The comparison of pure uterine serous carcinoma and mixed tumor with serous component: a single-institution review of 91 cases.

BACKGROUND: Pure uterine serous carcinoma (p-USC) and mixed tumors with serous component (m-USC) are aggressive subtypes of endometrial cancer associated with high mortality rates. This retrospective study aimed to compare clinicopathologic features and outcomes of p-USC and m-USC in a single center. METHODS: This study retrospectively reviewed patients diagnosed with USC at Peking University People's Hospital between 2008 and 2022. T-tests and chi-square tests were used to compare clinicopathological characteristics between p-USC and m-USC. Kaplan-Meier survival curve and Cox regression analysis were used to analyze the impact of clinical and pathological variables on OS and PFS. RESULTS: Among the 91 patients who underwent surgery, 65.9% (n = 60) were p-USC, and 34.1% (n = 31) were m-USC. Patients with p-USC had earlier menopause (P = 0.0217), a lower rate of progesterone receptor(PR) expression (P < 0.001), and were more likely to have positive peritoneal cytology (P = 0.0464). After a median follow-up time of 40 months, 28 (46.7%) p-USC and 9 (29%) m-USC patients had progression disease, 18 (30%) and 8 (25.8%) patients died of their disease. 5-year PFSR were 51.2% and 75.3%, respectively, and 5-year OS rates were 66% and 67.4%. Kaplan-Meier survival analysis showed that p-USC was more likely to relapse than m-USC (P = 0.034), but there was no significant difference in OS. Cox regression analysis showed that lymph node metastasis and surgical approach were risk factors for OS, and myoinvasion depth ≥ 1/2 was an independent risk factor for PFS. CONCLUSIONS: p-USC was more likely to relapse than m-USC, but there was no significant difference in OS between the two subtypes.

Sterile soil mitigates the intergenerational loss of gut microbial diversity and anxiety-like behavior induced by antibiotics in mice.

The decline in gut microbial diversity in modern humans is closely associated with the rising prevalence of various diseases. It is imperative to investigate the underlying causes of gut microbial loss and restoring methods. Although the impact of non-perinatal antibiotic use on gut microbiota has been recognized, its intergenerational effects remain unexplored. Our previous research has highlighted soil in the farm environment as a key factor for gut microbiome health by restoring gut microbial diversity and balance. In this study, we investigated the intergenerational consequences of antibiotic exposure and the therapeutic potential of sterile soil. We treated C57BL/6 mice with vancomycin and streptomycin for 2 weeks continuously, followed by a 4-8 week withdrawal period before breeding. The process was repeated across 3 generations. Half of the mice in each generation received an oral sterile soil intervention. We assessed gut microbial diversity, anxiety behavior, microglial reactivity, and gut barrier integrity across generations. Antibiotic exposure led to a decrease in gut microbial diversity over generations, along with aggravated anxiety behavior, microgliosis, and altered intestinal tight junction protein expression. Oral sterile soil intervention restored gut microbial diversity in adult mice across generations, concomitantly rescuing abnormalities in behavior, microgliosis, and intestinal barrier integrity. In conclusion, this study simulated an important process of the progressive loss of gut microbiota diversity in modern humans and demonstrated the potential of sterile soil to reverse this process. This study provides a theoretical and experimental basis for research and interventions targeting multiple modern chronic diseases related to intestinal microorganisms.

Ginsenoside Rh3 induces pyroptosis and ferroptosis through the Stat3/p53/NRF2 axis in colorectal cancer cells.

