Study of association of leptin with leukocyte telomere length in a Chinese rural population.

BACKGROUND: Previous studies have demonstrated the relationship between adipocyte factors, insulin resistance, and other indicators with telomere length. However, these studies did not consider the influence of changes in different indicators on telomere length over time. Therefore, the aim of this study is to elucidate the impact of changes in adipocyte factors, HOMA-IR, and other indicators on the dynamic variation of telomere length. METHODS: The data were from a cohort study conducted in Ningxia, China. A total of 1624 subjects were analyzed. Adipokines and relative leukocyte telomere length (RLTL) were measured, and changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), Homeostatic Model Assessment for ß-Cell Function (HOMA-ß), and Quantitative Insulin Sensitivity Check Index (QUICKI) were calculated. Generalized linear models evaluated associations between changes in adipokines and RLTL changes. Furthermore, univariate analyses examined the effects of changes in adipokines and insulin resistance indicators on ΔRLTL. RESULTS: The research findings indicate that females generally have shorter telomeres compared to males. In comparison to the low-level group of Δleptin (LEP), the high-level group of ΔLEP shows a negative correlation with ΔRLTL (B=-1.32, 95% CI (-2.38, -0.27)). Even after multivariable adjustments, this relationship persists (B=-1.31, 95% CI (-2.24, -0.23)). Further analysis reveals that after adjusting for ΔHOMA-IR, ΔHOMA-ß, and ΔQUICKI, the high-level group of ΔLEP still exhibits a significant negative correlation with ΔRLTL (B=-1.37, 95% CI (-2.43, -0.31)). However, the interaction effects between ΔHOMA-IR, ΔHOMA-ß, ΔQUICKI, and ΔLEP do not affect ΔRLTL. CONCLUSIONS: Elevated levels of leptin were significantly correlated with shortened telomere length. This suggests that increased leptin levels may impact overall individual health by affecting telomere length, underscoring the importance of measures to reduce leptin levels to mitigate the onset and progression of related diseases.

Multimodal nanoimmunotherapy engages neutrophils to eliminate Staphylococcus aureus infections.

The increasing prevalence of antimicrobial resistance in Staphylococcus aureus necessitates alternative therapeutic approaches. Neutrophils play a crucial role in the fight against S. aureus but suffer from deficiencies in function leading to increased infection. Here we report a nanoparticle-mediated immunotherapy aimed at potentiating neutrophils to eliminate S. aureus. The nanoparticles consist of naftifine, haemoglobin (Hb) and a red blood cell membrane coating. Naftifine disrupts staphyloxanthin biosynthesis, Hb reduces bacterial hydrogen sulfide levels and the red blood cell membrane modifies bacterial lipid composition. Collectively, the nanoparticles can sensitize S. aureus to host oxidant killing. Furthermore, in the infectious microenvironment, Hb triggers lipid peroxidation in S. aureus, promoting neutrophil chemotaxis. Oxygen supplied by Hb can also significantly enhance the bactericidal capability of the recruited neutrophils by restoring neutrophil respiratory burst via hypoxia relief. This multimodal nanoimmunotherapy demonstrates excellent therapeutic efficacy in treating antimicrobial-resistant S. aureus persisters, biofilms and S. aureus-induced infection in mice.

Incidence of thyroid dysfunction caused by immune checkpoint inhibitors combined with chemotherapy: A systematic review and meta-analysis.

