Long-term outcomes of pelvic exenterations for gynecological malignancies: a single-center retrospective cohort study.

BACKGROUND: Recently, with the advancement of medical technology, the postoperative morbidity of pelvic exenteration (PE) has gradually decreased, and it has become a curative treatment option for some patients with recurrent gynecological malignancies. However, more evidence is still needed to support its efficacy. This study aimed to explore the safety and long-term survival outcome of PE and the feasibility of umbilical single-port laparoscopic PE for gynecologic malignancies in a single medical center in China. PATIENTS AND METHODS: PE for gynecological cancers except for ovarian cancer conducted by a single surgical team in Sun Yat-sen University Cancer Center between July 2014 and December 2019 were included and the data were retrospectively analyzed. RESULTS: Forty-one cases were included and median age at diagnosis was 53 years. Cervical cancer accounted for 87.8% of all cases, and most of them received prior treatment (95.1%). Sixteen procedures were performed in 2016 and before, and 25 after 2016. Three anterior PE were performed by umbilical single-site laparoscopy. The median operation time was 460 min, and the median estimated blood loss was 600 ml. There was no perioperative death. The years of the operations was significantly associated with the length of the operation time (P = 0.0018). The overall morbidity was 52.4%, while the severe complications rate was 19.0%. The most common complication was pelvic and abdominal infection. The years of surgery was also significantly associated with the occurrence of severe complication (P = 0.040). The median follow-up time was 55.8 months. The median disease-free survival (DFS) was 17.9 months, and the median overall survival (OS) was 25.3 months. The 5-year DFS was 28.5%, and the 5-year OS was 30.8%. CONCLUSION: PE is safe for patient who is selected by a multi-disciplinary treatment, and can be a curative treatment for some patients. PE demands a high level of experience from the surgical team. Umbilical single-port laparoscopy was a technically feasible approach for APE, meriting further investigation.

Localization of RNAs in the nucleus: cis- and trans- regulation.

The subcellular localization of RNAs correlates with their function and how they are regulated. Most protein-coding mRNAs are exported into the cytoplasm for protein synthesis, while some mRNA species, long noncoding RNAs, and some regulatory element-associated unstable transcripts tend to be retained in the nucleus, where they function as a regulatory unit and/or are regulated by nuclear surveillance pathways. While the mechanisms regulating mRNA export and localization have been well summarized, the mechanisms governing nuclear retention of RNAs, especially of noncoding RNAs, are seldomly reviewed. In this review, we summarize recent advances in the mechanistic study of RNA nuclear retention, especially for noncoding RNAs, from the angle of cis-acting elements embedded in RNA transcripts and their interaction with trans-acting factors. We also try to illustrate the general principles of RNA nuclear retention and we discuss potential areas for future investigation.

[Effect of Low Molecular Weight Heparin Calcium Combined Compound Danshen Injection on Perinatal Outcomes of Nephrotic Syndrome Patients with Early Onset Severe Pre-eclampsia].

