Current landscape of mRNA technologies and delivery systems for new modality therapeutics.

Realizing the immense clinical potential of mRNA-based drugs will require continued development of methods to safely deliver the bioactive agents with high efficiency and without triggering side effects. In this regard, lipid nanoparticles have been successfully utilized to improve mRNA delivery and protect the cargo from extracellular degradation. Encapsulation in lipid nanoparticles was an essential factor in the successful clinical application of mRNA vaccines, which conclusively demonstrated the technology's potential to yield approved medicines. In this review, we begin by describing current advances in mRNA modifications, design of novel lipids and development of lipid nanoparticle components for mRNA-based drugs. Then, we summarize key points pertaining to preclinical and clinical development of mRNA therapeutics. Finally, we cover topics related to targeted delivery systems, including endosomal escape and targeting of immune cells, tumors and organs for use with mRNA vaccines and new treatment modalities for human diseases.

Uncommon P1 Anchor-featured Viral T Cell Epitope Preference within HLA-A*2601 and HLA-A*0101 Individuals.

The individual HLA-related susceptibility to emerging viral diseases such as COVID-19 underscores the importance of understanding how HLA polymorphism influences peptide presentation and T cell recognition. Similar to HLA-A*0101, which is one of the earliest identified HLA alleles among the human population, HLA-A*2601 possesses a similar characteristic for the binding peptide and acts as a prevalent allomorph in HLA-I. In this study, we found that, compared with HLA-A*0101, HLA-A*2601 individuals exhibit distinctive features for the T cell responses to SARS-CoV-2 and influenza virus after infection and/or vaccination. The heterogeneous T cell responses can be attributed to the distinct preference of HLA-A*2601 and HLA-A*0101 to T cell epitope motifs with negative-charged residues at the P1 and P3 positions, respectively. Furthermore, we determined the crystal structures of the HLA-A*2601 complexed to four peptides derived from SARS-CoV-2 and human papillomavirus, with one structure of HLA-A*0101 for comparison. The shallow pocket C of HLA-A*2601 results in the promiscuous presentation of peptides with "switchable" bulged conformations because of the secondary anchor in the median portion. Notably, the hydrogen bond network formed between the negative-charged P1 anchors and the HLA-A*2601-specific residues lead to a "closed" conformation and solid placement for the P1 secondary anchor accommodation in pocket A. This insight sheds light on the intricate relationship between HLA I allelic allomorphs, peptide binding, and the immune response and provides valuable implications for understanding disease susceptibility and potential vaccine design.

Integrated Single-cell and Transcriptome Sequencing Analyses Identified PREX1 as an Immune-related Prognostic Biomarker for Liver Hepatocellular Carcinoma.

Background: PtdIns (3,4,5) P3-dependent Rac exchanger 1 (PREX1), also known as PREX1, a member of the Rac guanine nucleotide exchange factors (Rac-GEF) family. Studies have suggested that PREX1 plays a role in mediating oncogenic pathway activation and controlling various biological mechanisms in different types of cancer, including liver hepatocellular carcinoma (LIHC). However, the function of PREX1 in the pathogenesis of LIHC and its potential role on immunological regulation is not clearly elucidated. Methods: The expression level and the clinical role of PREX1 in LIHC was analyzed based on database from the Cancer Genome Atlas (TCGA), TNM plotter and University of Alabama Cancer Database (UALCAN). We investigated the relationship between PREX1 and immunity in LIHC by TISIDB, CIBERSORT and single cell analysis. Immunotherapy responses were assessed by the immunophenoscores (IPS). Moreover, biological functional assays were performed to further investigate the roles of PREX1 in liver cancer cell lines. Results: Higher expression of PREX1 in LIHC tissues than in normal liver tissues was found based on public datasets. Further analysis revealed that PREX1 was associated with worse clinical characteristics and dismal prognosis. Pathway enrichment analysis indicated that PREX1 participated in immune-related pathways. Through CIBERSORT and single cell analysis, we found a remarkable correlation between the expression of PREX1 and various immune cells, especially macrophages. In addition, high PREX1 expression was found to be associated with a stronger response to immunotherapy. Furthermore, in vitro assays indicated that depletion of PREX1 can suppress invasion and proliferation of LIHC cells. Conclusion: Elevated expression of PREX1 indicates poor prognosis, influences immune modulation and predicts sensitivity of immunosuppression therapy in LIHC. Our results suggested that PREX1 may be a prognostic biomarker and therapeutic target, offering new treatment options for LIHC.

