Erratum: CXCL12-mediated monocyte transmigration into brain perivascular space leads to neuroinflammation and memory deficit in neuropathic pain: Erratum.

[This corrects the article DOI: 10.7150/thno.44364.].

[Characteristics of Cadmium Concentration and Transport of Pueraria thornsonii in Farmland with Different Cadmium Pollution Degrees].

This study aimed to elucidate the cadmium (Cd) concentration and transport characteristics of Pueraria thornsonii in farmland with different Cd pollution degrees, so as to provide a reference basis for phytoremediation of Cd-contaminated farmland. The multi-point experiments in farmland with different Cd pollution degrees[ω(Cd) 0.32-38.08 mg·kg-1] were conducted, and the biomass (dry weight), Cd content, accumulation, concentration, and transport of Cd in P. thornsonii tissues under the main growing period were assessed. According to the results, for P. thornsonii, the tuber dry weight ranged from 5.04 to 11.98 t·hm-2, biomass ranged from 13.21 to 29.07 t·hm-2, and Cd accumulation ranged from 15.74 to 106.03 g·hm-2in the study area. The pattern of Cd uptake by P. thornsonii showed that the main vine>leaf>lateral branches>basal part of sti>tuber. The Cd content in P. thornsonii tissues considerably increased with soil Cd content (P<0.05), whereas the biomass decreased significantly (P<0.05). The Cd concentration and transport factor of aboveground parts in P. thornsonii showed a trend of initially falling, then increasing and decreasing again, whereas the Cd enrichment and transport coefficient of tubers gradually decreased. Correlation analysis revealed that the amount of Cd in the soil was a major predictor of Cd accumulation in P. thornsonii. Under light to moderate Cd contamination, the commercial portion of P. thornsonii (arrowroot)[ω(Cd) 0.03-0.22 mg·kg-1] was less than the standard limit for medicinal plants (≤ 0.30 mg·kg-1). In P. thornsonii from moderately contaminated areas, the Cd concentration and transport factor of aboveground parts were 2.43-7.97 and 3.02-9.81, respectively. This indicates that P. thornsonii is a prospective plant ideal for remediating Cd-contaminated soil because of its high capacity to transfer and enrich Cd.

The potent analgesia of intrathecal 2R, 6R-HNK via TRPA1 inhibition in LF-PENS-induced chronic primary pain model.

BACKGROUND: Chronic primary pain (CPP) is an intractable pain of unknown cause with significant emotional distress and/or dysfunction that is a leading factor of disability globally. The lack of a suitable animal model that mimic CPP in humans has frustrated efforts to curb disease progression. 2R, 6R-hydroxynorketamine (2R, 6R-HNK) is the major antidepressant metabolite of ketamine and also exerts antinociceptive action. However, the analgesic mechanism and whether it is effective for CPP are still unknown. METHODS: Based on nociplastic pain is evoked by long-term potentiation (LTP)-inducible high- or low-frequency electrical stimulation (HFS/LFS), we wanted to develop a novel CPP mouse model with mood and cognitive comorbidities by noninvasive low-frequency percutaneous electrical nerve stimulation (LF-PENS). Single/repeated 2R, 6R-HNK or other drug was intraperitoneally (i.p.) or intrathecally (i.t.) injected into naïve or CPP mice to investigate their analgesic effect in CPP model. A variety of behavioral tests were used to detect the changes in pain, mood and memory. Immunofluorescent staining, western blot, reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and calcium imaging of in cultured dorsal root ganglia (DRG) neurons by Fluo-8-AM were used to elucidate the role and mechanisms of 2R, 6R-HNK in vivo or in vitro. RESULTS: Intrathecal 2R, 6R-HNK, rather than intraperitoneal 2R, 6R-HNK or intrathecal S-Ketamine, successfully mitigated HFS-induced pain. Importantly, intrathecal 2R, 6R-HNK displayed effective relief of bilateral pain hypersensitivity and depressive and cognitive comorbidities in a dose-dependent manner in LF-PENS-induced CPP model. Mechanically, 2R, 6R-HNK markedly attenuated neuronal hyperexcitability and the upregulation of calcitonin gene-related peptide (CGRP), transient receptor potential ankyrin 1 (TRPA1) or vanilloid-1 (TRPV1), and vesicular glutamate transporter-2 (VGLUT2) in peripheral nociceptive pathway. In addition, 2R, 6R-HNK suppressed calcium responses and CGRP overexpression in cultured DRG neurons elicited by the agonists of TRPA1 or/and TRPV1. Strikingly, the inhibitory effects of 2R, 6R-HNK on these pain-related molecules and mechanical allodynia were substantially occluded by TRPA1 antagonist menthol. CONCLUSIONS: In the newly designed CPP model, our findings highlighted the potential utility of intrathecal 2R, 6R-HNK for preventing and therapeutic modality of CPP. TRPA1-mediated uprgulation of CGRP and neuronal hyperexcitability in nociceptive pathways may undertake both unique characteristics and solving process of CPP.

