Exercise, Spinal Microglia and Neuropathic Pain: Potential Molecular Mechanisms.

As one of the most common neuropathic disorders, neuropathic pain often has a negative impact on patients with persistent pain, mood disorders and sleep disturbances. Currently, neuropathic pain is not treated with any specific drug, instead, drugs for other diseases are used as replacements in clinics, but most have adverse effects. In recent years, the role of spinal cord microglia in the pathogenesis of neuropathic pain has been widely recognized, and they are being explored as potential therapeutic targets. Spinal microglia are known to be involved in the pathogenic mechanisms of neuropathic pain through purine signaling, fractalkine signaling, and p38 MAPK signaling. Exercise is a safe and effective treatment, and numerous studies have demonstrated its effectiveness in improving neurological symptoms. Nevertheless, it remains unclear what the exact molecular mechanism is. This review summarized the specific molecular mechanisms of exercise in alleviating neuropathic pain by mediating the activity of spinal microglia and maintaining the phenotypic homeostasis of spinal microglia through purine signaling, fractalkine signaling and p38 MAPK signaling. In addition, it has been proposed that different intensities and types of exercise affect the regulation of the above-mentioned signaling pathways differently, providing a theoretical basis for the improvement of neuropathic pain through exercise.

[Pathogenesis of ferroptosis on chronic kidney disease and traditional Chinese medicine intervention: a review].

Chronic kidney disease(CKD) is an insidious disease that has become a significant global public health issue due to its high incidence rate, low awareness, low diagnostic rate, poor prognosis, and high medical costs. Recent studies have shown that CKD development is associated with varying degrees of ferroptosis features. Traditional Chinese medicine(TCM) can regulate iron metabolism, lipid peroxidation, antioxidant systems to inhibit ferroptosis and delay the progression of CKD. Consequently, the intervention mechanism of ferroptosis has become one of the focuses of CKD research. TCM has thousands of years of traditional experience and wisdom. It focuses on the overall regulation of human body functions and can stimulate the body's disease resistance and recovery capabilities, which has certain advantages in treating CKD. However, there is currently a lack of comprehensive articles on the application of TCM in intervening ferroptosis to treat CKD and the pathogenesis of ferroptosis in CKD. Therefore, this article summarizes the latest research progress both domestically and internationally, briefly introduces the main mechanisms of ferroptosis, and systematically reviews the relationship between ferroptosis and CKD. The article integrates TCM theories related to ferroptosis in CKD, including "deficiency" "stasis" "phlegm turbidity" and "toxins" and summarizes the research status of active ingredients and herbal formulas in intervening ferroptosis to treat CKD. By considering ferroptosis from a new perspective, this article aims to provide new targets and directions for the application of TCM in treating CKD.

P2Y1R and P2Y2R: potential molecular triggers in muscle regeneration.

Muscle regeneration is indispensable for skeletal muscle health and daily life when injury, muscular disease, and aging occur. Among the muscle regeneration, muscle stem cells' (MuSCs) activation, proliferation, and differentiation play a key role in muscle regeneration. Purines bind to its specific receptors during muscle development, which transmit environmental stimuli and play a crucial role of modulator of muscle regeneration. Evidences proved P2R expression during development and regeneration of skeletal muscle, both in human and mouse. In contrast to P2XR, which have been extensively investigated in skeletal muscles, the knowledge of P2YR in this tissue is less comprehensive. This review summarized muscle regeneration via P2Y1R and P2Y2R and speculated that P2Y1R and P2Y2R might be potential molecular triggers for MuSCs' activation and proliferation via the p-ERK1/2 and PLC pathways, explored their cascade effects on skeletal muscle, and proposed P2Y1/2 receptors as potential pharmacological targets in muscle regeneration, to advance the purinergic signaling within muscle and provide promising strategies for alleviating muscular disease.

One-year results for myopia control with aspheric base curve orthokeratology lenses: A prospective randomised clinical trial.

