Isolation, characterization, and application of a novel Pseudomonas fluorescens phage vB_PF_Y1-MI in contaminated milk.

The food industry has incurred substantial losses from contamination by Pseudomonas fluorescens, emphasizing the critical importance of implementing effective control strategies. Phages are potential sterilizers due to their specific killing abilities and the difficulty bacteria face in developing resistance. However, a significant barrier to their development is the lack of diversity among phage types. In this study, we characterized a novel lytic P. fluorescens phage, named vB_PF_Y1-MI. Phage vB_PF_Y1-MI displayed a latent period of nearly 10 min and a high burst size of 1493 PFU/cell. This phage showed good activity over a wide range of temperature (up to 70 °C) and pH (3-12). The genome of phage vB_PF_Y1-MI spans 93,233 bp with a GC content of 45%. It encompasses 174 open-reading frames and 19 tRNA genes, while no lysogeny or virulence-associated genes were detected. Phylogenetic analysis positions it as a novel unassigned evolutionary lineage within the Caudoviricetes class among related dsDNA phages. Our study provides foundational insights into vB_PF_Y1-MI and emphasizes its potential as an effective biological control agent against P. fluorescens. This research offers crucial theoretical groundwork and technical support for subsequent efforts in preventing and controlling P. fluorescens contamination.

Visualization of Mitochondrial DNA G-Quadruplexes with Isaindigotone Derived Near-Infrared Fluorogenic Probe.

Mitochondrial DNA G-quadruplexes (mtDNA G4s) play potential regulatory roles in mitochondrial functions. Fluorescent probes for imaging mtDNA G4s may provide useful information to unveil their regulating dynamics and functions. However, the existing probes for mtDNA G4s still exhibit short absorption and emission wavelengths and limited sensitivity. Here, we develop a new isaindigotone-derived near-infrared (NIR) fluorogenic probe for imaging mtDNA G4s in live cells and in vivo. Different fluorescent probes are engineered by conjugating the isaindigotone scaffold with varying electron-donating groups. It is shown that the probe ISAP using dimethylaminophenyl as the electron-donating group exhibits near-infrared absorption/emission and a high fluorescence activation fold in response to G4s. Molecular docking simulations reveal that ISAP binds to c-Myc G4 via multiple π-π stacking and hydrogen-bond interaction. Cellular studies show that ISAP exhibits an excellent mitochondrial targeting ability and allows specific imaging of mtDNA G4s. We further employed ISAP to image the dynamics of mtDNA G4s under glycolysis and oxidative stresses in live cells. Its capability to mtDNA G4s in vivo is showcased using a tumor-bearing mice model. This probe may serve as a useful tool to image mtDNA G4s and interrogate their biological roles in living systems.

KIAA0753 enhances osteoblast differentiation suppressed by diabetes.

Diabetes-related bone loss represents a significant complication that persistently jeopardizes the bone health of individuals with diabetes. Primary cilia proteins have been reported to play a vital role in regulating osteoblast differentiation in diabetes-related bone loss. However, the specific contribution of KIAA0753, a primary cilia protein, in bone loss induced by diabetes remains unclear. In this investigation, we elucidated the pivotal role of KIAA0753 as a promoter of osteoblast differentiation in diabetes. RNA sequencing demonstrated a marked downregulation of KIAA0753 expression in pro-bone MC3T3 cells exposed to a high glucose environment. Diabetes mouse models further validated the downregulation of KIAA0753 protein in the femur. Diabetes was observed to inhibit osteoblast differentiation in vitro, evidenced by downregulating the protein expression of OCN, OPN and ALP, decreasing primary cilia biosynthesis, and suppressing the Hedgehog signalling pathway. Knocking down KIAA0753 using shRNA methods was found to shorten primary cilia. Conversely, overexpression KIAA0753 rescued these changes. Additional insights indicated that KIAA0753 effectively restored osteoblast differentiation by directly interacting with SHH, OCN and Gli2, thereby activating the Hedgehog signalling pathway and mitigating the ubiquitination of Gli2 in diabetes. In summary, we report a negative regulatory relationship between KIAA0753 and diabetes-related bone loss. The clarification of KIAA0753's role offers valuable insights into the intricate mechanisms underlying diabetic bone complications.

