The effect of triclosan on intergeneric horizontal transmission of plasmid-mediated tigecycline resistance gene tet(X4) from Citrobacter freundii isolated from grass carp gut.

The transmission of antibiotic resistance genes (ARGs) in pathogenic bacteria affects culture animal health, endangers food safety, and thus gravely threatens public health. However, information about the effect of disinfectants - triclosan (TCS) on ARGs dissemination of bacterial pathogens in aquatic animals is still limited. One Citrobacter freundii (C. freundii) strain harboring tet(X4)-resistant plasmid was isolated from farmed grass carp guts, and subsequently conjugative transfer frequency from C. freundii to Escherichia coli C600 (E. coli C600) was analyzed under different mating time, temperature, and ratio. The effect of different concentrations of TCS (0.02, 0.2, 2, 20, 200 and 2000 µg/L) on the conjugative transfer was detected. The optimum conditions for conjugative transfer were at 37 °C for 8h with mating ratio of 2:1 or 1:1 (C. freundii: E. coli C600). The conjugative transfer frequency was significantly promoted under TCS treatment and reached the maximum value under 2.00 µg/L TCS with 18.39 times that of the control group. Reactive oxygen species (ROS), superoxide dismutase (SOD) and catalase (CAT) activities, cell membrane permeability of C. freundii and E. coli C600 were obviously increased under TCS stress. Scanning electron microscope showed that the cell membrane surface of the conjugative strains was wrinkled and pitted, even broken at 2.00 µg/L TCS, while lysed or even ruptured at 200.00 µg/L TCS. In addition, TCS up-regulated expression levels of oxidative stress genes (katE, hemF, bcp, hemA, katG, ahpF, and ahpC) and cell membrane-related genes (fimC, bamE and ompA) of donor and recipient bacteria. Gene Ontology (GO) enrichment demonstrated significant changes in categories relevant to pilus, porin activity, transmembrane transporter activity, transferase activity, hydrolase activity, material transport and metabolism. Taken together, a tet(X4)-resistant plasmid could horizontal transmission among different pathogens, while TCS can promote the propagation of the resistant plasmid.

Tracing Organophosphate Ester Pollutants in Hadal Trenches─Distribution, Possible Origins, and Transport Mechanisms.

Unraveling the mysterious pathways of pollutants to the deepest oceanic realms holds critical importance for assessing the integrity of remote marine ecosystems. This study tracks the transport of pollutants into the depths of the oceans, a key step in protecting the sanctity of these least explored ecosystems. By analyzing hadal trench samples from the Mariana, Mussau, and New Britain trenches, we found the widespread distribution of organophosphate ester (OPE) flame retardants but a complex transport pattern for the OPE in these regions. In the Mariana Trench seawater column, OPE concentrations range between 17.4 and 102 ng L-1, with peaks at depths of 500 and 4000 m, which may be linked to Equatorial Undercurrent and topographic Rossby waves, respectively. Sediments, particularly in Mariana (422 ng g-1 dw), showed high OPE affinity, likely due to organic matter serving as a transport medium, influenced by "solvent switching", "solvent depletion", and "filtering processes". Amphipods in the three trenches had consistent OPE levels (29.1-215 ng g-1 lipid weight), independent of the sediment pollution patterns. The OPEs in these amphipods appeared more linked to surface-dwelling organisms, suggesting the influence of "solvent depletion". This study highlights the need for an improved understanding of deep-sea pollutant sources and transport, urging the establishment of protective measures for these remote marine habitats.

Tomatidine activates autophagy to improve lung injury and inflammation in sepsis by inhibiting NF-κB and MAPK pathways.

