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The microstructures and mechanical properties of various heat-affected zones (HAZs) for 09MnNiDR pressure vessel steel are systematically analyzed. The results show that at − 70 °C, the thermally simulated subcritical heat-affected zone (SCHAZ) reaches the impact toughness of 270 J, which is the highest among various HAZs. Owing to the appearance of martensite–austenite (M–A) constituents distributed along the grain boundary in the thermally simulated critical heat-affected zone and fine-grained heat-affected zone, the impact toughness sharply decreases compared with that of the SCHAZ. The impact toughness of the coarse-grained heat-affected zone (CGHAZ) reaches 20 J, which makes the CGHAZ the weakest zone. The microstructure of the CGHAZ is composed of relatively coarse bainite and ferrite. Moreover, the proportion of high-angle grain boundaries (HAGBs) in CGHAZ is the lowest, at only 22%. Coarse grain size, microstructural transformation, and different proportions of HAGBs significantly affect the impact toughness in each zone of HAZs.

Reasonable design and synthesis of high-efficiency rare earth oxides-based materials as alternatives to noble-metal catalysts are of great significance for oxygen electrocatalysis. Herein, we report three-dimension (3D) Rosa centifolia-like CeO2 encapsulated with N-doped carbon (NC) composites (CeO2@NC) for enhancing oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) activities. This synthetic method allows CeO2 to tune the oxygen vacancy concentration and electronic structure of a series of CeO2@NC catalysts due to its large oxygen-storage-capacity (OSC) property. Moreover, benefiting from the exposed active sites in NC as well as the synergy between CeO2 and NC, among as-prepared samples, the resultant CeO2@NC-900 delivers a half-wave potential (E1/2) of 0.854 V, which is more positive compared with counterpart of NC-900 (0.806 V) and even comparable to that of commercial Pt/C catalyst (0.855 V). This indicates that the ORR electrocatalytic activity of CeO2@NC-900 is significantly improved. Meanwhile, CeO2@NC-900 exhibits satisfactory performance toward OER. For practical application, the CeO2@NC-900 involved rechargeable Zn-air battery possesses excellent energy efficiency, superior stability, and large energy density (666.1 Wh kgZn−1 at 5 mA cm−2). This approach provides a valid way to develop advanced rare earth oxides-based materials for energy applications.

Background: Human herpes virus-6B (HHV-6B) was suggested as an important etiologic factor of mesial temporal lobe epilepsy, while the mechanism is still unknown. Here, we aimed to analyze antigens representing latent, early and late HHV-6B infection and the association with inflammatory cytokines in brain tissue and cerebral spinal fluid (CSF) from MTLE patients with HHV-6B-positivity.Results: Nested polymerase chain reaction (nPCR) in brain tissue revealed HHV-6B DNA in 19 of 49 MTLE patients (39%) and 1 of 19 controls (5%) (PConclusions: Our finding suggests HHV-6B is a common etiologic agent of MTLE. Different virus life cycle may play an important modifying role in inflammatory biology that warrants further investigation. Though virus DNA is difficult detected in CSF, up-regulation of IL-1a and IL-7 in CSF indicates the two cytokines may be taken as indirect biomarker of HHV-6B infection.

In this study, fertilizer drawn forward osmosis (FDFO) process was applied for the treatment of shale gas wastewater. The forward osmosis (FO) experiments with simulated shale gas wastewater and real shale gas wastewater were carried out, respectively. The effects of reverse salt diffusion on the inorganic fouling to the membrane surface was systematically investigated. Two commercial FO membranes were selected and the optimized operating conditions were evaluated. It was found that calcium sulfate scaling can be alleviated by optimizing the operating parameters, including increasing flow rate and decreasing temperature. Furthermore, the Aquaporin FO membrane, which has lower reverse salt flux and less surface charge potential, exhibited lower fouling tendency. Under the optimal operating conditions, the effects of reverse salt diffusion on the barium sulfate scaling were also analyzed. The presence of calcium ions can alleviate barium sulfate scaling, while sodium chloride will aggravate the barium sulfate scaling. In addition, the scaling behavior of real shale gas wastewater was further explored. Inorganic scaling phenomenon seriously affected the FO membrane performance and lower pH had beneficial effect on recycling the real shale gas wastewater. The present study provided both theoretical fundamentals and industry applicable practices for implementing FO technology in the treatment and resource recovery of shale gas wastewater.

Polypyrrole (PPy) hollow micro/nanospheres have been widely designed to encapsulate active sulfur as cathodes in lithium–sulfur (Li–S) batteries to inhibit the polysulfide shuttle effect. Here, for...

An ynamide-mediated one-pot, two-step intermolecular esterification via the condensation of carboxylic acids with nucleophilic hydroxyl species was reported. A broad substrate scope with respect to carboxylic acids, alcohols, and phenols was observed. The α-acyloxyenamide intermediates formed by the addition of carboxylic acids to ynamides proved to be effective acylating reagents for the esterification of alcohol and phenol derivatives with the assistance of base catalysis. Notably, the racemization of the α-chiral center of carboxylic acids can be avoided.

