Repellency, Toxicity, and Chemical Composition of Plant Essential Oils from Myrtaceae against Asian Citrus Psyllid, Diaphorina citri Kuwayama (Hemiptera Liviidae).

Diaphorina citri Kuwayama (D. citri) is one of the major pests in the citrus industry, which spreads Citrus Huanglongbing disease. It has developed resistance to chemical insecticides. Therefore, searching for greener solutions for pest management is critically important. The main aim of this study was to evaluate the repellent and insecticidal efficacy of essential oils (EOs) from four species of Myrtaceae plants: Psidium guajava (PG), Eucalyptus robusta (ER), Eucalyptus tereticornis (ET), and Baeckea frutescens (BF) against D. citri and to analyze their chemical compositions. GC-MS analysis was performed, and the results indicated that the EOs of PG, ER, ET, and BF were rich in terpenoids, ketones, esters, and alcohol compounds. The repellent rate of all four EOs showed that it decreased with exposure time but increased with the concentration of EOs from 80.50% to 100.00% after treating D. citri for 6 h with four EOs at 100% concentration and decreased to 67.71% to 85.49% after 24 h of exposure. Among the compounds from the EOs tested, eucalyptol had the strongest repellent activity, with a 24 h repellency rate of 100%. The contact toxicity bioassay results showed that all EOs have insecticidal toxicity to D. citri; the LC50 for nymphs was 36.47-93.15 mL/L, and for adults, it was 60.72-111.00 mL/L. These results show that when PG is used as the reference material, the ER, ET, and BF EOs have strong biological activity against D. citri, which provides a scientific basis for the further development of plant-derived agrochemicals.

Effects of Tongluo Jiedu prescription on immune function and oxidative stress in patients with oral cancer.

BACKGROUND: Oral cancer, which is caused by mucous membrane variation, represents a prevalent malignant tumor in the oral and maxillofacial region, posing a significant threat to patients' lives and safety. While surgical intervention stands as a cornerstone treatment for oral cancer patients, it carries the risk of incomplete treatment or high rates of postoperative recurrence. Hence, a multifaceted approach incorporating diverse treatment modalities is essential to enhance patient prognosis. AIM: To analyze the application effect of Tongluo Jiedu prescription as adjuvant therapy and its influence on patient prognosis in patients with oral cancer. METHODS: Eighty oral cancer patients in our hospital were selected and divided into the observation group and control group by a random number table. The control group was treated with continuous arterial infusion chemotherapy of cisplatin and 5-fluorouracil. The observation group was additionally given Tongluo Jiadu prescription. The inflammatory stress level, peripheral blood T-cell subsets, and immune function of the two groups were subsequently observed. SPSS 21.0 was used for data analysis. RESULTS: The observation group demonstrated lower levels of interleukin-6 and C-reactive protein, and a higher level of tumor necrosis factor in comparison to the control group. After treatment, the immune function in the observation group was significantly better than in the control group. CONCLUSION: Tongluo Jiedu prescription can improve the immune function and oxidative stress level of patients with oral cancer and accelerate the recovery process.

Germline mutations of homologous recombination genes and clinical outcomes in pancreatic cancer: a multicenter study in Taiwan.

BACKGROUND: Cancer susceptibility germline mutations are associated with pancreatic ductal adenocarcinoma (PDAC). However, the hereditary status of PDAC and its impact on survival is largely unknown in the Asian population. METHODS: Exome sequencing was performed on 527 blood samples from PDAC individuals and analyzed for mutations in 80 oncogenic genes. Pathogenic and likely pathogenic (P/LP) germline variants were diagnosed according to the ACMG variant classification categories. The association between germline homologous recombination gene mutations (gHRmut, including BAP1, BRCA1, BRCA2, PALB2, ATM, BLM, BRIP1, CHEK2, NBN, MUTYH, FANCA and FANCC) and the treatment outcomes was explored in patients with stage III/IV diseases treated with first-line (1L) platinum-based versus platinum-free chemotherapy. RESULTS: Overall, 104 of 527 (19.7%) patients carried germline P/LP variants. The most common mutated genes were BRCA2 (3.60%), followed by ATR (2.66%) and ATM (1.9%). After a median follow-up duration of 38.3-months (95% confidence interval, 95% CI 35.0-43.7), the median overall survival (OS) was not significantly different among patients with gHRmut, non-HR germline mutations, or no mutation (P = 0.43). Among the 320 patients with stage III/IV disease who received 1L combination chemotherapy, 32 (10%) had gHRmut. Of them, patients receiving 1L platinum-based chemotherapy exhibited a significantly longer median OS compared to those with platinum-free chemotherapy, 26.1 months (95% CI 12.7-33.7) versus 9.6 months (95% CI 5.9-17.6), P = 0.001. However, the median OS of patients without gHRmut was 14.5 months (95% CI 13.2-16.9) and 12.6 months (95% CI 10.8-14.7) for patients receiving 1L platinum-based and platinum-free chemotherapy, respectively (P = 0.22). These results were consistent after adjusting for potential confounding factors including age, tumor stage, performance status, and baseline CA 19.9 in the multivariate Cox regression analysis. CONCLUSIONS: Our study showed that nearly 20% of Taiwanese PDAC patients carried germline P/LP variants. The longer survival observed in gHRmut patients treated with 1L platinum-based chemotherapy highlights the importance of germline testing for all patients with advanced PDAC at diagnosis.

Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children and adolescents. NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH), wherein hepatocellular inflammation and/or fibrosis coexist with steatosis. Circulating microRNA (miRNA) levels have been suggested to be altered in NAFLD, but the extent to which miRNA are related to NAFLD features remains unknown. This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents. AIM: To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD. METHODS: This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study. Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD. Plasma samples were collected during surgery for miRNA profiling. A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform. We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age, sex, race, and other key covariates. Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD. RESULTS: We identified 16 upregulated plasma miRNAs, including miR-193a-5p and miR-193b-5p, and 22 downregulated plasma miRNAs, including miR-1282 and miR-6734-5p, in adolescents with NAFLD. Moreover, 52, 16, 15, and 9 plasma miRNAs were associated with NASH, fibrosis, ballooning degeneration, and lobular inflammation, respectively. Collectively, 16 miRNAs were associated with two or more histological features of NAFLD. Among those miRNAs, miR-411-5p was downregulated in NASH, ballooning, and fibrosis, while miR-122-5p, miR-1343-5p, miR-193a-5p, miR-193b-5p, and miR-7845-5p were consistently and positively associated with all histological features of NAFLD. Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression, while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B. CONCLUSION: Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity. Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD.

Improved support vector machine classification for imbalanced medical datasets by novel hybrid sampling combining modified mega-trend-diffusion and bagging extreme learning machine model.

To handle imbalanced datasets in machine learning or deep learning models, some studies suggest sampling techniques to generate virtual examples of minority classes to improve the models' prediction accuracy. However, for kernel-based support vector machines (SVM), some sampling methods suggest generating synthetic examples in an original data space rather than in a high-dimensional feature space. This may be ineffective in improving SVM classification for imbalanced datasets. To address this problem, we propose a novel hybrid sampling technique termed modified mega-trend-diffusion-extreme learning machine (MMTD-ELM) to effectively move the SVM decision boundary toward a region of the majority class. By this movement, the prediction of SVM for minority class examples can be improved. The proposed method combines α-cut fuzzy number method for screening representative examples of majority class and MMTD method for creating new examples of the minority class. Furthermore, we construct a bagging ELM model to monitor the similarity between new examples and original data. In this paper, four datasets are used to test the efficiency of the proposed MMTD-ELM method in imbalanced data prediction. Additionally, we deployed two SVM models to compare prediction performance of the proposed MMTD-ELM method with three state-of-the-art sampling techniques in terms of geometric mean (G-mean), F-measure (F1), index of balanced accuracy (IBA) and area under curve (AUC) metrics. Furthermore, paired t-test is used to elucidate whether the suggested method has statistically significant differences from the other sampling techniques in terms of the four evaluation metrics. The experimental results demonstrated that the proposed method achieves the best average values in terms of G-mean, F1, IBA and AUC. Overall, the suggested MMTD-ELM method outperforms these sampling methods for imbalanced datasets.

Honokiol Prevents Intestinal Barrier Dysfunction in Mice with Severe Acute Pancreatitis and Inhibits JAK/STAT1 Pathway and Acetylation of HMGB1.

