[Determination of 13 perfluorinated and polyfluoroalkyl substances in fishes by QuEChERS-ultra-high performance liquid chromatography-tandem mass spectrometry].

Perfluorinated and polyfluoroalkyl substances (PFASs) are compounds characterized by at least one perfluorinated carbon atom in an alkyl chain linked to side-chain groups. Owing to their unique chemical properties, these compounds are widely used in industrial production and daily life. However, owing to anthropogenic activities, sewage discharge, surface runoff, and atmospheric deposition, PFASs have gradually infiltrated the environment and aquatic resources. With their gradual accumulation in environmental waters, PFASs have been detected in fishes and several fish-feeding species, suggesting that they are bioconcentrated and even amplified in aquatic organisms. PFASs exhibit high intestinal absorption efficiencies, and they bioaccumulate at higher trophic levels in the food chain. They can be bioconcentrated in the human body via food (e. g., fish) and thus threaten human health. Therefore, establishing an efficient analytical technique for use in analyzing PFASs in typical fish samples and providing technical support for the safety regulation and risk assessment of fish products is necessary. In this study, by combining solvent extraction and magnetic dispersion-solid phase extraction (d-SPE), an improved QuEChERS method with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed for the determination of 13 PFASs in fish samples. Fe3O4-TiO2 can be used as an ideal adsorbent in the removal of sample matrix interference and a separation medium for the rapid encapsulation of other solids to be isolated from the solution. Based on the matrix characteristics of the fish products and structural properties of the target PFASs, Fe3O4-TiO2 and N-propyl ethylenediamine (PSA) were employed as adsorbents in dispersive purification. The internal standard method was used in the quantitative analyses of the PFASs. To optimize the sample pretreatment conditions of analyzing PFASs, the selection of the extraction solvent and amounts of Fe3O4-TiO2 and PSA were optimized. Several PFASs contain acidic groups that are non-dissociated in acidic environments, thus favoring their entry into the organic phase. In addition, acidified acetonitrile can denature and precipitate the proteins within the sample matrix, facilitating their removal. Finally, 2% formic acid acetonitrile was used as the extraction solvent, and 20 mg Fe3O4-TiO2, 20 mg PSA and 120 mg anhydrous MgSO4 were used as purification adsorbents. Under the optimized conditions, the developed method exhibited an excellent linearity (R≥0.9973) in the range of 0.01-50 µg/L, and the limits of detection (LODs) and quantification (LOQs) ranged from 0.001-0.023 and 0.003-0.078 µg/L, respectively. The recoveries of the 13 PFASs at low, medium, and high spiked levels (0.5, 10, and 100 µg/kg) were 78.1%-118%, with the intra- and inter-day precisions of 0.2%-11.1% and 0.8%-8.7%, respectively. This method was applied in analyzing real samples, and PFASs including perfluorooctanesulfonic acid, perfluorooctanoic acid, perfluoroundecanoic acid, perfluorododecanoic acid, and perfluorotridecanoic acid, were detected in all 11 samples evaluated. This method is simple, sensitive, and suitable for use in analyzing PFASs in fish samples.

Geniposide alleviates heart failure with preserved ejection fraction in mice by regulating cardiac oxidative stress via MMP2/SIRT1/GSK3ß pathway.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome with cardiac dysfunction, fluid retention and reduced exercise tolerance as the main manifestations. Current treatment of HFpEF is using combined medications of related comorbidities, there is an urgent need for a modest drug to treat HFpEF. Geniposide (GE), an iridoid glycoside extracted from Gardenia Jasminoides, has shown significant efficacy in the treatment of cardiovascular, digestive and central nervous system disorders. In this study we investigated the therapeutic effects of GE on HFpEF experimental models in vivo and in vitro. HFpEF was induced in mice by feeding with HFD and L-NAME (0.5 g/L) in drinking water for 8 weeks, meanwhile the mice were treated with GE (25, 50 mg/kg) every other day. Cardiac echocardiography and exhaustive exercise were performed, blood pressure was measured at the end of treatment, and heart tissue specimens were collected after the mice were euthanized. We showed that GE administration significantly ameliorated cardiac oxidative stress, inflammation, apoptosis, fibrosis and metabolic disturbances in the hearts of HFpEF mice. We demonstrated that GE promoted the transcriptional activation of Nrf2 by targeting MMP2 to affect upstream SIRT1 and downstream GSK3ß, which in turn alleviated the oxidative stress in the hearts of HFpEF mice. In H9c2 cells and HL-1 cells, we showed that treatment with GE (1 µM) significantly alleviated H2O2-induced oxidative stress through the MMP2/SIRT1/GSK3ß pathway. In summary, GE regulates cardiac oxidative stress via MMP2/SIRT1/GSK3ß pathway and reduces cardiac inflammation, apoptosis, fibrosis and metabolic disorders as well as cardiac dysfunction in HFpEF. GE exerts anti-oxidative stress properties by binding to MMP2, inhibiting ROS generation in HFpEF through the SIRT1/Nrf2 signaling pathway. In addition, GE can also affect the inhibition of the downstream MMP2 target GSK3ß, thereby suppressing the inflammatory and apoptotic responses in HFpEF. Taken together, GE alleviates oxidative stress/apoptosis/fibrosis and metabolic disorders as well as HFpEF through the MMP2/SIRT1/GSK3ß signaling pathway.