PURPOSE: To compare the effect of orthokeratology (ortho-k) using aspheric or spherical base curve (BCA vs. BCS) contact lenses on axial elongation and the relative peripheral refraction change (RPRC) in Chinese children. METHODS: Children aged 8-12 years with myopia between -0.75 and -4.00 D and astigmatism ≤1.00 D were randomly assigned to the BCA or BCS group. Peripheral refraction was assessed at 10°, 20° and 30° along the temporal and nasal retina at baseline and at the 12-month visit. Axial length (AL) was measured under cycloplegia at baseline and at the 6- and 12-month visits. Only right eye data were analysed. Repeated-measures analysis of covariance was performed to examine the differences in axial elongation and the RPRC between the BCA and BCS groups. RESULTS: The 1-year results from 31 BCA and 32 BCS subjects were analysed. No significant between-group differences were found at baseline (p ≥ 0.28). At the 12-month visit, the BCA lens produced a greater absolute RPRC along the horizontal meridian than the BCS lens (p < 0.001). Axial elongation was slower in the BCA group (0.19 ± 0.20 mm) than in the BCS group (0.29 ± 0.14 mm; p = 0.03). Axial elongation was correlated with the RPRC at 10° (r = 0.43, p = 0.02) and 20° (r = 0.39, p = 0.03) along the temporal retina in the BCA group; however, these correlations were not observed in the BCS group. CONCLUSION: The BCA ortho-k lens could improve the efficacy of slowing axial elongation in children. The improved myopia control observed in the BCA group may be the result of a larger myopic shift in relative peripheral refraction within 20° along the temporal retina.

Higher-Order Aberrations and Visual Performance in Myopic Children Treated With Aspheric Base Curve-Designed Orthokeratology.

OBJECTIVES: To investigate the impact of aspheric base curve (BC)-designed orthokeratology (ortho-k) (AOK) lenses on higher-order aberrations (HOA) at different pupil diameters and visual performance. METHODS: This prospective clinical study included subjects randomized to wear spherical BC-designed ortho-k (SOK) or AOK lenses. The Pediatric Refractive Error Profile (PREP) questionnaire was completed before and after 3 months of lens wear. The Strehl ratio (SR) and root mean square of ocular higher-order aberrations (HOAs), spherical aberration (SA), coma, and trefoil were measured under 4-mm, 5-mm, and 6-mm pupil diameters at baseline and 3-month visits. Corneal topography, uncorrected low-contrast (LC) visual acuity (VA), and high-contrast (HC) VA were measured at baseline and at 1 day, 1 week, 1 month, and 3 month follow-ups. RESULTS: Sixty-five participants completed the study. After 3 months with the ortho-k lens, there were no significant differences in ocular HOA, SA, coma, or trefoil between the SOK group and AOK group at 4-mm, 5-mm, and 6-mm pupil diameters (all P>0.05), except for a significant increase in SA in the AOK group (P=0.01). Stratified analyses showed that the AOK group exhibited greater HOA and SA at 5-mm and 6-mm pupil diameters in the lower myopia subgroup and greater SA at 6 mm in the higher myopia subgroup (all P<0.05). There were no significant differences between the groups in SR, HC VA, LC VA, or PREP scores (all P>0.05). CONCLUSION: Aspheric BC-designed ortho-k lenses produced a significantly greater SA than SOK lenses, with more significance at lower diopters, without sacrificing subjective visual performance.

[Application of Deep Learning Algorithm in the Grading Assessment of Corneal Fluorescein Staining].