Anti-HIV activity in traditional Chinese medicine: clinical implications of monomeric herbal remedies and compound decoctions.

With the global spread of human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS), the pursuit of potent treatments has ascended as a paramount concern in global healthcare. Traditional Chinese medicine (TCM) has been used for thousands of years in China and other East Asian countries and it offers remedies for an extensive array of ailments, including HIV and AIDS. This review focuses on the clinical significance of single herbs and composite tonics in TCM with antiviral activity against HIV. Initially, the anti-HIV activity of single herbs was analyzed in detail. Many herbs have been shown to have significant anti-HIV activity. The active ingredients of these herbs exhibit their anti-HIV effects through various mechanisms, such as inhibiting viral replication, preventing viral binding to host cells, and interfering with the viral lifecycle. Furthermore, we delved into the clinical significance of HIV-associated formulations provided as a result of Chinese compound prescription. These combinations of herbal ingredients are designed to amplify therapeutic efficacy and minimize adverse effects. Clinical trials have demonstrated the therapeutic benefits of these prescriptions for individuals infected with HIV. The intricate composition of these prescriptions potentially augments their anti-HIV activity through synergistic effects. Additionally, this review underscores the clinical importance of TCM in the context of HIV treatment. While numerous herbs and prescriptions exhibit anti-HIV activity, their safety and efficacy in clinical applications warrant further investigation. When combined with contemporary antiretroviral drugs, TCM may serve as an adjunctive therapy, assisting in reducing side effects, and enhancing patients' quality of life. To optimally harness these natural resources, further exploration is imperative to ascertain their efficacy, safety, and optimal utilization, thereby offering a broader spectrum of therapeutic options for HIV-afflicted individuals.

Molecular characterization and expression patterns of MTP genes under heavy metal stress in mustard (Brassica juncea L.).

Members of the Metal Tolerance Protein (MTP) family are critical in mediating the transport and tolerance of divalent metal cations. Despite their significance, the understanding of MTP genes in mustard (Brassica juncea) remains limited, especially regarding their response to heavy metal (HM) stress. In our study, we identified MTP gene sets in Brassica rapa (17 genes), Brassica nigra (18 genes), and B. juncea (33 genes) using the HMMER (Cation_efflux; PF01545) and BLAST analysis. For the 33 BjMTPs, a comprehensive bioinformatics analysis covering the physicochemical properties, phylogenetic relationships, conserved motifs, protein structures, collinearity, spatiotemporal RNA-seq expression, GO enrichment, and expression profiling under six HM stresses (Mn2+, Fe2+, Zn2+, Cd2+, Sb3+, and Pb2+) were carried out. According to the findings of physicochemical characteristics, phylogenetic tree, and collinearity, the allopolyploid B. juncea's MTP genes were inherited from its progenitors, B. rapa and B. nigra, with minimal gene loss during polyploidization. Members of the BjMTP family exhibited conserved motifs, promoter elements, and expression patterns across subgroups, consistent with the seven evolutionary branches (G1, G4-G9, and G12) of the MTPs. Further, spatiotemporal expression profiling under HM stresses successfully identified specific genes and crucial cis-regulatory elements associated with the response of BjMTPs to HM stresses. These findings may contribute to the genetic improvement of B. juncea for enhanced HM tolerance, facilitating the remediation of HM-contaminated areas.

Quantitative trait locus analysis of gray leaf spot resistance in the maize IBM Syn10 DH population.

