DNA polymerase epsilon binds histone H3.1-H4 and recruits MORC1 to mediate meiotic heterochromatin condensation.

Heterochromatin is essential for genomic integrity and stability in eukaryotes. The mechanisms that regulate meiotic heterochromatin formation remain largely undefined. Here, we show that the catalytic subunit (POL2A) of Arabidopsis DNA polymerase epsilon (POL ε) is required for proper formation of meiotic heterochromatin. The POL2A N terminus interacts with the GHKL adenosine triphosphatase (ATPase) MORC1 (Microrchidia 1), and POL2A is required for MORC1's localization on meiotic heterochromatin. Mutations affecting the POL2A N terminus cause aberrant morphology of meiotic heterochromatin, which is also observed in morc1. Moreover, the POL2A C-terminal zinc finger domain (ZF1) specifically binds to histone H3.1-H4 dimer or tetramer and is important for meiotic heterochromatin condensation. Interestingly, we also found similar H3.1-binding specificity for the mouse counterpart. Together, our results show that two distinct domains of POL2A, ZF1 and N terminus bind H3.1-H4 and recruit MORC1, respectively, to induce a continuous process of meiotic heterochromatin organization. These activities expand the functional repertoire of POL ε beyond its classic role in DNA replication and appear to be conserved in animals and plants.

Activation of AIM2 by hepatitis B virus results in antiviral immunity that suppresses hepatitis C virus during coinfection.

IMPORTANCE: Clinical data suggest that Hepatitis C virus (HCV) levels are generally lower in Hepatitis B virus (HBV) co-infected patients, but the mechanism is unknown. Here, we show that HBV, but not HCV, activated absent in melanoma-2. This in turn results in inflammasome-mediated cleavage of pro-IL-18, leading to an innate immune activation cascade that results in increased interferon-γ, suppressing both viruses.

Development of a novel six DNA damage response-related prognostic signature in osteosarcoma.

DNA damage response (DDR) plays a vital role in the development of cancer. Nevertheless, in osteosarcoma, the potential of DDR-related genes (DDRGs) remains unclear. Thus, the current research is intended to investigate the mechanisms of DDRGs in the development of osteosarcoma and to explore potential DDR-related biomarkers in forecasting the prognosis of osteosarcoma patients. The osteosarcoma genomic data from TCGA, GEO and cBioPortal databases were utilized for screening and identification of differentially expressed DDRGs (DEDDRGs). Consensus clustering analysis was performed to identify different subtypes of osteosarcoma based on the expressions of DDRGs. Key DEDRRGs were identified by overlapping DEDRRGs between different subtypes and DEDRRGs between tumor and control samples. Univariate, as well as LASSO regressions, were further applied to obtain robust prognostic signatures. GSVA and ssGSEA analysis were implemented to explore the underlying mechanisms of prognostic DDRG signature in regulating osteosarcoma. In addition, the drug sensitivity of patients in low- and high-risk groups was evaluated using pRRophetic algorithm. A total of 43 key DEDRRGs were identified. Followed by univariate Cox along with LASSO regression analyses, CDK6, CSF1R, EGFR, ERBB4, GATA3 and SOCS1 were identified as prognostic signatures in osteosarcoma. Cox regressions revealed that the risk score was an independent prognostic factor in osteosarcoma.  DDR may affect osteosarcoma via regulating immune microenvironment along with influencing cell proliferation, migration, adhesion and apoptosis. The chemotherapeutic response between patients in low- and high-risk groups was much different. The role of DDRGs in osteosarcoma and identified six DDR-linked biomarkers for forecasting the prognosis of osteosarcoma patients. Our outcomes enhanced the understanding of DDR-related molecular mechanisms involved in osteosarcoma and provided potential therapeutic targets for osteosarcoma patients.

Association of Different Types of Osteoarthritis with Different Immune-Related Subtypes and Hub Genes.

