Identification of key antigenic sites in hemagglutinin of H10N3 avian influenza virus.

The H10 avian influenza viruses (AIV) have been detected in both birds and mammals. Recently, the cases of human infection with H10N8 and H10N3 in China pose high risk to public health. However, the antigenic sites in hemagglutinin (HA) of H10 are poorly understood. In this study, 3 monoclonal antibodies (MAb), designated as 1F4, 6B3 and 6G12, against the HA protein of the H10N3 strain A/chicken/Taizhou/498/2021(H10N3) (TZ498), were first generated. All of these MAb could effectively inhibit TZ498 in haemagglutination inhibition assay and microneutralization assay. Four novel antigenic sites at positions 135, 208, 227, and 266 (H10 numbering) were identified in the HA of TZ498 through escape mutants selected by these 3 MAb. Moreover, natural mutations at positions 135 and 227 were found in the H10 field strains. All these not only provide novel insights into the molecular markers for monitoring the antigenic variation of H10 but also be helpful for developing efficient control strategies against H10.

Phosphorylated NPY1R regulates phenotypic transition of vascular smooth muscle cells, inflammatory response and macrophage infiltration to promote intracranial aneurysm progression.

BACKGROUND: Rupture of intracranial aneurysm (IA) could give rise to spontaneous subarachnoid hemorrhage, leading to a high disability rate and even death. NPY1R expression was upregulated in aneurysm tissues of IA patients. However, the role and underlying mechanism of NPY1R remains unknown. METHODS: The IA model of mice was established using inducing systemic hypertension and injecting elastase. The expression of genes and proteins was detected by RT-qPCR and western blot. The number of T cells, macrophages, and neutrophils in IA mice was detected using flow cytometry and IF assay. The levels of inflammatory factors were measured using ELISA. Patho-morphology and inflammatory cells in aneurysm tissues were evaluated by HE staining. The interaction between TK and NPY1R was validated using Co-IP. RESULTS: NPY1R expression was greatly elevated in aneurysm tissues in IA patients and mice, which were positively related to macrophage infiltration. Besides, exogenous overexpression of NPY1R resulted in the promotion of contractile phenotype to the synthetic phenotype of vascular smooth muscle cells (VSMCs), inflammatory response and M1 macrophage polarization. In terms of the underlying mechanism, NPY1R protein could be modified by TK-mediated phosphorylation and TKI could decrease IA formation and suppresse contractile phenotype to synthetic phenotype of VSMCs, inflammatory response and M1 macrophage polarization in IA mice. Furthermore, ablating mouse macrophages abolished NPY1R overexpression-mediated promotion of IA formation and rupture in mice. CONCLUSION: Phosphorylated NPY1R contributed to IA progression through promoting contractile phenotype to synthetic phenotype of VSMCs, inflammatory response and M1 macrophage polarization in IA.

Tracing contaminants of emerging concern and their transformations in the whole treatment process of a municipal wastewater treatment plant using nontarget screening and molecular networking strategies.

This study employed nontarget screening with high-resolution mass spectrometry and molecular network strategy to characterize the occurrence and tranformation of contaminants of emerging concern (CECs) through a wastewater treatment plant in Guangzhou. We detected 70,631 compounds in positive mode and 14,423 in negative mode in influent, from which 94.5 % of these compounds were successfully eliminated after treatment. Among them, 510 chemicals were identified, with pharmaceuticals being the largest category excluding natural products, accounting for 146 compounds. And 29 CECs were semiquantified with concentrations ranging from 2.80 ng/L (Fluconazole) to 10,351 ng/L (Nicotine). The removal efficiency varied: 60 compounds were easily removable (>90 % removal), 17 were partially removable (40-90 % removal), and 44 were non-degradable (<40 % removal). Additionally, we tentatively identified transformation products (TPs) of CECs using a molecular network analysis, revealing over 20,000 compound pairs sharing common fragments, with 191 compounds potentially linked to 47 level 1 compounds, suggesting their role as TPs of CECs. These findings illuminated the actual treatment efficiency of wastewater treatment plants for CECs and the potential TPs, offering valuable insights for future improvements in wastewater management practices.

