Graphene Quantum Dots Nanoantibiotic-Sensitized TiO2- x Heterojunctions for Sonodynamic-Nanocatalytic Therapy of Multidrug-Resistant Bacterial Infections.

The exploration of sonodynamic therapy (SDT) as a possible replacement for antibiotics by creating reactive oxygen species (ROS) is suggested as a non-drug-resistant theranostic method. However, the low-efficiency ROS generation and complex tumor microenvironment which can deplete ROS and promote tumor growth will cause the compromised antibacterial efficacy of SDT. Herein, through an oxygen vacancy engineering strategy, TiO2- x microspheres with an abundance of Ti3+ are synthesized using a straightforward reductant co-assembly approach. The narrow bandgaps and Ti3+/Ti4+-mediated multiple-enzyme catalytic activities of the obtained TiO2- x microspheres make them suitable for use as sonosensitizers and nanozymes. When graphene quantum dot (GQD) nanoantibiotics are deposited on TiO2- x microspheres, the resulting GQD/TiO2- x shows an increased production of ROS, which can be ascribed to the accelerated separation of electron-hole pairs, as well as the peroxidase-like catalytic activity mediated by Ti3+, and the depletion of glutathione mediated by Ti4+. Moreover, the catalytic activities of TiO2- x microspheres are amplified by the heterojunctions-accelerated carrier transfer. In addition, GQDs can inhibit Topo I, displaying strong antibacterial activity and further enhancing the antibacterial activity. Collectively, the combination of GQD/TiO2- x-mediated SDT/NCT with nanoantibiotics can result in a synergistic effect, allowing for multimodal antibacterial treatment that effectively promotes wound healing.

Organic-Inorganic Heterointerface-Expediting Electron Transfer Realizes Efficient Plasmonic Catalytic Sterilization via a Carbon-Dot Nanozyme.

Plasmonic nanozymes bring enticing prospects for catalytic sterilization by leveraging plasmon-engendered hot electrons. However, the interface between plasmons and nanozymes as the mandatory path of hot electrons receives little attention, and the mechanisms of plasmonic nanozymes still remain to be elucidated. Herein, a plasmonic carbon-dot nanozyme (FeCG) is developed by electrostatically assembling catalytic iron-doped carbon dots (Fe-CDs) with plasmonic gold nanorods. The energy harvesting and hot-electron migration are remarkably expedited by a spontaneous organic-inorganic heterointerface holding a Fermi level-induced interfacial electric field. The accumulated hot electrons are then fully utilized by conductive Fe-CDs to boost enzymatic catalysis toward overproduced reactive oxygen species. By synergizing with localized heating from hot-electron decay, FeCG achieves rapid and potent disinfection with an antibacterial efficiency of 99.6% on Escherichia coli within 5 min and is also effective (94.2%) against Staphylococcus aureus. Our work presents crucial insights into the organic-inorganic heterointerface in advanced plasmonic biocidal nanozymes.

Effects of clarithromycin exposure on the growth of Microcystis aeruginosa and the production of algal dissolved organic matter.

Antibiotics are commonly found in the aquatic environment, which can affect microbial community compositions and activities, and even have potential adverse impacts on human and ecosystem health. The current understanding of the effects of antibiotics on microalgae growth and algal dissolved organic matter (DOM) remains indistinct. To understand the toxic effects of antibiotics on the microalgae, Microcystis aeruginosa was exposed to clarithromycin (CLA) in this study. Cell density determination, chlorophyll content determination, and organic spectrum analysis were conducted to show the effect of CLA exposure on the growth, photosynthetic activity, and organic metabolic processes of Microcystis aeruginosa. The findings revealed that the physiological status of algae could be significantly influenced by CLA exposure in aquatic environments. Specifically, exposure to 1 µg/L CLA stimulated the growth and photosynthetic activity of algal cells. Conversely, CLA above 10 µg/L led to the inhibition of algal cell growth and photosynthesis. Notably, the inhibitory effects intensified with the increasing concentration of CLA. The molecular weight of DOM produced by Microcystis aeruginosa increased when exposed to CLA. Under the exposure of 60 µg/L CLA, a large number of algal cells ruptured and died, and the intracellular organic matter was released into the algal liquid. This resulted in an increase in high molecular weight substances and soluble microbial-like products in the DOM. Exposure to 1 and 10 µg/L CLA stimulated Microcystis aeruginosa to produce more humic acid-like substances, which may be a defense mechanism against CLA. The results were useful for assessing the effects of antibiotic pollution on the stability of the microalgae population and endogenous DOM characteristics in aquatic ecosystems.