Background: Osteoarthritis (OA) is a diverse disorder that most frequently affects elderly people and makes them disabled. Many investigations have shown that the etiology of OA depends on cartilage wear, but immunology also plays a significant role. Thus, the goal of this study was to define the immune-related etiology of OA. Methods: Data from the "Gene Expression Omnibus (GEO)" database were used to find differentially expressed genes (DEGs), and the "Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm" was employed to calculate the quantity of distinct immune cells. We analyzed the results to identify patient subgroups and compare major active pathways. Results: The macrophage cell population accounts for the greatest percentage of infiltrating immune cells in OA. One hundred and twenty-two common intersection genes were identified, with the network analysis of protein-protein interactions revealing ten hub genes related to OA, including CXCL8, JUN, ATF3, DUSP1, PTGS2, IL6, MMP9, FOS, NFKBIA, and MYC. The random forest model showed that memory-activated CD4 T cells are strongly correlated with other immune cell types, while neutrophils have the weakest correlation with other immune cell types. Violin plots showed that OA patients had a significantly larger quantity of plasma cells and resting mast cells, with a significantly smaller quantity of resting memory CD4 T cells and activated mast cells than healthy controls. Conclusions: Two immune-related subgroups of OA were identified by semi-supervised clustering analysis of microarray data, and core genes were also determined by network analysis. A group of the immune infiltrating cells was selected by random forest analysis suggesting they are related to the pathogenesis of OA.

Runoff nitrogen losses under confluence and diverging drainage systems in the sloped plot scale: A comparative study.

The drainage system is a key measure for regulating runoff nutrient losses on sloping farmlands. Confluence and diverging drainage systems are two drainage layouts representing natural water network systems and are widely distributed in sloping farmlands; however, the effects of these drainage systems on runoff nutrient losses in the sloped plots remain unclear. This study investigated the effects of different drainage systems on the characteristics of runoff nitrogen (N) losses in sloped plots using laboratory rainfall simulations. Three treatments, including bare slope (without drainage system, CK), confluence drainage system (T1), and diverging drainage system (T2), were used to compare the changes in concentrations and losses of total nitrogen (TN), dissolved nitrogen (DN), and particulate nitrogen (PN), and the DN:TN ratio in runoff under a combination of 1.8 mm min-1 rainfall intensity and three slope gradients (5°, 10°, and 15°). The results showed that the time to runoff was significantly delayed in T2 compared with that in CK and T1 across all slopes (p < 0.05). Accumulated runoff depth was considerably lower in T1 and T2 than in CK across all slopes (p < 0.05). The TN and PN concentrations in T1 were markedly lower than those in T2 on the 10° and 15° slopes (p < 0.05). The DN concentration in T1 was lowest at the 5° slope (p < 0.05). TN loss in T1 was 14.7-33.9% and 17.9-30.3% lower than those in CK and T2 across all slopes, respectively (p < 0.05). The PN loss in T1 was 56.7% and 53.3% lower than that in T2 on the 10° and 15° slopes, respectively (p < 0.05). DN loss in T1 was 39.3-72.5% lower than that in CK for all slopes (p < 0.05). DN:TN in T2 was lower than that in CK and T1 at the 10° and 15° slopes (p < 0.05). Our results confirm the effectiveness of drainage systems in reducing runoff nutrient losses in a sloped plot and demonstrate that the confluence drainage system is better at reducing N losses in runoff than diverging drainage systems.

Metformin ameliorates calcium oxalate crystallization and stone formation by activating the Nrf2/HO-1 signaling pathway: Two birds with one stone.

Deposition of calcium oxalate (CaOx) crystals and oxidative stress-induced injury of renal tubular epithelial cell are the primary pathogenic factors of nephrolithiasis. In this study we investigated the beneficial effects of metformin hydrochloride (MH) against nephrolithiasis and explored the underlying molecular mechanism. Our results demonstrated that MH inhibited the formation of CaOx crystals and promoted the transformation of thermodynamically stable CaOx monohydrate (COM) to more unstable CaOx dihydrate (COD). MH treatment effectively ameliorated oxalate-induced oxidative injury and mitochondrial damage in renal tubular cells and reduced CaOx crystal deposition in rat kidneys. MH also attenuated oxidative stress by lowering MDA level and enhancing SOD activity in HK-2 and NRK-52E cells and in a rat model of nephrolithiasis. In both HK-2 and NRK-52E cells, COM exposure significantlylowered the expressions of HO-1 and Nrf2, which was rescued by MH treatment even in the presence of Nrf2 and HO-1 inhibitors. In rats with nephrolithiasis, MH treatment significantly rescued the down-regulation of the mRNA and protein expression of Nrf2 and HO-1 in the kidneys. These results demonstrate that MH can alleviate CaOx crystal deposition and kidney tissue injury in rats with nephrolithiasis by suppressing oxidative stress and activating the Nrf2/HO-1 signaling pathway, suggesting the potential value of MH in the treatment of nephrolithiasis.