OBJECTIVE: To investigate the effect of honokiol (HON) and the role of high-mobility group protein B1 (HMGB1) on the pathogenesis of severe acute pancreatitis (SAP). METHODS: Thirty mice were numbered according to weight, and randomly divided into 5 groups using a random number table, including control, SAP, SAP and normal saline (SAP+NS), SAP and ethyl pyruvate (SAP+EP), or SAP+HON groups, 6 mice in each group. Samples of pancreas, intestine, and blood were collected 12 h after SAP model induction for examination of pathologic changes, immune function alterations by enzyme linked immunosorbent assay (ELISA), and Western blot. In vitro experiments, macrophages were divided into 5 groups, the control, lipopolysaccharide (LPS), LPS+DMSO (DMSO), LPS+anti-HMGB1 monoclonal antibody (mAb), and LPS+ HON groups. The tight connection level was determined by transmission electron microscopy and fluorescein isothiocyanate-labeled. The location and acetylation of HMGB1 were measured by Western blot. Finally, pyridone 6 and silencing signal transducer and activator of the transcription 1 (siSTAT1) combined with honokiol were added to determine whether the Janus kinase (JAK)/ STAT1 participated in the regulation of honokiol on HMGB1. The protein expression levels of HMGB1, JAK, and STAT1 were detected using Western blot. RESULTS: Mice with SAP had inflammatory injury in the pancreas, bleeding of intestinal tissues, and cells with disrupted histology. Mice in the SAP+HON group had significantly fewer pathological changes. Mice with SAP also had significant increases in the serum levels of amylase, lipase, HMGB1, tumor necrosis factor- α, interleukin-6, diamine oxidase, endotoxin-1, and procalcitonin. Mice in the SAP+HON group did not show these abnormalities (P<0.01). Studies of Caco-2 cells indicated that LPS increased the levels of occludin and claudin-1 as well as tight junction permeability, decreased the levels of junctional adhesion molecule C, and elevated intercellular permeability (P<0.01). HON treatment blocked these effects. Studies of macrophages indicated that LPS led to low nuclear levels of HMGB1, however, HON treatment increased the nuclear level of HMGB1 (P<0.01). HON treatment also inhibited the expressions of JAK1, JAK2, and STAT1 (P<0.01) and increased the acetylation of HMGB1 (P<0.05). CONCLUSION: HON prevented intestinal barrier dysfunction in SAP by inhibiting HMGB1 acetylation and JAK/STAT1 pathway.

Aurantio-obtusin ameliorates obesity by activating PPARα-dependent mitochondrial thermogenesis in brown adipose tissues.

Obesity contributes to the progression of various chronic diseases, and shortens life expectancy. With abundant mitochondria, brown adipose tissue (BAT) dissipates energy through heat to limit weight gain and metabolic dysfunction in obesity. Our previous studies have shown that aurantio-obtusin (AO), a bioactive ingredient in Chinese traditional medicine Cassiae semen significantly improves hepatic lipid metabolism in a steatotic mouse model. In the current study we investigated the effects of AO on lipid metabolism in the BAT of diet-induced obesity mice and in oleic acid and palmitic acid (OAPA)-stimulated primary mature BAT adipocytes. Obese mice were established by feeding a HFHS diet for 4 weeks, and then administered AO (10 mg/kg, i.g.) for another 4 weeks. We showed that AO administration significantly increased the weight of BAT and accelerated energy expenditure to protect the weight increase in the obese mice. Using RNA sequencing and molecular biology analysis we found that AO significantly enhanced mitochondrial metabolism and UCP1 expression by activating PPARα both in vivo and in vitro in the primary BAT adipocytes. Interestingly, AO administration did not improve metabolic dysfunction in the liver and white adipose tissue of obese mice after interscapular BAT excision. We demonstrated that low temperature, a trigger of BAT thermogenesis, was not a decisive factor for AO to stimulate the growth and activation of BATs. This study uncovers a regulatory network of AO in activating BAT-dependent lipid consumption and brings up a new avenue for the pharmaceutical intervention in obesity and related comorbidities.

The efficacy and safety of apatinib plus capecitabine in platinum-refractory metastatic and/or recurrent nasopharyngeal carcinoma: a prospective, phase II trial.

