Electroacupuncture modulates the TLR4-NF-κB inflammatory signaling pathway to attenuate ocular surface inflammation in dry eyes of type 2 diabetic rats.

Bioinformatics analysis was performed to reveal the underlying pathogenesis of type 2 diabetes (T2DM) dry eye(DE) and to predict the core targets and potential pathways for electroacupuncture (EA) treatment of T2DM DE, in which key targets such as Toll-likereceptor4 (TLR4), NF-κB and Tumor necrosis factor-α (TNF-α) may be involved. Next, streptozotocin and a high-fat diet were used to generate T2DM-DE rats. Randomly picked EA, fluorometholone, model, and sham EA groups were created from successfully modelled T2DM DE rats. Six more rats were chosen as the blank group from among the normal rats. The results of DE index showed that EA improved the ocular surface symptoms.HE staining showed that EA attenuated the pathological changes in the cornea, conjunctiva and lacrimal gland of T2DM DE rats. EA decreased the expression of TLR4, MyD88, P-NF-κB P65, and TNF-α in the cornea, conjunctiva, and lacrimal gland, in accordance with immunofluorescence and Western blot data. Thus, EA reduced ocular surface symptoms and improved pathological changes of cornea, conjunctiva, and lacrimal gland induced by T2DM DE inT2DM DE rats, and the mechanism may be related to the inhibition of overactivation of the TLR4/NF-κB signaling pathway by EA and thus attenuating ocular surface inflammation.

Electroacupuncture regulates the P2X7R-NLRP3 inflammatory cascade to relieve decreased sensation on ocular surface of type 2 diabetic rats with dry eye.

Dry eye (DE) is a prevalent ocular surface disease in patients with type 2 diabetes (T2DM). However, current medications are ineffective against decreased sensation on the ocular surface. While electroacupuncture (EA) effectively alleviates decreased sensation on ocular surface of DE in patients with T2DM, the neuroprotective mechanism remains unclear. This study explored the pathogenesis and therapeutic targets of T2DM-associated DE through bioinformatics analysis. It further investigated the underlying mechanism by which EA improves decreased sensation on the ocular surface of DE in rats with T2DM. Bioinformatic analysis was applied to annotate the potential pathogenesis of T2DM DE. T2DM and DE was induced in male rats. Following treatment with EA and fluorometholone, comprehensive metrics were assessed. Additionally, the expression patterns of key markers were studied. Key targets such as NLRP3, Caspase-1, and NOD-like receptor signaling may be involved in the pathogenesis of T2DM DE. EA treatment improved ocular measures. Furthermore, EA potently downregulated P2X7R, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 expression within the trigeminal ganglion and spinal trigeminal nucleus caudalis. Targeted P2X7R antagonist (A-438079) and agonist (BzATP) employed as controls to decipher the biochemistry of the therapeutic effects of EA showed an anti-inflammatory effect with A-438079, while BzATP blocked the anti-inflammatory effect of EA. EA relieved DE symptoms and attenuated inflammatory damage to sensory nerve pathways in T2DM rats with DE. These findings suggest a crucial role of EA inhibition of the P2X7R-NLRP3 inflammatory cascade to provide these benefits.

The color of biodegradable mulch films is associated with differences in peanut yield and bacterial communities.

Biodegradable mulch films (BDMs) are increasingly used in agricultural production as desirable alternatives to the current widespread use of polyethylene (PE) mulch films in China. However, potential effects of different colors of BDMs on field crop production and microbiomes remain unexplored. Here, the differences in bacterial communities of peanut rhizosphere soil (RS) and bulk soil (BS) under non-mulching (CK), PE, and three different colors of BDMs were studied. The results indicated that all treatments could increase the soil temperature, which positively affected the growth of the peanut plants. Moreover, mulching affected the bacterial community structure in RS and BS compared to CK. Furthermore, certain BDM treatments significantly enriched N-fixing bacteria (Bradyrhizobium and Mesorhizobium) and functional groups, increased the closeness of bacterial networks, and harbored more beneficial bacteria as keystone taxa in the RS. This in turn facilitated the growth and development of the peanut plants under field conditions. Our study provides new insights into the micro-ecological effects of mulch films, which can be affected by both the mulch type and color. The observed effects are likely caused by temperature and prevalence of specific microbial functions under the employed films and could guide the development of optimized mulching materials.