OBJECTIVE: To observe the effect of low molecular weight heparin calcium (LMWHC) combined Compound Danshen Injection (DI) on nephrotic syndrome patients with early onset severe preeclampsia. METHODS: Totally 80 nephrotic syndrome patients with early onset severe pre-eclampsia were randomly assigned to four groups voluntarily, i.e., Group A (22 cases, treated by magnesium sulfate), B (19 cases, treated by magnesium sulfate plus LMWHC), C (21 cases, magnesium sulfate plus DI), D (18 cases, magnesium sulfate plus LMWHC and DI). Umbilical arterial S/D ratios, amniotic fluid index (AFI), prolonged gestational age, placenta weight, neonatal weight, and Apgar score were compared among the four groups. RESULTS: Compared with before treatment in the same group, umbilical arterial S/D ratios decreased in the four groups (P <0. 05). AFI decreased in Group A, while it increased in Group B, C, and D (P<0. 05). Compared with Group A at the same time point, umbilical arterial S/D ratios decreased, and AFI increased in Group B, C, and D (P <0. 01 , P <0. 05). Prolonged gestational age and neonatal weight were increased in Group B, C, and D (P <0. 01, P <0. 05). Placenta weight were increased in Group B and D (P <0. 05). Apgar scores at 1 and 5 min were improved in Group D (P <0. 05). Compared with Group B and C at the same time point, umbilical arterial S/D ratios decreased, and AFI increased in Group D (P<0. 05). Compared with Group B, prolonged gestational age and placenta weight were decreased in Group C, but prolonged gestational age and placenta weight were increased in Group D (P <0.05). Compared with Group C, prolonged gestational age, placenta weight, and neonatal weight were increased in Group D (P <0. 05). CONCLUSION: Treatment of nephrotic syndrome patients with early onset severe pre-eclampsia by LMWHC combined DI could prolong gestational ages, obviously improve prenatal outcomes, with better effect obtained than using any of them alone.

Predictive value of CXCL1+_FAP+ phenotype in CAFs for distant metastasis and its correlation with PD-L1 expression in locoregionally advanced nasopharyngeal carcinoma patients.

OBJECTIVE: There is a lack of effective biomarkers for predicting the distant metastasis in nasopharyngeal carcinoma (NPC). We aimed to explore the expression of FAP+Cancer-associated fibroblasts (CAFs) derived CXCL1 in NPC and its predictive values for distant metastasis and correlation with PD-L1 expression. MATERIALS AND METHODS: A total of 345 patients with locoregionally advanced NPC were retrospectively enrolled (the training cohort: the validation cohort = 160:185). Co-expression of CXCL1 and FAP and the expression of PD-L1 were detected by multi-immunofluorescence staining and immunohistochemistry, respectively. The primary end-point was distant metastasis-free survival (DMFS). The Kaplan-Meier method was used to calculate the survival. The Cox proportional hazards model was used to assess prognostic risk factors. RESULTS: A novel CXCL1+_FAP+ phenotype in CAFs was identified in NPC and then used to divide patients into low and high risk groups. Both in the training cohort and validation cohort, patients in the high risk group had poorer DMFS, overall survival (OS), progression-free survival (PFS) and locoregional relapse-free survival (LRFS) than patients in the low risk group. Multivariate analysis revealed CXCL1+_FAP+ phenotype was an independent prognostic factor for DMFS, OS, PFS and LRFS. Further results showed patients in the high risk group had higher PD-L1 expression than those in the low risk group. CONCLUSION: Our study showed CXCL1+_FAP+ phenotype in CAFs could effectively classified locoregionally advanced NPC patients into different risk groups for distant metastasis and might be a potential biomarker for anti-PD-1/PD-L1 immunotherapy.

Current enhancement of aluminum doped ZnO/n-Si isotype heterojunction solar cells by embedding silver nanoparticles.

To improve Plasmonic energy harvesting, the Al doped ZnO (AZO) and Si heterojunction was studied for plasmonic photovoltaic applications. Silver nanoparticles (Ag NPs) were embedded in AZO, resulting in direct energy absoption from Ag NPs, positioned close to the junction. This structure has a benefit of avoiding highly doped lossy layers of conventional solar cell structures. Al doped ZnO (AZO) was deposited on n-Si substrate by dual beam sputtering method to fabricate AZO/Si heterojunction solar cells. AZO provides a transparent current spreading effect and rectifying junction with n type silicon (Si). Silver nanoparticles (Ag NPs) were embedded in AZO film (240-270 nm thick) with a sandwich-like structure. The position of Ag NPs in the AZO film was controlled to be located at 10, 20 and 40 nm distance from the Si absorber layer. Fabricated solar cells show improved performance in terms of the short circuit current (J(sc)) and the quantum efficiency (QE). Finite difference time domain (FDTD) simulations were carried out to investigate the QE enhancement and optimize photocurrent gain under an AM1.5G solar spectrum. In calculation, absorption enhancement is maximized when Ag NPs are located close to the Si layer in the range of 10-40 nm. Experimentally, 20 nm distance of Ag NPs from the Si showed the best performance with 0.36 V of open circuit voltage (V(oc)), 28.3 mA/cm2 of J(sc) and 5.91% of coversion efficiency. The QE showed 15% of enhancement around lambda = 435 nm and 5-10% of enhancement within lambda = 600-1000 nm.

