In situ growth of Bi-MOF on cotton fabrics via ultrasonic synthesis strategy for recyclable photocatalytic textiles.

Bismuth-based metal-organic framework (Bi-MOF) materials have shown potential for treating organic pollutants. In this work, multifunctional textiles were produced by in situ synthesis of CAU-17 on carboxymethylated cotton fabrics by solvothermal and ultrasonic strategies and employed as recyclable photocatalysts. The compositional and structural features of the dense MOF crystal coatings on cotton fibers were confirmed by scanning electron microscopy, X-ray diffraction, and other characterization approaches. Under optimized conditions, the developed functionalized cotton fabrics achieved a photodegradation efficiency of 98.8% under visible light for RhB in water, as well as good recyclability. The described results have provided the basis and reference for the fabrication of MOF-functionalized textiles.

Status quo and influencing factors of multiprofessional and multidisciplinary teamwork for early mobilization in mechanically ventilated patients in ICUs: A multi-centre survey study.

AIM: To understand the status quo of multiprofessional and multidisciplinary collaboration for early mobilization of mechanically ventilated patients in Chinese ICUs and identify any factors that may influence this practice. DESIGN: A multi-centre cross-sectional survey. METHODS: From October to November 2022, the convenience sampling method was used to select ICU multiprofessional and multidisciplinary early mobility members (including physicians, nurses and physiotherapists) from 27 tertiary general hospitals in 14 provinces, cities and autonomous regions of China. They were asked to complete an author-developed questionnaire on the status of collaboration and the Assessment of Inter-professional Team Collaboration Scale. A multiple linear regression model was used to analyse the factors associated with the level of collaboration. RESULTS: Physicians, nurses and physiotherapists mostly suffered from the lack of normative protocols, unclear division of responsibilities and unclear multiprofessional and multidisciplinary teams when using a collaborative approach to early activities. Multiple linear regression analysis showed that the number of ICU patients managed, the existence of norms and processes, the attitude of colleagues around them, the establishment of a team, communication methods and activity leaders were significant influences on the level of collaboration among members of the multiprofessional and multidisciplinary early activities. CONCLUSION: The collaboration of multiprofessional and multidisciplinary early activity members for mechanically ventilated patients in the ICU remains unclear, and the collaboration strategy needs to be constructed and improved, taking into account China's human resources and each region's economic development level. IMPACT: This study investigates the collaboration status of multiprofessional and multidisciplinary activity members from the perspective of teamwork, analyses the reasons affecting the level of collaboration and helps to develop better teamwork strategies to facilitate the implementation of early activities. PATIENT OR PUBLIC CONTRIBUTION: The participants in this study were multiprofessional and multidisciplinary medical staff who performed early activities for ICU patients.

Complement activation in wasp venom-induced acute kidney injury.

Previous studies have highlighted the significant role of complement activation in kidney injuries induced by rhabdomyolysis, intravascular hemolysis, sepsis, and ischemia-reperfusion. Nevertheless, the specific role and mechanism of complement activation in acute kidney injury (AKI) caused by wasp venom remain unclear. The aim of this study was to elucidate the specific complement pathway activated and investigate complement activation in AKI induced by wasp venom. In this study, a complement-depleted mouse model was used to investigate the role of complement in wasp venom-induced AKI. Mice were randomly categorized into control, cobra venom factor (CVF), AKI, and CVF + AKI groups. Compared to the AKI group, the CVF + AKI group showed improved pathological changes in kidneys and reduced blood urea nitrogen (BUN) levels. The expression levels of renal complement 3 (C3), complement 5 (C5), complement 1q (C1q), factor B (FB), mannose-binding lectin (MBL), and C5b-9 in AKI group were upregulated compared with the control group. Conversely, the renal tissue expression levels of C3, C5, C1q, FB, MBL, and C5b-9 were decreased in the CVF + AKI group compared to those in the AKI group. Complement activation occurs through all three pathways in AKI induced by wasp venom. Furthermore, complement depletion by CVF attenuates wasp venom-induced nephrotoxicity, suggesting that complement activation plays a primary role in the pathogenesis of wasp venom-induced AKI.

AlphaFold2 assists in providing novel mechanistic insights into the interactions among the LUBAC subunits.

