Low-temperature plasma jet suppresses bacterial colonisation and affects wound healing through reactive species.

An argon-based low-temperature plasma jet (LTPJ) was used to treat chronically infected wounds in Staphylococcus aureus-laden mice. Based on physicochemical property analysis and in vitro antibacterial experiments, the effects of plasma parameters on the reactive nitrogen and oxygen species (RNOS) content and antibacterial capacity were determined, and the optimal treatment parameters were determined to be 4 standard litre per minute and 35 W. Additionally, the plasma-treated activation solution had a bactericidal effect. Although RNOS are related to the antimicrobial effect of plasma, excess RNOS may be detrimental to wound remodelling. In vivo studies demonstrated that medium-dose LTPJ promoted MMP-9 expression and inhibited bacterial growth during the early stages of healing. Moreover, LTPJ increased collagen deposition, reduced inflammation, and restored blood vessel density and TGF-ß levels to normal in the later stages of wound healing. Therefore, when treating chronically infected wounds with LTPJ, selecting the medium dose of plasma is more advantageous for wound recovery. Overall, our study demonstrated that low-temperature plasma jets may be a potential tool for the treatment of chronically infected wounds.

Single-Ended Eddy Current Micro-Displacement Sensor with High Precision Based on Temperature Compensation.

To measure the micro-displacement reliably with high precision, a single-ended eddy current sensor based on temperature compensation was studied in detail. At first, the principle of the eddy current sensor was introduced, and the manufacturing method of the probe was given. The overall design plan for the processing circuit was induced by analyzing the characteristics of the probe output signal. The variation in the probe output signal was converted to pulses with different widths, and then it was introduced to the digital phase discriminator along with a reference signal. The output from the digital phase discriminator was processed by a low-pass filter to obtain the DC component. At last, the signal was amplified and compensated to reduce the influence of temperature. The selection criteria of the frequency of the exciting signal and the design of the signal conditioning circuit were described in detail, as well as the design of the temperature-compensating circuit based on the digital potentiometer with an embedded temperature sensor. Finally, an experimental setup was constructed to test the sensor, and the results were given. The results show that nonlinearity exists in the single-ended eddy current sensor with a large range. When the range is 500 µm, the resolution can reach 46 nm, and the repeatability error is ±0.70% FR. Within the temperature range from +2 °C to +58 °C, the voltage fluctuation in the sensor is reduced to 44 mV after temperature compensation compared to the value of 586 mV before compensation. The proposed plan is verified to be feasible, and the measuring range, precision, and target material should be considered in real-world applications.

Exfoliation of Metal-Organic Frameworks to Give 2D MOF Nanosheets for the Electrocatalytic Oxygen Evolution Reaction.

The structure and properties of materials are determined by a diverse range of chemical bond formation and breaking mechanisms, which greatly motivates the development of selectively controlling the chemical bonds in order to achieve materials with specific characteristics. Here, an orientational intervening bond-breaking strategy is demonstrated for synthesizing ultrathin metal-organic framework (MOF) nanosheets through balancing the process of thermal decomposition and liquid nitrogen exfoliation. In such approach, proper thermal treatment can weaken the interlayer bond while maintaining the stability of the intralayer bond in the layered MOFs. And the following liquid nitrogen treatment results in significant deformation and stress in the layered MOFs' structure due to the instant temperature drop and drastic expansion of liquid N2, leading to the curling, detachment, and separation of the MOF layers. The produced MOF nanosheets with five cycles of treatment are primarily composed of nanosheets that are less than 10 nm in thickness. The MOF nanosheets exhibit enhanced catalytic performance in oxygen evolution reactions owing to the ultrathin thickness without capping agents which provide improved charge transfer efficiency and dense exposed active sites. This strategy underscores the significance of orientational intervention in chemical bonds to engineer innovative materials.

The Association Between Linguistic Characteristics of Physicians' Communication and Their Economic Returns: Mixed Method Study.

