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Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) is the primary treatment for ischemic stroke. However, rtPA treatment can substantially increase blood‐brain barrier (BBB) permeability and susceptibility to hemorrhagic transformation. Herein, the mechanism underlying the side effects of rtPA treatment is investigated and demonstrated that ferroptosis plays an important role. The ferroptosis inhibitor, liproxstatin‐1 (Lip) is proposed to alleviate the side effects. A well‐designed macrocyclic carrier, glucose‐modified azocalix[4]arene (GluAC4A), is prepared to deliver Lip to the ischemic site. GluAC4A bound tightly to Lip and markedly improved its solubility. Glucose, modified at the upper rim of GluAC4A, imparts BBB targeting to the drug delivery system owing to the presence of glucose transporter 1 on the BBB surface. The responsiveness of GluAC4A to hypoxia due to the presence of azo groups enabled the targeted release of Lip at the ischemic site. GluAC4A successfully improved drug accumulation in the brain, and Lip@GluAC4A significantly reduced ferroptosis, BBB leakage, and neurological deficits induced by rtPA in vivo. These findings deepen the understanding of the side effects of rtPA treatment and provide a novel strategy for their effective mitigation, which is of great significance for the treatment and prognosis of patients with ischemic stroke. [ABSTRACT FROM AUTHOR]

Tertiary lymphoid structure (TLS) can predict the prognosis and sensitivity of tumors to immune checkpoint inhibitors (ICIs) therapy, whether it can be noninvasively predicted by radiomics in hepatocellular carcinoma with liver transplantation (HCC‐LT) has not been explored. In this study, it is found that intra‐tumoral TLS abundance is significantly correlated with recurrence‐free survival (RFS) and overall survival (OS). Tumor tissues with TLS are characterized by inflammatory signatures and high infiltration of antitumor immune cells, while those without TLS exhibit uncontrolled cell cycle progression and activated mTOR signaling by bulk and single‐cell RNA‐seq analyses. The regulators involved in mTOR signaling (RHEB and LAMTOR4) and S‐phase (RFC2, PSMC2, and ORC5) are highly expressed in HCC with low TLS. In addition, the largest cohort of HCC patients is studied with available radiomics data, and a classifier is built to detect the presence of TLS in a non‐invasive manner. The classifier demonstrates remarkable performance in predicting intra‐tumoral TLS abundance in both training and test sets, achieving areas under receiver operating characteristic curve (AUCs) of 92.9% and 90.2% respectively. In summary, the absence of intra‐tumoral TLS abundance is associated with mTOR signaling activation and uncontrolled cell cycle progression in tumor cells, indicating unfavorable prognosis in HCC‐LT. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease associated with B‐cell hyperactivity. Telitacicept is a transmembrane activator, calcium modulator, and cyclophilin ligand interactor‐Fc fusion protein, which can neutralize both B‐cell lymphocyte stimulator and a proliferation‐inducing ligand. Patients with active SLE who received telitacicept were prospectively followed at month 1, 3, 6, 9, and 12 after telitacicept initiation. Thirty‐seven participants were involved and followed for 6.00 [3.00, 6.00] months. SRI‐4 rate at month 6 was 44.7%. The median dosage of prednisone was decreased by 43.8% (from 10 to 5.62 mg/d) at month 6. The anti‐dsDNA level was significantly decreased, while complement levels were significantly increased at month 6 from baseline. Continuously significant reductions in serum immunoglobin (Ig)G IgA, and IgM levels were also observed. Patients experienced significant decreases in the numbers of total and naive B cells, whereas memory B cells and T cell populations did not change. The number of NK cells was significantly increased during the follow‐up. At month 6, 58.3% (14 out of 24) patients experienced improved fatigue accessed by FACIT–Fatigue score exceeding the minimum clinically important difference of 4. Most adverse events were mild, but one each case of severe hypogammaglobulinemia, psychosis with suicidal behavior, and B‐cell lymphoma were occurred. In our first prospective real‐world study, telitacicept treatment led to a significant clinical and laboratory improvement of disease activity, as well as fatigue amelioration in patients with SLE. Safety profile was favorable overall, but more studies are greatly needed. [ABSTRACT FROM AUTHOR]

