Blood Urea Nitrogen-to-Serum Albumin Ratio Predicts Fatal Outcomes in Severe Fever with Thrombocytopenia Syndrome Patients.

There are no effective therapies for severe fever with thrombocytopenia syndrome (SFTS), and existing predictors of mortality are still controversial. This retrospective study aimed to identify reliable early-stage indicators for predicting fatal outcomes in 217 patients hospitalized with an SFTS diagnosis between March 2021 and November 2023; 157 of the patients survived, and 60 died. Demographics, clinical characteristics, and laboratory parameters were reassessed in both groups. The mean age of participants was 64.0 (interquartile range: 54.5-71.0) years, and 42.4% (92/217) were males. Based on a multivariate Cox regression analysis, the blood urea nitrogen-to-serum albumin ratio (BAR) (hazard ratio [HR]:4.751; 95% CI: 2.208-10.226; P <0.001), procalcitonin level (HR: 1.946; 95% CI: 1.080-3.507; P = 0.027), and central nervous system symptoms (HR: 3.257; 95% CI, 1.628-6.513; P = 0.001) were independent risk factors for mortality in SFTS patients. According to a receiver operating characteristic curve analysis, a BAR with an area under the curve of 0.913 (95% CI: 0.873-0.953; P <0.001), a sensitivity of 76.7%, and a specificity of 90.4% showed better predictive performance for fatal outcomes than other classical indicators reported. The Kaplan-Meier survival curve confirmed that an increased BAR was linked with an unfavorable prognosis in SFTS patients (P <0.001 by log-rank test). In conclusion, the results indicate that high BAR levels are markedly related to substandard outcomes and are a reliable and readily accessible predictor of fatal outcomes in SFTS patients.

Restoration of CD3+CD56+ NKT-like cell function by TIGIT blockade in inactive carrier and immune tolerant patients of chronic hepatitis B virus infection.

Chronic hepatitis B (CHB) virus infection, which can be divided into immune-tolerant (IT), immune-active (IA), inactive carrier (IC) phases, and HBeAg-negative hepatitis (ENEG), can induce liver cirrhosis and eventually hepatocellular carcinoma (HCC). CD3+CD56+ NKT-like cells play an important role in antiviral immune response. However, the mechanism of NKT-like cells to mediate immune tolerance remains largely elusive. In this study, we observed circulating NKT-like cells from IC and IT CHB patients were phenotypically and functionally impaired, manifested by increased expression of inhibitory receptor TIGIT and decreased capacity of secreting antiviral cytokines. Besides, TIGIT+ NKT-like cells of IC and IT CHB patients expressed lower levels of cytotoxic cytokines than the TIGIT- subset. Furthermore, increased expression of CD155, the ligand of TIGIT, on plasmacytoid dendritic cells (pDCs) was detected in IC and IT CHB patients. Importantly, the co-culture of NKT-like cells and pDCs showed that NKT-like cells restored their antiviral ability after TIGIT blockade upon HBV peptide stimulation in IC and IT CHB patients. In conclusion, our findings suggest that the TIGIT pathway may mediate immune tolerance in IT CHB patients and lead to functional impairment in IC patients, indicating that TIGIT may be a potential therapeutic checkpoint for immunotherapy of CHB patients.

Insights into how characteristics of dissolved algal organic matter affect the efficiency of modified clay in controlling harmful algal blooms.

Dissolved algal organic matter (dAOM) originating from harmful algal blooms (HABs) can deteriorate the quality of municipal water supplies, threaten the health of aquatic environments, and interfere with modified clay (MC)-based HABs control measures. In this study, we explored the composition of dAOM from Prorocentrum donghaiense, a typical HAB organism, and assessed the influence of dAOM on MC flocculation. Our results suggested that dAOM composition was complex and had a wide molecular weight (MW) distribution. MW and electrical properties were important dAOM characteristics affecting flocculation and algal removal efficiency of MC. Negatively charged high-MW components (>50 kDa) critically affected algal removal efficiency, reducing the zeta potential of MC particles and leading to small and weak flocs. However, the effect of dAOM depended on its concentration. When the cell density of P. donghaiense reached HAB levels, the high-MW dAOM strongly decreased the algal removal efficiency of MC.

