Peptide targeting improves the delivery and therapeutic index of glucocorticoids to treat rheumatoid arthritis.

Rheumatoid arthritis (RA) is a prevalent autoimmune disease characterized by excessive inflammation in the joints. Glucocorticoid drugs are used clinically to manage RA symptoms, while their dosage and duration need to be tightly controlled due to severe adverse effects. Using dexamethasone (DEX) as a model drug, we explored here whether peptide-guided delivery could increase the safety and therapeutic index of glucocorticoids for RA treatment. Using multiple murine RA models such as collagen-induced arthritis (CIA), we found that CRV, a macrophage-targeting peptide, can selectively home to the inflammatory synovium of RA joints upon intravenous injection. The expression of the CRV receptor, retinoid X receptor beta (RXRB), was also elevated in the inflammatory synovium, likely being the basis of CRV targeting. CRV-conjugated DEX increased the accumulation of DEX in the inflamed synovium but not in healthy organs of CIA mice. Therefore, CRV-DEX demonstrated a stronger efficacy to suppress synovial inflammation and alleviate cartilage/bone destruction. Meanwhile, CRV conjugation reduced immune-related adverse effects of DEX even after a long-term use. Last, we found that RXRB expression was significantly elevated in human patient samples, demonstrating the potential of clinical translation. Taken together, we provide a novel, peptide-targeted strategy to improve the therapeutic efficacy and safety of glucocorticoids for RA treatment.

Fe-Mn binary oxides improve the methanogenic performance and reduce the environmental health risks associated with antibiotic resistance genes during anaerobic digestion.

Increasing evidence indicates that metal oxides can improve the methanogenic performance during anaerobic digestion (AD) of piggery wastewater. However, the impacts of composite metal oxides on the methanogenic performance and risk of antibiotic resistance gene (ARG) transmission during AD are not fully understood. In this study, different concentrations of Fe-Mn binary oxides (FMBO at 0, 250, 500, and 1000 mg/L) were added to AD to explore the effects of FMBO on the process. The methane yield was 7825.1 mL under FMBO at 250 mg/L, 35.2% higher than that with FMBO at 0 mg/L. PICRUSt2 functional predictions showed that FMBO promoted the oxidation of acetate and propionate, and the production of methane from the substrate, as well as increasing the abundances of most methanogens and genes encoding related enzymes. Furthermore, under FMBO at 250 mg/L, the relative abundances of 14 ARGs (excluding tetC and sul2) and four mobile gene elements (MGEs) decreased by 24.7% and 55.8%, respectively. Most of the changes in the abundances of ARGs were explained by microorganisms, especially Bacteroidetes (51.20%), followed by MGEs (11.98%). Thus, the methanogenic performance of AD improved and the risk of horizontal ARG transfer decreased with FMBO, especially at 250 mg/L.

Facile and selective separation of anthraquinones by alizarin-modified iron oxide magnetic nanoparticles.

Anthraquinones are widely distributed in higher plants and possess broad biological activities. The conventional separation procedures for isolating anthraquinones from the plant crude extracts require multiple extraction, concentration, and column chromatography steps. In this study, we synthesized three alizarin (AZ)-modified Fe3O4 nanoparticles (Fe3O4@AZ, Fe3O4@SiO2-AZ, and Fe3O4@SiO2-PEI-AZ) by thermal solubilization method. Fe3O4@SiO2-PEI-AZ showed strong magnetic responsiveness, high methanol/water dispersion, good recyclability, and high loading capacity for anthraquinones. To evaluate the feasibility of using Fe3O4@SiO2-PEI-AZ for separating various aromatic compounds, we employed molecular dynamics simulations to predict the adsorption/desorption effects of PEI-AZ for various aromatic compounds in different methanol concentrations. The results showed that the anthraquinones could be efficiently separated from the monocyclic and bicyclic aromatic compounds by adjusting the methanol/water ratio. The Fe3O4@SiO2-PEI-AZ nanoparticles were then used to separate the anthraquinones from the rhubarb extract. At 5% methanol, all the anthraquinones were adsorbed by the nanoparticles, thus allowing their separation from other components in the crude extract. Compared with the conventional separation methods, this adsorption method has the advantages of high adsorption specificity, simple operation, and solvent saving. This method sheds light on the future application of functionalized Fe3O4 magnetic nanoparticles to selectively separate desired components from complex plant and microbial crude extracts.

