VEGI174 protein and its functional domain peptides exert antitumour effects on renal cell carcinoma

Vascular endothelial growth inhibitor (VEGI) has been identified as an anti‑angiogenic cytokine. However, the effects of VEGI174 protein, and its functional domain peptides V7 and V8, on renal cell carcinoma (RCC) remain unknown. In the present study, the protein and peptides were biosynthesised as experimental agents. The A498 and 786‑O RCC cell lines, and an established mouse xenograft model, were separately treated with VEGI174, V7 or V8. Cellular functions, including proliferation, migration and invasion, were subsequently detected. Cell migration and invasion were monitored using the xCELLigence system. Furthermore, tumour growth and mouse behaviours, including mobility, appetite and body weight, were assessed. The results demonstrated that VEGI174, V7 and V8 inhibited the proliferation, migration and invasion of A498 and 786‑O cell lines when administered at concentrations of 1 and 100 pM, 10 nM and 1 µM. The inhibitory effects exhibited dose‑ and time‑dependent antitumour activity. Furthermore, VEGI174, V7 and V8 inhibited tumour growth in A498 and 786‑O xenograft mice. In the A498 xenografts, the tumour growth inhibition (TGI) rates in the VEGI174‑, V7‑ and V8‑treated groups were 71, 20 and 31%, respectively. In the 786‑O xenografts, the TGI rates in the VEGI174‑, V7‑ and V8‑treated groups were 34, 26 and 31%, respectively. There was no significant loss in body weight and no cases of mortality were observed for all treated mice. In conclusion, VEGI174, V7 and V8 exhibited potential antitumour effects and were well tolerated in vivo. V7 and V8, as functional domain peptides of the VEGI174 protein, may be studied for the future treatment of RCC

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

The safety and efficacy of laparoscopic microwave ablation-assisted partial nephrectomy: a new avenue for the treatment of cystic renal tumors

AbstractPurpose Clinically, the management of cystic renal masses is tricky. The study aims to evaluate the safety and efficacy of laparoscopic microwave ablation-assisted partial nephrectomy (LMAPN) for cystic renal tumors.Methods and materials Between November 2017 and January 2022, LMAPN was performed on 43 patients (29 men and 14 women; age range: 22–80 years; median age 54 years) with Bosniak category III (n = 15) or IV (n = 28) cystic renal tumors (size range: 1.2–5.0 cm; mean size 2.8 cm). The median follow-up period was 26 months (range: 7–56 months). Baseline and perioperative data, pathological features, renal function, postoperative complications and oncologic outcomes were collected and evaluated.Results Forty-three cystic renal tumors were successfully managed by LMAPN. The mean operating time was 79 min (range: 40–130 min). The mean time of renal pedicle clamping was 19 min (range: 12–25 min). Mean intraoperative blood loss was 28.4 mL (range: 10–80 mL). The mean postoperative hospitalization duration was 4 days (range: 2–6 days). Negative surgical margins were diagnosed in all cases. During the follow-up, no patient appeared with distant metastasis, wound or peritoneal cavity implantation. No major but minor complications of Clavien–Dindo grade I were encountered after the operation. The 1-, 3- and 4-year overall survival rate was 100%, 96.6% and 88.5%, respectively.Conclusion This is the first study focusing on LMAPN for cystic renal tumors, demonstrating its favorable feasibility, safety and disease control. Long-term follow-up is necessary to draw conclusions on the preference and advantages of the new therapeutic approach

Oxidized/unmodified-polyethylene microplastics neurotoxicity in mice: Perspective from microbiota-gut-brain axis

Microplastics (MPs) are inevitably oxidized in the environment, and their potential toxicity to organisms has attracted wide attention. However, the neurotoxicity and mechanism of oxidized polyethylene (Ox-PE) MPs to organisms remain unclear. Herein, we prepared oxidized low-density polyethylene (Ox-LDPE) and established a model of MPs exposure by continuously orally gavage of C57BL/6 J mice with LDPE-MPs/Ox-LDPE-MPs for 28 days with or without oral administration of Lactobacillus plantarum DP189 and galactooligosaccharides (DP189&GOS). The experimental results indicated that LDPE-MPs or Ox-LDPE-MPs caused several adverse effects in mice, mainly manifested by behavioral changes, disruption of the intestinal and blood–brain barrier (BBB), and simultaneous oxidative stress, inflammatory reactions, and pathological damage in the brain and intestines. Brain transcriptomic analysis revealed that the cholinergic synaptic signaling pathways, which affect cognitive function, were significantly disrupted after exposure to LDPE-MPs or Ox-LDPE-MPs. Real-time quantitative polymerase chain reaction and Western Blotting results further demonstrated that the critical genes (Slc5a7, Chat and Slc18a3) and proteins (Chat and Slc18a3) in the cholinergic synaptic signaling pathway were significantly down-regulated after exposure to LDPE-MPs or Ox-LDPE-MPs. These alterations lead to reduced acetylcholine concentration, which causes cognitive dysfunction in mice. Importantly, the DP189&GOS interventions effectively mitigated the MPs-induced cognitive dysfunction and intestinal microbiota alteration, improved intestinal and BBB integrity, attenuated the oxidative stress and inflammatory response, and also saw a rebound in the release of acetylcholine. These results indicated that LDPE-MPs and Ox-LDPE-MPs exert neurotoxic effects on mice by inducing oxidative stress, inflammatory responses, and dysregulation of cholinergic signaling pathways in the mouse brain. That probiotic supplementation is effective in attenuating MPs-induced neurotoxicity in mice. Overall, this study reveals the potential mechanisms of neurotoxicity of LDPE-MPs and Ox-LDPE-MPs on mice and their improvement measures, necessary to assess the potential risks of plastic contaminants to human health

