Restoration of TET2 Function Blocks Aberrant Self-Renewal and Leukemia Progression.

Loss-of-function mutations in TET2 occur frequently in patients with clonal hematopoiesis, myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML) and are associated with a DNA hypermethylation phenotype. To determine the role of TET2 deficiency in leukemia stem cell maintenance, we generated a reversible transgenic RNAi mouse to model restoration of endogenous Tet2 expression. Tet2 restoration reverses aberrant hematopoietic stem and progenitor cell (HSPC) self-renewal in vitro and in vivo. Treatment with vitamin C, a co-factor of Fe2+ and α-KG-dependent dioxygenases, mimics TET2 restoration by enhancing 5-hydroxymethylcytosine formation in Tet2-deficient mouse HSPCs and suppresses human leukemic colony formation and leukemia progression of primary human leukemia PDXs. Vitamin C also drives DNA hypomethylation and expression of a TET2-dependent gene signature in human leukemia cell lines. Furthermore, TET-mediated DNA oxidation induced by vitamin C treatment in leukemia cells enhances their sensitivity to PARP inhibition and could provide a safe and effective combination strategy to selectively target TET deficiency in cancer. PAPERCLIP.

CDK7-dependent transcriptional addiction in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer that exhibits extremely high levels of genetic complexity and yet a relatively uniform transcriptional program. We postulate that TNBC might be highly dependent on uninterrupted transcription of a key set of genes within this gene expression program and might therefore be exceptionally sensitive to inhibitors of transcription. Utilizing kinase inhibitors and CRISPR/Cas9-mediated gene editing, we show here that triple-negative but not hormone receptor-positive breast cancer cells are exceptionally dependent on CDK7, a transcriptional cyclin-dependent kinase. TNBC cells are unique in their dependence on this transcriptional CDK and suffer apoptotic cell death upon CDK7 inhibition. An "Achilles cluster" of TNBC-specific genes is especially sensitive to CDK7 inhibition and frequently associated with super-enhancers. We conclude that CDK7 mediates transcriptional addiction to a vital cluster of genes in TNBC and CDK7 inhibition may be a useful therapy for this challenging cancer.

Chromothripsis as a pathogenic driver of multiple myeloma.

Analysis of the genetic basis for multiple myeloma (MM) has informed many of our current concepts of the biology that underlies disease initiation and progression. Studying these events in further detail is predicted to deliver important insights into its pathogenesis, prognosis and treatment. Information from whole genome sequencing of structural variation is revealing the role of these events as drivers of MM. In particular, we discuss how the insights we have gained from studying chromothripsis suggest that it can be used to provide information on disease initiation and that, as a consequence, it can be used for the clinical classification of myeloma precursor diseases allowing for early intervention and prognostic determination. For newly diagnosed MM, the integration of information on the presence of chromothripsis has the potential to significantly enhance current risk prediction strategies and to better characterize patients with high-risk disease biology. In this article we summarize the genetic basis for MM and the role played by chromothripsis as a critical pathogenic factor active at early disease phases.

Evaluation of metagenomic next-generation sequencing diagnosis for invasive pulmonary aspergillosis in immunocompromised and immunocompetent patients.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) can occur in both immunocompromised and non-immunocompromised hosts, and early diagnosis of IPA is difficult. Metagenomic next-generation sequencing (mNGS) is a novel non-migratory pathogen detection method; however, utilising this method for IPA diagnosis is challenging due to the current lack of a unified clinical interpretation standard following Aspergillus detection using mNGS. OBJECTIVES: To investigate the accuracy of IPA diagnosis by positive bronchoalveolar lavage fluid (BALF) mNGS results in immunocompromised and immunocompetent patients. METHODS: We retrospectively included patients with confirmed pulmonary infections having a BALF mNGS result of Aspergillus reads ≥1. We compared the accuracy of using mNGS for IPA diagnosis in patients with different immune statuses based on the revised EORTC/MSG criteria. RESULTS: Overall, 62 mNGS Aspergillus-positive patients were divided into two groups: with (41) and without IPA (21). In univariate logistic regression analysis, immunocompromised function, fever, halo sign on CT image, and multiple masses or nodules were associated with mNGS Aspergillus-positive IPA diagnosis. In multivariate logistic regression analysis, immunocompromised function (OR = 6.68, 95% CI: 1.73-25.87, p = .006) and a halo sign (OR = 7.993, 95% CI: 2.07-30.40, p = .003) were independent risk factors. The concordance rate of IPA diagnosis was significantly higher in immunocompromised patients [82.1% (23/28)] than in non-immunocompromised patients [52.9% (18/34); p = .016]. CONCLUSIONS: For immunocompromised patients, a combination of mNGS testing and lung CT imaging can be used for IPA diagnosis. However, caution is required in IPA diagnosis based on positive mNGS results in non-immunocompromised patients.

