ERK-activated CK-2 triggers blastema formation during appendage regeneration.

Appendage regeneration relies on the formation of blastema, a heterogeneous cellular structure formed at the injury site. However, little is known about the early injury-activated signaling pathways that trigger blastema formation during appendage regeneration. Here, we provide compelling evidence that the extracellular signal-regulated kinase (ERK)-activated casein kinase 2 (CK-2), which has not been previously implicated in appendage regeneration, triggers blastema formation during leg regeneration in the American cockroach, Periplaneta americana. After amputation, CK-2 undergoes rapid activation through ERK-induced phosphorylation within blastema cells. RNAi knockdown of CK-2 severely impairs blastema formation by repressing cell proliferation through down-regulating mitosis-related genes. Evolutionarily, the regenerative role of CK-2 is conserved in zebrafish caudal fin regeneration via promoting blastema cell proliferation. Together, we find and demonstrate that the ERK-activated CK-2 triggers blastema formation in both cockroach and zebrafish, helping explore initiation factors during appendage regeneration.

A comparative study on the features of breast sclerosing adenosis and invasive ductal carcinoma via ultrasound and establishment of a predictive nomogram.

Objective: To analyze the clinical and ultrasonic characteristics of breast sclerosing adenosis (SA) and invasive ductal carcinoma (IDC), and construct a predictive nomogram for SA. Materials and methods: A total of 865 patients were recruited at the Second Hospital of Shandong University from January 2016 to November 2022. All patients underwent routine breast ultrasound examinations before surgery, and the diagnosis was confirmed by histopathological examination following the operation. Ultrasonic features were recorded using the Breast Imaging Data and Reporting System (BI-RADS). Of the 865 patients, 203 (252 nodules) were diagnosed as SA and 662 (731 nodules) as IDC. They were randomly divided into a training set and a validation set at a ratio of 6:4. Lastly, the difference in clinical characteristics and ultrasonic features were comparatively analyzed. Result: There was a statistically significant difference in multiple clinical and ultrasonic features between SA and IDC (P<0.05). As age and lesion size increased, the probability of SA significantly decreased, with a cut-off value of 36 years old and 10 mm, respectively. In the logistic regression analysis of the training set, age, nodule size, menopausal status, clinical symptoms, palpability of lesions, margins, internal echo, color Doppler flow imaging (CDFI) grading, and resistance index (RI) were statistically significant (P<0.05). These indicators were included in the static and dynamic nomogram model, which showed high predictive performance, calibration and clinical value in both the training and validation sets. Conclusion: SA should be suspected in asymptomatic young women, especially those younger than 36 years of age, who present with small-size lesions (especially less than 10 mm) with distinct margins, homogeneous internal echo, and lack of blood supply. The nomogram model can provide a more convenient tool for clinicians.

Using Consensus Land Cover Data to Model Global Invasive Tree Species Distributions.

Invasive tree species threaten ecosystems, natural resources, and managed land worldwide. Land cover has been widely used as an environmental variable for predicting global invasive tree species distributions. Recent studies have shown that consensus land cover data can be an effective tool for species distribution modelling. In this paper, consensus land cover data were used as prediction variables to predict the distribution of the 11 most aggressive invasive tree species globally. We found that consensus land cover data could indeed contribute to modelling the distribution of invasive tree species. According to the contribution rate of land cover to the distribution of invasive tree species, we inferred that the cover classes of open water and evergreen broadleaf trees have strong explanatory power regarding the distribution of invasive tree species. Under consensus land cover changes, invasive tree species were mainly distributed near equatorial, tropical, and subtropical areas. In order to limit the damage caused by invasive tree species to global biodiversity, human life, safety, and the economy, strong measures must be implemented to prevent the further expansion of invasive tree species. We suggest the use of consensus land cover data to model global invasive tree species distributions, as this approach has strong potential to enhance the performance of species distribution modelling. Our study provides new insights into the risk assessment and management of invasive tree species globally.

Ultrasound Findings to Predict Risk of Recurrence in Pediatric Intussusception After Air Enema Reduction.