Senolytic effects of exercise in human muscles require acute inflammation.

Higher intensity exercise, despite causing more tissue damage, improved aging conditions. We previously observed decreased p16INK4a mRNA in human skeletal muscle after high-intensity interval exercise (HIIE), with no change following equivalent work in moderate-intensity continuous exercise. This raises the question of whether the observed senolytic effect of exercise is mediated by inflammation, an immune response induced by muscle damage. In this study, inflammation was blocked using a multiple dose of ibuprofen (total dose: 1200 mg), a commonly consumed nonsteroidal anti-inflammatory drug (NSAID), in a placebo-controlled, counterbalanced crossover trial. Twelve men aged 20-26 consumed ibuprofen or placebo before and after HIIE at 120% maximum aerobic power. Multiple muscle biopsies were taken for tissue analysis before and after HIIE. p16INK4a+ cells were located surrounding myofibers in muscle tissues. The maximum decrease in p16INK4a mRNA levels within muscle tissues occurred at 3 h post-exercise (-82%, p < 0.01), gradually recovering over the next 3-24 h. A concurrent reduction pattern in CD11b mRNA (-87%, p < 0.01) was also found within the same time frame. Ibuprofen treatment attenuated the post-exercise reduction in both p16INK4a mRNA and CD11b mRNA. The strong correlation (r = 0.88, p < 0.01) between p16INK4a mRNA and CD11b mRNA in muscle tissues suggests a connection between the markers of tissue aging and pro-inflammatory myeloid differentiation. In conclusion, our results suggest that the senolytic effect of high-intensity exercise on human skeletal muscle is mediated by acute inflammation.

Predicting short-term major postoperative complications in intestinal resection for Crohn's disease: A machine learning-based study.

BACKGROUND: Due to the complexity and numerous comorbidities associated with Crohn's disease (CD), the incidence of postoperative complications is high, significantly impacting the recovery and prognosis of patients. Consequently, additional studies are required to precisely predict short-term major complications following intestinal resection (IR), aiding surgical decision-making and optimizing patient care. AIM: To construct novel models based on machine learning (ML) to predict short-term major postoperative complications in patients with CD following IR. METHODS: A retrospective analysis was performed on clinical data derived from a patient cohort that underwent IR for CD from January 2017 to December 2022. The study participants were randomly allocated to either a training cohort or a validation cohort. The logistic regression and random forest (RF) were applied to construct models in the training cohort, with model discrimination evaluated using the area under the curves (AUC). The validation cohort assessed the performance of the constructed models. RESULTS: Out of the 259 patients encompassed in the study, 5.0% encountered major postoperative complications (Clavien-Dindo ≥ III) within 30 d following IR for CD. The AUC for the logistic model was 0.916, significantly lower than the AUC of 0.965 for the RF model. The logistic model incorporated a preoperative CD activity index (CDAI) of ≥ 220, a diminished preoperative serum albumin level, conversion to laparotomy surgery, and an extended operation time. A nomogram for the logistic model was plotted. Except for the surgical approach, the other three variables ranked among the top four important variables in the novel ML model. CONCLUSION: Both the nomogram and RF exhibited good performance in predicting short-term major postoperative complications in patients with CD, with the RF model showing more superiority. A preoperative CDAI of ≥ 220, a diminished preoperative serum albumin level, and an extended operation time might be the most crucial variables. The findings of this study can assist clinicians in identifying patients at a higher risk for complications and offering personalized perioperative management to enhance patient outcomes.

Relationship Between the Ovarian Cyst and Depression: A Two-Sample Mendelian Randomization Study.

Objective: Explore the causal relationship between the ovarian cyst and depression using a two-sample Mendelian randomization approach (MR). Methods: Based on data pooled from genome-wide association studies, genetic variants of the ovarian cyst and depression were selected as instrumental variables, as well as the Mendelian randomization analysis was conducted using inverse variance weighted (IVW) as the main analysis method and MR-Egger regression analysis, MR-PRESSO and other sensitivity analysis methods as supplements. Results: The IVW analysis showed a direct causal association between ovarian cysts and depression (OR=1.040; 95% CI: 1.003, 1.078; p=0.031). Meantime, there was a causal effect of genetically predicted depression on ovarian cysts (OR=1.327.; 95% CI: 1.197, 1.470; p<0.001). Sensitivity analyses such as MR-Egger regression analysis and MR-PRESSO indicated that the IVW results were robust and reliable. Conclusion: This study suggested since ovarian cysts and female depression are mutually causal, the comorbidity of ovarian cysts and depression in women should be actively attended to and given appropriate prevention and treatment besides the diagnosis and treatment of depression or ovarian cysts.