Expression of claudin-8 is induced by aldosterone in renal collecting duct principal cells.

Fine tuning of Na+ reabsorption takes place along the aldosterone-sensitive distal nephron, which includes the collecting duct (CD), where it is mainly regulated by aldosterone. In the CD, Na+ reabsorption is mediated by the epithelial Na+ channel and Na+ pump (Na+-K+-ATPase). Paracellular ion permeability is mainly dependent on tight junction permeability. Claudin-8 is one of the main tight junction proteins expressed along the aldosterone-sensitive distal nephron. We have previously shown a coupling between transcellular Na+ reabsorption and paracellular Na+ barrier. We hypothesized that aldosterone controls the expression levels of both transcellular Na+ transporters and paracellular claudin-8 in a coordinated manner. Here, we show that aldosterone increased mRNA and protein levels as well as lateral membrane localization of claudin-8 in cultured CD principal cells. The increase in claudin-8 mRNA levels in response to aldosterone was prevented by preincubation with 17-hydroxyprogesterone, a mineralocorticoid receptor antagonist, and by inhibition of transcription with actinomycin D. We also showed that a low-salt diet, which stimulated aldosterone secretion, was associated with increased claudin-8 abundance in the mouse kidney. Reciprocally, mice subjected to a high-salt diet, which inhibits aldosterone secretion, or treated with spironolactone, a mineralocorticoid receptor antagonist, displayed decreased claudin-8 expression. Inhibition of glycogen synthase kinase-3, Lyn, and Abl signaling pathways prevented the effect of aldosterone on claudin-8 mRNA and protein abundance, suggesting that signaling of protein kinases plays a permissive role on the transcriptional activity of the mineralocorticoid receptor. This study shows that signaling via multiple protein kinases working in concert mediates aldosterone-induced claudin-8 expression in the CD.NEW & NOTEWORTHY In this study, we showed that aldosterone modulates claudin-8 expression in cultured collecting duct principal cells and in the mouse kidney. The upregulation of claudin-8 expression in response to aldosterone is dependent on at least glycogen synthase kinase-3, Lyn, and Abl signaling pathways, indicating the participation of multiple protein kinases to the effect of aldosterone.

Interaction between Epithelial Sodium Channel γ-Subunit and Claudin-8 Modulates Paracellular Sodium Permeability in Renal Collecting Duct.

BACKGROUND: Water and solute transport across epithelia can occur via the transcellular or paracellular pathways. Tight junctions play a key role in mediating paracellular ion reabsorption in the kidney. In the renal collecting duct, which is a typical absorptive tight epithelium, coordination between transcellular sodium reabsorption and paracellular permeability may prevent the backflow of reabsorbed sodium to the tubular lumen along a steep electrochemical gradient. METHODS: To investigate whether transcellular sodium transport controls tight-junction composition and paracellular permeability via modulating expression of the transmembrane protein claudin-8, we used cultured mouse cortical collecting duct cells to see how overexpression or silencing of epithelial sodium channel (ENaC) subunits and claudin-8 affect paracellular permeability. We also used conditional kidney tubule-specific knockout mice lacking ENaC subunits to assess the ENaC's effect on claudin-8 expression. RESULTS: Overexpression or silencing of the ENaC γ-subunit was associated with parallel and specific changes in claudin-8 abundance. Increased claudin-8 abundance was associated with a reduction in paracellular permeability to sodium, whereas decreased claudin-8 abundance was associated with the opposite effect. Claudin-8 overexpression and silencing reproduced these functional effects on paracellular ion permeability. Conditional kidney tubule-specific ENaC γ-subunit knockout mice displayed decreased claudin-8 expression, confirming the cell culture experiments' findings. Importantly, ENaC ß-subunit or α-subunit silencing or kidney tubule-specific ß-ENaC or α-ENaC knockout mice did not alter claudin-8 abundance. CONCLUSIONS: Our data reveal the specific coupling between ENaC γ-subunit and claudin-8 expression. This coupling may play an important role in preventing the backflow of reabsorbed solutes and water to the tubular lumen, as well as in coupling paracellular and transcellular sodium permeability.

