Deciphering the Performance Enhancement, Cell Failure Mechanism, and Amelioration Strategy of Sodium Storage in Metal Chalcogenides-Based Andes.

Transition metal chalcogenides (TMCs) emerge as promising anode materials for sodium-ion batteries (SIBs), heralding a new era of energy storage solutions. Despite their potential, the mechanisms underlying their performance enhancement and susceptibility to failure in ether-based electrolytes remain elusive. This study delves into these aspects, employing CoS2 electrodes as a case in point to elucidate the phenomena. The investigation reveals that CoS2 undergoes a unique irreversible and progressive solid-liquid-solid phase transition from its native state to sodium polysulfides (NaPSs), and ultimately to a Cu1.8S/Co composite, accompanied by a gradual morphological transformation from microspheres to a stable 3D porous architecture. This reconstructed 3D porous structure is pivotal for its exceptional Na+ diffusion kinetics and resilience to cycling-induced stress, being the main reason for ultrastable cycling and ultrahigh rate capability. Nonetheless, the CoS2 electrode suffers from an inevitable cycle life termination due to the microshort-circuit induced by Na metal corrosion and separator degradation. Through a comparative analysis of various TMCs, a predictive framework linking electrode longevity is established to electrode potential and Gibbs free energy. Finally, the cell failure issue is significantly mitigated at a material level (graphene encapsulation) and cell level (polypropylene membrane incorporation) by alleviating the NaPSs shuttling and microshort-circuit.

Effects of Virtual Reality Therapy Combined With Conventional Rehabilitation on Pain, Kinematic Function, and Disability in Patients With Chronic Neck Pain: Randomized Controlled Trial.

BACKGROUND: Neck pain is a common condition that leads to neck motor dysfunction and subsequent disability, with a significant global health care burden. As a newly emerging tool, virtual reality (VR) technology has been employed to address pain and reduce disability among patients with neck pain. However, there is still a lack of high-quality studies evaluating the efficacy of VR therapy combined with conventional rehabilitation for patients with chronic neck pain, particularly in terms of kinematic function. OBJECTIVE: This study aims to investigate the effect of VR therapy combined with conventional rehabilitation on pain, kinematic function, and disability in patients with chronic neck pain. METHODS: We conducted an assessor-blinded, allocation-concealed randomized controlled trial. Sixty-four participants experiencing chronic neck pain were randomly allocated into the experimental group that underwent VR rehabilitation plus conventional rehabilitation or the control group receiving the same amount of conventional rehabilitation alone for 10 sessions over 4 weeks. Pain intensity, disability, kinematic function (cervical range of motion, proprioception, and mean and peak velocity), degree of satisfaction, and relief of symptoms were evaluated at 3 timepoints (baseline, postintervention, and at 3 months follow-up). A 2*3 mixed repeated measures analysis of variance was utilized for analyzing the difference across indicators, with a significant difference level of .05. RESULTS: Both groups demonstrated significant improvements in pain, disability, and kinematic functions (P<.05) at postintervention and at 3-month follow-up. The experimental group showed superior therapeutic outcomes compared to the control group in pain reduction (mean difference from the baseline: 5.50 vs 1.81 at posttreatment; 5.21 vs 1.91 at the 3-month follow-up, respectively; P<.001), disability improvement (mean difference from baseline: 3.04 vs 0.50 at posttreatment; 3.20 vs 0.85 at the 3-month follow-up, respectively; P<.001), and enhanced kinematic functions (P<.05). Moreover, participants in the experimental group reported better satisfaction and relief of symptoms than the control group (P<.05), with better initiative for exercising during the follow-up period. However, there was no between-group difference of improvement in proprioception. No adverse events were reported or observed in our research. CONCLUSIONS: The findings of our study support the efficacy of combining VR therapy with conventional rehabilitation in alleviating pain, enhancing kinematic function, and reducing disability of patients with chronic neck pain. Future research should focus on refining the therapeutic protocols and dosages for VR therapy as well as on optimizing its application in clinical settings for improved convenience and effectiveness. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000040132; http://www.chictr.org.cn/showproj.aspx?proj=64346.