Fertilization and cultivation management promotes soil phosphorus availability by enhancing soil P-cycling enzymes and the phosphatase encoding genes in bulk and rhizosphere soil of a maize crop in sloping cropland.

Fertilization and cultivation managements exert significant effects on crop growth and soil-associated nutrients in croplands. However, there is a lack of knowledge regarding how these practices affect soil phosphorus-cycling enzymes and functional genes involved in regulating global P-cycling, especially under intense agricultural management practices in sloping croplands. A long-term field (15-year) trial was conducted in a 15° sloping field based on five treatments: no fertilizer amendments + downslope cultivation (CK); mixed treatment of mineral fertilizer and organic manure + downslope cultivation (T1); mineral fertilizer alone + downslope cultivation (T2); 1.5-fold mineral fertilizer + downslope cultivation (T3); and mineral fertilizer + contour cultivation (T4). Bulk and rhizosphere soil samples were collected after the maize crop was harvested to determine the P fraction, P-cycling enzymes, and phosphatase-encoding genes. Results indicated that fertilization management significantly increased the inorganic (Pi) and organic soil (Po) P fractions compared to CK, except for NaOH-extractable Po in T1 and T3 in bulk and rhizosphere soils, respectively. For the cultivation treatments, the content of Pi pools in the downslope cultivation of T1 and T3 was significantly larger than that in the contour cultivation of T4 in bulk and rhizosphere soils. However, the content of NaOH-extractable Po in T1 and T3 was lower compared to T4 in bulk soil and vice versa for the NaHCO3-P and HCl-Po fractions in the rhizosphere. We also found that fertilization and cultivation managements significantly increased the activity of acid phosphatase (ACP), alkaline phosphatase (ALP), phytase, phosphodiesterases (PDE), and phoC and phoD gene abundance in bulk and rhizosphere soils, with a larger effect on the activity of ALP and the phosphatase encoding phoD gene, especially in T1 and T3 in the rhizosphere. Soil organic carbon (SOC) and microbial biomass C and P (MBC and MBP) were the main predictors for regulating P-cycling enzymes and phoC- and phoD gene abundance. A strong association of P-cycling enzymes, especially ALP and phytase, and the abundance of phoD genes with the P fraction indicated that the soil P cycle was mainly mediated by microbial-related processes. Together, our results demonstrated that an adequate amount of mineral fertilizer alone or combined with organic fertilizer plus downslope cultivation is more effective in promoting soil P availability by enhancing the activity of ALP, phytase, and phoD genes. This provides valuable information for sustaining soil microbial-regulated P management practices in similar agricultural lands worldwide.

Maternal exposure to dietary uranium causes oxidative stress and thyroid disruption in zebrafish offspring.

The contamination of uranium in aquatic ecosystems has raised growing global concern. However, the understanding of its chronic effects on aquatic organisms is limited, particularly with regards to transgenerational toxicity. In this study, we evaluated the maternal transfer risk of uranium using zebrafish. Sexually mature female zebrafish were exposed to 2 and 20 ng/g of uranium-spiked food for 28 days. The induced bioconcentration, thyroid disruption, and oxidative stress in both the adults (F0) and their embryos (F1) were further investigated. Element analysis showed that uranium was present in both F0 and F1, with higher concentrations observed in F1, indicating significant maternal offloading to the offspring. Meanwhile, an increased malformation and decreased swim speed were observed in the F1. Thyroid hormone analysis revealed significant decreases in the levels of triiodothyronine (T3) in both the F0 adults and F1 embryos, but thyroxine (T4) was not significantly affected. Additionally, the activities of antioxidant defenses, including catalase (CAT) and superoxide dismutase (SOD), and the expression of glutathione (GSH) and malondialdehyde (MDA) were significantly altered in the F0 and F1 larvae at 120 hpf. The hypothalamic-pituitary-thyroid (HPT) axis, oxidative stress, and apoptosis-related gene transcription expression were also significantly affected in both generations. Taken together, these findings highlight the importance of considering maternal transfer in uranium risk assessments.

Advantages of 3D registration technology (3DRT) in clinical application of unruptured intracranial aneurysm follow-up: A novel method to judge aneurysm growth.