A novel role of NLRP3-generated IL-1ß in the acute-chronic transition of peripheral lipopolysaccharide-elicited neuroinflammation: implications for sepsis-associated neurodegeneration.

BACKGROUND: Sepsis-associated acute brain inflammation, if unresolved, may cause chronic neuroinflammation and resultant neurodegenerative diseases. However, little is known how the transition from acute to chronic neuroinflammation, which is critical for the following progressive neurodegeneration, occurs in sepsis. The goal of this study was to investigate potential immune factors regulating the transition process using a widely used endotoxemia LPS mouse model. This model shows distinct acute and chronic phases of neuroinflammation and recapitulates many cardinal features of Parkinson's disease, thus, providing a unique opportunity for studying phase transition of neuroinflammation. METHODS: C57BL/6 J, NLRP3-/-, and IL-1R1-/- mice were employed. Mild and severe endotoxemia were produced by LPS ip injection at 1 or 5 mg/kg. Neuroinflammation in vitro and in vivo was assessed with proinflammatory cytokine expression by qPCR or ELISA and microglial activation by immunohistochemical analysis. Neurodegeneration was measured by manual and stereological counts of nigral dopaminergic neurons and immunohistochemical analysis of protein nitrosylation and α-synuclein phosphorylation. RESULTS: LPS-elicited initial increases in mouse brain mRNA levels of TNFα, IL-6, IL-1ß, and MCP-1, and nigral microglial activation were not dose-related. By contrast, the delayed increase in brain mature IL-1ß levels was dependent on LPS doses and protracted nigral microglial activation was only observed in high dose of LPS-treated mice. LPS-elicited increase in brain mature IL-1ß but not IL-1α level was NLRP3-dependent. After high dose LPS treatment, deficiency of NLRP3 or IL-1R1 did not prevent the initiation of acute neuroinflammation but abolished chronic neuroinflammation. Genetic or pharmacological inhibition of the NLRP3-IL-1ß axis repressed LPS-stimulated upregulation of chronic neuroinflammatory mediators including MHC-II, NOX2, and Mac1, and protected dopaminergic neurons. Ten months after LPS-elicited severe endotoxemia, nigral persisted microglial activation, elevated nitrosylated proteins and phosphorylated α-synuclein, and significant neuronal degeneration developed in wild-type mice but not in NLRP3-/- or IL-1R1-/- mice. CONCLUSIONS: This study uncovers a novel role of the NLRP3-IL-1ß signaling pathway in gauging the severity of sepsis-associated inflammation and determining whether acute neuroinflammation will resolve or transition to low grade chronic neuroinflammation. These findings also provide novel targets for developing therapy for severe systemic infection-related neurodegeneration.

Proteus faecis sp. nov., and Proteus cibi sp. nov., two new species isolated from food and clinical samples in China.

