[Molecular characteristics of Legionella pneumophila in shower water of public places in Ma'anshan city from 2019 to 2020].

Objective: To understand the epidemiological and pathogenic characteristics of Legionella pneumophila in shower water of public places in Ma'anshan City from 2019 to 2020, and to provide scientific basis for further prevention and control of legionellosis. Methods: From 2019 to 2020, according to population density distribution and business scale of bathing places in the main urban area of Ma'anshan City (Huashan District and Yushan District), 8 public bathing places (including 3 large, 3 medium and 2 small) were selected to collect 308 shower water and water storage pool water samples (294 shower water samples and 14 water storage pool water samples). After the collected water samples were treated, cultured, isolated and identified, the type characteristics of Legionella pneumophila were analyzed. Results: Legionella pneumophila were detected in 120 water samples among 308 shower water and water storage pool water samples, with an overall positive rate of 39.0% (120/308). A total of 154 Legionella pneumophila strains were detected, including 10 different serotypes, predominated by serotype 1 (LP1) and serotype 3 (LP3), accounting for 40.9% (63/154) and 22.7% (35/154). Among 154 strains of Legionella pneumophila, 23 strains of Legionella pneumophila were positive for all 14 virulence genes, accounting for 14.9% (23/154), including 19 serotype 1 (LP1) and 4 serotype 8 (LP8). Pulsed field gel electrophoresis (PFGE) cluster analysis of 154 Legionella pneumophila strains showed 60 different patterns. Conclusion: Legionella pneumophila was seriously polluted in the shower water environment of public places in Ma, anshan City. The serotypes are widely distributed and the virulence of the strains is strong. The results of molecular typing show that these strains have genetic diversity.

[Molecular epidemiological analysis of Norovirus in patients with foodborne diseases in sentinel hospital, Ma'anshan City, Anhui Province].

Objective: To understand the infection status and genetic characteristics of Norovirus from foodborne diseases in sentinel hospital of Ma'anshan city. Methods: The 911 stool samples and epidemiological data of the patients with foodborne disease were collected from three hospitals of Ma'anshan city during January 2015 to June 2018. The G Ⅰ and G Ⅱ Norovirus were detected by real-time reverse transcription PCR. Some of the positive specimens were amplified by conventional reverse transcription PCR, and the PCR products were sequenced for sequence alignment and phylogenetic analysis. Results: The positive rate of Norovirus was 14.7% (134/911), in which 7 strains were G Ⅰ, 124 strains were G Ⅱ and 3 strains were mixed infection. Norovirus can be detected throughout the year, with high positive rate from December to April of the next year [24.4%(20/82)-45.3%(24/53)]. The 78 males (15.5%) and 55 females (13.7%) were positive for Norovirus (χ(2)=0.58,P=0.448). There was no significant difference in different age groups (χ(2)=9.55, P=0.089). A total of 79 strains were successfully sequenced, 4 strains were G Ⅰ group(5.1%), 75 strains were G Ⅱ group (94.9%). The predominant strains were GⅡ.17 and GⅡ.4, aud the number were 35 and 15 respectively. The predominant strains were different in different years. The main strain was GⅡ.17 in 2015 (30, 68.2%),GⅡ.4 in 2016 (5/9) and 2017 (8/16), but GⅡ.3 in 2018 (3/6). Conclusion: Norovirus diarrhea was popular in Ma'anshan city throughout the year,especially in winter and spring. The prevalent strain was GⅡ,genotypes were diversified distribution,the dominant strains were GⅡ.17 and GⅡ.4. The predominant strains were different in different years.

Association between the PPARγ Pro12Ala polymorphism and risk of gestational diabetes mellitus: a meta-analysis.

