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Fiber-optic distributed strain sensing (FO-DSS) has been successful in monitoring strain changes along horizontal wellbores in hydraulically fractured reservoirs. However, the mechanism driving the various FO-DSS responses associated with near-wellbore hydraulic fracture properties is still unclear. To address this knowledge gap, we use coupled wellbore-reservoir-geomechanics simulations to study measured strain-change behavior and infer hydraulic fracture characteristics. The crossflow among fractures is captured through explicit modeling of the transient wellbore flow. In addition, local grid refinement is applied to accurately capture strain changes along the fiber. A Base Case model was designed with four fractures of varying properties, simulating strain change signals when the production well is shut-in for 10 d after 240 d of production and reopened for 2 d. Strain-pressure plots for different fracture clusters were used to gain insights into inferring fracture properties using DSS data. When comparing the model with and without the wellbore, distinct strain change signals were observed, emphasizing the importance of incorporating the wellbore in FO-DSS modeling. The effects of fracture spacing and matrix permeability on strain change signals were thoroughly investigated. The results of our numerical study can improve the understanding of the relation between DSS signals and fracture hydraulic properties, thus maximizing the value of the dataset for fracture diagnostics and characterization.

Abstract Iron storage proteins, e.g., vertebrate ferritin, and the ferritin-like bacterioferritin (Bfr) and bacterial ferritin (Ftn), are spherical, hollow proteins that catalyze the oxidation of Fe2+ at binuclear iron ferroxidase centers (FOC) and store the Fe3+ in their interior, thus protecting cells from unwanted Fe3+/Fe2+ redox cycling and storing iron at concentrations far above the solubility of Fe3+. Vertebrate ferritins are heteropolymers of H and L subunits with only the H subunits having FOC. Bfr and Ftn were thought to coexist in bacteria as homopolymers, but recent evidence indicates these molecules are heteropolymers assembled from Bfr and Ftn subunits. Despite the heteropolymeric nature of vertebrate and bacterial ferritins, structures have been determined only for recombinant proteins constituted by a single subunit type. Herein we report the structure of Acinetobacter baumannii bacterioferritin, the first structural example of a heteropolymeric ferritin or ferritin-like molecule, assembled from completely overlapping Ftn homodimers harboring FOC and Bfr homodimers devoid of FOC but binding heme. The Ftn homodimers function by catalyzing the oxidation of Fe2+ to Fe3+, while the Bfr homodimers bind a cognate ferredoxin (Bfd) which reduces the stored Fe3+ by transferring electrons via the heme, enabling Fe2+ mobilization to the cytosol for incorporation in metabolism.

Abstract The driving force behind the Cenozoic India-Asia collision remains elusive. Using global-scale geodynamic modeling, we find that the continuous motion of the Indian plate is driven by a prominent upper-mantle flow pushing the thick Indian lithospheric root, originated from the northward rollover of the detached Neo-Tethyan slab and sinking slabs below East Asia. The maximum mantle drag occurs within the strong Indian lithosphere and is comparable in magnitude to that of slab pull (1013 N m−1). The thick cratonic root enhances both lithosphere-asthenosphere coupling and upper-plate compressional stress, thereby sustaining the topography of Tibetan Plateau. We show that the calculated resistant force from the India-Asia plate boundary is also close to that due to the gravitational potential energy of Tibetan Plateau. Here, we demonstrate that this mantle flow is key for the formation of the Tibetan Plateau and represents part of a hemispheric convergent flow pattern centered on central Asia.

Abstract Paleolatitudes of volcanic rocks reveal that prominent changes in volcanic trend of the Hawaii-Emperor hotspot chain represent meridional migration of the magma source. However, models assuming latitudinal plume migration fail to explain the observed age distribution, rock composition, and erratic paleolatitude changes of the oldest Emperor seamounts. Here we use data-assimilation models to better reproduce the Hawaii-Emperor hotspot track by systematically considering plate reconstruction, plume-lithosphere interaction, and simplified melt generation and migration. Our results show that plate drag and plume-ridge interaction are both important in explaining the observed seamount ages. These shallow dynamic processes could account for 50% of the observed paleolatitude’s secular reduction and erratic variations over time, where the necessary southward migration of the Hawaiian plume root is significantly less than previously thought. We conclude that plume-lithosphere interaction represents a common mechanism in affecting hotspot track, and has important implications in understanding mantle dynamics and plate reference frames.

Modern rice production faces the dual challenges of increasing grain yields while reducing inputs of chemical fertilizer. However, the disequilibrium between the nitrogen (N) supplement from the soil and the demand for N of plants is a serious obstacle to achieving these goals. Plant-based diagnosis can help farmers make better choices regarding the timing and amount of topdressing N fertilizer. Our objective was to evaluate a non-destructive assessment of rice N demands based on the relative SPAD value (RSPAD) due to leaf positional differences. In this study, two field experiments were conducted, including a field experiment of different N rates (Exp. I) and an experiment to evaluate the new strategy of nitrogen-split application based on RSPAD (Exp. II). The results showed that higher N inputs significantly increased grain yield in modern high yielding super rice, but at the expense of lower nitrogen use efficiency (NUE). The N nutrition index (NNI) can adequately differentiate situations of excessive, optimal, and insufficient N nutrition in rice, and the optimal N rate for modern high yielding rice is higher than conventional cultivars. The RSPAD is calculated as the SPAD value of the top fully expanded leaf vs. the value of the third leaf, which takes into account the non-uniform N distribution within a canopy. The RSPAD can be used as an indicator for higher yield and NUE, and guide better management of N fertilizer application. Furthermore, we developed a new strategy of nitrogen-split application based on RSPAD, in which the N rate was reduced by 18.7%, yield was increased by 1.7%, and the agronomic N use efficiency was increased by 27.8%, when compared with standard farmers’ practices. This strategy of N fertilization shows great potential for ensuring high yielding and improving NUE at lower N inputs.

Abstract Eunicellane diterpenoids, containing a typical 6,10-bicycle, are bioactive compounds widely present in marine corals, but rarely found in bacteria and plants. The intrinsic macrocycle exhibits innate structural flexibility resulting in dynamic conformational changes. However, the mechanisms controlling flexibility remain unknown. The discovery of a terpene synthase, MicA, that is responsible for the biosynthesis of a nearly non-flexible eunicellane skeleton, enable us to propose a feasible theory about the flexibility in eunicellane structures. Parallel studies of all eunicellane synthases in nature discovered to date, including 2Z-geranylgeranyl diphosphate incubations and density functional theory-based Boltzmann population computations, reveale that a trans-fused bicycle with a 2Z-configuration alkene restricts conformational flexibility resulting in a nearly non-flexible eunicellane skeleton. The catalytic route and the enzymatic mechanism of MicA are also elucidated by labeling experiments, density functional theory calculations, structural analysis of the artificial intelligence-based MicA model, and mutational studies.

