Nonlinear mechanical response analysis and convolutional neural network enabled diagnosis of single-span rotor bearing system.

The wide application of rotating machinery has boosted the development of electricity and aviation, however, long-term operation can lead to a variety of faults. The use of different measures to deal with corresponding malfunctions is the key to generating benefits, so it is significant to carry out the fault diagnosis of rotating machinery. In this work, a test bench for single-span rotor bearings was established, three faults, including spindle bending, spindle crack without end loading and spindle crack with end loading, are experimental analyzed with basic mechanical response. Moreover, a diagnosis is performed using a convolutional neural network, according to the differences in mechanical responses of the three faults obtained from experiments. For three faults, the change in the properties of spindle itself results in different axis trajectories and spectra. Compared with spindle bending fault, spindle crack fault not only cause 1×, 2×, 3× frequency component excitation, also 4×, 5× frequency component excitation. Additionally, the classification accuracy of the training set and the test set under machine learning for the three types of working conditions is 100%. This indicates that the network can significantly identify signal features so as to make effective fault classification.

Long-term Changes in Low Anterior Resection Syndrome in Survivors of Rectal Cancer: Longitudinal Follow-up of a Randomized Controlled Trial.

BACKGROUND: Postoperative bowel dysfunction, also known as low anterior resection syndrome, is common in rectal cancer survivors and significantly impacts quality of life. Although long-term longitudinal follow-up is lacking, improvement of the syndrome is commonly believed to happen only within the first 2 years. OBJECTIVE: This study aimed to depict the longitudinal evolvement of low anterior resection syndrome beyond 3 years and explore factors associated with changes. DESIGN: Longitudinal long-term follow-ups were performed for the single center with the largest cohort within the multicenter FOWARC randomized controlled trial. SETTING: A quaternary referral center. PATIENTS: Individuals diagnosed with rectal cancer who received long-course neoadjuvant chemotherapy or chemoradiotherapy, followed by sphincter-preserving radical proctectomy. MAIN OUTCOME MEASUREMENTS: Change of low anterior resection syndrome score and stoma status. RESULTS: Of the 220 patients responding to the first follow-up at a median of 39 months, 178 (80.9%) responded to the second follow-up after a median of 83 months. During this interval, the mean low anterior resection syndrome score improved from 29.5 (95% CI, 28.3-30.7) to 18.6 (95% CI, 16.6-20.6). Fifty-six (31.5%) patients reported improvement from major to no/minor severity, and 6 (3.4%) patients had new stomas because of severe bowel dysfunction. Neoadjuvant radiotherapy ( p = 0.016) was independently and negatively associated with improvement of the score. LIMITATIONS: Loss of follow-up during the long-term follow-ups. CONCLUSIONS: Most rectal cancer survivors with low anterior resection syndrome continued to improve beyond 3 years after proctectomy. Neoadjuvant radiotherapy was negatively associated with long-term improvement of low anterior resection syndrome. See Video Abstract . CAMBIO A LARGO PLAZO DEL SNDROME DE RESECCIN ANTERIOR BAJA EN SUPERVIVIENTES DE CNCER DE RECTO SEGUIMIENTO LONGITUDINAL DE UN ENSAYO CONTROLADO ALEATORIO: ANTECEDENTES:La disfunción intestinal posoperatoria, también conocida como síndrome de resección anterior baja, es común en los sobrevivientes de cáncer de recto y afecta significativamente la calidad de vida. Aunque falta un seguimiento longitudinal a largo plazo, comúnmente se cree que la mejoría del síndrome ocurre sólo dentro de los primeros dos años.OBJETIVO:Este estudio tiene como objetivo representar la evolución longitudinal del síndrome de resección anterior baja más allá de los 3 años y explora los factores asociados con el cambio.DISEÑO:Se realizaron seguimientos longitudinales a largo plazo para el único centro con la cohorte más grande dentro del ensayo controlado aleatorio multicéntrico FOWARC.AJUSTE:Un centro de referencia cuaternario.PACIENTES:Individuos diagnosticados con cáncer de recto que recibieron quimioterapia neoadyuvante de larga duración o quimiorradioterapia, seguida de proctectomía radical con preservación del esfínter.PRINCIPALES MEDICIONES DE RESULTADO:Cambio en la puntuación del síndrome de resección anterior baja y el estado del estoma.RESULTADOS:De los 220 pacientes que respondieron al primer seguimiento con una mediana de 39 meses, 178 (80,9%) respondieron al segundo seguimiento después de una mediana de 83 meses. Durante el intervalo, la puntuación media del síndrome de resección anterior baja mejoró de 29,5 (intervalo de confianza [IC] del 95%: 28,3-30,7) a 18,6 (IC del 95%: 16,6-20,6). 56 (31,5%) pacientes informaron una mejoría de mayor a ninguna gravedad, y 6 (3,4%) pacientes tuvieron un nuevo estoma debido a una disfunción intestinal grave. La radiación neoadyuvante (p = 0,016) se asoció de forma independiente y negativa con la mejora de la puntuación.LIMITACIONES:Pérdida de seguimiento durante los seguimientos a largo plazo.CONCLUSIÓN:La mayoría de los sobrevivientes de cáncer de recto con síndrome de resección anterior baja continuaron mejorando más allá de los 3 años después de la proctectomía. La radiación neoadyuvante se asoció negativamente con la mejora a largo plazo del síndrome de resección anterior baja. (Traducción-Dr Yolanda Colorado ).