Aliphatic Hydrosilanes via Nickel-Catalyzed Reductive Csp3-Si Coupling of Primary Alkyl Bromides and Chlorohydrosilanes.

The reductive C-Si coupling of chlorosilanes offers efficient access to organosilanes, but its potential for constructing aliphatic ones remains largely unexplored. This manuscript presents a nickel-catalyzed Csp3-Si coupling reaction of unactivated alkyl-Br and R2Si(H)Cl. This work establishes a new approach for synthesizing highly functionalized aliphatic hydrosilanes from readily available chemical feedstocks. The reaction is easily scalable and can accommodate various functional groups, including carboxylic acids, which are usually incompatible with basic conditions.

Conjugated microporous polymer for solid-phase extraction of neonicotinoid insecticides from environmental water samples.

Conjugated microporous polymers (CMPs) have unique characteristics and have been used in a range of fascinating applications in separation sciences. In this study, a CMP, designated as CMP-1, was synthesized via the Sonogashira-Hagihara coupling reaction using 1,3,5-triphenylbenzene and 1,4-dibromobenzene as building blocks. CMP-1 features a large surface area, abundant micropore structures, and excellent stability, making it a promising solid-phase extraction adsorbent for the efficient enrichment of neonicotinoid insecticides (NEOs). Under the optimized conditions, CMP-1 was combined with high-performance liquid chromatography and diode array detection to enable the detection of NEOs with a wide linear range (0.5-200 µg·L-1), a low detection limit (0.26-0.58 µg·L-1), and acceptable precision. The developed method was applied to determine spiked NEOs in three types of environmental water samples, with recoveries of 73.7%-112.0% and relative standard deviations of 0.6%-9.4%.

[Study on the value of systemic immune inflammation index and nomogram in predicting the prognosis of patients with mucoepidermoid carcinoma].

PURPOSE: To investigate the relationship between preoperative systemic immune-inflammation index (SII) and relapse-free survival (RFS) after surgical resection of mucoepidermoid carcinoma(MEC). METHODS: The data of 135 patients with MEC who underwent surgical resection in the First Affiliated Hospital of Zhengzhou University from January 2016 to July 2019 were collected, and the receiver operating characteristic(ROC) curve was performed on the SII of patients. The optimal cut-off value was obtained by ROC analysis. Therefore, the patients' SII index was divided into high and low group, and survival analysis was performed by Kaplan-Meier method. Cox proportional regression model and least absolute shrinkage and selection operator (LASSO) were used to analyze the factors influencing prognosis, and a nomogram model was built to predict patients' relapse-free survival(RFS). Area under curve (AUC) and correction curve were used to evaluate the model and verify the consistency. RESULTS: Survival analysis showed that the RFS rate in low SII group was significantly higher than that in high SII group. Cox proportional hazard regression model showed high SII(HR=2.179, 95%CI: 1.072-4.426, P=0.031) and low tumor differentiation(HR=6.894, 95%CI: 2.770-17.158, P=0.000) and cervical lymph node metastasis (HR=2.091, 95%CI: 1.034-4.230, P=0.040) were significant predictors of poor RFS. CONCLUSIONS: The lower the preoperative SII, the better the prognosis of patients. The nomogram prognosis of MEC based on SII is effective.

