The OsZIP2 transporter is involved in root-to-shoot translocation and intervascular transfer of cadmium in rice.

Cadmium (Cd) is a toxic metal that poses serious threats to human health. Rice is a major source of dietary Cd but how rice plants transport Cd to the grain is not fully understood. Here, we characterize the function of the ZIP (ZRT, IRT-like protein) family protein, OsZIP2, in the root-to-shoot translocation of Cd and intervascular transfer of Cd in nodes. OsZIP2 is localized at the plasma membrane and exhibited Cd2+ transport activity when heterologously expressed in yeast. OsZIP2 is strongly expressed in xylem parenchyma cells in roots and in enlarged vascular bundles in nodes. Knockout of OsZIP2 significantly enhanced root-to-shoot translocation of Cd and alleviated the inhibition of root elongation by excess Cd stress; whereas overexpression of OsZIP2 decreased Cd translocation to shoots and resulted in Cd sensitivity. Knockout of OsZIP2 increased Cd allocation to the flag leaf but decreased Cd allocation to the panicle and grain. We further reveal that the variation of OsZIP2 expression level contributes to grain Cd concentration among rice germplasms. Our results demonstrate that OsZIP2 functions in root-to-shoot translocation of Cd in roots and intervascular transfer of Cd in nodes, which can be used for breeding low Cd rice varieties.

The heart rate non-dipping pattern was associated with target organ damage in patients with chronic kidney disease.

PURPOSE: We performed the study to investigate the association between heart rate (HR) non-dipping pattern and target organ damage in patients with chronic kidney disease (CKD) and hypertension. METHODS: In this cross-sectional study, 447 patients with CKD and hypertension were enrolled. 24 h ambulatory blood pressure monitoring was conducted. Linear regression and logistic regression analysis were conducted to investigate the association between HR non-dipping pattern and target organ damage, including estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMI), and left ventricular hypertrophy (LVH). RESULTS: Overall, 261 patients (58.4%) followed non-dipping patterns of HR. HR non-dipping pattern remained to be significantly associated with reduced eGFR (ß: -0.384; 95% CI: -0.719 to -0.050; p = 0.025) and the higher prevalence of CKD stages 4-5 (OR: 2.141; 95% CI: 1.153 to 3.977; p = 0.016). Meanwhile, HR non-dipping pattern was independently associated with LVMI (ß: 0.021; 95% CI: 0.000 to 0.041; p = 0.049) and LVH (OR: 1.78; 95% CI: 1.07 to 2.96; p = 0.027) after adjusting for confounding factors. CONCLUSIONS: HR non-dipping pattern was independently associated with impaired renal function and cardiac damage. Non-dipping HR deserves further attention and needs to be detected and treated during the management of CKD patients.

Microstructural Changes in the Cerebral White Matter After 12 Months of CPAP Treatment for Moderate to Severe Obstructive Sleep Apnoea: A TBSS Study.

Introduction: Continuous positive airway pressure (CPAP) therapy improves clinical symptoms in patients with obstructive sleep apnea (OSA); however, the mechanism of this clinical improvement and how it may be associated with the restoration of white matter (WM) structures in the brain is unclear. Therefore, this study investigated the relationship between the structural recovery of brain WM and improvements in cognitive function and emotion after long-term (12 months) CPAP treatment in patients with OSA. Methods: We collected data from 17 patients with OSA before and 12 months after CPAP treatment, including sleep monitoring, clinical assessment, and diffusion tensor imaging (DTI) magnetic resonance imaging. Results: We observed a partial reversible recovery of brain WM (mean and radial diffusion coefficients) after treatment. This recovery involved the commissural fibers (cingulum, body of corpus callosum), projection fibers (retrolenticular part of the internal capsule, posterior thalamic radiation, posterior limb of the internal capsule, superior corona radiata, posterior corona radiata), association fibers (external capsule, superior longitudinal fasciculus, inferior longitudinal fasciculus), and other regions. In addition, the improvements in WM fibers in one part of the brain significantly were correlated with the Hamilton Anxiety Scale and Hamilton Depression Scale scores. Discussion: Our results suggest that reversible recovery of reduced brain WM integrity due to OSA may require longer CPAP treatment. Moreover, changes in the integrity of the commissural fibers were associated with emotion regulation. These restored WM areas may explain the cognitive and mood improvements observed after OSA treatment.

