The Effects of Botulinum Toxin Type A on the Biological Behavior of Fibroblasts on Silicone Implants.

BACKGROUND: Capsular contracture is one of the most severe complications following breast augmentation surgery. It has been reported that botulinum toxin Type A (BTX-A) can inhibit capsular contracture, but the exact mechanisms remain unclear. Therefore, this study aims to explore the potential mechanisms behind BTX-A's inhibition of capsular contracture by observing its effects on the biological behavior of fibroblasts and its impact on the TGF-ß/Smad signaling pathway. METHODS: In vitro experiments involved culturing fibroblasts on PDMS surfaces, subsequently treating them with various concentrations of BTX-A. Fibroblast proliferation activity was assessed using the CCK-8 assay, while the migration and cytoskeletal morphology of the fibroblasts were meticulously examined. ELISA was utilized to quantify the expression of fibrosis-related cytokines. Gene and protein expressions related to the TGF-ß/Smad pathway were analyzed through real-time PCR and Western blotting techniques. RESULTS: BTX-A moderately enhanced the early proliferation and migration of fibroblasts on the surface of PDMS silicone sheets and reduced the synthesis of collagen types I and III. Furthermore, under the influence of BTX-A, the expression of TGF-ßR2 and α-SMA in the TGF-ß/Smad pathway was significantly inhibited. CONCLUSIONS: This study demonstrates that BTX-A can inhibit fibroblast differentiation by downregulating the expression of TGF-ßR2, thereby suppressing the TGF-ß/Smad pathway. This suggests a possible mechanism through which BTX-A mitigates capsular contracture. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Unveiling Dynamic Structure and Bond Evolutions in BiOIO3 Photocatalysts during CO2 Reduction.

We have established a correlation between photocatalytic activity and dynamic structure/bond evolutions of BiOIO3-based photocatalysts during CO2 reduction by combining operando X-ray diffraction with photoelectron spectroscopy. More specifically, the selective photo-deposition of PtOx species on BiOIO3 (010) facets could effectively promote the electron enrichment on Bi active sites of (100) facets for facilitating the adsorption/activation of CO2 molecules, leading to the formation of Bi sites with high oxidation state and the shrink of crystalline structures. With introducing light irradiation to drive CO2 reduction, the Bi active sites with high oxidation states transformed into normal Bi3+ state, accompanying with the expansion of crystalline structures. Owing to the dynamic structure, bond, and chemical-state evolutions, a significant improvement of photocatalytic activity for CO evolution has been achieved on PtOx-BiOIO3 (195.0 µmol g-1 ⋅ h-1), much higher than the pristine (61.9 µmol g-1 ⋅ h-1) as well as metal-Pt decorated BiOIO3 (70.3 µmol g-1 ⋅ h-1) samples. This work provides new insights to correlate the intrinsically dynamic structure/bond evolutions with CO2 reduction activity, which may help to guide future photocatalyst design.

Transcriptome-Wide Analysis of Core Transcription Factors Associated with Defense Responses in Autotetraploid versus Diploid Rice under Saline Stress and Recovery.

Saline stress is a major abiotic stress that inhibits plant growth and yields worldwide. The plant transcription factor (TF) family plays an important role in converting abiotic stress signals into gene expression changes. In this study, a transcriptome-based comparative analysis was performed to investigate the global gene expression of all the TFs in diploid and autotetraploid rice during the early stage of NaCl stress and recovery period. The phenotypic data indicated that the tetraploid rice exhibited a superior salt-tolerant ability compared to the diploid rice. A total of 55 TF families were co-expressed in the tetraploid and diploid rice, and the cumulative number of TF-expressed genes was relatively higher in the diploid rice than in the tetraploid rice at all time points. Unlike the diploid rice, the overall gene expression levels of the tetraploid rice were comparable to the control during recovery. The number of differentially expressed TFs (DE-TFs) in the tetraploid rice decreased after recovery, whereas it increased to a large extent in the diploid rice. GO and KEGG pathway enrichment analysis of the DE-TFs discovered the early switching of the ABA-activated signaling pathway and specific circadian rhythm in the tetraploid rice. Combining the PPI network and heatmap analysis, some core DE-TFs were found that may have potential roles to play in tetraploid salt tolerance. This study will pave the way for elucidating the complex network regulatory mechanisms of salt tolerance in tetraploid rice.

Effects and differences of sleep duration on the risk of new-onset chronic disease conditions in middle-aged and elderly populations.