A novel score to predict progression in anterior circulation single subcortical infarction patients.

OBJECTIVE: Progressive infarction (PI) has a negative effect on functional prognosis. Our study aimed to develop and validate a risk score for predicting PI in patients with anterior circulation single subcortical infarction (ACSSI). METHODS: Between January 2020 and October 2022, we retrospectively enrolled 638 eligible patients with ACSSI. Two-thirds of the eligible patients were randomly allocated to the training cohort (n = 425). Another resampling sample was formed through the bootstrap method and was used as the validation group (n = 425). Multivariate logistic regression analysis was used to identify the independent factors associated with PI. Each factor was then point assigned based on ß-coefficient and a risk scoring system was developed. This scoring system was internally validated through 1000-bootstrap resamplings. The C-statistic and Hosmer-Lemeshow test were used to assess model discrimination and calibration. RESULTS: PI occurred in 121 patients, accounting for 19.0% of the total patients. A 7-point NTS score system based on the initial NIHSS score, triglyceride-glucose index, and the number of infarct slices on axial diffusion-weighted imaging was developed. The NTS score showed good discrimination and calibration in the training cohort (C-statistic = 0.686; p value of Hosmer-Lemeshow test = 0.797) and validation cohort (C-statistic = 0.681; p value of Hosmer-Lemeshow test = 0.451). The three risk levels for predicting PI in the training and validation cohorts based on NTS score were as follows: low (0-2, 9.6% vs. 9.3%), intermediate (3-5, 28.2% vs. 26.7%), and high risk (6-7, 60.2% vs. 57.4%). INTERPRETATION: The NTS score is a valid and convenient risk score for predicting PI in ACSSI patients.

Dynamic analysis of slant cracked rotor system considering nonlinear oil film force.

In this paper, considering the combined effects of nonlinear oil film forces and cracks on the rotor-bearing system, the differential equations of motion with 4 degrees of freedom are established by Lagrangian method. Then, the Lundgren-Kutta method is used to solve them and the results of the model are compared with the experimental data. The study demonstrate that the cracked rotor-bearing system is relatively stable at subcritical speeds, mostly in the period-1 motion. But near 1/3 of the critical speed, there is an inner loop in its whirl orbit and a significant increase in the 2x frequency component. When the system speed rises to the region near 1/2 of the critical speed, though the bifurcation motion and a relatively high 2x frequency can be observed, there are no other reliable fault characteristics. The study proves that the rotor crack fault diagnosis method based on the whirl orbits is convincing for slant cracked rotors.

A durable non-contact reciprocated triboelectric nanogenerator for low-frequency vibration energy harvesting.

