Analysis of factors influencing vascular calcification in peritoneal dialysis patients and their impact on long-term prognosis.

BACKGROUND: This study aims to investigate the influencing factors of vascular calcification in peritoneal dialysis (PD) patients and its relationship with long-term prognosis. METHODS: This retrospective cohort study included chronic kidney disease patients undergoing peritoneal dialysis at the Peritoneal Dialysis Center of Beijing Luhu Hospital, Capital Medical University, from January 2019 to March 2019. Demographic and clinical laboratory data, including serum sclerostin (SOST), calcium (Ca), phosphate (P), serum albumin (ALB), and intact parathyroid hormone (iPTH) levels, were collected. Abdominal aortic calcification (AAC) was assessed using abdominal lateral X-ray examination to determine the occurrence of vascular calcification, and patients were divided into the AAC group and Non-AAC group based on the results. RESULTS: A total of 91 patients were included in the study. The AAC group consisted of 46 patients, while the Non-AAC group consisted of 45 patients. The AAC group had significantly older patients compared to the non-AAC group (P < 0.001) and longer dialysis time (P = 0.004). Multivariable logistic regression analysis indicated that risk factors for vascular calcification in PD patients included dialysis time, diabetes, hypertension, and SOST. Kaplan-Meier survival analysis showed that the AAC group had a significantly higher mortality rate than the non-AAC group (χ2 = 35.993, P < 0.001). Multivariable Cox regression analysis revealed that dialysis time, diabetes and AAC were risk factors for all-cause mortality in peritoneal dialysis patients. CONCLUSION: Longer dialysis time, comorbid diabetes, comorbid hypertension, and SOST are risk factors for vascular calcification in PD patients. Additionally, AAC, longer dialysis time, and comorbid diabetes are associated with increased risk of all-cause mortality in peritoneal dialysis patients.

Novel insights into whey protein among Yak, Yellow Cattle, and Cattle-Yak milk.

This study identified characteristic whey proteins from Zhongdian Yak (ZY), Diqing Yellow Cattle (DYC), and Cattle Yak (CY), revealing insights into their potential functions and released peptides. A total of 118 whey proteins were quantified in milk obtained from the three breeds of cattle, including seven characteristic proteins (IGL@ protein, 40S ribosomal protein S9, calreticulin, etc.) in CY milk and two characteristic proteins (RNA helicase and uncharacterized protein (A0A3Q1LFQ2)) in ZY milk. These characteristic proteins are involved in the phagosome and Fc gamma R-mediated phagocytosis pathways, exhibiting immunoprotective activities, verified through molecular docking. Furthermore, the molecular docking results showed five whey proteins (IGL@ protein, rho GDP-dissociation inhibitor 1, small monomeric GTPase, action-like protein 3, and adenylyl cyclase-associated protein) interacted with TLR4 through multiple hydrogen and hydrophobic bonds. Therefore, these proteins may exert immunomodulatory functions by inhibiting TLR4. Meanwhile, whey proteins produced bioactive peptides, such as antioxidant peptides and ACE inhibitory peptides after simulated gastrointestinal digestion (SGID). The whey proteins and bioactive peptides from CY exhibited more types and activities than the ZY and DYC whey proteins. This study provides a theoretical basis for promoting formula milk powder production.

Gondwanan flood basalts linked seismically to plume-induced lithosphere instability.