Direct oral anticoagulants (DOACs) versus low-molecular-weight heparin (LMWH) for extended thromboprophylaxis following major abdominal/pelvic cancer-related surgery: a systematic review and meta-analysis.

BACKGROUND: The use of direct oral anticoagulants (DOACs) as an alternative to low-molecular-weight heparin (LMWH) for extended thromboprophylaxis of abdominal/pelvic cancer-related postoperative thromboembolism (VTE) is unclear. We aim to investigate the efficacy and safety of DOACs vs. LMWH in these patients. METHODS: A systematic review was conducted using EMBASE, MEDLINE, CENTRAL, and Web of science through May 19th, 2023 for all randomized controlled trials (RCTs) and observational studies that compared the outcomes with DOACs vs. LMWH for extended thromboprophylaxis among patients undergoing abdominal/pelvic cancer surgery. Primary efficacy outcome was clinical VTE, and safety outcome was clinically relevant bleeding complications reported within the 30-day postoperative period. This study was registered in PROSPERO (CRD42023413175). RESULTS: We identified 5078 articles and selected 29 full-text articles for eligibility. A total of 9 studies (2 RCTs and 7 observational studies) encompassing 2651 patients were included for systematic review and 7 for meta-analysis. When compared with LMWH extended thromboprophylaxis, DOACs had a similar incidence of VTE (RR: 0.65 [95% CI: 0.32-1.33], I2 = 0%), major bleeding (RR: 1.68 [95% CI: 0.36-7.9], I2 = 26%), and clinically relevant non-major bleeding (RR: 0.68 [95% CI: 0.39-1.19], I2 = 0%). Subgroup analysis suggested no difference according to the study type (RCTs versus observational studies) regarding clinical VTE or major bleeding (Pinteraction = 0.43 and Pinteraction = 0.71, respectively). CONCLUSION: Our results suggest that DOACs for extended thromboprophylaxis were an effective and safe alternative to LMWH after major abdominal/pelvic cancer-related surgery.

Electroacupuncture Alleviates Dry Eye Ocular Pain Through TNF-ɑ Mediated ERK1/2/P2X3R Signaling Pathway in SD Rats.

Purpose: This study aimed to examine electroacupuncture's influence on ocular pain and its potential modulation of the TNF-ɑ mediated ERK1/2/P2X3R signaling pathway in dry eye-induced rat models. Methods: Male Sprague-Dawley rats with induced dry eye, achieved through extraorbital lacrimal gland removal, were treated with electroacupuncture. Comprehensive metrics such as the corneal mechanical perception threshold, palpebral fissure height, eyeblink frequency, eye wiping duration, behavioral changes in the open field test, and the forced swimming test were employed. Additionally, morphological changes in microglia and neurons were observed. Expression patterns of key markers, TNF-ɑ, TNFR1, p-ERK1/2, and P2X3R, in the trigeminal ganglion (TG) and spinal trigeminal nucleus caudalis (SpVc) regions, were studied with etanercept serving as a control to decipher the biochemistry of electroacupuncture's therapeutic effects. Results: Electroacupuncture treatment demonstrated a notable decrease in the corneal mechanical perception threshold, improvement in palpebral fissure height, and significant reductions in both eyeblink frequency and eye wiping duration. Moreover, it exhibited a promising role in anxiety alleviation. Notably, the technique effectively diminished ocular pain by curbing microglial and neuronal activation in the TG and SpVc regions. Furthermore, it potently downregulated TNF-ɑ, TNFR1, p-ERK1/2, and P2X3R expression within these regions. Conclusion: Electroacupuncture attenuated damage to sensory nerve pathways, reduced pain, and eased anxiety in dry eye-afflicted rats. The findings suggest a crucial role of TNF-ɑ mediated ERK1/2/P2X3R signaling pathway inhibition by electroacupuncture in these benefits.

Biodegradable mulch films significantly affected rhizosphere microbial communities and increased peanut yield.