Penicianstinoids F-K, six undescribed meroterpenoids from the marine algicolous fungus Penicillium sp. RR-DL-1-7.

Six previously undescribed meroterpenoids, penicianstinoids F-K (1-6), together with four known analogues, dehydroaustinol (7), dehydroaustin (8), penicianstinoid A (9), and furanoaustinol (10), were isolated from the cultures of the algicolous fungus Penicillium sp. RR-DL-1-7, derived from the red alga Rhodomela confervoides. Their structures and relative configuration were established by detailed spectroscopic analysis of NMR and HR-MS experiments, and the absolute configurations were assigned by X-ray diffraction and ECD spectral analysis. None of the isolates showed obvious growth inhibitory effects against five plankton and four bacteria species tested.

A mechanistic analysis of metformin's biphasic effects on lifespan and healthspan in C. elegans: Elixir in youth, poison in elder.

Aging, a complex biological process influenced by genetic, environmental, and pharmacological factors, presents a significant challenge in understanding its underlying mechanisms. In this study, we explored the divergent impacts of metformin treatment on the lifespan and healthspan of young and old C. elegans, demonstrating a intriguing "elixir in youth, poison in elder" phenomenon. By scrutinizing the gene expression changes in response to metformin in young (day 1 of adulthood) and old (days 8) groups, we identified nhr-57 and C46G7.1 as potential modulators of age-specific responses. Notably, nhr-57 and C46G7.1 exhibit contrasting regulation patterns, being up-regulated in young worms but down-regulated in old counterparts following metformin treatment. Functional studies employing knockdown approaches targeting nhr-57, a gene under the control of hif-1 with a documented protective function against pore-forming toxins in C. elegans, and C46G7.1, unveiled their critical roles in modulating lifespan and healthspan, as well as in mediating the biphasic effects of metformin. Furthermore, deletion of hif-1 retarded the influence of metformin, implicating the involvement of hif-1/nhr-57 in age-specific drug responses. These findings underscored the necessity of deciphering the mechanisms governing age-related susceptibility to pharmacological agents to tailor interventions for promoting successful aging.

Corrigendum to "Nutrient composition and functional constituents of daylily from different producing areas based on widely targeted metabolomics" [Food Chemistry: X Nutrient composition and functional constituents of daylily from different producing areas based on widely targeted metabolomics 21 (2024) 101239/FOCHX-D-23-01093].

[This corrects the article DOI: 10.1016/j.fochx.2024.101239.].

Association between frailty and acute kidney injury after cardiac surgery: unraveling the moderation effect of body fat through an international, retrospective, multi-cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication after cardiac surgery that significantly affects patient outcomes. Given the limited treatment options available, identifying modifiable risk factors is critical. Frailty and obesity, two heterogeneous physiological states, have significant implications for identifying and preventing AKI. Our study investigated the interplay among frailty, body composition, and AKI risk after cardiac surgery to inform patient management strategies. MATERIAL AND METHODS: This retrospective cohort study included three international cohorts. Primary analysis was conducted in adult patients who underwent cardiac surgery between 2014 and 2019 at Wuhan XX Hospital, China. We tested the generalizability of our findings with data from two independent international cohorts, the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU Collaborative Research Database. Frailty was assessed using a clinical lab-based frailty index (FI-LAB), while total body fat percentage (BF%) was calculated based on a formula accounting for BMI, sex, and age. Logistic regression models were used to analyze the associations between frailty, body fat, and AKI, adjusting for pertinent covariates. RESULTS: A total of 8785 patients across three international cohorts were included in the study. In the primary analysis of 3,569 patients from Wuhan XX Hospital, moderate and severe frailty were associated with an increased AKI risk after cardiac surgery. Moreover, a nonlinear relationship was observed between body fat percentage and AKI risk. When stratified by the degree of frailty, lower body fat correlated with a decreased incidence of AKI. Extended analyses using the MIMIC-IV and eICU cohorts (n=3,951 and n=1,265, respectively) validated these findings and demonstrated that a lower total BF% was associated with decreased AKI incidence. Moderation analysis revealed that the effect of frailty on AKI risk was moderated by the body fat percentage. Sensitivity analyses demonstrated results consistent with the main analyses. CONCLUSION: Higher degrees of frailty were associated with an elevated risk of AKI following cardiac surgery, and total BF% moderated this relationship. This research underscores the significance of integrating frailty and body fat assessments into routine cardiovascular care to identify high-risk patients for AKI and implement personalized interventions to improve patient outcomes.

