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Background: The impact of changes in skeletal muscle and sarcopenia on outcomes during neoadjuvant chemoradiotherapy (NACR) for patients with esophageal cancer remains controversial. Patients and Methods: We retrospectively analyzed the data of patients with locally advanced esophageal squamous cell cancer who received NACR followed by esophagectomy between June 2013 and December 2021. The images at third lumbar vertebra were analyzed to measure the cross-sectional area and calculate skeletal muscle index (SMI) before and after NACR. SMI less than 52.4 cm2/m2 for men and less than 38.5 cm2/m2 for women were defined as sarcopenia. The nonlinearity of the effect of percent changes in SMI (ΔSMI%) to survival outcomes was assessed by restricted cubic splines. Results: Overall, data of 367 patients were analyzed. The survival outcomes between sarcopenia and non-sarcopenia groups had no significant differences before NACR. However, patients in post-NACR sarcopenia group showed poor overall survival (OS) benefit (P = 0.016) and poor disease-free survival (DFS) (P = 0.043). Severe postoperative complication rates were 11.9% in post-NACR sarcopenia group and 5.0% in post-NACR non-sarcopenia group (P = 0.019). There was a significant non-linear relationship between ΔSMI% and survival outcomes (P < 0.05 for non-linear). On the multivariable analysis of OS, ΔSMI% > 12% was the independent prognostic factor (HR 1.76, 95% CI 1.03–2.99, P = 0.039) and significant difference was also found on DFS analysis (P = 0.025). Conclusions: Patients with post-neoadjuvant chemoradiotherapy sarcopenia have worse survival and adverse short-term outcomes. Moreover, greater loss in SMI is associated with increased risks of death and disease progression during neoadjuvant chemoradiotherapy, with maximum impact noted with SMI loss greater than 12%. [ABSTRACT FROM AUTHOR]

Aging and regeneration represent complex biological phenomena that have long captivated the scientific community. To fully comprehend these processes, it is essential to investigate molecular dynamics through a lens that encompasses both spatial and temporal dimensions. Conventional omics methodologies, such as genomics and transcriptomics, have been instrumental in identifying critical molecular facets of aging and regeneration. However, these methods are somewhat limited, constrained by their spatial resolution and their lack of capacity to dynamically represent tissue alterations. The advent of emerging spatiotemporal multi-omics approaches, encompassing transcriptomics, proteomics, metabolomics, and epigenomics, furnishes comprehensive insights into these intricate molecular dynamics. These sophisticated techniques facilitate accurate delineation of molecular patterns across an array of cells, tissues, and organs, thereby offering an in-depth understanding of the fundamental mechanisms at play. This review meticulously examines the significance of spatiotemporal multi-omics in the realms of aging and regeneration research. It underscores how these methodologies augment our comprehension of molecular dynamics, cellular interactions, and signaling pathways. Initially, the review delineates the foundational principles underpinning these methods, followed by an evaluation of their recent applications within the field. The review ultimately concludes by addressing the prevailing challenges and projecting future advancements in the field. Indubitably, spatiotemporal multi-omics are instrumental in deciphering the complexities inherent in aging and regeneration, thus charting a course toward potential therapeutic innovations. [ABSTRACT FROM AUTHOR]

Objectives: This study was to evaluate the application of automatic measurement based on convolutional neural network (CNN) technology in intracavitary ultrasound cine of anterior pelvic. Methods: A total of 500 patients who underwent pelvic floor ultrasound examination at Peking University Shenzhen Hospital from July 2021 to February 2022 were retrospectively retrieved by the picture archiving and communication system (PACS) system, and 300 cases were used as a training set. The training set was labeled by three experienced ultrasound physicians to train CNN models and develop an automatic measurement software. The remaining 200 cases were used as a test set. Automatic measurement software identified relevant anatomical structures frame by frame and determined the two frames with the greatest difference, calculated the bladder neck descent (BND), urethral rotation angle (URA), and retrovesical angle (RA). Meanwhile, two experienced ultrasound physicians evaluated the resting frame and the maximum Valsalva frame on the cines by manual visual evaluation, labeled the anatomical structures in the corresponding frame, such as the inferoposterior margin of pubic symphysis, the mid‐axis of pubic symphysis, bladder contour, and urethra in the front, and calculated BND, URA, and RA. Considering that the residual urine volume (RUV) in the bladder may affect the results, enrolled patients were grouped according to the RUV (10–50 mL, 50–100 mL, and >100 mL). The consistency of the results by automatic measurement and manual visual evaluation was evaluated using the intraclass correlation coefficient (ICC) and the Bland–Altman graph. Results: Of the 200 cases in the test set, 120 cases were successfully identified by the CNN automatic software with a 60% recognition rate. In the case of successful identification, the ICC of manual visual evaluation measurement and automatic measurement was 0.936 (BND), 0.911 (URA), 0.756 (RA in rest), and 0.877 (RA at maximum Valsalva), respectively. In addition, the RUV had a negligible effect on the consistency. The Bland–Altman plot shows the proportion of samples outside the limit was below 5%. Conclusions: CNN‐based automatic measurement software exhibited high reliability in anterior pelvic measurement, which results in a significantly enhanced measurement efficiency. [ABSTRACT FROM AUTHOR]

Aiming at the problem of difficult fault diagnosis work caused by the difficulty of data acquisition of the bearing in the traction part of a coal mining machine, a method of ADAMS simulation and HHT feature extraction of the bearing fault of a coal mining machine is proposed. First of all, take the traction section bearing as the research object, use the virtual prototype in the establishment of the healthy state of coal mining machine traction section model based on the establishment of the bearing inner ring fault, rolling body fault, outer ring fault of the coal mining machine traction section dynamics model, and then after the EMD decomposition, each IMF component of the Hilbert transform, to obtain the signal in the time-frequency plane of the time-frequency joint characteristics, to get the HHT marginal spectra and to different Under different working conditions, the bearing vibration signal features are mined by quantitative feature extraction. Finally, a variety of mainstream machine learning algorithms are introduced to classify the features, and the results show that the feature extraction method in this paper is universal and provides valuable theoretical support and technical guidance for the field application of coal mining machine-bearing fault diagnosis. [ABSTRACT FROM AUTHOR]

Skin wounds are characterized by injury to the skin due to trauma, tearing, cuts, or contusions. As such injuries are common to all human groups, they may at times represent a serious socioeconomic burden. Currently, increasing numbers of studies have focused on the role of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in skin wound repair. As a cell-free therapy, MSC-derived EVs have shown significant application potential in the field of wound repair as a more stable and safer option than conventional cell therapy. Treatment based on MSC-derived EVs can significantly promote the repair of damaged substructures, including the regeneration of vessels, nerves, and hair follicles. In addition, MSC-derived EVs can inhibit scar formation by affecting angiogenesis-related and antifibrotic pathways in promoting macrophage polarization, wound angiogenesis, cell proliferation, and cell migration, and by inhibiting excessive extracellular matrix production. Additionally, these structures can serve as a scaffold for components used in wound repair, and they can be developed into bioengineered EVs to support trauma repair. Through the formulation of standardized culture, isolation, purification, and drug delivery strategies, exploration of the detailed mechanism of EVs will allow them to be used as clinical treatments for wound repair. In conclusion, MSC-derived EVs-based therapies have important application prospects in wound repair. Here we provide a comprehensive overview of their current status, application potential, and associated drawbacks. [ABSTRACT FROM AUTHOR]

