Chronic intermittent hypoxia-induced oxidative stress activates TRB3 and phosphorylated JNK to mediate insulin resistance and cell apoptosis in the pancreas.

This study explores the potential mechanisms of obstructive sleep apnoea (OSA) complicates type 2 diabetes mellitus (T2DM) by which chronic intermittent hypoxia (CIH) induces insulin resistance and cell apoptosis in the pancreas through oxidative stress. Four- and eight-week CIH rat models were established, and Tempol (100 mg/kg/d), was used as an oxidative stress inhibitor. This study included five groups: 4-week CIH, 4-week CIH-Tempol, 8-week CIH, 8-week CIH-Tempol and normal control (NC) groups. Fasting blood glucose and insulin levels were measured in the serum. The expression levels of 8-hidroxy-2-deoxyguanosine (8-OHdG), tribbles homologue 3 (TRB3), c-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), insulin receptor substrate-1 (IRS-1), phosphorylated IRS-1 (Ser307) (p-IRS-1ser307 ), protein kinase B (AKT), phosphorylated AKT (Ser473) (p-AKTser473 ), B cell lymphoma protein-2 (Bcl-2), cleaved-caspase-3 (Cl-caspase-3), and the islet cell apoptosis were detected in the pancreas. CIH induced oxidative stress in the pancreas. Compared with that in the NC group and CIH-Tempol groups individually, the homeostasis model assessment of insulin resistance (HOMA-IR) and apoptosis of islet cells was increased in the CIH groups. CIH-induced oxidative stress increased the expression of p-IRS-1Ser307 and decreased the expression of p-AKTSer473 . The expression levels of TRB3 and p-JNK were higher in the CIH groups than in both the CIH-Tempol and NC groups. Meanwhile, the expressions of Cl-caspase-3 and Bcl-2 were upregulated and downregulated, respectively, in the CIH groups. Hence, the present study demonstrated that CIH-induced oxidative stress might not only induce insulin resistance but also islet cell apoptosis in the pancreas through TRB3 and p-JNK.

An improved comprehensive model for assessing the heavy metals exposure towards waterbirds: A case report from Black-necked cranes (Grus nigricollis) in Caohai Wetland, China.

Heavy metal contamination poses a significant environmental threat to wildlife on global scale, making accurate assessment of exposure risk crucial for conservation efforts, particularly for vulnerable species. Existing risk assessment models have been widely used, but their construction process lacks comprehensive considerations. In this study, we constructed an optimized health risk assessment model based on the well-established "Liu's model" and "ADI model", and applied the pollution allocation factor (AF) to accurately assess the risk of heavy metal exposure to wildlife. Our model was applied to assess exposure risk of heavy metal for the black-necked crane(Grus nigricollis), a flagship species in the alpine wetland ecosystem of Caohai Wetland. Soil, plant and black-necked crane fecal samples were collected from the Caohai Wetland and surrounding areas in Guizhou, China. We revealed varying degrees of As, Cd, Cr, Ni, Pb, and Zn contamination in soil and plants from different habitats, exceeding the background or plant limit values. This indicated that the black-necked crane and other waterbirds living in Caohai Wetland are suffering with the multi-elemental heavy metal contamination, especially in the gutterway and grassland. The exposure dose of As, Cd, Cr, Ni, Cu, and Zn toward black-necked cranes differed significantly in soil and plant pathways (P < 0.05). As, Cd, Cu, and Zn were mainly derived from plants consumption, while Cr and Ni originated from soil. Considering the contribution of soil and plant pathways to heavy metal exposure in black-necked cranes, the exposure doses of each elements calculated via food intake accounted for over half of the exposure calculated via feces (AF>0.5). The risk assessment model identified Cr and Pb were the highest risk elements for black-necked cranes, with exposure risk simulated through feces exceeding those through food. These findings suggested that current Liu's model may underestimate the effects of other pathways and medium. Therefore, we proposed a more comprehensive and accurate model for evaluating the exposure risk of black-necked cranes, incorporating AF to quantify the contribution of risk sources to black-necked cranes and understand their overall health risk. This model can serve as a useful tool for the conservation and habitat quality improvement of the black-necked cranes and other waterbirds.