Ginsenoside Rh3 (GRh3) is a seminatural product obtained by chemical processing after isolation from Chinese herbal medicine that has strong antitumor activity against human tumors. However, its antitumor role remains to be elucidated. The aim of this study is to explore the mechanisms underlying the tumor suppressive activity of GRh3 from the perspective of pyroptosis and ferroptosis. GRh3 eliminates colorectal cancer (CRC) cells by activating gasdermin D (GSDMD)-dependent pyroptosis and suppressing solute carrier family 7 member 11 (SLC7A11), resulting in ferroptosis activation through the Stat3/p53/NRF2 axis. GRh3 suppresses nuclear factor erythroid 2-related factor 2 (NRF2) entry into the nucleus, leading to the decrease of heme oxygenase 1 (HO-1) expression, which in turn promotes NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and caspase-1 expression. Finally, caspase-1 activates GSDMD-dependent pyroptosis. Furthermore, GRh3 prevents NRF2 from entering the nucleus, which suppresses SLC7A11, causing the depletion of glutathione (GSH) and accumulation of iron, lipid reactive oxygen species (ROS) and malondialdehyde (MDA), and eventually leading to ferroptosis in CRC cells. In addition, GRh3 effectively inhibits the proliferation of CRC cells in vitro and in nude mouse models. Collectively, GRh3 triggers pyroptotic cell death and ferroptotic cell death in CRC cells via the Stat3/p53/NRF2 axis with minimal harm to normal cells, showing great anticancer potential.

Soil causes gut microbiota to flourish and total serum IgE levels to decrease in mice.

Traditional farm environments induce protection from allergic diseases. In this study, farm environmental factors were classified into three categories, environmental microbes, soil, and organic matter. To explore the impact of soil and environmental microorganisms on gut microbiota and immune function, mice were fed sterilized soil and inhaling microbes, soil microbes, or non-sterilized soil. Metagenomic sequencing results showed the intake of sterile soil, that is, inhaling a small amount of soil microbes in the air increased gut microbial diversity and the abundance of type III secretion system (T3SS) genes, and decreased serum immune IgE levels induced by 2-4-dinitrofluorobenzene (DNFB). The intake of soil microbes increased the abundance of genes involved in the metabolism of short-chain fatty acids and amino acid biosynthesis. Meanwhile, the intake of soil increased gut microbial diversity, the abundance of T3SS genes and related infectious elements, and genes associated with the metabolism of short-chain fatty acids and amino acid biosynthesis, and decreased serum IgE levels. Therefore, soil may be useful as a potential 'prebiotic' promoting the reproduction and growth of some intestinal microorganisms that harbour bacterial secretion system genes, especially those of T3SS, whose abundance was positively and significantly correlated with innate immune function of mice.

Peripheral Tumor Location Predicts a Favorable Prognosis in Patients with Resected Small Cell Lung Cancer.

Background: Small cell lung cancer (SCLC) is an aggressive malignancy. Surgical resection is currently only recommended for clinical stage I patients who have been carefully staged. The clinical outcomes of patients with resected SCLCs vary because the disease is highly heterogeneous, suggesting that selected patients could be considered for surgical resection depending on their clinical and/or molecular characteristics. Methods: We collected data on a retrospective cohort of 119 limited-stage SCLC patients who underwent lobectomy with mediastinal lymph node dissection from March 2013 to March 2020 at Harbin Medical University Cancer Hospital. Correlations were derived using Fisher's exact test. Models of 2-year and 3-year survival were evaluated by deriving the area under receiver operating characteristic curves. Kaplan-Meier and Cox regression analyses were used to evaluate significant differences between the survival curves and hazard ratios. Results: The median disease-free survival (DFS) was 35.9 months (range 0.9-105.3 months), and the median overall survival (OS) was 45.2 months (range 4.8-105.3 months). Univariate analysis showed that TNM stage was significantly correlated with DFS and OS. The 2-year disease-free rates of patients with stage I, II, and III disease were 76.4%, 50.5%, and 36.1%, respectively, and the 3-year OS rates were 75.9%, 57.7%, and 34.4%, respectively. In pN + patients, multiple (or multiple-station) lymph node involvement significantly increased recurrence and reduced survival compared with patients with single or single-station metastases. Patients with peripheral SCLCs evidenced significantly better DFS and OS than did patients with central tumors. Multivariate analysis showed that TNM stage and tumor location were independently prognostic in Chinese patients with resected limited-stage SCLC. A combination of TNM stage and tumor location was helpful for prognosis. Conclusions: TNM stage and tumor location were independently prognostic in Chinese patients with resected SCLCs. Patient stratification by tumor location should inform the therapeutic strategy. The role of surgical resection for limited-stage SCLC patients must be reevaluated, as this may be appropriate for some patients.

A ten-gene methylation signature as a novel biomarker for improving prediction of prognosis and indicating gene targets in endometrial cancer.

