Identification of ROS and KEAP1-related genes and verified targets of α-hederin induce cell death for CRC.

In this study, we analyzed and verified differentially expressed genes (DEGs) in ROS and KEAP1 crosstalk in oncogenic signatures using GEO data sets (GSE4107 and GSE41328). Multiple pathway enrichment analyses were finished based on DEGs. The genetic signature for colorectal adenocarcinoma (COAD) was identified by using the Cox regression analysis. Kaplan-Meier survival and receiver operating characteristic curve analysis were used to explore the prognosis value of specific genes in COAD. The potential immune signatures and drug sensitivity prediction were also analyzed. Promising small-molecule agents were identified and predicted targets of α-hederin in SuperPred were validated by molecular docking. Also, expression levels of genes and Western blot analysis were conducted. In total, 48 genes were identified as DEGs, and the hub genes such as COL1A1, CXCL12, COL1A2, FN1, CAV1, TIMP3, and IGFBP7 were identified. The ROS and KEAP1-associated gene signatures comprised of hub key genes were developed for predicting the prognosis and evaluating the immune cell responses and immune infiltration in COAD. α-hederin, a potential anti-colorectal cancer (CRC) agent, was found to enhance the sensitivity of HCT116 cells, regulate CAV1 and COL1A1, and decrease KEAP1, Nrf2, and HO-1 expression significantly. KEAP1-related genes could be an essential mediator of ROS in CRC, and KEAP1-associated genes were effective in predicting prognosis and evaluating individualized CRC treatment. Therefore, α-hederin may be an effective chemosensitizer for CRC treatments in clinical settings.

Differences in metabolic transport and resistance mechanisms of Abemaciclib, Palbociclib, and Ribociclib.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) play a crucial role in cancer treatment, particularly in breast cancer, and their mechanism of drug resistance is a topic of global interest in research. Hence, it is vital to comprehend the distinctions between various CDK4/6i, including their mechanisms of action and resistance mechanisms. This article aims to summarize the metabolic and transport variations as well as the differences in resistance among the three FDA-approved CDK4/6 inhibitors: Abemaciclib, Palbociclib, and Ribociclib. It also aims to discuss how these differences impact the effectiveness and safety of anticancer drugs. It was conducted in March 2023 to search PubMed, Embase, and Web of Science for literature related to this topic. Despite all being CDK4/6i, differences in their metabolism and transport were found, which are related to their chemical structure. Moreover, there are variations in preclinical pharmacology, pharmacokinetics, and clinical safety and efficacy of the different inhibitors. Genetic mutations, drug tolerance, and other factors may influence CDK4/6 resistance mechanisms. Currently, the resistance mechanisms differences of the three drugs remain largely unknown, and there are differences in the resistance mechanisms among them, necessitating further exploration and research.

The Oncogenic Role of Cyclin-Dependent Kinase Inhibitor 2C in Lower-Grade Glioma.

Lower-grade gliomas (LGGs) are slow-growing, indolent tumors that usually affect younger patients and present a therapeutic challenge due to the heterogeneity of their clinical presentation. Dysregulation of cell cycle regulatory factors is implicated in the progression of many tumors, and drugs that target cell cycle machinery have shown efficacy as promising therapeutic approaches. To date, however, no comprehensive study has examined how cell cycle-related genes affect LGG outcomes. The cancer genome atlas (TCGA) data were used as the training set for differential analysis of gene expression and patient outcomes; the Chinese glioma genome atlas (CGGA) was used for validation. Levels of one candidate protein, cyclin-dependent kinase inhibitor 2C (CDKN2C), and its relationship to clinical prognosis were determined using a tissue microarray containing 34 LGG tumors. A nomogram was constructed to model the putative role of candidate factors in LGG. Cell type proportion analysis was performed to evaluate immune cell infiltration in LGG. Various genes encoding cell cycle regulatory factors showed increased expression in LGG and were significantly related to isocitrate dehydrogenase and chromosome arms 1p and 19q mutation status. CDKN2C expression independently predicted the outcome of LGG patients. High M2 macrophage values along with elevated CDKN2C expression were associated with poorer prognosis in LGG patients. CDKN2C plays an oncogenic role in LGG, which is associated with M2 macrophages.

