Cucurbitacin B attenuates osteoarthritis development by inhibiting NLRP3 inflammasome activation and pyroptosis through activating Nrf2/HO-1 pathway.

Osteoarthritis (OA) is a complicated joint disorder characterized by inflammation that causes joint destruction. Cucurbitacin B (CuB) is a naturally occurring triterpenoid compound derived from plants in the Cucurbitaceae family. The aim of this study is to investigate the potential role and mechanisms of CuB in a mouse model of OA. This study identified the key targets and potential pathways of CuB through network pharmacology analysis. In vivo and in vitro studies confirmed the potential mechanisms of CuB in OA. Through network pharmacology, 54 potential targets for CuB in treating OA were identified. The therapeutic potential of CuB is associated with the nod-like receptor pyrin domain 3 (NLRP3) inflammasome and pyroptosis. Molecular docking results indicate a strong binding affinity of CuB to nuclear factor erythroid 2-related factor 2 (Nrf2) and p65. In vitro experiments demonstrate that CuB effectively inhibits the expression of pro-inflammatory factors induced by interleukin-1ß (IL-1ß), including cyclooxygenase-2, inducible nitric oxide synthase, IL-1ß, and IL-18. CuB inhibits the degradation of type II collagen and aggrecan in the extracellular matrix (ECM), as well as the expression of matrix metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5. CuB protects cells by activating the Nrf2/hemeoxygenase-1 (HO-1) pathway and inhibiting nuclear factor-κB (NF-κB)/NLRP3 inflammasome-mediated pyroptosis. Moreover, in vivo experiments show that CuB can slow down cartilage degradation in an OA mouse model. CuB effectively prevents the progression of OA by inhibiting inflammation in chondrocytes and ECM degradation. This action is further mediated through the activation of the Nrf2/HO-1 pathway to inhibit NF-κB/NLRP3 inflammasome activation. Thus, CuB is a potential therapeutic agent for OA.

GOSpel for tiny allies.

Infant formulas are often supplemented to foster the development of a healthy gut microbiota. In this issue of Cell Host & Microbe, Heppner et al. present an elaborate clinical trial examining the impact of formula supplementation on the development and circadian rhythmicity of the microbiota during the first year of life.

Validation of the IMPEDE VTE score for prediction of venous thromboembolism in Chinese patients with multiple myeloma: A single-center retrospective cohort study.

Multiple myeloma (MM) significantly increases the risk of venous thromboembolism (VTE) within 6 months of treatment initiation. The IMPEDE VTE score is a VTE risk prediction model which is recently incorporated into the National Comprehensive Cancer Network (NCCN) guidelines, but it lacks validation among Asians, including Chinese MM patients. We performed a retrospective chart review of 405 Chinese with newly diagnosed MM who started therapy at Beijing Jishuitan Hospital between April 2013 to October 2022. The 6-month cumulative incidence of VTE was 3.8 % (95 % CI:1.6-7.6), 8.6 % (95 % CI: 5.3-21.9) and 40.5 % (95 % CI: 24.9-55.7) in the low-, intermediate- and high-risk groups (P < 0.001), respectively. The C-statistic of the IMPEDE VTE scores for predicting VTE within 6 months of treatment initiation was 0.74 (95 % CI: 0.65-0.83). Of note, in this single-center cohort study, we propose that the anticoagulant LMWH may be more effective than the antiplatelet aspirin in potentially preventing VTE in newly diagnosed MM patients. Our findings suggest that the IMPEDE VTE score is a valid evidence-based risk stratification tool in Chinese patients with newly diagnosed MM.