Identification of an ALK-2 inhibitor as an agonist for intercellular exchange and tumor delivery of nanomaterial.

Inefficient extravasation and penetration in solid tissues hinder the clinical outcome of nanoparticles (NPs). Recent studies have shown that the extravasation and penetration of NPs in solid tumor was mostly achieved via an active transcellular route. For this transport process, numerous efforts have been devoted to elucidate the endocytosis and subcellular trafficking of NPs. However, how they exit from one cell and re-enter into neighboring ones (termed intercellular exchange) remains poorly understood. We previously developed cellular assays that exclusively quantify the intercellular exchange of NPs in vitro. Our study showed that a significant portion of NPs are transferred inside extracellular vesicles (EVs). Pharmacological inhibition of EV biogenesis significantly reduced the tumor accumulation and vascular penetration of both inorganic and organic NPs in vivo. Intrigued by this result, we performed here a manual chemical screen with our assay, which identified that LDN-214117 (an inhibitor for activin receptor-like kinase-2, ALK-2) is an agonist of NP intercellular exchange. We further showed that LDN-214117 regulates the intercellular exchange by increasing the EV biogenesis. Mechanistic investigation showed that LDN-214117 functions via BMP (bone morphogenetic protein)-MAPK (mitogen-activated protein kinase) signaling pathway to increase EV biogenesis. We further demonstrated that LDN-214117 treatment in vivo enhanced the tumor accumulation and vascular penetration of a variety of NPs in multiple tumor models, which improves their antitumor efficacy. Overall, we showcase here the identification of a novel chemical compound with our intercellular exchange assays to modulate EV biogenesis and EV-mediated transport, thus boosting up the delivery and therapeutic efficacy of nanomaterial.

The effects on type 2 diabetes mellitus mouse femoral bone achieved by anti-osteoporosis exercise interventions.

Purpose: Exercise therapy and key regulators of bone quality exert anti-hyperglycemic effects on type 2 diabetes mellitus (T2DM) mice. A number of programs have been reported to have an effect on bone disease in T2DM. Major unanswered questions concern the potential correlation of exercise with the improvement of bone quality in T2DM mice and how the nonlinear optical properties of bone are correlated with changes to its crystal structure. Methods: Subjects were randomly divided into six groups: 1) control (C) group, which was fed a normal diet (n = 8); 2) T2DM quiet group, which was given a high-fat diet and quiet (n = 8); 3) T2DM plus swimming (T2DM+S) group, which received T2DM and swim training (n = 8); 4) T2DM plus resistance exercise (T2DM+RE) group, which was given T2DM and resistance exercise (n = 8); 5) T2DM plus aerobic exercise (T2DM+AE) group, with T2DM and medium-intensity treadmill exercise (n = 8); and 6) T2DM plus high-intensity interval training (T2DM+HIIT), with T2DM and high-intensity variable-speed intervention (n = 8). The levels of runt-related transcription factor 2 (RUNX2), osterix (OSX), and alkaline phosphatase (ALP), as well as the bone microstructure and morphometry, were measured at the end of the 8-week exercise intervention. Results: Compared with the C group, the bone microstructure indexes [bone mineral density (BMD), bone volume/tissue volume (BV/TV), cortical thickness (Ct.Th), and connectivity density (Conn.D)], the bone biomechanical properties (maximum load, fracture load, yield stress, and elastic modulus), and the osteogenic differentiation factors (RUNX2, OSX, and BMP2) of the T2DM group were significantly decreased (all p < 0.05). Compared with the T2DM group, there were obvious improvements in the osteogenic differentiation factor (OSX) and Th.N, while the separation of trabecular bone (Tb.Sp) decreased in the T2DM+AE and T2DM+HIIT groups (all p < 0.05). In addition, the bone microstructure indicators BV/TV, tissue mineral density (TMD), Conn.D, and degree of anisotropy (DA) also increased in the T2DM+HIIT group, but the yield stress and Ct.Th deteriorated compared with the T2DM group (all p < 0.05). Compared with the T2DM+S and T2DM+RE groups, the BV/TV, trabecular number (Tb.N), Tb.Sp, and Conn.D in the T2DM+AE and T2DM+HIIT groups were significantly improved, but no significant changes in the above indicators were found between the T2DM+S and T2DM+RE groups (all p < 0.05). In addition, the BMD and the expression of ALP in the T2DM+AE group were significantly higher than those in the T2DM+HIIT group (all p < 0.05). Conclusion: There was a significant deterioration in femur bone mass, trabecular bone microarchitecture, cortical bone geometry, and bone mechanical strength in diabetic mice. However, such deterioration was obviously attenuated in diabetic mice given aerobic and high-intensity interval training, which would be induced mainly by suppressing the development of T2DM. Regular physical exercise may be an effective strategy for the prevention of not only the development of diabetes but also the deterioration of bone properties in patients with chronic T2DM.

