A crossover study to evaluate the pharmacokinetics and bioequivalence of hydroxychloroquine tablets in healthy Chinese subjects.

AIMS: Hydroxychloroquine (HCQ) has a high variability and a long half-life in the human body. The purpose of this study was to evaluate the bioequivalence of a generic HCQ tablet (test preparation) versus a brand HCQ tablet (reference preparation) under fasting and fed conditions in a crossover design. MATERIALS AND METHODS: This was an open-label, two-period randomized, single-dose, crossover study in 47 healthy Chinese subjects who were sequentially and randomly allocated either to the fed group (high-fat meal; n = 23) or the fasting group (n = 24). Participants in each group were randomized to the two arms to receive either a single 200-mg dose of the test preparation or a 200-mg dose of the reference preparation. The application of the two preparations in each patient was separated by a 28-day washout period, regarded as sufficiently long to avoid significant interference from residual drug in the body. Whole blood samples were collected over 72 hours after drug administration. RESULTS: A total of 23 subjects completed both the fed and the fasting parts of the trial. There were no significant differences in Cmax, AUC0-72h, and T1/2 between the test and reference preparation (p < 0.05). Food had no significant effect on Cmax and T1/2 (p < 0.05), but AUC0-72h values were significantly reduced under fed condition compared to fasting condition (p < 0.05). The 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of Cmax and AUC0-72h were 0.84 - 1.05 and 0.89 - 0.98 in the fed study, and 0.97 - 1.07 and 0.97 - 1.05 in the fasting study, respectively. The carryover effect due to non-zero blood concentrations resulted in higher AUC0-72h values in the second period for both test and reference formulations and had no effect on the statistical results. No serious adverse events were reported. CONCLUSION: The investigation demonstrated that the test and reference preparations are bioequivalent and well tolerated under both fasting and fed conditions in healthy Chinese subjects.

Chemoreceptors from the commensal gut Roseburia rectibacter bind to mucin and trigger chemotaxis.

Chemotaxis is crucial for bacterial adherence and colonization of the host gastrointestinal tract. Previous studies have demonstrated that chemotaxis affects the virulence of causative pathogens and the infection in the host. However, the chemotactic abilities of non-pathogenic and commensal gut bacteria have rarely been explored. We observed that Roseburia rectibacter NSJ-69 exhibited flagella-dependent motility and chemotaxis to a variety of molecules, including mucin and propionate. A genome-wide analysis revealed that NSJ-69 has 28 putative chemoreceptors, 15 of which have periplasmic ligand-binding domains (LBDs). These LBD-coding genes were chemically synthesized and expressed heterologously in Escherichia coli. Intensive screening of ligands revealed four chemoreceptors bound to mucin and two bound to propionate. When expressed in Comamonas testosteroni or E. coli, these chemoreceptors elicited chemotaxis toward mucin and propionate. Hybrid chemoreceptors were constructed, and results showed that the chemotactic responses to mucin and propionate were dependent on the LBDs of R. rectibacter chemoreceptors. Our study identified and characterized R. rectibacter chemoreceptors. These results will facilitate further investigations on the involvement of microbial chemotaxis in host colonization.

Quantitative Relaxometry Assessment of Brain Microstructural Abnormality of Preschool Children With Autism Spectrum Disorder With Synthetic Magnetic Resonance Imaging.

