Bone marrow-derived IGF-1 orchestrates maintenance and regeneration of the adult skeleton.

Insulin-like growth factor I (IGF-1) is a key regulator of tissue growth and development in response to growth hormone stimulation. In the skeletal system, IGF-1 derived from osteoblasts and chondrocytes are essential for normal bone development; however, whether bone marrow (BM)-resident cells provide distinct sources of IGF-1 in the adult skeleton remains elusive. Here, we show that BM stromal cells (BMSCs) and megakaryocytes/platelets (MKs/PLTs) express the highest levels of IGF-1 in adult long bones. Deletion of Igf1 from BMSCs by Lepr-Cre leads to decreased bone formation, impaired bone regeneration, and increased BM adipogenesis. Importantly, reduction of BMSC-derived IGF-1 contributes to fasting-induced marrow fat accumulation. In contrast, deletion of Igf1 from MKs/PLTs by Pf4-Cre leads to reduced bone formation and regeneration without affecting BM adipogenesis. To our surprise, MKs/PLTs are also an important source of systemic IGF-1. Platelet-rich plasma (PRP) from Pf4-Cre; Igf1f/fmice showed compromised osteogenic potential both in vivo and in vitro, suggesting that MK/PLT-derived IGF-1 underlies the therapeutic effects of PRP. Taken together, this study identifies BMSCs and MKs/PLTs as two important sources of IGF-1 that coordinate to maintain and regenerate the adult skeleton, highlighting reciprocal regulation between the hematopoietic and skeletal systems.

A comprehensive analysis of transcriptomic data for comparison of cold tolerance in two Brassica napus genotypes.

Brassica napus is an important oil crop and cold stress severely limits its productivity. To date, several studies have reported the regulatory genes and pathways involved in cold-stress responses in B. napus. However, transcriptome-scale identification of the regulatory genes is still lacking. In this study, we performed comparative transcriptome analysis of cold-tolerant C18 (CT - C18) and cold-sensitive C6 (CS - C6) Brassica napus genotypes under cold stress for 7 days, with the primary purpose of identifying cold-responsive transcription in B. napus. A total of 6061 TFs belonging to 58 families were annotated in the B. napus genome, of which 3870 were expressed under cold stress in both genotypes. Among these, 451 TFs were differentially expressed (DE), with 21 TF genes expressed in both genotypes. Most TF members of the MYB (26), bHLH (23), and NAC (17) families were significantly expressed in the CT - C18 genotype compared with the CS - C6 B. napus genotype. GO classification showed a significant role in transcription regulation, DNA-binding transcription factor activity, response to chitin, and the ethylene-activated signaling pathway. KEGG pathway annotation revealed these TFs are involved in regulating more pathways, resulting in more tolerance. In conclusion, the results provide insights into the molecular regulation mechanisms of B. napus in response to freezing treatment, expanding our understanding of the complex molecular mechanisms in plants' response to freezing stress.

Preoperative Evaluation of Gd-EOB-DTPA-Enhanced MRI Radiomics-Based Nomogram in Small Solitary Hepatocellular Carcinoma (≤3 cm) With Microvascular Invasion: A Two-Center Study.

