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Endoscopic tattooing is a localization technique that is particularly important for identifying gastrointestinal lesions for follow-up and subsequent treatment. However, the dyes currently used for endoscopic tattooing have a short tattooing time, high cost, and many side effects. Herein, we designed and prepared polydopamine (PDA) nanoparticles modified with polyvinylpyrrolidone (PVP) for endoscopic tattooing using a physical encapsulation method. PDA has good stability and high adhesion properties, and its stability was further enhanced after PVP modification. In vitro and in vivo tests demonstrated that PDA/PVP has good biosafety. Endoscopic tattooing with PDA/PVP in a porcine model showed that the dye could be stabilized in the digestive tract for at least 60 days. Furthermore, our research results demonstrated that PDA/PVP has excellent reactive oxygen species (ROS) and reactive nitrogen species (RNS) scavenging ability and can promote wound healing. Overall, the strategy proposed herein will lead to the use of an innovative dye for endoscopic tattooing of gastrointestinal lesions.

Helicobacter pylori (H. pylori) is one of the major causes of gastrointestinal diseases, including gastric cancer. However, the acidic environment of the stomach and H. pylori resistance severely impair the antimicrobial efficacy of oral drugs. Here, a biocompatible chitosan-modified molybdenum selenide (MoSe 2 @CS) was designed for the simultaneous photothermal treatment of H. pylori infection and gastric cancer. MoSe 2 @CS showed a photothermal conversion efficiency was as high as 45.7 %. In the H. pylori-infected mice model, MoSe 2 @CS displayed a high bacteriostasis ratio of 99.9 % upon near-infrared irradiation. The antimicrobial functionality was also proved by transcriptomic sequencing study, which showed that MoSe 2 @CS combined with NIR laser irradiation modulated the gene expression of a variety of H. pylori bioprocesses, including cell proliferation and inflammation-related pathways. Further gut flora analysis results indicated that MoSe 2 @CS mediated PTT of H. pylori did not affect the homeostasis of gut flora, which highlights its advantages over traditional antibiotic therapy. In addition, MoSe 2 @CS exhibited a good photothermal ablation effect and significantly inhibited gastric tumor growth in vitro and in vivo. The comprehensive application of MoSe 2 @CS in the PTT of H. pylori infection and gastric cancer provides a new avenue for the clinical treatment of H. pylori infection and related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Marine microbes drive pivotal transformations in planetary-scale elemental cycles and have crucial impacts on global biogeochemical processes. Metaproteomics is a powerful tool for assessing the metabolic diversity and function of marine microbes. However, hundreds of liters of seawater are required for normal metaproteomic analysis due to the sparsity of microbial populations in seawater, which poses a substantial challenge to the widespread application of marine metaproteomics, particularly for deep seawater. Herein, a sensitive marine metaproteomics workflow, named sensitive marine metaproteome analysis (SMMP), was developed by integrating polycarbonate filter-assisted microbial enrichment, solid-phase alkylation-based anti-interference sample preparation, and narrow-bore nanoLC column for trace peptide separation and characterization. The method provided more than 8500 proteins from 1 L of bathypelagic seawater samples, which covered diverse microorganisms and crucial functions, e.g., the detection of key enzymes associated with the Wood-Ljungdahl pathway. Then, we applied SMMP to investigate vertical variations in the metabolic expression patterns of marine microorganisms from the euphotic zone to the bathypelagic zone. Methane oxidation and carbon monoxide (CO) oxidation were active processes, especially in the bathypelagic zone, which provided a remarkable energy supply for the growth and proliferation of heterotrophic microorganisms. In addition, marker protein profiles detected related to ammonia transport, ammonia oxidation, and carbon fixation highlighted that Thaumarchaeota played a critical role in primary production based on the coupled carbon-nitrogen process, contributing to the storage of carbon and nitrogen in the bathypelagic regions. SMMP has low microbial input requirements and yields in-depth metaproteome analysis, making it a prospective approach for comprehensive marine metaproteomic investigations.

Endoscopic tattooing plays a pivotal role in modern endoscopic localization of gastrointestinal lesions, facilitating further surgical intervention and aiding in the postoperative identification and repositioning of lesions. However, traditional endoscopic tattoo dyes often suffer from drawbacks such as side effects, short tattoo duration, and high overall costs. In this study, we developed polyvinylpyrrolidone (PVP)-modified polypyrrole (PPy) nanoparticles by oxidizing pyrrole in a PVP aqueous solution to create a PPy/PVP nanoparticle solution. This innovation aims to enhance endoscopic tattooing efficiency and mitigate the limitations associated with current tattooing methods. Both in vitro and in vivo evaluations confirmed the biosafety of PPy/PVP nanoparticles. Endoscopic tattooing experiments conducted in a pig model demonstrated the dye's stability within the digestive tract. Similarly, subcutaneous tissue tattooing experiments performed in a mouse model revealed the sustained stability of the PPy/PVP tattoo dye for at least 180 days. With its robust stability, safety, and longevity, PPy/PVP nanoparticles hold promise as novel tattoo dyes for marking intestinal lesion sites. This advancement has the potential to enhance the accuracy of lesion localization and long-term tracking., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Jiang, Chen, Zhang, An, Wang and Zhao.)

In emergencies, uncontrolled severe bleeding can result in undesired complications and even death of the injured. Designing advanced hemostatic agents is a potential solution for emergency hemostasis, yet it remains challenging to realize the persistent adhesion in a wet wound environment. In this study, based on dynamic reversible Schiff base bond and photo-initiated double-bond polymerization, a novel injectable hemostatic hydrogel (L-COC) consisting of methacrylated carboxymethyl chitosan (CMCSMA), oxidized konjac glucomannan (OKGM) and (+)-catechin hydrate (CH) was synthesized for emergency hemostasis. To our delight, the incorporated CH imparted enhanced blood procoagulantion to the L-COC hydrogel by intensifying the hydrogel-red blood cell interactions. As a result, the hemostatic effect of the engineered L-COC hydrogel was significantly superior to that of fluid gelatin Surgiflo TM for liver bleeding wounds in rats (Blood loss: 0.62 ± 0.11 g (L-COC), 0.90 ± 0.08 g (Surgiflo TM ); hemostasis time: 69.0 ± 2.9 s (L-COC), 84.0 ± 2.2 s (Surgiflo TM )). With the favorable antioxidant and antibacterial activities, as well as multifunctional properties, the bio-adhesive L-COC hydrogel and the underlying design principles may facilitate further development of practical hemostatic hydrogels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Eradication of oral Helicobacter pylori (H. pylori) not only reduces the infection rate from the transmission route but also improves the success rate of intragastric eradication. MAXPOWER Biological Bacteriostatic Liquid, developed in our previous work, is a composite biological preparation with strong antibacterial ability and unique antibacterial mechanism. The present study evaluated the efficacy of the MAXPOWER biocontrol solution on H. pylori and its success rate in eradicating oral H. pylori in clinical patients., Methods: Live-dead cell staining and hemolysis test were used to evaluate the cellular safety of MAXPOWER biocontrol solution; plate spreading, live-dead bacterial staining, and scanning electron microscopy methods were used to evaluate its antimicrobial effect against H. pylori. Transcriptomics was used to analyze the changes in H. pylori genes before and after treatment. After seven days of gavage treatment, H&E staining and mice feces were collected for 16SrDNA sequencing to evaluate the animals' safety. Oral H. pylori-positive patients were randomized to be given a placebo and MAXPOWER Bio-Bacteriostatic Liquid gargle for seven days to evaluate the effect on oral H. pylori eradication., Results: In vitro tests demonstrated that this product has excellent biocompatibility and hemocompatibility and can effectively eradicate oral H. pylori. In vivo tests further showed that it has good biosafety and virtually no adverse effect on intestinal microflora. Transcriptomics analysis revealed that it kills H. pylori cells mainly by disrupting their cell membranes and metabolism. Additionally, the results of randomized controlled trials on humans disclosed that the oral H. pylori eradication rates achieved by MAXPOWER Biological Antibacterial Liquid were 71.4% and 78.9% according to the intention-to-treat and the per-protocol analysis, respectively., Conclusion: MAXPOWER Biological Antibacterial Liquid is both safe and efficacious in the eradication of oral H. pylori., Trial Registration: This study was retrospectively registered in the ClinicalTrials.gov Trial Registry on 21/09/2023 (NCT06045832)., (© 2024. The Author(s).)