Proteomic analysis by 4D label-free MS-PRM identified that Nptx1, Ptpmt1, Slc25a11, and Cpt1c are involved in diabetes-associated cognitive dysfunction.

BACKGROUND: Diabetes-associated cognitive dysfunction (DACD) is a chronic ailment that exerts a substantial influence on the overall well-being of individuals. The hippocampus assumes a pivotal role in the progression and sustenance of cognitive impairment. The identification of differentially expressed proteins (DEPs) in the hippocampus is crucial for understanding the mechanisms of DACD. METHODS: A rat model of DACD was established by a high-fat diet combined with streptozotocin intraperitoneal injection. The Morris water maze (MWM), hematoxylin and eosin (H&E) staining, Nissl staining, and transmission electron microscope (TEM) were performed on the rats. The proteins expressed in the hippocampus were detected using 4D label-free quantitative proteomics. Four DEPs, namely Nptx1, Ptpmt1, Slc25a11, and Cpt1c, were validated using parallel reaction monitoring (PRM). RESULT: Our study found that hippocampal lesions were present in the DACD rat models. There were 59 up-regulated and 98 down-regulated DEPs in the Model group compared to the Control group. We found that the levels of Nptx1, Ptpmt1, Slc25a11, and Cpt1c were elevated in the Model group, which are important for cell mitochondrial function. It should be noted that in our study, we only used PRM to validate the expression of these proteins. However, more evidence is needed to establish the relationship between these protein changes and DACD. CONCLUSION: Our research results may provide further insight into the molecular pathology of hippocampal injury in DACD. In addition, further studies and clinical trials are required to confirm our findings and establish a more conclusive molecular mechanism for DACD.

Effect of diet on gut microbiota diversity in mandarin ducks (Aix galericulata) revealed by Illumina high-throughput sequencing.

The animal gut is a dynamic ecosystem. Many factors affect the structure and diversity of the gut microbiota, among which the composition of the diet is a direct determinant. To investigate the effect of dietary components on the gut microbiota of mandarin duck, nine fecal samples were collected from two foraging sites at Shiqian Mandarin Duck Lake National Wetland Park, Guizhou, China. We analyzed the chloroplast rbcL gene, mitochondrial COI gene, and 16S rRNA gene from the total DNA of the fecal samples by high-throughput sequencing to identify plant and animal components of the diet and the composition of the gut microbiota of mandarin duck. We found that the gut microbiota composition was significantly correlated with the number of species in the diet. Mandarin ducks with more diverse diets had a more complex gut microbiota with fewer pathogenic bacteria. This study provides further theoretical support for the effect of dietary differences on the structure of the host gut microbiota and clarifies the feeding preferences of mandarin duck in breeding areas.

A Photopolymerized Semi-Interpenetrating Polymer Networks-Based Hydrogel Incorporated with Nanoparticle for Local Chemotherapy of Tumors.