A case of Kernohan-Woltman notch phenomenon caused by an epidural hematoma: the diagnostic and prognostic value of PET/CT imaging.

BACKGROUND: Kernohan-Woltman notch phenomenon (KWNP) classically occurs when a lesion causes compression of the contralateral cerebral peduncle against the tentorium, resulting in ipsilateral hemiparesis. It has been studied clinically, radiologically and electrophysiologically which all confirmed to cause false localizing motor signs. Here, we demonstrate the potential use of fluorine-18 fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) to identify KWNP caused by an epidural hematoma. CASE PRESENTATION: A 29-year-old male patient post right-sided traumatic brain injury presenting with persistent ipsilateral hemiparesis. Patient underwent decompressive craniotomy and intracranial hematoma evacuation. Brain magnetic resonance imaging in the postoperative period showed a subtle lesion in the left cerebral peduncle. PET/CT was performed to exclude early brain tumor and explain his ipsilateral hemiparesis. PET/CT imaging demonstrated a focal region of intense 18 F-FDG uptake in the left cerebral peduncle. Throughout the treatment in outpatient neurorehabilitation unit, the patient exhibited a gradual recovery of his right hemiparesis. CONCLUSION: In our case report, for the first time, PET/CT offered microstructural and functional confirmation of KWNP. Moreover, our case suggests that 18 F-FDG PET/CT may serve as an important reference for the probability of functional recovery.

Electrochemical Reduction and Oxidation of Chlorinated Aromatic Compounds Enhanced by the Fe-ZSM-5 Catalyst: Kinetics and Mechanisms.

Devising cost-effective electrochemical catalyst system for the efficient degradation of chlorinated aromatic compounds is urgently needed for environmental pollution control. Herein, a Fe-ZSM-5 zeolite was used as a suspended catalyst to facilitate the degradation of lindane as a model chlorinated pesticide in an electrochemical system consisting of the commercial DSA (Ti/RuO2-IrO2) anode and graphite cathode. It was found that the Fe-ZSM-5 zeolite greatly accelerated the degradation of lindane, with the degradation rate constant more than 8 times higher than that without Fe-ZSM-5. In addition, the Fe-ZSM-5 zeolite widened the working pH range from 3 to 11, while efficient degradation of lindane in the absence of Fe-ZSM-5 was only obtained at pH ≤ 5. The degradation of lindane was primarily due to reductive dechlorination mediated by atomic H* followed by •OH oxidation. Fe-ZSM-5 zeolite could enrich lindane, H*, and •OH on its surface, thus provided a suitable local environment for lindane degradation. The Fe-ZSM-5 zeolite exhibited high stability and reusability, and reduced the energy consumption. This research provides a potential reduction-oxidation strategy for removing organochlorine compounds through a cost-efficient Fe-ZSM-5 catalytic electrochemical system.

Co-administration of Transportan Peptide Enhances the Cellular Entry of Liposomes in the Bystander Manner Both In Vitro and In Vivo.

Liposomes have been widely used as a drug delivery vector. One way to further improve its therapeutic efficacy is to increase the cell entry efficiency. Covalent conjugation with cell-penetrating peptides (CPPs) and other types of ligands has been the mainstream strategy to tackle this issue. Although efficient, it requires additional chemical modifications on liposomes, which is undesirable for clinical translation. Our previous study showed that the transportan (TP) peptide, an amphiphilic CPP, was able to increase the cellular uptake of co-administered, but not covalently coupled, metallic nanoparticles (NPs). Termed bystander uptake, this process represents a simpler method to increase the cell entry of NPs without chemical modifications. Here, we extended our efforts to liposomes. Our results showed that co-administration with the TP peptide improved the internalization of liposome into a variety of cell lines in vitro. This effect was also observed in primary cells, ex vivo tumor slices, and in vivo tumor tissues. On the other hand, this peptide-assisted liposome internalization did not apply to cationic CPPs, which were the main inducers for bystander uptake in previous studies. We also found that TP-assisted bystander uptake of liposome is receptor dependent, and its activity is more sensitive to the inhibitors of the macropinocytosis pathway, underlining the potential cell entry mechanism. Overall, our study provides a simple strategy based on TP co-administration to increase the cell entry of liposomes, which may open up new avenues to apply TP peptides in nanotherapeutics.