A Case Series of Refractory Pediatric Atopic Dermatitis Effectively Treated With Dupilumab in Combination With Abrocitinib.

Children with severe atopic dermatitis (AD), refractory to conventional systemic treatment as well as single-agent biologic and Janus kinase inhibitor (JAKi) such as abrocitinib, currently face a lack of treatment options. In response to this clinical conundrum, we present three cases of severe and refractory pediatric AD successfully managed with combined dupilumab and abrocitinib. These children had exhausted all conventional treatments and had undergone treatment with both dupilumab and abrocitinib individually, as well as dupilumab in conjunction with methotrexate. It was only when the combination of dupilumab and abrocitinib was introduced that they finally achieved noticeable and sustained improvements in disease control.

Up-regulated SLC25A39 promotes cell growth and metastasis via regulating ROS production in colorectal cancer.

Background: The mitochondrial transporter SLC25A39 has been implicated in the import of mitochondrial glutathione (mGSH) from the cytoplasm, crucial for mitigating oxidative stress and preserving mitochondrial function. Despite the well-established involvement of mitochondria in cancer, the functional impact of SLC25A39 on CRC progression remains elusive. Methods: The mRNA and protein expressions were detected by PCR, immunohistochemistry, and Western blot, respectively. Cell activity, cell proliferation, colony formation, and apoptosis were measured by CCK8 assay, EdU incorporation assay, plated colony formation assay, and flow cytometry, respectively. Cell migration was detected by wound healing and transwell chamber assay. The tumor microenvironment (TME), immune checkpoint molecules, and drug sensitivity of CRC patients were investigated using R language, GraphPad Prism 8 and online databases. Results: Here, we report a significant upregulation of SLC25A39 expression in CRC. Functional assays revealed that overexpression of SLC25A39 promoted CRC cell proliferation and migration while inhibiting apoptosis. Conversely, SLC25A39 knockdown suppressed cell growth and migration while enhancing apoptosis in vitro. Additionally, reduced SLC25A39 expression attenuated tumor growth in xenograft models. Mechanistically, elevated SLC25A39 levels correlated with reduced reactive oxygen species (ROS) accumulation in CRC. Furthermore, bioinformatic analyses unveiled the high SLC25A39 levels was associated with decreased expression of immune checkpoints and reduced responsiveness to immunotherapy. Single-cell transcriptomic profiling identified diverse cellular expression patterns of SLC25A39 and related immune regulators. Lastly, drug sensitivity analysis indicated potential therapeutic avenues targeting SLC25A39 in CRC. Conclusion Our findings underscore the pivotal role of SLC25A39 in CRC progression and suggest its candidacy as a therapeutic target in CRC management.

Uncovering the spatial characteristics of global net anthropogenic nitrogen input at high resolution and across 1.42 million lake basins.

Global Net Anthropogenic Nitrogen Input (NANI) at high resolution is crucial for assessing the impact of human activities on aquatic environments. Insufficient global high-resolution data sources and methods have hindered the effective examination of the global characteristics and driving forces of NANI. This study presents a general framework for calculating global NANI, providing estimates at a 5-arc-minute resolution and over 1.42 million lake basins in 2015. The results highlight the region near the Tropic of Cancer as a concentration area for high NANI and an inflection point for latitude-based accumulation variation. It also emphasizes the uneven distribution of NANI among continents, with Asia and Africa having the highest proportions, yet their high and low values are notably lower than those of Europe and South America. A similar pattern is observed in global lakes, where Asia has the smallest quantity and volume, but the highest NANI intensity. In contrast, North America and Europe have larger quantities and volumes but the lowest NANI intensity. The global distribution characteristics reveal a clustering pattern in high and low values, with 1.25 % of the area having a sum of NANI exceeding 20 %. The uncertainty analysis regarding model parameters indicates that continents with the highest NANI do not always exhibit the highest uncertainty. These results bridge the gap between global nitrogen sustainable management and anthropogenic nitrogen input. They support research on spatiotemporal changes and controlling factors of global river nutrient loads, as well as the impact of climatic factors on basin nitrogen loss and its variability.