PURPOSE: To address the issue of local drug delivery in tumor treatment, a novel nanoparticle-hydrogel superstructure, namely semi-interpenetrating polymer networks (semi-IPNs) hydrogel composed of poly (ethylene glycol) diacrylate (PEGDA) and hyaluronic acid (HA) and incorporated with paclitaxel (PTX) loaded PLGA nanoparticles (PEGDA-HA/PLGA-PTX), was prepared by in situ UV photopolymerization for the use of local drug delivery. METHODS: Using the gelation time, swelling rate and degradation rate as indicators, the optimal proportion of Irgacure 2959 initiator and the concentration of HA was screened and obtained for preparing hydrogels. Next, paclitaxel (PTX) loaded PLGA nanoparticles (PLGA-PTX NPs) were prepared by the emulsion solvent evaporation method. RESULTS: The mass ratio of the initiator was 1%, and the best concentration of HA was 5 mg/mL in PEGDA-HA hydrogel. In vitro experiments showed that PLGA-PTX NPs had similar cytotoxicity to free PTX, and the cell uptake ratio on NCI-H460 cells was up to 96% by laser confocal microscopy and flow cytometry. The drug release of the PEGDA-HA/PLGA-PTX hydrogel local drug delivery system could last for 13 days. In vivo experiments proved that PEGDAHA/PLGA-PTX hydrogel could effectively inhibit the tumor growth without causing toxic effects in mice. CONCLUSIONS: This study demonstrated that the PEGDA-HA/PLGA-PTX hydrogel is a promising local drug delivery system in future clinical applications for tumor therapy. A photopolymerized semi-interpenetrating polymer networks-based hydrogel incorporated with paclitaxel-loaded nanoparticles was fabricated by in situ UV photopolymerization, providing a promised nanoplatform for local chemotherapy of tumors.

Ultrasound-Targeted Microbubble Destruction (UTMD) Combined with Liposome Increases the Effectiveness of Suppressing Proliferation, Migration, Invasion, and Epithelial- Mesenchymal Transition (EMT) via Targeting Metadherin (MTDH) by ShRNA.

BACKGROUND Reports show that ultrasound-targeted microbubble destruction (UTMD) is a promising method of gene therapy, and metadherin (MTDH) is related to the development of breast cancer. Thus, we investigated the role of MTDH in breast cancer and compared the effect of suppressing MTDH by shRNA using liposome, UTMD, or the combination of these 2 methods. MATERIAL AND METHODS Graphing of survival curves of MTDH was analyzed by bioinformatics. UTMD was conducted using an ultrasonic therapeutic apparatus. Cell counting kit-8 (CCK-8) assay was used to measure cell viability. Migration and invasion rates were measured by wound healing test and Transwell invasion assay, respectively. The expression of MTDH, E-cadherin, metastasis-associated protein-1 (MTA-1), matrix metalloproteinase (MMP)-2, and MMP-9 were measured by Western blot and qPCR. RESULTS The prognosis of breast cancer can be decreased by the high expression of MTDH, and elevated expression of MTDH was discovered in MCF-7, MCF-10A, and T47D cell lines. UTMD combined with liposome is most efficient in transfecting shRNA, clearly suppressing the expression of MTDH and thereby decreasing cell viability, migration, invasion rate, and epithelial- mesenchymal transition (EMT) processes in the MCF-7 cell line. CONCLUSIONS UTMD combined with liposome could be used as a more efficient way to transfect shRNA into cells to suppress the expression of MTDH and thus lead to the downregulation of proliferation, migration, and EMT processes of the MCF-7 cell line, showing the potential for use in gene therapy.

Chronic intermittent hypoxia disturbs insulin secretion and causes pancreatic injury via the MAPK signaling pathway.

Obstructive sleep apnea (OSA) is a breathing disorder during sleep, with a most prominent character of chronic intermittent hypoxia (CIH), which induces the generation of reactive oxygen species (ROS) that damages multiple tissues and causes metabolic disorders. In this study, we established a rat model of varying OSA with different grades of CIH (12.5% O2, 10% O2, 7.5% O2, and 5% O2) for 12 weeks, and found that CIH stimulated insulin secretion, reduced the insulin:proinsulin ratio in pancreatic tissue, and caused pancreatic tissue lesions and cell apoptosis in a dose-dependent manner. Moreover, CIH promoted the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6, and activated mitogen-activated protein kinase (MAPK) family members, extracellular regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), and P38, depending on the O2 concentration. In summary, CIH disturbed insulin secretion, and caused inflammation, lesions, and cell apoptosis in pancreatic tissue via the MAPK signaling pathway, which may be of great significance for clinical treatment of OSA and type 2 diabetes mellitus (T2DM).

The compact mitochondrial genome of Zorotypus medoensis provides insights into phylogenetic position of Zoraptera.

