Alteration of ascending colon mucosal microbiota in patients after cholecystectomy.

BACKGROUND: Cholecystectomy is a successful treatment option for gallstones, although the incidence of colorectal cancer (CRC) has notably increased in post-cholecystectomy (PC) patients. However, it remains uncertain whether the altered mucosal microbiota in the ascending colon is related. AIM: To investigate the potential correlation between gut microbiota and the surgical procedure of cholecystectomy. METHODS: In total, 30 PC patients and 28 healthy controls underwent colonoscopies to collect mucosal biopsy samples. PC patients were divided based on their clinical features. Then, 16S-rRNA gene sequencing was used to analyze the amplicon, alpha diversity, beta diversity, and composition of the bacterial communities. Additionally, the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) database, sourced from the Kyoto Encyclopedia of Genes and Genomes, was used to predict the functional capabilities of the bacteria. RESULTS: PC patients were comparable with healthy controls. However, PC patients older than 60 years had a distinct composition compared to those under 60 years old. Bacteroidetes richness was considerably higher at the phylum level in PC patients. Bacteroides, Parabacteroides, and Bilophila were more abundant in the PC group than in the control group. Furthermore, PC patients exhibited greater enrichment in metabolic pathways, specifically those related to lipopolysaccharide biosynthesis and vancomycin group antibiotic production, than controls. CONCLUSION: This study indicated that the mucosal microbiota in PC patients was altered, perhaps offering new perspectives on the treatment possibilities for CRC and diarrhea following cholecystectomy.

Oncostatin M promotes epithelial barrier dysfunction in patients with eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Oncostatin M (OSM) may be involved in the promotion of mucosal epithelial barrier dysfunction in patients with eosinophilic chronic rhinosinusitis with nasal polyps (Eos CRSwNP) by inducing matrix metalloproteinase (MMP) -1 and -7. The aim was to evaluate the roles and mechanisms of action of OSM on MMP-1 and -7 synthesis from nasal epithelial cells (NECs). METHODS: OSM, OSM receptor (OSMR), MMP-1 and -7 expression was evaluated in nasal mucosa or primary NECs from scrapings by quantitative polymerase chain reaction (qPCR), immunofluorescence and immunohistochemistry. OSM and other cytokines were used to stimulate air-liquid interface (ALI) cultured NECs. qPCR, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence were used to evaluate the expression of OSMR, MMP-1, -7 and occludin in NECs. RESULTS: Elevated levels of OSMRß, MMP-1 and -7 were found in the tissues and scraped NECs of Eos CRSwNP in comparison to them obtained from the inferior turbinate (IT) and control subjects. The levels of OSM and OSMRß mRNA in tissues were positively correlated with the levels of MMP-1 and -7. OSM stimulation of NECs increased the expression of MMP-1 and -7, and the responses were suppressed by a STAT3 inhibitor, and a PI3K inhibitor respectively. In parallel studies, we found that stimulation with OSM disrupted the localization of occludin, a tight junction protein in NECs. The response was suppressed by a pan-MMP inhibitor. CONCLUSION: OSM induces the synthesis and release of MMP-1 and -7 in NECs. Furthermore, MMP-1 and -7 promote mucosal epithelial barrier dysfunction in patients with Eos CRSwNP.

Recent advances in the potential of Phyllanthus emblica L. and its related foods for combating metabolic diseases through methylglyoxal trapping.

