Functional Plasticity, Redundancy, and Specificity of Lanosterol 14α-Demethylase in Regulating the Sensitivity to DMIs in Calonectria ilicicola.

Cytochrome P450 sterol 14α-demethylase (CYP51) is a key enzyme involved in the sterol biosynthesis pathway and serves as a target for sterol demethylation inhibitors (DMIs). In this study, the 3D structures of three CPY51 paralogues from Calonectria ilicicola (C. ilicicola) were first modeled by AlphaFold2, and molecular docking results showed that CiCYP51A, CiCYP51B, or CiCYP51C proteins individually possessed two active pockets that interacted with DMIs. Our results showed that the three paralogues play important roles in development, pathogenicity, and sensitivity to DMI fungicides. Specifically, CiCYP51A primarily contributed to cell wall integrity maintenance and tolerance to abiotic stresses, and CiCYP51B was implicated in sexual reproduction and virulence, while CiCYP51C exerted negative regulatory effects on sterol 14α-demethylase activity within the ergosterol biosynthetic pathway, revealing its genus-specific function in C. ilicicola. These findings provide valuable insights into developing rational strategies for controlling soybean red crown rot caused by C. ilicicola.

Comparison of the efficacy of acupuncture with tuina with acupuncture-only in the treatment of peripheral facial paralysis: a network meta-analysis.

At present, traditional Chinese medicine treatment is considered safe for treating peripheral facial paralysis (PFP). Acupuncture-only and acupuncture combined with tuina are widely used for this purpose. However, it is not clear whether acupuncture combined with tuina is better for treating PFP than acupuncture-only. Conventional meta-analysis and network meta-analysis were used to compare the clinical efficacies of acupuncture combined with tuina and acupuncture-only in the treatment of PFP. Randomized controlled trials (RCTs), with the subjects being patients with PFP and treatment interventions including acupuncture combined with tuina, acupuncture-only, tuina-only, placebo, single Western medicine, and steroids combined with other Western medicine were searched from both Chinese and English databases. The primary outcomes included Modified House-Brackmann (MHBN) scores and Sunnybrook Facial Grading System, whereas the secondary outcomes included cure time, Portmann scores, and physical function scale of Facial Disability Index, using conventional meta-analysis and network meta-analysis. The study included 22 RCTs with a sample size of 1814 patients. The results of conventional meta-analysis (MD = 16.12, 95%CI 13.13,19.10) and network meta-analysis (MD = 14.53, 95%CI 7.57,21.49) indicate that acupuncture combined with tuina was better than acupuncture-only in improving MHBN and shortening the cure time (MD = - 6.09, 95%CI - 7.70, - 4.49). Acupuncture combined with tuina was the optimal therapy for improving MHBN (SUCRA was 100%) and shortening the cure time (SUCRA was 100%). The results of this meta-analysis indicate that acupuncture combined with tuina can significantly improve MHBN and shorten the cure time, compared with acupuncture-only. However, the current evidence is insufficient, and more high-quality clinical studies are needed.Registration: This study had been registered with PROSPERO (CRD42022379395).

The HOG-pathway related AaOS1 leads to dicarboximide-resistance in field strains of Alternaria alternata and contributes, together with the Aafhk1, to mycotoxin production and virulence.

BACKGROUND: Garlic leaf spot (GLS) caused by Alternaria alternata is one of the main diseases in the garlic production areas, and its management heavily relies on dicarboximide fungicides. However, the efficacy of dicarboximides against the GLS disease has decreased year on year. RESULTS: In the present study, 10 of 148 A. alternata strains separated from Jiangsu Province were moderately resistant (MR) to a dicarboximide fungicide procymidone (ProMR). Positive cross-resistance was observed between Pro and iprodione (Ipro) or fludioxonil (Fld), but not between Pro and fluazinam or azoxystrobin. Mutations at AaOS1, but not Aafhk1, were confirmed to confer the Pro resistance by constructing replacement mutants, whereas mutations at both AaOS1 and Aafhk1 decreased the gene expression level of AapksI, as well as the ability to produce mycotoxin AOH (polyketide-derived alternariol) and virulence. Additionally, more genes (AaOS1 and Aafhk1) harboring the mutations experienced a larger biological fitness penalty. CONCLUSION: To our knowledge, this is the first report on Pro resistance selected in garlic fields, and mutations at AaOS1 of A. alternata causing a decreased ability to produce the mycotoxin AOH. © 2024 Society of Chemical Industry.

