A comprehensive comparison of microbial communities between aerobic granular sludge and flocculent sludge for nutrient removal in full-scale wastewater treatment plants.

Understanding the microbial community structure of sludge is crucial for improving the design, operation and optimisation of full-scale wastewater treatment plants (WWTPs). This study aimed to have a comprehensive comparison of microbial communities between aerobic granular sludge and flocculent sludge from two full-scale sequential batch reactors-based WWTPs with nutrient removal for the first time. To better understand key functional bacteria such as polyphosphate accumulating bacteria (PAOs), competitive bacteria such as glycogen accumulating bacteria (GAOs) and nitrifying bacteria for both nitrogen and phosphorus removal, another two full-scale WWTPs with only carbon (C) removal and C and nitrogen (N) removal were compared too. It was found that the richness and diversity of the microbial population in sludge increased with pollutant removal from only C, C and N, to C,N, P removal. For C, N P removal, granule structure led to a more diverse and rich microbial community structure than flocculent structure. Although more abundant nitrifying bacteria were enriched in granular sludge than flocculent sludge, the abundance of total putative PAOs was equivalent. However, the most typical putative PAOs such as Tetrasphaera and Candidatus Accumulibacter seemed to be more correlated with biological phosphorus removal performance, which might be more proper to be used as an indication for P removal potential. The higher abundance of GAOs in flocculent sludge with better phosphorus removal performance might suggest that further investigation is needed to understand the functions of GAOs. In addition, the equivalent abundances of PAOs in the WWTPs with only C removal and with C, N, and P removal, respectively, indicate that many newly reported putative PAOs might not contribute to P removal. This study provides insight into the microbial communities and functional bacteria in aerobic granular sludge and flocculent sludge in full-scale SBRs, which can provide microbes-informed optimisation of reactor operation for better nutrient removal.

Therapeutic potential of urine-derived stem cells in renal regeneration following acute kidney injury: A comparative analysis with mesenchymal stem cells.

BACKGROUND: Acute kidney injury (AKI) is a common clinical syndrome with high morbidity and mortality rates. The use of pluripotent stem cells holds great promise for the treatment of AKI. Urine-derived stem cells (USCs) are a novel and versatile cell source in cell-based therapy and regenerative medicine that provide advantages of a noninvasive, simple, and low-cost approach and are induced with high multidifferentiation potential. Whether these cells could serve as a potential stem cell source for the treatment of AKI has not been determined. AIM: To investigate whether USCs can serve as a potential stem cell source to improve renal function and histological structure after experimental AKI. METHODS: Stem cell markers with multidifferentiation potential were isolated from human amniotic fluid. AKI severe combined immune deficiency (SCID) mice models were induced by means of an intramuscular injection with glycerol. USCs isolated from human-voided urine were administered via tail veins. The functional changes in the kidney were assessed by the levels of blood urea nitrogen and serum creatinine. The histologic changes were evaluated by hematoxylin and eosin staining and transferase dUTP nick-end labeling staining. Meanwhile, we compared the regenerative potential of USCs with bone marrow-derived mesenchymal stem cells (MSCs). RESULTS: Treatment with USCs significantly alleviated histological destruction and functional decline. The renal function was rapidly restored after intravenous injection of 5 × 105 human USCs into SCID mice with glycerol-induced AKI compared with injection of saline. Results from secretion assays conducted in vitro demonstrated that both stem cell varieties released a wide array of cytokines and growth factors. This suggests that a mixture of various mediators closely interacts with their biochemical functions. Two types of stem cells showed enhanced tubular cell proliferation and decreased tubular cell apoptosis, although USC treatment was not more effective than MSC treatment. We found that USC therapy significantly improved renal function and histological damage, inhibited inflammation and apoptosis processes in the kidney, and promoted tubular epithelial proliferation. CONCLUSION: Our study demonstrated the potential of USCs for the treatment of AKI, representing a new clinical therapeutic strategy.