Screening and preliminary identification of long non-coding RNAs critical for osteogenic differentiation of human umbilical cord mesenchymal stem cells.

Human umbilical cord mesenchymal stem cells (hUCMSCs) are attractive therapeutic cells for tissue engineering to treat bone defects. However, how the cells can differentiate into bone remains unclear. Long non-coding RNAs (lncRNAs) are non-coding RNAs that participate in many biological processes, including stem cell differentiation. In this study, we investigated the profiles and functions of lncRNAs in the osteogenic differentiation of hUCMSCs. We identified 343 lncRNAs differentially expressed during osteogenic differentiation, of which 115 were upregulated and 228 were downregulated. We further analyzed these lncRNAs using bioinformatic analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. GO and KEGG pathway analysis showed that 'intracellular part' and 'Phosphatidylinositol signaling system' were the most correlated molecular function and pathway, respectively. We selected the top 10 upregulated lncRNAs to construct six competing endogenous RNA networks. We validated the impact of the lncRNA H19 on osteogenic differentiation by overexpressing it in hUCMSCs. Overall, our results pave the way to detailed studies of the molecular mechanisms of hUCMSC osteogenic differentiation, and they provide a new theoretical basis to guide the therapeutic application of hUCMSCs.

A dual role of HIF1α in regulating osteogenesis-angiogenesis coupling.

OBJECTIVES: The hypoxia-inducible factor 1-α (HIF1α), a key molecule in mediating bone-vessel crosstalk, has been considered a promising target for treating osteoporosis caused by gonadal hormones. However, senile osteoporosis, with accumulated senescent cells in aged bone, has a distinct pathogenesis. The study aimed at revealing the unknown role of HIF1α in aged bone, thus broadening its practical application in senile osteoporosis. MATERIALS AND METHODS: Femurs and tibias were collected from untreated mice of various ages (2 months old, 10 months old, 18 months old) and treated mice (2 months old, 18 months old) underwent 4-w gavage of 2-methoxyestradiol (a kind of HIF1α inhibitor). Bone-vessel phenotypes were observed by microfil infusion, micro-CT and HE staining. Markers of senescence, osteogenesis, angiogenesis, oxidative stress and expression of HIF1α were detected by senescence ß-galactosidase staining, qRT-PCR, western blot and immunostaining, respectively. Furthermore, bone mesenchymal stem cells from young mice (YBMSCs) and aged mice (ABMSCs) were transfected by knockout siRNA and overexpression plasmid of HIF1α. Senescence ß-galactosidase staining, Cell Counting Kit-8, transwell assay, alkaline phosphatase staining, alizarin red-S staining and angiogenesis tests were utilized to assess the biological properties of two cell types. Then, Pifithrin-α and Nutlin-3a were adopted to intervene p53 of the two cells. Finally, H2O2 on YBMSCs and NAC on ABMSCs were exploited to change their status of oxidative stress to do a deeper detection. RESULTS: Senescent phenotypes, impaired osteogenesis-angiogenesis coupling and increased HIF1α were observed in aged bone and ABMSCs. However, 2-methoxyestradiol improved bone-vessel metabolism of aged mice while damaged that of young mice. Mechanically, HIF1α showed opposed effects in regulating the cell migration and osteogenesis-angiogenesis coupling of YBMSCs and ABMSCs, but no remarked effect on the proliferation of either cell type. Pifithrin-α upregulated the osteogenic and angiogenic markers of HIF1α-siRNA-transfected YBMSCs, and Nutlin-3a alleviated those of HIF1α-siRNA-transfected ABMSCs. The HIF1α-p53 relationship was negative in YBMSCs and NAC-treated ABMSCs, but positive in ABMSCs and H2O2-treated YBMSCs. CONCLUSION: The dual role of HIF1α in osteogenesis-angiogenesis coupling may depend on the ROS-mediated HIF1α-p53 relationship. New awareness about HIF1α will be conducive to its future application in senile osteoporosis.

Triterpenoids of Rhus chinensis Supressed Colorectal Cancer Progress by Enhancing Antitumor Immunity and CD8 + T Cells Tumor Infiltration.