Abnormal dynamic functional connectivity and topological properties of cerebellar network in male obstructive sleep apnea.

PURPOSE: To investigate dynamic functional connectivity (dFC) within the cerebellar-whole brain network and dynamic topological properties of the cerebellar network in obstructive sleep apnea (OSA) patients. METHODS: Sixty male patients and 60 male healthy controls were included. The sliding window method examined the fluctuations in cerebellum-whole brain dFC and connection strength in OSA. Furthermore, graph theory metrics evaluated the dynamic topological properties of the cerebellar network. Additionally, hidden Markov modeling validated the robustness of the dFC. The correlations between the abovementioned measures and clinical assessments were assessed. RESULTS: Two dynamic network states were characterized. State 2 exhibited a heightened frequency, longer fractional occupancy, and greater mean dwell time in OSA. The cerebellar networks and cerebrocerebellar dFC alterations were mainly located in the default mode network, frontoparietal network, somatomotor network, right cerebellar CrusI/II, and other networks. Global properties indicated aberrant cerebellar topology in OSA. Dynamic properties were correlated with clinical indicators primarily on emotion, cognition, and sleep. CONCLUSION: Abnormal dFC in male OSA may indicate an imbalance between the integration and segregation of brain networks, concurrent with global topological alterations. Abnormal default mode network interactions with high-order and low-level cognitive networks, disrupting their coordination, may impair the regulation of cognitive, emotional, and sleep functions in OSA.

Increase in HIV reservoir and T cell immune response after CoronaVac vaccination in people living with HIV.

Introduction: CoronaVac, an inactivated vaccine developed by Sinovac Life Sciences, has been widely used for protection against Coronavirus Disease 2019 (COVID-19). This study investigates its effect on the HIV reservoir and T cell repertoires in people living with HIV (PLWHs). Methods: Blood samples were collected from fifteen PLWHs who were administered at least two doses of CoronaVac between April 2021 and February 2022. The levels of cell-associated HIV RNA (CA HIV RNA) and HIV DNA, as well as the T cell receptor (TCR) repertoire profiles, TCR clustering and TCRß annotation, were studied. Results: A significant increase was observed in CA HIV RNA at 2 weeks (431.5 ± 164.2 copies/106 cells, P = 0.039) and 12 weeks (330.2 ± 105.9 copies/106 cells, P = 0.019) after the second dose, when compared to the baseline (0 weeks) (73.6 ± 23.7 copies/106 cells). Various diversity indices of the TCRß repertoire, including Shannon index, Pielou's evenness index, and Hvj Index, revealed a slight increase (P < 0.05) following CoronaVac vaccination. The proportion of overlapping TCRß clonotypes increased from baseline (31.9 %) to 2 weeks (32.5 %) and 12 weeks (40.4 %) after the second dose. We also found that the breadth and depth of COVID-19-specific T cells increased from baseline (0.003 and 0.0035) to 12 weeks (0.0066 and 0.0058) post the second dose. Conclusions: Our study demonstrated an initial increase in HIV reservoir and TCR repertoire diversity, as well as an expansion in the depth and breadth of COVID-19-specific T-cell clones among CoronaVac-vaccinated PLWHs. These findings provide important insights into the effects of COVID-19 vaccination in PLWHs.

Characterizing the Loss and Acquisition of Tn2-like Transposon in Klebsiella pneumoniae: Implications for Carbapemase Gene Dissemination.

Over one year, two KPC-producing and two non-KPC-producing Klebsiella pneumoniae strains were isolated from a patient. Genome and DNA hybridization analyses revealed the first three strains as a clonal lineage, with carbapenem resistance changes due to a Tn2-like transposon on an IncR/IncFII plasmid. The fourth strain, carrying three plasmids, caused a lethal infection and represented a different lineage. All strains belonged to the ST11-SL47-OL101 type. This study highlights the Tn2-like transposon's role in carbapenemase gene spread and the importance of distinguishing between bacterial colonization and infection.