Dietary Galacto-oligosaccharides Ameliorate Atopic Dermatitis-like Skin Inflammation and Behavioral Deficits by Modulating Gut Microbiota-Brain-Skin Axis.

Atopic dermatitis (AD), a chronic, highly pruritic, and inflammatory skin disorder, often coexists with psychiatric comorbidities including anxiety and depression, posing considerable challenges for treatment. The current research aims at evaluating the efficacy and potential therapeutic mechanism of galacto-oligosaccharides (GOS) on AD-like skin lesions and comorbid anxiety/depressive disorders. Macroscopical and histopathological examination showed that GOS could markedly relieve skin inflammation by decreasing the production of IgE, IL-4, IL-13, IFN-γ, and TNF-α and regulating the PPAR-γ/NF-κB signaling in DNFB-induced AD mice. Moreover, GOS significantly improved the anxiety- and depressive-like symptoms as mirrored by the behavior tests including FST, TST, OFT, and EZM through normalizing the neurotransmitter levels of 5-HT, DA, NE, and CORT in the brain. Mechanistically, by virtue of the high-throughput 16S rRNA gene sequencing and GC-MS techniques, GOS restructured the gut microbiota and specifically induced the proliferation of Lactobacillus and Alloprevotella, leading to an increase in the total content of fecal SCFAs, in particular acetate and butyrate. Pearson correlation analysis found a marked correlation among the altered gut microbiota/SCFAs, AD-associated skin manifestations, and comorbid behavioral phenotypes. Collectively, this work highlights that GOS is a promising strategy against both AD and associated depressive symptoms by modulating the gut microbiota-brain-skin axis.

Application of Patient-Based Real-Time Quality Control Based on Artificial Intelligence Monitoring Platform in Continuously Quality Risk Monitoring of Down Syndrome Serum Screening.

BACKGROUND: Patient-based real-time quality control (PBRTQC) has gained attention because of its potential to continuously monitor the analytical quality in situations wherein internal quality control (IQC) is less effective. Therefore, we tried to investigate the application of PBRTQC method based on an artificial intelligence monitoring (AI-MA) platform in quality risk monitoring of Down syndrome (DS) serum screening. METHODS: The DS serum screening item determination data and relative IQC data from January 4 to September 7 in 2021 were collected. Then, PBRTQC exponentially weighted moving average (EWMA) and moving average (MA) procedures were built and optimized in the AI-MA platform. The efficiency of the EWMA and MA procedures with intelligent and traditional control rules were compared. Next, the optimal EWMA procedures that contributed to the quality assurance of serum screening were run and generated early warning cases were investigated. RESULTS: Optimal EWMA and MA procedures on the AI-MA platform were built. Comparison results showed the EWMA procedure with intelligent QC rules but not traditional quality rules contained the best efficiency. Based on the AI-MA platform, two early warning cases were generated by using the optimal EWMA procedure, which finally found were caused by instrument failure. Moreover, the EWMA procedure could truly reflect the detection accuracy and quality in situations wherein traditional IQC products were unstable or concentrations were inappropriate. CONCLUSIONS: The EWMA procedure built by the AI-MA platform could be a good complementary control tool for the DS serum screening by truly and timely reflecting the detection quality risks.

Androgen signaling inhibits de novo lipogenesis to alleviate lipid deposition in zebrafish.

Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in males. However, the mechanisms by which testosterone acts on lipid metabolism are not yet fully understood, especially in teleosts. In this study, cyp17a1-/- zebrafish ( Danio rerio) exhibited excessive visceral adipose tissue (VAT), lipid content, and up-regulated expression and activity of hepatic de novo lipogenesis (DNL) enzymes. The assay for transposase accessible chromatin with sequencing (ATAC-seq) results demonstrated that chromatin accessibility of DNL genes was increased in cyp17a1-/- fish compared to cyp17a1+/+ male fish, including stearoyl-CoA desaturase ( scd) and fatty acid synthase ( fasn). Androgen response element (ARE) motifs in the androgen signaling pathway were significantly enriched in cyp17a1+/+ male fish but not in cyp17a1-/- fish. Both androgen receptor ( ar)-/- and wild-type (WT) zebrafish administered with Ar antagonist flutamide displayed excessive visceral adipose tissue, lipid content, and up-regulated expression and activity of hepatic de novo lipogenesis enzymes. The Ar agonist BMS-564929 reduced the content of VAT and lipid content, and down-regulated acetyl-CoA carboxylase a ( acaca), fasn, and scd expression. Mechanistically, the rescue effect of testosterone on cyp17a1-/- fish in terms of phenotypes was abolished when ar was additionally depleted. Collectively, these findings reveal that testosterone inhibits lipid deposition by down-regulating DNL genes via Ar in zebrafish, thus expanding our understanding of the relationship between testosterone and lipid metabolism in teleosts.

Granulation characteristics of anammox sludge in response to different signal-molecule-stimulants; mediated through programmed cell death.

During the anammox process, mitigation of biomass washout to increase sludge retention is an important parameter of process efficiency. Signal molecular stimulants (SMS) initiate the sludge granulations controlled by programmed cell death (PCD) of microorganisms. In this study, the aerobic granular sludge (AGS), cell fragments, extracellular polymeric substances (EPS), and AGS process effluent were tested as SMS to identify their effect on anammox granulation. The results showed that the addition of SMS increased the nitrogen removal efficiency to varying degrees, whereas the addition of AGS process supernatant, as SMS, increased the ammonia removal efficiency up to 96%. The addition of SMS was also found to increase EPS production and contributed to sludge granulation. In this process, the proportion of PCD increased and both Gaiella and Denitratisoma abundance increased from 3.54% to 5.59%, and from 1.8% to 3.42%, respectively. In conclusion, PCD was found important to increase anaerobic ammonia oxidation performance through the granulation mechanism.

Indirect co-culture of osteoblasts and endothelial cells in vitro based on a biomimetic 3D composite hydrogel scaffold to promote the proliferation and differentiation of osteoblasts.

The field of orthopedics has long struggled with the challenge of repairing and regenerating bone defects, which involves a complex process of osteogenesis requiring coordinated interactions among different types of cells. The crucial role of endothelial cells and osteoblasts in bone vascularization and osteogenesis underscores the importance of their intimate interaction. However, efforts to bioengineer bone tissue have been impeded by the difficulty in establishing proper angiogenesis and osteogenesis in tissue structures. This study presents a novel approach to bone tissue engineering, involving a three-dimensional composite hydrogel scaffold composed of sodium alginate microspheres encapsulated in type I collagen. Using this scaffold, a three-dimensional indirect co-culture system was established for osteoblasts and endothelial cells to evaluate the osteogenic differentiation potential of osteoblasts. Results demonstrate that the non-contact co-culture system of endothelial cells and osteoblasts constructed by the composite hydrogel scaffold loaded with microspheres holds promise for bone tissue engineering. The innovative concept of an indirect co-culture system presents exciting prospects for conducting intercellular communication studies and offers a valuable in vitro tissue platform to investigate tissue regeneration.

Circular RNA CircFOXO3 Functions as a Competitive Endogenous RNA for Acid-Sensing Ion Channel Subunit 1 Mediating Oxeiptosis in Nucleus Pulposus.