KEY MESSAGE: The exploration and dissection of a set of QTLs and candidate genes for gray leaf spot disease resistance using two fully assembled parental genomes may help expedite maize resistance breeding. The fungal disease of maize known as gray leaf spot (GLS), caused by Cercospora zeae-maydis and Cercospora zeina, is a significant concern in China, Southern Africa, and the USA. Resistance to GLS is governed by multiple genes with an additive effect and is influenced by both genotype and environment. The most effective way to reduce the cost of production is to develop resistant hybrids. In this study, we utilized the IBM Syn 10 Doubled Haploid (IBM Syn10 DH) population to identify quantitative trait loci (QTLs) associated with resistance to gray leaf spot (GLS) in multiple locations. Analysis of seven distinct environments revealed a total of 58 QTLs, 49 of which formed 12 discrete clusters distributed across chromosomes 1, 2, 3, 4, 8 and 10. By comparing these findings with published research, we identified colocalized QTLs or GWAS loci within eleven clustering intervals. By integrating transcriptome data with genomic structural variations between parental individuals, we identified a total of 110 genes that exhibit both robust disparities in gene expression and structural alterations. Further analysis revealed 19 potential candidate genes encoding conserved resistance gene domains, including putative leucine-rich repeat receptors, NLP transcription factors, fucosyltransferases, and putative xyloglucan galactosyltransferases. Our results provide a valuable resource and linked loci for GLS marker resistance selection breeding in maize.

miR­576­3p/M­phase phosphoprotein 8 axis regulates the malignant progression of hepatocellular carcinoma cells via the PI3K/Akt signaling pathway.

Hepatocellular carcinoma (HCC) is a fatal digestive system cancer with unclear pathogenesis. M-phase phosphoprotein 8 (MPP8) has been shown to play a vital role in several cancer types, such as non-small cell lung cancer, gastric cancer and melanoma; however, there have been no studies into its role in HCC. The present study aimed to evaluate the role of MPP8 in regulating malignant phenotypes of liver cancer cells, and to further investigate the underlying mechanism. Bioinformatics analysis was performed to analyze related data from a public database, and to predict the potential microRNAs (miRNAs) that might target MPP8 mRNA; reverse transcription-quantitative PCR was used to measure the levels of mRNA and miRNA; western blotting was employed to detect protein levels; Cell Counting Kit-8 (CCK-8) and plate colony formation assays, wound healing assay and Transwell invasion assay were performed to evaluate the ability of cell proliferation, migration and invasion, respectively; dual-luciferase reporter gene assay was performed to identify the target association. The results showed that MPP8 was a risk factor for the survival of patients with HCC, and was up-regulated in HCC tissue samples and cell lines; MPP8 knockdown inhibited the proliferation, migration and invasion of liver cancer cells; MPP8 knockdown suppressed the PI3K/Akt pathway, and activation of this pathway reversed the inhibited liver cancer cell phenotypes by down-regulating MPP8; miR-576-3p, which was low in liver cancer cells, negatively regulated MPP8 expression by directly targeting its mRNA; up-regulating MPP8 expression reversed the inhibited signaling pathway and malignant phenotypes of liver cancer cells by miR-576-3p overexpression. In conclusion, the miR-576-3p/MPP8 axis regulates the proliferation, migration, and invasion of liver cancer cells through the PI3K/Akt signaling pathway. These findings lead novel insights into HCC progression, and propose MPP8 as a potential therapeutic target for HCC.

The application of Global Trigger Tool in monitoring antineoplastic adverse drug events: a retrospective study.