Antioxidant potential evaluation of polysaccharides from Camellia oleifera Abel in vitro and in vivo.

The extraction process, structural characterization and free radical scavenging ability of polysaccharides from Camellia oleifera have already been widely studied. However, the antioxidant activities are still lack of systematic experiments. In this study, we used Hep G2 cells and Caenorhabditis elegans to evaluate the antioxidant potential of polysaccharides that from C. oleifera flowers (P-CF), leaves (P-CL), seed cakes (P-CC) and fruit shells (P-CS). The results showed all these polysaccharides could protect cells from oxidative damage induced by t-BHP. The highest cell viabilities were 66.46 ± 1.36 % (P-CF), 55.2 ± 2.93 % (P-CL), 54.49 ± 1.29 % (P-CC) and 61.45 ± 1.67 % (P-CS), respectively. Studies have shown that four polysaccharides may protect cells from apoptosis by reducing ROS levels and maintaining MMP balance. Moreover, P-CF, P-CL, P-CC and P-CS increased the survival rate of C. elegans under thermal stress, which reduced the production of ROS by 56.1 ± 0.67 %, 59.37 ± 1.79 %, 16.63 ± 2.51 % and 27.55 ± 2.62 %, respectively. P-CF and P-CL showed stronger protective effects on C. elegans by increasing the nuclear entry rate of DAF-16 and stimulating the expression of SOD-3. Our study suggested that C. oleifera polysaccharides have the potential to develop into a natural supplement agent.

An inhibitor with GSK3ß and DYRK1A dual inhibitory properties reduces Tau hyperphosphorylation and ameliorates disease in models of Alzheimer's disease.

Since Alzheimer's disease (AD) is a complex and multifactorial neuropathology, the discovery of multi-targeted inhibitors has gradually demonstrated greater therapeutic potential. Neurofibrillary tangles (NFTs), the main neuropathologic hallmarks of AD, are mainly associated with hyperphosphorylation of the microtubule-associated protein Tau. The overexpression of GSK3ß and DYRK1A has been recognized as an important contributor to hyperphosphorylation of Tau, leading to the strategy of using dual-targets inhibitors for the treatment of this disorder. ZDWX-12 and ZDWX-25, as harmine derivatives, were found good inhibition on dual targets in our previous study. Here, we firstly evaluated the inhibition effect of Tau hyperphosphorylation using two compounds by HEK293-Tau P301L cell-based model and okadaic acid (OKA)-induced mouse model. We found that ZDWX-25 was more effective than ZDWX-12. Then, based on comprehensively investigations on ZDWX-25 in vitro and in vivo, 1) the capability of ZDWX-25 to show a reduction in phosphorylation of multiple Tau epitopes in OKA-induced neurodegeneration cell models, and 2) the effect of reduction on NFTs by 3xTg-AD mouse model under administration of ZDWX-25, an orally bioavailable, brain-penetrant dual-targets inhibitor with low toxicity. Our data highlight that ZDWX-25 is a promising drug for treating AD.

Unexpected enrichment of antibiotic resistance genes and organic remediation genes in high-altitude lakes at Eastern Tibetan Plateau.