Excess free radicals at the wound site can cause an inflammatory response, which is not conducive to wound healing. Hydrogels with antioxidant properties can prevent inflammatory storms by scavenging free radicals from the wound site and inhibiting the release of inflammatory factors. In this study, we prepared the carboxymethyl chitosan (CMCS)/polyvinyl pyrrolidone (PVP)/Molybdenum (IV) Selenide (MoSe 2 ), and platelet-rich plasma (PRP) (CMCS/PVP/MoSe 2 /PRP) hydrogels for accelerating the repair of wounds. In the hydrogels, the MoSe 2 can scavenge various free radicals to reduce oxidative stress at the site of inflammation, endowed the hydrogels with antioxidant properties. Interestingly, growth factors released by PRP assisted the tissue repair by promoting the formation of new capillaries. CMCS as a backbone not only showed good biocompatibility and biodegradability but also played a significant role in maintaining the sustained release of growth factors. In addition, incorporating PVP enhanced the tissue adhesion and mechanical properties. The multifunctional composite antioxidant hydrogels have good swelling properties and biodegradability, which is completely degraded within 28 days. Thus, the antioxidant CMCS/PVP/MoSe 2 /PRP hydrogels provide a new idea for designing ideal multifunctional wound dressings., (© 2024. The Author(s).)

Background: Educational initiatives on Helicobacter pylori (H. pylori) constitute a highly effective approach for preventing its infection and establishing standardized protocols for its eradication. ChatGPT, a large language model, is a potentially patient-friendly online tool capable of providing health-related knowledge. This study aims to assess the accuracy and repeatability of ChatGPT in responding to questions related to H. pylori., Materials and Methods: Twenty-one common questions about H. pylori were collected and categorized into four domains: basic knowledge, diagnosis, treatment, and prevention. ChatGPT was utilized to individually answer the aforementioned 21 questions. Its responses were independently assessed by two experts on H. pylori. Questions with divergent ratings were resolved by a third reviewer. Cohen's kappa coefficient was calculated to assess the consistency between the scores of the two reviewers., Results: The responses of ChatGPT on H. pylori-related questions were generally satisfactory, with 61.9% marked as "completely correct" and 33.33% as "correct but inadequate." The repeatability of the responses of ChatGPT to H. pylori-related questions was 95.23%. Among the responses, those related to prevention (comprehensive: 75%) had the best response, followed by those on treatment (comprehensive: 66.7%), basic knowledge (comprehensive: 60%), and diagnosis (comprehensive: 50%). In the "treatment" domain, 16.6% of the ChatGPT responses were categorized as "mixed with correct or incorrect/outdated data." However, ChatGPT still lacks relevant knowledge regarding H. pylori resistance and the use of sensitive antibiotics., Conclusions: ChatGPT can provide correct answers to the majority of H. pylori-related queries. It exhibited good reproducibility and delivered responses that were easily comprehensible to patients. Further enhancement of real-time information updates and correction of inaccurate information will make ChatGPT an essential auxiliary tool for providing accurate H. pylori-related health information to patients., (© 2024 John Wiley & Sons Ltd.)

Globally kelp farming is gaining attention to mitigate land-use pressures and achieve carbon neutrality. However, the influence of environmental perturbations on kelp farming remains largely unknown. Recently, a severe disease outbreak caused extensive kelp mortality in Sanggou Bay, China, one of the world's largest high-density kelp farming areas. Here, through in situ investigations and simulation experiments, we find indications that an anomalously dramatic increase in elevated coastal seawater light penetration may have contributed to dysbiosis in the kelp Saccharina japonica 's microbiome. This dysbiosis promoted the proliferation of opportunistic pathogenic Enterobacterales, mainly including the genera Colwellia and Pseudoalteromonas . Using transcriptomic analyses, we revealed that high-light conditions likely induced oxidative stress in kelp, potentially facilitating opportunistic bacterial Enterobacterales attack that activates a terrestrial plant-like pattern recognition receptor system in kelp. Furthermore, we uncover crucial genotypic determinants of Enterobacterales dominance and pathogenicity within kelp tissue, including pathogen-associated molecular patterns, potential membrane-damaging toxins, and alginate and mannitol lysis capability. Finally, through analysis of kelp-associated microbiome data sets under the influence of ocean warming and acidification, we conclude that such Enterobacterales favoring microbiome shifts are likely to become more prevalent in future environmental conditions. Our study highlights the need for understanding complex environmental influences on kelp health and associated microbiomes for the sustainable development of seaweed farming.

The clinical treatment of inflammatory bowel disease (IBD) is challenging. We developed copper sulfate (CuS)/disulfiram (DSF)/methacrylic acid-ethyl acrylate copolymer (EL)/polyvinylpyrrolidone (PVP) nanoplatform (CuS/DSF/EL/PVP) and evaluated its efficiency for treating IBD. After oral administration, the pH-sensitive EL protected the CuS/DSF/EL/PVP against degradation by acidic gastric juices. Once the colon was reached, EL was dissolved, releasing DSF and Cu 2+ . Further, the main in vivo metabolite of DSF can bind to Cu 2+ and form copper (II) N, N-diethyldithiocarbamate (CuET), which significantly alleviated acute colitis in mice. Notably, CuS/DSF/EL/PVP outperformed CuS/EL/PVP and DSF/EL/PVP nanoplatforms in reducing colonic pathology and improving the secretion of inflammation-related cytokines (such as IL-4 and IL-10) in the colonic mucosa. RNA-seq analysis revealed that the nanoplatform reduced colonic inflammation and promoted intestinal mucosal repair by upregulating C-type lectin receptor (CLR)-related genes and signaling pathways. Furthermore, CuS/DSF/EL/PVP showed potential for improving colitis Th1/Th17 cells through innate immunity stimulation, down-regulation of inflammatory cytokines, and upregulation of anti-inflammatory cytokines. Additionally, the intervention with CuS/DSF/EL/PVP led to increased intestinal flora diversity, decreased Escherichia-Shigella abundance, and elevated levels of short-chain fatty acid (SCFA)-producing bacteria Prevotella, Lactobacillus, and Bifidobacterium, indicating their potential to modulate the dysregulated intestinal flora and suppress inflammation. STATEMENT OF SIGNIFICANCE: Our study introduces the CuS/DSF/EL/PVP nanoplatform as a therapeutic strategy for treating inflammatory bowel disease (IBD). This approach demonstrates significant efficacy in targeting the colon and alleviating acute colitis in mice. It uniquely modulates gut immunity and microbiota, exhibiting a notable impact on inflammation-related cytokines and promoting intestinal mucosal repair. The nanoplatform's ability to regulate gut flora diversity, combined with its cost-effective and scalable production, positions it as a potentially transformative treatment for IBD, offering new avenues for personalized medical interventions., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Hydrogels have been widely used as wound dressings to accelerate wound healing. However, due to the impaired skin barrier at the wound site, external bacteria can easily invade the wound and cause infection. In this study, we designed a dopamine-modified sodium alginate/carboxymethyl chitosan/polyvinylpyrrolidone (CPD) hydrogel, which was able to promote wound healing while preventing wound infection. Due to the high content of catechol groups, the CPD hydrogel exhibited good tissue adhesion ability and a significant scavenging ability for DPPH• and PTIO• radicals. Under near-infrared laser irradiation, the temperature of CPD hydrogel increased significantly, which significantly killed the Staphylococcus aureus and Escherichia coli. The cell migration test confirmed that CPD hydrogel could promote the cell migration ratio. In the in vivo wound healing test for infected full-thickness skin defect, CPD hydrogel significantly inhibited bacterial proliferation and enhanced wound healing rate. Therefore, the multifunctional hydrogel is expected to be applied to wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In recent years, the incidence of chronic pancreatitis has increased significantly. Pancreatic calculi obstruct the pancreatic duct and induce abdominal pain in the patients. Pancreatic duct stenting is the major treatment option for chronic pancreatitis with calculi. In this study, a new kind of drug-eluting stent, a pancreatic stent coated by methacrylated gelatin (GelMA) hydrogel loaded with citric acid (CA), was designed for the interventional treatment of pancreatic duct calculi. The CA loading capacity reached up to 0.7 g CA/g hydrogel-coated stent. The GelMA hydrogel coating has higher mechanical strength and lower swelling performance after loading with CA. The in vitro experiments of stents exhibited good performance in CA sustained release and the calculi can be dissolved in almost 3 days. The stents also showed good blood compatibility and cell compatibility. This research has important clinical value in the treatment of chronic pancreatitis with pancreatic calculi.