Semiconservative transmission of DNA N 6-adenine methylation in a unicellular eukaryote.

Although DNA N 6-adenine methylation (6mA) is best known in prokaryotes, its presence in eukaryotes has recently generated great interest. Biochemical and genetic evidence supports that AMT1, an MT-A70 family methyltransferase (MTase), is crucial for 6mA deposition in unicellular eukaryotes. Nonetheless, the 6mA transmission mechanism remains to be elucidated. Taking advantage of single-molecule real-time circular consensus sequencing (SMRT CCS), here we provide definitive evidence for semiconservative transmission of 6mA in Tetrahymena thermophila In wild-type (WT) cells, 6mA occurs at the self-complementary ApT dinucleotide, mostly in full methylation (full-6mApT); after DNA replication, hemi-methylation (hemi-6mApT) is transiently present on the parental strand, opposite to the daughter strand readily labeled by 5-bromo-2'-deoxyuridine (BrdU). In ΔAMT1 cells, 6mA predominantly occurs as hemi-6mApT. Hemi-to-full conversion in WT cells is fast, robust, and processive, whereas de novo methylation in ΔAMT1 cells is slow and sporadic. In Tetrahymena, regularly spaced 6mA clusters coincide with the linker DNA of nucleosomes arrayed in the gene body. Importantly, in vitro methylation of human chromatin by the reconstituted AMT1 complex recapitulates preferential targeting of hemi-6mApT sites in linker DNA, supporting AMT1's intrinsic and autonomous role in maintenance methylation. We conclude that 6mA is transmitted by a semiconservative mechanism: full-6mApT is split by DNA replication into hemi-6mApT, which is restored to full-6mApT by AMT1-dependent maintenance methylation. Our study dissects AMT1-dependent maintenance methylation and AMT1-independent de novo methylation, reveals a 6mA transmission pathway with a striking similarity to 5-methylcytosine (5mC) transmission at the CpG dinucleotide, and establishes 6mA as a bona fide eukaryotic epigenetic mark.

Improving water quality and mitigating CH4 and N2O production in urban landscape water simultaneously by optimizing calcium peroxide dosage.

Recent studies show that greenhouse gas (GHG) emissions from urban landscape water are significant and cannot be overlooked, underscoring the need to develop effective strategies for mitigating GHG production from global freshwater systems. Calcium peroxide (CaO2) is commonly used as an eco-friendly reagent for controlling eutrophication in water bodies, but whether CaO2 can reduce GHG emissions remains unclear. This study investigated the effects of CaO2 dosage on the production of methane (CH4) and nitrous oxide (N2O) in urban landscape water under anoxic conditions during summer. The findings reveal that CaO2 addition not only improved the physicochemical and organoleptic properties of simulated urban landscape water but also reduced N2O production by inhibiting the activity of denitrifying bacteria across various dosages. Moreover, CaO2 exhibited selective effects on methanogens. Specifically, the abundance of acetoclastic methanogen Methanosaeta and methylotrophic methanogen Candidatus_Methanofastidiosum increased whereas the abundance of the hydrogenotrophic methanogen Methanoregula decreased at low, medium, and high dosages, leading to higher CH4 production at increased CaO2 dosage. A comprehensive multi-objective evaluation indicated that an optimal dosage of 60 g CaO2/m2 achieved 41.21 % and 84.40 % reductions in CH4 and N2O production, respectively, over a 50-day period compared to the control. This paper not only introduces a novel approach for controlling the production of GHGs, such as CH4 and N2O, from urban landscape water but also suggests a methodology for optimizing CaO2 dosage, providing valuable insights for its practical application.

Hematochezia due to rectal invasion by an internal iliac artery aneurysm: A case report.