Polymorphisms in arsenic (+ 3 oxidation state) methyltransferase (AS3MT) have been shown to be related to interindividual variations in arsenic metabolism and to influence adverse health effects in acute promyelocytic leukemia (APL) patients treated with arsenic trioxide (As2O3). The occurrence of hyperleukocytosis with As2O3 treatment seriously affects the early survival rate of APL patients, but no definite explanation for such a complication has been clearly established. To clarify the causes of this situation, AS3MT polymorphisms 14215 (rs3740390), 14458 (rs11191439), 27215 (rs11191446), and 35991 (rs10748835) and profiles of plasma arsenic metabolites were evaluated in a group of 54 newly diagnosed APL patients treated with single-agent As2O3. High-performance liquid chromatography–hydride generation-atomic fluorescence spectrometry (HPLC–HG-AFS) was used to determine the concentrations of plasma arsenic metabolites. Plasma arsenic methylation metabolism capacity was evaluated by the percentage of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), primary methylation index (PMI, MMA/iAs), and secondary methylation index (SMI, DMA/MMA). The results showed that APL patients who developed hyperleukocytosis had a higher plasma iAs%, but a lower MMA% and PMI than those who did not develop hyperleukocytosis during As2O3 treatment. In addition, patients with the AS3MT 14215 (rs3740390) CC genotype had significantly higher plasma iAs% and incidence of hyperleukocytosis, but lower PMI than patients with the CT + TT genotype. Conversely, we did not observe statistically significant associations between the occurrence of hyperleukocytosis and AS3MT 14458 (rs11191439), 27215 (rs11191446), and 35991 (rs10748835) polymorphisms in our study subjects. These results indicated that AS3MT 14215 (rs3740390) might be used as an indicator for predicting the occurrence of hyperleukocytosis in APL patients treated with As2O3.

Stanene, composed of tin atoms and arranged in a single layer, is the tin analogue of graphene and predicted by the past studies to be a 2D topological insulator, which has aroused extensive resear...

Traditional rice landraces grown under on‐farm conservation conditions by indigenous farmers are extremely important for future crop improvement. However, little is known about how the natural selection and agriculture practices of indigenous farmers interact to shape and change the population genetics of rice landraces grown under on‐farm conservation conditions during the domestication. In this study, we sequenced DNA from 108 core on‐farm conserved rice landraces collected from the ethnic minority regions of Yunnan, China, including 56 accessions collected in 1980 and 52 accessions collected in 2007 and obtained 2,771,245 of credible SNPs. Our findings show that most genetic diversity was retained during the 27 years of domestication by on‐farm conservation. However, SNPs with marked allele frequency differences were found in some genome regions, particularly enriched in genic regions, indicating changes in genic regions may have played a much more prominent role in the short‐term domestication of 27 years. We identified 186 and 183 potential selective‐sweep regions in the indica and japonica genomes, respectively. We propose that on‐farm conserved rice landraces during the short‐term domestication had a highly polygenic basis with many loci responding to selection rather than a few loci with critical changes in response to selection. Moreover, loci affecting important agronomic traits and biotic or abiotic stress responses have been particularly targeted in selection. A genome‐wide association study identified 90 significant signals for six traits, 13 of which were in regions of selective sweeps. Moreover, we observed a number of significant and interesting associations between loci and environmental factors, which implies adaptation to local environment. Our results provide insights into short‐term evolutionary processes and shed light on the underlying mechanisms of on‐farm conservation.

For the actual welded joints, determination of the weakest zone in the welded and the effects of the weakest zone is very important in characterization of the welded joints. In this paper, microstructure feature and charpy toughness of the 12Cr2Mo1R for pressure vessels steel welded joints were systematically investigated. The standard Charpy V-notch impact test specimens were prepared on the base metal, weld metal and various zones of the heat affected zone. The weakest zone of the 12Cr2Mo1R welded joint and its effects on the impact toughness of the welded joint were studied. It shows that at −30 °C, the weakest zone of the welded joint is the coarse-grained heat affected zone (CGHAZ), which impact toughness is 65 J, and its microstructure is composed of a large number of coarse granular bainite and a few blocks ferrite. With the fraction of CGHAZ on the ligament at the notch tip increases, the impact toughness decreases. The closer the CGHAZ location from the notch is, the less the impact toughness of the sample is. Above two aspects fully reflect the effect of the weakest zone on the toughness of the joint. This work reveals the effect of fraction of weakest zone in front of the notch tip on the impact toughness of the 12Cr2Mo1R welded joints.

Conductive supports could improve the electrical conductivity of the electrode in lithium-sulfur (Li-S) batteries but suffer from the shuttle effect originated from the polysulfide dissolution, while the hydrophilic metal oxides could avoid the shuttle effect but with poor conductivity. Herein, a facile approach was developed to fabricate hierarchically porous tin oxide (SnO2) nanoparticle-anchored tubular polypyrrole (T-PPy) as a sulfur host, in order to integrate the advantages of conductive supports and metal oxides but overcome their shortcomings. In the unique structure, the T-PPy nanotubes acted as a conductive network to not only improve the electrical conductivity of cathodes but also accommodate the volume expansion of the sulfur cathode during cycling as well as relatively confine the polysulfide diffusion, while the SnO2 nanoparticles served as a high-efficient polysulfide trap to mitigate the shuttle effect due to the chemical bond between SnO2 and polysulfides. Moreover, the hierarchically porous structure and therefore large surface area of the proposed S/(T-PPy)@SnO2 cathode were favorable for the accommodation of sulfur and lithium sulfides. Consequently, S/(T-PPy)@SnO2 with 64.7% sulfur mass content exhibited excellent cyclic stability with a decay rate of only 0.05% per cycle along with 500 cycles at 1 C, rate capability of 383.7 mA h/g at 5 C, and Coulombic efficiency above 90%, outstanding among most of the reported PPy-based sulfur cathodes and PPy-based ternary sulfur cathodes.