Qingfei xieding prescription ameliorates mitochondrial DNA-initiated inflammation in bleomycin-induced pulmonary fibrosis through activating autophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingfei Xieding prescription was gradually refined and produced by Hangzhou Red Cross Hospital. The raw material includes Ephedra sinica Stapf, Morus alba L., Bombyx Batryticatus, Gypsum Fibrosum, Prunus armeniaca L. var. ansu Maxim., Houttuynia cordata Thunb. , Pueraria edulis Pamp. Paeonia L., Scutellaria baicalensis Georgi and Anemarrhena asphodeloides Bge. It is effective in clinical adjuvant treatment of patients with pulmonary diseases. AIM OF THE STUDY: To explore the efficacy and underlying mechanism of Qingfei Xieding (QF) in the treatment of bleomycin-induced mouse model. MATERIALS AND METHODS: TGF-ß induced fibrotic phenotype in vitro. Bleomycin injection induced lung tissue fibrosis mouse model in vivo. Flow cytometry was used to detect apoptosis, cellular ROS and lipid oxidation. Mitochondria substructure was observed by transmission electron microscopy. Autophagolysosome and nuclear entry of P65 were monitored by immunofluorescence. Quantitative real-time PCR was performed to detect the transcription of genes associated with mtDNA-cGAS-STING pathway and subsequent inflammatory signaling activation. RESULTS: TGF-ß induced the expression of α-SMA and Collagen I, inhibited cell viability in lung epithelial MLE-12 cells that was reversed by QF-containing serum. TGF-ß-mediated downregulation in autophagy, upregulation in lipid oxidation and ROS contents, and mitochondrial damage were rescued by QF-containing serum treatment, but CQ exposure, an autophagy inhibitor, prevented the protective role of QF. In addition to that, the decreased autophagolysosome in TGF-ß-exposed MLE-12 cells was reversed by QF and restored to low level in the combination treatment of QF and CQ. Mechanistically, QF-containing serum treatment significantly inhibited mtDNA-cGAS-STING pathway and subsequent inflammatory signaling in TGF-ß-challenged cells, which were abolished by CQ-mediated autophagy inhibition. In bleomycin-induced mouse model, QF ameliorated pulmonary fibrosis, reduced mortality, re-activated autophagy in lung tissues and restrained mtDNA-cGAS-STING inflammation pathway. However, the protective effects of QF in bleomycin-induced model mice were also abrogated by CQ. CONCLUSION: QF alleviated bleomycin-induced pulmonary fibrosis by activating autophagy, inhibiting mtDNA-cGAS-STING pathway-mediated inflammation. This research recognizes the protection role of QF on bleomycin-induced mouse model, and offers evidence for the potentiality of QF in clinical application for pulmonary fibrosis treatment.

Angucyclinones with IDO and TDO inhibitory activities isolated from the actinomycetes Umezawaea beigongshangensis.

Four previously undescribed angucyclinones umezawaones A-D (1-4) were isolated from the liquid cultures of Umezawaea beigongshangensis. Their structures were determined by spectroscopic analyses, single crystal X-ray diffraction, quantum chemical 13C NMR and electronic circular dichroism calculations. All compounds displayed strong inhibitory activities against indoleamine 2,3-dioxygenase and tryptophan-2,3-dioxygenase in enzymatic assay, especially compound 2.

The Efficacy and Safety of Shashen-Maidong Decoction Combined with Western Medicine in the Treatment of Omicron Infected Individuals Over 85 Years Old: A Retrospective Study.