Methylglyoxal (MG) serves as the primary precursor for the nonenzymatic glycation of proteins and DNA, leading to advanced glycation end products (AGEs). Regular intake of dietary MG is strongly correlated with low-grade inflammation, potentially accelerating the pathogenesis of metabolic diseases, including obesity, diabetes, cancers, liver diseases, Alzheimer's disease, cardiovascular diseases, aging, and bone loss. Although pharmaceutical agents (pimagedine and candesartan) have been developed to inhibit MG formation, they often come with serious side effects (nausea, diarrhea, headache, gastrointestinal disturbance, symptomatic hypotension, abnormal renal and liver function tests, development of antinuclear antibody, pernicious-like anemia, and hyperkalemia), highlighting the need for an efficient and safe approach to scavenging MG. Phyllanthus emblica Linn fruit, a nutritious edible fruit, and medicinal plant contains over 300 bioactive compounds. Among twenty-three herbals, 100 µg/mL of the aqueous extract of Phyllanthus emblica fruit (APF) exhibits the highest potency in trapping MG, achieving an 87.3 % reduction under d-fructose induced BSA-AGEs formation. However, there are few reports detailing APF and its related foods' specific impact on disease prevention through MG trapping. This review summarizes the mechanisms through which MG is linked to the development of metabolic diseases and provides several strategies for reducing MG levels using APF and its bioactive compounds. The potential antiglycation properties of APF may offer new applications in the food industry and pharmacological research.

Association between abdominal obesity indices and falls among older community-dwellers in Guangzhou, China: a prospective cohort study.

BACKGROUND: Central obesity was considered as a risk factor for falls among the older population. Waist circumference (WC), lipid accumulation product (LAP), visceral adiposity index (VAI), and the Chinese visceral adiposity index (CVAI) are considered as surrogate markers for abdominal fat deposition in increasing studies. Nevertheless, the longitudinal relationship between these indices and falls among the older population remains indistinct. This study aimed to explore the association between abdominal obesity indices and falls among older community-dwellers. METHODS: Our study included 3501 individuals aged ≥ 65 years from the Guangzhou Falls and Health Status Tracking Cohort at baseline in 2021 and then prospectively followed up in 2022. The outcome of interest was the occurrence of falls. The Kaplan-Meier curves and multivariable Cox regression analysis were used to explore the associations between abdominal obesity indices and falls. Moreover, the restricted cubic spline analysis (RCS) was conducted to test the non-linear relationships between abdominal obesity indices and hazards of falls incident. RESULTS: After a median follow-up period of 551 days, a total of 1022 participants experienced falls. The cumulative incidence rate of falls was observed to be higher among individuals with central obesity and those falling within the fourth quartile (Q4) of LAP, VAI, and CVAI. Participants with central obesity and those in Q4 of LAP, VAI, and CVAI were associated with higher risk of falls, with hazard ratios (HRs) of 1.422 (HR 95%CI: 1.255-1.611), 1.346 (1.176-1.541), 1.270 (1.108-1.457), 1.322 (1.154-1.514), respectively. Each 1-SD increment in WC, LAP, VAI, and CVAI was a significant increased risk of falls among participants. Subgroup analysis further revealed these results were basically stable and appeared to be significantly stronger among those females, aged 65-69 years, and with body mass index (BMI) ≥ 28 kg/m2. Additionally, RCS curves showed an overall upward trend in the risk of falls as the abdominal indices increased. CONCLUSIONS: Abdominal obesity indices, as WC, LAP, VAI, and CVAI were significantly associated with falls among older community-dwellers. Reduction of abdominal obesity indices might be suggested as the strategy of falls prevention.

Enhancement of Synergistic Photocatalytic Performance by Anchoring Cadmium Sulfide on Nanosphere Structured Coordination Polymers.

