CDCA5-EEF1A1 interaction promotes progression of clear cell renal cell carcinoma by regulating mTOR signaling.

BACKGROUND: Cell division cycle associated 5 (CDCA5) plays ontogenetic role in various human cancers. However, its specific function and regulatory mechanism in ccRCC remain uncertain. METHODS: Immunohistochemistry and western blots were performed to investigate the expression of CDCA5 in ccRCC tissues. Genetic knockdown and upregulation of CDCA5 were performed to investigate its functional roles in ccRCC proliferation, migration, apoptosis and sunitinib resistance. Furthermore, Co-IP assay and LC-MS/MS were performed to investigate the underlying mechanisms. RESULTS: We found that CDCA5 expression is frequently upregulated in ccRCC tumors and is associated with poor prognosis of ccRCC patients. Functionally, CDCA5 promotes proliferation, migration, and sunitinib resistance, while inhibiting apoptosis in ccRCC cells. In vivo mouse xenograft model confirms that silencing of CDCA5 drastically inhibits the growth of ccRCC. Mechanistically, we discovered that CDCA5 interacts with Eukaryotic Translation Elongation Factor 1 Alpha 1 (EEF1A1) to regulate mTOR signaling pathway, thereby promoting ccRCC progression. CONCLUSIONS: Taken together, our results demonstrate the significant role of CDCA5 in ccRCC progression. The findings may provide insights for the development of new treatment strategies targeting CDCA5 for ccRCC patients.

A bibliometric study on trends in chiropractic research from 1920 to 2023.

OBJECTIVE: An increasing body of evidence suggests a positive role of chiropractic in the treatment of neuro-musculoskeletal disorders. This study aims to explore current research hotspots and trends, providing insights into the broad prospects of this field. METHODS: A bibliometric review was conducted on all chiropractic articles included in the Web of Science Core Collection before December 31, 2023. RESULTS: Over the past century, the volume of research in the field of chiropractic has been fluctuating annually, with four peaks observed in total. The United States, Canada, Australia, and the United Kingdom are leading countries. Chu, Eric Chun-Pu is the author with the most publications, while Bronfort, Gert has the highest total citation count. The University of Southern Denmark has produced the most publications, while Queens University - Canada is the most central institution. The Journal of Manipulative and Physiological Therapeutics is the journal with the most publications and citations, while the Journal of the American Medical Association is the most central journal. The two most-cited articles were both authored by Eisenberg DM. Emerging keywords include "chronic pain" and "skills". The theoretical mechanisms and scientific basis of chiropractic, its clinical practice and safety, education and training, integration with other disciplines, and patient experiences and satisfaction are the frontiers and hotspots of research. CONCLUSION: This study integrates bibliometric analysis to summarize the current state of research and global network centers in the field of chiropractic, further highlighting the hotspots and trends in this field. However, Individual and national rankings should be interpreted with caution due to our focus on Web of Science rather than PubMed.

Classifying breast cancer subtypes on multi-omics data via sparse canonical correlation analysis and deep learning.

BACKGROUND: Classifying breast cancer subtypes is crucial for clinical diagnosis and treatment. However, the early symptoms of breast cancer may not be apparent. Rapid advances in high-throughput sequencing technology have led to generating large number of multi-omics biological data. Leveraging and integrating the available multi-omics data can effectively enhance the accuracy of identifying breast cancer subtypes. However, few efforts focus on identifying the associations of different omics data to predict the breast cancer subtypes. RESULTS: In this paper, we propose a differential sparse canonical correlation analysis network (DSCCN) for classifying the breast cancer subtypes. DSCCN performs differential analysis on multi-omics expression data to identify differentially expressed (DE) genes and adopts sparse canonical correlation analysis (SCCA) to mine highly correlated features between multi-omics DE-genes. Meanwhile, DSCCN uses multi-task deep learning neural network separately to train the correlated DE-genes to predict breast cancer subtypes, which spontaneously tackle the data heterogeneity problem in integrating multi-omics data. CONCLUSIONS: The experimental results show that by mining the associations among multi-omics data, DSCCN is more capable of accurately classifying breast cancer subtypes than the existing methods.

Pathogenesis or a response to lithium? A novel perspective for mitochondrial mass fluctuation of naïve T cells in patients with bipolar disorder.