The assumption that greater biodiversity enhances ecosystem stability, commonly known as 'portfolio effect', has attracted considerable research attention. However, the potential portfolio effects on spatial stability (the similarity of ecosystem functioning among forest communities) are still poorly examined especially at different spatial scales and under varying environmental stress conditions. Accordingly, this study investigates the biodiversity–spatial stability relationship among regional communities across different spatial scales and environmental conditions in a temperate forest region.We define spatial stability as the invariability of the productivity of woody plants among plots within a regional community. To test spatial stability, the N closest plots to a given plot were aggregated to form regional communities representing different spatial scales. Structural equation modelling was used to evaluate how biodiversity (including taxonomic [TD] and phylogenetic diversity [PD]) increases spatial stability via species asynchrony and/or population stability across spatial scales. Hierarchical Bayesian modelling was used to evaluate the environmental dependence of the portfolio effects on spatial stability.TD and PD both increased the spatial stability by increasing asynchrony, but decreased population stability. The portfolio effect of TD on spatial stability became stronger and reached saturation at the intermediate scale and then decreased as regional communities became larger. The portfolio effects of TD were weaker under the stressful conditions of drought, high precipitation seasonality and high elevation but unchanged across temperature seasonality and human disturbance. PD showed no discernable effect on spatial stability and did not change across spatial scale and environmental condition.Our results suggest that the positive effect of biodiversity on species asynchrony overcomes the negative biodiversity effect on population stability to buffer the spatial change in productivity in diverse communities. Future research of the biodiversity–spatial stability relationship may thus benefit from incorporating different spatial scales and environmental conditions into the analysis. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

Excessive hepatic lipid accumulation is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). A previous study showed that the circular RNA (circRNA) PTK2 was significantly downregulated in NAFLD mice. However, the detailed function of circ PTK2 in NAFLD remains unclear. A high‐fat diet (HFD) was used to establish a mouse model of NAFLD, and free fatty acid (FFA) treatment was used to establish an in vitro model of NAFLD. Oil red O staining was used to evaluate lipid accumulation. The pathological changes in mice were observed by HE staining. Western blotting and RT–qPCR were applied to assess protein and mRNA levels, respectively. A dual luciferase reporter assay and RIP were used to explore the relationship among circ PTK2, miR‐200c and SIK2. Circ PTK2 and SIK2 were downregulated and miR‐200c was upregulated in NAFLD. Upregulation of circ PTK2 reversed lipid accumulation in FFA‐treated HepG2 cells. Moreover, circ PTK2 bound to miR‐200c, and SIK2 was identified as the direct target of miR‐200c. Moreover, the miR‐200c inhibitor‐induced decrease in lipid accumulation was reversed by SIK2 knockdown. Furthermore, the impact of circ PTK2 overexpression on PI3K/Akt signaling was partially reversed by SIK2 silencing. Circ PTK2 overexpression alleviates NAFLD development via the miR‐200c/SIK2/PI3K/Akt axis. Thus, our work might provide new methods for NAFLD treatment. [ABSTRACT FROM AUTHOR]

Estimating forest above‐ground biomass (AGB) productivity constitutes one of the most fundamental topics in forest ecological research. Based on a 30‐ha permanent field plot in Northeastern China, we modeled AGB productivity as output, and topography, species diversity, stand structure, and a stand density variable as input across a series of area scales using the Random Forest (RF) algorithm. As the grain size increased from 10 to 200 m, we found that the relative importance of explanatory variables that drove the variation of biomass productivity varied a lot, and the model accuracy was gradually improved. The minimum sampling area for biomass productivity modeling in this region was 140 × 140 m. Our study shows that the relationship of topography, species diversity, stand structure, and stand density variables with biomass productivity modeled using the RF algorithm changes when moving from scales typical of forest surveys (10 m) to larger scales (200 m) within a controlled methodology. These results should be of considerable interest to scientists concerned with forest assessment. [ABSTRACT FROM AUTHOR]