Biodegradable mulch films are widely used to replace conventional plastic films in agricultural fields. However, their ecological effects on different microbial communities that naturally inhabit agricultural fields are scarcely explored. Herein, differences in bacterial communities recovered from biofilms, bulk soil, and rhizosphere soil were comparatively assessed for polyethylene film (PE) and biodegradable mulch film (BDM) application in peanut planted fields. The results showed that the plastic film type significantly influenced the bacterial community in different ecological niches of agricultural fields (P < 0.001). Specifically, BDMs significantly increased the diversity and abundance of bacteria in the rhizosphere soil. The bacterial communities in each ecological niche were distinguishable from each other; bacterial communities in the rhizosphere soil showed the most pronounced response among different treatments. Acidobacteria and Pseudomonas were significantly enriched in the rhizosphere soil when BDMs were used. BDMs also increased the rhizosphere soil bacterial network complexity and stability. The enrichment of beneficial bacteria in the rhizosphere soil under BDMs may also have implications for the observed increase in peanut yield. Deepening analyses indicated that Pseudoxanthomonas and Glutamicibacter are biomarkers in biofilms of PE and BDMs respectively. Our study provides new insights into the consequences of the application of different types of plastic films on microbial communities in different ecological niches of agricultural fields.

Rationally designed synthetic vectors for therapeutic nucleic acid delivery against human cytomegalovirus infection.

RNA therapy represents a great way to precisely regulate cellular processes by modulating the gene expression. Despite this potential, a profound gap exists in our knowledge of how to subsequently deliver these RNAs into the specific target cells and turn therapeutically active RNAs into practical medicines. An advanced series of interlocked, thermodynamically self-regulated processes that enable the precise assembly of functional synthetic carriers of siRNA to the target cells in vivo was developed. To demonstrate the efficacy of this delivery system, we used it to treat human cytomegalovirus (HCMV) infection in a humanized mouse model. In this study, we use small interfering RNA (siRNA) and small complementary RNA (scRNA) to inhibit the expressions of two HCMV genes, IE1 and IE2. The auto-regulated nanocarrier polywraplex with core-shell structure was designed to condense and package these RNAs for delivering. To allow these particles recognize the HCMV-infected cells, a ligand was coupled on the surface of nanoparticle, which would specifically target the HCMV-encoded CX3 CL1 chemokine receptor presented in the HCMV-infected cells. The results demonstrated that the polywraplex conjugated with the target molecule CX3 CL1 effectively and specifically delivered the siRNA/scRNA to HCMV infected cells and inhibited virus growth in vitro and in vivo.

Electroacupuncture Reduces Ocular Surface Neuralgia in Dry-Eyed Guinea Pigs by Inhibiting the Trigeminal Ganglion and Spinal Trigeminal Nucleus Caudalis P2X3R-PKC Signaling Pathway.

PURPOSE: To observe the effects of electroacupuncture on ocular surface neuralgia and the P2X3R-PKC signaling pathway in guinea pigs with dry eye. METHODS: A dry eye guinea pig model was established by subcutaneous injection of scopolamine hydrobromide. Guinea pigs were monitored for body weight, palpebral fissure height, number of blinks, corneal fluorescein staining score, phenol red thread test, and corneal mechanical perception threshold. Histopathological changes and mRNA expression of P2X3R and protein kinase C in the trigeminal ganglion and spinal trigeminal nucleus caudalis were observed. We performed a second part of the experiment, which involved the P2X3R-specific antagonist A317491 and the P2X3R agonist ATP in dry-eyed guinea pigs to further validate the involvement of the P2X3R-protein kinase C signaling pathway in the regulation of ocular surface neuralgia in dry eye. The number of blinks and corneal mechanical perception threshold were monitored before and 5 min after subconjunctival injection and the protein expression of P2X3R and protein kinase C was detected in the trigeminal ganglion and spinal trigeminal nucleus caudalis of guinea pigs. RESULTS: Dry-eyed guinea pigs showed pain-related manifestations and the expression of P2X3R and protein kinase C in the trigeminal ganglion and spinal trigeminal nucleus caudalis was upregulated. Electroacupuncture reduced pain-related manifestations and inhibited the expression of P2X3R and protein kinase C in the trigeminal ganglion and spinal trigeminal nucleus caudalis. Subconjunctival injection of A317491 attenuated corneal mechanoreceptive nociceptive sensitization in dry-eyed guinea pigs, while ATP blocked the analgesic effect of electroacupuncture. CONCLUSIONS: Electroacupuncture reduced ocular surface sensory neuralgia in dry-eyed guinea pigs, and the mechanism of action may be associated with the inhibition of the P2X3R-protein kinase C signaling pathway in the trigeminal ganglion and spinal trigeminal nucleus caudalis by electroacupuncture.

