Great genetic diversity of vector-borne bacteria and protozoan in wild rodents from Guangxi, China.

BACKGROUND: Rodents are recognized as the hosts of many vector-borne bacteria and protozoan parasites and play an important role in their transmission and maintenance. Intensive studies have focused on their infections in vectors, especially in ticks, however, vector-borne bacterial and protozoan infections in rodents are poorly understood although human cases presenting with fever may due to their infection have been found. METHODS: From May to October 2019, 192 wild rodents were trapped in wild environment of Guangxi Province, and the spleen samples were collected to reveal the presence of vector-borne bacterial and protozoan infections in them. The microorganisms in rodents were identified by detecting their DNA using (semi-)nested PCR. All the PCR products of the expected size were subjected to sequencing, and then analyzed by BLASTn. Furthermore, all the recovered sequences were subjected to nucleotide identity and phylogenetic analyses. RESULTS: As a result, 192 rodents representing seven species were captured, and Bandicota indica were the dominant species, followed by Rattus andamanensis. Based on the (semi-)nested PCR, our results suggested that Anaplasma bovis, Anaplasma capra, Anaplasma ovis, Anaplasma phagocytophilum, "Candidatus Neoehrlichia mikurensis", "Candidatus E. hainanensis", "Candidatus E. zunyiensis", three uncultured Ehrlichia spp., Bartonella coopersplainsensis, Bartonella tribocorum, Bartonella rattimassiliensis, Bartonella silvatica, two uncultured Bartonella spp., Babesia microti and diverse Hepatozoon were identified in six rodent species. More importantly, six species (including two Anaplasma, two Bartonella, "Ca. N. mikurensis" and Bab. microti) are zoonotic pathogens except Anaplasma bovis and Anaplasma ovis with zoonotic potential. Furthermore, dual infection was observed between different microorganisms, and the most common type of co-infection is between "Ca. N. mikurensis" and other microorganisms. Additionally, potential novel Bartonella species and Hepatozoon species demonstrated the presence of more diverse rodent-associated Bartonella and Hepatozoon. CONCLUSIONS: The results in this work indicated great genetic diversity of vector-borne infections in wild rodents, and highlighted the potential risk of human pathogens transmitted from rodents to humans through vectors.

Anaplasma, Bartonella, and Rickettsia infections in Daurian ground squirrels (Spermophilus dauricus), Hebei, China.

Rodents have been confirmed as hosts of various vector-borne zoonotic pathogens and are important for the maintenance of these microbes in nature. However, surveillance for zoonotic pathogens is limited for many wild rodent species in China, so our knowledge of pathogen ecology, genetic diversity, and the risk of cross-species transmission to humans is limited. In this study, 165 spleen samples of Daurian ground squirrels (Spermophilus dauricus) were collected from Weichang Manchu and the Mongolian Autonomous County of Hebei Province, China, and Rickettsia, Bartonella, and Anaplasma were identified by DNA detection using polymerase chain reaction (PCR). Sequence analysis identified eight bacterial pathogens: R. raoultii, R. sibirica, Candidatus R. longicornii, B. washoensis, B. grahamii, B. jaculi, A. capra, and Candidatus Anaplasma cinensis. Co-infection of B. grahamii and R. raoultii in one sample was observed. Our results demonstrated the genetic diversity of bacteria in Daurian ground squirrels and contributed to the distribution of these pathogens. Six species, A. capra, R. raoultii, R. sibirica, Candidatus R. longicornii, B. washoensis, and B. grahamii, are known to be pathogenic to humans, indicating a potential public health risk to the local human population, especially to herders who frequently have close contact with Daurian ground squirrels and are thus exposed to their ectoparasites.

Genetic diversity of vector-borne zoonotic pathogens in companion dogs and cats, Tianjin, China.

