First Report of Powdery Mildew caused by Erysiphe astragali on Sphaerophysa salsula.

Sphaerophysa salsula (Pall.) DC., also known as Yang Liao Pao, belongs to the Leguminosae family and is the only existing species in the Sphaerophysa genus. S. salsula is tolerance to cold, high salt, and alkaline soil, it is widely cultivated in China as a forage crop, and used as a Chinese folk medicine to treat hypertension (Ma et al., 2002). In 2023, signs and symptoms similar to powdery mildew were found on S. salsula planted in Tumd left (40.515°N, 110.424°E), Baotou City, Inner Mongolia Autonomous Region, China. The white powdery substance covered 90% of the leaf area, and the infected plants showed weak growth and senescence. More than 80% of plants (n=200) had these powdery mildew-like symptoms. Hyphal appressoria are solitary, conidiophores have few branches and septa. Conidia are cylindrical to clavate, 25-32 µm long and 8-15 µm wide (n=30), conidia form single subapical germ tubes, straight to curved-sinuous, with swollen apex or distinctly lobed conidial appressorium. Based on these morphological characteristics, the fungus was tentatively identified as an Erysiphe sp. (Schmidt and Braun 2020). Fungal structures were isolated from diseased leaves, and genomic DNA of the pathogen was extracted using the method described by Zhu et al. (2022). The internal transcribed spacer (ITS) region was amplified by PCR using the primers PMITS1/PMITS2 (Cunnington et al. 2003) and the amplicon sequenced by Invitrogen (Shanghai, China). The powdery mildew strain, named as KMD (GenBank accession no.: PP267067), showed an identity of 100% (645/645bp) with Erysiphe astragali, a powdery mildew reported on Astragalus glycyphyllos in Golestan, Iran (GenBank: OP806834) and identity of 99.6% (643/645bp) with Erysiphe astragali (GenBank: MW142495), a powdery mildew reported on A. scaberrimus in Inner Mongolia, China (Sun et al. 2023). Pathogenicity tests were conducted by brushing the conidia from infected S. salsula leaves onto leaves of four healthy plants, while four control plants were brushed in the same manner. All the treated plants were placed in separate growth chambers maintained at 19°C and 65% humidity, with a 16 h light/8 h dark photoperiod. Nine days after inoculation, the treated plants showed powdery mildew symptoms, while the control plants remained asymptomatic. The same results were obtained for two repeated pathogenicity experiments. The powdery mildew fungus was reisolated and identified as E. astragali based on morphological and molecular analysis, thereby fulfilling Koch's postulates. No report on the occurrence of powdery mildew on S. salsula plants has been found previously. The occurrence of this destructive powdery mildew may adversely affect the cultivation of S. salsula. Identifying the pathogen of powdery mildew will support future efforts to control and manage powdery mildew on S. salsula.

Qingfei Tongluo Mixture Attenuates Bleomycin-Induced Pulmonary Inflammation and Fibrosis through mTOR-Dependent Autophagy in Rats.

As an interstitial fibrosis disease characterized by diffuse alveolitis and structural alveolar disorders, idiopathic pulmonary fibrosis (IPF) has high lethality but lacks limited therapeutic drugs. A hospital preparation used for the treatment of viral pneumonia, Qingfei Tongluo mixture (QFTL), is rumored to have protective effects against inflammatory and respiratory disease. This study aims to confirm whether it has a therapeutic effect on bleomycin-induced IPF in rats and to elucidate its mechanism of action. Male SD rats were randomly divided into the following groups: control, model, CQ + QFTL (84 mg/kg chloroquine (CQ) + 3.64 g/kg QFTL), QFTL-L, M, H (3.64, 7.28, and 14.56 g/kg, respectively) and pirfenidone (PFD 420 mg/kg). After induction modeling and drug intervention, blood samples and lung tissue were collected for further detection. Body weight and lung coefficient were examined, combined with hematoxylin and eosin (H&E) and Masson staining to observe lung tissue lesions. The enzyme-linked immunosorbent assay (ELISA) and the hydroxyproline (HYP) assay kit were used to detect changes in proinflammatory factors (transforming growth factor-ß (TGF-ß), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß)) and HYP. Immunohistochemistry and Western blotting were performed to observe changes in proteins related to pulmonary fibrosis (α-smooth muscle actin (α-SMA) and matrix metalloproteinase 12 (MMP12)) and autophagy (P62 and mechanistic target of rapamycin (mTOR)). Treatment with QFTL significantly improved the adverse effects of bleomycin on body weight, lung coefficient, and pathological changes. Then, QFTL reduced bleomycin-induced increases in proinflammatory mediators and HYP. The expression changes of pulmonary fibrosis and autophagy marker proteins are attenuated by QFTL. Furthermore, the autophagy inhibitor CQ significantly reversed the downward trend in HYP levels and α-SMA protein expression, which QFTL improved in BLM-induced pulmonary fibrosis rats. In conclusion, QFTL could effectively attenuate bleomycin-induced inflammation and pulmonary fibrosis through mTOR-dependent autophagy in rats. Therefore, QFTL has the potential to be an alternative treatment for IPF in clinical practice.