BACKGROUND: This case report presents the rare occurrence of hematochezia due to an internal iliac artery aneurysm leading to an arterioenteric fistula, expanding the differential diagnosis for gastrointestinal bleeding. It emphasizes the importance of considering vascular origins in cases of atypical hematochezia, particularly in the absence of common gastrointestinal causes, and highlights the role of imaging and multidisciplinary management in diagnosing and treating such unusual presentations. CASE SUMMARY: A 75-year-old man with a history of hypertension presented with 12 d of hematochezia, experiencing bloody stools 7-8 times per day. Initial computed tomography (CT) scans revealed an aneurysmal rupture near the right internal iliac artery with suspected hematoma development. Hemoglobin levels progressively decreased to 7 g/dL. Emergency arterial angiography and iliac artery-covered stent placement were performed, followed by balloon angioplasty. Despite initial stabilization, minor rectal bleeding and abdominal pain persisted, leading to further diagnostic colonoscopy. This identified a neoplasm and potential perforation at the proximal rectum. An exploratory laparotomy confirmed the presence of a hematoma and an aneurysm invading the rectal wall, necessitating partial rectal resection, intestinal anastomosis, and ileostomy. Postoperative recovery was successful, with no further bleeding incidents and normal follow-up CT and colonoscopy results after six months. CONCLUSION: In cases of unusual gastrointestinal bleeding, it is necessary to consider vascular causes for effective diagnosis and intervention.

Single-cell transcriptomic sequencing identifies subcutaneous patient-derived xenograft recapitulated medulloblastoma.

BACKGROUND: Medulloblastoma (MB) is one of the most common malignant brain tumors that mainly affect children. Various approaches have been used to model MB to facilitate investigating tumorigenesis. This study aims to compare the recapitulation of MB between subcutaneous patient-derived xenograft (sPDX), intracranial patient-derived xenograft (iPDX), and genetically engineered mouse models (GEMM) at the single-cell level. METHODS: We obtained primary human sonic hedgehog (SHH) and group 3 (G3) MB samples from six patients. For each patient specimen, we developed two sPDX and iPDX models, respectively. Three Patch+/- GEMM models were also included for sequencing. Single-cell RNA sequencing was performed to compare gene expression profiles, cellular composition, and functional pathway enrichment. Bulk RNA-seq deconvolution was performed to compare cellular composition across models and human samples. RESULTS: Our results showed that the sPDX tumor model demonstrated the highest correlation to the overall transcriptomic profiles of primary human tumors at the single-cell level within the SHH and G3 subgroups, followed by the GEMM model and iPDX. The GEMM tumor model was able to recapitulate all subpopulations of tumor microenvironment (TME) cells that can be clustered in human SHH tumors, including a higher proportion of tumor-associated astrocytes and immune cells, and an additional cluster of vascular endothelia when compared to human SHH tumors. CONCLUSIONS: This study was the first to compare experimental models for MB at the single-cell level, providing value insights into model selection for different research purposes. sPDX and iPDX are suitable for drug testing and personalized therapy screenings, whereas GEMM models are valuable for investigating the interaction between tumor and TME cells.

Excitation of Terahertz Spoof Surface Plasmons on a Roofed Metallic Grating by an Electron Beam.

In this paper, both fundamental SSP modes on a roofed metallic grating and its effective excitation of the bounded SSP mode by an injected electron beam on the structure are numerically examined and investigated in the THz regime. Apart from the bounded SSP mode on the metallic grating with open space, the introduced roofed metallic grating can generate a closed waveguide mode that occupies the dispersion region outside the light line. The closed waveguide mode shifts gradually to a higher frequency band with a decreased gap size, while the bounded SSP mode line becomes lower. The effective excitation of the bounded SSP mode on this roofed metallic grating is also implemented and studied by using a particle-in-cell simulation studio. The output SSP power spectrums with various gap sizes by the same electron beam on this roofed metallic grating are obtained and analyzed. The simulation results reveal that the generated SSP spectra show a slight red shift with a decreased gap size. This work on the excitation of the SSP mode using an electron beam can benefit the development of high-power compact THz radiation sources by utilizing the strong near-field confinement of SSPs on metallic gratings.

