The enhanced connectivity between the frontoparietal, somatomotor network and thalamus as the most significant network changes of chronic low back pain.

The prolonged duration of chronic low back pain (cLBP) inevitably leads to changes in the cognitive, attentional, sensory and emotional processing brain regions. Currently, it remains unclear how these alterations are manifested in the interplay between brain functional and structural networks. This study aimed to predict the Oswestry Disability Index (ODI) in cLBP patients using multimodal brain magnetic resonance imaging (MRI) data and identified the most significant features within the multimodal networks to aid in distinguishing patients from healthy controls (HCs). We constructed dynamic functional connectivity (dFC) and structural connectivity (SC) networks for all participants (n = 112) and employed the Connectome-based Predictive Modeling (CPM) approach to predict ODI scores, utilizing various feature selection thresholds to identify the most significant network change features in dFC and SC outcomes. Subsequently, we utilized these significant features for optimal classifier selection and the integration of multimodal features. The results revealed enhanced connectivity among the frontoparietal network (FPN), somatomotor network (SMN) and thalamus in cLBP patients compared to HCs. The thalamus transmits pain-related sensations and emotions to the cortical areas through the dorsolateral prefrontal cortex (dlPFC) and primary somatosensory cortex (SI), leading to alterations in whole-brain network functionality and structure. Regarding the model selection for the classifier, we found that Support Vector Machine (SVM) best fit these significant network features. The combined model based on dFC and SC features significantly improved classification performance between cLBP patients and HCs (AUC=0.9772). Finally, the results from an external validation set support our hypotheses and provide insights into the potential applicability of the model in real-world scenarios. Our discovery of enhanced connectivity between the thalamus and both the dlPFC (FPN) and SI (SMN) provides a valuable supplement to prior research on cLBP.

Mesenchymal stromal cells and their small extracellular vesicles in allergic diseases: From immunomodulation to therapy.

Mesenchymal stromal cells (MSCs) have long been considered a potential tool for treatment of allergic inflammatory diseases, owing to their immunomodulatory characteristics. In recent decades, the medical utility of MSCs has been evaluated both in vitro and in vivo, providing a foundation for therapeutic applications. However, the existing limitations of MSC therapy indicate the necessity for novel therapies. Notably, small extracellular vesicles (sEV) derived from MSCs have emerged rapidly as candidates instead of their parental cells. The acquisition of abundant and scalable MSC-sEV is an obstacle for clinical applications. The potential application of MSC-sEV in allergic diseases has attracted increasing attention from researchers. By carrying biological microRNAs or active proteins, MSC-sEV can modulate the function of various innate and adaptive immune cells. In this review, we summarise the recent advances in the immunomodulatory properties of MSCs in allergic diseases, the cellular sources of MSC-sEV, and the methods for obtaining high-quality human MSC-sEV. In addition, we discuss the immunoregulatory capacity of MSCs and MSC-sEV for the treatment of asthma, atopic dermatitis, and allergic rhinitis, with a special emphasis on their immunoregulatory effects and the underlying mechanisms of immune cell modulation.

Identification and validation of two major QTL for grain number per spike on chromosomes 2B and 2D in bread wheat (Triticum aestivum L.).