BACKGROUND AND PURPOSE: Currently available methods for determining aneurysm growth are not accurate enough. Therefore, we introduced a more intuitive and accurate 3D registration technology (3DRT) to judge the growth of aneurysms. MATERIALS AND METHODS: We developed an in-house technique for 3DRT and calculated its derivative parameters, voxel change rate (VCR), maximum growth vector (MGV), and parent artery coincidence (PAC). To verify the accuracy, growing aneurysms and stable aneurysms matching 1:3 were selected, and a 3DRT measurement was performed. We calculated the sensitivity, specificity, and accuracy of cases with VCR > 20%, MGV > 1 mm, and combined indicator of VCR > 20% + MGV >1 mm. In addition, we analyzed the cause of the poor registration effect, where the registration effect of PAC > 0.7 was considered acceptable. We also collected 24 consecutive aneurysms for agreement analysis of 2D manual measurement and 3DRT. RESULTS: Twenty-seven growing aneurysms and 81 stable aneurysms were included in the normal model group, and 88 aneurysms with good registration effect in the adjusted model group. For aneurysms with VCR > 20%, the sensitivity and the specificity were the highest at 81.48% and 91.35%, respectively, while in the adjusted model group, the sensitivity and the specificity increased to 94.44% and 94.29%, respectively. When using VCR > 20% as the growth metric, the AUC value in the normal and the adjusted model group was 0.856 and 0.947, respectively. The ICC between 2D manual measurements and the 3DRT was 0.95 (95%CI: 0.88-0.98), and the time spent between the two groups had a significant difference (10.96 min vs. 3.44 min, p<0.01, 95% CI, 6.49-8.53). CONCLUSIONS: A 3DRT can be used to determine the growth of the aneurysm more efficiently, intuitively, and accurately.

Formation of carnation-like ZIF-9 nanostructure to achieve superior electrocatalytic oxygen evolution.

Rational design and controllable synthesis of metal-organic frameworks nanosheets is critical for electrochemical catalysis. Herein, a carnation-like ZIF-9 nanostructure made of nanosheets is grown on nickel foam (ZIF-9/NF) by a simple one-step solvothermal method, the morphology evolution and the electrocatalytic oxygen evolution properties have been investigated by controlling the solvothermal time. The binder-free ZIF-9-d/NF (60 h, solvothermal time is 60 h) electrode delivers efficient electrocatalytic oxygen evolution reaction activity with low overpotentials of 312 and 337 mV at 50 and 100 mA cm-2, respectively. Furthermore, ZIF-9-d/NF (60 h) exhibits excellent stability without obvious attenuation for at least 30 h at 200 mA cm-2. The excellent performances can be attributed to the combination of the highly exposed active sites in the ZIF-9-d nanosheets, as well as the effective electron conduction and mass transfer. This work provides much possibilities for ZIF-9 nanosheets as binder-free electrode for electrocatalyst.

The effect of serving as a danwei leader before retirement on self-rated post-retirement health: empirical evidence from China.

BACKGROUND: Worker health is often influenced by their occupation type, and the accumulative effect of occupation has a significant impact on their health after retirement. Studies show that the type and level of occupation before retirement directly impact workers' self-rated post-retirement health. However, there is little research on the self-rated post-retirement health of danwei leaders in China. This study seeks to examine the self-rated health level of Chinese danwei leaders after retirement. Furthermore, the differences between their self-rated health level and that of retirees from other occupations are explored by examining the accumulative effect of occupation and the mechanism underlying these differences. METHODS: Based on 5,910 samples' data from the 2018 China Longitudinal Aging Social Survey, ordinary least squares, logit, and propensity score matching models are used to investigate the self-rated health level of Chinese danwei leaders after retirement, their differences with other occupations, and the corresponding mechanism. RESULTS: The results show that retired danwei leaders have higher self-rated health levels than retirees in other occupations. This was mainly found among female, non-eastern, married, not living with children, and highly educated respondents. The difference in self-rated health between retired danwei leaders and other retired groups was influenced by their post-retirement income and social status. CONCLUSIONS: In China, retired danwei leaders rated their health higher than retirees from other occupations. Danwei leaders have high socioeconomic status due to their occupation. Compared with other groups, their advantages are significant and enjoyed for a long time. Additionally, most danwei leaders have high social influence even after retirement and their higher income and social status have a positive impact on their self-rated health compared with other employees. This study provides empirical evidence from China and extends current literature on the effects of occupational type and level on self-rated health after retirement.