Harvesting vibration energy using a triboelectric nanogenerator (TENG) is a promising approach in solving the power supply restriction of the Internet of Things. Currently, the low durability due to friction surface wearing is the primary limitation of TENGs, which restricts their applicability and practicability. This study introduces a non-contact-type TENG aimed at significantly enhancing its durability by increasing its anti-wear capability. The configuration of the proposed TENG includes permanent magnets and rolling-balls. The reciprocating motion of functional friction surfaces, facilitated by the permanent magnets, enhances the efficiency of harvesting low-frequency vibration energy. The embedded rolling-balls are utilized to separate two functional friction surfaces, which minimizes the friction surface wearing between different dielectric materials. The electrical output characteristics of this non-contact TENG under variable load resistances are explored according to sinusoidal excitation based on either variable frequencies or accelerations. The results demonstrate that the proposed nanogenerator can generate a short-circuit current of 2118.2 nA and achieve a peak power density of 9.891 mW/m2. The electrical responses of this non-contact TENG remain stable over 120 000 continuous working cycles, lasting for more than 200 min. Furthermore, the nanogenerator can identify and harvest energy from running or jumping motions performed by individuals in different postures and at various speeds or heights. With its exceptional durability and stability, this non-contact nanogenerator offers a novel approach to low-frequency vibration energy harvesting, paving the way for practical applications in the field.

Efficacy and Postoperative Complication Rates of Different Surgical Approaches for Calcaneal Fractures: A Network Meta-analysis.

Context: Calcaneal fractures (CFs) are the most common kind of tarsal fracture. The choice of surgical approach is a key element in the management of CFs, but the best method remains in dispute. Also, no single approach is appropriate for all kinds of CFs. Objective: The study intended to evaluate the relationship between six surgical approaches for clinical treatment of CFs and prevention of postoperative complications, to provide an evidence-based approach for treatment. Design: The research team performed a meta-analysis using the data from a previously published review and updating that data through a new narrative review. The team performed a systematic search in PubMed, Embase, the Cochrane Library, and the Chinese National Knowledge Internet (CNKI) from inception until January 2022, with no language restrictions. The search used the following keywords for the search: calcaneus, heel bone, surgical wounds, surgical incisions, prospective trials, prospective trials, and randomized controlled trials. Outcome Measures: The research team compared the complication rates, American Orthopedic Foot and Ankle Society (AOFAS) scores, and Bohler's angles for the six surgical approaches, which were: (1) the extensive lateral approach (ELA), (2) the sinus tarsi approach (STA), (3) the horizontal arc approach (HAA), (4) the longitudinal approach (LA), (5) the oblique lateral incision (OLI), and (6) the modified incision (MI)). The team summarized the results using a random effects model. Results: The research team analyzed the data from 19 RCTs with 1521 participants. They all were randomized controlled trials (RCTs). The complication rates were available for 18 studies, which included 1474 participants. The rates were significantly lower: (1) for HAA compared to ELA, [OR=-2.03; 95% CrI: [-3.63, -0.43)]; (2) for LA compared to ELA (OR=-1.83; 95% CrI: [-2.83, -0.84]); and (3) for STA compared to ELA (OR=- 1.22; 95% CrI: [-1.67, -0.78]). Of the 19 studies, 11 RCTs, with 942 participants, used the AOFAS scale. The probabilities for the surface under the cumulative ranking curve (SUCRA) indicated that OLI (0.694 ) >LA (0.596) >HAA (0.51) >STA (0.477) >ELA (0.224). In addition, ELA had the worst SUCRA (0.224). Of the 19 studies, 15 RCTs, with 1376 participants, used the Bohler angle as an outcome measure. The probability of SUCRA for the surgical approaches indicated that LA (0.723) >ELA (0.667) >STA (0.468) >HAA (0.373) >MI (0.27). Conclusions: The meta-analysis provides an evidence-based approach to the clinical treatment of CFs for six surgical approaches. HAA had the best outcomes, and ELA had the worst.

Use of network pharmacology and molecular docking to explore the mechanism of action of curcuma in the treatment of osteosarcoma.