Sepsis-induced acute lung injury (ALI) is a life-threatening medical condition with high mortality and morbidity. Autophagy is involved in the pathophysiological process of sepsis-induced ALI, including inflammation, which indicates that regulating autophagy may be beneficial for this disease. Tomatidine, a natural compound abundant in unripe tomatoes, has been reported to have anti-inflammatory, anti-tumorigenic, and lipid-lowering effects. However, the biological functions and mechanisms of tomatidine in sepsis-induced ALI remain unknown. The principal objective of this study was to investigate the effect of tomatidine on sepsis-induced ALI. Cecal ligation and puncture (CLP) was used to induce septic lung injury in mice, and 10 mg/kg tomatidine was intraperitoneally injected into mice 2 h after the operation. The results of hematoxylin and eosin staining and assessment of lung edema and total protein levels in bronchoalveolar lavage fluid (BALF) demonstrated that tomatidine alleviated CLP-induced severe lung injuries such as hemorrhage, infiltration of inflammatory cells, and interstitial and alveolar edema in mice. Additionally, the levels of proinflammatory cytokines in BALF and lung tissues were measured by enzyme-linked immunosorbent assay (ELISA), and the results showed that tomatidine inhibited CLP-induced inflammatory damage to lungs. Moreover, the results of western blotting showed that tomatidine promoted autophagy during CLP-induced ALI. Mechanistically, immunofluorescence staining and western blotting were used to measure the protein levels of TLR4, phosphorylated NF-κB, phosphorylated IκBα, and phosphorylated MAPKs, showing that tomatidine inactivated NF-κB and MAPK signaling in lung tissues of CLP-induced ALI mice. In conclusion, tomatidine exerts protective effects against sepsis-induced severe damage to the lungs by inhibiting inflammation and activating autophagy in CLP-treated mice through inactivating the NF-κB and MAPK pathways, which may be an effective candidate for treating septic ALI.

HPV infection and vaginal microecological disorders in women with intrauterine adhesion: cross-sectional study in a Chinese population.

BACKGROUND: The purpose of this study was to evaluate the vaginal microecology and the distribution of human papillomavirus (HPV) subtypes in patients with uterine adhesions and explore the correlation between HPV infection and vaginal microecology imbalance and the occurrence of intrauterine adhesion (IUA). METHODS: A total of 479 women were enrolled in the study, including 259 in the normal group and 220 in the IUA group. Vaginal microecological and HPV analyses were performed on all participants. Significant differences between the two groups were analyzed, and Spearman correlation analysis was performed. RESULTS: The incidence of IUA in patients between 31 and 40 years of age was high. The I-II degree of vaginal cleanliness in the IUA group was significantly lower than that in the normal group, and the number of III-IV degree was significantly higher than that in the normal group. Moreover, the incidences of VVC (vulvovaginal candidiasis) and vaginal disorders and infections with HPV 16 and HPV 52 subtypes were significantly higher in the IUA group than in the normal group. The incidence of high-risk HPV infection combined with vaginal disorders in the IUA group was higher than that in the normal group. Correlation analysis showed that the occurrence of IUAs was positively correlated with HPV infection and negatively correlated with PH and vaginal microecological imbalance. CONCLUSION: The HPV infection rate and vaginal microecology disorders affect the occurrence of IUAs. For patients with IUAs, control of the HPV infection rate and the prevention of vaginal microecological disorders should be improved.

Hepcidin from Onychostoma macrolepis: Response to Aeromonas hydrophila infection by down-regulating expression of inflammatory factor genes and regulating iron homeostasis potentially.