BACKGROUND: Previous studies have shown that monotherapy with apatinib, an oral tyrosine kinase inhibitor, has promising efficacy for treating recurrent or metastatic (RM) nasopharyngeal carcinoma (NPC) patients. In this study, we aimed to assess the efficacy and safety of apatinib combined with capecitabine as a second-line therapy or beyond for treating RM-NPC patients who failed the first-line platinum-based chemotherapy. METHODS: In this single-arm, phase II study, we enrolled RM-NPC patients who had at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The sample size was determined using Simon's two-stage design. All patients were administered with apatinib 500 mg once daily and capecitabine 1000 mg/m2 twice per day on days 1-14 of each 21-day cycle. The primary endpoint was the objective response rate (ORR), and the secondary endpoints comprised disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: We enrolled 64 patients from September 2018 to August 2020. The ORR and DCR were 39.1% (95% CI, 27.1-52.1) and 85.9% (95% CI, 75.0-93.4), respectively. The median DoR was 14.4 months (95% CI, 7.8-21.0). As of April 20, 2021, the median follow-up duration was 12.0 months. The median PFS was 7.5 months (95% CI, 5.0-10.0) and the median OS was 15.7 months (95% CI, 11.3-20.1). The most common toxicities of any grade were anemia (75.0%), hand-foot syndrome (65.6%), and proteinuria (64.0%). Grade 3-4 toxicities were observed in 36 (56.3%) patients, with hypertension (14.1%), mucositis (12.4%), and fatigue (10.9%) most commonly observed. CONCLUSIONS: Apatinib plus capecitabine shows promising efficacy as a second-line treatment option in pretreated platinum-refractory RM-NPC patients. Dose selection of this combination needs further investigation considering the toxicity. TRIAL REGISTRATION: Chi-CTR1800017229.

A metagenomics study of hexabromocyclododecane degradation with a soil microbial community.

Hexabromocyclododecanes (HBCDs) are globally prevalent and persistent organic pollutants (POPs) listed by the Stockholm Convention in 2013. They have been detected in many environmental media from waterbodies to Plantae and even in the human body. Due to their highly bioaccumulative characterization, they pose an urgent public health issue. Here, we demonstrate that the indigenous microbial community in the agricultural soil in Taiwan could decompose HBCDs with no additional carbon source incentive. The degradation kinetics reached 0.173 day-1 after the first treatment and 0.104 day-1 after second exposure. With additional C-sources, the rate constants decreased to 0.054-0.097 day-1. The hydroxylic debromination metabolites and ring cleavage long-chain alkane metabolites were identified to support the potential metabolic pathways utilized by the soil microbial communities. The metagenome established by Nanopore sequencing showed significant compositional alteration in the soil microbial community after the HBCD treatment. After ranking, comparing relative abundances, and performing network analyses, several novel bacterial taxa were identified to contribute to HBCD biotransformation, including Herbaspirillum, Sphingomonas, Brevundimonas, Azospirillum, Caulobacter, and Microvirga, through halogenated / aromatic compound degradation, glutathione-S-transferase, and hydrolase activity. We present a compelling and applicable approach combining metagenomics research, degradation kinetics, and metabolomics strategies, which allowed us to decipher the natural attenuation and remediation mechanisms of HBCDs.

Improved survival with induction chemotherapy and conversion surgery in locally advanced unresectable pancreatic cancer: a single institution experience.

Both efficacy and tolerability are critical issues in choosing neoadjuvant chemotherapy in patients with unresectable locally advanced pancreatic cancer (LAPC). The optimal regimen and the impact of conversion surgery on patient survival remains insufficiently reported in Asain population. Therefore, we conducted a retrospective study aiming to evaluate the resection rate after different induction chemotherapy regimen and its impact toward survival. All patients with pancreatic cancer treated in our institute from 2013 to 2020, a total of 730 patients, were reviewed and 131 patients with LAPC were identified. For cohort homogeneity, 14 patients receiving induction concurrent chemoradiotherapy initially were excluded and 117 patients receiving induction chemotherapy were included in the study. Most patients (90 of 117, 77%) received triplet induction chemotherapy, including the combination of S1, leucovorin, oxaliplatin and gemcitabine (SLOG) in 48, modified FOLFIRINOX in 21 and the combination of gemcitabine, oxaliplatin, fluorouracil and leucovorin (GOFL) in 21. The tumor response rate (19%-33%), the surgical exploration rate (38%-52%) and the mOS (15.4-23.0 months) were not significantly different among the three triplets. Both GOFL and SLOG regimen had comparable efficacy and less neutropenia as compared to mFOLFIRINOX. Conversion surgery was performed in 34 of 117 (29%) patients after induction chemotherapy. The median overall survival (mOS) in patients with and without conversion surgery were 29.1 and 14.1 months, respectively (P<0.0001). Radiological response alone was not a reliable indicator of successful conversion surgery. Patients who underwent conversion surgery had significantly better survival and thus highlighted the importance of surgical exploration in all patients who did not have progressive disease after induction chemotherapy.