Single-cell, single-nucleus and xenium-based spatial transcriptomics analyses reveal inflammatory activation and altered cell interactions in the hippocampus in mice with temporal lobe epilepsy.

BACKGROUND: Temporal lobe epilepsy (TLE) is among the most common types of epilepsy and often leads to cognitive, emotional, and psychiatric issues due to the frequent seizures. A notable pathological change related to TLE is hippocampal sclerosis (HS), which is characterized by neuronal loss, gliosis, and an increased neuron fibre density. The mechanisms underlying TLE-HS development remain unclear, but the reactive transcriptomic changes in glial cells and neurons of the hippocampus post-epileptogenesis may provide insights. METHODS: To induce TLE, 200 nl of kainic acid (KA) was stereotactically injected into the hippocampal CA1 region of mice, followed by a 7-day postinjection period. Single-cell RNA sequencing (ScRNA-seq), single-nucleus RNA sequencing (SnRNA-seq), and Xenium-based spatial transcriptomics analyses were employed to evaluate the changes in mRNA expression in glial cells and neurons. RESULTS: From the ScRNA-seq and SnRNA-seq data, 31,390 glial cells and 48,221 neuronal nuclei were identified. Analysis of the differentially expressed genes (DEGs) revealed significant transcriptomic alterations in the hippocampal cells of mice with TLE, affecting hundreds to thousands of mRNAs and their signalling pathways. Enrichment analysis indicated notable activation of stress and inflammatory pathways in the TLE hippocampus, while pathways related to axonal development and neural support were suppressed. Xenium analysis demonstrated the expression of all 247 genes across mouse brain sections, revealing the spatial distributions of their expression in 27 cell types. Integrated analysis of the DEGs identified via the three sequencing techniques revealed that Spp1, Trem2, and Cd68 were upregulated in all glial cell types and in the Xenium data; Penk, Sorcs3, and Plekha2 were upregulated in all neuronal cell types and in the Xenium data; and Tle4 and Sipa1l3 were downregulated in all glial cell types and in the Xenium data. CONCLUSION: In this study, a high-resolution single-cell transcriptomic atlas of the hippocampus in mice with TLE was established, revealing potential intrinsic mechanisms driving TLE-associated inflammatory activation and altered cell interactions. These findings provide valuable insights for further exploration of HS development and epileptogenesis.

Lipopolysaccharide Triggers Luminal Acidification to Promote Defense Against Bacterial Infection in Vaginal Epithelium.

The vaginal epithelium plays pivotal roles in host defense against pathogen invasion, contributing to the maintenance of an acidic microenvironment within the vaginal lumen through the activity of acid-base transport proteins. However, the precise defense mechanisms of the vaginal epithelium after a bacterial infection remain incompletely understood. This study showed that bacterial lipopolysaccharide (LPS) potentiated net proton efflux by up-regulating the expression of Na+-H+ exchanger 1 (NHE1) without affecting other acid-base transport proteins in vaginal epithelial cells. Pharmacologic inhibition or genetic knockdown of Toll-like receptor-4 and the extracellular signal-regulated protein kinase signaling pathway effectively counteracted the up-regulation of NHE1 and the enhanced proton efflux triggered by LPS in vaginal epithelial cells. In vivo studies revealed that LPS administration led to luminal acidification through the up-regulation of NHE1 expression in the rat vagina. Moreover, inhibition of NHE exhibited an impaired defense against acute bacterial infection in the rat vagina. These findings collectively indicate the active involvement of vaginal epithelial cells in facilitating luminal acidification during acute bacterial infection, offering potential insights into the treatment of bacterial vaginosis.

Association between adolescent depression and adult suicidal behavior: A systematic review and meta-analysis.

This meta-analysis aims to estimate the association between adolescent depression and adult suicidal behavior, while systematically evaluating gender differences reported in literature. A random-effects model was used to determine the pooled association, reporting odds ratios (ORs) with corresponding 95 % confidence intervals (CIs). Nine articles comprising over 6084 adolescents together showed that people with a history of depression in adolescence are more likely to gain suicidal behaviors during adulthood (OR = 3.97, 95 % Cl: 2.79, 5.63). Sex-specific analysis indicated that males who experienced depression in adolescence developed a higher incidence of suicidal behavior in adulthood compared to females with a similar history (Males: OR = 3.61, 95 % Cl: 1.02, 12.78; Females: OR = 3.56, 95 % Cl: 1.71, 7.43). Furthermore, suicide attempts emerged as the predominant outcome among various suicidal behaviors (OR = 3.43, 95 % Cl: 1.75, 6.71). This meta-analysis provides robust evidence that depression in adolescence significantly increases the risk of suicidal behavior in adulthood.