XELOX (capecitabine plus oxaliplatin) plus bevacizumab (anti-VEGF-A antibody) with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer: a multicenter, open-label, randomized, controlled, phase 3 trial.

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6-18.0) for the immunotherapy group compared with 9.9 months (8.0-11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40-0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3-32.8) for the control group (HR, 0.57 [95% CI, 0.33-0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

An allosteric mechanism for potent inhibition of SARS-CoV-2 main proteinase.

The main proteinase (Mpro) of SARS-CoV-2 plays a critical role in cleaving viral polyproteins into functional proteins required for viral replication and assembly, making it a prime drug target for COVID-19. It is well known that noncompetitive inhibition offers potential therapeutic options for treating COVID-19, which can effectively reduce the likelihood of cross-reactivity with other proteins and increase the selectivity of the drug. Therefore, the discovery of allosteric sites of Mpro has both scientific and practical significance. In this study, we explored the binding characteristics and inhibiting process of Mpro activity by two recently reported allosteric inhibitors, pelitinib and AT7519 which were obtained by the X-ray screening experiments, to probe the allosteric mechanism via molecular dynamic (MD) simulations. We found that pelitinib and AT7519 can stably bind to Mpro far from the active site. The binding affinity is estimated to be -24.37 ± 4.14 and - 26.96 ± 4.05 kcal/mol for pelitinib and AT7519, respectively, which is considerably stable compared with orthosteric drugs. Furthermore, the strong binding caused clear changes in the catalytic site of Mpro, thus decreasing the substrate accessibility. The community network analysis also validated that pelitinib and AT7519 strengthened intra- and inter-domain communication of Mpro dimer, resulting in a rigid Mpro, which could negatively impact substrate binding. In summary, our findings provide the detailed working mechanism for the two experimentally observed allosteric sites of Mpro. These allosteric sites greatly enhance the 'druggability' of Mpro and represent attractive targets for the development of new Mpro inhibitors.

DNA of Neutrophil Extracellular Traps Binds TMCO6 to Impair CD8+ T-cell Immunity in Hepatocellular Carcinoma.

Neutrophil extracellular traps (NET), formed by the extracellular release of decondensed chromatin and granules, have been shown to promote tumor progression and metastasis. Tumor-associated neutrophils in hepatocellular carcinoma (HCC) are prone to NET formation, highlighting the need for a more comprehensive understanding of the mechanisms of action of NETs in liver cancer. Here, we showed that DNA of NETs (NET-DNA) binds transmembrane and coiled-coil domains 6 (TMCO6) on CD8+ T cells to impair antitumor immunity and thereby promote HCC progression. TGFß1 induced NET formation, which recruited CD8+ T cells. Binding to NET-DNA inhibited CD8+ T cells function while increasing apoptosis and TGFß1 secretion, forming a positive feedback loop to further stimulate NET formation and immunosuppression. Mechanistically, the N-terminus of TMCO6 interacted with NET-DNA and suppressed T-cell receptor signaling and NFκB p65 nuclear translocation. Blocking NET formation by inhibiting PAD4 induced potent antitumor effects in wild-type mice but not TMCO6-/- mice. In clinical samples, CD8+ T cells expressing TMCO6 had an exhausted phenotype. TGFß1 signaling inhibition or TMCO6 deficiency combined with anti-PD-1 abolished NET-driven HCC progression in vivo. Collectively, this study unveils the role of NET-DNA in impairing CD8+ T-cell immunity by binding TMCO6 and identifies targeting this axis as an immunotherapeutic strategy for blocking HCC progression. SIGNIFICANCE: TMCO6 is a receptor for DNA of NETs that mediates CD8+ T-cell dysfunction in HCC, indicating that the NET-TMCO6 axis is a promising target for overcoming immunosuppression in liver cancer.