Background: Dogs and cats are the hosts of many vector-borne human pathogens that can be transmitted to humans. Given their direct and intimate contact with humans, companion dogs and cats are considered direct sentinels of vector-borne human pathogens. However, limited information is currently available regarding canine and feline zoonotic pathogens in China. This study detected canine and feline vector-borne human pathogens to better understand the potential risk to humans. Methods: Blood samples were collected from 275 domestic companion animals (117 dogs and 158 cats) living in Tianjin city, China, and the presence of DNA from Anaplasma, Babesia, Bartonella, and Rickettsia was detected by semi-nested polymerase chain reaction (PCR). The PCR products of the expected size were sequenced, and these newly generated sequences were subjected to BLASTN, nucleotide identity, and phylogenetic analyses. Results: A total of 24 blood samples tested positive for vector-borne pathogens in companion dogs and cats in Tianjin city, China, with a relatively low positive rate of 8.7%. Specifically, seven human pathogens, including Rickettsia raoultii, Candidatus Rickettsia jingxinensis, Rickettsia sibirica, Rickettsia felis, Babesia venatorum, Bartonella tribocorum, and Bartonella Henselae, were identified. In addition, Anaplasma ovis with zoonotic potential and Candidatus A. cinensis were detected. Conclusion: Our results indicate substantial genetic diversity in the vector-borne human pathogens circulating in companion dogs and cats. Interventions based on "One Health" should be taken to reduce the potential risks of contracting infection from companion dogs and cats in Tianjin, China.

Risk factors for postoperative delirium in elderly patients undergoing heart valve surgery with cardiopulmonary bypass.

BACKGROUND: The aim of this study was to identify the risk factors for postoperative delirium (POD) in elderly patients undergoing heart valve surgery with cardiopulmonary bypass (CPB). METHODS: Elderly patients undergoing elective heart valve surgery with CPB in The First Affiliated Hospital of Wenzhou Medical University between March 2022 and March 2023 were selected for this investigation. They were divided into a POD group and a non-POD group. Their baseline information was collected and recorded, and the patients were subjected to neurocognitive function assessment using the Mini-Mental State Examination and the Montreal Cognitive Assessment scales before surgery. We also recorded their intraoperative indicators such as duration of surgery, duration of CPB, duration of aortic cross-clamp, blood transfusion, and postoperative indicators such as duration of mechanical ventilation, postoperative 24-hour drainage volume, and pain score. Regional cerebral oxygen saturation was monitored intraoperatively by near-infrared spectroscopy based INVOS5100C Regional Oximeter. Patients were assessed for the occurrence of POD using Confusion Assessment Method for the Intensive Care Unit, and logistic regression analysis of risk factors for POD was performed. RESULTS: The study finally included 132 patients, with 47 patients in the POD group and 85 ones in the non-POD group. There were no significant differences in baseline information and preoperative indicators between the two groups. However, marked differences were identified in duration of surgery, duration of CPB, duration of aortic cross-clamp, duration of postoperative mechanical ventilation, postoperative length of stay in cardiac intensive care unit, postoperative length of hospital stay, intraoperative blood transfusion, postoperative pain score, and postoperative 24-hour drainage volume between the two groups (p < 0.05). Additionally, the two groups had significant differences in rScO2 at each intraoperative time point and in the difference of rScO2 from baseline at each intraoperative time point (p < 0.05). Multivariate logistic regression analysis showed that duration of surgery > 285 min (OR, 1.021 [95% CI, 1.008-1.035]; p = 0.002), duration of postoperative mechanical ventilation > 23.5 h (OR, 6.210 [95% CI, 1.619-23.815]; p = 0.008), and postoperative CCU stay > 3.5 d (OR, 3.927 [95% CI, 1.046-14.735]; p = 0.043) were independent risk factors of the occurrence of POD while change of rScO2 at T1>50.5 (OR, 0.832 [95% CI 0.736-0.941]; p = 0.003) was a protective factor for POD. CONCLUSION: Duration of surgery duration of postoperative mechanical ventilation and postoperative CCU stay are risk factors for POD while change of rScO2 at T1 is a protective factor for POD in elderly patients undergoing heart valve surgery with CPB.

Molecular evidence of Rickettsia canadensis in ticks, Hebei, China.