Updating mRNA variants of the human RSK4 gene and their expression in different stressed situations.

We determined RNA spectrum of the human RSK4 (hRSK4) gene (also called RPS6KA6) and identified 29 novel mRNA variants derived from alternative splicing, which, plus the NCBI-documented ones and the five we reported previously, totaled 50 hRSK4 RNAs that, by our bioinformatics analyses, encode 35 hRSK4 protein isoforms of 35-762 amino acids. Many of the mRNAs are bicistronic or tricistronic for hRSK4. The NCBI-normalized NM_014496.5 and the protein it encodes are designated herein as the Wt-1 mRNA and protein, respectively, whereas the NM_001330512.1 and the long protein it encodes are designated as the Wt-2 mRNA and protein, respectively. Many of the mRNA variants responded differently to different situations of stress, including serum starvation, a febrile temperature, treatment with ethanol or ethanol-extracted clove buds (an herbal medicine), whereas the same stressed situation often caused quite different alterations among different mRNA variants in different cell lines. Mosifloxacin, an antibiotics and also a functional inhibitor of hRSK4, could inhibit the expression of certain hRSK4 mRNA variants. The hRSK4 gene likely uses alternative splicing as a handy tool to adapt to different stressed situations, and the mRNA and protein multiplicities may partly explain the incongruous literature on its expression and comports.

Highly selective nanozyme-based glucose sensing platform via construction of artificial recognition sites on gold nanospheres.

Nanozymes have been regarded as the ideal alternatives to natural enzymes in bioassays due to their good stability and low cost. However, their applications in sensing usually suffer from poor selectivity. For example, Au-based nanozymes, as a kind of classical glucose oxidase mimic enzyme, could catalyze diverse monosaccharides. Therefore, it is of great necessity and urgency to endow the Au-based nanozymes with enhanced selectivity for the construction of specific glucose sensing platform. In our study, easily recyclable polydopamine (PDA)-supported Au-based nanozymes (PDA@Au NPs) were successfully prepared and could catalyze diverse monosaccharides including glucose, xylose, mannose, and sucrose. To enhance the selectivity of PDA@Au NPs, molecularly imprinted polymers (MIPs) were constructed on the surface of PDA@Au NPs using glucose and boronic acid derivatives as template and functional monomer. Impressively, the catalytic activity of the obtained molecularly imprinted nanozyme (PDA@Au NPs-MIPs) only shows a slight decrease (6.3%) while their selectivity is obviously enhanced (≥230%). Accordingly, the as-prepared sensor achieved the sensitive and selective detection of glucose in the concentration range of 10 µM-1 mM and a low detection limit (LOD) of 0.227 µM (S/N = 3), avoiding the influence of other monosaccharides exited in the sensing solutions to a great extent. As expected, the as-prepared sensors also showed good recovery, and long-term stability.

Phenotypic and functional exhaustion of circulating CD3+ CD56+ NKT-like cells in colorectal cancer patients.