Objective: This study aimed to establish an antineoplastic drugs trigger tool based on Global Trigger Tool (GTT), to examine the performance by detecting adverse drug events (ADEs) in patients with cancer in a Chinese hospital (a retrospective review), and to investigate the factors associating with the occurrence of antineoplastic ADEs. Methods: Based on the triggers recommended by the GTT and those used in domestic and foreign studies and taking into account the scope of biochemical indexes in our hospital, some of them were adjusted. A total of 37 triggers were finally developed. Five hundred medical records of oncology patients discharged in our hospital from 1 June 2020 to 31 May 2021 were randomly selected according to the inclusion and exclusion criteria. These records were reviewed retrospectively by antineoplastic drugs trigger tool. The sensitivity and specificity of the triggers were analyzed, as well as the characteristics and risk factors for the occurrence of ADEs. Results: Thirty-three of the 37 triggers had positive trigger, and the sensitivity rate was 91.8% (459/500). For the specificity, the positive predictive value of overall ADEs was 46.0% (715/1556), the detection rate of ADEs was 63.0% (315/500), the rate of ADEs per 100 admissions was 136.0 (95% CI, 124.1-147.9), and the rate of ADEs per 1,000 patient days was 208.33 (95% CI, 201.2-215.5). The top three antineoplastic drugs related to ADEs were antimetabolic drugs (29.1%), plant sources and derivatives (27.1%), and metal platinum drugs (26.3%). The hematologic system was most frequently involved (507 cases, 74.6%), followed by gastrointestinal system (89 cases, 13.1%). Multivariate logistic regression analysis showed that the number of combined drugs (OR = 1.14; 95% CI, 1.07-1.22; P < 0.001) and the previous history of adverse drug reaction (ADR) (OR = 0.38; 95% CI, 0.23-0.60; P < 0.001) were the risk factors for ADEs. The length of hospital stay (OR = 0.40; 95% CI, 0.14-1.12; P < 0.05) and the previous history of ADR (OR = 2.18; 95% CI, 1.07-4.45; P < 0.05) were the risk factors for serious adverse drug events (SAE). Conclusion: The established trigger tool could be used to monitor antineoplastic drugs adverse events in patients with tumor effectively but still needs to be optimized. This study may provide some references for further research in order to improve the rationality and safety of antineoplastic medications.

An activatable fluorescent-photoacoustic dual-modal probe for highly sensitive imaging of nitroxyl in vivo.

Nitroxyl (HNO) plays a vital role in various biological functions and pharmacological activities, so the development of an excellent near-infrared fluorescent (NIRF) and photoacoustic (PA) dual-modality probe is crucial for understanding HNO-related physiological and pathological progression. Herein, we proposed and synthesized a novel NIRF/PA dual probe (QL-HNO) by substituting an indole with quinolinium in hemicyanine for the sensitive detection of exogenous and endogenous HNO in vivo. The designed probe showed the highest sensitivity in NIRF mode and a desirable PA signal-to-noise ratio for HNO detection in vitro and was further applied for NIRF/PA dual-modal imaging of HNO with high contrast in living cells and tumor-bearing animals. Based on the excellent performance of QL-HNO, we believe that this study provides a promising molecular tool for further understanding of HNO-related physiological and pathological progression.

Progress in research on the effects of quinoa (Chenopodium quinoa) bioactive compounds and products on intestinal flora.

Quinoa is a highly nutritious whole-grain crop with unique values as both a food and medicinal supplement. At present, the roles played by the intestinal microflora in human health are gaining considerable attention from the research community, and studies to date have shown that the occurrence of a range of diseases may be associated with an imbalance of the intestinal flora. The bioactive compounds of quinoa affect the production of SCFAs and the adjustment of intestinal pH. In this article, we review the mechanisms underlying the effects of different quinoa constituents on the intestinal flora, the effects of these constituents on the intestinal flora of different hosts, and progress in research on the therapeutic properties of quinoa constituents, to provide a better understanding of quinoa in terms its dual medicinal and nutritional properties. We hope this review will provide a useful reference for approaches that seek to enhance the composition and activities of the intestinal flora.

Selective aneurysmal sac neck-targeted embolization during endovascular repair of abdominal aortic aneurysm with hostile neck anatomy.