Eight swarming motile bacteria were isolated from food and clinical samples in China. Cells were Gram-stain-negative, facultatively anaerobic and rod-shaped (0.5-0.8×1.0-3.0 µm) with hairlike pili and flagella. The 16S rRNA and partial rpoB housekeeping gene sequence analyses indicated that the strains belong to the genus Proteusin the family Enterobacteriaceae. Of the eight strains studied, seven and a single isolate formed two separate clades in the phylogeny of Proteusspecies, indicating two separate species. Both the in silico DNA-DNA hybridization and the average nucleotide identity values between these two groups and to the type strains of the genus Proteuswere below the recommended threshold for signifying their candidature as two separate species. The DNA G+C contents of strains TJ1636T and FJ2001126-3T were 37.8 and 38.1 mol%, respectively. The major cellular fatty acids of the two novel type strains were C16:0, cyclo C17:0, summed feature 3 and summed feature 8. The results supported that the strains belong to different taxonomic positions in the genus Proteus. The isolates were named Proteus faecis sp. nov., with type strain TJ1636T (=DSM 106180T=GDMCC 1.1245T), and Proteuscibi sp. nov., with type strain FJ2001126-3T (=DSM 106178T =GDMCC 1.1244T).

Mitotic MELK-eIF4B signaling controls protein synthesis and tumor cell survival.

The protein kinase maternal and embryonic leucine zipper kinase (MELK) is critical for mitotic progression of cancer cells; however, its mechanisms of action remain largely unknown. By combined approaches of immunoprecipitation/mass spectrometry and peptide library profiling, we identified the eukaryotic translation initiation factor 4B (eIF4B) as a MELK-interacting protein during mitosis and a bona fide substrate of MELK. MELK phosphorylates eIF4B at Ser406, a modification found to be most robust in the mitotic phase of the cell cycle. We further show that the MELK-eIF4B signaling axis regulates protein synthesis during mitosis. Specifically, synthesis of myeloid cell leukemia 1 (MCL1), an antiapoptotic protein known to play a role in cancer cell survival during cell division, depends on the function of MELK-elF4B. Inactivation of MELK or eIF4B results in reduced protein synthesis of MCL1, which, in turn, induces apoptotic cell death of cancer cells. Our study thus defines a MELK-eIF4B signaling axis that regulates protein synthesis during mitosis, and consequently influences cancer cell survival.

Primary cilia control the maturation of tubular lumen in renal collecting duct epithelium.

The key role of the primary cilium in developmental processes is illustrated by ciliopathies resulting from genetic defects of its components. Ciliopathies include a large variety of dysmorphic syndromes that share in common the presence of multiple kidney cysts. These observations suggest that primary cilia may control morphogenetic processes in the developing kidney. In this study, we assessed the role of primary cilium in branching tubulogenesis and/or lumen development using kidney collecting duct-derived mCCDN21 cells that display spontaneous tubulogenic properties when grown in collagen-Matrigel matrix. Tubulogenesis and branching were not altered when cilium body growth was inhibited by Kif3A or Ift88 silencing. In agreement with the absence of a morphogenetic effect, proliferation and wound-healing assay revealed that neither cell proliferation nor migration were altered by cilium body disruption. The absence of cilium following Kif3A or Ift88 silencing in mCCDN21 cells did not alter the initial stages of tubular lumen generation while lumen maturation and enlargement were delayed. This delay in tubular lumen maturation was not observed after Pkd1 knockdown in mCCDN21 cells. The delayed lumen maturation was explained by neither defective secretion or increased reabsorption of luminal fluid. Our results indicate that primary cilia do not control early morphogenetic processes in renal epithelium. Rather, primary cilia modulate tubular lumen maturation and enlargement resulting from luminal fluid accumulation in tubular structures derived from collecting duct cells.

Atg1-mediated myosin II activation regulates autophagosome formation during starvation-induced autophagy.

Autophagy is a membrane-mediated degradation process of macromolecule recycling. Although the formation of double-membrane degradation vesicles (autophagosomes) is known to have a central role in autophagy, the mechanism underlying this process remains elusive. The serine/threonine kinase Atg1 has a key role in the induction of autophagy. In this study, we show that overexpression of Drosophila Atg1 promotes the phosphorylation-dependent activation of the actin-associated motor protein myosin II. A novel myosin light chain kinase (MLCK)-like protein, Spaghetti-squash activator (Sqa), was identified as a link between Atg1 and actomyosin activation. Sqa interacts with Atg1 through its kinase domain and is a substrate of Atg1. Significantly, myosin II inhibition or depletion of Sqa compromised the formation of autophagosomes under starvation conditions. In mammalian cells, we found that the Sqa mammalian homologue zipper-interacting protein kinase (ZIPK) and myosin II had a critical role in the regulation of starvation-induced autophagy and mammalian Atg9 (mAtg9) trafficking when cells were deprived of nutrients. Our findings provide evidence of a link between Atg1 and the control of Atg9-mediated autophagosome formation through the myosin II motor protein.