OBJECTIVES: Intussusception is one of the most common abdominal emergencies in early children. Intussusception recurs in 8-20% of children after successful nonoperative reduction. The aim of this study was to explore the ultrasound findings to predict risk of recurrence in pediatric intussusception after air enema reduction. METHODS: A total of 336 intussusception children were followed up for 1 year after received successful air enema reduction. They were divided into the recurrent group and the non-recurrent group. The differences of clinical characteristics, ultrasonic features, and laboratory tests were analyzed by univariate analyses and the Cox proportional hazard model. RESULTS: Sixty-five children with recurrent intussusception were identified. There were statistically significances in the diameter of the mass, in the presence or absence of enlarged lymph nodes out of the sleeve, and in the sleeve between recurrent and non-recurrent groups (P < .05). Other ultrasonic features, clinical characteristics, and blood parameters had no differences (P > .05). Multivariate Cox proportional hazard model showed that the diameter of the mass and abdominal lymph nodes may be the risk factors of intussusception recurrence (HR = 1.395, 95% CI: 1.045~1.863 and HR = 2.078, 95% CI: 1.118~3.865, P < .05). The cut-off value of mass diameter was 2.55 cm, above which recurrence is more likely. CONCLUSIONS: Intussusception recurrence was prone with greater mass diameter (>2.55 cm) and enlarged abdominal lymph nodes. Although these ultrasound findings for recurrence do not necessarily reduce the rate of recurrence, it can predict the recurrent possibility, and help the emergency physicians to be more vigilant in these children and better counsel parents upon discharge.

Optimal Rex shunt procedures as a treatment for pediatric extrahepatic portal hypertension.

PURPOSE: To assess the long-term results after Rex bypass (RB) shunt and Rex transposition (RT) shunt and determine the optimal approach. METHODS: Between 2010 and 2019, traditional RB shunt was performed in 24 patients, and modified RT shunt was performed in 23 children with extrahepatic portal hypertension (pHTN). A retrospective study was conducted based on comparative symptoms, platelet counts, color Doppler ultrasonography and computed tomographic portography of the portal system, and gastroscopic gastroesophageal varices postoperatively. The portal venous pressure was evaluated intraoperatively. RESULTS: The operation in the RB group was notably more time-consuming than that in the RT group (P < 0.05). Compared to RT shunt, the reduction in gastroesophageal varix grading, the increases in platelets, and the caliber of the bypass were greater in the RB group (P < 0.05). Although not statistically significant, higher morbidity of surgical complications was found after RT shunt (17.4%) compared with RB shunt (8.3%) with patency rates of 82.6 and 91.7%, respectively. Additionally, patients exhibited a lower rate of rebleeding under the RB procedure (12.5%) than under the RT procedure (21.7%). CONCLUSIONS: The RT procedure is an alternative option for the treatment of pediatric extrahepatic pHTN, and RB shunt is the preferred procedure in our center.

Sonographic features of umbilical vein recanalization for a Rex shunt on cavernous transformation of portal vein in children.

BACKGROUND: The Rex shunt was widely used as the preferred surgical approach for cavernous transformation of the portal vein (CTPV) in children that creates a bypass between the superior mesenteric vein and the intrahepatic left portal vein (LPV). This procedure can relieve portal hypertension and restore physiological hepatopetal flow. However, the modified procedure is technically demanding because it is difficult to make an end-to-end anastomosis of a bypass to a hypoplastic LPV. Many studies reported using a recanalized umbilical vein as a conduit to resolve this problem. However, the feasibility of umbilical vein recanalization for a Rex shunt has not been fully investigated. AIM: To investigate the efficacy of a recanalized umbilical vein as a conduit for a Rex shunt on CTPV in children by ultrasonography. METHODS: A total of 47 children who were diagnosed with CTPV with prehepatic portal hypertension in the Second Hospital, Cheeloo College of Medicine, Shandong University, were enrolled in this study. Fifteen children received a recanalized umbilical vein as a conduit for a Rex shunt surgery and were enrolled in group I. Thirty-two children received the classic Rex shunt surgery and were enrolled in group II. The sonographic features of the two groups related to intraoperative and postoperative variation in terms of bypass vessel and the LPV were compared. RESULTS: The patency rate of group I (60.0%, 9/15) was significantly lower than that of group II (87.5%, 28/32) 7 d after (on the 8th d) operation (P < 0.05). After clinical anticoagulation treatment for 3 mo, there was no significant difference in the patency rate between group I (86.7%, 13/15) and group II (90.6%, 29/32) (P > 0.05). Moreover, 3 mo after (at the beginning of the 4th mo) surgery, the inner diameter significantly widened and flow velocity notably increased for the bypass vessels and the sagittal part of the LPV compared to intraoperative values in both shunt groups (P < 0.05). However, there was no significant difference between the two surgical groups 3 mo after surgery (P > 0.05). CONCLUSION: For children with hypoplastic LPV in the Rex recessus, using a recanalized umbilical vein as a conduit for a Rex shunt may be an effective procedure for CTPV treatment.