Background: During the Omicron variant outbreak of COVID-19 (2022-2023), Chinese healthcare institutions combined traditional Chinese medicine (TCM) with Western medical practices to treat COVID-19 patients, especially the elderly. The efficacy and safety of this approach, especially for individuals aged over 85, need further investigation. Methods: In this retrospective study, a cohort of 62 patients aged over 85 years, diagnosed with COVID-19 infection, was examined. Among them, 34 patients were administered Shashen-Maidong decoction in conjunction with Western medicine (SMD+WM group), while the remaining 28 patients received only Western medicine (WM group). Comparative analysis was conducted between the two groups, encompassing parameters such as the duration for the nucleic acid test to turn negative, length of intensive care unit (ICU) stay, mortality rate, utilization of high-flow nasal cannula oxygen (HFNC), occurrence of endo-tracheal intubation, frequency of recurrent respiratory infections within three months, and various laboratory indicators. Results: There were no significant differences observed between the two groups in terms of the duration for the nucleic acid test to turn negative, the length of ICU stay, mortality rate, utilization of HFNC, performance of endo-tracheal intubation, or the frequency of recurrent respiratory infections within three months (P > 0.05). However, in comparison to the WM group, the SMD+WM group exhibited notably lower growth rates in white blood cell (WBC) and neutrophil (NEUT) values. Additionally, the SMD+WM group demonstrated superior improvement in cardiac troponin I (cTnI) and B-type natriuretic peptide (BNP) values. Conclusion: In contrast to the administration of Western medicine alone, the combined use of Shashen-Maidong decoction with Western medicine significantly suppresses the increase in WBC count, particularly in NEUT levels, in elderly patients diagnosed with COVID-19. Moreover, this combined treatment exhibits a protective effect on cardiac function and demonstrates a relatively safe profile.

Dual-wavelength responsive CuS@COF nanosheets for high-performance photothermal/photodynamic combination treatments.

Photothermal therapy (PTT) makes it difficult to achieve good performance on tumor treatments due to insufficient photothermal conversion efficiency, etc. Combining PTT with photodynamic therapy (PDT) and other therapeutic tools can significantly enhance the tumor-killing ability and has been widely used in the development of therapeutic platforms. Copper sulfide nanoparticle (CuS NP) photothermal reagents have the advantages of low toxicity and simple synthesis; therefore, combining CuS NPs with PDT photosensitizers is an effective strategy to construct a PTT/PDT combination therapeutic platform. However, PDT photosensitizers and photothermal agents generally assembled through hydrophobic interaction, suffer from low coating efficiency or the risk of drug leakage, thus seriously restricting their applications. To address these challenges, CuS NPs with excellent photothermal conversion performance were selected as the core material to prepare CuS@COF nanosheets through a dual-ligand assistant strategy with 4,7-bis(4-aminophenyl)-2,1,3-benzothiadiazole (BTD) and 2,4,6-trihydroxybenzene-1,3,5-tricarbaldehyde (TP). As a PTT/PDT combination therapeutic platform, CuS@COF nanosheets possess a porous TP-BDT-based COF shell, and it can sufficiently contact oxygen to provide high singlet oxygen (1O2) yield under 505 nm laser irradiation. Upon illumination with a 1064 nm laser, CuS@COF nanosheets can effectively convert the photon energy into thermal energy with a photothermal conversion efficiency of 63.4%. The results of the CCK8 experiment showed that the phototoxicity of the PTT/PDT combination treatment reached 85.1%, which was much higher than the effect of a single treatment. It was also confirmed in vivo that the tumor inhibition effect of the PDT/PTT combination treatment group was much greater than that of the single treatment group.

Intervention Strategy for Anxiety Behaviors in Children in Perioperative Period of Outpatient Surgery: Process Formulation and Implementation Effects.