The construction of high-efficiency electrocatalysts for hydrogen evolution, oxygen reduction, and oxygen evolution reactions (HER/ORR/OER) is critical for the overall water splitting system, fuel cells, and rechargeable metal-air batteries. Here, we report a viable strategy for tuning the size of a Co-based zeolitic imidazolate framework (ZIF). As a result, a nitrogen-doped graphitic carbon-supported ultrafine Co nanoparticle electrocatalyst (Co/NGC-3) with multifunctional activity was developed. Owing to the smaller ZIF-67 polyhedrons with relatively uniform distribution, more effective active sites, and a strong coupling effect of Co-pyridinic-N, the proposed Co/NGC-3 catalyst exhibited an impressive HER activity. It also showed brilliant catalytic activity in both the ORR and OER, delivering a more positive half-wave potential and a lower overpotential than that of the Pt/C catalyst, respectively. Moreover, the Co/NGC-3 involved the Zn-air battery displayed satisfactory power density, excellent energy density, and superior stability. This approach provides an efficient strategy for the preparation of high-performance multifunctional electrocatalysts for energy-related applications.

Photocatalytic (PC) overall water splitting (OWS) is considered an ideal method for solar-to-fuel conversion, though its practical application is greatly limited by the loading of noble-metal co-catalysts. It is, therefore, of great significance to explore alternate non-noble-metal co-catalysts. Herein, a novel non-precious metal Mn2Co2C@C/Mn2N0.86 composite (denoted as MCMN), composed of Mn2N0.86 and N-doped graphitized carbon wrapped Mn2Co2C nanoparticles, was fabricated and then used to modify photocatalysts, such as g-C3N4 and SrTiO3 for the construction of MCMN/g-C3N4 and MCMN/SrTiO3 composite photocatalysts by a mechanical grinding method. When they were used for PC OWS under UV-Vis light irradiation, in the initial stage, the Mn2N0.86 in MCMN was hydrolyzed, and novel non-precious metal MnOOH and Mn2Co2C@C (MC) dual cocatalysts were photo-derived to grow in situ on the surfaces of photocatalysts. In the new kind of MC/g-C3N4/MnOOH PC system, the metallic MC acts as a co-catalyst for H2 generation, effectively trapping photoelectrons and accelerating H2 evolution reaction; meanwhile, MnOOH acts as a co-catalyst for O2 generation, favoring the adsorption of water molecules on the surface to boost the O2 evolution reaction. Consequently, the optimized MC/g-C3N4/MnOOH showed a prominent H2 evolution rate of 8.876 μmol h−1 for PC OWS, even higher than that of g-C3N4 loaded with 1 wt% Pt, and the corresponding AQE reached 2.54% and 1.45% at 400 and 420 nm, respectively. A similar promotion was also obtained on the SrTiO3 photocatalyst, demonstrating the versatility of this composite. This work provides a new avenue for the construction of novel noble-metal-free PC systems.

Polo-like kinase 1 (PLK-1) is a protein kinase that plays a significant role in the initiation, maintenance, and completion of mitotic processes in the cell cycle. PLK-1 has been recorded to be over-expressed in various human cancers and is associated with poor prediction; thus it is an attractive target for anticancer therapy. Novel α-santalol functionalized chitosan nanoparticles were synthesized using the sol gel method and were assessed for their in vitro (MTT, apoptotic staining assays, and cell cycle analysis) and in vivo activities. α-Santalol loaded chitosan NPs inhibited the proliferation of triple negative breast cancer (MDA-MB-231) at an inhibitory concentration of (IC50) about 4.5 μg mL; meanwhile, in normal cells, no adverse effects were exhibited up to 100 μg mL−1. The findings also implicated a decreased expression of the anti-apoptotic protein, BCL-2 with PLK-1 and an increase in the expression of BAD, caspases and BAX. However, in in vivo studies, the treated animal group exhibited no aberrant effects in vital organs or blood parameters. Tumor growth was significantly inhibited after i.v. injection of α-santalol loaded chitosan NPs at a dose of 5 mg kg−1. Taken together, the α-santalol functionalized chitosan NPs hold great potential in biomedical applications, especially cancer theranostics, due to their versatile nature as well as diagnostics for clinical tumor biology.

We describe an unusual case of corticosteroid-responsive autoimmune meningoencephalomyelitis with linear perivascular gadolinium enhancement but in the absence of anti- glial fibrillary acidic protein (GFAP) antibodies (ABs) in the cerebral spinal fluid (CSF).The patient's clinical symptoms, brain magnetic resonance imaging (MRI) features, serum and CSF analysis and treatment were reviewed.A 47-year-old female experienced a subacute course with bilateral lower limbs weakness, unsteady walking, and dysuria. Brain MRI revealed typical radial perivascular gadolinium enhancement extending from the lateral ventricles to the white matter; MRI spine revealed lesions distributed in the entire spinal cord. Immunohistochemical staining of a brain biopsy revealed CD3+ T cells and CD20+ B cells cuffing around brain vessels, accompanied by CD68+ macrophages. CSF was negative for anti-GFAP ABs while serum was positive for anti-GFAP ABs (1:100). The patient responded well to corticosteroid.There are no uniform diagnostic criteria for autoimmune GFAP astrocytopathy. Our case suggested the importance of typical MRI findings in the diagnosis of this rare disease. Early treatments are very important to alleviate symptoms.