An engineered multidomain fungicidal peptide against plant fungal pathogens.

Fungal pathogens represent major problems for human health and agriculture. As eukaryotic organisms, fungi share some important features with mammalian cells. Therefore, current anti-fungal antibiotics often can not distinguish between fungi and mammalian cells, resulting in serious side effects in mammalian cells. Accordingly, there is strong impetus to develop antifungal alternatives that are both safe and effective. The E1 family of colicin are channel-forming bacteriocins produced by Escherichia coli, which are bactericidal only to E. coli and related species. To target the channel-forming domain of colicin to fungal cell membrane, we engineered a sexual mating pheromone of Candida albicans, α-factor pheromone to colicin Ia. A peptide was constructed consisting of an α mating pheromone of C. albicans fused to the channel-forming domain of colicin Ia to create a new fusion protein, pheromonicin-CA (PMC-CA). Indirect immunolabeling showed that the PMC-CA bound to fungal cells and inhibited growth in the laboratory and field. In the field, the protective activity of pheromonicin against rice blast disease was significantly greater, on a molar basis, than that of triazoles, tricyclazole or isoprothiolane. These results suggest that fusion peptides may be of value as fungicidal agents under agricultural conditions.

Lacertus Syndrome: an Outcome Analysis After Lacertus Release.

Purpose: The lacertus fibrosus or bicipital aponeurosis is a sheet of ligamentous tissue just distal to the elbow joint and can be a compression point for the median nerve. Essentially, lacertus syndrome is a subset of pronator syndrome and an uncommon diagnosis by itself. Surgical release of the lacertus consists of a small 2-cm incision that can be performed under local anesthesia. This study aimed to evaluate the outcome of lacertus release in resolving median nerve symptoms. Methods: This retrospective study was performed at Prince Court Medical Centre, Kuala Lumpur, Malaysia, from January 2020 until June 2021. Ninety-three patients who presented with numbness of fingers, hand, or upper limb; forearm pain; and muscle weakness. They were diagnosed with lacertus syndrome on the basis of local tenderness at the lacertus fibrosus with either weakness of flexor pollicis longus and flexor digitorum profundus of the index finger or paresthesia over the thenar eminence. The patients underwent 3 months of hand therapy, and those with no symptom improvement were offered lacertus release performed by a single surgeon. The surgical technique consists of a surgical incision starting from a point 2 cm distally and 2 cm radially to the medial epicondyle. The incision projects 2 cm distally in an oblique fashion toward the radial styloid. A wide-awake local anesthesia no tourniquet (WALANT) technqiue was utilized and 20 mL of local anesthesic was injected subcutaneously around this region at least 20 minutes before the surgery. Careful dissection was made subcutaneously, and the lacertus fibrosus was identified as a thickened, shiny white structure and released. The Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score, grip strength, and pinch strength were tested before and after surgery. At 6 months after surgery, the QuickDASH score was again assessed with a WALANT satisfactory questionnaire. Results: A total of 93 patients were included in the study. The mean age of the patients was 38.7 years, and most were women (77.4%). The mean operating time was 70 minutes. The mean preoperative QuickDASH score was 53, which significantly reduced immediately after surgery to 7.8 (P < .001) and remained low at 6 months after surgery (10.6). The mean grip strength showed a significant increase from a preoperative mean of 16 kg to a postoperative mean of 24 kg (P < .001). Pinch strength also significantly increased from a preoperative mean of 9 kg to 13 kg after surgery (P < .001). Conclusions: Lacertus syndrome remains an underdiagnosed disease that can be treated efficiently with a directed minimal surgical incision under wide-awake local anesthesia. Lacertus release appears to significantly reduce pain and numbness with markedly improved hand grip and pinch strength. The corresponding QuickDASH scores also improved significantly after surgery. This study is vital to our understanding of proximal median nerve entrapment and to accurately diagnose it. Type of study/level of evidence: Therapeutic III.