BACKGROUND: Preoperative evaluation of microvascular invasion (MVI) in small solitary hepatocellular carcinoma (HCC; maximum lesion diameter ≤ 3 cm) is important for treatment decisions. PURPOSE: To apply gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI to develop and validate a nomogram for preoperative evaluation of MVI in small solitary HCC and to compare the effectiveness of radiomics evaluation models based on different volumes of interest (VOIs). STUDY TYPE: Retrospective. POPULATION: A total of 196 patients include 62 MVI-positive and 134 MVI-negative patients were enrolled (training cohort, n = 105; testing cohort, n = 45; external validation cohort, n = 46). FIELD STRENGTH/SEQUENCE: 3.0 T, fat suppressed fast-spin-echo T2-weighted and Gd-EOB-DTPA-enhanced T1-weighted magnetization-prepared rapid gradient-echo sequences. ASSESSMENT: Radiomics features were extracted on T2-weighted, arterial phase (AP), and hepatobiliary phase (HBP) images from different VOIs (VOIintratumor and VOIintratumor+peritumor ) and filtered by the least absolute shrinkage selection operator (LASSO) regression. From VOIintratumor and VOIintratumor+peritumor , eight radiomics models were constructed based on three MRI sequences (T2-weighted, AP, and HBP) and fused sequences (combined of three sequences). Nomograms were constructed of a clinical-radiological (CR) model and a clinical-radiological-radiomics (CRR) model. STATISTICAL TESTS: One-way analysis of variance, independent t-test, Chi-square test or Fisher's exact test, Wilcoxon rank-sum test, LASSO, logistic regression analysis, area under the curve (AUC), nomograms, decision curve, net reclassification improvement (NRI), integrated discrimination improvement (IDI) analyses, and DeLong test. RESULTS: Among eight radiomics models, the fused sequences-based VOIintratumor+peritumor radiomics model showed the best performance. The CRR model containing the best performance radiomics model and CR model with the AUC values were 0.934, 0.889, and 0.875, respectively. NRI and IDI analyses showed that the CRR model improved evaluation efficacy over the CR model for all three cohorts (all P-value <0.05). DATA CONCLUSION: The CRR model nomogram could preoperatively evaluate MVI in small solitary HCC. The radiomics model based on VOIintratumor+peritumor might achieve better evaluation results. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY STAGE: 2.

Enhanced Permanganate Activation under UVA-LED Irradiation: Unraveled Mechanism Involving Manganese Species and Hydroxyl Radical.

Permanganate [Mn(VII)] has gained broad attention in water treatment. However, its limited reactivity toward some refractory micropollutants hinders its application for micropollutant degradation. Herein, we introduced UVA-LED photolysis of Mn(VII) (UVA-LED/Mn(VII)) to degrade micropollutants (diclofenac (DCF), 4-chlorophenol (4-CP), atrazine, and nitrobenzene) by selecting DCF and 4-CP as target micropollutants. The effects of operating conditions (e.g., light intensity, radiation wavelengths, pH, and water constituents) on DCF and 4-CP degradation as well as the underlying mechanisms were systematically studied. The degradation rates of DCF and 4-CP linearly decreased with increasing radiation wavelengths (from 365 to 405 nm), likely due to the decreased molar absorption coefficients and quantum yields of Mn(VII). Reactive manganese species (RMnS), including Mn(V), Mn(III), and HO•, were generated in the UVA-LED/Mn(VII) process. Mn(V) and HO• were responsible for DCF degradation, while Mn(III), HO•, and likely Mn(V) accounted for 4-CP degradation. Competitive kinetic results revealed that contributions of RMnS and HO• decreased with increasing radiation wavelengths, wherein RMnS played the dominant role. Increasing pH displayed opposite effects on DCF and 4-CP degradation with higher degradation efficiency obtained at acidic pH for the former one but alkaline pH for the latter one. The presence of water background ions (e.g., Cl-, HCO3-, and Ca2+) barely influenced DCF and 4-CP degradation. Finally, in comparison with Mn(VII) alone, enhanced degradation of DCF and 4-CP by UVA-LED/Mn(VII) was observed in real waters. This work advances the understanding of the photochemistry of manganese species in micropollutant degradation and facilitates Mn(VII) oxidation in practical application.

A novel non-equilibrium memristor-based system with multi-wing attractors and multiple transient transitions.