Coordinated regulation of alternative pre-mRNA splicing is essential for germ cell development. However, the molecular mechanism underlying that control alternative mRNA expression during germ cell development remains poorly understood. Herein, we showed that hnRNPH1, an RNA-binding protein, is highly expressed in the reproductive system and localized in the chromosomes of meiotic cells but excluded from the XY body in pachytene spermatocytes and recruits the splicing regulators PTBP2 and SRSF3 and cooperatively regulates the alternative splicing of the critical genes that are required for spermatogenesis. Conditional knockout Hnrnph1 in spermatogenic cells caused many abnormal splicing events that affect genes related to meiosis and communication between germ cells and Sertoli cells, characterized by asynapsis of chromosomes and impairment of germ-Sertoli communications, ultimately leading to male sterility. We further showed that hnRNPH1 could directly bind to SPO11 and recruit the splicing regulators PTBP2 and SRSF3 to regulate the alternative splicing of the target genes cooperatively. Strikingly, Hnrnph1 germline-specific mutant female mice were also infertile, and Hnrnph1-deficient oocytes exhibited a similar defective synapsis and cell-cell junction as shown in Hnrnph1-deficient male germ cells. Collectively, our data reveal an essential role for hnRNPH1 in regulating pre-mRNA splicing during spermatogenesis and oogenesis and support a molecular model whereby hnRNPH1 governs a network of alternative splicing events in germ cells via recruiting PTBP2 and SRSF3.

Early screening and detection of individuals at high risk of high-frequency hearing loss and identification of risk factors are critical to reduce the prevalence at community level. However, unlike those for individuals facing occupational auditory hazards, a limited number of hearing loss screening models have been developed for community residents. Therefore, this study used lasso regression with 10-fold cross-validation for feature selection and model construction on 38 questionnaire-based variables of 4010 subjects and applied the model to training and testing cohorts to obtain a risk score. The model achieved an area under the curve (AUC) of 0.844 in the model validation stage and individuals’ risk scores were subsequently stratified into low-, medium-, and high-risk categories. A total of 92.79% (1094/1179) of subjects in the high-risk category were confirmed to have hearing loss by audiometry test, which was 3.7 times higher than that in the low-risk group (25.18%, 457/1815). Half of the key indicators were related to modifiable contexts, and they were identified as significantly associated with the incident hearing loss. These results demonstrated that the developed model would be feasible to identify residents at high risk of hearing loss via regular community-level health examinations and detecting individualized risk factors, and eventually provide precision interventions.

Description, ZBP1-MLKL necroptotic signaling bridges tumor cell damage to antitumor immune responses after radiation., Necroptosis, a form of regulated necrosis, participates in tumor development and dying cell immunogenicity. However, it remains unclear how tumor cell–intrinsic necroptotic signaling contributes to radiation-induced antitumor immunity. Here, we found that the ZBP1-MLKL necroptotic cascade in irradiated tumor cells was essential for antitumor immunity. ZBP1-dependent activation of MLKL potentiated type I interferon responses following tumor cell irradiation. Mechanistically, the ZBP1-MLKL necroptotic cascade induced cytoplasmic DNA accumulation in irradiated tumor cells and, in turn, autonomously activated cGAS-STING signaling, thus creating a positive feedback loop between those two pathways to drive persistent inflammation. Accordingly, ablation of caspase-8 enhanced STING pathway activation and the antitumor effects of radiation by activating MLKL. These findings reveal that ZBP1-MLKL necroptosis signaling maximized radiation-induced antitumor immunity through mutual interaction with the tumor cell–intrinsic STING pathway. This study provides insight into how radiotherapy bridges tumor cell damage to antitumor immune responses and an alternative strategy to improve radiotherapy.

During male meiosis, the constitutively unsynapsed XY chromosomes undergo meiotic sex chromosome inactivation (MSCI), and the DNA damage response (DDR) pathway is critical for MSCI establishment. Our previous study showed that UHRF1 (ubiquitin-like, with PHD and ring finger domains 1) deletion led to meiotic arrest and male infertility; however, the underlying mechanisms of UHRF1 in the regulation of meiosis remain unclear. Here, we report that UHRF1 is required for MSCI and cooperates with the DDR pathway in male meiosis. UHRF1-deficient spermatocytes display aberrant pairing and synapsis of homologous chromosomes during the pachytene stage. In addition, UHRF1 deficiency leads to aberrant recruitment of ATR and FANCD2 on the sex chromosomes and disrupts the diffusion of ATR to the XY chromatin. Furthermore, we show that UHRF1 acts as a cofactor of BRCA1 to facilitate the recruitment of DDR factors onto sex chromosomes for MSCI establishment. Accordingly, deletion of UHRF1 leads to the failure of meiotic silencing on sex chromosomes, resulting in meiotic arrest. In addition to our previous findings, the present study reveals that UHRF1 participates in MSCI, ensuring the progression of male meiosis. This suggests a multifunctional role of UHRF1 in the male germline.