Elevation has a strong effect on aquatic microbiome. However, we know little about the effects of elevation on functional genes, especially antibiotic resistance genes (ARGs) and organic remediation genes (ORGs) in freshwater ecosystems. In this study, we analyzed five classes of functional genes including ARGs, metal resistance genes (MRGs), ORGs, bacteriophages, and virulence genes between two high-altitude lakes (HALs) and two low-altitude lakes (LALs) in Mountain Siguniang at Eastern Tibetan Plateau by means of GeoChip 5.0. No differences (Student's t-test, p > 0.05) of gene richness including ARGs, MRGs, ORGs, bacteriophages, and virulence genes in HALs and LALs were found. The abundance of most ARGs and ORGs was higher in HALs than in LALs. For MRGs, the abundance of macro metal resistance genes of potassium, calcium, and aluminum was higher in HALs than in LALs (Student's t-test, p < 0.05; all Cohen's d > 0.8). The abundance of some heavy metal resistance genes of lead and mercury was lower in HALs than in LALs (Student's t-test, p < 0.05; all Cohen's d < -0.8). The composition of these functional genes in HALs differed significantly from in LALs. The functional gene network in HALs was also more complex than that in LALs. We speculate that enrichment of ARGs and ORGs in HALs is related to different microbial communities, exogenous ARGs, and enriched persistent organic pollutants through long-range atmospheric transport driven by the Indian monsoon. This study highlights the unexpected enrichment of ARGs, MRGs, and ORGs in remote lakes at high elevations.

Resveratrol Prevents Vibrio vulnificus-Induced Sepsis by Attenuating Necroptosis.

Objective: This study investigated how the natural phytophenol and potent SIRT1 activator resveratrol (RSV) regulate necroptosis during Vibrio vulnificus (V. vulnificus)-induced sepsis and the potential mechanism. Methods: The effect of RSV on V. vulnificus cytolysin (VVC)-induced necroptosis was analyzed in vitro using CCK-8 and Western blot assays. Enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry and survival analyses were performed to elucidate the effect and mechanism of RSV on necroptosis in a V. vulnificus-induced sepsis mouse model. Results: RSV relieved necroptosis induced by VVC in RAW264.7 and MLE12 cells. RSV also inhibited the inflammatory response, had a protective effect on histopathological changes, and reduced the expression level of the necroptosis indicator pMLKL in peritoneal macrophages, lung, spleen, and liver tissues of V. vulnificus-induced septic mice in vivo. Pretreatment with RSV downregulated the mRNA of the necroptosis indicator and protein expression in peritoneal macrophages and tissues of V. vulnificus-induced septic mice. RSV also improved the survival of V. vulnificus-induced septic mice. Conclusion: Our findings collectively demonstrate that RSV prevented V. vulnificus-induced sepsis by attenuating necroptosis, highlighting its potency in the clinical management of V. vulnificus-induced sepsis.

Metabolomics reveals arbuscular mycorrhizal fungi-mediated tolerance of walnut to soil drought.

BACKGROUND: Arbuscular mycorrhizal fungi (AMF) have a positive effect on drought tolerance of plants after establishing reciprocal resymbiosis with roots, while the underlying mechanism is not deciphered. Metabolomics can explain the mechanism of plant response to environmental stress by analyzing the changes of all small molecular weight metabolites. The purpose of this study was to use Ultra High Performance Liquid Chromatography Q Exactive Mass Spectrometer to analyze changes in root metabolites of walnut (Juglans regia) after inoculation with an arbuscular mycorrhizal fungus Diversispora spurca under well-watered (WW) and drought stress (DS). RESULTS: Sixty days of soil drought significantly inhibited root mycorrhizal colonization rate, shoot and root biomass production, and leaf water potential in walnut, while AMF inoculation significantly increased biomass production and leaf water potential, accompanied by a higher increase magnitude under DS versus under WW. A total of 3278 metabolites were identified. Under WW, AMF inoculation up-regulated 172 metabolites and down-regulated 61 metabolites, along with no changes in 1104 metabolites. However, under DS, AMF inoculation up-regulated 49 metabolites and down-regulated 116 metabolites, coupled with no changes in 1172 metabolites. Among them, juglone (a quinone found in walnuts) as the first ranked differential metabolite was up-regulated by AMF under WW but not under DS; 2,3,5-trihydroxy-5-7-dimethoxyflavanone as the first ranked differential metabolite was increased by AMF under DS but not under WW. The KEGG annotation showed a large number of metabolic pathways triggered by AMF, accompanied by different metabolic pathways under WW and DS. Among them, oxidative phosphorylation and phenylalanine metabolism and biosynthesis were triggered by AMF in response to WW and DS, where N-acetyl-L-phenylalanine was induced by AMF to increase under DS, while decreasing under WW. CONCLUSION: This study provides new insights into the metabolic mechanisms of mycorrhiza-enhanced drought tolerance in walnuts.

