training on depressive symptoms, respectively. CONCLUSION: The stress-reward complex results indicated an interaction between lowering stress levels and increasing reward circuitry activity associated with the alleviation of depressive symptoms among participants. The 12-week Tai Chi training was effective in improving the symptoms and quality of life of young adults with subthreshold depression. Trial Registration Chinese Registry of Clinical Trials (Registration Number: ChiCTR1900028289, Registered December 12, 2019).

Effects of dorsolateral prefrontal cortex stimulation on network topological attributes in young individuals with high-level perceived stress: A randomized controlled trial.

Individuals with high-level perceived stress are at higher risk of developing a psychiatric disorder. While repetitive transcranial magnetic stimulation (rTMS) is effective for improving emotional symptoms, there is little evidence of its effect on perceived stress. This randomized sham-controlled trial investigated the effect of rTMS on ameliorating high-level stress and explored the associated changes in brain network activity. Fifty participants with high-level perceived stress were randomly assigned to either the active or sham rTMS group and received 12 active/sham rTMS sessions over four weeks (three per week). Perceived stress score (PSS), Chinese affective scale (CAS) normal and now statuses, and functional network topology were measured. Our results showed greater improvements in PSS and CAS_Normal scores, and reduced path length in the default mode network after active rTMS. Functional activations of the angular gyrus, posterior insula, and prefrontal cortex were also modulated in the active group. There were significant associations between posterior insula efficiency and PSS scores, and between angular efficiency and CAS_Now scores in the active group. These cumulative findings suggest rTMS as a promising intervention for recovery from high-level perceived stress.

Systematic bibliometric and visualized analysis of research hotspots and trends in attention-deficit hyperactivity disorder neuroimaging.

Introduction: This study focused on the research hotspots and development trends of the neuroimaging of attention deficit hyperactivity disorder (ADHD) in the past thirty years. Methods: The Web of Science database was searched for articles about ADHD neuroimaging from January 1992 to September 2022. CiteSpace was used to analyze the co-occurrence of keywords in literature, partnerships between authors, institutions, and countries, the sudden occurrence of keywords, clustering of keywords over time, and analysis of references, cited authors, and cited journals. Results: 2,621 articles were included. More and more articles have been published every year in the last years. These articles mainly come from 435 institutions and 65 countries/regions led by the United States. King's College London had the highest number of publications. The study identified 634 authors, among which Buitelaar, J. K. published the largest number of articles and Castellanos, F. X. was co-cited most often. The most productive and cited journal was Biological psychiatry. In recent years, burst keywords were resting-state fMRI, machine learning, functional connectivity, and networks. And a timeline chart of the cluster of keywords showed that "children" had the longest time span. Conclusions: Increased attention has been paid to ADHD neuroimaging. This work might assist researchers to identify new insight on potential collaborators and cooperative institutions, hot topics, and research directions.

Strong enhancement of Goos-Hänchen shift through the resonant optical tunneling effect.

The resonant optical tunneling effect (ROTE) originates from the frustrated total reflection effect because unique transmission characteristics are used to study high-sensitivity sensors. In this study, we theoretically demonstrated that choosing a suitable transmission gap made it possible for the ROTE structure based on hexagonal boron nitride and graphene to obtain a large Goos-Hänchen shift as high as tens of thousands of times the incident wavelength at a specific incident angle. The amplitude of the Goos-Hänchen shift was found to be sensitive to the central layer thickness but was also modulated by the tunneling gap on both sides. In addition, adjusting the chemical potential and relaxation time of the graphene sheets could alter the Goos-Hänchen shift. Our work provides a new way to explore the Goos-Hänchen effect and opens the possibility for the application of high-precision measurement technology based on the ROTE.

Communication wavelength investigation of bound states in the continuum of one-dimensional two-material periodic ring optical waveguide network.