Sodium transport is modulated by p38 kinase-dependent cross-talk between ENaC and Na,K-ATPase in collecting duct principal cells.

In relation to dietary Na(+) intake and aldosterone levels, collecting duct principal cells are exposed to large variations in Na(+) transport. In these cells, Na(+) crosses the apical membrane via epithelial Na(+) channels (ENaC) and is extruded into the interstitium by Na,K-ATPase. The activity of ENaC and Na,K-ATPase must be highly coordinated to accommodate variations in Na(+) transport and minimize fluctuations in intracellular Na(+) concentration. We hypothesized that, independent of hormonal stimulus, cross-talk between ENaC and Na,K-ATPase coordinates Na(+) transport across apical and basolateral membranes. By varying Na(+) intake in aldosterone-clamped rats and overexpressing γ-ENaC or modulating apical Na(+) availability in cultured mouse collecting duct cells, enhanced apical Na(+) entry invariably led to increased basolateral Na,K-ATPase expression and activity. In cultured collecting duct cells, enhanced apical Na(+) entry increased the basolateral cell surface expression of Na,K-ATPase by inhibiting p38 kinase-mediated endocytosis of Na,K-ATPase. Our results reveal a new role for p38 kinase in mediating cross-talk between apical Na(+) entry via ENaC and its basolateral exit via Na,K-ATPase, which may allow principal cells to maintain intracellular Na(+) concentrations within narrow limits.

[Diagnostic value of serum procalcitonin in urinary tract infection].

OBJECTIVE: To analyze the serum level of procalcitonin (PCT) in urinary tract infection (UTI) patients with urinary obstruction or bacteremia, and to investigate the value of PCT in diagnosing UTI. METHODS: A total of 102 patients with UTI hospitalized from January to December 2013 in the Second Hospital of Tianjin Medical University were categorized into obstructed UTI (n=60) and non-obstructed UTI (n=42), whose serum PCT concentrations were compared. Blood cultures were implemented in 44 patients, including 13 with positive findings (bacteremia) and 31 with negative findings (non-bacteremia). Serum PCT levels were also compared between the bacteremia and non-bacteremia groups. Receiver operating characteristic (ROC) curves were constructed to illustrate the performance of PCT in diagnosing urinary obstruction and bacteremia. RESULTS: The median serum concentration of PCT in the obstructed UTI group (1.71 (0.10-53.20) mg/L)was higher than that in the non-obstructed UTI group (0.21 (0.10-10.00) mg/L, P<0.001); the serum concentration of PCT in the bacteremia group (2.73 (0.10-41.60) mg/L) was higher than that in the non-bacteremia group (0.42 (0.10-53.20) mg/L, P=0.030). The area under ROC curve of PCT in diagnosing urinary obstruction and bacteremia was 0.80 (95% CI 0.71-0.89) and 0.71 (95% CI 0.53-0.88). The maximum negative predictive value (NPV) was 0.90 and 0.87, respectively, when the serum concentrations of PCT diagnosing bacteremia and urinary obstruction was 0.51 mg/L and 0.35 mg/L. CONCLUSION: PCT may be of some value in diagnosing UTI with urinary obstruction or bacteremia.

Rumphellols A and B, new caryophyllene sesquiterpenoids from a Formosan gorgonian coral, Rumphella antipathies.

Two new marine-derived caryophyllene-type sesquiterpenoids, rumphellols A and B (1 and 2), were obtained from the gorgonian coral, Rumphella antipathies, collected off the waters of Taiwan. Although caryophyllene-type sesquiterpenes are rarely found in marine organisms, compounds of this type could be principal components of R. antipathies. The structures of new Compounds 1 and 2 were determined by analysis of their spectroscopic data, including 1D and 2D NMR experiments. Caryophyllene 1 and 2 were evaluated in terms of their anti-inflammatory activity by examining their inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils.