Total body irradiation is a standard procedure of bone marrow transplantation (BMT) which causes a rapid increase in reactive oxygen species (ROS) in the bone marrow microenvironment during BMT. The increase in ROS reduces the engraftment ability of donor cells, thereby affecting the bone marrow recovery of recipients after BMT. In the early weeks following transplantation, recipients are at high risk of severe infection due to weakened hematopoiesis. Thus, it is imperative to improve engraftment capacity and accelerate bone marrow recovery in BMT recipients. In this study, we constructed recombinant copper/zinc superoxide dismutase 1 (SOD1) fused with the cell-penetrating peptide (CPP), the trans-activator of transcription (Tat), and showed that this fusion protein has penetrating ability and antioxidant activity in both RAW264.7 cells and bone marrow cells in vitro. Furthermore, irradiated mice transplanted with SOD1-Tat-treated total bone marrow donor cells showed an increase in total bone marrow engraftment capacity two weeks after transplantation. This study explored an innovative method for enhancing engraftment efficiency and highlights the potential of CPP-SOD1 in ROS manipulation during BMT.

Background Understanding and identifying the factors responsible for genetic differentiation is of fundamental importance for efficient utilization and conservation of traditional rice landraces. In this study, we examined the spatial genetic differentiation of 594 individuals sampled from 28 locations in Yunnan Province, China, covering a wide geographic distribution and diverse growing conditions. All 594 accessions were studied using ten unlinked target genes and 48 microsatellite loci, and the representative 108 accessions from the whole collection were sampled for resequencing. Results The genetic diversity of rice landraces was quite different geographically and exhibited a geographical decline from south to north in Yunnan, China. Population structure revealed that the rice landraces could be clearly differentiated into japonica and indica groups, respectively. In each group, the rice accessions could be further differentiated corresponded to their geographic locations, including three subgroups from northern, southern and middle locations. We found more obvious internal geographic structure in the japonica group than in the indica group. In the japonica group, we found that genetic and phenotypic differentiation were strongly related to geographical distance, suggesting a pattern of isolation by distance (IBD); this relationship remained highly significant when we controlled for environmental effects, where the likelihood of gene flow is inversely proportional to the distance between locations. Moreover, the gene flow also followed patterns of isolation by environment (IBE) whereby gene flow rates are higher in similar environments. We detected 314 and 216 regions had been differentially selected between Jap-N and Jap-S, Ind-N and Ind-S, respectively, and thus referred to as selection signatures for different geographic subgroups. We also observed a number of significant and interesting associations between loci and environmental factors, which implies adaptation to local environment. Conclusions Our findings highlight the influence of geographical isolation and environmental heterogeneity on the pattern of the gene flow, and demonstrate that both geographical isolation and environment drives adaptive divergence play dominant roles in the genetic differentiation of the rice landraces in Yunnan, China as a result of limited dispersal.

Background: Adenocarcinomas of the nasal cavity and paranasal sinus, which includes non-intestinal adenocarcinoma of nasal cavity and paranasal sinuses (n-ITAC), are rare and heterogeneous. The diagnosis of n-ITAC is commonly achieved by exclusion, and several entities of considerable biological diversity are included. The literature on n-ITAC is rarely reported. It is reported in the literature that the prognosis of most sinonasal adenocarcinomas still remains poor. We hope that the analysis can provide recommendations for the treatment of n-ITAC.Objective: To analyze the clinical characteristics, outcomes, prognostic factors and the best treatment of n-ITAC.Methods: We located the time on the PACS system of Southern Hospital of Southern Medical University from February 1995 to February 2020. We searched the keyword " n-ITAC " and selected pathology. A total of 16 patients were searched, of which 2 were undiagnosed and 1 lost follow-up. Finally, we analyzed a total of 13 n-ITAC patients.Results: The follow-up time was 34.6 months in average. The 1-year overall survival (OS) rate of G1 tumors was 100%, and the 3-year OS rate was 71.4%. The 1-and 3-year OS rates of G3 tumors were 50% and 16.7%, respectively. It was significantly associated with OS (p=0.03). Pathological grade is an independent prognostic factor. The OS of the surgery group was significantly better than that of the non-surgery group (1-year OS was 90.9% vs 0%, 3-year OS was 54.5% vs 0% P < 0.001). Surgery is an indispensable means of treatment and benefit. Patients with certain risk factors were given radical radiotherapy. The radiation dose for cases without surgery or with positive surgical margin was 66-70Gy/33F, and the dose for cases with negative margin was 60Gy/28F. Conclusions: N-ITAC is a rare disease, and high-grade tumors have a poor prognosis. Surgery is still the main treatment for n-ITAC. Patients with no surgery, high-grade tumors and/or positive surgical margins should be given radical radiotherapy, and preventive radiotherapy in the drainage area of the lymph node at the same time. If the margins are negative, the radiation dose can be appropriately reduced. Whether combined with chemotherapy and targeted therapy needs further study.