In this study, a one-dimensional (1D) two-material period ring optical waveguide network (TMPROWN) was designed, and its optical properties were investigated. The key characteristics observed in the 1D TMPROWN include the following: (1) Bound states in continuum (BICs) can be generated in the optical waveguide network. (2) In contrast to the BICs previously reported in optical structures, the range of the BICs generated by the 1D TMPROWN is not only larger, but also continuous. This feature makes it possible for us to further study the electromagnetic wave characteristics in the range of the BICs. In addition, we analyzed the physical mechanisms of the BICs generated in the 1D TMPROWN. The 1D TMPROWN is simple in structure, demonstrates flexibility with respect to adjusting the frequency band of the BICs, and offers easy measurement of the amplitude and phase of electromagnetic waves. Hence, further research on high-power super luminescent diodes, optical switches, efficient photonic energy storage, and other optical devices based on the 1D TMPROWN designed in this study is likely to have implications in a broad range of applications.

Multi-domain computerized cognitive training for children with intellectual developmental disorder: A randomized controlled trial.

Purpose: To verify the effects of multi-domain computerized cognitive training on intellectual function and adaptive functioning in children with intellectual developmental disorder (IDD). Methods: Children with IDD were randomized to a multi-domain computerized cognitive training (CCT) group (n = 30) and control group (n = 30). Both groups received a 5-week training program. Intellectual function was assessed by Chinese-Wechsler Young Children scale (C-WYCSI) and adaptive functioning was assessed by the Chinese Vineland Adaptive Behavior Rating Scale (VABS-C), which were used at baseline, post-training, and 3-month follow-up. Results: There were significant differences for intellectual function and adaptive functioning between the two groups. The CCT group showed significant improvements in total full-scale intelligence quotient (FSIQ) score the Wechsler Intelligence Scale (F[60] = 31.97, p < 0.01) and its subdomain VIQ score (F[60] = 33.83, p < 0.01). For adaptive functioning, CCT had a better adaptive developmental quotient (ADQ) score (F[60] = 28.05, p < 0.01), and subdomain communication (F[60] = 10.86, p < 0.01) and socialization scores (F[60] = 4.35, p < 0.015). Moreover, there was a positive correlation between FSIQ changes and ADQ changes in the CCT group (rs = 0.74, p < 0.01). A greater increase in VIQ score was associated with a greater increase in adaptive functioning (bootstrapping CI: [0.16, 3.30]) in the CCT group. Conclusion: Multi-domain CCT improves the intellectual function and adaptive functioning of children with IDD.

A Bifunctional Silicon Dielectric Metasurface Based on Quasi-Bound States in the Continuum.

Quasi-bound states in the continuum provide an effective and observable way to improve metasurface performance, usually with an ultra-high-quality factor. Dielectric metasurfaces dependent on Mie resonances have the characteristic of significantly low loss, and the polarization can be affected by the parameter tuning of the structure. Based on the theory of quasi-bound states in the continuum, we propose and simulate a bifunctional resonant metasurface, whose periodic unit structure consists of four antiparallel and symmetrical amorphous silicon columns embedded in a poly(methyl methacrylate) layer. The metasurface can exhibit an extreme Huygens' regime in the case of an incident plane wave with linear polarization, while exhibiting chirality in the case of incident circular polarized light. Our structure provides ideas for promoting the multifunctional development of flat optical devices, as well as presenting potential in polarization-dependent fields.

[Effect of micro RNA-335-5p regulating bone morphogenetic protein 2 on osteogenic differentiation of human bone marrow mesenchymal stem cells].