Dynamic DNA N 6-adenine methylation (6mA) governs the encystment process, showcased in the unicellular eukaryote Pseudocohnilembus persalinus.

The formation of resting cysts commonly found in unicellular eukaryotes is a complex and highly regulated survival strategy against environmental stress that involves drastic physiological and biochemical changes. Although most studies have focused on the morphology and structure of cysts, little is known about the molecular mechanisms that control this process. Recent studies indicate that DNA N 6-adenine methylation (6mA) could be dynamically changing in response to external stimuli; however, its potential role in the regulation of cyst formation remains unknown. We used the ciliate Pseudocohnilembus persalinus, which can be easily induced to form cysts to investigate the dynamic pattern of 6mA in trophonts and cysts. Single-molecule real-time (SMRT) sequencing reveals high levels of 6mA in trophonts that decrease in cysts, along with a conversion of symmetric 6mA to asymmetric 6mA. Further analysis shows that 6mA, a mark of active transcription, is involved in altering the expression of encystment-related genes through changes in 6mA levels and 6mA symmetric-to-asymmetric conversion. Most importantly, we show that reducing 6mA levels by knocking down the DNA 6mA methyltransferase PpAMT1 accelerates cyst formation. Taken together, we characterize the genome-wide 6mA landscape in P. persalinus and provide insights into the role of 6mA in gene regulation under environmental stress in eukaryotes. We propose that 6mA acts as a mark of active transcription to regulate the encystment process along with symmetric-to-asymmetric conversion, providing important information for understanding the molecular response to environmental cues from the perspective of 6mA modification.

Enhancing Oral Mucosal Barrier, Mitigating Microinflammation, and Addressing Malnutrition in Dialysis Patients: The Impact of Tangerine Peel Lemon Glycerin.

Objective: This study investigates the efficacy of tangerine peel lemon glycerin extract oral spray in improving oral mucosal barrier, reducing microinflammation, and addressing malnutrition in maintenance dialysis (MHD) patients. Methods: Tangerine peel and dry lemon underwent glycerin extraction. From January 2021 to June 2022, 72 MHD patients with thirst were prospectively chosen at Sinopharm Gezhouba Central Hospital. Randomization divided them into an observation group (n=36) and a control group (n=36). Both received routine maintenance dialysis and chronic kidney disease management. Oral conditions were assessed using OHIP-14, a homemade visual thirst score scale, SFR, sAA, and saliva pH. Microinflammatory indexes (CRP, TNF-α, IL-6) and nutritional status indicators (Alb, PA, Hb) were measured. The observation group used 1ml of tangerine peel lemon glycerin extract with a pH value of 5.9~6.1 q6h, while the control group used 1ml of purified water q6h. Results: After 3 months, the observation group showed significant improvement in OHIP-14 and visual thirst score scale (P < .01). Saliva pH, CRP, TNF-α, and IL-6 levels decreased, and SAA activity, SFR, Alb, PA, and Hb levels increased significantly in the observation group compared to the control group (P < .01). Conclusions: Tangerine peel lemon glycerin spray demonstrates promise in improving the oral mucosal barrier, exhibiting antibacterial and anti-inflammatory properties that mitigate microinflammation and malnutrition. This finding suggests a connection between oral health, systemic pathology, psychological state, and social adaptability.

Effects of Dietary Supplementation with Chitosan on the Muscle Composition, Digestion, Lipid Metabolism, and Stress Resistance of Juvenile Tilapia (Oreochromis niloticus) Exposed to Cadmium-Induced Stress.

