The HTLV-I oncoprotein Tax inactivates the tumor suppressor FBXW7.

Human T-cell leukemia virus type 1 (HTLV-I) is the etiological agent of adult T-cell leukemia (ATL). Mutational analysis has demonstrated that the tumor suppressor, F-box and WD repeat domain containing 7 (FBXW7/FBW7/CDC4), is mutated in primary ATL patients. However, even in the absence of genetic mutations, FBXW7 substrates are stabilized in ATL cells, suggesting additional mechanisms can prevent FBXW7 functions. Here, we report that the viral oncoprotein Tax represses FBXW7 activity, resulting in the stabilization of activated Notch intracellular domain, c-MYC, Cyclin E, and myeloid cell leukemia sequence 1 (BCL2-related) (Mcl-1). Mechanistically, we demonstrate that Tax directly binds to FBXW7 in the nucleus, effectively outcompeting other targets for binding to FBXW7, resulting in decreased ubiquitination and degradation of FBXW7 substrates. In support of the nuclear role of Tax, a non-degradable form of the nuclear factor kappa B subunit 2 (NFκB2/p100) was found to delocalize Tax to the cytoplasm, thereby preventing Tax interactions with FBXW7 and Tax-mediated inhibition of FBXW7. Finally, we characterize a Tax mutant that is unable to interact with FBXW7, unable to block FBXW7 tumor suppressor functions, and unable to effectively transform fibroblasts. These results demonstrate that HTLV-I Tax can inhibit FBXW7 functions without genetic mutations to promote an oncogenic state. These results suggest that Tax-mediated inhibition of FBXW7 is likely critical during the early stages of the cellular transformation process. IMPORTANCE: F-box and WD repeat domain containing 7 (FBXW7), a critical tumor suppressor of human cancers, is frequently mutated or epigenetically suppressed. Loss of FBXW7 functions is associated with stabilization and increased expression of oncogenic factors such as Cyclin E, c-Myc, Mcl-1, mTOR, Jun, and Notch. In this study, we demonstrate that the human retrovirus human T-cell leukemia virus type 1 oncoprotein Tax directly interacts with FBXW7, effectively outcompeting other targets for binding to FBXW7, resulting in decreased ubiquitination and degradation of FBXW7 cellular substrates. We further demonstrate that a Tax mutant unable to interact with and inactivate FBXW7 loses its ability to transform primary fibroblasts. Collectively, our results describe a novel mechanism used by a human tumor virus to promote cellular transformation.

Integrated analysis of transcriptome and miRNAome reveals the heat stress response of Pinellia ternata seedlings.

Pinellia ternata (Thunb.) Briet., a valuable herb native to China, is susceptible to the "sprout tumble" phenomenon because of high temperatures, resulting in a significant yield reduction. However, the molecular regulatory mechanisms underlying the response of P. ternata to heat stress are not well understood. In this study, we integrated transcriptome and miRNAome sequencing to identify heat-response genes, microRNAs (miRNAs), and key miRNA-target pairs in P. ternata that differed between heat-stress and room-temperature conditions. Transcriptome analysis revealed extensive reprogramming of 4,960 genes across various categories, predominantly associated with cellular and metabolic processes, responses to stimuli, biological regulation, cell parts, organelles, membranes, and catalytic and binding activities. miRNAome sequencing identified 1,597 known/conserved miRNAs that were differentially expressed between the two test conditions. According to the analysis, genes and miRNAs associated with the regulation of transcription, DNA template, transcription factor activity, and sequence-specific DNA binding pathways may play a major role in the resistance to heat stress in P. ternata. Integrated analysis of the transcriptome and miRNAome expression data revealed 41 high-confidence miRNA-mRNA pairs, forming 25 modules. MYB-like proteins and calcium-responsive transcription coactivators may play an integral role in heat-stress resistance in P. ternata. Additionally, the candidate genes and miRNAs were subjected to quantitative real-time polymerase chain reaction to validate their expression patterns. These results offer a foundation for future studies exploring the mechanisms and critical genes involved in heat-stress resistance in P. ternata.