BACKGROUND: Few longitude cohort studies investigated the risk of the duration of nighttime sleep and naps to the new-onset common chronic disease conditions (CDCs) in middle-aged (45-60) and the elderly (age ≥ 60) populations using an age-stratified strategy. METHODS: The 7025 participants from The China Health and Retirement Longitudinal Study were screened as eligible subjects. Established 13 cohorts with CDCs, acquired their' sleep records in 2011, and obtained new-onset incidents of CDCs during follow-up in 2011-2018. Performed risk association analyses between sleep duration and 13 new-onset CDCs respectively. RESULTS: New-onset risk of four CDCs decreased with increasing nighttime sleep (p-nonlinear>0.05). The risk threshold was approximately 7 hours in middle-aged people and 6 hours in the elderly. For the middle-aged population, compared with 7-9hours sleep, <5hour and 5-7hours nighttime sleep were associated with 1.312∼1.675 times more risk of hypertension, kidney disease, diabetes or high blood sugar status, and multimorbidity; Compared with no nap, a 0-30 min nap was associated with 1.413(1.087∼1.837) times the heart disease risk. In the elderly, < 5 hours of night sleep was a significant risk factor for four CDCs including kidney disease and multimorbidity, etc. A long night's sleep (>9 hours) was connected with 61.2% reduction in risk of memory disease, a >90 min nap increased 62% risk of memory disease, and a 0-30 min nap was associated with higher risks of heart disease, hypertension, and a lower kidney disease risk. CONCLUSIONS: Nighttime sleep and daytime naps may have their own implications for the new-onset CDCs' risk in the aging process.

Effects of substrate topography on the regulation of human fibroblasts and capsule formation via modulating macrophage polarization.

The host-material interface is critical in determining the successful integration of medical devices into human tissue. The surface topography can regulate the fibrous capsule formation around implants through macrophage polarization, but the exact mechanism remains unclear. In this study, four types of microgrooves (10 or 50 µm in groove depths and 50 or 200 µm in groove widths) were fabricated on polydimethylsiloxane (PDMS) using lithography. The microgroove surfaces were characterized using the laser scanning confocal microscopy and fourier transform infrared spectroscopy. The effect of surface topography on macrophage phenotypes and conditioned medium (CM) collected from macrophages on human foreskin fibroblast 1 (HFF-1) were investigated. The result revealed that a deeper and narrower microgroove structure means a rougher surface. Macrophages tended to adhere and aggregate on group 50-50 surface (groove depths and widths of 50 µm). THP-1 cell polarized toward both inflammatory M1 and anti-inflammatory M2 macrophages on the surface of each group. Meanwhile, CM from macrophages culture on PDMS differentially up-regulated the proliferation, migration and fibrosis of HFF-1. Among them, the group 50-50 had the strongest promoting effect. In vivo, the inflammatory response and fibrotic capsule around the implants were observed at 1 week and 4 weeks. As time passed, the inflammatory response decreased, while the capsule thickness continued to increase. The rough material surface was more inclined to develop a severe fibrotic encapsulation. In conclusion, this finding further suggested a potential immunomodulatory effect of macrophages in mediating the fibrotic response to implants and facilitated the design of biomaterial interfaces for improving tissue integration.

Association of the depressive scores, depressive symptoms, and conversion patterns of depressive symptoms with the risk of new-onset chronic diseases and multimorbidity in the middle-aged and elderly Chinese population.

Background: The relationship between depressive symptoms (DS) and their conversion patterns over time and the new-onset risk of diseases in the middle-aged and elderly population has not been extensively studied. Methods: Based on The China Health and Retirement Longitudinal Study participants in 2013, we established 13 cohorts involving 12 types of chronic diseases and multimorbidity, who were identified by face-to-face questionnaires. We retrospectively assessed their DS during 2011 and 2013 through the 10-item Center for Epidemiological Studies Depression Scale (CES-D), which were classified into never, newly developed, relieved, and persistent DS, and these participants were followed from 2013 to 2018. Findings: CES-D scores were new-onset risk factors for 9 diseases. The new-onset risk of diseases increased with higher CES-D scores. When CES-D scores were higher than approximately 6, the hazard ratios (HRs) of emergent diseases were greater than 1. DS was independent new-onset risk factors for 8 diseases, with HRs (95% CI) ranging from 1.2635 (1.0061-1.5867) to 1.5231 (1.0717-2.165). Persistent DS was an independent risk factor for most diseases but might be an independent protective factor for new-onset cancer (HR, 95% CI: 0.276, 0.106-0.723). Interpretation: DS is closely associated with new-onset risk of chronic diseases and multimorbidity, and awareness of the risk associated with pre-DS status (6

Effect of Microgroove Structure in PDMS-Based Silicone Implants on Biocompatibility.