Benzimidazole fungicide biotransformation by comammox Nitrospira bacteria: Transformation pathways and associated proteomic responses.

Benzimidazole fungicides are frequently detected in aquatic environments and pose a serious health risk. Here, we investigated the metabolic capacity of the recently discovered complete ammonia-oxidizing (comammox) Nitrospira inopinata and kreftii to transform a representative set of benzimidazole fungicides (i.e., benzimidazole, albendazole, carbendazim, fuberidazole, and thiabendazole). Ammonia-oxidizing bacteria and archaea, as well as the canonical nitrite-oxidizing Nitrospira exhibited no or minor biotransformation activity towards all the five benzimidazole fungicides. In contrast, the investigated comammox bacteria actively transformed all the five benzimidazole fungicides, except for thiabendazole. The identified transformation products indicated hydroxylation, S-oxidation, and glycosylation as the major biotransformation pathways of benzimidazole fungicides. We speculated that these reactions were catalyzed by comammox-specific ammonia monooxygenase, cytochrome P450 monooxygenases, and glycosylases, respectively. Interestingly, the exposure to albendazole enhanced the expression of the antibiotic resistance gene acrB of Nitrospira inopinata, suggesting that some benzimidazole fungicides could act as environmental stressors that trigger cellular defense mechanisms. Altogether, this study demonstrated the distinct substrate specificity of comammox bacteria towards benzimidazole fungicides and implies their significant roles in the biotransformation of these fungicides in nitrifying environments.

Identification of differentially expressed genes induced by aberrant methylation in acute myeloid leukemia using integrated bioinformatics analyses.

Acute myeloid leukemia (AML) is a life-threatening hematological malignant disease. Methylation plays a crucial role in the etiology and pathogenesis of AML. The aim of the present study was to identify the aberrantly methylated differentially expressed genes (DEGs) in AML and determine the underlying mechanisms of tumorigenesis by conducting integrated bioinformatics analyses. Gene expression profiles (GSE109179, GSE142699, GSE49665 and GSE14772) and a gene methylation profile (GSE42042) were analyzed to identify the aberrantly methylated DEGs. Functional enrichment analyses of identified genes were conducted based on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and protein-protein interaction networks were established. Finally, the DEGs were validated by the reverse transcription-quantitative PCR analysis of patient samples. A total of seven downregulated hypermethylated genes and eight upregulated hypomethylated genes were validated. The differentially methylated DEGs were enriched in GO biological process terms associated with control of the immune response and the KEGG analysis indicated they were involved in AML, ferroptosis, TGF-ß signaling and necroptosis pathways. Additionally, five downregulated hypermethylated genes that were also tumor suppressor genes (TSGs) were identified. In vitro assays revealed that the overexpression of transcription factor 7 (TCF7) and integrin a M (ITGAM) significantly inhibited the proliferation of HL60 cells; by contrast, the knockdown of TCF7 and CAMK4 promoted HL60 cell proliferation. Overall, the present study identified differentially methylated DEGs and pathways associated with AML, which may enhance the understanding of the underlying molecular mechanisms of AML. In the future, abnormally methylated oncogenes and TSGs may function as biomarkers and treatment targets for the diagnosis and treatment of AML.

Yuan-Zhi decoction in the treatment of Alzheimer's disease: An integrated approach based on chemical profiling, network pharmacology, molecular docking and experimental evaluation.

Yuan-Zhi Decoction (YZD) is a traditional Chinese medical formulation with demonstrated clinical benefits in Alzheimer's disease (AD). We used liquid chromatography coupled with mass spectrometry to identify 27 unique chemical components of YZD. Analyzing these using network pharmacology and molecular docking models identified 34 potential interacting molecular targets involved in 26 biochemical pathways. When tested in an animal model of AD, the APP/PS1 transgenic mice showed measurable improvements in spatial orientation and memory after the administration of YZD. These improvements coincided with significantly reduced deposition of Aß plaques and tau protein in the hippocampi in the treated animals. In addition, a decreased BACE1 and beta-amyloid levels, a downregulation of the p-GSK-3ß/GSK-3ß, and an upregulation of the PI3K and p-AKT/AKT pathway was seen in YZD treated animals. These in vivo changes validated the involvement of molecular targets and pathways predicted in silico analysis of the chemical components of YZD. This study provides scientific support for the clinical use of YZD and justifies further investigations into its effects in AD. Furthermore, it demonstrates the utility of network pharmacology in elucidating the biochemical mechanisms underlying the beneficial effects of traditional Chinese medicines (TCM).

