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Soft electronics are rising electronic technologies towards applications spanning from healthcare monitoring to medical implants. However, poor adhesion strength and significant mechanical mismatches inevitably cause the interface failure of devices. Herein we report a self-adhesive conductive polymer that possesses low modulus (56.1-401.9 kPa), high stretchability (700%), high interfacial adhesion (lap-shear strength >1.2 MPa), and high conductivity (1-37 S/cm). The self-adhesive conductive polymer is fabricated by doping the poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) composite with a supramolecular solvent (β-cyclodextrin and citric acid). We demonstrated the solution process-based fabrication of self-adhesive conductive polymer-based electrodes for various soft devices, including alternating current electroluminescent devices, electromyography monitoring, and an integrated system for the visualization of electromyography signals during muscle training with an array of alternating current electroluminescent devices. The self-adhesive conductive polymer-based electronics show promising features to further develop wearable and comfortable bioelectronic devices with the physiological electric signals of the human body readable and displayable during daily activities. Poor adhesion and mechanical mismatches may cause interface failure of soft devices. Here, authors report a supramolecular solvent-doped, soft, adhesive, yet conductive polymer composite for stretchable, wearable, and comfortable electronic devices.

Mitochondrial membrane potential (MMP) and mitochondrial mass (MM) affect mitochondrial function and lymphocyte activation, but few studies on HBV infection exist. This study aimed to investigate the regulatory mechanism of mitochondrial dysfunction during HBV infection and its clinical significance by analyzing the alterations of MM and MMP in peripheral blood immune cells. The study enrolled 90 participants, including healthy volunteers(HC) and patients with HBV infection, HBV patients were divided into chronic hepatitis B patients (CHB) and liver cirrhosis (LC) according to the study, and CHB was also divided into an inflammation group and a non-inflammation group. Flow cytometry was used to analyze the changes of MM and MMP in peripheral blood immune cells. These analyses were correlated with the presence of CHB and LC and indexes related to liver inflammation. The study revealed significant variations in the percentage of MMP and MM of CD8 T cells associated with the progression of the disease. The MMP percentage of CD8 T cells in the LC group exhibited a notable decrease compared to the HC group and CHB groups. Moreover, MMP of CD8 T cells demonstrated potential in distinguishing CHB and LC (AUC=0.7341, P=0.0032). Furthermore, in exploring the link between mitochondrial function of immune cells and liver inflammation, the study found a negative correlation between the MMP ratio of CD4 T and CD8 T cells and AST (p=0.0039 and P=0.0070, r=-0.4405 and r=-0.4146), while the MM of CD8 T cells displayed a positive correlation with AST (p=0.0013, r=0.4865). In CHB patients with normal ALT but liver inflammation detected on B-scan ultrasonography, a significant decrease was observed in the MMP percentage of CD8 T (66.13 ± 14.27), CD56 NK(57.77 ± 17.40) and CD4 CD8 T (61.98 ± 15.98) cells. Furthermore, it was also found that the percentage of MMP in CD4 CD8 T cells could serve as an indicator for early liver inflammation and injury (AUC=0.8408, P=0.0052). In this study, we conducted a systematic analysis of the percentage of lymphocyte MMP and MM in various stages of HBV infection. Our findings revealed a correlation between MMP and MM and early liver inflammation, as well as the progression of the infection. This study marked the first demonstration of the clinical diagnostic value of MMP and MM in HBV infection. Furthermore, this was the first study to discuss the mitochondria of lymphocytes and liver inflammation in HBV infection. It enhanced the understanding of the role of T cells in liver inflammation, and elucidated potential markers for the early detection of liver injury and clinical cirrhosis.