A novel recombinant S-based subunit vaccine induces protective immunity against porcine deltacoronavirus challenge in piglets.

IMPORTANCE: As an emerging porcine enteropathogenic coronavirus that has the potential to infect humans, porcine deltacoronavirus (PDCoV) is receiving increasing attention. However, no effective commercially available vaccines against this virus are available. In this work, we designed a spike (S) protein and receptor-binding domain (RBD) trimer as a candidate PDCoV subunit vaccine. We demonstrated that S protein induced more robust humoral and cellular immune responses than the RBD trimer in mice. Furthermore, the protective efficacy of the S protein was compared with that of inactivated PDCoV vaccines in piglets and sows. Of note, the immunized piglets and suckling pig showed a high level of NAbs and were associated with reduced virus shedding and mild diarrhea, and the high level of NAbs was maintained for at least 4 months. Importantly, we demonstrated that S protein-based subunit vaccines conferred significant protection against PDCoV infection.

Origin of Manipulating Selectivity in Prins Cyclization by [Ga4L6]12- Supramolecular Catalysis through Host-Guest Interactions.

The host effect of the supramolecular [Ga4L6]12- tetrahedral metallocage on Prins cyclization reaction of the substrate by encapsulated citronellal has been investigated by means of molecular dynamics and quantum mechanics. The encapsulation process of the substrate into the [Ga4L6]12- cavity was simulated via attach-pull-release (APR) methods. Thermodynamic calculations and classical molecular dynamics simulations assessed the substrate's microenvironment inside the cavity, guiding DFT-level modeling of the reaction. DFT calculations show diol product predominance in acidic solution but high enol selectivity inside [Ga4L6]12-, consistent with experimental findings. [Ga4L6]12- alters the selectivity of the Prins cyclization reaction by inhibiting diol formation. The activation strain model-based decomposition analysis (ASM-DA) of the barrier difference among distortion and interaction terms indicates that the more positive interaction between a host and guest in the diol transition state than enol determines the product selectivity, particularly the fewer C-H···O and O-H···O hydrogen-bonding interactions. These theoretical insights could contribute to a deeper understanding of the nature of supramolecular catalysis and to further develop new supramolecular catalysts.

Landscape Fire Air Pollution as a Mediator in Drought and Childhood Stunting Pathway in Low- and Middle-Income Countries.

Drought induces dry hazards, including wildfire, and increased air pollution from wildfire may be a mechanism by which drought increases health risks. We examined whether the drought-wildfire pathway increases the risk of childhood stunting. We analyzed all geocoded children under five across 44 low- and middle-income countries (LMICs). We first conducted mixed-effect regressions to examine the three pairwise associations between standardized precipitation evapotranspiration index (SPEI), fire-sourced PM2.5, and childhood stunting. We then employed a causal mediation analysis to determine whether compounding drought-wildfire (cascading or co-occurring) events significantly impact the drought-stunting pathway. We found that each 1-unit decrease in SPEI exposure was associated with a 2.16% [95% confidence interval (CI): 0.79, 3.49%] increase in stunting risk and 0.57 (95% CI 0.55, 0.59%) µg/m3 increase in fire-sourced PM2.5. Additionally, each 1 µg/m3 increase in 24 month average fire-sourced PM2.5 was associated with an increased risk of 2.46% (95% CI: 2.16, 2.76%) in stunting. Drought-mediated fires accounted for 26.7% (95% CI: 14.5, 36.6%) of the linkage between SPEI and stunting. Our study revealed fire-sourced PM2.5 is a mediator in the drought-stunting pathway in LMICs. To protect child health under increasing drought conditions, personal interventions against wildfire should be considered to enhance climate resilience.

Stillbirths Associated with Particle Pollution are Disproportionally Contributed by Sand Dust: Findings from 52 Low- and Middle-Income Countries.