Muscle LIM protein of Macrobrachium nipponense (MnMLP) involved in immune and stress response.

The muscle LIM protein (MLP) is a member of the cysteine and glycine-rich protein (CSRP) family, composed of CSRP1, CSRP2 and CSRP3/MLP. MLP is involved in a multitude of functional roles, including cytoskeletal organization, transcriptional regulation, and signal transduction. However, the molecular mechanisms underlying its involvement in immune and stress responses remain to be elucidated. This study identified an MnMLP in the freshwater crustacean Macrobrachium nipponense. The isothermal titration calorimetry assay demonstrated that recombinant MnMLP was capable of coordinating with Zn2+. Upon challenge by Aeromonas veronii or WSSV, and exposure to CdCl2, up-regulation was recorded in the muscle and intestinal tissues, suggesting its involvement in immune and anti-stress responses. MnMLP protein was predominantly expressed in the cytoplasm of the transfected HEK-293T cells, but after treatment with LPS, Cd2+ or H2O2, the MnMLP was observed to be transferred into the nucleus. The comet assay demonstrated that the overexpression of MnMLP could mitigate the DNA damage induced by H2O2 in HEK-293T cells, suggesting the potential involvement of MnMLP in the DNA repair process. These findings suggest that DNA repair may represent a possible mechanism by which MnMLP may be involved in the host's defense against pathogens and stress.

Association Between Remnant Cholesterol and Nonalcoholic Fatty Liver Disease: A Systemic Review and Meta-Analysis.

Lipid disorders are related to the risk of nonalcoholic fatty liver disease (NAFLD). Remnant cholesterol (RC), a nonclassical and once-neglected risk factor for NAFLD, has recently received new attention. In this study, we assessed the relationship between the RC levels and NAFLD risk. We searched across PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure, with no restrictions on publication languages. Retrospective cohort studies and cross-sectional studies were enrolled from the inception of the databases until August 6, 2023. A random-effect model was applied to construct the mean difference, and a 95% confidence interval was applied to assess the relationship between the RC levels and NAFLD risk. We used two methods to estimate RC levels: Calculated-1 subtracts low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol from total cholesterol; Calculated-2 uses the Friedewald formula for LDL-C when triglycerides are <4.0 mmol/L, otherwise directly measured. A total of 265 published studies were selected through preliminary retrieval. Of these, six studies met the inclusion requirements and were enrolled in the meta-analysis. The RC level in the NAFLD group was significantly higher than that in the non-NAFLD group (mean difference: 0.18, 95% confidence interval: 0.10-0.26, P < 0.00001). We conducted subgroup analyses of computational methods and geographic regions. Notably, in the subgroup analysis of Calculation Method 2, the NAFLD group had significantly higher RC levels than the non-NAFLD group. On the other hand, in Calculation Method 1, the difference between the two groups was insignificant. In both the Asian and non-Asian populations, the RC levels were significantly higher in the NAFLD group than in the non-NAFLD group. The association of RC with an increased NAFLD risk was not dependent on the triglyceride. This meta-analysis suggests that elevated RC levels are associated with an increased risk of NAFLD. In addition to the conventional risk factors for fatty liver, clinicians should be concerned about the RC levels in the clinic.

Animal models of pulmonary arterial hypertension associated with atrial septal defect.

