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Background. CKD-MBD is a mineral and bone metabolism syndrome caused by chronic kidney disease. FGF23 is an important factor regulating phosphorus and is the main influencer in the CKD-MBD process. In this study, we observed the correlation among serum FGF23 and calcium, phosphorus and parathyroid hormone, and the correlation between FGF23 levels and cardiac structural changes in MHD patients. Methods. We examined serum FGF23 concentrations in 107 cases of MHD patients using the ELISA method, recorded demographic information and biochemical data, and analyzed the correlation between serum FGF23 levels and blood calcium and blood phosphorus and PTH levels. All patients were evaluated by cardiac color ultrasound, and we finally analyzed the association between the FGF23 level and cardiac structural changes. Results. In 107 cases of MHD patients, serum FGF23 levels were linearly associated with serum calcium (r = 0.27 P < 0.01 ) and parathyroid hormone levels (r = 0.25, P < 0.05 ). FGF 23 was negatively correlated with age (r = −0.44, P < 0.01 ).Serum FGF23 levels were correlated with right atrial hypertrophy in HD patients ( P < 0.05 ). No correlation was found among FGF23, left ventricular hypertrophy/enlargement, and valve calcification stenosis ( P > 0.05 ). Conclusion. Serum FGF23 showed a positive correlation among blood calcium levels and PTH levels in hemodialysis patients, and FGF23 levels can affect the incidence of right atrial hypertrophy in MHD patients.

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OBJECTIVE: To assess the safety and effectiveness of intravascular lithotripsy (IVL) treatment for de novo coronary lesion involving severely calcified vessels in a Chinese population. METHODS: The Clinical Trial of the ShOckwave Coronary IVL System Used to Treat CalcIfied Coronary ArtEries (SOLSTICE) was a prospective, single-arm, multicentre trial. According to the inclusion criteria, patients with severely calcified lesions were enrolled in the study. IVL was used to perform calcium modification prior to stent implantation. The primary safety endpoint was freedom from major adverse cardiac events (MACEs) at 30 days. The primary effectiveness endpoint was procedural success, defined as successful stent delivery with residual stenosis < 50% by core lab assessment without in-hospital MACEs. The morphological changes of calcium modification were assessed by optical coherence tomography (OCT) before and after IVL treatment. RESULTS: Patients (n = 20) were enrolled at three sites in China. Severe calcification by core lab assessment was present in all lesions, with a mean calcium angle and thickness of 300 ± 51° and 0.99 ± 0.12 mm (by OCT), respectively. The 30-day MACE rate was 5%. Both primary safety and effectiveness endpoints were achieved in 95% of patients. The final in-stent diameter stenosis was 13.1% ± 5.7% with no patient had a residual stenosis < 50% after stenting. No serious angiographic complications (severe dissection grade D or worse, perforation, abrupt closure, slow flow/no-reflow) observed at any time during the procedure. OCT imaging demonstrated visible multiplane calcium fracture in 80% of lesions with a mean stent expansion of 95.62% ± 13.33% at the site of maximum calcification and minimum stent area (MSA) of 5.34 ± 1.64 mm(2). CONCLUSIONS: The initial coronary IVL experience for Chinese operators resulted in high procedural success and low angiographic complications consistent with prior IVL studies, reflecting the relative ease of use of IVL technology.

The effect of trace solvent bisphenol A (BPA) in polyether sulfone hollow fiber membrane Enttex™-16LF (E60) (produced by 3 M) low-throughput dialyzer was tested in this study. Animal experiments were conducted to evaluate its genotoxicity, carcinogenicity, and teratogenicity upon chronic exposure. The dialyzer was operated at 200 mL/min and 400 mL/min and coupled with LC-20AT liquid chromatography to detect BPA, which showed that the BPA content was less than 5 μg/kg/d at both flow rates. In animal experiments, the tolerable intake (T.I.) was calculated to be 0.5 μg/kg/d. With hemodialysis three times per week, the average patient weight was calculated at 70 kg, and the average daily BPA exposure was 0.0306 μg/kg/d. The risk of residual BPA was within the acceptable limit with polyether sulfone membrane Enttex™-16LF (E60) hollow fiber dialyzer from 3 M, without inducing risk for disability, teratogenicity, or genotoxicity.