Skin wounds are characterized by injury to the skin due to trauma, tearing, cuts, or contusions. As such injuries are common to all human groups, they may at times represent a serious socioeconomic burden. Currently, increasing numbers of studies have focused on the role of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in skin wound repair. As a cell-free therapy, MSC-derived EVs have shown significant application potential in the field of wound repair as a more stable and safer option than conventional cell therapy. Treatment based on MSC-derived EVs can significantly promote the repair of damaged substructures, including the regeneration of vessels, nerves, and hair follicles. In addition, MSC-derived EVs can inhibit scar formation by affecting angiogenesis-related and antifibrotic pathways in promoting macrophage polarization, wound angiogenesis, cell proliferation, and cell migration, and by inhibiting excessive extracellular matrix production. Additionally, these structures can serve as a scaffold for components used in wound repair, and they can be developed into bioengineered EVs to support trauma repair. Through the formulation of standardized culture, isolation, purification, and drug delivery strategies, exploration of the detailed mechanism of EVs will allow them to be used as clinical treatments for wound repair. In conclusion, MSC-derived EVs-based therapies have important application prospects in wound repair. Here we provide a comprehensive overview of their current status, application potential, and associated drawbacks. [ABSTRACT FROM AUTHOR]

Background: Most bone-related injuries to grassroots troops are caused by training or accidental injuries. To establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops, it is imperative to develop new strategies and scaffolds to promote bone regeneration. Methods: In this study, a porous piezoelectric hydrogel bone scaffold was fabricated by incorporating polydopamine (PDA)-modified ceramic hydroxyapatite (PDA-hydroxyapatite, PHA) and PDA-modified barium titanate (PDA-BaTiO3, PBT) nanoparticles into a chitosan/gelatin (Cs/Gel) matrix. The physical and chemical properties of the Cs/Gel/PHA scaffold with 0–10 wt% PBT were analyzed. Cell and animal experiments were performed to characterize the immunomodulatory, angiogenic, and osteogenic capabilities of the piezoelectric hydrogel scaffold in vitro and in vivo. Results: The incorporation of BaTiO3 into the scaffold improved its mechanical properties and increased self-generated electricity. Due to their endogenous piezoelectric stimulation and bioactive constituents, the as-prepared Cs/Gel/PHA/PBT hydrogels exhibited cytocompatibility as well as immunomodulatory, angiogenic, and osteogenic capabilities; they not only effectively induced macrophage polarization to M2 phenotype but also promoted the migration, tube formation, and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) and facilitated the migration, osteo-differentiation, and extracellular matrix (ECM) mineralization of MC3T3-E1 cells. The in vivo evaluations showed that these piezoelectric hydrogels with versatile capabilities significantly facilitated new bone formation in a rat large-sized cranial injury model. The underlying molecular mechanism can be partly attributed to the immunomodulation of the Cs/Gel/PHA/PBT hydrogels as shown via transcriptome sequencing analysis, and the PI3K/Akt signaling axis plays an important role in regulating macrophage M2 polarization. Conclusion: The piezoelectric Cs/Gel/PHA/PBT hydrogels developed here with favorable immunomodulation, angiogenesis, and osteogenesis functions may be used as a substitute in periosteum injuries, thereby offering the novel strategy of applying piezoelectric stimulation in bone tissue engineering for the enhancement of combat effectiveness in grassroots troops. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19) remains a serious global threat. The metabolic analysis had been successfully applied in the efforts to uncover the pathological mechanisms and biomarkers of disease severity. Here we performed a quasi‐targeted metabolomic analysis on 56 COVID‐19 patients from Sierra Leone in western Africa, revealing the metabolomic profiles and the association with disease severity, which was confirmed by the targeted metabolomic analysis of 19 pairs of COVID‐19 patients. A meta‐analysis was performed on published metabolic data of COVID‐19 to verify our findings. Of the 596 identified metabolites, 58 showed significant differences between severe and nonsevere groups. The pathway enrichment of these differential metabolites revealed glutamine and glutamate metabolism as the most significant metabolic pathway (Impact = 0.5; −log10P = 1.959). Further targeted metabolic analysis revealed six metabolites with significant intergroup differences, with glutamine/glutamate ratio significantly associated with severe disease, negatively correlated with 10 clinical parameters and positively correlated with SPO2 (rs= 0.442, p = 0.005). Mini meta‐analysis indicated elevated glutamate was related to increased risk of COVID‐19 infection (pooled odd ratio [OR] = 2.02; 95% confidence interval [CI]: 1.17–3.50) and severe COVID‐19 (pooled OR = 2.28; 95% CI: 1.14–4.56). In contrast, elevated glutamine related to decreased risk of infection and severe COVID‐19, the pooled OR were 0.30 (95% CI: 0.20–0.44), and 0.44 (95% CI: 0.19–0.98), respectively. Glutamine and glutamate metabolism are associated with COVID‐19 severity in multiple populations, which might confer potential therapeutic target of COVID‐19, especially for severe patients. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS), caused by novel bunyavirus (SFTSV), is a hemorrhagic fever with a high mortality rate of over 10%. We have previously shown that granulocytic myeloid‐derived suppressor cell (gMDSC) might affect arginine metabolism, which was associated with decreased platelet count and T lymphocyte dysfunction in this disease. The study was designed to investigate the expression of the gMDSCs subsets in SFTS patients, and to evaluate its association with disease severity. A prospective study was performed on 166 confirmed SFTSV infected patients. Sequential blood samples were collected during hospitalization and after recovery. SFTSV RNA was quantified by real‐time RT‐PCR. The gMDSCs and NK cells were determined by flow cytometry analysis, which were associated with disease severity. Elevation of the activated gMDSC was observed in SFTS patients at the acute phase, with a significantly higher level of gMDSC attained in 79 severe and 29 fatal SFTS patients than in the mild patients. The NK cells were depleted at the early infection and not restored to normal level until 4 months after the disease. The expansion of gMDSC was accompanied by the elevated expressions of CD3‐ζ of NK and Arginase‐1, in contrast with the decreased reactive oxygen species (ROS) in gMDSC. The levels of NK, CD3‐ζ of NK, viral load, and platelet count were significantly associated with the level of gMDSC. Expansion of gMDSC was demonstrated in SFTS, which was associated with severe disease and suppressed antiviral NK cell via other mechanisms than Arginase‐1 or ROS. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES The aim of this study was to evaluate the short-term outcomes of neoadjuvant chemoimmunotherapy (NACI) followed by oesophagectomy for locally advanced oesophageal squamous carcinoma. METHODS Patients receiving NACI or chemoradiotherapy between September 2019 and September 2021 were identified. The primary outcomes were tumour response and survival. Secondary outcomes were toxic effects and postoperative complications. The propensity score matching for enrolled patients was performed. RESULTS Data of 149 patients with clinical stage II–IV oesophageal squamous cancer, including 55 receiving NACI and 94 receiving neoadjuvant chemoradiotherapy (NACR), were analysed after propensity score matching. With regard to tumour response score, 24 (43.6%) and 59 (62.8%) patients were scored 0/1 in the NACI and NACR groups, respectively (P  =   0.023). Of note, 17 (30.9%) patients in the NACI group achieved pathological complete response (CR) (ypT0N0), while 48 (51.1%) patients in NACR group achieved pathological CR (P  = 0.026). NACR was associated with the higher risk of postoperative pneumonia (P  =   0.034) and less lymph nodes and stations dissected (P  ≤   0.001). The 1-year cumulative overall survival rate was 94.5% and 86.2% in the NACI and NACR groups, respectively (P  = 0.170). CONCLUSIONS We found that NACI compared with NACR was associated with lower pneumonia rate and was safe and feasible for locally advanced oesophageal squamous cancer. However, the tumour regression score and the pathological CR rate of patients treated with neoadjuvant immunotherapy were lower than those of patients treated with NACR. The short-term follow-up results were comparable between 2 treatment modalities. [ABSTRACT FROM AUTHOR]