CD3+ CD56+ NKT-like cells are crucial to antitumor immune surveillance and defense. However, research on circulating NKT-like cells in colorectal cancer (CRC) patients is limited. This investigation selected 113 patients diagnosed with primary CRC for preoperative peripheral blood collection. The blood from 106 healthy donors at the physical examination center was acquired as a healthy control (HC). The distribution of lymphocyte subsets, immunophenotype, and functional characteristics of NKT-like cells was comprehensively evaluated. Compared to HC, primary CRC patients had considerably fewer peripheral NKT-like cells in frequency and absolute quantity, and the fraction of NKT-like cells was further reduced in patients with vascular invasion compared to those without. The NKT-like cells in CRC patients had a reduced fraction of the activating receptor CD16, up-regulated expression of inhibitory receptors LAG-3 and NKG2A, impaired production of TNF-α and IFN-γ, as well as degranulation capacity. Moreover, the increased frequency of NKG2A+ NKT-like cells and the decreased expression of activation-related molecules were significantly correlated with tumor progression. In detail, NKG2A+ NKT-like cells indicated increased PD-1 and Tim-3 and reduced TNF-α than NKG2A- subgroup. Blocking NKG2A in vitro restored cytokine secretion capacity in NKT-like cells from CRC patients. Altogether, this research revealed that circulating NKT-like cells in CRC patients exhibited suppressive phenotype and functional impairment, which was more pronounced in NKG2A+ NKT-like cells. These findings suggest that NKG2A blockade may restore anti-tumor effector function in NKT-like cells, which provides a potential target for immunotherapy in CRC patients.

Loss of UBE2S causes meiosis I arrest with normal spindle assembly checkpoint dynamics in mouse oocytes.

The timely degradation of proteins that regulate the cell cycle is essential for oocyte maturation. Oocytes are equipped to degrade proteins via the ubiquitin-proteasome system. In meiosis, anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin-ligase, is responsible for the degradation of proteins. Ubiquitin-conjugating enzyme E2 S (UBE2S), an E2 ubiquitin-conjugating enzyme, delivers ubiquitin to APC/C. APC/C has been extensively studied, but the functions of UBE2S in oocyte maturation and mouse fertility are not clear. In this study, we used Ube2s knockout mice to explore the role of UBE2S in mouse oocytes. Ube2s-deleted oocytes were characterized by meiosis I arrest with normal spindle assembly and spindle assembly checkpoint dynamics. However, the absence of UBE2S affected the activity of APC/C. Cyclin B1 and securin are two substrates of APC/C, and their levels were consistently high, resulting in the failure of homologous chromosome separation. Unexpectedly, the oocytes arrested in meiosis I could be fertilized and the embryos could become implanted normally, but died before embryonic day 10.5. In conclusion, our findings reveal an indispensable regulatory role of UBE2S in mouse oocyte meiosis and female fertility.

Ultralow Loading Copper-Intercalated MoO3 Nanobelts with High Activity against Antibiotic-Resistant Bacteria.

In recent years, the infection rate of antibiotic resistance has been increasing year by year, and the prevalence of super bacteria has posed a great threat to human health. Therefore, there is an urgent need to find new antibiotic alternatives with long-term inhibitory activity against a broad spectrum of bacteria and microorganisms in order to avoid the proliferation of more multidrug-resistant (MDR) bacteria. The presence of natural van der Waals (vdW) gaps in layered materials allows them to be easily inserted by different guest species, providing an attractive strategy for optimizing their physicochemical properties and applications. Here, we have successfully constructed a copper-intercalated α-MoO3 nanobelt based on nanoenzymes, which is antibacterial through the synergistic effect of multiple enzymes. Compared with α-MoO3, MoO3-x/Cu nanobelts with a copper loading capacity of 2.11% possess enhanced peroxidase (POD) catalytic activity and glutathione (GSH) depletion, indicating that copper intercalation significantly improves the catalytic performance of the nanoenzymes. The MoO3-x/Cu nanobelts are effective in inducing POD and oxidase (OXD) and catalase (CAT) activities in the presence of H2O2 and O2, which resulted in the generation of large amounts of reactive oxygen species (ROS), which were effective in bacterial killing. Interestingly, MoO3-x/Cu nanobelts can serve as glutathione oxidase (GSHOx)-like nanoenzymes, which can deplete GSH in bacteria and thus significantly improve the bactericidal effect. The multienzyme-catalyzed synergistic antimicrobial strategy shows excellent antimicrobial efficiency against ß-lactamase-producing Escherichia coli (ESBL-E. coli) and methicillin-resistant Staphylococcus aureus (MRSA). MoO3-x/Cu exhibits excellent spectral bactericidal properties at very low concentrations (20 µg mL-1). Our work highlights the wide range of antibacterial and anti-infective biological applications of copper-intercalated MoO3-x/Cu nanobelt catalysts.