BACKGROUND: Immune imbalances are associated with the pathogenesis and pharmacological efficacy of bipolar disorder (BD). The underlying mechanisms remain largely obscure but may involve immunometabolic dysfunctions of T-lymphocytes. METHODS: We investigated if inflammatory cytokines and the immunometabolic function of T-lymphocytes, including frequencies of subsets, mitochondrial mass (MM), and low mitochondrial membrane potential (MMPLow) differed between BD patients (n = 47) and healthy controls (HC, n = 43). During lithium treatment of hospitalized patients (n = 33), the association between weekly T-lymphocyte immune metabolism and clinical symptoms was analyzed, and preliminary explorations on possible mechanisms were conducted. RESULTS: In comparison to HC, BD patients predominantly showed a trend toward CD4+ naïve T (Tn) activation and exhibited mitochondrial metabolic disturbances such as decreased MM and increased MMPLow. Lower CD4+ Tn-MM correlated with elevated IL-6, IL-8, and decreased IL-17 A in BD patients. With lithium treatment effective, MM of CD4+ T/Tn was negatively correlated with depression score HAMD. When lithium intolerance was present, MM of CD4+ T/Tn was positively correlated with depression score HAMD and mania score BRMS. Lithium does not mediate through the inositol depletion hypothesis, but the mRNA level of IMPA2 in peripheral blood is associated with mitochondrial function in CD8+ T cells. LIMITATIONS: The cross-sectional design and short-term follow-up meant that we could not directly examine the causality of BD and immune dysregulation. CONCLUSION: The altered metabolism of CD4+ Tn was strongly associated with remodeling of the inflammatory landscape in BD patients and can also be used to reflect the short-term therapeutic effects of lithium.

Fumarate induces LncRNA-MIR4435-2HG to regulate glutamine metabolism remodeling and promote the development of FH-deficient renal cell carcinoma.

Fumarate hydratase (FH) deficient renal cell carcinoma (RCC) is a type of tumor with definite metabolic disorder, but the mechanism of metabolic remodeling is still unclear. LncRNA was reported to closely correlate with cancer metabolism, however the biological role of LncRNA in the development of progression of FH-deficent RCC was not well studied either. FH-deficient RCC samples were collected in my hospital and used for RNA-sequencing and Mass spectrometry analysis. FH-deficient RCC cell line UOK262 and control pFH cells were used for in vitro experiments, including proliferation assay, transwell assay, western-blot, mass spectrometry and so on. PDX mouse model was used for further drug inhibition experiments in vivo. In this study, we analyzed the profiles of LncRNA and mRNA in FH-deficienct RCC samples, and we found that the LncRNA-MIR4435-2GH was specifically highly expressed in FH-deficient RCC compared with ccRCC. In vitro experiments demonstrated that MIR4435-2HG was regulated by Fumarate through histone demethylation, and the deletion of this gene could inhibit glutamine metabolism. RNA-pulldown experiments showed that MIR4435-2HG specifically binds to STAT1, which can transcriptionally activate GLS1. GLS1 inhibitor CB-839 could significantly suppress tumor growth in PDX tumor models. This study analyzed the molecular mechanism of MIR4435-2HG in regulating metabolic remodeling of FH-deficient RCC in clinical samples, cells and animal models by combining transcriptional and metabolic methods. We found that that GLS1 was a therapeutic target for this tumor, and MIR4435-2HG can be used as a drug sensitivity marker.

Warm Acupuncture Reduces Pain and Inflammation in Rats with Lumbar Disc Herniation Induced by Autologous Nucleus Pulposus Transplantation via Regulating p38MAPK/NF-κB Pathway.

Background: : Warm acupuncture (WA) has analgesic and anti-inflammatory effects. However, the underlying mechanism of these effects remain unclear. Objectives: : To explore the analgesic and anti-inflammatory effects of WA and the potential underlying mechanism in male Sprague-Dawley rats with non-compressive lumbar disk herniation (LDH) caused by autologous nucleus pulposus (NP) transplantation. Methods: : We used low-frequency (2 Hz) electrical stimulation and WA (40℃) to treat GB30 and BL54 acupoints in rats for 30 mins per day. We monitored the paw withdrawal threshold of rats during the experiment and measured serum cytokine levels using commercial kits. Dorsal root ganglion (DRG) tissue pathology was analyzed via H&E staining. We used qRT-PCR to measure the mRNA expression levels of IL-1ß, IL-6, and TNF-α genes in DRG. Western blot was used to analyze the expression levels of IL-1ß, IL-6, TNFα, P-p38MAPK, p38MAPK, P-IκBα, IκB α, and NF-κB p65 proteins. Results: : WA treatment significantly increased the pain threshold of rats, reduced serum IL-6, PEG2, NO, SP, NP-Y, and MMP-3 levels, and effected histopathological improvements in the DRG in rats. Moreover, WA treatment significantly downregulated the expression levels of inflammation-associated genes (Il-1ß, Il-6, and Tnf-α) and proteins (IL-1ß, IL-6, TNF-α, P-p38MAPK, P-IκBα, and NF-κB p65) in the DRG of non-compressive LDH rats. Conclusion: : WA can alleviate pain and inhibit inflammatory response in rats with non-compressive LDH caused by autologous NP transplantation, and these effects are likely associated with the inhibition of the p38MAPK/NF-κB pathway.