The microbiomes in macroalgal holobionts play vital roles in regulating macroalgal growth and ocean carbon cycling. However, the virospheres in macroalgal holobionts remain largely underexplored, representing a critical knowledge gap. Here we unveil that the holobiont of kelp (Saccharina japonica) harbors highly specific and unique epiphytic/endophytic viral species, with novelty (99.7% unknown) surpassing even extreme marine habitats (e.g. deep-sea and hadal zones), indicating that macroalgal virospheres, despite being closest to us, are among the least understood. These viruses potentially maintain microbiome equilibrium critical for kelp health via lytic-lysogenic infections and the expression of folate biosynthesis genes. In-situ kelp mesocosm cultivation and metagenomic mining revealed that kelp holobiont profoundly reshaped surrounding seawater and sediment virus-prokaryote pairings through changing surrounding environmental conditions and virus-host migrations. Some kelp epiphytic viruses could even infect sediment autochthonous bacteria after deposition. Moreover, the presence of ample viral auxiliary metabolic genes for kelp polysaccharide (e.g. laminarin) degradation underscores the underappreciated viral metabolic influence on macroalgal carbon cycling. This study provides key insights into understanding the previously overlooked ecological significance of viruses within macroalgal holobionts and the macroalgae-prokaryotes-virus tripartite relationship., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

Compared to free-living viruses (< 0.22 m) in the ocean, planktonic viruses in the "cellular fraction" (0.22 ~ 3.0 μm) are now far less well understood, and the differences between them remain largely unexplored. Here, we revealed that even in the same seawater samples, the "cellular fraction" comprised significantly distinct virus communities from the free virioplankton, with only 13.87% overlap in viral contigs at the species level. Compared to the viral genomes deposited in NCBI RefSeq database, 99% of the assembled viral genomes in the "cellular fraction" represented novel genera. Notably, the assembled (near-) complete viral genomes within the "cellular fraction" were significantly larger than that in the "viral fraction," and the "cellular fraction" contained three times more species of giant viruses or jumbo phages with genomes > 200 kb than the "viral fraction." The longest complete genomes of jumbo phage (~ 252 kb) and giant virus (~ 716 kb) were both detected only in the "cellular fraction." Moreover, a relatively higher proportion of proviruses were predicted within the "cellular fraction" than "viral fraction." Besides the substantial divergence in viral community structure, the different fractions also contained their unique viral auxiliary metabolic genes; e.g., those potentially participating in inorganic carbon fixation in deep sea were detected only in the "cellular-fraction" viromes. In addition, there was a considerable divergence in the community structure of both "cellular fraction" and "viral fraction" viromes between the surface and deep-sea habitats, suggesting that they might have similar environmental adaptation properties. The findings deepen our understanding of the complexity of viral community structure and function in the ocean., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The conventional method of using montmorillonite hemostatic materials affects the hemostatic effect due to easy dislodgement on the wound surface. In this paper, a multifunctional bio-hemostatic hydrogel (CODM) was prepared based on hydrogen bonding and Schiff base bonding using modified alginate, polyvinylpyrrolidone (PVP), and carboxymethyl chitosan. The amino group-modified montmorillonite was uniformly dispersed in the hydrogel by its amido bond formation with the carboxyl groups of carboxymethyl chitosan and oxidized alginate. The catechol group, -CHO, and PVP can form hydrogen bonds with the tissue surface to afford the firm tissue adhesion to afford the wound hemostatic. The addition of montmorillonite-NH 2 further improves the hemostatic ability, making it better than commercial hemostatic materials. Moreover, the photothermal conversion ability (derived from the polydopamine) was synergized with the phenolic hydroxyl group, quinone group, and the protonated amino group to effectively kill the bacteria in vitro and in vivo. Based on its in vitro and in vivo biosafety and satisfactory degradation ratio anti-inflammatory, antibacterial, and hemostatic properties, the CODM hydrogel holds promising potential for emergency hemostasis and intelligent wound management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The interaction between marine phyto- and bacterioplankton is regulated by multiple environmental and biological factors. Among them, phages as the major regulators of bacterial mortality are considered to have important impacts on algae-associated bacteria and algae-bacteria relationship. However, little is currently known about the actual impact of phages from this perspective. Here, we revealed that phage infection improved the maximum quantum efficiency of photosystem II of Phaeodactylum tricornutum by regulating the associated bacterial community. Specifically, phage infection weakened bacterial abundance and eliminated their negative effects on the diatom. Unexpectedly, the structure of the bacterial community co-cultured with the diatom was not significantly affected, likely because the shaping effect of the diatom on the bacterial community structure can far outcompete or mask the impact of phage infection. Our results established a link between algae, bacteria, and phages, suggesting that phage infection benefits the diatom by regulating the associated bacterial community., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Recently, electrical stimulation, as a non-pharmacological physical stimulus, has been widely exploited in biomedical and clinical applications due to its ability to significantly enhance cell proliferation and differentiation. As a kind of dielectric material with permanent polarization characteristics, electrets have demonstrated tremendous potential in this field owing to their merits of low cost, stable performance, and excellent biocompatibility. This review provides a comprehensive summary of the recent advances in electrets and their biomedical applications. We first provide a brief introduction to the development of electrets, as well as typical materials and fabrication methods. Subsequently, we systematically describe the recent advances of electrets in biomedical applications, including bone regeneration, wound healing, nerve regeneration, drug delivery, and wearable electronics. Finally, the present challenges and opportunities have also been discussed in this emerging field. This review is anticipated to provide state-of-the-art insights on the electrical stimulation-related applications of electrets.