Effect of the staging comprehensive treatment with acupuncture-moxibustion on Bell's facial palsy in the acute stage. / 针灸分期综合治疗急性期贝尔面瘫疗效观察.

OBJECTIVES: To compare the clinical effect on Bell's facial palsy in the acute stage between the staging comprehensive treatment with acupuncture-moxibustion and western medication. METHODS: Sixty patients with Bell's facial palsy in the acute stage were randomly divided into an observation group and a control group, with 30 cases in each one. The patients in the control group were administered orally with prednisone acetate tablets and methylcobalamin tablets until the 28th day of illness. In the observation group, the staging comprehensive treatment with acupuncture-moxibustion was adopted. On the affected side, Qianzheng (EX-HN 16), Yifeng (TE 17), Sibai (ST 2), Yangbai (GB 14), Jiache (ST 6), Dicang (ST 4) and Touwei (ST 8), etc. were stimulated. In the acute stage (Day 1 to 7 of illness), the routine acupuncture and the point-toward-point needle insertion were delivered, no any manipulation was exerted at acupoints, and the needles were retained for 30 min. In the subacute stage (Day 8 to 14 of illness), on the base of the treatment as the acute stage, the depth of needle insertion was adjusted at a part of acupoints and the even needling technique was operated by twisting needle. Besides, electroacupuncture (EA) was attached to Qianzheng (EX-HN 16) and Dicang (ST 4), with continuous wave of low intensity and high frequency, 100 Hz, for 20 min. In the recovery stage (Day 15 to 28 of illness), on the base of the treatment as the subacute stage, the heavy stimulation of acupuncture was given, in which, the sticking and lifting needle techniques were delivered after the needles were inserted from Sibai (ST 2) toward Dicang (ST 4), and from Dicang (ST 4) toward Jiache (ST 6), separately; warm needling was operated at Yifeng (TE 17), and EA changed to stimulate the acupoints with the intermittent wave of high intensity and low frequency, 2 Hz, for 30 min. Acupuncture-moxibustion was given once every other day until the end of the 28th day of illness. The level of House-Brackmann facial nerve function rating scale (H-B grade),the score of Sunnybrook facial nerve grading system (Sunnybrook), the score of facial disability index (FDI), the temperature difference in the infrared thermal imaging facial area and electromyogram (EMG) situation of the affected muscle group were observed before and after treatment in the two groups. Using musculoskeletal ultrasound,the facial nerve diameter was detected and the clinical effect was compared between the two groups. RESULTS: After treatment, the level of H-B grade, Sunnybrook score, the scores of physical function and social life function in FDI were improved when compared with those before treatment in the patients of either group (P<0.01, P<0.05), and the results of these evaluations in the observation group were better than those of the control group (P<0.05). After treatment, the temperature difference of the frontal area, the eye area, the zygomatic area and the mouth corner was declined in comparison with that before treatment in the two groups (P<0.05), and the temperature difference in each area in the observation group was lower than that of the control group (P<0.05).The root mean square (RMS) of the frontal muscle group, the zygomatic muscle group and the orbicularis muscle group on the affected side increased in comparison with that before treatment in the two groups (P<0.01), and RMS of the observation group was higher than that of the control group (P<0.05) after treatment. Before treatment, the diameter of the facial nerve on the affected side was larger than that on the healthy side (P<0.01), and after treatment, the diameter on the affected side was reduced when compared with that before treatment in the two groups (P<0.01); the diameter of the facial nerve on the affected side in the observation group was smaller than that of the control group (P<0.05), while, the diameter on the affected side was larger when compared with the healthy side in the control group (P<0.05). The total effective rate of the observation group was 93.3% (28/30), higher than that of the control group (83.3% [25/30], P<0.05). CONCLUSIONS: The staging comprehensive treatment with acupuncture-moxibustion is clearly effective on Bell's facial palsy in the acute stage, which affirms the effectiveness of acupuncture-moxibustion for the acute stage of Bell's facial palsy in comparison with conventional western medication.

Estimating surgical probability: Development and validation of a prognostic model for patients with lumbar disc herniation treated with acupuncture.