Comparison of Dydrogesterone and GnRH-a Effects After Laparoscopic Surgery in Patients with Stage III and IV Endometriosis.

Objective: To compare the spontaneous pregnancy rates between dydrogesterone and Gonadotropin-releasing hormone agonist (GnRH-a) treatments in patients with endometriosis stage III and IV after laparoscopy. Methods: The clinical data of patients with endometriosis stage III and IV administered laparoscopic surgery in our hospital from January 2018 to March 2020 were retrospectively analyzed. Totally 151 cases were divided into two groups according to postoperative medication, including the study (70 cases) and control (81 cases) groups treated with dydrogesterone and GnRH-a, respectively. The spontaneous pregnancy and subsequent pregnancy outcomes were assessed within 12 months. Results: Totally 49 patients had spontaneous pregnancy. Among them, there were 31 cases in the dydrogesterone group (spontaneous pregnancy rate of 44.3%, 31/70), including 25 live birth cases (35.7%, 25/70), 4 miscarriage cases, and 2 ectopic pregnancy cases. The time to conception was 1-10 months (median value of 5 months). Totally 18 cases in the GnRH-a group had spontaneous pregnancy (22.2%, 18/81), including 16 live birth cases (19.8%, 16/81). 81) and 2 miscarriage cases; the time to conception was 3-11 months (median value of 6 months). There were significant differences in spontaneous pregnancy rate and cumulative spontaneous pregnancy rate between the two groups (P = 0.005 and 0.003, respectively). Conclusion: Dydrogesterone after laparoscopic surgery in patients with endometriosis stage III and IV improved the natural pregnancy rate.

Molecular insight into the specific enzymatic properties of TREX1 revealing the diverse functions in processing RNA and DNA/RNA hybrids.

In various autoimmune diseases, dysfunctional TREX1 (Three prime Repair Exonuclease 1) leads to accumulation of endogenous single-stranded DNA (ssDNA), double-stranded DNA (dsDNA) and DNA/RNA hybrids in the cytoplasm and triggers immune activation through the cGAS-STING pathway. Although inhibition of TREX1 could be a useful strategy for cancer immunotherapy, profiling cellular functions in terms of its potential substrates is a key step. Particularly important is the functionality of processing DNA/RNA hybrids and RNA substrates. The exonuclease activity measurements conducted here establish that TREX1 can digest both ssRNA and DNA/RNA hybrids but not dsRNA. The newly solved structures of TREX1-RNA product and TREX1-nucleotide complexes show that 2'-OH does not impose steric hindrance or specific interactions for the recognition of RNA. Through all-atom molecular dynamics simulations, we illustrate that the 2'-OH-mediated intra-chain hydrogen bonding in RNA would affect the binding with TREX1 and thereby reduce the exonuclease activity. This notion of higher conformational rigidity in RNA leading TREX1 to exhibit weaker catalytic cleavage is further validated by the binding affinity measurements with various synthetic DNA-RNA junctions. The results of this work thus provide new insights into the mechanism by which TREX1 processes RNA and DNA/RNA hybrids and contribute to the molecular-level understanding of the complex cellular functions of TREX1 as an exonuclease.

Solitary pulmonary nodule in an early adolescent.

An early adolescent boy presented with 1-week history of left-sided chest pain, localised to the anterior aspect of seventh intercostal space. A chest radiograph revealed a round opacity measuring 2.6×2.4 cm in the left mid zone. A CT scan of the chest confirmed a solitary well-circumscribed pulmonary nodule measuring 2.7×2.4 cm in the central left upper lobe, adjacent to the anterior segmental bronchus. Positron emission tomography scan showed mild to moderate fluorodeoxyglucose uptake (maximum standardized uptake value 5.2) in the nodule. He underwent a video-assisted left upper lobectomy. Histology of the nodule was consistent with sclerosing pneumocytoma, a rare benign lung neoplasm that occurs predominantly in middle-aged women of Asian descent. This case highlights the challenges in diagnosis and management of solitary pulmonary nodules in children, especially those who remain symptomatic or only have minimal symptoms and provides a pragmatic approach to this condition.