Evaluation of serum neurofilament light chain and glial fibrillary acidic protein in the diagnosis of Alzheimer's disease.

Purpose: This study aimed to evaluate the use of serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in the diagnosis of Alzheimer's disease (AD) and the differential diagnosis between AD and mild cognitive impairment (MCI). Methods: From September 2021 to October 2022, we collected venous blood from patients and healthy individuals who visited our hospital's Neurology Department, and we isolated serum to detect NfL and GFAP using direct chemiluminescence. The results were analyzed using one-way analysis of variance (ANOVA) analysis and receiver operating characteristic (ROC) curves. Results: Pairwise comparisons among the three groups showed that compared with the health checkup (HC) group, serum NfL and GFAP were increased in both AD and MCI (PNfL < 0.05, PGFAP < 0.01). There were significant differences in GFAP between MCI and AD groups, and the level in AD group was higher (p < 0.01), while there was no difference in NfL. Both serum NfL and serum GFAP levels can independently diagnose AD (p < 0.01). The ROC curve showed that GFAP had a higher diagnostic efficacy, with an area under the ROC curve (AUC) of 0.928. The cut-off values of the two serum markers for the diagnosis of AD were NfL > 40.09 pg./mL and GFAP >31.40 pg./mL. Sensitivity and specificity for NfL in the diagnosis of AD were 59.6 and 76.2%, respectively, and for GFAP, they were 90.4 and 82.1%, respectively. The combined diagnosis of GFAP and NfL improved the diagnostic efficiency (AUC = 0.931, sensitivity = 78.8%, specificity = 92.3%). The cut-off value of GFAP for the differential diagnosis of MCI and AD was 46.05 pg./mL. Conclusion: Both serum NfL and serum GFAP can be used as biomarkers for the diagnosis of AD. Serum GFAP has better diagnostic efficacy and can distinguish AD from MCI. A combined diagnosis can improve diagnostic specificity.

Nanozyme with tailored selectivity and highly catalytic activity for efficient sensing of endotoxin and sourcing gram-negative bacteria.

Endotoxin detection is important for determining bacterial contamination and infection in fields of food, pharmaceutical and clinical disease diagnosis. The horseshoe crab deformed cell lysate analysis is regarded as the gold-standard method, but the endangered and high-cost horseshoe crab animals required in sensing process further raise animal ethical issues and hinder their applications. The colorimetric methods based on nanozymes are simple and economical, but the low selectivity and sensitivity are still the bottleneck for their further application. Herein, we successfully developed a phenylboronic acid functionalized iron-based nanozyme with higher selectivity and highly catalytic activity for endotoxin sensing. The as-prepared colorimetric sensor using the obtained nanozyme as sensing probes shows a good linear relationship for endotoxin sensing in the range of 1-20 µg mL-1, with a LOD = 0.42 µg mL-1, along with good selectivity and reproducibility. The sensor can also be well applied to detecting endotoxin in practical samples such as beer and serum. Moreover, the parameters including time and temperature which could affect the endotoxin release from E. coli were also studied and optimized, based on the relationship between endotoxin and Gram-negative bacteria, the as-prepared sensor achieves the qualitative and quantification of E. coli.

Spin-state Conversion by Asymmetrical Orbital Hybridization in Ni-doped Co3 O4 to Boost Singlet Oxygen Generation for Microbial Disinfection.