Diabetic kidney disease (DKD) is the most common complication of type 2 diabetes mellitus (T2DM), and its pathogenesis is not yet fully understood and lacks noninvasive and effective diagnostic biomarkers. In this study, we performed urine metabolomics to identify biomarkers for DKD and to clarify the potential mechanisms associated with disease progression.We applied a liquid chromatography-mass spectrometry-based metabolomics method combined with bioinformatics analysis to investigate the urine metabolism characteristics of 79 participants, including healthy subjects (n = 20), T2DM patients (n = 20), 39 DKD patients that included 19 DKD with microalbuminuria (DKD + micro) and 20 DKD with macroalbuminuria (DKD + macro).Seventeen metabolites were identified between T2DM and DKD that were involved in amino acid, purine, nucleotide and primarily bile acid metabolism. Ultimately, a combined model consisting of 2 metabolites (tyramine and phenylalanylproline) was established, which had optimal diagnostic performance (area under the curve (AUC) = 0.94). We also identified 19 metabolites that were co-expressed within the DKD groups and 41 metabolites specifically expressed in the DKD + macro group. Ingenuity pathway analysis revealed three interaction networks of these 60 metabolites, involving the sirtuin signaling pathway and ferroptosis signaling pathway, as well as the downregulation of organic anion transporter 1, which may be important mechanisms that mediate the progression of DKD.This work reveals the metabolic alterations in T2DM and DKD, constructs a combined model to distinguish them and delivers a novel strategy for studying the underlying mechanism and treatment of DKD.

Within the framework of dispersion theory, we study the the processes $e^+e^-\to \phi(2170) \to \phi \pi\pi(K\bar{K})$. The strong pion-pion final-state interactions, especially the $K\bar{K}$ coupled channel in the $S$-wave, are taken into account in a model-independent way using the Omn\`es function solution. Through fitting the experimental data of the $\pi\pi$ and $\phi\pi$ invariant mass distributions of the $e^+e^- \to \phi(2170) \to \phi \pi^+\pi^-$ process, the low-energy constants in the chiral Lagrangian are determined. The theoretical prediction for the cross sections ratio ${\sigma(e^+e^- \to \phi(2170)\to \phi K^+ K^-)}/{\sigma(e^+e^- \to \phi(2170)\to \phi\pi^+\pi^-)}$ is given, which could be useful for selecting the physical solution when the fit to the $e^+e^- \to \phi K^+ K^-$ cross section distribution is available in the future. Our results suggest that above the kinematical threshold of $\phi K\bar{K}$, the mechanism $e^+e^- \to \phi K^+ K^-$ with the kaons rescattering to a pion pair plays an important role in the $e^+e^- \to \phi\pi^+\pi^-$ transition., Comment: 14 pages, 3 figures. arXiv admin note: text overlap with arXiv:1902.10957, arXiv:2104.01752

Within the framework of dispersion theory, we study the the processes e+e−→ϕ(2170)→ϕππ(KK¯). The strong pion–pion final-state interactions, especially the KK¯ coupled channel in the S wave, are taken into account in a model-independent way using the Omnès function solution. Through fitting the experimental data of the ππ and ϕπ invariant mass distributions of the e+e−→ϕ(2170)→ϕπ+π− process, the low-energy constants in the chiral Lagrangian are determined. The theoretical prediction for the cross sections’ ratio σ(e+e−→ϕ(2170)→ϕK+K−)/σ(e+e−→ϕ(2170)→ϕπ+π−) is given, which could be useful for selecting the physical solution, when the fit to the e+e−→ϕK+K− cross-section distribution is available in the future. Our results suggest that above the kinematical threshold of ϕKK¯, the mechanism e+e−→ϕK+K−, with the kaons rescattering to a pion pair, plays an important role in the e+e−→ϕπ+π− transition.

One strategy to obtain user location information in a wireless network operating at millimeter wave (mmWave) is based on the exploitation of the geometric relationships between the channel parameters and the user position. These relationships can be easily built from the LoS path and/or first order reflections, but high resolution channel estimates are required for high accuracy. In this paper, we consider a mmWave MIMO system based on a hybrid architecture, and develop first a low complexity channel estimation strategy based on MOMP suitable for high dimensional channels, as those associated to operating with large planar arrays. Then, a deep neural network (DNN) called PathNet is designed to classify the order of the estimated channel paths, so that only the line-of-sight (LOS) path and first order reflections are selected for localization purposes. Next, a 3D localization strategy exploiting the geometry of the environment is developed to operate in both LOS and non-line-of-sight (NLOS) conditions, while considering the unknown clock offset between the transmitter (TX) and the receiver (RX). Finally, a Transformer based network exploiting attention mechanisms called ChanFormer is proposed to refine the initial position estimate obtained from the geometric system of equations that connects user position and channel parameters. Simulation results obtained with realistic vehicular channels generated by ray tracing indicate that sub-meter accuracy (, Journal

