Effects of berberine hydrochloride on antioxidant response and gut microflora in the Charybdis japonica infected with Aeromonas hydrophila.

This study used berberine hydrochloride to treat the Asian paddle crab, Charybdis japonica infected with the Gram-negative bacterium Aeromonas hydrophila at concentrations of 0, 100, 200 and 300 mg/L. The effect of berberine hydrochloride on the survival rate and gut microbiota of C. japonica was investigated. Berberine hydrochloride improved the stability of the intestinal flora, with an increase in the abundance of probiotic species and a decrease in the abundance of both pathogenic bacteria after treatment with high concentrations of berberine hydrochloride. Berberine hydrochloride altered peroxidase activity (POD), malondialdehyde (MDA), and lipid peroxidation (LPO) in the intestinal tract compared to the control. Berberine hydrochloride could modulate the energy released from the enzyme activities of hexokinase (HK), phosphofructokinase (PFK), and pyruvate kinase (PK) in the intestinal tract of C. japonica infected with A. hydrophila. Zona occludens 1 (ZO-1), Zinc finger E-box binding homeobox 1 (ZEB1), occludin and signal transducer, and activator of transcription5b (STAT5b) expression were also increased, which improved intestinal barrier function. The results of this study provide new insights into the role of berberine hydrochloride in intestinal immune mechanisms and oxidative stress in crustaceans.

Organic amendments increased Chinese milk vetch symbiotic nitrogen fixation by enriching Mesorhizobium in rhizosphere.

Symbiotic nitrogen fixation of Chinese milk vetch (Astragalus sinicus L.) can fix nitrogen from the atmosphere and serve as an organic nitrogen source in agricultural ecosystems. Exogenous organic material application is a common practice of affecting symbiotic nitrogen fixation; however, the results of the regulation activities remain under discussion. Studies on the impact of organic amendments on symbiotic nitrogen fixation have focused on dissolved organic carbon content changes, whereas the impact on dissolved organic carbon composition and the underlying mechanism remain unclear. In situ pot experiments were carried out using soils from a 40-year-old field experiment platform to investigate symbiotic nitrogen fixation rate trends, dissolved organic carbon concentration and component, and diazotroph community structure in roots and in rhizosphere soils following long-term application of different exogenous organic substrates, i.e., green manure, green manure and pig manure, and green manure and rice straw. Remarkable increases in rate were observed in and when compared with that in green manure treatment, with the greatest enhancement observed in the treatment. Moreover, organic amendments, particularly pig manure application, altered diazotroph community composition in rhizosphere soils, therefore increasing the abundance of the host-specific genus Mesorhizobium. Furthermore, organic amendments influence the diazotroph communities through two primary mechanisms. Firstly, the components of dissolved organic carbon promote an increase in available iron, facilitated by the presence of humus substrates. Secondly, the elevated content of dissolved organic carbon and available iron expands the niche breadth of Mesorhizobium within the rhizosphere. Consequently, these alterations result in a modified diazotroph community within the rhizosphere, which in turn influences Mesorhizobium nodulation in the root and symbiotic nitrogen fixation rate. The results of the present study enhance our understanding of the impact of organic amendments on symbiotic nitrogen fixation and the underlying mechanism, highlighting the key role of dissolved organic carbon composition on diazotroph community composition in the rhizosphere.

Targeted Therapy of Non-Small Cell Lung Cancer and Liver Cancer: Functional Nanocarriers for the Delivery of Cisplatin and Tissue Factor Pathway Inhibitor-2.