Abstract Background Certain occupations may predispose individuals to urolithiasis, a multi-factorial disease. The study aimed to evaluate the prevalence and related factors of nephrolithiasis in medical staff in Qingdao, China. Methods Physical examination results of 5115 in-service medical staff aged 22–60 years old were retrospectively analyzed. Multivariable logistic regression analysis and stratified analyses by age and gender were applied to explore the related factors of nephrolithiasis in these medical staff. Results The overall nephrolithiasis prevalence in medical staff in Qingdao, China was 4.65%. Doctors were more prone to nephrolithiasis than nurses (5.63% vs. 3.96%, P = 0.013) and the peak prevalence (6.69%) was observed in medical staff working in the emergency department (ED). Male gender (OR = 1.615, 95% CI = 1.123–2.323, P = 0.010), overweight or obesity (OR = 1.674, 95% CI = 1.266–2.214, P

Abstract Resistance to chemotherapy has been a major hurdle that limits therapeutic benefits for many types of cancer. Here we systematically identify genetic drivers underlying chemoresistance by performing 30 genome-scale CRISPR knockout screens for seven chemotherapeutic agents in multiple cancer cells. Chemoresistance genes vary between conditions primarily due to distinct genetic background and mechanism of action of drugs, manifesting heterogeneous and multiplexed routes towards chemoresistance. By focusing on oxaliplatin and irinotecan resistance in colorectal cancer, we unravel that evolutionarily distinct chemoresistance can share consensus vulnerabilities identified by 26 second-round CRISPR screens with druggable gene library. We further pinpoint PLK4 as a therapeutic target to overcome oxaliplatin resistance in various models via genetic ablation or pharmacological inhibition, highlighting a single-agent strategy to antagonize evolutionarily distinct chemoresistance. Our study not only provides resources and insights into the molecular basis of chemoresistance, but also proposes potential biomarkers and therapeutic strategies against such resistance.

Abstract Aquaculture is a rapidly growing food production technology, but there are significant concerns related to its environmental impact and adverse social effects. We examine aquaculture outcomes in a three pillars of sustainability framework by analyzing data collected using the Aquaculture Performance Indicators. Using this approach, comparable data has been collected for 57 aquaculture systems worldwide on 88 metrics that measure social, economic, or environmental outcomes. We first examine the relationships among the three pillars of sustainability and then analyze performance in the three pillars by technology and species. The results show that economic, social, and environmental outcomes are, on average, mutually reinforced in global aquaculture systems. However, the analysis also shows significant variation in the degree of sustainability in different aquaculture systems, and weak performance of some production systems in some dimensions provides opportunity for innovative policy measures and investment to further align sustainability objectives.

ABSTRACT: Cinnamomi Cortex was a material as medicinal and edible resources and it has been demonstrated that Cinnamomi Cortex aqueous extract (CCAE) possess hypoglycemic effect, but there were no active compounds identified as quality standard of CCAE to be used in the investigate of hypoglycemic activity. Hence, in this study, the quality standard and the hypoglycemic effect of CCAE were investigated. Cinnamaldehyde and coumarin as the quality control in CCAE were analyzed by high performance liquid chromatography (HPLC) method. The results showed that the average yield of extraction was 10.06%. The concentration of coumarin was linear with peak area ranging from 0.02–1.00 μg/mL (r = 0.999 6, n = 6) and that of cinnamaldehyde also demonstrated a good linear relationship with peak area in the range of 1.05–52.50 μg/mL (r = 0.999 7, n = 6). The average recovery rate of coumarin and cinnamaldehyde was 99.42% and 100.11%, respectively. The investigation of hypoglycemic effect revealed that CCAE could improve weight loss, lower liver and pancreas indices, improve organ damage caused by diabetes, and lower fasting blood glucose, glycosylated serum protein (GSP) and total cholesterol (TC) levels. The results showed that CCAE can reduce fasting blood glucose and blood lipid levels in diabetic mice.

Abstract The western United States is one of Earth’s most tectonically active regions, characterized by extensive crustal deformation through intraplate earthquakes and geodetic motion. Such intracontinental deformation is usually ascribed to plate boundary forces, lithospheric body forces, and/or viscous drag from mantle flow. However, their relative importance in driving crustal deformation remains controversial due to inconsistent assumptions on crustal and mantle structures in prior estimations. Here, we utilize a fully dynamic three-dimensional modeling framework with data assimilation to simultaneously compute lithospheric and convective mantle dynamics within the western United States. This approach allows for quantitative estimations of crustal deformation while accounting for the realistic three-dimensional lithospheric structure. Our results show the critical role of the complex lithospheric structure in governing intraplate deformation. Particularly, the interaction between the asthenospheric flow and lithospheric thickness step along the eastern boundary of the Basin and Range represents a key driving mechanism for localized crustal deformation and seismicity.

The thermal evolution of the Earth’s interior and its dynamic effects are the focus of Earth sciences. However, the commonly adopted grid-based temperature solver is usually prone to numerical oscillations, especially in the presence of sharp thermal gradients, such as when modeling subducting slabs and rising plumes. This phenomenon prohibits the correct representation of thermal evolution and may cause incorrect implications of geodynamic processes. After examining several approaches for removing these numerical oscillations, we show that the Lagrangian method provides an ideal way to solve this problem. In this study, we propose a particle-in-cell method as a strategy for improving the solution to the energy equation and demonstrate its effectiveness in both one-dimensional and three-dimensional thermal problems, as well as in a global spherical simulation with data assimilation. We have implemented this method in the open-source finite-element code CitcomS, which features a spherical coordinate system, distributed memory parallel computing, and data assimilation algorithms.

Recently developed ‘super’ rice cultivars with greater yield potentials often suffer from the problem of poor grain filling, especially in inferior spikelets. Here, we studied the activities of enzymes related to starch metabolism in rice stems and grains, and the microstructures related to carbohydrate accumulation and transportation to investigate the effects of different water regimes on grain filling. Two ‘super’ rice cultivars were grown under two irrigation regimes of well-watered (WW) and alternate wetting and moderate soil drying (AWMD). Compared with the WW treatment, the activities of ADP glucose pyrophosphorylase (AGPase), starch synthase (StSase) and starch branching enzyme (SBE), and the accumulation of non-structural carbohydrates (NSCs) in the stems before heading were significantly improved, and more starch granules were stored in the stems in the AWMD treatment. After heading, the activities of α-amylase, β-amylase, sucrose phosphate synthase (SPS) and sucrose synthase in the synthetic direction (SSs) were increased in the stems to promote the remobilization of NSCs for grain filling under AWMD. During grain filling, the enzymatic activities of sucrose synthase in the cleavage direction (SSc), AGPase, StSase and SBE in the inferior spikelets were increased, which promoted grain filling, especially for the inferior spikelets under AWMD. However, there were no significant differences in vascular microstructures. The grain yield and grain weight could be improved by 13.1 and 7.5%, respectively, by optimizing of the irrigation regime. We concluded that the low activities of key enzymes in carbon metabolism is the key limitation for the poor grain filling, as opposed to the vascular microstructures, and AWMD can increase the amount of NSC accumulation in the stems before heading, improve the utilization rate of NSCs after heading, and increase the grain filling, especially in the inferior spikelets, by altering the activities of key enzymes in carbon metabolism.