Whether maternal exposure to dust-sourced particulate matter (hereafter, dust PM2.5) is associated with stillbirth remains unknown. We adopted a sibling-matched case-control design to analyze 9332 stillbirths and 17,421 live births. We associated the risk of stillbirth simultaneously with dust and nondust components of PM2.5 and developed a nonlinear joint exposure-response function. Next, we estimated the burden of stillbirths attributable to the PM2.5 mixture. The concentration index was used to evaluate whether the burden of PM2.5-related stillbirths was disproportionally distributed among pregnancies exposed to dust-rich particles. Each 10 µg/m3 increase in dust PM2.5 was associated with a 14.5% (95% confidence interval: 5.5, 24.2%) increase in the odds of stillbirth. Based on the risk assessment across 137 countries, sand dust contributed to about 15% of the PM2.5 exposure but to about 45% of the PM2.5-related stillbirths during 2003-2019. In 2015, 30% of the PM2.5-related stillbirths were concentrated within 15% of pregnancies exposed to the dust-richest PM2.5. The index increased in subregions, such as South Asia, suggesting the growth of health inequality due to exposure to dust PM2.5. Based on our findings, land management, such as halting desertification, will help prevent stillbirths and reduce global maternal health inequality.

Burden of Child Anemia Attributable to Fine Particulate Matters Brought by Sand Dusts in Low- and Middle-Income Countries.

Addressing environmental factors has recently been recommended to curb the growing trend of anemia in low- and middle-income countries (LMICs). Fine particulate matter (PM2.5) generated by dust storms were concentrated in place with a high prevalence of anemia. In a multicounty, multicenter study, we analyzed the association between anemia and life-course averaged exposure to dust PM2.5 among children aged <5 years based on 0.65 million records from 47 LMICs. In the fully adjusted mixed effects model, each 10 µg/m3 increase in life-course averaged exposure to dust PM2.5 was associated with a 9.3% increase in the odds of anemia. The estimated exposure-response association was nonlinear, with a greater effect of dust PM2.5 exposure seen at low concentrations. Applying this association, we found that, in 2017, among all children aged <5 years in the 125 LMICs, dust PM2.5 contributed to 37.98 million cases of anemia. Results indicated that dust PM2.5 contributed a heavier burden than all of the well-identified risk factors did, except for iron deficiency. Our study revealed that long-term exposure to dust PM2.5 can be a novel risk factor, pronouncedly contributed to the burden of child anemia in LMICs, affected by land degradations or arid climate.

The Association Between Urbanization and Electrocardiogram Abnormalities in China: a Nationwide Longitudinal Study.

The health effects of urbanization are controversial. The association between urbanization and reversible subclinical risks of cardiovascular diseases (e.g., electrocardiogram (ECG) abnormalities) has rarely been studied. This study aimed to assess the association between urbanization and ECG abnormalities in China based on the China National Stroke Screening Survey (CNSSS). We used changes in the satellite-measured impervious surfaces rate and nighttime light data to assess the level of urbanization. Every interquartile increment in the impervious surfaces rate or nighttime light was related to a decreased risk of ECG abnormalities, with odds ratios of 0.894 (95% CI, 0.869-0.920) or 0.809 (95% CI, 0.772-0.847), respectively. And we observed a U-shaped nonlinear exposure-response relationship curve between the impervious surfaces rate and ECG abnormalities. In conclusion, the current average level of urbanization among the studied Chinese adults remains a beneficial factor for reducing cardiovascular risks.

Cdc42GAP deficiency contributes to the Alzheimer's disease phenotype.