OBJECTIVE: To investigate the effect of micro RNA (miR)-335-5p regulating bone morphogenetic protein 2 (BMP-2) on the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). METHODS: hBMSCs were cultured in vitro and randomly divided into control group (group A), miR-335-5p mimics group (group B), miR-335-5p mimics negative control group (group C), miR-335-5p inhibitor group (group D), and miR-335-5p inhibitor negative control group (group E). After grouping treatment and induction of osteogenic differentiation, the osteogenic differentiation of cells in each group was detected by alkaline phosphatase (ALP) and alizarin red staining; the expressions of miR-335-5p and BMP-2, Runt-related transcription factor 2 (Runx2), osteopontin (OPN), and osteocalcin (OCN) mRNAs were detected by real-time fluorescence quantitative PCR analysis; the expressions of Runx2, OPN, OCN, and BMP-2 proteins were detected by Western blot. RESULTS: Compared with group A, the relative proportion of ALP positive cells and the relative content of mineralized nodules, the relative expressions of BMP-2, miR-335-5p, OPN, OCN, Runx2 mRNAs, the relative expressions of Runx2, OPN, OCN, and BMP-2 proteins in group B were significantly increased ( P<0.05); the above indexes in group D were significantly decreased ( P<0.05); the above indexes between groups C, E and group A were not significantly different ( P>0.05). CONCLUSION: miR-335-5p can up-regulate BMP-2 expression and promote osteogenic differentiation of hBMSCs.

Transcriptome sequencing analysis of SH-SY5Y cells infected with EV71 reveals the potential neuropathic mechanisms.

Enterovirus A71 (EV71) remains the most common causative agent of hand, foot, and mouth disease (HFMD), and the neurological complications induced by EV71 are usually the leading cause of death in children with HFMD. However, the mechanism of nervous system changes caused by EV71 infection is still unclear. Therefore, in the current study, EV71 was inoculated into the human neuroblastoma cell line SH-SY5Y and subsequent transcriptome sequencing was used to examine the alterations of the transcriptome in infected SH-SY5Y cells. It is expected to determine the underlying mechanism of neurological diseases in response to EV71 infection. As a result, a total of 82,406,974, 112,410,808 and 87,780,371 clean reads were found in the control, EV71-12 h and EV71-24 h groups, respectively. Moreover, 160 and 745 differentially expressed genes were identified in the EV71-12 h and EV71-24 h groups, respectively, as compared to the control group. Next, to further explore the pathogenic mechanism triggered by EV71 infection, we mainly focused on the common differentially expressed genes at different time points of EV71 infection. And it was discovered that there were 95 common differentially expressed genes, which were used to conduct GO and pathway analysis. GO enrichment analysis demarcated related biological processes, molecular functions and cellular components, and KEGG pathway analysis enabled annotations of metabolic pathways and revealed interactions among the significantly enriched pathways. The results showed that the enriched GO term "Nervous system development" and enriched pathway "CCKR signaling map" might be important contributors to EV71-induced neuropathological mechanisms. In addition, we also screened 10 up- and down-regulated non-protein coding genes with significantly different expression in our transcriptome profiling, which suggested that these abnormally regulated non-protein-encoding genes might also play important roles in the pathogenesis of EV71 infection. Eventually, RT-qPCR technology was adopted to validate the transcriptome sequencing data and the experiment demonstrated that the RT-qPCR and transcriptome sequencing results were basically consistent. In summary, this is the first transcriptome analysis of SH-SY5Y cells in response to EV71 infection and provides valuable cues for further exploring the mechanism of nervous system changes caused by EV71 infection.

MMP-9 gene polymorphisms (rs3918242, rs3918254 and rs4810482) and the risk of psoriasis vulgaris: No evidence for associations in a Chinese Han population.

Several previous studies including one of them co-authored by our group have revealed that serum and psoriatic plaque expression of matrix metalloproteinase-9 (MMP-9) was significantly upregulated in psoriasis. The aim of this study was to investigate the association of three single nucleotide polymorphisms (SNPs) and haplotypes of MMP-9 (rs3918242, rs3918254 and rs4810482) with psoriasis vulgaris in a Chinese Han population. The serum levels of MMP-9 in 245 psoriasis vulgaris cases and 256 healthy controls were assessed using ELSA kits, and the three SNPs were genotyped using polymerase chain reaction-ligation detection reaction (PCR-LDR) method. Four haplotypes based on the three SNPs were also analyzed. Our study showed that the serum MMP-9 levels in patients with psoriasis vulgaris were significantly higher than that in controls (P<0.05). However, the three SNPs were not significantly associated with psoriasis vulgaris susceptibility (all P>0.05). Similar results were found in further subgroup analysis based on gender, age of onset, family history, and serum MMP-9 levels, except that a protective effect of psoriasis vulgaris was detected among female subjects with the CT genotype of rs3918254 (OR=0.47, 95% CI=0.23-0.96, P=0.038), but this association did not survive after Bonferroni correction (P(adj)=0.076). The haplotype analysis also failed to show any association with psoriasis vulgaris. We found no evidence for the association between the MMP-9 polymorphisms and psoriasis vulgaris susceptibility in a Chinese Han population.