Delamination of the continental lithospheric mantle is well recorded beneath several continents. However, the fate of the removed continental lithosphere has been rarely noted, unlike subducted slabs reasonably well imaged in the upper and mid mantle. Beneath former Gondwana, recent seismic tomographic models indicate the presence of at least 5 horizontal fast-wavespeed anomalies at ~600 km depths that do not appear to be related to slab subduction, including fast structures in locations consistent with delamination associated with the Paraná Flood Basalt event at ~134 Ma and the Deccan Traps event at ~66 Ma. These fast-wavespeed anomalies often lie above broad slow seismic wavespeed trunks at 500 to 700 km depths beneath former Gondwana, with slow wavespeed anomalies branching around them. Numerical experiments indicate that delaminated lithosphere tends to stagnate in the transition zone and mid-mantle above a mantle plume where it shapes subsequent plume upwelling. For hot plumes, the melt volume generated during plume-influenced delamination can easily reach ~2 to 4 × 106 km3, consistent with the basalt eruption volume at the Deccan Traps. This seismic and numerical evidence suggests that observed high-wavespeed mid-mantle anomalies beneath the locations of former flood basalts are delaminated fragments of former continental lithosphere, and that lithospheric delamination events in the presence of subcontinental plumes induced several of the continental flood basalts associated with the multiple breakup stages of Gondwanaland. Continued upwelling in these plumes can also have entrained subcontinental lithosphere in the mid-mantle to bring its distinctive geochemical signal to the modern mid-ocean spreading centers that surround southern and western Africa.

Bullying Victimization and Malevolent Creativity in Rural Adolescents: The Longitudinal Mediational Role of Hostile Attribution.

Extensive research has documented bully victimization as a pivotal risk factor contributing to aggressive behaviors among adolescents. Particularly, the negative outcome of increased aggressive behaviors may be exacerbated when the aggressive actions are novel and difficult to detect. The present study aims to explore the complex relationships between cyberbullying and school bullying victimization and malevolent creativity and the potential mediating role of hostile attribution using two-wave longitudinal data. The present study analyzed data from 262 rural adolescents. The results revealed that cyberbullying victimization significantly predicted malevolent creativity, whereas school bullying victimization did not. Hostile attribution served as a mediator in the relationship between cyberbullying victimization and malevolent creativity in the longitudinal models. These findings provide significant implications for mitigating the negative influence of bullying victimization on the emergence of malevolent creativity in rural adolescents.

Experiences of financial toxicity among caregivers of cancer patients: a meta-synthesis of qualitative studies.

OBJECTIVES: The purpose of this study was to explore the experience of financial toxicity among caregivers of cancer patients and to provide recommendations for subsequent intervention strategies. METHODS: Computer searches of PubMed, EmBase, The Cochrane Library, Web of Science, CINAHL (EBSCO), CNKI, Wanfang database, and SinoMed for qualitative studies experience of financial toxicity among caregivers cancer patients. The search time frame was from the establishment of the database to May 2023. The quality of included studies was assessed using the Qualitative Research Checklist from the Joanna Briggs Institute (JBI) Reviewer's Manual. The meta-synthesis was integrated following the meta-aggregation method proposed by the Joanna Briggs Institute (JBI) and reported following the Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) guidelines. RESULTS: A total of nine studies were included, distilling 25 qualitative findings into nine new categories and synthesizing three synthesized findings: caregivers have strong negative experiences that affect their family relationships, daily work and life; caregivers use different strategies to cope with financial toxicity; needs and expectations of caregivers coping with financial toxicity. CONCLUSIONS: Financial toxicity among caregivers of cancer patients affects their daily lives. Receiving timely recognition of this financial burden and providing assistance to enhance their coping skills are crucial in mitigating its impact. Healthcare professionals should focus on the financial toxicity experienced by caregivers of people with cancer, address their supportive needs, and develop a comprehensive support system to improve caregivers' coping abilities and quality of life.

Two successful pregnancies in a membranous nephropathy patient: Case report and literature review.

BACKGROUND: Pregnancy in patients with nephrotic syndrome presents enormous challenges to both the mother and fetus, and there are no treatment guidelines for these patients. METHODS: We show a case of a woman with anti-PLA2R antibody-positive membranous nephropathy who did not have a kidney biopsy. Her clinical course during both pregnancies was closely followed and her medications were guided. RESULTS: She gave birth to 2 healthy babies and her condition was very well controlled with the help of medication. CONCLUSION: Patients with nephrotic syndrome can have successful pregnancies after drug treatment. In addition, similar to the non-pregnant population, percutaneous kidney biopsy is not required for the diagnosis of idiopathic membranous nephropathy (IMN) in pregnant nephrotic syndrome patients with anti-PLA2R antibody positive, but the etiology of secondary MN should be excluded.