Curcuma has been used as an adjuvant treatment for osteosarcoma (OS) due to its anticancer compounds. However, the underlying mechanism remains unclear. Therefore, this study aimed to explore the mechanism of action of curcuma in the treatment of OS using network pharmacology and molecular docking. In this study, anticancer compounds were obtained from relevant literature, and curcuma-related targets and OS treatment targets were obtained from public databases. Protein‒protein interaction networks were constructed to screen out the hub genes using the STRING database and Cytoscape software. Cluster analysis of the protein modules was then performed using the Cytoscape MCODE plugin. Furthermore, Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed for common targets among curcuma targets and OS-related targets using the DAVID database. Finally, molecular docking was performed, and the results were verified by Auto dock Tool and PyMOL software. Our research identified 11 potential active compounds, 141 potential therapeutic targets and 14 hub genes for curcuma. AKT1, TNF, STAT3, EGFR, and HSP90AA1 were the key targets closely related to the PI3K/Akt signaling pathways, HIF-1 signaling pathways, ErbB signaling pathways, and FOXO signaling pathways, which are involved in angiogenesis, cancer cell proliferation, metastasis, invasion, and chemotherapy resistance in the microenvironment of OS. Molecular docking suggested that the core compound had a strong affinity for key targets, with a binding energy of less than - 5 kJ/mol. The study showed that curcuma-mediated treatment of OS was a complex process involving multiple compounds, targets, and pathways. This study will enhance the understanding of how curcuma affects the proliferation and invasion of OS cells and reveal the potential molecular mechanism underlying the effect of curcuma on OS lung metastasis and chemotherapy resistance.

Safety and long-term prognosis of simultaneous versus staged resection in synchronous colorectal cancer with liver metastasis: a systematic review and meta-analysis.

PURPOSE: The optimal time point for surgical resection of synchronous colorectal liver metastases (SCLMs) is still controversial. This meta-analysis evaluated the safety and long-term prognoses of simultaneous and staged resection of SCLM to provide a reference for clinical selection. METHODS: A systematic literature search for studies published by October 2022 was performed using PubMed, Web of Science, Embase, Scopus and Cochrane Library. The evaluated outcome parameters were total, gastrointestinal and hepatic complications, as well as perioperative mortality, intraoperative blood loss, total hospital stay, 5-year disease-free survival (DFS) and 5-year overall survival (OS). RESULTS: This meta-analysis included 22 nonrandomised and one randomised study comprising 4862 patients. The patients undergoing simultaneous resection of SCLM had similar total (OR = 0.88, 95% CI [0.66-1.19], P = 0.409), gastrointestinal (OR = 1.19, 95% CI [0.89-1.59], P = 0.241) and hepatic (OR = 1.04, 95% CI [0.83-1.31], P = 0.734) complications, as well as perioperative mortality (OR = 1.79, 95% CI [0.88-3.64], P = 0.108), 5-year DFS (HR = 1.26, 95% CI [0.96-1.66], P = 0.098) and 5-year OS (HR = 1.13, 95% CI [0.95-1.34], P = 0.164). Lower intraoperative blood loss (SMD = - 0.39, 95% CI [- 0.60 to - 0.18], P < 0.001) and shorter total hospital stay (WMD = - 5.43, 95% CI [- 7.29 to - 3.58], P < 0.001) were observed in the simultaneous-resection group versus the staged group. CONCLUSIONS: Simultaneous resection is safe and effective for SCLM patients. The long-term prognosis is equivalent to that of the traditional staged resection. Correct selection of resectable SCLM patients for the simultaneous resection of the primary tumour and liver metastases can be the first choice. Owing to the potential heterogeneity, more RCTs should be included to verify our conclusions.

Non-pharmaceutical treatments to relieve pain or reduce opioid analgesic intake and improve quality of life after total hip replacement: a meta analysis.