In recent years, multifunctional hydrogel nanoplatforms for the synergistic treatment of tumors have received a great deal of attention. Here, we prepared an iron/zirconium/polydopamine/carboxymethyl chitosan hydrogel with Fenton and photothermal effects, promising for future use in the field of synergistic therapy and prevention of tumor recurrence. The iron (Fe)-zirconium (Zr)@ polydopamine (PDA) nanoparticles were synthesized by a simple one-pot hydrothermal method using iron (III) chloride hexahydrate (FeCl 3 •6H 2 O), zirconium tetrachloride (ZrCl 4 ), and dopamine, followed by activation of the carboxyl group of carboxymethyl chitosan (CMCS) using 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC)/N(4)-hydroxycytidine (NHS). Finally, the Fe-Zr@PDA nanoparticles and the activated CMCS were mixed to form a hydrogel. On the one side, Fe ions can use hydrogen peroxide (H 2 O 2 ) which is rich in the tumor microenvironment (TME) to produce toxic hydroxyl radicals (•OH) and kill tumor cells, and Zr can also enhance the Fenton effect; on the other side, the excellent photothermal conversion efficiency of the incorporated PDA is used to kill tumor cells under the irradiation of near-infrared light. The ability of Fe-Zr@PDA@CMCS hydrogel to produce •OH and the ability of photothermal conversion were verified in vitro, and swelling and degradation experiments confirmed the effective release and good degradation of this hydrogel in an acidic environment. The multifunctional hydrogel is biologically safe at both cellular and animal levels. Therefore, this hydrogel has a wide range of applications in the synergistic treatment of tumors and the prevention of recurrence.

In this study, a composite hydrogel (QMPD hydrogel) composed of methacrylate anhydride (MA) grafted quaternary ammonium chitosan (QCS-MA), polyvinylpyrrolidone (PVP), and dopamine (DA) was designed for the sequential wound inflammation elimination, infection inhibition, and wound healing. The QMPD hydrogel formation was initiated by the ultraviolet light-triggered polymerization of QCS-MA. Furthermore, hydrogen bonds, electrostatic interactions, and "π-π" stacking between QCS-MA, PVP, and DA were involved in the hydrogel formation. In this hydrogel, the quaternary ammonium groups of quaternary ammonium chitosan and the photothermal conversion of polydopamine are capable of killing bacteria on wounds, which showed the bacteriostatic ratios of 85.6 % and 92.5 % toward Escherichia coli and Staphylococcus aureus, respectively. Moreover, the oxidation of DA sufficiently scavenged free radicals and introduced the QMPD hydrogel with good anti-oxidant and anti-inflammatory abilities. Together with the extracellular matrix-mimic tropical structure, the QMPD hydrogel significantly promoted the wound management of mice. Therefore, the QMPD hydrogel is expected to provide a new method for the design of wound healing dressings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Glucose is used as an important nutrient to support cell growth. The glucose oxidase (GOx) can transform glucose into gluconic acid and toxic H 2 O 2 , which can be used for tumor starvation therapy. However, the leakage of GOx may cause severe side effects to the normal tissue. To prevent the accidental leakage of GOx, this study proposes the chemical modification of GOx on the photothermal transducing agent surface, to realize the safe and combined starvation and photothermal therapy of colorectal tumors. Polyvinylpyrrolidone (PVP)-modified WS 2 nanobowls (WS 2 -PVP) as a photothermal transducing agent were produced using a one-pot preparation method. Then, α-lipoic acid (LA) molecules were immobilized at the sulfur-deficient sites on the surface of WS 2 nanobowls to afford the chemical loading of GOx through amide bonds. Under the irradiation of a near-infrared laser (808 nm), thermal energy is generated by WS 2 to kill colorectal cancer cells locally. The photothermal conversion efficiency of WS 2 -PVP-LA was 27.2%. This study is anticipated to open up an alternative avenue for the rational design of multifunctional nanotherapeutics for tumor therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The postoperative recurrence has adversely affected the treatment of tumors. Besides, the potential bacterial infection at the wound site may lead to a series of tissue necrosis. Here, we developed an injectable γ-polyglutamic acid/carboxymethyl chitosan/polydopamine hydrogel (PCP) for simultaneously reducing the postoperative infection and preventing the tumor recurrence. On the one hand, the aqueous solution of carboxymethyl chitosan oxidized the dopamine into polydopamine; on the other, the carboxymethyl chitosan was cross-linked with the activated γ-polyglutamic acid to form a hydrogel. After local implantation, the PCP hydrogel effectively killed tumor cells and bacteria under 808 nm laser irradiation. In addition, carboxymethyl chitosan rendered the hydrogel with anti-bacterial properties as well as anti-tumor efficiencies. The anti-tumor recurrence and anti-bacterial efficiencies of PCP hydrogel were proved on a tumor-removed mouse model and a Staphylococcus aureus-infected mouse model, respectively. Moreover, the hydrogel has the advantages of good biocompatibility and simple preparation, and thus has potential application prospects in the prevention of tumor recurrence and wound bacterial infection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Hydrogel is a kind of hemostatic agent with good application prospect. However, the water molecules on the wound made the hydrogel less adhesive to wet wound tissue. Herein, the carboxymethyl chitosan (CMCS)/oxidized dextran (OD)/γ-polyglutamic acid (γ-PGA) hydrogel was prepared using a double-barreled syringe for hemostasis of diffuse and incompressible wound bleeding. The hydrogel formation was based on the intramolecular lactam bonds, intermolecular amide bonds, and Schiff base bonds. In the hydrogel, the super hydrophilic γ-PGA could drain the surface moisture of the wound and create a local dry environment for enhanced surface adhesion. In vivo study showed that the CMCS/ODex/γ-PGA hydrogel possesses a good biosafety and biodegradability. Interestingly, the CMCS/ODex/γ-PGA hydrogel exhibited excellent hemostatic abilities in dynamic humid environment and resisted a high blood pressure of 238 mmHg, which exceeds the threshold systolic blood pressure of healthy adults (i.e., 120 mmHg). Together with the antibacterial and reactive nitrogen species scavenging activities, this study is expected to provide a new method to design the wet-surface adhesives for the efficient hemostatic application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In this study, a methacrylic gelatin/oxidized dextran/montmorillonite‑strontium/polypyrrole (GOMP) hydrogel was prepared. The GOMP hydrogel had dual network structure which was formed through photoinitiator-initiated double bond polymerization and Schiff base reaction. The network structure led to a sustained release of the antitumor drug, doxorubicin (DOX). Polypyrrole introduced the conductivity and high photothermal conversion capacity to the GOMP hydrogel, which showed a photothermal conversion efficiency of 31.61 % under 808 nm laser radiation. The GOMP hydrogel had good swelling properties in solvents. Further study showed that the GOMP hydrogel had good biocompatibility and excellent biodegradability in vitro and in vivo. The experiments of in vitro tumor therapy and in vivo anti-tumor recurrence indicated that the DOX-loaded GOMP hydrogel had synergistic effects on tumor cell apoptosis based on chemotherapy and photothermal therapy. In addition, montmorillonite‑strontium (MMT-Sr) doped in the hydrogel not only improved the mechanical properties of the hydrogel but also promoted potential bone regeneration. The multifunctional DOX-loaded GOMP