Annexin A2 (ANXA2) is reported to be associated with cancer development. To investigate the roles ANXA2 plays during the development of cancer, the RNAi method was used to inhibit the ANXA2 expression in caco2 (human colorectal cancer cell line) and SMMC7721 (human hepatocarcinoma cell line) cells. The results showed that when the expression of ANXA2 was efficiently inhibited, the growth and motility of both cell lines were significantly decreased, and the development of the motility relevant microstructures, such as pseudopodia, filopodia, and the polymerization of microfilaments and microtubules were obviously inhibited. The cancer cell apoptosis was enhanced without obvious significance. The possible regulating pathway in the process was also predicted and discussed. Our results suggested that ANXA2 plays important roles in maintaining the malignancy of colorectal and hepatic cancer by enhancing the cell proliferation, motility, and development of the motility associated microstructures of cancer cells based on a possible complicated signal pathway.

Background Androgen plays a pivotal role in spermatogenesis, accompanying a question how androgen acts on germ cells in testis since germ cells lack of androgen receptors (AR). Promyelocytic leukemia zinc-finger (PLZF) is essential for maintenance of undifferentiated spermatogonia population which is terminologically called spermatogonia progenitor cells (SPCs). Aims We aim to figure out the molecular connections between androgen and fates of PLZF+ SPCs population. Method Immunohistochemistry was conducted to confirm that postnatal testicular germ cells lacked endogenous AR. Subsequently, total cells were isolated from 5 dpp (day post partum) mouse testes, and dihydrotestosterone (DHT) and/or bicalutamide treatment manifested that Plzf was indirectly regulated by androgen. Then, Sertoli cells were purified to screen downstream targets of AR using ChIP-seq, and gene silence and overexpression were used to attest these interactions in Sertoli cells or SPCs-Sertoli cells co-culture system. Finally, these connections were further verified in vivo using androgen pharmacological deprivation mouse model. Results Gata2 is identified as a target of AR, and β1-integrin is a target of Wilms’ tumor 1 (WT1) in Sertoli cells. Androgen signal negatively regulate β1-integrin on Sertoli cells via Gata2 and WT1, and β1-integrin on Sertoli cells interacts with E-cadherin on SPCs to regulate SPCs fates. Conclusion Androgen promotes differentiation of PLZF+ spermatogonia pool via indirect regulatory pattern.

The search for non-precious-metal catalysts with low cost, high activity and stability to substitute Pt in oxygen reduction reaction (ORR) attracts tremendous attention. Herein, novel ORR electrocatalysts of cerium species embedded N-doped carbon (CENC) materials are prepared by the chemical oxidative polymerization and pyrolysis methods, using polyaniline-coated cerium organic complex (Ce(TTA)3Phen) as the precursor. The experimental results have revealed that the electrocatalytic activity of the obtained electrocatalysts for ORR is affected by the pyrolysis temperature. Remarkably, the as-prepared CENC-1000 exhibits a good catalytic activity in terms of limiting current density, onset potential and half wave potential, as well as superior tolerance to methanol crossover for ORR as comparable to commercial Pt/C in alkaline media. The high performance is attributed to the introduction of nitrogen active sites and Ce active species (generated from the pyrolysis of CENC precursor), which endow CENC-1000 with enhanced electrocatalytic activity. This approach makes CENC-1000 a promising candidate as cathode catalyst in renewable energy conversion devices.

Roughing filters have been successfully employed as a pretreatment method in rural water supply, but few studies have reported the performance of up-flow roughing filters (URFs) packed with ceramic media. In this study, two pilot-scale URFs filled with ceramic media were designed. Filter performance, height profiles and head loss development were fully investigated. The average DOC, UV

Background: Moxibustion is increasingly used for treatment of irritable bowel syndrome (IBS). This study investigated the long-term effects of moxibustion for IBS with diarrhea (IBS-D). Methods: Patients with IBS-D were assigned to receive moxibustion or sham moxibustion (52 each, 3× per week, 6 weeks) and were followed up to 24 weeks. The acupoints were bilateral ST25 and ST36, body surface temperatures at acupoints were 43°C ± 1°C and 37°C ± 1°C for the moxibustion and sham groups, respectively. Primary outcome was changes in IBS Adequate Relief (IBS-AR) from baseline to 6 weeks. Secondary outcomes included the following: IBS symptom severity scale (IBS-SSS), Bristol stool form scale (BSS), IBS quality of life (IBS-QOL), and Hospital Anxiety and Depression Scale (HADS). Results: Based on an intention-to-treat analysis, the rate of IBS-AR in the moxibustion group was significantly higher than the sham group at 6 weeks (76.9% versus 42.3%; p 50 points in IBS-SSS of the treatment group was significantly higher than that of the sham ( p Conclusions: Moxibustion treatment benefits the long-term relief of symptoms in IBS-D patients. Trial registration: Clinical trials.gov (NCT02421627). Registered on 20 April 2015.

Objective: To investigate the expression and clinical significance of hypoxia inducible factors HIF-1a, Gli-1 and MMP9 in breast cancer. Methods: Eighty patients with invasive ductal carcinoma of the breast and 40 normal tissues adjacent to cancer were selected. Immunohistochemical methods were used to detect the expression of HIF-1a, Gli-1 and MMP9 in breast cancer and normal tissues adjacent to cancer, and their relationship with clinicopathological features of breast cancer and prognosis was explored. Results: The positive rates of HIF-1a, Gli-1 and MMP9 in breast cancer tissues were significantly higher than those in normal breast tissues. HIF-1a, Gli-1 and MMP9 expressions are positively correlated in breast cancer. Conclusion: HIF-1a, Gli-1 and MMP9 proteins are involved in the pathogenesis of breast cancer.

