Characterization of Pseudomonas spp. contamination and in situ spoilage potential in pasteurized milk production process.

To investigate the prevalence of Pseudomonas in the pasteurized milk production process and its effect on milk quality, 106 strains of Pseudomonas were isolated from the pasteurized milk production process of a milk production plant in Shaanxi Province, China. The protease, lipase and biofilm-producing capacities of the 106 Pseudomonas strains were evaluated, and the spoilage enzyme activities of their metabolites were assessed by simulating temperature incubation in the refrigerated (7 °C) and transport environment (25 °C) segments and thermal treatments of pasteurization (75 °C, 5 min) and ultra-high temperature sterilization (121 °C, 15 s). A phylogenetic tree was drawn based on 16S rDNA gene sequencing and the top 5 strains were selected as representative strains to identify their in situ spoilage potential by examining their growth potential and ability to hydrolyze proteins and lipids in milk using growth curves, pH, whiteness, Zeta-potential, lipid oxidation, SDS-PAGE and volatile flavor compounds. The results showed that half and more of the isolated Pseudomonas had spoilage enzyme production and biofilm capacity, and the spoilage enzyme activity of metabolites was affected by the culture temperature and sterilization method, but ultra-high temperature sterilization could not completely eliminate the enzyme activity. The growth of Pseudomonas lundensis and Pseudomonas qingdaonensis was less affected by temperature and time, and the hydrolytic capacity of extracellular protease and lipase secreted by Pseudomonas lurida was the strongest, which had the greatest effect on milk quality. Therefore, it is crucial to identify the key contamination links of Pseudomonas, the main bacteria responsible for milk spoilage, and the influence of environmental factors on its deterioration.

Direct injection ultra-performance liquid chromatography-tandem mass spectrometry for the high-throughput determination of etomidate and etomidate acid in wastewater.

Etomidate (ET), a hypnotic agent used for the induction of anesthesia, is rapidly metabolized to etomidate acid (ETA) in the liver. Recently, ET has become one of the most serious alternative drugs of abuse in China. Therefore, an urgent need exists to develop a fast and convenient analysis method for monitoring ET. The current work presents a simple, fast, and sensitive direct injection method for the determination of ET and ETA in wastewater. After the optimization of the ultra-performance liquid chromatography-tandem mass spectrometry and sample filtration conditions, the method exhibited satisfactory limits of detection (1 ng/L) and good filtration loss. The validated method was successfully applied to determine the concentrations of ET and ETA in wastewater samples (n = 245) from several wastewater treatment plants in China. The concentrations of the targets in positive samples ranged from less than the lower limits of quantitation to 47.71 ng/L. The method can meet ET monitoring and high-throughput analysis requirements.

Discovery of Novel Ortho-Aminophenol Derivatives Targeting Lipid Peroxidation with Potent Antiferroptotic Activities.

The concept of ferroptosis inhibition has gained growing recognition as a promising therapeutic strategy for addressing a wide range of diseases. Here, we present the discovery of four series of ortho-aminophenol derivatives as potential ferroptosis inhibitors beginning with the endogenous substance 3-hydroxyanthranilic acid (3-HA) by employing quantum chemistry techniques, in vitro and in vivo assays. Our findings reveal that these ortho-aminophenol derivatives exhibit unique intra-H bond interactions, compelling ortho-amines to achieve enhanced alignment with the aromatic π-system, thereby expanding their activity. Notably, compounds from all four series display remarkable activity against RSL3-induced ferroptosis, showcasing an activity 100 times more than that of 3-HA. Furthermore, these compounds also demonstrate robust in vivo efficacy in protecting mice from kidney ischemia-reperfusion injury and acetaminophen-induced hepatotoxicity. In summary, we provide four distinct series of active scaffolds that significantly expand the chemical space of ferroptosis inhibitors, serving as valuable insights for future structural modifications.

Combining chemical analysis and toxicological methods to access the ecological risk of complex contamination in Daye Lake.