hydrogel with bone regeneration, photothermal therapy, and chemotherapy functions has great potential application for treating osteosarcoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Hydrogel is a three-dimensional network polymer material rich in water. It is widely used in the biomedical field because of its unique physical and chemical properties and good biocompatibility. In recent years, the incidence of inflammatory bowel disease (IBD) has gradually increased, and the disadvantages caused by traditional drug treatment of IBD have emerged. Therefore, there is an urgent need for new treatments to alleviate IBD. Hydrogel has become a potential therapeutic platform. However, there is a lack of comprehensive review of functional hydrogels for IBD treatment. This paper first summarizes the pathological changes in IBD sites. Then, the action mechanisms of hydrogels prepared from chitosan, sodium alginate, hyaluronic acid, functionalized polyethylene glycol, cellulose, pectin, and γ-polyglutamic acid on IBD were described from aspects of drug delivery, peptide and protein delivery, biologic therapies, loading probiotics, etc. In addition, the advanced functions of IBD treatment hydrogels were summarized, with emphasis on adhesion, synergistic therapy, pH sensitivity, particle size, and temperature sensitivity. Finally, the future development direction of IBD treatment hydrogels has been prospected., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Recently, the healing of chronic wounds such as extensive burns has become a serious and intractable clinical problem. Avoiding wound infection and retaining an appropriate level of moisture around wounds are significant challenges in wound care. Herein, a dual-network hydrogel composed of sodium alginate (SA) and platelet-rich plasma (PRP) was designed to facilitate the wound healing. The preparation of hydrogel was achieved through a simple one-step thrombin activation process. The morphological characterization results revealed the three-dimensional network structure of the hydrogel. Then, certain levels of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) were detected in phosphate buffer solution (PBS) cultured hydrogel, which led to the possibility of cell proliferation and vascular regeneration. When topically applied to the wound skin of rats, the hydrogel presented high wound closure effectiveness. In conclusion, this strategy provides a simple and feasible approach to overcoming the shortcomings of conventional wound dressings., Competing Interests: Declaration of Competing Interest The authors declare no potential competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Currently, hydrogels are widely studied for wound dressings. However, wound healing is often hindered by bacterial infection. In this study, in situ cross-linked carboxymethyl chitosan (CMCS)/oxidized dextran (OD)/poly-γ-glutamic acid (γ-PGA) (COP) hydrogel was prepared for antimicrobial and hemostasis of diffuse wounds. In the COP hydrogel, γ-PGA was able to drain the surface moisture of the wound to enhance the surface adhesion. Moreover, γ-PGA could concentrate blood by absorbing plasma, and CMCS could electrostatically adsorb negative RBCs. The antibacterial properties of CMCS and OD endowed the COP hydrogel with certain antibacterial effects. In the inhibition zone experiment, an obvious inhibition zone appeared around the COP hydrogel. In vivo studies showed that the COP hydrogel significantly inhibited bacterial growth and promoted wound healing. In the rat tail diffuse hemorrhage wound model, the COP hydrogel showed superior hemostasis ability. Therefore, the multifunctional COP hydrogel is expected to find different applications in wound hemostasis and healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The degradation of extracellular matrix (ECM) to increase drug permeability is an attractive approach to enhancing pancreatic cancer therapy efficiency. Herein, polypyrrole nanoparticles (PPy NPs) were prepared by a template-guided chemical oxidation method. These PPy NPs with abundant surface pores were used to load the anticancer drug doxorubicin (DOX). In order to intelligently control the DOX release, PPy/DOX NPs were further entrapped with a thermoresponsive ligand, lauric acid (LA), to form PPy-LA/DOX NPs. Bromelain (BL) was then grafted onto the surface of PPy-LA NPs or PPy-LA/DOX NPs through an amidation reaction with the carboxyl group of LA. It was found that the DOX release of PPy-LA/DOX NPs was pH and temperature responsive, reaching a maximum amount of 85.9% within 48 h at pH = 5.4 and 50 °C. Moreover, it was demonstrated that the resultant PLB (PPy-LA-BL) NPs could efficiently hydrolyze the collagen in ECM and enhance the permeability of DOX to the pancreatic tumor. Remarkably, PLB NPs not only featured admirable photothermal conversion but also exhibited obvious photoacoustic imaging capability, which enabled imaging-guided enhanced tumor ablation. This study is anticipated to provide a feasible strategy to improve the permeability of nanoparticles to tumors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Massive bleeding is a great threat to the life safety of patients, which is a challenging clinical problem. Therefore, it is urgent to develop a kind of multifunctional dressing material with hemostatic ability and antibacterial performance to promote wound healing and repair. To resolve this issue, in this study, a carboxymethyl chitosan (CMCS)/sodium alginate (SA)/oxidized dextran (ODE) (CSO) multifunctional hydrogel was developed. The hydrogel could rapidly gel through Schiff base reaction and amide reaction and firmly adhere to the skin at the wound, to realize the fast hemostasis. Importantly, it was verified that the hydrogel could prevent the Staphylococcus aureus-caused wound infection, owing to the antibacterial effect of CMCS and ODE. In addition, the CSO hydrogel had good water retention capacity and was able to mimic the three-dimensional structure of the natural extracellular matrix, thereby promoting wound repair in mice. In vitro whole-blood clotting assay demonstrated that red blood cells could be adhered to the surface of hydrogel, showing good hemostasis in rat liver injury and tail amputation models. Together with the biocompatible feature, CSO hydrogel holds a great application prospect in hemostasis and wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Acute pancreatitis (AP) is a complex inflammatory disease caused by multiple etiologies, the pathogenesis of which has not been fully elucidated. Oxidative stress is important for the regulation of inflammation-related signaling pathways, the recruitment of inflammatory cells, the release of inflammatory factors, and other processes, and plays a key role in the occurrence and development of AP. In recent years, antioxidant therapy that suppresses oxidative stress by scavenging reactive oxygen species has become a research highlight of AP. However, traditional antioxidant drugs have problems such as poor drug stability and low delivery efficiency, which limit their clinical translation and applications. Nanomaterials bring a brand-new opportunity for the antioxidant treatment of AP. This review focuses on the multiple advantages of nanomaterials, including small size, good stability, high permeability, and long retention effect, which can be used not only as effective carriers of traditional antioxidant drugs but also directly as antioxidants. In this review, after first discussing the association between oxidative stress and AP, we focused on summarizing the literature related to antioxidant nanomaterials for the treatment of AP and highlighting the effects of these nanomaterials on the indicators related to oxidative stress in pathological states, aiming to provide references for follow-up research and promote clinical application.