The relationship between the Pro12Ala polymorphism of PPARγ and the risk of gestational diabetes mellitus remains unresolved. Here, we attempted to resolve this inconsistency. Case-control studies pertaining to the effect of the Pro12Ala polymorphism in the PPARγ protein and risk of gestational diabetes mellitus were extracted from the HuGE, PubMed, Web of Science, CNKI, and SinoMed databases after an extensive literature search. The studies were statistically analyzed using STATA (v.12.0) software. Twelve case-control studies composed of 2968 GDM cases and 5576 controls that fulfilled the inclusion criteria were included in this meta-analysis. We identified no significant relation between the Pro12Ala polymorphism of PPAR-γ and risk of GDM, when analyzed by the allele [G vs C: odds ratio (OR) = 0.85; 95% confidence interval (CI): 0.71-1.01] and dominant (CG+GG vs CC: OR = 0.86; 95% CI: 0.72-1.03) models. Subgroup analysis by ethnicity revealed that East Asian and Middle Eastern females expressing the A allele showed reduced susceptibility to GDM. Additionally, we observed significant differences between the East Asian, Middle Eastern, and Caucasian females (P = 0.008) with respect to GDM susceptibility. The results of this meta-analysis indicated the influence of ethnicity in determining GDM susceptibility, in the presence of a Pro12Ala polymorphism in PPARγ.

Successful ABO-incompatible living-related intestinal transplantation: a 2-year follow-up.

ABO-incompatible intestinal transplantation has rarely been performed due to poor patient outcomes. Herein we present a case of successful ABO-incompatible intestinal transplantation with a 2-year follow-up. A 16-year-old female with a history of extensive bowel resection received an ABO-incompatible living donor bowel graft from her father (blood type AB graft into a type A recipient). Posttransplant immunosuppression consisted of an initial anti-CD20, plasmapheresis/intravenous immunoglobulin before transplantation, followed by an anti-thymocyte globulin (ATG) induction and splenectomy, and maintenance with tacrolimus and prednisone. Her postoperative course was remarkable for a single episode of rejection on day 14 which responded promptly to treatment with methyprednisolone and ATG. Three months after transplantation, the patient developed an abdominal abscess requiring open surgical drainage. No viral infections were encountered. Posttransplant anti-B antibody titers and anti-B7 donor-specific antibody levels remained low. At a 2-year follow-up, the patient showed a progressive weight gain of 5.0 kg. This case illustrates that ABO-incompatible living-related bowel transplantation is immunologically feasible and is associated with good outcomes for the recipient. The management of blood type antibodies and the use of adequate immunosuppression in the early period of the procedure may be the keys to the success of future cases.

[Current status of palliative care for patients with unresectable metastatic colorectal cancer in China: a questionnaire-based survey].

Objective: To analyze the current adoption of palliative care by patients with unresectable metastatic colorectal cancer (mCRC) in China. Methods: From 1 March 2023 to 30 June 2023, a questionnaire survey was conducted by random sampling. An exclusive research platform for the Blue Book on Clinical Diagnosis and Treatment of Metastatic Colorectal Cancer. An online questionnaire was sent to medical oncologists (including chief physicians, associate chief physicians, attending physicians and residents) in general hospitals and oncology hospitals in four major regions of East, Central, South and Northeast China. The questionnaire contained 28 questions requesting basic information about doctors, the number of patients with mCRC, the status of treatment from first to fourth line and beyond, points concerning treatment of pain in patients with mCRC, and expectations for the future. A medical team was responsible for the quality control of data collected, whereas statisticians performed the data cleaning and sorting and statistical analysis. Results: A total of 300 clinical questionnaires were collected, including 217 (72%) from doctors in general hospitals and 83 (28%) from doctors in oncology hospitals. Senior physicians (including associate chief physicians and chief physicians) accounted for 65% of the respondents, attending physicians 30%, and residents 5%. Within 3 months (average for each month), 46.4±26.6% patients were diagnosed with recurrent or unresectable mCRC by each physician, 51.6±26.8% of the patients being in cancer hospitals and 44.4±26.3% in general hospitals. One hundred percent of patients receiving first-line treatment received palliative care, as did 80.3% of those receiving second-line treatment, 58.2% of those receiving third-line treatment, and 35.1% of those receiving ≥fourth-line treatment. The primary factor governing selection of first-line treatment was guideline recommendations, whereas comorbidities and the patients' physical status dictated second line to fourth line treatment. Standard first-line treatment was administered to 93.8% of eligible patients, standard second-line treatment to 94.3%; and standard third-line treatment to 73.5%. First-line therapy included targeted therapy in 63.6% of patients and immunotherapy in 2.8%; second-line therapy included targeted therapy in 63.0% of patients and immunotherapy in 2.0%; third-line therapy included targeted therapy in 59.2% of patients and immunotherapy in 2.2%; and fourth-line therapy included targeted therapy in 48.7% of patients and immunotherapy in 3.1%. First-line treatment lasted an average of 9.6 months, second-line treatment 6.7 months, third-line treatment 4.9 months, and fourth-line treatment 3.7 months. More than 70% of the patients maintained a good quality of life after receiving first and second-line treatment and more than 60% of them had ECOG performance scores of 0-1. After receiving third- and fourth-line treatment, 50%-60% of patients maintained a good quality of life and 40%-50% of them maintained ECOG performance scores of 0-1. The survey also revealed that the main deficiencies in treatment were limited effectiveness of third-line treatment, insufficient availability and opportunity for clinical research, popularity of new drugs or new drug combination strategies, and limited channels for participation in multidisciplinary diagnosis and treatment. Clinicians reported looking forward to participating in more clinical research on new drugs, hearing about the experience of experts in the field, and discovery of new targets and new drugs that increased the options for posterior line treatment of colorectal cancer. Conclusions: This report objectively summarizes the current situation, treatment difficulties, and expectations of frontline physicians concerning management of mCRC, thus providing a basis for decision-making and future direction for the diagnosis and research on treatment of mCRC.