Singlet oxygen (1 O2 ) plays a significant role in environmental and biomedical disinfection fields. Electrocatalytic processes hold great potential for 1 O2 generation, but remain challenging. Herein, a facile Ni doping converted spin-state transition approach is reported for boosting 1 O2 production. Magnetic analysis and theoretical calculations reveal that Ni occupied at the octahedral site of Co3 O4 can effectively induce a low-to-high spin-state transition. The high-spin Ni-Co3 O4 generate appropriate binding strength and enhance electron transfer between the Co centers with oxygen intermediates, thereby improving the catalytic activity of Ni-Co3 O4 for effective generating 1 O2 . In neutral conditions, 1×106  CFU mL-1 Gram-negative ESBL-producing Escherichia coli (E. coli) could be inactivated by Ni-Co3 O4 system within 5 min. Further antibacterial mechanisms indicate that 1 O2 can lead to cell membrane damage and DNA degradation so as to irreversible cell death. Additionally, the developed Ni-Co3 O4 system can effectively inactivate bacteria from wastewater and bioaerosols. This work provides an effective strategy for designing high-spin electrocatalysis to boost 1 O2 generation for disinfection process.

MoOxNWs with mechanical damage - oriented synergistic photothermal / photodynamic therapy for highly effective treating wound infections.

Reactive oxygen species (ROS)-based therapy has emerged as a promising antibacterial strategy. However, it faces the limitations of uncontrollable space-time release and excessive lipid peroxidation, which may lead to a series of metabolic disorders and decreased immune function. In this study, mechanical damage by molybdenum oxide nanowires (MoOxNWs) is introduced as a synergistic factor to enhance the photothermal and photodynamic effects for controllable and efficient antibacterial therapy. Through their sharp ends, the nanowires can effectively pierce and damage the bacterial cells, thus facilitating the entry of externally generated ROS into the cells. The ROS are generated via photodynamic effect of the nanowires under a mere 5 min of near-infrared light irradiation. This approach enhances the photothermal (by 27.3 %) and photodynamic properties of ROS generation. MoOxNWs (100 µg·mL-1) achieve sterilisation rates of 97.67 % for extended-spectrum ß-lactamase-producing E. coli and 96.34 % for methicillin-resistant Staphylococcus aureus, which are comparable or even exceeding the efficacy of most MoOx-based antibacterial agents. Moreover, they exhibit good biocompatibility and low in vivo toxicity.

Single substrate-functionalized molybdenum oxide nanozyme for specific colorimetric monitoring of xanthine oxidase activity.

Xanthine-functionalized molybdenum oxide nanodots (X-MoO3-x NDs) with peroxidase (POD)-like activity were developed for selective, sensitive, and facile colorimetric quantification of xanthine oxidase (XO). Xanthine functionalization can not only be favorable for the successful nanozyme preparation, but also for the specific recognition of XO as well as the simultaneous generation of hydrogen peroxide, which was subsequently transformed into hydroxyl radical to oxidize the chromogenic reagent based on the POD-like catalysis. Under the optimized conditions, the colorimetric biosensing platform was established for XO assay without addition of further substrates, showing good linearity relationship between absorbance difference (ΔA) and XO concentrations in the range 0.05-0.5 U/mL (R2 = 0.998) with a limit of detection (LOD) of 0.019 U/mL. The quantification of XO occurs in 25 min, which is superior to the previously reported and commercial XO assays. The proposed method has been successfully used in the assay of human serum samples, showing its high potential in the field of clinical monitoring.

Defect-Engineering-Mediated Long-Lived Charge-Transfer Excited-State in Fe-Gallate Complex Improves Iron Cycle and Enables Sustainable Fenton-Like Reaction.

Fenton reactions are inefficient because the Fe(II) catalyst cannot be recycled in time due to the lack of a rapid electron transport pathway. This results in huge H2 O2 wastage in industrial applications. Here, it is shown that a sustainable heterogeneous Fenton system is attainable by enhancing the ligand-to-metal charge-transfer (LMCT) excited-state lifetime in Fe-gallate complex. By engineering oxygen defects in the complex, the lifetime is improved from 10-90 ps. The lengthened lifetime ensures sufficient concentrations of excited-states for an efficient Fe cycle, realizing previously unattainable H2 O2 activation kinetics and hydroxyl radical (• OH) productivity. Spectroscopic and electrochemical studies show the cyclic reaction mechanism involves in situ Fe(II) regeneration and synchronous supply of oxygen atoms from water to recover dissociated Fe─O bonds. Trace amounts of this catalyst effectively destroy two drug-resistant bacteria even after eight reaction cycles. This work reveals the link among LMCT excited-state lifetime, Fe cycle, and catalytic activity and stability, with implications for de novo design of efficient and sustainable Fenton-like processes.