Lumbar disc herniation (LDH) is a common cause of pain in the lumbar spine and legs. While acupuncture has become the primary conservative treatment for LDH, some patients experience treatment failure and require surgery, causing substantial concern for clinicians. We developed an effective personalized clinical prediction model to identify the independent risk factors associated with acupuncture failure in patients with LDH. Our model aimed to predict the probability of surgery within 6 months of acupuncture failure in patients with LDH. A total of 738 patients with LDH who underwent acupuncture at 4 Chinese hospitals between January 2019 and October 2021 were selected. The patients were divided into training (n = 496) and validation (n = 242) cohorts. Seven predictive variables, including smoking, Oswestry Disability Index (ODI) score, lower-limb herniation, disc herniation type, lumbar spinal stenosis, lumbar lateral recess stenosis, and acupuncture frequency, were selected as risk factors using least absolute shrinkage and selection operato (LASSO) regression. A prediction model was developed using multivariate logistic regression analysis and a nomogram was constructed. The model exhibited good discrimination, with an area under the ROC curve (AUC) of 0.903 for the development cohort and 0.899 for the validation cohort. The Hosmer-Lemeshow goodness-of-fit test was a good fit for both cohorts (P = .956 for the development cohort; P = .513 for the validation cohort). Decision curve analysis (DCA) demonstrated that the threshold probabilities for the 2 cohorts ranged from > 4% and 5-95%, respectively. Therefore, the prediction model had a good net benefit. The nomogram established in this study, incorporating 7 risk factors, demonstrated a good predictive ability. It could predict acupuncture failure in LDH patients and the risk of surgery within 6 months, enabling physicians to conduct individualized treatment measures.

The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial.

BACKGROUND: Early control of elevated blood pressure is the most promising treatment for acute intracerebral haemorrhage. We aimed to establish whether implementing a goal-directed care bundle incorporating protocols for early intensive blood pressure lowering and management algorithms for hyperglycaemia, pyrexia, and abnormal anticoagulation, implemented in a hospital setting, could improve outcomes for patients with acute spontaneous intracerebral haemorrhage. METHODS: We performed a pragmatic, international, multicentre, blinded endpoint, stepped wedge cluster randomised controlled trial at hospitals in nine low-income and middle-income countries (Brazil, China, India, Mexico, Nigeria, Pakistan, Peru, Sri Lanka, and Viet Nam) and one high-income country (Chile). Hospitals were eligible if they had no or inconsistent relevant, disease-specific protocols, and were willing to implement the care bundle to consecutive patients (aged ≥18 years) with imaging-confirmed spontaneous intracerebral haemorrhage presenting within 6 h of the onset of symptoms, had a local champion, and could provide the required study data. Hospitals were centrally randomly allocated using permuted blocks to three sequences of implementation, stratified by country and the projected number of patients to be recruited over the 12 months of the study period. These sequences had four periods that dictated the order in which the hospitals were to switch from the control usual care procedure to the intervention implementation of the care bundle procedure to different clusters of patients in a stepped manner. To avoid contamination, details of the intervention, sequence, and allocation periods were concealed from sites until they had completed the usual care control periods. The care bundle protocol included the early intensive lowering of systolic blood pressure (target <140 mm Hg), strict glucose control (target 6·1-7·8 mmol/L in those without diabetes and 7·8-10·0 mmol/L in those with diabetes), antipyrexia treatment (target body temperature ≤37·5°C), and rapid reversal of warfarin-related anticoagulation (target international normalised ratio <1·5) within 1 h of treatment, in patients where these variables were abnormal. Analyses were performed according to a modified intention-to-treat population with available outcome data (ie, excluding sites that withdrew during the study). The primary outcome was functional recovery, measured with the modified Rankin scale (mRS; range 0 [no symptoms] to 6 [death]) at 6 months by masked research staff, analysed using proportional ordinal logistic regression to assess the distribution in scores on the mRS, with adjustments for cluster (hospital site), group assignment of cluster per period, and time (6-month periods from Dec 12, 2017). This trial is registered at Clinicaltrials.gov (NCT03209258) and the Chinese Clinical Trial Registry (ChiCTR-IOC-17011787) and is completed. FINDINGS: Between May 27, 2017, and July 8, 2021, 206 hospitals were assessed for eligibility, of which 144 hospitals in ten countries agreed to join and were randomly assigned in the trial, but 22 hospitals withdrew before starting to enrol patients and another hospital was withdrawn and their data on enrolled patients was deleted because regulatory approval was not obtained. Between Dec 12, 2017, and Dec 31, 2021, 10 857 patients were screened but 3821 were excluded. Overall, the modified intention-to-treat population included 7036 patients enrolled at 121 hospitals, with 3221 assigned to the care bundle group and 3815 to the usual care group, with primary outcome data available in 2892 patients in the care bundle group and 3363 patients in the usual care group. The likelihood of a poor functional outcome was lower in the care bundle group (common odds ratio 0·86; 95% CI 0·76-0·97; p=0·015). The favourable shift in mRS scores in the care bundle group was generally consistent across a range of sensitivity analyses that included additional adjustments for country and patient variables (0·84; 0·73-0·97; p=0·017), and with different approaches to the use of multiple imputations for missing data. Patients in the care bundle group had fewer serious adverse events than those in the usual care group (16·0% vs 20·1%; p=0·0098). INTERPRETATION: Implementation of a care bundle protocol for intensive blood pressure lowering and other management algorithms for physiological control within several hours of the onset of symptoms resulted in improved functional outcome for patients with acute intracerebral haemorrhage. Hospitals should incorporate this approach into clinical practice as part of active management for this serious condition. FUNDING: Joint Global Health Trials scheme from the Department of Health and Social Care, the Foreign, Commonwealth & Development Office, and the Medical Research Council and Wellcome Trust; West China Hospital; the National Health and Medical Research Council of Australia; Sichuan Credit Pharmaceutic and Takeda China.