China was affected severely by tick-borne rickettsiosis, and more than 10 Rickettsia species pathogenic to humans have been identified. In recent years, several Rickettsia members, with unknown pathogenicity, firstly identified abroad have been found in China. In this study, parasitic and questing ticks were recovered from two sampling sites in Hebei, China. Specific primers targeting outer membrane protein B (ompB) gene were designed to test the presence of Rickettsia canadensis by nested Polymerase Chain Reaction (PCR). As a result, a total of 428 ticks, including 232 ticks (including 230 Haemaphysalis longicornis and two H. japonica) from Laiyuan County and 196 (H. longicornis) from Luanping County, were collected. Sequencing of PCR products with the expected size and subsequently BLAST showed that 38H. longicornis ticks tested positive for R. canadensis, with an overall positive rate of 8.8%. In addition, 800-bp ompB gene and nearly complete citrate synthase (gltA) gene were recovered from six randomly selected positive samples to better understand their genetic characteristics. Nucleotide identity and phylogenetic analyses showed that R. canadensis presented geographical clustering with evidence that variants identified in the current study presented closer genetic relationship with others identified in Asian than those found in North America. In addition, epidemiological data suggested that H. longicornis may be the competent vector, and more attention should be paid to R. canadensis due to its zoonotic potential. In sum, R. canadensis was confirmed to be present in Hebei Province, China, and its surveillance in ticks should be strengthened due to potential pathogenicity, higher positive rate in ticks and wide distribution of possible vector tick species.

Habitat-related plastome evolution in the mycoheterotrophic Neottia listeroides complex (Orchidaceae, Neottieae).

BACKGROUND: Mycoheterotrophs, acquiring organic carbon and other nutrients from mycorrhizal fungi, have evolved repeatedly with substantial plastid genome (plastome) variations. To date, the fine-scale evolution of mycoheterotrophic plastomes at the intraspecific level is not well-characterized. A few studies have revealed unexpected plastome divergence among species complex members, possibly driven by various biotic/abiotic factors. To illustrate evolutionary mechanisms underlying such divergence, we analyzed plastome features and molecular evolution of 15 plastomes of Neottia listeroides complex from different forest habitats. RESULTS: These 15 samples of Neottia listeroides complex split into three clades according to their habitats approximately 6 million years ago: Pine Clade, including ten samples from pine-broadleaf mixed forests, Fir Clade, including four samples from alpine fir forests and Fir-willow Clade with one sample. Compared with those of Pine Clade members, plastomes of Fir Clade members show smaller size and higher substitution rates. Plastome size, substitution rates, loss and retention of plastid-encoded genes are clade-specific. We propose to recognized six species in N. listeroides complex and slightly modify the path of plastome degradation. CONCLUSIONS: Our results provide insight into the evolutionary dynamics and discrepancy of closely related mycoheterotrophic orchid lineages at a high phylogenetic resolution.

Hypoglycemic mechanisms of Polygonatum sibiricum polysaccharide in db/db mice via regulation of glycolysis/gluconeogenesis pathway and alteration of gut microbiota.

Polygonatum rhizoma polysaccharide (PP) is a main ingredient of Polygonatum rhizoma , which is both food and traditional herbal medicine. In this study, we aimed to investigate the hypoglycemic effect of PP and the underlying mechanisms in db/db mice. Our finding showed that PP significantly ameliorates diabetic symptoms by reducing glucose levels in blood and urine and increasing insulin and leptin abundance in the serum. Histopathological examination revealed that PP improved the pathological state and increased hepatic glycogen storage in liver. Additionally, RT-qPCR results indicated that PP significantly down-regulated the expression of phosphoenolpyruvate carboxykinase 1. Furthermore, 16s rRNA sequencing results demonstrated that PP intervention resulted in an increase in beneficial bacteria genus and a reduction in harmful genus. Redundancy analysis revealed the correlation between intestinal flora and clinical factors. Taken together, these results suggest that PP has a significant hypoglycemic effect on type 2 diabetes (T2D) through up-regulating serum insulin and leptin, as well as hepatic glycogen storage, and down-regulating hepatic phosphoenolpyruvate carboxykinase 1 expression, as well as modulating gut microbiota composition. In conclusion, this study investigated the mechanisms of PP in the treatment of diabetes in db/db mice. To the best of our knowledge, this is the first study to explore the positive and negative correlations between gut microbiota and clinical factors, such as oxidative stress injury in liver and glucose related indicators in the blood.

Near-Infrared Fluorescent Nanoprobes for Adenosine Triphosphate-Guided Imaging in Cancer and Fatty Liver Mice.