To reduce pain after total hip replacement (THR), researchers are interested in drug-free interventions. However, there is still a lack of consensus on their prevention efficacy. We performed a meta-analysis to evaluate the use of nonpharmaceutical interventions for postoperative pain management after THR. We searched the Cochrane Library, MEDLINE, EMBASE, Web of Science, PEDRO, and ClinicalTrials.gov databases for articles published between and 1991 and 2020. The main outcome measures were postoperative pain, opioid consumption, and quality of life (QoL). In total, 1,942 patients were studied. We found moderate evidence indicating postoperative pain relief measured by the Western Ontario and McMaster Universities Arthritis Index Scale, with mean differences (MDs) of -0.28 (95% confidence interval [CI], -0.49 to -0.07; P=0.01; I2 =0%) within three months, -0.19 (95% CI, -0.40 to 0.02; P=0.07; I2 =0%) between 3-6 months, and -0.13 (95% CI, -0.35 to 0.08; P=0.21; I2 =0%) between 6-12 months. Additionally, we found that acupuncture therapy could reduce opioid analgesic consumption (MD, -0.98; 95% CI, -1.18 to -0.79; fentanyl [mg/h]; P<0.01; I2 =72.2%) and significantly improve pain relief with an MD of 0.90 (95% CI, 0.47 to 1.33; P<0.01; I2 =0%) measured using the visual analog scale. Electrotherapy slightly improved perceived pain with an MD of 0.22 (95% CI, -0.27 to 0.70; P=0.37; I2 =0%). Moreover, moderate evidence has shown that preoperative exercises improve QoL. This meta-analysis suggested that continuous passive motion did not improve pain or QoL. Postoperative exercise was associated with pain relief and improved QoL. Acupuncture therapy after THR has been shown to reduce opioid analgesic consumption.

Improvement of low anterior resection syndrome beyond 2 years after total mesorectal excision.

AIM: Bowel dysfunction after sphincter-preserving proctectomy, also known as low anterior resection syndrome (LARS), has significant impact on survivors of rectal cancer. This study aimed to assess the temporal change of LARS beyond 2 years after proctectomy, which has not been fully studied. METHODS: We longitudinally enrolled consecutive patients who had received total mesorectal excision in a tertiary academic medical center, with preoperative neoadjuvant therapy if indicated. LARS score was longitudinally assessed by two serial follow-ups, with a fixed interval of 18 months. RESULTS: Overall, 107 patients responded for the first follow-up after a median of q20 months, 96 of whom responded for the second follow-up after a median of 38 months. At the first follow-up, 48 patients (44.9%) reported major LARS, compared with 23 (24.0%) at the second follow-up (p < 0.001). Mean LARS score improved from 27.3 to 18.6, mostly from "urgency" (12.2 vs. 6.2, p < 0.001) and "clustering of stools" (9.7 vs. 7.7, p = 0.001). Anastomosis less than 3 cm from the anal verge was independently associated with LARS improvement. CONCLUSION: Bowel dysfunction continues to improve 2 years after total mesorectal excision, with most symptom relief in urgency and stool clustering, especially in patients with lower anastomosis.

The natural orifice specimen extraction surgery compared with conventional laparoscopy for colorectal cancer: A meta-analysis of efficacy and long-term oncological outcomes.

PURPOSE: Natural orifice specimen extraction surgery (NOSES) has gradually become established in treating colorectal cancer. This meta-analysis assesses NOSES in the treatment of colorectal cancer compared with conventional laparoscopy (CL) and determines the effect of long-term prognosis. METHODS: Various medical databases were searched up to May 2021. We included retrospective and randomized trials on the treatment of colorectal cancer with NOSES. Pooled weighted/standardized mean differences (WMD/SMD), odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CIs) were calculated using either fixed- or random-effects models. STATA was conducted for the meta-analysis. RESULTS: This meta-analysis included 16 studies comprising 2266 patients. Compared with CL, NOSES had more benefits in terms of overall postoperative complications (OR = 0.47, 95%CI [0.35,0.64]; Z = 4.91, P < 0.001), incision-related complications (OR = 0.15, 95%CI [0.07,0.31]; Z = 4.97, P < 0.001), time to first flatus (SMD = -0.58, 95%CI [-0.68,-0.48]; Z = 11.21, P < 0.001), hospital stay (WMD = -1.03, 95%CI [-1.55,-0.51]; Z = 3.86, P < 0.001), cosmetic scores (WMD = 1.37, 95%CI [0.59,2.14]; Z = 3.47, P = 0.001), the visual analogue scale on postoperative day 1（WMD = -1.46, 95%CI [-2.39,-0.52]; Z = 3.06, P = 0.002), additional analgesics usage (OR = 0.33, 95%CI [0.26, 0.43]; Z = 8.43, P < 0.001), whereas the operative time of NOSES was prolonged (WMD = 13.09, 95%CI [7.07,19.11]; Z = 4.26, P < 0.001). Postoperative anastomotic complications, intra-abdominal infection, pelvic floor function, intraoperative blood loss, number of lymph node dissection, 3-year disease-free and overall survival in the NOSES group were comparable with those in the CL group. CONCLUSIONS: NOSES is a safe and reliable surgical procedure for the treatment of colorectal cancer and provides good long-term oncological outcomes. Large-scale multicenter studies are required to confirm its clinical benefits.