Hepcidin, as an antimicrobial peptide, is associated with innate immunity and is considered a potential antibiotic substitute. In the present study, the hepcidin gene from the cavefish - Onychostoma macrolepis was identified and analyzed. The recombinant hepcidin protein (rOmhepc) was obtained by prokaryotic expression, evaluating the inhibitory effect of 5 pathogenic bacteria in vitro. Sixty O. macrolepis injected with 100 µL A. hydrophila (1.5 × 108 CFU/mL) were randomly divided into the therapeutic group and infection group, and therapeutic group was injected with 100 µL rOmhepc (100 µg/mL) at 6 and 18 h. The survival rates of O. macrolepis and bacterial load in liver were measured at 24 h. The liver tissues were collected at 0, 6, 12, and 24 h after A. hydrophila injection for investigating expression levels of immune-related, inflammatory factor genes and FPN1 gene. The results demonstrated that the hepcidin CDS contained 279 bp and encoded 93 aa. Hepcidin protein has a hydrophobic surface formed by multiple hydrophobic residues (CCGCCYC), and the theoretical pI was 7.53. Omhepc gene was expressed at varying levels in tested tissues, with the liver showing the highest expression, followed by the spleen. The expression of hepcidin gene following A. hydrophila infection was up-regulated and then down-regulated in liver, and the highest expression level was found at 12 h with a 10.93-fold. The rOmhepc remarkably inhibited the growth of A. hydrophila, Staphylococcus aureus, and Streptococcus agalactiae, with inhibition rates reaching 69.67 %, 42.97 %, and 65.74 % at 100 µg/mL. The mortality rates of O. macrolepis and bacterial load in liver were significantly decreased in the therapeutic group than that of infection group (p < 0.05). After the rOmhepc therapeutic, interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) were significantly down-regulated with 14.4-fold and 106.07-fold at 24 h. Furthermore, the expression of immune-related genes (C3, TNF-α, IFN-γ) and Ferroportin gene (FPN1) significantly decreased (p < 0.05). The integrated analyses indicated that the rOmhepc could significantly inhibit the growth of A. hydrophila both in vitro and in vivo, attenuating the over-expression of inflammatory factor, FPN1 and immune-related genes.

Effects of 4-tert-butylpyrocatechol and tea polyphenol on growth, physiology and antioxidant responses in Microcystis aeruginosa.

Global warming has increased the frequency of Microcystis aeruginosa blooms, leading to the deterioration of water quality and loss of biodiversity. Therefore, developing effective strategies for controlling M. aeruginosa blooms has become an important research topic. Plant extracts, 4­tert-butylpyrocatechol (TBC) and tea polyphenol (TP) are commonly used for water purification and to increase fish immunity, which have great potential to inhibit cyanobacterial blooms. The inhibitory effects of TBC and TP on M. aeruginosa were investigated in terms of growth characteristics, cell membrane morphology, physiological, photosynthetic activities, and antioxidant enzymes activities. The results showed that TBC and TP inhibited the growth of M. aeruginosa by decreasing the chlorophyll fluorescence transients or increasing the antioxidant enzymes activities of M. aeruginosa. TBC damaged the cell morphology of M. aeruginosa, reduced extracellular polysaccharides and protein contents, and up-regulated the antioxidant activity-related gene (sod and gsh) expressions of M. aeruginosa. TP significantly decreased the photosynthetic pigment content, influenced the phycobiliprotein content, and strongly down-regulated the photosynthesis-related gene (psbA, psaB, and rbcL) relative expressions of M. aeruginosa. TBC caused significant oxidative stress, dysfunction of physiological metabolic processes, and damaged crucial biomacromolecules (e.g., lipids, proteins and polysaccharides), prompted the loss of cell integrity, ultimately leading to the death of M. aeruginosa. However, TP depressed photosynthetic activities and consequently inhibited the transfer of electrons, affected the electron transfer chain, decreased the photosynthetic efficiency, and eventually caused the death of M. aeruginosa cells. Our study showed the inhibitory effects and algicidal mechanisms of TBC and TP on M. aeruginosa, and provide a theoretical basis for restrain the overgrowth of M. aeruginosa.

Risk of insomnia during COVID-19: effects of depression and brain functional connectivity.

Normal sleepers may be at risk for insomnia during COVID-19. Identifying psychological factors and neural markers that predict their insomnia risk, as well as investigating possible courses of insomnia development, could lead to more precise targeted interventions for insomnia during similar public health emergencies. Insomnia severity index of 306 participants before and during COVID-19 were employed to determine the development of insomnia, while pre-COVID-19 psychometric and resting-state fMRI data were used to explore corresponding psychological and neural markers of insomnia development. Normal sleepers as a group reported a significant increase in insomnia symptoms after COVID-19 outbreak (F = 4.618, P = 0.0102, df = 2, 609.9). Depression was found to significantly contribute to worse insomnia (ß = 0.066, P = 0.024). Subsequent analysis found that functional connectivity between the precentral gyrus and middle/inferior temporal gyrus mediated the association between pre-COVID-19 depression and insomnia symptoms during COVID-19. Cluster analysis identified that postoutbreak insomnia symptoms followed 3 courses (lessened, slightly worsened, and developed into mild insomnia), and pre-COVID-19 depression symptoms and functional connectivities predicted these courses. Timely identification and treatment of at-risk individuals may help avoid the development of insomnia in the face of future health-care emergencies, such as those arising from COVID-19 variants.