Background: In recent years, preoperative nutrition has received great attention, especially for patients who received surgical reconstruction of the digestive tract such as esophagectomy. Preoperative nutrition therapy was reported to accelerate the patient's postoperative recovery. In addition, immune suppression, nausea, and vomiting may lead to poor immune and nutritional status of patients with esophageal cancer who underwent neoadjuvant chemotherapy (NAC), which is not conducive to surgery. Therefore, preoperative nutritional treatment is necessary for patients with esophageal cancer who underwent NAC.Method: Patients with esophageal cancer who received NAC at Nanjing Jinling Hospital from January 2018 to September 2020 were retrospectively identified. Patients were divided into enteral immunonutrition (EIN) group (those who received a conventional diet and immunonutrition supplement, Peptisorb, Nutricia, 500 mL/day * 7 via oral intake), and control group (those who only received a conventional diet were divided into). The primary outcomes were immune and nutritional indicators changes, including immunoglobulin M (IgM), immunoglobulin A (IgA), immunoglobulin G (IgG), and albumin (ALB), which were measured at preoperative day (PRD) 7, PRD-1, postoperative day (POD) 1 and POD-7. The secondary outcomes were postoperative complications, adverse reactions, and length of hospital stay.Results: A total of 124 eligible patients were included in the study, with 21 patients in EIN group. After 1:2 matching, significant difference in baseline characteristics between the two groups was not observed (EIN: n = 21, Control group: n = 42). Compared with the control group, the IgA is significantly increased in the EIN group at POD-7 (p = 0.017). However, we observed that the IgM level in the control group was significantly higher than those in the EIN group at POD-7 (p = 0.007). The incidence of pneumonia and total complications in the EIN group were significantly lower than those in control group (p = 0.024, p = 0.028, respectively). There is no significant difference in ALB and adverse reactions between two groups (p = 0.303, p = 0.108, respectively).Conclusion: Immunonutritional supplement after NAC is an effective strategy to improve the postoperative immune status of esophageal cancer patients and could reduce the incidence of infectious complication. More well-designed prospective studies are needed to verify and update our finding. [ABSTRACT FROM AUTHOR]

Background: Malnutrition is highly prevalent in critically ill patients. The modified Nutrition Risk in the Critically ill (mNUTRIC) score has been introduced to evaluate the nutritional risk of patients in an intensive care unit (ICU). The mNUTRIC score is a predictive factor of mortality for patients in a medical or mixed ICU, whereas the relationship between mNUTRIC and prognosis of patients in a cardiothoracic surgery recovery unit (CSRU) is unclear and related researches are limited. Methods: We conducted this retrospective cohort study to explore the value of mNUTRIC score in CSRU patients. We identified totally 4059 patients from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III) database. Results: The optimal cut‐off value of mNUTRIC score was 4 and a total of 1498 (36.9%) patients were considered to be at high nutritional risk (mNUTRIC ≥ 4). A multivariate logistic regression model indicated that patients at high nutritional risk have higher hospital mortality compared to those at low nutritional risk (odds ratio = 2.49, 95% confidence interval (CI) = 1.32‐4.70, p = 0.005]. Furthermore, a Cox regression model was established adjusted for age, white blood cell and body mass index. The Kaplan–Meier curve indicated that patients at high nutritional risk have poorer 365‐days [hazard ratio (HR) = 1.76, 95% CI = 1.30‐2.37, p < 0.001] and 1000‐days (HR = 2.30, 95% CI = 1.87–2.83, p < 0.001) overall survival. Conclusions: The mNUTRIC score could not only predict hospital mortality, but also be an independent prognostic factor for long‐term survival in CSRU patients. More well‐designed clinical trials are needed to verify and update our findings. [ABSTRACT FROM AUTHOR]

Intensive crop rotation is one of the main causes of the continued depletion in soil potassium (K) content in the Yangtze River basin (YRB). However, recent studies have shown that soil K content is increasing in the YRB. Therefore, in this study, experimental and statistical data were collected to evaluate the soil K changes caused by K fertilizer application and straw return across the YRB. The results showed that soil available K increased, on average, by 21.7% across the YRB as a result of balanced K fertilization and an increasing proportion of straw return. From 1990 to 2019, K fertilizer input has increased from 10.1% to 24.1%, respectively. Meanwhile, from 2003 to 2011, the proportion of straw return increased by 32.8%. Considering these changes, we evaluated the effect of K fertilizer application and straw return on the soil K status. Overall, crop yield and soil available K increased by 9.9%, 7.3%, 16.3%, and 42.5%, 23.8%, and 66.4%, respectively, with K fertilization, straw return, and the concurrent use of both practices. Further, a synergistic increase in indigenous K input and soil available K alleviated the soil K negative balance and reduced the soil K fixation rate. In general, balanced K fertilization and an increasing proportion of straw return are the most vital measures for realizing the sustainable development of soil K across the YRB. The results of this research will provide useful information for sustainable K management and incentive policymaking. [ABSTRACT FROM AUTHOR]

The long-term outcomes of robotic-assisted McKeown esophagectomy (RAME) compared to thoraco-laparoscopic McKeown esophagectomy (TLME) for the patients with esophageal squamous cell carcinoma (ESCC) remain unclear. The aim of this study was to compare the number of dissected lymph nodes and long-term survival between RAME and TLME using a propensity score-matched (PSM) analysis. A total of 721 patients undergoing minimally invasive McKeown esophagectomy at our department from February 2015 to October 2019 were analyzed, including 310 patients in RAME group and 411 in TLME group. The exact numbers of lymph nodes including those among thoracic and abdominal categories as well as those along the recurrent laryngeal nerve (RLN) were all recorded. PSM analysis was applied to generate matched pairs for further comparison. All patients with R0 resection were followed with a strict follow-up period which range from 1 to 56 months. The effect of lymphadenectomy was compared between all patients in unmatched and matched groups. Long-term outcomes consisting of overall survival (OS), disease-free survival (DFS) and recurrence rate (including regional recurrence rate, systemic recurrence rate and mediastinal lymph nodes recurrence rate) were compared in R0 resection patients. Finally, 292 patients were identified for each cohort after PSM. RAME was found to yield significantly more left RLN lymph nodes (mean: 2.27 ± 0.90 vs. 2.09 ± 0.79; P  = 0.011) and more thoracic lymph nodes (mean: 12.60 ± 4.22 vs. 11.83 ± 3.12, P  = 0.012) compared with TLME after PSM analysis. There was no significant difference in the OS and DFS between the RAME and TLME group. Besides, total recurrences were recognized in 33 (11.7%) patients in the RAME group and 36 (12.9%) in the TLME group (P  = 0.676). The mediastinal lymph nodes recurrence rate in the RAME group was tended to be lower than that in the TLME group (2.5% vs. 5.4%, P  = 0.079). Therefore, RAME might be an alternative approach for the treatment of ESCC with more lymph nodes dissected and similar long-term survival outcomes compared to TLME. [ABSTRACT FROM AUTHOR]