Objective: To explore the application value of applying deep learning (DL) algorithm in the grading assessment of corneal fluorescein staining. Methods: A cross-sectional study was carried out, covering 600 corneal fluorescein staining photos acquired in the Contact Lens Clinic, West China Hospital, Sichuan University between 2020 and 2022. Out of the 600 photos, 500 were used to construct the algorithm and the remaining 100 were used for the validation of the algorithm and a comparative analysis of the difference in grading accuracy (ACC) and the length of diagnostic time between artificial intelligence (AI) and optometry students. One month after finishing the first grading analysis, assessment by AI and optometry students was conducted for a second time and results from the two rounds of assessment were compared to examine the intrarater agreement ( kappa value) of the two analyses. The grading analysis results of 3 experienced optometrists were used as the gold standard in the study. Results: Findings of the cross validation with the complete dataset, the training dataset, and the test dataset showed that ResNet34 had the highest predictive accuracy among four DL models. ResNet34 DL model achieved an accuracy of 93.0%, sensitivity of 89.5%, and specificity of 89.6% in the grading of corneal staining. In the comparison of the grading accuracy of AI and two optometry students, AI showed better accuracy, with the respective grading accuracy being 87.0%, 78.0%, and 52.0% for AI, student 1, and student 2 ( P ACC=0.001). In addition, the average diagnostic time of AI was shorter than that of optometry students ( t AI=1.00 s, t S1=11.86 s, t S2=13.25 s, P t =0.001). In the comparative analysis of the intrarater agreement between the two assessments, AI ( kappa AI=0.658, P AI=0.001) achieved better consistency than the two optometry students did （ kappa S1=0.575, P S1=0.001; kappa S2=0.609, P S2=0.001). Conclusion: Applying deep learning algorithms in the grading assessment of corneal fluorescein staining has considerable feasibility and clinical value. In the performance comparison between AI and optometry students, AI achieved higher accuracy and better consistency, which indicates that AI has potential application value for assisting optometrists to make clinical decisions with speed and accuracy.

[Observational Comparison of the Safety and Effectiveness of Myopic Children Wearing Defocus Incorporated Soft Contact Lenses or Orthokeratology Lenses].

Objective: To observe and compare the effectiveness and safety of controlling myopia in children by wearing defocus incorporated soft contact (DISC) lenses or orthokeratology (OrthoK) lenses. Methods: A total of 75 children who came to our hospital between January 2018 and September 2020 were enrolled for this retrospective study. The DISC group consisted of 30 myopic children (60 eyes) wearing peripheral defocal soft incorporated contact lenses during daytime. There were 10 males and 20 females aged (9.9±1.00) years old in this group and their spherical equivalent refractions were (-2.78±0.70) D. The OrthoK group consisted of 45 myopic children (90 eyes) wearing OrthoK lenses. There were 30 female and 15 males aged (9.67±1.11) and their spherical equivalent refractions were (-2.67±0.71) D. All subjects had previously worn prescription glasses for 12 months or longer before they started wearing contact lenses. The subjects were followed up for 12 months once they started wearing contact lenses. The axial changes and corneal and conjunctival complications of the two groups of myopic children were compared and analyzed. Results: Myopic children in both groups experienced relatively rapid increase in ocular axial length while they were wearing prescription glasses, with the ocular axial length increase in the prescription-glass-wearing period being (0.34±0.09) mm in the OrthoK group and (0.37± 0.07) mm in the DISC group. In the 12 months of wearing contact lenses, the ocular axial length of children in the OrthoK group increased by (0.18±0.04) mm, while that of the DISC group increased by (0.19±0.05) mm. The increase in ocular axial length was reduced in both groups after the children were switched to the new myopia prevention methods, showing significant difference ( P<0. 05). The two groups using two different contact lenses had similar axial length increase, showing no significant difference ( P>0.05). During the 12-month period while the subjects wore the two types of contact lenses, the incidence of chronic follicular conjunctivitis was 11.20% in the OrthoK group and 20.00% in the DISC group, with that of the DISC group being slightly higher without showing significant difference ( P>0.05). The incidence of grade-1corneal staining was 66.70% in the OrthoK group and 56.70% in the DISC group, and the incidence of grade-2 corneal staining was 17.80% in the OrthoK group and 16.70% in the DISC group. In other words, the OrthoK group had slightly higher findings, but the difference was not significant ( P>0.05). The incidence of contact lens-associated papillary conjunctivitis was 2.20% in the OrthoK group and 10.00% in the DISC group, which was slightly higher than that in the orthokeratology lens group, but the difference was not significant( P>0.05). Conclusion: Both DISC lenses and OrthoK lenses can effectively control the increase in axial length in myopic children, and their have better effects than those of prescription glasses. The two tyes of contact lenses showed similar effects for controlling axial length increase. Both contact lenses have fewer corneal and conjunctival complications and better safety.