Endovascular treatment versus standard medical treatment in patients with established large infarct: a cohort study.

BACKGROUND: Previous trials confirmed the benefit of endovascular treatment (EVT) in acute large core stroke, but the effect of EVT on outcomes in these patients based on non-contrast computed tomography (NCCT) in real-world clinical practice was unclear. The aim of this study was to explore the effect of EVT versus standard medical treatment (SMT) in patients with large ischemic core stroke defined as Alberta Stroke Program Early CT Score (ASPECTS)≤5 based on NCCT alone. MATERIALS AND METHODS: Patients with acute large core stroke at 38 Chinese centers between November 2021 and February 2023 were reviewed from prospectively maintained databases. The primary outcome was favorable functional outcome (modified Rankin Scale score [mRS], 0-3) at 90 days. Safety outcomes included 48-hour symptomatic intracerebral hemorrhage (sICH) and 90-day mortality. RESULTS: Of 745 eligible patients recruited at 38 stroke centers between November 2021 and February 2023, 490 were treated with EVT and 255 with SMT alone. One hundred and eighty-one (36.9%) in the EVT group achieved favorable functional independence versus 48 (18.8%) treated with SMT only (adjusted risk ratio [RR], 1.86; 95% CI, 1.43 to 2.42, P<0.001; adjusted risk difference [RD], 13.77; 95% CI, 7.40 to 20.15, P<0.001). The proportion of sICH was significantly higher in patients undergoing EVT (13.3% vs. 2.4%; adjusted RR, 5.17; 95% CI, 2.17 to 12.32, P<0.001; adjusted RD, 10.10; 95% CI, 6.12 to 14.09, P<0.001). No significant difference of mortality between the groups was observed (41.8% vs. 49.0%; adjusted RR, 0.91; 95% CI, 0.77 to 1.07, P=0.24; adjusted RD, -5.91; 95% CI, -12.91 to 1.09, P=0.1). CONCLUSION: Among patients with acute large core stroke based on NCCT in real world, EVT is associated with better functional outcomes at 90 days despite of higher risk of sICH. Rates of procedure-related complications were high in the EVT group.

Association of hepatic steatosis and liver fibrosis with chronic obstructive pulmonary disease among adults.

With high prevalence and substantial mortality, metabolic dysfunction-associated steatotic liver disease and chronic obstructive pulmonary disease (COPD) are significant public health concerns. Utilizing a large, population-based dataset from the National Health and Nutrition Examination Survey, our study probes the relationship between COPD prevalence and hepatic steatosis and fibrosis, as measured by Vibration-Controlled Transient Elastography. We analyzed data from 693 individuals with COPD and 7229 without. Through weighted multivariate logistic regression analysis, a restricted cubic spline curve, and threshold effect analysis, we investigated the correlation between the severity of hepatic steatosis and fibrosis and the presence of COPD. Our findings revealed a positive correlation between the controlled attenuation parameter (CAP) and COPD prevalence [OR = 1.03 (95% CI 1.01, 1.05)], even after multivariate adjustment. Furthermore, we observed a U-shaped association between CAP and COPD, where the inflection point, CAP value of 264.85 dB/m, corresponded to the lowest COPD prevalence. Our study emphasizes a substantial and complex link between hepatic steatosis and COPD. These findings urge healthcare professionals to factor liver health into COPD management and prompt further exploration into the underlying mechanisms. This could pave the way for the development of improved prevention and treatment strategies.

Real-world applications of the new grading system in lung adenocarcinoma: A study of 907 patients focusing on revealing the relationship between pathologic grade and genetic status.