KEY MESSAGE: Major QTL for grain number per spike were identified on chromosomes 2B and 2D. Haplotypes and candidate genes of QGns.cib-2B.1 were analyzed. Grain number per spike (GNS) is one of the main components of wheat yield. Genetic dissection of their regulatory factors is essential to improve the yield potential. In present study, a recombinant inbred line population comprising 180 lines developed from the cross between a high GNS line W7268 and a cultivar Chuanyu12 was employed to identify quantitative trait loci (QTL) associated with GNS across six environments. Two major QTL, QGns.cib-2B.1 and QGns.cib-2D.1, were detected in at least four environments with the phenotypic variations of 12.99-27.07% and 8.50-13.79%, respectively. And significant interactions were observed between the two major QTL. In addition, QGns.cib-2B.1 is a QTL cluster for GNS, grain number per spikelet and fertile tiller number, and they were validated in different genetic backgrounds using Kompetitive Allele Specific PCR (KASP) markers. QGns.cib-2B.1 showed pleotropic effects on other yield-related traits including plant height, spike length, and spikelet number per spike, but did not significantly affect thousand grain weight which suggested that it might be potentially applicable in breeding program. Comparison analysis suggested that QGns.cib-2B.1 might be a novel QTL. Furthermore, haplotype analysis of QGns.cib-2B.1 indicated that it is a hot spot of artificial selection during wheat improvement. Based on the expression patterns, gene annotation, orthologs analysis and sequence variations, the candidate genes of QGns.cib-2B.1 were predicted. Collectively, the major QTL and KASP markers reported here provided a wealth of information for the genetic basis of GNS and grain yield improvement.

Hoffmann's sign in cervical spondylotic myelopathy patients: pathological insights from neuroimaging.

OBJECTIVE: Hoffmann's sign testing is a commonly used physical examination in clinical practice for patients with cervical spondylotic myelopathy (CSM). However, the pathophysiological mechanisms underlying its occurrence and development have not been thoroughly investigated. Therefore, the present study aimed to explore whether a positive Hoffmann's sign (PHS) in CSM patients is associated with spinal cord and brain remodeling and to identify potential neuroimaging biomarkers with diagnostic value. METHODS: Seventy-six patients with CSM and 40 sex- and age-matched healthy controls (HCs) underwent multimodal MRI. Based on the results of the Hoffmann's sign examination, patients were divided into two groups: those with a PHS (n = 38) and those with a negative Hoffmann's sign (NHS; n = 38). Quantification of spinal cord and brain structural and functional parameters of the participants was performed using various methods, including functional connectivity analysis, voxel-based morphometry, and atlas-based analysis based on functional MRI and structural MRI data. Furthermore, this study conducted a correlation analysis between neuroimaging metrics and neurological function and utilized a support vector machine (SVM) algorithm for the classification of PHS and NHS. RESULTS: In comparison with the NHS and HC groups, PHS patients exhibited significant reductions in the cross-sectional area and fractional anisotropy (FA) of the lateral corticospinal tract (CST), reticulospinal tract (RST), and fasciculus cuneatus, concomitant with bilateral reductions in the volume of the lateral pallidum. The functional connectivity analysis indicated a reduction in functional connectivity between the left lateral pallidum and the right angular gyrus in the PHS group. The correlation analysis indicated a significant positive association between the CST and RST FA and the volume of the left lateral pallidum in PHS patients. Furthermore, all three variables exhibited a positive correlation with the patients' motor function. Finally, using multimodal neuroimaging metrics in conjunction with the SVM algorithm, PHS and NHS were classified with an accuracy rate of 85.53%. CONCLUSIONS: This research revealed a correlation between structural damage to the pallidum and RST and the presence of Hoffmann's sign as well as the motor function in patients with CSM. Features based on neuroimaging indicators have the potential to serve as biomarkers for assessing the extent of neuronal damage in CSM patients.

Conventional and multi-omics assessments of subacute inhalation toxicity due to propylene glycol and vegetable glycerin aerosol produced by electronic cigarettes.