Complete genome sequence of a novel victorivirus infecting Aspergillus niger.

Aspergillus niger is an important filamentous phytopathogenic fungus with a broad host range. A novel double-stranded (ds) RNA mycovirus, named Aspergillus niger victorivirus 1 (AnV1), isolated from A. niger strain baiyun3.23-4, was sequenced and analyzed. The AnV1 genome is 5317 nucleotides long with a GC content of 56%. AnV1 contains two open reading frames (ORF1 and 2), overlapping at a tetranucleotide sequence (AUGA). ORF1 encodes a putative capsid protein (CP) of 778 amino acids (aa), while ORF2 potentially encodes a putative RNA-dependent RNA polymerase (RdRp) of 826 aa. Phylogenetic analysis indicated that AnV1 is a new member of the genus Victorivirus in the family Totiviridae. As far as we know, this is the first report of the complete genome sequence of a victorivirus infecting A. niger.

Complete genome sequence of a novel chrysovirus infecting Talaromyces neofusisporus.

A double-stranded RNA (dsRNA) mycovirus was isolated from Talaromyces neofusisporus isolate HJ1-6 and named "Talaromyces neofusisporus chrysovirus 1" (TnCV1). It was found to consist of four dsRNA segments (TnCV1-1, TnCV1-2, TnCV1-3, and TnCV1-4) with lengths of 3595 bp, 3063 bp, 3054 bp, and 2876 bp, respectively. Sequence analysis showed that TnCV1-1 contains an open reading frame (ORF) encoding a putative RNA-dependent RNA polymerase (RdRp) of 1136 amino acids (aa), TnCV1-2 contains an ORF encoding a hypothetical protein of 906 aa, TnCV1-3 contains an ORF encoding a putative capsid protein (CP) of 938 aa, and TnCV1-4 contains an ORF encoding a hypothetical protein of 849 aa. The 5' and 3' untranslated regions (UTRs) of TnCV1-1, TnCV1-2, TnCV1-3, and TnCV1-4 showed a high degree of sequence similarity to each other. Phylogenetic analysis based on RdRp sequences suggested that TnCV1 is a new member of the genus Alphachrysovirus in the family Chrysoviridae. This is the first chrysovirus isolated from T. neofusisporus.

Design, synthesis and structure-activity relationship optimization of phenanthridine derivatives as new anti-vitiligo compounds.

Humans have been suffering from vitiligo for a long time. Target vitiligo drugs have yet been approved. Activation of Wnt/ß-catenin signalling has potential in the therapeutic use of vitiligo, so exploring new drugs that specifically directly activate Wnt is worthwhile to obtain new anti-vitiligo agents. In this work, two portions design and synthesis were put into effect. firstly, 17 phenanthridine derivatives with C-4 substitutes were designed and synthesized, which compounds 4, 6, 12, 13 served as H-acceptor with protein showed enhance melanogenesis activity; Secondly, 7 hybrid new scaffolds of compounds were designed and synthesized, scaffold hopping compound 36 that aromatic benzene was replaced pyrazole on ring C showed enhance melanogenesis and tyrosinase activity; The last and most important, a comprehensive optimization and SARs of compound 36 were carried out, compounds 41 and 43 shared phenolic hydroxyl or 3-methyl-pyridine substitutes at C-7 position remarkably improved the capacity of melanogenesis and tyrosinase activity. Compound 43 were identified as new anti-vitiligo agents that specifically activate the Wnt/ß-catenin signalling pathway by targeting Axin. Structure-activity relationship analysis implied that H-acceptor substitutions at the C-4 position and phenolic hydroxyl or pyridine substitutions at the C-7 position would improve the activities of the compounds. These findings reveal a new therapeutic strategy for vitiligo, and compounds 41 and 43 may represent potential compounds for vitiligo treatment.

Virtual reality-based vision therapy versus OBVAT in the treatment of convergence insufficiency, accommodative dysfunction: a pilot randomized controlled trial.