Identification and molecular mechanism of novel bifunctional peptides from Duroc × (Landrace × Yorkshire) pig dry-cured ham: A peptidomics and in silico analysis.

Duroc × (Landrace × Yorkshire) pigs are popular in the Chinese market because of their rapid growth, leanness, and economic value. Despite their widespread use in dry-cured ham processing, there is a lack of research on the bioactive peptides of Duroc × (Landrace × Yorkshire) pig ham (DLYH). This study aimed to investigate the presence of peptides with antioxidant and α-glucosidase inhibitory activities in DLYH using peptidomics and in silico analysis. A total of 453 peptides were identified from DLYH, originating mainly from myosin, actin, and the EF-hand domain-containing protein. Notably, two peptides, YDEAGPSIVH (YH10) and FAGDDAPRAVF (FF11), emerged as novel bioactive peptides with antioxidant and α-glucosidase inhibitory activities. Among these peptides, YH10 exhibited a high DPPH radical scavenging activity (IC50 = 1.93 mM), ABTS radical scavenging activity (IC50 = 0.10 mM), α-glucosidase inhibitory activity (IC50 = 2.13 mM), and good gastrointestinal tolerance. Molecular docking analysis showed that YH10 was bound to the ABTS and DPPH radicals and the active site of α-glucosidase (3A4A) primarily through hydrogen bonding and hydrophobic interactions. Furthermore, molecular dynamics (MD) simulation indicated that the YH10-3A4A complexes maintained stable and compact conformations. In conclusion, our findings indicated that peptide YH10 derived from DLYH possesses bifunctional properties of α-glucosidase inhibition and antioxidant activity, which could be beneficial for maintaining ham quality and promoting human health.

The Pivotal Radical Intermediate [Au21(SR)15]+ in the Ligand-Exchange-Induced Size-Reduction of [Au23(SR)16]- to Au16(SR)12.

The atomic precision of sub-nanometer-sized metal nanoclusters makes it possible to elucidate the kinetics of metal nanomaterials from the molecular level. Herein, the size reduction of an atomically precise [Au23(CHT)16]- (HCHT = cyclohexanethiol) cluster upon ligand exchange with HSAdm (1-adamantanethiol) has been reported. During the 16 h conversion of [Au23(CHT)16]- to Au16(SR)12, the neutral 6e Au21(SR)15, and its 1e-reduction state, i.e. the 5e, cationic radical, [Au21(SR)15]+, are active intermediates to account for the formation of thermodynamically stable Au16 products. The combination of spectroscopic monitoring (with UV-vis and ESI-MS) and DFT calculations indicates the preferential size-reduction on the corner Au atoms on the core surface and the terminal Au atoms on longer AunSn+1 staples. This study provides a reassessment on the electronic state of the Au21 structure and highlights the single electron transfer processes in cluster systems and thus the importance of the EPR analysis on the mechanistic issues.

Population Pharmacokinetic Analysis to Support and Facilitate Switching from Risperidone Formulations to Rykindo in Patients with Schizophrenia.

INTRODUCTION: RYKINDO® (Rykindo) is a novel, long-acting injectable risperidone formulation administered biweekly (Q2W) through intramuscular gluteal injection for the treatment of schizophrenia in adult patients. This analysis was conducted to demonstrate that the clinical outcomes of Rykindo are equivalent to those of RISPERDAL CONSTA® (Consta; Q2W), and to establish a dosing methodology to switch from Consta to Rykindo, as well as to introduce Rykindo to patients who are currently on oral RISPERDAL® (Risperdal). METHODS: Population pharmacokinetic (PK) models for Rykindo and Consta were developed using a nonlinear mixed-effects model with the data from phase 1 studies. A model-based simulation was also conducted using NONMEM. RESULTS: The PK profiles of Rykindo and Consta were adequately represented by a one-compartment model with an immediate release followed by an intermediate and third main release. Drug release of Rykindo was faster than for Consta, reaching steady state approximately 2-3 weeks earlier. The exposures of the active moiety of Rykindo and Consta were comparable at steady state. Model-based simulation indicated that switching from Consta to Rykindo requires administration of the first Rykindo injection within 4-5 weeks following the last Consta injection. For patients taking Risperdal, introducing Rykindo with 1 week of Risperdal supplemental for once-daily dosing (QD) can achieve comparable or superior exposure to that of Consta with 3 weeks of oral QD supplements. A dosing window of ± 3 days for Rykindo was recommended. CONCLUSIONS: This established approach provides guidance to physicians to initiate Rykindo therapy in adult patients with schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02055287, NCT02186769 and NCT02091388.