Carbon dots for staining bacterial dead cells and distinguishing dead/alive bacteria.

The small molecular dyes such as propidium iodide (PI) always suffer from photo-bleaching and potential toxicity. To tackle the problems, a type of nontoxic carbon dots (CDs) was obtained for dead/alive bacterial distinguishing. This kind of carbon dots has an average size of 1.91 nm and owns carboxyl groups, emerging as excellent candidates for imaging bacterial cells. The negative charges of carboxyl groups lead their avoidance of alive cells while their small size facilitates penetration of dead cells. This kind of nontoxic CDs has effectively differentiated between and alive ones, presenting a highly promising green dye comparing with traditional small molecular dyes.

A single-cell atlas of the peripheral immune response in patients with influenza A virus infection.

Influenza A virus (IAV) remains a pressing global health concern, yet our understanding of the specific nature and functional roles of certain circulating cell subsets in relation to this viral infection remains unclear. We performed single-cell RNA sequencing (scRNA-seq) on single-cell whole-blood (scWB) isolated from various populations using the Singleron Matrix platform. Our investigation showed a significant upregulation of the IFN-stimulated gene, IFN-α-inducible protein 27 (IFI27), in patients affected by IAV infection and further found that the heightened expression of IFI27 was primarily concentrated in specific immune cell populations, including monocytes and conventional dendritic cells (cDCs). Notably, we identified a specific subset of neutrophils, neutrophil_ISG15, which implicates interferon (IFN) signaling in IAV infection. Our findings provide a comprehensive understanding of the cellular subtypes and molecular characteristics of scWB across different populations with IAV infection.

Epidemiology of Nontuberculous Mycobacteria in Tuberculosis suspects, Southwest of China, 2017-2022.

Objectives: This study summarizes the epidemiological characteristics, species distribution, and drug sensitivity of clinical nontuberculous mycobacteria (NTM) isolates at the Public Health Clinical Center of Chengdu, China, from January 2017 to December 2022. Methods: We retrospectively analyzed data from patients with clinically isolated NTM strains. Chi-square analysis assessed the rate of Mycobacterium strain isolation over 6 years. Results: The number of samples tested for Mycobacterium tuberculosis (MTB) and/or NTM increased each year, while MTB detection decreased and NTM detection rose significantly each year (P=0.03). The average age of NTM patients was 51 ± 17.53 years, with a 14.1% HIV infection rate. The predominant isolates were Mycobacterium avium-intracellulare (MAC) and M. chelonae/M. abscessus, with 96.4% of cases being of Han ethnicity. Amikacin, moxifloxacin, and clarithromycin were effective against M. avium and M. intracellulare; linezolid, amikacin, and cefoxitin were effective against M. chelonae/M. abscessus. Over 90% of NTM cases originated from the respiratory tract. Conclusion: The NTM isolation rate in Southwest China has risen in recent years, primarily among elderly patients with a high HIV co-infection rate. The main NTM isolates were MAC and M. chelonae/M. abscessus. Amikacin, moxifloxacin, clarithromycin, and linezolid exhibited strong antibacterial activity against SGM, while amikacin and linezolid displayed relatively better antibacterial activity against RGM. The prevalence of NTM infection may be positively associated with regional economic development and health conditions.

Combination of AS101 and Mefloquine Inhibits Carbapenem-Resistant Pseudomonas aeruginosa in vitro and in vivo.