Propylene glycol (PG) and vegetable glycerin (VG) are the most common solvents used in electronic cigarette liquids. No long-term inhalation toxicity assessments have been performed combining conventional and multi-omics approaches on the potential respiratory effects of the solvents in vivo. In this study, the systemic toxicity of aerosol generated from a ceramic heating coil-based e-cigarette was evaluated. First, the aerosol properties were characterized, including carbonyl emissions, the particle size distribution, and aerosol temperatures. To determine toxicological effects, rats were exposed, through their nose only, to filtered air or a propylene glycol (PG)/ glycerin (VG) (50:50, %W/W) aerosol mixture at the target concentration of 3 mg/L for six hours daily over a continuous 28-day period. Compared with the air group, female rats in the PG/VG group exhibited significantly lower body weights during both the exposure period and recovery period, and this was linked to a reduced food intake. Male rats in the PG/VG group also experienced a significant decline in body weight during the exposure period. Importantly, rats exposed to the PG/VG aerosol showed only minimal biological effects compared to those with only air exposure, with no signs of toxicity. Moreover, the transcriptomic, proteomic, and metabolomic analyses of the rat lung tissues following aerosol exposure revealed a series of candidate pathways linking aerosol inhalation to altered lung functions, especially the inflammatory response and disease. Dysregulated pathways of arachidonic acids, the neuroactive ligand-receptor interaction, and the hematopoietic cell lineage were revealed through integrated multi-omics analysis. Therefore, our integrated multi-omics approach offers novel systemic insights and early evidence of environmental-related health hazards associated with an e-cigarette aerosol using two carrier solvents in a rat model.

Mesenchymal stromal cells-derived small extracellular vesicles modulate DC function to suppress Th2 responses via IL-10 in patients with allergic rhinitis.

Mesenchymal stromal cells (MSCs) are well known for their immunoregulatory roles on allergic inflammation particularly by acting on T cells, B cells, and dendritic cells (DCs). MSC-derived small extracellular vesicles (MSC-sEV) are increasingly considered as one of the main factors for the effects of MSCs on immune responses. However, the effects of MSC-sEV on DCs in allergic diseases remain unclear. MSC-sEV were prepared from the induced pluripotent stem cells (iPSC)-MSCs by anion-exchange chromatography, and were characterized with the size, morphology, and specific markers. Human monocyte-derived DCs were generated and cultured in the presence of MSC-sEV to differentiate the so-called sEV-immature DCs (sEV-iDCs) and sEV-mature DCs (sEV-mDCs), respectively. The phenotypes and the phagocytic ability of sEV-iDCs were analyzed by flow cytometry. sEV-mDCs were co-cultured with isolated CD4+ T cells or peripheral blood mononuclear cells (PBMCs) from patients with allergic rhinitis. The levels of Th1 and Th2 cytokines produced by T cells were examined by ELISA and intracellular flow staining. And the following mechanisms were further investigated. We demonstrated that MSC-sEV inhibited the differentiation of human monocytes to iDCs with downregulation of the expression of CD40, CD80, CD86, and HLA-DR, but had no effects on mDCs with these markers. However, MSC-sEV treatment enhanced the phagocytic ability of mDCs. More importantly, using anti-IL-10 monoclonal antibody or IL-10Rα blocking antibody, we identified that sEV-mDCs suppressed the Th2 immune response by reducing the production of IL-4, IL-9, and IL-13 via IL-10. Furthermore, sEV-mDCs increased the level of Treg cells. Our study identified that mDCs treated with MSC-sEV inhibited the Th2 responses, providing novel evidence of the potential cell-free therapy acting on DCs in allergic airway diseases.

Identification and validation of quantitative trait loci for fertile spikelet number per spike and grain number per fertile spikelet in bread wheat (Triticum aestivum L.).