Increased T cell glucose uptake reflects acute rejection in lung grafts.

Although T cells are required for acute lung rejection, other graft-infiltrating cells such as neutrophils accumulate in allografts and are also high glucose utilizers. Positron emission tomography (PET) with the glucose probe [(18)F]fluorodeoxyglucose ([(18)F]FDG) has been employed to image solid organ acute rejection, but the sources of glucose utilization remain undefined. Using a mouse model of orthotopic lung transplantation, we analyzed glucose probe uptake in the grafts of syngeneic and allogeneic recipients with or without immunosuppression treatment. Pulmonary microPET scans demonstrated significantly higher [(18)F]FDG uptake in rejecting allografts when compared to transplanted lungs of either immunosuppressed or syngeneic recipients. [(18)F]FDG uptake was also markedly attenuated following T cell depletion therapy in lung recipients with ongoing acute rejection. Flow cytometric analysis using the fluorescent deoxyglucose analog 2-NBDG revealed that T cells, and in particular CD8(+) T cells, were the largest glucose utilizers in acutely rejecting lung grafts followed by neutrophils and antigen-presenting cells. These data indicate that imaging modalities tailored toward assessing T cell metabolism may be useful in identifying acute rejection in lung recipients.

[Effect of peritoneum reconstruction on postoperative complications after laparoscopic low anterior resection for rectal cancer].