OBJECTIVE: This study aimed to perform an assessment of brain microstructure in children with autism aged 2 to 5 years using relaxation times acquired by synthetic magnetic resonance imaging. MATERIALS AND METHODS: Thirty-four children with autism spectrum disorder (ASD) (ASD group) and 17 children with global developmental delay (GDD) (GDD group) were enrolled, and synthetic magnetic resonance imaging was performed to obtain T1 and T2 relaxation times. The differences in brain relaxation times between the 2 groups of children were compared, and the correlation between significantly changed T1/T2 and clinical neuropsychological scores in the ASD group was analyzed. RESULTS: Compared with the GDD group, shortened T1 relaxation times in the ASD group were distributed in the genu of corpus callosum (GCC) ( P = 0.003), splenium of corpus callosum ( P = 0.002), and right thalamus (TH) ( P = 0.014), whereas shortened T2 relaxation times in the ASD group were distributed in GCC ( P = 0.011), left parietal white matter ( P = 0.035), and bilateral TH (right, P = 0.014; left, P = 0.016). In the ASD group, the T2 of the left parietal white matter is positively correlated with gross motor (developmental quotient [DQ] 2) and personal-social behavior (DQ5), respectively ( r = 0.377, P = 0.028; r = 0.392, P = 0.022); the T2 of the GCC was positively correlated with DQ5 ( r = 0.404, P = 0.018); and the T2 of the left TH is positively correlated with DQ2 and DQ5, respectively ( r = 0.433, P = 0.009; r = 0.377, P = 0.028). All significantly changed relaxation values were not significantly correlated with Childhood Autism Rating Scale scores. CONCLUSIONS: The shortened relaxometry times in the brain of children with ASD may be associated with the increased myelin content and decreased water content in the brain of children with ASD in comparison with GDD, contributing the understanding of the pathophysiology of ASD. Therefore, the T1 and T2 relaxometry may be used as promising imaging markers for ASD diagnosis.

First Report of Root Rot Caused by Pythium dissotocum on Tobacco in China.

Tobacco (Nicotiana tabacum L.) is an important economic crop that is widely grown around the world. Its annual production in China is estimated at 2.2 million tons (Berbec and Matyka 2020). Since 2022, a root rot disease was sporadically observed on tobacco seedlings on cultivar Yunyan 87 in cultivated tobacco fields in the Hunan province of China. A disease incidence of about 10% occurred across 48 ha of tobacco fields. The affected tobacco plants had slow and stunted growth with yellowing leaves. The roots turned grayish brown, decayed, and died. Diseased roots were collected from six fields and cut into small pieces (5 mm ×5 mm) from the edge of the rotted portions, and then sterilized with 70% ethanol for 10 s, 0.1% HgCl2 for 1 min, and washed in sterilized water three times. All the sterilized tissue were placed on potato dextrose agar (PDA) medium and cultured at 26 ℃ in the dark. About 3 days later, colonies with similar morphology were removed and sub-cultured on fresh PDA. A total of six strains were obtained from six tobacco samples. Strains were white and had radial growth on PDA. Hyphae were aseptate and the sporangia were filamentous. The oogonia were subglobose, smooth, 16.04 ± 0.25 µm (n=50) in diameter, and developed on unbranched stalks. The antheridia were barrel shaped and clavate. Oospores were globose, aplerotic or nearly plerotic, measuring 6.62 ± 0.33 µm (n=50). These morphological characteristics were consistent with the description of Pythium spp. (van der Plaats-Niterink 1981). For molecular identification, the internal transcribed spacer (ITS) region of rDNA and cytochrome c oxidase subunit I (Cox I) of a representative isolate, GF-3, were amplified and sequenced (GenBank accession nos. OR228424 for ITS and OR237556 for Cox I) using universal primers ITS1/ITS4 (White et al. 1990) and FM58/FM66, respectively (Villa et al. 2006). BLASTn analysis revealed that the ITS and Cox I sequences were 99.76 % (838/840 bp) and 99.85% (671/672 bp) identical to the corresponding sequences of P. dissotocum strain CBS 166.68 (AY598634.2) and UM982 (MT981147.1), respectively. A neighbor-joining phylogenetic tree based on the Cox I sequence showed that GF-3 grouped in the P. dissotocum branch. Based on morphological and molecular characteristics, GF-3 was identified to be P. dissotocum. For pathogenicity testing, four- to five-leaf-old healthy potted tobacco seedlings of the Yunyan 87 cultivar were inoculated with a zoospore suspension (1 × 105 zoospores/ml), which was induced on V8-juice medium. The zoospore suspension was introduced into the soil around plant roots and 10 mL of inoculum was used for each plant. In the control group, plants were inoculated with sterilized water. All of the treated plants were kept in humid chambers at 26°C under a 12 h/12 h photoperiod. The pathogenicity assays were performed twice, with each treatment having three replicated plants. After 5 days, tobacco seedlings inoculated with P. dissotocum showed symptoms resembling that observed in the field. However, the control plants remained healthy. Pythium dissotocum was re-isolated from the infected plants and identified by morphological and molecular methods, thus confirming Koch's postulates. Pythium dissotocum has been reported causing root rot in other plants, including hydroponic lettuce (McGehee et al. 2018) and spinach (Huo et al. 2020). Also, many Pythium species have recently been recovered from float-bed tobacco transplant production greenhouses (Zhang et al. 2022). However, to our knowledge, this is the first report of root rot on tobacco caused by P. dissotocum in China. Since this disease could greatly affect tobacco seedling establishment in the field, appropriate management strategies need to be developed to reduce further losses in tobacco planting fields.