As one of the nine primary non-ferrous metal smelting bases in China, Daye Lake basin was polluted due to diverse human activities. But so far the pollution status and related ecological risks of this region have not been detailly investigated. In current study, pollutants including heavy metals, polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs) in eight sediment samples from Daye Lake were quantified. 18S rRNA gene sequencing was employed to profile the nematode community structure within these sediments. Model organism Caenorhabditis elegans (C. elegans) were further applied for a comprehensive ecological risk assessment of Daye Lake. Notably, Cadmium (Cd) was identified as a key driver of ecological risk, reaching an index of 1287.35. At sample point S4, OCPs particularly p,p'-DDT, displayed an extreme ecological risk with a value of 23.19. Cephalobidae and Mononchida showed strong sensitivity to pollutant levels, reinforcing their suitability as robust bioindicators. The composite pollutants in sampled sediments caused oxidative stress in C. elegans, with gene Vit-2 and Mtl-1 as sensitive biomarkers. By employing the multiple analysis methods, our data can offer valuable contributions to environmental monitoring and health risk assessment for composite polluted areas.

The value of patient-reported outcomes to predict for symptom burden and health-related quality of life after chemoradiation for cervical cancer: A prospective study.

PURPOSE: Cervical cancer patients undergoing chemoradiation have high symptom burden. We performed an analysis of prospectively collected patient-reported outcomes(PROs) to determine characteristics predictive of poor treatment experience. METHODS: Between 2021-2023, we prospectively collected PROs from cervical cancer patients undergoing definitive chemoradiation. EORTC-QLQ-C30 and EORTC-QLQ-CX24 were completed at baseline(BL) and at the end of treatment(EOT). Poor treatment experience was defined as EOT poor health-related quality of life (HRQOL), low physical function, or significant overall symptom burden. Predictive factors analyzed included demographic, clinical, disease-specific factors, and baseline financial toxicity, depression, social function, and emotional function. ROC analysis provided appropriate predictive cut-off values. Univariable(UVA) and multivariable(MVA) linear regression analyses were performed. RESULTS: Fourty-nine patients completed BL and EOT questionnaires. Median age was 43 (range, 18-85). Most patients (59%) had stage III disease. Baseline financial toxicity ≥66.7, depression ≥66.7, social function ≤50 and emotional function ≤58 on the EORTC linear transformed scale of 0-100 were significant predictors for poor treatment experience (p≤0.04) based on ROC analysis. On MVA poor BL social function was associated with reduced EOT HRQOL (ß-9.3,_95%CI_-16.1_to_-2.6,_p<0.008), decreased physical function (ß-24.4,_95%CI_-36.3_to_-12.6,_p<0.001), and high symptom burden_(ß26.9,_95%CI_17.5_to_36.3,_p<0.001). Earlier disease stage predicted for decreased symptom burden_(ß-6.7,_95%CI_-13.1_to_-0.3,_p=0.039). BL financial toxicity was a significant predictor on UVA (p=0.001-0.044) and showed a significant interaction term on MVA (p=0.024-0.041) for all three domains of poor treatment experience. Demographic and treatment-related factors were not predictive. CONCLUSION: Cervical cancer patients with poor baseline social function or high financial toxicity were at-risk for increased symptom burden and poor HRQOL. Screening for these factors provides an opportunity for early intervention to improve treatment experience.

Selenium-Mediated (-)-Epigallocatechin-3-Gallate Dynamics via Flavanone-3-Hydroxylase Regulation of Flavonoid Biosynthesis in Fu Tea (Camellia sinensis (L.) O. Kuntze).

Tea (Camellia sinensis (L.) O. Kuntze) is a highly selenium enrichment capacity plant; high selenium concentration contributes to the occurrence of oxidative stress and protein misfolding in tea plants, whereas flavonoids can chelate heavy metals to protect plants from oxidative stress caused by metal exposure. Nevertheless, the role of catechins in flavonoid synthesis and nutrient metabolism under selenium stress remains unidentified. Combining Word2vec and HNSW utilizing UHPLC-Q-Orbitrap HRMS-MS/MS to implement rapid matching annotation of the structural information on metabolites in Fu tea, we found that selenium-mediated changes in catechins in Fu tea were mainly associated with flavonoid biosynthesis pathways. The results demonstrated that selenium treatment increased benign selenol analogues (glutathioselenol) in tea and identified the novel selenopeptide PRSeMW (m/z 636.22571, Pro-Arg-SeMet-Trp) in selenium-enriched Fu tea samples to enhance the health benefits of tea. The selenium levels were negatively correlated with N5-ethyl-l-glutamine (11.63 to 4.26 mg kg-1) and (-)-epigallocatechin (13.26 to 11.19 mg kg-1), increasing the accumulation of tea polyphenols ((-)-catechin gallate, (-)-epigallocatechin 3-gallate, and (+)-gallocatechin), and decreasing the level of caffeine. These discoveries provide new insights into the mechanism of tea polyphenol-mediated transformation of selenium in Fu tea and theoretical support for the quality assessment of selenium-enriched tea.