Oxeiptosis is a reactive oxygen species (ROS)-induced pathway of cell death. The involvement of circular RNAs (circRNAs) has been confirmed in the incidence and progression of intervertebral disc degeneration (IVDD). However, whether oxeiptosis occurs in IVDD and how circRNAs regulate oxeiptosis is still unclear. In this study, we discovered that oxeiptosis could be induced in nucleus pulposus cells (NPCs), and circFOXO3 was significantly upregulated after oxeiptosis induction. Transfection using circFOXO3 small interfering RNA (siRNA) significantly inhibited oxeiptosis in NPCs. Mechanistically, circFOXO3 upregulated acid-sensing ion channel subunit 1 (ASIC1) expression by functioning as a molecular sponge for miR-185-3p and miR-939-5p. Subsequent rescue experiments validated that circFOXO3 could regulate oxeiptosis in NPCs via the miR-185-3p/miR-939-5p-ASIC1 axis. Further research on ASIC1 functions indicated that this regulation was achieved by affecting the Calcium ion (Ca2+) influx mediated by ASIC1. A mouse IVDD model was established, and silencing circFOXO3 in vivo was found to inhibit IVDD development and the activation of the oxeiptosis-related pathway. Overall, circFOXO3 is one of the factors contributing to the progression of IVDD by mediating oxeiptosis.

Parenting behaviors, inhibitory control, and aggression: Moderation by serotonin receptor 2A haplotypes.

Despite the well-established relationship between parenting and child aggression, the mechanisms by which children incur this risk and whether genetic sources contribute to the heterogeneity in their vulnerability are not entirely clear. This study utilized a longitudinal sample of adolescents (n = 1,047, 50.2% females, Mage = 13.32 ± 0.48 years at Time 1) to examine the effects of positive and negative parenting on aggression, as mediated by inhibitory control and moderated by the serotonin receptor 2A (5-HTR2A) haplotype. Mediation analysis revealed that inhibitory control indirectly mediated the link between both positive and negative parenting and overt aggression but not relational aggression. Further, the indirect effect of negative parenting on overt aggression via inhibitory control was moderated by the 5-HTR2A haplotype. Compared to adolescents carrying zero copies of Thymine-Thymine haplotype, those with one copy of Thymine-Thymine haplotype had better inhibitory control when experiencing less negative parenting, which buffers the risk for overt aggression. However, the mediating role of inhibitory control did not hold in the positive parenting model. These findings elucidate the manner by which adolescents with different genetic predispositions develop aggressive behaviors in the context of family and suggest different etiology of overt and relational aggression. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Imaging signs for preoperative diagnosis of dural ossification in patients with thoracic ossification of the ligamentum flavum: a blind, randomized diagnostic accuracy study.

Background: Dural ossification (DO) is the leading cause of surgery-related dural tear in patients with ossification of the ligamentum flavum (OLF). An accurate preoperative diagnosis of DO is conducive to the selection of appropriate surgical methods. Although several imaging signs, such as Banner cloud sign (BCs), tram-track sign (TTs), and comma sign (Cs) have been proposed for the preoperative diagnosis of DO, their diagnostic value has not been well studied. The aim of this study was to explore the diagnostic value of BCs, TTs, and Cs, and provide evidence-based data for their clinical application. Methods: This is a blind, randomized diagnostic study using retrospectively collected data from 102 consecutive patients who were diagnosed with OLF and underwent decompression surgery between January 2018 and June 2019. A total of 8 surgeons with different qualifications were recruited to read these imaging signs to identify the presence of DO. Surgical records were used as the reference standard. Sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve (AUC) were used to evaluate the diagnostic accuracy of each imaging sign and their different combinations. Results: Of the 102 patients, 21 were diagnosed with DO. BCs had a significantly higher diagnostic accuracy than TTs and Cs, with the AUC of 0.704, 0.607, and 0.593, respectively. The specificity of BCs, Cs, TTs, and their combination in diagnosing DO was 91.5%, 92.1%, 68.3%, and 62.2%, respectively. In the combined diagnostic test, the results showed that the combined diagnosis accuracy of BCs and Cs was the highest, and the AUC was 0.738. The combination of BCs, Cs, and TTs increased the sensitivity of diagnosing DO (77.5%), but did not improve the diagnostic accuracy, and the AUC was 0.699. Conclusions: BCs had higher diagnostic accuracy than TTs and Cs. BCs and Cs were highly specific for DO, whereas TTs could be confusing due to their non-specific presentations. The combination of BCs, TTs, and Cs improved the sensitivity of DO diagnosis, but not the specificity and accuracy.