BACKGROUND: Virtual reality is being increasingly applied in vision therapy. However, the differences in effectiveness, optimal treatment cycle, and prognosis between virtual reality-based vision therapy and traditional therapies remain unknown. The purpose of this study was to compare the effectiveness of virtual reality-based vision therapy and office-based vergence/accommodative therapy in young adults with convergence insufficiency or accommodative dysfunction. METHODS: The patients were randomly assigned to either the virtual reality-based vision therapy group or the office-based vergence/accommodative therapy group. The vision therapy lasted 12 weeks (1 h/week) in both groups. Binocular visual functions (vergence and accommodation) were measured and a subjective questionnaire-based assessment was performed at baseline and after 6 and 12 weeks of therapy. RESULTS: In total, 33 patients with convergence insufficiency and 30 with accommodative dysfunction completed the study. After 12 weeks of treatment for convergence insufficiency, the Convergence Insufficiency Symptom Survey score (F2,31 = 13.704, P < 0.001), near point of convergence (F2,31 = 21.774, P < 0.001), positive fusional vergence (F2,31 = 71.766, P < 0.001), and near horizontal phoria (F2,31 = 16.482, P < 0.001) improved significantly in both groups. Moreover, the monocular accommodative amplitude (F2,25 = 22.154, P < 0.001) and monocular accommodative facility (F2,25 = 86.164, P < 0.001) improved significantly in both groups after 12 weeks of treatment. A statistically significant difference was observed in monocular accommodative facility (F1,25 = 8.140, P = 0.009) between the two groups, but not in other vergence and accommodative functions (0.098 < P < 0.687). CONCLUSION: Virtual reality-based vision therapy significantly improved binocular vision functions and symptoms in patients with convergence insufficiency and accommodative dysfunction, thereby suggesting its effectiveness as a new optional or additional treatment for young adults with these conditions. TRIAL REGISTRATION: This study was registered at the Chinese Clinical Trials Registry on 16/04/2019 (identifier: ChiCTR1900022556 ).

Comparison of compliance with care procedures performed by orthokeratology wearers and their parents and factors affecting compliance.

PURPOSE: To compare the levels of compliance with care routines of orthokeratology (ortho-k) wearers and their parents and to identify factors affecting compliance in a hospital setting in Chengdu, China. METHODS: Patients who had worn ortho-k lenses for at least one month were invited to participate in a survey on compliance. Wearers or their parents were required to complete a questionnaire to determine their compliance with hand hygiene, ortho-k lenses and accessory care procedures. RESULTS: A total of 200 wearers, 78 male wearers and 122 female wearers, median age 12 (range 8-18) years were enrolled. Except for use of lens solution, the percentage of participants reporting total compliance with all procedures did not differ significantly between lens wearers and their parents. However, compliance for some items was significantly higher when performed by parents p < 0.001-0.01). 'Eye care practitioner provided instructions' was a significant protective factor for most procedures (p < 0.001-0.04). Age and sex were significant risk factors for some items (p < 0.001-0.04; p = 0.03-0.04, respectively), with girls having higher compliance than boys. 'Parental supervision' was a significant protective factor for some items (p = 0.02-0.04) when wearers performed the procedures themselves. When parents performed lens care procedures, only 'eye care practitioner provided instructions' was a significant variable (p = 0.001-0.04). CONCLUSION: Some degree of non-compliance was noted in the majority of ortho-k wearers, particularly for the care of the lens case and suction holder. Compliance with care of some items was higher when performed by parents. Regular reinforcement of care procedures by practitioners is important, especially for older and male lens wearers. Parental supervision is necessary when children perform lens care procedures themselves, even for older wearers.

Factors determining the myopia control effect of an orthokeratology lens: A two-year multi-level model.