Aim: Understanding the biodiversity–stability relationship has become a central issue in ecology and conservation biology. Although the stabilizing effects of tree species diversity on ecosystem productivity are well recorded in small local communities, they remain poorly understood across scales (from local to larger spatial scales). This study evaluates biodiversity–stability effects from local to larger spatial scales in a large temperate forest region, considering a range of environmental conditions and environmental heterogeneity. Location: North‐eastern China (c. 700,000 km2). Time period: 2005–2017. Major taxa studied: Woody plants. Methods: We define stability as the temporal invariability of biomass productivity. Regional metacommunities representing larger spatial scales were developed by aggregating multiple sets of local field plots. Simple regression analysis was used to test biodiversity–stability relationships in metacommunities. Piecewise structural equation modelling was then used to disentangle the effects of diversity and abiotic variables on forest stability at local and larger spatial scales. Multiple mixed‐effects regression models were used to determine the relative contribution of individual predictive variables to stability across spatial scales. Results: We found that local diversity (alpha diversity) was positively related to the stability of local communities (alpha stability), whereas species turnover across space (beta diversity) was positively related to asynchronous dynamics among local communities (spatial asynchrony), regardless of whether abiotic factors were considered or not. We also found that environmental conditions and environmental heterogeneity affected forest stability across scales. The effect of spatial asynchrony on gamma stability was greater than that of alpha stability. Main conclusions: Our results imply that spatial asynchrony is a key to maintaining the stability of ecosystem productivity within a large temperate forest region. We suggest that diverse forests and heterogeneous landscapes should be sustained at multiple spatial scales to buffer the negative effects of climate change and forest degradation. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) is a subtype of lung cancer (LC), which is the most common tumor worldwide. Accumulating evidence has elucidated an important role of microRNAs (miRNAs) in mediating the development and progression of several tumors. The purpose of this study was to explore the role and underlying mechanism of miR‐15b in LUAD. Methods: CCK‐8 and Transwell assays were conducted to measure the capacities of cell viability and migration in SPC‐A1 cells. Luciferase assay was utilized to verifymiR‐15b direct binding to BCL2 mRNA 3′‐UTR. Results: We determined that miR‐15b was overexpressed in LUAD and miR‐15b overexpression predicted a significantly worse outcome in patients with LUAD. miR‐15b improved LUAD growth in vitro and vivo. miR‐15b enhanced cell migration and epithelial–mesenchymal transition (EMT) in LUAD. miR‐15b promoted cell viability, migration and EMT through inhibiting BCL2 expression by targeting to its mRNA 3′‐UTR. BCL2 reversed functions of miR‐15b on promoting cell proliferation, migration and EMT in SPC‐A1 cells. Conclusions: miR‐15b promoted cell viability, migration and EMT by targeting BCL2 in LUAD. The newly identified miR‐15b/BCL2 axis provides a novel insight into the pathogenesis of LUAD. [ABSTRACT FROM AUTHOR]

The tridentate organic ligand 4,4′,4′′‐(4,4,8,8,12,12‐hexamethyl‐8,12‐dihydro‐4H‐benzo[9,1]quinolizino[3,4,5,6,7‐defg]acridine‐2,6,10‐triyl)tribenzoic acid (H3L) has been synthesized (as the methanol 1.25‐solvate, C48H39NO6·1.25CH3OH). As a donor–acceptor motif molecule, H3L possess strong intramolecular charge transfer (ICT) fluorescence. Through hydrogen bonds, H3L molecules construct a two‐dimensional (2D) network, which pack together into three‐dimensional (3D) networks with an ABC stacking pattern in the crystalline state. Based on H3L and M(NO3)2 salts (M = Cd and Zn) under solvothermal conditions, two metal–organic frameworks (MOFs), namely, catena‐poly[[triaquacadmium(II)]‐μ‐10‐(4‐carboxyphenyl)‐4,4′‐(4,4,8,8,12,12‐hexamethyl‐8,12‐dihydro‐4H‐benzo[9,1]quinolizino[3,4,5,6,7‐defg]acridine‐2,6‐diyl)dibenzoato], [Cd(C48H37NO6)(H2O)3]n, I, and poly[[μ3‐4,4′,4′′‐(4,4,8,8,12,12‐hexamethyl‐8,12‐dihydro‐4H‐benzo[9,1]quinolizino[3,4,5,6,7‐defg]acridine‐2,6,10‐triyl)tribenzoato](μ3‐hydroxido)zinc(II)], [Zn2(C48H36NO6)(OH)]n, II, were synthesized. Single‐crystal analysis revealed that both MOFs adopt a 3D structure. In I, partly deprotonated HL2− behaves as a bidentate ligand to link a CdII ion to form a one‐dimensional chain. In the solid state of I, the existence of weak interactions, such as O—H...O hydrogen bonds and π–π interactions, plays an essential role in aligning 2D nets and 3D networks with AB packing patterns for I. The deprotonated ligand L3− in II is utilized as a tridentate building block to bind ZnII ions to construct 3D networks, where unusual Zn4O14 clusters act as connection nodes. As a donor–acceptor molecule, H3L exhibits fluorescence with a photoluminescence quantum yield (PLQY) of 70% in the solid state. In comparison, the PL of both MOFs is red‐shifted with even higher PLQYs of 79 and 85% for I and II, respectively. [ABSTRACT FROM AUTHOR]