Mir-21-5p and Mir-455-5p as Markers for Diagnosis and Prognosis of Rectal Adenocarcinoma may Reduce Local CD4+ and CD8+ Lymphocyte Infiltration.

OBJECTIVE: This study aimed to verify miRNAs and the molecular mechanisms of diagnostic and prognostic biomarkers for rectal adenocarcinoma. METHODS: Two miRNA datasets of rectal adenocarcinoma were obtained from GEO and TCGA. GEO2R tool, Venn diagram, Kaplan-Meier survival analysis, KEGG pathway analyses, DIANA TOOLS, and Wilcoxon rank-sum test were used for biological information analysis. The diagnostic utility of miRNAs and immune infiltration of tumors in Chinese patients were validated by RTqPCR and immunofluorescence analysis. RESULTS: MiR-21-5P and miR-455-5p were both found to have a significant correlation with poor prognosis and higher expression in rectal adenocarcinoma. Besides, the ability to prognosis was independent of the clinicopathological stage. MiR-21-5P and miR-455-5p were enriched in the TGF-beta, Wnt, MAKP, and PI3K-AKT signaling pathways. Meanwhile, the high expression phenotype of miR-21-5P and miR-455-5p decreased CD4+ and CD8+ T cells. CONCLUSION: In summary, we found two significant diagnostic and prognostic miRNAs of rectal adenocarcinoma via integrated bioinformatics approach and clinical trials, which might decrease CD4+ and CD8+ T cells.

Exploring the regulatory effect of acupuncture for Ningshen Tongqiao on the functional connectivity between the anterior cingulate cortex and the whole brain in the patients with subjective tinnitus based on fMRI. / 基于fMRIåˆæŽ¢å®ç¥žé€šçªæ³•é’ˆåˆºå¯¹ä¸»è§‚æ€§è€³é¸£æ‚£è€ å‰æ‰£å¸¦å›žä¸Žå ¨è„‘åŠŸèƒ½è¿žæŽ¥çš„è°ƒæŽ§ä½œç”¨.