BACKGROUND: The status of the lung adenocarcinoma (LUAD) grading system and the association between LUAD differentiation, driver genes, and clinicopathological features remain to be elucidated. METHODS: We included patients with invasive non-mucinous LUAD, evaluated their differentiation, and collected available clinicopathological information, gene mutations, and analyzed clinical outcomes. RESULTS: Among the 907 patients with invasive non-mucinous LUAD, 321 (35.4 %) were poorly differentiated, 422 (46.5 %) were moderately differentiated, and 164 (18.1 %) were well differentiated. EGFR mutation was more common in the LUADs accompanied without CGP (complex glandular pattern) than LUADs with CGP (p < 0.001). Correlation analysis between mutations and clinical characteristics showed that EGFR gene mutation (p < 0.001), KRAS gene mutation (p < 0.05), and ALK gene rearrangement (p < 0.001) were significantly related to the degree of tumor differentiation, and the KRAS and ALK gene mutation frequencies were higher in the low-differentiation group than in the high and medium differentiation groups. The EGFR mutation frequency was higher in the well/moderately differentiated adenocarcinoma group. CONCLUSIONS: Our study adds to the evidence regarding the role of the grading system in prognosis. EGFR, KRAS, and ALK are related to the degree of tumor differentiation.

Effect of dental chew on reducing dental plaque, dental calculus and halitosis in beagle dogs.

Periodontosis is the most common clinical disease in adult dogs, which is mainly caused by plaque accumulation and seriously endangers the oral health of dogs and even cause kidney, myocardial, and liver problems in severe cases. The aim of this study was to determine the clinical efficacy of dental chew (Cature Brushing Treats product) with mechanical and chemical properties in beagles. The dogs in the experimental group were fed with a dental chew twice a day after meals; The control group had no treatment. Dental plaque was evaluated on the 14th day and 29th day, respectively. The concentration of volatile sulfur compounds (VSC) in the breath and dental calculus were also evaluated on the 29th day. The results showed that there was no significant difference in the indexes of dental plaque on the 14th day. While they had significantly reduced accumulation of plaque (37.63%), calculus (37.61%), and VSC concentration (81.08%) compared to when receiving no chew on the 29th day.

xSiGra: Explainable model for single-cell spatial data elucidation.

Recent advancements in spatial imaging technologies have revolutionized the acquisition of high-resolution multi-channel images, gene expressions, and spatial locations at the single-cell level. Our study introduces xSiGra, an interpretable graph-based AI model, designed to elucidate interpretable features of identified spatial cell types, by harnessing multi-modal features from spatial imaging technologies. By constructing a spatial cellular graph with immunohistology images and gene expression as node attributes, xSiGra employs hybrid graph transformer models to delineate spatial cell types. Additionally, xSiGra integrates a novel variant of Grad-CAM component to uncover interpretable features, including pivotal genes and cells for various cell types, thereby facilitating deeper biological insights from spatial data. Through rigorous benchmarking against existing methods, xSiGra demonstrates superior performance across diverse spatial imaging datasets. Application of xSiGra on a lung tumor slice unveils the importance score of cells, illustrating that cellular activity is not solely determined by itself but also impacted by neighboring cells. Moreover, leveraging the identified interpretable genes, xSiGra reveals endothelial cell subset interacting with tumor cells, indicating its heterogeneous underlying mechanisms within the complex cellular communications.

Global insect herbivory and its response to climate change.

Herbivorous insects consume a large proportion of the energy flow in terrestrial ecosystems and play a major role in the dynamics of plant populations and communities. However, high-resolution, quantitative predictions of the global patterns of insect herbivory and their potential underlying drivers remain elusive. Here, we compiled and analyzed a dataset consisting of 9,682 records of the severity of insect herbivory from across natural communities worldwide to quantify its global patterns and environmental determinants. Global mapping revealed strong spatial variation in insect herbivory at the global scale, showing that insect herbivory did not significantly vary with latitude for herbaceous plants but increased with latitude for woody plants. We found that the cation-exchange capacity in soil was a main predictor of levels of herbivory on herbaceous plants, while climate largely determined herbivory on woody plants. We next used well-established scenarios for future climate change to forecast how spatial patterns of insect herbivory may be expected to change with climate change across the world. We project that herbivore pressure will intensify on herbaceous plants worldwide but would likely only increase in certain biomes (e.g., northern coniferous forests) for woody plants. Our assessment provides quantitative evidence of how environmental conditions shape the spatial pattern of insect herbivory, which enables a more accurate prediction of the vulnerabilities of plant communities and ecosystem functions in the Anthropocene.

Trends in prevalence of multimorbidity for chronic diseases in China: serial cross-sectional surveys from 2009 to 2018.