KEY MESSAGE: A major and stable QTL for fertile spikelet number per spike and grain number per fertile spikelet identified in a 4.96-Mb interval on chromosome 2A was validated in different genetic backgrounds. Fertile spikelet number per spike (FSN) and grain number per fertile spikelet (GNFS) contribute greatly to wheat yield improvement. To detect quantitative trait loci (QTL) associated with FSN and GNFS, we used a recombinant inbred line population crossed by Zhongkemai 13F10 and Chuanmai 42 in eight environments. Two Genomic regions associated with FSN were detected on chromosomes 2A and 6A using bulked segregant exome sequencing analysis. After the genetic linkage maps were constructed, four QTL QFsn.cib-2A, QFsn.cib-6A, QGnfs.cib-2A and QGnfs.cib-6A were identified in three or more environments. Among them, two major QTL QFsn.cib-2A (LOD = 4.67-9.34, PVE = 6.66-13.05%) and QGnfs.cib-2A (LOD = 5.27-11.68, PVE = 7.95-16.71%) were detected in seven and six environments, respectively. They were co-located in the same region, namely QFsn/Gnfs.cib-2A. The developed linked Kompetitive Allele Specific PCR (KASP) markers further validated this QTL in a different genetic background. QFsn/Gnfs.cib-2A showed pleiotropic effects on grain number per spike (GNS) and spike compactness (SC), and had no effect on grain weight. Since QFsn/Gnfs.cib-2A might be a new locus, it and the developed KASP markers can be used in wheat breeding. According to haplotype analysis, QFsn/Gnfs.cib-2A was identified as a target of artificial selection during wheat improvement. Based on haplotype analysis, sequence differences, spatiotemporal expression patterns, and gene annotation, the potential candidate genes for QFsn/Gnfs.cib-2A were predicted. These results provide valuable information for fine mapping and cloning gene(s) underlying QFsn/Gnfs.cib-2A.

Visible-Light-Activated Carbon Dot Photocatalyst for ROS-Mediated Inhibition of Algae Growth.

The growing occurrence of detrimental algal blooms resulting from industrial and agricultural activities emphasizes the urgency of implementing efficient removal strategies. In this study, we have successfully synthesized stable and biocompatible carbon dots (R-CDs) capable of generating reactive oxygen species (ROS) upon exposure to natural light irradiation. Phaeocystis globosa Scherffel (PGS) was selected as a representative model for conducting anti-algal experiments. Remarkably, in the presence of R-CDs, the complete eradication of harmful algae within a simulated light exposure period of 27 h was achieved. Furthermore, fluorescence lifetime imaging microscopy (FLIM) was first employed to study the physiological processes involved in the oxidative stress induced by PGS when subjected to ROS attack. The findings of this study demonstrate the potential of R-CDs as a highly promising anti-algal agent. This elucidation of the mechanism contributes to a comprehensive understanding of the efficacy and effectiveness of such agents in combating algal growth, further inspiring the development of other anti-algal agents.

Students' Psychological State, Creative Development, and Music Appreciation: The Influence of Different Musical Act Modes (Exemplified by a Video Clip, an Audio Recording, and a Video Concert).

This paper aims to study how different musical act modes influence the student's psychological state, creative development, and music appreciation. In particular, the research focuses on concert videos, video clips, and audio records. Based on the Likert scale, the authors determined that video clips significantly influenced students' learning process since they contributed to the combination of visual and sound effects. Video concerts were less important. Concerts are mainly staged actions with frequent use of pre-recorded music, affecting the accuracy of singing techniques. The authors concluded that the most effective approach is systematical learning using the effect of colors and sounds with a preliminary analysis of musical compositions. The results showed that the most significant number of students significantly improved their knowledge (87%, with an average score of 0.92), and the elements of a musical act (rhythm, color scheme, text, and performance) influenced their development. The practical significance of the paper lies in the use of approaches to learning using colors and sound effects with an emphasis on the development of certain elements. The study prospects involve determining how effectively the elements of a musical act influence the psychological state resulting from comparing music genres.

Synergistic Chaotropic Effect and Cathode Interface Thermal Release Effect Enabling Ultralow Temperature Aqueous Zinc Battery.

Although rechargeable zinc-ion batteries are promising candidates for next-generation energy storage devices, their inferior performance at subzero temperatures limits their practical application. Here, a strategy to destroy the H-bond network by adding synergistic chaotropic regents is reported, thus reducing the freezing point of the aqueous electrolyte below -90 °C. Owing to the synergistic chaotropic effect between urea and Zn(ClO4 )2 and the thermal release effect on the cathode interface during charging, Zn//VO2 batteries feature a specific capacity of 111.4 mAh g-1 and stability after ≈1000 cycles with 81.9% capacity retention at -40 °C. This work demonstrates that the synergistic chaotropic effect and the thermal effect on the interface can effectively widen the operation range of temperature of aqueous electrolytes and maintain fast kinetics, which provides a new design strategy for all-weather aqueous zinc batteries.