Developing dialogue relation extraction (DRE) systems often requires a large amount of labeled data, which can be costly and time-consuming to annotate. In order to improve scalability and support diverse, unseen relation extraction, this paper proposes a method for leveraging the ability to capture triggers and relate them to previously unseen relation names. Specifically, we introduce a model that enables zero-shot dialogue relation extraction by utilizing trigger-capturing capabilities. Our experiments on a benchmark DialogRE dataset demonstrate that the proposed model achieves significant improvements for both seen and unseen relations. Notably, this is the first attempt at zero-shot dialogue relation extraction using trigger-capturing capabilities, and our results suggest that this approach is effective for inferring previously unseen relation types. Overall, our findings highlight the potential for this method to enhance the scalability and practicality of DRE systems.

Tropical cyclone (TC) annual frequency forecasting is significant for disaster prevention and mitigation in Guangdong Province. Based on the NCEP-NCAR reanalysis and NOAA Extended Reconstructed global sea surface temperature (SST) V5 data in winter, the TC frequency climatic features and prediction models have been studied. During 1951-2019, 353 TCs directly affected Guangdong with an annual average of about 5.1. TCs have experienced an abrupt change from abundance to deficiency in the mid to late 1980 with a slightly decreasing trend and a normal distribution. 338 primary precursors are obtained from statistically significant correlation regions of SST, sea level pressure, 1000hPa air temperature, 850hPa specific humidity, 500hPa geopotential height and zonal wind shear in winter. Then those 338 primary factors are reduced into 19 independent predictors by principal component analysis (PCA). Furthermore, the Multiple Linear Regression (MLR), the Gaussian Process Regression (GPR) and the Long Short-term Memory Networks and Fully Connected Layers (LSTM-FC) models are constructed relying on the above 19 factors. For three different kinds of test sets from 2010 to 2019, 2011 to 2019 and 2010 to 2019, the root mean square errors (RMSEs) of MLR, GPR and LSTM-FC between prediction and observations fluctuate within the range of 1.05-2.45, 1.00-1.93 and 0.71-0.95 as well as the average absolute errors (AAEs) 0.88-1.0, 0.75-1.36 and 0.50-0.70, respectively. As for the 2010-2019 experiment, the mean deviations of the three model outputs from the observation are 0.89, 0.78 and 0.56, together with the average evaluation scores 82.22, 84.44 and 88.89, separately. The prediction skill comparisons unveil that LSTM-FC model has a better performance than MLR and GPR. In conclusion, the deep learning model of LSTM-FC may shed light on improving the accuracy of short-term climate prediction about TC frequency. The current research can provide experience on the development of deep learning in this field and help to achieve further progress of TC disaster prevention and mitigation in Guangdong Province.

Loss of the von Hippel–Lindau (VHL) tumor suppressor gene function accounts for 70% to 80% of all clear-cell renal cell carcinoma (ccRCC) cases, the most prevalent form of RCC. Accumulating evidence has indicated that ccRCC arises from sites of chronic inflammation, yet how ccRCC tumor cells interact with immune components of the microenvironment has not been fully elucidated. In this study, we used unbiased proteomic and genomic analyses on components of the tumor microenvironment under different conditions, identifying the molecular and cellular mechanisms that underlie the cross-talk between VHL-deficient kidney tubule cells and macrophages. In vitro and in a Vhlh conditional knockout mouse model, VHL-deficient noncancerous kidney epithelial cells, representing the early stage of ccRCC initiation, secreted IL6 that induced macrophage infiltration and polarization toward the protumorigenic M2 phenotype. Activated human macrophages secreted CCL18 and TGFβ1 to stimulate epithelial-to-mesenchymal transition (EMT) of the kidney tubule cells. Treatment with IL6-neutralizing antibody rescued inflammatory, proliferative, and EMT phenotypes of kidney epithelial cells in Vhlh conditional knockout mice. Furthermore, in a human ccRCC xenograft model, exogenous human primary or cultured macrophages significantly promoted primary tumor growth and metastasis in a CCL18-dependent manner. These findings identify specific factors involved in reciprocal cross-talk between tumor cells and immune components in the microenvironment, thus providing an avenue for early intervention in ccRCC. Significance: The identification of VHL-deficient kidney tubule cell cross-talk with macrophages regulated by IL6 and CCL18 reveals potential targets for the prevention and treatment of ccRCC.