Adenosine triphosphate (ATP), as an indispensable biomolecule, is the main energy source of cells and is used as a marker for diseases such as cancer and fatty liver. It is of great significance to design a near-infrared fluorescent nanoprobe with excellent performance and apply it to various disease models. Here, a near-infrared fluorescent nanoprobe (ZIF-90@SiR) based on a zeolitic imidazole framework is proposed. The fluorescent nanoprobes are synthesized by encapsulating the dye (SiR) into the framework of ZIF-90. Upon the addition of ATP, the structure of the ZIF-90@SiR nanoprobe is disrupted and SiR is released to generate near-infrared fluorescence at 670 nm. In the process of ATP detection, ZIF-90@SiR shows high sensitivity and good selectivity. Moreover, the ZIF-90@SiR nanoprobe has good biocompatibility due to its low toxicity to cells. It is used for fluorescence imaging of ATP in living cells and thus distinguishing normal cells and cancer cells, as well as distinguishing fatty liver cells. Due to excellent near-infrared fluorescence properties, the ZIF-90@SiR nanoprobe can not only distinguish normal mice and tumor mice but also differentiate normal mice and fatty liver mice for the first time.

Downregulation of DDIT4 ameliorates abnormal behaviors in autism by inhibiting ferroptosis via the PI3K/Akt pathway.

Autism spectrum disorder (ASD) is a complex disease with unclear etiology. Studies have shown that ferroptosis is also related to ASD progression, but the specific mechanism is still unclear. Valproic acid (VPA) induced neuronal ferroptosis in vitro. Mechanistic studies showed that both VPA and ferroptosis inducers promoted the expression of DDIT4 in neurons, thereby inhibiting the activation of the PI3K/Akt pathway. DDIT4 increased the accumulation of ROS, MDA and Fe2+, inhibited neuronal viability and downregulated GPX4 expression by inactivating the PI3K/Akt pathway. Ferroptosis inhibitors reversed the anti-survival effect of DDIT4, indicating that DDIT4 enhances ferroptosis through the PI3K/Akt pathway, thereby inhibiting neuronal viability. Further in vivo experiments found that autistic mice had high levels of ROS, MDA and Fe2+, increased DDIT4 expression, and downregulated expression levels of GPX4, p-PI3K and p-Akt; after downregulation of DDIT4 expression, the accumulation of ROS, MDA and Fe2+ was significantly reduced, while the expression levels of GPX4, p-PI3K and p-Akt were upregulated, indicating that DDIT4 knockdown reduces ferroptosis in autistic mice. In addition, DDIT4 downregulation, PI3K/Akt pathway activation, and ferroptosis inhibitors all improved social behavior deficits, repetitive stereotyped and compulsive behaviors, anxiety and exploratory behaviors in autistic mice, but PI3K/Akt pathway inhibitors significantly blocked the rescue of abnormal behaviors by DDIT4 downregulation in autistic mice. Therefore, downregulation of DDIT4 expression ameliorates abnormal behaviors in autism by inhibiting ferroptosis via the PI3K/Akt pathway, indicating that DDIT4, the PI3K/Akt pathway and ferroptosis have key roles in autism.

Untying the Gordian knot of plastid phylogenomic conflict: A case from ferns.

Phylogenomic studies based on plastid genome have resolved recalcitrant relationships among various plants, yet the phylogeny of Dennstaedtiaceae at the level of family and genera remains unresolved due to conflicting plastid genes, limited molecular data and incomplete taxon sampling of previous studies. The present study generated 30 new plastid genomes of Dennstaedtiaceae (9 genera, 29 species), which were combined with 42 publicly available plastid genomes (including 24 families, 27 genera, 42 species) to explore the evolution of Dennstaedtiaceae. In order to minimize the impact of systematic errors on the resolution of phylogenetic inference, we applied six strategies to generate 30 datasets based on CDS, intergenic spacers, and whole plastome, and two tree inference methods (maximum-likelihood, ML; and multispecies coalescent, MSC) to comprehensively analyze the plastome-scale data. Besides, the phylogenetic signal among all loci was quantified for controversial nodes using ML framework, and different topologies hypotheses among all datasets were tested. The species trees based on different datasets and methods revealed obvious conflicts at the base of the polypody ferns. The topology of the "CDS-codon-align-rm3" (CDS with the removal of the third codon) matrix was selected as the primary reference or summary tree. The final phylogenetic tree supported Dennstaedtiaceae as the sister group to eupolypods, and Dennstaedtioideae was divided into four clades with full support. This robust reconstructed phylogenetic backbone establishes a framework for future studies on Dennstaedtiaceae classification, evolution and diversification. The present study suggests considering plastid phylogenomic conflict when using plastid genomes. From our results, reducing saturated genes or sites can effectively mitigate tree conflicts for distantly related taxa. Moreover, phylogenetic trees based on amino acid sequences can be used as a comparison to verify the confidence of nucleotide-based trees.