Three important short-chain fatty acids (SCFAs) attenuate the inflammatory response induced by 5-FU and maintain the integrity of intestinal mucosal tight junction.

BACKGROUND: 5-Fluorouracil (5-FU) is a used chemotherapy drug for cancer, and its main side effect is intestinal mucositis which causes chemotherapy to fail. It was known that short-chain fatty acids (SCFAs) can inhibit immune cell release of various proinflammatory factors and inhibit excessive intestinal inflammation. However, the inhibitory effect of SCFAs on 5-FU-induced intestinal mucositis is still unclear. RESULTS: To simulate the effects of SCFAs on immune and intestinal epithelial cells, the cells (THP-1 cells and Caco-2 cells) were pretreated with sodium acetate (NaAc), sodium propionate (NaPc) and sodium butyrate (NaB), then inflammation was induced by 5-FU. The expressions of reactive oxygen species (ROS), Beclin-1, LC3-II, NF-κB p65, NLRP3 inflammasome, proinflammatory/anti-inflammatory cytokines and mucosal tight junction proteins were determined. In our results, the three SCFAs could inhibit ROS expressions, NLRP3, Caspase-1, IL-1ß, IL-6, IL-18, Beclin-1 and LC3-II, when induced by 5-FU. In a 5-FU-induced chemoentermuctis mouse model, Lactobacillus rhamnoides can increase the concentrations of three SCFAs in faeces and increase the concentrations of IL-1ß, IL-6 and IgA in serum, and decrease the expressions of NLRP3 and IL-17 in spleen cells. The expressions of ZO-1 and Occludin in intestinal mucosa were significantly increased. CONCLUSIONS: These results indicated that the three SCFAs can effectively suppress the inflammation of THP-1 cells and Caco-2 cells and maintain tight junction integrity in intestinal mucosal epithelial cells.

Geniposide-Loaded Liposomes for Brain Targeting: Development, Evaluation, and In Vivo Studies.

Geniposide (GE) possesses excellent neuroprotective effects but with poor brain targeting and short half-life. Liposome was considered to have great potential for brain diseases. Therefore, this research aimed to develop a geniposide liposome (GE-LP) as a brain delivery system for cerebral ischemia reperfusion injury (CIRI) therapy and evaluate its characterization, pharmacokinetics, brain targeting, and neuroprotective effects in vivo. Then, a reverse-phase evaporation method was applied to develop the GE-LP and optimize the formulation. Notably, the GE-LP had suitable size, which was 223.8 nm. Subsequently, the pharmacokinetic behavior of GE solution and GE-LP in mice plasma was investigated, and the brain targeting was also researched. The results showed that GE in plasma of GE-LP displayed three folds longer distribution half-life and a higher bioavailability and brain targeting compared to GE solution. In vivo neuroprotective effects was evaluated through the middle cerebral artery occlusion (MCAO) rat model, and GE-LP exhibited a stronger tendency in preventing the injury of CIRI, which can significantly improve neurological deficits. Overall, this study demonstrates GE-LP as a new formulation with ease of preparation, sustained release, and high brain targeting, which has significant development prospects on CIRI; this is expected to improve the efficacy of GE and reduce the frequency of administration.

Spexin/NPQ Induces FBJ Osteosarcoma Oncogene (Fos) and Produces Antinociceptive Effect against Inflammatory Pain in the Mouse Model.