Precisely tuning how and where a reaction occurs in a one-step selective system is important but challenging owing to the similar electronic environments in multiple active sites. In this work, highly selective and effective reaction sites were obtained by generating copper coordination polymers (Cu-CP) of a range of sizes and morphologies, from bulk solid crystals (1) to uniform nanosphere structures (1a), by controlling the amount of surfactant hexadecyl trimethylammonium bromide (CTAB). The results indicated that the morphology and size of the uniform nanosphere structures were affected by the proportion of CTAB; uniform distribution of nanosphere structures was achieved with a premade building carrier when the content of CTAB was 0.005 mmol, generating a well-established platform. Photocatalytic cadmium sulfide (CdS) was then immobilized on the surface of the premade platform unit 1a through an in situ process to generate CdS@1a composites with well-dispersed catalytic CdS active sites. Furthermore, the well-defined CdS@1a composite platform was utilized as photocatalysts to explore the selective one-step depolymerization reaction under blue-light irradiation. Notably, the CdS0.149@1a composite, which featured a unique structure with evenly dispersed, closely spaced catalytic sites, exhibiting remarkable photoelectrochemical behaviors for selective one-step depolymerization of lignin model substances to aromatic monomer phenol and acetophenone framework products. This work demonstrates the use of an inherently morphological process to construct outstanding photocatalysts that could enable a wide range of photocatalytic reactions.

Ultra-Widefield Imaging of Bilateral Streaky Multifocal Choroiditis in a 12-Year-Old Boy.

This case report describes a diagnosis of streaky multifocal choroiditis in a boy who presented with distorted vision in his left eye for 3 years.

Peroxiredoxin 1 modulates oxidative stress resistance and cell apoptosis through stemness in liver cancer under non-thermal plasma treatment.

The role of peroxiredoxin 1 (PRDX1), a crucial enzyme that reduces reactive oxygen and nitrogen species levels in HepG2 human hepatocellular carcinoma (HCC) cells, in the regulation of HCC cell stemness under oxidative stress and the underlying mechanisms remain largely unexplored. Here, we investigated the therapeutic potential of non-thermal plasma in targeting cancer stem cells (CSCs) in HCC, focusing on the mechanisms of resistance to oxidative stress and the role of PRDX1. By simulating oxidative stress conditions using the plasma-activated medium, we found that a reduction in PRDX1 levels resulted in a considerable increase in HepG2 cell apoptosis, suggesting that PRDX1 plays a key role in oxidative stress defense mechanisms in CSCs. Furthermore, we found that HepG2 cells had higher spheroid formation capability and increased levels of stem cell markers (CD133, c-Myc, and OCT-4), indicating strong stemness. Interestingly, PRDX1 expression was notably higher in HepG2 cells than in other HCC cell types such as Hep3B and Huh7 cells, whereas the expression levels of other PRDX family proteins (PRDX 2-6) were relatively consistent. The inhibition of PRDX1 expression and peroxidase activity by conoidin A resulted in markedly reduced stemness traits and increased cell death rate. Furthermore, in a xenograft mouse model, PRDX1 downregulation considerably inhibited the formation of solid tumors after plasma-activated medium (PAM) treatment. These findings underscore the critical role of PRDX 1 in regulating stemness and apoptosis in HCC cells under oxidative stress, highlighting PRDX1 as a promising therapeutic target for NTP-based treatment in HCC.

New CRISPR/Cas9-based Fgfr2C361Y/+ mouse model of Crouzon syndrome exhibits skull and behavioral abnormalities.