INTRODUCTION: The aim of the study was to construct folic acid-modified PEGylated paramagnetic nanoparticles (MNPs) co-carrying tissue factor pathway inhibitor-2 (TFPI-2) and cisplatin (CDDP), and to study the molecular-targeting and inhibitory effects of the nanocomposite on non-small cell lung cancer (NSCLC) and liver cancer. METHODS: Nanocomposites were prepared using amino-modified iron oxide nanoparticles as carriers, co-loading CDDP and PEGylated FA/TFPI-2. Transmission electron microscopy, UV absorption spectrum, and dynamic light scattering were employed to characterize the morphology, structure, particle size, and zeta potential of the nanocomposite. The phenylenediamine method was used to detect the loading of CDDP, and the CCK-8 assay was used to detect the toxic effect of the nanocomposite on HUVECs, A549, and NCI-H460 cells. In tumor-bearing mice models, the antitumor effects of the nanocomposites were assessed using TUNEL staining (at the molecular level), reverse transcriptase quantitative polymerase chain reaction (at the gene level), hematoxylin and eosin staining (at the cellular level), and the appearance of the mice models. RESULTS: The synthesized FA-MNP/CDDP/TFPI-2 nanocomposite was uniformly dispersed and spherical in shape (approximate diameter: 10 nm). The zeta potential of particles was -9.44 mV, and the average particle size was 25 nm. The loading amount of CDDP was 70.24 µg/mL (23.33%). The nanocomposite was nontoxic to HUVECs, while it showed a favorable inhibitory effect on A549 and NCI-H460 cells. In vivo experiments in mice demonstrated satisfactory imaging properties and therapeutic effects of nanocomposite against liver cancer. DISCUSSION: FA-MNP/CDDP/TFPI-2 may provide insights for the development of new chemotherapeutic drugs.

Trial-to-Trial Variability of Spiking Delay Activity in Prefrontal Cortex Constrains Burst-Coding Models of Working Memory.

A hallmark neuronal correlate of working memory (WM) is stimulus-selective spiking activity of neurons in PFC during mnemonic delays. These observations have motivated an influential computational modeling framework in which WM is supported by persistent activity. Recently, this framework has been challenged by arguments that observed persistent activity may be an artifact of trial-averaging, which potentially masks high variability of delay activity at the single-trial level. In an alternative scenario, WM delay activity could be encoded in bursts of selective neuronal firing which occur intermittently across trials. However, this alternative proposal has not been tested on single-neuron spike-train data. Here, we developed a framework for addressing this issue by characterizing the trial-to-trial variability of neuronal spiking quantified by Fano factor (FF). By building a doubly stochastic Poisson spiking model, we first demonstrated that the burst-coding proposal implies a significant increase in FF positively correlated with firing rate, and thus loss of stability across trials during the delay. Simulation of spiking cortical circuit WM models further confirmed that FF is a sensitive measure that can well dissociate distinct WM mechanisms. We then tested these predictions on datasets of single-neuron recordings from macaque PFC during three WM tasks. In sharp contrast to the burst-coding model predictions, we only found a small fraction of neurons showing increased WM-dependent burstiness, and stability across trials during delay was strengthened in empirical data. Therefore, reduced trial-to-trial variability during delay provides strong constraints on the contribution of single-neuron intermittent bursting to WM maintenance.SIGNIFICANCE STATEMENT There are diverging classes of theoretical models explaining how information is maintained in working memory by cortical circuits. In an influential model class, neurons exhibit persistent elevated memorandum-selective firing, whereas a recently developed class of burst-coding models suggests that persistent activity is an artifact of trial-averaging, and spiking is sparse in each single trial, subserved by brief intermittent bursts. However, this alternative picture has not been characterized or tested on empirical spike-train data. Here we combine mathematical analysis, computational model simulation, and experimental data analysis to test empirically these two classes of models and show that the trial-to-trial variability of empirical spike trains is not consistent with burst coding. These findings provide constraints for theoretical models of working memory.

Efficient genome-wide first-generation phenotypic screening system in mice using the piggyBac transposon.