High expression of p300 is linked to aggressive features and poor prognosis of nasopharyngeal carcinoma.

BACKGROUND: Increased expression of transcriptional coactivator p300 has been observed in a variety of human cancers. However, the expression status of p300 protein/mRNA in nasopharyngeal carcinoma (NPC) tissues and its clinicopathologic/prognostic implication are poorly understood. METHODS: In our study, mRNA and protein expression levels of p300 was explored by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting (WB) and immunohistochemistry (IHC) in nasopharyngeal mucosal and NPC tissues. The data were analyzed by receiver operating characteristic (ROC) curve analysis, spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model. RESULTS: Up-regulated expression of p300 mRNA/p300 protein was detected in NPC tissues by RT-PCR and WB, when compared to nasopharyngeal mucosal tissues. Based on ROC curve analysis, the cutoff score for p300 high expression was defined when more than 35% of the tumor cells were positively stained. High expression of p300 was observed in 127/209 (60.7%) of NPCs. In NPCs, high expression of p300 was positively associated with later T classification, later N classification, distant metastasis and later clinical stage (P < 0.05). In univariate survival analysis, overexpression of p300 was found to be an indicator of progression-free (P = 0.002) and overall survival (P = 0.001) in NPCs. More importantly, p300 expression was evaluated as an independent prognostic factor for NPC in multivariate analysis (P = 0.036). CONCLUSIONS: Our findings support that high expression of p300 protein might be important in conferring a more aggressive behavior, and is an independent molecular marker for shortened survival time of patients with NPC.

[Clinical effectiveness assessment of compound danshen injection on early onset severe preeclampsia patients].

OBJECTIVE: To analyze the clinical effectiveness of Compound Danshen Injection (CDI) in treating patients with early onset severe preeclampsia. METHODS: One hundred and twenty patients with early onset severe preeclampsia were recruited and their gestational age ranged between 26 and 34 weeks. Sixty patients who volunteered to receive CDI were recruited as the treatment group, while 60 inpatients were recruited as the control group at the same time period. The routine therapy was given to those in the control group. CDI was intravenously dripped to those in the treatment group additionally by adding in 250 mL 5% glucose injection, once daily. The treatment for all lasted for 7 successive days. The D-dimer (DD), fibrinogen (Fg), hematocrit (HCT), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), mean arterial pressure (MAP), 24 h urine volume (UV), 24 h urine protein (24 hUP), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A (apoA1), apolipoprotein B (apoB), umbilical arterial S/D ratio (S/D), and amniotic fluid index (AFI) were compared between the two groups before and after treatment. The placenta weight (PW), neonatal weight (NW), 1 min Apgar scoring were compared between the two groups before and after treatment. RESULTS: There was no difference in DD, Fg, HCT, t-PA, PAI-1, MAP, UV, 24 hUP, TC, TG, HDL-C, LDL-C, apoA1, apoB, S/D, or AFI between the two groups before treatment (P>0.05). In the treatment group PAI-1, Fg, and 24 hUP decreased more after treatment, and they were lower than those of the control group after treatment. The UV and AFI increased and they were higher than those of the control group after treatment with statistical difference shown (P<0.05, P<0.01). In the control group the UV increased and 24 hUP decreased after treatment (P<0.01). There was no improvement in the rest indices (P>0.05). The PW, NW,and 1 min Apgar score > or = 7 were all higher in the treatment group than in the control group, showing statistical difference (P<0.05). CONCLUSION: CDI was helpful to improve the high condensation state of patients with early onset severe preeclampsia, protect important organs of the mother, and improve the prognosis of neonates.