The absence of CD8+ T cells in the tumor center has become a major obstacle in the immunotherapy of colorectal cancer. Therefore, new therapeutic strategies are urgently needed to promote the accumulation of CD8+ T cells in the tumor center. Previous studies have shown that triterpenoid of Rhus chinensis (TER) is involved in the proliferation and apoptosis of colorectal cancer cells, and can regulate their immune activity, but its mechanism needs to be further elucidated. In this study, the antitumor effect and adaptive immune response of TER on tumor-bearing mice were evaluated and compared with 5-fluorouracil. The results showed that TER could significantly inhibit tumor growth and prolong the survival time of tumor-bearing mice. The In Vivo studies have shown that TER can not only enhance antitumor immunity and promote the accumulation of CD8 + T cells to tumor sites, but also inhibit tumor progression by regulating the expression of PD-1 and PD-L1 and significantly reducing the mortality of mice. Our study demonstrated for the first time that TER has oncolytic effect, and recruited adaptive immune cells to enhance the efficacy of anti-PD-1/PD-L1 in colorectal cancer, which provides a potential therapeutic target for combined immunotherapy of colorectal cancer.

The stiffness of transplanted kidneys changes with time after renal transplantation.

BACKGROUND: Kidney transplantation is one of the most effective ways to treat end-stage kidney disease. However, 5000 renal transplant recipients start or restart dialysis because of chronic allograft nephropathy (CAN) every year in the United States. Detecting changes in the stiffness of transplanted kidneys can help diagnose transplanted kidney disease. PURPOSE: To explore changes in the stiffness of transplanted kidneys after renal transplantation using shear wave elastography (SWE). MATERIAL AND METHODS: This study conducted consecutive follow-up observations on 10 patients after kidney transplantation. SWE examination was performed in the first week, second week, first month, second month, third month, fourth month, fifth month, and sixth month after surgery. This study also analyzed the graft stiffness of 86 patients with stable renal function recovery one month after surgery. RESULTS: The results show that there is a change in the stiffness of the transplanted kidney over time after renal transplantation. It decreases rapidly within one month after renal transplantation and tends to be stable after one month. The mean renal cortical and pyramidal stiffness of patients with stable renal function were 28.48 ± 4.27 kPa and 21.97 ± 3.90 kPa, respectively. CONCLUSION: Consecutive stiffness measurement of transplanted kidneys is an effective method for monitoring the function of transplanted kidneys. According to the change in transplanted kidney stiffness, we can designate a more scientific review plan to determine the functional status of the transplanted kidney.

Diagnostic Accuracy of Three-Dimensional Endoanal Ultrasound for Anal Fistula: A Systematic Review and Meta-analysis.

BACKGROUND: Anal fistula is a relatively common anorectal disease. An accurate assessment of the main anal fistula type and the anatomy of the internal opening before surgery is necessary to obtain the best surgical results. Whether three-dimensional endoanal ultrasound (3D-EAUS) should be used as the first-line diagnostic tool for anal fistula is still controversial. The purpose of this study is to conduct a meta-analysis of the published literature on 3D-EAUS and anal fistula, and compare the results of 3D-EAUS and surgery to evaluate the diagnostic value of 3D-EAUS for anal fistula. METHODS: An online search of databases in English included PubMed, Embase, and Cochrane Library. After the diagnostic accuracy of 3D-EAUS of all anal fistula types was integrated, a single-group rate meta-analysis was performed; we analyzed 3D-EAUS separately for the diagnosis of different anal fistula types, and conducted a meta-analysis of test accuracy. The analysis combined sensitivity, specificity, and the respective 95% CI, to draw a summary receiver operating characteristic curve (SROC), and estimate the area under curve (AUC). RESULTS: Based on the inclusion criteria, we selected 8 studies covering 1057 cases of anal fistula and 548 cases of internal opening. The meta-analysis data show that 3D-EAUS has a total accuracy rate of 91% (95% CI, 88-94%). It has high sensitivity and specificity for different anal fistula classifications. The SROC curves for anal fistula internal openings were plotted, and the AUC was calculated to be 0.86 (95% CI, 0.83-0.89). CONCLUSIONS: 3D-EAUS can be used as the first-line diagnostic tool for anal fistula, because it has a high diagnostic accuracy for most anal fistulas. However, due to the insufficient diagnostic accuracy of 3D-EAUS for complex fistulas, 3D-EAUS combined with MRI examination can be used to more accurately detect the secondary extension of complex fistulas, so as to describe the complete anatomy of the fistula in more detail.