Abstract Background Jasmonate (JA) is the important phytohormone to regulate plant growth and adaption to stress signals. MYC2, an bHLH transcription factor, is the master regulator of JA signaling. Although MYC2 in maize has been identified, its function remains to be clarified. Results To understand the function and regulatory mechanism of MYC2 in maize, the joint analysis of DAP-seq and RNA-seq is conducted to identify the binding sites and target genes of ZmMYC2. A total of 3183 genes are detected both in DAP-seq and RNA-seq data, potentially as the directly regulating genes of ZmMYC2. These genes are involved in various biological processes including plant growth and stress response. Besides the classic cis-elements like the G-box and E-box that are bound by MYC2, some new motifs are also revealed to be recognized by ZmMYC2, such as nGCATGCAnn, AAAAAAAA, CACGTGCGTGCG. The binding sites of many ZmMYC2 regulating genes are identified by IGV-sRNA. Conclusions All together, abundant target genes of ZmMYC2 are characterized with their binding sites, providing the basis to construct the regulatory network of ZmMYC2 and better understanding for JA signaling in maize.

Abstract Compelling evidence indicates that continental crust can subduct to >300 km and even enter the mantle transition zone (MTZ). However, detecting continental materials within the deep Earth is challenging due to our incomplete knowledge about their physical properties at mantle conditions. We use a newly compiled mineral‐physical database coupled with thermodynamic modeling to calculate seismic velocities of the subducted continental crust (SCC) beyond 150 km. Results show that the SCC has one seismically detectable window depth (300–390 km) with ∼4% VP anomaly. Besides, the upper crust has another two window depths (

With the massive participation of new energy in the operation of distribution network (DN), the uncertainties arising from both load and renewable generation have brought challenges to its secure and reliable operation. In this paper, a model of day-ahead and intraday optimal scheduling based on dynamic partitioning (DP) of DN is constructed to realize the refinement of operation in both temporal and spatial dimensions, as well as to improve the reliability of system operation. For the strong fluctuation characteristics of the source-load in DN, the DP is achieved under the premise that the partition structure in each period is tight and the internal power supply has the ability to balance the power fluctuations. In order to improve the regional autonomy of DN, a day-ahead multi-objective optimal scheduling model is constructed based on the DP with the optimization objectives of weak inter-partition power coupling, lowest deficiency rate of flexibility, and lowest operating cost. And a scheme for articulation is proposed to ensure the effective guidance of day-ahead for intraday. Then the intraday dispatch model is constructed by shifting the focus to the incorporate characteristics of DP and quickly smooth the net load fluctuations. Finally, the performance and reliability of the proposed models are verified via case studies.

Spikelet degeneration is a critical physiological issue that limits grain yield in rice (Oryza sativa L.), influenced by soil moisture conditions during meiosis. The study aimed to investigate the role and mechanism of moderate soil drying in spikelet degeneration and grain yield, as well as to establish a strategy and irrigation regime for suppressing spikelet degeneration to increase grain yield in rice. Field experiments were conducted involving two irrigation regimes: conventional well-watered (C-WW) and moderate soil drying (M-SD) during meiosis. Transgenic rice lines and chemical regulators were employed to elucidate the underlying partial biological mechanisms of this process. The results showed that M-SD regime effectively reduced spikelet degeneration rate and increased grain yield compared to C-WW. This improvement under M-SD regime was primarily attributed to the enhanced proline and aquaporin-mediated osmotic balance and redox homeostasis in young rice panicles, as well as the increased root activity during meiosis. The increased levels of brassinosteroids (BRs) and decreased levels of ethylene (ETH) in young panicles under the M-SD were closely associated with the enhanced proline and aquaporin-mediated osmotic balance and redox homeostasis, decreased oxidative damage, and reduced spikelet degeneration rate. The intrinsic relationship among key aquaporin genes expression and proline levels, osmotic balance and redox homeostasis, spikelet degeneration rate, as well as BRs and ETH levels, was further confirmed through the use of transgenic rice lines and chemical regulators. Collectively, an M-SD regime during meiosis can effectively suppress spikelet degeneration and thereby enhance grain yield, primarily through well-maintained osmotic balance and redox homeostasis in rice.

Abstract Sodium layered oxide with anion redox activity (SLO‐A) stands out as a promising cathode material for sodium‐ion batteries due to its impressive capacity and high voltage resulting from Mn‐ and O‐redox processes. However, the SLO‐A faces significant challenges in cycling stability and rate performance, primarily due to the poor reversibility and sluggish kinetics of the O‐redox. In this study,a novel Ti‐doped material, Na2/3Li2/9Mn53/72Ti1/24O2 (NLMTO), exhibiting remarkable characteristics such as a notable rate capacity (130 mAh g−1 at 3C, where 1C equals 200 mA g−1) and excellent cycling retention (85.4% after 100 cycles at 0.5C) is introduced. Employing electrochemical differential analyses, the contributions to the superior performance arising from the Mn‐ and O‐redox processes are quantitatively delineated. The optimized performance of NLMTO is attributed, in part, to the enhanced stability of both bulk and interface structures. The introduction of Ti through substitution not only contributes to this stability but also allows for the fine‐tuning of the material's electron configurations. This is achieved by augmenting the density of states near the Fermi energy level, as well as elevating the O 2p and Mn 3d orbits. This research advances sodium‐ion battery technology.

Abstract The sparsity of a direct record for the moment of subduction zone initiation has led to various models describing the infancy and evolution of modern oceanic subduction systems. Recently, with increases in available samples and geochemical data for subduction zone initiation-to-mature-arc lavas, better constraints on subduction evolution are possible. Here, by systemically modeling the time-space pattern and geochemical characters of forearc magmas with forward numerical modeling, we attempt to search for a best-fit geodynamic scenario where Izu-Bonin-Mariana-type subduction tends to develop. Our modeling and geochemical constraints have identified a necessary and possibly transitory pre-subduction zone initiation trenchward contraction consistent with observed Izu-Bonin-Mariana forearc magma geochemistry. Our results also reveal a typical maturation process for Izu-Bonin-Mariana-type oceanic subductions, controlled by the pace of the upper plate’s rifting and solidification.

Abstract Objectively exploring global variations in crust and upper mantle structure helps constrain fundamental aspects of Earth's plate tectonic and convective processes. Here we adopted a Variational Auto‐Encoder to explore the degrees of freedom of global Rayleigh wave dispersion maps at 4–40 mHz. We found that two latent variables sufficiently represent the global variations, suggesting inherent coupling between crustal and mantle seismic properties. We propose that the two extracted latent variables mostly correspond with crustal thickness and upper mantle thermal structure. The first variable shows low values for continental mountain belts and ocean spreading ridges, contrasted by high values for abyssal plains. The second variable shows low values for most oceanic lithosphere and Phanerozoic continental areas, contrasted by high values for Archean cratons. Latent space correlations indicate that continental lithosphere has more strongly coupled depth features than beneath the oceans, which might be a consequence of its longevity.

Designing rubber formulations can greatly benefit from using a database that stores the formulations and corresponding property data of rubber composites. Such a database can expedite the decision-making process by swiftly identifying the most suitable formulations for specific applications. However, the management of a rubber formulation database encounters various issues, including missing formulation and property data, as well as data entry errors. These issues can impede the decision-making processes and even result in incorrect decisions being made. In this study, machine learning (ML) algorithms were applied to analyze rubber formulation databases. Our findings highlight the success of the ML algorithm in effectively filling in missing data and identifying erroneous data. Furthermore, it demonstrates the accurate prediction of properties for untested formulations within the pre-determined database space. The results underline the outstanding performance of ML algorithms in expediting the rubber formulation design process and emphasize their immense potential to play a prominent role in the advancement of rubber composites.