Radiomics combined with clinical characteristics predicted the progression-free survival time in first-line targeted therapy for advanced non-small cell lung cancer with EGFR mutation.

OBJECTIVE: This study was to explore the most appropriate radiomics modeling method to predict the progression-free survival of EGFR-TKI treatment in advanced non-small cell lung cancer with EGFR mutations. Different machine learning methods may vary considerably and the selection of a proper model is essential for accurate treatment outcome prediction. Our study were established 176 discrimination models constructed with 22 feature selection methods and 8 classifiers. The predictive performance of each model were evaluated using the AUC, ACC, sensitivity and specificity, where the optimal model was identified. RESULTS: There were totally 107 radiomics features and 7 clinical features obtained from each patient. After feature selection, the top-ten most relevant features were fed to train 176 models. Significant performance variations were observed in the established models, with the best performance achieved by the logistic regression model using gini-index feature selection (AUC = 0.797, ACC = 0.722, sensitivity = 0.758, specificity = 0.693). The median R-score was 0.518 (IQR, 0.023-0.987), and the patients were divided into high-risk and low-risk groups based on this cut-off value. The KM survival curves of the two groups demonstrated evident stratification results (p = 0.000).

[Investigation on serology, risk factor and awareness of angiostrongylus cantonensis in Hainan province].

Five survey sites were selected from Hainan Province and one village were randomly extracted in each site. A survey that covered knowledge and risk factor on angiostrongyliasis cantonensis was conducted and infection rate of Angiostrongylus cantonensis tested by ELISA. Among 393 sampled people, the sero-positive IgG rate was 20.6% and about 39.7% residents were found with a history of eating snails in recent half year, 12.5% from respondents had the habit of eating raw snails. Questionnairing showed that the ratio of awareness on A. cantonensis was 8.4%. All factors were analyzed by multi-logistic module and showed that the history of snail-eating and resident area may be the risk factors.

[Epidemiology of soil-transmitted nematode infections in central mountain area of Hainan province].

The epidemiology of soil-transmitted intestinal nematodes were observed in the central mountain area without anti-helminthic therapy from 1986 to 2008. The results showed that the overall prevalence decreased from 96.4% in 1986 to 35.7% in 2008. The prevalence of Ancylostoma duodenale, Ascaris lumbricoides and Trichuris trichiura decreased from 84.7%. 80.9%, 31.8% in 1986 to 32.5%, 0.3%, 4.2% in 2008, respectively. The proportion of light infection with Ancylostoma duodenale, Ascaris lumbricoides and Trichuris trichiura increased from 56.6%, 41.2%, and 66.9% in 1986 to 97.9%, 100%, and 83.7% in 2008, respectively. While that of heavy infection decreased from 6.8%, 11.9%, and 3.8% in 1986 all to zero in 2008. Water and toilet renovation, rural income increase and the improvement of sanitation and living conditions made the prevalence of soil-transmitted intestinal nematode decreased.

Defending the homeland: microbiome molecules provide protection to their vertebrate hosts.

Aim: The resident bacterial microbiome may shape and protect the health of vertebrate host. An array of molecules secreted by microbiome may contribute to the ecological stability of the microbiome itself. Material & methods: ELISA, radioactivity, immunofluorescence and cytokines measurements were used to observe the bioactivity and stability of colicin Ia level in oviparous and viviparous animal circulation. Results: Colicin Ia, a protein antimicrobial produced by Escherichia coli, is not present in animals at birth, but increases in concentration with the establishment of a stable gut microbiome and drops when the microbiome is experimentally disrupted. Colicin introduced in vivo is transported to tissues at concentrations able to prevent or eliminate bacterial infection. Conclusion: Our findings suggest an unexpected benefit provided by the presence of a resident microbiome in the form of active, circulating, bacterially-synthesized antimicrobial molecules.

