Regulating Tumor-Associated Macrophage Polarization by Cyclodextrin-Modified PLGA Nanoparticles Loaded with R848 for Treating Colon Cancer.

Purpose: This study aimed to develop a novel and feasible modification strategy to improve the solubility and antitumor activity of resiquimod (R848) by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodextrin (2-HP-ß-CD). Methods: R848-loaded PLGA nanoparticles modified with 2-HP-ß-CD (CD@R848@NPs) were synthesized using an enhanced emulsification solvent-evaporation technique. The nanoparticles were then characterized in vitro by several methods, such as scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, particle size analysis, and zeta potential analysis. Then, the nanoparticles were loaded with IR-780 dye and imaged using an in vivo imaging device to evaluate their biodistribution. Additionally, the antitumor efficacy and underlying mechanism of CD@R848@NPs in combination with an anti-TNFR2 antibody were investigated using an MC-38 colon adenocarcinoma model in vivo. Results: The average size of the CD@R848@NPs was 376 ± 30 nm, and the surface charge was 21 ± 1 mV. Through this design, the targeting ability of 2-HP-ß-CD can be leveraged and R848 is delivered to tumor-supporting M2-like macrophages in an efficient and specific manner. Moreover, we used an anti-TNFR2 antibody to reduce the proportion of Tregs. Compared with plain PLGA nanoparticles or R848, CD@R848@NPs increased penetration in tumor tissues, dramatically reprogrammed M1-like macrophages, removed tumors and prolonged patient survival. Conclusion: The new nanocapsule system is a promising strategy for targeting tumor, reprogramming tumor -associated macrophages, and enhancement immunotherapy.

Representing Context and Priority in Working Memory.

The ability to prioritize among contents in working memory (WM) is critical for successful control of thought and behavior. Recent work has demonstrated that prioritization in WM can be implemented by representing different states of priority in different representational formats. Here, we explored the mechanisms underlying WM prioritization by simulating the double serial retrocuing task with recurrent neural networks. Visualization of stimulus representational dynamics using principal component analysis revealed that the network represented trial context (order of presentation) and priority via different mechanisms. Ordinal context, a stable property lasting the duration of the trial, was accomplished by segregating representations into orthogonal subspaces. Priority, which changed multiple times during a trial, was accomplished by separating representations into different strata within each subspace. We assessed the generality of these mechanisms by applying dimensionality reduction and multiclass decoding to fMRI and EEG data sets and found that priority and context are represented differently along the dorsal visual stream and that behavioral performance is sensitive to trial-by-trial variability of priority coding, but not context coding.

Design of Bombyx mori (B. mori) Silk Fibroin Microspheres for Developing Biosafe Sunscreen.

Sunscreens play a crucial role in protecting the skin from ultraviolet (UV) damage. However, present commercial sunscreens have a tendency to generate free radicals in the UV window, resulting in serious inflammatory responses and health problems. In this study, we demonstrate that silk fibroin microspheres (SFMPs) assembled from regenerated silk fibroin (SF) could scavenge free radicals while preventing UV irradiation and thus present a promising sunscreen. The SFMP reflected more UV light than SF and presented a higher stability than that of organic commercial sunscreens. In vitro analysis proved that SFMP could more efficiently scavenge the hydroxy radical and reduce the intracellular reactive oxygen than titanium dioxide (TiO2). In vivo experiments exhibited that SFMP provided stronger skin protection against UV irradiation than commercial sunscreens and TiO2. Furthermore, SFMP treatment significantly inhibited the skin inflammatory response. This work suggests that the SFMP has great potential to be developed into a biosafe sunscreen.

Estimating the economic burden of stroke in China: a cost-of-illness study.