Abnormal HCK/glutamine/autophagy axis promotes endometriosis development by impairing macrophage phagocytosis.

The presence of extensive infiltrated macrophages with impaired phagocytosis is widely recognised as a significant regulator for the development of endometriosis (EMs). Nevertheless, the metabolic characteristics and the fundamental mechanism of impaired macrophage phagocytosis are yet to be clarified. Here, we observe that there is the decreased expression of haematopoietic cellular kinase (HCK) in macrophage of peritoneal fluid from EMs patients, which might be attributed to high oestrogen and hypoxia condition. Of note, HCK deficiency resulted in impaired macrophage phagocytosis, and increased number and weight of ectopic lesions in vitro and in vivo. Mechanistically, this process was mediated via regulation of glutamine metabolism, and further upregulation of macrophage autophagy in a c-FOS/c-JUN dependent manner. Additionally, macrophages of EMs patients displayed insufficient HCK, excessive autophagy and phagocytosis dysfunction. In therapeutic studies, supplementation with glutamine-pre-treated macrophage or Bafilomycin A1 (an autophagy inhibitor)-pre-treated macrophage leads to the induction of macrophage phagocytosis and suppression of EMs development. This observation reveals that the aberrant HCK-glutamine-autophagy axis results in phagocytosis obstacle of macrophage and further increase the development risk of Ems. Additionally, it offers potential therapeutic approaches to prevent EMs, especially patients with insufficient HCK and macrophage phagocytosis dysfunction.

The Applicability of Polyetheretherketone and Titanium Mesh in Cranioplasty: A Retrospective Comparative Analysis.

OBJECTIVE: To compare the clinical application effect and safety of polyetheretherketone (PEEK) and titanium mesh (TM) in cranioplasty. METHODS: Four-year retrospective comparison of patients (96 cases) undergoing synthetic cranioplasty with PEEK or TM. The patients were divided into the PEEK group (24 cases) and the TM group (72 cases) according to the implants, and the patient demographics, general conditions before the operation, postoperative complications, length of postoperative hospital stay, total costs, satisfaction with shaping and long-term complications were compared between the 2 groups. RESULTS: Patients in the PEEK group were younger than those in the TM group (P=0.019). Hospitalization costs were significantly higher in the PEEK group than in the TM group (P<0.001). The incidence of postoperative subcutaneous effusion was 33% in the PEEK group and 6.9% in the TM group, which suggests that patients in the PEEK group had a higher risk of postoperative subcutaneous effusion (P=0.001). There was no significant difference in the incidence of long-term complications and cosmetic satisfaction between the 2 groups at 4 years postoperatively. CONCLUSIONS: In this study, both titanium mesh and PEEK are reliable implants for cranioplasty. Titanium mesh is widely used in cranioplasty due to its cost-effective performance. PEEK has gradually gained recognition due to the characteristics of the material and surgical procedure, but the price needs to be further reduced, and attention should be paid to the occurrence and treatment of early postoperative subcutaneous effusion.

The incidence, risk factors, and prognosis of acute kidney injury in patients after cardiac surgery.