The Spectroscopic Properties and Microscopic Imaging of Thulium-Doped Upconversion Nanoparticles Excited at Different NIR-II Light.

Lanthanide-doped upconversion nanoparticles (UCNPs) are promising bioimaging nanoprobes due to their excellent photostability. As one of the most commonly used lanthanide activators, Tm3+ ions have perfect ladder-type electron configuration and can be directly excited by bio-friendly near-infrared-II (NIR-II) wavelengths. Here, the emission characteristics of Tm3+-doped nanoparticles under laser excitations of different near-infrared-II wavelengths were systematically investigated. The 1064 nm, 1150 nm, and 1208 nm lasers are proposed to be three excitation strategies with different response spectra of Tm3+ ions. In particular, we found that 1150 nm laser excitation enables intense three-photon 475 nm emission, which is nearly 100 times stronger than that excited by 1064 nm excitation. We further optimized the luminescence brightness after investigating the luminescence quenching mechanism of bare NaYF4: Tm (1.75%) core. After growing an inert shell, a ten-fold increase of emission intensity was achieved. Combining the advantages of NIR-II wavelength and the higher-order nonlinear excitation, a promising facile excitation strategy was developed for the application of thulium-doped upconversion nanoparticles in nanoparticles imaging and cancer cell microscopic imaging.

Prediction of tumor size in patients with invasive ductal carcinoma using FT-IR spectroscopy combined with chemometrics: a preliminary study.

Precise detection of tumor size is essential for early diagnosis, treatment, and evaluation of the prognosis of breast cancer. However, there are some errors between the tumor size of breast cancer measured by conventional imaging methods and the pathological tumor size. Invasive ductal carcinoma (IDC) is a common pathological type of breast cancer. In this study, serum Fourier transform infrared spectroscopy (FT-IR) combined with chemometric methods was used to predict the maximum diameter and maximum vertical diameter of tumors in IDC patients. Three models were evaluated based on the pathological tumor size measured after surgery and included grid search support vector machine regression (GS-SVR), back propagation neural network optimized by genetic algorithm (GA-BP-ANN), and back propagation neural network optimized by particle swarm optimization (PSO-BP-ANN). The results show that three models can accurately predict tumor size. The GA-BP-ANN model provided the best fitting quality of the largest tumor diameter with the determination coefficients of 0.984 in test set. And the GS-SVR model provided the best fitting quality of the largest vertical tumor diameter with the determination coefficients of 0.982 in test set. The GS-SVR model had the highest prediction efficiency and the lowest time complexity of the models. The results indicate that serum FT-IR spectroscopy combined with chemometric methods can predict tumor size in IDC patients. In addition, compared with traditional imaging methods, we found that the experimental results of the three models are better than traditional imaging methods in terms of correlation and fitting degree. And the average fitting error of PSO-BP-ANN and GA-BP-ANN models was less than 0.3 mm. The minimally invasive detection method is expected to be developed into a new clinical diagnostic method for tumor size estimation to reduce the diagnostic trauma of patients and provide new diagnostic experience for patients. Graphical Abstract.

Detection of breast cancer of various clinical stages based on serum FT-IR spectroscopy combined with multiple algorithms.