Testosterone synthesis was inhibited in the testis metabolomics of a depression mouse model.

INTRODUCTION: Depression is a common emotional disorder. Previous studies have suggested that depression is associated with the central nervous system. Recent studies have suggested that reduced testosterone level is the core inducement of depression. Testis is the vital organ for the synthesis of testosterone. How does testis mediate depression is still unknown. OBJECTIVES: We adopted a classical depression model of mouse caused through chronic mild stress (CMS). The metabolomics liquid chromatography-mass spectrometry was adopted to analyse the influence of CMS on testis metabolism. Then we confirmed the possible abnormal metabolism of the testis in depression mice by pathway analysis and molecular biological technique. RESULTS: Compared with control mice, 16 differential metabolites were found in CMS mice by multivariate statistical analysis. In comparison with control mice, CMS mice showed higher levels for campesterol, ribitol, citric acid, platelet activating factor, guanosine, cytosine and xanthine and lower levels for docosahexaenoic acid, hippuric acid, creatine, testosterone, dehydroepiandrosterone, progesterone, l-carnitine, acetyl carnitine and propionyl carnitine. The pathway analysis indicated that these differential metabolites are associated with steroid hormone synthesis, purine metabolism and phenylalanine metabolism. In addition, we also first discovered that testicular morphology in depression mice was damaged and steroid hormone synthetases (including steroidogenic acute regulatory protein and P450 cholesterol side chain cleavage) were inhibited. CONCLUSION: These findings may be helpful to parse molecular mechanisms of pathophysiology of depression. It also pointed out the direction to search for potential therapy schedules for male depression and provide novel insights into exploring the pathogenesis of male depression.

M1 macrophage-derived oncostatin M induces osteogenic differentiation of ligamentum flavum cells through the JAK2/STAT3 pathway.

Background: M1 macrophages (Mφs) are involved in osteogenic differentiation of ligamentum flavum (LF) cells and play an important role in heterotopic ossification. However, the mechanism by which M1 Mφs influence osteogenic differentiation of LF cells has not been studied. Methods: The effect of conditioned medium including secretions of M1 Mφs (CM-M1) on LF cells was analyzed by GeneChip profiling and ingenuity pathway analysis (IPA). THP-1 cells were polarized into M1 Mφs and CM-M1 was used to induce LF cells. In addition, LF cells were induced by CM-M1 in the presence of cyclooxygenase 2 (COX-2) inhibitors or oncostatin M (OSM)-neutralizing antibodies. Based on the presence of OSM, knockout of OSMR or GP130 receptors, or addition of the Janus kinase 2 (JAK2) inhibitor AZD1480 or signal transducer and activator of transcription 3 (STAT3) inhibitor Stattic were examined for effects on osteogenic differentiation of LF cells. OSM secretion was quantified by ELISA, while qPCR and western blot were used to evaluate expression of osteogenic genes and receptor and signaling pathway-related proteins, respectively. Results: GeneChip and IPA results indicate that the OSM signaling pathway and its downstream signaling molecules JAK2 and STAT3 are significantly activated. ELISA results indicate that OSM is highly expressed in cells treated with CM-M1 and lowly expressed in cells treated with CM-M1 and a COX-2 inhibitor. Besides, CM-M1 induces osteogenic differentiation of LF cells, which is weakened when COX-2 inhibitors or OSM-neutralizing antibody are added to it. Recombinant OSM could induce osteogenic differentiation of LF cells and upregulate expression of OSMR, GP130, phosphorylated (P)-JAK2, and P-STAT3. Upon knockdown of OSMR or GP130, or the addition of AZD1480 or Stattic, P-JAK2 and P-STAT3 expression were decreased and osteogenic differentiation was reduced. Conclusion: M1 Mφ-derived OSM induces osteogenic differentiation of LF cells and the JAK2/STAT3 signaling pathway plays an important role.