Regeneration of the architecturally complex blood vascular system requires precise temporal and spatial control of cell behaviours. Additional components must be integrated into the structure to achieve clinical success for in situ tissue engineering. Consequently, this study proposed a universal method for including any substrate type in vascular cell extracellular matrices (VCEM) via regulating selective adhesion to promote vascular tissue regeneration. The results uncovered that the VCEM worked as cell adhesion substrates, exhibited cell type specificity, and functioned as an address signal for recognition by vascular cells, which resulted in matching with the determined cells. The qPCR and immunofluorescence results revealed that a cell type-specific VCEM could be designed to promote or inhibit cell adhesion, consistenting with the expression patterns of eyes absent 3 (Eya3). In addition, a 3D vascular graft combined with VCEM which could recapitulate the vascular cell-like microenvironment was fabricated. The vascular graft revealed a prospective role for cellular microenvironment in the establishment of vascular cell distribution and tissue architecture, and potentiated the orderly regeneration and functional recovery of vascular tissues in vivo. The findings demonstrate that differential adhesion between cell types due to the cellular microenvironment is sufficient to drive the complex assembly of engineered blood vessel functional units, and underlies hierarchical organization during vascular regeneration.

IntroductionEmerging proof suggests that Apocynum venetum flowers polysaccharide (AVFP) has immunomodulatory effects in vitro. However, the action mechanism of AVFA is still unclear in vivo. The purpose of this study is to probe into the potential mechanism of AVFA in immunosuppressed mice by investigating organ index, cytokine levels, anti-oxidative stress capacity, transcriptomics, and gut microbiota.MethodsImmunocompromised mice induced by cyclophosphamide (CTX) were divided into six groups. The enzyme-labeled method, hematoxylin and eosin, transcriptomics, and high-throughput sequencing were used to detect the regulatory effects of AVFP on immunocompromised mice and the function of AVFP on the concentration of short-chain fatty acids (SCFAs) by high-performance liquid chromatography (HPLC) analysis. The Spearman correlation analysis was used to analyze the correlation between the intestinal microbiota and biochemical indexes.ResultsThe experimental results illustrated that AVFP has protective effects against CTX-induced immunosuppression in mice by prominently increasing the organ index and levels of anti-inflammatory factors in serum in addition to enhancing the antioxidant capacity of the liver. Meanwhile, it could also signally decrease the level of pro-inflammatory cytokines in serum, the activity of transaminase in serum, and the content of free radicals in the liver, and alleviate the spleen tissue damage induced by CTX. Transcriptomics results discovered that AVFP could play a role in immune regulation by participating in the NF-κB signaling pathway and regulating the immune-related genes Bcl3, Hp, Lbp, Cebpd, Gstp2, and Lcn2. Gut microbiota results illustrated that AVFP could increase the abundance of beneficial bacteria, reduce the abundance of harmful bacteria, and regulate the metabolic function of intestinal microorganisms while dramatically improving the content of SCFAs, modulating immune responses, and improving the host metabolism. The Spearman analysis further evaluated the association between intestinal microbiota and immune-related indicators.ConclusionThese findings demonstrated that AVFP could enhance the immune effects of the immunosuppressed mice and improve the body’s ability to resist oxidative stress.

We report the biochemical, structural, and functional characterization of the protein coded by gene PA4880 in the P. aeruginosa PAO1 genome. The PA4880 gene had been annotated as coding a probable bacterioferritin. Our structural work shows that the product of gene PA4880 is a protein that adopts the Dps subunit fold, which oligomerizes into a 12-mer quaternary structure. Unlike Dps, however, the ferroxidase di-iron centers and iron coordinating ligands are buried within each subunit, in a manner identical to that observed in the ferroxidase center of P. aeruginosa bacterioferritin. Since these structural characteristics correspond to Dps-like proteins, we term the protein as P. aeruginosa Dps-like, or Pa DpsL. The ferroxidase centers in Pa DpsL catalyze the oxidation of Fe2+ utilizing O2 or H2O2 as oxidant, and the resultant Fe3+ is compartmentalized in the interior cavity. Interestingly, incubating Pa DpsL with plasmid DNA results in efficient nicking of the DNA and at higher concentrations of Pa DpsL the DNA is linearized and eventually degraded. The nickase and endonuclease activities suggest that Pa DpsL, in addition to participating in the defense of P. aeruginosa cells against iron-induced toxicity, may also participate in the innate immune mechanisms consisting of restriction endonucleases and cognate methyl transferases.

IntroductionCannulated screws are widely used in the treatment of slipped capital femoral epiphysis, which can be removed after physeal closure on patient's request. This study aimed to analysis the potential risk factors for difficult removal in children with slipped capital femoral epiphysis treated by cannulated screws.Patients and methodsThis study enrolled 32 hips that had undergone removal of cannulated screws after treatment of slipped capital femoral epiphysis at our department. The primary outcomes were the difficult screw removal. The secondary outcomes were functional outcome assessed by using a modified Harris Hip Score and complications of fractures and surgical site infection. Related risk factors for difficult removal were recorded and analyzed by multivariable logistic regression.ResultsIn total, 32 hips were evaluated, with a mean age of 14.9 ± 1.3 years old (range, 13–19 years). Six (18.8%) hips presented with difficult removal, including 4 cases of screws’ slip and 2 breakages. The average implantation time in the difficult removal group (5.7 ± 1.0) was also significantly longer than that in the easily removed group (3.8 ± 0.9, p = 0.001). The mean surgical time in patients with difficult removal was 66.3 ± 11.6 min, which was also significantly longer than that (54.8 ± 8.3) in the other patients (p = 0.008). The duration of screw implantation was an independent risk factor for difficult removal.ConclusionsProlonged screw duration was a predictor for difficult removal in children with slipped capital femoral epiphysis treated by cannulated screws. An early surgery after physeal closure might benefit those with a request for screw removal.

Aims: Despite its implication in various human cancers, the expression and functional significance of Kinesin family member 15 (KIF15) in chordomas remain unexplored. Main methods: The evaluation of KIF15 protein levels was conducted through immunohistochemistry (IHC) staining and Western blot analysis. Cell proliferation was quantified using MTT and CCK8 assays, whereas cell migration was examined using wound healing and Transwell assays. Furthermore, flow cytometric analysis was utilized to assess cell apoptosis and the cell cycle. Additionally, in vivo experiments were performed using a mouse xenograft model. Key findings: Our study revealed significantly higher expression of KIF15 in stage III chordoma tissues compared to stage II tissues. Knockdown of KIF15 led to notable inhibition of cell proliferation and migration, along with enhanced apoptosis and cell cycle arrest. In vivo studies further confirmed the inhibitory effects of KIF15 knockdown on chordoma tumour growth. In terms of mechanism, we identified the involvement of the PI3K-AKT signalling pathway mediated by KIF15 in chordomas. Notably, the anti-tumour effects of KIF15 deficiency on chordomas were partially reversed by the addition of an AKT activator. Significance: KIF15 promotes chordoma development and progression through the activation of the PI3K-AKT signalling pathway. Thus, targeting KIF15 might be a promising therapeutic strategy for treating chordomas.