Spexin/NPQ is a novel highly conserved neuropeptide. It has a widespread expression in the periphery and central nervous system. However, the effects of central spexin on acute inflammatory pain are still unknown. This study explored the mechanisms and effects of supraspinal spexin on inflammatory pain. The results from the mouse formalin test show that i.c.v. administration of spexin decreased licking/biting time during the late and early phases. The nonamidated spexin had no effect on pain response. The antinociception of spexin was blocked by galanin receptor 3 antagonist SNAP 37889. The Galr3 and Adcy4 mRNA levels in the brain were increased after injection with spexin. The antinociceptive effects of spexin were completely reversed by opioid receptor antagonist naloxone and κ-opioid receptor antagonist nor-binaltorphimine dihydrochloride. Spexin up-regulated the dynorphin and κ-opioid receptor gene and protein expression. PCR array assay and real-time PCR analysis show that spexin up-regulated the mRNA level of the FBJ osteosarcoma oncogene (Fos). T-5224, the inhibitor of c FBJ osteosarcoma oncogene (c-Fos)/activator protein 1 (AP-1), blocked the increased mRNA level of Pdyn and Oprk1 induced by spexin. I.C.V. spexin (2.43 mg/kg) increased the number of c-Fos-positive neurons in most subsections of periaqueductal gray. In addition, in the acetic acid-induced writhing test, i.c.v. spexin produced an antinociceptive effect. Our results indicate that spexin might be a novel neuropeptide with an antinociceptive effect against acute inflammatory pain.

Expression of DCUN1D1 in laryngeal squamous cell carcinoma and its inhibiting effect on TU-177 cells after interfered by RNA.

Expression of DCUN1D1 in laryngeal squamous cell carcinoma (LSCC) and its inhibition by small interfering RNA (siRNA) target in the TU-177 cells was investigated. Immunohistochemistry was used to detect the expression level of DCUN1D1 in LSCC tissue in 140 cases and to analyze its relationship with clinical pathological characteristics. siRNA expression plasmid targeting DCUN1D1 was constructed and transferred into TU-177 cells. The effect of siRNA target DCUN1D1 gene silencing on proliferation, invasion and migration of TU-177 cells were observed by MTS assay and Transwell experiment. The expression levels of focal adhesion kinase (FAK) and matrix metalloproteinase-2(MMP-2) were detected by western blot. Expression level of DCUN1D1 protein increased significantly in T3 + T4, N+, and III + IV stages of LSCC patients (P < .05). After DCUN1D1 was targeted by siRNA, the DCUN1D1 protein level decreased 67% in siRNA-3 group, where average absorbance value was lower than the control and blank group with significant difference(F = 6.076, P < .05) in MTS assay, meantime migration, and invasion cells in each vision were the same (F = 19.851, F = 25.454, P < .01) in the Transwell experiment. The expression level of FAK and MMP-2 was significantly down-regulated in siRNA-3 group (F = 28.896, F = 40.240, P < .01). DCUN1D1 is associated with progression and prognosis of LSCC. After siRNA based target on DCUN1D1, TU-177 cells growth was inhibited and invasion of malignant tumour was diminished by reducing the expression of FAK and MMP-2. DCUN1D1 is could become a potential new target for the treatment of LSCC.

Exendin-4 does not modify growth or apoptosis of human colon cancer cells.

AIM: Glucagon-like peptide-1 (GLP-1) receptor agonists are a kind of very popular antidiabetes drugs. They promote cell proliferation and survival through activation of signaling pathways in human islet cells involving phosphate idylinositol 3 kinase (PI3K) and extracellular regulated kinases 1 and 2 (ERK1/2), which are frequently activated in human colon cancer cells. Then, it is possible that taking GLP-1 receptor (GLP-1R) agonists persistently would induce proliferation of ß cells as well as colon cancer cells. So, clarifying the effects and mechanisms of GLP-1R agonists on colon cancer cells has important clinical implications. MATERIALS AND METHODS: We investigated GLP-1R expression in human colon cancer tissue samples with immunohistochemisty analysis and explored the effects of exendin-4, a GLP-1 receptor agonist, on colon cancer cells in vitro and in vivo. RESULTS: The results showed lack of GLP-1R expression in both human colon cancer tissues and colon cancer cell lines. Exendin-4 did not enhance the proliferation and migration of colon cancer cell lines in vitro, and nor did it inhibit apoptosis induced by cytotoxic agents such as 5-fluorouracil (5-FU) or irinotecan. In addition, exendin-4 did not promote the propagation of colon cancer cells in vivo. CONCLUSION: Our study suggests that GLP-1R agonists do not modify the growth or survival of human colon cancer cells and may be safe for diabetic patients with colon cancer.