Standard-definition White-light, High-definition White-light versus Narrow-band Imaging Endoscopy for Detecting Colorectal Adenomas: A Multicenter Randomized Controlled Trial.

OBJECTIVE: This study aimed to compare the performance of standard-definition white-light endoscopy (SD-WL), high-definition white-light endoscopy (HD-WL), and high-definition narrow-band imaging (HD-NBI) in detecting colorectal lesions in the Chinese population. METHODS: This was a multicenter, single-blind, randomized, controlled trial with a non-inferiority design. Patients undergoing endoscopy for physical examination, screening, and surveillance were enrolled from July 2017 to December 2020. The primary outcome measure was the adenoma detection rate (ADR), defined as the proportion of patients with at least one adenoma detected. The associated factors for detecting adenomas were assessed using univariate and multivariate logistic regression. RESULTS: Out of 653 eligible patients enrolled, data from 596 patients were analyzed. The ADRs were 34.5% in the SD-WL group, 33.5% in the HD-WL group, and 37.5% in the HD-NBI group (P=0.72). The advanced neoplasm detection rates (ANDRs) in the three arms were 17.1%, 15.5%, and 10.4% (P=0.17). No significant differences were found between the SD group and HD group regarding ADR or ANDR (ADR: 34.5% vs. 35.6%, P=0.79; ANDR: 17.1% vs. 13.0%, P=0.16, respectively). Similar results were observed between the HD-WL group and HD-NBI group (ADR: 33.5% vs. 37.7%, P=0.45; ANDR: 15.5% vs. 10.4%, P=0.18, respectively). In the univariate and multivariate logistic regression analyses, neither HD-WL nor HD-NBI led to a significant difference in overall adenoma detection compared to SD-WL (HD-WL: OR 0.91, P=0.69; HD-NBI: OR 1.15, P=0.80). CONCLUSION: HD-NBI and HD-WL are comparable to SD-WL for overall adenoma detection among Chinese outpatients. It can be concluded that HD-NBI or HD-WL is not superior to SD-WL, but more effective instruction may be needed to guide the selection of different endoscopic methods in the future. Our study's conclusions may aid in the efficient allocation and utilization of limited colonoscopy resources, especially advanced imaging technologies.

Spray Vaccination with a Newcastle Disease Virus (NDV)-Vectored Infectious Laryngotracheitis (ILT) Vaccine Protects Commercial Chickens from ILT in the Presence of Maternally Derived Antibodies.

Infectious laryngotracheitis (ILT) poses a significant threat to the poultry industry, and vaccines play an important role in protection. However, due to the increasing scale of poultry production, there is an urgent need to develop vaccines that are suitable for convenient immunization methods such as spraying. Previous studies have shown that Newcastle disease virus (NDV)-ILT vaccines administered via intranasal and intraocular routes to commercial chickens carrying maternally derived antibodies (MDAs) are still protective against ILT. In this study, a recombinant NDV (rNDV) was generated to express infectious laryngotracheitis virus (ILTV) glycoprotein B (gB), named rLS-gB, based on a full-length cDNA clone of the LaSota strain. The protective effect of different doses of rLS-gB administered by spray vaccination to commercial chickens at 1 day of age (DOA) was evaluated. The chickens were exposed to 160-µm aerosol particles for 10 min for spray vaccination, and no adverse reactions were observed after vaccination. Despite the presence of anti-NDV MDAs and anti-ILTV MDAs in chickens, the ILTV- and NDV-specific antibody titers were significantly greater in the vaccinated groups than in the unvaccinated group. After challenge with a virulent ILTV strain, no clinical signs were observed in the 107 EID50/ml group compared to the other groups. Furthermore, vaccination with 107 EID50/ml rLS-gB significantly reduced the ILTV viral load and ameliorated gross and microscopic lesions in the trachea of chickens. Overall, these results suggested that rLS-gB is a safe and efficient candidate spray vaccine for ILT and is especially suitable for scaled chicken farms.