Global crotonylome identifies EP300-regulated ANXA2 crotonylation in cumulus cells as a regulator of oocyte maturation.

Lysine crotonylation (Kcr), a newly discovered post-translational modification, played a crucial role in physiology and disease progression. However, the roles of crotonylation in oocyte meiotic resumption remain elusive. As abnormal cumulus cell development will cause oocyte maturation arrest and female infertility, we report that cumulus cells surrounding human meiotic arrested oocytes showed significantly lower crotonylation, which was associated with decreased EP300 expression and blocked cumulus cell expansion. In cultured human cumulus cells, exogenous crotonylation or EP300 activator promoted cell proliferation and reduced cell apoptosis, whereas EP300 knockdown induced the opposite effect. Transcriptome profiling analysis in human cumulus cells indicated that functions of crotonylation were associated with activation of epidermal growth factor receptor (EGFR) pathway. Importantly, we characterized the Kcr proteomics landscape in cumulus cells by LC-MS/MS analysis, and identified that annexin A2 (ANXA2) was crotonylated in cumulus cells in an EP300-dependent manner. Crotonylation of ANXA2 enhanced the ANXA2-EGFR binding, and then activated the EGFR pathway to affect cumulus cell proliferation and apoptosis. Using mouse oocytes IVM model and EP300 knockout mice, we further confirmed that crotonylation alteration in cumulus cells affected the oocyte maturation. Together, our results indicated that EP300-mediated crotonylation is important for cumulus cells functions and oocyte maturation.

HIF1α Elevations at Tissue and Serum Levels and Their Association With Metabolic Disorders in Children With Obesity.

OBJECTIVE: We aimed to examine the expression profile and circulating level of hypoxia-inducible factor 1 alpha (HIF1α) in children and the relationships with metabolic disorders. METHODS: A total of 519 children were recruited, with paired subcutaneous and omental adipose tissues collected from 17 children and serum samples from the remaining children. All children underwent anthropometric and biochemical analyses. The mRNA, protein, and serum levels of HIF1α were determined by real-time PCR, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. RESULTS: Both HIF1α mRNA and protein levels, especially in omental adipose tissue, were increased in overweight or obese (OV/OB) children (P < .05). Likewise, serum HIF1α level was remarkably higher in OV/OB children than in normal-weight children (P < .05). Serum HIF1α level was positively correlated with BMI z-score, fat mass percentage, waist to height ratio, systolic blood pressure, alanine aminotransferase, total triglycerides, uric acid, and homeostasis model assessment of insulin resistance (IR). Furthermore, a binary logistic regression analysis of serum HIF1α level indicated that the risks for IR, nonalcoholic fatty liver disease (NAFLD), and metabolic syndrome remained significant in the presence of all potential confounding variables. Finally, the area under the receiver operating characteristic curves for serum HIF1α level in children who were diagnosed with IR, NAFLD, and metabolic syndrome were 0.698 (95% CI, 0.646-0.750; P < .001), 0.679 (95% CI, 0.628-0.731; P < .001), and 0.900 (95% CI, 0.856-0.945; P < .001). CONCLUSION: HIF1α expression is higher in the adipose tissue, especially omental, of children with obesity than in children with normal weight. Elevated serum HIF1α level is associated with adiposity and metabolic disorder, which may predict a higher risk of obesity complications.

Connecting the Dots: The Cerebral Lymphatic System as a Bridge Between the Central Nervous System and Peripheral System in Health and Disease.