Vitamin D intake as well as circulating 25-hydroxyvitamin D level and risk for the incidence and recurrence of colorectal cancer precursors: A meta-analysis.

Objective: Vitamin D consumption and circulating 25(OH)D level are associated with decreased risk of colorectal cancer (CRC) and colorectal adenoma (CRA), but few studies have assessed their relationship with the incidence and recurrence of CRC precursors. Therefore, we performed this meta-analysis to further evaluate the association. Methods: We searched PubMed, Web of Science, Scopus and Embase databases in English until August 2021. Studies evaluating the association of vitamin D intake and circulating 25(OH)D level with risk of CRC precursors were included. A random-effects model was used to pool the risk estimates. Results: A total of 48 studies were selected for inclusion. The CRC precursors incidence was negatively correlated with total vitamin D intake (RR = 0.84 95%CI: 0.80-0.88) and circulating 25(OH)D level (RR = 0.79 95%CI: 0.67-0.92). However, vitamin D intake and circulating 25(OH)D level did not show significant effects on the risk of CRC precursors recurrence. For dose-response analysis, evidence of a linear association was found between CRC precursors incidence and circulating 25(OH)D level, and the risk decreased by 14% per 10 ng/ml increment of circulating 25(OH)D level (RR = 0.86 95% CI: 0.75-0.99). Conclusion: Vitamin D intake and circulating 25(OH)D level can play an effective role in reducing the risk of incidence of CRC precursors. However, they have not prevented the recurrence of CRC precursors.

Comments on "Effect of type 2 diabetes mellitus in the prognosis of acute-on-chronic liver failure patients in China".

A study addressing the influence of type 2 diabetes on the prognosis of acute-on-chronic liver failure patients was reviewed. Some statistical deficiencies were found in the reviewed article, and the sample size was too small to support the study. In addition, age should have been considered as one of the prognostic factors.

Comment "Asymptomatic small intestinal ulcerative lesions: Obesity and Helicobacter pylori are likely to be risk factors".

There are many causes of anemia. It is unreasonable to simply associate anemia with asymptomatic ulcers in the small intestine.

A novel particulate matter sampling and cell exposure strategy based on agar membrane for cytotoxicity study.

Laboratories use different strategies to sample and extract atmospheric particulate matter (PM), some of which can be very complicated. Due to the absence of a standard protocol, it is difficult to compare the results of PM toxicity assessment across different laboratories. Here, we proposed a novel PM sampling and cell exposure strategy based on agar membrane. The agar membrane, prepared by a simple freeze-drying method, has a relatively flat surface and porous interior. We demonstrated that the agar membrane was a reliable substitute material for PM sampling. Then the PM on the agar membranes was directly extracted with the culture medium by vortex method, and the PM on the polytetrafluoroethylene (PTFE) filters was extracted with water by the traditional ultrasonic method for comparison. The extraction efficiency was evaluated and in vitro cytotoxicity assays were carried out to investigate the toxic effects of PM extracted with two strategies on macrophage cells. The results showed that the PM extracted from agar membranes induced higher cytotoxicity and more differentially expressed proteins. Overall, the novel PM sampling-cell exposure strategy based on the agar membrane is easy to operate, biocompatible and comparable, and has low disturbance, could be an alternative sampling and extraction method for PM toxicity assessment.

Stem signatures associating SOX2 antibody helps to define diagnosis and prognosis prediction with esophageal cancer.