Objective: To determine the effect of peritoneum reconstruction on postoperative complications after laparoscopic low anterior resection (LAR) for rectal cancer. Methods: Retrospective cohort study and propensity score matching were conducted. Case inclusion criteria: (1) pathologically confirmed rectal adenocarcinoma; (2) 18 to 80 years; (3) patients with middle to low rectal cancer undergoing laparoscopic LAR; (4) patients staging cT1-4aN0-2M0 or ycT1-4aN0-2M0 after neoadjuvant therapy; (5) the distance of 4-10 cm from tumor low margin to anal verge. Exclusion criteria: (1) abdominal surgery history (except appendicitis, cholecystitis, ectopic pregnancy); (2) anastomosis above the peritoneal reflection; (3) tumor distant metastasis or clinical staging of T4b during surgery; (4) conversion to open surgery; (5) severe incapacitating disease (American Society of Anesthesiologists classification IV or V, ASA). A total of 666 patients with middle to low rectal cancer undergoing laparoscopic LAR in The First Affiliated Hospital of Army Medical University from January 2017 to June 2020 were enrolled. There were 473 males and 193 females with the median age of 59 (18-80) years. Laparoscopic LAR with peritoneum reconstruction was performed in 188 cases (PR group), and laparoscopic LAR without peritoneum reconstruction was performed in 478 cases (NPR group). After 1:1 propensity score matching according to 1:1 based on age, gender, body mass index, TNM staging, ASA classification, intraoperative blood loss, distance from tumor low margin to anal edge, 153 cases were included in each group. Postoperative complications were classified according to Clavien-Dindo classification. Anastomotic leakage was defined and graded according to the International Study Group of Rectal Cancer (ISGRC) criteria. Results: After propensity score matching, there were no significant differences in baseline demographic characteristics between the 2 groups (all P>0.05), indicating that these two groups were comparable. (1) Operative conditions: All the patients in both groups completed operation successfully. Compared with the NPR group, the PR group had longer operation time [(181.3±60.3) minutes vs. (168.9±51.5) minutes, t=2.185, P=0.029], shorter postoperative median hospital stay [8 (7, 10) days vs. 9 (7, 11) days, Z=-2.282, P=0.022], and the differences were statistically significant (P<0.05). (2) Postoperative complications: The overall morbidity of postoperative complication in PR group and NPR group was 20.3% (31/153) and 24.2% (37/153) respectively, and the incidence of anastomotic leakage was 9.8% (15/153) and 11.1%(17/153) respectively, whose differences were not statistically significant (both P>0.05). Compared with NPR group, PR group had lower morbidity of grade III to IV complications [3.9% (6/153) vs. 11.1% (17/153), χ(2)=5.688, P=0.017] and lower secondary operation rate [1.3% (2/153) vs. 5.9% (9/153), χ(2)=4.621, P=0.032], the differences were statistically significant (both P<0.05). Though PR group had lower incidence of grade C anastomoic leakage [1.3% (2/153) vs. 3.9% (6/153), χ(2)=2.054, P=0.152], but the differences were not statistically significant. (3) Postoperative inflammation: The difference of the procalcitonin level of both PR and NPR groups at postoperative 1-d, 3-d, and 5-d was statistically significant (F=5.222, P=0.010) in time-dependent manner, while the difference was not significant in the interaction effect (P>0.05). No statistically significant differences in the C-reactive protein level between two groups at postoperative 1-d, 3-d, and 5-d were found (all P>0.05). Conclusion: Peritoneum reconstruction in laparoscopic LAR can decrease the morbidity of postoperative complication of grade III to IV and the reoperation rate, and plays an important role in controlling the inflammatory reaction, which has great clinical value.

Natural arrangement of fiber-like aragonites and its impact on mechanical behavior of mollusk shells: A review.

During billions of years of evolution, creatures in nature have possessed nearly perfect structures and functions for survival. Multiscale structures in biological materials over several length scales play a pivotal role in achieving structural and functional integrity. Fiber, as a common principal structural element in nature, can be easily constructed in different ways, thus resulting in various natural structures. In this review, we summarized the decades of investigations on a typical biological structure constructed by fiber aragonites in mollusk shells. Crossed-lamellar structure, as one of the most widespread structures in mollusk shells, reconciles the strength-toughness trade-off dilemma successfully due to the presence of highly-hierarchical architectures. This distinctive structure includes several orders of sub-lamellae, and the different order lamellae present a cross-ply feature in one macro crossed-lamellar layer. When a mollusk shell has more than one macro-layer, the crossed-lamellar structure exhibits various forms of architectures including 0°/90°, 0°/90°/0° typical-sandwich, 15°/75°/0° quasi-sandwich, and 0°/90°/0°/90° arranged modes. The fracture resistance and the relevant toughening mechanisms are directly related to the highly-hierarchical crossed-lamellar structures on different length scales. This article is aimed to review the different arranged modes of crossed-lamellar structures existing in nature, with special attention to their impact on the mechanical behavior and salient toughening mechanisms over several length scales, for seeking the design guidelines for the fabrication of bio-inspired advanced engineering materials that are adaptive to different loading conditions.

Kinking and cracking behavior in nacre under stepwise compressive loading.

The damage evolution of nacre under compressive loading has not been well understood, despite numerous investigations on its compressive behavior. In the present work, quasi-in-situ loading-unloading-reloading stepwise compressive tests were performed on nacre in Pinctada maxima shell, which exhibits a distinctive gradient feature with the thickness of platelets decreasing from the external to internal parts. In the loading direction parallel to the platelets, multiple microcracks and kink bands can absorb much deformation energy, leading to a graceful failure. Kinking only occurs at the final stage of fracture process, and it thus has no obvious influence on the strength of nacre, but contributes to a much larger strain. In the loading direction perpendicular to the platelets, nacre exhibits concurrently much higher compressive strength and fracture strain, as the damage can be effectively restricted. This is attributed to the presence of gradient structure, which disperses the stress concentration in front of the crack tip, and arouses the toughening mechanisms including damage localization and crack deflection. The findings obtained in this study are expected to provide fundamental insights into the design of bio-inspired advanced engineering materials.