PDGF-loaded microneedles promote tendon healing through p38/cyclin D1 pathway mediated angiogenesis.

Tendon injury is one of the most serious orthopedic diseases often leading to disability of patients. Major shortages of tendon healing are due to its multiple comorbidities, uncertainty of therapeutic efficacy and insufficient of angiogenesis. With a deeper understanding of angiogenic mechanism of tendon healing, we investigated an innovative microneedle patch loaded with platelet derived growth factor (PDGF) to achieve a constant systemic administration of PDGF to enhance topical tendon healing. Rat achilles tendon injury model was performed as in vivo animal models. Histological staining showed an enhancement of tendon healing quality, especially angiogenesis. Biomechanical studies demonstrated an increase of tendon stiffness, maximum load and maximum stress with treatment of PDGF-loaded microneedles. Furthermore, MAPK/p38/Cyclin D1 pathway and angiogenesis were found to play an important role in tendon healing process by using a biological high throughput RNA-sequence method and bioinformatic analysis. The high throughput RNA-seq tendon healing results were confirmed by histochemical staining and western blot. These results suggest the novel therapeutic potential of PDGF-loaded microneedle patch in tendon surgery.

[Effect of electroacupuncture on ocular surface sensory neuralgia and expression of P2X3 receptor and PKC in cornea and trigeminal ganglion of dry eye guinea pigs].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on ocular surface sensory neuralgia and the expression of P2X3 receptor (P2X3R) and protein kinase C(PKC)in cornea and trigeminal ganglion (TG) in dry eye disease (DED) guinea pigs, so as to explore its mechanism underlying improvement of ocular surface sensory neuralgia in DED. METHODS: Male British tricolor short haired guinea pigs were randomly divided into control, model, medication (pranoprofen), EA and sham acupuncture groups, with 8 guinea pigs in each group. The dry eye model was induced by subcutaneous injection of scopolamine hydrobromide solution (0.6 mg/0.2 mL,once daily) for 10 d. Guinea pigs in the medication group were treated by applying pranoprofen eye drops to eyes, 1 drop for one eye each time, three times a day. Guinea pigs of the EA group received EA stimulation (4 Hz/20 Hz,1 mA) of bilateral "Cuanzhu" (BL2) and "Taiyang" (HN5) and acupuncture at "Jingming" (BL1) "Sizhukong" (TE23), "Tongziliao" (GB1) for 15 min, once a day. Guinea pigs in the sham acupuncture group received blunt stimu-lation at the surface of the same acupoint with the tip of the acupuncture needle, once a day. All the treatments were conducted for 14 d. The corneal epithelium fluorescein staining score (0-3 points) was given according to the number of fluorescence-positive dots and flake-like coloration, the corneal mechanical perception thread (CMPT) detected using a corneal perception meter, and the palpebral fissure height measured. The number of sensory neurons in the cornea and TG was determined by using cholera toxin subunit B conjugated with Alexa Fluor 488 fluorescence labelling, and the expression levels of P2X3R and PKC in the cornea and TG detected by using immunohistochemistry and Western blot, separately. RESULTS: Compared with the control group, the corneal fluorescein staining score, immunoactivity and expression of P2X3R proteins in both cornea and TG, PKC proteins in TG were significantly increased (P<0.01), whereas the CMPT and the height of palpebral fissure and the number of TG neurons significantly decreased in the model group (P<0.05,P<0.01). In comparison with the model group, the fluorescein staining score in the medication and EA groups, the immunoactivity and expression of P2X3R in cornea and TG in the EA group, and that of TG PKC in the EA group and the sham acupuncture groups were significantly decreased (P<0.05, P<0.01), while the height of palpebral fissure and CMPT after EA and the number of labelling TG sensory neurons were remarkably increased in the EA group (P<0.01) rather than in the medication and sham acupuncture groups (P>0.05). CONCLUSION: EA can alleviate the damage of corneal epithelium and sensory neurons in dry eye model guinea pigs, which may be related to its functions in down-regu-lating the expression of P2X3R and PKC in the cornea and TG.

Effect of Long-Term Biodegradable Film Mulch on Soil Physicochemical and Microbial Properties.