Crouzon syndrome (CS), a syndromic craniosynostosis, is a craniofacial developmental deformity caused by mutations in fibroblast growth factor receptor 2 (FGFR2). Previous CS mouse models constructed using traditional gene editing techniques faced issues such as low targeting efficiency, extended lineage cycles, and inconsistent and unstable phenotypes. In this study, a CRISPR/Cas9-mediated strategy was employed to induce a functional augmentation of the Fgfr2 point mutation in mice. Various techniques, including bone staining, micro-CT, histological methods, and behavioral experiments, were employed to systematically examine and corroborate phenotypic disparities between mutant mice (Fgfr2C361Y/+) and their wild-type littermates. Confirmed via PCR-Sanger sequencing, we successfully induced the p.Cys361Tyr missense mutation in the Fgfr2 IIIc isoform of the extracellular domain (corresponding to the p.Cys342Tyr mutation in humans) based on Fgfr2-215 transcript (ENSMUST00000122054.8). Fgfr2C361Y/+ mice exhibited characteristics consistent with the phenotypic features associated with CS, including skull-vault craniosynostosis, skull deformity, shallow orbits accompanied by exophthalmos, midface hypoplasia with malocclusion, and shortened skull base, notably without any apparent limb defects. Furthermore, mutant mice displayed behavioral abnormalities encompassing deficits in learning and memory, social interaction, and motor dysfunction, without anxiety-related disorders. Histopathological examination of the hippocampal region revealed structural abnormalities, suggesting possible brain development impairment secondary to craniosynostosis. In conclusion, we constructed a novel gene-edited Fgfr2C361Y/+ mice strain based on CRISPR/Cas9, which displayed skull and behavioral abnormalities, serving as a new model for studying genetic molecular mechanisms and exploring treatments for CS. KEY MESSAGES: CRISPR/Cas9 crafted a Crouzon model by enhancing Fgfr2-C361Y in mice. Fgfr2C361Y/+ mice replicate CS phenotypes-craniosynostosis and midface anomalies. Mutant mice show diverse behavioral abnormalities, impacting learning and memory. Fgfr2C361Y/+ mice offer a novel model for cranial suture studies and therapeutic exploration.

Enhancing homology-directed repair efficiency with HDR-boosting modular ssDNA donor.

Despite the potential of small molecules and recombinant proteins to enhance the efficiency of homology-directed repair (HDR), single-stranded DNA (ssDNA) donors, as currently designed and chemically modified, remain suboptimal for precise gene editing. Here, we screen the biased ssDNA binding sequences of DNA repair-related proteins and engineer RAD51-preferred sequences into HDR-boosting modules for ssDNA donors. Donors with these modules exhibit an augmented affinity for RAD51, thereby enhancing HDR efficiency across various genomic loci and cell types when cooperated with Cas9, nCas9, and Cas12a. By combining with an inhibitor of non-homologous end joining (NHEJ) or the HDRobust strategy, these modular ssDNA donors achieve up to 90.03% (median 74.81%) HDR efficiency. The HDR-boosting modules targeting an endogenous protein enable a chemical modification-free strategy to improve the efficacy of ssDNA donors for precise gene editing.

The effects of gaze stability exercises on balance, gait ability, and fall efficacy in patients with chronic stroke: A 2-week follow-up from a randomized controlled trial.

BACKGROUND: This study aimed to examine the effect of gaze stability exercises on balance, gait ability, and fall efficacy in patients with chronic stroke, as well as to investigate whether any observed effects were maintained 2 weeks later. METHODS: In this experiment, 30 chronic stroke patients were selected. The patients were randomly divided into 3 groups (10 patients in each group). All patients in the 3 groups performed basic neurodevelopmental treatment. Group 1 performed balance exercises accompanied by gaze stability exercises. Group 2 performed gaze stability exercises, and group 3 performed balance exercises. Each exercise program for 40 minutes 3 times a week for 4 weeks. After the intervention period, the patient's balance, gait ability, and fall efficacy were measured again. In order to know whether the training effect is maintained, a 2-week follow-up test was conducted after the training. RESULTS: The results of this study showed that there was a significant improve in balance (overall stability index, limit of stability test, and Berg Balance Scale), gait ability (gait velocity, cadence, step time and step length, Timed Up and Go [TUG] test), and fall efficacy over the different time within the 3 groups. The effect was observed to be maintained in follow-up tests after 2 weeks. In the comparison among 3 groups, the overall stability index, limit of stability test in the balance test and the gait velocity, cadence, step time, step length and Timed Up and Go test in the gait test all showed statistically significant differences, and the other items did not have significant differences. In most of the assessments, group 1 that used balance exercise combined with gaze stability exercise showed a better improvement than the other 2 groups. CONCLUSION: As a result, for stroke patients, gaze stability exercise is an effective arbitration method to improve balance and gait ability and fall efficacy. With balance exercise combined with gaze stability exercise, a greater effect can be seen than with gaze stability exercise or balance exercise alone. Thus, this combination exercise program can be recommended as effective.