We propose LLM-Eval, a unified multi-dimensional automatic evaluation method for open-domain conversations with large language models (LLMs). Existing evaluation methods often rely on human annotations, ground-truth responses, or multiple LLM prompts, which can be expensive and time-consuming. To address these issues, we design a single prompt-based evaluation method that leverages a unified evaluation schema to cover multiple dimensions of conversation quality in a single model call. We extensively evaluate the performance of LLM-Eval on various benchmark datasets, demonstrating its effectiveness, efficiency, and adaptability compared to state-of-the-art evaluation methods. Our analysis also highlights the importance of choosing suitable LLMs and decoding strategies for accurate evaluation results. LLM-Eval offers a versatile and robust solution for evaluating open-domain conversation systems, streamlining the evaluation process and providing consistent performance across diverse scenarios., Accepted at 5th NLP4ConvAI

Ahlfors' theory of covering surfaces is one of the major mathematical achievement of last century. The most important part of his theory is the Second Fundamental Theorem (SFT). We are interested in the relation of errors of Ahlfors' SFT with the same boundary curve. In this paper we will prove a result which is used to establish the best bound of the constant in Ahlfors' SFT in arXiv.2307.04623. Precisely speaking, we will prove that for any surface $\Sigma\in\mathcal{F}_r(L,m)$, a new surface $\Sigma_1$ can be constructed based on it, such that $R(\Sigma_1)\ge R(\Sigma)$ and $L(\partial\Sigma_1)\le L(\partial\Sigma)$, where $R(\Sigma)$ is Ahlfors' error term and $L(\partial\Sigma)$ is the boundary length of the surface $\Sigma$, and the covering degree of $\Sigma_1$ has an upper bound independent of surfaces. Meanwhile, this conclusion suggests that the supremum of $H(\Sigma)=R(\Sigma)/L(\partial\Sigma)$ can be achieved by surfaces in the space $\mathcal{F}_r'(L,m)$., Comment: 21 pages, 2 figures

Background Where the gene is expressed determines the function of the gene. Neuregulin 1 (Nrg1) encodes a tropic factor and is genetically linked with several neuropsychiatry diseases such as schizophrenia, bipolar disorder and depression. Nrg1 has broad functions ranging from regulating neurodevelopment to neurotransmission in the nervous system. However, the expression pattern of Nrg1 at the cellular and circuit levels in rodent brain is not full addressed. Methods Here we used CRISPR/Cas9 techniques to generate a knockin mouse line (Nrg1Cre/+) that expresses a P2A-Cre cassette right before the stop codon of Nrg1 gene. Since Cre recombinase and Nrg1 are expressed in the same types of cells in Nrg1Cre/+ mice, the Nrg1 expression pattern can be revealed through the Cre-reporting mice or adeno-associated virus (AAV) that express fluorescent proteins in a Cre-dependent way. Using unbiased stereology and fluorescence imaging, the cellular expression pattern of Nrg1 and axon projections of Nrg1-positive neurons were investigated. Results In the olfactory bulb (OB), Nrg1 is expressed in GABAergic interneurons including periglomerular (PG) and granule cells. In the cerebral cortex, Nrg1 is mainly expressed in the pyramidal neurons of superficial layers that mediate intercortical communications. In the striatum, Nrg1 is highly expressed in the Drd1-positive medium spiny neurons (MSNs) in the shell of nucleus accumbens (NAc) that project to substantia nigra pars reticulata (SNr). In the hippocampus, Nrg1 is mainly expressed in granule neurons in the dentate gyrus and pyramidal neurons in the subiculum. The Nrg1-expressing neurons in the subiculum project to retrosplenial granular cortex (RSG) and mammillary nucleus (MM). Nrg1 is highly expressed in the median eminence (ME) of hypothalamus and Purkinje cells in the cerebellum. Conclusions Nrg1 is broadly expressed in mouse brain, mainly in neurons, but has unique expression patterns in different brain regions.