BACKGROUND: The combination of immune checkpoint inhibitors (ICIs) and chemotherapy as a first-line treatment for triple-negative breast cancer (TNBC) has been associated with many adverse reactions. Thyroid dysfunction, the most common adverse reaction of the endocrine system, has also attracted significant attention. This study aimed to analyse the effect of ICIs combined with chemotherapy on thyroid function in patients with TNBC. METHODS: As of November 4, 2023, we searched the PubMed, Web of Science, and Cochrane Library databases for clinical trials of ICIs combined with chemotherapy for the treatment of TNBC. The incidence of hypothyroidism and hyperthyroidism was calculated using a random-effects model. RESULTS: In the final analysis, 3,226 patients from 19 studies were included. The total incidence of all-grade hypothyroidism induced by the combination of ICIs and chemotherapy in treating TNBC (12% (95% confidence intervals(CI): 0.10-0.15)) was higher than that of hyperthyroidism (5% (95% CI: 0.04-0.06)). Pembrolizumab combined with chemotherapy caused the highest incidence of all grades of hypothyroidism for 13% (95% CI: 0.05-0.06). Durvalumab combined with chemotherapy caused the highest incidence of all grades of hyperthyroidism, at 7% (95% CI: 0.03-0.11). ICIs combined with chemotherapy caused a higher incidence of all grades of hypothyroidism in advanced TNBC (15% (95% CI: 0.13-0.17)) than in early stage TNBC (10% (95% CI: 0.07-0.13)). CONCLUSION: In TNBC, the incidence of hypothyroidism caused by the combination of ICIs and chemotherapy was significantly higher than that caused by hyperthyroidism. Pembrolizumab combined with chemotherapy resulted in the highest incidence of hypothyroidism. The incidence of hypothyroidism in patients with advanced TNBC was significantly higher than that in patients with early stage TNBC. In addition, ICIs combined with chemotherapy resulted in 16 out of 3,226 patients experiencing grade ≥ 3 thyroid dysfunction. Although the incidence of severe thyroid dysfunction is low, it requires attention. PROSPERO: CRD42023477933.

Impact of pelvic anteversion on spinopelvic alignment in an asymptomatic population: a dynamic perspective of standing and sitting.

BACKGROUND CONTEXT: A subgroup of patients with pelvic anteversion can present with an unusually large degree of lumbar lordosis (LL), a highly sloped sacrum, and a relatively small pelvic incidence (PI). Prior to lumbar surgery, it is can be important to consider such unique sagittal alignment. However, until now, there has been a lack of a predictive model considering different pelvic alignments. Furthermore, the dynamic characteristics of an anteverted pelvis (AP) subgroup have also been unclear. PURPOSE: To build linear predictive formulas for LL that take pelvic anteversion into consideration and to explore the dynamic characteristics of an AP subgroup. STUDY DESIGN: Monocentric, cross-sectional study. PATIENT SAMPLE: 565 asymptomatic Chinese men and women between the ages of 18 and 80 years. OUTCOME MEASURES: Sagittal parameters including LL, lumbar lordosis minus thoracic kyphosis (LL-TK), (PI), pelvic tilt (PT), pelvic incidence minus lumbar lordosis (PI-LL), sacral slope (SS), sacral slope divided by pelvic incidence (SS/PI), sagittal vertical axis (SVA), thoracic kyphosis (TK), and T1 (first thoracic vertebra) pelvic angle (TPA) were measured on whole spine radiographs obtained with participants in standing and sitting positions. METHODS: All participants underwent radiography in the standing position; 235 of them underwent additional radiography in the sitting position to allow measurement of sagittal parameters. The participants with pelvic anteversion were placed in an AP (anteverted pelvis) group. Sagittal parameters were compared between the AP group and the non-AP group, and predictive formulas for LL based on PI were created in both groups. In addition, changes in sagittal parameters from standing to sitting were compared in the AP group and a PI-matched control group. RESULTS: Of the 565 participants, 171 (30.3%) had pelvic anteversion. In comparison with the non-AP group, the AP group presented with larger LL, a larger SS, and a smaller PT, with relatively small PI. The predictive formulas for LL were LL = 0.60°â€¯× PI + 21.60° (R2 = 0.268; P < 0.001) in the whole cohort, LL = 0. 83 × PI + 18.75° (R2 = 0.427; P < 0.001) in AP group, and LL = 0.79°â€¯× PI + 9.66° (R2 = 0.451; P < 0.001) in the non-AP group. In moving from standing to sitting, the AP group presented with a larger decrease in SS and LL compared with the control group, indicating different patterns of spinopelvic motion. CONCLUSIONS: In the cohort examined, 30.3% present with pelvic anteversion. Those with AP present with unique characteristics of spinopelvic alignment. In moving from standing to sitting, they exhibit different patterns of spinopelvic motion. We found that identifying the degree of anteversion in each person improves the accuracy of linear models for predicting the degree of LL, which in turn can make plans for spine surgery more accurate.

[Integrated Analysis of Soil Organic Matter Molecular Composition Changes Under Different Land Uses].