Impacts of changing cropping pattern on virtual water flows related to crops transfer: a case study for the Hetao irrigation district, China.

BACKGROUND: Analysis of cropping patterns is a prerequisite for their optimisation, and evaluation of virtual water flows could shed new light on water resources management. This study is intended to explore the effects of cropping pattern changes between 1960 and 2008 on virtual water flows related to crops transfer in the Hetao irrigation district, China. RESULTS: (1) The sown area of crops increased at an average rate of 3.57 × 10(3) ha year(-1) while the proportion of sown grain crops decreased from 92.83% in the 1960s to 50.22% in the 2000s. (2) Virtual water content decreased during the study period while net virtual water exports increased since the 1980s. (3) Assuming that the cropping pattern was constant and was equal to the average 1960s value, accumulated net virtual water export in 1980-2008 would have been 4.76 × 10(9) m(3) greater than that in the actual cropping pattern scenario. CONCLUSION: Cropping pattern changes in the Hetao irrigation district could not only be seen as resulting from the pursuit for higher economic returns, but also as a feedback response to limited water resources. A systematic framework is still needed for future cropping pattern planning by taking food security, continued agricultural expansion and other constraints into consideration.

Blindness in Right Eyes after Enema: A Case of Klebsiella pneumoniae-Related Invasive Liver Abscess Syndrome with Endophthalmitis-Caused Blindness as the First Symptom.

We report a case of Klebsiella pneumoniae invasive liver abscess syndrome (KPILAS) with endophthalmitis-caused blindness as the first symptom after enema. The patient had diabetes, and his blood glucose was poorly controlled. She developed hematuria after four enemas for cosmetic purposes and later became blind. The eye discharge was cultured, which revealed a Klebsiella pneumoniae infection. B ultrasound did not show liver lesions, but computed tomography exhibited abscesses in the right lobe of the liver. Magnetic resonance imaging of the head indicated abscesses. These confirmed the diagnosis of invasive liver abscess syndrome. The patient was given ophthalmic and systemic anti-infection treatments, and her condition was effectively controlled. Unfortunately, the diseased eye still needed to be removed. This case underlines the necessity of avoiding unnecessary risky procedures (such as enemas) in vulnerable populations, the importance of early detection of invasive liver abscess syndrome, and the advantage of computed tomography in detecting liver abscesses.

A new nomogram prediction model for pulmonary embolism in older hospitalized patients.

Purpose: Diagnosing pulmonary embolism (PE) in older adults is relatively difficult because of the atypical clinical symptoms of PE in older adults accompanied by multiple complications. This study aimed to establish a nomogram model to better predict the occurrence of PE in older adults. Methods: Data were collected from older patients (≥65 years old) with suspected PE who were hospitalized between January 2012 and July 2021 and received confirmatory tests (computed tomographic pulmonary angiography or ventilation/perfusion scanning). The PE group and non-PE (control) group were compared using univariable and multivariable analyses to identify independent risk factors. A nomogram prediction model was constructed with independent risk factors and verified internally. The effectiveness of the nomogram model, Wells score, and revised Geneva score was assessed using the area under the receiver operating characteristic curve (AUC). Results: In total, 447 eligible older patients (290 PE patients and 157 non-PE patients) were enrolled. Logistic regression analysis revealed nine independent risk factors: smoking, inflammation, dyspnea, syncope, mean corpuscular hemoglobin concentration, indirect bilirubin, uric acid, left atrial diameter, and internal diameter of the pulmonary artery. The AUC, sensitivity, and specificity of the nomogram prediction model were 0.763 (95 % confidence interval, 0.721-0.802), 74.48 %, and 67.52 %, respectively. The nomogram showed superior AUC compared to the Wells score (0.763 vs. 0.539, P < 0.0001) and the revised Geneva score (0.763 vs. 0.605, P < 0.0001). Conclusions: This novel nomogram may be a useful tool to better recognize PE in hospitalized older adults.