A Brief Overview of Different Aspect of Civil Engineering and Structural Engineering

The COP9 signalosome (Csn) complex is an evolutionarily conserved complex that regulates various important cellular processes. However, the function of the Csn complex in pathogenic fungi remains elusive. Here, the distribution of Csn subunits in the fungal kingdom was surveyed, and their biological functions were systematically characterized in the fungal pathogen Fusarium graminearum, which is among the top 10 plant fungal pathogens. The results obtained from bioinformatic analyses suggested that the F. graminearum Csn complex consisted of seven subunits (Csn1–Csn7) and that Csn5 was the most conserved subunit across the fungi kingdom. Yeast two-hybrid assays demonstrated that the seven Csn subunits formed a complex in F. graminearum. The Csn complex was localized to both the nucleus and cytoplasm and necessary for hyphal growth, asexual and sexual development and stress response. Transcriptome profiling revealed that the Csn complex regulated the transcription abundance of TRI genes necessary for mycotoxin deoxynivalenol (DON) biosynthesis, subsequently regulating DON production to control fungal virulence. Collectively, the roles of the Csn complex in F. graminearum were comprehensively analyzed, providing new insights into the functions of the Csn complex in fungal virulence and suggesting that the complex may be a potential target for combating fungal diseases.

Background Two important flavonoids, kaempferol and quercetin possess remarkably potent biological impacts on human health. However, their structural complexity and low abundance in nature make both bulk chemical synthesis and extraction from native plants difficult. Therefore microbial production via heterologous expression of plant enzymes can be a safe and sustainable route for their production. Despite several attempts reported in microbial hosts, the production levels of kaempferol and quercetin still stay far behind compared to many other microbial-produced flavonoids. Results In this study, Saccharomyces cerevisiae was engineered for high production of kaempferol and quercetin in minimal media from glucose. First, the kaempferol biosynthetic pathway was reconstructed via screening various F3H and FLS enzymes. In addition, we demonstrated that amplification of the rate-limiting enzyme AtFLS could reduce the dihydrokaempferol accumulation and improve kaempferol production. Increasing the availability of precursor malonyl-CoA further improved the production of kaempferol and quercetin. Furthermore, the highest amount of 956 mg L− 1 of kaempferol and 930 mg L− 1 of quercetin in yeast was reached in fed-batch fermentations. Conclusions De novo biosynthesis of kaempferol and quercetin in yeast was improved through increasing the upstream naringenin biosynthesis and debugging the flux-limiting enzymes together with fed-batch fermentations, up to gram per liter level. Our work provides a promising platform for sustainable and scalable production of kaempferol, quercetin and compounds derived thereof.

The compact binary systems, spanning from the stellar to supermassive black hole, encode a wealth of information concerning stellar evolution, galaxy formation and evolution, and cosmology. An enormous number of these systems, both resolved and unresolved, emit substantial gravitational waves during their final evolutionary stages, thereby creating a stochastic gravitational wave background (SGWB). We calculate the merger rates of stellar compact binaries and massive black hole binaries using a semi-analytic galaxy formation model -- Galaxy Assembly with Binary Evolution (GABE) in a unified and self-consistent approach, followed by an estimation of the multi-band SGWB contributed by the binary systems. We find that the amplitudes of the principal peaks of the SGWB energy density are within one order of magnitude $\Omega_{GW} \sim 10^{-9}- 10^{-8}$. This SGWB can be easily detected by the Square Kilometre Array (SKA), as well as planned interferometric detectors, such as the Einstein Telescope (ET) and the Laser Interferometer Space Antenna (LISA). The energy density of this background varies as $\Omega_{GW} \propto f^{2/3}$ in the SKA band. The shape of the SGWB spectrum in the frequency range $\sim[10^{-4}$,$1]$Hz could allow the space-based detector LISA to distinguish the black hole seed models. The amplitude of the SGWB from merging stellar binary black holes (BBHs) at $\sim 100$ Hz is approximately 10 and 100 times greater than those from merging binary neutron stars (BNSs) and neutron-star-black-hole (NSBH) mergers, respectively., Comment: 9 pages, 4 figures