Objective: Hypertension is one of the most common public health issues worldwide. However, few existing studies examining health-related quality of life (HRQoL) were conducted on elderly patients with hypertension in China. Hence, this study aimed to assess the HRQoL of elderly patients with hypertension and its influencing factors using EuroQol five-dimensional-three-level (EQ-5D-3L) in China.Methods: Data were obtained from the 6th National Health Service Survey in Heilongjiang province from June to July 2018, with a stratified multistage random cluster sampling method. All eligible participants were interviewed using a standardized questionnaire, which included the EQ-5D-3L, socio-demographics characteristics, clinical and lifestyle characteristics. The mean EQ-5D index scores for the different subgroups were evaluated using ANOVA. A Tobit regression model was also employed to analyze the potential factors influencing HRQoL.Results: A total of 705 elderly patients with hypertension were included in this study. The mean EQ-5D utility score was 0.79 [standard deviation (SD) = 0.23]. The proportion of participants reporting pain/discomfort problems was the highest (57.0%), while problems in self-care was the lowest (17.2%). Influencing factors of HRQoL for elderly patients with hypertension included gender, age, income, education level, physical activity, health examination and coexisting diseases. Specifically, the female gender, being above 80 years old, having a lower education and/or higher income, and the presence of coexisting diseases were associated with lower utility index. In contrast, regular physical activity and medical examination had a positive impact on the HRQoL of elderly hypertension patients.Conclusion: Overall, elderly patients with hypertension in China have a lower HRQoL than the general population. To improve the HRQoL of elderly patients with hypertension, it is imperative that better public health education is provided to enhance the knowledge of hypertension, encourage the adoption of healthy habits such as regular physical activity and medical examination, and improve the management of coexisting diseases. More care should also be directed to males with hypertension who are above 80 years old.

Additional file 1: Text S1. Minimum inhibitory concentrations (MICs) determination. Fig S1. The MIC of Copper ions to wild-type E. coli K12.

In the present study, we explored expression changes in the transcriptomes of two molting stages (post-molt (M) and Intermolt (NM)) of the red swamp crayfish. A total of 307608398 clean reads, with an average length of 145bp were obtained. Further clustering and assembly of the transcripts generated 139100 unigenes. The results were searched against the NCBI, NR, KEGG, Swissprot, and KOG databases, in order to annotate gene descriptions, associate them with gene ontology terms, and assign them to pathways. Several genes and other factors involved in a number of molecular events critical for molting, such as energy requirements, hormonal regulation, immune response, and exoskeleton formation were identified, evaluated, and characterized. The information presented here provides a basic understanding of the molecular mechanisms underlying the crayfish molting process, with respect to energy requirements, hormonal regulation, immune response, and skeletal related activities during post-molt stage and the intermolt stage.

Ethnopharmacological relevance The traditional Chinese formula Danning tablets exhibit wide clinical applications in liver and gallbladder diseases, and currently it is reported to be effective on fatty liver disease in clinical trials. However, the underlying mechanisms remain elusive. Aim of the study The purpose of the present study was to assess the effects and potential pharmacological mechanisms of Danning tablet against high fat diet (HFD)-induced obesity, fatty liver, and related metabolic disorders in mice. Materials and methods C57BL/6 J male mice were treated with HFD for 12 weeks to trigger obesity and fatty liver condition. Then those mice were randomly divided into 5 groups, namely HFD, Danning tablet (0.75, 1.5 or 3 g/kg bodyweight) or lovastatin (30 mg/kg bodyweight) for extra 6 weeks’ treatment of HFD. Food intake and bodyweight were recorded each week. In the last week, before the mice were sacrificed, fasting blood glucose levels and insulin levels were measured. Furthermore, insulin and glucose tolerance tests were performed. Blood and hepatic lipid levels were examined, the lipid metabolism-associated gene expressions and protein levels in the liver or adipose tissues were assayed after sacrificing all mice. Results Our results demonstrated that a high dose of Danning tablet (3 g/kg) treatment mitigated body weight gain, reduced blood and hepatic cholesterol and triglyceride levels. The morphology analysis showed that Danning tablets could reduce lipid accumulation in both liver and brown adipose tissue. Moreover, Danning tablets could improve fasting blood glucose levels and ameliorate glucose and insulin tolerance in HFD-induced obese mice. Furthermore, qRT-PCR analysis revealed that the mRNA expressions of SREBP-1 and SREBP-2 as well as their target genes were remarkedly down-regulated in the liver and adipose tissue of diet-induced obesity (DIO) mice after treating those mice with Danning tablets. Conclusion Our results indicated that Danning tablets could improve the obesity-induced metabolic associated fatty liver disease (MAFLD) and related metabolic disorders. The potential mechanism may probably involve the regulation of the SREBP pathway.