HPV and vaginal microecological disorders in infertile women: a cross-sectional study in the Chinese population.

BACKGROUND: The purpose of this study was to evaluate the distributions of vaginal microbiome dysbiosis and human papillomavirus (HPV) subtypes in infertile women and explore the correlations of HPV infection and vaginal microbiome dysbiosis with infertility. METHODS: In total, 1464 women aged 18-50 years were included in this study; 649 participants were included in the infertility group, and 815 participants were included in the normal group. The participants were tested for HPV, and their vaginal microecology was examined. The χ2 test and Spearman regression were used for statistical analysis, and binary logistic regression was performed to identify the risk factors for infertility. RESULTS: The patients in the infertility group were younger than those in the normal group, and the proportions of bacterial vaginosis and vaginal imbalance in the infertility group were significantly higher than those in the normal group. The incidence proportions of high-risk HPV types in the infertility group were significantly higher than those in the normal group, and the proportions of high-risk subtytes HPV16, HPV39, HV52, HPV56, and HPV68 were significantly higher in the infertility group than in the normal group. However, there were no significant differences in the incidences of low-risk HPV types. The incidence proportions of vaginal flora imbalance and HPV infection in the infertility group were significantly higher than those in the normal group. HPV16, HPV33, HPV51, HPV52and HPV58 infections were independent risk factors for infertility. CONCLUSIONS: Vaginal microecological imbalance and HPV infection are directly related to infertility, and precautions should be taken.

The different roles of sleep on false memory formation between young and older adults.

Aging is accompanied by an increase in the probability of false memory. However, what role sleep plays in the age effect in false memory is less understood. Our study utilized a simplified conjoint recognition (SCR)-based Deese-Roediger-McDermott (DRM) paradigm to investigate the role of sleep on false memory in young and older adults. The results showed that sleep effect in false memory was modulated by age, manifested as sleep increased young adults' falsely recognized critical lures, while it reduced older adults'. In addition, in a more fine-grained analysis, the results of multinomial processing tree (MPT) modeling further revealed that young adults were more likely to retrieve memory based on gist traces than older adults, and young adults were more susceptible to guess a probe as "old" than older adults in the sleep condition. Combined findings from the number and ratio of falsely recognized critical lures and the MPT modeling, the current study suggested that sleep might increase young adults' false memory via gist extraction, while it decreased older adults' false memory via verbatim trace consolidation. The study contributes to a comprehensive view on the age-by-sleep effect on false recognition, with the segregation of cognitive components of verbatim memory, gist memory, and response bias.

Sleep Quality Modulates the Association between Dynamic Functional Network Connectivity and Cognitive Function in Healthy Older Adults.

Aging is associated with changes in sleep, brain activity, and cognitive function, as well as the association among these factors; however, the precise nature of these changes has not been elucidated. This study systematically investigated the modulatory effect of sleep on the relationship between brain functional network connectivity (FNC) and cognitive function in older adults. In total, 107 community-dwelling healthy older adults were recruited and assigned into poor sleep and good sleep groups based on the Pittsburgh Sleep Quality Index. The static functional network connectivity (sFNC), the temporal variability of dynamic FNC (dFNC) from variance (dFNC-var), and the dFNC from clustering state (dFNC-state) were calculated. Corresponding cognition-predictive models were constructed for each sleep group. dFNC but not sFNC, was able to significantly predict the cognitive function in older adults. Specifically, sleep played a modulatory role in the association between dFNC and cognitive function, with sleep-specific variations at both microscopic (i.e., specific edges) and macroscopic levels (i.e., specific states) of dFNC.

Molecular characterization and antibacterial ability of galectin-3 and galectin-9 in Onychostoma macrolepis.