Vitisin B, a resveratrol tetramer from Vitis thunbergii var. taiwaniana, ameliorates impaired glucose regulations in nicotinamide/streptozotocin-induced type 2 diabetic mice.

Background and aim: In Taiwan, Vitis thunbergii var. taiwaniana (VTT) is used in traditional medicine and as a local tea. VTT rich in resveratrol and resveratrol oligomers have been reported to exhibit anti-obesity and anti-hypertensive activities in animal models; however, no studies have investigated type 2 diabetes mellitus (T2DM) treatments. This study aimed to investigate the anti-T2DM effects of resveratrol tetramers isolated from the VTT in nicotinamide/streptozotocin (STZ)-induced Institute of Cancer Research (ICR) mice. Experimental procedure: The oral glucose tolerance test (OGTT) was used to imitate postprandial blood glucose (BG) regulations in mice by pre-treatment with VTT extracts, resveratrol tetramers of vitisin A, vitisin B, and hopeaphenol 30 min before glucose loads. Vitisin B (50 mg/kg) was administered to treat T2DM-ICR mice once daily for 28 days to investigate its hypoglycemic activity. Results and conclusion: Mice pre-treated with VTT-S-95EE, or vitisin B (100 mg/kg) 30-min before glucose loading showed significant reductions (P < 0.001) in the area under the curve at 120-min (BG-AUC0-120) than those without pre-treatment with VTT-S-95 E E or vitisin B. Vitisin B-treated T2DM mice showed hypoglycemic activities via a reduction in plasma dipeptidyl peptidase (DPP)-IV activities to maintain insulin actions and differed significantly than those of untreated T2DM mice (P < 0.05), and also reduced BG-AUC0-120 and insulin-AUC0-120 in the OGTT.These in vivo results showed that VTT containing vitisin B would be beneficial for developing nutraceuticals and/or functional foods for glycemic control in patients with T2DM, which should be investigated further.

Artesunate, as an Hsp90 inhibitor, inhibits the proliferation of Burkitt's lymphoma cells by inhibiting AKT and ERK.

Introduction: Artesunate, a derivative of artemisinin, has anti-malarial effects, and in recent years has also been reported to have anti-tumor activity. However, its anti-tumor mechanisms are not well understood. Methods: In this study, we focused on the targeting of Hsp90 by artesunate to inhibit tumor cell proliferation, which we examined using immunoprecipitation, a proliferation assay, flow cytometry, western blotting, a tumor xenograft animal model, and immunohistochemistry. Furthermore, to examine the tumor-suppressive effects of artesunatein nude mice, we used artesunate-loaded PLGA-PEG nanoparticles. Results: The binding of artesunate to Hsp90 was found to reduce the expression of its client proteins AKT, ERK, p-AKT, p-ERK, and EGFR, thereby blocking the cell cycle at the G0/G1 → S stage in lymphoma cells and inducing apoptosis. In addition, the results of tumor xenograft experiments revealed that artesunate reduced the expression of AKT and ERK proteins in tumor tissues, inhibited tumor proliferation, and reduced tumor size and weight. Furthermore, nanoparticle encapsulation was demonstrated to enhance the anti-cancer activity of artesunate. Discussion: We thus established that artesunate inhibits the proliferation of lymphoma cells by targeting the Hsp90 protein, and we accordingly believe that this compound has potential for development as a novelanti-tumor drug.

Effects of food-borne docosahexaenoic acid supplementation on bone lead mobilisation, mitochondrial function and serum metabolomics in pre-pregnancy lead-exposed lactating rats.