The application of biomarkers to study the molecular composition of soil organic matter (SOM) can be used to analyze the source and degradation of SOM and reveal the stability mechanism of soil organic carbon (SOC) at the molecular level. In order to further clarify the effects of different land use patterns (farmland, grassland, and forest) on the molecular composition of SOM, the changes in molecular composition of organic matter (free lipids, cutin, suberin, and lignin) on a global scale were studied using a meta-analysis method. The results showed that there were significant differences in the molecular composition of organic matter under different land use patterns. The contents of free lipids (n-alkanes, n-alkanols, n-alkanoic acids, and cyclic lipids), cutin, and lignin phenols in forest soil were significantly higher than those in grassland and farmland. There was no significant difference in the content of suberin between grassland and forest soil. The ratio of suberin to cutin in grassland was the highest, with an average of 2.96, and the averages of farmland and forest were 1.68 and 2.21, respectively. The ratio of syringic acid to syringaldehyde (Ad/Al)S and the ratio of vanillic acid to vanillin (Ad/Al)V of farmland soil were the largest, which were 1.25 and 1.58, respectively, and were significantly higher than those in grassland (0.46 and 0.69) and forest (0.78 and 0.7). The results of correlation analysis showed that in farmland soil, suberin was significantly correlated with mean annual precipitation (MAP) and clay; cutin was significantly correlated with clay; and lignin was significantly correlated with mean annual temperature (MAT), MAP, sand, and bulk density. In grassland soil, total free lipids were significantly correlated with MAP and bulk density; suberin and cutin were significantly correlated with MAT and MAP; and lignin was significantly correlated with MAP, pH, sand, and bulk density. However, only lignin was significantly correlated with MAP and sand in forest soils. Overall, the contents of SOC and molecular components in forest soil were higher under the three land use practices, and the contribution of plant roots to SOM in grassland soil was greater. In farmland soil, the degradation of lignin was accelerated due to human farming activities. Future research should focus on the regulation of soil physicochemical properties and climatic conditions on the molecular composition of SOM.

Tetramethylpyrazine-loaded electroconductive hydrogels promote tissue repair after spinal cord injury by protecting the blood-spinal cord barrier and neurons.

Spinal cord injury (SCI) usually induces profound microvascular dysfunction. It disrupts the integrity of the blood-spinal cord barrier (BSCB), which could trigger a cascade of secondary pathological events that manifest as neuronal apoptosis and axonal demyelination. These events can further lead to irreversible neurological impairments. Thus, reducing the permeability of the BSCB and maintaining its substructural integrity are essential to promote neuronal survival following SCI. Tetramethylpyrazine (TMP) has emerged as a potential protective agent for treating the BSCB after SCI. However, its therapeutic potential is hindered by challenges in the administration route and suboptimal bioavailability, leading to attenuated clinical outcomes. To address this challenge, traditional Chinese medicine, TMP, was used in this study to construct a drug-loaded electroconductive hydrogel for synergistic treatment of SCI. A conductive hydrogel combined with TMP demonstrates good electrical and mechanical properties as well as superior biocompatibility. Furthermore, it also facilitates sustained local release of TMP at the implantation site. Furthermore, the TMP-loaded electroconductive hydrogel could suppress oxidative stress responses, thereby diminishing endothelial cell apoptosis and the breakdown of tight junction proteins. This concerted action repairs BSCB integrity. Concurrently, myelin-associated axons and neurons are protected against death, which meaningfully restore neurological functions post spinal cord injury. Hence, these findings indicate that combining the electroconductive hydrogel with TMP presents a promising avenue for potentiating drug efficacy and synergistic repair following SCI.

Investigation of Zhenjiang Aromatic Vinegar Production Using a Novel Dry Gelatinization Process.

The traditional process of producing Zhenjiang aromatic vinegar faces challenges such as high water usage, wastewater generation, raw material losses, and limitations in mechanization and workshop conditions. This study introduces and evaluates a novel dry gelatinization process, focusing on fermentation efficiency and the vinegar flavor profile. The new process shows a 39.1% increase in alcohol conversion efficiency and a 14% higher yield than the traditional process. Vinegar produced through the dry gelatinization process has a stronger umami taste and a higher lactic acid concentration. Both processes detected 33 volatile substances, with the dry gelatinization process showing a notably higher concentration of 2-methylbutanal, which imparts a distinct fruity and chocolate aroma. These findings suggest that the dry gelatinization process outperforms the traditional process in several aspects.

Metabolic change in monocytes and postoperative morbidity after major abdominal surgery in elderly patients: A prospective cohort study.