Exploring the bidirectional relationship between pain and mental disorders: a comprehensive Mendelian randomization study.

BACKGROUND: The close relationship between pain and mental health problems is well-known, and psychological intervention can provide an effective alternative to medication-based pain relief. However, previous studies on the connection between pain and psychological problems, the findings thus far have been inconclusive, limiting the potential for translating psychological interventions into clinical practice. To complement the gap, this study utilized genetic data and Mendelian randomization (MR) to examine the potential relationship between pain in different parts and common mental disorders. METHODS: Based on the instrumental variables selected from the Genome-wide association study summary statistics of localized pain and mental disorders, we conducted bidirectional two-sample MR analyses to infer bidirectional causal associations between pain and mental disorders. The inverse-variance weighted MR method and MR-Egger were used as the primary statistical method according to the horizontal pleiotropy and heterogeneity level. We reported the odds ratio to infer the causal effect between pain and mental disorders. F statistic was calculated to measure the statistical efficacy of the analyses. RESULTS: Insomnia is causally related to the genetic susceptibility of multisite pain including head (OR = 1.09, 95% CI: 1.06-1.12), neck/shoulder (OR = 1.12, 95% CI: 1.07-1.16), back (OR = 1.12, 95% CI: 1.07-1.18) and hip (OR = 1.08, 95% CI: 1.05-1.10). Reversely, headache (OR = 1.14, 95% CI: 1.05-1.24), neck/shoulder pain (OR = 1.95, 95% CI: 1.03-3.68), back pain (OR = 1.40, 95% CI: 1.22-1.60), and hip pain (OR = 2.29, 95% CI: 1.18-4.45) promote the genetic liability of insomnia. Depression is strongly associated with the predisposition of multisite pain including headache (OR = 1.28, 95% CI: 1.08-1.52), neck/shoulder pain (OR = 1.32, 95% CI: 1.16-1.50), back pain (OR = 1.35, 95% CI: 1.10-1.66) and stomach/abdominal pain (OR = 1.14, 95% CI: 1.05-1.25), while headache (OR = 1.06, 95% CI: 1.03-1.08), neck/shoulder (OR = 1.09, 95% CI: 1.01-1.17), back (OR = 1.08, 95% CI: 1.03-1.14), and stomach/abdominal pain (OR = 1.19, 95% CI: 1.11-1.26) are predisposing factors for depression. Additionally, insomnia is associated with the predisposition of facial, stomach/abdominal, and knee pain, anxiety was associated with the predisposition of neck/shoulder and back pain, while the susceptibilities of hip and facial pain are influenced by depression, but these associations were unidirectional. CONCLUSIONS: Our results enhance the understanding of the complex interplay between pain and mental health and highlight the importance of a holistic approach to pain management that addresses both physical and psychological factors.

Protective effect of L­carnitine against oxidative stress injury in human ovarian granulosa cells.

Granulosa cells (GCs) are important for supporting and nourishing oocytes during follicular development and maturation. Oxidative stress (OS) injury of GCs can lead to decreased responsiveness of follicles to follicular stimulating hormone (FSH), which will accelerate ovarian senescence and adversely affect oocyte and embryo quality. Since L-carnitine has been previously reported to exert strong antioxidant activity, the present study aimed to explore the possible effects of L-carnitine on OS injury and FSH receptor (FSHR) expression in ovarian GCs, results of which may be of significance for GCs protection. In the present study, OS was induced in vitro in KGN cells by treatment with H2O2. KGN cells were cultured and divided into the following four groups: Blank, OS, and 40 and 80 µmol/l L-carnitine pre-treatment groups. In the OS group, cells showed nuclear pyknosis, mitochondria swelled irregularly whilst featuring fractured cristae. In addition, cell viability, ROS levels, superoxide dismutase levels, glutathione levels, malondialdehyde levels, the mitochondrial membrane potential and FSHR expression, as determined by Cell Counting Kit-8 (CCK-8), 2,7-dichloro-dihydrofluorescein diacetate, spectrophotometry, ELISA, spectrophotometry, JC-1 and western blot analyses, respectively, were all significantly different in the OS group compared with those in the control group. However, malonaldehyde levels, reactive oxygen species levels and the apoptosis rate according to flow cytometry were all significantly increased compared with those in the control. Compared with those in the OS group, the morphology of cells and mitochondria in the L-carnitine pre-treatment groups were improved, whilst cell viability and the expression of FSHR were significantly increased but oxidative stress injury was decreased. The present results suggest that L-carnitine can protect the cells from OS damage induced by H2O2, enhance antioxidant activity whilst suppressing the apoptosis of GCs, in addition to preserving FSHR expression in GCs under OS. Therefore, the present study revealed that the introduction of L-carnitine in clinical medicine or dietary supplement may protect GCs, improve follicular quality and female reproductive function.