The linear ubiquitin chain assembly complex (LUBAC) is the only known E3 ligase complex in which the ubiquitin-like (UBL) domains of SHARPIN and HOIL-1L interact with HOIP to determine the structural stability of LUBAC. The interactions between subunits within LUBAC have been a topic of extensive research. However, the impact of the LTM motif on the interaction between the UBL domains of SHARPIN and HOIL-1L with HOIP remains unclear. Here, we discover that the absence of the LTM motif in the AlphaFold2-predicted LUBAC structure alters the HOIP-UBA structure. We employ GeoPPI to calculate the changes in binding free energy (ΔG) caused by single-point mutations between subunits, simulating their protein-protein interactions. The results reveal that the presence of the LTM motif decreases the interaction between the UBL domains of SHARPIN and HOIL-1L with HOIP, leading to a decrease in the structural stability of LUBAC. Furthermore, using the AlphaFold2-predicted results, we find that HOIP (629‒695) and HOIP-UBA bind to both sides of HOIL-1L-UBL, respectively. The experiments of Gromacs molecular dynamics simulations, SPR and ITC demonstrate that the elongated domain formed by HOIP (629‒695) and HOIP-UBA, hereafter referred to as the HOIP (466‒695) structure, interacts with HOIL-1L-UBL to form a structurally stable complex. These findings illustrate the collaborative interaction between HOIP-UBA and HOIP (629‒695) with HOIL-1L-UBL, which influences the structural stability of LUBAC.

Hepatic progenitor cell-originated ductular reaction facilitates liver fibrosis through activation of hedgehog signaling.

Background: It is poorly understood what cellular types participate in ductular reaction (DR) and whether DR facilitates recovery from injury or accelerates hepatic fibrosis. The aim of this study is to gain insights into the role of hepatic progenitor cell (HPC)-originated DR during fibrotic progression. Methods: DR in liver specimens of PBC, chronic HBV infection (CHB) or NAFLD, and four rodent fibrotic models by different pathogenic processes was evaluated. Gli1 expression was inhibited in rodent models or cell culture and organoid models by AAV-shGli1 or treating with GANT61. Results: Severity of liver fibrosis was positively correlated with DR extent in patients with PBC, CHB or NAFLD. HPCs were activated, expanded, differentiated into reactive cholangiocytes and constituted "HPC-originated DR", accompanying with exacerbated fibrosis in rodent models of HPC activation & proliferation (CCl4/2-AAF-treated), Μdr2-/- spontaneous PSC, BDL-cholestatic fibrosis or WD-fed/CCl4-treated NASH-fibrosis. Gli1 expression was significantly increased in enriched pathways in vivo and in vitro. Enhanced Gli1 expression was identified in KRT19+-reactive cholangiocytes. Suppressing Gli1 expression by administration of AAV-shGli1 or GANT61 ameliorated HPC-originated DR and fibrotic extent. KRT19 expression was reduced after GANT61 treatment in sodium butyrate-stimulated WB-F344 cells or organoids or in cells transduced with Gli1 knockdown lentiviral vectors. In contrast, KRT19 expression was elevated after transducing Gli1 overexpression lentiviral vectors in these cells. Conclusions: During various modes of chronic injury, Gli1 acted as an important mediator of HPC activation, expansion, differentiation into reactive cholangiocytes that formed DR, and subsequently provoked hepatic fibrogenesis.

Evaluation of metagenomic and pathogen-targeted next-generation sequencing for diagnosis of meningitis and encephalitis in adults: A multicenter prospective observational cohort study in China.