Transcriptome Analysis Reveals a Gene Expression Pattern That Contributes to Sugarcane Bud Propagation Induced by Indole-3-Butyric Acid.

Sugarcane is a cash crop that plays an integral part in the sugar industry. The Sustainable Sugarcane Initiative (SSI) has been adopted globally, ensuring enough and aiming for more yield, helping increase disease-free sugarcane cultivation. Single-bud seeds could be the best approach for sugarcane cultivation. Indole-3-butyric acid (IBA) is a rooting agent utilized significantly in seedling propagation. Greenhouse experiment results discovered the significant growth promotion in sugarcane seedlings and accumulation of plant hormones at 100 ppm IBA. Next, we performed transcriptomic analysis of sugarcane buds using RNA sequencing and compared their gene expression during root development due to affect of IBA (100 ppm). A total of 113,475 unigenes were annotated with an average length of 836 bp (N50 = 1,536). The comparative RNA-seq study between the control (CK) and IBA-treated (T) buds showed significant differentially expressed unigenes (494 upregulated and 2086 downregulated). The IBA influenced major biological processes including metabolic process, the cellular process, and single-organism process. For cellular component category, cell, cell part, organelle, membrane, and organelle part were mainly affected. In addition, catalytic activity and binding were primarily affected in the molecular function categories. Furthermore, the expression of genes related to plant hormones and signaling pathways was analyzed by qRT-PCR, which was consistent with the RNA-seq expression profile. This study provides new insights into the IBA response to the bud sprouting in sugarcane based on RNA sequencing, and generated information could help further research on breeding improvement of sugarcane.

Application of the Full-Width-at-Half-Maximum Image Segmentation Method to Analyse Retinal Vascular Changes in Patients with Diabetic Retinopathy.

This study used spectral domain optical coherence tomography (SD-OCT) and full-width-at-half-maximum image segmentation to investigate the morphological changes of retinal blood vessels in patients with diabetic retinopathy (DR). Seventy-five patients with type 2 diabetes mellitus (T2DM) without DR and 65 patients with DR were studied. Vascular images of superior temporal region B of the retina were obtained by SD-OCT. The edges of retinal vessels were identified by the full-width-at-half-maximum image segmentation method. The lumen diameter, wall thickness (WT), wall cross-sectional area (WCSA), and wall-to-lumen ratio (WLR) were investigated. We found that, compared with the no diabetic retinopathy (NDR) group, patients in the DR group had an increased retinal arteriolar lumen diameter (RALD), retinal arteriolar outer diameter (RAOD), and WT (128.80 µm versus 104.88 µm; 147.01 µm versus 135.60 µm; 18.29 µm versus 15.26 µm, P < 0.05, respectively). The retinal venular lumen diameter (RVLD), retinal venular outer diameter (RVOD), and venular WT in the DR group were also increased (146.17 µm versus 133.66 µm; 180.20 µm versus 156.43 µm; 17.01 µm versus 11.38 µm, P < 0.05, respectively). The morphological changes in retinal vessels were significantly correlated with DR stage. In conclusion, in diabetic patients with DR, both retinal arteries and veins are widened and exhibit increased vascular thickness.

Association between Human Genetic Variants and the Vaginal Bacteriome of Pregnant Women.