Biodegradable mulches have become the focus of attention, as pollution caused by leftover plastic mulch material becomes increasingly severe. However, the impact of biodegradable mulches to the soil needs to be further investigated. An experiment was conducted to evaluate the impact of no-mulch, biodegradable film mulch (BM) and polyethylene film mulch (PM) on the soil's physical, chemical and biological properties after six years (2013-2019) of mulching in garlic growing season in a garlic-maize rotation. Results showed that the soil bulk density of the 10-20 cm soil layer under BM decreased by 12.09-17.17% compared with that under PM. The soil total nitrogen content increased significantly by 14.75-28.37%, and the soil available phosphorus and potassium content increased by 64.20% and 108.82%, respectively. In addition, BM increased the soil's microbial, soil urease, and soil catalase activities compared with those for PM. To sum up, BM can reduce soil bulk density, and long-term use of BM does not cause a decrease in soil nutrient content and microbial activity. On the contrary, it can improve soil quality. This study helps accumulate data for the environmental safety evaluation of BM and provides theoretical and technical support for the large-scale promotion of biodegradable mulches.

Current progress on plastic/microplastic degradation: Fact influences and mechanism.

Plastic pollution, particularly non-degradable residual plastic films and microplastics (MPs), is a serious environmental problem that continues to worsen each year. Numerous studies have characterized the degradation of plastic fragments; however, there is known a lack of about the state of current physicochemical biodegradation methods used for plastics treatment and their degradation efficiency. Therefore, this review explores the effects of different physicochemical factors on plastics/MPs degradation, including mechanical comminution, ultraviolet radiation, high temperature, and pH value. Further, this review discusses different mechanisms of physicochemical degradation and summarizes the degradation efficiency of these factors under various conditions. Additionally, the important role of enzymes in the biodegradation mechanism of plastics/MPs is also discussed. Collectively, the topics discussed in this review provide a solid basis for future research on plastics/MPs degradation methods and their effects.

Effects of biodegradable film mulching on bacterial diversity in soils.

The spread of biodegradable plastic films (BDFs) not only increases grain yield but also reduces environmental pollution from plastic film to a large extent. Soil microbes are considered to be involved in biodegradation processes. However, the study of microbe diversity in soil mulched with biodegradable plastic film remains limited. Here, we compared the diversity of microbes between soils with biodegradable film and nonbiodegradable film (NBDF) mulch. The results showed that BDFs affected total C, P and NH4+-N, especially organism C content, as well as microbe species richness (ACE; Chao1) and diversity (Simpson index; Shannon index). In terms of dominant phyla and genera, BDFs and NBDF can influence the abundance of disparate species. Furthermore, BDFs could also contribute to improving the richness of the important functional bacterial groups in soil, e.g., Pedomicrobium and Comamonas, both of which are involved in the degradation of plastic residues in soil. Finally, we found that BDFs improved the transformation of nitrogen by significantly increasing the abundances of Nitrobacter and Nitrospira. Our results highlight the impact of BDF mulch on the abundance of functional bacteria in the soil.

Deciphering the diversity and functions of plastisphere bacterial communities in plastic-mulching croplands of subtropical China.

Considering the inhomogeneity of plastisphere and surrounding soil, it is plausible that the microbial community colonizing it also varies, affecting soil services and sustainability. Herein, we analyzed the soil and film residue from fifty-five plastic-mulching croplands in the subtropical areas of China. Based on the outcomes of this analysis, we explored the diversity and functions of the associated bacterial communities. Alpha-diversity and phylogenetic diversity of the plastisphere bacterial community was significantly lower than the surrounding soil. The average net relatedness and net nearest taxa indices of samples were less than zero. Four phyla and twenty genera were enriched in the plastisphere compared to the surrounding soil. Ecological networks of the plastisphere community showed multiple nodes, but fewer interactions, and the members of Bradyrhizobium, Rhodospirillaceae, and Bacillus were indicated as the hub species. Predicted pathways related to human disease, as well as the metabolisms of cofactors, vitamins, amino acids, and xenobiotic biodegradation, were reinforced in the plastisphere, and meanwhile, accompanied by an increase in abundance of genes related to carbon, nitrogen, and phosphorus cycles. These results demonstrated the diversity and functions of the plastisphere microbiome and highlighted the necessity for exploring the ecological and health risks of plastic residue in croplands.