Pulmonary arterial hypertension (PAH) is a well-known complication of congenital heart disease (CHD). The lack of a satisfactory animal model for PAH associated with CHD (PAH-CHD) has limited progress in understanding the pathogenesis of PAH and the development of therapeutic agents. The development of a rat model for PAH associated with atrial septal defect (ASD) was achieved through atrial septal puncture and thermal ablation. Two and 4 weeks after modeling, hematoxylin and eosin staining showed that the vascular thickness, vascular thickness index, vascular area, and vascular area index in pulmonary arteries with an outer diameter of 50-300 µm in the PAH-ASD 2 and 4 weeks group were higher than those in the sham group (all P < 0.05). Alpha-smooth muscle actin (ɑ-SMA) staining showed that the medial thickness, medial thickness index, medial area, and medial area index in pulmonary arteries with an outer diameter of 50-300 µm at 2 and 4 weeks after modeling were significantly higher than those in the sham group (all P < 0.05). Additionally, mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) in the PAH-ASD 2 and 4 weeks groups were significantly higher than those in the sham group (both P < 0.05). Elastin van Gieson staining showed that the vascular obstruction score in the PAH-ASD 2 and 4 weeks group was significantly higher than that in the sham group (both P < 0.05). The PAH-ASD rats were successfully generated. These findings suggest that our model would be useful for further research into the pathogenesis, prevention, and treatment of PAH-ASD.

The different paradigms of NK cell death in patients with severe trauma.

Lymphocyte decline, particularly the depletion of NK cells, is a prominent feature of immunosuppression following severe tissue injury, heightening the susceptibility of severe trauma patients to life-threatening infections. Previous research indicates that the reduction in the number of NK cells is closely associated with the process of cell death. Nonetheless, the precise mechanism of NK cell death remains unknown. Here, we discovered that following severe traumatic injury, NK cells undergo several cell death pathways, dominated by apoptosis and pyroptosis with coexistence of necrotic cell death, immunogenic cell death, ferroptosis, and autophagy. These NK cells with different paradigms of death have diverse cytokine expression profiles and diverse interactions with other immune cells. Further exploration revealed that hypoxia was strongly associated with this diverse paradigm of NK cell death. Detailed investigation of paradigms of cell death may help to enhance comprehension of lymphopenia post-severe trauma, to develop new strategy in preventing immunosuppression, and then to improve outcome for severe trauma population.

The therapeutic effect and metabolic mechanism analysis of Guilingji on idiopathic oligo-asthenoteratozoospermia.

Introduction: Guilingji, a famous traditional Chinese medicine (TCM) formula, has been used to combat aging and male sexual dysfunction in China for centuries. To date, there has been little evidence-based clinical research on the use of Guilingji to treat idiopathic oligo-asthenoteratozoospermia (OAT), and the therapeutic mechanism from a metabolic perspective needs to be investigated further. Methods: This was a multicenter, double-blind, randomized controlled clinical study of 240 patients with idiopathic OAT recruited from four hospitals between January 2020 and January 2022. Patients were randomly assigned in a 1꞉1 ratio to receive oral Guilingji capsules or placebo for 12 weeks. The total progressive motile sperm count (TPMSC) was considered the primary outcome, and the other sperm parameters, seminal plasma parameters and serum hormones were considered the secondary outcome. A nontargeted metabolomics analysis of serum from OAT patients before and after Guilingji administration was performed by HPLC-MS to identify key metabolites. Furthermore, we used a rat model to show spermatogenesis phenotypes to validate the effect of the key metabolites screened from the patients. Results: At weeks 4, 8 and 12, TPMSC and other sperm parameters were significantly improved in the Guilingji group compared with the placebo group (P < 0.05 for all comparisons). At week 4, superoxide dismutase (SOD) and acrosomal enzyme activity of seminal plasma were significantly elevated in the Guilingji group compared with the placebo group, while reactive oxygen species (ROS) levels were significantly reduced (P < 0.05). Lactate dehydrogenase-X (LDHX) levels appeared to be significantly increased after 12 weeks continuous medication compared with Placebo group (P = 0.032). The metabolomics analysis of serum from OAT patients before and after Guilingji administration showed that the glucose-6-phosphate (G6P) concentration in patients' serum was significantly elevated after Guilingji treatment. Compared to the control, when Kidney-Yang deficiency model rats were treated with Guilingji or its key intermediate metabolite G6P, their sperm concentration and spermatozoic activity were improved similarly, and their structural damage of rat's testicular and epididymal tissues were recovered. Conclusion: This study provided valuable clinical evidence for the utility of Guilingji as a treatment for OAT. These findings thus demonstrate that G6P is involved in the therapeutic mechanism of Guilingji in OAT treatment based on clinical and rat intervention studies.