Introduction: Among the many possible postoperative complications, anastomotic leakage (AL) is the most common and serious. Therefore, the purpose of this study was to explore the ability of various inflammatory and nutritional markers to predict postoperative AL in patients after esophagectomy.Methods: A total of 273 patients were retrospectively evaluated and enrolled into this study. Perioperative, surgery-related, tumor-related and laboratory tests data were extracted and analyzed. The discriminatory ability and optimal cut-off value was evaluated according to the receiver operating characteristic (ROC) curve analysis. Univariate and multivariate analyses were performed to access the potential risk factors for AL.Results: The overall incidence of AL was 12.5% (34/273). C-reactive protein-to-albumin ratio (CRP/ALB ratio) [AUC 0.943 (95% confidence interval (CI) = 0.911-0.976, p <  0.001)] and operation time [AUC 0.747 (95% CI = 0.679-0.815, p <  0.001)] had the greatest discrimination on AL prediction. Multivariate analysis demonstrated that CRP/ALB ratio and operation time were two independent risk factors for AL, and CRP/ALB ratio (OR = 102.909, p <  0.001) had an advantage over operation time (OR = 9.363, p = 0.020; Table 3).Conclusion: Operation time and postoperative CRP/ALB ratio were two independent predictive indexes for AL. Postoperative CRP/ALB ratio greater than 3.00 indicated a high risk of AL. For patients with abnormal postoperative CRP/ALB ratio, early non-operative treatment or surgical intervention are needed to reduce the serious sequelae of AL. [ABSTRACT FROM AUTHOR]

Although robotic techniques have been used for oesophagectomy for many years, whether robot-assisted minimally invasive oesophagectomy (RAMIE) can actually improve outcomes and surpass thoraco-laparoscopic minimally invasive oesophagectomy (MIE) in the success rate of lymph node dissection remains to be empirically demonstrated. Therefore, we performed this systematic review and meta-analysis of case–control studies to systematically compare the effect of lymph node dissection and the incidence of vocal cord palsy between RAMIE and MIE. The PubMed, EMBASE, and Web of Science databases were systematically searched up to December 1, 2019, for case–control studies that compared RAMIE with MIE. Thirteen articles were included, with a total of 1,749 patients with esophageal cancer, including 866 patients in the RAMIE group and 883 patients in the MIE group. RAMIE yielded significantly larger numbers of total dissected lymph nodes (WMD = 1.985; 95% CI, 0.448–3.523; P  = 0.011) and abdominal lymph nodes (WMD = 1.686; 95% CI, 0.420–2.951; P  = 0.009) as well as lymph nodes along RLN (WMD = 0.729; 95% CI, 0.348–1.109; P  < 0.001) than MIE. Additionally, RAMIE could significantly decrease estimated blood loss (WMD = -11.208; 95% CI, -19.358 to -3.058; P  = 0.007) and the incidence of vocal cord palsy (OR = 0.624; 95% CI, 0.411–0.947; P  = 0.027) compared to MIE. Compared with MIE, RAMIE resulted in a higher total lymph node yield and a higher lymph node yield in the abdomen and along RLN, along with reduced blood loss during surgery and the incidence of vocal cord palsy. Therefore, RAMIE could be considered to be a standard treatment, with less blood loss, lower incidence of vocal cord palsy, and more radical lymph node dissection, exhibiting superiority over MIE. [ABSTRACT FROM AUTHOR]

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus, SFTS virus (SFTSV), with fatal outcome developed in approximately 17% of the cases. Thrombocytopenia is a hallmark feature of SFTS, and associated with a higher risk of fatal outcome, however, the pathophysiological involvement of platelet in the clinical outcome of SFTS remained under-investigated. In the current study, by retrospectively analyzing 1538 confirmed SFTS patients, we observed that thrombocytopenia was associated with enhanced activation of the cytokine network and the vascular endothelium, also with a disturbed coagulation response. The platelet phenotypes were also extensively altered in the process of thrombocytopenia development of SFTS patients. More importantly, all these disturbed host responses were related to the severity of thrombocytopenia, thus were considered to play in a synergistic way to influence the disease outcome. Moreover, the clinical effect of platelet transfusion was assessed by comparing two groups of patients with or without receiving this therapy. As a result, we observed no therapy effect in altering frequencies of fatal outcome, clinical bleeding development, or dynamic change of platelet count during the hospitalization. It's suggested that platelet supplementation alone acted a minor role in improving disease outcome, therefore new therapeutic intervention to regulate host response should be proposed. The current results revealed some evidence of interrelationship between platelet count and clinical outcome of SFTS disease from the perspective of activation of the cytokine network, the vascular endothelium, and the coagulation/fibrinolysis system. These evaluations might help to attain a better understanding of the pathogenesis and therapy choice in SFTS. Author summary: Thrombocytopenia in SFTSV is a multifactor-process involving a combination of platelet size or morphology alterations, fibrinolysis activation and coagulation abnormalities, increased inflammatory response and endothelial injury. Platelet supplementation alone shows minor role in improving disease, therefore new therapeutic intervention to regulate host response should be proposed. [ABSTRACT FROM AUTHOR]

Background: According to previously published studies, esophagectomy with modified Collard anastomosis has been reported to have low incidences of anastomotic leak and stricture. However, the optional anastomotic method after esophagectomy is still controversial. We conducted this study to compare the incidence of postoperative anastomotic stricture formation and dysphagia over three years after an esophagectomy with modified Collard anastomosis (MC) or end‐to‐side (ETS) hand‐sewn anastomosis. Meanwhile, the early postoperative anastomotic leakage and other complications, hospital stay and 30‐ and 90‐day mortality were also evaluated. Methods: The clinical data of 905 patients undergoing McKeown esophagectomy were retrospectively reviewed. The rate of postoperative stricture formation after three years was demonstrated by stricture‐free survival which is the primary end‐point of this study. The incidence of dysphagia, first time of onset of stricture and number of dilatations were also recorded during follow‐up. Results: The incidence of anastomotic leak tended to be higher in the MC group compared with that in the ETS group (13.0% vs. 8.7%, P = 0.064). The rates of anastomotic stricture in the MC group were significantly less than in the ETS group (P = 0.004). The number of dilatations in the MC group were significantly greater than those in the ETS group (2.34 vs. 2.46, P = 0.011). Conclusions: A modified Collard cervical esophagogastric anastomosis was associated with lower rates of anastomotic stricture and dysphagia, compared with ETS hand‐sewn anastomosis. However, the modified Collard anastomosis is accompanied by an increased anastomotic leakage rate. [ABSTRACT FROM AUTHOR]

It is important to reduce oilseed rape (Brassica napus L.) yield loss subjected to waterlogging in the Yangtze River Basin under simplified fertilization background. How to alleviate the waterlogging loss by way of nitrogen (N) fertilizer application was studied. Three factors, including different N rates (0, 60, 120, 180, 240 and 300 kg N/hm²), N sources (controlled release urea and common urea) and water managements (waterlogging at seedling stage and normal drainage), were set in a field experiment. Yield and agronomy efficiency of oilseed rape at varying N rates were investigated, to identify effects of waterlogging at seedling on oilseed rape with different N fertilizer rates and their responses with controlled release urea one-off application (CRU1) and common urea split application (U4), respectively. Results showed that oilseed rape yield increased with the increase rate of N fertilizer application, plateaued at 240 kg N/hm². Yield of CRU1 were higher than that of U4 at 60-180 kg N/hm², but similar at 240-300 kg N/hm². N fertilizer application increased plant population density at harvest (PPDh), pod number per plant and seed number per plant, which resulted greater oilseed rape yield. Waterlogging at seedling stage decreased oil-seed rape yield by 1.1%-41.9%. The yield loss increased as N rates added, then decreased as CRU1 and U4 added to 120 and 180 kg N/hm², respectively. The largest yield loss of CRU1 and U4 were 29.8% and 41.9%, respectively. In case of waterlogging, PPDh decreased significantly (with decrease of 29.4-45.0%), but pod number per plant increased at the N rate of 0-60 kg N/hm². When N rate was at 120-180 kg N/hm², both PPDh and pod number per plant decreased by 19.5-33.7% and 1.4-17.7% once subjected to waterlogging, respectively. While as N rate was more than180 kg N/hm², both the PPDh and pod number per plant decrease was reduced (with the decrease of 5-30.9% and 3.6-9.5%, respectively). Yield losses induced by waterlogging of CRU1 were larger than that of U4 at same N rate. Waterlogging at seedling stage decreased N agronomy efficiency by 8.4-51.9%. Generally, the agronomy efficiency decrease with sufficient N supply (240-300 kg N/hm²) was less than that of insufficient N supply treatments (120-180 kg N/hm²), and CRU1 (with the average agronomy efficiency decrease of 36.5%) had greater agronomy efficiency decrease relative to U4 treatments (with the average agronomy efficiency decrease of 17.3%)). In a word, waterlogging at seedling stage had greater impact on direct-sown winter oilseed rape yield with CRU1 application relative to U4. In the area with low indigenous N supply capacity, available N topdressing with appropriate rate after waterlogging can alleviate the yield loss and ensure the high production of oilseed rape. [ABSTRACT FROM AUTHOR]