Crack initiation and growth in a special quasi-sandwich crossed-lamellar structure in Cymbiola nobilis seashell.

Sandwich structure consisting of three crossed-lamellar layers (inner, middle and outer) is one of the most common structures found in mollusk shells, and is normally arranged in a 0°/90°/0° or 90°/0°/90° mode. However, the Cymbiola nobilis seashell in the present study is observed to exhibit a unique quasi-sandwich structure, where the inner and middle layers have an ~15° rotation in comparison with those of typical sandwich structures, resulting in a 15°/75°/0° or 75°/15°/90° mode. This has been identified as the weak/tough/weak and tough/weak/tough modes, and the sample arranged in the 15°/75°/0° mode with a tough layer in the middle has a higher strength than that arranged in the 75°/15°/90° mode with a weak layer in the middle. The fracture resistances of these two types of structural arrangements depend mainly on crack propagation. The interfaces between the macrolayers can effectively arrest the crack propagation especially when the tough layer is positioned in the middle (15°/75°/0° mode), hence increasing the strength and toughness of materials. Salient toughening mechanisms involving crack deflection together with zig-zag crack propagation paths as well as the fiber pull-out of second-order lamellae are identified. Moreover, triangular fracture paths with a convex morphology are observed to form due to the concurrent occurrence of fiber fracturing and channel cracking in single 1st-order lamellae. These findings shed light on the superb crack propagation resistance of the unique quasi-sandwich structure in the C. nobilis shell, thus paving the way for the development of bio-inspired advanced structural materials.

LncRNA MEG3 aggravates palmitate-induced insulin resistance by regulating miR-185-5p/Egr2 axis in hepatic cells.

OBJECTIVE: Long non-coding RNA (LncRNA) has been reported to play an important role in type 2 diabetes (T2D). We investigated the role of LncRNA maternally expressed gene 3 (MEG3) and its potential interaction with miR-185-5p in palmitate-induced hepatocyte insulin resistance. PATIENTS AND METHODS: High-fat diet (HFD) mice and insulin resistant hepatocyte were employed. Relative mRNA expressions of MEG3, miR-185-5p, and early growth response proteins-2 (Egr2) were measured by qRT-PCR. Western blot was performed to evaluate Egr2 protein expression levels. Glycogen contents and plasma insulin levels were tested by the corresponding assay. RESULTS: MEG3 and Egr2 were upregulated, but miR-185-5p was downregulated in palmitate-treated insulin resistance hepatocytes and HFD mice. MEG3 knockdown alleviated the influence of palmitate on insulin resistance in vitro and in vivo. miR-185-5p expression was upregulated upon MEG3 knockdown. Expression of Egr2 was positively correlated with MEG3 knockdown or overexpression, which could be negatively managed by abnormal expression of miR-185-5p. CONCLUSIONS: Our data demonstrated that LncRNA MEG3 aggravated palmitate-induced insulin resistance by regulating miR-185-5p/Egr2 axis, providing new insights into T2D therapeutic strategies.

Deformation and fracture behavior of a natural shell ceramic: Coupled effects of shell shape and microstructure.

Common seashells possess their most adaptive functions benefiting from the macro-geometry and unique microstructures. The Cymbiola nobilis shell exhibits a logarithmic spiral-like shape and it is hierarchically constructed by the fiber-like crossed-lamellar structure. Three-point bending tests are conducted on three groups of samples taken from different locations (G1 with two macro-layers, G2 with three macro-layers, and G3 containing three macro-layers but with an arch-like curved shape). A novel method was developed to evaluate the bending stress of the curved samples and understand the bending fracture resistance of such curved samples. Due to the presence of a horizontal force that can decrease or shield the bending moment at the bottom center of samples, the arch-like G3 samples demonstrate the highest bending fracture resistance, revealing the significance of the curved shape of shell in the protection against the external attacks. The number of macro-layers and the curved shape of shell play an important role in the mechanical properties of the shell. The orientation of building blocks in a single crossed-lamellar layer is critical to the fracture resistance, and five types of fracture modes based on interfacial debonding, inter- and trans-lamella fracture are identified. The results obtained in this study would help open a new pathway to the development of bio-inspired high-performance structural materials.