Sex-specific association of peripheral blood cell indices and inflammatory markers with depressive symptoms in early adolescence.

BACKGROUND: Previous studies have reported the correlation of dysregulated blood cell indices and peripheral inflammatory markers with depression in adults but limited studies have examined this correlation in early adolescents. METHODS: This study used data from the Chinese Early Adolescents Cohort Study, which was conducted in Anhui, China. Students' depression symptoms were repeatedly measured using the Chinese version of the Center for Epidemiological Studies Depression Scale for Children. Students' blood samples were collected in September 2019 and September 2021. The peripheral blood cell counts and inflammatory marker levels were determined using routine blood tests. Multivariable regression models were used to explore the associations between blood cell indices and adolescent depressive symptoms in both the whole sample and the sex-stratified samples. RESULTS: The white blood cell (WBC) count, neutrophil count (NC), platelet (PLT) count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, and systemic immune inflammation index (SII) were positively correlated with the severity of depressive symptoms during follow-up. The mean corpuscular volume (MCV), mean hemoglobin (HGB) volume (MCH), and mean corpuscular HGB concentration (MCHC) exhibited negative temporal correlations with depressive symptoms. Additionally, several sex-specific blood cell markers were correlated with depression. Male adolescents with increased red blood cell (RBC) and female adolescents with decreased HGB levels and upregulated WBC, NC, NLR, and SII levels exhibited severe depressive symptoms at follow-up. CONCLUSIONS: These findings suggested the potential usefulness of peripheral blood cell indices in the assessment of depression in early adolescents.

Functional Analysis of Forkhead Transcription Factor Fd59a in the Spermatogenesis of Drosophila melanogaster.

Spermatogenesis is critical for insect reproduction and is regulated by many different genes. In this study, we found that Forkhead transcription factor Fd59a functions as a key factor in the spermatogenesis of Drosophila melanogaster. Fd59a contains a conversed Forkhead domain, and it is clustered to the FoxD subfamily with other FoxD members from some insect and vertebrate species. Mutations in Fd59a caused swelling in the apical region of the testis. More importantly, fewer mature sperm were present in the seminal vesicle of Fd59a mutant flies compared to the control flies, and the fertility of Fd59a2/2 mutant males was significantly lower than that of the control flies. Immunofluorescence staining showed that the homeostasis of the testis stem cell niche in Fd59a2/2 mutant and Fd59a RNAi flies was disrupted and the apoptosis of sperm bundles was increased. Furthermore, results from RNA sequencing and qRT-PCR suggested that Fd59a can regulate the expression of genes related to reproductive process and cell death. Taken together, our results indicated that Fd59a plays a key role in the spermatogenesis of Drosophila.

Deletion of the alr gene in Brucella suis S2 attenuates virulence by enhancing TLR4-NF-κB-NLRP3- mediated host inflammatory responses.

Brucella is an intracellular parasitic bacterium lacking typical virulence factors, and its pathogenicity primarily relies on replication within host cells. In this study, we observed a significant increase in spleen weight in mice immunized with a Brucella strain deleted of the gene for alanine racemase (Alr), the enzyme responsible for alanine racemization (Δalr). However, the bacterial load in the spleen markedly decreased in the mutant strain. Concurrently, the ratio of white pulp to red pulp in the spleen was increased, serum IgG levels were elevated, but no significant damage to other organs was observed. In addition, the inflammatory response was potentiated and the NF-κB-NLRP3 signaling pathway was activated in macrophages (RAW264.7 Cells and Bone Marrow-Derived Cells) infect ed with the Δalr mutant. Further investigation revealed that the Δalr mutant released substantial amounts of protein in a simulated intracellular environment which resulted in heightened inflammation and activation of the TLR4-NF-κB-NLRP3 pathway in macrophages. The consequent cytoplasmic exocytosis reduced intracellular Brucella survival. In summary, cytoplasmic exocytosis products resulting from infection with a Brucella strain deleted of the alr gene effectively activated the TLR4-NFκB-NLRP3 pathway, triggered a robust inflammatory response, and reduced bacterial survival within host cells. Moreover, the Δalr strain exhibits lower toxicity and stronger immunogenicity in mice.