Objective: To survey the health-related quality of life (HRQoL) and its influencing factors among patients with COVID-19 in their first medical follow up. Methods: All patients diagnosed with COVID-19 were discharged from 12 hospitals in Wenzhou, Zhejiang from Jan 17, 2020 to Mar 20, 2020. Prospectively collected and analyzed data included demographics, clinical symptoms, comorbidity, and chest CT imaging features at the first follow up, 1 month after discharge. All patients underwent the HRQoL evaluation with the Chinese version of Short-Form 36-item questionnaire (SF-36) as well as a general condition questionnaire. Factors associated with SF-36 were constructed using linear regression. Predictors of impaired physical component summary (PCS) and a mental component summary (MCS) were identified by logistic regression. Results: SF-36 demonstrated a significant difference in HRQoL in patients with COVID-19, except in physical function (PF), when compared to the general Chinese population (p <0.05). The multiple linear regressions demonstrated that age was negatively associated with PF, role physical (RP), but positively associated with vitality (VT) (p <0.05). PF, bodily pain (BP), and role-emotional (RE) were negatively associated with the female sex (p <0.05). For mental health, the clinical subtypes were significant associated factors (p < 0.05). Length of stay (LOS) was strongly negatively associated with RE and RP, and positively associated with VT (p < 0.05). Logistical regression revealed that non-obese overweight (OR 3.71) and obesity (OR 3.94) were risk factors for a low PCS and female sex (OR 2.22) was a risk factor for a low MCS. Conclusions: Health-related quality of life was poor among COVID-19 patients at the 1 month follow-up. Patients suffered from significant physical and psychological impairment. Therefore, prospective monitoring of individuals exposed to SARS-CoV-2 is needed in order to fully understand the long-term impact of COVID-19, as well as to inform prompt and efficient interventions to alleviate suffering. [ABSTRACT FROM AUTHOR]

Background: Anemarrhenae rhizoma (AR) is widely used for the treatment of febrile diseases, cough, and diabetes in traditional Chinese medicines. AR mainly contains flavonoids and steroidal saponins, such as neomangiferin, mangiferin, timosaponin BII, timosaponin BIII, and timosaponin AIII, which showed various biological activities. Objective: The main objective of the study is to establish an ultra-high-performance liquid chromatography-tandem mass spectrometry (MS/MS) method to determine the concentrations of five bioactive constituents in rats' plasma and various tissues. Materials and Methods: The analytes were separated on a C18reversed-phase column. A triple-quadrupole MS/MS equipped with an electrospray ionization source was used as a detector. The main pharmacokinetic parameters were estimated with Drug and Statistics 2.0 Software Package. Results: Neomangiferin and mangiferin exhibit poor oral absorption and slow clearance from the body. Timosaponin BII and timosaponin BIII could be quickly absorbed into the blood circulation and showed double plasma concentration peaks. Timosaponin AIII exhibited a single peak in the plasma concentration-time plot and pharmacokinetic parameters of timosaponin AIII indicated slower absorption, longer body residence time, and slower elimination than timosaponin BII and timosaponin BIII. The five analytes were widely distributed to most of the tissues. Neomangiferin and mangiferin exhibited the maximum concentration in the lung at 6 h after oral administration, the highest levels of timosaponin BII and timosaponin BIII were also observed in the lung at 1 h after oral administration, and the maximum concentration of timosaponin AIII was observed in the liver. Conclusion: The findings of the present study might be helpful to better understand the pharmacokinetics and distribution of AR bioactive constituents in vivo, which would facilitate the clinical application of AR. [ABSTRACT FROM AUTHOR]

Three new glycosides (1–3), together with six known ones (4–9), were isolated from the root bark of Lycium chinense. Their structures were elucidated on the basis of MS and NMR spectroscopic data. Five compounds (3, 5, 6, 8, and 9) exhibited potent antihyperlipidemic activities in HepG2 cells as assessed by Oil Red O staining and significant inhibition of intracellular triglyceride (TG) levels, whereas two compounds (5 and 9) significantly reduced total cholesterol (TC) levels. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is caused by a novel bunyavirus SFTSV. Currently our knowledge of the host-related factors that influence the pathogenesis of disease is inadequate to allow prediction of fatal outcome. Here we conducted a prospective study of the largest database on the SFTS patients, to identify the presence of comorbidities in SFTS, and estimate their effect on the fatal outcome. Among 2096 patients eligible for inclusion, we identified nine kinds of comorbidities, from which hyperlipidemia (12.2%; 95% CI: 10.8%–13.6%), hypertension (11.0%; 95% CI: 9.6%–12.3%), chronic viral hepatitis (CVH) (9.3%; 95% CI: 8.1%–10.5%), and diabetes mellitus (DM) (6.8%; 95% CI: 5.7%–7.9%) were prevalent. Higher risk of death was found in patients with DM (adjusted OR = 2.304; 95% CI: 1.520–3.492; P<0.001), CVH (adjusted OR = 1.551; 95% CI: 1.053–2.285; P = 0.026) and chronic obstructive pulmonary diseases (COPD) (adjusted OR = 2.170; 95% CI: 1.215–3.872; P = 0.009) after adjusting for age, sex, delay from disease onset to admission and treatment regimens. When analyzing the comorbidities separately, we found that the high serum glucose could augment diseases severity. Compared to the group with max glucose < 7.0 mmol/L, patients with glucose between 7.0–11.1 mmol/L and glucose ≥11.1 mmol/L conferred higher death risk, with the adjusted OR to be 1.467 (95% CI: 1.081–1.989; P = 0.014) and 3.443 (95% CI: 2.427–4.884; P<0.001). Insulin therapy could effectively reduce the risk of severe outcome in DM patients with the adjusted OR 0.146 (95% CI: 0.058–0.365; P<0.001). For CVH patients, severe damage of liver and prolongation of blood coagulation time, as well as high prevalence of bleeding phenotype were observed. These data supported the provocative hypothesis that treating SFTS related complications can attain potentially beneficial effects on SFTS. [ABSTRACT FROM AUTHOR]

A compact dual-wideband (DWB) bandpass filter utilizing open-shorted coupled lines (OSCL) is proposed in this paper. The introduction of the folded structure not only reduces the overall size but also contribute to the split of the transmission zero (TZ), which improves the selectivity effectively. Six transmission poles and five TZs are realized utilizing the shorted-circuit stub and OSCL. The characteristic of the flexible adjustment method of TZs guarantees an independently wide adjustable range of the bandwidth. For demonstration, a DWB filter (3 dB bandwidth 120 and 28%, respectively) is designed and fabricated. The filter is compact and has the characteristics of extraordinary wide bandwidth, low insertion loss, as well as high selectivity. [ABSTRACT FROM AUTHOR]