Objective: There have been studies shown the efficacy of psychological interventions in reducing preoperative anxiety in children undergoing surgery. We constructed an intervention strategy, based on the concept of co-design, for perioperative anxiety behavior in children's outpatient surgery and conducted a prospective randomized controlled research to confirm its effectiveness. Method: This research comprised a total of 100 kids who received surgery in our outpatient clinic between January 2019 and January 2020. According to the random number table approach, all kids were divided into observation as well as control categories, each of which had 50 instances.The behavioral intervention tactics included cognitive intervention before behavioral intervention and behavioral interventions in the environment. The observation cohort was offered behavioral intervention tactics before anesthesia, whereas the control category had surgery under standard anesthesia. The two categories' preoperative visit (T1) mean arterial pressure (MAP) & heart rates (HR) in the anesthesia preparation room (T2), during induction of anesthesia (T3) and 1 hour after surgery (T4) were compared, and the two groups' modified facial expression score (FLACC) at T1 and T4 was compared as well; At T3, the children' degree of cooperation and anxiety were evaluated with Induction Cooperation Scale (ICC) and modified Yale Perioperative Anxiety Scale (mYPAS). The satisfaction degree of the children's family with the surgery was collected 7d after the operation with a Satisfaction Rating Scale prepared by our hospital. Results: The MAP in the observation group was 58.49±6.35 at T1 time, which was not a significant diference from that of the control group (60.12±7.03). Also, the HR in the observation group was 100.27±12.38 at T1 time, with no difference from that in control group. MAP and HR at T2-T4 were remarkably higher in both groups than at T1 (P < .05); & During T2-T4, the group being observed appeared to have lower MAP & HR compared to the group acting as a control (P < .05). At T3, the observation category's ICC & mYPAS scores were significantly poorer than those of the control category (P < .05). On the seventh day following surgery, the satisfaction level of the observation category's family with the procedure was greater than that of the control category. (P < .05). Conclusion: The behavioral intervention strategy help children undergoing outpatient surgery maintain stable hemodynamic indicators during the perioperative period, reduce their anxiety and improve their cooperation for surgery. In future, the apply of the behavioral intervention strategy will effectively improve the satisfaction of children's family members with surgery.

Oil candidate genes in seeds of cotton (Gossypium hirsutum L.) and functional validation of GhPXN1.

BACKGROUND: Cottonseed oil is a promising edible plant oil with abundant unsaturated fatty acids. However, few studies have been conducted to explore the characteristics of cottonseed oil. The molecular mechanism of cottonseed oil accumulation remains unclear. RESULTS: In the present study, we conducted comparative transcriptome and weighted gene co-expression network (WGCNA) analysis for two G. hirsutum materials with significant difference in cottonseed oil content. Results showed that, between the high oil genotype 6053 (H6053) and the low oil genotype 2052 (L2052), a total of 412, 507, 1,121, 1,953, and 2,019 differentially expressed genes (DEGs) were detected at 10, 15, 20, 25, and 30 DPA, respectively. Remarkably, a large number of the down-regulated DEGs were enriched in the phenylalanine metabolic processes. Investigation into the dynamic changes of expression profiling of genes associated with both phenylalanine metabolism and oil biosynthesis has shed light on a significant competitive relationship in substrate allocation during cottonseed development. Additionally, the WGCNA analysis of all DEGs identified eight distinct modules, one of which includes GhPXN1, a gene closely associated with oil accumulation. Through phylogenetic analysis, we hypothesized that GhPXN1 in G. hirsutum might have been introgressed from G. arboreum. Overexpression of the GhPXN1 gene in tobacco leaf suggested a significant reduction in oil content compared to the empty-vector transformants. Furthermore, ten other crucial oil candidate genes identified in this study were also validated using quantitative real-time PCR (qRT-PCR). CONCLUSIONS: Overall, this study enhances our comprehension of the molecular mechanisms underlying cottonseed oil accumulation.

Dynamic characteristics of net anthropogenic phosphorus input to the upper Yangtze River Basin from 1989 to 2019: Focus on the phosphate ore rich area in China.