Fully Endoscopic Microvascular Decompression for Hemifacial Spasm Using Improved Retrosigmoid Infrafloccular Approach: Clinical Analysis of 81 Cases.

BACKGROUND: Microvascular decompression (MVD) is widely accepted as the preferred treatment for hemifacial spasm (HFS). Endoscopy has been implemented to provide a comprehensive view of neurovascular conflicts and minimize the damage caused by brain retraction while exploring the facial nerve root exit zone of the brain stem. OBJECTIVE: To preliminarily evaluate the surgical safety and efficacy of fully endoscopic MVD for HFS using an improved retrosigmoid infrafloccular approach. METHODS: The clinical data of 81 patients with HFS who underwent fully endoscopic MVD using an improved endoscopic retrosigmoid infrafloccular approach from June 2019 to December 2020 were retrospectively analyzed. The reliability and advantages of this surgical technique in the treatment of HFS were evaluated according to the intraoperative situation, outcomes of postoperative symptoms, and main complications. RESULTS: During the follow-up period, 77 cases (95.1%) were completely cured, with immediate facial twitch disappearance in 56 cases and a delayed cure in 21 cases; in 4 cases (4.9%), there was no obvious improvement. There were no cases of recurrence. There were 4 cases (4.9%) of transient facial paralysis after MVD, all of which were completely cured in 3 months. Three cases (3.7%) had hearing loss postoperatively, of whom 2 showed good improvement. At the end of the follow-up period, 1 case (1.2%) still had tinnitus. There were no cases of postoperative intracranial hemorrhage, cerebellar swelling, or death. CONCLUSION: Fully endoscopic MVD using an improved retrosigmoid infrafloccular approach not only has the advantages of panoramic surgical visualization but also takes into account the requirements of minimally invasive surgery.

Synergistic Entry of Individual Nanoparticles into Mammalian Cells Driven by Free Energy Decline and Regulated by Their Sizes.

Cell entry is one of the common prerequisites for nanomaterial applications. Despite extensive studies on a homogeneous group of nanoparticles (NPs), fewer studies have been performed when two or more types of NPs were coadministrated. We previously described a synergistic cell entry process for two heterogeneous groups of NPs, where NPs functionalized with TAT (transactivator of transcription) peptide (T-NPs) stimulate the cellular uptake of coadministered unfunctionalized NPs (bystander NPs, B-NPs). Here, we show that the synergistic cell entry of NPs is driven by free energy decline and depends on B-NP sizes. Simulations showed that when separately placed initially, two NPs first move toward each other instead of initiating cell entry individually. Only T-NP invokes an inward bending of membrane mimicking endocytosis, which attracts the nearby NPs into the same "vesicle". A two-phase free energy decline of the entire system occurred as two NPs get closer until contact, which is likely the thermodynamic driver for synergistic NP coentry. Experimentally, we found that T-NPs increase the apparent affinity of B-NPs to plasma membrane, suggesting that T-NPs help B-NPs "trapped" in the endocytic vesicles. Next, we varied the sizes of B-NPs and found that bystander activity peaks around 50 nm. Simulations also showed that the size of B-NPs influences the free energy decline, and thus the tendency and dynamics of NP coentry. These efforts provide a system to further understand the synergistic cell entry among individual NPs or multiple NP types on a biophysical basis and shed light on the future design of nanostructures for intracellular delivery.

Elucidating the beneficial effects of diatomite for reducing abundances of antibiotic resistance genes during swine manure composting.