BACKGROUND: Next-generation sequencing (NGS) might aid in the identification of causal pathogens. However, the optimal approaches applied to cerebrospinal fluid (CSF) for detection are unclear, and studies evaluating the application of different NGS workflows for the diagnosis of intracranial infections are limited. METHODS: In this multicenter, prospective observational cohort study, we described the diagnostic efficacy of pathogen-targeted NGS (ptNGS) and metagenomic NGS (mNGS) compared to that of composite microbiologic assays, for infectious meningitis/encephalitis (M/E). RESULTS: In total, 152 patients diagnosed with clinically suspected M/E at four tertiary hospitals were enrolled; ptNGS and mNGS were used in parallel for pathogen detection in CSF. Among the 89 patients who were diagnosed with definite infectious M/E, 57 and 39 patients had causal microbial detection via ptNGS and mNGS, respectively. The overall accuracy of ptNGS was 65.1%, with a positive percent agreement (PPA) of 64% and a negative percent agreement (NPA) of 66.7%; and the overall accuracy of mNGS was 47.4%, with a PPA of 43.8% and an NPA of 52.4% after discrepancy analysis. There was a significant difference in the detection efficiency between these two methods both for PPA (sensitivity) and overall accuracy for pathogen detection (P < 0.05). CONCLUSIONS: NGS tests have provided new information in addition to conventional microbiologic tests. ptNGS seems to have superior performance over mNGS for common causative pathogen detection in CSF for infectious M/E.

Correction: Mechanistic insights into Ag+ induced size-growth from [Au6(DPPP)4]2+ to [Au7(DPPP)4]2+ clusters.

[This corrects the article DOI: 10.1039/D2NA00301E.].

Neutrophil ALDH2 is a new therapeutic target for the effective treatment of sepsis-induced ARDS.

Acetaldehyde dehydrogenase 2 (ALDH2) mutations are commonly found in a subgroup of the Asian population. However, the role of ALDH2 in septic acute respiratory distress syndrome (ARDS) remains unknown. Here, we showed that human subjects carrying the ALDH2rs671 mutation were highly susceptible to developing septic ARDS. Intriguingly, ALDH2rs671-ARDS patients showed higher levels of blood cell-free DNA (cfDNA) and myeloperoxidase (MPO)-DNA than ALDH2WT-ARDS patients. To investigate the mechanisms underlying ALDH2 deficiency in the development of septic ARDS, we utilized Aldh2 gene knockout mice and Aldh2rs671 gene knock-in mice. In clinically relevant mouse sepsis models, Aldh2-/- mice and Aldh2rs671 mice exhibited pulmonary and circulating NETosis, a specific process that releases neutrophil extracellular traps (NETs) from neutrophils. Furthermore, we discovered that NETosis strongly promoted endothelial destruction, accelerated vascular leakage, and exacerbated septic ARDS. At the molecular level, ALDH2 increased K48-linked polyubiquitination and degradation of peptidylarginine deiminase 4 (PAD4) to inhibit NETosis, which was achieved by promoting PAD4 binding to the E3 ubiquitin ligase CHIP. Pharmacological administration of the ALDH2-specific activator Alda-1 substantially alleviated septic ARDS by inhibiting NETosis. Together, our data reveal a novel ALDH2-based protective mechanism against septic ARDS, and the activation of ALDH2 may be an effective treatment strategy for sepsis.

Fructus Xanthii and Magnolia liliiflora Volatile Oils Liposomes-Loaded Thermosensitive in situ Gel for Allergic Rhinitis Management.

Purpose: The aim of the present study was to fabricate a Fructus Xanthii and Magnolia liliiflora volatile oils liposomes-loaded thermosensitive in situ gel (gel/LIP/volatile oil) for effectively treating allergic rhinitis via intranasal administration. Patients and Methods: Particle size, polymer dispersity index (PDI), entrapment effectiveness, and cumulative drug permeation of the developed liposomes were assessed. Then, a thermoreversible in situ gel was created using the liposomes loaded with volatile oils of Fructus Xanthii and Magnolia liliiflora. The effectiveness of this treatment for allergic rhinitis was confirmed by evaluating nasal symptoms, and hematological results, after injecting the formulation into the ovalbumin (OVA)-sensitized mice, we conducted hematoxylin-eosin staining (HE) and immunohistochemistry to evaluate the outcomes. The effects of the gel/LIP/volatile oil formulation for nasal delivery of volatile oil in the treatment of rhinitis were then assessed. Results: The average particle size was 95.1 ± 3.6 nm, and the encapsulation efficiencies of Fructus Xanthii and Magnolia liliiflora volatile oils were 70.42 ± 5.41% and 67.10 ± 6.08%, respectively. Drug loadings of Fructus Xanthii and Magnolia liliiflora volatile oils were 9.10 ± 0.98% and 16.10 ± 1.03%, respectively. The binary formulation produced a gel rapidly in the nasal cavity with a strong mucosal adherence at a temperature of delivering volatile oil to the nasal mucosa steadily and continuously. After nasal administration, the gel/LIP/volatile oil sustained the volatile oil delivery into the mucosa. In comparison to the monolithic formulations, the gel/LIP/volatile oil binary formulation exhibited superior performance in terms of drug delivery capability and pharmacodynamic effects. Conclusion: This binary preparation displayed the ability to deliver drugs to the nasal mucosa and exhibited positive pharmacodynamic effects in treating OVA-induced rhinitis in mice. As a result, it has the potential to serve as a delivery platform for Traditional Chinese medicine in the treatment of allergic rhinitis.