BACKGROUND: Web-based health care has the potential to improve health care access and convenience for patients with limited mobility, but its success depends on active physician participation. The economic returns of internet-based health care initiatives are an important factor that can motivate physicians to continue their participation. Although several studies have examined the communication patterns and influences of web-based health consultations, the correlation between physicians' communication characteristics and their economic returns remains unexplored. OBJECTIVE: This study aims to investigate how the linguistic features of 2 modes of physician-patient communication, instrumental and affective, determine the physician's economic returns, measured by the honorarium their patients agree to pay per consultation. We also examined the moderating effects of communication media (web-based text messages and voice messages) and the compounding effects of different communication features on economic returns. METHODS: We collected 40,563 web-based consultations from 528 physicians across 4 disease specialties on a large, web-based health care platform in China. Communication features were extracted using linguistic inquiry and word count, and we used multivariable linear regression and K-means clustering to analyze the data. RESULTS: We found that the use of cognitive processing language (ie, words related to insight, causation, tentativeness, and certainty) in instrumental communication and positive emotion-related words in affective communication were positively associated with the economic returns of physicians. However, the extensive use of discrepancy-related words could generate adverse effects. We also found that the use of voice messages for service delivery magnified the effects of cognitive processing language but did not moderate the effects of affective processing language. The highest economic returns were associated with consultations in which the physicians used few expressions related to negative emotion; used more terms associated with positive emotions; and later, used instrumental communication language. CONCLUSIONS: Our study provides empirical evidence about the relationship between physicians' communication characteristics and their economic returns. It contributes to a better understanding of patient-physician interactions from a professional-client perspective and has practical implications for physicians and web-based health care platform executives.

Inhibition of Bcl-6 Expression Ameliorates Asthmatic Characteristics in Mice.

OBJECTIVE: The function of Bcl-6 in T follicular helper (Tfh) cell maturation is indispensable, and Tfh cells play a pivotal role in asthma. This study investigated the impact of Bcl-6 on asthmatic traits. METHODS: The microscopic pathological alterations, airway resistance (AR), and lung compliance (LC) were determined in asthmatic mice and Bcl-6 interference mice. The surface molecular markers of Tfh cells and the Bcl-6 mRNA and protein expression were determined by flow cytometry, RT-qPCR, and Western blotting, respectively. The relationships between the Tfh cell ratio and the IgE and IgG1 concentrations in peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage fluid (BALF) were determined. RESULTS: Asthmatic inflammatory changes were observed in the lung tissue and were attenuated by Bcl-6 siRNA and dexamethasone (DXM). Asthmatic mice exhibited an increased AR and a decreased LC, while Bcl-6 siRNA or DXM mitigated these changes. The percentages of Tfh cells and eosinophils were significantly increased in the asthmatic mice, and they significantly decreased after Bcl-6 inhibition or DXM treatment. RT-qPCR and Western blotting analyses revealed that the Bcl-6 expression level in PBMCs was significantly higher in asthmatic mice, and it decreased following Bcl-6 inhibition or DXM treatment. The IgE expression in the serum and BALF and the B cell expression in PBMCs exhibited a similar trend. In asthmatic mice, the ratio of Tfh cells in the peripheral blood showed a strong positive correlation with the IgE levels in the serum and BALF, but not with the IgG1 levels. CONCLUSION: The amelioration of airway inflammation and airway hyper-responsiveness is achieved through Bcl-6 suppression, which effectively hinders Tfh cell differentiation, ultimately resulting in a concurrent reduction in IgE production.

Sustained store-operated calcium entry utilizing activated chromatin state leads to instability in iTregs.

Thymus-originated tTregs and in vitro induced iTregs are subsets of regulatory T cells. While they share the capacity of immune suppression, their stabilities are different, with iTregs losing their phenotype upon stimulation or under inflammatory milieu. Epigenetic differences, particularly methylation state of Foxp3 CNS2 region, provide an explanation for this shift. Whether additional regulations, including cellular signaling, could directly lead phenotypical instability requires further analysis. Here, we show that upon TCR (T cell receptor) triggering, SOCE (store-operated calcium entry) and NFAT (nuclear factor of activated T cells) nuclear translocation are blunted in tTregs, yet fully operational in iTregs, similar to Tconvs. On the other hand, tTregs show minimal changes in their chromatin accessibility upon activation, in contrast to iTregs that demonstrate an activated chromatin state with highly accessible T cell activation and inflammation related genes. Assisted by several cofactors, NFAT driven by strong SOCE signaling in iTregs preferentially binds to primed-opened T helper (TH) genes, resulting in their activation normally observed only in Tconv activation, ultimately leads to instability. Conversely, suppression of SOCE in iTregs can partially rescue their phenotype. Thus, our study adds two new layers, cellular signaling and chromatin accessibility, of understanding in Treg stability, and may provide a path for better clinical applications of Treg cell therapy.