Corrigendum: Exploring the Mechanism of Total Flavonoids of Drynariae Rhizoma to Improve Large Bone Defects by Network Pharmacology and Experimental Assessment.

[This corrects the article DOI: 10.3389/fphar.2021.603734.].

Exploring the Mechanism of Total Flavonoids of Drynariae Rhizoma to Improve Large Bone Defects by Network Pharmacology and Experimental Assessment.

Drynariae Rhizoma (DR) has been demonstrated to be effective in promoting fracture healing in clinical use. In the study, we tried to predicate potential signaling pathways and active ingredients of DR via network pharmacology, uncover its regulation mechanism to improve large bone defects by in vivo and in vitro experiment. We total discovered 18 potential active ingredients such as flavonoids and 81 corresponding targets, in which mitogen-activated protein kinase (MAPK) signaling pathway has the highest correlation with bone defects in pathway and functional enrichment analysis. Therefore, we hypothesized that flavonoids in DR improve large bone defects by activating MAPK signaling pathway. Animal experiments were carried out and all rats randomly divided into TFDR low, medium, and high dosage group, model group and control group. 12 weeks after treatment, according to X-ray and Micro-CT, TFDR medium dosage group significantly promote new bone mineralization compared with other groups. The results of HE and Masson staining and in vitro ALP level of BMSC also demonstrated the formation of bone matrix and mineralization in the TFDR groups. Also, angiographic imaging suggested that flavonoids in DR promoting angiogenesis in the defect area. Consistently, TFDR significantly enhanced the expression of BMP-2, RUNX-2, VEGF, HIF-1 in large bone defect rats based on ELISA and Real-Time PCR. Overall, we not only discover the active ingredients of DR in this study, but also explained how flavonoids in DR regulating MAPK signaling pathway to improve large bone defects.

Total flavonoids of rhizoma drynariae ameliorates bone formation and mineralization in BMP-Smad signaling pathway induced large tibial defect rats.

Osteogenesis and angiogenesis acts as an essential role in repairing large tibial defects (LTDs). Total flavonoids of rhizoma drynariae (TFRD), a traditional Chinese medicinal herb, is reported to show anabolic effects on fracture healing. However, whether TFRD could improve the bone formation and angiogenesis in LTDs remains unknown. The purpose of this study was to evaluate the effect of TFRD on bone formation and angiogenesis in LTDs in distraction osteogenesis (DO). Using a previously established fracture model, LTD rats was established with circular external fixator (CEF). All rats then randomly divided into TFRD low dosage group (with DO), TFRD medium dosage group (with DO), TFRD high dosage group (with DO), model group (with DO) and blank group (without DO). Twelve weeks after treatment, according to X-ray and Micro-CT, TFRD groups (especially in medium dosage group) can significantly promote the formation of a large number of epiphyses and improve new bone mineralization compared with model group, and the results of HE and Masson staining and in vitro ALP level of BMSC also demonstrated the formation of bone matrix and mineralization in the TFRD groups. Also, angiographic imaging suggested that total flavonoids of TFRD was able to promote angiogenesis in the defect area. Consistently, TFRD significantly increased the levels of BMP-2, SMAD1, SMAD4, RUNX-2, OSX and VEGF in LTD rats based on ELISA and Real-Time PCR. In addition, we found that ALP activity of TFRD medium dosage group reached a peak after 10 days of induction through BMSC cell culture in vitro experiment. TFRD promoted bone formation in LTD through activation of BMP-Smad signaling pathway, which provides a promising new strategy for repairing bone defects in DO surgeries.