Large bone lead (Pb) resulting from high environmental exposure during childhood is an important source of endogenous Pb during pregnancy and lactation. Docosahexaenoic acid (DHA) attenuates Pb toxicity, however, the effect of DHA on bone Pb mobilisation during lactation has not been investigated. We aimed to study the effects of DHA supplementation during pregnancy and lactation on bone Pb mobilisation during lactation and its potential mechanisms. Weaning female rats were randomly divided into control (0.05% sodium acetate) and Pb-exposed (0.05% Pb acetate) groups, after a 4-week exposure by ad libitum drinking and a subsequent 4-week washout period, all female rats were mated with healthy males until pregnancy. Then exposed rats were randomly divided into Pb and Pb + DHA groups, and the latter was given a 0.14% DHA diet, while the remaining groups were given normal feed until the end of lactation. Pb and calcium levels, bone microarchitecture, bone turnover markers, mitochondrial function and serum metabolomics were analyzed. The results showed that higher blood and bone Pb levels were observed in the Pb group compared to the control, and there was a significant negative correlation between blood and bone Pb. Also, Pb increased trabecular bone loss along with slightly elevated serum C-telopeptide of type I collagen (CTX-I) levels. However, DHA reduced CTX-I levels and improved trabecular bone microarchitecture. Metabolomics showed that Pb affected mitochondrial function, which was further demonstrated in bone tissue by significant reductions in ATP levels, Na+-K+-ATPase, Ca2+-Mg2+-ATPase and CAT activities, and elevated levels of MDA, IL-1ß and IL-18. However, these alterations were partially mitigated by DHA. In conclusion, DHA supplementation during pregnancy and lactation improved bone Pb mobilisation and mitochondrial dysfunction in lactating rats induced by pre-pregnancy Pb exposure, providing potential means of mitigating bone Pb mobilisation levels during lactation, but the mechanism still needs further study.

Physalis pubescens L. branch and leaf extracts inhibit lymphoma proliferation by inducing apoptosis and cell cycle arrest.

Physalis pubescens L. is an annual or perennial plant in the family Solanaceae It is used in traditional medicine for treating sore throats, coughs, urinary discomfort, and astringent pain, and externally for pemphigus and eczema in northern China. The proliferation inhibitory activity and mechanisms of the ethyl acetate extract (PHY-EA) from the leaves of Physalis pubescens were investigated. High performance liquid chromatography was used to identify the chemical composition of PHY-EA; sulforhodamine B was used to detect the proliferation inhibitory effect of PHY-EA on MCF-7, CA-46, Hela, HepG2, B16, and other tumor cells; flow cytometry was used to detect the effect of PHY-EA on the lymphoma cell cycle and apoptosis; Western blot was used to detect the expression of the cycle- and apoptosis-related proteins. The expression of Ki-67 and cleaved caspase 3 was detected by immunohistochemistry. The results showed that PHY-EA contained physalin B, physalin O, and physalin L. PHY-EA blocked the cell cycle of G2/M→G0/G1 in lymphoma cells and induced apoptosis in tumor cells. Mouse transplantation tumor experiments showed that PHY-EA had a significant inhibitory effect on mouse transplantation tumors, and the tumor volume and weight were significantly reduced. In conclusion, PHY-EA has a good antiproliferative effect on Burkkit lymphoma, indicating its potential medicinal value.

Metabolomics insights into the effects of pre-pregnancy lead exposure on bone metabolism in pregnant rats.

Today's women of childbearing age with a history of high lead (Pb) exposure in childhood have large Pb body burdens, which increases Pb release during pregnancy by promoting bone Pb mobilisation. The purpose of this study was to investigate the metabolic mechanisms underlying bone Pb mobilisation and explore the bone metabolism-related pathways during pregnancy. Drinking water containing 0.05% sodium acetate or Pb acetate was provided to weaned female rats for 4 weeks followed by a 4-week washout period, and then rats were co-caged with healthy males of the same age until pregnancy. Blood and bone tissues of the female rats were collected at gestational day (GD) 3 (early pregnancy), GD 10 (middle pregnancy), and GD 17 (late pregnancy), respectively. Pb and calcium concentrations, biomarkers for bone turnover, bone microstructure, serum metabolomics, and metabolic indicators were intensively analyzed. The results demonstrated that pre-pregnancy Pb exposure elevated blood lead levels (BLLs) at GD17, accompanied by a negative correlation between BLLs and trabecular bone Pb levels. Meanwhile, Pb-exposed rats had low bone mass and aberrant bone architecture with a larger number of mature osteoclasts (OCs) compared to the control group. Moreover, the metabolomics uncovered that Pb exposure caused mitochondrial dysfunction, such as enhanced oxidative stress and inflammatory response, and suppressed energy metabolism. Additionally, the levels of ROS, MDA, IL-1ß, and IL-18 involved in redox and inflammatory pathways of bone tissues were significantly increased in the Pb-exposed group, while antioxidant SOD and energy metabolism-related indicators including ATP levels, Na+-K+-ATPase, and Ca2+-Mg2+-ATPase activities were significantly decreased. In conclusion, pre-pregnancy Pb exposure promotes bone Pb mobilisation and affects bone microstructure in the third trimester of pregnancy, which may be attributed to OC activation and mitochondrial dysfunction.