OBJECTIVES: To explore the effect of acupuncture for Ningshen Tongqiao (tranquilizing the spirit and unblocking the orifices) on the functional connectivity (FC) between the anterior cingulate cortex (ACC) and the whole brain in the patients with subjective tinnitus using the resting-state functional magnetic resonance imaging (fMRI). METHODS: Forty patients with subjective tinnitus and 40 healthy subjects were recruited. The patients with subjective tinnitus were treated with acupuncture for Ningshen Tongqiao at Yamen (GV 15) and Baihui (GV 20), as well as Tinggong (SI 19), Touqiaoyin (GB 11) and Shuaigu (GB 8) on the affected side; and Tinggong (SI 19) and Touqiaoyin (GB 11) were attached to the electric acupuncture apparatus and stimulated with disperse-dense wave and 2 Hz/50 Hz in frequency. Acupuncture was operated once daily, 3 times a week and 10 treatments were required. Before and after treatment, the scores of tinnitus evaluation questionnaire (TEQ), tinnitus handicap inventory (THI) and tinnitus visual analogue scale (VAS) were evaluated; and the clinical therapeutic effect was assessed. Separately, the patients with subjective tinnitus received one time of fMRI within 2 days before and after treatment, and the healthy subjects underwent one time of fMRI after enrollment. The bilateral ACC was taken as the region of interest (ROI). Using matlab R2017b software, FC between ACC and the whole brain was calculated. RESULTS: After treatment, the scores of THI, TEQ and VAS were reduced in the subjective tinnitus patients compared with those before treatment (P<0.01); and the total effective rate was 92.5% (37/40). Before treatment, compared with the healthy subjects, FC between the right ACC and the left middle temporal gyrus, the left superior temporal gyrus and the left superior frontal gyrus decreased in the subjective tinnitus patients. FC between the right ACC and the left middle frontal gyrus and the bilateral angular gyrus was dropped, while that between the left ACC and the left middle frontal gyrus, the left thalamus, the left angular gyrus and the left middle temporal gyrus was decreased in the subjective tinnitus patients when compared with the healthy subjects after treatment. Compared with those before treatment, FC between the right ACC and the left lingual gyrus and the left thalamus were declined, and that between the left ACC and the right middle frontal gyrus and the right superior frontal gyrus was decreased in the subjective tinnitus patients after treatment. CONCLUSIONS: Acupuncture can effectively relieve the clinical symptoms of subjective tinnitus patients, and promote the functional re-construction of the auditory regions (temporal lobe, frontal lobe and thalamus) and the emotion-related brain regions.

Acupuncture decreases amygdala functional connectivity in subjective tinnitus.

Introduction: Subjective tinnitus is a common and intractable ear disease. The effectiveness of acupuncture in the treatment of subjective tinnitus has been confirmed, but its mechanism of action is not clear. The structures of the amygdala (AMYG) are mainly closely related to emotion in the human brain. This study aimed to investigate the changes in functional connectivity (FC) of AMYG in subjective tinnitus to elucidate the neural mechanism of acupuncture. Methods: Correlation scale scores of 26 patients with subjective tinnitus were collected, including Tinnitus Evaluation Questionnaire (TEQ), Tinnitus Handicap Inventory (THI) and Visual Analog Scale (VAS). Meanwhile, rs-fMRI data were collected before and after acupuncture treatment in the patients, and in healthy controls (HC) matching the patient's gender and age. Then, AMYG was selected as region of interest to perform FC analysis. Finally, FC patterns of AMYG were first compared between patients with subjective tinnitus and HC, and then within subjects pre-acupuncture and post-acupuncture. Simple linear regression models between correlation scale scores and FC-values were established as well. Results: Acupuncture treatment relieved the severity of tinnitus. With the acupuncture treatment, the total THI score, TEQ score, and VSA score of patients were significantly lower than before (p < 0.05). Compared with HC, FC of tinnitus patients between AMYG and right inferior temporal gyrus and right precuneus significantly decreased before acupuncture (voxel p < 0.001, cluster p < 0.05, corrected with GRF), while FC of tinnitus patients between AMYG and left superior frontal gyrus and right superior temporal gyrus significantly decreased after acupuncture treatment (voxel p < 0.001, cluster p < 0.05, corrected with GRF). FC of tinnitus patients between the AMYG and right superior frontal gyrus and left paracingulate gyrus showed significant decrease after acupuncture treatment (voxel p < 0.001, cluster p < 0.05, corrected with GRF). Besides, the linear regression models of the effect of THI on FC and VAS on FC performed were statistically significant (p < 0.05). Discussion: The findings demonstrate that acupuncture can decrease FC of AMYG, which could be positively correlated with the relief of tinnitus symptoms. This result suggests that acupuncture stimulation can effectively relieve the severity of tinnitus by decreasing FC of AMYG in subjective tinnitus patients.

Strength of Coarse-Grained Soil Stabilized by Poly (Vinyl Alcohol) Solution and Silica Fume under Wet-Dry Cycles.