Based on the pure mathematical model of the memristor, this paper proposes a novel memristor-based chaotic system without equilibrium points. By selecting different parameters and initial conditions, the system shows extremely diverse forms of winglike attractors, such as period-1 to period-12 wings, chaotic single-wing, and chaotic double-wing attractors. It was found that the attractor basins with three different sets of parameters are interwoven in a complex manner within the relatively large (but not the entire) initial phase plane. This means that small perturbations in the initial conditions in the mixing region will lead to the production of hidden extreme multistability. At the same time, these sieve-shaped basins are confirmed by the uncertainty exponent. Additionally, in the case of fixed parameters, when different initial values are chosen, the system exhibits a variety of coexisting transient transition behaviors. These 14 were also where the same state transition from period 18 to period 18 was first discovered. The above dynamical behavior is analyzed in detail through time-domain waveforms, phase diagrams, attraction basin, bifurcation diagrams, and Lyapunov exponent spectrum . Finally, the circuit implementation based on the digital signal processor verifies the numerical simulation and theoretical analysis.

The influence of spiritual leadership on the subjective well-being of Chinese registered nurses.

BACKGROUND: Challenging working conditions and job characteristics can result in nurses experiencing significant workplace stress and adversity. AIM: To examine how and why spiritual leadership may have a positive influence on nurses' subjective well-being. METHOD: A total of 339 registered nurses from five public hospitals in Mainland China participated in this study. Hypotheses were tested using the PROCESS macro. RESULTS: Spiritual leadership influenced the subjective well-being indirectly through workplace spirituality. The interaction between spiritual leadership and power distance orientation on workplace spirituality was significant. Power distance orientation moderates the indirect effect of spiritual leadership on the subjective well-being through workplace spirituality, and this indirect effect is more positive for nurse with lower power distance orientation. CONCLUSIONS: Spiritual leadership is a significant contextual factor in the workplace that may influence the nurses' workplace spirituality and subjective well-being. Based on their power distance orientation, nurses may have different responses to spiritual leadership, resulting in differing levels of workplace spirituality. IMPLICATIONS FOR NURSING MANAGEMENT: Spirituality can satisfy the internal needs of nurses. Spiritual leadership can facilitate a spiritual working context for sustaining the subjective well-being of nurses. Hospitals should provide training programmes to help existing leaders engage in spiritual leadership.

Trimetazidine Protects Against Atherosclerosis by Changing Energy Charge and Oxidative Stress.

BACKGROUND This study investigated the effect and the possible mechanism of trimetazidine in atherosclerosis. MATERIAL AND METHODS We established an atherosclerotic rat model by high-fat diet and vitamin D injection. Rats were separated into 3 different groups: control, atherosclerosis, and trimetazidine (n=10). The aortic artery was isolated and its morphological features were examined by hematoxylin and eosin (HE) staining. Serum low-density lipoprotein cholesterol (LDL-c), total cholesterol (TC), and triglycerides (TG) were analyzed using an automatic biochemical analyzer. Human aortic smooth muscle cells (HASMCs) were cultured and divided into 5 groups: no treatment, H2O2 treatment only, trimetazidine preincubation before H2O2 treatment, oxidized low-density lipoprotein (oxLDL) treatment only, and trimetazidine preincubation before oxLDL treatment. HASMCs proliferation was tested using the Cell Counting Kit-8. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity of the aortic artery, and HASMCs were measured using commercially available kits. RESULTS HE staining assay showed that trimetazidine suppressed the progression of atherosclerosis and reduced foam cell formation in the aortic artery without affecting serum lipid levels. HASMCs proliferation assay revealed that trimetazidine alleviated the inhibitory effect of H2O2 on HASMCs proliferation and inhibited oxLDL-induced proliferation of HASMCs. Moreover, trimetazidine ameliorated ROS up-regulation elicited by H2O2 or oxLDL in HASMCs. Additionally, trimetazidine restored SOD activity and reduced MDA content of HASMCs. CONCLUSIONS Trimetazidine suppressed the progression of atherosclerosis by enhancing energy value, decreasing ROS level of aortic artery, modulating HASMCs proliferation, and reducing oxidative stress in HASMCs.

A two-center study of a combined nomogram based on mammography and MRI to predict ALN metastasis in breast cancer.