Environmental arsenic pollution induced liver oxidative stress injury by regulating miR-155 through inhibition of AUF1.

Arsenic (As), a common environmental pollutant, has become a hot topic in recent years due to its potentially harmful effects. Liver damage being a central clinical feature of chronic arsenic poisoning. However, the underlying mechanisms remain unclear. We demonstrated that arsenic can lead to oxidative stress in the liver and result in structural and functional liver damage, significantly correlated with the expression of AUF1, Dicer1, and miR-155 in the liver. Interestingly, knockdown AUF1 promoted the up-regulatory effects of arsenic on Dicer1 and miR-155 and the inhibitory effects on SOD1, which exacerbated oxidative damage in rat liver. However, overexpression of AUF1 reversed the up-regulatory effects of arsenic on Dicer1 and miR-155, restored arsenic-induced SOD1 depletion, and attenuated liver oxidative stress injury. Further, we verified the mechanism and targets of miR-155 in regulating SOD1 by knockdown/overexpression of miR-155 and nonsense mutant SOD1 3'UTR experiments. In conclusion, these results powerfully demonstrate that arsenic inhibits AUF1 protein expression, which in turn reduces the inhibitory effect on Dicer1 expression, which promotes miR-155 to act on the SOD1 3'UTR region after high expression, thus inhibiting SOD1 protein expression and enzyme activity, and inducing liver injury. This finding provides a new perspective for the mechanism research and targeted prevention of arsenic poisoning, as well as scientific evidence for formulating strategies to prevent and control environmental arsenic pollution.

Elevated of NDUFA4L2 expression in colon adenocarcinoma is correlated with an unfavorable prognosis and increased immune cell infiltration.

Background: Colon adenocarcinoma (COAD) is a prevalent malignancy worldwide, yet, its underlying pathogenesis and genetic characteristics are still unclear. Previous studies have suggested that NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) may affect tumor progression across various cancers. However, this effect on COAD has rarely been reported. Thus, this study investigated NDUFA4L2's prognostic and diagnostic relevance and explored its potential connection with immune cell infiltration in COAD. Methods: To achieve this, RNA sequencing data from Cancer Genome Atlas (TCGA) was analyzed to assess NDUFA4L2's prognostic value in COAD, and factors relevant to the prognosis of COAD, including NDUFA4L2, were scrutinized using Kaplan-Meier analyses as well as univariate and multivariate Cox regression. A nomogram model was created to project prognosis based on the results of multivariate Cox analysis. Furthermore, gene set enrichment analysis (GSEA) was employed to pinpoint key NDUFA4L2-related pathways, and single-sample GSEA (ssGSEA) on TCGA data was employed to investigate the connections of NDUFA4L2 with cancer immune infiltrations. Results: Our findings revealed significant associations of high NDUFA4L2 expression with poor overall survival, progression-free interval, and disease-specific survival of COAD patients. GSEA indicated close links of NDUFA4L2 with several signaling pathways implicated in tumorigenesis, including extracellular matrix receptor interaction, the intestinal immune network for immunoglobulin A production, natural killer (NK) cell-mediated cytotoxicity, pathways in cancer, cell adhesion molecules, mitogen-activated protein kinase signaling pathway, Hedgehog signaling pathway, transforming growth factor beta signaling pathway, and chemokine signaling pathway. Additionally, ssGSEA identified a positive link between increased NDUFA4L2 expression and higher infiltration degree of various immune cells, such as immature dendritic cells, macrophages, NK cells and dendritic cells. Conclusions: Collectively, our findings demonstrate the association of increased NDUFA4L2 expression with adverse prognosis and heightened immune cell infiltration in COAD patients.