To investigate an environmentally benign stabilizer for coarse-grained soil in southeast Tibet, poly (vinyl alcohol) (PVA) and silica fume were used to improve the geotechnical properties of coarse-grained soil. Unconfined compressive strength (UCS) and wet-dry cycle tests were conducted on prepared samples to evaluate the effect of the additive content and curing age on the strength and durability of coarse-grained soil. The results reveal that the UCS of the samples increased with the additive content of PVA solution and the curing age. The optimal value for the additive content of PVA solution and the curing age is 12% and 7 days, respectively. With the optimal PVA solution content, the PVA solution combined with silica fume stabilizer exhibited better reinforcement compared with pristine PVA. The UCS of the samples stabilized by PVA solution and silica fume increased depending on the curing age, and plateaued after 14 days. Samples with 12% PVA solution and 6% silica fume achieved a satisfactory UCS of 1543.17 kPa after curing for 28 days. As the number of wet-dry cycles increased, the UCS of the samples stabilized by the PVA solution and silica fume exhibited an upward trend during the first three wet-dry cycles, owing to the filling of pores by the gel produced by the silica fume, but began to decline as the number of wet-dry cycles increased. All samples retained a high UCS value after 10 wet-dry cycles compared with the samples that were not subjected to wet-dry cycles.

Clinical Observation of Alternative Wave Electroacupuncture Combined with Lee's Naprapathy in Treating Knee Osteoarthritis (Blood Stasis due to Qi Stagnation).

Objective: We aim to explore the clinical therapeutic effect of alternative wave electroacupuncture combined with Lee's naprapathy therapy on knee osteoarthritis (KOA) (blood stasis due to qi stagnation). Method: 122 patients with KOA treated in our hospital from January 2018 to October 2021 were randomly grouped into a combined group (n = 61) and a control group (n = 61). The combined group was treated with alternative wave electroacupuncture combined with Lee's naprapathy, while the control group was treated with alternative wave electroacupuncture alone. Clinical efficacy of the two groups was observed. The Visual Analogue Scale (VAS), Lysholm Scale, Indexes of Severity for Osteoarthritis (ISOA), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were compared before and after treatment, followed up for 3 months and 6 months. The adverse reactions of the two groups were observed. Result: The overall response rate of the combined group (96.72%) was higher than that of the control group (81.97%), and the difference was statistically significant (P < 0.05). After treatment and follow-up for 3 months and 6 months, the Lysholm score of the combined group was higher than that of the control group, while the VAS, ISOA, and WOMAC scores were lower than those of the control group, and the difference between the two was statistically significant (P < 0.05). There were no serious adverse reactions in both groups (P > 0.05). Conclusion: The alternative wave electroacupuncture combined with Lee's naprapathy is effective and safe in treating KOA (blood stasis due to qi stagnation).

Experimental Study on PVA-MgO Composite Improvement of Sandy Soil.

Materials with violent hydration reaction such as cement are used to solidify sandy soil slopes, which will cause destructive damage to the ecology of the slopes. In this paper, polyvinyl alcohol (PVA) and activated magnesium oxide (MgO) are used to improve sandy soil, and the effects of the dosage and curing age of modifiers on the mechanical properties of solidified sandy soil are studied. The dry-wet durability of the composite improved sandy soil is analyzed using a dry-wet cycle test, and the improvement mechanism of PVA and activated magnesium oxide is revealed using an electron microscope. The results show that the curing effect of polyvinyl alcohol and activated magnesium oxide on sand particles is better than that of polyvinyl alcohol alone. The compressive strength of improved soil samples increases with the increase of curing time, and magnesium oxide as an improved material needs appropriate reaction conditions to give full play to its role. The compressive strength of composite improved samples increases first and then decreases during the dry-wet cycle. Through the observation of microstructure, it can be seen that the cementing material wraps and connects the sand particles, and the cementing material of the sample after the dry-wet cycle develops more completely; if the magnesium oxide content is high, cracks may appear inside the sample.

Activity of a SDHI fungicide penflufen and the characterization of natural-resistance in Fusarium fujikuroi.