Alzheimer's disease, the most common cause of dementia, is a chronic degenerative disease with typical pathological features of extracellular senile plaques and intracellular neurofibrillary tangles and a significant decrease in the density of neuronal dendritic spines. Cdc42 is a member of the small G protein family that plays an important role in regulating synaptic plasticity and is regulated by Cdc42GAP, which switches Cdc42 from active GTP-bound to inactive GDP-bound states regulating downstream pathways via effector proteins. However, few studies have focused on Cdc42 in the progression of Alzheimer's disease. In a heterozygous Cdc42GAP mouse model that exhibited elevated Cdc42-GTPase activity accompanied by increased Cdc42-PAK1-cofilin signalling, we found impairments in cognitive behaviours, neuron senescence, synaptic loss with depolymerization of F-actin and the pathological phenotypes of Alzheimer's disease, including phosphorylated tau (p-T231, AT8), along with increased soluble and insoluble Aß1-42 and Aß1-40, which are consistent with typical Alzheimer's disease mice. Interestingly, these impairments increased significantly with age. Furthermore, the results of quantitative phosphoproteomic analysis of the hippocampus of 11-month-old GAP mice suggested that Cdc42GAP deficiency induces and accelerates Alzheimer's disease-like phenotypes through activation of GSK-3ß by dephosphorylation at Ser9, Ser389 and/or phosphorylation at Tyr216. In addition, overexpression of dominant-negative Cdc42 in the primary hippocampal and cortical neurons of heterozygous Cdc42GAP mice reversed synaptic loss and tau hyperphosphorylation. Importantly, the Cdc42 signalling pathway, Aß1-42, Aß1-40 and GSK-3ß activity were increased in the cortical sections of Alzheimer's disease patients compared with those in healthy controls. Together, these data indicated that Cdc42GAP is involved in regulating Alzheimer's disease-like phenotypes such as cognitive deficits, dendritic spine loss, phosphorylated tau (p-T231, AT8) and increased soluble and insoluble Aß1-42 and Aß1-40, possibly through the activation of GSK-3ß, and these impairments increased significantly with age. Thus, we provide the first evidence that Cdc42 is involved in the progression of Alzheimer's disease-like phenotypes, which may provide new targets for Alzheimer's disease treatment.

Correlation of serum homocysteine and cystatin C levels with prognosis in heart failure with preserved ejection fraction patients.

OBJECTIVE: This study investigated the relationship of serum homocysteine (Hcy) and cystatin C (Cys C) levels with the prognosis of patients with heart failure with preserved ejection fraction (HFpEF). METHODS: A total of 178 patients with HFpEF who were admitted to our hospital between December 2019 and November 2020 were included. Patients were grouped based on their serum Hcy and Cys C levels: high Hcy level, normal Hcy level, high Cys C level, and normal Cys C level. Cardiac function, ventricular remodeling indices, and prognosis were compared among patients in these groups. Additionally, the predictive value of serum Hcy and Cys C levels for adverse cardiovascular events in HFpEF patients was analyzed. RESULTS: Patients' mean age in the high Hcy level, normal Hcy level, high Cys C level, and normal Cys C level groups was 69.21 ± 4.17,67.74 ± 4.28,69.95 ± 4.98, and 67.06 ± 4.13 years old, respectively. The high Hcy level group exhibited a lower proportion of class II cardiac function according to the New York Heart Association (NYHA) classification and a higher proportion of class IV cardiac function than the normal Hcy level group, with statistically significant differences. Similarly, the high Cys C level group had a lower proportion of class II cardiac function and a higher proportion of class IV cardiac function compared with the normal Cys C level group, with statistically significant differences. Left ventricular end-diastolic internal diameter (LVEDD), left ventricular end-systolic internal diameter (LVESD), and left ventricular mass index (LVMI) were significantly higher in both the high Hcy level and high Cys C level groups compared with the normal group, with statistically significant differences. The rates of all-cause mortality and class I endpoint events were significantly higher in the high Hcy level and high Cys C level groups than in the normal group. Multifactorial logistic regression analysis demonstrated that adverse cardiovascular events were significantly associated with cardiac function class, LVEDD, LVESD, LVMI, Hcy, and Cys C in patients with HFpEF. The area under the curve (AUC) values for Hcy and Cys C, determined using receiver operating characteristic (ROC) curve analysis, were 0.778 (optimal critical value, 25.38) and 0.681 (optimal critical value, 1.56), respectively, for predicting adverse cardiovascular events. Both Hcy and Cys C serum levels were positively correlated with LVEDD, LVESD, LVMI, and NYHA classification. CONCLUSION: Serum levels of Hcy and Cys C were closely associated with cardiac function, ventricular remodeling indices, and prognosis in patients with HFpEF. These levels may serve as valuable indices for assessing HFpEF patients' health status and prognosis, providing important insights into their potential role as biomarkers for HFpEF management and prognosis.