A case of neonatal tsutsugamushi disease diagnosed with the aid of rickettsial macrogenomic detection.

BACKGROUND: Tsutsugamushi, also known as bush typhus, is a naturally occurring disease caused by Orientia tsutsugamushi. We reported a case of vertical mother-to-newborn transmission of Orientia tsutsugamushi infection in a newborn from Yunnan (China). CASE PRESENTATION: Decreased fetal movements were observed at 39 weeks of gestation. After birth, the newborn (female) had recurrent fever, shortness of breath, and bruising around the mouth and extremities. At 5 h 58 min of age, the newborn was admitted for fever, shortness of breath and generalized rash. The liver was palpable 3 cm below the costal margin, and the limbs showed pitting edema. There was subcutaneous bleeding. Investigations suggested heavy infection, myocardial damage, decreased platelets. Treatment with cefotaxime and ampicillin failed. The mother was hospitalized at 29 weeks of gestation with a fever for 4 consecutive days, and an ulcerated crust was found in the popliteal fossa. Due to this pregnancy history, A diagnosis of Orientia tsutsugamushi infection was suspected in our index case and confirmed by macrogenomic testing and she was treated with vancomycin and meropenem, and later azithromycin for 1 week. The newborn was discharged in good general condition, gradually normalizing body temperature, and decreasing rash and jaundice. There were no abnormalities on subsequent blood macrogenomic tests for the baby. And one month later she showed good mental health, sleep, and food intake and no fever, rash, or jaundice. CONCLUSION: Determining the cause of symptoms is the key to treating diseases, especially the rare diseases that can be misdiagnosed. SUITABLE FOR PEOPLE WITH: Infectious Diseases; Neonatology; Obstetrics.

Co-exposure to fluoride and sulfur dioxide induces abnormal enamel mineralization in rats via the FGF9-mediated MAPK signaling pathway.

Fluoride (F) and sulfur dioxide (SO2) contamination is recognized as a public health concern worldwide. Our previous research has shown that Co-exposure to F and SO2 can cause abnormal enamel mineralization. Ameloblastin (AMBN) plays a crucial role in the process of enamel mineralization. However, the process by which simultaneous exposure to F and SO2 influences enamel formation by regulating AMBN expression still needs to be understood. This study aimed to establish in vivo and in vitro models of F-SO2 Co-exposure and investigate the relationship between AMBN and abnormal enamel mineralization. By overexpressing/knocking out the Fibroblast Growth Factor 9 (FGF9) gene, we investigated the impact of FGF9-mediated Mitogen-Activated Protein Kinase (MAPK) signaling on AMBN synthesis to elucidate the mechanism underlying the induction of abnormal enamel mineralization by F-SO2 Co-exposure in rats. The results showed that F-SO2 exposure damaged the structure of rat enamel and ameloblasts. When exposed to F or SO2, gradual increases in the protein expression of FGF9 and phosphorylated p38 mitogen-activated protein kinase (p-P38) were observed. Conversely, the protein levels of AMBN, phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated c-Jun N-terminal kinase (p-JNK) were decreased. AMBN expression was significantly correlated with FGF9, p-ERK, and p-JNK expression in ameloblasts. Interestingly, FGF9 overexpression reduced the levels of p-ERK and p-JNK, worsening the inhibitory effect of F-SO2 on AMBN. Conversely, FGF9 knockout increased the phosphorylation of ERK and JNK, partially reversing the F-SO2-induced downregulation of AMBN. Taken together, these findings strongly demonstrate that FGF9 plays a critical role in F-SO2-induced abnormal enamel mineralization by regulating AMBN synthesis through the JNK and ERK pathways.

Gender differences in all-cause and cardiovascular mortality among US adults: from NHANES 2005-2018.