The occurrence of bakanae disease of rice caused by the fungus Fusarium fujikuroi in Zhejiang Province has become increasingly aggravated in recent years, concomitant with the development of resistance to the widely applied fungicides, prochloraz and phenamacril. In this study, the activity of a novel succinate dehydrogenase inhibitor (SDHI) fungicide, penflufen, against different fungi was evaluated in addition to the potential of penflufen in controlling F. fujikuroi infections. Penflufen exhibited good bioactivity against F. fujikuroi, but weak activity against Fusarium spp. and other investigated plant-pathogenic fungi including Colletotrichum spp. In addition to inhibiting mycelial growth, penflufen effectively inhibited F. fujikuroi conidium production. For germination, penflufen could effectively inhibit that of small conidia, but only delay the germination of large conidia. In addition, the sensitivity to penflufen among 100 F. fujikuroi isolates that were collected in areas that were never exposed to SDHIs was determined based on mycelium growth. Sensitivities surprisingly exhibited bimodal distributions, indicating the presence of natural resistance. Cross-resistance was not observed between penflufen in F. fujikuroi and two fungicides that have been extensively applied in field including prochloraz (a DMI) and phenamacril (a 2-cyanoacrylate fungicide), nor with the three SDHIs, fluopyram, benzovindiflupyr, and pydiflumetofen. Additional analysis identified five different point mutations in SDH-A (i.e., at residues 46, 225, 283, 430, and 586) of naturally resistant isolates. These results inform the potential application of the new SDHI fungicide penflufen for managing crop diseases and understanding possible resistance mechanisms among pathogens.

Acupuncture Enhances Dorsal Raphe Functional Connectivity in Knee Osteoarthritis With Chronic Pain.

INTRODUCTION: Knee osteoarthritis is a common disease in the elderly. Patients suffer from long-term chronic pain and reduced life quality. Acupuncture has been proven to be an effective treatment for KOA. However, the neural mechanism of acupuncture is unclear, so far. Periaqueductal gray (PAG) and raphe nuclei (RPN) are essential structures associated with chronic pain in human brains. This study aims to investigate functional connectivity (FC) changes of PAG and RPN in KOA to interpret the neural mechanism of acupuncture. METHODS: In 15 patients with KOA and 15 healthy controls (HC), we acquired Visual Analog Scale (VAS) scores and resting-state fMRI images of each participant before and after acupuncture stimulation on EX-LE5 acupoint. Then, PAG and RPN were selected as seeds to perform FC analysis based on resting-state fMRI images. Finally, we compared FC patterns of PAG and RPN between patients with KOA and HC, then between pre-acupuncture and post-acupuncture. Correlations between FC values and VAS scores were calculated as well. RESULTS: For PAG, FC of patients with KOA was lower in the right lingual gyrus at post-acupuncture compared with HC (p <0.001, uncorrected). For dorsal RPN, FC of patients with KOA was significantly higher in right putamen at post-acupuncture compared with HC (p <0.001, corrected with FDR), and FC changes were significant between pre-acupuncture and post-acupuncture in patients with KOA. Post-acupuncture FC values between dorsal RPN and right putamen were correlated with VAS scores. For medial RPN, FC of patients with KOA was lower in the right cerebellum at post-acupuncture compared with HC (p <0.001, uncorrected), but no significant FC changes were found between pre-acupuncture and post-acupuncture in patients with KOA. FC values between medial RPN and right cerebellum were not correlated with VAS scores at pre-acupuncture and post-acupuncture. DISCUSSION: Our study demonstrated that acupuncture enhanced FC between dorsal RPN and the right putamen in patients with KOA, which was associated with chronic pain intensity. This result suggests that acupuncture stimulation can enhance FC between dorsal raphe and striatum, illustrating a neural mechanism that acupuncture can drive the patients' brain, with KOA, to perceive pain.

Bone Marrow Stromal Antigen 2 is a Potential Unfavorable Prognostic Factor for High-Grade Glioma.

BACKGROUND: Bone marrow stromal antigen 2 (BST2) is considered as a transmembrane glycoprotein and plays essential roles in innate immunity. It has been recently reported that up-regulation of BST2 was associated with the development of breast carcinoma. However, the clinical significance of BST2 in glioma has not been identified. The purpose of the present study is to explore the expression pattern and the role of BST2 in the progression of high-grade glioma. METHODS: Expression levels of BST2 were tested in glioma tissues by analyzing the GEO database and immunohistochemistry staining. The prognostic role of BST2 in glioma was evaluated through univariate and multivariate analyses. In vitro and in vivo assays were conducted to confirm the role of BST2 on promoting glioma proliferation. RESULTS: The mRNA level of BST2 was higher in glioma tissues than that in nontumorous brain tissues. High protein level of BST2 was correlated with larger tumor size and advanced WHO grade. Glioma patients with a high BST2 level had worse overall survival. In addition, BST2 was defined as an independent risk factor for glioma prognosis. Cellular and xenograft studies revealed that BST2 can significantly promote glioma proliferation. CONCLUSION: Our study revealed that a high BST2 expression level was closely related to the unfavorable clinical features and poor prognosis of high-grade glioma patients. BST2 may serve as an invaluable prognostic indicator and novel therapeutic target for glioma treatment considering its membrane localization.