PURPOSE: To evaluate the efficacy and safety of selective aneurysmal sac neck-targeted embolization in endovascular aneurysm repair (EVAR) in patients with a hostile neck anatomy (HNA). MATERIALS AND METHODS: Between October 2020 and June 2022, patients with an abdominal aortic aneurysm (AAA) and HNA who underwent EVAR with a low-profile stent graft and a selective aneurysmal sac neck-targeted embolization technique were analysed. An HNA was defined by the presence of any of the following parameters: infrarenal neck angulation > 60°; neck length < 15 mm; conical neck; circumferential calcification ≥ 50%; or thrombus ≥ 50%. Before occluding the entire aneurysm during the procedure, a buddy wire was loaded prophylactically into the sac through the contralateral limb side. If a type Ia endoleak (ELIa) occurred and persisted despite adjunctive treatment such as balloon moulding or cuff extension, this preloaded wire could be utilized to enable a catheter to reach the space between the stent graft and sac neck to perform coil embolization. In the absence of ELIa, the wire was simply retracted. The primary outcome of this study was freedom from sac expansion and endoleak-related reintervention during the follow-up period; secondary outcomes included technical success and intraoperative and in-hospital postoperative complications. RESULTS: Among the 28 patients with a hostile neck morphology, 11 (39.5%) who presented with ELIa underwent intraprocedural treatment involving sac neck-targeted detachable coil embolization. Seventeen individuals (60.7%) of the total patient population did not undergo coiling. All patients in the coiling group underwent balloon moulding, and 2 patients additionally underwent cuff extension. In the noncoiling group, 14 individuals underwent balloon moulding as a treatment for ELIa, while 3 patients did not exhibit ELIa during the procedure. The coiling group showed longer operating durations (81.27 ± 11.61 vs. 70.71 ± 7.17 min, P < 0.01) and greater contrast utilization than the noncoiling group (177.45 ± 52.41 vs. 108.24 ± 17.49 ml, P < 0.01). In the entire cohort, the technical success rate was 100%, and there were no procedure-related complications. At a mean follow-up of 18.6 ± 5.2 months (range 12-31), there were no cases of sac expansion (19 cases of sac regression, 67.86%; 9 cases of stability, 32.14%) or endoleak-related reintervention. CONCLUSIONS: Selective aneurysmal sac neck-targeted embolization for the treatment of ELIa in AAA patients with an HNA undergoing EVAR is safe and may prevent type Ia endoleak and related sac expansion after EVAR.

Rapid Separation of Asiatic Acid, Quercetin, and Kaempferol from Traditional Chinese Medicine Centella asiatica (L.) Urban Using HSCCC-Semi-Prep-HPLC and the Assessment of Their Potential as Fatty Acid Synthase Inhibitors.

The main objective of this study was to rapidly separate asiatic acid (AA), quercetin (QCN), and kaempferol (KPL) from Centella asiatica (L.) Urban using high-speed counter-current chromatography (HSCCC) in tandem with the UV detector of semipreparative high-performance liquid chromatography (Semi-Prep-HPLC) and to evaluate their potential as inhibitors of fatty acid synthetase (FAS). To efficiently prepare large amounts of AA, QCN, and KPL from Centella asiatica (L.) Urban, rapid and simple methods by HSCCC were established respectively based on the partition coefficients (K values) of crude samples. The conditions of HSCCC-Semi-Prep-HPLC for the large-scale separation of AA, QCN, and KPL from Centella asiatica (L.) Urban were established and optimized. This included selecting the solvent system, flow rate, rotation speed, and so on. HSCCC-Semi-Prep-HPLC was successfully applied to separate and purify AA, QCN, and KPL, with n-hexane-n-butanol-methanol-water (3 : 1 : 3 : 3, V : V : V : V) as the solvent system for AA, which was detected at a wavelength of 210 nm with the stationary phase retention of 70%, and with n-hexane-ethyl acetate-methanol-water (0.8 : 0.9 : 1.2 : 1, V : V : V : V) as the solvent system for the co-separation of QCN and KPL, which was detected at a wavelength of 254 nm with the stationary phase retention of 65%. AA could be isolated at a large scale with high purity (>91.0%) in only one-step HSCCC-Semi-Prep-HPLC separation (within 150 min) under the optimized conditions. Meanwhile, QCN and KPL could be simultaneously isolated at a large scale with high purity (>99.1%) by another one-step HSCCC-Semi-Prep-HPLC separation (within 240 min) under the optimized conditions. The assessment of inhibition potential revealed that AA exhibited the strongest inhibitory effect on FAS, with an IC50 of 9.52 ± 0.76 µg/mL. Madecassic acid (MA) followed closely with IC50 values of 10.84 ± 0.92 µg/mL. QCN and KPL showed similar and relatively weaker inhibitory effects on FAS, with IC50 values of 43.09 ± 2.98 µg/mL and 36.90 ± 1.83 µg/mL, respectively. Overall, the HSCCC-Semi-Prep-HPLC method proved to be a highly efficient and reliable technique for separating AA, QCN, and KPL from Centella asiatica (L.) Urban, and the isolated compounds showed potential as FAS inhibitors.