A pyrene-based highly selective turn-on fluorescent sensor for copper(II) ion and its application in live cell imaging.

A new pyrene derivative (chemosensor 1) containing a picolinohydrazide moiety exhibits high selectivity for Cu(2+) ion detection in mixed aqueous media (CH(3)OH:H(2)O = 7:3). Significant fluorescence enhancement was observed with chemosensor 1 in the presence of Cu(2+). However, the metal ions Ag(+), Ca(2+), Cd(2+), Co(2+), Cu(2+), Fe(2+), Fe(3+), Hg(2+), K(+), Mg(2+), Mn(2+), Ni(2+), Pb(2+), and Zn(2+) produced only minor changes in fluorescence for the system. The apparent association constant (K(a)) of Cu(2+) binding in chemosensor 1 was found to be 2.75*10(3) M(-1). The maximum fluorescence enhancement caused by Cu(2+) binding in chemosensor 1 was observed over the pH range 5-8. Moreover, by means of fluorescence microscopy experiments, it is demonstrated that 1 can be used as a fluorescent probe for detecting Cu(2+) in living cells.

[Expression, clinical and pathological significance of KIAA1173 gene in skin squamous cell carcinoma].

OBJECTIVE: To clone, prepare probe for and explore the expression levels of KIAA1173 gene in skin squamous cell carcinoma (SSCC) and investigate its expression, clinical and pathological significance. METHODS: KIAA1173 gene fragment (354 bp) was cloned and its cDNA probe prepared. The expression of KIAA1173 gene in 133 SSCC tissue samples (including 52 specimens of I, 37 specimens of II, 31 specimens of III and 13 specimens of IV) and 47 normal controls were examined by in situ hybridization (ISH). And all specimens were embedded in paraffin. RESULTS: ISH showed brown positive granules in the cytoplasm of parenchymal cells. The positive rate of KIAA1173 mRNA was 38.3% (51/133) in SSCC and 93.6% (44/47) in normal controls. The rate was lower in cancer groups than that in normal tissues (chi(2) = 42.567, P < 0.01). The strongly positive rates were significantly lower in SSCC groups (6.0%, 8/133) than that in normal control (48.9%, 23/47, chi(2) = 44.876, P < 0.01). The negative rates of KIAA1173 mRNA were 53.8% (28/52) in SSCC I, 62.2% (23/37) in SSCC II, 67.7% (21/31) in SSCC III and 76.9% (10/13) in SSCC IV (chi(2) = 4.005, P > 0.05). The negative rates of KIAA1173 mRNA in the dys-good differentiation group (70.5%, 31/44) was higher than that in the good differentiation group (57.3%, 51/89), but there was not significant difference between the two groups (chi(2) = 2.154, P > 0.05). CONCLUSION: KIAA1173 gene is highly expressed in normal skin, but it becomes down-regulated in SSCC. It may play an important role in the development of SSCC.

Acitretin systemic and retinoic acid 0.1% cream supression of basal cell carcinoma.

Retinoids have been used for years as monotherapy and/or in combination for treatment and suppression of cutaneous malignancies in patients with basal cell nevus syndrome, xeroderma pigmentosum, or cutaneous T-cell lymphoma (CTCL) basal cell carcinoma (BCC). We report 4 cases with BCC confirmed by histopathology who were treated by short-term systemic acitretin combined with retinoic acid 0.1% cream. The 4 cases with BCC showed good response to the treatment without severe adverse effects during treatment and follow-up. The finding suggests that acitretin may be an appropriate treatment option for elderly patients who require less invasive treatment for BCC.