As a recently discovered waste removal system in the brain, cerebral lymphatic system is thought to play an important role in regulating the homeostasis of the central nervous system. Currently, more and more attention is being focused on the cerebral lymphatic system. Further understanding of the structural and functional characteristics of cerebral lymphatic system is essential to better understand the pathogenesis of diseases and to explore therapeutic approaches. In this review, we summarize the structural components and functional characteristics of cerebral lymphatic system. More importantly, it is closely associated with peripheral system diseases in the gastrointestinal tract, liver, and kidney. However, there is still a gap in the study of the cerebral lymphatic system. However, we believe that it is a critical mediator of the interactions between the central nervous system and the peripheral system.

Assessing the prognostic significance of mean pulmonary artery velocity in heart failure with slightly reduced ejection fraction.

OBJECTIVE: In this study, we assessed the prognostic significance of the mean velocity of the pulmonary artery (mvPA) using CMR in patients who have heart failure with mildly reduced ejection fraction (HFmrEF) and pulmonary hypertension, both as a combined condition and individually. METHODS: This retrospective study involved 284 consecutive patients diagnosed with HFmrEF who were hospitalized and underwent CMR imaging to assess RV-PA coupling parameters, including mvPA. We collected baseline data clinical profiles, lab test results, and cardiac imaging findings of patients with HFmrEF who had at least two echocardiograms conducted three months apart. The primary endpoint was a composite of all-cause mortality or readmission due to heart failure. RESULTS: A total of 139 patients met the primary endpoint during an average follow-up of 49 months. The most effective threshold value for predicting the primary endpoint, determined by a receiver operating curve analysis, was 9. cm/s for mvPA. According to the Kaplan-Meier survival plots, when mvPA ≤ 9.05 cm/s, there was a significantly higher mortality rate (Log-Rank: 71.93, p < 0.001). It is important to highlight that the predictive value of mvPA remained consistent, irrespective of RV function. mvPA ≤ 9.05 cm/s served as an independent prognostic indicator, alongside ischemic cardiomyopathy and hyponatremia. CONCLUSIONS: mvPA has affirmed its significance as an initial prognostic indicator by identifying a group of high-risk patients who have sustained RV function. While the results of this study displayed potential in stratifying the extended prognosis of patients with HFmrEF, additional research is required.

Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia.

Elevated serum uric acid (UA) level is related to type 2 diabetic retinopathy (DR). Vascular endothelial growth factor (VEGF), high-sensitivity C-reactive protein (hs-CRP), and cystatin C (Cys-C) have involvement in type 2 DR complicated with hyperuricemia (HUA) (HUDR), and we explored their clinical values in HUDR. Type 2 DR patients were allocated into HUDR/DR groups, with type 2 diabetes mellitus (T2DM) patients as the control group. Serum VEGF and inflammation markers hs-CRP, and Cys-C levels were assessed by ELISA and immunoturbidimetry. The correlations between serum UA level and VEGF/hs-CRP/Cys-C were analyzed by Pearson tests, diagnostic values of VEGF/hs-CRP/Cys-C were analyzed by receiver operating characteristic curves, and the independent risk factors in HUDR were analyzed by logistic multivariate regression. Serum VEGF/hs-CRP/Cys-C level differences among the T2DM/DR/HUDR groups were statistically significant, with the levels in HUDR > DR > T2DM. Serum UA level in HUDR patients was positively correlated with serum VEGF/hs-CRP/Cys-C. Serum VEGF/hs-CRP/Cys-C assisted in HUDR diagnosis, with their combination showing the greatest diagnostic value. UA/FPG/HbA1C/VEGF/hs-CRP/Cys-C were independent risk factors for HUDR. The incidence of proliferative DR was increased in HUDR patients. Collectively, serum VEGF, hs-CRP, and Cys-C levels in HUDR patients were increased, and HUA might promote DR progression.

Neuroprotective Effects and Therapeutic Potential of Dichloroacetate: Targeting Metabolic Disorders in Nervous System Diseases.