BACKGROUND: Zoraptera, generally regarded as a member of Polyneoptera, represents one of the most enigmatic insect orders. Although phylogenetic analyses based on a wide array of morphological and/or nuclear data have been performed, the position of Zoraptera is still under debate. Mitochondrial genome (mitogenome) information is commonly considered to be preferable to reconstruct phylogenetic relationships, but no efforts have been made to incorporate it in Zorapteran phylogeny. To characterize Zoraptera mitogenome features and provide insights into its phylogenetic placement, here we sequenced, for the first time, one complete mitogenome of Zoraptera and reconstructed the phylogeny of Polyneoptera. RESULTS: The mitogenome of Zorotypus medoensis with an A+T content of 72.50% is composed of 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and a noncoding A+T-rich region. The gene content and arrangement are identical to those considered ancestral for insects. This mitogenome shows a number of very unusual features. First, it is very compact, comprising 14,572 bp, and is the smallest among all known polyneopteran mitogenomes. Second, both noncoding sequences and coding genes exhibit a significant decrease in size compared with those of other polyneopterans. Third, Z. medoensis mitogenome has experienced an accelerated substitution rate. Fourth, truncated secondary structures of tRNA genes occur with loss of dihydrouridine (DHU) arm in trnC, trnR, and trnS(AGN) and loss of TΨC arm in trnH and trnT. The phylogenetic analyses based on the mitogenome sequence information indicate that Zoraptera, represented by Z. medoensis, is recovered as sister to Embioptera. However, both Zoraptera and Embioptera exhibit very long branches in phylogenetic trees. CONCLUSIONS: Characterization of Z. medoensis mitogenome contributes to our understanding of the enigmatic Zoraptera. Mitogenome data demonstrate an overall strong resolution of deep-level phylogenies of Polyneoptera but not Insecta. It is preferable to expand taxon sampling of Zoraptera and other poorly represented orders in future to break up long branches.

Gene redundancy and gene compensation of insulin-like peptides in the oocyte development of bean beetle.

Bean beetle (Callosobruchus maculatus) exhibits clear phenotypic plasticity depending on population density; However, the underlying molecular mechanism remains unknown. Compared to low-density individuals, high-density individuals showed a faster terminal oocyte maturity rate. Four insulin-like peptide (ILP) genes were identified in the bean beetle, which had higher expression levels in the head than in the thorax and abdomen. The population density could regulate the expression levels of CmILP1-3, CmILP2-3, and CmILP1 as well as CmILP3 in the head, thorax, and abdomen, respectively. RNA interference results showed that each CmILP could regulate terminal oocyte maturity rate, indicating that there was functional redundancy among CmILPs. Silencing each CmILP could lead to down-regulation of some other CmILPs, however, CmILP3 was up-regulated in the abdomen after silencing CmILP1 or CmILP2. Compared to single gene silencing, silencing CmILP3 with CmILP1 or CmILP2 at the same time led to more serious retardation in oocyte development, suggesting CmILP3 could be up-regulated to functionally compensate for the down-regulation of CmILP1 and CmILP2. In conclusion, population density-dependent plasticity in terminal oocyte maturity rate of bean beetle was regulated by CmILPs, which exhibited gene redundancy and gene compensation.

Analysis of winter diet in Guizhou golden monkey (Rhinopithecus brelichi) using DNA metabarcoding data.

The Guizhou golden monkey (Rhinopithecus brelichi) is a critically endangered wildlife species, and understanding its diet composition may be useful for assessing its feeding strategies. DNA metabarcoding was used to determine the dietary diversity of R. brelichi. DNA was extracted from 31 faecal samples and amplified chloroplast rbcL and mitochondrial COI DNA was sequenced using the Illumina NovaSeq platform. A comparative analysis of the sequences revealed that the five most abundant plant genera were Magnolia, Morinda, Viburnum, Tetradium and Eurya. In winter, R. brelichi mostly consumed shrubs, herbs and shrubs/trees according to the habit of plant genera with higher abundances comparatively. The five most abundant families in animal diet were Psychodidae, Trichinellidae, Staphylinidae, Scarabaeidae and Trichoceridae. This study is the first to show the composition of the winter animal diets of R. brelichi based on DNA metabarcoding. These results provide an important basis for understanding the diet of wild R. brelichi, which inhabits only the Fanjingshan National Nature Reserve, China.