Remarkably Weak Anisotropy in Thermal Conductivity of Two-Dimensional Hybrid Perovskite Butylammonium Lead Iodide Crystals.

Two-dimensional (2D) hybrid organic-inorganic perovskites consisting of alternating organic and inorganic layers are a new class of layered structures. They have attracted increasing interest for photovoltaic, optoelectronic, and thermoelectric applications, where knowing their thermal transport properties is critical. We carry out both experimental and computational studies on thermal transport properties of 2D butylammonium lead iodide crystals and find their thermal conductivity is ultralow (below 0.3 W m-1 K-1) with very weak anisotropy (around 1.5) among layered crystals. Further analysis reveals that the unique structure with the preferential alignment of organic chains and complicated energy landscape leads to moderately smaller phonon lifetimes in the out-of-plane direction and comparable phonon group velocities in in-plane and out-of-plane directions. These new findings may guide the future design of novel hybrid materials with desired thermal conductivity for various applications.

Study on the nasal drug delivery system of PPX microcapsules in situ thermosensitive gel.

Pramipexole hydrochloride (PPX) is a dopamine receptor agonist for the treatment of Parkinson's disease. It does not penetrate easily into the brain due to the presence of the blood-brain barrier (BBB), which hinders the treatment of the disease. The nasal mucosal drug delivery system is an effective method to deliver drugs to the brain bypassing the blood-brain barrier and the concentration of drugs targeted to the brain by intranasal administration is quite low due to the limitation of the permeability of the nasal mucosa and the nasal environment. Therefore, this study innovatively encapsulates prepared PPX microcapsules in a temperature-sensitive in situ gel for intranasal drug delivery to increase the target concentration of the drug in the brain and prolong the duration of treatment. The gel formulation containing 24% poloxamer 407 and 6% poloxamer 188 and 0.3% ice chips as absorption enhancers formed a hard gel at 30.44-31.36oC and allowed a slow release within 12 hours. A pharmacokinetic comparison of the developed PPX microencapsulated temperature-sensitive in situ gel (PPX-MTISG) with PPX temperature-sensitive in situ gel (PPX-TISG) revealed that the microencapsulated nasal mucosal in situ gel was a more effective PPX brain-targeted drug delivery system.

Hepatitis B Virus-Induced Imbalance of Inflammatory and Antiviral Signaling by Differential Phosphorylation of STAT1 in Human Monocytes.

It is not clear how hepatitis B virus (HBV) modulates host immunity during chronic infection. In addition to the key mediators of inflammatory response in viral infection, monocytes also express a high-level IFN-stimulated gene, CH25H, upon response to IFN-α exerting an antiviral effect. In this study, the mechanism by which HBV manipulates IFN signaling in human monocytes was investigated. We observed that monocytes from chronic hepatitis B patients express lower levels of IFN signaling/stimulated genes and higher levels of inflammatory cytokines compared with healthy donors. HBV induces monocyte production of inflammatory cytokines via TLR2/MyD88/NF-κB signaling and STAT1-Ser727 phosphorylation and inhibits IFN-α-induced stat1, stat2, and ch25h expression through the inhibition of STAT1-Tyr701 phosphorylation and in an IL-10-dependent, partially autocrine manner. Further, we found that enhancement of STAT1 activity with a small molecule (2-NP) rescued HBV-mediated inhibition of IFN signaling and counteracted the induction of inflammatory cytokines. In conclusion, HBV contributes to the monocyte inflammatory response but inhibits their IFN-α/ß responsiveness to impair antiviral innate immunity. These effects are mediated via differential phosphorylation of Tyr701 and Ser727 of STAT1.

Dysregulated ferroptosis-related genes indicate potential clinical benefits for anti-PD-1/PD-L1 immunotherapy in lung adenocarcinoma.