Dichloroacetate (DCA) is an investigational drug used to treat lactic acidosis and malignant tumours. It works by inhibiting pyruvate dehydrogenase kinase and increasing the rate of glucose oxidation. Some studies have documented the neuroprotective benefits of DCA. By reviewing these studies, this paper shows that DCA has multiple pharmacological activities, including regulating metabolism, ameliorating oxidative stress, attenuating neuroinflammation, inhibiting apoptosis, decreasing autophagy, protecting the blood‒brain barrier, improving the function of endothelial progenitor cells, improving mitochondrial dynamics, and decreasing amyloid ß-protein. In addition, DCA inhibits the enzyme that metabolizes it, which leads to peripheral neurotoxicity due to drug accumulation that may be solved by individualized drug delivery and nanovesicle delivery. In summary, in this review, we analyse the mechanisms of neuroprotection by DCA in different diseases and discuss the causes of and solutions to its adverse effects.

The central core size effect in quinoxaline-based non-fullerene acceptors for high VOC organic solar cells.

For organic solar cells (OSCs), obtaining a high open circuit voltage (VOC) is often accompanied by the sacrifice of the circuit current density (JSC) and filling factor (FF), and it is difficult to strike a balance between VOC and JSC × FF. The trade-off of these parameters is often the critical factor limiting the improvement of the power conversion efficiency (PCE). Extended backbone conjugation and side chain engineering of non-fullerene acceptors (NFAs) are effective strategies to optimize the performance of OSCs. Herein, based on the quinoxaline central core and branched alkyl chains at the ß position of the thiophene unit, we designed and synthesized three NFAs with different sized cores. Interestingly, Qx-BO-3 with a smaller central core showed better planarity and more appropriate crystallinity. As a result, PM6:Qx-BO-3-based devices obtained more suitable phase separation, more efficient exciton dissociation, and charge transport properties. Therefore, the OSCs based on PM6:Qx-BO-3 yielded an outstanding PCE of 17.03%, significantly higher than the devices based on PM6:Qx-BO-1 (10.57%) and PM6:Qx-BO-2 (11.34%) although the latter two devices have lower VOC losses. These results indicated that fine-tuning the central core size can effectively optimize the molecular geometry of NFAs and the film morphology of OSCs. This work provides an effective method for designing high-performance NFA-OSCs with high VOCs.

Plant-derived rennet: research progress, novel strategies for their isolation, identification, mechanism, bioactive peptide generation, and application in cheese manufacturing.

Rennet, an aspartate protease found in the stomach of unweaned calves, effectively cuts the peptide bond between Phe105-Met106 in κ-casein, hydrolyzing the casein micelles to coagulate the milk and is a crucial additive in cheese production. Rennet is one of the most used enzymes of animal origin in cheese making. However, using rennet al.one is insufficient to meet the increasing demand for cheese production worldwide. Numerous studies have shown that plant rennet can be an alternative to bovine rennet and exhibit a good renneting effect. Therefore, it is crucial and urgent to find a reliable plant rennet. Based on our team's research on rennet enzymes of plant origin, such as from Dregea sinensis Hemsl. and Moringa oleifer Lam., for more than ten years, this paper reviews the relevant literature on rennet sources, isolation, identification, rennet mechanism, functional active peptide screening, and application in cheese production. In addition, it proposes the various techniques for targeted isolation and identification of rennet and efficient screening of functionally active peptides, which show excellent prospects for development.

Activity of Different AunSn+1 Staples in the Ligand Exchange of Au23(SR)16- with a Single Foreign Thiolate Ligand.