The entropy of a quantum state measures information or uncertainty contained in the quantum system and plays a crucial role in quantum information theory. Many entropic properties, such as the subadditivity, have been studied for the discrete system with a finite-dimensional state space, while much less is explored in the infinite-dimensional system. In this work, we study the entropic properties of the continuous system that models a collection of Gaussian modes or fields. In particular, we identify the parameter range for the Rényi, Tsallis, and Unified entropies of Gaussian states that they are additive, subadditive, and strong subadditive. We show that the Rényi entropies are subadditive, further giving rise to the subadditivity of the Tsallis and Unified entropies in certain parameter range. We also find that the Tsallis and Unified entropies are not strong subadditive, while the Rényi entropies with the order ranging from 1 to 2 are conjectured to admit the strong subadditivity. Our results are useful in studying quantum correlations and channel capacities in Gaussian systems.

Optimizing the function of ecosystem services (ESs) is vital for implementing regional ecological management strategies. In this study, we used multi-source data and integrated modelling methods to assess the spatiotemporal variations in eight typical ESs on the Chinese Loess Plateau from 2000 to 2015, including grain production, raw material provision, water conservation, carbon storage service, soil conservation, oxygen production, recreation, and net primary productivity (NPP) services. Then, we divided the ecosystem service bundles (ESBs) according to relationships among the eight ESs, obtaining four types of eco-functional areas at the county (city or banner or district) level based on the spatial clustering of similarities in different ES types. We also identified and assessed the contributions of influencing factors to these eco-functional areas using principal component analysis (PCA) across spatiotemporal scales. We found that the spatiotemporal variations in different ESs were noticeable, with an overall increase in grain production and soil conservation services, no significant change in carbon storage service, and overall decreases in raw material provision, water conservation, oxygen production, recreation, and NPP services. From 2000 to 2015, the number of significant synergistic ES pairs decreased, while that of significant trade-off pairs increased. To the changes of ESBs in the eco-functional areas, the results indicated that the indirect loss of these ESs from forest and grassland due to urban expansion should be reduced in ecological development area (ESB 2) and multi ecological functional area (ESB 3). Meanwhile, crop planting structures and planting densities should be adjusted to reduce ES trade-offs associated with water conservation service in grain-producing area (ESB 4). Lastly, ESB-based eco-functional zoning can be used to improve ecological restoration management strategies and optimize ecological compensation schemes in ecologically fragile area (ESB 1).

Abstract Background Multiple rib fractures can lead to flail chest with up to 35% mortality rate due to severe pulmonary complications. Current treatments of flail chest remain controversial. Studies have shown that surgical treatments can improve outcomes and reduce mortality, comparing to non-operative treatments. Current surgical fixation methods focus on stabilization of ribs on the outward facing side, and they require division of intercostal muscles. Damages to surrounding nerves and vessels may lead to chronic pain. This study tests a novel interior fixation method that minimizes neurovascular injuries. Methods Twelve healthy canines were divided in two surgical operation groups for exterior and interior fixation using titanium metal plates. Osteotomy with oblique fractures was prepared under general anesthesia. Exterior fixation was performed in open surgery. Interior fixation was minimally invasive using custom made tools including a flexible shaft extension screwdriver, solid plate stand, guiding wire loop and metal plates with threaded holes. Results Respiratory and cardiovascular functions (RR, PO2, PCO2, SpO2, and HR) together with body temperature were measured before anesthesia and within 48 h after surgery. The difference in measurements was not statistically significant between the two groups before surgery with P values greater than 0.05. However, the interior group canines had better RR and PO2 values starting from the 24th hour, and better PCO2, SpO2, and HR values starting from the 48th hour. It took longer operation time to complete the minimally invasive interior fixation surgery (P value less than 0.001), but the total blood loss was less than the exterior fixation group (P value less than 0.001). Results also showed that interior group canines suffered less pain, and they had quicker recovery in gastrointestinal and physical mobility. Conclusions The investigative interior fixation method was safe and effective in rib stabilization on a canine rib fracture model, comparing to the exterior fixation method. The interior fixation was minimally invasive, with less damages to tissues and nerves surrounding the ribs, leading to better postoperative outcomes.

Abstract Background The RNA recognition motif (RRM) is primarily engaged in the processing of mRNA and rRNA following gene transcription as well as the regulation of RNA transport; it is critical in preserving RNA stability. Results In this study, we identified 102 members of the RRM1 gene family in Brassica rapa, which were dispersed across 10 chromosomes with the ninth chromosome being the most extensively distributed. The RRM1 gene family members of Brassica rapa and Arabidopsis thaliana were grouped into 14 subclades (I–XIV) using phylogenetic analysis. Moreover, the results of transcriptome analysis and RT-qPCR indicated that the expression of Brapa05T000840 was upregulated in the cultivars ‘Longyou 7’ and ‘Longyou 99’ following exposure to cold stress at a temperature of 4 °C for 24 h. The levels of expression in the leaves and growth cones of the ‘Longyou 7’ variety were found to be significantly higher than those observed in the ‘Longyou 99’ variety under conditions of low temperature and NaCl stress. It illustrates the involvement of the RRM1 gene in the physiological response to both low temperature and salt stress. In addition, it was observed that the survival rate of transgenic BrRBP (Brapa05T000840) Arabidopsis thaliana plants was notably higher compared to that of wild-type plants when subjected to varying durations of low temperature treatment. Furthermore, the expression of the BrRBP gene in transgenic plants exhibited an upward trend as the duration of low temperature treatment increased, reaching its peak at 24 h. The in-vivo enzymatic activity of reactive oxygen species-scavenging enzymes were found to be significantly elevated in comparison to wild-type plants, suggesting that the BrRBP gene may enhance the cold tolerance of Arabidopsis thaliana. Conclusions This study offers a significant foundation for comprehending the regulation mechanism of the RRM1 gene family in winter Brassica rapa subjected to cold stress, as well as for finding key genes associated with cold resistance.

Abstract The Cenozoic India-Eurasia collision has had profound impacts on shaping the Tibetan plateau, but its early history remains controversial due to uneven availability of constraints. Recent plate reconstructions reveal two prominent counterclockwise rotation (azimuthal change) rate peaks of the Indian plate at 52-44 and 33-20 Ma, respectively, which could bear key information about this collision history. Using fully dynamic three-dimensional numerical modeling, we show that the first rotation rate peak reflected the initial diachronous collision from the western-central to eastern Indian front, and the second peak reflected the full collision leading to strong coupling between India and Eurasia. Further comparison with observation suggests that the initial and complete India-Eurasia collision likely occurred at 55 ± 5 and 40 ± 5 Ma, respectively, an inference consistent with key geological observations. We suggest that this collision history is instructive for studying the tectonic history of the Tibetan plateau and its surrounding areas.