Lymphovenous anastomosis and complex decongestive therapy for severe deformed lymphedema with recurrent infection: A case report.

BACKGROUND: Lower extremity lymphedema is a common complication following treatment for gynecological malignancies. Its incidence rate can reach up to 70%, affecting ~20 million people worldwide. However, specialized treatment centers are scarce, and there is a lack of consensus on treatment approaches. Furthermore, there are even fewer reports on the systematic and effective treatment of severe lymphedema with malformations. Effective management of this condition remains a significant challenge for clinicians. CASE SUMMARY: A 40-year-old woman developed bilateral leg swelling 6 years after receiving treatment for endometrial cancer. Since August 2018, she experienced > 30 episodes of lymphangitis. Upon presentation, she exhibited bilateral leg swelling and deformation, with four large swellings in the posterior thigh that impeded movement, and pain in the limbs. Skin manifestations included lichenoid lesions and features of deep sclerosis. Radionuclide lymphoscintigraphy confirmed the diagnosis of lower limb lymphedema. After 6 mo of complex decongestive therapy (CDT) and three lymphaticovenous anastomosis (LVA) treatments, the patient lost 49 kg in weight. She also experienced a maximum circumference reduction of 35.2 cm in the left lower limb and 37.5 cm in the right lower limb. The leg pain disappeared, her swelling significantly decreased, and she regained the ability to walk, cycle, and run normally. CONCLUSION: The combined application of CDT and LVA therapy demonstrates significant positive effects in the treatment of severe, deformed stage III lymphedema.

The additive effect of the triglyceride-glucose index and estimated glucose disposal rate on long-term mortality among individuals with and without diabetes: a population-based study.

BACKGROUND: The triglyceride-glucose (TyG) index and estimated glucose disposal rate (eGDR), which are calculated using different parameters, are widely used as markers of insulin resistance and are associated with cardiovascular diseases and prognosis. However, whether they have an additive effect on the risk of mortality remains unclear. This study aimed to explore whether the combined assessment of the TyG index and eGDR improved the prediction of long-term mortality in individuals with and without diabetes. METHODS: In this cross-sectional and cohort study, data were derived from the National Health and Nutrition Examination Survey (NHANES) 2001-2018, and death record information was obtained from the National Death Index. The associations of the TyG index and eGDR with all-cause and cardiovascular mortality were determined by multivariate Cox regression analysis and restricted cubic splines. RESULTS: Among the 17,787 individuals included in the analysis, there were 1946 (10.9%) all-cause deaths and 649 (3.6%) cardiovascular deaths during a median follow-up of 8.92 years. In individuals with diabetes, the restricted cubic spline curves for the associations of the TyG index and eGDR with mortality followed a J-shape and an L-shape, respectively. The risk of mortality significantly increased after the TyG index was > 9.04 (all-cause mortality) or > 9.30 (cardiovascular mortality), and after eGDR was < 4 mg/kg/min (both all-cause and cardiovascular mortality). In individuals without diabetes, the association between eGDR and mortality followed a negative linear relationship. However, there was no association between the TyG index and mortality. Compared with individuals in the low TyG and high eGDR group, those in the high TyG and low eGDR group (TyG > 9.04 and eGDR < 4) showed the highest risk for all-cause mortality (hazard ratio [HR] = 1.592, 95% confidence interval [CI] 1.284-1.975) and cardiovascular mortality (HR = 1.683, 95% CI 1.179-2.400) in the overall population. Similar results were observed in individuals with and without diabetes. CONCLUSIONS: There was a potential additive effect of the TyG index and eGDR on the risk of long-term mortality in individuals with and without diabetes, which provided additional information for prognostic prediction and contributed to improving risk stratification.

Rhein targets macrophage SIRT2 to promote adipose tissue thermogenesis in obesity in mice.