Background: In recent years, carbapenem-resistant Pseudomonas aeruginosa (CRPA) has spread around the world, leading to a high mortality and close attention of medical community. In this study, we aim to find a new strategy of treatment for CRPA infections. Methods: Eight strains of CRPA were collected, and PCR detected the multi-locus sequence typing (MLST). The antimicrobial susceptibility test was conducted using the VITEK@2 compact system. The minimum inhibitory concentration (MIC) for AS101 and mefloquine was determined using the broth dilution method. Antibacterial activity was tested in vitro and in vivo through the chessboard assay, time killing assay, and a mouse model. The mechanism of AS101 combined with mefloquine against CRPA was assessed through the biofilm formation inhibition assay, electron microscopy, and detection of reactive oxygen species (ROS). Results: The results demonstrated that all tested CRPA strains exhibited multidrug resistance. Moreover, our investigation revealed a substantial synergistic antibacterial effect of AS101-mefloquine in vitro. The assay for inhibiting biofilm formation indicated that AS101-mefloquine effectively suppressed the biofilm formation of CRPA-5 and CRPA-6. Furthermore, AS101-mefloquine were observed to disrupt the bacterial cell wall and enhance the permeability of the cell membrane. This effect was achieved by stimulating the production of ROS, which in turn hindered the growth of CRPA-3. To evaluate the therapeutic potential, a murine model of CRPA-3 peritoneal infection was established. Notably, AS101-mefloquine administration resulted in a significant reduction in bacterial load within the liver, kidney, and spleen of mice after 72 hours of treatment. Conclusion: The present study showed that the combination of AS101 and mefloquine yielded a notable synergistic bacteriostatic effect both in vitro and in vivo, suggesting a potential clinical application of this combination in the treatment of CRPA.

Synthesis of γ-Cyclodextrin-Reduced Fe(III) Nanoparticles with Peroxidase-like Catalytic Activity for Bacteriostasis of Food.

Foodborne pathogens are a primary cause of human foodborne illness, making it imperative to explore novel antibacterial strategies for their control. In this study, Fe-γ-CD was successfully synthesized as a food antibacterial agent for use in milk and orange juice. The Fe-γ-CD consists of 6/11 Fe(II) and 5/11 Fe(III), which catalyze a Fenton-like catalytic reaction with H2O2 to generate •OH. Consequently, Fe-γ-CD exhibits exceptional peroxidase-like activity and broad-spectrum antibacterial efficacy. Fe-γ-CD not only disrupts the wall structure of ESBL-E. coli but also induces protein leakage and genetic destruction, ultimately leading to its death. Furthermore, Fe-γ-CD inhibits biofilm formation by MRSA and eradicates mature biofilms, resulting in MRSA's demise. Importantly, Fe-γ-CD demonstrates negligible cytotoxicity toward normal mammalian cells, making it an ideal candidate for application as an antibacterial agent in foodstuffs. These findings highlight that Fe-γ-CD is an effective tool for combating the spread of foodborne pathogens and food safety.

A Nano-Autophagy Inhibitor Triggering Reciprocal Feedback Control of Cholesterol Depletion for Solid Tumor Therapy.

Solid tumors are characterized by enhanced metabolism of lipid, particularly cholesterol, inspiring the exploration of metabolic therapy through cholesterol oxidase (COD)-mediated cholesterol deprivation. However, the therapeutic efficacy of COD is limited due to the hypoxic tumor microenvironment and the protective autophagy triggered by cholesterol deprivation. Herein, a combination therapy for metabolically treating solid tumors through COD in conjunction with molybdenum oxide nanodots (MONDs), which serve as both potent oxygen generators and autophagy inhibitors, is reported. MONDs convert H2 O2 (arising from COD-mediated cholesterol oxidation) into O2 , which is then recycled by COD to form reciprocal feedback for cholesterol depletion. Concurrently, MONDs can overcome autophagy-induced therapeutic resistance frequently occurring in conventional nutrient deprivation therapy by activating AKT/mTOR pathway phosphorylation. Combination therapy in the xenograft model results in an ≈5-fold increase in therapeutic efficiency as compared with COD treatment alone. This functionally cooperative metabolic coupling strategy holds great promise as a novel polytherapy approach that will benefit patients with solid tumors.