Silk was easily dyed in traditional textile industry because of its strong affinity to many colorants. Herein, the biocompatible silk fibroin was firstly extracted from Bombyx mori silkworm cocoons. And SF nanoparticles (SFNPs) were prepared for dyeing indocyanine green (ICG) and construct a therapeutic nano-platform (ICG-SFNPs) for photo-thermal therapy of glioblastoma. ICG was easily encapsulated into SFNPs with a very high encapsulation efficiency reaching to 97.7 ± 1.1%. ICG-SFNPs exhibited a spherical morphology with a mean particle size of 209.4 ± 1.4 nm and a negative zeta potential of −31.9 mV, exhibiting a good stability in physiological medium. Moreover, ICG-SFNPs showed a slow release profile of ICG in vitro, and only 24.51 ± 2.27% of the encapsulated ICG was released even at 72 h. Meanwhile, ICG-SFNPs exhibited a more stable photo-thermal effect than free ICG after exposure to near-infrared irradiation. The temperature of ICG-SFNPs rapidly increased by 33.9 °C within 10 min and maintained for a longer time. ICG-SFNPs were also easily internalized with C6 tumor cells in vitro, and a strong red fluorescence of ICG was observed in cytoplasm for cellular imaging. In vivo imaging showed that ICG-SFNPs were effectively accumulated inside tumor site of C6 glioma-bearing Xenograft nude mice through vein injection. Moreover, the temperature of tumor site was rapidly rising up to kill tumor cells after local NIR irradiation. After treatment, its growth was completely suppressed with the relative tumor volume of 0.55 ± 033 while free ICG of 33.72 ± 1.90. Overall, ICG-SFNPs may be an effective therapeutic means for intraoperative phototherapy and imaging. [ABSTRACT FROM AUTHOR]

The tenacious prevalence of human pancreatic cancer such as diabetes mellitus and adenocarcinoma has prompted huge research interest in better understanding of pancreatic organogenesis. The plethora of signaling pathways involved in pancreas development is activated in a highly coordinated manner to assure unmitigated development and morphogenesis in vertebrates. Therefore, a complex mesenchymal–epithelial signaling network has been implicated to play a pivotal role in organogenesis through its interactions with other germ layers, specifically the endoderm. The Fibroblast Growth Factor Receptor FGFR2-IIIb splicing isoform (FGFR2b) and its high affinity ligand Fibroblast Growth Factor 10 (FGF10) are expressed in the epithelium and mesenchyme, respectively, and therefore are well positioned to transmit mesenchymal to epithelial signaling. FGF10 is a typical paracrine FGF and chiefly mediates biological responses by activating FGFR2b with heparin/heparan sulfate (HS) as cofactor. A substantial number of studies using genetically engineered mouse models have demonstrated an essential role of FGF10 in the development of many organs and tissues including the pancreas. During mouse embryonic development, FGF10 signaling is crucial for epithelial cell proliferation, maintenance of progenitor cell fate and branching morphogenesis in the pancreas. FGF10 is also implicated in pancreatic cancer, and that overexpression of FGFR2b is associated with metastatic invasion. A thorough understanding of FGF10 signaling machinery and its crosstalk with other pathways in development and pathological states may provide novel opportunities for pancreatic cancer targeted therapy and regenerative medicine. [ABSTRACT FROM AUTHOR]

Arginine deficiency is involved in thrombocytopenia and immunosuppression in severe fever with thrombocytopenia syndrome. Arginine arbitrates thrombocytopenia: SFTS virus is a bunyavirus named for the disease it causes, severe fever with thrombocytopenia syndrome. It has only recently been discovered, and little is known about its pathogenesis or how to intervene. Li et al. conducted an observational study in a hospital setting to identify differences between fatal cases and those that went on to recover and discovered that decreased arginine was associated with thrombocytopenia and death. They then performed a randomized controlled clinical trial to supplement patients with arginine. Patients receiving arginine had decreased platelet activation and faster viral clearance. This study may pave the way for a better understanding and treatment for SFTS virus. Severe fever with thrombocytopenia syndrome (SFTS) caused by a recently identified bunyavirus, SFTSV, is an emerging infectious disease with extensive geographical distribution and high mortality. Progressive viral replication and severe thrombocytopenia are key features of SFTSV infection and fatal outcome, whereas the underlying mechanisms are unknown. We revealed arginine deficiency in SFTS cases by performing metabolomics analysis on two independent patient cohorts, suggesting that arginine metabolism by nitric oxide synthase and arginase is a key pathway in SFTSV infection and consequential death. Arginine deficiency was associated with decreased intraplatelet nitric oxide (Plt-NO) concentration, platelet activation, and thrombocytopenia. An expansion of arginase-expressing granulocytic myeloid-derived suppressor cells was observed, which was related to T cell CD3-ζ chain down-regulation and virus clearance disturbance, implicating a role of arginase activity and arginine depletion in the impaired anti-SFTSV T cell function. Moreover, a comprehensive measurement of arginine bioavailability, global arginine bioavailability ratio, was shown to be a good prognostic marker for fatal prediction in early infection. A randomized controlled trial demonstrated that arginine administration was correlated with enhanced Plt-NO concentration, suppressed platelet activation, and elevated CD3-ζ chain expression and eventually associated with an accelerated virus clearance and thrombocytopenia recovery. Together, our findings revealed the arginine catabolism pathway–associated regulation of platelet homeostasis and T cell dysregulation after SFTSV infection, which not only provided a functional mechanism underlying SFTS pathogenesis but also offered an alternative therapy choice for SFTS. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is caused by a novel bunyavirus, SFTSV. We assessed whether the single nucleotide polymorphisms (SNPs) in the tumor necrosis factor-alpha (TNF-α) were associated with risk to severity of SFTS. Five TNF-α SNPs (SNP1: T-1031C; SNP2: C-863A; SNP3: C-857T; SNP4: G-308A; SNP5: G-238A) were genotyped in 987 hospitalized SFTS patients and 633 asymptomatic/mild SFTSV-infected subjects of Chinese Han origin. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). The hospitalized SFTS patients had significantly lower frequency of G-238A A allele than those with mild/asymptomatic infection (P = 0.006). Furthermore, T-1031C C allele (P < 0.001) and G-238A A allele (P < 0.001) were significantly associated with decreased risk of death. Multiple haplotypes were significantly associated with decreased risk of SFTS hospital admission (SNP1-2, CC; SNP1-3, CCC; SNP1-4, CCCG; SNP1-5, CCCGA; SNP2-4, CCGA; SNP3-5, CGA; SNP4-5, GA) and death (SNP1-2, CA; SNP1-3, CAG; SNP1-4, CACG; SNP1-5, CACGG; SNP2-3, AC; SNP2-4, ACG; SNP2-5, ACGG) after correction for multiple comparisons. By using the ELISA assay, we observed that TNF-α concentration of hospitalized patients was significantly increased in acute phase than in convalescent phase (P < 0.001). Elevated TNF-α concentration was also revealed from fatal patients (P < 0.001). The -238A allele was associated with decreased serum TNF-α levels in SFTS patients in acute phase (P = 0.01). Our findings suggest that polymorphisms in TNF-α gene may play a role in mediating the risk to disease severity of SFTS in Chinese Han population. [ABSTRACT FROM AUTHOR]