Genome-wide phenotypic screens provide an unbiased way to identify genes involved in particular biological traits, and have been widely used in lower model organisms. However, cost and time have limited the utility of such screens to address biological and disease questions in mammals. Here we report a highly efficient piggyBac (PB) transposon-based first-generation (F1) dominant screening system in mice that enables an individual investigator to conduct a genome-wide phenotypic screen within a year with fewer than 300 cages. The PB screening system uses visually trackable transposons to induce both gain- and loss-of-function mutations and generates genome-wide distributed new insertions in more than 55% of F1 progeny. Using this system, we successfully conducted a pilot F1 screen and identified 5 growth retardation mutations. One of these mutants, a Six1/4 PB/+ mutant, revealed a role in milk intake behavior. The mutant animals exhibit abnormalities in nipple recognition and milk ingestion, as well as developmental defects in cranial nerves V, IX, and X. This PB F1 screening system offers individual laboratories unprecedented opportunities to conduct affordable genome-wide phenotypic screens for deciphering the genetic basis of mammalian biology and disease pathogenesis.

Modelling the effect of rainfall patterns on the runoff control performance of permeable pavements.

With the implementation of low impact development (LID) in urban areas, it is necessary to quantify the actual effectiveness of LID facilities. In this study, a coupled hydrology-hydrodynamic numerical model was utilized to investigate the runoff control effectiveness of permeable pavements in the city centre of Shijiazhuang, China. Two groups of designed rainfall events with the same duration but different rainfall amounts and peak rainfall intensity locations were presented, and the effectiveness of permeable pavement was demonstrated by the reduction in the total runoff volume, water depth, and inundated area. The results indicate that the rainfall amount is the main factor affecting the runoff control of permeable pavements, and their effectiveness decreases with increasing rainfall amounts and peak intensity coefficients. Moreover, permeable pavements are more effective in reducing the residential waterlogging area, and the proportion of the inundated area above a depth of 0.2 m is considerably diminished. This study reveals the response of the runoff control of permeable pavements to different rainfall patterns, which is essential for supporting the design and practical operation of permeable pavements.

[Common Troubles of Vacuum Components in Elekta Linear Accelerator and Fast Solutions].

The transportation of electron is inseparable from vacuum environment. The maintenance of the vacuum system of Elekta linear accelerator depends on two sputtering ionic pumps at the gun end and the target end. The traveling wave acceleration were used in Elekta linear accelerators. And the design of the electron gun filament is detachable. Because of these two reasons, the vacuum stability is relatively weak. Only two vacuum values are used to reflect the operation state of the whole vacuum system, which causes a few failures but will not trigger a the machine interlock. Considering the complexity of whole vacuum system, the problem of vacuum caused by the failure of various components in vacuum system is analyzed in this paper. It is hoped that some useful repairing experience and suggestions for the maintenance engineers of linear accelerator to solve the vacuum fault and rebuild the vacuum can be provided quickly.

Complete mitochondrial genome of Odontobutis haifengensis (Perciformes, Odontobutiae): A unique rearrangement of tRNAs and additional non-coding regions identified in the genus Odontobutis.

Herein, the complete mitochondrial genome of Odontobutis haifengensis was sequenced for the first time. The O. haifengensis mitogenome was 17,016bp in length and included 13 protein-coding genes, 22 transfer RNAs (tRNAs), 2 ribosomal RNAs (rRNAs), and a control region (CR). The genome organization, base composition, codon usage, and gene rearrangement was similar to other Odontobutis species. Furthermore, a tRNA gene rearrangement within the SLH cluster was found to be identical to other Odontobutis species. Moreover, the gene order and the positions of additional intergenic non-coding regions suggests that the observed unique gene rearrangement resulted from a tandem duplication and random loss of large-scale gene regions. Additionally, phylogenetic analysis showed that Odontobutis species form a monophyletic clade due to the conserved mitochondrial gene rearrangement. This study provides useful information that aids in a better understanding of mitogenomic diversity and evolutionary patterns of Odontobutidae species.

Dynamics of the bacterial community in a channel catfish nursery pond with a cage-pond integration system.