miR-200c is a tumor suppressor miRNA that plays a critical role in regulating epithelial phenotype and cancer stemness. p53 deficiency downregulates the expression of miR-200c and leads to epithelial-mesenchymal transition (EMT) and stemness phenotype, which contributes to the progression of breast cancers. In this study, we demonstrated that CRISPR-mediated knockout (KO) of miR-200c induces metabolic features similar to the metabolic rewiring caused by p53 hot-spot mutations, and that impairing this metabolic reprogramming interferes with miR-200c deficiency–induced stemness and transformation. Moreover, restoring miR-200c expression compromised EMT, stem-cell properties, and the Warburg effect caused by p53 mutations, suggesting that mutant p53 (MTp53) induces EMT-associated phenotypes and metabolic reprogramming by downregulating miR-200c. Mechanistically, decreased expression of PCK2 was observed in miR-200c– and p53-deficient mammary epithelial cells, and forced expression of miR-200c restored PCK2 in p53 mutant–expressing cells. Reduced PCK2 expression not only led to attenuated oxidative phosphorylation (OXPHOS) and increased stemness in normal mammary epithelial cells but also compromised the enhanced OXPHOS and suppression of cancer stemness exerted by miR-200c in p53 mutation–bearing basal-like breast cancer (BLBC) cells. Clinically, PCK2 expression is negatively associated with EMT markers and is downregulated in basal-like subtype and cases with low miR-200c expression or p53 mutation. Notably, low expression of PCK2 is associated with poor overall survival (OS) in patients with breast cancer.Implications:Together, our results suggest that p53 and miR-200c regulate OXPHOS and stem/cancer stemness through PCK2, and loss of the p53–miR-200c–PCK2 axis might provide metabolic advantages that facilitate cancer stemness, leading to the progression of BLBCs.

S1. miR-200c-deficiency induced biological effects in mammary epithelial cells. S2. Expression of EMT inducers and stemness genes in miR-200c KO or overexpressing cells. S3. miR-200c-deficiency induces Warburg effect in mammary epithelial cells. S4. The mitochondrial oxidative phosphorylation is elevated by miR-200c in basal-like breast cancer cells. S5. Cell growth of miR-200c KO cells is not affected by low-dosage 2DG pretreatment for two days. S6. 2-DG and NADH treatment enhance oxidative phosphorylation in miR-200c deficient MCF12A cells. S7. NADH treatment fails to affect EMT-phenotype in miR-200c-deficient MCF12A cells. S8. p53 hot-spot mutations induce Warburg effect in mammary epithelial cells. S9. Examples of metabolites affected by miR-200c KO or MTp53-R280K overexpression. S10. miR-200c deficiency leads to altered expression of metabolic genes in central metabolic pathway. S11. PCK2 expression is regulated by ZEB1 and BMI1 in miR-200c-KO or p53 mutated mammary epithelial cells and basal-like breast cancer cells. S12. Expressional correlation between PCK2, miR-200c, and miR-200c direct target ZEB1/ ZEB2 in breast cancer patients. S13. PCK2 expression shows a slight to moderate negative association with EMT and stemness markers in breast cancer patients. S14. Interference of PCK2 expression compromised miR-200c-exeted tumor suppressive effect on p53 mutated BLBC cells.

Supplementary Materials and Methods

Clear-cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal cell carcinoma (RCC), and its progression has been linked to chronic inflammation. About 70% of the ccRCC cases are associated with inactivation of the von Hippel–Lindau (VHL) tumor-suppressor gene. However, it is still not clear how mutations in VHL, encoding the substrate-recognition subunit of an E3 ubiquitin ligase that targets the alpha subunit of hypoxia-inducible factor-α (HIFα), can coordinate tissue inflammation and tumorigenesis. We previously generated mice with conditional Vhlh knockout in kidney tubules, which resulted in severe inflammation and fibrosis in addition to hyperplasia and the appearance of transformed clear cells. Interestingly, the endothelial cells (EC), although not subject to genetic manipulation, nonetheless showed profound changes in gene expression that suggest a role in promoting inflammation and tumorigenesis. Oncostatin M (OSM) mediated the interaction between VHL-deficient renal tubule cells and the ECs, and the activated ECs in turn induced macrophage recruitment and polarization. The OSM-dependent microenvironment also promoted metastasis of exogenous tumors. Thus, OSM signaling initiates reconstitution of an inflammatory and tumorigenic microenvironment by VHL-deficient renal tubule cells, which plays a critical role in ccRCC initiation and progression.Significance:A novel mechanism of cross-talk between ECs and VHL-deficient kidney tubules that stimulates inflammation and tumorigenesis is discovered, suggesting OSM could be a potential target for ccRCC intervention.