The compact, simple, and fast-reaction pneumatic microactuator is significant for the integration and high efficiency of pneumatic systems. In this work, the structure, working principle, and multiphysical model of an on-chip pneumatic microactuator are presented. The on-chip pneumatic microactuator is mainly composed of two parts: a polydimethylsiloxane (PDMS) thin membrane and an actuated chamber. The air pressure in the actuated chamber drives the thin elastic membrane to deformation. Dynamic response mathematical models of the actuated chamber for charging and exhaust with variable volume are established, and the deformation characteristics of the polydimethylsiloxane (PDMS) actuated membrane, the capacity of the actuated chamber, and the valve opening of the on-off membrane microvalve are simulated and analyzed to explore the response characteristics of the proposed pneumatic microactuator. Samples valving analysis of the on-chip membrane microvalve and mixing performance of the micromixer integrated with the pneumatic microactuator are tested to evaluate the driving capability of the pneumatic microactuator, and the results show that the response performance of the actuated time fully satisfies the needs of a pneumatic microfluidic chip for most applications.

Background Idiopathic pulmonary fibrosis (IPF) is a group of chronic interstitial pulmonary diseases characterized by myofibroblast proliferation and extracellular matrix (ECM) deposition. However, current treatments are not satisfactory. Therefore, more effective therapies need to be explored. Cepharanthine (CEP) is a naturally occurring alkaloid that has recently been reported to have multiple pharmacological effects, particularly in chronic inflammation. Methods For in vivo experiments, first, a pulmonary fibrosis murine model was generated via tracheal injection of bleomycin (BLM). Second, the clinical manifestations and histopathological changes of the mice were used to verify that treatment with CEP might significantly reduce BLM-induced fibrosis. Furthermore, flow cytometric analysis was used to analyze the changes in the number of M2 macrophages in the lung tissues before and after treatment with CEP to explore the relationship between macrophage M2 polarization and pulmonary fibrosis. In vitro, we constructed two co-culture systems (THP-1 and MRC5 cells, RAW264.7 and NIH 3T3 cells), and measured the expression of fibrosis-related proteins to explore whether CEP could reduce pulmonary fibrosis by regulating macrophage M2 polarization and fibroblast activation. Results The results showed that the intranasal treatment of CEP significantly attenuated the symptoms of pulmonary fibrosis induced by BLM in a murine model. Our findings also indicated that CEP treatment markedly reduced the expression of fibrosis markers, including TGF-β1, collagen I, fibronectin and α-SMA, in the mouse lung. Furthermore, in vitro studies demonstrated that CEP attenuated pulmonary fibrosis by inhibiting fibroblast activation through modulating macrophage M2 polarization and reducing TGF-β1 expression. Conclusions This study demonstrated the potential and efficacy of CEP in the treatment of pulmonary fibrosis. In particular, this study revealed a novel mechanism of CEP in inhibiting fibroblast activation by regulating macrophage M2 polarization and reducing the expression of fibrosis-associated factors. Our findings open a new direction for future research into the treatment of pulmonary fibrosis.

A compact, rapid, and portable off-chip pneumatic control valve is significant for the miniaturization and integration of external pneumatic systems for microfluidic chips. In this work, an off-chip microvalve with a high-speed electromagnetic switch actuator and a polydimethylsiloxane (PDMS) material valve body has been designed to be easily encapsulated, simulated using MATLAB/Simulink software, and tested in a micromixer. Multi-physical coupling mathematical models are developed based on the elastic deformation force of the valve membrane, the driving force of the valve core, and the fluid force in the microchannel. Two single microvalves are used to form a three-way microvalve, which can control the air pressure in a pneumatic microchannel on the microfluidic chip. The relationship between the flow–duty cycle, the flow–pressure difference of the single electromagnetic microvalve, and the load pressure of the three-way microvalve is simulated and analyzed. Sample mixing performance controlled by the proposed off-chip three-way microvalve was tested to evaluate the pneumatic control capability, and the results show that the undertaking can fully satisfy the needs of a pneumatic microfluidic chip for most applications.