Antibiotic resistance is a major threat to human health. It is necessary to explore all the potential sources and comprehend the pathways that antibiotic resistance genes (ARGs) are transmitted. In this study, by applying high-throughput quantitative PCR and high-throughput sequencing, ARGs and microbial community structure were determined, to understand the reservoirs and spread of ARGs in the Xilingol grassland system. A total of 151,140 and 138 different ARGs were observed in manure, soil, and water samples, respectively. Only 12 ARGs were shared in all environmental and animal manure samples. Multidrug defense system, such as efflux pump, was the most dominant factor in manure and soil samples, followed by antibiotic deactivation processes. These genes coffering resistance to major classes of antibiotics including β_Lactamase (blaSFO, fox5, blaCTX-M-04, blaOXY), vancomycin (vanC-03, vanXD), MLSB (vatE-01, mphA-01), aminoglycoside (aadA2-01), Multidrug (oprJ) and others (oprD, qacEdelta1-02), except sulfonamide and tetracycline. The 12 ARGs were significantly enriched in water samples compared to manure and soil samples (p

In order to study the effect of rolling amplitude on the heat release of aviation kerosene, an experimental oil pool was designed. The rolling frequency of the oil pool was used as a fixed amount. The rolling amplitudes were 0, 15°, 30° and 45°, respectively. The initial thickness of aviation kerosene was 0.646 mm, 1.291 mm and 1.940 mm, respectively. The results show that the heat release rate of aviation kerosene increases significantly with the increase of rolling amplitude, and the total heat release of aviation kerosene increases with the increase of swing amplitude. When the initial aviation kerosene was relatively thin, the upward trend was not obvious, with only slight changes; the thicker the oil pool is, the more obvious the upward trend is and the greater the total heat released is.

In order to achieve the purpose of assessing the fire risk in the WUI, this paper digitizes the fire risk influencing factors based on the remote sensing data, meteorological data and vegetation information of the southwest corner of Qingyuan Mountain in Quanzhou City, and obtains a total of 8 indicators in 4 categories of meteorological factors, vegetation factors, terrain factors and human factors as the primary indicators for fire risk assessment, and divides the 4 categories of factors into natural factors and human factors as the secondary indicators to construct a hierarchical structure model. Spatial modelling was performed by ArcGIS, AHP was used to assess the fire risk in the WUI, and weighted superposition analysis was performed on the burning probabilities calculated from different fire risk factors, and finally the results of fire risk zoning in the forest-town junction domain were obtained. The results showed that the high-risk area mainly existed within the area east of Pu Xian Road to the southwest corner of Qingyuan Mountain. The assessment results show that the method can provide a reference basis for fire risk assessment and zoning in the WUI.

A 20-year-old female presented with fine motor deficits and visual field defect was admitted to our hospital. CSF tests for autoimmune encephalitis antibodies and onconeuronal antibodies were unremarkable. MRI showed unilateral lesion involving left basal ganglia, external capsule, insula, hippocampus, and amygdala, which was considered to be demyelinating pseudotumor after surgical intervention. The patient's symptoms relieved so she didn't consent to immunotherapy. Two years and a half later our patient reported sudden anosmia. Reexamination by MRI demonstrated a new lesion. We then detected anti-CASPR2 antibodies in the patient's serum and gave her immunotherapy.

Objective: To explore the expression of human myxovirus resistance protein A (MxA) in triple negative breast cancer (TNBC) and its relationship with prognosis. Methods: 144 cases of TNBC confirmed by pathology before or after surgery from January 2014 to January 2017 in the First Central Hospital of Baoding City were retrospectively collected. Western blotting was used to detect the expression of MxA protein in TNBC and adjacent breast tissues. According to the expression of MxA protein, 144 TNBC patients were divided into low MxA protein expression group (n = 91) and MxA protein high expression group (n = 53) for subsequent comparison of prognosis of patients in between these two groups. Results: The expression of MxA protein in TNBC tissue was lower than that of adjacent breast tissue, and the difference was statistically significant (P

Nitrogen-containing bisphosphonates (N-BPs), such as alendronate, are the most widely prescribed medications for diseases involving bone, with nearly 200 million prescriptions written annually. Recently, widespread use of N-BPs has been challenged due to the risk of rare but traumatic side effects such as atypical femoral fracture (AFFs) and osteonecrosis of the jaw (ONJ). N-BPs bind to and inhibit farnesyl diphosphate synthase (FDPS), resulting in defects in protein prenylation. Yet it remains poorly understood what other cellular factors might allow N-BPs to exert their pharmacological effects. Here, we performed genome-wide studies in cells and patients to identify the poorly characterized gene, ATRAID. Loss of ATRAID function results in selective resistance to N-BP-mediated loss of cell viability and the prevention of alendronate-mediated inhibition of prenylation. ATRAID is required for alendronate inhibition of osteoclast function, and ATRAID-deficient mice have impaired therapeutic responses to alendronate in both postmenopausal and senile (old age) osteoporosis models. Lastly, we performed exome sequencing on patients taking N-BPs that suffered ONJ or an AFF. ATRAID is one of three genes that contain rare non-synonymous coding variants in patients with ONJ or AFF that is also differentially expressed in poor outcome groups of patients treated with N-BPs. We functionally validated this patient variation in ATRAID as conferring cellular hypersensitivity to N-BPs. Our work adds key insight into the mechanistic action of N-BPs and the processes that might underlie differential responsiveness to N-BPs in people.One Sentence SummaryATRAID is essential for responses to the commonly prescribed osteoporosis drugs nitrogen-containing bisphosphonates.OverlineBONE