Two new species of Hemielimaea Brunner von Wattenwyl from China.

Two new species Hemielimaea (Hemielimaea) paracari sp. nov. and H. (H.) parva sp. nov. from southwestern China are described. Characteristics of the stridulatory file on underside of male left tegmen, male stridulatory area on left and right tegmen, and abdominal apex of male are provided. Important and necessary illustrations of the new species are presented. Materials come from the following two depositories: Institute of Zoology, Chinese Academy of Sciences, Beijing, China (IZCAS), and China Agricultural University, Beijing, China (CAU).

Winter Dietary Analysis Reveals the Foraging Differences of Wild Boar (Sus scrofa) in Different Regions of a Karst Mountainous Area.

Wild boars (Sus scrofa) are extremely common in southern China, but little study has been conducted regarding reporting the dietary habits of wild boars using high-throughput sequencing technology, especially in karst areas, due to the difficulty in obtaining stomach contents of wild boars. In our study, the stomach contents of 14 wild boars in southern China were analyzed by DNA metabarcoding. The results showed that there were 153 genera, 93 families, and 48 orders of plant food sources for wild boars. The main plant food component were Cissus, Dioscorea, Quercus, Actinidia, and Houttuynia. The most numerous taxa of animal food sources were Elaphodus, Amynthas, Chonaphe, Rattus, and Tanytarsus. It is noteworthy that Elaphodus cephalophus were detected in most of the stomach samples, accounting for a large portion of animal food sources. The results showed that there were significant differences in the diets of wild boars in different regions; however, no significant differences were noted between male and female wild boars. Our study revealed the dietary preference of wild boars under the special forest conditions in the mountainous area of southwest China, as well as the relationship between the dietary habits of wild boars and their habitats from the perspective of resource utilization, thus providing a key scientific basis for the prevention and control of wild boars, along with resource protection.

Host genetic background rather than diet-induced gut microbiota shifts of sympatric black-necked crane, common crane and bar-headed goose.

Introduction: Gut microbiota of wild birds are affected by many factors, and host genetic background and diet are considered to be two important factors affecting their structure and function. Methods: In order to clarify how these two factors influence the gut microbiota, this study selected the sympatric and closely related and similar-sized Black-necked Crane (Grus nigricollis) and Common Crane (Grus grus), as well as the distantly related and significantly different-sized Bar-headed Goose (Anser indicus). The fecal samples identified using sanger sequencing as the above three bird species were subjected to high-throughput sequencing of rbcL gene and 16S rRNA gene to identify the feeding types phytophagous food and gut microbiota. Results: The results showed significant differences in food diversity between black-necked cranes and Common Cranes, but no significant differences in gut microbiota, Potatoes accounted for approximately 50% of their diets. Bar-headed Geese mainly feed on medicinal plants such as Angelica sinensis, Alternanthera philoxeroides, and Ranunculus repens. Black-necked cranes and Common Cranes, which have a high-starch diet, have a similar degree of enrichment in metabolism and synthesis functions, which is significantly different from Bar-headed Geese with a high-fiber diet. The differences in metabolic pathways among the three bird species are driven by food. The feeding of medicinal plants promotes the health of Bar-headed Geese, indicating that food influences the functional pathways of gut microbiota. Spearman analysis showed that there were few gut microbiota related to food, but almost all metabolic pathways were related to food. Conclusion: The host genetic background is the dominant factor determining the composition of the microbiota. Monitoring the changes in gut microbiota and feeding types of wild birds through bird feces is of great reference value for the conservation of other endangered species.