The G protein-coupled receptor COLD1 promotes chilling tolerance in maize during germination.

The geographic range and yield of the staple crop maize (Zea mays L.) are both strongly limited by low-temperature conditions. One of the most economical and effective measures for improvement of maize production is chilling tolerance enhancement. In this study, a chilling-tolerance gene in maize, ZmCOLD1, was cloned and characterized. This gene encodes a G protein-coupled receptor that is localized to the plasma membrane and the endoplasmic reticulum. A single nucleotide polymorphism (SNP) in ZmCOLD1, SNP2738, was found to confer chilling tolerance and to have promoted maize adaptations during speciation from teosinte. Overexpression of the excellent haplotype ZmCOLD1Hap11 significantly enhanced chilling tolerance, whereas knocking down ZmCOLD1 increased sensitivity to low temperatures during the germination and seedling stages. ZmCOLD1 was associated with an influx of extracellular Ca2+, increases in abscisic acid content, and decreases in gibberellic acid and indole-3-acetic acid content under low temperatures during the germination stage. ZmCOLD1 interacted with the G protein α subunit ZmCT2 at the plasma membrane, and ZmCT2 interacted with ZmLanCL in the nucleus. These proteins are components of the chilling tolerance signaling pathway in maize that are triggered by abscisic acid and photosynthesis. These results offer novel strategies for improvement of chilling tolerance in key crop species.

Molecular and biochemical investigations of the anti-fatigue effects of tea polyphenols and fruit extracts of Lycium ruthenicum Murr. on mice with exercise-induced fatigue.

Background: The molecular mechanisms regulating the therapeutic effects of plant-based ingredients on the exercise-induced fatigue (EIF) remain unclear. The therapeutic effects of both tea polyphenols (TP) and fruit extracts of Lycium ruthenicum (LR) on mouse model of EIF were investigated. Methods: The variations in the fatigue-related biochemical factors, i.e., lactate dehydrogenase (LDH), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-2 (IL-2), and interleukin-6 (IL-6), in mouse models of EIF treated with TP and LR were determined. The microRNAs involved in the therapeutic effects of TP and LR on the treatment of mice with EIF were identified using the next-generation sequencing technology. Results: Our results revealed that both TP and LR showed evident anti-inflammatory effect and reduced oxidative stress. In comparison with the control groups, the contents of LDH, TNF-α, IL-6, IL-1ß, and IL-2 were significantly decreased and the contents of SOD were significantly increased in the experimental groups treated with either TP or LR. A total of 23 microRNAs (21 upregulated and 2 downregulated) identified for the first time by the high-throughput RNA sequencing were involved in the molecular response to EIF in mice treated with TP and LR. The regulatory functions of these microRNAs in the pathogenesis of EIF in mice were further explored based on Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses with a total of over 20,000-30,000 target genes annotated and 44 metabolic pathways enriched in the experimental groups based on GO and KEGG databases, respectively. Conclusion: Our study revealed the therapeutic effects of TP and LR and identified the microRNAs involved in the molecular mechanisms regulating the EIF in mice, providing strong experimental evidence to support further agricultural development of LR as well as the investigations and applications of TP and LR in the treatment of EIF in humans, including the professional athletes.