PURPOSE: A multi-level model was used to analyse factors, including environmental factors, affecting the controlling effect of orthokeratology on myopia progression. METHODS: A 2-year prospective study was conducted in the West China Hospital, Sichuan University. Age, sex, height, baseline spherical equivalent refraction, choroidal thickness, axial length and other biometric ocular parameters were collected. Additionally, data on the following environmental factors were obtained: near-work distance and time, sleep time and time spent outdoors. After the baseline measurements, participants were followed up every 3 months for 2 years of lens wear. The primary outcome measure was axial length elongation over 2 years of orthokeratology. All variables were included in a univariate, three-level analysis model with inclusion in the final multivariate multi-level model if statistically significant. RESULTS: Thirty-three participants (average age 9.73 ± 1.55 years) were included in this study. During the 2-year period of lens wearing, binocular changes in axial length increased significantly from the ninth month and continued until the end of the follow-up. Changes in axial length after 2 years of lens wearing were 0.44 ± 0.30 mm and 0.37 ± 0.26 mm in the right and left eyes, respectively (both p < 0.001). Based on the 2-year multi-level model, age, sex, baseline spherical equivalent refraction, flatter keratometry meridian and near-work time influence the effect of orthokeratology. CONCLUSIONS: This is the first study to use a multi-level model to analyse factors, including environmental factors, that affect myopia control using orthokeratology. These results showed that younger age, being female, having lower myopia at baseline, a steeper flattest keratometry meridian and no more than 5 h of near work per day were associated with better myopia control effect using orthokeratology over a 2-year treatment period.

In Vitro Inhibitory Effects of Maqian Essential Oil against Ectopic Endometrial Stromal Cells and LPS-Induced Endometrial Epithelial Cells.

Previous studies revealed that MQEO (Maqian fruits essential oil), which is extracted from the fruit of Maqian (Zanthoxylum myriacanthum var. Pubescens), had a good anti-inflammatory effect, but the effect on endometriosis in vitro remains unknown. In the present study, the inhibitory effects of MQEO against the EESCs (ectopic endometrial stromal cells) were investigated. Cells were treated with a concentration gradient (from 0.025 % to 0.15 %) of MQEO for 24 h and cell viability was detected by CCK-8. In addition, apoptotic rates were investigated using flow cytometry. The effect of MQEO on cell migration was determined by wound-healing and transwell assay. The expression of apoptosis-associated and cell adhesion-related proteins was assessed by western blotting. The transcriptional levels of IL-1, IL-6 and TNF-α were determined by Real-time qPCR. RNA-seq was used to identify the DEGs (differentially expressed genes) in MQEO-pretreated EESCs. We found that the MQEO condition dosage-dependently reduced the cell viability of EESCs. Based on flow cytometry results, the number of apoptotic cells increased significantly with dosage. The wound-healing and transwell results showed that MQEO group exhibited a significantly decreased cell motility and migration ability in comparison with the normal group. Western blotting results showed that MQEO down-regulated the expression of Bcl-2, ICAM-1 (intercellular adhesion molecule 1) and CD44, but up-regulated the cleaved caspase-3 expression in EESCs. What's more, MQEO also inhibited the LPS-induced inflammation in human EECs (endometrial epithelial cells). RNA-seq revealed that 221 DEGs were up-regulated genes and 284 DEGs were down-regulated in MQEO-pretreated EESCs. Our data uncovered the beneficial effects of MQEO in endometriosis and provided new insights into the mechanism of the effect of MQEO on EESCs, suggesting MQEO could be a promising new therapeutic agent for endometriosis.

[Compound Chamomile and Lidocaine Hydrochloride Gel applied at different time-windows for premature ejaculation: A prospective single-center randomized controlled study].

OBJECTIVE: To investigate the efficacy and safety of Compound Chamomile and Lidocaine Hydrochloride Gel (CCLH) (Kamistad) applied at different time-windows on premature ejaculation (PE). METHODS: This prospective study included 72 PE patients treated by application of CCLH to the glans and penile body in our hospital from February to October 2021. According to the time of drug administration before insertion into the vagina, we randomly divided the patients into a 5-minute group (n = 39) and a 15-minute group (n = 33). Before and after 1 and 2 weeks of treatment, we compared the intravaginal ejaculation latency time (IELT), PE diagnostic tool (PEDT) score, quality of life, and adverse reactions between the two groups of patients. RESULTS: Totally 62 of the patients completed the follow-up, 35 in the 5-minute group and 27 in the 15-minute group, and all showed significant improvement in IELT (P < 0.01) and PEDT score (P < 0.05) after treatment compared with the baseline. No allergic reactions, such as redness and swelling, developed at the application site in any of the patients, and no adverse significant effect was observed on the erectile hardness in 61 of the cases. Six cases showed increased erectile hardness instead. Fifty-seven of the patients experienced no obvious penile numbness or reduced sexual satisfaction, and all could complete their sexual activities. CONCLUSION: Compound Chamomile and Lidocaine Hydrochloride Gel applied at different time-windows is effective on PE, with a 5-minute rapid onset of action before intercourse, and no obvious adverse effects.