BACKGROUND: Breast cancer screening is time consuming, requires expensive equipment, and has demanding requirements for doctors. Hence, a large number of breast cancer patients may miss screening and early treatment, which greatly threatens their health around the world. Infrared spectroscopy may be able to be used as a screening tool for breast cancer detection. Fourier transform infrared (FT-IR) spectroscopy of serum was combined with traditional machine learning algorithms to achieve an auxiliary diagnosis that could quickly and accurately distinguish patients with different stages of breast cancer, including stage 1 disease, from control subjects without breast cancer. MATERIALS AND METHODS: FT-IR spectroscopy were performed on the serum of 114 non-cancer control subjects, 35 patients with stage I, 43 patients with stage II, and 29 patients with stage III & IV breast cancer. Due to the experimental sample imbalance, we used the oversampling to process the four classes of sample. The oversampling selected Synthetic Minority Oversampling Technique (SMOTE). Subsequently, we used the random discarding method in undersampling to do experiments as well. The average FT-IR spectroscopy results for the four groups showed differences in phospholipids, nucleic acids, lipids, and proteins between non-cancer control subjects and breast cancer patients at different stages. Based on these differences, four classification models were used to classify stage I, II, III & IV breast cancer patients and non-cancer control subjects. First, standard normal variate transformation (SNV) was used to preprocess the original data, and then partial least squares (PLS) was used for feature extraction. Finally, the five models were established including extreme learning machine (ELM), k-nearest neighbor (KNN), genetic algorithms based on support vector machine (GA-SVM), particle swarm optimization-support vector machine (PSO-SVM) and grid search-support vector machine (GS-SVM). CONCLUSION: In oversampling experiment, the GS-SVM classifier obtained the highest average classification accuracy of 95.45 %; the diagnostic accuracy of non-cancer control subjects was 100 %; breast cancer stage I was 90 %; breast cancer stage II was 84.62 %; and breast cancer stage III & IV was 100 %. In undersampling experiment, the GA-SVM model obtained the highest average classification accuracy of 100 %; the diagnostic accuracy of non-cancer control subjects was 100 %; breast cancer stage I was 100 %; breast cancer stage II was 100 %; and breast cancer stage III & IV was 100 %. The results show that FT-IR spectroscopy combined with powerful classification algorithms has great potential in distinguishing patients with different stages of breast cancer from non-cancer control subjects. In addition, this research provides a reference for future multiclassification studies of cervical cancer, ovarian cancer and other female high-incidence cancers through serum FT-IR spectroscopy.

Bisphenol A(BPA), BPS and BPB-induced oxidative stress and apoptosis mediated by mitochondria in human neuroblastoma cell lines.

The analogues of biphenol A (BPA), including bisphenol S (BPS) and bisphenol B (BPB), are commonly used to replace the application of BPA in containers and wrappers of daily life. However, their safeties are questioned due to their similar chemical structure and possible physiological effects as BPA. To investigate the neurotoxic effects of BPA, BPS, and BPB as well as their underlying mechanism, IMR-32 cell line from male and SK-N-SH cell line from female were exposed respectively to BPA, BPS and BPB with concentrations of 1 nM, 10 nM, 100 nM, 1 µM, 10 µM, and 100 µM for 24 h. Additionally, 24 h exposure of BPA combining epigallocatechin gallate (EGCG) (4 µM and 8 µM for IMR-32 and SK-N-SH respectively) were conducted. Results demonstrated that BPs exposure could promote reactive oxygen species production and increase level of malondialdehyde (MDA) while decrease levels of superoxide dismutase (SOD). Intensive study revealed that after exposure to BPA mitochondrial membrane potential (MMP) dropped down and the protein expression levels of Bak-1, Bax, cytochrome c and Caspase-3 were up-regulated but Bcl-2 were down-regulated significantly. Moreover, apoptosis rate was raised and cell activity declined remarkably in the neuroblastoma cells. All the effects induced by BPA could be alleviated by the adding of EGCG, which similar alleviations could be inferred in IMR-32 and SK-N-SH cells induced by BPS and BPB. Furthermore, BPS showed lower neurotoxic effects compared to BPA and BPB. Interestingly, the neurotoxic effects of BPA on IMR-32 cells were significantly higher than those on SK-N-SH cells. In conclusion, the results suggested that BPA, BPS and BPB could induce oxidative stress and apoptosis via mitochondrial pathway in the neuroblastoma cells and male is more susceptible to BPs than female.

Berberine promotes peri-implant osteogenesis in diabetic rats by ROS-mediated IRS-1 pathway.