Enzyme-targeted near-infrared fluorescent probe for organophosphorus pesticide residue detection.

Pesticide residues significantly affect food safety and harm human health. In this work, a series of near-infrared fluorescent probes were designed and developed by acylating the hydroxyl group of the hemicyanine skeleton with a quenching moiety for monitoring the presence of organophosphorus pesticides in food and live cells. The carboxylic ester bond on the probe was hydrolyzed catalytically in the presence of carboxylesterase and thereby the fluorophore was released with near-infrared emission. Notably, the proposed probe 1 exhibited excellent sensitivity against organophosphorus based on the carboxylesterase inhibition mechanism and the detection limit for isocarbophos achieved 0.1734 µg/L in the fresh vegetable sample. More importantly, probe 1 allowed for situ visualization of organophosphorus in live cells and bacteria, meaning great potential for tracking the organophosphorus in biological systems. Consequently, this study presents a promising strategy for tracking pesticide residues in food and biological systems.

Characterizations of microRNAs involved in the molecular mechanisms underlying the therapeutic effects of noni (Morinda citrifolia L.) fruit juice on hyperuricemia in mice.

Background: Hyperuricemia is generally defined as the high level of serum uric acid and is well known as an important risk factor for the development of various medical disorders. However, the medicinal treatment of hyperuricemia is frequently associated with multiple side-effects. Methods: The therapeutic effect of noni (Morinda citrifolia L.) fruit juice on hyperuricemia and the underlying molecular mechanisms were investigated in mouse model of hyperuricemia induced by potassium oxonate using biochemical and high-throughput RNA sequencing analyses. Results: The levels of serum uric acid (UA) and xanthine oxidase (XOD) in mice treated with noni fruit juice were significantly decreased, suggesting that the noni fruit juice could alleviate hyperuricemia by inhibiting the XOD activity and reducing the level of serum UA. The contents of both serum creatinine and blood urine nitrogen of the noni fruit juice group were significantly lower than those of the model group, suggesting that noni fruit juice promoted the excretion of UA without causing deleterious effect on the renal functions in mice. The differentially expressed microRNAs involved in the pathogenesis of hyperuricemia in mice were identified by RNA sequencing with their target genes further annotated based on both Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases to explore the metabolic pathways and molecular mechanisms underlying the therapeutic effect on hyperuricemia by noni fruit juice. Conclusion: Our study provided strong experimental evidence to support the further investigations of the potential application of noni fruit juice in the treatment of hyperuricemia.

Comparative Efficacy and Safety of Five Anti-calcitonin Gene-related Peptide Agents for Migraine Prevention: A Network Meta-analysis.

OBJECTIVES: Anti-calcitonin gene-related peptide (CGRP) agents are some of the newest preventive medications for migraine. There is limited literature comparing the efficacy of the most recent CGRP antagonist, atogepant, to CGRP monoclonal antibodies for migraine prevention. In this network meta-analysis, the efficacy and safety of migraine treatments including different doses of atogepant and CGRP monoclonal antibodies were evaluated to provide a reference for future clinical trials. MATERIALS AND METHODS: A search using PubMed, Embase, and Cochrane Library identified all randomized controlled trials published through May 2022 and including patients diagnosed with episodic or chronic migraine and treated with erenumab, fremanezumab, eptinezumab, galcanezumab, atogepant, or placebo. The primary outcomes were the reduction of monthly migraine days, 50% response rate, and the number of adverse events (AEs). The Cochrane Collaboration tool was used to assess the risk of bias. RESULTS: In this study, 24 articles were considered for analysis. Regarding efficacy, all interventions were superior to placebo with a statistically significant difference. The most effective intervention was monthly fremanezumab 225 mg in change from baseline of migraine days (standard mean difference = -0.49, 95% CI: -0.62, -0.37) and 50% response rate (risk ratio = 2.98, 95% CI: 2.16,4.10), while the optimal choice for reducing acute medication days was monthly erenumab 140 mg (standard mean difference = -0.68, 95% CI: -0.79, -0.58). In terms of AEs, all therapies and placebo did not achieve statistical significance except for monthly galcanezumab 240 mg and quarterly fremanezumab 675 mg. There was no significant difference in discontinuation due to AEs between interventions and placebo. DISCUSSION: All anti-CGRP agents were more effective than placebo in migraine prevention. Overall, monthly fremanezumab 225 mg, monthly erenumab 140 mg, and daily atogepant 60 mg were effective interventions with fewer side effects.