The changes in the bacterial community composition in a channel catfish nursery pond with a cage-pond integration system were investigated by sequencing of the 16S rRNA gene through Illumina MiSeq sequencing platforms. A total of 1 362 877 sequences and 1440 operational taxonomic units were obtained. Further analysis showed that the dominant phyla in the cage and pond groups were similar, including Actinobacteria, Cyanobacteria, Proteobacteria, and Bacteroidetes, although a significant difference was detected between them by ANOSIM (P < 0.05). Temporal changes and site variation were significantly related to the variation of the bacterial community. A comprehensive analysis of the diversity and evenness of the bacterial 16S rRNA gene, redundancy analysis (RDA), and partial Mantel test showed that the bacterial community composition in a cage-pond integration system was shaped more by temporal variation than by site variation. RDA also indicated that water temperature, total dissolved solids, and Secchi depth had the largest impact on bacterial populations.

The optimal timing of hemoperfusion component in combined hemodialysis-hemoperfusion treatment for uremic toxins removal.

The combination of hemodialysis-hemoperfusion (HDHP) has been proved to be superior to hemodialysis (HD) in eliminating uremic toxins. There are two methods of combination of HD and HP: the HP regime is utilized during the first two-hour an early HP conducted HDHP (EHDHP) or the last two-hour late HP conducted HDHP (LHDHP) of 4 h regular HD session. The present study was to compare these two methods in uremic toxins removal. Twenty adult chronic HD patients were enrolled in this self-control method study. The patients were randomized to receive one session of EHDHP or LHDHP. Two weeks later, the dialysis modalities were switched. The reduction ratio (RR) of targeted uremic toxins for each session was assessed. Both EHDHP and LHDHP showed a significant removal of small water-soluble solutes, middle-sized toxins and cytokines as well (p < 0.05). There were no significant differences between two methods in RR of small water-soluble solutes, like urea and creatinine. For middle-sized molecules and cytokines, such as PTH, ß(2)-M, IL-1, IL-6, and TNF-α, the RR was markedly increased in LHDHP than that in EHDHP (p < 0.05). LHDHP showed no more intradialytic events than EHDHP. The combination of HD and HP in the last two hours in one hemodialysis session had more effect on eliminating middle-sized toxins and cytokines.

Synthesis and reactivity of carbachlorins and carbaporphyrins.

Acid-catalyzed condensation of 3-ethoxymethylenecyclopentene-1-carbaldehyde with a tripyrrane, followed by oxidation with aqueous ferric chloride solutions, afforded moderate yields of a carbachlorin. This porphyrinoid exhibited a porphyrin-like UV-vis spectrum with a slightly intensified peak at 650 nm. The proton NMR spectrum showed that the carbachlorin is highly diatropic, and this has been confirmed by nucleus independent chemical shift (NICS) calculations. Oxidation of the carbachlorin with DDQ gave the first example of a carbaporphyrin that is unsubstituted on the carbocyclic ring. Reaction of the carbachlorin with silver(I) acetate gave the corresponding silver(III) organometallic complex. When the carbachlorin was refluxed with methyl iodide and potassium carbonate in acetone, the 22-methyl derivative was formed. Treatment of the N-alkylation product with palladium(II) acetate afforded an unstable palladium(II) carbachlorin that was partially converted into a palladium(II) carbaporphyrin via an oxidation-methyl group migration process. Improved yields of the carbaporphyrin complex were obtained when the reaction mixture was stirred with aqueous ferric chloride solutions. These results open up the field of carbachlorin and carbaporphyrin chemistry for further study.

The dynamics of toxic and nontoxic Microcystis during bloom in the large shallow lake, Lake Taihu, China.