Thermodynamic and microstructural study of Ti2AlNb oxides at 800 °C.

The high-temperature structural applications of Ti2AlNb-based alloys, such as in jet engines and gas turbines, inevitably require oxidation resistance. The objective of this study is to seek fundamental insight into the oxidation behavior of a Ti2AlNb-based alloy via detailed microstructural characterization of oxide scale and scale/substrate interface after oxidation at 800 °C using X-ray diffraction (XRD), scanning electron microscopy (SEM), electron probe microanalysis (EPMA), and transmission electron microscopy (TEM). The oxide scale exhibits a complex multi-layered structure consisting of (Al,Nb)-rich mixed oxide layer (I)/mixed oxide layer (II)/oxygen-rich layer (III)/substrate from the outside to inside, where the substrate is mainly composed of B2 and O-Ti2AlNb phases. High-resolution TEM examinations along with high-angle annular dark-field (HAADF) imaging reveal: (1) the co-existence of two types (α and δ) of Al2O3 oxides in the outer scale, (2) the presence of metastable oxide products of TiO and Nb2O5, (3) an amorphous region near the scale/substrate interface including the formation of AlNb2, and (4) O-Ti2AlNb phase oxidized to form Nb2O5, TiO2 and Al2O3.

IMP3 promotes TNBC stem cell property through miRNA-34a regulation.

OBJECTIVE: To explore the expression and function of insulin-like growth factor II (IGFII) mRNA binding protein (IMP3) in the Triple Negative Breast Cancer (TNBC). MATERIALS AND METHODS: According to previously reported gene expression array, we found that IMP3 had significantly higher expression in the CD44+CD24-ESA+ cell cluster, tumor initiating cell or cancer stem cell (CSCs), compared to other tumor cells. Based on the GEO database (GEO accession No. GSE6883), we detected the mRNA levels of IMP 1,2 and 3 by quantitative polymerase chain reaction (q-PCR) in CD44+CD24-ESA+ cell cluster and other breast tumor cell clusters. Besides, we measured IMP3 expression in microsphere of breast cancer, which exerted more significant tumor stem cell properties. The effects of IMP3 on breast cancer cell stem cell properties were studied by RNA interference and overexpression approaches in vitro. Furthermore, we predicted and identified microRNA, which could target and regulate IMP3 from bioinformatics analysis, and verified the interaction by luciferase assays and rescue experiments. RESULTS: Previously reported data showed that IMP3 expression was significantly upregulated in CD44+CD24-ESA+ cell cluster from breast cancer tissues. Besides, we found IMP3 had higher expression in mesenchymal cells rather than epithelial cells, which was also significantly elevated in SUM159 and T49D cell lines cultured as microsphere rather than adherent cells or differentiated cells. CD44+CD24-ESA+ cell cluster proportion was significantly decreased after silencing IMP3 in SUM1315, and its ability to develop into microsphere was significantly inhibited. By re-expressing IMP3 in SUM315, we restored the self-renewal capacity and tumorigenesis potential of SUM315. Through relative predicting website, we found several miRNAs which could regulate IMP3. miR-34a with highest score was chosen for further analysis. Mimicking miR-34a significantly downregulated IMP3 expression and inhibited its ability to develop into microsphere, while overexpressing IMP3 could rescue this process. CONCLUSIONS: IMP3 plays a vital role in maintaining stem cell properties of breast cancer cells, which could be regulated by mir-34a.

MiR-638 serves as a tumor suppressor by targeting HOXA9 in glioma.