The Efficacy and Safety of Manual Therapy for Symptoms Associated with Multiple Sclerosis: A Systematic Review and Meta-Analysis.

Background: Multiple sclerosis (MS) is a chronic neurological autoimmune disease, affecting the psychological and physical health of patients. Manual therapies have been proven to relieve pain, strengthen muscles, and improve bladder and bowel problems with a high safety and low adverse event profile. Previous studies have reported the results of manual therapy in alleviating symptoms associated with MS, but the conclusions were controversial. Objective: The purpose of this meta-analysis is to comprehensively analyze and determine the efficacy and safety of manual therapy in relieving symptoms associated with MS. Methods: Eight electronic databases were searched from inception of the database to April 30, 2021. Randomized controlled trials (RCTs) using manual therapy in patients to relieve symptoms associated with MS were considered eligible for this study. Two reviewers independently extracted data using pre-established standards. Results: Finally, 10 eligible RCTs with 631 subjects were included in this meta-analysis. These data establish that massage therapy can significantly ameliorate fatigue, pain, and spasms, while reflexology was only effective in relieving pain in MS patients. No adverse events were reported in eligible RCTs. Conclusions: The present study provides strong evidence that massage therapy could alleviate fatigue, pain, and spasms in MS patients, while reflexology plays a positive role in relieving pain. Physicians could consider massage therapy or reflexology as a safe and effective complementary and alternative treatment. Larger RCTs with higher methodological quality are needed in the future, which aim to provide more meaningful evidence for further proof of efficacy.

Yijinjing Qigong intervention shows strong evidence on clinical effectiveness and electroencephalography signal features for early poststroke depression: A randomized, controlled trial.

Objective: Although Traditional Chinese Yijinjing Qigong Exercise (YJJQE) as mind-body intervention is popularly used among adults to ameliorate depressive symptoms in China, no randomized controlled trials (RCTs) are available to evaluate the effects of YJJQE in patients with poststroke depression (PSD). This study aims to explore the clinical efficacy and the neurological and psychiatric mechanism in brain network functional connectivity underlying electroencephalography (EEG). Materials and methods: A total of 60 patients, diagnosed with mild PSD, were randomly (1:1) assigned to YJJQE group (n = 30) and control group of routine segmental rehabilitation training group (n = 30) for a 60-min exercise session once a day for 3 weeks. All outcome measures were collected at baseline and 3-weeks ending intervention. The primary outcome was the 24-item Hamilton Depression Scale (HAMD-24) score, evaluation at more time points for 1 month of follow-up. The secondary outcomes were EEG data in four frequency domains (δ, θ, α, and ß), global efficiency (GE), local efficiency (LE), GE/LE curve [areas under the curve (AUC)], Phase Lag Index (PLI), (HAMD-24) Score and EEG correlation analysis. Results: All patients showed no significant differences in baseline data. After 3 weeks and 1 month of follow-up, the YJJQE group demonstrated significant decreasing changes compared to the control group on the HAMD-24 scores (p < 0.001). Furthermore, the YJJQE group also showed a significant reduction in θ wave, and an increase in both GE and LE. Compared to the control group, the YJJQE Qigong group showed significantly greater functional connectivity in the δ, θ, and ß frequency bands in the brain network of the degree of phase synchronization (p < 0.001). HAMD-24 Score and EEG correlation analysis negative correlation in the Qigong group θ wave (p < 0.001). Conclusion: Our findings demonstrated that YJJQE is estimated to effectively alleviate the depressed mood of patients with PSD by promoting the efficiency in information transmission of network functional connectivity and its integration ability in different brain regions. Therefore, the YJJQE would be useful as a non-pharmacological treatment to prevent PSD. Clinical trial registration: [http://www.chictr.org.cn/showproj.aspx?proj=55789], identifier [ChiCTR2000035588].