Abstract Changing thermal regime is one of the key mechanisms driving seismogenic behaviors at cold megathrusts, but it is difficult to interpret warm subduction zones such as Vanuatu for the temperatures are higher than that accommodates shallow brittle failures. We construct a 3-D thermomechanical model to clarify the thermal structure that controls tectonic seismicity in Vanuatu and predict a warm circumstance associated with abundant seismicity. Results reveal a heterogeneous slab ranging from 300 °C to over 900 °C from the Moho to subvolcanic depth. The subduction seismicity corresponds well to the plate interface where dynamic thermal dehydration is focused. The transformation from hydrated basalts to eclogites along the slab facilitates the occurrence of intense earthquakes and slips. Multistage mineralogical metamorphism affects the dynamic stability of megathrusts and favors the generation of active interplate large events. Therefore, slab thermal dehydration plays a greater role than slab temperature condition in influencing the subduction earthquake distribution in warm subduction systems.

Abstract Purpose The optimal procedure is still controversial about Siewert type II AEG, We are attempt to explore the efficacy and feasibility of total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis for Siewert type II AEG. Method Data of patients with Siewert type II AEG who received total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis in the Hebei General Hospital were collected from October 2020 to October 2021, The operation time, surgical blood loss, the number of dissected lymph nodes, duration of drainage tube, the length of stay in ICU, the resume oral feeding time, the length of postoperative hospital stay, postoperative complications and other related indicators of the patients were collected to evaluate the safety and feasibility of this operation. Result A total of 17 patients received total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosisin the treatment of Siewert type II AEG were analyzed in our research. The mean operation time was 253 ± 24.8 min (196–347 min); The median surgical blood loss was 250 ml (20–2400 ml); The average number of dissected lymph nodes were 28 ± 4.6 (17–36); The median duration of drainage tube was 5 days (3–7days); The median length of stay in ICU was 18 h(10–34 h); The median time of resume oral feeding was 6 days (5–7days); The median postoperative hospital stay was 11 days (8–15 days). Among the all enrolled patients, one patient underwent the conversion to laparotomy due to the massive intraoperative bleeding, one patient developed anastomotic stenosis at jejunum side-to-side anastomosis on the first month after surgery, there was no case of death during the operation and postoperative anastomotic fistula. All patients achieved R0 resection with an average distance of 6 cm (4–8.5 cm) from the upper margin of the tumor to the resection margin. Conclusion The operation of total laparoscopic total gastric and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis is technically feasible and sufficiently safe in the treatment of Seiwert type II AEG from our primary clinical experience. This procedure could be one of the alternatives for the radical treatment of Siewert type II AEG.

Introduction: The oriental fruit fly Bactrocera dorsalis is one of the most destructive agricultural pests worldwide, with highly debated species delimitation, origin, and global spread routes. Objectives: Our study intended to (i) resolve the taxonomic uncertainties between B. dorsalis and B. carambolae, (ii) reveal the population structure and global invasion routes of B. dorsalis across Asia, Africa, and Oceania, and (iii) identify genomic regions that are responsible for the thermal adaptation of B. dorsalis. Methods: Based on a high-quality chromosome-level reference genome assembly, we explored the population relationship using a genome-scale single nucleotide polymorphism dataset generated from the resequencing data of 487 B. dorsalis genomes and 25 B. carambolae genomes. Genome-wide association studies and silencing using RNA interference were used to identify and verify the candidate genes associated with extreme thermal stress. Results: We showed that B. dorsalis originates from the Southern India region with three independent invasion and spread routes worldwide: (i) from Northern India to Northern Southeast Asia, then to Southern Southeast Asia; (ii) from Northern India to Northern Southeast Asian, then to China and Hawaii; and (iii) from Southern India toward the African mainland, then to Madagascar, which is mainly facilitated by human activities including trade and immigration. Twenty-seven genes were identified by a genome-wide association study to be associated with 11 temperature bioclimatic variables. The Cyp6a9 gene may enhance the thermal adaptation of B. dorsalis and thus boost its invasion, which tended to be upregulated at a hardening temperature of 38 °C. Functional verification using RNA interference silencing against Cyp6a9, led to the specific decrease in Cyp6a9 expression, reducing the survival rate of dsRNA-feeding larvae exposed to extreme thermal stress of 45 °C after heat hardening treatments in B. dorsalis. Conclusion: This study provides insights into the evolutionary history and genetic basis of temperature adaptation in B. dorsalis.

Abstract Cardiovascular disease (CVD) is the leading cause of death in the world, with a high incidence and a youth-oriented tendency. RNA modification is ubiquitous and indispensable in cell, maintaining cell homeostasis and function by dynamically regulating gene expression. Accumulating evidence has revealed the role of aberrant gene expression in CVD caused by dysregulated RNA modification. In this review, we focus on nine common RNA modifications: N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N7-methylguanosine (m7G), N4-acetylcytosine (ac4C), pseudouridine (Ψ), uridylation, adenosine-to-inosine (A-to-I) RNA editing, and modifications of U34 on tRNA wobble. We summarize the key regulators of RNA modification and their effects on gene expression, such as RNA splicing, maturation, transport, stability, and translation. Then, based on the classification of CVD, the mechanisms by which the disease occurs and progresses through RNA modifications are discussed. Potential therapeutic strategies, such as gene therapy, are reviewed based on these mechanisms. Herein, some of the CVD (such as stroke and peripheral vascular disease) are not included due to the limited availability of literature. Finally, the prospective applications and challenges of RNA modification in CVD are discussed for the purpose of facilitating clinical translation. Moreover, we look forward to more studies exploring the mechanisms and roles of RNA modification in CVD in the future, as there are substantial uncultivated areas to be explored.

Abstract Background Whole-exome sequencing (WES) significantly improves the diagnosis of the etiology of fetal structural anomalies. This study aims to evaluate the diagnostic value of prenatal WES and to investigate the pathogenic variants in structurally abnormal fetuses. Methods We recruited 144 fetuses with structural anomalies between 14 and 2020 and 15 December 2021 in the study. Genetic screening was performed by WES combined with karyotyping and chromosomal microarray analysis. The molecular diagnostic yield of prenatal WES for each type of fetal structural anomaly and the identified pathogenic genes and mutations were reported. Results In this study, we retrospectively analyzed the clinical and genetic data of 145 structurally anomalous fetuses. These cases were classified into 9 phenotypic classes based on antenatal ultrasound findings. Thirty-eight pathogenic variants in 24 genes were identified in 35 of the 145 cases, including 14 novel variants in 13 genes (EP300, MYH3, TSC2, MMP9, CPLANE1, INVS, COL1A1, EYA1, TTC21B, MKS1, COL11A2, PDHA1 and L1CAM). Five additional pathogenic variants were classified as incidental findings. Our study showed that the overall diagnosis rate of WES was 28.1% (27/96) in the parent-fetus trio cases and 16.3% (8/49) in the proband-only cases. Fetuses with musculoskeletal anomalies had the highest diagnostic yield (51.4%, 19/37). In addition, FGFR3 and COL1A1 were the most common pathogenic genes. Conclusions Our work expands the mutation spectrum of the genes associated with fetal structural anomalies and provides valuable information for future parental genetic counselling and pregnancy management of the structurally anomalous fetuses.