Mitogenome of the stink bug Aelia fieberi (Hemiptera: Pentatomidae) and a comparative genomic analysis between phytophagous and predatory members of Pentatomidae.

Aelia fieberi Scott, 1874 is a pest of crops. The mitogenome of A. fieberi (OL631608) was decoded by next-generation sequencing. The mitogenome, with 41.89% A, 31.70% T, 15.44% C and 10.97% G, is 15,471 bp in size. The phylogenetic tree showed that Asopinae and Phyllocephalinae were monophyletic; however, Pentatominae and Podopinae were not monophyletic, suggesting that the phylogenetic relationships of Pentatomoidae are complex and need revaluation and revision. Phytophagous bugs had a ~20-nucleotide longer in nad2 than predatory bugs. There were differences in amino acid sequence at six sites between phytophagous bugs and predatory bugs. The codon usage analysis indicated that frequently used codons used either A or T at the third position of the codon. The analysis of amino acid usage showed that leucine, isoleucine, serine, methionine, and phenylalanine were the most abundant in 53 species of Pentatomoidae. Thirteen protein-coding genes were evolving under purifying selection, cox1, and atp8 had the strongest and weakest purifying selection stress, respectively. Phytophagous bugs and predatory bugs had different evolutionary rates for eight genes. The mitogenomic information of A. fieberi could fill the knowledge gap for this important crop pest. The differences between phytophagous bugs and predatory bugs deepen our understanding of the effect of feeding habit on mitogenome.

Mitochondrial genome analysis, phylogeny and divergence time evaluation of Strixaluco (Aves, Strigiformes, Strigidae).

Background Prior research has shown that the European peninsulas were the main sources of Strixaluco colonisation of Northern Europe during the late glacial period. However, the phylogenetic relationship and the divergence time between S.aluco from Leigong Mountain Nature Reserve, Guizhou Province, China and the Strigiformes from overseas remains unclear. The mitochondrial genome structure of birds is a covalent double-chain loop structure that is highly conserved and, thus, suitable for phylogenetic analysis. This study examined the phylogenetic relationship and divergence time of Strix using the whole mitochondrial genome of S.aluco. New information In this study, the complete mitochondrial genome of Strixaluco, with a total length of 18,632 bp, is reported for the first time. A total of 37 genes were found, including 22 tRNAs, two rRNAs, 13 protein-coding genes and two non-coding control regions. Certain species of Tytoninae were used as out-group and PhyloSuite software was applied to build the ML-tree and BI-tree of Strigiformes. Finally, the divergence time tree was constructed using BEAST 2.6.7 software and the age of Miosurniadiurna fossil-bearing sediments (6.0-9.5 Ma) was set as internal correction point. The common ancestor of Strix was confirmed to have diverged during the Pleistocene (2.58-0.01 Ma). The combined action of the dramatic uplift of the Qinling Mountains in the Middle Pleistocene and the climate oscillation of the Pleistocene caused Strix divergence between the northern and southern parts of mainland China. The isolation of glacial-interglacial rotation and glacier refuge was the main reason for the divergence of Strixuralensis and S.aluco from their common ancestor during this period. This study provides a reference for the evolutionary history of S.aluco.

Turning Waste into Treasure: The Full Technological Process and Product Performance Characterization of Flushable Wet Wipes Prepared from Corn Stalk.