Background: Acute kidney injury (AKI) represents a significant complication following cardiac surgery, associated with increased morbidity and mortality rates. Despite its clinical importance, there is a lack of universally applicable and reliable methods for the early identification and diagnosis of AKI. This study aimed to examine the incidence of AKI after cardiac surgery, identify associated risk factors, and evaluate the prognosis of patients with AKI. Method: This retrospective study included adult patients who underwent cardiac surgery at Changhai Hospital between January 7, 2021, and December 31, 2021. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Perioperative data were retrospectively obtained from electronic health records. Logistic regression analyses were used to identify independent risk factors for AKI. The 30-day survival was assessed using the Kaplan-Meier method, and differences between survival curves for different AKI severity levels were compared using the log-rank test. Results: Postoperative AKI occurred in 257 patients (29.6%), categorized as stage 1 (179 patients, 20.6%), stage 2 (39 patients, 4.5%), and stage 3 (39 patients, 4.5%). The key independent risk factors for AKI included increased mean platelet volume (MPV) and the volume of intraoperative cryoprecipitate transfusions. The 30-day mortality rate was 3.2%. Kaplan-Meier analysis showed a lower survival rate in the AKI group (89.1%) compared to the non-AKI group (100%, P < 0.001). Conclusion: AKI was notably prevalent following cardiac surgery in this study, significantly impacting survival rates. Notably, MPV and administration of cryoprecipitate may have new considerable predictive significance. Proactive identification and management of high-risk individuals are essential for reducing postoperative complications and mortality.

Metformin-Induced Invertase Unfolding: Enzyme Kinetics and Activity Regulation.

The effects of metformin on invertase activity and its inhibition on sucrose digestion were studied. The rapid unfolding kinetics of invertases, followed a two-state model with an inactive intermediate formation. The dynamic interaction between metformin and invertase caused the secondary structure of the enzyme to become less ß-sheet, more α-helix, and random coiling oriented, which weakened the binding force between enzyme and its substrate. Metformin acted as a chaotrope and disrupted the hydrogen bonds of water, which facilitated the unfolding of invertase. However, some sugar alcohols, which promoted the H-bond formation of water, could repair the secondary structure of metformin-denatured invertase and therefore regulate the enzyme activity. This research enriches our understanding of the mechanism of enzyme unfolding induced by guanidine compounds. Moreover, because metformin and sugar substitutes are of concern to diabetes, this research also provides useful information for understanding the activity of the digestive enzyme that coexists with metformin and sugar alcohols.

NIR Light and GSH Dual-Responsive Upconversion Nanoparticles Loaded with Multifunctional Platinum(IV) Prodrug and RGD Peptide for Precise Cancer Therapy.

Platinum(II) drugs as a first-line anticancer reagent are limited by side effects and drug resistance. Stimuli-responsive nanosystems hold promise for precise spatiotemporal manipulation of drug delivery, with the aim to promote bioavailability and minimize side effects. Herein, a multitargeting octahedral platinum(IV) prodrug with octadecyl aliphatic chain and histone deacetylase inhibitor (phenylbutyric acid, PHB) at axial positions to improve the therapeutic effect of cisplatin was loaded on the upconversion nanoparticles (UCNPs) through hydrophobic interaction. Followed attachment of DSPE-PEG2000 and arginine-glycine-aspartic (RGD) peptide endowed the nanovehicles with high biocompatibility and tumor specificity. The fabricated nanoparticles (UCNP/Pt(IV)-RGD) can be triggered by upconversion luminescence (UCL) irradiation and glutathione (GSH) reduction to controllably release Pt(II) species and PHB, inducing profound cytotoxicity. Both in vitro and in vivo experiments demonstrated that UCNP/Pt(IV)-RGD exhibited remarkable antitumor efficiency, high tumor-targeting specificity, and real-time UCL imaging capacity, presenting an intelligent platinum(IV) prodrug-loaded nanovehicle for UCL-guided dual-stimuli-responsive combination therapy.

Replacement of sedentary behavior with various physical activities and the risk of incident depression: a prospective analysis of accelerator-measured and self-reported UK Biobank data.