Recent advances in C(sp3)-N bond formation via metallaphoto-redox catalysis.

The C(sp3)-N bond is ubiquitous in natural products, pharmaceuticals, biologically active molecules and functional materials. Consequently, the development of practical and efficient methods for C(sp3)-N bond formation has attracted more and more attention. Compared to the conventional ionic pathway-based thermal methods, photochemical processes that proceed through radical mechanisms by merging photoredox and transition-metal catalyses have emerged as powerful and alternative tools for C(sp3)-N bond formation. In this review, recent advances in the burgeoning field of C(sp3)-N bond formation via metallaphotoredox catalysis have been highlighted. The contents of this review are categorized according to the transition metals used (copper, nickel, cobalt, palladium, and iron) together with photocatalysis. Emphasis is placed on methodology achievements and mechanistic insight, aiming to inspire chemists to invent more efficient radical-involved C(sp3)-N bond-forming reactions.

Compatible multilayer magnetic field system for quantum sensing with atoms.

Magnetic fields provide a valuable method to manipulate atomic energy levels and interactions in quantum precision measurements, but achieving precise measurements requires collaboration between the magnetic field system and the optical detection system. We propose a magnetic field system that incorporates a fast-switching magnetic field and an alternating magnetic field. Specifically, we enhance the switching speed by making structural improvements during the switching operation. An independent control approach is employed to reduce the switching time caused by electromagnetic induction across the coil using multilayer coils. The results demonstrate an inverse correlation between the rise and fall times of the magnetic field switch and the number of independently stacked coil layers, indicating the possibility of achieving further improvements in switching speed through structural enhancements. The system developed here has considerable potential for application to diverse quantum systems.

Whole-exome sequencing-based mutational profiling of hepatocellular adenoma malignant transformation to hepatocellular carcinoma.

Hepatocellular adenoma (HCA) represents a rare benign hepatic neoplasm with potential for malignant transformation into hepatocellular carcinoma (HCC), yet the underlying mechanism remains elusive. In this study, we investigated the genomic landscape of this process to identify therapeutic strategies for blocking malignant transformation. Using micro-detection techniques, we obtained specimens of adenoma, cancerous neoplasm and adjacent normal liver from three patients undergoing hepatic resection surgery. Whole-exome sequencing (WES) was performed, and genomic interactions between HCA and HCC components within the same tumour were evaluated using somatic variant calling, copy number variation (CNV) analysis, clonality evaluation and mutational signature analysis. Our results revealed genomic heterogeneity among patient cases, yet within each sample, HCA and HCC tissues exhibited a similar mutational landscape, suggesting a high degree of homology. Using nonnegative matrix factorization and phylogenetic trees, we identified shared and distinct mutational characteristics and uncovering necessary pathways associated with HCA-HCC malignant transformation. Remarkably, we found that HCA and HCC shared a common monoclonal origin while displaying significant genetic diversity within HCA-HCC tumours, indicating fundamental genetic connections or evolutionary pathways between the two. Moreover, elevated immune therapy-related markers in these patients suggested heightened sensitivity to immune therapy, providing novel avenues for the treatment of hepatic malignancies. This study sheds light on the genetic mechanisms underlying HCA-HCC progression, offering potential targets for therapeutic intervention and highlighting the promise of immune-based therapies in managing hepatic malignancies.

Aerobic Se(IV) reducing bacteria and their reducing characteristics in estuarine sediment.