Diatomite (DE) has been used for nitrogen conservation during the composting of feces but its effects on antibiotic resistance genes (ARGs) and the associated mechanisms are still unclear. In this study, DE was added at three different proportions (0%, 4%, and 8%) to swine manure during composting. The results showed that adding DE helped to reduce the abundances of ARGs and the maximum decrease (88.99%) occurred with the highest dose. DE amendment promoted the transformation of reducible copper into a more stable form, i.e., the residual fraction, which reduced the selective pressure imposed by copper and further decreased the abundances of ARGs. Tn916/1545 and intI1 were critical genetic components related to ARGs, and thus the reductions in the abundances of ARGs may be attributed to the suppression of horizontal transfer due to the decreased abundances of mobile genetic elements (MGEs). The microbial community structure (bacterial abundance and diversity) played key role in the evolution of ARGs. DE could enhance the competition between hosts and non-hosts of ARGs by increasing the bacterial community diversity. Compared with CK, DE amendment optimized the bacterial community by reducing the abundances of the potential hosts of ARGs and pathogens such as Corynebacterium, thereby improving the safety of the compost product. In addition, KEGG function predictions revealed that adding DE inhibited the metabolic pathway and genes related to ARGs. Thus, composting with 8% DE can reduce the risk of ARG transmission and improve the practical value for agronomic applications.

The fate of antibiotic resistance genes and their influential factors in swine manure composting with sepiolite as additive.

Manures are storages for antibiotic resistance genes (ARGs) entering the environment. This study investigated the effects of adding sepiolite at 0%, 2.5%, 5%, and 7.5% (CK, T1, T2, and T3, respectively) on the fates of ARGs during composting. The relative abundances (RAs) of the total ARGs in CK and T3 decreased by 0.23 and 0.46 logs, respectively, after composting. The RAs of 10/11 ARGs decreased in CK, whereas they all decreased in T3. The reduction in the RA of the total mobile genetic elements (MGEs) was 1.26 times higher in T3 compared with CK after composting. The bacterial community accounted for 47.93% of the variation in the abundances of ARGs. Network analysis indicated that ARGs and MGEs shared potential host bacteria (PHB), and T3 controlled the transmission of ARGs by reducing the abundances of PHB. Composting with 7.5% sepiolite is an effective strategy for reducing the risk of ARGs proliferating.

The Role of Long Non-coding RNA, Nuclear Enriched Abundant Transcript 1 (NEAT1) in Cancer and Other Pathologies.

Nuclear enriched abundant transcript 1 (NEAT1), consisting of two kinds of lncRNAs of 3.7 kB NEAT1-1 and 23 kB NEAT1-2, can be highly expressed in organs and tissues such as the ovary, prostate, colon, and pancreas, and is involved in paraspeckle formation and mRNA editing and gene expression. Therefore, NEAT1 is a potential biomarker for the treatment of a variety of diseases, which may be caused by two factors (isoforms of NEAT1 and NEAT1 sponging miRNA as ceRNA). However, there is still much confusion about the mechanism and downstream effector between the abnormal expression of NEAT1 and various diseases. This review summarizes recent research progress on NEAT1 in cancer and other pathologies and provides a more reliable theoretical basis for the treatment of related diseases.

Impact of Subthalamic Deep Brain Stimulation on Hyposmia in Patients With Parkinson's Disease Is Influenced by Constipation and Dysbiosis of Microbiota.

Background: Non-motor symptoms in PD usually arise at very early stage and vary during the whole disease progression. Deep brain stimulation (DBS) is considered as a highly efficient treatment option for PD's motor function. However, the effect of DBS on NMS, especially hyposmia, has not been fully understood and the deep connection between different NMS such as hyposmia and constipation is still unknown. Objective: The objective of this study was to evaluate the therapeutic effect of DBS on hyposmia in PD patients with or without constipation and find potential factors which might influence the efficacy. Methods: A retrospective analysis of 65 PD patients accepted STN-DBS operation in Qilu Hospital during 2019-2020 were conducted to evaluate the exact therapeutic effect of DBS on hyposmia in PD. Sub-group analyses about the relationship between hyposmia and constipation were carried out. Analysis of flora in nasal mucosa was also conducted to evaluate the abundance and variety in different PD groups. Results: Our study showed that DBS had clearly improved olfactory function in Parkinson patients (P = 0.012) and subgroup analysis found that PD patients with constipation have lower olfactory function scores (25.27 ± 3.44 vs. 33.90 ± 6.633, p = 0.014) and worse improvement after DBS operation (ΔTDI 12.11 ± 3.2 vs. 8.78 ± 2.91, p = 0.0072). Analysis of flora indicated the obvious discrepancy on olfactory function scores and degree of improvement might be related to the abundance and dysbiosis of microbiota. Conclusion: In summary, this article presents a study on PD with hyposmia and constipation after DBS operation, explored the relationship between different NMS and offer a potential explanation on why PD patients with constipation usually have worse olfactory function for the less abundance and variety of microbiota.