Arthrobacter is a universal responder to di-n-butyl phthalate (DBP) contamination in soils from various geographical locations.

Plasticizer phthalic acid esters (PAEs) are commonly found as contaminants in various soils. Previous studies indicated that their natural degradation can substantially differ among soil types; however, potential implications of the soil microbiome remained largely unexplored. Here, we have collected ten soil types from nine different geographical regions of China to investigate the degradation of DBP therein and role of bacteria in this process. Results showed that the degradation rate of DBP was lowest in nutrient-poor red soils from Jiangxi Province, while it was highest in fluvo-aquatic soil from Hebei Province. Bacterial community responses to DBP substantially differed in each of the analyzed soils. Arthrobacter is known for its broad-spectrum activity in terms of DBP degradation in soil and was therefore implemented as bioremediating inoculant in many polluted environments. In the present study, network analyses indicated that synergism between soil bacteria increased following exposure to DBP. Arthrobacter and Sphingomonas were found to expand their positive interactions with other members of the microbiome in DBP-contaminated soils. The overall findings of our study provide a basis for biomarker development for detection of DBP contaminations and an extended basis for future bioremediation approaches based on beneficial bacteria.

The time-dependent variations of zebrafish intestine and gill after polyethylene microplastics exposure.

Microplastics (MPs) are common environmental contaminants that present a growing health concern due to their increasing presence in aquatic and human systems. However, the mechanisms behind MP effects on organisms are unclear. In this study, zebrafish (Danio rerio) were used as an in vivo model to investigate the potential risks and molecular mechanisms of the toxic effects of polyethylene MPs (45-53 µm). In the zebrafish intestine, 6, 5, and 186 genes showed differential expression after MP treatment for 1, 5, and 10 days, respectively. In the gills, 318, 92, and 484 genes showed differential expression after MP treatment for 1, 5, and 10 days, respectively. In both the intestine and the gills, Gene Ontology (GO) annotation showed that the main enriched terms were biological regulation, cellular process, metabolic process, cellular anatomical entity, and binding. KEGG enrichment analysis on DEGs revealed that the dominant pathways were carbohydrate metabolism and lipid metabolism, which were strongly influenced by MPs in the intestine. The dominant pathways in the gills were immune and lipid metabolism. The respiratory rate of gills, the activity of SOD and GSH in the intestine significantly increased after exposure to MPs compared with the control (p < 0.05), while the activity of SOD did not change in the gills. GSH activity was only significantly increased after MP exposure for 5 days. Also, the MDA content was not changed in the intestine but was significantly decreased in the gills after MP exposure. The activity of AChE significantly decreased only after MPs exposure for 5 days. Overall, these results indicated that MPs pollution significantly induced oxidative stress and neurotoxicity, increased respiratory rate, disturbed energy metabolism and stimulated immune function in fish, displaying an environmental risk of MPs to aquatic ecosystems.

Exenatide Microspheres for Monthly Controlled-Release Aided by Magnesium Hydroxide.

GLP-1 receptor agonists are a class of diabetes medicines offering self-regulating glycemic efficacy and may best be administrated in long-acting forms. Among GLP-1 receptor agonists, exenatide is the one requiring the least dose so that controlled-release poly(d, l-lactic-co-glycolic acid) (PLGA) microspheres may best achieve this purpose. Based on this consideration, the present study extended the injection interval of exenatide microspheres from one week of the current dosage form to four weeks by simply blending Mg(OH)2 powder within the matrix of PLGA microspheres. Mg(OH)2 served as the diffusion channel creator in the earlier stage of the controlled-release period and the decelerator of the self-catalyzed degradation of PLGA (by the formed lactic and glycolic acids) in the later stage due to its pH-responsive solubility. As a result, exenatide gradually diffused from the microspheres through Mg(OH)2-created diffusion channels before degradation of the PLGA matrix, followed by a mild release due to Mg(OH)2-buffered degradation of the polymer skeleton. In addition, an extruding-settling process comprising squeezing the PLGA solution through a porous glass membrane and sedimentation-aided solidification of the PLGA droplets was used to prepare the microspheres to ensure narrow size distribution and 95% encapsulation efficiency in an aqueous continuous phase. A pharmacokinetic study using rhesus monkey model confirmed the above formulation design by showing a steady blood concentration profile of exenatide with reduced CMAX and dosage form index. Mg·(OH)2.