OBJECTIVE: MiR-638 is constantly downregulated and serves as a tumor suppressor in various cancers. Its role in gliomas remains unclear. This study is designed to investigate the clinical significance and the pathogenic role of miR-638 in human gliomas. PATIENTS AND METHODS: Quantitative Real-time PCR was performed to analyze the expression of miR-638 in the tumor and adjacent tissues of 24 glioma patients. The association between the expression of miR-638 and clinical features were examined. Survival of patients was studied by Kaplan-Meier curves. The impact of miR-638 on cell growth and apoptosis was determined by CCK-8 assay, colony formation assay, cell cycle analysis and Annexin V-FITC-PI apoptosis assay. The effect of miR-638 on HOXA9 was determined by luciferase assay and Western blot. The effect of miR-638 and HOXA9 on expression of oncogenes, Cyclin D1 and C-MYC was determined by Western blot. RESULTS: MiR-638 expression was constantly downregulated in glioma tumor tissue, which is negatively correlated with the WHO grade. MiR-638 expression was associated with clinical features such as tumor size, KPS score and WHO grade. Patients with low miR-638 had a worse overall survival than those with high expression. Experimentally, miR-638 directly targeted HOXA9 to suppress its expression, leading to attenuations of cell proliferation, colony formation and cell cycle progression and enhanced basal apoptosis level. MiR-638/HOXA9 axis also suppressed the expression of Wnt/beta-catenin-regulated oncogenes, Cyclin D1 and C-MYC. CONCLUSIONS: MiR-638 is a constantly downregulated microRNA in gliomas and is associated with its prognosis. MiR-638 regulates cellular malignancy of gliomas through targeting HOXA9. Thus, miR-638/HOXA9 signaling axis may have therapeutic potential in gliomas.

High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas.

The development and progression of thyroid tumors is signaled by phenotype-specific mutations of genes involved in growth control. Molecular events associated with undifferentiated thyroid cancer are not known. We examined normal, benign, and malignant thyroid tissue for structural abnormalities of the p53 tumor suppressor gene. Mutations were detected by single-strand conformation polymorphisms of PCR-amplified DNA, using primers bracketing the known hot spots on either exons 5, 6, 7, or 8. The prevalence of mutations was as follows: normal thyroid 0/6; follicular adenomas 0/31; papillary carcinomas 0/37; medullary carcinomas 0/2; follicular carcinomas 1/11; anaplastic carcinomas 5/6; thyroid carcinoma cell lines 3/4. Positive cases were confirmed by direct sequencing of the PCR products. All five anaplastic carcinoma tissues and the anaplastic carcinoma cell line ARO had G:C to A:T transitions leading to an Arg to His substitution at codon 273. In both tumors and cell lines, examples of heterozygous and homozygous p53 mutations were identified. The only thyroid carcinoma cell line in which p53 mutations were not detected in exons 5-8 had markedly decreased p53 mRNA levels, suggesting the presence of a structural abnormality of either p53 itself or of some factor controlling its expression. The presence of p53 mutations almost exclusively in poorly differentiated thyroid tumors and thyroid cancer cell lines suggests that inactivation of p53 may confer these neoplasms with aggressive properties, and further loss of differentiated function.

Mechanical properties of crossed-lamellar structures in biological shells: A review.

The self-fabrication of materials in nature offers an alternate and powerful solution towards the grand challenge of designing advanced structural materials, where strength and toughness are always mutually exclusive. Crossed-lamellar structures are the most common microstructures in mollusks that are composed of aragonites and a small amount of organic materials. Such a distinctive composite structure has a fracture toughness being much higher than that of pure carbonate mineral. These structures exhibiting complex hierarchical microarchitectures that span several sub-level lamellae from microscale down to nanoscale, can be grouped into two types, i.e., platelet-like and fiber-like crossed-lamellar structures based on the shapes of basic building blocks. It has been demonstrated that these structures have a great potential to strengthen themselves during deformation. The observed underlying toughening mechanisms include microcracking, channel cracking, interlocking, uncracked-ligament bridging, aragonite fiber bridging, crack deflection and zig-zag, etc., which play vital roles in enhancing the fracture resistance of shells with the crossed-lamellar structures. The exploration and utilization of these important toughening mechanisms have attracted keen interests of materials scientists since they pave the way for the development of bio-inspired advanced composite materials for load-bearing structural applications. This article is aimed to review the characteristics of hierarchical structures and the mechanical properties of two kinds of crossed-lamellar structures, and further summarize the latest advances and biomimetic applications based on the unique crossed-lamellar structures.

Core-multishell globular oxidation in a new TiAlNbCr alloy at high temperatures.