Lake Taihu is a large shallow freshwater lake (surface area 2,338 km(2), mean depth 1.9 m) in China, which has experienced toxic cyanobacterial bloom dominated by Microcystis annually during the last few decades. In the present study, the dynamics of toxic and nontoxic Microcystis in three sampling stations (Meiliang Bay (site N2), Gonghu Bay (site N4), and the lake center area (site S4)) were quantified using quantitative real-time PCR (qPCR) during bloom periods from April to September, 2010. Our data showed that the abundance of toxic Microcystis and the toxic proportion gradually increased from April to August in water samples and reached the peak in August. During the study period, toxic Microcystis genotypes comprised between 26.2 and 64.3, between 4.4 and 22.1, and between 10.4 and 20.6 % of the total Microcystis populations in the three sampling sites, respectively. Correlation analysis suggested that there was a strong positive relationship between total Microcystis, toxic Microcystis and the toxic proportion. Chlorophyll a, total phosphorus, and water temperature were positively correlated with the abundances of total Microcystis and toxic Microcystis. Furthermore, the toxic proportion was positively correlated with total phosphorus (P < 0.05) and water temperature (P < 0.01), showing that global warming together with eutrophication could promote more frequent toxic blooms.

Underdog entrepreneurship in the digital era: The effect of digital servitization on household entrepreneurship in China.

In today's digital era, households are empowered by digital servitization, which could potentially impact their ability to become entrepreneurs. Using data from the China Family Panel Studies (CFPS) and the National Bureau of Statistics of China, we construct the digital servitization index to analyze the impact of digital servitization on household entrepreneurship. The results show that the utilization of digital servitization by households significantly increases the likelihood of them engaging in entrepreneurial endeavors. This result remains robust after a series of robustness tests. We also find that digital servitization can help households identify entrepreneurial opportunities and access entrepreneurial resources by alleviating information and financial constraints, and increasing social capital. Further, the effect is more among households with rural residences, low material assets, elderly household heads, and household heads with low cognitive abilities, which means that digital servitization can promote underdog entrepreneurship. In conclusion, this paper provides micro-level evidence supporting the idea that digital servitization can foster household entrepreneurship, particularly among underprivileged groups. Ultimately, this paper highlights the potential of digitization as an essential resource to drive economic growth and help households in need become successful entrepreneurs.

Comparison of two laser power levels in the subthreshold MicroPulse Yellow Laser Treatment of Acute Central Serous Chorioretinopathy.

AIMS: To compare the efficacy of two power levels in the 577 nm sub-threshold micro pulse laser (SML) treatment of acute central serous chorioretinopathy (aCSC). METHODS: A retrospective comparative study was conducted. A total of 65 patients (65 eyes) with aCSC were enrolled. Of which, 32 patients received low power treatment and 33 patients received high power treatment of 577-nm SML. Best-corrected visual acuity (BCVA), central macular thickness (CMT), fundus-monitored microperimetry and height of subfoveal choroidal thickness (SFCT) as well as subretinal fluid (SRF) were evaluated at baseline and 3 months. RESULTS: The height of SFCT and retinal sensitivity in the low power treatment group was significantly better than that in the high power treatment group at 4 weeks (all p < 0.001). Mean BCVA improved from baseline to 3 months after treatments but with no significant difference between the two groups after 3 months (p > 0.05). In the low power group, the CMT decreased from 379.76 ± 139.23 µm at baseline to 176.56 ± 37.78 µm at 3 months, and in the high power group, the CMT decreased from 364.97 ± 143.08 at baseline to 191.77 ± 38.26 µm at 3 months. There was no significant difference at 3 months between the two groups (p > 0.05). Similar results were also found in term of SRF. CONCLUSIONS: Timely intervention with 577 nm SML with low power treatment can improve visual acuity, and included anatomic success without adverse events.

In Vivo Confocal Microscopy Findings of a Rare Cryptococcus neoformans Keratitis.