Rhein, a component derived from rhubarb, has been proven to possess anti-inflammatory properties. Here, we show that rhein mitigates obesity by promoting adipose tissue thermogenesis in diet-induced obese mice. We construct a macrophage-adipocyte co-culture system and demonstrate that rhein promotes adipocyte thermogenesis through inhibiting NLRP3 inflammasome activation in macrophages. Moreover, clues from acetylome analysis identify SIRT2 as a potential drug target of rhein. We further verify that rhein directly interacts with SIRT2 and inhibits NLRP3 inflammasome activation in a SIRT2-dependent way. Myeloid knockdown of SIRT2 abrogates adipose tissue thermogenesis and metabolic benefits in obese mice induced by rhein. Together, our findings elucidate that rhein inhibits NLRP3 inflammasome activation in macrophages by regulating SIRT2, and thus promotes white adipose tissue thermogenesis during obesity. These findings uncover the molecular mechanism underlying the anti-inflammatory and anti-obesity effects of rhein, and suggest that rhein may become a potential drug for treating obesity.

Binding Behavior of Human Hepatoma-Derived Growth Factor on SMYD1.

The protein-induced fluorescence change technique was employed to investigate the interactions between proteins and their DNA substrates modified with the Cy3 fluorophore. It has been reported that the human hepatoma-derived growth factor (HDGF), containing the chromatin-associated N-terminal proline-tryptophan-tryptophan-proline (PWWP) domain (the N-terminal 100 amino acids of HDGF) capable of binding the SMYD1 promoter, participates in various cellular processes and is involved in human cancer. This project investigated the specific binding behavior of HDGF, the PWWP domain, and the C140 domain (the C-terminal 140 amino acids of HDGF) sequentially using protein-induced fluorescence change. We found that the binding of HDGF and its related proteins on Cy3-labeled 15 bp SMYD1 dsDNA will cause a significant decrease in the recorded Cy3 fluorophore intensity, indicating the occurrence of protein-induced fluorescence quenching. The dissociation equilibrium constant was determined by fitting the bound fraction curve to a binding model. An approximate 10-time weaker SMYD1 binding affinity of the PWWP domain was found in comparison to HDGF. Moreover, the PWWP domain is required for DNA binding, and the C140 domain can enhance the DNA binding affinity. Furthermore, we found that the C140 domain can regulate the sequence-specific binding capability of HDGF on SMYD1.

Strategies for enhancing non-small cell lung cancer treatment: Integrating Chinese herbal medicines with epidermal growth factor receptor-tyrosine kinase inhibitors therapy.

Non-small cell lung cancer (NSCLC) poses a global health threat, and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib, afatinib, and osimertinib have achieved significant success in clinical treatment. However, the emergence of resistance limits the long-term efficacy of these treatments, necessitating urgent exploration of novel EGFR-TKIs. This review provides an in-depth summary and exploration of the resistance mechanisms associated with EGFR-TKIs, with a specific focus on representative drugs like gefitinib, afatinib, and osimertinib. Additionally, the review introduces a therapeutic strategy involving the combination of Chinese herbal medicines (CHMs) and chemotherapy drugs, highlighting the potential role of CHMs in overcoming NSCLC resistance. Through systematic analysis, we elucidate the primary resistance mechanisms of EGFR-TKIs in NSCLC treatment, emphasizing CHMs as potential treatment medicines and providing a fresh perspective for the development of next-generation EGFR-TKIs. This comprehensive review aims to guide the application of CHMs in combination therapy for NSCLC management, fostering the development of more effective and comprehensive treatment modalities to ultimately enhance patient outcomes.

L-Cysteine: A promising nutritional supplement for alleviating anxiety disorders.