Ambient temperature anomalies induce electrocardiogram abnormalities: Findings from a nationwide longitudinal study.

Electrocardiogram (ECG) outcomes serve as early manifestations of cardiovascular functional or structural changes. While temperature fluctuation has been demonstrated to be a risk factor for cardiovascular diseases, few epidemiological studies have reported its relationship with ECG outcomes. In this study, we employed temperature anomaly (TA) as an innovative indicator of temperature fluctuation to quantify its detrimental impacts on ECG outcomes. A longitudinal study design was conducted using the repeated ECG records of the China National Stroke Screening Survey from 2013 to 2019. Only individuals undergoing at least two ECG tests were included. The daily temperature was assimilated by combining three kinds of data: in situ observations, satellite remote sensing measurements and weather research forecast simulations. We used generalized estimating equations to control for autocorrelation among repeated records and to estimate the association between TA and the risk of ECG abnormalities. We found 6837 events of ECG abnormalities in 47,286 individuals with 102,030 visits. Each unit increment of TA increased the risk of ECG abnormalities [odds ratio (OR) = 1.009, 95% confidence interval (CI): 1.001-1.017] and the risk of myocardial ischemia (OR = 1.061, 95% CI: 1.012-1.111). Hierarchic analyses presented a similar association of TA with both ECG abnormalities (OR = 1.017, 95% CI: 1.008-1.026) and myocardial ischemia (OR = 1.061, 95%CI: 1.011-1.114) in Northern China, but not in Southern China. The exposure-response relationship was estimated as a U-shaped curve centered at the TA value of zero. Sudden warming tended to increase the risk of ECG abnormalities and myocardial ischemia, and sudden cooling tended to increase the risk of atrial fibrillation. All these detrimental effects of TA could be modified by specific individual characteristics. In summary, ambient temperature fluctuation increased the risk of ECG abnormalities. This result indicated that regular ECG tests could be an early-warning measure for monitoring the adverse health effects of temperature fluctuations.

Association between exposure to greenspace and ECG abnormalities in China: a nationwide longitudinal study.

BACKGROUND: Greenspace is an important modifiable environmental factor that is associated with health and well-being. Although previous research has shown that exposure to greenspace is beneficial for cardiovascular diseases, studies have rarely focused on early subclinical health outcomes such as electrocardiogram (ECG) abnormality. METHODS: We developed a longitudinal study using data from the China National Stroke Screening Survey (2013-2019). Monthly exposure to greenspace was assessed by the Normalized Difference Vegetation Index (NDVI) values. ECG abnormality was diagnosed by physicians based on the results of the 12-lead electrocardiogram. We used fixed-effects logistic regression with participant-specific intercepts to estimate the association between exposure to greenspace and ECG abnormalities. RESULTS: A total of 132,108 visits from 61,029 participants with ≥ 2 ECG measurements were included. At baseline, the lag-1 month average NDVI value was 0.29 (SD = 0.15). In the fully adjusted model, per 0.1-unit increment in lag-1 month average NDVI value was associated with a 3.0% (95% CI -1.6 ∼ 7.4%) decreased risk of ECG abnormality. In urban areas, the decreased risk associated with per 0.1-unit increment in NDVI was 14.81% (95% CI 9.38 ∼ 19.92%). CONCLUSION: Our study found that higher exposure to greenspace was associated with a decreased risk of ECG abnormality, especially in urban areas. Our findings suggested that monthly exposure to greenspace might be beneficial to cardiovascular health, and greenspace provision and maintenance could be considered an important public health intervention in urban planning.

Isolation, structure modification, and anti-rheumatoid arthritis activity of isopimarane-type diterpenoids from Orthosiphon aristatus.