OBJECTIVES: To develop and validate a predictive method for axillary lymph node (ALN) metastasis of breast cancer by using radiomics based on mammography and MRI. MATERIALS AND METHODS: A retrospective analysis of 492 women from center 1 (The affiliated Hospital of Qingdao University) and center 2 (Yantai Yuhuangding Hospital) with primary breast cancer from August 2013 to May 2021 was carried out. The radscore was calculated using the features screened based on preoperative mammography and MRI from the training cohort of Center 1 (n = 231), then tested in the validation cohort (n = 99), an internal test cohort (n = 90) from Center 1, and an external test cohort (n = 72) from Center 2. Univariate and multivariate analyses were used to screen for the clinical and radiological characteristics most associated with ALN metastasis. A combined nomogram was established in combination with radscore that predicted the clinicopathological and radiological characteristics. Calibration curves were used to test the effectiveness of the combined nomogram. The receiver operating characteristic (ROC) curve was used to evaluate the performance of the combined nomogram and then compare with the clinical and radiomic models. The decision curve analysis (DCA) value was used to evaluate the combined nomogram for clinical applications. RESULTS: The constructed combined nomogram incorporating the radscore and MRI-reported ALN metastasis status exhibited good calibration and outperformed the radiomics signatures in predicting ALN metastasis (area under the curve [AUC]: 0.886 vs. 0.846 in the training cohort; 0.826 vs. 0.762 in the validation cohort; 0.925 vs. 0.899 in the internal test cohort; and 0.902 vs. 0.793 in the external test cohort). The combination nomogram achieved a higher AUC in the training cohort (0.886 vs. 0.786) and the internal test cohort (0.925 vs. 0.780) and similar AUCs in the validation (0.826 vs. 0.811) and external test (0.902 vs. 0.837) cohorts than the clinical model. CONCLUSION: A combined nomogram based on mammography and MRI can be used for preoperative prediction of ALN metastasis in primary breast cancer.

LOXL2 reduces 5-FU sensitivity through the Hedgehog/BCL2 signaling pathway in colorectal cancer.

Elevated expression of lysyl oxidase-like 2 (LOXL2) contributes to the malignant tumor progression in multiple cancers. However, the role of LOXL2 in the 5-fluorouracil (5-FU) resistance of colorectal cancer (CRC) remains unclear. This study aimed to explore the effects of LOXL2 on 5-FU sensitivity in CRC. The mRNA and protein levels of LOXL2 were explored in public databases by bioinformatics, validated in clinical tissues using immunohistochemistry, and detected in 5-FU treated cell lines. The 50% inhibitory concentrations (IC50) values were quantified based on the cell viability at different concentrations of 5-FU with CCK-8 assays. Colony formation and flow cytometry assays were performed to measure the proliferation and apoptosis rates. Gene set enrichment and correlation analyses were conducted to identify the probable mechanism of LOXL2 in TCGA samples. Critical molecules of the Hedgehog signaling pathway and anti-apoptotic BCL2 in protein levels were detected with Western blotting. It concluded that LOXL2 was up-regulated and positively linked to the unfavorable prognosis of CRC patients. The LOXL2 expression increased with the rising 5-FU concentrations, especially at 20 and 40 µM. Elevated LOXL2 promoted the resistance to 5-FU, augmented the proliferation, and inhibited 5-FU-induced apoptosis of CRC cells. LOXL2 activated the Hedgehog signaling pathway by promoting the expression of SMO, GLI1, and GLI2, leading to the upregulation of downstream target gene BCL2 in CRC cells. Moreover, the Hedgehog signaling pathway inhibitor cyclopamine blocked the BCL2 upregulation mediated by LOXL2. This study has demonstrated that LOXL2 can reduce 5-FU sensitivity through the Hedgehog/BCL2 signaling pathway in CRC.

[Effect of surgical timing on effectiveness of thoracic spinal tuberculosis with myelopathy].