Anxiety disorders are prevalent chronic psychological disease with complex pathogenic mechanisms. Current anxiolytics have limited efficacy and numerous side effects in many anxiety patients, highlighting the urgent need for new therapies. Recent research has been focusing on nutritional supplements, particularly amino acids, as potential therapies for anxiety disorders. Among these, L-Cysteine plays a crucial role in various biological processes. L-Cysteine exhibits antioxidant properties that can enhance the antioxidant functions of the central nervous system (CNS). Furthermore, metabolites of L-cysteine, such as glutathione and hydrogen sulfide have been shown to alleviate anxiety through distinct molecular mechanisms. Long-term administration of L-Cysteine has anxiolytic, antidepressant, and memory-improving effects. L-Cysteine depletion can lead to increased oxidative stress in the brain. This review delves into the potential mechanisms of L-Cysteine and its main products, glutathione (GSH) and hydrogen sulfide (H2S) in the management of anxiety and related diseases.

Alkaline phosphatase-activated prodrug system based on a bifunctional CuO NP tandem nanoenzyme for on-demand bacterial inactivation and wound disinfection.

Nanozymes are promising antimicrobials, as they produce reactive oxygen species (ROS). However, the intrinsic lack of selectivity of ROS in distinguishing normal flora from pathogenic bacteria deprives nanozymes of the necessary selectivities of ideal antimicrobials. Herein, we exploit the physiological conditions of bacteria (high alkaline phosphatase (ALP) expression) using a novel CuO nanoparticle (NP) nanoenzyme system to initiate an ALP-activated ROS prodrug system for use in the on-demand precision killing of bacteria. The prodrug strategy involves using 2-phospho-L-ascorbic acid trisodium salt (AAP) that catalyzes the ALP in pathogenic bacteria to generate ascorbic acid (AA), which is converted by the CuO NPs, with intrinsic ascorbate oxidase- and peroxidase-like activities, to produce ROS. Notably, the prodrug system selectively kills Escherichia coli (pathogenic bacteria), with minimal influence on Staphylococcus hominis (non-pathogenic bacteria) due to their different levels of ALP expression. Compared to the CuO NPs/AA system, which generally depletes ROS during storage, CuO NPs/AAP exhibits a significantly higher stability without affecting its antibacterial activity. Furthermore, a rat model is used to indicate the applicability of the CuO NPs/AAP fibrin gel in wound disinfection in vivo with negligible side effects. This study reveals the therapeutic precision of this bifunctional tandem nanozyme platform against pathogenic bacteria in ALP-activated conditions.

Correcting directional dark field x-ray imaging artefacts using position dependent image deblurring and attenuation removal.

In recent years, a novel x-ray imaging modality has emerged that reveals unresolved sample microstructure via a "dark-field image", which provides complementary information to conventional "bright-field" images, such as attenuation and phase-contrast modalities. This x-ray dark-field signal is produced by unresolved microstructures scattering the x-ray beam resulting in localised image blur. Dark-field retrieval techniques extract this blur to reconstruct a dark-field image. Unfortunately, the presence of non-dark-field blur such as source-size blur or the detector point-spread-function can affect the dark-field retrieval as they also blur the experimental image. In addition, dark-field images can be degraded by the artefacts induced by large intensity gradients from attenuation and propagation-based phase contrast, particularly around sample edges. By measuring any non-dark-field blurring across the image plane and removing it from experimental images, as well as removing attenuation and propagation-based phase contrast, we show that a directional dark-field image can be retrieved with fewer artefacts and more consistent quantitative measures. We present the details of these corrections and provide "before and after" directional dark-field images of samples imaged at a synchrotron source. This paper utilises single-grid directional dark-field imaging, but these corrections have the potential to be broadly applied to other x-ray imaging techniques.

PAFerroptosis Combined with Metabolic Disturbance of Mito by p52-ZER6 for Enhanced Cancer Immunotherapy induced by Nano-Bacilliform-Enzyme.