Capsule and capsule contracture around implants are important concerns in a clinic. The physical topology of the material surface regulates the formation of the capsule, but the specific regulatory mechanism is unclear. In this study, four types of silicone implant materials with different microgroove structures (groove depths of 10 and 50 µm and widths of 50 and 200 µm) were constructed using lithography to form different gradient surface topologies. Mass spectrometry, Cell Counting Kit-8, 5-ethynyl-2'-deoxycytidine (EdU), enzyme-linked immunosorbent assay, western blot, immunofluorescence, and immunohistochemistry were used to explore the changes in protein adsorption, cell adhesion, cell proliferation, and collagen deposition on the surface of the materials. At the same time, RNA-seq was used to detect transcriptome differences caused by different structures. Furthermore, collagen deposition and capsule formation were observed in the rats. The groove structure was observed to significantly increase the surface roughness of the material. The deeper groove and the narrower width of the polydimethylsiloxane would increase the surface roughness of the material and the surface water contact angle but reduce the total amount of adsorbed protein in the first two hours. In vitro cell experiments revealed that microtopology affected cell proliferation and adhesion and regulated collagen secretion. Further analysis indicated the deeper and narrower groove (group 50-50) on the surface of the material caused more evident collagen deposition around the material, forming a thicker envelope. Surface roughness of the material was thus related to collagen deposition and envelope thickness. The thickness of the envelope tissue around smooth materials does not exceed that of the materials with surface roughness. In conclusion, the narrower and deeper grooves in the micron range exhibited poor histocompatibility and led to formation of thicker envelopes around the materials. The appropriate grooves can reduce envelope thickness.

Effect of different pulse numbers of transcranial magnetic stimulation on motor cortex excitability: Single-blind, randomized cross-over design.

AIMS: We aimed to investigate the effect of different pulse numbers of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the motor cortex on cortical excitability in healthy participants. METHODS: Fifteen healthy participants received 600 and 1200 pulses of 5-Hz rTMS on separate days in a random order. Stimulation (duration, 2 seconds and interval, 1 seconds) was delivered over the left primary motor cortex for the hand, at 90% of resting motor threshold (rMT). The rMT and motor evoked potential (MEP) were measured before stimulation, and at 0 and 30 minutes after rTMS. RESULTS: No significant differences were observed between the two conditions for MEP (P = .919) or rMT (P = .266). Compared with baseline, MEP was increased significantly at 0 (P < .001) and 30 minutes (P < .001) after stimulation. After stimulation, rMT was decreased at 0 minute for the 600 and 1200 pulse conditions (P < .001), but had recovered by 30 minutes (P = .073). CONCLUSION: Subthreshold 5-Hz rTMS increased motor cortex excitability in healthy humans. However, the number of pulses may exhibit a ceiling effect in that beyond a certain point, that is, increasing the number of pulses may exhibit no further increase in cortical excitability.

Down-Regulation of Neuregulin1/ErbB4 Signaling in the Hippocampus Is Critical for Learning and Memory.

Hippocampal function is important for learning and memory, and dysfunction of the hippocampus has been linked to the pathophysiology of neuropsychiatric diseases such as schizophrenia. Neuregulin1 (NRG1) and ErbB4, two susceptibility genes for schizophrenia, reportedly modulate long-term potentiation (LTP) at hippocampal Schaffer collateral (SC)-CA1 synapses. However, little is known regarding the contribution of hippocampal NRG1/ErbB4 signaling to learning and memory function. Here, quantitative real-time PCR and Western blotting were used to assess the mRNA and protein levels of NRG1 and ErbB4. Pharmacological and genetic approaches were used to manipulate NRG1/ErbB4 signaling, following which learning and memory behaviors were evaluated using the Morris water maze, Y-maze test, and the novel object recognition test. Spatial learning was found to reduce hippocampal NRG1 and ErbB4 expression. The blockade of NRG1/ErbB4 signaling in hippocampal CA1, either by neutralizing endogenous NRG1 or inhibiting/ablating ErbB4 receptor activity, enhanced hippocampus-dependent spatial learning, spatial working memory, and novel object recognition memory. Accordingly, administration of exogenous NRG1 impaired those functions. More importantly, the specific ablation of ErbB4 in parvalbumin interneurons also improved learning and memory performance. The manipulation of NRG1/ErbB4 signaling in the present study revealed that NRG1/ErbB4 activity in the hippocampus is critical for learning and memory. These findings might provide novel insights on the pathophysiological mechanisms of schizophrenia and a new target for the treatment of Alzheimer's disease, which is characterized by a progressive decline in cognitive function.