Orthosiphon aristatus is a well-known folkloric medicine and herb for Guangdong soup for the treatment of rheumatism in China. Eight isopimarane-type and migrated pimarane-type diterpenoids (1-8), including a new one with a rarely occurring α,ß-unsaturated diketone C-ring, were isolated from O. aristatus. Their structures were determined by spectroscopic methods and quantum chemical calculations. Furthermore, the most abundant compound, orthosiphol K, was structurally modified by modern synthetic techniques to give seven new derivatives (9-15). The anti-rheumatoid arthritis activity of these diterpenoids were evaluated on a TNF-α induced MH7A human rheumatoid fibroblast-like synoviocyte model. Compound 10 showed the most potent activity among these compounds. Based on their inhibitory effects on the release levels of IL-1ß, the preliminary structure-activity relationships were concluded. Furthermore, western blot analysis revealed that 10 could increase the expression of IκBα and decrease the expression of NF-κB p65, and the expression levels of COX-2 and NLRP3 proteins were consequently down-regulated.

Evaluation of the Effectiveness of In-Hospital Exercise Rehabilitation in Middle-Aged and Elderly Patients with Type 2 Diabetes Mellitus Combined with Sarcopenia Effect of Lifestyle Management on Disease Status in Patients with Type 2 Diabetes Mellitus.

OBJECTIVE: The aim of this study was to explore the effects of in-hospital exercise rehabilitation on glucose and lipid metabolism and healthy physical fitness in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM) combined with sarcopenia, and to provide a reference for the effective implementation of exercise rehabilitation for middle-aged and elderly patients with T2DM combined with sarcopenia in healthcare institutions. METHODS: This study retrospectively included 122 patients with T2DM combined with sarcopenia treated at the General Hospital of Ningxia Medical University from August 2017 to August 2020 and randomly divided into a control group and an experimental group. The control group was given conventional treatment and the experimental group was given exercise rehabilitation in the hospital for 12 weeks to compare the indexes related to glucose and lipid metabolism and healthy fitness in the two groups. RESULTS: After the intervention, the experimental group showed significant decreases in fasting blood glucose (FBG), glycated hemoglobin (HbA1c), insulin resistance index (HOMA-IR), triglycerides (TG), total cholesterol (TC), low-density cholesterol (LDL-C) and body fat percentage (p < 0.05), while high-density cholesterol (HDL-C), grip strength, lower limb extension, lower limb flexion, peak oxygen uptake were significantly higher (p < 0.05) and were more significant at 12 weeks compared to the 6-week intervention (p < 0.05). However, there were no significant changes in any of the glucose metabolism indicators in the control group before and after the intervention. A two-way repeated measures ANOVA showed that at control baseline levels, HbA1c decreased significantly in the experimental group after both 6 and 12 weeks of intervention compared to the control group (p < 0.05). After 6 weeks of intervention, the experimental group showed a significant decrease in body fat percentage and a significant increase in grip strength. After 12 weeks of intervention, the experimental group showed an increase in glycemic control from 33.3% to 73.3%, a significant decrease in body fat percentage and a significant increase in grip strength, lower limb extension and lower limb flexion strength and peak oxygen uptake. CONCLUSION: In-hospital exercise rehabilitation can effectively improve the glycemic and lipid profiles of patients with T2DM combined with sarcopenia and enhance their health fitness, with good clinical rehabilitation effects.

CT analysis of frontal recess air cell and fluid dynamics simulation of frontal sinus in people with different frontal sinus development after Draf1-3 surgery.

OBJECTIVE: To explore the effects of Draf1-3 on frontal sinus airflow and frontal sinus irrigation in people with different frontal sinus development METHODS: The development of the frontal sinus and the distribution of the frontal recess cells were evaluated by CT scan in 150 adults (300 sides). The airflow changes into the frontal sinus and frontal recess after Draf were analyzed by Fluent software under a steady state and quiet inspiratory state. Nasal irrigation after Draf in adults with well-developed frontal sinus was simulated using 120 mL saline at a rate of 12 mL/s in a position at 45° to observe the changes in transient flow distribution. RESULTS: The moderately developed type of the frontal sinus was the most common. The airflow patterns in the frontal sinus and frontal recess in the moderate development group were laminar, while several large vortexes were formed between the frontal sinus and frontal recess in the well-development group. The Draf exerted more significant effects on the patterns, pressure, and velocity of the airflow in the frontal sinus and frontal recess in the well development group than in the moderate development group. The volume fraction of saline in the frontal sinus increased significantly from Draf1 to Draf3, and the time required for a complete infiltration of saline in the frontal sinus mucosa was significantly reduced. CONCLUSIONS: Draf1-3 has different effects on the airflow field of the frontal sinus with different developmental types; and Draf1-3 can significantly improve the postoperative flushing of the frontal sinus.