Fabrication of well-aligned Co-MOF arrays through a controlled and moderate process for the development of a flexible tetrabromobisphenol A sensor.

Tetrabromobisphenol A (TBBPA) has attracted a great deal of attention due to its side effects and potential bioaccumulation properties. It is of great importance to construct and develop novel electrochemical sensors for the sensitive and selective detection of TBBPA. In the present study, cobalt (Co) based metal-organic frameworks (MOFs) were synthesized on carbon cloth (CC) by using cobalt nitrate hexahydrate and 2-methylimidazole. The morphological characterization was carried out by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). The results showed that Co-MOFs/CC have a leaf-like structure and abundant surface functional groups. The electrochemical properties of the sensor were investigated by differential pulse voltammetry (DPV). The effects of different ratios of metal ions to organic ligands, reaction temperature, time, concentration, pH value of the electrolyte, and incubation time on the oxidation peak current of TBBPA were studied. Under the optimal conditions, the linear range of the designed sensor was 0.1 µM-100 µM, and the limit of detection was 40 nM. The proposed sensor is simple, of low cost and efficient, which can greatly facilitate the detection tasks of environmental monitoring workers.

Exploring gene-patient association to identify personalized cancer driver genes by linear neighborhood propagation.

BACKGROUND: Driver genes play a vital role in the development of cancer. Identifying driver genes is critical for diagnosing and understanding cancer. However, challenges remain in identifying personalized driver genes due to tumor heterogeneity of cancer. Although many computational methods have been developed to solve this problem, few efforts have been undertaken to explore gene-patient associations to identify personalized driver genes. RESULTS: Here we propose a method called LPDriver to identify personalized cancer driver genes by employing linear neighborhood propagation model on individual genetic data. LPDriver builds personalized gene network based on the genetic data of individual patients, extracts the gene-patient associations from the bipartite graph of the personalized gene network and utilizes a linear neighborhood propagation model to mine gene-patient associations to detect personalized driver genes. The experimental results demonstrate that as compared to the existing methods, our method shows competitive performance and can predict cancer driver genes in a more accurate way. Furthermore, these results also show that besides revealing novel driver genes that have been reported to be related with cancer, LPDriver is also able to identify personalized cancer driver genes for individual patients by their network characteristics even if the mutation data of genes are hidden. CONCLUSIONS: LPDriver can provide an effective approach to predict personalized cancer driver genes, which could promote the diagnosis and treatment of cancer. The source code and data are freely available at https://github.com/hyr0771/LPDriver .

Retroperitoneoscopic Clampless, Sutureless Hybrid Therapy in the Management of Renal Hilar Tumors.

OBJECTIVE: We aimed to investigate the outcomes and feasibility of a retroperitoneoscopic clampless, sutureless hybrid technique in the management of renal hilar tumors. METHODS: A retrospective cohort of consecutive patients with renal hilar tumors who received retroperitoneoscopic clampless, sutureless hybrid therapy between January 2017 and April 2021 was included. The hybrid surgical technique involved microwave ablation (MWA), followed by clampless tumor enucleation and sutureless hemostasis. Surgical, pathological, and oncological outcomes were recorded and analyzed. RESULTS: Sixty patients were included in this study. The median tumor size was 3.5 cm (2-5), the median RENAL score was 7 (range 6-10), the median operative time was 110 min (70-130), and the median estimated blood loss was 80 mL (30-130). The median length of postoperative hospital stay was 3 days (2-4), and no warm ischemia time was observed, except in one patient who required conversion to conventional on-clamp laparoscopic partial nephrectomy (LPN) with a 10 min warm ischemia time. Three minor complications (Clavien-Dindo grade I) and one major complication (Clavien-Dindo grade III) were recorded postoperatively. Thus far, no blood transfusions have been required. Renal dysfunction or tumor recurrence did not occur within a median follow-up of 45 months. CONCLUSION: The retroperitoneoscopic hybrid technique involving MWA, clampless tumor enucleation, and sutureless hemostasis is a feasible and safe option for the management of selective renal hilar tumors. Complete tumor removal with maximal renal function preservation can be achieved, with a low complication rate.