Mesenchymal stem cells regulate type 2 innate lymphoid cells via regulatory T cells through ICOS-ICOSL interaction.

Group 2 innate lymphoid cells (ILC2s) are recognized as key controllers and effectors of type 2 inflammation. Mesenchymal stem cells (MSCs) have been shown to alleviate type 2 inflammation by modulating T lymphocyte subsets and decreasing TH 2 cytokine levels. However, the effects of MSCs on ILC2s have not been investigated. In this study, we investigated the potential immunomodulatory effects of MSCs on ILC2s in peripheral blood mononuclear cells (PBMCs) from allergic rhinitis patients and healthy subjects. We further investigated the mechanisms involved in the MSC modulation using isolated lineage negative (Lin- ) cells. PBMCs and Lin- cells were cocultured with induced pluripotent stem cell-derived MSCs (iPSC-MSCs) under the stimulation of epithelial cytokines IL-25 and IL-33. And the ILC2 levels and functions were examined and the possible mechanisms were investigated based on regulatory T (Treg) cells and ICOS-ICOSL pathway. iPSC-MSCs successfully decreased the high levels of IL-13, IL-9, and IL-5 in PBMCs in response to IL-25, IL-33, and the high percentages of IL-13+ ILC2s and IL-9+ ILC2s in response to epithelial cytokines were significantly reversed after the treatment of iPSC-MSCs. However, iPSC-MSCs were found directly to enhance ILC2 levels and functions via ICOS-ICOSL interaction in Lin- cells and pure ILC2s. iPSC-MSCs exerted their inhibitory effects on ILC2s via activating Treg cells through ICOS-ICOSL interaction. The MSC-induced Treg cells then suppressed ILC2s by secreting IL-10 in the coculture system. This study revealed that human MSCs suppressed ILC2s via Treg cells through ICOS-ICOSL interaction, which provides further insight to regulate ILC2s in inflammatory disorders.

Bifunctional Nitrogen and Fluorine Co-Doped Carbon Dots for Selective Detection of Copper and Sulfide Ions in Real Water Samples.

Copper ions (Cu2+) and sulfur ions (S2-) are important elements widely used in industry. However, these ions have the risk of polluting the water environment. Therefore, rapid and quantitative detection methods for Cu2+ and S2- are urgently required. Using 2,4-difluorobenzoic acid and L-lysine as precursors, nitrogen and fluorine co-doped dots (N, F-CDs) were synthesized in this study via a hydrothermal method. The aqueous N, F-CDs showed excellent stability, exhibited satisfactory selectivity and excellent anti-interference ability for Cu2+ detection. The N, F-CDs, based on the redox reactions for selective and quantitative detection of Cu2+, showed a wide linear range (0-200 µM) with a detection limit (215 nM). By forming the N, F-CDs@Cu2+ sensing platform and based on the high affinity of S2- to Cu2+, the N, F-CDs@Cu2+ can specifically detect S2- over a linear range of 0-200 µM with a detection limit of 347 nM. In addition, these fluorescent probes achieved good results when used for Cu2+ and S2- detection in environmental water samples, implying the good potential for applications.

[Bladder wall neourethra technique improves early urinary continence after laparoscopic radical prostatectomy].