Amphibious Multifunctional Hydrogel Flexible Haptic Sensor with Self-Compensation Mechanism.

In recent years, hydrogel-based wearable flexible electronic devices have attracted much attention. However, hydrogel-based sensors are affected by structural fatigue, material aging, and water absorption and swelling, making stability and accuracy a major challenge. In this study, we present a DN-SPEZ dual-network hydrogel prepared using polyvinyl alcohol (PVA), sodium alginate (SA), ethylene glycol (EG), and ZnSO4 and propose a self-calibration compensation strategy. The strategy utilizes a metal salt solution to adjust the carrier concentration of the hydrogel to mitigate the resistance drift phenomenon to improve the stability and accuracy of hydrogel sensors in amphibious scenarios, such as land and water. The ExpGrow model was used to characterize the trend of the ∆R/R0 dynamic response curves of the hydrogels in the stress tests, and the average deviation of the fitted curves ϵ¯ was calculated to quantify the stability differences of different groups. The results showed that the stability of the uncompensated group was much lower than that of the compensated group utilizing LiCl, NaCl, KCl, MgCl2, and AlCl3 solutions (ϵ¯ in the uncompensated group in air was 276.158, 1.888, 2.971, 30.586, and 13.561 times higher than that of the compensated group in LiCl, NaCl, KCl, MgCl2, and AlCl3, respectively; ϵ¯ in the uncompensated group in seawater was 10.287 times, 1.008 times, 1.161 times, 4.986 times, 1.281 times, respectively, higher than that of the compensated group in LiCl, NaCl, KCl, MgCl2 and AlCl3). In addition, for the ranking of the compensation effect of different compensation solutions, the concentration of the compensation solution and the ionic radius and charge of the cation were found to be important factors in determining the compensation effect. Detection of events in amphibious environments such as swallowing, robotic arm grasping, Morse code, and finger-wrist bending was also performed in this study. This work provides a viable method for stability and accuracy enhancement of dual-network hydrogel sensors with strain and pressure sensing capabilities and offers solutions for sensor applications in both airborne and underwater amphibious environments.

Borneol-modified docetaxel plus tetrandrine micelles for treatment of drug-resistant brain glioma.

OBJECTIVE: Glioma is the most common and deadly primary malignant tumor in adults. Treatment outcomes are ungratified due to the presence of blood-brain barrier (BBB), glioma stem cells (GSCs) and multidrug resistance (MDR). Docetaxel (DTX) is considered as a potential drug for the treatment of brain tumor, but its effectiveness is limited by its low bioavailability and drug resistance. Tetrandrine (TET) reverses the resistance of tumor cells to chemotherapy drugs. Borneol (BO) modified in micelles has been shown to promote DTX plus TET to cross the BBB, allowing the drug to better act on tumors. Therefore, we constructed BO-modified DTX plus TET micelles to inhibit chemotherapeutic drug resistance. SIGNIFICANCE: Provide a new treatment method for drug-resistant brain gliomas. METHODS: In this study, BO-modified DTX plus TET micelles were prepared by thin film dispersion method, their physicochemical properties were characterized. Its targeting ability was investigated. The therapeutic effect on GSCs was investigated by in vivo and in vitro experiments. RESULTS: The BO-modified DTX plus TET micelles were successfully constructed by thin film dispersion method, and the micelles showed good stability. The results showed that targeting micelles increased bEnd.3 uptake and helped drugs cross the BBB in vitro. And we also found that targeting micelles could inhibit cell proliferation, promote cell apoptosis and inhibit the expression of drug-resistant protein, thus provide a new treatment method for GSCs in vitro and in vivo. CONCLUSIONS: BO-modified DTX plus TET micelles may provide a new treatment method for drug-resistant brain gliomas.