Background: Postoperative complications in aging patients remain a significant cause of increased costs, hospital length of stay, and patient distress. Although alterations in energy metabolism have been closely linked to aging process and surgery, it is still unclear whether metabolic changes during surgery is associated with postoperative complications in elderly patients. This study was conducted to investigate whether metabolic changes during surgery predicts postoperative complications in elderly patients. Methods: We conducted a prospective single-center observational cohort study. 244 adults (aged ≥65 years) who were scheduled for elective major non-cardiac surgery were recruited. Blood samples for each patient were taken before and after surgery. All patients were randomly divided into two groups (122 in each group), then oxygen consumption rate (OCR) or extracellular acidification rate (ECAR) was measured on isolated monocytes in each group. Results: 14 of 110 (12.7%) patients went through OCR measurement and 15 of 122 patients (12.3%) went through ECAR measurement experienced moderate to severe complications. Overall, there was an intensification of glycolysis in monocytes after surgery. Among all variables, only the change (preoperative -postoperative) of glycolytic reserve (GR)/glycolysis (G) and GR/non-glycolytic acidification (NG) were predictors of moderate to severe complications (AUC = 0.70; 95% CI, 0.56-0.81; P = 0.019 and AUC = 0.67; 95% CI, 0.55-0.80; P = 0.031). Decreased postoperative GR/G were associated with worse postoperative complications (RR = 9.08; 95% CI, 1.23-66.81; P = 0.024). Conclusions: Compared with mitochondria function, the change of glycolytic function in monocyte was more valuable in predicting postoperative complications after major abdominal surgery. Our study gave us a new insight into identifying patients at high risk in aging patients.

Fertility preservation in hematological cancer patients.

Among adolescents and young adults, hematological malignancies are the most common malignancies. Although the survival rate of hematological malignancies in young patients has been dramatically improved, due to the continuous improvement and development of tumor diagnosis and treatment options, cytotoxic therapies can significantly reduce a patient's reproductive capacity and cause irreversible infertility. The most two established solutions are embryo cryopreservation and oocyte cryopreservation which can be considered in single female. Sperm or testicular tissue cryopreservation in adult male are feasible approaches that must be considered before gonadotoxic therapy. A comprehensive consultation with reproductive specialists when once diagnosed is a significantly issue which would help those survivors who want to have children. In this article, we review germ cell toxicity, which happens during the treatment of hematological malignancies, and aims to propose safety, efficacy fertility preservation methods in younger patients with hematological malignancies.

Spatiotemporal drivers of urban water pollution: Assessment of 102 cities across the Yangtze River Basin.

Effective management of large basins necessitates pinpointing the spatial and temporal drivers of primary index exceedances and urban risk factors, offering crucial insights for basin administrators. Yet, comprehensive examinations of multiple pollutants within the Yangtze River Basin remain scarce. Here we introduce a pollution inventory for urban clusters surrounding the Yangtze River Basin, analyzing water quality data from 102 cities during 2018-2019. We assessed the exceedance rates for six pivotal indicators: dissolved oxygen (DO), ammonia nitrogen (NH3-N), chemical oxygen demand (COD), biochemical oxygen demand (BOD), total phosphorus (TP), and the permanganate index (CODMn) for each city. Employing random forest regression and SHapley Additive exPlanations (SHAP) analyses, we identified the spatiotemporal factors influencing these key indicators. Our results highlight agricultural activities as the primary contributors to the exceedance of all six indicators, thus pinpointing them as the leading pollution source in the basin. Additionally, forest coverage, livestock farming, chemical and pharmaceutical sectors, along with meteorological elements like precipitation and temperature, significantly impacted various indicators' exceedances. Furthermore, we delineate five core urban risk components through principal component analysis, which are (1) anthropogenic and industrial activities, (2) agricultural practices and forest extent, (3) climatic variables, (4) livestock rearing, and (5) principal polluting sectors. The cities were subsequently evaluated and categorized based on these risk components, incorporating policy interventions and administrative performance within each region. The comprehensive analysis advocates for a customized strategy in addressing the discerned risk factors, especially for cities presenting elevated risk levels.

Adaptation and learning as strategies to maximize reward in neurofeedback tasks.