Outcomes of radiofrequency ablation (RFA) and CO2 laser for early glottic cancer.

OBJECTIVE: In the present study, the voice and functional outcomes of radiofrequency ablation (RFA) and CO2 laser for early glottic cancer were evaluated. METHODS: One hundred sixty eight patients with early glottic cancer from October 2007 to June 2015 were included. Ninety-seven patients underwent RFA and seventy-one patients underwent CO2 laser. The operation time and score of visual analog scale (VAS) for pain on the second day after surgery were recorded. The electronic laryngoscopy was performed at one week, one month and three months of postoperation. RESULTS: The operation time in RFA was shorter than that in CO2 laser (8.52±1.43min vs. 11.76±1.67min, P<0.05). There was no statistical difference in VAS scores between two operation methods (2.86±0.52 vs. 2.89±0.68, P>0.05). One month after operation, the mucosal recovery in RFA group was better than that in CO2 laser group (P<0.05). The alterations of acoustic parameters Jitter, Shimmer and HNR at three time points after operation showed statistical significances in both RFA and CO2 laser groups (P<0.05). The significant differences in acoustic parameters between two groups were also observed (P<0.05). There were no differences in three-year survival rate, local recurrence rate, recurrence rate with anterior commissure involvement and postoperative adhesion rate with anterior commissure between the patients with RFA and CO2 laser (P>0.05). No patient underwent tracheotomy and had symptoms of bucking, dyspnea, severe pain, hemoptysis and other serious complications. CONCLUSION: Both RFA and CO2 laser are safe and effective for the treatment of early glottic cancer. RFA has the advantage of quick voice recovery, low mucosa injury and short operation time, which is worthy for wide clinical application.

[Bacterial Community Structure of Typical Lake Sediments in Yinchuan City and Its Response to Heavy Metals].

Lake wetlands are extremely important and special ecosystems, which are important for regional water resource storage, environmental protection, and biodiversity maintenance. Sediment bacteria are an important component of lake ecosystems and are a major driver of biogeochemical cycling in lakes. In order to investigate the community structure of bacteria in typical lake sediments in Yinchuan City and their influencing factors, three typical lakes in Yinchuan City (Yuehai Lake, Mingcui Lake, and Xiniu Lake) were selected for the study and surface sediments were collected in January, April, July, and October 2021. The composition of the sediment bacterial community was examined using 16S rDNA high-throughput sequencing technology, and the response relationships between them and heavy metals were explored. The results showed that the ecological hazard coefficient for heavy metals in the sediments of three typical lakes in Yinchuan City was far less than 40, and the ecological hazard index was far less than 150, all of which indicated a minor ecological hazard. There were no significant differences in bacterial community diversity among the three lakes, but there were significant variations in diversity among the lakes in different seasons and significant differences in community composition. The dominant phyla (top three in terms of relative abundance) in Yuehai Lake, Mingcui Lake, and Xiniu Lake were Proteobacteria, Bacteroidetes, and Chloroflexi. The dominant lower orders were Gammaproteobacteria, Alphaproteobacteria, and Deltaproteobacteria. The main divergent species that occurred at the phylum level in typical lakes in Yinchuan were Proteobacteria, Bacteroidetes, Euryarchaeota, Firmicutes, Actinobacteria, and Acidobacteria. The sediment bacterial community structure of Yuehai Lake was significantly correlated with Cu, Fe, Mn, Zn, As, and Pb; the sediment bacterial community structure of Lake Mingcui was significantly correlated with Fe, Pb, and Cr; and the sediment bacterial community structure of Xiniu Lake was not significantly correlated with heavy metals. The types and contents of sediment heavy metals had a significant effect on the bacterial community structure of sediments in Yinchuan Yuehai Lake and Mingcui Lake and were important environmental factors that caused changes in the bacterial community structure of lake sediments.