As a daily consumable, wet wipes are mostly synthetic fibers, which are incinerated or landfilled after use. The nanoplastics generated during this process will lead to environmental pollution. The application of flushable wet wipes, which are dispersible and fully degradable, is of great significance. The main raw material for flushable wipes is wood pulp, which has a long growth cycle and high cost. Corn is widely planted and has a short growth cycle. Currently most corn stalk is treated by incineration, which produces a lot of smoke that pollutes the environment. Therefore, using corn stalk as the raw material for flushable wet wipes, replacing wood pulp, is both cost-effective and environmentally friendly. In this study, aiming at industrial production, we explored the full process of producing flushable wet wipes from corn stalk to pulp board, then to the final wipes. The corn stalk was treated using alkali and a bleaching agent to obtain corn stalk pulp, which was then made into pulp board through the nonwoven wet-laid process. The optimal parameters for the alkali treatment and bleaching were obtained. The properties of the corn stalk pulp board were compared with the commercial wood pulp board. Further, we mixed the corn stalk pulp with Lyocell fiber to prepare wet-laid webs, which were then bonded using a chemical binder poloxamer. Then, the evenness of the web, mechanical properties, absorption, and dispersibility of the flushable wipes were characterized. Results showed that the pulp obtained using the optimal treatment process has a high yield and better whiteness. The properties of the corn stalk pulp board are comparable with the commercial wood pulp board, which can therefore potentially be replaced by the corn stalk board prepared in our study. The prepared flushable wet wipes had good evenness and their water absorption rate was more than 600%. The mechanical strength in dry and wet states achieved 595.94 N/m and 179.00 N/m, respectively. Most importantly, the wet wipes can completely disperse under the standardized testing method. A good balance of dispersibility and wet strength of the wet wipes was achieved.

Remodeling liver microenvironment by L-arginine loaded hollow polydopamine nanoparticles for liver cirrhosis treatment.

Liver cirrhosis is a liver disease with a high mortality rate worldwide, and antifibrotic drugs are commonly used clinically to alleviate the symptoms, but there are still many challenges. Many studies have shown that excessive reactive oxygen species (ROS) in the microenvironment of liver lesions is an important factor leading to the development of liver cirrhosis. Herein, a nanomedicine-mediated antioxidant therapy was utilized to remodel liver microenvironment and hence reverse the process of cirrhosis from the root. Firstly, L-arginine (L-Arg) loaded and pPB peptide modified PEGylated hollow polydopamine (HPDA) nanoparticles (L-Arg@HPDA-PEG-pPB, L@HPp) were prepared successfully. The in vitro and in vivo experiment showed that L@HPp significantly inhibited oxidative stress and inflammatory reaction, reduced the activation of hepatic stellate cells (HSCs), inhibited the pro-fibrosis molecular pathway, and reduced the deposition of extracellular matrix (ECM), thereby effectively inhibiting liver fibrosis. The pPB peptide modification increased the targeting effect to HSCs. In addition, the oxidative microenvironment in liver cirrhosis promoted the transformation of the loaded L-Arg to nitric oxide (NO), and the latter one caused vascular dilation and further relieved portal hypertension, a typical complication of liver cirrhosis. Therefore, L@HPp had a good prospect of clinical application in the treatment of liver cirrhosis and its complications.

pH-Responsive Delivery of H2 through Ammonia Borane-Loaded Hollow Polydopamine for Intervertebral Disc Degeneration Therapy.

An imbalance in oxidative and inflammatory regulation is the main contributor to intervertebral disc degeneration (IDD). Hydrogen (H2) therapy is a promising antioxidation and anti-inflammatory approach. However, the key to the treatment is how to maintain the long-term effective H2 concentration in the intervertebral disc (IVD). Therefore, we developed a pH-responsive delivery of H2 through ammonia borane-loaded hollow polydopamine (AB@HPDA) for IDD therapy, which has sufficient capacity to control long-term H2 release in an acid-dependent manner in degenerative IVD. The characterization, toxicity, and pH-responsive H2 release of AB@HPDA was detected in vitro. The metabolization of AB@HPDA in the degenerated IVD was tested by in vivo imaging. The therapeutic effect of AB@HPDA on IDD was tested in vivo by X-ray, MRI, water content of the disc, and histological changes. Nuclear extracellular matrix (ECM) components, oxidative stress, and inflammation were also tested to explore potential therapeutic mechanisms. AB@HPDA has good biocompatibility at concentrations less than 500 µg/mL. The H2 release of AB@HPDA was pH responsive. Therefore, AB@HPDAs can provide efficient hydrogen therapy with controlled H2 release in response to the acidic degenerated IVD microenvironment. The metabolization of AB@HPDA in IVD was slow and lasted up to 11 days. HPDA and AB@HPDA significantly inhibited IDD, as tested by X-ray, MRI, disc water content, and histology (P < 0.05). pH-responsive H2 delivery through AB@HPDAs has the potential to efficiently treat IDD by inhibiting ECM degradation and rebalancing oxidative stress and inflammation in degenerative IVDs.