BACKGROUND: esophageal cancer is one of the deadliest diseases worldwide. Due to the ineffectual screening methods referring to early diagnosis, most people have lost their chance of radical resection when diagnosed with esophageal cancer. This aim of this study was designed to evaluate the latent values of the stem signatures-associated autoantibodies (AABS) in predicting the early diagnosis, and particularly seeking the precise predictive outcomes with sensitive SOX2. We also studied the potential immunotherapeutic targets and prospective long-term prognosis predicators of esophageal cancer. METHODS: The serum concentrations of selective antibodies were quantitated by enzyme-linked immunosorbent assay (ELISA), and a total of 203 local cases were enrolled. The TCGA databases were used to analyse distinct expression patterns and prognostic values of related genes. The TIMER database was used to explore the signatures of immune cell infiltration in related genes. The TISIDB database was used to analyse the association between related genes and immune regulators. RESULTS: The stem signatures-associated with antibodies of TP53, PGP9.5, SOX2, and CAGE were highly expressed in esophageal cancer and were negatively correlated with the test group, the diagnostic sensitivity of P53, SOX2, PGP9.5 and CAGE reached to 54.3%, 56.5%, 80.4% and 47.8%, respectively, and the specificity reached 77.7%, 93.6%, 76.4% and 86.6%. Especially in stage I esophageal cancer, the diagnostic sensitivity of SOX2 reached 82.4% with a specificity of 85.4%, which demonstrated good value in early diagnosis. CONCLUSIONS: The stem signatures-associated antibodies could be used as an effective indicator in early esophageal cancer diagnosis and could help to precisely predicate survival and prognosis.Key MessagesThe stem signatures-associated immune-antibodies could be used as effective indicators in early diagnosis of esophageal cancer and help to precisely predicate the survival and prognosis.The potential immunotherapeutic targets referring to esophageal cancer are screened and analysed, and the high sensitivity of SOX2 in detecting early esophageal cancer will yield early and effective treatments.

Serum Anti-14-3-3 Zeta Autoantibody as a Biomarker for Predicting Hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide. Alpha-fetoprotein (AFP) is still the only serum biomarker widely used in clinical settings. However, approximately 40% of HCC patients exhibit normal AFP levels, including very early HCC and AFP-negative HCC; for these patients, serum AFP is not applicable as a biomarker of early detection. Thus, there is an urgent need to identify novel biomarkers for patients for whom disease cannot be diagnosed early. In this study, we screened and identified novel proteins in AFP-negative HCC and evaluated the feasibility of using autoantibodies to those protein to predict hepatocarcinogenesis. First, we screened and identified differentially expressed proteins between AFP-negative HCC tissue and adjacent non-tumor liver tissue using SWATH-MS proteome technology. In total, 2,506 proteins were identified with a global false discovery rate of 1%, of which 592 proteins were expressed differentially with 175 upregulated and 417 downregulated (adjusted p-value <0.05, fold-change FC ≥1.5 or ≤0.67) between the tumor and matched benign samples, including 14-3-3 zeta protein. For further serological verification, autoantibodies against 14-3-3 zeta in serum were evaluated using enzyme-linked immunosorbent, Western blotting, and indirect immunofluorescence assays. Five serial serum samples from one patient with AFP-negative HCC showed anti-14-3-3 zeta autoantibody in sera 9 months before the diagnosis of HCC, which gradually increased with an increase in the size of the nodule. Based on these findings, we detected the prevalence of serum anti-14-3-3 zeta autoantibody in liver cirrhosis (LC) patients, which is commonly considered a premalignant liver disease of HCC. We found that the prevalence of autoantibodies against 14-3-3 zeta protein was 16.1% (15/93) in LC patient sera, which was significantly higher than that in patients with chronic hepatitis (0/75, p = 0.000) and normal human sera (1/60, 1.7%, p = 0.01). Therefore, we suggest that anti-14-3-3 zeta autoantibody might be a biomarker for predicting hepatocarcinogenesis. Further follow-up and research of patients with positive autoantibodies will be continued to confirm the relationship between anti-14-3-3 zeta autoantibody and hepatocarcinogenesis.

Rapamycin recruits SIRT2 for FKBP12 deacetylation during mTOR activity modulation in innate immunity.