Tumor location as an indication for adjuvant radiotherapy in pT3N0 rectal cancer after surgery.

BACKGROUND: The optimal care for pT3N0 rectal cancer remains controversial. And whether tumor location can be used to guide the administration of adjuvant radiotherapy for pT3N0 rectal cancer is not fully confirmed. The current study was designed to identify the benefit of adjuvant radiotherapy for pT3N0 rectal cancer. METHODS: We performed a retrospective study of 265 pT3N0 rectal cancer patients who were treated by surgery and adjuvant therapy from Mar. 2005 to Sept. 2015. All patients were divided into two groups according to receiving adjuvant radiotherapy or not. Overall survival (OS), disease-free survival (DFS) were compare between patients who did and did not receive adjuvant radiotherapy. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS). RESULTS: For patients with lower tumor, DFS in adjuvant chemo-radiotherapy group was higher than that in adjuvant chemotherapy group. Besides, the rates of local recurrence and distant metastasis were found lower in patients who did receive adjuvant radiotherapy than those who did not. For patients with upper tumor, the 5-year OS and DFS were similar between groups of adjuvant chemotherapy and adjuvant chemo-radiotherapy. Multivariable analysis indicated both the CEA and tumor location were independent predictors of LRFS. And adjuvant radiotherapy predicted the DFS, LRFS and DMFS in lower rectal cancer patients. CONCLUSION: Tumor location can serve as an indication for the administration of adjuvant radiotherapy in pT3N0 rectal cancer patients.

A review on the engine performance and exhaust emission characteristics of diesel engines fueled with biodiesel blends.

Biodiesels have gained much popularity because they are cleaner alternative fuels and they can be used directly in diesel engines without modifications. In this paper, a brief review of the key studies pertaining to the engine performance and exhaust emission characteristics of diesel engines fueled with biodiesel blends, exhaust aftertreatment systems, and low-temperature combustion technology is presented. In general, most biodiesel blends result in a significant decrease in carbon monoxide and total unburned hydrocarbon emissions. There is also a decrease in carbon monoxide, nitrogen oxide, and total unburned hydrocarbon emissions while the engine performance increases for diesel engines fueled with biodiesels blended with nano-additives. The development of automotive technologies, such as exhaust gas recirculation systems and low-temperature combustion technology, also improves the thermal efficiency of diesel engines and reduces nitrogen oxide and particulate matter emissions.

Extraskeletal osteosarcoma in right neck subcutaneous tissue: A case report of an extremely rare tumour.

Extraskeletal osteosarcoma (ESOS) is a rare soft-tissue sarcoma that is treated with surgical resection, chemotherapy and radiotherapy; however, as it is now considered to be radiation resistance, it is associated with conflicting management principles and poor outcomes. A multimodality approach is currently used to treat ESOS, which entails the incorporation of multidrug chemotherapy and/or radiotherapy coupled with surgery to obtain the best outcome; however, there are many factors that influence the treatment effects and clinical outcomes of ESOS. In the present study, a case of an 81-year-old man who suffered from primary ESOS in the subcutaneous tissue of the right-hand side of the neck was reported. The patient was treated several times with partial resection and once with radiotherapy, and was still living following 3 years of follow-up. Thus, the present case report demonstrated that surgical resection and postoperative radiotherapy regimens may be favourable in the short term with a disease-free survival of ~15 months; however, patients are prone to relapse.

Elevated circulating tumor cells and squamous cell carcinoma antigen levels predict poor survival for patients with locally advanced cervical cancer treated with radiotherapy.