Transportan Peptide Stimulates the Nanomaterial Internalization into Mammalian Cells in the Bystander Manner through Macropinocytosis.

Covalent coupling with cell-penetrating peptides (CPPs) has been a common strategy to facilitate the cell entry of nanomaterial and other macromolecules. Though efficient, this strategy requires chemical modifications on nanomaterials, which is not always desired for their applications. Recent studies on a few cationic CPPs have revealed that they can stimulate the cellular uptake of nanoparticles (NPs) simply via co-administration (bystander manner), which bypasses the requirement of chemical modification. In this study, we investigated the other classes of CPPs and discovered that transportan (TP) peptide, an amphiphilic CPP, also exhibited such bystander activities. When simply co-administered, TP peptide enabled the cells to engulf a variety of NPs, as well as common solute tracers, while these payloads had little or no ability to enter the cells by themselves. This result was validated in vitro and ex vivo, and TP peptide showed no physical interaction with co-administered NPs (bystander cargo). We further explored the cell entry mechanism for TP peptide and its bystander cargo, and showed that it was mediated by a receptor-dependent macropinocytosis process. Together, our findings improve the understanding of TP-assisted cell entry, and open up a new avenue to apply this peptide for nanomaterial delivery.

Identification of minimal hepatic encephalopathy based on dynamic functional connectivity.

To investigate whether dynamic functional connectivity (DFC) metrics can better identify minimal hepatic encephalopathy (MHE) patients from cirrhotic patients without any hepatic encephalopathy (noHE) and healthy controls (HCs). Resting-state functional MRI data were acquired from 62 patients with cirrhosis (MHE, n = 30; noHE, n = 32) and 41 HCs. We used the sliding time window approach and functional connectivity analysis to extract the time-varying properties of brain connectivity. Three DFC characteristics (i.e., strength, stability, and variability) were calculated. For comparison, we also calculated the static functional connectivity (SFC). A linear support vector machine was used to differentiate MHE patients from noHE and HCs using DFC and SFC metrics as classification features. The leave-one-out cross-validation method was used to estimate the classification performance. The strength of DFC (DFC-Dstrength) achieved the best accuracy (MHE vs. noHE, 72.5%; MHE vs. HCs, 84%; and noHE vs. HCs, 88%) compared to the other dynamic features. Compared to static features, the classification accuracies of the DFC-Dstrength feature were improved by 10.5%, 8%, and 14% for MHE vs. noHE, MHE vs. HC, and noHE vs. HCs, respectively. Based on the DFC-Dstrength, seven nodes were identified as the most discriminant features to classify MHE from noHE, including left inferior parietal lobule, left supramarginal gyrus, left calcarine, left superior frontal gyrus, left cerebellum, right postcentral gyrus, and right insula. In summary, DFC characteristics have a higher classification accuracy in identifying MHE from cirrhosis patients. Our findings suggest the usefulness of DFC in capturing neural processes and identifying disease-related biomarkers important for MHE identification.

Searching for biological feedstock material: 3D printing of wood particles from house borer and drywood termite frass.

Frass (fine powdery refuse or fragile perforated wood produced by the activity of boring insects) of larvae of the European house borer (EHB) and of drywood termites was tested as a natural and novel feedstock for 3D-printing of wood-based materials. Small particles produced by the drywood termite Incisitermes marginipennis and the EHB Hylotrupes bajulus during feeding in construction timber, were used. Frass is a powdery material of particularly consistent quality that is essentially biologically processed wood mixed with debris of wood and faeces. The filigree-like particles flow easily permitting the build-up of wood-based structures in a layer wise fashion using the Binder Jetting printing process. The quality of powders produced by different insect species was compared along with the processing steps and properties of the printed parts. Drywood termite frass with a Hausner Ratio HR = 1.1 with ρBulk = 0.67 g/cm3 and ρTap = 0.74 g/cm3 was perfectly suited to deposition of uniformly packed layers in 3D printing. We suggest that a variety of naturally available feedstocks could be used in environmentally responsible approaches to scientific material sciences/additive manufacturing.