Foxp3-mediated blockage of ryanodine receptor 2 underlies contact-based suppression by regulatory T cells.

The suppression mechanism of Tregs remains an intensely investigated topic. As our focus has shifted toward a model centered on indirect inhibition of DCs, a universally applicable effector mechanism controlled by the transcription factor forkhead box P3 (Foxp3) expression has not been found. Here, we report that Foxp3 blocked the transcription of ER Ca2+-release channel ryanodine receptor 2 (RyR2). Reduced RyR2 shut down basal Ca2+ oscillation in Tregs, which reduced m-calpain activities that are needed for T cells to disengage from DCs, suggesting a persistent blockage of DC antigen presentation. RyR2 deficiency rendered the CD4+ T cell pool immune suppressive and caused it to behave in the same manner as Foxp3+ Tregs in viral infection, asthma, hypersensitivity, colitis, and tumor development. In the absence of Foxp3, Ryr2-deficient CD4+ T cells rescued the systemic autoimmunity associated with scurfy mice. Therefore, Foxp3-mediated Ca2+ signaling inhibition may be a central effector mechanism of Treg immune suppression.

Achieved 18.9% Efficiency by Fine-Tuning Non-Fullerene Acceptor Content to Simultaneously Increase the Short-Circuit Current and Fill Factor of Organic Solar Cells.

In this study, using PM6:L8-BO as the main system and non-fullerene acceptor IDIC as the third component, a series of ternary organic solar cells (TOSCs) are fabricated. The results reveal that IDIC plays a significant role in enhancing the performance of TOSCs by optimizing the morphology of blended films and forming interpenetrating nanostructure. The improved film morphology facilitates exciton dissociation and collection in TOSCs, which causes an increase in the short-circuit current density (JSC ) and fill factor (FF). Further, by optimizing the IDIC content, the power conversion efficiency (PCE) of TOSCs reaches 18.9%. Besides, the prepared TOSCs exhibit a JSC of 27.51 mA cm-2 and FF of 76.64%, which are much higher than those of PM6:L8-BO-based organic solar cells (OSCs). Furthermore, the addition of IDIC improves the long-term stability of the OSCs. Meanwhile, TOSCs with a large effective area of 1.00 cm2 have been prepared, which exhibit a PCE of 12.4%. These findings suggest that modifying the amount of the third component can be a useful strategy to construct hight-efficiency TOSCs with practical application potential.

FAM46C-mediated tumor heterogeneity predicts extramedullary metastasis and poorer survival in multiple myeloma.

Cancers originate from a single cell according to Nowell's theory of clonal evolution. The enrichment of the most aggressive clones has been developed and the heterogeneity arises for genomic instability and environmental selection. Multiple myeloma (MM) is a multiple relapse plasma cell cancer generated from bone marrow. Although there were accumulating researches in multiple myeloma pathogenesis, the heterogeneity remains poorly understood. The participants enrolled in this study were 4 EMP+ (EMP, Extramedullary plasmacytoma) and 2 EMP- primarily untreated MM patients. Single cell RNA sequencing and analysis were conducted for the single cell suspension, which was sorted by flow cytometry from peripheral blood mononuclear cells or bone marrow cells. In our research, the results of single cell RNA sequencing show that FAM46C determines MM tumor heterogeneity predicting extramedullary metastasis by influencing RNA stability. Further, we integrated and analyzed 2280 multiple myeloma samples from 7 independent datasets, which uncover that FAM46C mediated tumor heterogeneity predicts poorer survival in multiple myeloma.

Behavioral and oscillatory signatures of switch costs in highly proficient bilinguals.