Prognostic Value of Coronary Microvascular Dysfunction Assessed by Coronary Angiography-Derived Index of Microcirculatory Resistance in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: CaIMR is proposed as a novel angiographic index designed to assess microcirculation without the need for pressure wires or hyperemic agents. We aimed to investigate the impact of caIMR on predicting clinical outcomes in STEMI patients. METHODS: One hundred and forty patients with STEMI who received PCI in Putuo Hospital of Shanghai from October 2021 to September 2022 were categorized into CMD and non-CMD groups according to the caIMR value. The baseline information, patient-related examinations, and the occurrence of MACE at the 12-month follow-up were collected to investigate risk factors in patients with STEMI. RESULTS: We divided 140 patients with STEMI enrolled into two groups according to caIMR results, including 61 patients diagnosed with CMD and 79 patients diagnosed with non-CMD. A total of 21 MACE occurred during the 1 year of follow-up. Compared with non-CMD group, patients with CMD showed a significantly higher risk of MACE. A multivariate Cox regression model was conducted for the patients, and it was found thatcaIMR was a significant predictor of prognosis in STEMI patients (HR: 8.921). Patients with CMD were divided into culprit vascular CMD and non-culprit vascular CMD, and the result found that culprit vascular CMD was associated with the incidence of MACE (OR: 4.75) and heart failure (OR: 7.50). CONCLUSION: CaIMR is a strong predictor of clinical outcomes and can provide an objective risk stratification for patients with STEMI. There is a strong correlation among leukocyte index, the use of furosemide, Killips classification, and clinical outcomes.

Cushing's syndrome caused by giant Ewing's sarcoma of the kidney: A case report and review of literature.

BACKGROUND: Primary renal Ewing's sarcoma (ES) is extremely rare, and only two cases causing Cushing's syndrome (CS) have been reported to date. We report that the case of an 18-year-old patient is diagnosed primary renal ES with typical CS characterized by purple stripes, weight gain, and hypertension. CASE SUMMARY: CS was first diagnosed by laboratory testing. A huge tumor was revealed in the kidney following an imaging examination. Moreover, brain and bone metastases were observed. After comprehensive treatment, primarily based on surgery, primary renal ES was pathologically diagnosed with a typical EWSR1-FLI1 genetic mutation through genetic testing. Furthermore, the glucocorticoid level returned to normal. By the ninth postoperative month of follow-up, the patient was recovering well. Cushing-related symptoms had improved, and a satisfactory curative effect was achieved. CONCLUSION: Primary renal ES, a rare adult malignant tumor, can cause CS and a poor prognosis.

A dysprosium(III)-based triple helical-like complex as a turn-on/off fluorescence sensor for Al(III) and 4,5-dimethyl-2-nitroaniline.

A novel triple helical-like complex [Dy2K2L3(NO3)2]·3DMF (1) based on a designed Schiff base N'1,N'3-bis((E)-3-ethoxy-2-hydroxybenzylidene)-malonohydrazide (H4L) was synthesized with good chemical and thermal stabilities. Single-crystal X-ray structural analysis showed that 1 presents a tetranuclear triple helical-like structure via the coordination mode of Dy : K : L with 2 : 2 : 3 stoichiometry. Fluorescence measurements showed that 1@EtOH has excellent fluorescence turn-on/off response ability for aluminium ions and 4,5-dimethyl-2-nitroaniline (DMNA) with outstanding selectivity, sensitivity, and anti-interference ability. The calculated limit of detection (LOD) values for 1@EtOH to Al3+ and DMNA were found to be 0.53 and 3.33 µM, respectively. Density functional theory (DFT) calculation showed that the fluorescence response mechanism can be explained by the photoinduced electron transfer (PET) mechanism; meanwhile, the inner filter effect (IFE) of DMNA can also affect the emission of 1@EtOH.