Hollow-polydopamine-nanocarrier-based near-infrared-light/pH-responsive drug delivery system for diffuse alveolar hemorrhage treatment.

Introduction: Diffuse alveolar hemorrhage (DAH) is a serious complication caused by systemic lupus erythematosus (SLE). Tissue damage and changes in immune response are all associated with excessive free radical production. Therefore, removing excess reactive oxygen species are considered a feasible scheme for diffuse alveolar hemorrhage treatment. Cyclophosphamide is often used as the main therapeutic drug in clinics. However, CTX carries a high risk of dose-increasing toxicity, treatment intolerance, and high recurrence rate. The combination of therapeutic drugs and functional nanocarriers may provide an effective solution. PDA is rich in phenolic groups, which can remove the reactive oxygen species generated in inflammatory reactions, and can serve as excellent free radical scavengers. Methods: We developed a hollow polydopamine (HPDA) nanocarrier loaded with CTX by ionization to prepare the novel nanoplatform, CTX@HPDA, for DAH treatment. The monodisperse silica nanoparticles were acquired by reference to the typical Stober method. PDA was coated on the surface of SiO2 by oxidation self-polymerization method to obtain SiO2@PDA NPs. Then, HPDA NPs were obtained by HF etching. Then HPDA was loaded with CTX by ionization to prepare CTX@HPDA. Then we tested the photothermal effect, animal model therapeutics effect, and biosafety of CTX@HPDA. Results: Material tests showed that the CTX@ HPDA nanoplatform had a uniform diameter and could release CTX in acidic environments. The vitro experiments demonstrated that CTX@HPDA has good photothermal conversion ability and photothermal stability. Animal experiments demonstrated that the CTX@HPDA nanoplatform had good biocompatibility. The nanoplatform can dissociate in acidic SLE environment and trigger CTX release through photothermal conversion. Combining HPDA, which scavenges oxygen free radicals, and CTX, which has immunosuppressive effect, can treat pulmonary hemorrhage in SLE. Micro-CT can be used to continuously analyze DAH severity and lung changes in mice after treatment. The pulmonary exudation in the various treatment groups improved to varying degrees. Discussion: In this study, we report a photothermal/PH-triggered nanocarrier (CTX@HPDA) for the precise treatment of SLE-DAH. CTX@HPDA is a simple and efficient nanocarrier system for DAH therapy. This work provides valuable insights into SLE treatment.

Monitoring the in vivo siRNA release from lipid nanoparticles based on the fluorescence resonance energy transfer principle.

The siRNA-loaded lipid nanoparticles have attracted much attention due to its significant gene silencing effect and successful marketization. However, the in vivo distribution and release of siRNA still cannot be effectively monitored. In this study, based on the fluorescence resonance energy transfer (FRET) principle, a fluorescence dye Cy5-modified survivin siRNA was conjugated to nanogolds (Au-DR-siRNA), which were then wrapped with lipid nanoparticles (LNPs) for monitoring the release behaviour of siRNA in vivo. The results showed that once Au-DR-siRNA was released from the LNPs and cleaved by the Dicer enzyme to produce free siRNA in cells, the fluorescence of Cy5 would change from quenched state to activated state, showing the location and time of siRNA release. Besides, the LNPs showed a significant antitumor effect by silencing the survivin gene and a CT imaging function superior to iohexol by nanogolds. Therefore, this work provided not only an effective method for monitoring the pharmacokinetic behaviour of LNP-based siRNA, but also a siRNA delivery system for treating and diagnosing tumors.