Phosphorus (P), a non-renewable essential resource, faces heavy exploitation and contributes to eutrophication in aquatic environments. Assessing P input is vital for a healthier P cycle in the Upper Yangtze River (UYR), a phosphate ore rich basin, where P mining and P chemical enterprises have prominent pollution problems. This study modified the net anthropogenic phosphorus input (NAPI) model to include ore mining P input (Pore). We analyzed the evolutionary characteristics of P input in five sub-basins of UYR from 1989 to 2019 using prefecture-level data, and assessed the uncertainty of the data. NAPI in all sub-basins exhibited an upward and then downward trend during 1989-2019, with the inflection point occurring in 2015 or 2016, showing a net increase of about 1.1 times (568-1162 kg P km-2 yr-1) in the whole UYR basin. Among the components of NAPI, P fertilizer inputs (Pfer) and food/non-food and feed P inputs (Pf/nf&feed) contributed comparably, though the growth rate of Pfer was most notable basin-wide. Pore proportion increased significantly (about 3-fold), with a peak of 20%, especially in Wujiang sub-basin. The multi-year (1989-2019) average NAPI in UYR rose sequentially from west to east, with hotspot areas mainly concentrated in the Sichuan-Chongqing urban agglomeration and cities of Hubei province. The regional P input closely related to the population density and the level of agricultural development, certainly the phosphate mining was also unignorable. This study emphasizes that based on current status of NAPI development in UYR, targeted management for different regions should focus on improving agricultural P use efficiency and rational exploitation of P mineral resources.

Efficacy of Jiao's scalp acupuncture in combination with Xiangshao granules on chronic tension-type headache with concomitant nonalcoholic fatty liver disease in climacteric women.

OBJECTIVE: This study aimed to assess the efficacy of Jiao's scalp acupuncture in combination with Xiangshao granules on chronic tension-type headache (CTTH) with concomitant nonalcoholic fatty liver disease (NAFLD) in climacteric women. METHODS: In this study, we enrolled 150 climacteric women with CTTH and concomitant NAFLD. The participants were divided into three groups based on the random number table: medication group, acupuncture group, and acupuncture-medication group. Treatment continued for 2 months. The efficacy of CTTH was assessed based on the visual analog scale/score (VAS). The influence on NAFLD was assessed based on body mass index (BMI), controlled attenuation parameter (CAP), and the ratio of hepatic-splenic computed tomography (CT) value. The Participant Health Questionnaire-9 (PHQ-9) score was compared among the three groups. RESULTS: A total of 123 participants completed the trial, including 37 participants in the medication group, 41 participants in the acupuncture group, and 45 participants in the acupuncture-medication group. Results are summarized hereinafter. (1) The total clinical efficiency rates of the medication group, acupuncture group, and acupuncture-medication group were 89.19% (33 of 37), 90.24% (37 of 41), and 95.65% (44 of 46), respectively. (2) Except for the BMI of the medication group ( P = 0.063), a significant difference in VAS, BMI, CAP, the ratio of hepatic-splenic CT value, and PHQ-9 score was found in the three groups ( P < 0.01). (3) There was a significant difference in VAS, BMI, CAP, and PHQ-9 among the three groups ( P < 0.01), with those in the acupuncture-medication group being superior. No difference in the ratio of hepatic-splenic CT value was found ( P = 0.440). (4) The efficacy differed significantly among the three groups ( χ2 = 8.130, P = 0.017), and it was significantly superior in the acupuncture-medication group ( P = 0.008, P = 0.013). CONCLUSIONS: Jiao's scalp acupuncture, in combination with Xiangshao granules, was superior in treating CTTH in climacteric women compared with either acupuncture or medication. Jiao's scalp acupuncture, in combination with Xiangshao granules, was superior in subsiding the negative moods in participants with CTTH and concomitant NAFLD.

Effects of nano-selenium on cecum microbial community and metabolomics in chickens challenged with Ochratoxin A.