OBJECTIVES: Stroke imposes a heavy economic burden and loss of productivity on individuals and society. This study assessed a range of crucial factors, including direct costs and indirect costs, to gauge the economic implications of stroke in China. These outcomes were evaluated with specific reference to the year 2018, using the Chinese yuan (¥) as the unit of measurement and providing the corresponding purchasing power parity dollar ($PPP) currency value. METHODS: A cost-of-illness methodology was used to ascertain the economic implications of stroke in 2018. Within the constraints of this approach, economic costs were defined as 'direct costs' or 'indirect costs'. We estimated direct costs from sample data, the National Health Service Survey and the National Health Account and Health Statistical Yearbook. A human capital method was used to conservatively estimate indirect costs. RESULTS: In 2018, of the economic burden of stroke in China, the direct costs were ¥247.8 billion ($PPP 58.6 billion) and indirect costs were ¥704.4 billion ($PPP 166.5 billion). The curative care expenditure for stroke was ¥193.1 billion ($PPP 45.7 billion), consuming nearly 5.5% of curative expenditure. The cost of stroke treatment relied heavily on public financing, with 58% from social health insurance and 14% from government sources. CONCLUSIONS: A significant economic burden is imposed by stroke on China's economy, and there is a risk of underestimating this burden if indirect costs are not comprehensively considered. The importance of implementing effective preventive measures and screening strategies for stroke, with a particular focus on high-risk populations, is underscored by this study's findings. Such investments in public health have the potential to yield substantial benefits.

Chemerin promotes invasion of oral squamous cell carcinoma by stimulating IL-6 and TNF-α production via STAT3 activation.

AIMS: Elevated levels of adipokine chemerin have been identified in oral squamous cell carcinoma (OSCC) and found to be associated with metastasis to the cervical lymph nodes. The underlying mechanism through which chemerin affects OSCC progression is unclear. The aims of this study were firstly to determine chemerin levels and cytokine concentrations in serum from patients with OSCC and in OSCC cell cultures, and secondly to observe chemerin effects on OSCC cell cytokine secretion, migration, and invasion in vitro. METHODS: Serum samples were collected from 20 patients diagnosed with OSCC, including groups with (LN+) and without (LN-) cervical lymph node metastasis. A Luminex liquid suspension assay was used to quantify serum concentrations of 27 types of cytokines. Correlations between chemerin and cytokines (i.e., IL-6, IL-15, GM-CSF, RANTES, TNF-α, and VEGF) were analyzed. ELISAs (enzyme-linked immunosorbent assays) were used to determine concentrations of chemerin and selected cytokines in serum and in supernatants of OSCC cell cultures (SCC9 and SCC25 cell lines). OSCC cells were stimulated with human recombinant chemerin, STAT3 inhibitor, or IL-6 together with TNF-α neutralizing antibodies. Phosphorylated STAT3 protein levels were measured with western blot analysis. OSCC cell migration and invasion were investigated with Transwell assays. RESULTS: Compared to the LN- group, OSCC patients with cervical lymph node metastasis had higher levels of IL-6 (P = 0.006), IL-15 (P = 0.020), GM-CSF (P = 0.036), RANTES (P = 0.032), TNF-α (P = 0.005), VEGF (P = 0.006), and chemerin (P = 0.001). Patients' serum chemerin levels correlated directly with IL-6, GM-CSF, TNF-α, and VEGF levels in OSCC patients. Exogenous recombinant chemerin treatment promoted secretion of IL-6 and TNF-α via activation of STAT3 in OSCC cells. Chemerin induced OSCC-cell migration and invasion, and these effects were reduced by IL-6 and TNF-α neutralizing antibodies. CONCLUSION: Our findings indicate that chemerin may play a role in advancing OSCC progression by increasing production of IL-6 and TNF-α, perhaps via a mechanism involving STAT3 signaling.

Combinational delivery of TLR4 and TLR7/8 agonist enhanced the therapeutic efficacy of immune checkpoint inhibitors to colon tumor.

Immunotherapy is regarded as a potent cancer treatment, with DC vaccines playing a crucial role. Although clinical trials have demonstrated the safety and efficacy of DC vaccines, loading antigens in vitro is challenging, and their therapeutic effects remain unpredictable. Moreover, the diverse subtypes and maturity states of DCs in the body could induce both immune responses and immune tolerance, potentially affecting the vaccine's efficacy. Hence, the optimization of DC vaccines remains imperative. Our study discovered a new therapeutic strategy by using CT26 and MC38 mouse colon cancer models, as well as LLC mouse lung cancer models. The strategy involved the synergistic activation of DCs through intertumoral administration of TLR4 agonist high-mobility group nucleosome binding protein 1 (HMGN1) and TLR7/8 agonist (R848/resiquimod), combined with intraperitoneal administration of TNFR2 immunosuppressant antibody. The experimental results indicated that the combined use of HMGN1, R848, and α-TNFR2 had no effect on LLC cold tumors. However, it was effective in eradicating CT26 and MC38 colon cancer and inducing long-term immune memory. The combination of these three drugs altered the TME and promoted an increase in anti-tumor immune components. This may provide a promising new treatment strategy for colon cancer.