PURPOSE: To report a rare case of fungal keratitis caused by Cryptococcus neoformans, highlighting its unique morphological features using in vivo confocal microscopy (IVCM). METHODS: This was a retrospective case report. A 66-year-old man presented with foreign body sensation and blurred vision in his left eye for over 10 months. RESULTS: His best-corrected visual acuity was 20/20. Slit-lamp examination revealed a gray-white lesion approximately 4-5 mm in the superficial layer of the central cornea without epithelial defects. The IVCM images revealed numerous round or round-like pathogens, each with a central highly reflective body surrounded by a dark ring, ranging in size from 5 to 30 µm, and to a maximum of 85 µm, observed in the corneal epithelium and superficial stroma. No obvious inflammatory cell infiltration was observed in the lesions or endothelium. C. neoformans infection was confirmed. The round pathogens completely disappeared after 8 weeks of treatment with topical amphotericin B and voriconazole eye drops. CONCLUSION: Fungal keratitis caused by C. neoformans is rare and easily overlooked due to atypical clinical signs and symptoms. This case reports the unique morphological features of C. neoformans in the cornea using IVCM for the first time, facilitating rapid, noninvasive auxiliary diagnosis of C. neoformans keratitis and treatment follow-up.

Electrospinning-derived transition metal/carbon nanofiber composites as electrocatalysts for Zn-air batteries.

The sluggish kinetics of the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) significantly impede the broader implementation of Zn-air batteries (ZABs), underscoring the necessity for advanced high-efficiency materials to catalyze these electrochemical processes. Recent advancements have highlighted the potential of transition metal/carbon nanofiber (TM/CNF) composite materials, synthesized via electrospinning technology, due to their expansive surface area, profusion of active sites, and elevated catalytic efficacy. This review comprehensively examines the structural characteristics of TM/CNFs, with a particular emphasis on the pivotal role of electrospinning technology in fabricating diverse structural configurations. Additionally, it delves into the mechanistic underpinnings of various strategies aimed at augmenting the catalytic activity of TM/CNFs. A meticulous discourse is also presented on the application scope of TM/CNFs in the realm of electrocatalysis, with a special focus on their impact on the performance of assembled ZABs. Lastly, this review encapsulates the challenges and future prospects in the development of TM/CNF composite materials via electrospinning, aiming to provide an exhaustive understanding of the current state of research in this domain and to foster further advancements in the commercialization of ZABs.

Long-term organic amendments increase the vulnerability of microbial respiration to environmental changes: Evidence from field and laboratory studies.

Organic amendments can improve soil fertility and microbial diversity, making agroecosystems more resilient to stress. However, it is uncertain whether organic amendments will enhance the functional capacity of soil microbial communities, thereby mitigating fluctuations in microbial respiration caused by environmental changes. Here, we examined the impacts of long-term organic amendments on the dynamics of microbial catabolic capacity (characterized by enzyme activities and carbon source utilization) and microbial respiration, as well as their interrelationships during a period with fluctuating temperature and rainfall in the field. We then subjected the field soil samples to laboratory heating disturbances to further evaluate the importance of microbial catabolic capacity in explaining patterns of microbial respiration. In both field and laboratory experiments, organic amendments tended to increase the stability of microbial catabolic capacity, but significantly increased the vulnerability of microbial respiration to environmental changes. However, the direction and driving factors of microbial respiration affected by environmental changes differed between the field and laboratory experiments. Environmental changes in the field suppressed the promotional effects of organic amendments on microbial respiration mainly through reducing microbial catabolic capacity, while laboratory heating further enhanced microbial respiration mainly due to increased soil resource availability. Together, these findings suggest that increased microbial respiration variations under organic amendments may potentially increase the uncertainty in predicting soil carbon emissions in the scenario of ongoing climate/anthropogenic changes, and highlight the necessity of linking laboratory studies on environmental changes to field conditions.

Hypertension, fluid overload and micro inflammation are associated with left ventricular hypertrophy in maintenance hemodialysis patients.