A method was established for the simultaneous determination of 3-methoxytyramine and adrenaline in dairy products by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) compled with isotope dilution. Sample was extracted by perchloric acid solution, cleaned by weak cationic solid phase extraction column. The analyte was separated by ACQUITY UPLC BEH C18 (100 mm×2.1 mm, 1.7 μm) column and agradient elution of mobile phase with 0.1% formic acid aqueous solution-methanol. The detection was achieved by HPLC-MS/MS with electrospray ion source and positive ion scanning mode as well as multiple reaction monitoring (MRM) mode. The quantification was accomplished by the internal standard method. It was demonstrated that the linear relationships of 3-methoxytyramine and adrenaline were good in the range of 0.5~12.0 ng/mL and 50~1200 ng/mL (r>0.99), respectively. The detection limits and the limit of quantification of 3-methoxytyramine were 0.2 and 0.5 μg/kg, respectively. At the concentrations of 0.5, 1.0 and 3.0 μg/kg, the recoveries of the 3-methoxytyramine ranged from 76.97% to 119.20%, with the corresponding precision (n=6) of 1.53%~9.61%. While the recoveries of adrenaline at 50, 100 and 300 μg/kg were 90.65%~108.55% and the relative standard deviations were in the range of 1.29%~3.95%. The method would be accurate in results and good in repeatability, and it can be an important measure to monitor 3-methoxytyramine and adrenaline in dairy products.

Reconstructing the state of quantum many-body systems is of fundamental importance in quantum information tasks, but extremely challenging due to the curse of dimensionality. In this work, we present an efficient quantum tomography protocol that combines the state-factored with eigenvalue mapping to address the rank-deficient issue and incorporates a momentum-accelerated gradient descent algorithm to speed up the optimization process. We implement extensive numerical experiments to demonstrate that our factored gradient descent algorithm efficiently mitigates the rank-deficient problem and admits orders of magnitude better tomography accuracy and faster convergence. We also find that our method can accomplish the full-state tomography of random 11-qubit mixed states within one minute.

The positive effects of afforestation in karst rocky desertification areas are often limited by soil nitrogen (N) availability. However, how plant N limitation evolves in response to prolonged afforestation as well as the mechanisms underlying plant N limitation and soil N availability are poorly understood. In this study, plant leaves and soil samples were collected from cropland, Dodonaea viscosa plantations 10, 20 and 40 years after their establishment on abandoned cropland in a karst rocky desertification area. The natural succession of shrubland served as the control. Foliar N/phosphorus (P) stoichiometry was used to evaluate plant N limitation, and the N concentration and δ15N value of foliar and soil were measured to evaluate the changes in soil N availability. Soil N transformation rates were also determined, using 15N tracing technique to elucidate the mechanism underlying soil inorganic N availability. The plant community-level foliar N/P ratio (13.5) was lower than 14 following 10-y afforestation, indicating that plant growth is predominantly N limited. With the prolonged afforestation, the plant community-level foliar N/P ratio increased to 14.0–15.5, suggesting decreased plant N limitation. This could be attributed to increased soil N availability confirmed by the raises in the N concentration and δ15N of plant community-level foliar and soil δ15N with prolonged afforestation. Compared to cropland, D. viscosa afforestation increased the soil inorganic N supply capacity, by stimulating organic N mineralization, heterotrophic nitrification and the release of adsorbed ammonium, more obviously with prolonged afforestation. The rates of mineralization, heterotrophic nitrification and the release of adsorbed ammonium correlated significantly and positively with the plant community-level foliar N concentration, N/P ratio, and δ15N, indicating that a larger soil inorganic N supply alleviates plant N limitation. This effect can be attributed to the increases in organic matter content, bacterial and fungal abundances and soil structure improvement following afforestation, all of which facilitate mineralization and heterotrophic nitrification. However, plant N limitation after 40 years of afforestation still exists, suggesting that monoculture afforestation may need to be adapted to maximize soil N availability and to alleviate plant N limitation in karst rocky desertification areas.

IntroductionActivation of complement through the alternative pathway (AP) has a key role in the pathogenesis of IgA nephropathy (IgAN). We previously showed, by intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE), C57BL/6 mice develop mild kidney damage in association with glomerular IgA deposition. To further address complement activity in causing glomerular histological alterations as suggested in the pathogenesis of IgAN, here we used mice with factor H mutation (FHW/R) to render AP overactivation in conjunction with LCWE injection to stimulate intestinal production of IgA.MethodsDose response to LCWE were examined between two groups of FHW/R mice. Wild type (FHW/W) mice stimulated with LCWE were used as model control.ResultsThe FHW/R mice primed with high dose LCWE showed elevated IgA and IgA-IgG complex levels in serum. In addition to 100% positive rate of IgA and C3, they display elevated biomarkers of kidney dysfunction, coincided with severe pathological lesions, resembling those of IgAN. As compared to wild type controls stimulated by the same high dose LCWE, these FHW/R mice exhibited stronger complement activation in the kidney and in circulation.DiscussionThe new mouse model shares many disease features with IgAN. The severity of glomerular lesions and the decline of kidney functions are further aggravated through complement overactivation. The model may be a useful tool for preclinical evaluation of treatment response to complement-inhibitors.

High levels of copper released in the soil, mainly from anthropogenic activity, can be hazardous to plants, animals, and humans. The present research aimed to estimate the suitability and effectiveness of rapeseed (Brassica napus L.) as a possible soil remediation option and to uncover underlying adaptive mechanisms A pot experiment was conducted to explore the effect of copper stress on agronomic and yield traits for 32 rapeseed genotypes. The copper-tolerant genotype H2009 and copper-sensitive genotype ZYZ16 were selected for further physiological, metabolomic, and transcriptomic analyses. The results exhibited a significant genotypic variation in copper stress tolerance in rapeseed. Specifically, the ratio of seed yield under copper stress to control ranged from 0.29 to 0.74. Furthermore, the proline content and antioxidant enzymatic activities in the roots were greater than those in the shoots. The accumulated copper in the roots accounted for about 50% of the total amount absorbed by plants; thus, the genotypes possessing high root volumes can be used for rhizofiltration to uptake and sequester copper. Additionally, the pectin and hemicellulose contents were significantly increased by 15.6% and 162%, respectively, under copper stress for the copper-tolerant genotype, allowing for greater sequestration of copper ions in the cell wall and lower oxidative stress. Comparative analysis of transcriptomes and metabolomes revealed that excessive copper enhanced the up-regulation of functional genes or metabolites related to cell wall binding, copper transportation, and chelation in the copper-tolerant genotype. Our results suggest that copper-tolerant rapeseed can thrive in heavily copper-polluted soils with a 5.85% remediation efficiency as well as produce seed and vegetable oil without exceeding food quality standards for the industry. This multi-omics comparison study provides insights into breeding copper-tolerant genotypes that can be used for the phytoremediation of heavy metal-polluted soils.

IntroductionIgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis globally. While nephrotic syndrome (NS) is uncommon in IgAN, its significance remains unclear.MethodsWe conducted a retrospective analysis of 170 IgAN patients, classifying them into NS (n = 85) and non-NS (n = 85) groups. Our study aims to compare their clinical characteristics, treatment responses, and prognoses. Patients were selected based on renal biopsy from 2003 to 2020. Propensity score matching ensured comparability. Clinical, pathological, and immunological data were analyzed. Composite endpoints were defined as end-stage kidney disease (ESKD) or a 30% decline in estimated glomerular filtration rate (eGFR).ResultsNS patients showed higher eGFR (74.3 ± 36.8 vs. 61.5 ± 33.6 mL/min.1.73 m2, p = 0.02), severe hematuria (35.0 (4.7,147.5) vs. 4.0 (1.8,45,0) cells/μl, p

Several studies have demonstrated that Ag2S QDs are promising near-infrared II-emitting nanoprobes. They Ag2S QDs can be used in the fields of bio-imaging, fluorescence detection and photodetectors. In this work, we achieved the first successful construction of a dual-input logic gate IMPLICATION gate based on the specific detection of Fe3+ by silver sulfide quantum dots and the reduction of Fe3+ by ascorbic acid. The Ag2S QDs were successfully prepared from glutathione and silver nitrate and characterized by fluorescence spectroscopy analysis, XPS analysis, and transmission electron microscopy TEM analysis. The prepared Ag2S QDs can achieve selective detection of Fe3+ with a detection limit of LOD of 0.15 mM. This work provides a new method for the detection of Fe3+.

Abstract Background The progression of acute lung injury (ALI) involves numerous pathological factors and complex mechanisms, and cause the destruction of epithelial and endothelial barriers. Pigment epithelium-derived factor (PEDF) is an angiogenesis inhibitor and a potential anti-inflammatory factor. The purpose of this study was to investigate the effect of PEDF on lipopolysaccharide (LPS)-induced ALI in rats. Methods In vivo, pathological and injury related factors examination were performed on rat lung to investigate the effect of PEDF on ALI. In vitro, the effect of PEDF on inflammatory injury and apoptosis of lung epithelial type II RLE-6TN cell was evaluated, and the expression of inflammatory factors and related pathway proteins and PPAR-γ (in the presence or absence of PPAR-γ inhibitors) were analyzed. Results In vivo results showed that PEDF inhibited the inflammatory factor expression (TNF-α, IL-6 and IL-1β) and progression of ALI and reduced lung cell apoptosis in rats. In vitro results showed that PEDF could effectively inhibit LPS-stimulated inflammatory damage and apoptosis of RLE-6TN cells. PEDF inhibited the RLE-6TN cell injury by enhancing the expression of PPAR-γ. Conclusions PEDF is an anti-inflammatory factor, which can inhibit apoptosis of lung epithelial cells by upregulating the expression of PPAR-γ and reducing LPS-induced ALI in rats.

Abstract Non-small cell lung cancer (NSCLC) is the most prevalent type of cancer and the leading cause of cancer-related death. Chemotherapeutic resistance is a major obstacle in treating NSCLC patients. Here, we discovered that the E3 ligase Skp2 is overexpressed, accompanied by the downregulation of necroptosis-related regulator MLKL in human NSCLC tissues and cell lines. Knockdown of Skp2 inhibited viability, anchorage-independent growth, and in vivo tumor development of NSCLC cells. We also found that the Skp2 protein is negatively correlated with MLKL in NSCLC tissues. Moreover, Skp2 is increased and accompanied by an upregulation of MLKL ubiquitination and degradation in cisplatin-resistant NSCLC cells. Accordingly, inhibition of Skp2 partially restores MLKL and sensitizes NSCLC cells to cisplatin in vitro and in vivo. Mechanistically, Skp2 interacts and promotes ubiquitination-mediated degradation of MLKL in cisplatin-resistant NSCLC cells. Our results provide evidence of an Skp2-dependent mechanism regulating MLKL degradation and cisplatin resistance, suggesting that targeting Skp2-ubiquitinated MLKL degradation may overcome NSCLC chemoresistance.

Abstract Background As a chronic mountain sickness(CMS) with the highest incidence and the greatest harm, the pathogenesis of high altitude polycythemia (HAPC) is still not fully understood. Methods 37 HAPC patients and 42 healthy subjects were selected from plateau, and peripheral venous blood samples were collected for transcriptome sequencing on Illumina NovaSeq platform. The sequenced data were analyzed by bioinformatics and phenotypic association analysis. Results The results showed significant differences in multiple clinical indicators including RBC and HGB et al. existed between HAPC and control. Based on the RNA-seq data, 550 genes with significant differential expression were identified in HAPC patients. GO and KEGG pathway enrichment analysis showed that the up-regulated genes were mainly enriched in processes such as erythrocyte differentiation and development and homeostasis of number of cells, while the down-regulated genes were mainly enriched in categories such as immunoglobulin production, classical pathway of complement activation and other biological processes. The coupling analysis of differential expression genes(DEGs) and pathological phenotypes revealed that 91 DEGs were in close correlation with in the phenotype of red blood cell volume distribution (width-CV and width-SD), and they were all up-regulated in HAPC and involved in the process of erythrocyte metabolism. Combined with the functional annotation of DEGs and literature survey, we found that the expression of several potential genes might be responsible for pathogenesis of HAPC. Besides, cell type deconvolution analysis result suggested that the changes in the number of some immune cell types was significantly lower in HAPC patients than control, implying the autoimmune level of HAPC patients was affected to a certain extent. Conclusion This study provides an important data source for understanding the pathogenesis and screening pathogenic genes of HAPC. We found for the first time that there was a significant correlation between HAPC and the pathological phenotype of width-CV and width-SD, wherein the enriched genes were all up-regulated expressed and involved in the process of erythrocyte metabolism. Although the role of these genes needs to be further studied, the candidate genes can provide a starting point for functionally pinning down the underlying mechanism of HAPC.

Abstract Objective Dermatomyositis (DM) positive with anti-melanoma differentiation-associated gene 5 (anti-MDA5-DM) is a systemic autoimmune disease with high mortality. This study aimed to explore the risk factors of death in anti-MDA5-DM and validate a prediction model for all-cause mortality in anti-MDA5-DM. Method We conducted a retrospective study using a single-centre cohort of patients with newly onset anti-MDA5-DM from June 1, 2018 to August 31, 2021. Patients were divided into four groups according to baseline ground-glass opacity (GGO) score: Group A, GGO ≤ 1; Group B, 1 3. The primary outcome was death during the follow-up. Secondary outcomes included death within 3, 6, 12 months, severe infection, and remission during the first 12 months. Results A total of 200 patients were included in the study. Based on multivariable Cox regression, the prognostic factors at baseline were identified as CRP > 5 mg/L, serum ferritin (SF) > 600ng/ml, positive anti-Ro52 antibody, prophylactic use of compound sulfamethoxazole (SMZ Co), four-category GGO score: GGO ≤ 1, 1 3. The final mortality of four groups was 16.4, 22.2, 48.5, 92.0%, respectively. Compared with Group A, the Hazards Ratio (HR) of Group B was 1.408, (p = 0.408), HR of Group C was 3.433 (p = 0.005), HR of Group D was 4.376 (p = 0.001). Conclusions GGO score is a reliable predictor for risk stratification in anti-MDA5-DM and may provide guidance for individualized managements of patients.