Endometrial cancer (EC) is a common female reproductive tumor worldwide. Nonetheless, the pathogenesis of EC still remains ambiguous and associated epigenetic mechanism still to be explored. The goal of this study is to investigate whether gene methylation signature is associated with overall survival (OS) for EC patients. In this study, a 10-gene methylation risk model was built and the OS in high- and low-risk groups was significant different. The area under the ROC curve (AUC) of this model was 0.856 at 5 years survival. The nomogram could accurately predict the OS in EC patients, with concordance index and AUC at 5 year survival reached 0.796 and 0.792, respectively. Furthermore, we verified the nomogram with 24 patients in our center and the Kaplan-Meier survival curve also proved to be significantly different (p < 0.01). WGCNA revealed a key gene group for the model and further bioinformatics analysis indicated 6 genes as the hub genes in the module. Knockdown of MMP12 inhibited the proliferation, invasion and metastasis of EC cells. After all, a methylation signature and a nomogram based on this signature were constructed, and they could both predict survival in patients with EC. Moreover, WGCNA model identified MMP12 as a potential target for the treatment of EC.

[Association of serum uric acid with cardiovascular risk factors and their clustering among children and adolescents in Yinchuan City].

OBJECTIVE: To investigate the relationship between serum uric acid and cardiovascular risk factors and cardiovascular risk factor clustering(CVRFC) in children and adolescents in Yinchuan, Ningxia. METHODS: A present study design was adopted, and 1486 children and adolescents aged 10-18 years in urban areas of Yinchuan City were selected as study subjects with a mean age of(14.3±1.4) years in 2015, 2017 to 2018 by stratified clustering sampling, including 728(49.0%) boys, 1157(77.9%) Han, 170(11.4%) Hui and 159(10.7%) from other ethnic groups. All study subjects completed questionnaires, physical measurements and biochemical tests. RESULTS: Hyperuricemia(HUA) was significantly positive associated with abdominal obesity(OR=3.23, 95%CI 2.37-4.40), hypertension(OR=1.64, 95%CI 1.21-2.23), dyslipidemia(OR=1.51, 95%CI 1.17-1.96), CVRFC≥2(OR=3.71, 95%CI 2.80-4.93) and CVRFC≥3(OR=6.92, 95% CI 4.18-11.64)(P<0.05). There was an additive interaction between HUA and gender on cardiovascular risk factors and their aggregation. Compared with non-HUA girls, HUA girls have 3.57 times(95%CI 2.26-5.64) the risk of abdominal obesity, dyslipidemia, CVRFC≥2 and CVRFC≥3, respectively, 1.65 times(95%CI 1.10-2.47), 4.10 times(95%CI 1.10-2.47) and 7.63 times(95%CI 3.67-15.89). HUA boys have 1.75 times(95%CI 1.16-2.65) the risk of abdominal obesity, dyslipidemia, CVRFC≥2 and CVRFC≥3, respectively, 2.14(95%CI 1.51-3.03) times, 4.27 times(95%CI 2.98-6.13) and 7.97 times(95%CI 4.11-15.44), (P<0.05). CONCLUSION: Hyperuricemia was significantly positive associated with cardiovascular risk factors and their aggregation in children and adolescents in Yinchuan, and there was an additive interaction between hyperuricemia and gender.

[Prevalence of cardiovascular metabolic risk factors among 12-18 years old adolescents in Yinchuan City from 2017 to 2019].