Evaluation of the effects of compound curing agents on the lipid profiles and volatile flavors in Nuodeng ham based on lipidomics and GC-IMS analysis.

Eighteen raw legs were evenly divided into two groups and salted with 100% NaCl and compound curing agent (60% NaCl + 40% KCl + 90 mg/kg NaNO2) to investigate the effect of compound curing agent on lipid metabolites and volatile flavor compounds in Nuodeng ham. The results of UHPLC-QE-MS and GC-IMS combined with multivariate statistical analysis showed that 27 lipid metabolites and 30 characteristic volatile flavor compounds were identified as characteristic markers in different treatment groups. The compound curing agent promoted the release of TG, SQDG, Hex1Cer, and LPC in Nuodeng ham, and accelerated the formation of volatile compounds such as 2-propanone, nonanal-d, gamma-butyrolactone, ethhyl acetate and benzeneacetaldehyde et al. Through correlation analysis, ketones were positively correlated with some PUFAs and negatively correlated with most MUFAs. Processing Nuodeng ham with compound curing agents has a positive effect on improving its quality. These findings provide a scientific theoretical basis for the development and utilization of compound curing agent.

Autocrine motility factor receptor promotes the malignancy of glioblastoma by regulating cell migration and invasion.

OBJECTIVE: One of the important causes of death in cancer patients is malignant metastasis, invasion, and metastasis of tumor cells. Metastasis is also the most basic physiological characteristics and pathogenesis of various tumors. Previously published studies have suggested that autocrine motor factor receptor (AMFR) is the key regulator of tumor cell migration and invasion. Meanwhile, AMFR is highly expressed in esophageal tumors, gastrointestinal tumors, and bladder cancer, and it is also involved in its pathogenesis. However, the role of AMFR in glioblastoma has not been reported. METHODS: In order to study the role of AMFR in the cell migration and invasion of glioblastoma, AMFR was silenced using siRNA and overexpressed using cDNA. Immunoblotting analysis and real-time quantitative polymerase chain reaction (PCR) were employed to assess the expression of AMFR. We conducted wound healing assay, cell migration assay, and tumorsphere formation assay to detect the invasion and metastatic ability of glioblastoma. RESULTS: This study found that the level of AMFR expression was significantly correlated with the malignant degree of glioma tissue in clinic samples. AMFR silencing decreased cell migration and invasion of LN229. Overexpression of AMFR significantly increased cell migration and invasion of U251. CONCLUSION: This study suggests that AMFR could be used as a therapeutic strategy for the clinical treatment of glioblastoma.

Effects of azithromycin exposure during pregnancy at different stages, doses and courses on testicular development in fetal mice.

Azithromycin is a commonly used antibiotic during pregnancy, but some studies have suggested its potential developmental toxicity. Currently, the effects and mechanisms of prenatal azithromycin exposure (PAzE) on fetal testicular development are still unclear. The effects of prenatal exposure to the same drug on fetal testicular development could vary depending on different stages, doses, and courses. Hence, in this study, based on clinical medication characteristics, Kunming mice was administered intragastrically with azithromycin at different stages (mid-/late-pregnancy), doses (50, 100, 200 mg/kg·d), and courses (single-/multi-course). Fetal blood and testicular samples were collected on GD18 for relevant assessments. The results indicated that PAzE led to changes in fetal testicular morphology, reduced cell proliferation, increased apoptosis, and decreased expression of markers related to Leydig cells (Star), Sertoli cells (Wt1), and spermatogonia (Plzf). Further investigation revealed that the effects of PAzE on fetal testicular development were characterized by mid-pregnancy, high dose (clinical dose), and single course having more pronounced effects. Additionally, the TGFß/Smad and Nrf2 signaling pathways may be involved in the changes in fetal testicular development induced by PAzE. In summary, this study confirmed that PAzE influences fetal testicular morphological development and multicellular function. It provided theoretical and experimental evidence for guiding the rational use of azithromycin during pregnancy and further exploring the mechanisms underlying its developmental toxicity on fetal testicles.