Bilinguals with a high proficiency in their first (L1) and second language (L2) often show comparable reaction times when switching from their L1 to L2 and vice-versa ("symmetrical switch costs"). However, the neurophysiological signatures supporting this effect are not well understood. Here, we ran two separate experiments and assessed behavioral and MEG responses in highly proficient Spanish-Basque bilinguals while they overtly name pictures in a mixed-language context. In the behavioral experiment, bilinguals were slower when naming items in switch relative to non-switch trials, and this switch cost was comparable for both languages (symmetrical). The MEG experiment mimicked the behavioral one, with switch trials showing more desynchronization than non-switch trials across languages (symmetric neural cost) in the alpha band (8-13 Hz). Source-localization revealed the engagement of right parietal and premotor areas, which have been linked to language selection and inhibitory control; and of the left anterior temporal lobe (ATL), a cross-linguistic region housing conceptual knowledge that generalizes across languages. Our results suggest that highly proficient bilinguals implement a language-independent mechanism, supported by alpha oscillations, which is involved in cue-based language selection and facilitates conceptually-driven lexical access in the ATL, possibly by inhibiting non-target lexical items or disinhibiting target ones.

Solid Additive Enables Organic Solar Cells with Efficiency up to 18.6.

Additive strategies play a critical role in improving the performance of organic solar cells (OSCs). There are only a few reports on the application of solid additives for OSCs, which leaves a large space for further improvement of solid additives and further study on the relationship between material structure and property. PM6:BTP-eC9-based organic solar cells (OSCs) were prepared by using a small molecule BTA3 as a solid additive, and a high energy conversion efficiency of 18.65% is achieved. BTA3 has good compatibility with the acceptor component (BTP-eC9) and optimizes the morphology of the thin films. Moreover, the introduction of a small amount of BTA3 (5 wt %) effectively promotes exciton dissociation and charge transfer and suppresses charge recombination, and the relationship between the BTA3 content and the device parameter is deeply revealed. The use of BTA3 in the active layers is an attractive and effective strategy for high-performance OSCs.

Balancing WNT signalling in early forebrain development: The role of LRP4 as a modulator of LRP6 function.

The specification of the forebrain relies on the precise regulation of WNT/ß-catenin signalling to support neuronal progenitor cell expansion, patterning, and morphogenesis. Imbalances in WNT signalling activity in the early neuroepithelium lead to congenital disorders, such as neural tube defects (NTDs). LDL receptor-related protein (LRP) family members, including the well-studied receptors LRP5 and LRP6, play critical roles in modulating WNT signalling capacity through tightly regulated interactions with their co-receptor Frizzled, WNT ligands, inhibitors and intracellular WNT pathway components. However, little is known about the function of LRP4 as a potential modulator of WNT signalling in the central nervous system. In this study, we investigated the role of LRP4 in the regulation of WNT signalling during early mouse forebrain development. Our results demonstrate that LRP4 can modulate LRP5- and LRP6-mediated WNT signalling in the developing forebrain prior to the onset of neurogenesis at embryonic stage 9.5 and is therefore essential for accurate neural tube morphogenesis. Specifically, LRP4 functions as a genetic modifier for impaired mitotic activity and forebrain hypoplasia, but not for NTDs in LRP6-deficient mutants. In vivo and in vitro data provide evidence that LRP4 is a key player in fine-tuning WNT signalling capacity and mitotic activity of mouse neuronal progenitors and of human retinal pigment epithelial (hTERT RPE-1) cells. Our data demonstrate the crucial roles of LRP4 and LRP6 in regulating WNT signalling and forebrain development and highlight the need to consider the interaction between different signalling pathways to understand the underlying mechanisms of disease. The findings have significant implications for our mechanistic understanding of how LRPs participate in controlling WNT signalling.

"Neural dynamics supporting longitudinal plasticity of action naming across languages: MEG evidence from bilingual brain tumor patients".