PURPOSE: To examine the dose‒response relationships of sedentary behavior (SB) and physical activities (PAs) with depression, and to explore the effects of replacing SB with PAs on depression risk. METHODS: The study used data from UK Biobank aged 37 to 73 years. Light physical activity (LPA), moderate-to-vigorous activity (MVPA), sleep duration, and total sedentary behavior (TSB) were measured by accelerometers. Self-reported SB was also adopted when daily screen-sedentary behavior time (SSB) and leisure-sedentary behavior time (LSB) were the focus. Incident depression was obtained from the part of mental and behavioral disorders in the "first occurrence fields" of UK Biobank. A Cox proportional hazard model and isotemporal substitution model were performed to explore the associations of LPA, MVPA, TSB, LSB, SSB, and sleep on depression and the effects of replacing SB time with equal PA time. RESULTS: Highest levels of MVPA (HR = 0.58, 95%CI: 0.50-0.68) were associated with decreased depression risk compared with the lowest level (Q1). Longer SSB time (HR = 1.18, 95%CI: 1.06-1.32), LSB time (HR = 1.19, 95%CI: 1.07-1.32), and TSB time (HR = 1.17, 95%CI: 1.00-1.38) could increase depression risk significantly. Replacing 1h/day TSB, SSB, and LSB with MVPA brought the greatest risk reductions [31% (HR = 0.69, 95%CI: 0.62-0.77), 30% (HR = 0.70, 95%CI: 0.65-0.77), and 29% (HR = 0.71, 95%CI: 0.65-0.77)]. Under the same conditions, the effects of LPA replacement were also significant, but weaker than those of MVPA. Subgroup analyses showed that replacing 1h/d TSB with LPA could significantly decrease the depression risk for the females, but not for the males. CONCLUSION: Large benefits for reducing the risk of incident depression could be attained by replacing a period of TSB, SSB, or LSB with equal PA time, especially for MVPA. Regular PA and less SB were recommended for improving mental health.

Aflatoxin B1 decreased flesh flavor and inhibited muscle development in grass carp (Ctenopharyngodon idella).

In nature, aflatoxins, especially aflatoxin B1 (AFB1), are the common mycotoxins, which cause serious health problems for humans and animals. This paper aimed to study the effects of AFB1 on flesh flavor and muscle development of grass carp (Ctenopharyngodon idella) and its mechanism. There were 1440 individual fish in total, with 6 treatments and each treatment replicated 3 times. The 6 treatments were fed a control diet with different doses of AFB1 (0.04, 29.48, 58.66, 85.94, 110.43 and 146.92 µg/kg diet) for 60 d. AFB1 increased myofiber diameter, as well as decreased myofiber density of grass carp muscle (P < 0.05). The contents of free amino acid decreased gradually (P < 0.05) as dietary AFB1 increased in the muscle of grass carp. The levels of reactive oxygen species, malonaldehyde and protein carbonyl (PC) were increased (P < 0.05) with the dietary AFB1 increased. The levels of antioxidant enzyme (glutathione peroxidase, glutathione, glutathione reductase, total antioxidant capacity, anti-superoxide anion, and anti-hydroxyl radical) were decreased (P < 0.05) with the dietary AFB1 increased. In addition, dietary AFB1 decreased the content of collagen, and downregulated the mRNA and protein levels of transforming growth factor-ß (TGF-ß)/Smads signaling pathway in grass carp muscle (P < 0.05). The mRNA and protein levels of myogenic regulatory factors were downregulated in grass carp muscle (P < 0.05). Furthermore, the activities of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were increased (P < 0.05), and the protein levels of phosphorylate-38 mitogen-activated protein kinase (p-p38MAPK), phosphorylate-c-Jun N-terminal kinase, urokinase-type plasminogen activator (uPA), MMP-2 and MMP-9 were upregulated (P < 0.05), but collagen Ⅰ, laminin ß1 and fibronectin were downregulated (P < 0.05) with the dietary AFB1 increased in the muscle of grass carp. Based on the results of this study, we can draw the following conclusion: dietary AFB1 might damage flesh flavor and inhibit the muscle development through MAPK/uPA/MMP/extracellular matrix (ECM) signaling pathway in grass carp. Moreover, the recommended safe limit of AFB1 in feed is no more than 26.77 µg/kg diet according to the PC levels in grass carp muscle.

Prenylated Acetophenone Derivatives from the Leaves of Acronychia pedunculata and Their Anti-proliferative Activities.

Four new prenylated acetophenone derivatives, including one acetophenone dimer [acronyrone D (1)] and three acetophenone monomers [acronyrones E-G (2-4)], along with seven known analogues (5-11) were obtained from the leaves of Acronychia pedunculata. Their structures and absolute configurations were established by analysis of HRMS and NMR data, single crystal X-ray diffraction studies and quantum chemical calculations. In addition, the isolates were tested for their anti-proliferative acivity against HCT-116, RKO and SW480 cancer cell lines. Remarkably, compound 5 exhibited significant anti-proliferative effects on the three cell lines, with IC50 values ranging from 0.24 to 5.3 µM.