Microorganisms play a critical role in the biogeochemical cycling of selenium in natural ecosystems, particularly in reducing selenite (Se(IV)) to element selenium (Se(0)) which reduces its mobility and bioavailability. However, Se(IV)-reducing bacteria and their reducing characteristics in estuarine sediments remain inadequately understood. In this study, the reduction of Se(IV) was confirmed to be microbially driven through the cultivation of a mixture of estuarine sediment and Se(IV) under aerobic conditions. Community analysis indicates that Bacillus was primarily involved in the reduction of Se(IV). A strain with high salt tolerance (7.5 % NaCl) and Se(IV) resistance (up to 200 mM), Bacillus cereus SD1, was isolated from an estuarine sediment. The reduction of Se(IV) occurred concomitantly with the onset of microbial growth, and reduction capacity increased approximately 5-fold by adjusting the pH. In addition, Se(IV) reduction in Bacillus cereus SD1 was significantly inhibited by sulfite, and the key enzyme activity tests revealed the possible presence of a sulfite reductase-mediated Se(IV) reduction pathway. These research findings provide new insights into the bioreducing characteristics and the biogeochemical cycling of selenium in estuarine environments.

The role of CO2 in the genesis of Dabie-type porphyry molybdenum deposits.

Porphyry-type molybdenum deposits, many of which are in China, supply most of the World's molybdenum. Of particular importance are the molybdenum deposits located in the Qinling-Dabie region that are responsible for more than half of China's molybdenum production. A feature that distinguishes this suite of deposits from the better-known Climax and Endako sub-types of porphyry molybdenum deposits is their formation from CO2-rich magmatic-hydrothermal fluids. The role of CO2, if any, in the transport of molybdenum by these fluids, however, is poorly understood. We conducted experiments on the partitioning of molybdenum between H2O-CO2, H2O-NaCl, and H2O-NaCl-CO2 fluids and a felsic melt at 850 °C and 100 and 200 MPa. Here we show that the exsolution of separate (immiscible) brine and vapor leads to the very high brine DMo values needed for efficient extraction of Mo from the magmas forming Dabie-type porphyry molybdenum deposits.

Preparation of white rot fungal inoculum and its application to bioremediation of chlorimuron-ethyl-contaminated soil.

Chlorimuron-ethyl is currently the primary herbicide used for chemical weed control in a soybean field. In this study, a solid microbial inoculum (corn stalk-white rot fungus (W-1)) was prepared for the remediation of farmland soil contaminated by chlorimuron-ethyl. Firstly, the preparation method of the microbial inoculum was studied. Secondly, the degradation rate of the chlorimuron-ethyl in the ground by the solid microbial inoculum is improved by optimizing the proportion of the protective agent. Then the effects of applying solid microbial inoculum, free bacteria and corn straw on the degradation rate of chlorimuron-ethyl in soil were weighed. Finally, Illumina MiSeq sequencing was used to measure the composition and diversity of bacterial and fungal communities in the ground before and after using microbial inoculum. The degradation rate of chlorimuron-ethyl in soil by solid microbial inoculum was 84.87% after 20 d using corn straw as the support, room temperature drying, 4% Ca3(PO4)2 as the protective drying agent, and 1%(w) dextrin as the ultraviolet protective agent. Inoculation of white rot fungi could significantly affect the community structure of bacteria and fungi in the soil, making the chlorimuron-ethyl degrading communities become the dominant communities and playing an essential role in the degradation of chlorimuron-ethyl. The results showed that using solid microbial inoculum was an effective way to repair farmland soil polluted by chlorimuron-ethyl.

Screening for colorectal cancer: Study on the shedding cells of feces.