OBJECTIVE: To understand the prevalence of cardiovascular metabolic risk factors among 12-18 years old children and adolescents in Yinchuan City. METHODS: A survey was conducted among 12-18 years old middle school students in Yinchuan from September 2017 to September 2019. A total of 1956 subjects were collected by using convenient sampling method, with an average age of(14. 4±1. 4) years. Boys and girls accounted for 52. 1% and 47. 9%, respectively, The Han and Hui nationalities accounted for 77. 7% and 16. 4%, respectively. Basic data such as age and gender were collected through questionnaire survey, and physical examination was used to measure height, weight, waist circumference and blood pressure. Fasting blood glucose, triglyceride(TG), total cholesterol(TC), high density lipoprotein cholesterol(HDL-C) and low density lipoprotein cholesterol(LDL-C) were measured by laboratory blood pressure biochemistry. RESULTS: The detection rates of obesity, abdominal obesity, hypertension, hyperglycemia, high TG, high LDL-C, low HDL-C, high LDL-C and dyslipidemia among 12-and 18-year-olds in Yinchuan City were 8. 3%, 17. 9%, 12. 4%, 1. 9%, 13. 2%, 2. 4%, 18. 6%, 1. 9% and 30. 1%, respectively. The detection rates of obesity, hyperglycemia, low HDL-C, high TG and dyslipidemia in boys were significantly higher than those in girls. Obesity, abdominal obesity and hypertension in 12-15-year-old group were higher than those in 16-18-year-old group, and the detection rates of high TC, low HDL-C, high LDL-C and dyslipidemia were lower than those in 16-18-year-old group(P& lt; 0. 05). The prevalence of cardiovascular risk factors in different age groups of boys and girls were compared. The detection rates of obesity, abdominal obesity and hypertension in the 12-15 age group were higher than those in the 16-18 age group, while the rates of high TG, low HDL-C, high LDL-C and dyslipidemia were higher in the 12-15 age group, but these differences were only significant in boys. Among girls, the detection rate of high TC and high LDL-C was higher in the age group of 12 to 15 years old(P& lt; 0. 05). The detection rate of metabolic syndrome in 12-18-year-old adolescents was 7. 9%. The detection rate of metabolic syndrome in boys(10. 1%) was higher than that in girls(5. 5%). The detection rates of metabolic syndrome in 12-15 years old and 16-18 years old were 9. 1% and 4. 9% respectively, and the differences were statistically significant(P& lt; 0. 05). CONCLUSION: The prevalence of cardiovascular metabolic risk factors in 12-18 years old adolescents in Yinchuan City is at a high level, boys are higher than girls, and the prevalence of obesity, abdominal obesity and hypertension are higher in 12-15 years old group. Dyslipidemia varies greatly in different gender and age groups.

[Combined influence of lipid accumulation product and body mass index on cardiometabolic risk factors among Yinchuan City children and adolescents].

OBJECTIVE: To analyze the relationship between children lipid accumulation product(CLAP) and body mass index(BMI) and cardiovascular risk factors in children and adolescents. METHODS: A current situation study design was adopted. A total of 936 children and adolescents aged 12 to 18 years old in Yinchuan City were selected from September 2017 to September 2019 by a convenient sampling method. Among them, 537(57. 40%) boys and an average age of(14. 82±2. 08) years old, the number of Han and other ethnic groups were 705(75. 30%) and 231(24. 70%) respectively. And conduct questionnaire surveys(using Yinchuan Children's Blood Pressure Survey-standard questionnaire, which mainly includes basic information, birth and infant feeding, physical activity and sleep, etc. ), physical examination(including height, weight, blood pressure and body components) and biochemical index detection(including fasting blood glucose and blood lipids), using binary classification Logistics regression to analyze the correlation between CLAP and BMI and cardiovascular risk factors, and ROC curve analysis of the accuracy of CLAP and BMI in the diagnosis of cardiovascular risk factors. RESULTS: The association between CLAP≥P75 and BMI normal weight and cardiovascular risk factor aggregation≥2 was 38. 13(95%CI 23. 83-61. 00) times(P<0. 05) of CLAP<P75 and BMI non-obese, which was higher than that of other different combinations and cardiovascular risk factors Correlation. The accuracy of CLAP≥P75 combined with BMI in the diagnosis of cardiovascular risk factor aggregation≥2 was 0. 87(95%CI 0. 85-0. 89), higher than other diagnoses. CONCLUSION: CLAP and BMI are associated with cardiovascular risk factors.

Biodegradable Polymersomes with Structure Inherent Fluorescence and Targeting Capacity for Enhanced Photo-Dynamic Therapy.