Objective: To explore the feasibility of posterior debridement, decompression, bone grafting, and fixation in treatment of thoracic spinal tuberculosis with myelopathy, and investigate the effects of surgical timing on postoperative outcomes. Methods: The clinical data of 26 patients with thoracic spinal tuberculosis with myelopathy between August 2012 and October 2015 was retrospectively analyzed. All patients underwent posterior unilateral transpedicular debridement, decompression, bone grafting, and fixation and were divided into two groups according to surgical timing. Group A included 11 patients with neurological dysfunction lasting less than 3 months; group B included 15 patients with neurological dysfunction lasting more than 3 months. No significant difference was found between the two groups in gender, age, involved segments, preoperative erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Cobb angle of involved segment, and preoperative American Spinal Injury Association (ASIA) classification ( P>0.05). The operation time, intraoperative blood loss, hospitalization stay, perioperative complications, and bone fusion time were recorded and compared between the two groups. The change of pre- and post-operative Cobb angle of involved segments was calculated. Neurological function was assessed according to ASIA classification. Results: All patients were followed up 25-60 months (mean, 41.6 months). No cerebrospinal fluid leakage occurred intra- and post-operation. The hospitalization stay and perioperative complications in group A were significantly less than those of group B ( P<0.05). There was no significant difference in operation time, intraoperative blood loss, and bone fusion time between the two groups ( P>0.05). At last follow-up, there was no significant difference in ESR and CRP between groups A and B ( P>0.05), but they were all significantly lower than those before operation ( P<0.05). In group A, 1 patient with T 6, 7 tuberculosis developed sinus that healed after dressing; the implants were removed at 20 months with bony union and no recurrence was found after 36 months of follow-up. One patient with T 4, 5 tuberculosis in group B underwent revision because of recurrence and distal junctional kyphosis of the thoracic spine at 26 months after operation. There was no internal fixation-related complications or tuberculosis recurrence occurred in the remaining patients. At last follow-up, the Cobb angles in the two groups significantly improved compared with those before operation ( P<0.05), but there was no significant difference in the Cobb angle and correction degree between the two groups ( P>0.05). At last follow-up, the ASIA classification of spinal cord function was grade C in 1 case and grade E in 10 cases in group A, and grade D in 2 cases and grade E in 13 cases in group B; the ASIA classification results in the two groups significantly improved compared with preoperative ones ( P<0.05), but no significant difference was found between the two groups ( Z=-0.234, P=1.000). Conclusion: Posterior unilateral transpedicular debridement, decompression, bone grafting, and fixation is effective in treatment of thoracic spinal tuberculosis with myelopathy. Early surgery can reduce the hospitalization stays and incidence of perioperative complications.

One stage posterior debridement, non-structural bone graft in the surgical treatment of single segment thoracic tuberculosis: A retrospective single-center cohort study.

OBJECTIVE: To compare the clinical efficacy of non-structural with structural bone graft in the surgical treatment of single segment thoracic tuberculosis after one stage posterior debridement. METHODS: 61 patients with single segment thoracic tuberculosis treated by one stage posterior debridement, bone graft fusion and internal fixation were retrospectively analyzed. Among them, 35 cases were admitted from 2015 to 2017 in the non-structural bone graft group and 26 cases were admitted from 2011 to 2015 in the structural bone graft group. The visual analogue scale (VAS), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), neurological function, operation time, operative blood loss, hospital stay, correction and loss of Cobb angle, bone graft fusion time and complications were recorded and analyzed. RESULTS: Compared with structural bone graft group, the operation time of non-structural bone graft group was shorter and the operative blood loss was less, but the hospital stay was longer (P < 0.05). With the follow-up of 14-44 months, the VAS score, ESR, CRP and neurological function in the two groups were both improved (P < 0.05). The correction and loss of Cobb angle in the non-structural bone graft group were both smaller than those in the structural bone graft group (P < 0.05). The bone graft fusion time of the non-structural bone graft group was significantly shorter than the structural bone graft group (P < 0.05). No significant difference was found in the incidence of complications between the two groups (n.s.). CONCLUSION: Non-structural bone graft has less surgical trauma and shorter bone fusion time compared with structural bone graft in the surgical treatment of single segment thoracic tuberculosis. The two methods may achieve comparable clinical efficacy in alleviating symptoms, correcting kyphosis and improving neurological function for appropriate cases.