Mitochondrial mass of circulating NK cells as a novel biomarker in severe SARS-CoV-2 infection.

BACKGROUND: Severe SARS-CoV-2 infection results in lymphopenia and impaired function of T, B, and NK (TBNK-dominant) lymphocytes. Mitochondria are essential targets of SARS-CoV-2 and the efficacy of lymphocyte mitochondrial function for immunosurveillance in COVID-19 patients has not been evaluated. METHODS: Multi-parametric flow cytometry was used to characterize mitochondrial function, including mitochondrial mass (MM) and low mitochondrial membrane potential (MMPlow), in TBNK-dominant lymphocytes from severe (n = 93) and moderate (n = 77) hospitalized COVID-19 patients. We compared the role of novel lymphocyte mitochondrial indicators and routine infection biomarkers as early predictors of severity and death in COVID-19 patients. We then developed a mortality decision tree prediction model based on immunosurveillance indicators through machine learning. RESULTS: At admission, the MM of circulating NK cells (NK-MM) was the best discriminator of severe/moderate disease (AUC = 0.8067) compared with the routine infection biomarkers. The NK cell count and NK-MM displayed superior diagnostic effects to distinguish patients with non-fatal or fatal outcomes. Interestingly, NK-MM was significantly polarized in non-survivors, with some patients showing a decrease and others showing an abnormal increase. Kaplan-Meier analysis showed that NK-MM had the optimal predictive efficacy (hazard ratio = 11.66). The decision tree model has the highest proportion of importance for NK-MM, which is superior to the single diagnostic effect of the above indicators (AUC = 0.8900). CONCLUSION: NK-MM was not only associated with disease severity, its abnormal increases or decreases also predicted mortality risk. The resulting decision tree prediction model is the first to focus on immune monitoring indicators to provide decision-making clues for COVID-19 clinical management.

SPAG5, the upstream protein of Wnt and the target of curcumin, inhibits hepatocellular carcinoma.

The inhibitory role of curcumin on sperm-associated antigen 5 (SPAG5) and its effects on the cancer­related Wnt classical signaling pathway has been previously demonstrated. Nevertheless, research on the modulatory role of curcumin on the Wnt signaling pathway by acting on SPAG5 has yet to be reported. The activation of the Wnt/ß­catenin pathway is frequently observed in patients suffering from hepatocellular carcinoma (HCC), suggesting that small molecular drugs that target Wnt could present a promising therapeutic strategy. However, these drugs often result in substantial side effects. In the present study, the presence of SPAG5 in the cancer tissues of patients with HCC and cell lines was validated using immunohistochemistry, cellular immunofluorescence, reverse transcription­quantitative polymerase chain reaction, and western blot analyses. Subsequently, the effect of SPAG5 and the regulatory role of curcumin on SPAG5 and the Wnt/ß­catenin pathway were examined using cell function tests, flow cytometry, and western blotting. Techniques of gene knockout and overexpression were employed. The findings revealed a significant overexpression of SPAG5 in the cancer tissues of patients with HCC. Both the mRNA and protein levels of SPAG5 in Huh7 and HCCLM3 cell lines were markedly elevated. Treatment with curcumin led to a decrease in SPAG5 expression, while also inhibiting cell migration and promoting apoptosis. Additionally, suppression of SPAG5 expression resulted in the decreased expression of ß­catenin. Furthermore, curcumin was observed to reduce the expression of cyclin D1 in SPAG5­overexpressing cell lines. However, the degree of inhibition was diminished once SPAG5 expression was silenced. These initial findings indicate that SPAG5 may function as an upstream regulatory protein of the Wnt/ß­catenin pathway, hence offering a potential alternative target for HCC. Moreover, as curcumin has the capacity to inhibit Wnt via suppressing SPAG5, it could potentially serve as a natural drug component for early intervention and treatment of HCC.