Accompanying with diabetes mellitus-induced osteoporosis (DM-OS), diabetic patients show poor peri-implant osteogenesis after implantation for dentition defect. Berberine (BBR), a candidate oral hypoglycemic agent, is a promising agent for treating DM-OS. In this study, BBR was applied on DM rats and high-glucose-cultured bone mesenchymal stem cells (BMSCs) to investigate its therapeutic mechanism on DM-OS, thus laying a theoretical basis for the future application of BBR in implant restoration. Phenotypes were assessed in the DM rats after 4 w of gavage with BBR. Furthermore, BMSCs were cultured with high glucose and BBR. Cell Counting Kit-8, 2',7'-dichlorofluorescin diacetate (H2 DCF-DA), quantitative real-time PCR (qRT-PCR), and western blot were performed to estimate the cell proliferation, oxidative stress, and osteogenic differentiation. Moreover, the DM rats treated with BBR and insulin receptor substrate-1 anti-sense oligonucleotide (IRS-1-ASO) underwent a 4-w implant-healing period and then micro computed tomography (Micro-CT) and histology were performed to verify the mechanism. Results showed that the 4-w administration of BBR markedly improved the glucose metabolism and bone metabolism in the DM rats. in vitro experiments revealed that BBR alleviated high-glucose-inhibited osteogenesis of the BMSCs by upregulating reactive oxygen species (ROS)-mediated IRS-1 signaling. Besides, injection of IRS-1-ASO abolished the BBR promotion of implant osseointegration in the DM rats. In conclusion, targeting ROS-mediated IRS-1 signaling, BBR acted as an efficient agent to advance osseointegration in DM, which indicated that BBR use is a good strategy for future implants restoration in diabetic patients.

Rapid identification of cervical adenocarcinoma and cervical squamous cell carcinoma tissue based on Raman spectroscopy combined with multiple machine learning algorithms.

Cervical cancer has a long latency, and early screening greatly reduces mortality. In this study, cervical adenocarcinoma and cervical squamous cell carcinoma tissue data were collected by Raman spectroscopy, and then, the adaptive iteratively reweighted penalized least squares (airPLS) algorithm and Vancouver Raman algorithm (VRA) were used to subtract the background of the collected data. The following five feature extraction algorithms were applied: partial least squares (PLS), principal component analysis (PCA), kernel principal component analysis (KPCA), isometric feature mapping (isomap) and locally linear embedding (LLE). The k-nearest neighbour (KNN), extreme learning machine (ELM), decision tree (DT), backpropagation neural network (BP), genetic optimization backpropagation neural network (GA-BP) and linear discriminant analysis (LDA) classification models were then established through the features extracted by different feature extraction algorithms. In total, 30 types of classification models were established in this experiment. This research includes eight good models, airPLS-PLS-KNN, airPLS-PLS-ELM, airPLS-PLS-GA-BP, airPLS-PLS-BP, airPLS-PLS-LDA, airPLS-PCA-KNN, airPLS-PCA-LDA, and VRA-PLS-KNN, whose diagnostic accuracy was 96.3 %, 95.56 %, 95.06 %, 94.07 %, 92.59 %, 85.19 %, 85.19 % and 85.19 %, respectively. The experimental results showed that the model established in this article is simple to operate and highly accurate and has a good reference value for the rapid screening of cervical cancer.

Effects and mechanisms of fatty acid metabolism­mediated glycolysis regulated by betulinic acid­loaded nanoliposomes in colorectal cancer.

Although previous studies have demonstrated that triterpenoids, such as betulinic acid (BA), can inhibit tumor cell growth, their potential targets in colorectal cancer (CRC) metabolism have not been systematically investigated. In the present study, BA­loaded nanoliposomes (BA­NLs) were prepared, and their effects on CRC cell lines were evaluated. The aim of the present study was to determine the anticancer mechanisms of action of BA­NLs in fatty acid metabolism­mediated glycolysis, and investigate the role of key targets, such as acyl­CoA synthetase (ACSL), carnitine palmitoyltransferase (CPT) and acetyl CoA, in promoting glycolysis, which is activated by inducing hexokinase (HK), phosphofructokinase­1 (PFK­1), phosphoenolpyruvate (PEP) and pyruvate kinase (PK) expression. The results demonstrated that BA­NLs significantly suppressed the proliferation and glucose uptake of CRC cells by regulating potential glycolysis and fatty acid metabolism targets and pathways, which forms the basis of the anti­CRC function of BA­NLs. Moreover, the effects of BA­NLs were further validated by demonstrating that the key targets of HK2, PFK­1, PEP and PK isoenzyme M2 (PKM2) in glycolysis, and of ACSL1, CPT1a and PEP in fatty acid metabolism, were blocked by BA­NLs, which play key roles in the inhibition of glycolysis and fatty acid­mediated production of pyruvate and lactate. The results of the present study may provide a deeper understanding supporting the hypothesis that liposomal BA may regulate alternative metabolic pathways implicated in CRC adjuvant therapy.