[Analysis of Characteristic Eye Movement Behaviors of Young Adults with Different Degrees of Myopia].

Objective: To measure the parameters of eye movement of young adult patients of myopia, to compare the differences in the parameters of patient groups with varied degrees of myopia, and to analyze the correlation between eye movement parameters and axial length (AL) and spherical equivalent refraction (SER). Methods: A total of 91 young adult patients of myopia were recruited. The subjects were divided into three groups of low, moderate, and high myopia according to their SER. Information on the subjects' age and sex was collected and general clinical examination was completed. The subjects' binocular fixation, reflexive saccade, and antisaccade were measured with eye tracker. One-way ANOVA or Kruskal-wallis test was used to compare the general data and eye movement parameters of the three groups of myopic patients. Pearson or Spearman correlation analysis was used to analyze AL and SER's correlation with 95% bivariate contour ellipse area (BCEA) and saccadic parameters. Results: The 95% BCEA for mild, moderate, and high myopia groups were 2.08 (0.54, 14.69) deg 2, 4.99 (0.94, 49.22) deg 2, and 5.79 (2.18, 64.91) deg 2, respectively. There was significant difference between the 95% BCEA of the three groups ( P=0.029). The 95% BCEA of the mild myopia group was significantly smaller than that of the high myopia group ( P=0.01). There were no significant differences in saccadic parameters among the three groups ( P>0.05). There was a significant positive correlation between 95% BCEA and AL ( r=0.342, P=0.001). There was a significant negative correlation between 95% BCEA and SER ( r=-0.322, P=0.002). There was no significant correlation between the parameters of saccadic movement and the AL or SER ( P>0.05). Conclusion: For young adult myopic patients, the longer the AL is, the higher the degree of the myopia and the worse the fixation stability becomes. The fixation stability of patients with high myopia was significantly worse than that of patients with mild myopia. There was no significant difference in saccadic parameters in patients with different degrees of myopia.

Nicotine exhausts CD8+ T cells against tumor cells through increasing miR-629-5p to repress IL2RB-mediated granzyme B expression.

The mechanism exhausting CD8+ T cells is not completely clear against tumors. Literature has demonstrated that cigarette smoking disables the immunological activity, so we propose nicotine is able to exhaust CD8+ T cells. The CD8+ T cells from healthy volunteers with and without cigarette smoking and the capacity of CD8+ T cells against tumor cells were investigated. RNAseq was used to investigate the gene profiling expression in CD8+ T cells. Meanwhile, small RNAseq was also used to search novel microRNAs involved in the exhaustion of CD8+ T cells. The effect of nicotine exhausting CD8+ T cells was investigated in vitro and in the humanized tumor xenografts in vivo. We found that CD8+ T cells were able to reduce cell viability in lung cancer HCC827 and A549 cells, that secreted granzyme B, but CD8+ T cells from the healthy cigarette smokers lost anti-HCC827 effect. Moreover, nicotine suppressed the anti-HCC827 effect of CD8+ T cells. RNAseq revealed lower levels of IL2RB and GZMB in the exhausted CD8+ T cells. We identified that miR-629-5p was increased by nicotine, that targeted IL2RB. Transfection of miR-629-5p mimic reduced IL2RB and GZMB levels. We further validated that nicotine reduced granzyme B levels using a nuclear imaging technique, and demonstrated that nicotine exhausted peripheral blood mononuclear cells against HCC827 growth in the humanized tumor xenografts. This study demonstrated that nicotine exhausted CD8+ T cells against HCC827 cells through increasing miR-629-5p to suppress IL2RB.