Comparative analysis of salvage partial nephrectomy versus radical nephrectomy after the failure of initial partial nephrectomy.

OBJECTIVES: To compare the oncologic outcomes and renal function discrepancy of salvage partial nephrectomy (sPN) and salvage radical nephrectomy (sRN) after an initial failed PN. MATERIALS AND METHODS: Retrospective data from multiple centers between 2008 and 2022 were analyzed in this study. Patients who received sPN or sRN after an initial failed PN were identified. Comparative analysis and propensity score matching (PSM) was performed and the RENAL score, tumor size, and pathological T stage at salvage surgery were used to match the 2 groups. Local recurrence-free survival (LRFS) and recurrence-free survival (RFS) were assessed using the Cox proportional hazards model and log-rank tests. Renal function after salvage surgery was assessed using the Wilcoxon rank sum test. RESULTS: A total of 140 patients who underwent salvage surgery were evaluated, of whom 60 were considered for PSM analysis after matching. At a median follow-up of 27.0 months, LRFS and RFS showed no significant difference between sPN and sRN, either before (LRFS, HR = 0.673 [95% CI: 0.171-2.644], P = 0.610; RFS, HR = 0.744 [95% CI: 0.271-1.344], P = 0.595) or after matching (LRFS, HR = 1.080 [95% CI: 0.067-17.30], P = 0.957; RFS, HR = 1.199 [95% CI: 0.241-5.983], P = 0.822). During long-term follow-up, sPN preserved renal function (after matching, eGFR, 71.4 vs. 54.0, P < 0.001) and prevented eGFR loss (after matching: 6.6% vs. 25.6%, P < 0.001). CONCLUSION: Salvage partial nephrectomy offers a better alternative than sRN for recurrence after initial PN, as sPN preserves renal function better while maintaining parallel tumor control and acceptable complication rates.

Qishen granules regulate intestinal microecology to improve cardiac function in rats with heart failure.

Introduction: Qishen Granule (QSG), a clinically approved traditional Chinese medicine, has been researched for treating heart failure (HF) for many years. However, the effect of QSG on intestinal microecology remains unconfirmed. Therefore, this study aimed to elucidate the possible mechanism of QSG regulating HF in rats based on intestinal microecological changes. Methods: A rat model with HF induced by myocardial infarction was prepared by left coronary artery ligation. Cardiac functions were assessed by echocardiography, pathological changes in the heart and ileum by hematoxylin-eosin (HE) and Masson staining, mitochondrial ultrastructure by transmission electron microscope, and gut microbiota by 16S rRNA sequencing. Results: QSG administration improved cardiac function, tightened cardiomyocytes alignment, decreased fibrous tissue and collagen deposition, and reduced inflammatory cell infiltration. Electron microscopic observation of mitochondria revealed that QSG could arrange mitochondria neatly, reduce swelling, and improve the structural integrity of the crest. Firmicutes were the dominant component in the model group, and QSG could significantly increase the abundance of Bacteroidetes and Prevotellaceae_NK3B31_group. Furthermore, QSG significantly reduced plasma lipopolysaccharide (LPS), improved intestinal structure, and recovered barrier protection function in rats with HF. Conclusion: These results demonstrated that QSG was able to improve cardiac function by regulating intestinal microecology in rats with HF, suggesting promising therapeutic targets for HF.

Minimizing enzyme mass to decompose flux distribution for identifying biologically relevant elementary flux modes.

The flux distribution in metabolic network can be decomposed as non-negative linear combinations of elementary flux modes (EFMs). Identifying biologically relevant EFM combination by decomposing flux distribution in metabolic network is a useful method to study metabolisms in systems biology. However, the occurrence of biologically irrelevant EFMs hinders the application of such methods. In this paper, we introduce a novel method for identifying EFM combination by minimizing enzyme mass. Our proposed method, called EMMD (Enzyme Mass Minimization Decomposition), takes into consideration both thermodynamic and enzymatic constraints in stoichiometry metabolic models. By implementing EMMD, we can decompose the flux distributions in metabolic network to detect biologically relevant EFM combinations. We demonstrate the effectiveness of our method by applying it to the core Escherichia coli metabolic network and show that the optimal EFM combinations identified by EMMD are unique. Moreover, the optimal EFM combination identified by EMMD not only aligns more closely with experimental values in terms of estimated growth rate, but it also demonstrates more favorable thermodynamics. Finally, we investigated the growth of the core Escherichia coli metabolic network in Luria-Bertani medium containing different carbon sources, revealing the impact of various carbon sources on the growth rate of flux distribution. EMMD thus could be a promising complement to the existing flux decomposition tools.