Correlation Between Endorectal Ultrasound and Magnetic Resonance Imaging for Predicting the Circumferential Resection Margin in Patients With Mid-Low Rectal Cancer Without Preoperative Chemoradiotherapy.

OBJECTIVES: To assess the correlation between endorectal ultrasound (ERUS) and magnetic resonance imaging (MRI) in predicting the circumferential resection margin (CRM) status of patients with mid-low rectal cancer without preoperative chemoradiotherapy. METHODS: Twenty patients with rectal cancer who did not receive preoperative chemoradiotherapy and underwent ERUS and MRI examinations before total mesorectal excision from May 2018 to April 2019 were included in this study. The patient and tumor characteristics, lymph nodes, tumor stages, ERUS and MRI predictors of the CRM status, and postoperative pathologic results were recorded. The closest distance between the deepest portion of lesion invasion and the mesorectal fascia was independently measured on MRI and ERUS images by 2 observers. The observers were blinded to the pathologic results. Measurements from ERUS and MRI were compared. RESULTS: The mean distance between the distal edge of the lesion and the anal verge was 5.7 cm (range, 3.1-8.1 cm). The ERUS and pathologic evaluations of CRM involvement were consistent in 90% of the cases. The MRI and pathologic evaluations of CRM involvement were concordant in 95% of the cases. The Cohen κ coefficient of ERUS and MRI was 0.608 (P = .007). The correlation coefficient of ERUS and MRI for assessing the closest distance from the edge of cancer invasion to the mesorectal fascia was 0.99 (P = .0005). CONCLUSIONS: Endorectal ultrasound and MRI assessments of the preoperative CRM status appear to be highly consistent. Endorectal ultrasound can be used as a complementary tool with MRI to predict the CRM status of patients with mid-low rectal cancer without preoperative chemoradiotherapy.

Randomized Trial on Comparison of the Efficacy of Extracorporeal Shock Wave Therapy and Dry Needling in Myofascial Trigger Points.

OBJECTIVE: The aim of the study was to compare the efficacy of radial extracorporeal shock wave therapy and dry needling in the treatment of myofascial trigger points in the upper trapezius muscle. DESIGN: A total of 65 patients with myofascial trigger points were randomly divided into extracorporeal shock wave therapy group (n = 32) and dry needling group (n = 33). Patients received 3 wks of treatment at 1-wk intervals (in both groups). Visual analog scale, pressure pain threshold, Neck Disability Index, and shear modulus were evaluated before treatment, immediately after the first therapy, 1 mo, and 3 mos after the completion of the third therapy. RESULTS: Significant improvements of visual analog scale, pressure pain threshold, and Neck Disability Index scores were observed at all time points after treatment (P < 0.01) in both treatment groups. The shear modulus of myofascial trigger points was reduced in both dry needling group (P < 0.05) and extracorporeal shock wave therapy group (P < 0.01) immediately after the first treatment. Significant reductions in shear modulus were maintained up to 3-mo posttreatment in both groups (P < 0.01). There were no significant differences between the radial extracorporeal shock wave therapy group and dry needling group. CONCLUSIONS: The extracorporeal shock wave therapy is as effective as dry needling for relieving pain, improving function, and reducing shear modulus for patients with myofascial trigger points after a series of three treatments.

Idiomarina mangrovi sp. nov., isolated from rhizosphere soil of a mangrove Avicennia marina forest.

A Gram-staining negative, aerobic, motile and rod-shaped bacterium, designated ZQ330T, was isolated from rhizosphere soil of a mangrove (Avicennia marina) forest of Zhangzhou, Fujian Province, China. The growth range of NaCl concentration was 0.5-10.0 % (w/v), with an optimum at 2.5-3.0 % (w/v), the temperature range for growth was 10-40 °C, with an optimum at 28-30 °C, the pH range for growth was pH 6.0-9.5, with an optimum at pH 7.5. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain ZQ330T exhibited less than 97.0 % sequence similarity to all type strains with validly published names and revealed that strain ZQ330T formed a distinct lineage in the genus Idiomarina. The average nucleotide identity, and in silico DNA-DNA hybridization values between strain ZQ330T and the reference strains were 64.8-69.9 % and 27.5-28.4 %, respectively. Chemotaxonomic analysis indicated that the main respiratory quinone was Q-8, the predominant cellular fatty acids were iso-C15 : 0, iso-C17 : 0, summed feature 9 (C16 : 0 10-methyl and/or iso-C17 : 1ω9c), iso-C15 : 1F, C16 : 0, C18 : 0, summed feature 3 (C16 : 1ω8c and/or iso-C16 : 1 2-OH) and summed feature 8 (C18 : 1ω6c and/or C18 : 1ω7c). The polar lipid profile was composed of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, an unidentified glycolipid, an unidentified aminolipid, an unidentified phospholipid and two unidentified lipids. Based on the genotypic, phenotypic, chemotaxonomic and phylogenetic features, strain ZQ330T is considered to represent a novel species, for which the name Idiomarina mangrovi sp. nov. is proposed. The type strain is ZQ330T (=MCCC 1K03495T=KCTC 62455T).