BACKGROUND: Ferroptosis is an iron-dependent programmed cell death mechanism that influences the development of malignancy. Lung adenocarcinoma (LUAD) is the most common type of lung cancer with no known cure. Anti-PD-1/PD-L immunotherapy is effective for patients with partial LUAD. Therefore, there is an immediate requirement of novel markers to predict the individualised benefits of immunotherapy. METHODS: We manually collected the ferroptosis-related gene (FERG) set and employed the Wilcoxon rank-sum test to identify the differentially expressed FERGs. Subsequently, we constructed a recursive partitioning and regression tree (RPART) model to predict the benefits of anti-PD-1/PD-L1 immunotherapy. Subsequently, the ROC curve and AUC were used to evaluate the model efficiency in an independent dataset. RESULTS: In this study, we found that the dysregulated FERGs were closely associated with multiple metabolic processes in LUAD. Furthermore, we identified three ferroptosis-related tumour subtypes (F1, F3 and F3). The F3 subtype exhibited higher immunoactivity and lower tumour purity, mutation count and aneuploidy and had better survival outcomes compared with the other two subtypes, implying that FERGs played an important role in intertumoral immune heterogeneity. We further explored the role of FERGs in the anti-PD-1/PD-L1 immunotherapy. We identified a set of three-FERGs signature (CD44, G6PD and ZEB1) that acted as a promising indicator (AUC = 0.697) for the prediction of the benefits of anti-PD-1/PD-L1 immunotherapy. CONCLUSION: Ferroptosis, as emerging programmed cell death mechanism, was associated with cancer development. We used ferroptosis-related genes to predict the immunotherapy benefits that may facilitate the development of individualised anti-cancer treatment strategies.

Waterborne uranium causes toxic effect and thyroid disruption in zebrafish larvae.

Uranium is a radioactive element that is widely present in aquatic environment. However, limited knowledge is available about the effect of uranium on thyroid system, which plays a key role in the development of animals. In this study, zebrafish embryos were exposed to different environmentally relevant concentrations of uranium (2, 20 and 100 µg/L) for 120 h. The bioaccumulation, developmental toxicities, changes of thyroid hormones (THs) and key genes related to the hypothalamic-pituitary-thyroid (HPT) axis in larvae were analyzed after exposure. Results showed that uranium could bioaccumulate in zebrafish larvae, with the bioconcentration factors ranging from 49.6 to 523. Consequently, significant developmental toxicities and changes in locomotor activities were observed with a concentration-dependent manner. The levels of triiodothyronine (T3) levels in larvae were substantially decreased, whereas those of thyroxine (T4) were increased in fish bodies. The levels of THs were regulated by the negative feedback loops through HPT axis related genes, most of which (NIS, Deio1, Deio2, TRα, TSHß and UGT1ab) were significantly depressed after exposure to uranium. Our results suggest the potential toxicities and thyroid disruption of uranium on zebrafish, which would provide baseline data set for better understanding the impact of waterborne uranium on aquatic organisms and the associated mechanisms. This study also highlights the key role of thyroid disruption in the ecological risk assessment of uranium pollution.

A deep semantic segmentation correction network for multi-model tiny lesion areas detection.

BACKGROUND: Semantic segmentation of white matter hyperintensities related to focal cerebral ischemia (FCI) and lacunar infarction (LACI) is of significant importance for the automatic screening of tiny cerebral lesions and early prevention of LACI. However, existing studies on brain magnetic resonance imaging lesion segmentation focus on large lesions with obvious features, such as glioma and acute cerebral infarction. Owing to the multi-model tiny lesion areas of FCI and LACI, reliable and precise segmentation and/or detection of these lesion areas is still a significant challenge task. METHODS: We propose a novel segmentation correction algorithm for estimating the lesion areas via segmentation and correction processes, in which we design two sub-models simultaneously: a segmentation network and a correction network. The segmentation network was first used to extract and segment diseased areas on T2 fluid-attenuated inversion recovery (FLAIR) images. Consequently, the correction network was used to classify these areas at the corresponding locations on T1 FLAIR images to distinguish between FCI and LACI. Finally, the results of the correction network were used to correct the segmentation results and achieve segmentation and recognition of the lesion areas. RESULTS: In our experiment on magnetic resonance images of 113 clinical patients, our method achieved a precision of 91.76% for detection and 92.89% for classification, indicating a powerful method to distinguish between small lesions, such as FCI and LACI. CONCLUSIONS: Overall, we developed a complete method for segmentation and detection of WMHs related to FCI and LACI. The experimental results show that it has potential clinical application potential. In the future, we will collect more clinical data and test more types of tiny lesions at the same time.

Periodically hydrologic alterations decouple the relationships between physicochemical variables and chlorophyll-a in a dam-induced urban lake.