Role of intraoperative patients positioning in endoscopic full-thickness resection of large gastric tumors under general anesthesia.

Full thickness endoscopic resection of large submucosal gastric tumors (>3 cm) is a big challenge for endoscopists. Issues include how to efficiently resect the lesion, obtain homeostasis, and suture the defect. There are no guidelines regarding the importance of patient position on the success of endoscopic resections in anesthetized patients. Typically, the patient is placed in left lateral position for the endoscopic therapy and during the procedure patient's position is changed to maintain the tumor above the gastric fluids to prevent gastric juices and tumor or tumor fragments from falling into the peritoneal cavity in the event of perforation. This study emphasized the importance of planning the procedure to ensure that the patient's position and anesthetist's concerns are met and allow optimal access to the lesion for endoscopic resection. Prior to sedation the patient should be positioned so that the tumor is in the up position which also prevents blood obscuring the operative field, helps detect bleeding points for immediately hemostasis. In addition, due to gravitational effect, the resected tumor will fall into the gastric cavity exposing the root of the tumor making resection easier and reduce procedure time. Preplanning avoids unnecessary readjustment of positioning and improves the ease and safety of the procedure.

Evaluation of macular microvascular density using optical coherence tomography angiography in patients with Posner-Schlossman syndrome.

BACKGROUND: Optical coherence tomography angiography (OCTA) is a novel technology that provides a noninvasive, dye-less method to visualize the blood vessels of the retina. In the present study, we investigate macular microvascular density and the correlation of ocular and demographic factors using OCTA in Posner-Schlossman syndrome (PSS) patients. METHODS: This is a prospective observational study. All PSS patients and age- and sex-matched healthy subjects underwent complete ophthalmologic examination, and RE, BCVA, IOP, CCT, AL, CMT, GCIPI, RNFL, C/D ratio were recorded. The whole-image vessel density (wiVD) and whole-image perfusion density (wiPD), three-circle (1 mm central ring, 3 mm inner ring, 6 mm outer ring), and four-quadrant segmental VD and PD were calculated. RESULTS: Seventeen PSS patients and 17 healthy subjects were enrolled in this study. The mean age was 42.65 ± 11.22 years in PSS patients and 42.71 ± 10.50 years in healthy controls. IOP, CCT, and C/D ratio were higher in PSS-attacked eyes, and BCVA, OPP and RNFL thickness was lower than those in the fellow eyes (p < 0.05). BCVA and OPP were improved in the PSS-attacked eyes in intermittent period (p < 0.05). The wiVD and wiPD were lower in the PSS-affected eyes than in the fellow eyes and in the control eyes in the PSS-attacked period (p < 0.05). All segmental VD and PD was lower in the PSS affected eyes than in the healthy control eyes (p < 0.05). In intermittent period, the wiVD and wiPD were lower in the PSS-affected eyes than in the fellow eyes (p < 0.05). Age, CCT, and SSI were associated with macular wiVD and wiPD in PSS attacked period. Age and CCT were associated with macular wiVD and wiPD in PSS intermittent period. CONCLUSION: Decreased macular superficial VD and PD was found in patients with Posner-Schlossman syndrome in attacked period and in remission. Macular wiVD and wiPD were associated with age, CCT and SSI in PSS patients.

Atractylenolide III from Atractylodes macrocephala Koidz promotes the activation of brown and white adipose tissue through SIRT1/PGC-1α signaling pathway.