Identification of characteristic flavor compounds and small molecule metabolites during the ripening process of Nuodeng ham by GC-IMS, GC-MS combined with metabolomics.

To investigate effects of metabolites and volatile compounds on the quality of Nuodeng ham, gas chromatography-mass spectrometry (GC-MS), ultra-high performance liquid chromatography-Q exactive orbitrap-mass spectrometry (UHPLC-QE-MS), and gas chromatography-ion transfer spectroscopy (GC-IMS) were used to analyze the differences of free fatty acids, small molecule metabolites and volatile compounds of Nuodeng ham at different ripening stages (the first, second and third year sample). 40 free fatty acids were detected. 757 and 300 metabolites were detected in positive and negative ion modes, respectively. 48 differential metabolites (VIP ≥ 1.5, P < 0.05) might important components affecting flavor differences of Nuodeng ham. Metabolic pathways revealed that fermenting-ripening of ham was associated with 31 metabolic pathways, among, 19 pathways were significant (Impact > 0.01, P < 0.05). 58 volatile compounds were identified, combined with PCA and PLS-DA, 15 flavor markers were screened out. These findings provide a scientific basis for further research on the flavor formation mechanism of Nuodeng ham.

A polymeric nanocarrier that eradicates breast cancer stem cells and delivers chemotherapeutic drugs.

BACKGROUND: Drug nanocarriers can markedly reduce the toxicities and side effects of encapsulated chemotherapeutic drugs in the clinic. However, these drug nanocarriers have little effect on eradicating breast cancer stem cells (BCSCs). Although compounds that can inhibit BCSCs have been reported, these compounds are difficult to use as carriers for the widespread delivery of conventional chemotherapeutic drugs. METHODS: Herein, we synthesize a polymeric nanocarrier, hyaluronic acid-block-poly (curcumin-dithiodipropionic acid) (HA-b-PCDA), and explore the use of HA-b-PCDA to simultaneously deliver chemotherapeutic drugs and eradicate BCSCs. RESULTS: Based on molecular docking and molecular dynamics studies, HA-b-PCDA delivers 35 clinical chemotherapeutic drugs. To further verify the drug deliver ability of HA-b-PCDA, doxorubicin, paclitaxel, docetaxel, gemcitabine and camptothecin are employed as model drugs to prepare nanoparticles. These drug-loaded HA-b-PCDA nanoparticles significantly inhibit the proliferation and stemness of BCSC-enriched 4T1 mammospheres. Moreover, doxorubicin-loaded HA-b-PCDA nanoparticles efficiently inhibit tumor growth and eradicate approximately 95% of BCSCs fraction in vivo. Finally, HA-b-PCDA eradicates BCSCs by activating Hippo and inhibiting the JAK2/STAT3 pathway. CONCLUSION: HA-b-PCDA is a polymeric nanocarrier that eradicates BCSCs and potentially delivers numerous clinical chemotherapeutic drugs.

UHPLC-MS/MS-based lipidomics for the evaluation of the relationship between lipid changes and Zn-protoporphyrin formation during Nuodeng ham processing.