OBJECTIVE: To study the effect of the bladder wall neourethra (BWN) technique on early urinary continence after laparoscopic radical prostatectomy (LRP). METHODS: We prospectively selected 40 cases of LRP performed in our hospital from August 2020 to August 2021 and randomly divided them into a BWN group (n = 20) and a control group (n = 20). We recorded the urinary continence rate of the two groups of patients at 7, 30, 90 and 180 days, and measured the maximum urethral pressure (MUP), functional urethral length (FUL) and functional urethral area (UFA) and observed the shape of the neourethra closure by MRI at 1 month after catheter removal. RESULTS: The urinary continence rates were significantly higher in the BWN than in the control group at 7 days (90.0% vs 25.0%, P < 0.001), 30 days (95.0% vs 35.0%, P < 0.001), 90 days (100% vs 60.0%, P < 0.05) and 180 days (100% vs 90.0%, P > 0.05) after catheter removal. No statistically significant difference was observed in MUP between the two groups (P > 0.05). FUL and FUA were remarkably higher in the BWN than in the control group (P < 0.01). MRI showed tight closure of the neourethra in the BWN group in the urine storage period. CONCLUSION: The BWN technique can significantly prolong FUL and improve early urinary continence after LRP.

Identification of a major and stable QTL on chromosome 5A confers spike length in wheat (Triticum aestivum L.).

Spike length (SL) is the key determinant of plant architecture and yield potential. In this study, 193 recombinant inbred lines (RILs) derived from a cross between 13F10 and Chuanmai 42 (CM42) were evaluated for spike length in six environments. Sixty RILs consisting of 30 high and 30 low SLs were genotyped using the bulked segregant analysis exome sequencing (BSE-Seq) analysis for preliminary quantitative trait locus (QTL) mapping. A 6.69 Mb (518.43-525.12 Mb) region on chromosome 5AL was found to have a significant effect on the SL trait. Fifteen competitive allele-specific PCR (KASP) markers were successfully converted from the single nucleotide polymorphisms (SNPs) in the SL target region. Combined with four novel simple sequence repeat (SSR) markers, a genetic linkage map spanning 21.159 cM was constructed. The mapping result confirmed the identity of a major and stable QTL named QSl.cib-5A in the targeted region that explained 7.88-26.60% of the phenotypic variation in SL. QSl.cib-5A was narrowed to a region of 4.84 cM interval corresponding to a 4.67 Mb (516.60-521.27 Mb) physical region in the Chinese Spring RefSeq v2.0 containing 17 high-confidence genes with 25 transcripts. In addition, this QTL exhibited pleiotropic effects on spikelet density (SD), with the phenotypic variances proportion ranging from 11.34 to 19.92%. This study provides a foundational step for cloning the QSl.cib-5A, which is involved in the regulation of spike morphology in common wheat. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01249-6.

Effects of myeloid and plasmacytoid dendritic cells on ILC2s in patients with allergic rhinitis.

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) were reported to serve a critical role in allergic diseases. Myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) play significant roles in allergic immune response. However, effects of DCs on ILC2s in allergic diseases, especially for patients with allergic rhinitis (AR), remain unclear. OBJECTIVE: We sought to address the roles of mDCs and pDCs in regulating ILC2 function in AR. METHODS: mDCs and pDCs were cocultured with human PBMCs isolated from patients with AR or ILC2s to measure soluble or intracellular TH2 cytokines, transcription factors, signaling pathways in ILC2s, and the following mechanisms were further investigated. The levels of peripheral IL-33+mDCs, pDCs, and ILC2s were studied in patients under an inhaled allergen challenge. RESULTS: We confirmed the presence of ILC2s, mDCs, and pDCs in the nasal mucosa of patients with AR. Both allogenic and autologous mDCs were found to activate ILC2s from patients with AR to produce TH2 cytokines, and increase the levels of GATA-3 and signal transducer and activator of transcription signaling pathways, in which IL-33-producing mDCs exerted the major role by binding on ST2 on ILC2s. We further identified high levels of IL-33+mDCs and ILC2s in patients with AR under antigen challenge. Activated pDCs inhibited the cytokine production of ILC2s isolated from patients with AR by secretion of IL-6. CONCLUSIONS: mDCs promote ILC2 function by the IL-33/ST2 pathway, and activation of pDCs suppresses ILC2 function through IL-6 in patients with AR. Our findings provide new understanding of the interplay between DCs and ILC2s in allergic diseases.