Metabolomics Insights into Oleate-Induced Disorders of Phospholipid Metabolism in Macrophages.

BACKGROUND: Diet-induced disordered phospholipid metabolism and disturbed macrophage metabolism contribute to the pathogenesis of metabolic diseases. However, the effects of oleate, a main dietary fatty acid, on macrophage phospholipid metabolism are unclear. OBJECTIVES: We aimed to discover oleate-induced disorders of macrophage phospholipid metabolism and potential therapeutic targets for treating diet-related metabolic diseases. METHODS: RAW 264.7 cells were exposed to 65 µg oleate/mL, within the blood concentration range of humans and mice, to trigger disorders of phospholipid metabolism. Meanwhile, WY-14643 and pioglitazone, 2 drugs widely used for treating metabolic diseases, were employed to prevent oleate-induced disorders of macrophage phospholipid metabolism. Subsequently, an untargeted metabolomics approach based on liquid chromatography-mass spectrometry was used to discover relevant metabolic disorders and potential therapeutic targets. RESULTS: We showed that 196 metabolites involved in phospholipid metabolism were altered upon oleate treatment and interventions of WY-14643 and pioglitazone (P < 0.05, 2-tailed Mann-Whitney U test). Notably, most lysophospholipids were decreased, whereas most phospholipids were increased in oleate-treated macrophages. Phosphatidylethanolamines accumulated most among phospholipids, and their acyl chain polyunsaturation increased in oleate-treated macrophages. Additionally, saturated fatty acids were decreased, whereas polyunsaturated fatty acids were increased in oleate-treated macrophages. Furthermore, changes in phosphatidylglycerols, phosphatidylinositols, cardiolipins, phosphatidates, lysophosphatidylglycerols, and acylcarnitines in oleate-treated macrophages could be attenuated or even abolished by WY-14643 and/or pioglitazone treatment. CONCLUSIONS: Oleate induced accumulation of various phospholipids, increased acyl chain polyunsaturation of phosphatidylethanolamines, and decreased lysophospholipids in RAW 264.7 macrophages. This study suggests macrophage phospholipid and fatty acid metabolism as potential therapeutic targets for intervening diet-related metabolic diseases.

A novel mycovirus infecting Aspergillus nidulans that is closely related to viruses in a new genus of the family Partitiviridae.

The bisegmented genome of a novel double-stranded (ds) RNA mycovirus, named "Aspergillus nidulans partitivirus 1" (AnPV1), isolated from the fungus Aspergillus nidulans strain HJ5-47, was sequenced and analyzed. AnPV1 contains two segments, AnPV1-1 and AnPV1-2. AnPV1-1 has 1837 bp with an open reading frame (ORF) that potentially encodes a putative RNA-dependent RNA polymerase (RdRp) of 572 amino acids (aa). AnPV1-2 has 1583 bp with an ORF encoding a putative capsid protein (CP) of 488 aa. Phylogenetic analyses indicated that AnPV1 and related viruses clustered in a group that could represent a new unclassified genus in the family Partitiviridae.

Phenanthridine Derivative Host Heat Shock Cognate 70 Down-Regulators as Porcine Epidemic Diarrhea Virus Inhibitors.

Porcine epidemic diarrhea virus (PEDV) has become increasingly problematic around the world, not only for its hazards to livestock but also due to the possibility that it is a zoonotic disease. Although vaccine therapy has made some progress toward PEDV control, additional effective therapeutic strategies against PEDV are needed, such as the development of chemotherapeutic agents. The aim of this work was to identify novel anti-PEDV agents by designing and synthesizing a series of phenanthridine derivatives. Among them, three compounds (compounds 1, 2, and 4) were identified as potent anti-PEDV agents exhibiting suppression of host cell heat shock cognate 70 (Hsc70) expression. Mechanism studies revealed that host Hsc70 is involved in the replication of PEDV, and its expression can be suppressed by destabilization of the mRNA, resulting in inhibition of PEDV replication. Activity against PEDV in vivo in PEDV-infected piglets suggested that phenanthridine derivatives are the first host-acting potential anti-PEDV agents.