Macropinocytosis as a cell entry route for peptide-functionalized and bystander nanoparticles.

Endocytic pathways provide the primary route for therapeutic and diagnostic nanoparticles (NPs) to enter cells and subcellular compartments. A better understanding of these cell entry processes will not only aid in nanomaterial applications but also broaden our knowledge of cell biology. Among the endocytic routes, macropinocytosis has unique characteristics for engulfing NPs and other large cargo, yet its molecular machinery and involvement in NP uptake are far less characterized relative to other pathways. In this review, we summarize the current knowledge on the macropinocytic machinery, and its involvement in NP internalization. Particularly, we differentiate ligand (specifically peptide)-functionalized and unfunctionalized NPs (bystander NPs). While most of previous research focused on ligand-functionalized NPs, we showcase here a synergistic effect between these two NP types during their cell entry through receptor-mediated macropinocytosis. The regulation of NP uptake efficiency by extracellular amino acids is also highlighted in the context of interconnections between macropinocytosis and metabolic signaling. These discussions may fuel future research interests in improving NP internalization through this pathway, and open a new avenue to study the interplay among endocytosis, metabolism and nanomedicine.

Curcumin suppresses colorectal tumorigenesis via the Wnt/ß-catenin signaling pathway by downregulating Axin2.

Colorectal cancer (CRC) is the third most common cancer worldwide, with high incidence and mortality rates. Conventional therapies, including surgery, chemotherapy and radiation, are extensively used for the treatment of CRC. However, patients present with adverse effects, such as toxicity, hepatic injury and drug resistance. Thus, there is an urgent requirement to identify effective and safe therapy for CRC. Curcumin (CUR), a polyphenol substrate extracted from the rhizome of Curcuma longa, has been extensively studied for the treatment of CRC due to its high efficacy and fewer side effects. Previous studies have reported that several signaling pathways, such as NF-κB, Wnt/ß-catenin, are involved in the antitumor effects of CUR in vitro. However, the effect and mechanisms in vivo are not yet fully understood. The present study aimed to determine the molecular mechanism of colorectal cancer in vivo. Reverse transcription-quantitative PCR, western blot and immunohistochemistry analyses were performed to determine the underlying molecular mechanism of curcumin's anti-cancer effect in azoxymethane-dextran sodium sulfate induced colorectal cancer. The results of the present study demonstrated that CUR suppressed tumorigenesis in AOM-DSS induced CRC in mice, and anticancer effects were exerted by suppressing the expression of pro-inflammatory cytokines, and downregulating Axin2 in the Wnt/ß-catenin signaling pathway. Taken together, these results exhibit the potential in vivo mechanisms of the anticancer effects of CUR, and highlight Axin2 as a potential therapeutic target for CRC.

Microscale magnetic field modulation using rapidly patterned soft magnetic microstructures.

The ability to locally modulate the magnetic field distribution is a prerequisite for efficient manipulation in magnetic force-based microfluidic devices. Here, we report a simple, robust, and fast fabrication method of magnetic microstructures for locally modulating magnetic fields. In the proposed method, a photosensitive magnetic composite consisting of carbonyl-iron microparticles in a poly(ethylene glycol) diacrylate (PEGDA) matrix was utilized to photolithographically fabricate magnetic microstructures. The magnetic behavior of the composite was first evaluated, and then various complicated patterns were fabricated on a glass slide within a few minutes. To demonstrate the capability of magnetic microstructures as a magnetic field concentrator, magnetic microstructures with different orientations to the external magnetic field were designed and fabricated, such as square arrays and grid-like magnetic microstructures. The modulated magnetic fields from such magnetic microstructures were numerically analyzed and then experimentally validated by trapping magnetic hydrogel beads. Further, the magnetically labeled cells were applied to the magnetic microstructures to prove the possibility of cell confinement via magnetic guidance in regions that exhibit enhanced magnetic field gradients. Overall, the proposed approach facilitates simple and fast fabrication of soft magnetic microstructures for microscale modulation of magnetic fields, which exhibits an immense application potential in magnetic force-based microfluidic techniques.