[Clinical efficacy of Longjintonglin Capsules on chronic prostatitis with damp-heat stasis syndrome Re-evaluation based on multicenter real-world study].

OBJECTIVE: To re-evaluate the clinical efficacy of Longjintonglin Capsules (LJTL) in the treatment of chronic prostatitis with damp-heat stasis syndrome. METHODS: This multicenter real-world study included 1 352 cases of chronic prostatitis with damp-heat and stagnation syndrome treated with LJTL (3 capsules once, tid, 30 minutes after meals, for 2 four-week courses) in addition to routine treatment. Before and after treatment, we analyzed the NIH-CPSI scores, the scores of Chinese medicine symptom quantitative classification and changes in individual symptom scores, and observed adverse reactions to medication. RESULTS: The total effectiveness rate of LJTL was 93.64%. Compared with the baseline, the NIH-CPSI scores were significantly decreased after treatment (ï¼»24.27 ± 6.04ï¼½ vs ï¼»8.17 ± 4.21ï¼½, P < 0.05), and so were the scores on the pain symptoms (ï¼»9.63 ± 3.65ï¼½ vs ï¼»3.02 ± 2.23ï¼½, P < 0.05), voiding symptoms (ï¼»5.65 ± 2.15ï¼½ vs ï¼»1.62 ± 1.36) and quality of life (ï¼»8.96 ± 2.32ï¼½ vs ï¼»3.16 ± 1.89ï¼½, P < 0.05). The effectiveness rate of LJTL was 95.9% on the Chinese medicine symptom frequent urination, 90.4% on painful urination, and 91.4% scanty dark urine, with a total effectiveness rate of 82.4% － 95.9%, all with statistically significant difference in comparison with the baseline (P < 0.05). CONCLUSION: Longjintonglin Capsules combined with routine treatment can significantly improve the clinical symptoms of chronic prostatitis with damp-heat stasis syndrome, especially effective on the symptoms of frequent urination, painful urination and scanty dark urine. Besides, it recommendable for its antidepressant and antianxiety effects, and the effect of improving the quality of life of the chronic prostatitis patients with damp-heat stasis.

Current Advances and Limitations of Deep Learning in Anticancer Drug Sensitivity Prediction.

Anticancer drug screening can accelerate drug discovery to save the lives of cancer patients, but cancer heterogeneity makes this screening challenging. The prediction of anticancer drug sensitivity is useful for anticancer drug development and the identification of biomarkers of drug sensitivity. Deep learning, as a branch of machine learning, is an important aspect of in silico research. Its outstanding computational performance means that it has been used for many biomedical purposes, such as medical image interpretation, biological sequence analysis, and drug discovery. Several studies have predicted anticancer drug sensitivity based on deep learning algorithms. The field of deep learning has made progress regarding model performance and multi-omics data integration. However, deep learning is limited by the number of studies performed and data sources available, so it is not perfect as a pre-clinical approach for use in the anticancer drug screening process. Improving the performance of deep learning models is a pressing issue for researchers. In this review, we introduce the research of anticancer drug sensitivity prediction and the use of deep learning in this research area. To provide a reference for future research, we also review some common data sources and machine learning methods. Lastly, we discuss the advantages and disadvantages of deep learning, as well as the limitations and future perspectives regarding this approach.

Alisma Shugan Decoction (ASD) Ameliorates Hepatotoxicity and Associated Liver Dysfunction by Inhibiting Oxidative Stress and p65/Nrf2/JunD Signaling Dysregulation In Vivo.

BACKGROUND Liver fibrosis, defined as the aberrant accumulation of extracellular matrix (ECM) proteins such as collagen in the liver, is a common feature of chronic liver disease, and often culminates in portal hypertension, liver cirrhosis, and hepatic failure. Though therapeutically manageable, fibrosis is not always successfully treated by conventional antifibrotic agents. While the traditional Chinese medicine (TCM) Alisma Shugan Decoction (ASD) has several health benefits, including anti-inflammation, anti-oxidation, and limitation of cardiovascular and respiratory disorders, it remains unclear if it has any hepato-protective potential. MATERIAL AND METHODS The present study examined the therapeutic effect of ASD in thioacetamide (TAA)-induced liver injury and fibrosis rat models. RESULTS We demonstrated that 50 mg/kg ASD significantly reversed TAA-induced elevation of alanine or aspartate transaminase levels, elicited no dyscrasia, and conferred a 40% (p<0.01) or 20% (p<0.05) survival advantage, compared to rats treated with TAA or TAA+ASD, respectively. Treatment with ASD reversed TAA-induced liver injury and fibrogenesis via repression of alpha-SMA protein and reduction of the collagen area and fibrosis score. Concurrently, ASD markedly suppressed the mRNA expression of fibrogenic procollagen, ICAM-1, MMP2, MMP9, and MMP13, and production of TIMP-1, ICAM-1, CXCL7, or CD62L cytokine in rat liver injury models. Interestingly, ASD-elicited reduction of liver injury and fibrogenesis was mediated by dysregulated p65/NrF-2/JunD signaling, with a resultant 3.18-fold (p<0.05) increase in GSH/GSSH ratio, and a 3.61-fold (p<0.01) or 1.51-fold (p<0.01) reduction in the 4-hydroxynonenal and malondialdehyde (MDA) levels, respectively, indicating reduced oxidative stress in the ASD-treated rats, and suggesting an hepato-protective role for ASD. CONCLUSIONS In conclusion, the present study provides supplementary evidence of the therapeutic benefit of ASD as an efficient treatment option in cases of liver injury and fibrosis. Further large-cohort validation of these findings is warranted.