Introduction: Ochratoxin A (OTA) is a widely distributed mycotoxin. Nano-selenium (Nano-Se) is an emerging form of selenium known for its superior bioavailability, remarkable catalytic efficiency, and robust adsorbing capacity. Despite these characteristics, its impact on the microbial community and metabolomics in the cecum of chickens exposed to OTA has been infrequently investigated. This research examined the microbiota and metabolomic alterations linked to OTA in chickens, with or without Nano-Se present. Methods: A cohort of 80 healthy chickens at the age of 1 day was randomly distributed into four groups of equal numbers, namely the Se cohort (1 mg/kg Nano-Se), the OTA cohort (50 µg/kg OTA), the OTA-Se cohort (50 µg/kg OTA + 1 mg/kg Nano-Se), and the control group. Each chicken group's caecal microbiome and metabolome were characterized using 16S rRNA sequencing and Liquid chromatography coupled with mass spectrometry (LC-MS) analyses. Results and discussion: Our results showed that the on day 21, the final body weight was significantly reduced in response to OTA treatments (p < 0.05), the average daily gain in the OTA group was found to be inferior to the other groups (p < 0.01). In addition, Nano-Se supplementation could reduce the jejunum and liver pathological injuries caused by OTA exposure. The 16S rRNA sequencing suggest that Nano-Se supplementation in OTA-exposed chickens mitigated gut microbiota imbalances by promoting beneficial microbiota and suppressing detrimental bacteria. Moreover, untargeted metabolomics revealed a significant difference in caecal metabolites by Nano-Se pretreatment. Collectively, the dataset outcomes highlighted that Nano-Se augmentation regulates intestinal microbiota and associated metabolite profiles, thus influencing critical metabolic pathways, and points to a possible food-additive product.

Enhancement effect of l-cysteine on lactic acid fermentation production.

BACKGROUND: Environmental stress resistance is still a bottleneck for economical process for l-lactic acid fermentation. Chronological lifespan (CLS) extension has represented a promising strategy for improving stress resistance of microbial cell factories. MAIN METHODS AND MAJOR RESULTS: In this study, addition of anti-aging drug cysteine, a kind of extending CLS of microbial cell factories, was systematically evaluated on cell viability and l-lactic acid production in Bacillus coagulans CICC 23843. The results revealed that 16 mm l-cysteine supplement significantly improved l-lactic acid titer in B. coagulans. The enhanced total antioxidant capacity (T-AOC) and key enzymes activities involving in glycolytic pathway as well as differentially expressed genes involved in cysteine synthesize and cysteine precursor synthesize pathways, and fatty acid degradation pathway may help to further understand the relative mechanism of l-cysteine effect on improving l-lactic acid accumulation. Finally, based on 16 mm l-cysteine supplement, a final l-lactic acid titer of 130.5 g L-1 with l-lactic acid productivity of 4.07 g L-1  h-1 and the conversion rate of 0.94 g g-1 total sugar was achieved in a 5 L bioreactor. CONCLUSIONS AND IMPLICATIONS: This study provided a valuable option for engineering lactic acid bacteria lifespan for enhancement of lactic acid yield.

Music Therapy for Gait and Speech Deficits in Parkinson's Disease: A Mini-Review.

Parkinson's disease (PD) is a progressive central nervous system disease with a common motor symptom of gait disturbance in PD, which is more pronounced in the later stages. Although FDA-approved treatments, including dopaminergic pharmacotherapy, deep brain stimulation, and rehabilitation, have some benefits in improving gait dysfunction, a fair amount of advanced PD patients can develop a disability, social isolation, and high mortality and morbidity. Recently, clinicians and scientists have applied music to clinical therapy, namely music therapy. It has been used as a unique rehabilitation tool to improve PD-induced gait and speech disorders. Based on relevant studies in recent years, this paper reviews the published literature about music in treating gait disorders and speech problems in PD patients. Additionally, we discuss current studies' limitations and emphasize the future potential research fields.

Phosphorus-induced greater enhancement in carbon supply and storage for oil synthesis during the crucial period made cottonseed kernel oil yield have a higher increment than protein.