Biodegradable nanostructures displaying aggregation-induced emission (AIE) are desirable from a biomedical point of view, due to the advantageous features of loading capacity, emission brightness, and fluorescence stability. Herein, biodegradable polymers comprising poly (ethylene glycol)-block-poly(caprolactone-gradient-trimethylene carbonate) (PEG-P(CLgTMC)), with tetraphenylethylene pyridinium-TMC (PAIE) side chains have been developed, which self-assembled into well-defined polymersomes. The resultant AIEgenic polymersomes are intrinsically fluorescent delivery vehicles. The presence of the pyridinium moiety endows the polymersomes with mitochondrial targeting ability, which improves the efficiency of co-encapsulated photosensitizers and improves therapeutic index against cancer cells both in vitro and in vivo. This contribution showcases the ability to engineer AIEgenic polymersomes with structure inherent fluorescence and targeting capacity for enhanced photodynamic therapy.

Positron-emitting tracer imaging of fluoride transport and distribution in tea plant.

BACKGROUND: Tea (Camellia sinensis (L.) O. Kuntze) is a hyper-accumulator of fluoride (F). To understand F uptake and distribution in living plants, we visually evaluated the real-time transport of F absorbed by roots and leaves using a positron-emitting (18 F) fluoride tracer and a positron-emitting tracer imaging system. RESULTS: F arrived at an aerial plant part about 1.5 h after absorption by roots, suggesting that tea roots had a retention effect on F, and then was transported upward mainly via the xylem and little via the phloem along the tea stem, but no F was observed in the leaves within the initial 8 h. F absorbed via a cut petiole (leaf 4) was mainly transported downward along the stem within the initial 2 h. Although F was first detected in the top and ipsilateral leaves, it was not detected in tea roots by the end of the monitoring. During the monitoring time, F principally accumulated in the node. CONCLUSION: F uptake by the petiole of excised leaf and root system was realized in different ways. The nodes indicated that they may play pivotal roles in the transport of F in tea plants. © 2020 Society of Chemical Industry.

An elevated preoperative serum calcium level is a significant predictor for positive peritoneal cytology in endometrial carcinoma.

OBJECTIVE: To evaluate preoperative serum calcium concentration and investigate the association between calcium level and positive peritoneal cytology in endometrial carcinoma (EC). METHODS: A total of 510 patients who were diagnosed with EC and had surgery were initially enrolled in this study at Peking University People's Hospital between January 2012 and December 2016. Clinical characteristics and preoperative serum calcium, albumin, carbohydrate antigen (CA)125, CA19-9, carcinoembryonic antigen (CEA) were extracted from patient records and evaluated according to postoperative peritoneal cytology. Predictive factors were assessed with Cox univariate and multivariate analyses. Factors selected from multivariate analysis results were used to build a predictive model. RESULTS: A total of 510 patients are identified in our database and 444 patients who fulfilled inclusion and exclusion criteria are included in this study. Univariate analysis revealed that ionized calcium concentration was closely related to positive peritoneal cytology, tumor grade and lymph-vascular space invasion (LVSI). Moreover, peritoneal cytology was significantly associated with hypertension, tubal ligation, serum CA125, CA19-9, CEA and ionized calcium level. Multivariate analysis revealed that albumin-adjusted calcium level, CA125 and tubal ligation were independent predictive factors of positive peritoneal cytology (P<0.05). A combination of ionized calcium level with the other two indexes yielded significantly great area under the curve (AUC=0.824). CONCLUSIONS: This study enhanced the value of preoperative ionized calcium level. We also identified several potential biomarkers to predict positive peritoneal cytology in EC patients before surgery.

Overexpressing PRMT1 Inhibits Proliferation and Invasion in Pancreatic Cancer by Inverse Correlation of ZEB1.