Electron Lock Manipulates the Catalytic Selectivity of Nanozyme.

Nanomaterials with enzyme-mimicking functions, termed nanozymes, offer attractive opportunities for biocatalysis and biomedicine. However, manipulating nanozyme selectivity poses an insurmountable hurdle. Here, we propose the concept of an energy-governed electron lock that controls electron transfer between nanozyme and substrates to achieve selectivity manipulation of enzyme-like catalysis. An electron lock can be constructed and opened, via modulating the nanozyme's electron energy to match the energy barrier of enzymatic reactions. An iron-doped carbon dot (FeCD) nanozyme with easy-to-regulate electron energy is selected as a proof of concept. Through regulating the conduction band which dominates electron energy, activatable oxidase and selective peroxidase (POD) with substrate affinity 123-fold higher than that of natural horseradish peroxidase (HRP) is achieved. Furthermore, while maintaining selectivity, FeCDs exhibit catalytic kinetics comparable to that of HRP upon transforming photons into electrons. Superior selectivity, efficient catalysis, and undetectable biotoxicity energize FeCDs as potent targeted drugs on antibiotic-resistant bacterial abscesses. An electron lock provides a robust strategy to manipulate selectivity toward advanced nanozymes.

Inactivation of pathogenic microorganisms in water by electron beam excitation multi-wavelength ultraviolet irradiation: Efficiency, influence factors and mechanism.

Due to the limitations of traditional ultraviolet (UV) in microbial inactivation in water, it is necessary to explore a more suitable and efficient UV disinfection method. In this study, an electron beam excitation multi-wavelength ultraviolet (EBE-MW-UV) system was established and aims to analyze its differential microbial inactivation capabilities in comparison to single-wavelength UV-LEDs in waterborne applications. Furthermore, the inactivation mechanisms of this system on microorganisms were explored. The results showed that EBE-MW-UV had significantly higher inactivation effects on the Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Candida albicans in water compared to UV-LEDs (p＜0.05), and the inactivation effect of EBE-MW-UV on Escherichia coli and Pseudomonas aeruginosa at the same UV dose was 3.8 and 1.9 log higher than that of UV-LEDs, respectively, EBE-MW-UV exhibited better inactivation effects on Gram-negative bacteria. Further research found that, under the majority of irradiation doses, neither EBE-MW-UV nor UV-LEDs were significantly affected by the concentration of suspended solids (5 and 20 mg/L) or humic acids (2 and 5 mg/L) in the water. Mechanism analysis revealed that during the disinfection process of EBE-MW-UV, microbial DNA and proteins were initially damaged, which prevented the occurrence of dark repair and led to bacterial inactivation. In addition, UV irradiation led to the production of additional reactive oxygen species (ROS) inside the cells, increasing cell membrane permeability and exacerbating membrane damage. This was accompanied by a decrease in energy metabolism and depletion of ATP, ultimately resulting in microbial inactivation. Therefore, EBE-MW-UV demonstrated more effective disinfection than single-wavelength UV-LEDs, showing great potential. Our research gives new insights into the characteristics of multiple wavelength ultraviolet, and provides scientific basis for the selection of new light sources in the field of ultraviolet disinfection.

A numerical model for water hydration on nanosurfaces: from friction to hydrophilicity and hydrophobicity.