Activatable Near-Infrared Fluorescent and Photoacoustic Dual-Modal Probe for Highly Sensitive Imaging of Sulfatase In Vivo.

Sulfatase is an important biomarker closely associated with various diseases. However, the state-of-the-art sulfatase probes are plagued with a short absorption/emission wavelength and limited sensitivity. Developing highly sensitive fluorescent probes for in vivo imaging of sulfatase remains a grand challenge. Herein, for the first time, an activatable near-infrared fluorescence/photoacoustic (NIRF/PA) dual-modal probe (Hcy-SA) for visualizing sulfatase activity in living cells and animals is developed. Hcy-SA is composed of a sulfate ester moiety as the recognition unit and a NIR fluorophore hemicyanine (Hcy-OH) as the NIRF/PA reporter. The designed probe exhibits a rapid response, excellent sensitivity, and high specificity for sulfatase detection in vitro. More importantly, cells and in vivo experiments confirm that Hcy-SA can be successfully applied for PA/NIRF dual-modal imaging of sulfatase activity in living sulfatase-overexpressed tumor cells and tumor-bearing animals. This probe can serve as a promising tool for sulfatase-related pathological research and cancer diagnosis.

Nano silicon dioxide reduces cadmium uptake, regulates nutritional homeostasis and antioxidative enzyme system in barley seedlings (Hordeum vulgare L.) under cadmium stress.

Cadmium (Cd) toxicity is one of the most severe environmental threats inhibiting crop growth and productivity. Strategies to mitigate the adverse effects of Cd stress on plants are under scrutiny. Nano silicon dioxide (nSiO2) is an emerging material and could protect plants against abiotic stress. Can nSiO2 alleviate Cd toxicity in barley, and the possible mechanisms are poorly understood. A hydroponic experiment was conducted to study the mitigation effects of nSiO2 on Cd toxicity in barley seedlings. The results showed that the application of nSiO2 (5, 10, 20, and 40 mg/L) increased barley plant growth and chlorophyll and protein content, improving photosynthesis, compared with Cd-treated alone. Specifically, 5-40 mg/L nSiO2 addition increased net photosynthetic rate (Pn) by 17.1, 38.0, 30.3, and - 9.7%, respectively, relative to the Cd treatment alone. Furthermore, exogenous nSiO2 reduced Cd concentration and balanced mineral nutrient uptake. The application of 5-40 mg/L nSiO2 decreased Cd concentration in barley leaves by 17.5, 25.4, 16.7, and 5.8%, respectively, relative to the Cd treatment alone. Moreover, exogenous nSiO2 lowered malondialdehyde (MDA) content by 13.6-35.0% in roots, and by 13.5-27.2% in leaves, respectively, compared with Cd-treated alone. Besides, nSiO2 altered antioxidant enzyme activities and alleviated detrimental effects on Cd-treated plants, attaining maximal values at 10 mg/L nSiO2. These findings revealed that exogenous nSiO2 application may be a viable option for addressing Cd toxicity of barley plants.