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Background: Bone loss caused by microgravity exposure presents a serious threat to the health of astronauts, but existing treatment strategies have specific restrictions. This research aimed to investigate whether salidroside (SAL) can mitigate microgravity-induced bone loss and its underlying mechanism. Methods: In this research, we used hindlimb unloading (HLU) and the Rotary Cell Culture System (RCCS) to imitate microgravity in vivo and in vitro. Results: The results showed that salidroside primarily enhances bone density, microstructure, and biomechanical properties by stimulating bone formation and suppressing bone resorption, thereby preserving bone mass in HLU rats. In MC3T3-E1 cells cultured under simulated microgravity in rotary wall vessel bioreactors, the expression of osteogenic genes significantly increased after salidroside administration, indicating that salidroside can promote osteoblast differentiation under microgravity conditions. Furthermore, the Nrf2 inhibitor ML385 diminished the therapeutic impact of salidroside on microgravity-induced bone loss. Overall, this research provides the first evidence that salidroside can mitigate bone loss induced by microgravity exposure through stimulating the Nrf2/HO-1 pathway. Conclusion: These findings indicate that salidroside has great potential for treating space-related bone loss in astronauts and suggest that Nrf2/HO-1 is a viable target for counteracting microgravity-induced bone damage. [ABSTRACT FROM AUTHOR]

Background: Bone loss caused by microgravity exposure presents a serious threat to the health of astronauts, but existing treatment strategies have specific restrictions. This research aimed to investigate whether salidroside (SAL) can mitigate microgravity-induced bone loss and its underlying mechanism. Methods: In this research, we used hindlimb unloading (HLU) and the Rotary Cell Culture System (RCCS) to imitate microgravity in vivo and in vitro. Results: The results showed that salidroside primarily enhances bone density, microstructure, and biomechanical properties by stimulating bone formation and suppressing bone resorption, thereby preserving bone mass in HLU rats. In MC3T3-E1 cells cultured under simulated microgravity in rotary wall vessel bioreactors, the expression of osteogenic genes significantly increased after salidroside administration, indicating that salidroside can promote osteoblast differentiation under microgravity conditions. Furthermore, the Nrf2 inhibitor ML385 diminished the therapeutic impact of salidroside on microgravity-induced bone loss. Overall, this research provides the first evidence that salidroside can mitigate bone loss induced by microgravity exposure through stimulating the Nrf2/HO-1 pathway. Conclusion: These findings indicate that salidroside has great potential for treating space-related bone loss in astronauts and suggest that Nrf2/HO-1 is a viable target for counteracting microgravity-induced bone damage. [ABSTRACT FROM AUTHOR]

Objective: This survey explored the relationships between burnout, moral injury, and suicidal/self-harm ideation among Chinese health professionals in mainland China. Methods: Health professionals were surveyed online using the Maslach Burnout Inventory-Human Services Survey for Medical Personnel, Patient Health Questionnaire-9, and the Moral Injury Symptom Scale-Health Professional version. Results: A total of 6,146 health professionals participated in the study. The average age of participants was 34.9 ± 8.5 years, and suicidal/self-harm ideation was present in 2,338 participants (38.0%). The prevalence of suicidal/self-harm ideation was more common among those with severe burnout (vs. mild burnout), particularly in the dimensions of emotional exhaustion, depersonalization, and decreased personal accomplishment. The prevalence of suicidal/self-harm ideation among those with significant moral injury symptoms was higher than in those without moral injury. Unconditional logistic regression analysis demonstrated that those with moderate or severe emotional exhaustion, moderate or severe reduced sense of professional accomplishment, and moderate or severe depersonalization were at increased risk of suicidal/self-harm ideation. Structural equation modelling demonstrated that burnout significantly mediated the relationship between moral injury and suicidal/self-harm ideation. The proportion of mediation (PM) by burnout was 43.0%. Conclusions: This study found that burnout and moral injury were significant predictors of suicidal/self-harm ideation among health professionals in China. Both moral injury and burnout had positive and direct effects on suicidal/self-harm ideation, and burnout mediated the relationship between moral injury and suicidal/self-harm ideation. Interventions to address moral injury and subsequent burnout in Chinese healthcare workers may enhance the mental health of these healthcare professionals and increase the quality of care that they provide. [ABSTRACT FROM AUTHOR]