BACKGROUND: Multimorbidity, individuals suffering from two or more chronic diseases, has become a major health challenge worldwide, especially in populous and prosperous cities, where studies of this phenomenon in China are limited. We examined the prevalence, trends, patterns, and associated factors of multimorbidity from 2009 to 2018 among community-dwelling adults in Guangzhou, China. METHODS: We conducted serial cross-sectional surveys for chronic diseases in Guangzhou, China, in 2009, 2013, and 2018. General and stratified prevalence were standardized using demographic data. Multivariable logistic regression and hierarchical cluster analysis were applied to identify associated factors and to assess the correlations and patterns of multimorbidity, respectively. RESULTS: This study included 23,284 adults aged 18 and over in 2009, 18,551 in 2013, and 15,727 in 2018. The standardized prevalence of multimorbidity increased substantially, with 12.69% (95% CI: 10.45-15.33) in 2009, 25.44% (95% CI: 23.47-27.52) in 2013, and 35.13% (95% CI:32.64-37.70) in 2018 (P for trend <0.001). The highest bi- and triple-conditions of multimorbidity were dyslipidemia (DP) and overweight or obesity (OO) (12.54%, 95% CI: 11.68-13.46), and DP, OO, and Hypertension (HT) (3.99%, 95% CI: 3.47-4.58) in 2018. From 2009 to 2018, (1) The majority of multimorbidity patterns showed a high prevalence; (2) The percentage of participants with only one chronic condition was found lower, while the percentage with multiple conditions was higher. CONCLUSIONS: The prevalence of chronic disease multimorbidity in Guangzhou China, has increased substantially among adults. Effective policies targeting multimorbidity are urgently needed, especially for the health management of primary medical institutions.

Chronic exposure to tris(1,3-dichloro-2-propyl) phosphate: Effects on intestinal microbiota and serum metabolism in rats.

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a widely used organophosphate ester that can adversely affect animal or human health. The intestinal microbiota is critical to human health. High-dose exposure to TDCIPP can markedly affect the intestinal ecosystem of mice, but the effects of long-term exposure to lower concentrations of TDCIPP on the intestinal flora and body metabolism remain unclear. In this study, TDCIPP was administered to Sprague-Dawley rats by gavage at a dose of 13.3 mg/kg bw/day for 90 days. TDCIPP increased the relative weight of the kidneys (P = 0.017), but had no effect on the relative weight of the heart, liver, spleen, lungs, testes, and ovaries (P > 0.05). 16 S rRNA gene sequencing revealed that long-term TDCIPP exposure affected the diversity, relative abundance, and functions of rat gut microbes. The serum metabolomics of the rats showed that TDCIPP can disrupt the serum metabolic profiles, result in the up-regulation of 26 metabolites and down-regulation of 3 metabolites, and affect multiple metabolic pathways in rat sera. In addition, the disturbed genera and metabolites were correlated. The functions of some disturbed gut microbes were consistent with the affected metabolic pathways in the sera, and these metabolic pathways were all associated with kidney disease, suggesting that TDCIPP may cause kidney injury in rats by affecting the intestinal flora and serum metabolism.

The DNA loop release factor WAPL suppresses Epstein-Barr virus latent membrane protein expression to maintain the highly restricted latency I program.