Cottonseed has a high utilization value due to its luxuriant oil and protein, but low phosphorus (P) in cropland reduces its yield and quality. A limited understanding of the physiological mechanism underlying these results restricted the exploration of P efficient management in cotton cultivation. A 3-year experiment was performed with Lu 54 (low-P sensitive) and Yuzaomian 9110 (low-P tolerant) under 0 (deficient-P), 100 (critical-P), and 200 (excessive-P) kg P2O5 ha-1 in a field having 16.9 mg kg-1 available P to explore the key pathway for P to regulate cottonseed oil and protein formation. P application markedly increased cottonseed oil and protein yields, with the enhanced acetyl-CoA and oxaloacetate contents during 20-26 days post anthesis being a vital reason. Notably, during the crucial period, decreased phosphoenolpyruvate carboxylase activity weakened the carbon allocation to protein, making malonyl-CoA content increase greater than free amino acid; Meanwhile, P application accelerated the carbon storage in oil but retarded that in protein. Consequently, cottonseed oil yield increased more than protein. Oil and protein synthesis in Lu 54 was more susceptible to P, resulting in greater increments in oil and protein yields than Yuzaomian 9110. Based on acetyl-CoA and oxaloacetate contents (the key substrates), the critical P content in the subtending leaf to cotton boll needed by oil and protein synthesis in Lu 54 (0.35%) was higher than Yuzaomian 9110 (0.31%). This study provided a new perception of the regulation of P on cottonseed oil and protein formation, contributing to the efficient P management in cotton cultivation.

A new framework to model the distributed transfer and retention of nutrients by incorporating topology structure of small water bodies.

Small water bodies such as interval water-flooded ditches, ponds, and streams serve as important nutrient sinks in many landscapes, especially in the multi-water continuum system. Yet watershed nutrient cycling models often fail to or insufficiently capture these waters, resulting in great uncertainty in quantifying the distributed transfer and retention of nutrients across diverse landscapes in a watershed. In this study, we present a network-based predictive framework of the nutrient transport process in nested small water bodies, which incorporates topology structure, hydrological and biogeochemical processes, and connectivity to perform a nonlinear and distributed scaling of nutrient transfer and retention. The framework was validated and applied to N transport in a multi-water continuum watershed in the Yangtze River basin. We show that the importance of N loading and retention depends on the spatial context of grid source and water bodies because of the great variation in location, connectivity, and water types. Our results demonstrate that hotspots in nutrient loading and retention could be accurately and efficiently identified through hierarchical network effects and spatial interactions. This offers an effective approach for the reduction of watershed-scale nutrient loads. This framework can be used in modeling to identify where and how to restore small water bodies for reduced non-point pollution from agricultural watersheds.

Enhancing the targeting performance and prolonging the antibacterial effects of clove essential oil liposomes to Campylobacter jejuni by antibody modification.

The application of plant essential oil liposomes to prevent and control food safety risks caused by Campylobacter jejuni (C. jejuni) still faces challenges such as lack of targeting and low release rate. Here, a bacteria-targeted and protease-activated antibacterial liposome (ACCLPs) was successfully synthesized through encapsulation of clove essential oil (CEO) by film dispersion method, embedding of casein by freeze-thaw method, and conjugation of C. jejuni antibody on the liposome membrane by post-insertion method. The average particle size, the essential oil encapsulation rate, the casein mosaic rate, and the antibody coupling efficiency of ACCLPs were determined as185.87 nm,16.9%,70.1% and 87.5%, respectively. The modification with C. jejuni antibody could significantly improve the targeting of ACCLPs to C. jejuni. Controlled release experiments showed that the exocrine protease from C. jejuni could hydrolyze the embedded casein and perforation on the ACCLPs, thus leading to a bacteria-dependent CEO release and significant prolonging the antibacterial effects of ACCLPs. Application results of ACCLPs on C. jejuni-contaminated foods showed that ACCLPs could effectively inhibit C. jejuni in a variety of meat products, fruits and vegetables and extend their shelf life without significantly affecting food quality. The results above in this work would provide a new view for the development of high efficient liposome-based antibacterial system of plant essential oil.