The aim of this study was to investigate the effects of dietary chitosan supplementation on the muscle composition, digestion, lipid metabolism, and stress resistance, and their related gene expression, of juvenile tilapia (Oreochromis niloticus) subjected to cadmium (Cd2+) stress. Juvenile tilapia with an initial body weight of 21.21 ± 0.24 g were fed with a formulated feed containing five different levels (0%, 0.5%, 1.0%, 1.5%, and 2.0%) of chitosan for 60 days, while the water in all experimental groups contained a Cd2+ concentration of 0.2 mg/L. The results showed that, compared with the control group (0% chitosan), the contents of crude fat and crude protein in the muscle, the activities of lipase, trypsin, and amylase in the intestine, as well as the relative expression levels of metallothionein (mt), cytochrome P450 1A (cyp1a), carnitine palmitoyltransferase-1 (cpt-1), peroxisome proliferator-activated receptor alpha (pparα), peroxisome proliferator-activated receptor gamma (pparγ), hormone-sensitive lipase (hsl), lipoprotein lipase (lpl), malate dehydrogenase (mdh), leptin (lep), fatty acid synthase (fas), sterol regulatory element-binding protein 1 (srebp1), and stearoyl-CoA desaturase (scd) genes in the liver of juveniles were significantly increased (p < 0.05). In conclusion, dietary chitosan supplementation could alleviate the effects of Cd2+ stress on the muscle composition, digestive enzymes, lipid metabolism, and stress resistance, and their related gene expression, of juvenile tilapia, and to some extent reduce the toxic effect of Cd2+ stress on tilapia.

Recent insights into the effect of endoplasmic reticulum stress in the pathophysiology of intestinal ischaemia‒reperfusion injury.

Intestinal ischaemia‒reperfusion (I/R) injury is a surgical emergency. This condition is associated with a high mortality rate. At present, there are limited number of efficient therapeutic measures for this injury, and the prognosis is poor. Therefore, the pathophysiological mechanisms of intestinal I/R injury must be elucidated to develop a rapid and specific diagnostic and treatment protocol. Numerous studies have indicated the involvement of endoplasmic reticulum (ER) stress in the development of intestinal I/R injury. Specifically, the levels of unfolded and misfolded proteins in the ER lumen are increased due to unfolded protein response. However, persistent ER stress promotes apoptosis of intestinal mucosal epithelial cells through three signalling pathways in the ER, impairing intestinal mucosal barrier function and leading to the dysfunction of intestinal tissues and distant organ compartments. This review summarises the mechanisms of ER stress in intestinal I/R injury, diagnostic indicators, and related treatment strategies with the objective of providing novel insights into future therapies for this condition.

Alpha-lipoic acid (ALA) ameliorates early brain injury after subarachnoid hemorrhage in Sprague-Dawley (SD) rats via inhibiting STING-NLRP3 inflammatory signaling.

Neuroinflammation is intimately associated with poor prognosis in patients with subarachnoid hemorrhage (SAH). Alpha-lipoic acid (ALA), a disulfide antioxidant, has been shown to be neuroprotective in an in vivo model of neurological injury; however, the role of ALA in SAH has never been evaluated. In this study, the Sprague-Dawley rats SAH model was induced by endovascular perforation method. ALA was transplanted intravenously into rats, and SR-717, a stimulator of interferon genes (STING) agonist, was injected intraperitoneally. The effects of ALA on early brain injury were assayed by neurological score, hematoxylin and eosin staining and Nissl staining. Immunohistochemistry staining and Western blotting were used to analyze various proteins. ALA significantly reduced STING- NLRP3 protein expression and decreased cell death, which in turn mitigated the neurobehavioral dysfunction following SAH. Furthermore, coadministration of ALA and SR-717 promoted STING-NLRP3 signaling pathway activation following SAH, which reversed the inhibitory effect of ALA on STING-NLRP3 protein activation and increased the neurological deficits. In conclusion, ALA may be a promising therapeutic strategy for alleviating early brain injury after SAH.

The elite eating quality alleles Wxb and ALKb are regulated by OsDOF18 and coordinately improve head rice yield.