Local risk factors for one-year dental implant loss and late loss in 287 failed implants caused by peri-implantitis or infection after prosthesis loading: a retrospective study.

The purpose of this paper was to retrospectively assess the local factors that are likely to be associated with the risks for one-year dental implant loss.A retrospective study was designed and implemented. The sample consisted of patients who underwent an implant loss or removal caused by peri-implantitis or infection after prosthesis loading. The chi-squared test and generalised estimating equations (GEE) were used to explore the potential risk factors for one-year implant loss. A total of 279 patients with 287 failed implants were enrolled in this study. Immediate implant placement exhibited a 3.373 (95% CI: 1.652 to 6.886) significantly increased risk to experience one-year implant loss than early and late implant placement (p = 0.001). In addition, implants loaded during a healing period fewer than two months after implant placement were at 18.139 (95% CI: 8.925 to 36.866) significantly higher risk of one-year implant loss when compared with those that loaded within more than two months after implant placement (p < 0.001). Smokers were 1.866 (OR = 1.866,95% CI: 0.993 to 3.510) times as high risk for one-year implant loss as non-smokers, but there were no significant statistical differences (p = 0.053). Immediate implant placement and early implant loading were considered risk factors for one-year implant loss.

Ionic Current Saturation Enabled by Cation Gating Effect in Metal-Organic-Framework Membranes.

Ion transport through nanoporous two-dimensional (2D) membranes is predicted to be tunable by controlling the charging status of the membranes' planar surfaces, the behavior of which though remains to be assessed experimentally. Here we investigate ion transport through intrinsically porous membranes made of 2D metal-organic-framework layers. In the presence of certain cations, we observe a linear-to-nonlinear transition of the ionic current in response to the applied electric field, the behavior of which is analogous to the cation gating effect in the biological ion channels. Specifically, the ionic currents saturate at transmembrane voltages exceeding a few hundreds of millivolts, depending on the concentration of the gating cations. This is attributed to the binding of cations at the membranes' surfaces, tuning the charging states there and affecting the entry/exit process of translocating ions. Our work also provides 2D membranes as candidates for building nanofluidic devices with tunable transport properties.

The functional diversity-productivity relationship of woody plants is climatically sensitive.

Plot-scale experiments indicate that functional diversity (FD) plays a pivotal role in sustaining ecosystem functions such as net primary productivity (NPP). However, the relationships between functional diversity and NPP across larger scale under varying climatic conditions are sparsely studied, despite its significance for understanding forest-atmosphere interactions and informing policy development. Hence, we examine the relationships of community-weighted mean (CWM) and functional dispersion (FDis) of woody plant traits on NPP across China and if such relationships are modulated by climatic conditions at the national scale. Using comprehensive datasets of distribution, functional traits, and productivity for 9120 Chinese woody plant species, we evaluated the distribution pattern of community-weighted mean and functional dispersion (including three orthogonal trait indicators: plant size, leaf morphology, and flower duration) and its relationships with NPP. Finally, we tested the effects of climatic conditions on community-weighted mean/functional dispersion-NPP relationships. We first found overall functional diversity-NPP relationships, but also that the magnitude of these relationships was sensitive to climate, with plant size community-weighted mean promoting NPP in warm regions and plant size functional dispersion promoting NPP in wet regions. Second, warm and wet conditions indirectly increased NPP by its positive effects on community-weighted mean or functional dispersion, particularly through mean plant size and leaf morphology. Our study provides comprehensive evidence for the relationships between functional diversity and NPP under varying climates at a large scale. Importantly, our results indicate a broadening significance of multidimensional plant functional traits for woody vegetation NPP in response to rising temperatures and wetter climates. Restoration, reforestation actions and natural capital accounting need to carefully consider not only community-weighted mean and functional dispersion but also their interactions with climate, to predict how functional diversity may promote ecosystem functioning under future climatic conditions.