Injectable Bombyx mori (B. mori) silk fibroin/MXene conductive hydrogel for electrically stimulating neural stem cells into neurons for treating brain damage.

Brain damage is a common tissue damage caused by trauma or diseases, which can be life-threatening. Stem cell implantation is an emerging strategy treating brain damage. The stem cell is commonly embedded in a matrix material for implantation, which protects stem cell and induces cell differentiation. Cell differentiation induction by this material is decisive in the effectiveness of this treatment strategy. In this work, we present an injectable fibroin/MXene conductive hydrogel as stem cell carrier, which further enables in-vivo electrical stimulation upon stem cells implanted into damaged brain tissue. Cell differentiation characterization of stem cell showed high effectiveness of electrical stimulation in this system, which is comparable to pure conductive membrane. Axon growth density of the newly differentiated neurons increased by 290% and axon length by 320%. In addition, unfavored astrocyte differentiation is minimized. The therapeutic effect of this system is proved through traumatic brain injury model on rats. Combined with in vivo electrical stimulation, cavities formation is reduced after traumatic brain injury, and rat motor function recovery is significantly promoted.

Unveiling the exciton dissociation dynamics steered by built-in electric fields in conjugated microporous polymers for photoreduction of uranium (VI) from seawater.

Developing highly efficient photocatalysts based on conjugated microporous polymers (CMPs) are often impeded by the intrinsically large exciton binding energy and sluggish charge transfer kinetics that result from their vulnerable driving force. Herein, a family of pyrene-based nitrogen-implanted CMPs were constructed, where the nitrogen gradient was regulated. Accordingly, the built-in electric field endowed by the nitrogen gradient dramatically accelerates the dissociation of exciton into free carriers, thereby enhancing charge separation efficiency. As a result, PyCMP-3N generated by polymerization of 1,3,6,8-tetrakis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrene and 2,4,6-tris(4-bromophenyl)-1,3,5-triazine featured an optimized built-in electric field and exhibited the highest photocatalytic removal efficiency of uranium (VI) (99.5 %). Our proposed strategy not only provides inspiration for constructing the built-in electric field by controlling nitrogen concentration gradients, but also offers an in-depth understanding the crucial role of built-in electric field in exciton dissociation and charge transfer, efficiently promoting CMPs photocatalysis.

Heavy metal migration dynamics and solid-liquid distribution strategy in abandoned tailing soils.

The tailings soil originating from an abandoned sulfur-iron mine in Sichuan Province, China, exhibits elevated concentrations of heavy metals (HMs) and possesses limited soil conservation capacity. Variability soil particle size fractions (PSFs) contributes to an increased risk of HMs ion migration. Existing research on HMs behavior has focused on the bulk soil scale, resulting in a dearth of comprehensive information concerning different particle sizes and colloid scales. We collected soil samples from upstream source (XWA), migration path (XWB), and downstream farmland (XWC) of an abandoned tailing and categorized into sand, silt, clay, colloid and dissolved, respectively. The investigation primarily aimed to elucidate the solid-liquid distribution trade-off strategies of soil HMs along migration pathway. Results show that PSFs composition predominantly influences HMs solid-liquid distribution. In the mining area, large particles serve as the principal component for HMs enrichment. However, along the migration pathway, the proportion of highly mobile fine particles increases, shifting HMs from solid to liquid phase. Furthermore, inorganic elements such as Mg, Al, and Fe influence on HMs distribution within PSFs through various reactions, whereas organic matter and glomalin-related soil protein (GRSP) also exert regulatory roles. Increasing the proportion of large particles can reduce the risk of HMs migration.

Regenerated silk fibroin coating stable liquid metal nanoparticles enhance photothermal antimicrobial activity of hydrogel for wound infection repair.