Molecular doping, as an effective technique for controlling the electrical property of organic semiconductors (OSCs) by introducing additional charges, has been proven to adjust important device parameters in organic thin-film transistors (OTFTs). Doping highly crystalline OSCs without disrupting structural order is a crucial challenge, as it significantly affects the charge carrier mobility. Here, we demonstrate a molecular doping method without disrupting the molecular ordering to improve the charge carrier mobility of 2,7-dioctyl[1]benzothieno[3,2-b][1]benzothiophene (C8-BTBT) based OTFTs via a simple thermal spin-coating method. The key is to introduce micro-nano pores into C8-BTBT thin-film for channel doping, which is achieved by mixing with the unsubstituted BTBT as it can be easily removed from the thin-film through an ordinary annealing process. Micro-nano pores allow the dopant molecules (2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane, F4-TCNQ) to access the conductive channel of OTFT, which is beneficial for charge injection. Indeed, we further discover that F4-TCNQ doped porous C8-BTBT thin-films exhibit better charge mobility than those of neat and F4-TCNQ doped C8-BTBT films in OTFTs. This work proposes an effective way to expose OSC conjugated core to the dopant, which not only improves the charge transfer reaction between organic/dopant semiconductor through cofacial stacking, but also reduces the trap density and contact resistance. [ABSTRACT FROM AUTHOR]

Background: Expression of glycoprotein A dominant repeat (GARP) has been reported to occur only in activated human naturally occurring regulatory T cells (Tregs) and their clones, and not in activated effector T cells, indicating that GARP is a marker for bona fide Tregs. A different phenotype of chronic obstructive pulmonary disease (COPD) may have a different immunologic mechanism.Objective: To investigate whether the distribution of Tregs defined by GARP is related to the multi-organ loss of tissue phenotype in COPD.Methods: GARP expression on T cells from peripheral blood and bronchoalveolar lavage (BAL) collected from patients with COPD was examined by flow cytometry. The correlation of GARP expression to clinical outcomes and clinical phenotype, including the body mass index, lung function and quantitative computed tomography (CT) scoring of emphysema, was analyzed.Results: Patients with more baseline emphysema had lower forced expiratory volume, body mass index (BMI), worse functional capacity, and more osteoporosis, thus, resembling the multiple organ loss of tissue (MOLT) phenotype. Peripheral Foxp3+GARP+ Tregs are reduced in COPD patients, and this reduction reversely correlates with quartiles of CT emphysema severity in COPD. Meanwhile, the frequencies of Foxp3+GARP- Tregs, which are characteristic of pro-inflammatory cytokine production, are significantly increased in COPD patients, and correlated with increasing quartiles of CT emphysema severity in COPD. Tregs in BAL show a similar pattern of variation in peripheral blood.Conclusion: Decreased GARP expression reflects more advanced disease in MOLT phenotype of COPD. Our results have potential implications for better understanding of the immunological nature of COPD and the pathogenic events leading to lung damage. [ABSTRACT FROM AUTHOR]

Surface plasmon resonance and biolayer interferometry are two common real-time and label-free assays that quantify binding events by providing kinetic parameters. There is increased interest in using these techniques to characterize whole virus-ligand interactions, as the methods allow for more accurate characterization than that of a viral subunit-ligand interaction. This review aims to summarize and evaluate the uses of these technologies specifically in virus–ligand and virus-like particle–ligand binding cases to guide the field towards studies that apply these robust methods for whole virus-based studies. [ABSTRACT FROM AUTHOR]