[Risk Assessment of Antibiotics in Agricultural Environment].

Antibiotics are widely used in animal husbandry, planting, and aquaculture in agricultural industries. A large amount of the parent antibiotics used are released into the environment through discharge via feces and urine, posing potential risks to human health and ecosystems. It is thus very important to understand how antibiotics in the agricultural environment threaten the ecological environment and human health. Accordingly, risk assessment of antibiotics in the environment has become the research focus in recent years. The aim of this study was to review the risk assessment methods of antibiotics. The results showed that the ecological environment risk has mainly been assessed by the risk quotient (RQ). Predicted no-impact concentrations (PNECs) are an important indicator for ecological environment risk assessment, but a definite value is still controversial. The hazard quotient (HQ) is generally used to assess health risks. At present, it is necessary to clarify the selection of antibiotic exposure pathways and toxicological thresholds. However, neither of these two methods have currently considered either mixed pollution or the risk of antibiotic metabolites. Further analysis indicated that the ecological risks of antibiotics in the water environment and feces/manure/soil environment were widespread, which had an impact on both the soil and water environment. The types of antibiotics with high risk were different for various cultivated types. The factors including test species, testing conditions, calculation methods, and soil types all affected the detection of PNECs. Human health risk caused by dietary intake of antibiotics was minimal, but it cannot be ignored given the seafood consumption in coastal areas. Moreover, quinolones have both high ecological and human health risks in the agricultural environment. Based on the amount of antibiotics in agriculture and the residual concentration or toxicity of antibiotics in the related environment, this study proposed a priority-control list of antibiotics in the agricultural environment and summarized the main problems in the current antibiotic risk assessment. It will provide helpful support for the scientific optimization of antibiotic risk assessment and the effective control of antibiotics in agricultural environments.

Dual-Mechanism Peptide SR25 has Broad Antimicrobial Activity and Potential Application for Healing Bacteria-infected Diabetic Wounds.

The rise of antibiotic resistance poses a significant public health crisis, particularly due to limited antimicrobial options for the treatment of infections with Gram-negative pathogens. Here, an antimicrobial peptide (AMP) SR25 is characterized, which effectively kills both Gram-negative and Gram-positive bacteria through a unique dual-targeting mechanism without detectable resistance. Meanwhile, an SR25-functionalized hydrogel is developed for the efficient treatment of infected diabetic wounds. SR25 is obtained through genome mining from an uncultured bovine enteric actinomycete named Nonomuraea Jilinensis sp. nov. Investigations reveal that SR25 has two independent cellular targets, disrupting bacterial membrane integrity and restraining the activity of succinate:quinone oxidoreductase (SQR). In a diabetic mice wound infection model, the SR25-incorporated hydrogel exhibits high efficacy against mixed infections of Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA), accelerating wound healing. Overall, these findings demonstrate the therapeutic potential of SR25 and highlight the value of mining drugs with multiple mechanisms from uncultured animal commensals for combating challenging bacterial pathogens.

A Tumor-Targeting Dual-Modal imaging probe for nitroreductase in vivo.

Nitroreductase (NTR) overexpression often occurs in tumors, highlighting the significance of effective NTR detection. Despite the utilization of various optical methods for this purpose, the absence of an efficient tumor-targeting optical probe for NTR detection remains a challenge. In this research, a novel tumor-targeting probe (Cy-Bio-NO2) is developed to perform dual-modal NTR detection using near-infrared fluorescence and photoacoustic techniques. This probe exhibits exceptional sensitivity and selectivity to NTR. Upon the reaction with NTR, Cy-Bio-NO2 demonstrates a distinct fluorescence "off-on" response at 800 nm, with an impressive detection limit of 12 ng/mL. Furthermore, the probe shows on-off photoacoustic signal with NTR. Cy-Bio-NO2 has been successfully employed for dual-modal NTR detection in living cells, specifically targeting biotin receptor-positive cancer cells for imaging purposes. Notably, this probe effectively detects tumor hypoxia through dual-modal imaging in tumor-bearing mice. The strategy of biotin incorporation markedly enhances the probe's tumor-targeting capability, facilitating its engagement in dual-modal imaging at tumor sites. This imaging capacity holds substantial promise as an accurate tool for cancer diagnosis.