Metastasis-associated protein 1 (MTA1) regulates the catecholamine production homeostasis via transcriptional repression of aromatic l-amino acid decarboxylase (Aadc) in the interstitial cells of Cajal of mouse prostate.

Based on the lately identified role for the interstitial cells of Cajal (ICCs) of mouse prostate in catecholamine production, as well as the well-established role for the master coregulator metastasis-associated protein 1 (MTA1) in inflammation, we probed into the functional link between aberrant MTA1 expression and pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) using both a MTA1-/- mouse model of experimental autoimmune prostatitis (EAP) and an in vitro chronic prostatitis model in cultured murine ICCs. EAP-induced MTA1 expression was enriched in ICCs of mouse prostate. EAP resulted in a higher increase in the pelvic pain response in MTA1-/- mice compared to WT mice. Consistently, the ICCs from MTA1-/- mice produced higher levels of catecholamines upon induction of in vitro chronic prostatitis. Mechanistically, MTA1 could directly suppress the transcription of Aadc, a rate-limiting enzyme during catecholamine synthesis, in a HDAC2-depdendent manner. Importantly, treatment with AADC inhibitor NSD-1015 significantly ameliorated EAP-elicited pain response and catecholamine overactivity in MTA1-/- mice. Taken together, our findings reveal an inherent regulatory role of the MTA1/AADC pathway in the maintenance of catecholamine production homeostasis in prostate ICCs, and also point to a potential use of HDAC inhibitors and/or AADC inhibitors to treat CP/CPPS.

FOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20A.

BACKGROUND: Docetaxel resistance affects prognosis in advanced prostate cancer (PCa). The precise mechanisms remain unclear. Transcription factor Forkhead box M1 (FOXM1), which participates in cell proliferation and cell cycle progression, has been reported to affect the sensitivity of chemotherapy. This study explores the role of FOXM1 in PCa docetaxel resistance and its association with kinesin family member 20 A (KIF20A), which is known to promote therapeutic resistance in some cancers. METHODS: We monitored cell growth using MTT and colony formation assays, and cell apoptosis and cell cycle progression using flow cytometry. Wound-healing and transwell assays were used to detect cell invasion and migration. mRNA and protein expression were analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. We monitored FOXM1 binding to the KIF20A promoter using a ChIP assay. Tumorigenicity in nude mice was used to assess in vivo tumorigenicity. RESULTS: FOXM1 knockdown induced cell apoptosis and G2/M cell cycle arrest, suppressing cell migration and invasion in docetaxel-resistant PCa cell lines (DU145-DR and VCaP-DR). Exogenous FOXM1 overexpression was found in their parental cells. Specific FOXM1 inhibitor thiostrepton significantly weakened docetaxel resistance in vitro and in vivo. We also found that FOXM1 and KIF20A exhibited consistent and highly correlated overexpression in PCa cells and tissues. FOXM1 also regulated KIF20A expression at the transcriptional level by acting directly on a Forkhead response element (FHRE) in its promoter. KIF20A overexpression could partially reverse the effect on cell proliferation, cell cycle proteins (cyclinA2, cyclinD1 and cyclinE1) and apoptosis protein (bcl-2 and PARP) of FOXM1 depletion. CONCLUSIONS: Our findings indicate that highly expressed FOXM1 may help promote docetaxel resistance by inducing KIF20A expression, providing insight into novel chemotherapeutic strategies for combatting PCa docetaxel resistance.

Effects of tumor distance from anal verge on survival outcomes for rectal NENs and lymphatic metastasis risk score for colorectal NENs.