Previous evidence suggests that distinct ventral and dorsal streams respectively underpin the semantic processing of object and action knowledge. Recently, we found that brain tumor patients with dorsal gliomas in frontoparietal hubs show a selective longitudinal compensation (post-vs. pre-surgery) during the retrieval of lexico-semantic information about actions (but not objects), indexed by power increases in beta rhythms (13-28 Hz). Here, we move one-step further and ask whether a similar organizational principle also stands across the different languages a bilingual speaks. To test this hypothesis, we combined a picture-naming task with MEG recordings and evaluated highly proficient Spanish-Basque bilinguals undergoing surgery for tumor resection in left frontoparietal regions. We assessed patients before and three months after surgery. At the behavioral level, we observed a similar performance across sessions irrespectively of the language at use, suggesting overall successful function preservation. At the oscillatory level, we found longitudinal selective power increases in beta for action naming in Spanish and Basque. Nevertheless, tumor resection triggered a differential reorganization of the L1 and the L2, with the latter one additionally recruiting the right hemisphere. Overall, our results provide evidence for (i) the specific involvement of frontoparietal regions in the semantic retrieval/representation of action knowledge across languages; (ii) a key role of beta oscillations as a signature of language compensation and (iii) the existence of divergent plasticity trajectories in L1 and L2 after surgery. By doing so, they provide new insights into the spectro-temporal dynamics supporting postoperative recovery in the bilingual brain.

Curcumin prevents Alzheimer's disease progression by upregulating JMJD3.

The main purpose of this research was to explore the molecular mechanisms of Jumonji Domain-Containing Protein 3 (JMJD3) in Alzheimer's disease (AD) and to analyze its role in the anti-AD mechanism of curcumin (CUR). In the in vitro study of AD, JMJD3 overexpression promoted the trimethylation of histone H3 lysine 27 (H3K27me3), downregulated brain-derived neurotrophic factor (BDNF ), improved the abnormality of mitochondrial stress response (MSR) markers, Aß accumulation, increased cell proliferation and inhibited apoptosis. Upregulating BDNF also achieved above similar results. Knockout of JMJD3 could downregulate BDNF, upregulate the level of H3K27me3 methylation and inhibit MSR markers, while transfection of JMJD3 RNAi could counteract the upregulated effect of BDNF. Then, MSR activator could also improve AD. In addition, JMJD3 in AD in vitro models was obviously upregulated under CUR stimulation, and it triggered a series of reactions as mentioned above. In the in vivo study, the levels of JMJD3, the mRNA and protein levels of BDNF in the right brain tissues of AD mice were downregulated, the methylation of H3K27me3 increased, and the MSR markers (ClpP, HSP6, HSP-60, ATFS-1, etc.) were downregulated; the above indexes were improved in varying degrees with the intervention of CUR. Thus, we conclude that CUR can induce the upregulation of JMJD3 and improve BDNF expression by promoting the demethylation of H3K27me3, thereby maintaining the balance of MSR and thus, preventing AD development.

FLUOROFENIDONE ATTENUATES PULMONARY INFLAMMATION AND FIBROSIS BY INHIBITING THE IL-11/MEK/ERK SIGNALING PATHWAY.

ABSTRACT: Idiopathic pulmonary fibrosis is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause. Interleukin (IL)-11 plays an important role in the pathogenesis of idiopathic pulmonary fibrosis. In this study, we explore whether a potential antifibrotic agent fluorofenidone (FD) exerts its anti-inflammatory and antifibrotic effects through suppressing activation of the IL-11/MEK/ERK signaling pathway in vivo and in vitro. Male C57BL/6 J mice were intratracheally injected with bleomycin or saline. Fluorofenidone was administered throughout the course of the experiment. Lung tissue sections were stained with hemotoxylin and eosin, and Masson trichrome. Cytokines were measured using the enzyme-linked immunosorbent assay. The α-smooth muscle actin (α-SMA), fibronectin, and collagen I were measured using immunohistochemistry, and the phosphorylated extracellular signal-regulated kinase, phosphorylated mitogen-activated protein kinase, IL-11RA, and gp130 were measured using Western blot. The RAW264.7 cells and the normal human lung fibroblasts were treated with IL-11 and/or FD, IL-11RA-siRNA, or MEK inhibitor. The expressions of phosphorylated extracellular signal-regulated kinase, phosphorylated mitogen-activated protein kinase, IL-11RA, gp130, α-SMA, fibronectin, and collagen I were measured using Western blot and/or real-time polymerase chain reaction, and the cytokines were measured using enzyme-linked immunosorbent assay. Results showed that FD markedly reduced the expressions of IL-8, IL-18, IL-11, monocyte chemotactic protein-1, α-SMA, fibronectin, and collagen I in mice lung tissues. In addition, FD attenuated IL-11-induced expressions of α-SMA, fibronectin, and collagen I and inhibited IL-11RA, gp130, and phosphorylation of the ERK and MEK protein expression, as well as reduced the expressions of IL-8, IL-18, and monocyte chemotactic protein-1 in vitro. This study demonstrated that FD attenuated bleomycin-induced pulmonary inflammation and fibrosis in mice by inhibiting the IL-11/MEK/ERK signaling pathway.