Temporal and Spatial Changes of Non-Point Source N and P and Its Decoupling from Agricultural Development in Water Source Area of Middle Route of the South-to-North Water Diversion Project

The quantitative estimation of non-point source (NPS) pollution provides the scientific basis for sustainability in ecologically sensitive regions. This study combined the export coefficient model and Revised Universal Soil Loss Equation to estimate the NPS nitrogen (NPS-N) and NPS phosphorus (NPS-P) loads and then evaluated their relationship with Primary Industrial Output Value (PIOV) in the water source area of the middle route of South-to-North Water Diversion Project (SNWDP) for 2000⁻2015. The estimated results show that: (1) dissolved nitrogen (DN) load increased 0.55%, and dissolved phosphorus (DP) load decreased 4.60% during the 15 years. Annual loads of adsorbed nitrogen (AN) and adsorbed phosphorus (AP) increased significantly before 2005 and then decreased after 2005. Compared with 2000, AN and AP loads in 2015 significantly decreased by 32.72% and 30.81%, respectively. Hanzhong Basin and Ankang Basin are key areas for controlling dissolved pollution, and southern and northern regions are key areas for adsorbed pollution. (2) From 2000 to 2005, NPS pollutants and PIOV showed weak decoupling status. By 2015, NPS pollutants had strong decoupling from PIOV in most counties. (3) Land use has been the main source of NPS-N and NPS-P pollution, accounting for about 75% of NPS-N and 50% of NPS-P based on the average value over the study period. In the future, various measures—such as returning cropland to forest and reducing the number of livestock—could be adopted to reduce the risk of NPS pollution. NPS pollution caused by livestock was grown over the past 15 years and had not yet been effectively controlled, which still needs to be urgently addressed. Collecting ground monitoring data and revising parameters are effective means to improve the accuracy of simulation, which deserve further study. The results will also provide scientific support for sustainable development in similar regions

Efficacy of Bacillus subtilis ANSB060 Biodegradation Product for the Reduction of the Milk Aflatoxin M1 Content of Dairy Cows Exposed to Aflatoxin B1

This study was conducted to determine the effect of Bacillus subtilis ANSB060 biodegradation product (BDP) in reducing the milk aflatoxin M1 (AFM1) content of dairy cows fed a diet contaminated with aflatoxin B1 (AFB1). Twenty-four Chinese Holstein cows (254 ± 19 d in milk; milk production 19.0 ± 1.2 kg d−1) were assigned to three dietary treatments, as follows: (1) control diet (CON), consisting of a basal total mixed ration (TMR); (2) aflatoxin diet (AF), containing CON plus 63 μg of AFB1 kg−1 of diet dry matter; and (3) aflatoxin diet plus BDP (AF + BDP), containing AF plus BDP at 0.2% of diet dry matter. The experiment lasted 12 days, including an AFB1-dosing period from days one to eight, followed by a clearance period from days nine to twelve. Milk samples were collected on days 2, 4, 6, and 8–12, and the plasma was sampled on day 9, before morning feeding. Short-term AFB1 exposure did not affect the milk production and composition. The plasma biochemical indices, except for lactic dehydrogenase (LDH), were also not changed by the AFB1 intake. The plasma LDH level was significantly elevated (p < 0.05) following dietary treatment with AFB1, while no significant difference was observed between the AF + BDP and CON treatments. Adding BDP to the AFB1-contaminaed diet resulted in a significant reduction in AFM1 concentration (483 vs. 665 ng L−1) in the milk, AFM1 excretion (9.14 vs. 12.71 μg d−1), and transfer rate of dietary AFB1 to milk AFM1 (0.76 vs. 1.06%). In conclusion, the addition of BDP could be an alternative method for reducing the dietary AFB1 bioavailability in dairy cows