BACKGROUND: Hypothermia is a complex pathophysiological response that can be life-threatening in low-temperature environment because of impaired thermoregulation. However, there is currently no clinically effective drugs that can prevent or treat this disease. Brown adipose tissue (BAT) activation or browning of white adipose tissue (WAT) is a promising therapeutic strategy to prevent or treat hypothermia. Atractylodes macrocephala Koidz extract (AE) and its active compound Atractylenolide III (AIII) has been reported to regulate glycolipid metabolism, which might be relevant to BAT activation. However, the thermogenic effect and mechanism of AE and AIII on adipose tissues have not been explored yet. Therefore, this study firstly investigated the role of AE and AIII on hypothermia by promoting heat production of BAT and WAT. PURPOSE: To explore the anti-cold effect of AE and AIII in cold exposure model and explore their biological function and mechanism underlying thermogenesis. METHODS: The effect of thermogenesis and anti-hypothermia of AE and AIII on C57BL/6J mice were evaluated with several experiment in cold environment, such as toxicity test, cold exposure test, metabolism estimation, histology and immunohistochemistry, and protein expression. Additionally, BAT, inguinal WAT (iWAT) and brown adipocytes were utilized to explore the mechanism of AE and AIII on thermogenesis in vivo and in vitro. Finally, SIRT1 agonist and inhibitor in brown adipocytes to verify that AIII activated BAT through SIRT1/PGC-1α pathway. RESULTS: Both AE and AⅢ could significantly maintain the core body temperature and body surface temperature of mice during cold exposure. Besides, AE and AⅢ could significantly improve the capacity of total antioxidant and glucose, lipid metabolism of mice. In addition, AE and AIII reduced mitochondrial membrane potential and ATP content both in BAT and brown adipocytes, and decreased the size of lipid droplets. Moreover, AE and AⅢ promoted the expression of proteins related to heat production in BAT and iWAT. And AIII might activate BAT via SIRT1/PGC-1α pathway. CONCLUSION: AE and AⅢ were potential candidate drugs that treated hypothermia by improving the heat production capacity of the mice. Mechanistically, they may activate SIRT1/PGC-1α pathway, thus enhancing the function of BAT, and promoting the browning of iWAT, to act as anti-hypothermia candidate medicine.

Biotransformation of lincomycin and fluoroquinolone antibiotics by the ammonia oxidizers AOA, AOB and comammox: A comparison of removal, pathways, and mechanisms.

In this study, we evaluated the biotransformation mechanisms of lincomycin (LIN) and three fluoroquinolone antibiotics (FQs), ciprofloxacin (CFX), norfloxacin (NFX), and ofloxacin (OFX), which regularly enter aquatic environments through human activities, by different ammonia-oxidizing microorganisms (AOM). The organisms included a pure culture of the complete ammonia oxidizer (comammox) Nitrospira inopinata, an ammonia oxidizing archaeon (AOA) Nitrososphaera gargensis, and an ammonia-oxidizing bacterium (AOB) Nitrosomonas nitrosa Nm90. The removal of these antibiotics by the pure microbial cultures and the protein-normalized biotransformation rate constants indicated that LIN was significantly co-metabolically biotransformed by AOA and comammox, but not by AOB. CFX and NFX were significantly co-metabolized by AOA and AOB, but not by comammox. None of the tested cultures transformed OFX effectively. Generally, AOA showed the best biotransformation capability for LIN and FQs, followed by comammox and AOB. The transformation products and their related biotransformation mechanisms were also elucidated. i) The AOA performed hydroxylation, S-oxidation, and demethylation of LIN, as well as nitrosation and cleavage of the piperazine moiety of CFX and NFX; ii) the AOB utilized nitrosation to biotransform CFX and NFX; and iii) the comammox carried out hydroxylation, demethylation, and demethylthioation of LIN. Hydroxylamine, an intermediate of ammonia oxidation, chemically reacted with LIN and the selected FQs, with removals exceeding 90%. Collectively, these findings provide important fundamental insights into the roles of different ammonia oxidizers and their intermediates on LIN and FQ biotransformation in nitrifying environments including wastewater treatment systems.

Quantitative assessment and determinants of the papillary microvasculature in healthy subjects.