4,4′‐{9,9′‐Spirobi[10H‐acridine]‐10,10′‐diyl}dibenzoic acid (L, C29H26N2O4) was designed and synthesized as a new donor–acceptor motif molecule. Due to the large dihedral angle between the planes of the carboxyphenyl group and the spiroacridine moiety, L possess thermally activated delayed fluorescence (TADF). By applying L as a ligand and using Cd as a metal connector, we synthesized the coordination polymer catena‐poly[hemi‐μ‐aqua‐aqua(μ3‐4,4′‐{9,9′‐spirobi[10H‐acridine]‐10,10′‐diyl}dibenzoato)cadmium(II)], [Cd(C29H24N2O4)(H2O)1.5]n, (I). X‐ray crystallographic analysis revealed that this coordination polymer exhibits one‐dimensional chains constructed from molecular twist‐ring moieties, with Cd2O11 clusters as the connection nodes. The stacking pattern of the two‐dimensional network was formed by C—H...π interactions in the solid state. Similar to L, (I) presents a sky‐blue TADF emission, together with a photoluminescence quantum yield (PLQY) of 40%. It is worth noting that the photocatalytic activity toward the generation of singlet oxygen of this coordination polymer is confirmed. [ABSTRACT FROM AUTHOR]

There is a new knowledge for clinical presentations and findings of imagine in patients with osteonecrosis of the femoral head ( ONFH) in recent more than ten years. According to clinical data in Chinese huge patients with ONFH, the guideline for diagnosis and treatment of ONFH has been put forward by Chinese specialists. The newer contents of guideline include the definition for predisposing risk factors of ONFH, the new knowledge for clinical manifestations, the new interpretation for changes of imagine, important differential diagnosis. Based on the supplementary and revision for widely used staging and classification system, the new Chinese staging and classification system have been established. The advantages of Chinese staging and classification system accord with clinical and pathological features, it could be predicted the prognosis, and clinical applications are convenient. The guideline gives a brief account of principles for treatment selection and treatment methods for enhancement of diagnosis and treatment for ONFH. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Our aim was to address the potential effect of the geographical range size of species on the relationships between plant traits, soil and climate in Chinese grasslands. Previous analyses tended to examine plant-environment relationships across many species while ignoring that species with different range sizes may respond differently to the environment. Here we hypothesized that leaf traits of narrow-ranging species would be more strongly correlated with soil and climatic variables than those of wide-ranging species. Location Chinese grasslands. Methods Data on leaf traits, including nitrogen and phosphorus concentrations, carbon/nitrogen ratio, nitrogen/phosphorus ratio and specific leaf area, as well as species range sizes for 208 species distributed across 178 sites in Chinese grasslands were collected. Soil and climate information for each study site was also gathered. The effects of range size on leaf traits were tested using one-way ANOVA. Correlations between leaf traits, soil and climate were calculated for all species pooled together and for species partitioned into range size quartiles, from the first (narrowest- ranging 25%) to the fourth (widest-ranging 25%). Results Narrow-ranging species tended to occur at high altitude with lower temperature but higher soil nutrient concentrations compared with wide-ranging species. No direct link between leaf traits and species range sizes was detected. However, patterns of leaf-soil nutrient relationships changed significantly across levels of range size. Narrow-ranging species tended to be more sensitive to variation in soil nutrient availability than wide-ranging species, resulting in a shift from a positive leaf-soil nutrient relationship for narrow-ranging plants to no relationship for wide-ranging plants. Species responses to climatic variables were unrelated to their range sizes. Main conclusions The close relationship between leaf and soil nutrients indicates a specialization of narrow-ranging species to particular habitats whereas wide-ranging species may be able to better withstand changes in environment such as soil fertility over a large area. [ABSTRACT FROM AUTHOR]