Objective: The objective of this study was to explore the enrichment efficiency of an improved fecal exfoliated cell enrichment method and its application in colorectal cancer screening. Material and Methods: Samples were collected from a cohort of 100 colorectal cancer patients being treated at the First Hospital of Hebei Medical University from January 2021 to June 2022. Patient samples were equally divided between control and experimental groups corresponding to the enrichment method being applied to the fecal exfoliated cells. Samples consisted of natural stool and bowel cleansing enema solution samples. The control group received the traditional three-layer integrated screen method, and the experimental group used nano-Fe3O4 folic acid magnetic beads to enrich the fecal exfoliated cells. The morphology of the extracted cells was observed by light microscopy through hematoxylin and eosin staining, and the positive rate of fecal occult blood test (FOBT) and the detection rate of colorectal cancer was compared between the two groups. Results: The FOBT-positive rates of natural feces and intestinal cleansing liquid in the control group were 74.00% and 90.00%, respectively, and the FOBT-positive rates of natural feces and intestinal cleansing liquid in the experimental group were 76.00% and 92.00%, respectively. The positive FOBT rate was high, and the difference was statistically significant (P = 0.037 and P = 0.029). The sensitivities of natural fecal exfoliation cytology in the control and experimental groups were 82.00% and 92.00%, respectively. The sensitivity of the experimental group was higher than that of the control group, and the difference was not statistically significant (P = 0.137). The sensitivities of the exfoliated cytology examination of the intestinal cleansing liquid in the control and experimental groups were 88.00% and 98.00%, respectively. The sensitivity of the experimental group was significantly higher than that of the control group, and the difference was statistically significant (P = 0.050). Cell smear results show that the exfoliated cells collected by the three-layer integrated sieve method are unevenly distributed, with overlapping cells and a large number of impurities blurring the background, seriously affecting the observation of cell morphology. The cell structure is blurred, stained unevenly, and arranged in a disorderly manner. The exfoliated cells collected by the nanofolic acid magnetic bead enrichment method are relatively evenly distributed, with no overlapping of cells in patches. The background is clear, and the morphology of each cell can be clearly observed. The cell structure is relatively clear, stained evenly, and distributed evenly. Conclusion: In the cytological examination of fecal exfoliation of colorectal cancer, the nano-Fe3O4 folic acid magnetic bead enrichment method can enrich more target cells compared with the traditional three-layer integrated screen method, improve the detection rate of colorectal cancer, and ensure the exfoliation The cell smears are of higher quality, providing a better sample for clinical assessment of the exfoliated cells. Nano-Fe3O4 folic acid magnetic beads enrichment method can become a simple, efficient, and relatively safe screening method for colorectal cancer, positively affecting early screening developments and diagnosis of colorectal cancer.

A syrup containing L-arabinose and D-xylose appears superior to PEG-4000 as a bowel cleansing agent.

Adequate bowel cleansing is crucial for endoscopic diagnosis and treatment, and the recovery of gut microbiota after intestinal cleansing is also important. A hypertonic syrup predominantly comprising L-arabinose and D-xylose (20% xylo-oligosaccharides) can be extracted from the hemicellulose of corn husks and cobs. L-Arabinose and xylo-oligosaccharides have been reported to relieve constipation and improve the gut microbial environment. This study evaluated the bowel cleansing effect of the aforementioned syrup and its influence on the organism and intestinal microbiota after cleansing in comparison with polyethylene glycol-4000 (PEG-4000) in mice. Bowel cleansing was performed using syrup or PEG-4000 in C57BL/6J mice, and the effect of intestinal preparation and its influence on serum electrolytes and gut microbiota after bowel cleansing were evaluated. The volume of intestinal residual feces in the syrup group was significantly lower than that in the PEG-4000 group. Additionally, syrup disturbed serum electrolytes more mildly than PEG-4000. Alpha diversity in the gut microbiota was significantly higher in the syrup group than in the PEG-4000 group on the first day after bowel cleansing. However, no difference in beta diversity was observed between the two groups. Syrup increased the abundance of Bifidobacteria and Christensenella and decreased the abundance of Akkermansia in comparison with PEG-4000 on the first day after bowel cleansing. Thus, this syrup has potential clinical use as a bowel cleansing agent given the above effects, its benefits and safety, and better taste and acceptability.

Autophagy inhibition mediated via an injectable and NO-releasing hydrogel for amplifying the antitumor efficacy of mild magnetic hyperthermia.