[Pollution Characteristics and Risk Assessment of Polycyclic Aromatic Hydrocarbons in Farmland Soil and Crops in the Suburbs of Urumqi].

In order to understand the occurrence of PAHs in soil and crops, the enrichment capacity of different crops for PAHs, and the distribution characteristics of PAHs in different parts of crops, the crops and soil planted in the farmland around Urumqi were studied as examples. Samples were collected in the farmland gathering area in the suburb of Urumqi in July 2021. A total of 100 crop samples were collected, including 21 crop species and 45 surface soil samples. The results showed that 16 types of PAHs were detected in the soil and crops. The total concentration of PAHs in farmland soil ranged from 19.06 to 1870.86 µg·kg-1, and the average concentration was 127.40 µg·kg-1. Seven carcinogenic PAHs accounted for 42.85%-79.20% of the 16 types of PAHs, among which BaP was the main pollutant in the soil. Through the characteristic ratio method, it was found that the main sources of PAHs in the soil were biomass and coal combustion. Total PAHs in crops ranged from 1.86 µg·kg-1 to 974.05 µg·kg-1, with an average of 303.30 µg·kg-1. Different crops had different enrichment capacities for PAHs. Among the 21 crops sampled, the accumulative content of PAHs in pumpkin was the highest (431.75 µg·kg-1). In leaf vegetable crops, the content of PAHs in leaves was higher than that in roots and fruits. In fruit and vegetable crops, the PAH content in fruit was higher than that in the root or leaf. There was a significant correlation between high cyclic PAHs in soil and PAHs in plant leaves. The health risk assessment of PAHs in crops showed that dietary intake had potential carcinogenic risk and even had high carcinogenic risk in adult male and female groups, which requires further attention.

External validation of a deep learning detection system for glaucomatous optic neuropathy: a real-world multicentre study.

OBJECTIVES: To conduct an external validation of an automated artificial intelligence (AI) diagnostic system using fundus photographs from a real-life multicentre cohort. METHODS: We designed external validation in multiple scenarios, consisting of 3049 images from Qilu Hospital of Shandong University in China (QHSDU, validation dataset 1), 7495 images from three other hospitals in China (validation dataset 2), and 516 images from high myopia (HM) population of QHSDU (validation dataset 3). The corresponding sensitivity, specificity and accuracy of this AI diagnostic system to identify glaucomatous optic neuropathy (GON) were calculated. RESULTS: In validation datasets 1 and 2, the algorithm yielded accuracy of 93.18% and 91.40%, area under the receiver operating curves (AUC) of 95.17% and 96.64%, and significantly higher sensitivity of 91.75% and 91.41%, respectively, compared to manual graders. On the subsets complicated with retinal comorbidities, such as diabetic retinopathy or age-related macular degeneration, in validation datasets 1 and 2, the algorithm achieved accuracy of 87.54% and 93.81%, and AUC of 97.02% and 97.46%, respectively. In validation dataset 3, the algorithm achieved comparable accuracy of 81.98% and AUC of 87.49%, with a sensitivity of 83.61% and specificity of 81.76% on GON recognition specifically in the HM population. CONCLUSIONS: With acceptable generalization capability across varying levels of image quality, different clinical centres, or certain retinal comorbidities, such as HM, the automatic AI diagnostic system had the potential to provide expert-level glaucoma detection.

A naphthalimide-based and Golgi-targetable fluorescence probe for quantifying hypochlorous acid.