Fluidic transport down to the nanometer scale is of great importance for a wide range of applications such as energy harvesting, seawater desalination, and water treatment and may help to understand many biological processes. In this work, we studied the interfacial friction of liquid water on a series of nanostructures through molecular dynamics (MD) simulations. Our results reveal that the friction coefficient of the water-solid interface cannot be described using a previously reported simple function of the free energy corrugation. Considering that the water-solid friction is firmly correlated with the microscopic water motion, we proposed a probability parameter P(d, t) to classify water motion modes on a surface. We demonstrate that this parameter can be used to accurately predict the water-solid friction by simply monitoring the water binding time on a nanosurface. More importantly, according to the relationship between P(d, t) and friction, we found that the friction coefficient can be used as an indicative criterion for quantitatively assessing hydrophobic or hydrophilic materials, where the borderline is roughly 2 × 105 N s m-3. That is if the water-solid friction is less than 2 × 105 N s m-3, the surface is considered hydrophobic. But if the friction is larger than this value, the surface is hydrophilic. The present findings could help to better understand fluidic transport at the nanoscale and guide the future design of functional materials, such as super-hydrophobic and super-hydrophilic surfaces by structure engineering.

New insight into the effect of microplastics on antibiotic resistance and bacterial community of biofilm.

Microplastics (MPs) could serve as substrates for microbial colonization and biofilm formation. However, research on the effects of different types of microplastics and natural substrates on biofilm formation and community structure in the presence of antibiotic-resistant bacteria (ARB) is limited. In this study, we employed by means of microcosm experiments to analyze the situation of biofilms conditions, bacterial resistance patterns, antibiotic resistance genes (ARGs) distribution, and bacterial community on different substrates using microbial cultivation, high throughtput sequencing and PCR. The result showed that biofilms on different substrates markedly increased with time, with MPs surfaces formed more biofilm than stone. Analyses of antibiotic resistant showed negligible differences in the resistance rate to the same antibiotic at 30 d, but tetB would be selectively enriched on PP and PET. The microbial communities associated with biofilms on MPs and stones exhibited variations during different stages of formation. Notably, phylum WPS-2 and Epsilonbacteraeota were identified as the dominant microbiomes of biofilms on MPs and stones at 30 d, respectively. Correlation analysis suggested that WPS-2 could potentially be a tetracycline-resistant bacterium, while Epsilonbacteraeota did not correlate with any detected ARB. Our results emphasized the potential threat posed by MPs as attachment carriers for bacteria, particularly ARB, in aquatic environments.

Bioinspired hot-spot engineering strategy towards ultrasensitive SERS sandwich biosensor for bacterial detection.

Surface-enhanced Raman spectroscopy (SERS) sandwich biosensors have received tremendous attention in early diagnosis of bacterial infections. However, efficiently engineering nanoscale plasmonic hots pots (HS) towards ultrasensitive SERS detection still remains challenging. Herein, we propose a bioinspired synergistic HS engineering strategy to construct ultrasensitive SERS sandwich bacterial sensor (named USSB), by coupling bioinspired signal module and plasmonic enrichment module to synergistically boost the number and intensity of HS. The bioinspired signal module is based on dendritic mesoporous silica nanocarrier (DMSN) loaded with plasmonic nanoparticles and SERS tag, while magnetic Fe3O4 nanoparticles coated with Au shell are employed in plasmonic enrichment module. We demonstrate that DMSN effectively shrank nanogaps between plasmonic nanoparticles to improve HS intensity. Meanwhile, plasmonic enrichment module contributed to plenty of additional HS inside and outside individual "sandwich". Ascribing to the boosted number and intensity of HS, the constructed USSB sensor exhibits ultrahigh detection sensitivity (7 CFU/mL) and selectivity towards model pathogenic bacteria of Staphylococcus aureus. Remarkably, the USSB sensor enables fast and accurate bacterial detection in real blood samples of septic mice, achieving early diagnosis of bacterial sepsis. The proposed bioinspired synergistic HS engineering strategy opens up a new direction for constructing ultrasensitive SERS sandwich biosensors, and may promote their advancing applications in the early diagnosis and prognosis of devastating diseases.