Introduction: Adaptation and learning have been observed to contribute to the acquisition of new motor skills and are used as strategies to cope with changing environments. However, it is hard to determine the relative contribution of each when executing goal directed motor tasks. This study explores the dynamics of neural activity during a center-out reaching task with continuous visual feedback under the influence of rotational perturbations. Methods: Results for a brain-computer interface (BCI) task performed by two non-human primate (NHP) subjects are compared to simulations from a reinforcement learning agent performing an analogous task. We characterized baseline activity and compared it to the activity after rotational perturbations of different magnitudes were introduced. We employed principal component analysis (PCA) to analyze the spiking activity driving the cursor in the NHP BCI task as well as the activation of the neural network of the reinforcement learning agent. Results and discussion: Our analyses reveal that both for the NHPs and the reinforcement learning agent, the task-relevant neural manifold is isomorphic with the task. However, for the NHPs the manifold is largely preserved for all rotational perturbations explored and adaptation of neural activity occurs within this manifold as rotations are compensated by reassignment of regions of the neural space in an angular pattern that cancels said rotations. In contrast, retraining the reinforcement learning agent to reach the targets after rotation results in substantial modifications of the underlying neural manifold. Our findings demonstrate that NHPs adapt their existing neural dynamic repertoire in a quantitatively precise manner to account for perturbations of different magnitudes and they do so in a way that obviates the need for extensive learning.

A DNA origami device spatially controls CD95 signalling to induce immune tolerance in rheumatoid arthritis.

DNA origami is capable of spatially organizing molecules into sophisticated geometric patterns with nanometric precision. Here we describe a reconfigurable, two-dimensional DNA origami with geometrically patterned CD95 ligands that regulates immune cell signalling to alleviate rheumatoid arthritis. In response to pH changes, the device reversibly transforms from a closed to an open configuration, displaying a hexagonal pattern of CD95 ligands with ~10 nm intermolecular spacing, precisely mirroring the spatial arrangement of CD95 receptor clusters on the surface of immune cells. In a collagen-induced arthritis mouse model, DNA origami elicits robust and selective activation of CD95 death-inducing signalling in activated immune cells located in inflamed synovial tissues. Such localized immune tolerance ameliorates joint damage with no noticeable side effects. This device allows for the precise spatial control of cellular signalling, expanding our understanding of ligand-receptor interactions and is a promising platform for the development of pharmacological interventions targeting these interactions.

Role of plasma EBV-DNA load and EBER status on newly diagnosed peripheral T-cell lymphoma.

PURPOSE: To explore the prognostic and therapeutic role of Epstein-Barr Virus (EBV) on peripheral T-cell lymphoma (PTCL). METHODS: Totally 262 newly diagnosed PTCL patients who were hospitalized from January 2014 to December 2022 were retrospectively enrolled. Molecular analysis included 31 eligible patients. EBV-encoded RNA (EBER) presence in tumor tissue and EBV DNA levels in patients at baseline (DNA1) and after 4 cycles of chemotherapy (DNA4) were assessed. RESULTS: Our findings revealed that the EBER-positive cohort exhibited significant differences compared to counterparts in overall survival (OS, P = 0.047) and progression-free survival (PFS, P = 0.009). Both DNA1 and DNA4 were significantly associated with inferior OS. Multivariate analysis demonstrated that DNA4 independently affected PTCL prognosis for OS (hazard ratio = 5.1617; 95% confidence interval 1.1017-24.1831; P = 0.037). Treatment with the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus azacytidine regimen showed a better OS compared to CHOP or CHOP plus etoposide for patients with partially positive EBER and EBER positive statuses (P = 0.192), although the improvement was not statistically significant. This study delineated the genetic paradigm of PTCL, comparing genetic differences by EBV status and found that EBER partially positive plus positive patients were more likely to have DNMT3A (P = 0.002), RHOAG17V (P = 0.023), and TET2 mutations (P = 0.032). CONCLUSION: EBER, DNA1, and DNA4 emerged as sensitive markers for prognosis. CHOP plus azacytidine might present a preferable option for PTCL patients with DNA methylation due to EBV infection.

Fabrication of multifunctional facial masks from phenolic acid grafted chitosan/collagen peptides via aqueous electrospinning.