OBJECTIVE: To explore whether the distance of rectal neuroendocrine neoplasms from the anal margin has an impact on the prognosis of patients and evaluate lymphatic metastases risk score for colorectal neuroendocrine neoplasms (NENs). METHODS: Clinical pathological and follow-up data of 71 patients identified as colorectal neuroendocrine neoplasms by pathology from July 2011 to July 2019 were carefully collected. RESULTS: Among 71 patients with colorectal NENs, most of the tumors were rectal NENs (62 cases). A total of 26 patients were in the presence of lymph node metastasis, and 44 patients had negative lymph nodes. Patients with lesions from the anal margin > 5 cm in rectum have a better prognosis (P = 0.022). Tumor stage (P = 0.034) and grade (P = 0.001) were independent risk predictors of lymphatic metastases. We developed a lymphatic metastasis risk score for rectal NENs, and patients with the score ≥ 7.5 were more likely to develop lymph node metastases (area 0.958, 95% CI 0.903-1.000, P = 0.000) with a sensitivity of 72.2% and a specificity of 97.3%. CONCLUSION: Patients with lesions from the anal margin > 5 cm and lymphatic metastasis risk score ≥ 7.5 should be treated actively.

Involvement of prostatic interstitial cells of Cajal in inflammatory cytokines-elicited catecholamines production: Implications for the pathophysiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

In a previous work using guinea pig prostate, we have identified a novel interstitial cells of Cajal (ICCs) which possess close contacts between sympathetic nerve bundles and smooth muscle cells. The ability of prostatic ICCs in mediating excitatory neural inputs was therefore studied using isolated murine prostate ICCs by collagenase digestion combined with FACS method. RT-PCR and Western blotting analyses revealed that prostatic ICCs under a quiescent state expressed abundantly the rate-limiting enzymes essential for catecholamine synthesis. Moreover, distinct proinflammatory cytokines (e.g. IL-1ß, IL-8, ICAM-1 and TNF-α) could significantly stimulate the expression levels of the rate-limiting enzymes of catecholamine production in prostate ICCs. Mechanistically, the above-mentioned stimulatory effects of proinflammatory cytokines appeared to be mediated via activation of NF-κB, HIF-1α and HDACs signaling pathways. Considering that prostatic catecholamine overactivity serves as an essential etiology of pelvic pain by indirectly stimulating the smooth muscle cell proliferation, or by directly causing muscular spasm, our results collectively suggest that targeting the NF-κB, HIF-1α and HDACs pathways in prostate ICCs be considered as a new strategy for treatment of chronic pelvic pain syndrome (CPPS) induced by chronic prostatitis (CP). Overall, the current study should shed novel light on the biology of this unique prostate ICCs.

TaAAP6-3B, a regulator of grain protein content selected during wheat improvement.

BACKGROUND: The content of grain protein (GPC) in cereals is an important part of total protein in human food. Exploring and utilizing new GPC genes is one of the most effective approaches for wheat quality breeding. RESULTS: Three homoeologues of TaAAP6(-3A, 3B, 3D)were cloned by homology cloning from OsAAP6.Temporal and spatial expression analysis showed that TaAAP6homoeologues were preferentially expressed in developing grains, and TaAAP6-3B may play a major role in regulating GPC in wheat. Association analysis indicated thatTaAAP6-3B-I is significantly correlated with higher GPC than that of TaAAP6-3B-II for 115 wheat lines in all five environments. TaAAP6-3B-I, the favored allele of TaAAP6-3B, was preferentially expressed in preliminary developing grain stage. Two functional markers were developed to discriminate 197F2populations and the result showed that TaAAP6-3B-I (high-protein content) was completely dominant. Two cis-regulatory elements appear to be associated with high GPC were found in the 5'UTR of TaAAP6-3B-I.The change of the TaAAP6-3B locus types indicated that the gene was subjected to selection pressures during long process of artificial selection. CONCLUSIONS: TaAAP6-3B is a regulator of GPC and its favored allele TaAAP6-3B-I exhibits an obvious potential application in wheat high-GPC breeding.