Silk was easily dyed in traditional textile industry because of its strong affinity to many colorants. Herein, the biocompatible silk fibroin was firstly extracted from Bombyx mori silkworm cocoons. And SF nanoparticles (SFNPs) were prepared for dyeing indocyanine green (ICG) and construct a therapeutic nano-platform (ICG-SFNPs) for photo-thermal therapy of glioblastoma. ICG was easily encapsulated into SFNPs with a very high encapsulation efficiency reaching to 97.7 ± 1.1%. ICG-SFNPs exhibited a spherical morphology with a mean particle size of 209.4 ± 1.4 nm and a negative zeta potential of −31.9 mV, exhibiting a good stability in physiological medium. Moreover, ICG-SFNPs showed a slow release profile of ICG in vitro, and only 24.51 ± 2.27% of the encapsulated ICG was released even at 72 h. Meanwhile, ICG-SFNPs exhibited a more stable photo-thermal effect than free ICG after exposure to near-infrared irradiation. The temperature of ICG-SFNPs rapidly increased by 33.9 °C within 10 min and maintained for a longer time. ICG-SFNPs were also easily internalized with C6 tumor cells in vitro, and a strong red fluorescence of ICG was observed in cytoplasm for cellular imaging. In vivo imaging showed that ICG-SFNPs were effectively accumulated inside tumor site of C6 glioma-bearing Xenograft nude mice through vein injection. Moreover, the temperature of tumor site was rapidly rising up to kill tumor cells after local NIR irradiation. After treatment, its growth was completely suppressed with the relative tumor volume of 0.55 ± 033 while free ICG of 33.72 ± 1.90. Overall, ICG-SFNPs may be an effective therapeutic means for intraoperative phototherapy and imaging. [ABSTRACT FROM AUTHOR]

Ischaemia-reperfusion injury (I/RI) is a common cause of acute kidney injury (AKI). The molecular basis underlying I/RI-induced renal pathogenesis and measures to prevent or reverse this pathologic process remains to be resolved. Basic fibroblast growth factor (FGF2) is reported to have protective roles of myocardial infarction as well as in several other I/R related disorders. Herein we present evidence that FGF2 exhibits robust protective effect against renal histological and functional damages in a rat I/RI model. FGF2 treatment greatly alleviated I/R-induced acute renal dysfunction and largely blunted I/R-induced elevation in serum creatinine and blood urea nitrogen, and also the number of TUNEL-positive tubular cells in the kidney. Mechanistically, FGF2 substantially ameliorated renal I/RI by mitigating several mitochondria damaging parameters including pro-apoptotic alteration of Bcl2/Bax expression, caspase-3 activation, loss of mitochondrial membrane potential and KATP channel integrity. Of note, the protective effect of FGF2 was significantly compromised by the KATP channel blocker 5-HD. Interestingly, I/RI alone resulted in mild activation of FGFR, whereas FGF2 treatment led to more robust receptor activation. More significantly, post-I/RI administration of FGF2 also exhibited robust protection against I/RI by reducing cell apoptosis, inhibiting the release of damage-associated molecular pattern molecule HMBG1 and activation of its downstream inflammatory cytokines such as IL-1α, IL-6 and TNF α. Taken together, our data suggest that FGF2 offers effective protection against I/RI and improves animal survival by attenuating mitochondrial damage and HMGB1-mediated inflammatory response. Therefore, FGF2 has the potential to be used for the prevention and treatment of I/RI-induced AKI. [ABSTRACT FROM AUTHOR]

Background: Pathogenesis of severe fever with thrombocytopenia syndrome (SFTS) has not been well described yet. Recent studies indicate that SFTSV could replicate in endothelial cells. Here we performed a case-control study to determine whether endothelial activation/dysfunction occurred in SFTSV infection and to identify the biomarkers reflecting endothelial dysfunction. Methodology/Principal findings: In a case-control study of 134 SFTS patients and 68 healthy controls, serum levels of plasminogen activator inhibitor 1, tissue plasminogen activator, P-selectin, platelet endothelial cell adhesion molecular, CD40 ligand, E-selectin, vascular endothelial growth factor A, serum amyloid antigen 1 (SAA-1) and vascular cell adhesion molecular 1 were significantly enhanced in the patients than the controls (all P<0.05), indicating the occurrence of endothelial activation/dysfunction in SFTS. The intercellular adhesion molecular 1 (ICAM-1) and SAA-1 at the convalescent phase were also significantly associated with severe patients, after adjusting for the potential confounders. The odds ratio was estimated to be 3.364 (95% CI 1.074–10.534) for ICAM-1, and 1.881 (95% CI 1.166–3.034) for SAA-1, respectively. Cutoff value of 1.1×107 pg/mL SAA-1 or 1.2×106 pg/mL ICAM-1 were found to have moderate power of predicting fatal cases. Conclusions: The endothelial dysfunction may be one of the pathogenic mechanism of SFTS. The serum levels of ICAM-1 and SAA-1 might be used to predict adverse outcome. [ABSTRACT FROM AUTHOR]

The insulin-sensitive glucose transporter 4 (GLUT4) is a predominant facilitative glucose transporter in vascular smooth muscle cells (VSMCs) and is significantly upregulated in rabbit neointima. This study investigated the role of GLUT4 in VSMC proliferation, the cellular mechanism underlying PDGF-BB-stimulated GLUT4 translocation, and effects of SM22α, an actin-binding protein, on this process. Chronic treatment of VSMCs with PDGF-BB significantly elevated GLUT4 expression and glucose uptake. PDGF-BB-induced VSMC proliferation was dependent on GLUT4-mediated glucose uptake. Meanwhile, the response of GLUT4 to insulin decreased in PDGF-BB-stimulated VSMCs. PDGF-BB-induced GLUT4 translocation partially rescued glucose utilization in insulin-resistant cells. Immunofluorescence and western blot analysis revealed that PDGF-BB induced GLUT4 translocation in an actin dynamics-dependent manner. SM22α disruption facilitated GLUT4 translocation and glucose uptake by promoting actin dynamics and cortical actin polymerization. Similar results were observed in VSMCs of SM22α mice. The in vivo experiments showed that the glucose level in the neointima induced by ligation was significantly increased in SM22α mice, accompanied by increased neointimal thickness, compared with those in wild-type mice. These findings suggest that GLUT4-mediated glucose uptake is involved in VSMC proliferation, and provide a novel link between SM22α and glucose utilization in PDGF-BB-triggered proliferation. Key Messages: • GLUT4-mediated glucose uptake is required for the VSMC proliferation. • PDGF-BB-induced GLUT4 translocation partially rescues glucose uptake in insulin resistance. • SM22α disruption enhances PDGF-BB-induced GLUT4 translocation. • Glucose level in injured vascular tissue is positively correlated with neointimal hyperplasia. [ABSTRACT FROM AUTHOR]

Many traumatic brain injury (TBI) survivors sustain neurological disability and cognitive impairments due to the lack of defined therapies to reduce TBI-induced blood-brain barrier (BBB) breakdown. Exogenous basic fibroblast growth factor (bFGF) has been shown to have neuroprotective function in brain injury. The present study therefore investigates the beneficial effects of bFGF on the BBB after TBI and the underlying mechanisms. In this study, we demonstrate that bFGF reduces neurofunctional deficits and preserves BBB integrity in a mouse model of TBI. bFGF suppresses RhoA and upregulates tight junction proteins, thereby mitigating BBB breakdown. In vitro, bFGF exerts a protective effect on BBB by upregulating tight junction proteins claudin-5, occludin, zonula occludens-1, p120-catenin, and β-catenin under oxygen glucose deprivation/reoxygenation (OGD) in human brain microvascular endothelial cells (HBMECs). Both the in vivo and in vitro effects are related to the activation of the downstream signaling pathway, PI3K/Akt/Rac-1. Inhibition of the PI3K/Akt or Rac-1 by specific inhibitors LY294002 or si-Rac-1, respectively, partially reduces the protective effect of bFGF on BBB integrity. Overall, our results indicate that the protective role of bFGF on BBB involves the regulation of tight junction proteins and RhoA in the TBI model and OGD-induced HBMECs injury, and that activation of the PI3K/Akt /Rac-1 signaling pathway underlies these effects. [ABSTRACT FROM AUTHOR]