Criteria Air Pollutant and Greenhouse Gases Emissions from U.S. Refineries Allocated to Refinery Products.

Using Greenhouse Gas Reporting Program data (GHGRP) and National Emissions Inventory data from 2014, we investigate U.S. refinery greenhouse gas (GHG) emissions (CO2, CH4, and N2O) and criteria air pollutant (CAP) emissions (VOC, CO, NO x, SO2, PM10, and PM2.5). The study derives (1) combustion emission factors (EFs) of refinery fuels (e.g., refinery catalyst coke and refinery combined gas), (2) U.S. refinery GHG emissions and CAP emissions per crude throughput at the national and regional levels, and (3) GHG and CAP emissions attributable to U.S. refinery products. The latter two emissions were further itemized by source: combustion emission, process emission, and facility-wide emission. We estimated U.S. refinery product GHG and CAP emissions via energy allocation at the refinery process unit level. The unit energy demand and unit flow information were adopted from the Petroleum Refinery Life Cycle Inventory Model (PRELIM version 1.1) by fitting individual U.S. refineries. This study fills an important information gap because it (1) evaluates refinery CAP emissions along with GHG emissions and (2) provides CAP and GHG emissions not only for refinery main products (gasoline, diesel, jet fuel, etc.) but also for refinery secondary products (asphalt, lubricant, wax, light olefins, etc.).

The roles of inoculants' carbon source use in the biocontrol of potato scab disease.

Despite the application of multiple strains in the biocontrol of plant diseases, multistrain inoculation is still constrained by its inconsistency in the field. Nutrients, especially carbons, play an important role in the biocontrol processes. However, little work has been done on the systematic estimation of inoculants' carbon source use on biocontrol efficacies in vivo. In the present study, 7 nonpathogenic Streptomyces strains alone and in different combinations were inoculated as biocontrol agents against the potato scab disease, under field conditions and greenhouse treatments. The influence of the inoculants' carbon source use properties on biocontrol efficacies was investigated. The results showed that increasing the number of inoculated strains did not necessarily result in greater biocontrol efficacy in vivo. However, single strains with higher growth rates or multiple strains with less carbon source competition had positive effects on the biocontrol efficacies. These findings may shed light on optimizing the consistent biocontrol of plant disease with the consideration of inoculants' carbon source use properties.

[Pulsatilla decoction treat inflammatory bowel disease by activating NLRP3].

OBJECTIVE: To investigate the molecular mechanisms underlying the treatment of inflammatory bowel disease (IBD) by Pulsatilla decoction. METHODS: 84 BALB/c mice were randomly divided into ethanol control group, model group, SASP group, Pulsatilla decoction group (further divided into low, middle and high dose group) and zVAD group (n = 12). Intragastric and celiac drug administration were used in each group respectively. The expression of NLRP3, ASC, Caspase-1, IL-18 and IL-1beta in the colons were detected by fluorescence quantitative RT-PCR, Elisa and immunohistochemistry after treatment respectively. RESULTS: Compared with the model group, SASP group, middle and high dose group could treat IBD effectively (P < 0.01), while this effect was restrained in zVAD group (P < 0.05). In the meantime, middle and high dose group could effectively raise the expression of NLRP3, ASC, Caspase-1, IL-18 and IL-1beta in the colons (P < 0.05), while this effect was also inhibited in zVAD group (P < 0.05). CONCLUSION: Pulsatilla decoction is likely to exert their therapeutic effect by activating NLRP3 inflammasome which further promote the formation of the corresponding inflammation factors such as 1L-18 and IL-1beta.