The integration of liquid metal (LM) and regenerated silk fibroin (RSF) hydrogel holds great potential for achieving effective antibacterial wound treatment through the LM photothermal effect. However, the challenge of LM's uncontrollable shape-deformability hinders its stable application. To address this, we propose a straightforward and environmentally-friendly ice-bath ultrasonic treatment method to fabricate stable RSF-coated eutectic gallium indium (EGaIn) nanoparticles (RSF@EGaIn NPs). Additionally, a double-crosslinked hydrogel (RSF-P-EGaIn) is prepared by incorporating poly N-isopropyl acrylamide (PNIPAAm) and RSF@EGaIn NPs, leading to improved mechanical properties and temperature sensitivity. Our findings reveal that RSF@EGaIn NPs exhibit excellent stability, and the use of near-infrared (NIR) irradiation enhances the antibacterial behavior of RSF-P-EGaIn hydrogel in vivo. In fact, in vivo testing demonstrates that wounds treated with RSF-P-EGaIn hydrogel under NIR irradiation completely healed within 14 days post-trauma infection, with the formation of new skin and hair. Histological examination further indicates that RSF-P-EGaIn hydrogel promoted epithelialization and well-organized collagen deposition in the dermis. These promising results lay a solid foundation for the future development of drug release systems based on photothermal-responsive hydrogels utilizing RSF-P-EGaIn.

Outpatient depression current care expenditure changes in Liaoning Province from 2015 to 2020: a study based on the "system of health accounts 2011".

Introduction: Depression is the leading cause of disability worldwide and has become a health issue of global concern. Based on the "System of Health Accounts 2011" (SHA 2011) for patients with depression, this paper studies the changes in the current curative expenditure (CCE) of outpatient depression in Liaoning Province, China, and provides policy recommendations. Method: A stratified multistage random sample of 56,994 patients with depression included from 1,227 healthcare facilities in Liaoning Province were included. The significance of differences in variables within groups was analyzed by univariate analysis (including descriptive statistics analysis, Mann-Whitney U test and Kruskal-Wallis H test), and factors influencing depression outpatient CCE were analyzed by multiple linear regression analysis and constructing structural equation models (SEM). Results: The CCE of outpatient depression was ranging from CNY 75.57 million to CNY 100.53 million in 2015-2020, with the highest of CNY 100.53 million in 2018, CNY 103.28 million in 2019. Medical expenditures are mainly concentrated in general hospitals and provincial healthcare institutions, accounting for about 90% of all provincial scope expenditures. The multiple regression results show that provincial healthcare institutions, purchase of drug, select medical treatment for depression, general hospitals and urban employees' health insurance are the main influencing factors for depression outpatient CCE. The results of SEM show that insurance status negative impact outpatient expenditure. Conclusion: Health insurance is an important factor in equitable access to healthcare resources for patients, and medication expenditure is the influential factor affecting the high expenditure of outpatient clinics. It is of great importance to reduce the medical burden of patients by increasing the coverage of medical insurance, increasing the proportion of bills that are eligible for reimbursement, and improving the system by guaranteeing the supply of psychotropic medication.

Posterior Percutaneous Endoscopic Cervical Discectomy for Single-Level Soft, Huge Central Disc Herniation.

BACKGROUND: Posterior percutaneous endoscopic cervical discectomy (PPECD) has been proven safe and effective for foraminal cervical disc herniation (CDH). However, central CDH has long been considered as the contraindication of PPECD, because the path is obstructed by the spinal cord and nerve root. OBJECTIVES: To preliminarily assess the feasibility, safety, and effectiveness of PPECD for single-level soft, huge central CDH. STUDY DESIGN: A retrospective cohort study. SETTING: Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College). METHODS: Between 2017 and 2020, 31 patients diagnosed with single-level soft, huge central CDH were treated by PPECD. Primary outcomes included the measures of neck and radicular pain based on the numeric rating scale (NRS) and cervical neurologic status based on the Japanese Orthopedic Association (JOA) score. The global outcome was assessed using the Odom's criteria at one-year follow-up. RESULTS: Compared to the baseline, there was a constant and significant reduction of NRS-rated pain and improvement of JOA-rated cervical neurologic status postoperatively (P < 0.01). According to the Odom's criteria, 96.8% (30/31) of patients had satisfactory postoperative clinical improvement (excellent or good outcomes) at one-year follow-up. Complications included C5 nerve root palsy and spinal cord injury. The total complication rate was 16.5% (2/31), but these complications were temporary and not catastrophic. LIMITATIONS: The limitations of this study include the volume of the sample, a short follow-up period, and the lack of a control group. CONCLUSIONS: Our preliminary experience indicates that PPECD is a feasible and promising alternative for symptomatic single-level soft, huge central CDH.

Ultrafast Bi-Directional Bending Moisture-Responsive Soft Actuators through Superfine Silk Rod Modified Bio-Mimicking Hierarchical Layered Structure.