The blood-spinal cord barrier (BSCB) plays important roles in the recovery of spinal cord injury (SCI), and caveolin-1 is essential for the integrity and permeability of barriers. Basic fibroblast growth factor (bFGF) is an important neuroprotective protein and contributes to the survival of neuronal cells. This study was designed to investigate whether bFGF is beneficial for the maintenance of junction proteins and the integrity of the BSCB to identify the relations with caveolin-1 regulation. We examined the integrity of the BSCB with Evans blue dye and fluorescein isothiocyanate-dextran extravasation, measured the junction proteins and matrix metalloproteinases, and evaluated the locomotor function recovery. Our data indicated that bFGF treatment improved the recovery of BSCB and functional locomotion in contusive SCI model rats, reduced the expression and activation of matrix metalloproteinase-9, and increased the expressions of caveolin-1 and junction proteins, including occludin, claudin-5, p120-catenin, and β-catenin. In the brain, in microvascular endothelial cells, bFGF treatment increased the levels of junction proteins, caveolin-1 small interfering RNA abolished the protective effect of bFGF under oxygen-glucose deprivation conditions, and the expression of fibroblast growth factor receptor 1 and co-localization with caveolin-1 decreased significantly, which could not be reversed by bFGF treatment. These findings provide a novel mechanism underlying the beneficial effects of bFGF on the BSCB and recovery of SCI, especially the regulation of caveolin-1. [ABSTRACT FROM AUTHOR]

Introduction:The accumulation of unfolded protein in the endoplasmic reticulum (ER) initiates an unfolded protein response (UPR) via three signal transduction cascades, which involve protein kinase RNA-like ER kinase (PERK), inositol requiring enzyme-1α (IRE1α) and activating transcription factor-6α (ATF6α). An ER stress response is observed in nearly all physiologies related to acute and chronic liver disease and therapeutic targeting of the mechanisms implicated in UPR signaling have attracted considerable attention. Areas covered:This review focuses on the correlation between ER stress and liver disease and the possible targets which may drive the potential for novel therapeutic intervention. Expert Commentary:We describe pathways which are involved in UPR signaling and their potential correlation with various liver diseases and underlying mechanisms which may present opportunities for novel therapeutic strategies are discussed. [ABSTRACT FROM PUBLISHER]

Clinical translation of growth factor therapies faces multiple challenges; the most significant one is the short half-life of the naked protein. Gelatin nanostructured lipid carriers (GNLs) had previously been used to encapsulate the basic fibroblast growth factor to enhance the functional recovery in hemiparkinsonian rats. In this research, we comparatively study the enhanced therapy between nerve growth factor (NGF) loaded GNLs (NGF-GNLs) and NGF only in spinal cord injury (SCI). The effects of NGF-GNLs and NGF only were tested by the Basso-Beattie-Bresnahan (BBB) locomotion scale, inclined plane test, and footprint analysis. Western blot analysis and immunofluorescent staining were further performed to identify the expression of ER stress-related proteins, neuron-specific marker neuronal nuclei (NeuN), and growth-associated protein 43 (GAP43). Correlated downstream signals Akt/GSK-3β and ERK1/2 were also analyzed with or without inhibitors. Results showed that NGF-GNLs, compared to NGF only, enhanced the neuroprotection effect in SCI rats. The ER stress-induced apoptosis response proteins CHOP, GRP78 and caspase-12 inhibited by NGF-GNL treatment were more obvious. Meanwhile, NGF-GNLs in the recovery of SCI are related to the inhibition of ER stress-induced cell death via the activation of downstream signals PI3K/Akt/GSK-3β and ERK1/2. [ABSTRACT FROM AUTHOR]

Growth factors are a class of cytokines that stimulate cell growth and are widely used in clinical practice, such as wound healing, revascularization, bone repair, and nervous system disease. However, free growth factors have a short half-life and are instable in vivo. Therefore, the search of excellent carriers to enhance sustained release of growth factors in vivo has become an area of intense research interest. The development of controlled-release systems that protect the recombinant growth factors from enzymatic degradation and provide sustained delivery at the injury site during healing should enhance the growth factor’s application in tissue regeneration. Thus, this study reviews current research on commonly used carriers for sustained release of growth factors and their sustained release effects for preservation of their bioactivity and their accomplishment in tissue engineering approaches. [ABSTRACT FROM AUTHOR]

In adaptation to oncogenic signals, pancreatic ductal adenocarcinoma (PDAC) cells undergo epithelial-mesenchymal transition (EMT), a process combining tumor cell dedifferentiation with acquisition of stemness features. However, the mechanisms linking oncogene-induced signaling pathways with EMT and stemness remain largely elusive. Here, we uncover the inflammation-induced transcription factor NFATc1 as a central regulator of pancreatic cancer cell plasticity. In particular, we show that NFATc1 drives EMT reprogramming and maintains pancreatic cancer cells in a stem cell-like state through Sox2-dependent transcription of EMT and stemness factors. Intriguingly, NFATc1-Sox2 complexmediated PDAC dedifferentiation and progression is opposed by antithetical p53-miR200c signaling, and inactivation of the tumor suppressor pathway is essential for tumor dedifferentiation and dissemination both in genetically engineered mouse models (GEMM) and human PDAC. Based on these findings, we propose the existence of a hierarchical signaling network regulating PDAC cell plasticity and suggest that the molecular decision between epithelial cell preservation and conversion into a dedifferentiated cancer stem cell-like phenotype depends on opposing levels of p53 and NFATc1 signaling activities. [ABSTRACT FROM AUTHOR]

Ca-alginate-poly- l-lysine-alginate (APA-Ca) and Ba-alginate-poly- l-lysine-alginate (APA-Ba) microcapsules were prepared and their thickness and surface were examined by light microscopy and scanning electron microscopy. Specifically, light microscopy with frozen section was used to visualize and quantify the thickness of APA membrane, and monitor temporal changes in the thickness of microcapsules during a month long culture in vitro. The section graph of APA microcapsule represents the accurate measurement of layer thickness of APA-Ca with diameter 900 ± 100 and 500 ± 100 μm at 6.01 ± 1.02 and 9.54 ± 2.42 μm ( p < 0.05), and layer thickness of APA-Ba with diameter 900 ± 100 and 500 ± 100 μm at 5.47 ± 0.90 and 8.21 ± 1.97 μm ( p < 0.05), regardless of the alginate composition used to generate the microcapsules. The microcapsule was stable during the culture for 30 days in vitro. Field emission scanning electron microscopy with freeze drying method was used to detect the surface and thickness of dried microcapsules. From the results, the outer surface of APA-Ca and APA-Ba membrane were smooth and dense, the film thickness of the APA-Ca was about 450-690 nm, while the APA-Ba was approximately 335 nm. In vivo experiment, little significant difference was seen in the change of film thickness of microcapsules in intrapertioneal site for 30 days after transplantation ( p > 0.05), except that the recovery of APA-Ba was higher than the APA-Ca microcapsules. The paper showed an easy method to prepare APA-Ca and APA-Ba, and examine their thickness and surface, which could be utilized to study other types of microcapsules. [ABSTRACT FROM AUTHOR]