To evaluate EBUS-TBNA needle rinse fluid versus biopsy tissue for molecular diagnosis of intrathoracic lymph node tuberculosis (TB). Retrospective analysis of 63 patients with intrathoracic lymph node TB undergoing EBUS-TBNA (2018-2024). Rinse fluid and biopsy tissue were tested via TB-DNA (n=32) and Xpert MTB/RIF (n=31); positivity rates compared. The study cohort had a median age of 31 years (interquartile range: 25-50.1 years), with 57.1% (36/63) being male. The most frequently sampled lymph node stations were subcarinal (station 7, 82.5%) and right lower mediastinal (station 4R, 66.7%). Clinically, 82.5% (52/63) of patients had concomitant pulmonary TB, while 17.5% (11/63) presented with isolated intrathoracic lymph node TB. For TB-DNA detection, the positivity rate of rinse fluid (71.9%, 23/32) was significantly higher than that of biopsy tissue (46.9%, 15/32; χ²=4.146, P = 0.042). Similarly, the Xpert MTB/RIF assay showed a higher positivity rate in rinse fluid (77.4%, 24/31) compared to tissue (41.9%, 13/31; χ²=8.11, P = 0.004). EBUS-TBNA rinse fluid demonstrates higher sensitivity than biopsy tissue for intrathoracic lymph node TB via TB-DNA/Xpert MTB/RIF. Routine rinse fluid testing improves diagnostic yield.

Background: As an immune checkpoint, upregulation of B and T lymphocyte attenuator (BTLA) contributes to T-cell exhaustion in chronic infection. However, the characteristics of BTLA on T cells of patients with pulmonary tuberculosis (PTB) are still uncovered. Aims: The aim of the study was to elucidate the dynamics and clinical significance of BTLA expression on circulating CD4+ and CD8+ T cells of PTB patients. Materials and Methods: BTLA expression on T cells from PTB patients with smear positivity (n = 86) and healthy controls (HCs) (n = 40) were determined using flow cytometry. Results: The levels of BTLA expression on circulating CD4+ and CD8+ T cells of PTB patients with smear positivity were both upregulated, compared with HC. At the same time, the levels of BTLA expression on CD4+ and CD8+ T cells of patients with retreatment were both higher than that of those with initial treatment and gradually upregulated along with the increase of the bacillary load in sputum. In addition, the patients with lung cavity were discovered to present higher levels of BTLA expression on CD4+ and CD8+ T cells than those without lung cavity. Whereas we noted that there was no correlation between the levels of BTLA expression and the positivity or negativity of anti-Mycobacterium tuberculosis antibody. Conclusions: The levels of BTLA expression were upregulated on CD4+ and CD8+ T cells of PTB patients and associated with disease progression. Thereby, BTLA expression on T cells may be considered as a potential clinical indicator and utilized as a therapeutic target for PTB.

We performed a prospective study to investigate the association between pre-diagnosis exposure to fluoroquinolone (FQ) and laboratory testing results among tuberculosis (TB) patients. Each TB-suspected patient provided sputum specimen for mycobacteria growth indicator tube (MGIT) culture and GeneXpert among pulmonary TB patients. Confirmed TB patients and clinically diagnosed TB patients were further enrolled in the final analysis. A total of 661 TB patients were included in the final analysis. The distribution of rural TB patients in the FQ-exposed group was significantly higher than that of urban TB patients ( =0.02). GeneXpert showed significantly better positive rate than MGIT technology for TB cases with prior FQ exposure (30.6% for GeneXpert vs 20.1% for MGIT, =0.01). The positive rate of GeneXpert was significantly higher than that of MGIT for 7-13 days ( =0.04) and ≥14 days FQ exposure ( =0.01) groups, respectively. We also found that the positive rate of MGIT was significantly decreased from 31.5% for <7 days levofloxacin (LFX) exposure group to 9.4% for ≥14 days LFX exposure group ( =0.01), whereas the positive rate of MGIT displayed significant decrease after 7-13 days exposure to moxifloxacin ( =0.04). In conclusion, our data demonstrate that TB patients prior to sputum collection are prone to yield negative culture results. GeneXpert could bring additional benefits for the detection of pulmonary TB patients with prior exposure to FQs. In addition, the exposure to moxifloxacin affected mycobacterial culture at an earlier stage compared with LFX.