Development of stimulus-responsive materials is crucial for novel soft actuators. Among these actuators, the moisture-responsive actuators are known for their accessibility, eco-friendliness, and robust regenerative attributes. A major challenge of moisture-responsive soft actuators (MRSAs) is achieving significant bending curvature within short response times. Many plants naturally perform large deformation through a layered hierarchical structure in response to moisture stimuli. Drawing inspiration from the bionic structure of Delosperma nakurense (D. nakurense) seed capsule, here the fabrication of an ultrafast bi-directional bending MRSAs is reported. Combining a superfine silk fibroin rod (SFR) modified graphene oxide (GO) moisture-responsive layer with a moisture-inert layer of reduced graphene oxide (RGO), this actuator demonstrated large bi-directional bending deformation (-4.06 ± 0.09 to 10.44 ± 0.00 cm-1 ) and ultrafast bending rates (7.06 cm-1  s-1 ). The high deformation rate is achieved by incorporating the SFR into the moisture-responsive layers, facilitating rapid water transmission within the interlayer structure. The complex yet predictable deformations of this actuator are demonstrated that can be utilized in smart switch, robotic arms, and walking device. The proposed SFR modification method is simple and versatile, enhancing the functionality of hierarchical layered actuators. It holds the potential to advance intelligent soft robots for application in confined environments.

Botulinum toxin type A ameliorates rat dorsal root ganglia neuron pyroptosis in postherpetic neuralgia by upregulating cathelicidin antimicrobial peptide to inhibit neutrophil elastase.

Botulinum toxin type A (BoNT/A) has exhibited efficacy in postherpetic neuralgia (PHN) treatment, and this study aims to uncover its underlying mechanisms. Resiniferatoxin (RTX)-induced PHN rats were given BoNT/A. Rat postoperative pain behaviors were assessed by Von Frey test. Cleaved-synaptosomal protein 25 kDa (cl-SNAP-25) or cathelicidin antimicrobial peptide (CAMP) expression in rat dorsal root ganglia (DRG) was detected by immunofluorescence or immunohistochemistry. Healthy rat-derived DRG neurons were transfected, incubated with lipopolysaccharides (LPS)/adenosine 5'-triphosphate (ATP) to stimulate pyroptosis and treated with BoNT/A. The CCK-8, Western blot, ELISA, and qRT-PCR were used to assess the viability, levels of pyroptosis-related proteins proinflammatory cytokine levels, as well as CAMP and ELANE mRNA levels. BoNT/A (30 U/kg) promoted cl-SNAP-25 expression in rat DRG and reversed RTX-induced decrease of rat paw withdrawal thresholds and CAMP expression and increase of pyroptosis-associated protein and inflammatory factor expression in rat DRG. CAMP interacted with ELANE in rat DRG neurons. BoNT/A attenuated LPS/ATP-stimulated inhibition of viability and CAMP expression and upregulation of inflammatory mediators, pyroptosis-related proteins, and ELANE expression in rat DRG neurons, which was counteracted by CAMP silencing. However, ELANE knockdown offset the effect of CAMP silencing in LPS/ATP/BoNT/A-treated rat DRG neurons. On the whole, BoNT/A alleviates rat DRG neuron pyroptosis during PHN by upregulating CAMP to inhibit ELANE.

Phytochemical analysis and hepatotoxicity assessment of braised Polygoni Multiflori Radix (Wen-He-Shou-Wu).

Polygoni Multiflori Radix (PMR) is a medicinal herb commonly used in China and Eastern Asia. Recently, the discovery of hepatotoxicity in PMR has received considerable attention from scientists. Processing is a traditional Chinese medicine technique used for the effective reduction of toxicity. One uncommon technique is the braising method-also known as 'Wen-Fa' in Chinese-which is used to prepare tonics or poisonous medications. Braised PMR (BPMR)-also known as 'Wen-He-Shou-Wu'-is one of the processed products of the braising method. However, the non-volatile components of BPMR have not been identified and examined in detail, and therefore, the hepatotoxic advantage of BPMR remains unknown. In this study, we compared the microscopic characteristics of different samples in powder form using scanning electron microscopy (SEM), investigated the non-volatile components, assessed the effects of different processed PMR products on the liver, and compared the differences between BPMR and PMR Praeparata recorded in the Chinese Pharmacopoeia (2020 edition). We found that the hepatotoxicity of BPMR was dramatically decreased, which may be related to an increase in polysaccharide content and a decrease in toxic substances. The present study provides an important foundation for future investigations of the processing mechanisms of BPMR.