In this study, a polyvinylpyrrolidone (PVP)-decorated MoSe 2 (MoSe 2 -PVP) nanoparticle with excellent photothermal transforming ability and chlorin E6 (Ce6) loading capacity is designed for combined tumor photothermal therapy (PTT), tumor photodynamic therapy (PDT), and immunotherapy. The light-to-heat conversion efficiency under irradiation with an 808 nm near-infrared laser is as high as 59.28%. The MoSe 2 -PVP NPs could function as an artificial catalase and catalyze the decomposition of H 2 O 2 . Their catalytic activity and thermal durability are higher than the native catalase, which relieve the tumor hypoxia status and sensitize the tumor PDT. The data show that the synthetic MoSe 2 -PVP is biodegradable, owing to the oxidation of the Mo 4+ to Mo 6+ . Moreover, its degradation products could increase the proportion of mature dendritic cells and CD8 + thymus (T) cells and promote the infiltration of active CD8 + T cells in tumors. The immune checkpoint inhibitor, programmed cell death protein 1 monoclonal antibody is combined with MoSe 2 -PVP and it is found that its degradation product could efficiently change the immune microenvironment of the tumor., (© 2022 Wiley-VCH GmbH.)

This research proposes the one-pot preparation of polydopamine (PDA) decorated mesoporoussilica nanoparticle (PMSN) for the thermal and tumor micro-environment (TME) responsive colorectal tumor therapy. The pores of PMSN were used for the Fe 3+ loading. Lauric acid (LA), a phase-change ligand, was selected as a "doorkeeper" to coat the surface of Fe 3+ -loaded PMSN and prevent the undesired leakage of Fe 3+ . Bovine serum albumin (BSA) was selected as a stabilizer to endow the PMSN-Fe-LA-BSA nanopartilces (PMFLB) with colloidal stability. Under the near infrared laser, the light-sensitive PDA produced significant heat to kill the colorectal cancer cells via hyperthermia. Moreover, the heat induced the phase-change of LA and triggered the release of Fe 3+ , which further reacted with the endogenous H 2 S in the colorectal TME. After that, the Fe 3+ was transformed into Fe 2+ , which triggered the Fenton reaction with the H 2 O 2 in the TME and effectively generated hydroxyl radical (·OH). Finally, the Fe 2+ was transformed into Fe 3+ , which repeatedly reacted with the H 2 S and produced more ·OH to enhance the chemodynamic therapy of colorectal tumor. Such a thermosensitive PMFLB which operates in synergy with the colorectal TME opens an alternative avenue for the rational design of multifunctional nano-therapeutic agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Viruses carrying phoH genes are an important functional group that may boost phosphate metabolism of their prokaryote hosts and affect phosphorus cycle in the ocean. However, at present, very little is known about the phoH-carrying viruses' community structure and diversity in marine sediments, as well as their correlation network with prokaryotes and environment. Here, via a large spatial scale investigation along the Bohai Sea, Yellow Sea, and East China Sea, for the first time, diverse unknown benthic phoH-carrying viruses were uncovered, which were mainly affiliated to three clusters. Interestingly, these viruses presented a very distinct community structure compared to those in seawaters. Correlation network analysis implied that these viruses might mainly infect the prokaryotes of Gamm-/Delta-proteobacteria, Thaumarchaeota, and Cyanobacteria in sediments. Distinct virus-prokaryote correlation network modules were shown in different sea areas. These modules' highly nested feature implied their coevolution with prokaryotes during long-term arms race. Their distribution in sediments was influenced by multiple factors including geographic separation and the key environmental variables of total organic carbon and total phosphorus, and responded to terrestrial inputs and coastal aquaculture activities. The results of this study provide novel insights into the benthic virus communities potentially participating in phosphorus cycling in the ocean., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Exogenous antioxidant materials mimicking endogenous antioxidant systems are commonly used for the treatment of oxidative stress-induced injuries. Thus, artificial enzymes have emerged as promising candidates for balancing and treating the dysregulation of redox homeostasis in vivo. Herein, a one-pot hydrothermal strategy for the facile preparation of MoSe 2 -polyvinylpyrrolidone (PVP) nanoparticles (NPs) is reported. The synthesized NPs were biodegradable due to their exposure to oxygen and exhibited high stability. Moreover, they effectively mimicked various naturally occurring enzymes (including catalase, superoxide dismutase, peroxidase, and glutathione peroxidase) and scavenged free radicals, such as 3-ethylbenzothiazoline-6-sulfonic acid, ·OH, ·O 2- , and 1,1-diphenyl-2-picrylhydrazyl radical. Further apoptosis detection studies revealed that MoSe 2 -PVP NPs significantly increased the cell survival probability in H 2 O 2 in a concentration-dependent manner. The cytoprotective effect of MoSe 2 -PVP NPs was explored for an animal model of acute pancreatitis, which confirmed its remarkable therapeutic efficacy. Owing to the biodegradable and biocompatible nature of MoSe 2 -PVP NPs, the findings of this work can stimulate the development of other artificial nanoenzymes for antioxidant therapies., (© 2022. The Author(s).)

Viruses are ubiquitous in the oceans. Even in the deep sediments of the Mariana Trench, viruses have high productivity. However, little is known about their species composition and survival strategies in that environment. Here, we uncovered novel viral communities (3,206 viral scaffolds) in the upper slope sediments of the Mariana Trench via metagenomic analysis of 15 sediment samples. Most (99%) of the viral scaffolds lack known viral homologs, and ca. 59% of the high-quality viral genomes (total of 111 with completeness of >90%) represent novel genera, including some Phycodnaviridae and jumbo phages. These viruses contain various auxiliary metabolic genes (AMGs) potentially involved in organic carbon degradation, inorganic carbon fixation, denitrification, and assimilatory sulfate reduction, etc. This study provides novel insight into the almost unknown benthic viral communities in the Mariana Trench. IMPORTANCE The Mariana Trench harbors a substantial number of infective viral particles. However, very little is known about the identity, survival strategy, and potential functions of viruses in the trench sediments. Here, through metagenomic analysis, unusual benthic viral communities with high diversity and novelty were discovered. Among them, 59% of the viruses with a genome completeness of >90% represent novel genera. Various auxiliary metabolic genes carried by these viruses reflect the potential adaptive characteristics of viruses in this extreme environment and the biogeochemical cycles that they may participate in. This study gives us a deeper understanding of the peculiarities of viral communities in deep-sea/hadal sediments.

Proton pump inhibitors (PPIs) are the mainstay of therapy for gastroesophageal reflux disease (GERD) but up to 60% of patients have inadequate response to therapy. Acid sensing ion channels (ASICs) play important roles in nociception. This study aimed to investigate whether the increased expression of ASICs results in neuronal hyperexcitability in GERD. Esophageal biopsies were taken from GERD patients and healthy subjects to compare expression of ASIC1 and 3. Next, gene and protein expression of ASIC1 and 3 from esophageal mucosa and dorsal root ganglia (DRG) neurons were measured by qPCR, Western-blot and immunofluorescence in rodent models of reflux esophagitis (RE), non-erosive reflux disease (NERD), and sham operated groups. Excitability of DRG neurons in the GERD and sham groups were also tested by whole-cell patch-clamp recordings. We demonstrated that ASIC1 and 3 expression were significantly increased in patients with RE compared with healthy controls. This correlated positively with symptom severity of heartburn and regurgitation (p < .001). Next, ASIC1 and 3 gene and protein expression in rodent models of RE and NERD were similarly increased in esophageal mucosa as well as T3-T5 DRG neurons compared with sham operation. DRG neurons from RE animals showed hyperexcitability compared with sham group. However, intrathecal injection of ASIC specific inhibitors, PcTx1 and APTEx-2, as well as silencing ASIC1 and 3 genes with specific siRNAs prevented visceral hypersensitivity. Overall, upregulation of ASIC1 and 3 may lead to visceral hypersensitivity in RE and NERD and may be a potential therapeutic target for PPI non-responsive patients., (© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

In this research, a hydrogel that combined the tumor photodynamic therapy (PDT) and photothermal therapy (PTT) ability was designed, using dopamine-modified sodium carboxymethyl cellulose (CMC-DA) as the matrix and Chlorin e6 (Ce6) as the photosensitizer. The gel formation was initiated by adding the oxidizing agent sodium periodate (NaIO 4 ) to the CMC-DA solution, during which the dopamine was simultaneously oxidized to polydopamine (PDA) and NaIO 4 was reduced to sodium iodide (NaI). The formed NaI was encapsulated in the hydrogel and endowed the hydrogel with computerized tomography (CT) imaging ability to monitor the hydrogel degradation and the tumor therapy process. Moreover, the photosensitizer Ce6 can be loaded by the gel system via directly soaking the hydrogel in the Ce6 solution. Under the near-infrared light irradiation, Ce6 can produce cytotoxic reactive oxygen species and the PDA can produce heat to trigger the tumor PDT and PTT respectively to eradicate the tumor recurrence. In general, the designed hydrogel is biocompatible and biodegradable, has a good photothermal conversion, drug loading and CT imaging ability, which laid the foundation for the rational design of biodegradable hydrogels for multifunctional applications., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Featured with a three-dimensional network structure, electrostatic spinning nanofibrous membranes can maintain the hygroscopic balance in the wound place and promote the wound healing, thus have been extensively studied as a promising wound healing dressing. In this study, amoxicillin (AMX), MXene, and polyvinyl alcohol (PVA) were mixed and electrospun into an antibacterial nanofibrous membrane (MXene-AMX-PVA nanofibrous membrane). In the composite nanofibrous membrane, the PVA matrix could control the release of AMX to combat bacterial infection, while the MXene could transform the near-infrared laser into heat, leading to local hyperthermia to promote the AMX release. Meanwhile, the local hyperthermia could also destroy the noncellular components of bacteria and synergistically cause the bacterial inactivation. The bacteriostatic activity and wound healing ability of the composite nanofibrous membrane were systematically verified on the S. aureus in vitro and the S. aureus-infected mouse skin defect model in vivo. This membrane not only functioned as a physical barrier to co-load the AMX and MXene, but also exhibited the high antibacterial and accelerated wound healing capacity, which will advance the design of novel wound healing dressings and antibacterial strategies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