Galectins belong to the ß-galactoside binding protein family, which have conserved carbohydrate-recognition domains (CRDs) and participate in innate and acquired immunity in animals. In this study, two galectin genes were cloned from Onychostoma macrolepis, OmGal-3 (galectin-3) and OmGal-9 (galectin-9). The open reading frames (ORFs) of OmGal-3 and OmGal-9 contain 732 and 978 base pairs, encoding 243 and 325 amino acids, respectively. OmGal-3 contains a C-terminal CRD, but OmGal-9 contains an N-terminal CRD and a C-terminal CRD. Two galectins were expressed at varying levels in all tissues examined, with the liver showing the highest expression. The relative gene expression levels of OmGal-3 and OmGal-9 following Aeromonas hydrophila infection were significantly up-regulated in the liver and spleen, and OmGal-9 had a greater increase than OmGal-3. The recombinant OmGal-3 and OmGal-9 proteins (rOmGal-3 and rOmGal-9) were authenticated and verified by SDS-PAGE and western blotting. ROmGal-3 and rOmGal-9 agglutinated all tested bacteria, including 3 g-positive bacteria (Aeromonas hydrophila, Escherichia coli, and Vibrio parahaemolyticus) and 3 g-negative bacteria (Streptococcus agalactiae, Staphylococcus aureus, and Bacillus cereus) in vivo without Ca2+. ROmGal-3 showed strong binding both to gram-positive and gram-negative bacteria and OmGal-9 had a stronger binding activity against gram-positive bacteria. Furthermore, rOmGal-3 and rOmGal-9 exhibited dose-dependent binding capability to two classic pathogens associated molecular pattern (LPS and PGN) and two sugars (d-lactose and d-galactose), and rOmGal-3 has better binding activity at lower concentrations in LPS and PGN than rOmGal-3. The integrated analyses indicate that the two galectins probably play an important role in innate immune defense by binding to bacterial cells via the CRD domain against pathogen infection.

Geology, environment, and life in the deepest part of the world's oceans.

The hadal zone, mostly comprising of deep trenches and constituting of the deepest part of the world's oceans, represents the least explored habitat but one of the last frontiers on our planet. The present scientific understanding of the hadal environment is still relatively rudimentary, particularly in comparison with that of shallower marine environments. In the last 30 years, continuous efforts have been launched in deepening our knowledge regarding the ecology of the hadal trench. However, the geological and environmental processes that potentially affect the sedimentary, geochemical and biological processes in hadal trenches have received less attention. Here, we review recent advances in the geology, biology, and environment of hadal trenches and offer a perspective of the hadal science involved therein. For the first time, we release high-definition images taken by a new full-ocean-depth manned submersible Fendouzhe that reveal novel species with an unexpectedly high density, outcrops of mantle and basaltic rocks, and anthropogenic pollutants at the deepest point of the world's ocean. We advocate that the hydration of the hadal lithosphere is a driving force that influences a variety of sedimentary, geochemical, and biological processes in the hadal trench. Hadal lithosphere might host the Earth's deepest subsurface microbial ecosystem. Future research, combined with technological advances and international cooperation, should focus on establishing the intrinsic linkage of the geology, biology, and environment of the hadal trenches.

Analysis of Antibiotic Resistance Genes, Environmental Factors, and Microbial Community From Aquaculture Farms in Five Provinces, China.