Oxidation resistance is one of key properties of titanium aluminide (TiAl) based alloys for high-temperature applications such as in advanced aero-engines and gas turbines. A new TiAlNbCr alloy with micro-addition of yttrium has been developed, but its oxidation behavior is unknown. To provide some fundamental insights, high-temperature oxidation characteristics of this alloy are examined via scanning electron microscopy, transmission electron microscopy, electron probe microanalysis, and X-ray diffraction. We show that distinctive core-multishell globular oxidation and "daisy" flower-like oxidation occur exclusively around Y2O3 particles. Globular oxides exhibit multi-layered Y2O3/TiO2/Al2O3-rich/TiO2-rich shell structures from the inside to outside. Flower-like inner oxides consist of core Y2O3 particles surrounded by divergent Al2O3 and oxygen-rich α2-Ti3Al in the near-scale substrate. As the scale-substrate interface moves inward, the inner oxide structures suffer deeper oxidation and transform into the globular oxide structures. Our results demonstrate that the unique oxidation characteristics and the understanding of formation mechanisms pave the way for the exploration and development of advanced oxidation-resistant TiAl-based materials.

Successful Rescue of Late-onset Antibody-mediated Rejection 12 Years After Living-donor Intestinal Transplantation: A Case Report.

BACKGROUND: Antibody-mediated rejection (ABMR) has recently surfaced as a potential form of graft dysfunction after intestinal transplantation. METHODS: We present a case of an intestinal transplant recipient who developed late-onset ABMR 12 years after living-donor transplantation. An 18-year-old male recipient with a history of extensive intestinal resection secondary to acute bowel volvulus exhibited an excellent baseline immune profile for transplantation, including ABO-identical and HLA-haploidentical to the donor; a negative cross-match with a panel reactive antibody of 3.0%. RESULTS: Post-transplantation immunosuppression consisted of tacrolimus, mycophenolate mofetil (MMF), and prednisone within the first year, followed by tacrolimus and MMF in the second year, and maintenance with tacrolimus monotherapy thereafter. The recipient experienced a single episode of indetermined acute cellular rejection 3 months after transplantation. Since then, he did not require any parenteral nutrition and had completely reintegrated with society. Twelve years later, the patient developed persistent diarrhea associated with transplant biopsy diffuse C4d deposition and circulating donor-specific antibodies. After the use of rituximab and intravenous immunoglobulin, the recipient stabilized 17 years after transplantation with complete recovery of intestinal mucosal damage. CONCLUSION: Late-onset ABMR can emerge after transplantation and must be considered a possible cause of graft dysfunction in long-term intestinal transplantation survivors.

[Mononuclear cells of umbilical cord blood differentiation to granulocyte cell in vitro].

Objective: To explore an optimal method for granulocyte cell production from umbilical cord blood mononuclear cells. Methods: Erythrocytes were precipitated by hydroxyethyl starch. Mononuclear cells were isolated through Ficoll density gradient centrifugation. Different media, additives and cultivation model were chosen for granulocyte induction. Cell morphology was observed by microscopy, and cell phenotype was detected by flow cytometry. The CD18 expression of granulocytes was tested by immunofluorescence assay, and phagocytosis test was executed as well. Results: Compared to fetal bovine serum (FBS) treatment group, cell viability, counts and differentiation rate of granulocytes induced by X-VIVO(TM) 15 combined with TPO, SCF, G-CSF but without FBS were superior. And X-VIVO(TM)15 medium was better than SCGM medium at effectiveness and cost. Using two-stage mode of hematopoietic stem cell expansion followed by granulocyte induction with X-VIVO(TM)15 combining TPO, SCF and G-CSF, cell proliferation was nearly 132 times at day 21. Flow cytometry showed that the differentiation was lagged in 2-stage mode than in direct induction mode, CD15 expression was (69.60± 1.06) % vs (97.73±0.39) %; Wright-Giemsa staining demonstrated mature granulocytes; immunofluorescence showed the expression of lysosomal proteins CD18. A strong phagocytic function of mature granulocytes was demonstrated by phagotrophic efficiency of (51.43±0.05) %. And granulocyte had chemotaxis ability under the role of chemotactic factor IL-8. Conclusion: Optimized culture media and cultivation mode are achieved for functional granulocytes induction in vitro.