Expression and prognostic role of orphan receptor GPR110 in glioma.

Glioma is the most common type of malignancy in the central nervous system, which has a poor prognosis due to its rapid progression and diffuse invasion. Identification of novel biomarkers for glioma would be invaluable for studying disease mechanism and improving prognosis. Orphan G protein-coupled receptor 110 (GPR110) belongs to the subfamily VI of adhesion GPCR. The knowledge of the ligand, signaling pathway or physiology function of GPR110 is poorly elucidated. The potential role of GPR110 as an oncogene in mouse has been recently reported by mutagenesis screen. However, its expression and role in human glioma hasn't been identified. Here in the current study, we initially explored the RNA and protein expression of GPR110 in patients with glioma. Statistical analysis proved that GPR110 was highly expressed in some patients, which was correlated with advanced disease stages. Furthermore, univariate and multivariate analyses revealed its role as an independent prognostic biomarker for the overall survival of glioma patients. Interestingly, cellular studies showed that overexpression or knockdown of GPR110 in U87 cells didn't affect cell proliferation and migration. However, the invasion of U87 cells was significantly enhanced by GPR110-overepxression, while inhibited by GPR110-knockdown. The detailed mechanisms remain further investigation although our results suggested the possible participation of STAT3 instead of ERK in the GPR110 signaling pathways.

Enhanced Giant Piezoresistance Performance of Sandwiched ZnS/Si/SiO2 Radial Heterostructure Nanotubes for Nonvolatile Stress Memory with Repeatable Writing and Erasing.

It is a challenge to realize nonvolatile stress-writing memory. Herein, we propose a strategy to construct rewritable stress information storage devices, consisting of deliberately designing individual sandwiched ZnS/Si/SiO2 radial heterostructure nanotubes synthesized by one-step thermal evaporation method. A bulk trap-related Poole-Frenkel hopping mechanism is proposed. Carriers are localized in a narrow bandgap Si intermediate layer; moreover, incorporated impurities and heterointerface defects can serve as charge trap centers or storage mediators. Compressive strain can induce trap barrier height to decrease at relatively low operation bias voltage, whereas tensile strain can induce it to increase, resulting in a giant piezoresistance effect. After both loading compressive and tensile strains at low bias voltage, additionally, the emptying of trap states results in a high resistance state. However, the emptied trap states can be filled by applying a relatively high bias voltage without strains and, correspondingly, the memories return to low resistance state. The emptying and filling of trap states, respectively applied by strains and high electric field, result in a repeatable writing/erasing nonvolatile memory effect. The results indicate that the creation and modification of trap states in multiscale nanostructures can give an avenue to the development of novel nanodevices for rewritable nonvolatile stress sensor and memory.

Positive expression of KIF20A indicates poor prognosis of glioma patients.

Glioma patients have a poor overall survival; however, patients can show distinct clinical outcomes due to the high heterogeneity of the tumor, which may be indicated by certain clinicobiological parameters. Kinesin family member 20A (KIF20A), which participates in cytokinesis and intracellular transportation, has been recently reported to be upregulated in pancreatic cancer, breast cancer, and bladder cancer. In the current study, we investigated the expression of KIF20A in gliomas and its significance in predicting the prognosis after surgery. We found that KIF20A positive expression in glioma tissues correlated significantly with Ki67 protein expression and advanced World Health Organization grade. Univariate and multivariate analysis revealed that KIF20A can act as an independent prognostic factor for predicting the overall survival of glioma patients. Moreover, we demonstrated that KIF20A can positively regulate the expression of Ki67 in glioma cell lines. Correspondingly, overexpression of KIF20A can promote cell proliferation and invasion, whereas knockdown of KIF20A can inhibit cell viability and invasion capacity. In vitro study also showed that under the treatment of plumbagin, an anticancer drug, KIF20A expression decreased in a dose-dependent manner. In addition, the overexpression of KIF20A can also increase the drug resistance toward plumbagin, which provided the possibility that KIF20A may contribute to the chemotherapy resistance of gliomas.