Total infectome characterization of respiratory infections in pre-COVID-19 Wuhan, China.

At the end of 2019 Wuhan witnessed an outbreak of "atypical pneumonia" that later developed into a global pandemic. Metagenomic sequencing rapidly revealed the causative agent of this outbreak to be a novel coronavirus denoted SARS-CoV-2. To provide a snapshot of the pathogens in pneumonia-associated respiratory samples from Wuhan prior to the emergence of SARS-CoV-2, we collected bronchoalveolar lavage fluid samples from 408 patients presenting with pneumonia and acute respiratory infections at the Central Hospital of Wuhan between 2016 and 2017. Unbiased total RNA sequencing was performed to reveal their "total infectome", including viruses, bacteria and fungi. We identified 35 pathogen species, comprising 13 RNA viruses, 3 DNA viruses, 16 bacteria and 3 fungi, often at high abundance and including multiple co-infections (13.5%). SARS-CoV-2 was not present. These data depict a stable core infectome comprising common respiratory pathogens such as rhinoviruses and influenza viruses, an atypical respiratory virus (EV-D68), and a single case of a sporadic zoonotic pathogen-Chlamydia psittaci. Samples from patients experiencing respiratory disease on average had higher pathogen abundance than healthy controls. Phylogenetic analyses of individual pathogens revealed multiple origins and global transmission histories, highlighting the connectedness of the Wuhan population. This study provides a comprehensive overview of the pathogens associated with acute respiratory infections and pneumonia, which were more diverse and complex than obtained using targeted PCR or qPCR approaches. These data also suggest that SARS-CoV-2 or closely related viruses were absent from Wuhan in 2016-2017.

Rational construction of controllable autoimmune diabetes model depicting clinical features.

Through animal models, particularly non-obesity diabetes model (NOD), pathological understandings of human autoimmune diabetes have been gained. However, features of those mouse models and the human disease are not sufficiently analogous; it is therefore not unexpected that interventions based on the mouse data fail at an alarming rate in clinical settings. An improvised model that maximally resembles the real pathological course is highly desirable. Here we devised a 'double-hit' strategy, pancreas was first hit by chemical damage (streptozotocin, STZ) to unleash auto-antigens, then hit second time by transient immune-inflammation (regulatory T cell depletion). Comparing to NOD model, this strategy not only induced classical diabetic symptoms, but also depicted the crucial pathogenic features absent in conventional models, such as CD8+ T cell dominant infiltrates, strong ketoacidosis and epitope-specific T cell responses. In addition, this model allowed synchronized control of disease onset, permitting more refined temporal analysis of disease progression. We believe that this model would yield research outcomes with clinically relevant prediction power unattainable previously.

Oscillatory dynamics underlying noun and verb production in highly proficient bilinguals.

Words representing objects (nouns) and words representing actions (verbs) are essential components of speech across languages. While there is evidence regarding the organizational principles governing neural representation of nouns and verbs in monolingual speakers, little is known about how this knowledge is represented in the bilingual brain. To address this gap, we recorded neuromagnetic signals while highly proficient Spanish-Basque bilinguals performed a picture-naming task and tracked the brain oscillatory dynamics underlying this process. We found theta (4-8 Hz) power increases and alpha-beta (8-25 Hz) power decreases irrespectively of the category and language at use in a time window classically associated to the controlled retrieval of lexico-semantic information. When comparing nouns and verbs within each language, we found theta power increases for verbs as compared to nouns in bilateral visual cortices and cognitive control areas including the left SMA and right middle temporal gyrus. In addition, stronger alpha-beta power decreases were observed for nouns as compared to verbs in visual cortices and semantic-related regions such as the left anterior temporal lobe and right premotor cortex. No differences were observed between categories across languages. Overall, our results suggest that noun and verb processing recruit partially different networks during speech production but that these category-based representations are similarly processed in the bilingual brain.