Cancer cells are known for their capacity to rewire metabolic pathways to support survival and proliferation under various stress conditions. Ketone bodies, though produced in the liver, are not consumed in normal adult liver cells. We find here that ketone catabolism or ketolysis is re-activated in hepatocellular carcinoma （HCC） cells under nutrition deprivation conditions. Mechanistically, 3-oxoacid CoA-transferase 1 （OXCT1）, a rate-limiting ketolytic enzyme whose expression is suppressed in normal adult liver tissues, is re-induced by serum starvation-triggered mTORC2- AKT-SP1 signaling in HCC cells. Moreover, we observe that enhanced ketolysis in HCC is critical for repression of AMPK activation and protects HCC cells from excessive autophagy, thereby enhancing tumor growth. Importantly, analysis of clinical HCC samples reveals that increased OXCT1 expression predicts higher patient mortality. Taken together, we uncover here a novel metabolic adaptation by which nutrition-deprived HCC cells employ ketone bodies for energy supply and cancer progression.

Background Negative regulatory T cells (Tregs) not only deplete effector T cells but also inhibit the clearance of HIV during infection, which may allow Tregs to be used as informative diagnostic markers. To facilitate both diagnosis and treatment, a thorough understanding of these regulators by characterizing them on temporal and spatial scales is strongly required. Methods Hundred HIV‐infected/AIDS patients, including 87 males, with an average age of 35.8 years, as well as 20 healthy controls, were enrolled. Flow cytometry was used to analyze CD3+T cells, CD4+T cells, and CD8+T cells to evaluate the immune status of the participants. Then, a group of representative negative regulatory T cells, including CD4+PD‐1+T cells, CD4+PD‐1highT cells, CD8+PD‐1+T cells, and CD4+CD25high Tregs was also analyzed to explore their effects on disease progression and intercorrelation. Results The percentages of CD4+PD‐1+T cells and CD4+CD25highTregs increased in patients with the same ultrahigh significance. Temporally, the patients with both intermediate‐stage and late‐stage disease had higher percentages of CD4+PD‐1+T cells; however, the percentage of CD4+CD25highTregs only increased in the patients with late‐stage disease. In addition, CD4+PD‐1+T cells but not CD4+CD25highTregs were negatively correlated with the absolute CD4+T cell count. Spatially, no correlations between CD4+PD‐1+T cells and CD4+CD25highTregs were observed, which suggests these Tregs function differently during immunosuppression. Conclusions This study characterized negative regulatory T cells in HIV‐infected/AIDS patients at both temporal and spatial scales and found that CD4+CD25+Tregs and CD4+PD‐1+T cells could be used as potential diagnostic markers for identifying different disease stages and monitoring disease progression. At late‐stage (CD4+T cells <200/μl) and intermediate‐stage (CD4+T cells = 200–500/μl), CD4+PD‐1+T were higher than that at early stage (CD4+T cells >500/μl). The percentage of CD4+CD25highTregs in the group of CD4+T cells <200/μl was higher than those of the groups of CD4+T cells = 200–500/μl and CD4+T cells >500/μl. It reveals that the CD4+PD‐1+T cells increased in patients when their absolute CD4+ is less than 500/μl, while CD4+CD25highTregs only increased when absolute CD4+ count is lower than 500/μL. This new discovery indicated that CD4+CD25highTregs are generated at a later stage of HIV infection, which could be used as a clinical indicator for poor disease status. We also found the percentage of CD4+PD‐1+T had a negative correlation with absolute CD4+ count in the HIV infected/AIDS patients and the percentage of CD4+CD25highTregs was not correlated with absolute CD4+ count. This provides a new quantitative maker for evaluating the progress of immunosuppression.