The influence of human genetic variants on the vaginal bacterial traits (VBTs) of pregnant women is still unknown. Using a genome-wide association approach based on the 16S rRNA bacteriome analysis, a total of 72 host genetic variant (single nucleotide polymorphisms [SNPs], indels, or copy number variations [CNVs])-VBT associations were found that reached the genome-wide significance level (P < 5 × 10-8) with an acceptable genomic inflation factor λ of <1.1. The majority of these SNPs that reached the genome-wide significance level had a relatively low minor allele frequency (MAF), and only seven of them had MAFs greater than 0.05. rs303212, located at the IFIT1 gene on chromosome 10, was the most eye-catching variant, which had a genome-wide association with the relative abundance (RAB) of Actinobacteria and Bifidobacteriaceae and also had a suggestive association with the RAB of a few common vaginal bacteria including Actinobacteriota, Firmicutes, Lactobacillus, and Gardnerella vaginalis and the beta diversity weighted UniFrac (P < 1 × 10-5). The findings of the study suggest that the vaginal bacteriome may be influenced by a number of genetic variants across the human genome and that interferon signaling may have an important influence on vaginal bacterial communities during pregnancy. IMPORTANCE Knowledge about the influence of host genetics on the vaginal bacteriome in pregnancy is still limited. Although a number of environmental and behavioral factors may exert influences on the structure of vaginal bacterial communities, the vaginal bacteriome often undergoes a relatively fixed transition to a more stable and less diverse state as the menstrual cycle stops, which raises questions on the effects of human genetics. We utilized a genome-wide approach to identify the associations between genetic variants and multiple VBTs and performed enrichment analyses. The human genetics during pregnancy may be involved in multiple pathways. The results may disclose innate functional factors involved in shaping the vaginal bacteriome during pregnancy and provide insight into the establishment of specific strategies for prevention and clinical treatment of pregnancy complications.

Overt and occult hepatitis B infection after neonatal vaccination: mother-to-infant transmission and HBV vaccine effectiveness.

OBJECTIVES: Overt and occult hepatitis B infection (HBI) among mothers and infants were investigated, and the effectiveness of vaccination against HBI was evaluated based on transmission types. METHODS: A hospital-based cohort was built with 2,734 mothers and 330 mother-infant pairs. Their demographic data were collected. Serological HBV markers, nested-PCR for HBV genes, viral load detection, and phylogenetic analysis were done. RESULTS: The overall prevalence of HBI among mothers was 12.1% (330/2,734), with 10.4% for the overt type and 1.8% for the occult type. In 330 out of 1,650 (20%) mother-infant pairs, the overall, type-I (from overt mother to overt infant), type-II (from overt mother to occult infant), and type-Ⅲ (from occult mother to occult infant) transmissions were 1.9% (1/54), 5.6% (3/54) and 0.0% (0/7). The refinement of HBI classification improved the estimate of vaccine effectiveness against HBI from 74.4%-80.9% to 94.4%, which was more prominent for type-II. One mother-infant pair with type-II transmission shared nearly identical complete sequences. However, the high rate of lost-to-follow-up could not be ignored. CONCLUSIONS: During the transition period, HBV is mainly transmitted from the overt type of HBI mother to infant. Intensive prenatal screening for mothers is vital.

Efficient hexabromocyclododecane-biodegrading microorganisms isolated in Taiwan.

The potential toxicity of hexabromocyclododecane (HBCD), its persistence in the environment, and its high bioaccumulation characteristics pose a need to remediate HBCD in the environment. Bacillus cereus and B. subtilis species complexes we isolated from Taiwan soil are capable of degrading HBCD. B. cereus can degrade HBCD with a half-life only 0.911 days. The highest efficiency of HBCD degradation by B. cereus was achieved at pH 7.0, 35 °C, and 0.10 ppm HBCD. The removal mechanism of HBCD by B. cereus is debromination and its pathway was proposed. The addition of surfactant Tween 60 improved HBCD removal but the addition of CaO2, slow-releasing oxygen, did not. These findings can facilitate the bioremediation of HBCD in the environment.

Apoptotic effect of novel pyrazolone-based derivative [Cu(PMPP-SAL)(EtOH)] on HeLa cells and its mechanism.

Pyrazolone complexes have strong anti-tumor and antibacterial properties, but the anti-tumor mechanism of pyrazolone-based copper complexes has not been fully understood. In this study, the possible mechanism and the inhibitory effect of a novel pyrazolone-based derivative compound [Cu(PMPP-SAL)(EtOH)] on human cervical cancer cells (HeLa cells) was investigated. [Cu(PMPP-SAL)(EtOH)] effectively inhibited proliferation of HeLa cells in vitro with an IC50 value of 2.082 after treatment for 72 h. Cell cycle analysis showed apoptosis was induced by blocking the cell cycle in the S phase. [Cu(PMPP-SAL)(EtOH)] promoted the loss of mitochondrial membrane potential, release of cytochrome c, PARP cleavage, and activation of caspase-3/9 in HeLa cells. Additionally, [Cu(PMPP-SAL)(EtOH)] inhibited the PI3K/AKT pathway and activated the P38/MAPK, and JNK/MAPK pathways. [Cu(PMPP-SAL)(EtOH)] also inhibited the phosphorylation of Iκ-Bα in the NF-κB pathway activated by TNF-α, thus restricting the proliferation of HeLa cells which were activated by TNF-α. In conclusion, [Cu(PMPP-SAL)(EtOH)] inhibited the growth of HeLa cells and induced apoptosis possibly via the caspase-dependent mitochondria-mediated pathway. These results suggest that [Cu(PMPP-SAL)(EtOH)] can be a potential candidate for the treatment of cervical cancer.