Dasatinib plus prednisone as induction and consolidation for adults with Ph-positive acute lymphoblastic leukaemia: A single-arm, multicentre, phase 2 trial.

To reducing chemotherapy-related toxicity, the chemo-free regimens become a new trend of Ph + ALL treatment. Therefore, we conducted a phase 2 trial of dasatinib plus prednisone, as induction (Course I) and early consolidation (Courses II and III) treating newly diagnosed Ph + ALL. The trial was registered at www.chictr.org.cn, ChiCTR2000038053. Forty-one patients were enrolled from 15 hospitals. The complete remission (CR) was 95% (39/41), including two elderly induction deaths. By the end of Course III, 25.6% (10/39) of patients achieved a complete molecular response. With a median follow-up of 15.4 months, 2-year disease-free survival (DFS) were 100% and 33% for patients who receiving haematopoietic stem cell transplantation (HSCT) at CR1 and receiving chemotherapy alone respectively. When censored at time of HSCT, 2-year DFS were 51% and 45% for young and elderly patients (p = 0.987). 2-year overall survival were 45%, 86% and 100% for patients without HSCT, receiving HSCT after relapse and receiving HSCT at CR1 respectively. A total of 12 patients had marrow recurrences and one had CNS relapse, with 38% occurred early (between Courses I and III). IKZF1 gene deletion was shown to be associated with relapse (p = 0.019). This chemo-free induction and early consolidation regimen was efficacious and well-tolerated in de novo Ph + ALL. Allogeneic HSCT conferred definite survival advantage after chemo-free induction.

Methylmercury induced ferroptosis by interference of iron homeostasis and glutathione metabolism in CTX cells.

Environmental methylmercury (MeHg) exposure has gained global attention owing to its serious health hazards, especially neurotoxicity. Ferroptosis is a novel form of programmed cell death characterized by lipid peroxidation and iron overload. However, the occurrence of ferroptosis and its underlying mechanisms have not been fully elucidated in the methylmercury-induced neurotoxicity and the role of Nrf2 in MeHg-induced ferroptosis remains unexplored. In this study, we verified that MeHg decreased cell viability in a dose- and time-dependent manner in the Rat Brain Astrocytes cells (CTX cells). MeHg (3.5 µmol/L) exposure induced CTX cells to undergo ferroptosis, as evidenced by glutathione (GSH) depletion, lipid peroxidation, and iron overload, which was significantly rescued by the ferroptosis-specific inhibitors Ferrostatin-1 and Deferoxamine. MeHg directly disrupted the process of GSH metabolism by downregulating of SLC7A11 and GPX4 and interfered with intracellular iron homeostasis through inhibition of iron storage and export. Simultaneously, the expression of Nrf2 was upregulated by MeHg in CTX cells. Hence, the inhibition of Nrf2 activity further downregulated the levels of GPX4, SLC7A11, FTH1, and SLC40A1, which aggravated MeHg-induced ferroptosis to a greater extent. Overall, our findings provided evidence that ferroptosis played a critical role in MeHg-induced neurotoxicity, and suppressing Nrf2 activity further exacerbated MeHg-induced ferroptosis in CTX cells.

A green synthesized medicine residue carbon-based iron composite for the removal of chromium (VI) and cadmium (II): Performance, kinetics and mechanism.