Head rice yield (HRY) measures rice milling quality and determines final grain yield and commercial value. Here, we report that two major quantitative trait loci for milling quality in rice, qMq-1 and qMq-2, represent allelic variants of Waxylv/Waxyb (hereafter Wx) encoding Granule-Bound Starch Synthase I (GBSSI) and Alkali Spreading Value ALKc/ALKb encoding Soluble Starch Synthase IIa (SSIIa), respectively. Complementation and overexpression transgenic lines in indica and japonica backgrounds confirmed that Wx and ALK coordinately regulate HRY by affecting amylose content, the number of amylopectin branches, amyloplast size, and thus grain filling and hardness. The transcription factor OsDOF18 acts upstream of Wx and ALK by activating their transcription. Furthermore, rice accessions with Wxb and ALKb alleles showed improved HRY over those with Wxlv and ALKc. Our study not only reveals the novel molecular mechanism underlying the formation of HRY but also provides a strategy for breeding rice cultivars with improved HRY.

Identification of arnicolide C as a novel chemosensitizer to suppress mTOR/E2F1/FANCD2 axis in non-small cell lung cancer.

BACKGROUND AND PURPOSE: The mammalian target of rapamycin (mTOR) pathway plays critical roles in intrinsic chemoresistance by regulating Fanconi anaemia complementation group D2 (FANCD2) expression. However, the mechanisms by which mTOR regulates FANCD2 expression and related inhibitors are not clearly elucidated. Extracts of Centipeda minima (C. minima) showed promising chemosensitizing effects by inhibiting FANCD2 activity. Here, we have aimed to identify the bioactive chemosensitizer in C. minima extracts and elucidate its underlying mechanism. EXPERIMENTAL APPROACH: The chemosensitizing effects of arnicolide C (ArC), a bioactive compound in C. minima, on non-small cell lung cancer (NSCLC) were investigated using immunoblotting, immunofluorescence, flow cytometry, the comet assay, small interfering RNA (siRNA) transfection and animal models. The online SynergyFinder software was used to determine the synergistic effects of ArC and chemotherapeutic drugs on NSCLC cells. KEY RESULTS: ArC had synergistic cytotoxic effects with DNA cross-linking drugs such as cisplatin and mitomycin C in NSCLC cells. ArC treatment markedly decreased FANCD2 expression in NSCLC cells, thus attenuating cisplatin-induced FANCD2 nuclear foci formation, leading to DNA damage and apoptosis. ArC inhibited the mTOR pathway and attenuated mTOR-mediated expression of E2F1, a critical transcription factor of FANCD2. Co-administration of ArC and cisplatin exerted synergistic anticancer effects in the A549 xenograft mouse model by suppressing mTOR/FANCD2 signalling in tumour tissues. CONCLUSION AND IMPLICATIONS: ArC suppressed DNA cross-linking drug-induced DNA damage response by inhibiting the mTOR/E2F1/FANCD2 signalling axis, serving as a chemosensitizing agent. This provides insight into the anticancer mechanisms of ArC and offers a potential combinatorial anticancer therapeutic strategy.

Characterisation and identification of chemical constituents in aqueous extract of Fomes officinalis Ames based on ultrahigh-performance liquid chromatography tandem quadrupole-Orbitrap high-resolution mass spectrometry.