Pancreatic cancer (PC) is one of the most malign human cancers, with its underlying molecular mechanisms largely unknown. In this work, we investigated the mechanistic role of protein arginine methyltransferase 1 (PRMT1) gene in PC. Expression of PRMT1 in immortal PC cell lines and clinical human PC tumors was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. In PANC-1 and SW1990 cells, PRMT1 was either downregulated by lentiviral-mediated short hairpin RNA (shRNA) or upregulated by overexpression plasmid. The effects of PRMT1 downregulation or upregulation on PC proliferation and invasion in vitro, and xenograft in vivo, were evaluated. Gene expression of PRMT1 downstream target, zinc finger E-box binding homeobox 1 (ZEB1) was measured in PRMT1-downregulated PC cells. ZEB1 was also upregulated in PRMT1-downregulated PC cells to evaluate its functional role in PRMT1-mediated regulation in PC. PRMT1 was downregulated in both PC cell lines and human tumors. PRMT1 downregulation in PANC-1 and SW1990 cells significantly suppressed cancer proliferation and invasion in vitro and xenograft in vivo. However, PRMT1 overexpression did not have function impact in PC cells. ZEB1 gene expression was suppressed in PRMT1-downregulated PC cells. Subsequently, overexpressing ZEB1 reversed the antitumor effects of PRMT1 downregulation in PC cells. PRMT1 was aberrantly upregulated in PC. PRMT1 inhibition, possibly inversely acting through ZEB1, might be an effective molecular intervention to inhibit PC growth and invasion. © 2018 IUBMB Life, 70(10):1032-1039, 2018.

Anti-inflammatory Meroterpenoids from Baeckea frutescens.

Frutescones H-R (1-11), new sesqui- or monoterpene-based meroterpenoids, were isolated from the aerial parts of Baeckea frutescens. Their structures and absolute configurations were established by means of spectroscopic analyses (HRESIMS, 1D and 2D NMR, and ECD), as well as single-crystal X-ray crystallography of 1, (-)-7, and 9. The anti-inflammatory activities of all isolates were evaluated by measuring their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophages, and the structure-activity relationships of 1-11 are also discussed. Compound 8 exhibited anti-inflammatory activity with an IC50 value of 0.36 µM, which might be related to the regulation of the NF-κB signaling pathway via the suppression of p65 nuclear translocation and the consequent decrease of IL-6 and TNF-α.

A Low-Complexity Method for Two-Dimensional Direction-of-Arrival Estimation Using an L-Shaped Array.

In this paper, a new low-complexity method for two-dimensional (2D) direction-of-arrival (DOA) estimation is proposed. Based on a cross-correlation matrix formed from the L-shaped array, the proposed algorithm obtains the automatic pairing elevation and azimuth angles without eigendecomposition, which can avoid high computational cost. In addition, the cross-correlation matrix eliminates the effect of noise, which can achieve better DOA performance. Then, the theoretical error of the algorithm is analyzed and the Cramer-Rao bound (CRB) for the direction of arrival estimation is derived . Simulation results demonstrate that, at low signal-to-noise ratios (SNRs) and with a small number of snapshots, in contrast to Tayem's algorithm and Kikuchi's algorithm, the proposed algorithm achieves better DOA performance with lower complexity, while, for Gu's algorithm, the proposed algorithm has slightly inferior DOA performance but with significantly lower complexity.

The mitochondrion interfering compound NPC-26 exerts potent anti-pancreatic cancer cell activity in vitro and in vivo.

The development of novel anti-pancreatic cancer agents is extremely important. Here, we investigated the anti-pancreatic cancer activity by NPC-26, a novel mitochondrion interfering compound. We showed that NPC-26 was anti-proliferative and cytotoxic to human pancreatic cancer cells, possibly via inducing caspase-9-dependent cell apoptosis. Pharmacological inhibition or shRNA-mediated silence of caspase-9 attenuated NPC-26-induced pancreatic cancer cell death and apoptosis. Further, NPC-26 treatment led to mitochondrial permeability transition pore (mPTP) opening in the cancer cells, which was evidenced by mitochondrial depolarization, ANT-1(adenine nucleotide translocator-1)-Cyp-D (cyclophilin-D) association and oxidative phosphorylation disturbance. mPTP blockers (cyclosporin and sanglifehrin A) or shRNA-mediated knockdown of key mPTP components (Cyp-D and ANT-1) dramatically attenuated NPC-26-induced pancreatic cancer cell apoptosis. Importantly, we showed that NPC-26, at a low concentration, potentiated gemcitabine-induced mPTP opening and subsequent pancreatic cancer cell apoptosis. In vivo, NPC-26 intraperitoneal injection significantly suppressed the growth of PANC-1 xenograft tumors in nude mice. Meanwhile, NPC-26 sensitized gemcitabine-mediated anti-pancreatic cancer activity in vivo. In summary, the results of this study suggest that NPC-26, alone or together with gemcitabine, potently inhibits pancreatic cancer cells possibly via disrupting mitochondrion.