Predicting Disease-Associated N7-Methylguanosine (m7G) Sites via Random Walk on Heterogeneous Network.

Recent studies revealed that the modification of N7-methylguanosine (m7G) has associations with many human diseases. Effectively identifying disease-associated m7G methylation sites would provide crucial clues for disease diagnosis and treatment. Previous studies have developed computational methods to predict disease-associated m7G sites based on similarities among m7G sites and diseases. However, few have focused on the influence of the known m7G-disease association information on calculating similarity measures of m7G site and disease, which potentially promotes the identification of the disease-associated m7G sites. In this work, we propose а computational method called m7GDP-RW to predict m7G-disease associations by random walk algorithm. m7GDP-RW first incorporates the feature information of m7G site and disease with the known m7G-disease associations to compute m7G site similarity and disease similarity. Then m7GDP-RW combines the known m7G-disease associations with the computed similarity of m7G site and disease to construct a m7G-disease heterogeneous network. Finally, m7GDP-RW utilizes a two-pass random walk with restart algorithm to find novel m7G-disease associations on the heterogeneous network. The experimental results show that our method achieves higher prediction accuracy compared to the existing methods. The study case also demonstrates the effectiveness of m7GDP-RW in discovering potential m7G-disease associations.

T cells: an emerging cast of roles in bipolar disorder.

Bipolar disorder (BD) is a distinctly heterogeneous and multifactorial disorder with a high individual and social burden. Immune pathway dysregulation is an important pathophysiological feature of BD. Recent studies have suggested a potential role for T lymphocytes in the pathogenesis of BD. Therefore, greater insight into T lymphocytes' functioning in patients with BD is essential. In this narrative review, we describe the presence of an imbalance in the ratio and altered function of T lymphocyte subsets in BD patients, mainly in T helper (Th) 1, Th2, Th17 cells and regulatory T cells, and alterations in hormones, intracellular signaling, and microbiomes may be potential causes. Abnormal T cell presence explains the elevated rates of comorbid inflammatory illnesses in the BD population. We also update the findings on T cell-targeting drugs as potentially immunomodulatory therapeutic agents for BD disease in addition to classical mood stabilizers (lithium, valproic acid). In conclusion, an imbalance in T lymphocyte subpopulation ratios and altered function may be involved in the development of BD, and maintaining T cell immune homeostasis may provide an overall therapeutic benefit.

NetPro: Neighborhood Interaction-Based Drug Repositioning via Label Propagation.

Drug repositioning is an important approach for predicting new disease indications of the existing drugs in drug discovery. A great progress has been achieved in drug repositioning. However, effectively utilizing the localized neighborhood interaction features of drug and disease in drug-disease associations remains challenging. This paper proposes a neighborhood interaction-based method called NetPro for drug repositioning via label propagation. In NetPro, we first formulate the known drug-disease associations, various disease and drug similarities from different perspectives to construct drug-drug and disease-disease networks. Meanwhile we employ the nearest neighbors and their interactions in the constructed networks to devise a new approach for computing drug similarity and disease similarity. To implement the prediction of new drugs or diseases, a preprocessing step is applied to renew the known drug-disease associations using our calculated drug and disease similarities. We then employ a label propagation model to predict drug-disease associations by the drug and disease linear neighborhood similarities derived from the renewed drug-disease associations. The experimental results on three benchmark datasets show that NetPro can effectively identify potential drug-disease associations and achieve better prediction performance than the existing methods. Case studies further demonstrate that NetPro is capable of predicting promising candidate disease indications for drugs.

Effect of the pectin contents and nanostructure on the stem straightness of two Paeonia lactiflora cultivars.