INTRODUCTION: Fungal species are an attractive resource for physiologically functional food and drug precursor. Fomes officinalis Ames, a medicinal fungus, is traditionally used as a folk medicine in traditional Chinese medicine prescription for the therapy of cough and asthma. The water-soluble substances in Chinese herbal medicines are likely to play an important physiological function. However, information on probing and identifying chemical components of the aqueous extract of Fomes officinalis Ames (AFO) remains unknown. OBJECTIVE: This study was conducted to screen and characterise the chemical components of AFO. MATERIAL AND METHODS: An effective and sensitive ultrahigh-performance liquid chromatography tandem quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS) method with the Full MS/PIL/dd-MS2 acquisition approach was applied for the profiling of chemical components in AFO. An HSS T3 column was used for component separation, and a strategy of simultaneous targeted and untargeted multicomponent characterisation was implemented. Multiple identification approaches were used, including accurate molecular mass and elemental composition matching, literature and database searching, and fragmentation rules elucidation. RESULTS: A total of 115 components, including 20 amino acids and derivatives, six nucleobases, nine nucleosides, 75 dipeptides, two tripeptides, and three other components, were tentatively identified. Among them, the targeted exploring method screened six nucleobases and nine nucleosides including modified nucleosides. To our best knowledge, this is the first time a report has been done on the presence of the 115 compounds in AFO. CONCLUSION: Profiling and characterisation compounds of AFO enriched its material basis, which would lay the foundation for improving potential medicinal and nutritional values and effecting comprehensive quality control of Fomes officinalis Ames.

Lanthanum promotes Solanum nigrum L. growth and phytoremediation of cadmium and lead through endocytosis: Physiological and biochemical response, heavy metal uptake and visualization.

Rare earth elements (REEs) are important to enhance agricultural productivity. The utilization of phytoremediation as a green technology for addressing heavy metal (HMs) contamination in soil and wastewater has gained significant attention. In our research, we conducted indoor hydroponic experiments to examine the impacts of lanthanum (La) on the growth and enrichment capacity of Solanum nigrum L. (S. nigrum). S. nigrum was cultivated in 10 mg·L-1 of cadmium (Cd), 25 mg·L-1 of lead (Pb), and a mixture of both (5 mg·L-1 Cd + 15 mg·L-1 Pb). Additionally, S. nigrum were subjected to foliar spray or hydroponic supplementation of La(III). The treatment with La(III) significantly increased total fresh weight by 17.82 % to 42.20 %, compared to the treatment without La(III). Furthermore, La(III) facilitated the endocytosis of roots and enhanced Cd2+ flux ranging from 15.64 % to 75.99 % when compared to the treatment without La(III). Foliar and hydroponic application of La(III) resulted in an increase in the translocation factors (TF) in plants of Cd and Pb compared to treatments without La(III). These findings can offer valuable insights into the potential of La(III) to enhance the phytoremediation of soil or wastewater polluted with compounds.

Foliar spraying of lanthanum activates endocytosis in lettuce (Lactuca sativa L.) root cells, increasing Cd and Pb accumulation and their bioaccessibility.

Cadmium (Cd) and lead (Pb) accumulate easily in leafy vegetables and can harm human health. Lanthanum (La) have been used to improve agricultural yield and quality, but the effect of La application on Cd/Pb enrichment in leafy vegetables remains incomplete currently. A previous study reported that the endocytosis in lettuce leaf cells can be activated by La, leading to an increase in Pb accumulation in lettuce leaves. However, it has not been investigated whether foliar application of La enhances root cellular endocytosis and promotes its uptake of Cd and Pb. In this study, the influence of La on the uptake of Cd and Pb, Cd bioaccessibility, and the safety risks of cultivating lettuce under Cd and Pb stress were explored. It was found that La increased Cd (16-30 % in shoot, 16-34 % in root) and Pb (25-29 % in shoot, 17-23 % in root) accumulation in lettuce. The increased accumulation of Cd and Pb could be attributed to La-enhanced endocytosis. Meanwhile, La enhanced the toxicity of both Cd and Pb, inhibited lettuce growth, and aggravated the damage to the photosynthetic and antioxidant systems. Finally, gastrointestinal simulation experiments showed that La increased the Cd bioaccessibility in both gastric and intestinal phase by 7-108 % and 9-87 %, respectively. These results offer valuable insights into the safety of REEs for agricultural applications.