KIF2C: a novel link between Wnt/ß-catenin and mTORC1 signaling in the pathogenesis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the fourth-leading cause of cancer-related deaths worldwide. HCC is refractory to many standard cancer treatments and the prognosis is often poor, highlighting a pressing need to identify biomarkers of aggressiveness and potential targets for future treatments. Kinesin family member 2C (KIF2C) is reported to be highly expressed in several human tumors. Nevertheless, the molecular mechanisms underlying the role of KIF2C in tumor development and progression have not been investigated. In this study, we found that KIF2C expression was significantly upregulated in HCC, and that KIF2C up-regulation was associated with a poor prognosis. Utilizing both gain and loss of function assays, we showed that KIF2C promoted HCC cell proliferation, migration, invasion, and metastasis both in vitro and in vivo. Mechanistically, we identified TBC1D7 as a binding partner of KIF2C, and this interaction disrupts the formation of the TSC complex, resulting in the enhancement of mammalian target of rapamycin complex1 (mTORC1) signal transduction. Additionally, we found that KIF2C is a direct target of the Wnt/ß-catenin pathway, and acts as a key factor in mediating the crosstalk between Wnt/ß-catenin and mTORC1 signaling. Thus, the results of our study establish a link between Wnt/ß-catenin and mTORC1 signaling, which highlights the potential of KIF2C as a therapeutic target for the treatment of HCC.

Super-enhancer-driven AJUBA is activated by TCF4 and involved in epithelial-mesenchymal transition in the progression of Hepatocellular Carcinoma.

Background and Aims: Aberrant transcriptional programs are highly regulated processes that play important roles in the development and progression of hepatocellular carcinoma (HCC). Emerging evidence suggests that super-enhancers (SEs) often drive critical oncogene expression. However, SE-associated genes in HCC pathogenesis are still poorly understood. Methods: We performed integrative ChIP-seq and Hi-C analyses of HCC cells and identified ajuba LIM protein (AJUBA) as a SE-associated gene. We evaluated AJUBA expression in HCC using immunohistochemistry, immunoblotting, and qRT-PCR. ChIP and luciferase reporter assays were performed to demonstrate that transcription factor 4 (TCF4) bound to AJUBA-associated SEs. We then assessed the role of AJUBA in HCC using both in vitro and in vivo assays. Epithelial-mesenchymal transition (EMT) was examined using immunofluorescence and immunoblotting assays. Furthermore, we used immunoprecipitation and BiFC assays to explore the underlying mechanisms. Results: We identified AJUBA as a SE-associated oncogene in HCC regulated by TCF4. High AJUBA expression was related to an aggressive phenotype and unfavorable outcome in HCC patients. AJUBA knockdown significantly reduced cell migration and invasion capacities both in vitro and in vivo. Furthermore, AJUBA overexpression in HCC recruited tumor necrosis factor associated factor 6 (TRAF6), enhancing the phosphorylation of Akt and increasing Akt activity toward GSK-3ß, thus promoting EMT. Conclusions: Our results provide functional and mechanistic links between the SE-associated gene AJUBA and tumor EMT in aggressive HCC.

Density and distribution of lymphocytes in pretherapeutic rectal cancer and response to neoadjuvant therapy.

BACKGROUND: Lymphocytic density in rectal cancer has been reported to be associated with therapeutic response, but the role of the lymphocytic distribution pattern remains to be determined. This study aimed to evaluate the association between the distribution and density of lymphocytes in rectal-cancer tissue with tumor response to neoadjuvant therapy. METHODS: We retrospectively analysed 134 patients with rectal cancer receiving neoadjuvant therapy within a prospectively maintained cohort. Pretherapeutic biopsy samples were stained with immunohistochemistry (CD4 and CD8). Densities of intratumoral periglandular lymphocytes (IPLs) and tumor-infiltrating lymphocytes (TILs) were assessed separately. Logistic-regression analysis was used to assess associations of lymphocyte densities with tumor regression grade (TRG), controlling for clinicopathological, molecular, and regimen features. RESULTS: Compared with cases in the lowest quartile of CD8+ TILs, those in the highest quartile were significantly associated with better TRG (multivariate odds ratio, 0.23; 95% confidence interval, 0.07 to 0.76; P < 0.001). In contrast, CD8+ IPLs, CD4+ IPLs, and CD4+ TILs were not significantly associated with TRG (P = 0.033, 0.156, and 0.170, respectively). Sensitivity analyses detected no interaction between CD8+ TILs and regimen of neoadjuvant radiation (P interaction = 0.831) or chemotherapy (P interaction = 0.879) on TRG. CONCLUSIONS: Our data suggest that CD8+ TILs, but not IPLs, are independently associated with response to neoadjuvant therapy, regardless of the regimen of radiation or chemotherapy.