An Estimate of Natural Gas Methane Emissions from California Homes.

We estimate postmeter methane (CH4) emissions from California's residential natural gas (NG) system using measurements and analysis from a sample of homes and appliances. Quiescent whole-house emissions (i.e., pipe leaks and pilot lights) were measured using a mass balance method in 75 California homes, while CH4 to CO2 emission ratios were measured for steady operation of individual combustion appliances and, separately, for transient operation of three tankless water heaters. Measured quiescent whole-house emissions are typically <1 g CH4/day, though they exhibit long-tailed gamma distributions containing values >10 g CH4/day. Most operating appliances yield undetectable CH4 to CO2 enhancements in steady operation (<0.01% of gas consumed), though storage water heaters and stovetops exhibit long-tailed gamma distributions containing high values (∼1-3% of gas consumed), and transients are observed for the tankless heaters. Extrapolating results to the state-level using Bayesian Markov chain Monte Carlo sampling combined with California housing statistics and gas use information suggests quiescent house leakage of 23.4 (13.7-45.6, at 95% confidence) Gg CH4, with pilot lights contributing ∼30%. Emissions from steady operation of appliances and their pilots are 13.3 (6.6-37.1) Gg CH4/yr, an order of magnitude larger than current inventory estimates, with transients likely increasing appliance emissions further. Together, emissions from residential NG are 35.7 (21.7-64.0) Gg CH4/yr, equivalent to ∼15% of California's NG CH4 emissions, suggesting leak repair, improvement of combustion appliances, and adoption of nonfossil energy heating sources can help California meet its 2050 climate goals.

FoxO1 expression in osteoblasts modulates bone formation through resistance to oxidative stress in mice.

Accumulation of reactive oxygen species (ROS) induced by oxidative stress (OS) affects cell survival, cell function and even results in cell death. As a major transcription factor of forkhead O (FoxOs) family, FoxO1 orchestrates multiple osteoblastic biological processes, thus regulating osteoblast physiology and bone metabolism. However, the outcome of osteoblast behaviors varies under different physiological and pathological conditions. Also, the underlying impact of FoxO1 on oxidative stress and further on bone metabolism still remains unclear. In this study, using osteoblast-specific FoxO1 knockout (FoxO1OB-/-) mice, we investigated the potential roles of FoxO1 on bone formation and osteoblast bioactivity under physiological condition. We show herein that FoxO1-knockout decreased bone volume and bone formation rate in FoxO1OB-/- mice, which might be related to the decreased osteoblasts number. We also found that FoxO1-knockout increased apoptosis-related caspase-3 activity of osteoblasts, and inhibited the expression of osteogenic phenotypic markers (i.e. Runx2, Osx, ALP and OPN), leading to reduced osteoblasts differentiation. The alterations of bone formation and osteoblasts bioactivity were further testified to be linked to the elevated intracellular oxidative stress levels in FoxO1-deficient osteoblasts. Besides, administration of the antioxidant N-acetyl-l-cysteine (NAC) normalized the increased ROS levels in FoxO1-deficient osteoblasts, restoring the decreased osteoblasts differentiation, suppressing apoptosis-related caspase-3 activity, and promoting the expression of osteogenic markers in FoxO1-deficient osteoblasts. These results together illustrated that as a major regulator in redox homeostasis and osteoblast physiology, FoxO1 provides a favorable intracellular environment for osteoblast functions by defensing against the adverse effects of oxidative stress.