The excessive use of antibiotics speeds up the dissemination and aggregation of antibiotic resistance genes (ARGs) in the environment. The ARGs have been regarded as a contaminant of serious environmental threats on a global scale. The constant increase in aquaculture production has led to extensive use of antibiotics as a means to prevent and treat bacterial infections; there is a universal concern about the environmental risk of ARGs in the aquaculture environment. In this study, a survey was conducted to evaluate the abundance and distributions of 10 ARGs, bacterial community, and environmental factors in sediment samples from aquatic farms distributed in Anhui (AP1, AP2, and AP3), Fujian (FP1, FP2, and FP3), Guangxi (GP1, GP2, and GP3), Hainan (HP1, HP2, and HP3), and Shaanxi (SP1, SP2, and SP3) Province in China. The results showed that the relative abundance of total ARGs was higher in AP1, AP2, AP3, FP3, GP3, HP1, HP2, and HP3 than that in FP1, FP2, GP1, GP2, SP1, SP2, and SP3. The sul1 and tetW genes of all sediment samples had the highest abundance. The class 1 integron (intl1) was detected in all samples, and the result of Pearson correlation analysis showed that the intl1 has a positive correlation with the sul1, sul2, sul3, bla OXA, qnrS, tetM, tetQ, and tetW genes. Correlation analysis of the bacterial community diversity and environmental factors showed that the Ca2+ concentration has a negative correlation with richness and diversity of the bacterial community in these samples. Of the identified bacterial community, Proteobacteria, Firmicutes, Chloroflexi, and Bacteroidota were the predominant phyla in these samples. Redundancy analysis showed that environmental factors (TN, TP, Cl-, and Ca2+) have a positive correlation with the bacterial community (AP1, GP1, GP2, GP3, SP1, SP2, and SP3), and the abundance of ARGs (sul1, tetW, qnrS, and intl1) has a positive correlation with the bacterial community (AP2, AP3, HP1, HP2, and HP3). Based on the network analysis, the ARGs (sul1, sul2, bla CMY, bla OXA, qnrS, tetW, tetQ, tetM, and intl1) were found to co-occur with bacterial taxa from the phyla Chloroflexi, Euryarchaeota, Firmicutes, Halobacterota, and Proteobacteria. In conclusion, this study provides an important reference for understanding the environmental risk associated with aquaculture activities in China.

A C-type lectin with a single CRD from Onychostoma macrolepis mediates immune recognition against bacterial challenge.

C-type lectins (CTL) are a large group of pattern-recognition proteins and to play important roles in glycoprotein metabolism, multicellular integration, and immunity. Based on their overall domain structure, they can be classified as different groups that possess different physiological functions. A typical C-type lectin (named as OmLec1) was identified from the fish, Onychostoma macrolepis, an important cultured fish in China. Open reading frame of OmLec1 contains a 570 bp, encoding a protein of 189 amino acids that includes a signal peptide and a single carbohydrate-recognition domain. The phylogenetic analysis showed that OmLec1 could be grouped with C-type lectin from other fish. OmLec1 was expressed in all the tissues in our study, and the expression level was highest in liver. And its relative expression levels were significantly upregulated following infection with Aeromonas hydrophila. The recombinant OmLec1 protein (rOmLec1) could agglutinate some Gram-negative bacteria and Gram-positive bacteria in vitro in the presence of Ca2+, showing a typical Ca2+-dependent carbohydrate-binding protein. Furthermore, rOmLec1 purified from E. coli BL21 (DE3), strongly bound to LPS and PGN, as well as all tested bacteria in a Ca2+-dependent manner. These results indicate that OmLec1 plays a central role in the innate immune response and as a pattern recognition receptor that recognizes diverse pathogens among O. macrolepis.

A C-type lectin (OmCTL) in Onychostoma macrolepis: Binding ability to LPS, PGN and agglutinating activity against bacteria.

C-type lectins (CTLs) are calcium-dependent carbohydrate-binding proteins that mainly bind to carbohydrate-based or other ligands to mediate cell adhesion, recognize pathogens, and play important roles in the immune system. In the present study, a novel C-type lectin (OmCTL) isolated from Onychostoma macrolepis was investigated. The open reading frame of OmCTL comprises 468 bp, encoding a 155 amino acid polypeptide with an 18 amino acid putative signaling peptide. The predicted primary OmCTL structure contains a signal peptide, a single carbohydrate recognition domain (CRD) and an EPN/WND motif required for carbohydrate-binding specificity. Using tissue expression pattern analysis, OmCTL has been shownto be highly expressed in the liver, and is also detected in other tissues. OmCTL was significantly upregulated in the liver and spleen following infection with Aeromonas hydrophila, suggesting its involvement in immune response. The recombinant OmCTL protein (rOmCTL) agglutinated two gram-negative bacteria, Escherichia coli and A. hydrophila, in vitro in the presence of Ca2+, showing that it is a typical Ca2+-dependent carbohydrate-binding protein.Furthermore, rOmCTL purified from E. coli BL21 (DE3) strongly bound to LPS and PGN, as well as all tested bacteria in a Ca2+-independent manner. These results indicate that OmCTL plays a central role in the innate immune response and as a pattern recognition receptor that recognizes diverse pathogens among O. macrolepis.