Facial masks have become ubiquitous in our daily life to endow skin enough moisture and activated nutrition through mask nonwovens infused with skincare ingredients. However, the active nutrients in wet masks are prone to deterioration and deactivation. Herein, a novel multifunctional nanofiber dry mask was successfully prepared using aqueous-electrospun phenolic acid grafted chitosan/collagen peptides. When used, the functional nanofibers in the mask dissolve through spraying moisture, activating active ingredients in response to water and providing in-situ free radical scavenging, moisturizing and antibacterial effects to the skin. In this work, a series of gallic acid (GA), caffeic acid (CA), and protocatechuic acid (PA) have been studied to be grafted with chitosan to improve water solubility of chitosan (CS). Also, through aqueous electrospinning of phenolic acid-grafted chitosan/collagen peptides, a one-step green multifunctional nanofiber mask was obtained. The results showed that the mask had a 12.14 % moisturizing rate and a 94.09 % activity for removing free radicals from the skin after encountering moisture. Considering its high efficiency, controllable function release, and easy processability, the nanofiber multifunctional mask may provide a competitive alternative to facial masks and promote potential value-added applications of bio-based macro-molecules.

Long-term survival after neoadjuvant therapy for triple-negative breast cancer under different treatment regimens: a systematic review and network meta-analysis.

BACKGROUND: Triple-negative breast cancer (TNBC) is a life-threatening subtype of breast cancer with limited treatment options. Therefore, this network meta-analysis (NMA) aimed to evaluate and compare the effect of various neoadjuvant chemotherapy (NCT) options on the long-term survival of patients with TNBC. METHODS: PubMed, Embase, Medline, Cochrane Library, Web of Science, and major international conference databases were systematically searched for randomized controlled trials (RCTs) on the efficacy of various NCT options in patients with TNBC. Searches were performed from January 2000 to June 2023. Study heterogeneity was assessed using the I2 statistic. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to evaluate disease-free survival (DFS) and overall survival (OS). Odds ratios (ORs) and 95% CIs were used to evaluate the pathologic complete response (pCR). The primary outcome was DFS. RESULTS: We conducted an NMA of 21 RCTs involving 8873 patients with TNBC. Our study defined the combination of anthracyclines and taxanes as the preferred treatment option. On this basis, the addition of any of the following new drugs is considered a new treatment option: bevacizumab (B), platinum (P), poly-ADP-ribose polymerase inhibitors (PARPi), and immune checkpoint inhibitor (ICI). Based on the surface under the cumulative ranking curve (SUCRA) values, the top three SUCRA area values of DFS were taxanes, anthracycline, and cyclophosphamide (TAC; 89.23%); CT (84.53%); and B (81.06%). The top three SUCRA area values of OS were CT (83.70%), TAC (62.02%), and B-containing regimens (60.06%). The top three SUCRA area values of pCR were B + P-containing regimens (82.7%), ICI + P-containing regimens (80.2%), and ICI-containing regimens (61.8%). CONCLUSIONS: This NMA showed that standard chemotherapy is a good choice with respect to long-term survival. Moreover, B associated with P-containing regimens is likely to be the optimal treatment option for neoadjuvant TNBC in terms of pCR.

Effects of sleep deprivation on anxiety-depressive-like behavior and neuroinflammation.

BACKGROUND: Depression is defined by a persistent low mood and disruptions in sleep patterns, with the WHO forecasting that major depression will rank as the third most prevalent contributor to the global burden of disease by the year 2030. Sleep deprivation serves as a stressor that triggers inflammation within the central nervous system, a process known as neuroinflammation. This inflammatory response plays a crucial role in the development of depression by upregulating the expression of inflammatory mediators that contribute to symptoms such as anxiety, hopelessness, and loss of pleasure. METHODS: In this study, sleep deprivation was utilized as a method to induce anxiety and depressive-like behaviors in mice. The behavioral changes in the mice were then evaluated using the EZM, EPM, TST, FST, and SPT. H&E staining and Nissl staining was used to detect morphological changes in the medial prefrontal cortical (mPFC) regions. Elisa to assess serum CORT levels. Detection of mRNA levels and protein expression of clock genes, high mobility genome box-1 (Hmgb1), silent message regulator 6 (Sirt6), and pro-inflammatory factors by RT-qPCR, Western blotting, and immunofluorescence techniques. RESULTS: Sleep deprivation resulted in decreased exploration of unfamiliar territory, increased time spent in a state of despair, and lower sucrose water intake in mice. Additionally, sleep deprivation led to increased secretion of serum CORT and upregulation of clock genes, IL6, IL1ß, TNFα, Cox-2, iNOS, Sirt6, and Hmgb1. Sleep. CONCLUSIONS: Sleep deprivation induces anxiety-depressive-like behaviors and neuroinflammation in the brain. Transcription of clock genes and activation of the Sirt6/Hmgb1 pathway may contribute to inflammatory responses in the mPFC.