Background: Gender disparities in mortality have drawn great interest, with previous studies identifying various biological, social, and behavioral factors contributing to the observed gender differences. This study aims to identify the sources of gender disparities in mortality rates and quantify the extent to which these factors mediate the gender differences in all-cause mortality. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2018 were analyzed. A total of 38,924 participants were included in the study. Gender information, socioeconomic status, lifestyle factors, and baseline disease status were obtained through questionnaires. Blood samples were collected to assess serological indicators. All-cause and cardiovascular mortality were considered as primary and secondary outcomes, respectively. Results: The study with an average age of 50.1 ± 17.9 years. Among the participants, 50.7% were women, and 41.8% were non-Hispanic White. The median follow-up length was 87 months [Inter-Quartile Range (IQR): 47-128]. Men showed higher rates of all-cause and cardiovascular mortality compared to women in both the general population and the population with cardiovascular disease. After adjustment for potential confounders (age, race, marital status, socioeconomic status, lifestyle level, smoking status, cardiovascular disease, hypertension, diabetes and cancer), the men: women hazard ratios (HRs) for all-cause and cardiovascular mortality were 1.58 [95% Confidence Interval (CI): 1.48-1.68] and 1.60 (95%CI:1.43-1.80) in the general population. Among individuals with cardiovascular disease, the fully adjusted HR for all-cause mortality was 1.34 (95% CI: 1.20 to 1.51), and for cardiovascular mortality, the fully adjusted HRs was 1.52 (95% CI: 1.26 to 1.83). Mediation analysis revealed that uric acid levels significantly mediated the association between gender and all-cause mortality, accounting for 17.53% (95% CI: 11.0% to 23.7%) in the general population and 27.47% (95% CI: 9.0% to 13.6%) in the population with cardiovascular disease. Conclusions: The study highlights the complex interplay of biological and social factors contributing to gender disparities in mortality. Uric acid was identified as key mediators of the gender-mortality association. These findings can inform targeted interventions aimed at reducing gender disparities in mortality and promoting better public health outcomes.

Coactivation of Hydrogen Peroxide Using Pyrogenic Carbon and Magnetite for Sustainable Oxidation of Organic Pollutants.

Pyrogenic carbon and magnetite (Fe3O4) were mixed together for the activation of hydrogen peroxide (H2O2), aiming to enhance the oxidation of refractory pollutants in a sustainable way. The experimental results indicated that the straw-derived carbon obtained by pyrolysis at 500-800 °C was efficient on coactivation of H2O2, and the most efficient one was that prepared at 700 °C (C700) featured with abundant defects. Specifically, the reaction rate constant (kobs) for removal of an antibiotic ciprofloxacin in the coactivation system (C700/Fe3O4/H2O2) is 12.5 times that in the magnetite-catalyzed system (Fe3O4/H2O2). The faster pollutant oxidation is attributed to the sustainable production of •OH in the coactivation process, in which the carbon facilitated decomposition of H2O2 and regeneration of Fe(II). Besides the enhanced H2O2 utilization in the coactivation process, the leaching of iron was controlled within the concentration limit in drinking water (0.3 mg·L-1) set by the World Health Organization.

The impact of varying trolley case usage modes and weights on body posture.

OBJECTIVE: To study the body posture characteristics when walking with trolley case, and to explore the effects of different usage methods and weights of trolley case on body posture characteristics. METHODS: Fifteen subjects pushed and pulled(Condition 1 and 2) the case with three load weights of 10 %, 20 % and 30 % of their own body weight with 0 % no load as baseline for both conditions. The basic gait parameters, kinematic and kinetic data were collected using the VICON infrared motion capture system and a 3D force platform. Two repeated measures factor (condition×weight) analysis of variance was used for statistical analysis of the gait temporal and spatial parameters, as well as trunk angle, kinetic ground reaction force, shoulder joint force, and trunk moment. RESULTS: Significant condition*weight interactions were detected in DLST (Double Limb Stance Time) (F=5.341，P = 0.006), GRF (Ground Reaction Force) in frontal plane (F=10.507, p < 0.001) and vertical plane (F=3.751, p = 0.021), shoulder joint force in sagittal plane (F=21.129, p < 0.001), and flexion-extension angle of the trunk in the sagittal plane (F=4.888, p < 0.010). Significant main effects were detected in walking speed (F=35.842, p < 0.001), right support time (F=12.156, p < 0.001), left swing time (F=8.506, p < 0.001), left support time (F=1.122, p < 0.001), right step length (F=33.900, p < 0.001), and left step length (F=14.960, p < 0.001) under different weights. A significant main effect was detected in sagittal GRF (F=11.77, p < 0.001), trunk rotation angle (F=4.124, p = 0.016), amplitude of COM (F=2.993, p = 0.046), under different weights. CONCLUSION: When the weight of the case exceeds 20 % of the body weight, from the perspective of energy efficiency, the push method is more advantageous than the pull method. When walking with luggage, people tend to maintain the stability of their trunk posture by adjusting the force on their arms more often.