Age-related alterations of default mode network in autobiographical memory: Recent versus remote events.

Previous studies have shown that the vividness of autobiographical memory decreases over time, and older adults often retrieve fewer details than young adults. However, the age-by-temporal distance (i.e., recent versus remote events) effect on autobiographical memory and underlying neural mechanisms are less understood. We recruited 25 young adults and 27 older adults to perform an fMRI-adapted autobiographical memory task with different temporal distances. The results showed that older adults' vividness ratings were generally higher than that of young adults, but were less sensitive to temporal distances. For neural imaging, an age-by-temporal distance effect was found in the left precuneus, manifested as young adults had more activation for recent events than for remote events, whereas no temporal distance effect was found in older adults. Interestingly, for older adults, the temporal distance effect was reflected by functional connectivity within the default mode network (DMN), with a stronger anterior DMN-posterior DMN coupling for remote events than for recent events, whereas no temporal distance difference on functional connectivity was found in young adults. The results suggest that older adults exhibit age-related neural differences in both activation and functional connectivity during the processing of autobiographical memory with different temporal distances, shedding new light for the understanding of the relationship between the DMN, autobiographical memory, and aging.

Pharmacokinetic/pharmacodynamic analysis of meropenem, by Monte Carlo simulation, in both plasma and cerebrospinal fluid in patients with cerebral hemorrhage after external ventricular drainage
.

OBJECTIVE: Patients with cerebral hemorrhage are often prone to intracranial infection, and meropenem is recommended for treatment. But whether the widely used dosing regimen (1 g, 2-hour infusion, every 12 hours) is suitable for antibiotic therapy is still unclear. The purpose of this study was to perform pharmacokinetic/pharmacodynamic (PK/PD) analyses of meropenem in both plasma and cerebrospinal fluid (CSF) in these patients. MATERIALS AND METHODS: Ten patients were enrolled in the present study. The blood samples and CSF samples were taken at predetermined time points and determined by our previously developed HPLC method. Pharmacokinetic parameters were then calculated, and the probability of target attainment (PTA) was calculated by the time that drug concentrations were above the minimum inhibitory concentration (%T>MIC). RESULTS: The peak meropenem concentration (Cmax) of 17.79 ± 3.38 µg/mL in plasma was reached at 2 hours, and the area under the curve (AUC) was 46.95 ± 4.37 h×µg/mL. The Cmax of 6.51 ± 1.11 µg/mL in CSF was reached at 3.50 ± 0.53 hours, and the AUC was 24.53 ± 4.28 h×µg/mL. The average penetration rate of meropenem in these patients was 52.25%. In the case where the MIC value was ≤ 1 µg/mL and using 40%T>MIC as a PK/PD index, the PTA of meropenem in both plasma and CSF were able to provide good coverage with MIC ≤ 1 µg/mL. CONCLUSION: In conclusion, this is the first study on the PK/PD analysis of meropenem in both plasma and CSF in patients with cerebral hemorrhage. The results will assist in selecting appropriate dosing regimens of meropenem in these patients.

Seasonal variability of water characteristics in the Challenger Deep observed by four cruises.

Thirty conductivity-temperature-depth profiler casts in the Challenger Deep were conducted during four cruises from December 2015 to February 2017. Two cruises took place in the summer, and two in the winter. The results demonstrated that water characteristics varied seasonally. The temperature minimum values were the same between the four cruises, but its depth was noticeably shallower in the winter than that in the summer. The θ-S diagram indicated that deep water is more saline in the summer than that in winter at the same potential temperature. Mixing is more intense between 5000 and 6800 m in the summer than that in the winter. The dissipation rate and eddy diffusivity vertically averaged between 5000 and 6800 m in the summer were εT = 3.277 × 10-8 m2s-3 and KzT = 2.58 × 10-2 m2s-1, respectively. The geostrophic flows below the reference level of 3000 dbar were cyclonic in the summer, travelling westwards in the northern and eastwards in the southern areas of the Challenger Deep.