Confined Cascade Metabolic Reprogramming Nanoreactor for Targeted Alcohol Detoxification and Alcoholic Liver Injury Management.

Alcoholic liver injury (ALI) is the leading cause of serious liver disease, whereas current treatments are mostly supportive and unable to metabolize alcohol directly. Here we report a metabolic reprogramming strategy for targeted alcohol detoxification and ALI management based on a confined cascade nanoreactor. The nanoreactor (named AA@mMOF) is designed by assembling natural enzymes of alcohol oxidase (AOx) and aldehyde dehydrogenase (ALDH) in the cavity of a mesoporous metal organic framework (mMOF) nanozyme with intrinsic catalase (CAT)-like activity. By conducting confined AOx/CAT/ALDH cascade reactions, AA@mMOF enables self-accelerated alcohol degradation (>0.5 mg·mL-1·h-1) with negligible aldehyde diffusion and accumulation, reprogramming alcohol metabolism and allowing high-efficiency detoxification. Administered to high-dose alcohol-intoxicated mice, AA@mMOF shows surprising liver targeting and accumulation performance and dramatically reduces blood alcohol concentration and rapidly reverses unconsciousness and acute liver injury to afford targeted alcoholism treatment. Moreover, AA@mMOF dramatically alleviates fat accumulation and oxidative stress in the liver of chronic alcoholism mice to block and reverse the progression of ALI. By conducting confined AOx/CAT/ALDH cascade reactions for high-efficiency alcohol metabolism reprogramming, AA@mMOF nanoreactor offers a powerful modality for targeted alcohol detoxification and ALI management. The proposed confined cascade metabolic reprogramming strategy provides a paradigm shift for the treatment of metabolic diseases.

The Treatment Satisfaction in Patients and Their Partners Treated with Low-Intensity Extracorporeal Shock Wave Therapy and Sildenafil: A Prospective Non-Randomized Controlled Study.

Background: Phosphodiesterase 5 inhibitors (PDE5Is) and other more invasive options merely provide symptomatic relief rather than a permanent improvement in erectile dysfunction (ED), whereas the long-term improvement in ED via low-intensity extracorporeal shockwave therapy (Li-ESWT) has been confirmed. So far, no comparative study of sildenafil versus Li-ESWT has been conducted with respect to treatment satisfaction. Objective: In this study, we aim to compare erectile function status and satisfaction rates in patients who received sildenafil or Li-ESWT for ED. Methods: Patients complaining of ED were considered candidates. Participants chose to enter one of two active treatment groups according to their treatment intention-either a 9-week Li-ESWT regimen or 100 mg on-demand sildenafil. The erectile function was evaluated using the erectile function domain of the International Index of Erectile Function questionnaires (IIEF-EF), while the treatment satisfaction was evaluated using the Erectile Dysfunction Inventory of Treatment Satisfaction questionnaires (EDITS). Results: We enrolled 72 participants in the study (42 in the Li-ESWT group and 30 in the sildenafil group). Patients in both groups were young men. Four weeks after the last session, the IIEF-EF score for Li-ESWT and sildenafil was 16.3± 5.5 and 18.3± 6.5 (P > 0.05), respectively. The total EDITS index of the patient version and the partner version were similar in the two groups. Among EDITS questions measuring overall satisfaction and efficacy duration, the score was higher in the Li-ESWT group. Conclusion: We found that Li-ESWT may have better satisfaction than on-demand sildenafil for young ED patients. However, further studies are needed to determine the factors influencing satisfaction.

Metal-organic frameworks for high performance desalination through thickness control and structural fine-tuning.