The mammalian target of rapamycin (mTOR) is a serine-threonine kinase involved in cellular innate immunity, metabolism, and senescence. FK506-binding protein 12 (FKBP12) inhibits mTOR kinase activity via direct association. The FKBP12-mTOR association can be strengthened by the immunosuppressant rapamycin, but the underlying mechanism remains elusive. We show here that the FKBP12-mTOR association is tightly regulated by an acetylation-deacetylation cycle. FKBP12 is acetylated on the lysine cluster (K45/K48/K53) by CREB-binding protein (CBP) in mammalian cells in response to nutrient treatment. Acetyl-FKBP12 associates with CBP acetylated Rheb. Rapamycin recruits SIRT2 with a high affinity for FKBP12 association and deacetylation. SIRT2-deacetylated FKBP12 then switches its association from Rheb to mTOR. Nutrient-activated mTOR phosphorylates IRF3S386 for the antiviral response. In contrast, rapamycin strengthening FKBP12-mTOR association blocks mTOR antiviral activity by recruiting SIRT2 to deacetylate FKBP12. Hence, on/off mTOR activity in response to environmental nutrients relies on FKBP12 acetylation and deacetylation status in mammalian cells.

[In-situ Sludge Reduction Technology Based on Ozonation].

The process parameters and sludge properties of an in-situ sludge ozone-reduction system were investigated under different ozone dosages and sludge ages. Subsequently, 75 mg·g-1 (as O3/MLVSS) was selected as the appropriate ozone dosage to satisfy the wastewater treatment capacity and in-situ sludge ozone-reduction. The calibration coefficient results of the sludge yield formula indicated that Yh was reduced from 0.331 g·g-1 to 0.326 g·g-1 (to MLVSS/COD m) by ozone treatment and Kd was increased from 0.046 d-1 to 0.050 d-1 at 75 mg·g-1. The effluent quality of the SBR system was satisfactory when the sludge age was 10 d. The ozone dosage of 75 mg·g-1 and sludge age of 10 d were selected as the appropriate process conditions, at which the excess sludge was reduced by 12%. The high-throughput sequencing results concluded that the microorganisms in the excess sludge after ozonation were different in phylum and genus. After ozone treatment, the abundance of Bacteroidetes increased by 1.2 times and the relative abundance of Proteobacteria with nitrification and denitrification ability decreased from 24% to 18%. The reduction in the abundance of nitrobacteria affected the denitrification capacity of the sewage treatment system, but the total effluent nitrogen still met the I B discharge standard of pollutants for municipal wastewater treatment plants. The relative abundance of Lactococcus increased from 0.4% to 21.6%. Simultaneously, the concentration of macromolecular organic substances in the EPS of the excess sludge increased from 40.6 mg·g-1 to 54.6 mg·g-1, while the CST increased from 15 s to 17 s after ozone treatment. The zeta potential decreased from -10.04 mV to -15.20 mV and the SVI of the excess sludge increased from 54 mL·g-1 to 62 mL·g-1, thereby indicating that the sedimentation performance and dewaterability were affected to some extent. However, the SS of the effluent and the solids content of the sludge cake after extraction did not change significantly, the system could still operate stably, and the subsequent dewaterability of the excess sludge was not significantly affected.

Stem signatures associated antibodies yield early diagnosis and precise prognosis predication of patients with non-small cell lung cancer.

BACKGROUND: This study was designed to detect patients with early NSCLC with tentatively using the stem signatures associated autoantibodies (AAbs), and to evaluate its latent values in the early diagnosis and precise prognosis prediction. METHODS: The serum concentrations of selective antibodies were quantitated by enzyme-linked immunosorbent assay (ELISA), and a total of 458 cases were enrolled (training set = 401; validation set = 57). TCGA databases were used to analyze the distinct expressions and prognostic values of related genes. The optimal cut-off values were 11.60 U/ml for P53, 4.90 U/ml for MAGEA1, 3.85 U/ml for SOX2, and 7.05U/ml for PGP9.5. RESULTS: We found that the stem signatures associated antibodies of MAGEA1, PGP9.5, SOX2, and TP53 exhibited high expressions in NSCLC, negatively correlating with the overall survival (OS) (P < 0.05). In the test groups, the diagnosis sensitivity of P53, PGP9.5, SOX2, and MAGEA1 reached to 21.5%, 39.0%, 50.3%, and 35.0%, respectively, and the specificity reached to 98.7%, 99.4%, 92.2%, and 97.4%. The four candidates' panel gave a sensitivity of 71.8% with a specificity of 89%. In the validation group, the detection of the four antibodies in early diagnosis of NSCLC also exhibited high specificity and sensitivity, further consolidating their potential application. CONCLUSIONS: The detection regarding stem signatures associated antibodies could be used as effective tools in early NSCLC diagnosis, but not for localized screening of cancers, and their abnormal expression was in accordance with poorer survival.