[Effects of Chromium Pollution on Soil Bacterial Community Structure and Assembly Processes].

With the rapid development of industry, chromium (Cr) has become one of the main soil heavy metal pollutants in China, seriously affecting the soil ecological environment and health of residents. In this study, contaminated soil samples were taken around the tannery sludge yard area in Heibei Province. The Illumina MiSeq high-throughput sequencing technology was employed to analyze the structure and assembly processes of soil bacterial communities at different pollution levels. Results showed that chromium pollution significantly influences soil properties and soil bacterial communities. The composition and structure of bacterial communities were significantly shifted at different pollution levels. Furthermore, the α diversity of bacterial communities may decrease with relatively high concentrations of chromium. Bacterial communities in chromium polluted soil can be divided into 55 phyla, where Proteobacteria, Actinobacteria, Acidobacteria, Chloroflexi, and Firmicutes are the dominant phyla (relative abundance>5%). Moreover, the soil bacterial communities were dominated by the deterministic assembly process (homogeneous selection) and the stochastic ratios decreased with increases in the concentration of chromium in soil. The total concentration of chromium, soil moisture, pH, and organic matter were significantly correlated (P<0.05) with the bacterial communities. Therefore, these soil properties might be the driving factors affecting the structure of bacterial communities.

Algal density affects the influences of polyethylene microplastics on the freshwater rotifer Brachionus calyciflorus.

Most previous researches focused on the toxicity of polystyrene microplastics (MPs) to marine organisms, but less on polyethylene MPs and freshwater zooplanktons. The present study aims to elucidate the toxicity of polyethylene (PE) MPs (diameter = 10-22 µm) to the typical freshwater rotifer Brachionus calyciflorus. Firstly, fluorescent microscope observation showed that rotifers could ingest PE MPs and accumulate them in their digestive tracts. Life-table experiments revealed that exposure to 0.5 × 103, 2.5 × 103, and 1.25 × 104 particles/mL PE MPs significantly reduced net reproductive rate and intrinsic rate of pollution increase of rotifers under algal densities (Scenedesmus obliquus) of 0.1 × 106, and 0.5 × 106 cells/mL, but no significant effects were observed under 2.5 × 106 cells/mL algal density. These results showed that PE MPs suppressed the reproduction of rotifer and this negative effect could be alleviated by increasing food supply. The swimming linear speed of rotifers significantly decreased with increasing MP concentrations. The activities of superoxide dismutase and Na+-K+-ATPase significantly decreased in treatments with high concentration of PE MPs under 0.1 × 106 cells/mL algal density, but did not change significantly in MP treatments under 0.5 × 106 and 2.5 × 106 cells/mL, compared to the control. Glutathione peroxidase activity significantly increased in treatments with 1.25 × 104 particles/mL and 2.5 × 103 particles/mL under 0.1 × 106 and 0.5 × 106 cells/mL algal density, respectively, but did not change significantly in all MP treatments under 2.5 × 106 cells/mL. Exposure to PE MPs might lower the gathering capacity of algae, induce oxidative stress, trigger cell membrane damages and disturb energy metabolism in rotifers, which can explain the PE MPs toxicity to rotifer reproduction.

Assembling structurally customizable synthetic carriers of siRNA through thermodynamically self-regulated process.

This study demonstrates that our previously reported polywraplex, a synthetic siRNA carrier consisting of a uni-molecular polyplex core of customizable size and a self-assembled tri-block copolymer envelop, may be constructed using dendrimers as the crosslinking junctions. Replacing the branched low molecular weight PEI with polyamidoamine (PAMAM) dendrimer in the zeta potential regulated polymerization resulted in the similar network structured cationic polymer with electron microscopically visible crosslinking junctions. This visibility may offer a convenient way to characterize the molecular structure of the rationally designed networked siRNA-packing cationic polymer without altering its chemical properties and biologic functions. A series of physical-chemical characterizations and biological assays, comprising size, zeta potential, pre-phagocytic siRNA leaking and degradation, and silencing of functional genes, confirmed that the advanced properties of polywraplexes remained with the dendrimer junctions. Although sixth generation PAMAM dendrimer was used as the crosslinking junctions in the size-customizable polymerization for electron microscopic observation, lower generation dendrimer should also work in case more practical and structurally defined cationic polymer is needed.