Exploring the role of aquaporin proteins in the pre-protective action of Sanwei sandalwood decoction from adriamycin-induced chronic heart failure: A mechanistic study.

This study employed network pharmacology, molecular docking technology, and modern pharmacological research methods to explore the pre-protective effect and underlying mechanism, Sanwei sandalwood decoction, against Adriamycin-induced Chronic Heart Failure, with a particular focus on the involvement of aquaporins. Additionally, the study highlighted aquaporins as a significant factor, affecting processes such as cell proliferation and response to reactive oxygen species. The results of in vivo experiments demonstrated that the administration of Sanwei sandalwood decoction in rats with chronic heart failure led to an enhancement in the ejection fraction and improved heart ejection function. Additionally, the decoction significantly reduced the serum levels of Creatine Kinase, Creatine Kinase-MB, and N-terminal pro-B-type natriuretic peptide. Furthermore, the relative expression of Aquarporin-1, 4, and 7mRNAs and proteins in the hearts of rats with chronic heart failure was down-regulated upon treatment. Overall, Sanwei sandalwood decoction can have an effective cardioprotective effect in preventing Adriamycin-induced Chronic Heart Failure in rats.

A novel metabolism-related gene signature in patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) remains a global challenge as it is the sixth most common neoplasm worldwide and the third leading cause of cancer-related death. A key feature of HCC is abnormal metabolism, which promotes cancer cell proliferation, survival, invasion, and metastasis. However, the significance of metabolism-related genes (MRGs) in HCC remains to be elucidated. Here, we aim to establish a novel metabolism-related prognostic signature for the prediction of patient outcomes and to investigate the value of MRG expression in the prognostic prediction of HCC. In our research, a Metabolism-Related Risk Score (MRRS) model was constructed using 14 MRGs (DLAT, SEPHS1, ACADS, UCK2, GOT2, ADH4, LDHA, ME1, TXNRD1, B4GALT2, AK2, PTDSS2, CSAD, and AMD1). The Kaplan-Meier curve confirmed that the MRRS has a high accuracy in predicting the prognosis of HCC patients (p < 0.001). According to the MRRS model, the area under the curve (AUC) values for predicting the prognosis of patients with hepatocellular carcinoma at 1, 3, and 5 years reached 0.829, 0.760, and 0.739, respectively. Functional analyses revealed that signaling pathways associated with the cell cycle were largely enriched by differential genes between high and low-risk groups. In addition, dendritic cells (DCs) (p < 0.001), CD4+ T cells (p < 0.01), CD8+ T cells (p < 0.001), B cells (p < 0.001), neutrophils (p < 0.001), macrophages (p < 0.001) had a higher proportion of infiltrates in high-risk populations. Low GOT2 expression is associated with poor prognosis in patients with hepatocellular carcinoma. Knockdown of GOT2 significantly increased the migration capacity of the Huh7 and MHCC97H hepatocellular carcinoma lines. Our research reveals that GOT2 is negatively related to the survival of patients with hepatocellular carcinoma and GOT2 may contribute to tumor progression by inhibiting the ability of tumor cells to migrate.

Sanwei sandalwood decoction improves function of the gut microbiota in heart failure.

Objective: To investigate the effects of Sanwei sandalwood decoction on improving function of the intestinal flora in doxorubicin-induced heart failure in rats. Materials and methods: Thirty Sprague-Dawley rats were screened and randomly assigned into a blank group, a model group, and a Sanwei sandalwood decoction group (treatment group). The rat model of heart failure was prepared and established in the latter two groups. After successful model establishment, the treatment group received Sanwei sandalwood decoction by continuous gavage at 2 g/kg, once daily for 4 weeks. The other groups were given an equivalent volume of saline. After the final dose, fecal samples were collected from each group and analyzed by macrogenomics and nontargeted metabolomics to characterize the intestinal flora and associated metabolites. Results: The composition of gut microbiota was significantly different between the three groups. There were 778,808 common genes between the blank and model groups, while 49,315 genes were lost and 521,008 were gained in the model group relative to the blank group. At the phylum level, all groups of rat fecal samples were dominated by Firmicutes, Bacteroidota, Actinobacteria, and Proteobacteria. At the genus level, the microbial community composition in all experimental groups of rat fecal samples was dominated by Lactobacillus, Bifidobacterium, Limosilactobacillus, Allobaculum, Prevotella, and Ligilactobacillus spp. Interestingly, cluster analysis was performed on the top 30 KEGG ontology (KO) terms displaying significant differences in relative abundance in the rat fecal microbiome among experimental groups. The relative frequency of posttranslational modification, coenzyme transport and metabolism, cell wall, membrane, and envelope biogenesis in the eggNOG and CAZy databases. In the nontargeted metabolomics, the group principal component analysis revealed that the groups were well distinguished from one another. The different metabolites were screened with VIP >1, and the KEGG different metabolite classification and enrichment analysis revealed that there includes 15 metabolites pathway, including loxoprofen, conifery-l-acetate, trichilin A, and others. The arachidonic acid pathway also accounted for a significant portion of the KEGG pathway classification analysis. Conclusion: Sanwei sandalwood decoction positively affects the intestinal microbial environment of rats with heart failure, improving the gut dysbiosis that is caused by the condition. This treatment intervention inhibits the growth of pathogenic bacteria and promotes the growth of beneficial species.