[Treatment of thoracolumbar spinal tuberculosis by posterior focus debridement and bone grafting and fixation combined with psoas abscess debridement and local chemotherapy via different approachs].

Objective: To compare the effectiveness of posterior and anterior psoas abscess debridement and local chemotherapy in abscess cavity combined with focus debridement, bone grafting, and fixation via posterior approach in treatment of thoracolumbar spinal tuberculosis, and explore the feasibility of psoas abscess debridement via posterior approach. Methods: Between June 2012 and December 2015, the clinical data of 37 patients with thoracolumbar spine tuberculosis and psoas abscess were retrospectively analyzed. All the patients underwent posterior focus debridement, bone grafting, and internal fixation, and were divided into two groups according to different approaches to psoas abscess debridement. Twenty-one patients in group A underwent abscess debridement and local chemotherapy in abscess cavity via posterior approach; 16 patients in group B underwent abscess debridement and local chemotherapy in abscess cavity via anterior approach. No significant difference was found between two groups in gender, age, disease duration, involved segments, preoperative erythrocyte sedimentation rate (ESR), preoperative C-reactive protein (CRP), side of psoas abscess, maximum transverse diameter and sagittal diameter of psoas abscess, accompanying abscess, abscess cavity separation, preoperative Cobb angle of involved segments, preoperative American Spinal Injury Association (ASIA) classification ( P>0.05). The operation time, intraoperative blood loss, hospitalization time, time of abscess absorption and bone fusion were recorded and compared between 2 groups. The change of pre- and post-operative involved segments Cobb angle was observed. Neurological function was assessed according to ASIA classification. Results: Except that the operation time of group B was significantly longer than that of group A ( t=-2.985, P=0.005), there was no significant difference in intraoperative blood loss, hospitalization time, time of abscess absorption and bone fusion between 2 groups ( P>0.05). All patients were followed up 18-47 months (mean, 31.1 months). No cerebrospinal fluid leakage occurred intra- and post-operation. Four patients in group A underwent second-stage operation of abscess debridement and local chemotherapy in abscess cavity via anterior approach. All patients got abscess absorption, meanwhile ESR and CRP level normalized at last follow-up. The involved segments Cobb angle improved significantly when compared with preoperative values in both 2 groups ( P<0.05); and there was no significant difference between 2 groups at last follow-up ( P>0.05). Nine patients with spinal cord injury had significant neurological recovery at last follow-up ( Z=-2.716, P=0.007). Conclusion: Posterior focus debridement, bone grafting, and internal fixation combined with abscess debridement and local chemotherapy in abscess cavity is effective in treatment of thoracolumbar spinal tuberculosis, but in some cases anterior abscess debridement is still required.

Caragaphenol a induces reactive oxygen species related apoptosis in human gastric cancer cells.

Caragaphenol A (CAA) is a novel resveratrol trimer isolated from the roots of Caraganastenophylla. However, the biological activity of CAA is still unknown. In the present study, we investigated the anticancer effects of CAA on gastric cancer cells. CAA selectively inhibited cell growth of human gastric cancer cells. Moreover, CAA potently induced cell cycle arrest at G2/M phase and apoptosis with the increased intracellular reactive oxidative species (ROS) level. Inhibition of ROS could partially rescue CAA-induced cell apoptosis. Additionally, DNA is not the target of CAA. CAA in combination with DDP or 5FU synergistically inhibited the growth of human gastric cancer cells. Altogether, our study provides the evidence for the potential therapeutic application of CAA on human gastric cancer.