Food Effect on the Pharmacokinetics of VC004, a Tropomyosin Receptor Kinase Inhibitor: A Randomized Crossover Trial in Healthy Chinese Subjects.

BACKGROUND AND OBJECTIVE: VC004 is a novel next-generation tropomyosin receptor kinase (TRK) inhibitor that is approved for the treatment of advanced or metastatic NTRK fusion-positive solid tumors and abrogated the drug resistance of the first-generation TRK inhibitors. The objective of the present study was to evaluate the effect of food on the pharmacokinetics and safety of VC004. METHODS: The study was a randomized, open-label, two-period crossover, single-dose, phase I clinical trial. A total of 16 healthy subjects participated the trial. Subjects fasted for 10 h before drug administration in both fasting and fed states. Subjects received VC004 50 mg orally in the fasting state and after a high caloric food in the fed state. Blood samples at the designated time points were collected to determine the plasma concentration of VC004. Safety evaluation in both the fasted and fed periods were assessed via vital sign monitoring and clinical laboratory tests. RESULTS: The maximum plasma concentration (Cmax) of VC004 in fed group decreased by 32.8%, corresponding with the slower absorption rate (time to Cmax (Tmax) delayed by almost 3 h) compared with the fasting group. Ratios of geometric means (GMRs) and 90% confidence intervals (90% CIs) of Cmax, the area under the curve of plasma concentration-time from zero to the last measurable concentration (AUC0-t), and AUC from zero to infinity (AUC0-∞) for VC004 between the two states were 67.18 (58.16-77.60), 103.59 (95.04-112.92) and 103.55 (95.63-112.11), respectively. No serious adverse events (AEs) occurred; only three grade 1 or grade 2 adverse events occurred in the fasted group, who recovered by the end of the study. CONCLUSIONS: The intake of high calorie food decreased the absorption rate and increased the Tmax of VC004, while the AUC values were similar in both groups. No serious adverse event was reported. In conclusion, food does not alter the pharmacokinetics and safety profile of VC004 in a clinically meaningful manner. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT055528120.

Sensitivity of Botrytis cinerea from Vineyards to Boscalid, Isofetamid, and Pydiflumetofen in Shandong Province, China.

Succinate dehydrogenase inhibitor (SDHI) fungicides are the most commonly and effectively used class of fungicides for controlling gray mold. Among them, only boscalid has been registered in China for controlling grape gray mold, whereas isofetamid and pydiflumetofen are two new SDHI fungicides that have demonstrated high efficacy against various fungal diseases. However, the sensitivity of Botrytis cinerea isolates from vineyards in China to these three fungicides is currently unknown. In this study, the sensitivity of 55 B. cinerea isolates from vineyards to boscalid, isofetamid, and pydiflumetofen was determined, with the effective concentrations for inhibiting 50% of spore germination (EC50) values ranging from 1.10 to 393, 0.0300 to 42.0, and 0.0990 to 25.5 µg ml-1, respectively. The resistance frequencies for boscalid, isofetamid, and pydiflumetofen were 60.0, 7.2, and 12.8%, respectively. Three mutations (H272R, H272Y, and P225F) were detected in the SdhB subunit, with H272R being the most prevalent (75.7%), followed by H272Y (16.2%) and P225F (8.1%). All three mutations are associated with resistance to boscalid, and of them, H272R mutants exhibited high resistance. Only P225F and H272Y mutants exhibited resistance to isofetamid and pydiflumetofen, respectively. A weakly positive cross-resistance relationship was observed between boscalid and pydiflumetofen (r = 0.38, P < 0.05). Additionally, the H272R mutants showed no significant fitness costs, whereas the remaining mutants exhibited reduced mycelial growth (P225F) and sporulation (H272Y and P225F). These results suggest that isofetamid and pydiflumetofen are effective fungicides against B. cinerea in vineyards, but appropriate rotation strategies must be implemented to reduce the selection of existing SDHI-resistant isolates.