Ln3+ Induced Thermally Activated Delayed Fluorescence of Chiral Heterometallic Clusters Ln2Ag28.

A series of TADF-active compounds: 0D chiral Ln-Ag(I) clusters L-/D-Ln2Ag28-0D (Ln=Eu/Gd) and 2D chiral Ln-Ag(I) cluster-based frameworks L-/D-Ln2Ag28-2D (Ln=Gd) has been synthesized. Atomic-level structural analysis showed that the chiral Ag(I) cluster units {Ag14S12} in L-/D-Ln2Ag28-0D and L-/D-Ln2Ag28-2D exhibited similar configurations, linked by varying numbers of [Ln(H2O)x]3+ (x=6 for 0D, x=3 for 2D) to form the final target compounds. Temperature-dependent emission spectra and decay lifetimes measurement demonstrated the presence of TADF in L-Ln2Ag28-0D (Ln=Eu/Gd) and L-Gd2Ag28-2D. Experimentally, the remarkable TADF properties primarily originated from {Ag14S12} moieties in these compounds. Notably, {Ag14S12} in L-Eu2Ag28-0D and L-Gd2Ag28-2D displayed higher promote fluorescence rate and shorter TADF decay times than L-Gd2Ag28-0D. Combined with theoretical calculations, it was determined that the TADF behaviors of {Ag14S12} cluster units were induced by 4 f perturbation of Ln3+ ions. Specially, while maintaining ΔE(S1-T1) small enough, it can significantly increase k(S1→S0) and reduce TADF decay time by adjusting the type or number of Ln3+ ions, thus achieving the purpose of improving TADF for cluster-based luminescent materials.

Astrocyte-derived SerpinA3N promotes neuroinflammation and epileptic seizures by activating the NF-κB signaling pathway in mice with temporal lobe epilepsy.

Impaired activation and regulation of the extinction of inflammatory cells and molecules in injured neuronal tissues are key factors in the development of epilepsy. SerpinA3N is mainly associated with the acute phase response and inflammatory response. In our current study, transcriptomics analysis, proteomics analysis, and Western blotting showed that the expression level of Serpin clade A member 3N (SerpinA3N) is significantly increased in the hippocampus of mice with kainic acid (KA)-induced temporal lobe epilepsy, and this molecule is mainly expressed in astrocytes. Notably, in vivo studies using gain- and loss-of-function approaches revealed that SerpinA3N in astrocytes promoted the release of proinflammatory factors and aggravated seizures. Mechanistically, RNA sequencing and Western blotting showed that SerpinA3N promoted KA-induced neuroinflammation by activating the NF-κB signaling pathway. In addition, co-immunoprecipitation revealed that SerpinA3N interacts with ryanodine receptor type 2 (RYR2) and promotes RYR2 phosphorylation. Overall, our study reveals a novel SerpinA3N-mediated mechanism in seizure-induced neuroinflammation and provides a new target for developing neuroinflammation-based strategies to reduce seizure-induced brain injury.

Experimental realization of free-space continuous-variable quantum key distribution based on fiber Sagnac interferometer.

The Gaussian-modulated coherent state (GMCS) is a well-known continuous-variable quantum key distribution (CV-QKD) protocol that is robust to incoherent background noise and can effectively suppress ambient light in free space. However, it is difficult to implement this protocol in free space using existing polarization coding schemes. In this Letter, we propose a polarization coding structure based on a self-compensating fiber Sagnac interferometer, which can reduce the required modulation voltage by two orders of magnitude and achieve fast and arbitrary polarization modulation, and experimentally demonstrate polarization coding-based GMCS CV-QKD for, it is believed, the first time. The proposed polarization modulation structure, which uses off-the-shelf fiber components, is compact, simple, and suitable for mobile terminals, such as flying lifts.