Periodically hydrologic alterations driven by seasonal change and water storage capacity management strongly modify physicochemical properties and chlorophyll-a (Chl-a) and their interactions in dam-induced lakes. However, the extent and magnitude of these changes still remain unclear. This study aimed to determine the effects of periodically hydrologic alterations on physicochemical variables and Chl-a in the dam-induced urban Hanfeng Lake, upstream of Three Gorges Reservoir. Shifts in Chl-a and 13 physicochemical variables were recorded monthly in the lake from January 2013 to December 2014. Chl-a was neither seasonal nor inter-annual differences while a few physical variables such as flow velocity (V) exhibited significantly seasonal variabilities, and chemical variables like total nitrogen (TN), nitrate-nitrogen (NO3-N), total phosphorus (TP), dissolved silica (DSi) were markedly inter-annual differences. Higher TN:TP (40:1) and lower NO3-N:DSi (0.8:1) relative to balanced stoichiometric ratios suggested changes in composition of phytoplankton communities and potentially increased proportion of diatom in Hanfeng Lake. Chl-a was predicable by combination of dissolved oxygen (DO), TN and DSi in dry season, and by V alone in wet season. During the whole study period, Chl-a was solely negatively correlated with TN:TP, indicating decline in N concentration and increase in P could therefore increase Chl-a. Our results highlight pronounced decoupling of linkages between Chl-a and physicochemical variables affected by periodically hydrologic alterations in dam-induced aquatic systems.

Highly Distorted Chiral Two-Dimensional Tin Iodide Perovskites for Spin Polarized Charge Transport.

Incorporating chiral organic molecules into organic/inorganic hybrid 2D metal-halide perovskites results in a novel family of chiral hybrid semiconductors with unique spin-dependent properties. The embedded chiral organic moieties induce a chiroptical response from the inorganic metal-halide sublattice. However, the structural interplay between the chiral organic molecules and the inorganic sublattice, as well as their synergic effect on the resulting electronic band structure need to be explored in a broader material scope. Here we present three new layered tin iodide perovskites templated by chiral (R/S-)methylbenzylammonium (R/S-MBA), i.e., (R-/S-MBA)2SnI4, and their racemic phase (rac-MBA)2SnI4. These MBA2SnI4 compounds exhibit the largest level of octahedral bond distortion compared to any other reported layered tin iodide perovskite. The incorporation of chiral MBA cations leads to circularly polarized absorption from the inorganic Sn-I sublattice, displaying chiroptical activity in the 300-500 nm wavelength range. The bandgap and chiroptical activity are modulated by alloying Sn with Pb, in the series of (MBA)2Pb1-xSnxI4. Finally, we show that vertical charge transport through oriented (R-/S-MBA)2SnI4 thin films is highly spin-dependent, arising from a chiral-induced spin selectivity (CISS) effect. We demonstrate a spin-polarization in the current-voltage characteristics as high as 94%. Our work shows the tremendous potential of these chiral hybrid semiconductors for controlling both spin and charge degrees of freedom.

Regulatory NK cells mediated between immunosuppressive monocytes and dysfunctional T cells in chronic HBV infection.

BACKGROUND AND AIMS: HBV infection represents a major health problem worldwide, but the immunological mechanisms by which HBV causes chronic persistent infection remain only partly understood. Recently, cell subsets with suppressive features have been recognised among monocytes and natural killer (NK) cells. Here we examine the effects of HBV on monocytes and NK cells. METHODS: Monocytes and NK cells derived from chronic HBV-infected patients and healthy controls were purified and characterised for phenotype, gene expression and cytokines secretion by flow cytometry, quantitative real-time (qRT)-PCR, ELISA and western blotting. Culture and coculture of monocytes and NK cells were used to determine NK cell activation, using intracellular cytokines staining. RESULTS: In chronic HBV infection, monocytes express higher levels of PD-L1, HLA-E, interleukin (IL)-10 and TGF-ß, and NK cells express higher levels of PD-1, CD94 and IL-10, compared with healthy individuals. HBV employs hepatitis B surface antigen (HBsAg) to induce suppressive monocytes with HLA-E, PD-L1, IL-10 and TGF-ß expression via the MyD88/NFκB signalling pathway. HBV-treated monocytes induce NK cells to produce IL-10, via PD-L1 and HLA-E signals. Such NK cells inhibit autologous T cell activation. CONCLUSIONS: Our findings reveal an immunosuppressive cascade, in which HBV generates suppressive monocytes, which initiate regulatory NK cells differentiation resulting in T cell inhibition.