An in-situ formed hemostatic hydrogel (GelMA/OD/Borax) was prepared for the emergency wound hemostasis and anti-inflammation applications. Gelatin was chosen as the backbone and modified with methacrylic anhydride (MA) to synthesize GelMA, which showed the admirable UV light activatable polymerizing ability. Aldehyde groups, which cross-linked with the -NH 2 on the tissue surface and afforded the tissue adhesion, were produced by oxidizing the o-hydroxyl groups of dextran. Further, the sodium tetraborate formed dynamic boric acid ester bonds with the oxidized dextran (OD). With this triple-network structure, the as-prepared hydrogel presented excellent hemostatic capacity and surmounted a high blood pressure of 165 mmHg, which is higher than the threshold systolic blood pressure of healthy adults (i.e., 120 mmHg). The mechanical property, morphology, biocompatibility and degradation of the hydrogel were character Borax, the hydrogel successfully blocked the bleeding and accelerated the wound healing. This research provides a new modality for the design of a multifunctional hemostatic hydrogel for effective hemostasis and wound healing., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has attracted attention due to its enhanced tumor therapy effect. This study proposes a novel nanoenzyme-based theranostic nanoplatform, IrO 2 @MSN@PDA-BSA(Ce6), for the combined PTT and PDT of tumors. IrO 2 was prepared by a simple hydrolysis method and coated with a thin layer of mesoporous silica (MSN) to facilitate the physical adsorption of Chlorin e6 (Ce6). The PDA coating and IrO 2 NPs of the nanoplatform demonstrated an improved photothermal conversion efficiency of 29.8% under NIR irradiation. Further, the Ce6 loading imparts materials with the ability to produce reactive oxygen species (ROS) under 660 nm NIR laser irradiation. It was also proved that the IrO 2 NPs could catalyze the hydrogen peroxide (H 2 O 2 ) in the tumor microenvironment (TME) to generate endogenous oxygen (O 2 ), thereby enhancing the efficiency of PDT. The in vitro and in vivo experiments indicated that the nanocomposite was highly biocompatible and could produce a satisfactory tumor therapeutic effect. Thus, the findings of the present study demonstrate the viability of using theranostic nanoenzymes for translational medicine.

Abstract: Pancreatic cancer (PC) is a malignant tumor which ranks fourth in cancer-related death. However, the specificity and sensitivity of traditional biomarkers such as carbohydrate antigen 19-9 no longer meet the clinical requirements.Tools as ONCOMINE and Gene Expression Profiling Interactive Analysis (GEPIA) were used to analyze the differential expression of matrix metalloproteinases (MMPs) in PC and adjacent tissues. For further analysis, we adopted database for annotation, visualization and integrated discovery (DAVID 6.8), transcriptional regulatory relationships unraveled by sentence-based text (TRRUST) and other tools. We also identified drugs targeted the selected MMPs.Eight MMPs (MMP1, MMP2, MMP7, MMP9, MMP11, MMP12, MMP14, and MMP28) were differentially expressed in PC and adjacent tissue. MMP1 (P = .0189), MMP7 (P = .000216), MMP11 (P = .0209), MMP14 (P = .00611) were correlated with the pathological stages of PC. Patients with higher expression of MMP1 (P = .0011), MMP2 (P = .011), MMP7 (P = .0081), MMP9 (P = .046), MMP11 (P = .0019), MMP12 (P = .0011), MMP14 (P = .0011), and MMP28 (P = 6.3e-06) showed poor prognosis. Ten transcription factors were associated with the up-regulation of selected MMPs. Marimastat (DB00786) was found to target selected MMPs.Our research revealed that selected MMPs played an important role in the early diagnosis and prognosis of PC., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

To avoid the negative effects of antibiotics, using phage to prevent animal disease becomes a promising method in aquaculture. Here, a lytic phage provisionally named vB&#95;VcaS&#95;HC that can infect the pathogen (i.e., Vibrio campbellii 18) of prawn was isolated. The phage has an isometric head and a non-contractile tail. During phage infection, the induced host mortality in 5.5 h reached ca. 96%, with a latent period of 1.5 h and a burst size of 172 PFU/cell. It has an 81,566 bp circular dsDNA genome containing 121 open reading frames (ORFs), and ca. 71% of the ORFs are functionally unknown. Comparative genomic and phylogenetic analysis revealed that it is a novel phage belonging to Delepquintavirus, Siphoviridae, Caudovirales. In the phage genome, besides the ordinary genes related to structure assembly and DNA metabolism, there are 10 auxiliary metabolic genes. For the first time, the pyruvate phosphate dikinase (PPDK) gene was found in phages whose product is a key rate-limiting enzyme involving Embden-Meyerhof-Parnas (EMP) reaction. Interestingly, although the phage has a strong bactericidal activity and contains a potential lysogeny related gene, i.e., the recombinase (RecA) gene, we did not find the phage turned into a lysogenic state. Meanwhile, the phage genome does not contain any bacterial virulence gene or antimicrobial resistance gene. This study represents the first comprehensive characterization of a lytic V. campbellii phage and indicates that it is a promising candidate for the treatment of V. campbellii infections.

Owing to the hypoxia status of the tumor, the reactive oxygen species (ROS) production during photodynamic therapy (PDT) of the tumor is less efficient. Herein, a facile method which involves the synthesis of Mg-Mn-Al layered double hydroxides (LDH) clay with MoS 2 doping in the surface and anionic layer space of LDH was presented, to integrate the photo-thermal effect of MoS 2 and imaging and catalytic functions of Mg-Mn-Al LDH. The designed LDH-MoS 2 (LMM) clay composite was further surface-coated with bovine serum albumin (BSA) to maintain the colloidal stability of LMM in physiological environment. A photosensitizer, chlorin e6 (Ce6), was absorbed at the surface and anionic layer space of LMM@BSA. In the LMM formulation, the magnetic resonance imaging of Mg-Mn-Al LDH was enhanced thanks to the reduced and acid microenvironment of the tumor. Notably, the ROS production and PDT efficiency of Ce6 were significantly improved, because LMM@BSA could catalyze the decomposing of the overexpressed H 2 O 2 in tumors to produce oxygen. The biocompatible LMM@BSA that played the synergism with tumor microenvironment is a promising candidate for the effective treatment of cancer.

Rationale: Acute pancreatitis (AP) is a serious acute condition affecting the abdomen and shows high morbidity and mortality rates. Its global incidence has increased in recent years. Inflammation and oxidative stress are potential therapeutic targets for AP. This study was conducted to investigate the intrinsic anti-oxidative and anti-inflammatory effects of Prussian blue nanozyme (PBzyme) on AP, along with its underlying mechanism. Methods: Prussian blue nanozymes were prepared by polyvinylpyrrolidone modification method. The effect of PBzyme on inhibiting inflammation and scavenging reactive oxygen species was verified at the cellular level. The efficacy and mechanism of PBzyme for prophylactically treating AP were evaluated using the following methods: serum testing in vivo , histological scoring following hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling fluorescence staining, polymerase chain reaction array, Kyoto Encyclopedia of Genes and Genomes analysis and Western blotting analysis. Results: The synthetic PBzyme showed potent anti-oxidative and anti-inflammatory effects in reducing oxidative stress and alleviating inflammation both in vitro and in vivo in the prophylactic treatment of AP. The prophylactic therapeutic efficacy of PBzyme on AP may involve inhibition of the toll-like receptor/nuclear factor-κB signaling pathway and reactive oxygen species scavenging. Conclusion: The single-component, gram-level mass production, stable intrinsic biological activity, biosafety, and good therapeutic efficacy suggest the potential of PBzyme in the preventive treatment of AP. This study provides a foundation for the clinical application of PBzyme., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Although the oral administration of Bifidobacterium longum ( B. longum ) relieves the signs of irritable bowel syndrome (IBS) in clinical settings, the mechanisms underlying its effects are unclear. In this study, we evaluated the precise effects of B. longum on IBS via regulation of Paneth cell function. We confirmed the beneficial effects of B. longum on defecation habits and visceral hypersensitivity in WAS rats. Further analysis revealed that B. longum enhanced mucosal repair, promoted lysozyme production, and ameliorated dysbiosis of the microbiota in WAS rats. These processes are closely correlated with Paneth cell functions. In vitro , we incubated primary cultured enteroids with B. longum and found that B. longum promoted the proliferation of these organoids; this may be attributed to the upregulation of the stem niche factors WNT3A and TGF-β, which are secreted by Paneth cells. Based on our findings, we propose that B. longum relieves IBS by restoring the antimicrobial activity and stem niche maintenance function of Paneth cells.