The lung microbiota have been found to be substantially altered in numerous pulmonary disorders, and crosstalk between the host pathophysiology and lung microbiota plays critical roles in the regulation of disease states. The aim of this study was to investigate dynamic changes in the lung microbiota during different stages of acute lung injury and acute respiratory distress syndrome (ALI/ARDS). Rats receiving an intraperitoneal administration of lipopolysaccharide (LPS) were sacrificed at 12 and 48 h after injection, and the hematological parameters, serum cytokine levels, and histological characteristics of the lung tissue and lung microbiota were assessed. After LPS injection, along with fluctuations of systemic cytokine levels and the onset and regression of pulmonary edema, the diversity, components, and functionalities of the pulmonary microbiota underwent significant dynamic changes. The volatility of the α-diversity indices narrowed after LPS injection, and the indices significantly decreased 48 h later. The abundance of 18 genera and functionality of adenosine triphosphate–binding cassette (ABC) transporters, pentose phosphate, and bacterial chemotaxis pathways were found to significantly differ between specified time points. Several significant correlations between the components and functionalities of the lung microbiota and indicative symptoms of ALI/ARDS were also observed. Brevibacterium was correlated with cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-10, and IL-6 and with hematological percentage of neutrophils (NEU%); Wnt, Notch, and chronic myeloid leukemia signaling pathways were correlated with IL-1β; mitogen-activated protein kinase (MAPK) signaling pathway–yeast was correlated with IL-10; and the pathways of ascorbate and aldarate metabolism and basal transcription factors were correlated with platelet-related indicators. The correlations between the lung microbiota and indicative symptoms of ALI/ARDS identified in this study support further investigation into the underlying mechanism of host–microbiota interactions during lung injury and repair. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is one of the most common co-morbid conditions in patients with idiopathic pulmonary fibrosis (IPF) and negatively affects the prognosis of IPF; Current guidelines for the management of IPF do not give a clear statement on how to manage these patients, and traditional chemotherapy for lung cancer had a limited efficiency rate. Here, we present a rare case of primary lung squamous carcinoma in a patient with IPF whose tumor completely regressed following gemcitabine plus cisplatin therapy; the cancer was no longer detectable after 2 years upon follow-up.Case Presentation: Sixty-seven year-old male patient with IPF was admitted to hospital due to acute onset hemoptysis. In addition to a definite usual interstitial pneumonia (UIP) pattern, a chest CT scan showed a non-enhancing nodular opacity in the right upper lobe and an enhancing nodule in the right lower lobe. Bronchoscopic biopsy of the nodule in the right lower lobe revealed squamous lung cancer. After 2 cycles of chemotherapy with gemcitabine and cisplatin, the tumor in the right lower lobe was no longer detectable after 2 years of follow-up; however, the nodule in the right upper lobe had increased significantly. Finally, Mycobacterium tuberculosis (MTB) was cultured from the bronchoalveolar (BAL) sample submitted at the last evaluation, and the patient was confirmed to have active pulmonary TB.Conclusion: We report the first documented case of complete pulmonary squamous carcinoma regression in IPF following gemcitabine plus cisplatin. Traditional chemotherapy is considered inadequate to cause the resulting regression of the tumor. The concomitant active pulmonary tuberculosis possibly underlies the mechanism. [ABSTRACT FROM AUTHOR]

Aim: Klotho expression significantly declines in alveolar macrophages and airway epithelial cells in chronic obstructive pulmonary disease (COPD) patients, and cigarette smoke extract dramatically inhibits the expression and secretion of α-Klotho. This suggests that the silencing of Klotho is the major factor promoting COPD related inflammatory responses. This study aims to investigate the mechanism of Klotho downregulation and its effect on the inflammatory cytokines secretion and cell apoptosis. Methods: Expression of DNA methyltransferases (DNMTs) and Notch signaling activation were quantified in MH-S and 16HBE cells stimulated with cigarette smoke extract (CSE) solution. Specific inhibitors of DNMTs or Notch pathway were added together with CSE into treated and control cells. Inflammatory cytokines, cell viability and cell death were determined to explore the effect of Klotho on COPD related inflammation. Results: CSE treatment statistically increased the level of DNMTs expression, Klotho promoter methylation, and activated the Notch signaling pathway. Notch signal activation played a critical role in the process of modification of Klotho promoter methylation. The inhibition of DNMTs and Notch pathway rescued Klotho levels and inhibited inflammation and cell apoptosis after CSE treatment. Conclusion: Notch-mediated Klotho hypermethylation inhibited Klotho expression, which promoted inflammatory response and cell apoptosis that were associated with the development of COPD. [ABSTRACT FROM AUTHOR]