The virtual water content of major grain crops and virtual water flows between regions in China.

BACKGROUND: The disproportionate distribution of arable land and water resources has become a bottleneck for guaranteeing food security in China. Virtual water and virtual water trade theory have provided a potential solution to improve water resources management in agriculture and alleviate water crises in water-scarce regions. The present study evaluates the green and blue virtual water content of wheat, maize and rice at the regional scale in China. It then assesses the water-saving benefits of virtual water flows related to the transfer of the three crops between regions. RESULTS: The national average virtual water content of wheat, maize and rice were 1071 m(3) per ton (50.98% green water, 49.02% blue water ), 830 m(3) per ton (76.27% green water, 23.73% blue water) and 1294 m(3) per ton (61.90% green water, 38.10% blue water), respectively. With the regional transfer of wheat, maize and rice, virtual water flows reached 30.08 Gm(3) (59.91% green water, 40.09% blue water). Meanwhile, China saved 11.47 Gm(3) green water, while it consumed 7.84 Gm(3) more blue water than with a no-grain transfer scenario in 2009. CONCLUSION: In order to guarantee food security in China, the government should improve water productivity (reduce virtual water content of crops) during the grain production process. Meanwhile, under the preconditions of economic feasibility and land-water resources availability, China should guarantee the grain-sown area in southern regions for taking full advantage of green water resources and to alleviate the pressure on water resources.

[Brain mappings in non-fluent late Chinese-English bilinguals].

OBJECTIVE: To discuss the distribution characteristics of language areas in Chinese-English non-fluent late bilinguals. METHODS: Six Chinese-English bilinguals with eloquent tumors underwent awake-surgeries. The activated areas of BOLD-fMRI were obtained as the patients performed pure naming, verb generation, and abstract/concrete judgment tasks. Direct cortical stimulation(DCS) as the golden standard of language mapping were performed during awake-surgeries on the exposed cortical areas. BOLD-fMRI results of 3 language tasks were compared with DCS results. The statistical method was McNemer. RESULTS: Sixteen positive sites(22.5%) were comfirmed out of 71 stimulations. There were 3 specific language sites, in which 2 sites were specific English sites and 1 site was specific Chinese site. When activated areas of BOLD-fMRI were compared with the DCS results, verb generation task had the highest concordance rate 40.9% (95%CI:30.2%-52.5%) . There were significant differences between the results of BOLD-fMRI and DCS of all 3 bilingual tasks(P < 0.017). CONCLUSIONS: There are specific language areas in Chinese-English non-fluent late bilinguals. The BOLD-fMRI language mapping could not substitute DCS in the context of mapping language areas in bilinguals.

Comparison of quality/quantity mNGS and usual mNGS for pathogen detection in suspected pulmonary infections.

Improved metagenomic next-generation sequencing (mNGS), for example, quality/quantity mNGS (QmNGS), is being used in the diagnosis of pulmonary pathogens. There are differences between QmNGS and the usual mNGS (UmNGS), but reports that compare their detection performances are rare. In this prospective study of patients enrolled between December 2021 and March 2022, the bronchoalveolar lavage fluid of thirty-six patients with suspected pulmonary infection was assessed using UmNGS and QmNGS. The sensitivity of QmNGS was similar to that of UmNGS. The specificity of QmNGS was higher than that of UmNGS; however, the difference was not statistically significant. The positive likelihood ratios (+LR) of QmNGS and UmNGS were 3.956 and 1.394, respectively, and the negative likelihood ratios (-LR) were 0.342 and 0.527, respectively. For the co-detection of pathogens, the depth and coverage of the QmNGS sequencing were lower than those of UmNGS, while for the detection of pathogens isolated from patients with pulmonary infection, the concordance rate was 77.2%. In the eleven patients with nonpulmonary infection, only viruses were detected using QmNGS, while UmNGS detected not only viruses but also bacteria and fungi. This study provides a basis for the selection of mNGS for the diagnosis of suspected pulmonary infection.