While mild hyperthermia holds great potential in the treatment of solid tumors, the thermal stress-triggered self-repairing autophagy significantly compromises its efficacy. To circumvent this obstacle, an injectable hydrogel (NO-Gel) composed of thermosensitive poly(ethylene glycol)-polypeptide copolymers modified with abundant NO donors on their side chains is developed. Meanwhile, ferrimagnetic Zn0.5Fe2.5O4 magnetic nanoparticles (MNPs) with high magnetic-heat conversion efficiency are synthesized and loaded into NO-Gel to obtain MNPs@NO-Gel. The MNPs@NO-Gel system exhibits a sol-gel transition upon heating, and has the ability to perform multiple magnetic hyperthermia therapy (MHT) after only one administration due to the even distribution and strong immobilization of MNPs in NO-Gel. NO can be continuously liberated from NO-Gel and this process is markedly accelerated by MHT. Additionally, MNPs@NO-Gel maintains its integrity in vivo for over one month and the released MNPs are metabolized by the spleen. After a single administration of MNPs@NO-Gel at the tumor site, three mild MHT treatments with similar effects are fulfilled, and the sufficient supply of NO effectively inhibits MHT-induced autophagic flux via blocking the formation of autophagosomes and synchronously destroying lysosomes, thereby substantially boosting the efficacy of mild MHT. As a consequence, CT-26 colon tumors are completely eliminated without causing severe side-effects.

A Carbamoyl Oxime-Based Highly Specific Fluorescent Chemodosimeter for Monitoring Labile Fe2+ in Food and Living Organisms.

Iron is an essential element in the composition of living organisms and plays a crucial role in a wide range of biological activities. The human body primarily obtains essential iron through the consumption of food. Therefore, it is vital for the health of human body to maintain iron homeostasis. The reducing character of the cellular microenvironment enables Fe2+ to occupy a dominant position within the cell. Hence, there is an urgent need for a simple and sensitive tool that can detect a large amount of Fe2+ in organisms. In this work, a highly specific fluorescent chemodosimeter NPCO ("NP" represents the naphthalimide fluorophore, and "CO" represents the carbamoyl oxime structure) for the detection of Fe2+ with excellent sensitivity (LOD = 82 nM) was constructed by incorporating a novel carbamoyl oxime structure as the recognition group. NPCO can be effectively employed for the detection of Fe2+ in food samples, living cells, and zebrafish. Furthermore, by using soybean sprouts as a model plant, the application of NPCO was expanded to detect Fe2+ in plants. Therefore, NPCO could be used as an excellent assay tool for detecting Fe2+ in organisms and is expected to be an important aid in exploring the mechanism of iron regulation.

Unlocking the crucial role of cancer-associated fibroblasts in tumor metastasis: Mechanisms and therapeutic prospects.

BACKGROUND: Tumor metastasis represents a stepwise progression and stands as a principal determinant of unfavorable prognoses among cancer patients. Consequently, an in-depth exploration of its mechanisms holds paramount clinical significance. Cancer-associated fibroblasts (CAFs), constituting the most abundant stromal cell population within the tumor microenvironment (TME), have garnered robust evidence support for their pivotal regulatory roles in tumor metastasis. AIM OF REVIEW: This review systematically explores the roles of CAFs at eight critical stages of tumorigenic dissemination: 1) extracellular matrix (ECM) remodeling, 2) epithelial-mesenchymal transition (EMT), 3) angiogenesis, 4) tumor metabolism, 5) perivascular migration, 6) immune escape, 7) dormancy, and 8) premetastatic niche (PMN) formation. Additionally, we provide a compendium of extant strategies aimed at targeting CAFs in cancer therapy. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review delineates a structured framework for the interplay between CAFs and tumor metastasis while furnishing insights for the potential therapeutic developments. It contributes to a deeper understanding of cancer metastasis within the TME, facilitating the utilization of CAF-targeting therapies in anti-metastatic approaches.

Highly reversible transition metal migration in superstructure-free Li-rich oxide boosting voltage stability and redox symmetry.

The further practical applications of Li-rich layered oxides are impeded by voltage decay and redox asymmetry, which are closely related to the structural degradation involving irreversible transition metal migration. It has been demonstrated that the superstructure ordering in O2-type materials can effectively suppress voltage decay and redox asymmetry. Herein, we elucidate that the absence of this superstructure ordering arrangement in a Ru-based O2-type oxide can still facilitate the highly reversible transition metal migration. We certify that Ru in superstructure-free O2-type structure can unlock a quite different migration path from Mn in mostly studied cases. The highly reversible migration of Ru helps the cathode maintain the structural robustness, thus realizing terrific capacity retention with neglectable voltage decay and inhibited oxygen redox asymmetry. We untie the knot that the absence of superstructure ordering fails to enable a high-performance Li-rich layered oxide cathode material with suppressed voltage decay and redox asymmetry.