The effects of changes in lipids on the formation of Zn-protoporphyrin (ZnPP) during the processing of Nuodeng ham were analyzed using a lipidomics approach based on UHPLC-MS/MS. The Nuodeng ham samples had a strong fluorescence emission peak at 590 nm, and the fluorescence intensity increased with the processing time. Lipid profiles were mainly affected by processing time. A total of 5 lipid classes were detected, of which glycerophospholipids (GP) and glycerolipids (GL) were the most abundant lipids. Fifty differential lipid compounds were screened, which were mainly GP and GL. Correlation analysis showed that 13 differential lipid compounds were significantly positively correlated with ZnPP content, and they contained more linoleic acid and oleic acid branch chains. Meanwhile, all triglycerides (TG) were negatively correlated with heme content, and they were enriched in stearic acid and palmitic acid branch chains. These findings can deepen the understanding of the relationship between ZnPP and lipids.

The food safety assessment of all-female common carp (Cyprinus carpio) (cyp17a1+/-;XX genotype) generated using genome editing technology.

There are several technical challenges and public issues concerning genome editing applications before they become viable in commercial aquaculture. Recently, we developed a novel strategy to generate all-female (AF) common carp, which exhibited a growth advantage over the control carp, using genetic editing through single gene-targeting manipulation. Here, we found that the body weight of the AF common carp was higher by 22.58% than that of the control common carp. Because the genotype of the AF common carp was cyp17a1+/-;XX, the contents of sex steroids were normally synthesized, as they were comparable to that of the control female carp. To evaluate the food safety of the AF carp, Wistar rats were fed a diet containing control female carp (control, C) or all-female (AF) carp at an incorporation rate of 5, 10 and 20% (w/w) for 90 days. Compared with those fed control carp, the rats fed AF common carp exhibited no significant difference in body weight, food intake, feed conversion ratio, hematology, serum biochemistry, urine test, relative organ weight, gross necropsy, and histopathological examination. This is the first food safety assessment of the farmed fish strain cultured using CRISPR/Cas9, which will further advance the fishery development of genome-edited animals.

Zinc attenuates sulfamethoxazole-induced lipotoxicity by reversing sulfamethoxazole-induced mitochondrial dysfunction and lysosome impairment in a freshwater teleost.

Sulfamethoxazole (SMZ) and zinc (Zn) are widespread harmful materials in aquatic ecosystems and cause toxic effects to aquatic animals under their individual exposure. Although they often co-exist in aquatic environments, little is known about their joint effects and mechanism influencing aquatic animals. Herein, SMZ induced mitochondrial and lysosomal dysfunction, inhibited autophagy flux, and induced lipotoxicity. However, SMZ-induced changes of these physiological and metabolic processes above were reversed by Zn exposure, indicating the antagonism between Zn and SMZ. SOD1-knockdown abrogated the reversing effects of Zn on mitochondria dysfunction and autophagy flux blockage induced by SMZ, suggesting that SOD1 was essential for Zn to reverse SMZ-induced mitochondria dysfunction and autophagy impairment. Our further investigation found that Zn regulated STAT3 translocation to lysosomes and mitochondria to attenuate SMZ-induced lipotoxicity, and SOD1 was required for these processes. Mechanistically, STAT3 was associated with ATP6V1 A in a coiled-coil domain-dependent manner, and pS710-STAT3-and pY753-STAT3-independent manners. Moreover, SMZ suppressed autophagic degradation of damaged mitochondria via inhibiting interaction between STAT3 and ATP6V1 A and increasing pS710-STAT3 level; SMZ impaired mitochondrial ß-oxidation via decreasing pY753-STAT3 level and STAT3 mitochondrial localization. Zn reversed these SMZ-induced effects to alleviate SMZ-induced lipotoxicity. Taken together, our data showed that SMZ impaired mitochondrial ß-oxidation and lysosomal acidification via the downregulation of SOD1, leading to lipotoxicity, and that Zn reversed SMZ-induced changes of these important biological processes and attenuated SMZ-induced lipotoxicity. Thus, our study identified previously unidentified mechanisms for the antagonistic mechanisms of Zn and SMZ on aquatic animals, which provided novel insights into the environmental risk assessments of the joint exposure between heavy metals and antibiotics in the aquatic organisms.