Two-dimensional nanoporous membranes hold great promise for the design of state-of-the-art desalination architectures to alleviate the increasing global water scarcity. Herein, by employing molecular dynamics simulations, we demonstrate the great potential of two recently reported metal-organic frameworks (MOF) membranes, namely NiIT and NiAT, as efficient desalination membranes that reach super high water flux and high salt rejection. The desalination performance of the MOF membrane is highly tunable through controlling the membrane thickness from one layer to five layers. Double layer NiIT membrane exhibits excellent salt rejection of 100% for NaCl, and meanwhile achieving high water permeability of ∼45 L/cm2/MPa/day. While for the convertible double-layer NiAT, it effectively rejects ∼96% ions with an improved water permeation of over 70 L/cm2/MPa/day. Quantitative analysis of water distribution reveals a denser water solvation shell around NiAT membrane than NiIT and a higher water velocity through the nanopore of NiAT than that of NiIT, contributing to the enhanced water permeability. Through calculating free energy for water/ions translocating through two membranes, a clear energy barrier is observed for ions to penetrate through the sub-nanosized pores in both membranes, leading to the high salt rejection. The present study suggests that these two MOF membranes can serve as a promising semipermeable membrane for energy-efficient desalination which is highly prospective in industrial applications.

Comprehensive characterization of three classes of Arabidopsis SWI/SNF chromatin remodelling complexes.

Although SWI/SNF chromatin remodelling complexes are known to regulate diverse biological functions in plants, the classification, compositions and functional mechanisms of the complexes remain to be determined. Here we comprehensively characterized SWI/SNF complexes by affinity purification and mass spectrometry in Arabidopsis thaliana, and found three classes of SWI/SNF complexes, which we termed BAS, SAS and MAS (BRM-, SYD- and MINU1/2-associated SWI/SNF complexes). By investigating multiple developmental phenotypes of SWI/SNF mutants, we found that three classes of SWI/SNF complexes have both overlapping and specific functions in regulating development. To investigate how the three classes of SWI/SNF complexes differentially regulate development, we mapped different SWI/SNF components on chromatin at the whole-genome level and determined their effects on chromatin accessibility. While all three classes of SWI/SNF complexes regulate chromatin accessibility at proximal promoter regions, SAS is a major SWI/SNF complex that is responsible for mediating chromatin accessibility at distal promoter regions and intergenic regions. Histone modifications are related to both the association of SWI/SNF complexes with chromatin and the SWI/SNF-dependent chromatin accessibility. Three classes of SWI/SNF-dependent accessibility may enable different sets of transcription factors to access chromatin. These findings lay a foundation for further investigation of the function of three classes of SWI/SNF complexes in plants.

Electric Field-Controlled Peptide Self-Assembly through Funnel-Shaped Two-Dimensional Nanopores.

Self-assembly of biomolecules is critical for the realization of biological functions. Thus, the precise control of self-assembly has great significance in the design of biochips and biomedical agents. In this report, we design a Y-shaped funnel on a two-dimensional (2D) heterostructure, called 2D funnel, based on monolayered polyaniline carbon nitride (C3N) and boron carbide (BC3), and study its application in the self-assembly state regulation of the peptide oligomer, using Aß16-21 as the representative model. Structurally, the 2D funnel is composed of three regions: channel area, triangle area, and barrier area. The channel and triangle areas show higher binding affinity to the peptide than that of the barrier area, which leads to the confinement of the peptide in the 2D funnel. Our results show that when an external electric field is applied along the 2D funnel, the oligomer is driven to migrate across the funnel. Its trajectory is confined inside the narrow channel area, which effectively causes peptide dissociation into the individual peptide chains. Then, when the external electric field is turned off, the separated peptide chains spontaneously assemble in the triangle area and tend to reunite. Our present findings propose a novel heterostructure platform, which enables the manipulation of the self-assembly state of peptides by switching the electric field, which could guide the design and fabrication of nanodevices for sensing and sequencing applications.

Decoy Nanozymes Enable Multitarget Blockade of Proinflammatory Cascades for the Treatment of Multi-Drug-Resistant Bacterial Sepsis.