Epstein-Barr virus (EBV) uses latency programs to colonize the memory B-cell reservoir, and each program is associated with human malignancies. However, knowledge remains incomplete of epigenetic mechanisms that maintain the highly restricted latency I program, present in memory and Burkitt lymphoma cells, in which EBNA1 is the only EBV-encoded protein expressed. Given increasing appreciation that higher order chromatin architecture is an important determinant of viral and host gene expression, we investigated roles of Wings Apart-Like Protein Homolog (WAPL), a host factor that unloads cohesins to control DNA loop size and that was discovered as an EBNA2-associated protein. WAPL knockout (KO) in Burkitt cells de-repressed LMP1 and LMP2A expression but not other EBV oncogenes to yield a viral program reminiscent of EBV latency II, which is rarely observed in B-cells. WAPL KO also increased LMP1/2A levels in latency III lymphoblastoid cells. WAPL KO altered EBV genome architecture, triggering formation of DNA loops between the LMP promoter region and the EBV origins of lytic replication (oriLyt). Hi-C analysis further demonstrated that WAPL KO reprograms EBV genomic DNA looping. LMP1 and LMP2A de-repression correlated with decreased histone repressive marks at their promoters. We propose that EBV coopts WAPL to negatively regulate latent membrane protein expression to maintain Burkitt latency I. Author Summary: EBV is a highly prevalent herpesvirus etiologically linked to multiple lymphomas, gastric and nasopharyngeal carcinomas, and multiple sclerosis. EBV persists in the human host in B-cells that express a series of latency programs, each of which is observed in a distinct type of human lymphoma. The most restricted form of EBV latency, called latency I, is observed in memory cells and in most Burkitt lymphomas. In this state, EBNA1 is the only EBV-encoded protein expressed to facilitate infected cell immunoevasion. However, epigenetic mechanisms that repress expression of the other eight EBV-encoded latency proteins remain to be fully elucidated. We hypothesized that the host factor WAPL might have a role in restriction of EBV genes, as it is a major regulator of long-range DNA interactions by negatively regulating cohesin proteins that stabilize DNA loops, and WAPL was found in a yeast 2-hybrid screen for EBNA2-interacting host factors. Using CRISPR together with Hi-ChIP and Hi-C DNA architecture analyses, we uncovered WAPL roles in suppressing expression of LMP1 and LMP2A, which mimic signaling by CD40 and B-cell immunoglobulin receptors, respectively. These proteins are expressed together with EBNA1 in the latency II program. We demonstrate that WAPL KO changes EBV genomic architecture, including allowing the formation of DNA loops between the oriLyt enhancers and the LMP promoter regions. Collectively, our study suggests that WAPL reinforces Burkitt latency I by preventing the formation of DNA loops that may instead support the latency II program.

Social network analysis of a decade-long collaborative innovation network between hospitals and the biomedical industry in China.

Collaborative innovation between hospitals and biomedical enterprises is crucial for ensuring breakthroughs in their development. This study explores the structural characteristics and examines the main roles of associated key actors of collaborative innovation between hospitals and biomedical enterprises in China. Using the jointly owned patent data within the country's healthcare industry, a decade-long collaborative innovation network between hospitals and biomedical enterprises in China was established and analyzed through social network analysis. The results revealed that the overall levels of collaborative innovation network density, collaborative frequency, and network connectivity were significantly low, especially in less-developed regions. In terms of actors with higher degree centrality, hospitals accounted for the majority, whereas a biomedical enterprise in Shenzhen had the highest degree centrality. Organizations in underdeveloped and northwest regions and small players were more likely to implement collaborative innovation. In conclusion, a collaborative innovation network between hospitals and biomedical enterprises in China demonstrated high dispersion and poor development levels. Stimulating organizations' initiatives for collaborative innovation may enhance quality and quantity of such innovation. Policy support and economic investments, strategic collaborative help, and resource and partnership optimization, especially for small players and in less-developed and northwest regions, should be encouraged to enhance collaborative innovation between hospitals and the biomedical industry in China and other similar countries or regions.

Diversity inhibits foliar fungal diseases in grasslands: Potential mechanisms and temperature dependence.

A long-standing debate exists among ecologists as to how diversity regulates infectious diseases (i.e., the nature of diversity-disease relationships); a dilution effect refers to when increasing host diversity inhibits infectious diseases (i.e., negative diversity-disease relationships). However, the generality, strength, and potential mechanisms underlying negative diversity-disease relationships in natural ecosystems remain unclear. To this end, we conducted a large-scale survey of 63 grassland sites across China to explore diversity-disease relationships. We found widespread negative diversity-disease relationships that were temperature-dependent; non-random diversity loss played a fundamental role in driving these patterns. Our study provides field evidence for the generality and temperature dependence of negative diversity-disease relationships in grasslands, becoming stronger in colder regions, while also highlighting the role of non-random diversity loss as a mechanism. These findings have important implications for community ecology, disease ecology, and epidemic control.