The Effects of Lysimachia christinae Hance Extract Fractions on Endothelium-Dependent Vasodilatation.

BACKGROUND: Endothelium-dependent dilatation is a predictor for vascular function. NADPH oxidase-derived O2- can inactivate nitric oxide and induce vascular injury. METHOD: The crude ethanolic extract of Lysimachia christinae Hance were separated out 4 fractions of different olarities by petroleum ether, ethyl acetate, n-butanol (NB), and aqueous. The endothelial integrity was appraised by vascular tension measurement. Dihydroethidium was utilized to observe the vascular reactive oxygen species (ROS) production. Western-blot was adopted to detect protein expression. RESULTS: Among the 4 fractions of L. christinae Hance, the NB fraction showed the most potent capacity of promoting endothelium-dependent vascular relaxation and inhibiting ROS formation in aortic rings, which were likely attributed by suppressing the expression of NAD(P)H oxidase subunit (gp91phox, p47phox, and p67phox) and enhancing the phosphorylation of endothelial NOS in vascular tone. CONCLUSIONS: These results suggest that the NB fraction possess the strongest vascular pharmacological activities among the crude ethanolic extract of L. christinae Hance, which may help us for purifying bioactive constituents and discovering new drugs from this herb in future.

Curcumin protects against diabetic cardiomyopathy by promoting autophagy and alleviating apoptosis.

The effects of curcumin on regulating cardiac apoptosis and autophagy were analyzed in diabetic models both in vivo and in vitro. In vivo, experimental diabetes was induced in mice by low-dose STZ injection combined with a high-fat diet. In vitro, cultured H9c2 cardiomyoblasts were exposed to high d-glucose concentrations combined with palmitate. Our results showed that apoptosis was increased and autophagy was suppressed in the hearts of diabetic mice, which was ameliorated by curcumin treatment, ultimately improving cardiac function. Moreover, the inhibition of autophagy exacerbated apoptotic death in cardiac cells under diabetic condition. Curcumin activated AMPK and JNK1, which phosphorylated Bcl-2 and Bim and subsequently disrupted their interactions with Beclin1, thereby promoting autophagy and alleviating apoptosis respectively. In addition, AMPK-mediated inhibition of mTORC1 pathway likely played a role in regulating autophagy by curcumin under diabetic condition. Our study suggests that curcumin protects against diabetic cardiomyopathy by modulating the crosstalk between autophagic and apoptotic machinery. Modulation of autophagy may be an effective strategy for the treatment of cardiovascular diseases associated with diabetes.

Legumain protein as a potential predictive biomarker for Asian patients with breast carcinoma.

BACKGROUND: Treatment for breast cancer is mainly performed by surgical resection of primary tumors and chemotherapy. However, after tumor invasion and metastases, breast cancer is hard to control. Clarification of the pathogenic mechanisms would be helpful to the prognosis or therapy for the breast cancer. The aim of this study is to investigate the clinical and prognostic implications of legumain protein Materials and Methods: In this study, we examined mastectomy specimens from 114 breast cancer and matching, 26 adjacent non-cancerous tissues using immunohistochemistry. RESULTS: The results indicated that positive expression of legumain protein in breast cancer was 51.8 % (59/114) and the positive expression of legumain protein in adjacent non-cancerous tissue was 11.5% (3/26). It appeared to be related with lymph node metastasis of breast cancer (p=0.02) and correlation analysis indicated that legumain expression was correlated positively with the estrogen receptor (ER) and mutant-type p53 expression (both p<0.05). Positive legumain expression was significantly associated with shorter overall survival time in breast cancer patients (log-rank p<0.01). Multivariate survival analysis suggested that the positive legumain expression was an independent predictor of poorer overall survival in patients with breast cancer (HR=0.24; 95%CI 0.11-0.65, p=0.03). CONCLUSIONS: Legumain might be a new potential biomarker for breast cancer, which may reflect the prognosis and overall survival.