Two residues predominantly dictate functional difference in motility between Shewanella oneidensis flagellins FlaA and FlaB.

Nearly half of flagellated microorganisms possess a multiple-flagellin system. Although a functional filament can be formed from one of multiple flagellins alone in many bacteria, it is more common that one flagellin is the major constituent and others contribute. Underlying mechanisms proposed for such scenarios cover flagellin regulation of various levels, including transcription, translation, post-translational modification, secretion, and filament assembly. In Shewanella oneidensis, the flagellar filament is composed of FlaA and FlaB flagellins; the latter is the major one in terms of motility. In this study, we showed that regulation of all levels except for filament assembly is indistinguishable between these two flagellins. Further analyses revealed that two amino acid residues predominantly dictated functional difference with respect to motility. Given that Shewanella prefer a solid surface-associated life style, of which filaments consisting of either FlaA or FlaB are equally supportive, we envision that roles of flagella in surface adhesion and formation of bacterial communities are particularly important for their survival and proliferation in these specific niches.

Bone regeneration using a freeze-dried 3D gradient-structured scaffold incorporating OIC-A006-loaded PLGA microspheres based on ß-TCP/PLGA.

To reveal the latent capacity of the growth factor-like low-molecular-weight material OIC-A006 in tissue regeneration, it is essential to design a porous scaffold in order to concurrently accommodate cells and drug release in a controlled manner. Consequently, we fabricated poly (L-lactide-co-glycolide) (PLGA)-based microspheres with an OIC-A006-loaded gradient-structured ß-TCP/PLGA scaffold by freeze-drying which could then be used for drug delivery and bone regeneration. The OIC-A006-loaded ß-TCP/PLGA scaffold consisted of two parts which loaded different doses of OIC-A006 (6.25 µM, outside; 12.5 µM, inside). The porosity, compressive strength, SEM, degradation, and cumulative amount of drug release in vitro were characterized. Furthermore, we confirmed the incorporation of OIC-A006 into the PLGA-based microspheres within the scaffolds using UV-spectrophotometry, and the amount of drug remaining in the scaffold was maintained by 10 % for up to 28 days. The drug release was slower in the normal-structured drug-loaded scaffold. The OIC-A006 released action from the OIC-A006-loaded ß-TCP/PLGA scaffold with ideal therapeutic prospects in tissue regeneration. In vitro cell culture results showed that this gradient-structured composite scaffold can induce the adhesion and proliferation of rat bone marrow stromal cells towards osteoblasts. These results showed that the newly developed OIC-A006-loaded scaffolds with gradient structure can be potentially applied to bone regeneration in clinical applications.

Protection from oxidative stress relies mainly on derepression of OxyR-dependent KatB and Dps in Shewanella oneidensis.

Shewanella thrives in redox-stratified environments where accumulation of H2O2 becomes inevitable because of the chemical oxidation of reduced metals, sulfur species, or organic molecules. As a research model, the representative species Shewanella oneidensis has been extensively studied for its response to various stresses. However, little progress has been made toward an understanding of the physiological and genetic responses of this bacterium to oxidative stress, which is critically relevant to its application as a dissimilatory metal-reducing bacterium. In this study, we systematically investigated the mechanism underlying the response to H2O2 at cellular, genomic, and molecular levels. Using transcriptional profiling, we found that S. oneidensis is hypersensitive to H2O2 in comparison with Escherichia coli, and well-conserved defense genes such as ahpCF, katB, katG, and dps appear to form the first line of defense, whereas iron-sulfur-protecting proteins may not play a significant role. Subsequent identification and characterization of an analogue of the E. coli oxyR gene revealed that S. oneidensis OxyR is the master regulator that mediates the bacterial response to H2O2-induced oxidative stress by directly repressing or activating the defense genes. The sensitivity of S. oneidensis to H2O2 is likely attributable to the lack of an inducible manganese import mechanism during stress. To cope with stress, major strategies that S. oneidensis adopts include rapid removal of the oxidant and restriction of intracellular iron concentrations, both of which are achieved predominantly by derepression of the katB and dps genes.