OBJECTIVE: To evaluate the prognostic effects of combining serum circulating tumor cells (CTCs) and squamous cell carcinoma antigen (SCC-Ag) levels on patients with locally advanced cervical cancer treated with radiotherapy. METHODS: Ninety-nine patients with locally advanced cervical cancer ([FIGO] stage IIB-IVA) undergoing radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) were identified. The association between serum CTC level and clinicopathological parameters was examined. Univariate and multivariate survival analyses were performed by using Cox's proportional hazards regression model. RESULTS: Elevated CTC and SCC-Ag levels were significantly associated with poor disease-free survival (DFS). Multivariate analysis suggest that serum CTC level, FIGO stage and serum SCC-Ag level were independent prognostic factors for two-year DFS. When CTC and SCC-Ag levels were combined into a new risk model to predict disease progression of cervical cancer patients, it performed a significantly better predictive efficiency compared with either biomarker alone. CONCLUSION: Serum CTC and SCC-Ag levels are potentially useful biomarkers for prediction of prognosis in locally advanced cervical cancer patients and their combination significantly improves predictive ability for survival in locally advanced cervical cancer patients.

Identification of starch grains in microscopic images based on granulometric operations.

This study demonstrates the feasibility of feature extraction and similarity measurement for the identification of starch grains, which are often found in microscopic images of Chinese Materia Medica (CMM) and as such is an important feature for use in the authentication of CMM with abundance of starch grains and otherwise without other special microscopic characteristics. Our proposed image signature, namely, the size distribution, indicates that it is effective to characterize starch grains in microscopic images of those CMM. Experimental results in a small scale study show that the recognition rate for the proposed signature using different measures of discrepancy is around 90%, which is considered very good while the benchmark wavelet-based energy signature has only about 60% recognition. Moreover, the extraction of the size distribution only requires moderate level of computational complexity. In this study, our proposed image signature provides greater accuracy and flexibility in capturing starch grains information for the authentication of CMM, compared with other existing preliminary identification approach in which manual image segmentation is necessary.

Anti-tumor activity of metformin: from metabolic and epigenetic perspectives.

Metformin has been used to treat type 2 diabetes for over 50 years. Epidemiological, preclinical and clinical studies suggest that metformin treatment reduces cancer incidence in diabetes patients. Due to its potential as an anti-cancer agent and its low cost, metformin has gained intense research interest. Its traditional anti-cancer mechanisms involve both indirect and direct insulin-dependent pathways. Here, we discussed the anti-tumor mechanism of metformin from the aspects of cell metabolism and epigenetic modifications. The effects of metformin on anti-cancer immunity and apoptosis were also described. Understanding these mechanisms will shed lights on application of metformin in clinical trials and development of anti-cancer therapy.

Regulation of SESAME-mediated H3T11 phosphorylation by glycolytic enzymes and metabolites.

Cancer cells prefer aerobic glycolysis, but little is known about the underlying mechanism. Recent studies showed that the rate-limiting glycolytic enzymes, pyruvate kinase M2 (PKM2) directly phosphorylates H3 at threonine 11 (H3T11) to regulate gene expression and cell proliferation, revealing its non-metabolic functions in connecting glycolysis and histone modifications. We have reported that the yeast homolog of PKM2, Pyk1 phosphorylates H3T11 to regulate gene expression and oxidative stress resistance. But how glycolysis regulates H3T11 phosphorylation remains unclear. Here, using a series of glycolytic enzyme mutants and commercial available metabolites, we investigated the role of glycolytic enzymes and metabolites on H3T11 phosphorylation. Mutation of glycolytic genes including phosphoglucose isomerase (PGI1), enolase (ENO2), triosephosphate isomerase (TPI1), or folate biosynthesis enzyme (FOL3) significantly reduced H3T11 phosphorylation. Further study demonstrated that glycolysis regulates H3T11 phosphorylation by fueling the substrate, phosphoenonylpyruvate and the coactivator, FBP to Pyk1. Thus, our results provide a comprehensive view of how glycolysis modulates H3T11 phosphorylation.