Ligand exchange has been widely used to synthesize novel thiolated gold nanoclusters and to regulate their specific properties. Herein, density functional theory (DFT) calculations were conducted to investigate the kinetic profiles of the ligand exchange of the [Au23(SCy)16]- nanocluster with an aromatic thiolate (2-napthalenethiol). The three types of staple motifs (i.e., trimetallic Au3S4, monometallic AuS2, and the bridging thiolates) of the Au23 cluster precursor could be categorized into eight groups of S sites with different chemical environments. The ligand exchange of all of them occurs favorably via the SN1-like pathway, with one site starting with the Au-S dissociation and seven other sites starting with the H-transfer steps. By contrast, the SN2-like pathway (i.e., the synergistic SCy-to-SAr exchange prior to the H-transfer step) is unlikely in the target systems. Meanwhile, the Au-S bond on the capping Au atom of the bicapped icosahedral Au15 core is the most active one, while the S sites on Au3S4 (except for the one remote from the metallic core) are all competitive exchanging sites. The ligand exchange activity of the bridging thiolate and the remote S site on Au3S4 is significantly less reactive. The calculation results correlate with the multiple ligand exchange within only a few minutes and the preferential etching of the AuS2 staple with the foreign ligands reported in earlier experiments. The relative activity of different staples might be helpful in elucidating the inherent principles in the ligand exchange-induced size-evolution of metal nanoclusters.

MiR-3529-3p from PDGF-BB-induced cancer-associated fibroblast-derived exosomes promotes the malignancy of oral squamous cell carcinoma.

AIMS: This study aims to explore the role of exosomes from cancer-associated fibroblasts (CAFs) induced by PDGF-BB in promoting the malignancy of oral squamous cell carcinoma (OSCC) and provide new insight into the mechanism of OSCC progression and its treatment. MAIN METHODS: Exosomes were extracted from human oral mucosa fibroblasts (hOMFs) and CAFs. Differentially expressed miRNAs of exosomes between hOMFs and CAFs were analysed using high-throughput sequencing and self-programmed R software. Cal-27, a human tongue squamous carcinoma cell line, was treated with exosomes. Differentially expressed miRNAs between clinical cancer tissues and adjacent tissues and between hOMF and CAF exosomes were verified by qRT‒PCR. The effect of miR-3529-3p on Cal-27 cells was clarified by overexpressing or knocking down miR-3529-3p in Cal-27 cells. Sample expression and differentially expressed miRNA expression were compared between cancer and paracarcinoma tissues. KEY FINDINGS: We found that exosomes from CAFs (CAF-Exos) were internalized by tongue squamous carcinoma cells and promoted their proliferation, migration, invasion, and antiapoptotic effects. MiR-3529-3p was a significant differentially expressed miRNA between CAF-Exos and exosomes from hOMFs (hOMF-Exos). The overexpression of miR-3529-3p promoted proliferation, migration, and invasion and inhibited apoptosis of Cal-27 cells. SIGNIFICANCE: This study explores the role of PDGF-BB-induced CAFs in promoting malignancy in OSCC. This study will provide new insight into the mechanism of OSCC progression and its treatment.

BCp12/PLA combination: A novel antibacterial agent targeting Mur family, DNA gyrase and DHFR.

The combination of natural antimicrobial peptide BCp12/phenyllatic acid (BCp12/PLA) presents a more efficient antibacterial effect, but its antibacterial mechanism remains unclear. This study studied the synergistic antibacterial mechanism of BCp12 and PLA against S. aureus. The results demonstrated that the BCp12/PLA combination presented a synergistic antibacterial effect against S. aureus, with a fractional inhibitory concentration of 0.05. Furthermore, flow cytometry and scanning electron microscope analysis revealed that BCp12 and PLA synergistically promoted cell membrane disruption compared with the group treated only with one compound, inducing structural cell damage and cytoplasmic leakage. In addition, fluorescence spectroscopy analysis suggested that BCp12 and PLA synergistically influenced genomic DNA. BCp12 and PLA targeted enzymes related to peptidoglycan and DNA synthesis and interacted by hydrogen bonding and hydrophobic interactions with mur enzymes (murC, murD, murE, murF, and murG), dihydrofolate reductase, and DNA gyrase. Additionally, the combined treatment successfully inhibited microbial reproduction in the storage of pasteurized milk, indicating that the combination of BCp12 and PLA can be used as a new preservative strategy in food systems. Overall, this study could provide potential strategies for preventing and controlling foodborne pathogens.