Nowadays, clean-up of heavy metals from wastewaters using waste residue carbon-based material has received increasing attention. In this work, a novel Chinese medicine residue carbon-based nano zero-valent iron composite (CM-nZVI) had been successfully prepared using the combined Chinese medicine residue, FeCl3 and green tea extract. Cr(VI) and/ or Cd(II) removal in water by the CM-nZVI were systematacially investigated with a series of batch experiments. The most relevant findings indicated the adsorption efficiecy and capacity of Cr(VI) by CM-nZVI were respecitvely nearly 98% and 26 mg/g under optimized reaction conditions. The negative influences of the cations on the Cr(VI) removal followed the order of Al3+ > Ca2+ > Mg2+ Na+ > K+, but the anions followed the order of HCO3- > PO43- > NO3- > Cl- > SO42-. Humic acid (HA) and ionic strength with high concentrations severely inhibited Cr(VI) removal. The Cr(VI) adsorption on CM-nZVI fitted well by the pseudo-second-order kinetic and Langmuir models. A monolayer endothermic chemisorption occurred on Cr(VI) adsorption over CM-nZVI, and Cr(VI) removal by CM-nZVI primarily involved in the absorption, reduction, precipitation and complexation processes. Both Cr(VI) and Cd(II) removals had been achieved by CM-nZVI at their low concentrations. This CM-nZVI showed a better reusability proprity for Cr(VI) and Cd(II) removal with the regeneration of CM-nZVI through simple pickling. The outcomes of this work show that CM-nZVI could be used an effective material for heavy metals removal from water.

Programing Cell Assembly via Ink-Free, Label-Free Magneto-Archimedes Based Strategy.

Tissue engineering raised a high requirement to control cell distribution in defined materials and structures. In "ink"-based bioprintings, such as 3D printing and photolithography, cells were associated with inks for spatial orientation; the conditions suitable for one ink are hard to apply on other inks, which increases the obstacle in their universalization. The Magneto-Archimedes effect based (Mag-Arch) strategy can modulate cell locomotion directly without impelling inks. In a paramagnetic medium, cells were repelled from high magnetic strength zones due to their innate diamagnetism, which is independent of substrate properties. However, Mag-Arch has not been developed into a powerful bioprinting strategy as its precision, complexity, and throughput are limited by magnetic field distribution. By controlling the paramagnetic reagent concentration in the medium and the gaps between magnets, which decide the cell repelling scope of magnets, we created simultaneously more than a hundred micrometer scale identical assemblies into designed patterns (such as alphabets) with single/multiple cell types. Cell patterning models for cell migration and immune cell adhesion studies were conveniently created by Mag-Arch. As a proof of concept, we patterned a tumor/endothelial coculture model within a covered microfluidic channel to mimic epithelial-mesenchymal transition (EMT) under shear stress in a cancer pathological environment, which gave a potential solution to pattern multiple cell types in a confined space without any premodification. Overall, our Mag-Arch patterning presents an alternative strategy for the biofabrication and biohybrid assembly of cells with biomaterials featured in controlled distribution and organization, which can be broadly employed in tissue engineering, regenerative medicine, and cell biology research.

Lipid-based nanoformulation optimization for achieving cutaneous targeting: Niosomes as the potential candidates to fulfill this aim.

The present study screened the utility of topically-applied nanoformulations to target the drugs/actives into the skin reservoir with the reduction of possible systemic absorption. The lipid-based nanoformulations selected in this study included solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), nanoemulsions (NEs), liposomes, and niosomes. We loaded flavanone and retinoic acid (RA) as the penetrants. The prepared nanoformulations were assessed for their average diameter, polydispersity index (PDI), and zeta potential. An in vitro permeation test (IVPT) was utilized to determine the skin delivery into/across pig skin, atopic dermatitis (AD)-like mouse skin, and photoaged mouse skin. We found an increased skin absorption of lipid nanoparticles following the increase of solid lipid percentage in the formulations (SLNs > NLCs > NEs). The use of liposomes even reduced the dermal/transdermal selectivity (S value) to lessen the cutaneous targeting. The niosomes resulted in significantly greater RA deposition and reduced permeation in the Franz cell receptor compared to the other nanoformulations. The S value of the RA delivery via stripped skin was increased by 26-fold in the niosomes compared to the free RA. The dye-labeled niosomes displayed a strong fluorescence in the epidermis and upper dermis through the visualization of fluorescence and confocal microscopies. The cyanoacrylate skin biopsy manifested greater hair follicle uptake of the niosomes compared to the free penetrants by 1.5 to three-fold. The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay indicated an increase in antioxidant ability from 55% to 75% after flavanone entrapment in the niosomes. In the activated keratinocytes, the niosomal flavanone could suppress the overexpressed CCL5 to the baseline control because of the facile cell internalization. After the formulation optimization, the niosomes with higher phospholipid amount had a superior effect in delivering penetrants into the skin reservoir, with limited permeation to the receptors.