Ultra-high performance liquid chromatography-quadrupole/time-of-flight mass spectrometry-based lipidomics reveals key lipid molecules as potential therapeutic targets of Polygonum cuspidatum against hyperlipidemia in a hamster model.

Polygonum cuspidatum is a homology of traditional medicine and functional food widely distributed around the world. Our previous study on the hyperlipidemic animal model demonstrated that Polygonum cuspidatum was effective in ameliorating hyperlipidemia, which is characterized by lipid disorders. Herein, the regulatory effect of Polygonum cuspidatum on lipid metabolism needs to be known if its hypolipidemic mechanism is desired to clarify. In this study, an ultra-high performance liquid chromatography-quadrupole/time-of-flight mass spectrometry-based lipidomic strategy was first applied to investigate the lipidomic patterns of high-fat diet-induced hyperlipidemic hamsters when treated with Polygonum cuspidatum. The results showed that Polygonum cuspidatum improved the lipidomic profile of hyperlipidemia. A total of 65 differential lipids related to the hypolipidemic effect of Polygonum cuspidatum were screened out and identified, and these differential lipids covered various categories, such as phosphatidylcholines, phosphatidylethanolamines, triacylglycerols, sphingomyelins and so on. Orally administrated Polygonum cuspidatum restored these differential lipids back to normal or nearly normal levels. This study adopted lipidomics to reveal the key lipid molecules as potential therapeutic targets of Polygonum cuspidatum against hyperlipidemia, which would provide a scientific basis for its clinical application.

Autophagy-Targeted Calcium Phosphate Nanoparticles Enable Transarterial Chemoembolization for Enhanced Cancer Therapy.

Transarterial chemoembolization (TACE) is commonly used for treating advanced hepatocellular carcinoma (HCC). However, the instability of lipiodol-drug emulsion and the altered tumor microenvironment (TME, such as hypoxia-induced autophagy) postembolization are responsible for the unsatisfactory therapeutic outcomes. Herein, pH-responsive poly(acrylic acid)/calcium phosphate nanoparticles (PAA/CaP NPs) were synthesized and used as the carrier of epirubicin (EPI) to enhance the efficacy of TACE therapy through autophagy inhibition. PAA/CaP NPs have a high loading capacity of EPI and a sensitive drug release behavior under acidic conditions. Moreover, PAA/CaP NPs block autophagy through the dramatic increase of intracellular Ca2+ content, which synergistically enhances the toxicity of EPI. TACE with EPI-loaded PAA/CaP NPs dispersed in lipiodol shows an obvious enhanced therapeutic outcome compared to the treatment with EPI-lipiodol emulsion in an orthotopic rabbit liver cancer model. This study not only develops a new delivery system for TACE but also provides a promising strategy targeting autophagy inhibition to improve the therapeutic effect of TACE for the HCC treatment.

Electroacupuncture alleviates perioperative hypothalamus-pituitary-adrenal axis dysfunction via circRNA-miRNA-mRNA networks.

Electroacupuncture (EA) has long been used to alleviate surgery-induced hypothalamic-pituitary-adrenal axis dysfunction. However, its downstream gene targets in the brain remain unclear. The aim of the present study was to clarify the potential targets of EA based on RNA sequencing techniques (RNA-seq). Rats were divided into normal control (NC), hepatectomy surgery (HT), HT + EA, and HT + sham EA groups followed by RNA-seq of two representative nuclei in the hypothalamus and amygdala. Weighted Gene Co-expression Network Analysis and Gene Set Enrichment Analysis identified six gene modules associated with neuroendocrine transmitters and neural remodeling in the hypothalamus. Furthermore, circRNA-miRNA-mRNA interaction networks revealed EA-related candidate miRNAs and circRNAs, of which opioid receptor mu 1 might be an EA-specific target, and showed regulation by competing endogenous RNA. We identified the neuroendocrine circRNA-miRNA-mRNA networks through which EA has an effect on HPA axis dysfunction, thus providing potential targets and future research directions for EA treatment.