Synovium microenvironment-responsive injectable hydrogel inducing modulation of macrophages and elimination of synovial fibroblasts for enhanced treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a progressive autoimmune disease accompanied by joint swelling, cartilage erosion and bone damage. Drug therapy for RA has been restricted due to poor therapeutic effect, recurrence and adverse effects. Macrophages and synovial fibroblasts both play important roles in the pathology of RA. Macrophages secrete large amount of pro-inflammatory cytokines, while synovial fibroblasts are tightly correlated with hypoxia synovium microenvironment, cytokine release, recruitment of pro-inflammatory cells, bone and cartilage erosion. Therefore, in this timely research, an injectable and pH-sensitive peptide hydrogel loading methotrexate (MTX) and bismuthene nanosheet/polyethyleneimine (BiNS/PEI) has been developed to reduce the activity of macrophages and eliminate over-proliferated synovial fibroblasts simultaneously. MTX can reduce the cytokine secretion of macrophages/anti-apoptosis property of synovial fibroblasts and BiNS/PEI can eliminate synovial fibroblasts via photodynamic therapy (PDT) and photothermal therapy (PTT) routes. The hydrogel was injected into the acidic inflammatory synovium for precise targeting and served as a drug reservoir for pH responsive and sustained drug release, while improving the bioavailability and reducing the toxicity of MTX. Excellent therapeutic efficacy has been achieved in both in vivo and in vitro studies, and this unique drug delivery system provides a new and robust strategy to eliminate synovial fibroblasts and modulate immune system for RA treatment in clinical.

Disorder-Broadened Phase Boundary with Enhanced Amorphous Superconductivity in Pressurized In2Te5.

As an empirical tool in materials science and engineering, the iconic phase diagram owes its robustness and practicality to the topological characteristics rooted in the celebrated Gibbs phase law (F = C - P + 2). When crossing the phase diagram boundary, the structure transition occurs abruptly, bringing about an instantaneous change in physical properties and limited controllability on the boundaries (F = 1). Here, we expand the sharp phase boundary to an amorphous transition region (F = 2) by partially disrupting the long-range translational symmetry, leading to a sequential crystalline-amorphous-crystalline (CAC) transition in a pressurized In2Te5 single crystal. Through detailed in-situ synchrotron diffraction, we elucidate that the phase transition stems from the rotation of immobile blocks [In2Te2]2+, linked by hinge-like [Te3]2- trimers. Remarkably, within the amorphous region, the amorphous phase demonstrates a notable 25% increase of the superconducting transition temperature (Tc), while the carrier concentration remains relatively constant. Furthermore, we propose a theoretical framework revealing that the unconventional boost in amorphous superconductivity might be attributed to an intensified electron correlation, triggered by a disorder-augmented multifractal behavior. These findings underscore the potential of disorder and prompt further exploration of unforeseen phenomena on the phase boundaries. This article is protected by copyright. All rights reserved.

Total Synthesis of Quebrachamine and Kopsiyunnanine D.

The total syntheses of (±)-quebrachamine and (±)-kopsiyunnanine D are reported. Key transformations include an intermolecular Horner-Wadsworth-Emmons olefination to merge the two fragments convergently and an intramolecular Mitsunobu reaction to introduce the synthetically challenging nine-membered azonane ring efficiently.

[Low disease activity and remission status of systemic lupus erythematosus in a real-world study].

OBJECTIVE: To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus (SLE) in a real-world setting, and to analyze the related factors of low disease activity and clinical remission. METHODS: One thousand patients with SLE were enrolled from 11 teaching hospitals. Demographic, clinical and laboratory data, as well as treatment regimes were collec-ted by self-completed questionnaire. The rates of low disease activity and remission were calculated based on the lupus low disease activity state (LLDAS) and definitions of remission in SLE (DORIS). Charac-teristics of patients with LLDAS and DORIS were analyzed. Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission. RESULTS: 20.7% of patients met the criteria of LLDAS, while 10.4% of patients achieved remission defined by DORIS. Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration, compared with non-remission group. Moreover, the rates of anemia, creatinine elevation, increased erythrocyte sedimentation rate (ESR) and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group. Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission. The results of Logistic regression analysis showed that increased ESR, positive anti-dsDNA antibodies, low level of complement (C3 and C4), proteinuria, low household income were negatively related with LLDAS and DORIS remission. However, hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission. CONCLUSION: LLDAS and DORIS remission of SLE patients remain to be improved. Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.