Nano-Drug Delivery Systems Based on Natural Products.

Natural products have proven to have significant curative effects and are increasingly considered as potential candidates for clinical prevention, diagnosis, and treatment. Compared with synthetic drugs, natural products not only have diverse structures but also exhibit a range of biological activities against different disease states and molecular targets, making them attractive for development in the field of medicine. Despite advancements in the use of natural products for clinical purposes, there remain obstacles that hinder their full potential. These challenges include issues such as limited solubility and stability when administered orally, as well as short durations of effectiveness. To address these concerns, nano-drug delivery systems have emerged as a promising solution to overcome the barriers faced in the clinical application of natural products. These systems offer notable advantages, such as a large specific surface area, enhanced targeting capabilities, and the ability to achieve sustained and controlled release. Extensive in vitro and in vivo studies have provided further evidence supporting the efficacy and safety of nanoparticle-based systems in delivering natural products in preclinical disease models. This review describes the limitations of natural product applications and the current status of natural products combined with nanotechnology. The latest advances in nano-drug delivery systems for delivery of natural products are considered from three aspects: connecting targeting warheads, self-assembly, and co-delivery. Finally, the challenges faced in the clinical translation of nano-drugs are discussed.

Cigarette tar accelerates atherosclerosis progression via RIPK3-dependent necroptosis mediated by endoplasmic reticulum stress in vascular smooth muscle cells.

BACKGROUND: Tar is the main toxic of cigarettes, and its effect on atherosclerosis progression and the underlying mechanisms remain largely unknown. Vascular smooth muscle cells (VSMCs) play a key role in atherogenesis and plaque vulnerability. The present study sought to investigate the mechanism of atherosclerosis progression through tar-induced VSMC necroptosis, a recently described form of necrosis. METHODS: The effect of tar on atherosclerosis progression and VSMC necroptosis was examined in ApoE-/- mice and cultured VSMCs. The role of necroptosis in tar-induced plaque development was evaluated in RIPK3-deletion mice (ApoE-/-RIPK3-/-). The key proteins of necroptosis in carotid plaques of smokers and non-smokers were also examined. Quantitative proteomics of mice aortas was conducted to further investigate the underlying mechanism. Pharmacological approaches were then applied to modulate the expression of targets to verify the regulatory process of tar-induced necroptosis. RESULTS: Tar administration led to increased atherosclerotic plaque area and reduced collagen and VSMCs in ApoE-/- mice. The expression of RIPK1、RIPK3、and MLKL in VSMCs of plaques were all increased in tar-exposed mice and smokers. RIPK3 deletion protected against VSMC loss and plaque progression stimulated by tar. In mechanistic studies, quantitative proteomics analysis of ApoE-/- mice aortas suggested that tar triggered endoplasmic reticulum (ER) stress. PERK-eIF2α-CHOP axis was activated in tar-treated VSMCs and atherosclerotic plaque. Inhibition of ER stress using 4PBA significantly reduced plaque progression and VSMC necroptosis. Further study revealed that ER stress resulted in calcium (Ca2+) release into mitochondria and cytoplasm. Elevated Ca2+ levels lead to mitochondrial dysfunction and excessive reactive oxygen species (ROS) production, which consequently promote RIPK3-dependent necroptosis. In addition, Ca2+/calmodulin-dependent protein kinase II (CaMKII) activated by cytosolic Ca2+ overload binds to RIPK3, accounting for necroptosis. CONCLUSION: The findings revealed that cigarette tar promoted atherosclerosis progression by inducing RIPK3-dependent VSMC necroptosis and identified novel avenues of ER stress and Ca2+ overload.