Herbaceous peony (Paeonia lactiflora Pall.) is an ancient ornamental crop and, in recent decades, an emerging popular cut flower. Straight stems are a vital criterion for cut herbaceous peony selection, while many cultivars bend as the plant develops. Pectin helps maintain the mechanical strength of the cell wall. However, little is known about its role in the stem bending of herbaceous peony. Two herbaceous peony cultivars with contrasting stem morphologies ('Dong Fang Shao Nv', upright; 'Lan Tian Piao Xiang', bending gradually) at five developmental stages were used as materials to investigate the effects of pectin content and nanostructure on straightness using the carbazole colorimetric method and atomic force microscopy observations. The contents of water-soluble pectin (WSP), CDTA-soluble pectin (CSP), and sodium carbonate-soluble pectin (SSP) differed significantly between the two cultivars, and the contents and angle of the flower and branch showed correlations. For the pectin nanostructure, WSP showed agglomerates and long chains, with a higher proportion of broad agglomerates at the later stages of the bending cultivar than the upright cultivar. CSP showed branched chains, and the proportion of broad chains was higher in the upright cultivar at later stages, while CSP shape changed from agglomerates to chains in the bending cultivar. SSP mainly consisted of short linear main chains, and side chains in the upright stem were stacked, and the bent cultivar had more broad and short chains. It can be concluded that the contents, nanometric shape, and size of the three kinds of pectin are highly likely to affect herbaceous peony stem straightness. This study provides a theoretical basis for the role of pectin in the production and breeding of herbaceous peony cut flowers.

Xylem development and phloem conductivity in relation to the stem mechanical strength of Paeonia lactiflora.

The quality of cut Paeonia lactiflora flowers is limited by their low stem mechanical strength, but the underlying mechanism of this low strength is poorly understood. In this study, two P. lactiflora cultivars with distinct stem mechanical strengths (Chui Touhong with low stem mechanical strength and Da Fugui with high stem mechanical strength) were used as test materials. The xylem development was examined at the cellular level, and the phloem conductivity was analyzed by evaluating phloem geometry. The results showed that the secondary cell wall formation of the xylem of Chui Touhong was affected primarily in fiber cells but was affected little in vessel cells. The formation of the secondary cell walls in the xylem fiber cells of Chui Touhong was delayed, resulting in longer and thinner fiber cells with a lack of cellulose and S-lignin in the secondary cell walls. Moreover, the phloem conductivity of Chui Touhong was lower than that of Da Fugui, and more callose was accumulated in the lateral walls of the phloem sieve elements of Chui Touhong. Consequently, the delayed deposition of the secondary cell walls of the xylem fiber cells was the main factor leading to the low stem mechanical strength of Chui Touhong, and the low stem mechanical strength was closely related to the low conductivity of sieve tubes and extensive callose accumulation in the phloem. These findings provide a new perspective on enhancing P. lactiflora stem mechanical strength by targeting single cell level, and lay the foundation for future works on the correlation between phloem long-distance transport and stem mechanical strength.

Altered brain activities in mesocorticolimbic pathway in primary dysmenorrhea patients of long-term menstrual pain.

Background: Patients with primary dysmenorrhea (PDM) often present with abnormalities other than dysmenorrhea including co-occurrence with other chronic pain conditions and central sensitization. Changes in brain activity in PDM have been demonstrated; however, the results are not consistent. Herein, this study probed into altered intraregional and interregional brain activity in patients with PDM and expounded more findings. Methods: A total of 33 patients with PDM and 36 healthy controls (HCs) were recruited and underwent a resting-state functional magnetic resonance imaging scan. Regional homogeneity (ReHo) and mean amplitude of low-frequency fluctuation (mALFF) analysis were applied to compare the difference in intraregional brain activity between the two groups, and the regions with ReHo and mALFF group differences were used as seeds for functional connectivity (FC) analysis to explore the difference of interregional activity. Pearson's correlation analysis was conducted between rs-fMRI data and clinical symptoms in patients with PDM. Results: Compared with HCs, patients with PDM showed altered intraregional activity in a series of brain regions, including the hippocampus, the temporal pole superior temporal gyrus, the nucleus accumbens, the pregenual anterior cingulate cortex, the cerebellum_8, the middle temporal gyrus, the inferior temporal gyrus, the rolandic operculum, the postcentral gyrus and the middle frontal gyrus (MFG), and altered interregional FC mainly between regions of the mesocorticolimbic pathway and regions associated with sensation and movement. The anxiety symptoms are correlated with the intraregional activity of the right temporal pole superior temporal gyrus and FC between MFG and superior frontal gyrus. Conclusion: Our study showed a more comprehensive method to explore changes in brain activity in PDM. We found that the mesocorticolimbic pathway might play a key role in the chronic transformation of pain in PDM. We, therefore, speculate that the modulation of the mesocorticolimbic pathway may be a potential novel therapeutic mechanism for PDM.