The last few decades have witnessed the development of many high-performance separation methods that use biologically related binding agents. The combination of HPLC with these binding agents results in a technique known as high performance affinity chromatography (HPAC). This review will discuss the general principles of HPAC and related techniques, with an emphasis on their use for the analysis of biological compounds and pharmaceutical agents. Various types of binding agents for these methods will be considered, including antibodies, immunoglobulin-binding proteins, aptamers, enzymes, lectins, transport proteins, lipids, and carbohydrates. Formats that will be discussed for these methods range from the direct detection of an analyte to indirect detection based on chromatographic immunoassays, as well as schemes based on analyte extraction or depletion, post-column detection, and multi-column systems. The use of biological agents in HPLC for chiral separations will also be considered, along with the use of HPAC as a tool to screen or study biological interactions. Various examples will be presented to illustrate these approaches and their applications in fields such as biochemistry, clinical chemistry, and pharmaceutical research. [ABSTRACT FROM AUTHOR]

Ultrafast affinity extraction and a two-dimensional high performance affinity chromatographic system were used to measure the free fractions for various drugs in serum and at typical therapeutic concentrations. Pooled samples of normal serum or serum from diabetic patients were utilized in this work. Several drug models (i.e., quinidine, diazepam, gliclazide, tolbutamide, and acetohexamide) were examined that represented a relatively wide range of therapeutic concentrations and affinities for human serum albumin (HSA). The two-dimensional system consisted of an HSA microcolumn for the extraction of a free drug fraction, followed by a larger HSA analytical column for the further separation and measurement of this fraction. Factors that were optimized in this method included the flow rates, column sizes, and column switching times that were employed. The final extraction times used for isolating the free drug fractions were 333-665 ms or less. The dissociation rate constants for several of the drugs with soluble HSA were measured during system optimization, giving results that agreed with reference values. In the final system, free drug fractions in the range of 0.7-9.5 % were measured and gave good agreement with values that were determined by ultrafiltration. Association equilibrium constants or global affinities were also estimated by this approach for the drugs with soluble HSA. The results for the two-dimensional system were obtained in 5-10 min or less and required only 1-5 μL of serum per injection. The same approach could be adapted for work with other drugs and proteins in clinical samples or for biomedical research. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

In diabetes, the elevated levels of glucose in the bloodstream can result in the nonenzymatic glycation of proteins such as human serum albumin (HSA). This type of modification has been shown to affect the interactions of some drugs with HSA, including several sulfonylurea drugs that are used to treat type II diabetes. This study used high-performance affinity chromatography (HPAC) to examine the interactions of glipizide (i.e., a second-generation sulfonylurea drug) with normal HSA or HSA that contained various levels of in vitro glycation. Frontal analysis indicated that glipizide was interacting with both normal and glycated HSA through two general groups of sites: a set of relatively strong interactions and a set of weaker interactions with average association equilibrium constants at pH 7.4 and 37 °C in the range of 2.4-6.0 × 10 and 1.7-3.7 × 10 M, respectively. Zonal elution competition studies revealed that glipizide was interacting at both Sudlow sites I and II, which were estimated to have affinities of 3.2-3.9 × 10 and 1.1-1.4 × 10 M. Allosteric effects were also noted to occur for this drug between the tamoxifen site and the binding of R-warfarin at Sudlow site I. Up to an 18 % decrease in the affinity for glipizide was observed at Sudlow site I ongoing from normal HSA to glycated HSA, while up to a 27 % increase was noted at Sudlow site II. This information should be useful in indicating how HPAC can be used to investigate other drugs that have complex interactions with proteins. These results should also be valuable in providing a better understanding of how glycation may affect drug-protein interactions and the serum transport of drugs such as glipizide during diabetes. [ABSTRACT FROM AUTHOR]

A multi-dimensional chromatographic approach was developed to measure the free fractions of drug enantiomers in samples that also contained a binding protein or serum. This method, which combined ultrafast affinity extraction with a chiral stationary phase, was demonstrated using the drug warfarin and the protein human serum albumin. [ABSTRACT FROM AUTHOR]

The authors would like to call the reader's attention to the following corrections in this article. In the description given for the process of preparing glycated human serum albumin under "In vitro glycation of HSA", the concentrations of D-glucose that were employed were 15 mM and 30 mM. [ABSTRACT FROM AUTHOR]