BACKGROUND: It is critical to monitor the optic disc's vessel density using Optical coherence tomography angiography (OCTA) and evaluate its determinants. In the current study, we investigate the superficial vessel density (VD) of the papillary microvasculature and its determinants in healthy subjects of Southern China. METHODS: This was a prospective, cross-sectional study. Superficial VD in healthy individuals' optic disc region was measured by OCTA. The factors associated with ocular and systemic parameters were analyzed using a generalized estimation equation (GEE) model. RESULTS: A total of 510 eyes of 260 healthy subjects were analyzed in the study. The total VD in the optic disc area was 17.21 ± 2.15 mm- 1 (95% CI, 17.02-17.40 mm- 1). The VD in the inner ring and the outer ring of the optic disc were significantly higher compared with the central ring, while the VD of the superior quadrant and inferior quadrant was significantly higher compared with the temporal and nasal quadrant. After adjusting for the ocular factors and systemic factors, AL (ß = - 0.4917, P = 0.0003), disc area (ß = - 0.3748, P = 0.0143), CMT (ß = - 0.0183, P = 0.0003) and SSI (ß = 1.0588, P < 0.001) were significantly associated with total VD of the optic disc. CONCLUSION: The mean total VD in the optic disc area was 17.21 ± 2.15 mm- 1 in healthy subjects, and the superior and inferior VD was significantly higher than the temporal and nasal VD. AL, disc area, CMT, and SSI may affect the total VD in the optic disc area and should be considered in clinical practice.

CXCL12-mediated monocyte transmigration into brain perivascular space leads to neuroinflammation and memory deficit in neuropathic pain.

Emerging clinical and experimental evidence demonstrates that neuroinflammation plays an important role in cognitive impairment associated with neuropathic pain. However, how peripheral nerve challenge induces remote inflammation in the brain remains largely unknown. Methods: The circulating leukocytes and plasma C-X-C motif chemokine 12 (CXCL12) and brain perivascular macrophages (PVMs) were analyzed by flow cytometry, Western blotting, ELISA, and immunostaining in spared nerve injury (SNI) mice. The memory function was evaluated with a novel object recognition test (NORT) in mice and with Montreal Cognitive Assessment (MoCA) in chronic pain patients. Results: The classical monocytes and CXCL12 in the blood, PVMs in the perivascular space, and gliosis in the brain, particularly in the hippocampus, were persistently increased following SNI in mice. Using the transgenic CCR2RFP/+ and CX3CR1GFP/+ mice, we discovered that at least some of the PVMs were recruited from circulating monocytes. The SNI-induced increase in hippocampal PVMs, gliosis, and memory decline were substantially prevented by either depleting circulating monocytes via intravenous injection of clodronate liposomes or blockade of CXCL12-CXCR4 signaling. On the contrary, intravenous injection of CXCL12 at a pathological concentration in naïve mice mimicked SNI effects. Significantly, we found that circulating monocytes and plasma CXCL12 were elevated in chronic pain patients, and both of them were closely correlated with memory decline. Conclusion: CXCL12-mediated monocyte recruitment into the perivascular space is critical for neuroinflammation and the resultant cognitive impairment in neuropathic pain.

Tissue concentrations, trophic transfer and human risks of antibiotics in freshwater food web in Lake Taihu, China.

The objective of this study was to evaluate the tissue distributions of antibiotics in the fish, the bioaccumulation and trophic transfer in freshwater food web in Taihu Lake, a large shallow freshwater lake. Twenty four out of 41 antibiotics were detected in the biotas of the food web; and antibiotic concentrations followed the orders: fish plasma ~ fish muscle < fish liver ~ fish bile and fish < invertebrates ~ plankton. Antibiotic concentrations in the liver of piscivores were higher than those in omnivores and planktivores. Most bioaccumulation factors (BAFs) of sulfonamides (SAs), macrolides (MLs), ionophores (IPs) and lincomycin (LIN) were less than 2000 L/kg, indicating low bioaccumulation ability of these compounds in fish. Fluoroquinolones (FQs) were frequently detected in fish liver, invertebrates and plankton with much of BAFs great than 5000 L/kg, indicating that FQs have the potential of bioaccumulation in fish. Relationship analysis between BAFs and physicochemical properties of antibiotics showed that the bioaccumulation of antibiotics in the biota was related with their adsorption ability. Generally, the antibiotics in the food web of Lake Taihu including plankton, invertebrates and fish showed trophic dilution. The normalized estimated daily intake (EDI) values are less than the acceptable daily intake (ADI) values, and then hazard quotients were much less than 1. This result suggests the consumption of fish, crab and shrimp in Lake Taihu would probably not pose direct detrimental effects on humans.