This cross-sectional study aims to identify the potential risk factors of left ventricular hypertrophy (LVH) in hemodialysis (HD) patients. Echocardiography, anthropometric measurements and biochemical analyses were performed for 112 HD patients. In univariate analysis, body mass index, systolic blood pressure, diastolic blood pressure, glycosylated hemoglobin, glycated albumin, high sensitivity C-reactive protein (hs-CRP), cardiac troponin T (cTnT), amino-terminal pro-B-natriuretic peptide (NT-proBNP) and carotid artery intima-media thickness were positively correlated with left ventricular mass index (LVMI); pre-albumin, serum creatinine, left ventricular ejection fraction (LVEF) and fractional shortening were negatively correlated with LVMI. Linear regression analysis showed systolic blood pressure, NT-proBNP and LVEF were independently associated with LVMI. According to a binary logistic regression model, higher systolic blood pressure, NT-proBNP and hs-CRP levels showed independent correlation with LVH. Receiver operator characteristic curves analysis showed the associations between NT-proBNP and LVH more closely than hs-CRP and cTnT. The area under the curve for NT-proBNP, hs-CRP and cTnT was 0.762 (95% CI: 0.660-0.864, p < 0.001), 0.734 (95% CI: 0.624-0.844, p < 0.001) and 0.677 (95% CI: 0.563-0.790, p = 0.004), respectively. These data support the main conclusions: hypertension, fluid overload and micro inflammation are associated with LVH in maintenance HD patients. It demonstrates traditional and nontraditional risk factors all play important roles in the development of LVH.

Complete mitochondrial genome and phylogenetic analysis of Sineleotris saccharae (Perciformes, Odontobutiae).

The freshwater sleeper, Sineleotris saccharae Herre, 1940 is a member of the Odontobutiae family, widely distributed in southern China. In the present study, we determined the complete mitochondrial genome of S. saccharae for the first time and analyzed its evolutionary relationship. The complete mitochondrial genome of S. saccharae was 16,487 bp long, and had 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), 2 ribosomal RNA (rRNAs) and a control region (CR). The mitogenome of S. saccharae shared the same gene organization and orientation as other teleosts. According to phylogenetic research, S. saccharae was sister to S. chalmersi with high support value, providing the monophyly of the genus Sineleotris. These results will be helpful for understanding the systematics of the odontobutids.

Injectable Bioadhesive Hydrogels Scavenging ROS and Restoring Mucosal Barrier for Enhanced Ulcerative Colitis Therapy.

Despite the progress in the therapy of ulcerative colitis (UC), long-lasting UC remission can hardly be achieved in the majority of UC patients. The key pathological characteristics of UC include an impaired mucosal barrier and local inflammatory infiltration. Thus, a two-pronged approach aiming at repairing damaged mucosal barrier and scavenging inflammatory mediators simultaneously might hold great potential for long-term remission of UC. A rectal formulation can directly offer preferential and effective drug delivery to inflamed colon. However, regular intestinal peristalsis and frequent diarrhea in UC might cause transient drug retention. Therefore, a bioadhesive hydrogel with strong interaction with intestinal mucosa might be preferable for rectal administration to prolong drug retention. Here, we designed a bioadhesive hydrogel formed by the cross-linking of sulfhydryl chondroitin sulfate and polydopamine (CS-PDA). The presence of PDA would ensure the mucosa-adhesive behavior, and the addition of CS in the hydrogel network was expected to achieve the restoration of the intestinal epithelial barrier. To scavenge the key player (excessive reactive oxygen species, ROS) in inflamed colon, sodium ferulic (SF), a potent ROS inhibitor, was incorporated into the CS-PDA hydrogel. After rectal administration, the SF-loaded CS-PDA hydrogel could adhere to the colonic mucosa to allow prolonged drug retention. Subsequently, sustained SF release could be achieved to persistently scavenge ROS in inflammatory areas. Meanwhile, the presence of CS would promote the restoration of the mucosal barrier. Ultimately, scavenging ROS and restoring the mucosal barrier could be simultaneously achieved via this SF-loaded bioadhesive hydrogel scaffold. Our two-pronged approach might provide new insight for effective UC treatment.