Hierarchically patterned protein scaffolds with nano-fibrillar and micro-lamellar structures modulate neural stem cell homing and promote neuronal differentiation.

Biophysical factors are essential in cell survival and behaviors, but constructing a suitable 3D microenvironment for the recruitment of stem cells and exerting their physiological functions remain a daunting challenge. Here, we present a novel silk fibroin (SF)-based fabrication strategy to develop hierarchical microchannel scaffolds for biomimetic nerve microenvironments in vitro. We first modulated the formation of SF nanofibers (SFNFs) that mimic the nanostructures of the native extracellular matrix (ECM) by using graphene oxide (GO) nanosheets as templates. Then, SFNF-GO systems were shaped into 3D porous scaffolds with aligned micro-lamellar structures by freeze-casting. The interconnected microchannels successfully induced cell infiltration and migration to the SFNF-GO scaffolds' interior. Meanwhile, the nano-fibrillar structures and the GO component significantly induced neural stem cells (NSCs) to differentiate into neurons within a short timeframe of 14 d. Importantly, these 3D hierarchical scaffolds induced a mild inflammatory response, extensive cell recruitment, and effective stimulation of NSC neuronal differentiation when implanted in vivo. Therefore, these SFNF-GO lamellar scaffolds with distinctive nano-/micro-topographies hold promise in the fields of nerve injury repair and regenerative medicine.

Deposition behaviors of carboxyl-modified polystyrene nanoplastics with goethite in aquatic environment: Effects of solution chemistry and organic macromolecules.

The ubiquitous nanoplastics (NPs) in the environment are emerging contaminants due to their risks to human health and ecosystems. The interaction between NPs and minerals determines the environmental and ecological risks of NPs. In this study, the deposition behaviors of carboxyl modified polystyrene nanoplastics (COOH-PSNPs) with goethite (α-FeOOH) were systematically investigated under various solution chemistry and organic macromolecules (OMs) conditions (i.e., pH, ionic type, humic acid (HA), sodium alginate (SA), and bovine serum albumin (BSA)). The study found that electrostatic interactions dominated the interaction between COOH-PSNPs and goethite. The deposition rates of COOH-PSNPs decreased with an increase in solution pH, due to the enhanced electrostatic repulsion by higher pH. Introducing cations or anions could compress the electrostatic double layers and compete for interaction sites on COOH-PSNPs and goethite, thereby reducing the deposition rates of COOH-PSNPs. The stabilization effects, which were positive with ions valence, followed the orders of NaCl ≈ KCl < CaCl2, NaNO3 ≈ NaCl < Na2SO4 < Na3PO4. Specific adsorption of SO42- or H2PO4- caused a potential reversal of goethite from positive to negative, leading to the electrostatic forces between COOH-PSNPs and goethite changed from attraction to repulsion, and thus significantly decreasing deposition of COOH-PSNPs. Organic macromolecules could markedly inhibit the deposition of COOH-PSNPs with goethite because of enhanced electrostatic repulsion, steric hindrance, and competition of surface binding sites. The ability for inhibiting the deposition of COOH-PSNPs followed the sequence of SA > HA > BSA, which was related to their structure (SA: linear, semi-flexible, HA: globular, semi-rigid, BSA: globular, with protein tertiary structure) and surface charge density (SA > HA > BSA). The results of this study highlight the complexity of the interactions between NPs and minerals under different environments and provide valuable insights in understanding transport mechanisms and environmental fate of nanoplastics in aquatic environments.