Biodiversity has a close relationship with ecosystem functioning. For most biodiversity–ecosystem‐functioning studies, biodiversity has been linked to a single indicator variable of ecosystem functioning. However, there are generally multiple ecosystem processes contributing to ecosystem functioning and they differ in their dependence on biodiversity. Thus, the relationship between biodiversity and ecosystem functioning can be stronger when multiple rather than single ecosystem processes are considered. Using both mass‐balance and stable‐isotope approaches, we explored the effects of plant diversity on nitrogen (N) removal sustained by multiple N‐cycling processes in experimental microcosms simulating constructed wetlands, an ecosystem treating wastewater with high N loading. Four species were used to assemble different plant communities, ranging in richness from one to four species. The removal of N, indicated by low levels of total inorganic N concentration (TIN) present in the effluent, was considered as an integrated measure of ecosystem functioning, combining three constituent N‐cycling processes: plant uptake, denitrification, and substrate adsorption. Our results showed that (1) species richness had a positive effect on N removal, in particular, the four‐species mixture reduced effluent TIN to a lower level than any monoculture; however, polycultures (two‐, three‐, and four‐species mixtures) did not outperform the most efficient monoculture when each of the three constituent N‐cycling processes was considered by itself; (2) species identity had significant impacts on single processes. Communities with the species Coix lacryma‐jobi showed the greatest capacity for N uptake and communities with Phragmites australis had the highest denitrification rates; (3) isotope fractionation in the rhizosphere of Coix lacryma‐jobi was primarily due to microbial denitrification while multistep isotope fractionation was detected for Phragmites australis and Acorus calamus (indicating recycling of N), suggesting that species differed in the way they transformed N; (4) the enhanced N removal at high diversity may be due to mutualistic interactions among species belonging to different functional types. Our findings demonstrated that although plant species richness had negligible effects on individual N‐cycling processes, it enhanced the overall ecosystem functioning (N removal) when these processes were considered collectively. Our study thus contributes to improve the treatment efficiency of constructed wetlands through proper vegetation management. [ABSTRACT FROM AUTHOR]

Knowledge of plant functional traits and trait-environment interactions is important for characterizing species strategies and understanding ecological processes. However, comprehensive field data on both above- and belowground traits, together with their environmental variables are scarce. Biome-scale studies are particularly lacking. Here we present two large-scale data sets that include functional traits of leaves and fine roots and their corresponding soil and climatic variables in China's grasslands. Leaf, fine root, and soil samples were collected in three biogeographic regions: temperate grassland on the Inner Mongolia Plateau, alpine grassland on the Tibetan Plateau, and mountain grassland in the Xinjiang mountain areas. Field data were collected over two periods. The first data set collected between 2003 and 2004 includes 13 foliar traits (leaf mass per area, LMA; photosynthetic nitrogen use efficiency, PNUE; water use efficiency, WUE; stomatal conductance for water vapor, Gs; transpiration rate, TR; mass- and area-based photosynthetic capacity, Amass and Aarea; mass- and area-based carbon concentrations, Cmass and Carea; nitrogen concentrations, Nmass and Narea; and phosphorus concentrations, Pmass and Parea) for 170 species at 173 sites. The second data set collected between 2006 and 2007 includes six sets of analogous traits for both leaves and fine roots (C, N, and P concentrations; leaf thickness/root diameter; specific leaf area, SLA; specific root length, SRL; and tissue density) for 139 species at 82 sites, along with soil attributes (soil total and organic carbon, STC and SOC; total and available N, STN and SAN; total and available P, STP and SAP; pH, bulk density, and moisture). Moreover, associated information was also gathered, including geographical location (latitude, longitude, and altitude), climate (mean annual temperature, MAT; mean annual precipitation, MAP; growing season temperature, GST; growing season precipitation, GSP; potential evapotranspiration, PET; and actual evapotranspiration, AET) and site descriptions (vegetation and soil types). The data sets are unique because they integrate plant above- and belowground traits, climate, and soil factors over broad regional, elevational, and taxonomic ranges in understudied regions (e.g., the Tibetan Plateau). This is the only database on China's grassland species for unrestricted global access. These data sets will make a valuable contribution to future large-scale trait-based ecological studies. [ABSTRACT FROM AUTHOR]

The title complex, [MnHg(NCS)4(C2H5NO)2]n, consists of slightly distorted MnN4O2 octahedra and HgS4 tetrahedra. Each Mn(II) cation is bound to four N atoms of the NCS groups and two O atoms of the N-methylformamide (NMF) ligands in a cis configuration. Each Hg(II) cation is coordinated to four S atoms of NCS groups. Each pair of Mn(II) and Hg(II) cations is connected by an -NCS- bridge, forming an infinite three-dimensional -Mn-NCS-Hg- network.