The confused gene expressions and molecular mechanisms for mitochondrial dysfunction of traditional nanoenzymes is a challenge for tumor therapy. Herein, a nano-bacilliform-enzyme obtains the ability to inhibit p52-ZER6 signal pathway, regulate the genes related to mitochondrial metabolism, and possess the GOx/CAT/POD-like property. NBE acquires catalytic activity from the electronic energy transition. The tannin of NBE as a mitochondrial (Mito)-targeting guide overloads MitoROS, and then metabolic disorder and lipid peroxidation of Mito membrane occurs, thus leading to a novel death pathway called PAFerroptosis (pyroptosis, apoptosis, and Ferroptosis). Simultaneously, in order to refrain from mitophagy, hydroxychloroquine is mixed with NBE to form a combo with strength pyroptosis. As a result, NBE/combo improves the PAFerroptosis obviously by activation of CD8+T cells and inactivation of MDSC cells, up-regulating expression of caspase-3 signal pathway, intercepting DHODH pathway to arrive excellent antitumor effect (93%). Therefore, this study establishes a rational nanoenzyme for mitochondrial dysfunction without mitophagy for effective antitumor therapy.

Regulation of Nrf2/A20/eEF1A2 Axis by Ginsenoside Rb1: A Key Pathway in Alleviating Cerebral Ischemia-Reperfusion Injury.

BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) is a prevalent neurological disorder, characterized by the oxidative stress and inflammatory response induced during the ischemia-reperfusion process, leading to significant damage to brain cells. Ginsenoside Rb1, a natural medicinal ingredient, possesses potential neuroprotective effects. This study aims to investigate the mechanism of action of ginsenoside Rb1 in CIRI and its protective effects on brain injury. METHODS: We utilized a mouse CIRI model and randomly divided the mice into control group, CIRI group, and ginsenoside Rb1 treatment group. The effects of Rb1 on brain tissue damage, apoptosis, expression of inflammatory factors, and pyroptotic cell numbers in CIRI mice were observed through triphenyl tetrazolium chloride (TTC) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, real-time reverse transcription polymerase chain reaction (qRT-PCR), and electron microscopy. In a cell model, the regulatory effect of Rb1 on oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 cell pyroptosis via the nuclear respiratoty factor 2/tumor necrosis factor-α (TNF-α)-induced Protein 3 (TNFAIP3, aka A20)/eukaryotic translation elongation factor 1A2 (Nrf2/A20/eEF1A2) axis was detected using Western blot and TUNEL staining. Additionally, the impact of Nrf2 inhibitor ML385 and eEF1A2 overexpression on the neuroprotective effect of Rb1 was assessed. Using the comprehensive experimental methods mentioned above, the neuroprotective mechanism of Rb1 in CIRI was thoroughly evaluated. RESULTS: Our findings demonstrate that treatment with ginsenoside Rb1 alleviated behavioral deficits induced by CIRI and reduced pathological damage in brain tissue. Furthermore, ginsenoside Rb1 treatment notably decreased oxidative stress and the inflammatory response induced by CIRI, leading to lower levels of inflammatory factors (p < 0.05). Further experimental results indicated that ginsenoside Rb1 promoted antioxidant and anti-inflammatory responses by regulating the activity of the Nrf2/A20/eEF1A2 axis. Additionally, ginsenoside Rb1 inhibited the activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, thereby reducing the release of inflammatory factors and the occurrence of cell apoptosis. CONCLUSION: Our study results suggest that ginsenoside Rb1 exerts neuroprotective effects and alleviates brain injury induced by CIRI by regulating the Nrf2/A20/eEF1A2 axis and inhibiting the activation of the NLRP3 inflammasome. These findings provide new treatment insights for CIRI and support ginsenoside Rb1's development as a therapeutic drug. However, despite the promising nature of our findings, further research is required to validate these discoveries and explore the feasibility and safety of ginsenoside Rb1 in clinical applications. We hope that our study can provide new directions and strategies for the treatment and prevention of CIRI, contributing to the development of neuroprotective drugs.