Sepsis is a life-threatening organ dysfunction characterized by severe systemic inflammatory response to infection. Effective treatment of bacterial sepsis remains a paramount clinical challenge, due to its astonishingly rapid progression and the prevalence of bacterial drug resistance. Here, we present a decoy nanozyme-enabled intervention strategy for multitarget blockade of proinflammatory cascades to treat multi-drug-resistant (MDR) bacterial sepsis. The decoy nanozymes (named MCeC@MΦ) consist mesoporous silica nanoparticle cores loaded with CeO2 nanocatalyst and Ce6 photosensitizer and biomimetic shells of macrophage membrane. By acting as macrophage decoys, MCeC@MΦ allow targeted photodynamic eradication of MDR bacteria and realize simultaneous endotoxin/proinflammatory cytokine neutralization. Meanwhile, MCeC@MΦ possess intriguing superoxide dismutase and catalase-like activities as well as hydroxyl radical antioxidant capacity and enable catalytic scavenging of multiple reactive oxygen species (ROS). These unique capabilities make MCeC@MΦ to collaboratively address the issues of bacterial infection, endotoxin/proinflammatory cytokine secretion, and ROS burst, fully cutting off the path of proinflammatory cascades to reverse the progression of bacterial sepsis. In vivo experiments demonstrate that MCeC@MΦ considerably attenuate systemic hyperinflammation and rapidly rescue organ damage within 1 day to confer higher survival rates (>75%) to mice with progressive MDR Escherichia coli bacteremia. The proposed decoy nanozyme-enabled multitarget collaborative intervention strategy offers a powerful modality for bacterial sepsis management and opens up possibilities for the treatment of cytokine storm in the COVID-19 pandemic and immune-mediated inflammation diseases.

Fecal Microbiota Transplantation Combined with a Low FODMAP Diet for the Treatment of Irritable Bowel Syndrome with Predominant Diarrhea.

Background: Fecal microbiota transplantation (FMT) has been found to be effective in irritable bowel syndrome with predominant diarrhea (IBS-D). We conducted this study to determine the impact of a low FODMAP diet (LFD) on the gut microbiota and the efficacy of FMT in the treatment of IBS-D. Methods: A retrospective analysis of a single-arm open-label prospective study was conducted to investigate the impact of FMT alone (n = 40) and FMT+LFD (n = 40) in refractory IBS-D. The IBS-quality of life (QOL), IBS-severity scoring system (SSS), gastrointestinal symptom rating scale (GSRS), Hamilton anxiety scale (HAMA), and Hamilton depression scale (HAMD) were used to evaluate the efficacy, and partial 16S rDNA amplicon sequencing was used to profile the microbiota. Results: The response rates were higher in the FMT+LFD group than in the FMT group (1 mo, 3 mo, 6 mo: 70.0% vs. 55.0%, 67.5% vs. 57.5%, 62.5% vs. 27.5%, respectively). The FMT+LFD group showed significantly better improvement in IBS-QOL at 1, 3, and 6 months; IBS-SSS at 6 months; and GSRS at 1 month compared to FMT alone. Changes in HAMA and HAMD were similar in the two groups. The LFD significantly upregulated the FMT-induced microbial diversity (OTUs: 666 vs. 574, Adonis: P = 0.02) and significantly strengthened the upregulation of Bacteroides, Alistipes, and Ruminococcaceae_UCG-002 and the downregulation of Bifidobacterium. Conclusion: An LFD enhanced the efficacy of FMT, increased the gut microbial diversity after FMT, and strengthened the inhibitory effect of FMT on conditional pathogens.

Colon cancer patient with long-term colon stent placement: Case report and literature review.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer mortality globally. Large bowel obstruction (occurring in 15-30% of patients with CRCs) accounts for approximately 80% of medical emergencies related to CRC. Currently, there is no standard treatment of this condition. The European Society of Gastrointestinal Endoscopy (ESGE) recommends self-expandable metal stent (SEMS) as a bridge (two weeks) to surgery for left-sided obstructing colon cancer. In the present report, we describe an 81-year-old male with colon cancer who underwent colon stent placement for 32 months, but later underwent radical resection. A follow-up of more than four-months revealed that his condition was normal. The history as well as application and advantages of SEMS are discussed in this report.