A New Wide Bandgap Donor Polymer for Efficient Nonfullerene Organic Solar Cells with a Large Open-Circuit Voltage.

Significant progress has been made in nonfullerene small molecule acceptors (NF-SMAs) that leads to a consistent increase of power conversion efficiency (PCE) of nonfullerene organic solar cells (NF-OSCs). To achieve better compatibility with high-performance NF-SMAs, the direction of molecular design for donor polymers is toward wide bandgap (WBG), tailored properties, and preferentially ecofriendly processability for device fabrication. Here, a weak acceptor unit, methyl 2,5-dibromo-4-fluorothiophene-3-carboxylate (FE-T), is synthesized and copolymerized with benzo[1,2-b:4,5-b']dithiophene (BDT) to afford a series of nonhalogenated solvent processable WBG polymers P1-P3 with a distinct side chain on FE-T. The incorporation of FE-T leads to polymers with a deep highest occupied molecular orbital (HOMO) level of -5.60-5.70 eV, a complementary absorption to NF-SMAs, and a planar molecular conformation. When combined with the narrow bandgap acceptor ITIC-Th, the solar cell based on P1 with the shortest methyl chain on FE-T achieves a PCE of 11.39% with a large V oc of 1.01 V and a J sc of 17.89 mA cm-2. Moreover, a PCE of 12.11% is attained for ternary cells based on WBG P1, narrow bandgap PTB7-Th, and acceptor IEICO-4F. These results demonstrate that the new FE-T is a highly promising acceptor unit to construct WBG polymers for efficient NF-OSCs.

Sulfur-Containing Bent N-Heteroacenes.

A series of novel sulfur-containing bent N-heteroacenes were constructed and characterized by NMR and UV/Vis spectroscopy, cyclic voltammetry, and single-crystal X-ray diffraction. By introducing sulfur-containing groups (thio, sulfinyl, and sulfonyl) into bent azaacenes, their electronic delocalization was improved and frontier energy levels were modulated. The target products displayed tunable optical and electronic properties through altering the valence of sulfur and fused length of the azaacenes. For the first time, typical products were utilized as organic field effect transistor materials, affording promising results.

Bevacizumab synergises with the BCL 2 inhibitor venetoclax to effectively treat B-cell non-Hodgkin's lymphoma.

OBJECTIVES: Our present study has shown a potential role for VEGF-A-mediated autocrine signalling to promote survival and proliferation of SU-DHL-6 cells, but the cells could not undergo apoptosis but rather decrease proliferation after bevacizumab treatment. Therefore, we would like to further study the antitumour efficacy of venetoclax (BCL2 inhibitor) in combination with bevacizumab in B-cell NHL. METHODS: The human cytokine antibody array, RT-qPCR, Western blot, ELISA, apoptosis assay and xenografted mouse model et al were used. RESULTS: We described a unique phenomenon that SU-DHL-6 cells showed cell density-dependent survival and growth. Then, we suggested the expression of VEGF-A was positively correlated with the cell density using a human cytokine antibody array and indicated an important role of VEGF-A in the survival and proliferation of SU-DHL-6 cells. Additionally, xenografted SU-DHL-6 cells formed tumours in mice that grew in response to VEGF stimulation. GEO data set also suggested that high VEGF-A expression reflected poor prognosis. The combination therapy with bevacizumab and navitoclax could significantly induce of cell death in vitro and reduce the tumour size and weight with well tolerated in vivo. CONCLUSIONS: Our findings propose a novel combined strategy in which bevacizumab synergises with the BCL2 inhibitor venetoclax that is effective against B-cell NHL.