Aerobic degradation and the effect of hexabromocyclododecane by soil microbial communities in Taiwan.

Hexabromocyclododecane (HBCD) is one of the most frequently used brominated flame retardants (BFRs) in the industries nowadays. Despite being listed as persistent organic pollutant (POP), it is still in use until 2025. Because of its bio-accumulative and toxic characteristics, the applicable remediation approach is required. The aim of this study is to identify the microbial community from soil with HBCD degradation ability. The soil suspension and soil samples from Chiang Chun Soil and River Bank Soil showed to degrade HBCD by 60% 4 days after treatment, the debromination ratio was around 60%, and the total HBCD removal ratio reached 70% and 77.9%, respectively. The HBCD debromination metabolites, and oxidation metabolites were identified by GC-MS. The microbial taxonomic diversity was observed with DGGE approach to evaluate the effect of HBCD of microbial community. Bacillus spp. and Clostridium spp. were identified as the dominant microbes in the Chiang Chun Soil, but the amount of Bacillus spp. were showed to be affected by HBCD. In conclusion, HBCD could be removed by the microbial consortium in soil under aerobic culturing condition by various metabolic pathways.

Biodegradation of hexabromocyclododecane by Rhodopseudomonas palustris YSC3 strain: A free-living nitrogen-fixing bacterium isolated in Taiwan.

The persistent organic pollutant, brominated flame retardant, hexabromocyclododecane (HBCD), identified as an emerging contaminant has been detected in various environmental matrix. The increased level of this toxic organic compound in the environment has been associated with serious human health risks. The results obtained from this study revealed that various Rhodopseudomonas palustris strains isolated from paddy soil in Taiwan possessed good HBCD biodegradation capability when they were cultured aerobically. Among these strains, YSC3 was considered as one of the most potential isolates for HBCD degradation. The optimum HBCD biodegradation occurred at neutral pH and at 35 °C in all our pH and temperature tests at an initial HBCD concentration of 1 ppm. HBCD degradation kinetics generally decreased with the increase of initial HBCD concentration. The study also suggested that the cultivation temperature played a vital role on YSC3 for its initiation of cellular HBCD degradation. The relative-molar ratio of the released bromide ions during the biodegradation of HBCD was observed in the range between 1 and 3.5, suggesting that the debromination reactions occurred. Concomitant with the loss of HBCD, there was a concurrent production of two metabolites, pentabromocyclododecanol and pentabromocyclododecene, which were determined by liquid chromatography and mass spectrometry techniques. On the basis of the obtained results, the possible biodegradation pathways were also proposed in this study.

Author Correction: A full-width half-maximum method to assess retinal vascular structural changes in patients with ischemic heart disease and microvascular angina.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A full-width half-maximum method to assess retinal vascular structural changes in patients with ischemic heart disease and microvascular anginga.

Chest pain patients without obstructive ischemic heart disease (IHD) have increased attention in the clinical practice as carrying higher cardiovascular (CV) risk and impaired life quality. Retinal vasculature is a novel but reliable risk factor of atherosclerosis and systemic vascular diseases. However, the association of retinal blood vessels and unobstructed IHD, as known as microvascular anginga (MA) is poorly understood. This study compared retinal vascular structures of obstructive IHD and MA using spectral domain optical coherence tomography (SD-OCT) and full-width half-maximum (FWHM) methods to provide new risk predictive evidence of MA. Fundus vessels of 120 IHD patients, including 91epicardial IHD and 29 MA patients, and 66 control subjects were evaluated. Significant differences in the retinal arterial lumen diameter (RALD), retinal arterial outer diameter (RAOD), and arteriovenous ratio (AVR) have been found (P < 0.05). The severity of IHD was negatively correlated with diameters of RAOD, RALD and AVR (P < 0.05). In conclusion, there were significant differences in the retinal vascular structure between IHD patients and patients with MA. Thus, assessment of retinal vascular structure is suggested to evaluate CV risk of IHD patients, despite having no obstructive IHD.