The Golgi apparatus (GA) is a vital organelle in biological systems and excess reactive oxygen species (ROS) is produced during stress in the Golgi apparatus. Hypochlorous acid (HOCl) is a significant reactive oxygen species and has strong oxidative and antibacterial activity, but excessive secretion of hypochlorous acid can affect Golgi structure or function abnormally, it will lead to a series of diseases including Alzheimer's disease, neurodegenerative diseases, autoimmune diseases, and Parkinson's disease. In present work, a novel fluorescent probe for Golgi localization utilizing naphthalimide derivatives was constructed to detect hypochlorous acid. The fluorescent probe used a derivatived 1,8-naphthalimide as the emitting fluorescence group, phenylsulfonamide as the localization group and dimethylthiocarbamate as the sensing unit. When HOCl was absent, the intramolecular charge transfer (ICT) process of the developed probe was hindered and the probe exhibited a weak fluorescence. When HOCl was present, the ICT process occurred and the probe showed strong green fluorescence. When the HOCl concentration was altered from 5.0 × 10-7 to 1.0 × 10-5 mol·L-1, the fluorescence intensity of the probe well linearly correlated with the HOCl concentration. The detection limit of 5.7 × 10-8 mol·L-1 was obtained for HOCl. The HOCl fluorescent probe possessed a rapid reaction time, a high selectivity and a broad working pH scope. In addition, the probe possessed good biocompatibility and had been magnificently employed to image Golgi HOCl in Hela cells. These characteristics of the probe demonstrated its ability to be used for sensing endogenous and exogenous hypochlorous acids within the Golgi apparatus of living cells.

Anthocyanins from Malus spp. inhibit the activity of Gymnosporangium yamadae by downregulating the expression of WSC, RLM1, and PMA1.

Malus plants are frequently devastated by the apple rust caused by Gymnosporangium yamadae Miyabe. When rust occurs, most Malus spp. and cultivars produce yellow spots, which are more severe, whereas a few cultivars accumulate anthocyanins around rust spots, forming red spots that inhibit the expansion of the affected area and might confer rust resistance. Inoculation experiments showed that Malus spp. with red spots had a significantly lower rust severity. Compared with M. micromalus, M. 'Profusion', with red spots, accumulated more anthocyanins. Anthocyanins exhibited concentration-dependent antifungal activity against G. yamadae by inhibiting teliospores germination. Morphological observations and the leakage of teliospores intracellular contents evidenced that anthocyanins destroyed cell integrity. Transcriptome data of anthocyanins-treated teliospores showed that differentially expressed genes were enriched in cell wall and membrane metabolism-related pathways. Obvious cell atrophy in periodical cells and aeciospores was observed at the rust spots of M. 'Profusion'. Moreover, WSC, RLM1, and PMA1 in the cell wall and membrane metabolic pathways were progressively downregulated with increasing anthocyanins content, both in the in vitro treatment and in Malus spp. Our results suggest that anthocyanins play an anti-rust role by downregulating the expression of WSC, RLM1, and PMA1 to destroy the cell integrity of G. yamadae.

Microstructure of Brain Nuclei in Early Parkinson's Disease: Longitudinal Diffusion Kurtosis Imaging.

BACKGROUND: Diffusion kurtosis imaging provides in vivo measurement of microstructural tissue characteristics and could help guide management of Parkinson's disease. OBJECTIVE: To investigate longitudinal diffusion kurtosis imaging changes on magnetic resonance imaging in the deep grey nuclei in people with early Parkinson's disease over two years, and whether they correlate with disease progression. METHODS: We conducted a longitudinal case-control study of early Parkinson's disease. 262 people (Parkinson's disease: n = 185, aged 67.5±9.1 years; 43% female; healthy controls: n = 77, aged 66.6±8.1 years; 53% female) underwent diffusion kurtosis imaging and clinical assessment at baseline and two-year timepoints. We automatically segmented five nuclei, comparing the mean kurtosis and other diffusion kurtosis imaging indices between groups and over time using repeated-measures analysis of variance, and Pearson correlation with the two-year change in Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III. RESULTS: At baseline, mean kurtosis was higher in Parkinson's disease than controls in the substantia nigra, putamen, thalamus and globus pallidus when adjusting for age, sex, and levodopa equivalent daily dose (p < 0.027). These differences grew over two years, with mean kurtosis increasing for the Parkinson's disease group while remaining stable for the control group; evident in significant "group ×time" interaction effects for the putamen, thalamus and globus pallidus (ηp2= 0.08-0.11, p < 0.015). However, we did not detect significant correlations between increasing mean kurtosis and declining motor function in the Parkinson's disease group. CONCLUSION: Diffusion kurtosis imaging of specific grey matter structures shows abnormal microstructure in PD at baseline and abnormal progression in PD over two years.