Starvation therapy (ST) and chemodynamic therapy (CDT) are emerging tumor therapy methods in recent years. In this study, a simple approach was reported to prepare MoS 2 and glucose oxidase (GOx)-containing sodium alginate (ALG)-Fe 3+ (MAF) hydrogel. In the hydrogel, there exists an enzymatic reaction to consume glucose to form hydrogen peroxide (H 2 O 2 ), and a redox reaction between Fe 3+ and MoS 2 to form Fe 2+ and MoO 4 2- . The formed Fe 2+ could be oxidized to Fe 3+ , which reacts with MAF hydrogel again to continuously produce Fe 2+ . The consumption of glucose resulted in an obvious tumor ST. Moreover, the produced Fe 2+ induced a Fenton reaction to enable the persistent conversion of H 2 O 2 to cytotoxic hydroxyl radicals (·OH) for the CDT of tumors. Together with the high photothermal transforming capability of MoS 2 , the hydrogel was used for the combined tumor photothermal therapy (PTT), ST, and CDT. This work provides a window for the safe use of enzymes for achieving high tumor therapeutic efficacy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The combination of reactive oxygen species (ROS)-induced chemodynamic therapy (CDT) and photothermal therapy (PTT) holds a promising application prospect for their superb anticancer efficiency. Herein, we created a novel Fe 3 O 4 @polydopamine (PDA)@bovine serum albumin (BSA)-Bi 2 S 3 composite as a theranostic agent, by chemically linking the Fe 3 O 4 @PDA with BSA-Bi 2 S 3 via the amidation between the carboxyl groups of BSA and the amino groups of PDA. In this formulation, the Fe 3 O 4 NPs could not only work as a mimetic peroxidase to trigger Fenton reactions of the innate H 2 O 2 in the tumor and generate highly cytotoxic hydroxyl radicals (•OH) to induce tumor apoptosis but also serve as the magnetic resonance imaging (MRI) contrast agent to afford the precise cancer diagnosis. Meanwhile, the PDA could prevent the oxidization of Fe 3 O 4 , thus supporting the long-term Fenton reactions and the tumor apoptosis in the tumor. The Bi 2 S 3 component exhibits excellent photothermal transducing performance and computed tomography (CT) imaging capacity. In addition, the PDA and Bi 2 S 3 endow the Fe 3 O 4 @PDA@BSA-Bi 2 S 3 composite with an excellent photothermal transforming ability which could lead to tumor hyperthermia. All of these merits play the synergism with the tumor microenvironment and qualify the Fe 3 O 4 @PDA@BSA-Bi 2 S 3 NPs for a competent agent in the MRI/CT-monitored enhanced PTT/CDT synergistic therapy. Findings in this research will evoke new interests in future cancer therapeutic strategies based on biocompatible nanomaterials.

In this study, sodium alginate (ALG)/poly dopamine (PDA)-polyvinylpyrrolidone (PVP) nanocomposites was synthesized via a one-step electrostatic spraying method. The spinning solution of ALG and dopamine was electrostatically sprayed into an alkaline solution of PVP, calcium chloride and tris buffer (pH = 8.5), in which the gelation of ALG and the polymerization of dopamine could be simultaneously triggered. PDA hence produced possesses a high photothermal conversion efficiency, while the PVP that was facilely conjugated onto the surface of nanocomposites improves the colloidal stability and compatibility of the material. Moreover, the ALG renders the nanocomposite excellent drug (doxorubicine, DOX) loading capacity. Promisingly, the temperature increment during the PTT process could promote the DOX release, thus enhancing its therapeutic effect. The in vitro/in vivo biosafety and tumor treatment experiments further corroborate that the ALG/PDA-PVP nanocomposites have remarkable biocompatibility and synergism for tumor hyperthermia and chemotherapy. Consequently, such a one-step electrospray strategy provides a new way for designing nanomaterials and is expected to significantly promote the development of organic photothermal therapeutic agents with excellent bio-compatibility.

The coastal sediments were considered to contain diverse phages playing important roles in driving biogeochemical cycles based on genetic analysis. However, till now, benthic phages in coastal sediments were very rarely isolated, which largely limits our understanding of their biological characteristics. Here, we describe a novel lytic phage (named Shewanella phage S0112) isolated from the coastal sediments of the Yellow Sea infecting a sediment bacterium of the genus Shewanella . The phage has a very high replication capability, with the burst size of ca. 1170 phage particles per infected cell, which is 5-10 times higher than that of most phages isolated before. Meanwhile, the latent period of this phage is relatively longer, which might ensure adequate time for phage replication. The phage has a double-stranded DNA genome comprising 62,286 bp with 102 ORFs, ca. 60% of which are functionally unknown. The expression products of 16 ORF genes, mainly structural proteins, were identified by LC-MS/MS analysis. Besides the general DNA metabolism and structure assembly genes in the phage genome, there is a cluster of auxiliary metabolic genes that may be involved in 7-cyano-7-deazaguanine (preQ 0 ) biosynthesis. Meanwhile, a pyrophosphohydrolase (MazG) gene being considered as a regulator of programmed cell death or involving in host stringer responses is inserted in this gene cluster. Comparative genomic and phylogenetic analysis both revealed a great novelty of phage S0112. This study represents the first report of a benthic phage infecting Shewanella , which also sheds light on the phage-host interactions in coastal sediments.

The purpose of this study was to design an injectable hydrogel with temperature-sensitive property for safe and high efficient in vivo colon cancer hyperthermia and chemotherapy. Chitosan (CS) solution was injected into the tumor at room temperature and automatically gelled after warming to body temperature in the present of β-glycerophosphate (β-GP). Combined localized tumor photothermal and chemotherapy were achieved by dissolving photothermal material MoS 2 /Bi 2 S 3 -PEG (MBP) nanosheets and drug molecule doxorubicin (DOX) into the hydrogel, and the gel system could encapsulate DOX and MBP nanosheets and prevent them from entering the blood circulation and damaging normal tissues and cells. More importantly, the CS/MBP/DOX (CMD) hydrogel exhibited a photothermal efficiency of 22.18% and 31.42% in the first and second near infrared light (NIR I and NIR II) biowindows respectively at a low MBP concentration (0.5 mg/mL). Besides, the release of the DOX from CMD hydrogel was controllable since the gel temperature could be governed by NIR laser irradiation. Moreover, the chitosan-based hydrogel had antibacterial effects. The designed composite hydrogel is anticipated to act as a platform for the high efficient treatment of tumors owing to the different penetration depths of NIR I and NIR II., (Copyright © 2019 Elsevier Ltd. All rights reserved.)