Supplementary Table 3

Supplementary Figure from IL6 and CCL18 Mediate Cross-talk between VHL-Deficient Kidney Cells and Macrophages during Development of Renal Cell Carcinoma

Supplementary Tables

Supplementary Methods and Materials

Supplementary Table 4

Supplementary Figures

Loss of the von Hippel–Lindau (VHL) tumor suppressor gene function accounts for 70% to 80% of all clear-cell renal cell carcinoma (ccRCC) cases, the most prevalent form of RCC. Accumulating evidence has indicated that ccRCC arises from sites of chronic inflammation, yet how ccRCC tumor cells interact with immune components of the microenvironment has not been fully elucidated. In this study, we used unbiased proteomic and genomic analyses on components of the tumor microenvironment under different conditions, identifying the molecular and cellular mechanisms that underlie the cross-talk between VHL-deficient kidney tubule cells and macrophages. In vitro and in a Vhlh conditional knockout mouse model, VHL-deficient noncancerous kidney epithelial cells, representing the early stage of ccRCC initiation, secreted IL6 that induced macrophage infiltration and polarization toward the protumorigenic M2 phenotype. Activated human macrophages secreted CCL18 and TGFβ1 to stimulate epithelial-to-mesenchymal transition (EMT) of the kidney tubule cells. Treatment with IL6-neutralizing antibody rescued inflammatory, proliferative, and EMT phenotypes of kidney epithelial cells in Vhlh conditional knockout mice. Furthermore, in a human ccRCC xenograft model, exogenous human primary or cultured macrophages significantly promoted primary tumor growth and metastasis in a CCL18-dependent manner. These findings identify specific factors involved in reciprocal cross-talk between tumor cells and immune components in the microenvironment, thus providing an avenue for early intervention in ccRCC.Significance:The identification of VHL-deficient kidney tubule cell cross-talk with macrophages regulated by IL6 and CCL18 reveals potential targets for the prevention and treatment of ccRCC.

Supplementary Data from IL6 and CCL18 Mediate Cross-talk between VHL-Deficient Kidney Cells and Macrophages during Development of Renal Cell Carcinoma

Supplementary Figures

In this paper, we have creatively employed the shadow radius to study the thermodynamics of a charged AdS black hole with a nonlinear electrodynamics(NLED) term. First, the connection between the shadow radius and event horizon is constructed with the aid of the geodesic analysis. It turns out that the black hole shadow radius shows a positive correlation as a function of the event horizon radius. Then in the shadow context, we found that the black hole temperature and heat capacity can be presented by the shadow radius. And further analysis shows that the shadow radius can do as well as the event horizon in revealing black hole phase transition process. In this sense, we constructed the thermal profile of the charged AdS black hole with inclusion of the NLED effect. In P < Pc case, it is found that the N-type trend of the temperature given by the shadow radius is always coincide with that obtained by using the event horizon. So, we can concluded for the charged AdS black hole that the phase transition process can be intuitively presented as the thermal profile in the shadow context. Finally, the effects of NLED have been carefully analysed through out the paper., 17 pages, 21 figures

ObjectiveEmerging evidence suggests that elevated remnant cholesterol (RC) correlates with several health conditions. To explore the association of plasma RC with MCI incidence and the relationship between plasma RC and different domains of cognition in MCI patients.MethodsThirty-six MCI patients and 38 cognitively healthy controls (HC) were enrolled in the present cross-sectional study. Using total cholesterol (TC) minus high-density lipoprotein cholesterol (HDL-C) minus low-density lipoprotein cholesterol (LDL-C) as the formula for calculating fasting RC. Cognition was assessed using the Chinese version of the Montreal cognitive assessment (MoCA), Auditory Verbal Learning Test (AVLT), Digit Symbol Substitution Test (DSST), Trail Making Test (TMT), and Rey-Osterrieth Complex Figure Test (ROCF).ResultsCompared to healthy controls, MCI patients had a higher level of RC, the median difference in RC levels between these two groups was 8.13 mg/dl (95.0%CI: 0.97–16.1). Concurrently, plasma RC level was positively associated with MCI risk (OR = 1.05, 95%CI: 1.01–1.10). Notably, elevated RC level was correlated with impaired cognition in MCI patients, such as DSST (pr = −0.45, p = 0.008), ROCF- Long Delayed Recall (pr = −0.45, p = 0.008), AVLT-Immediate Recall (pr = −0.38, p = 0.028), and TMT-A (pr = 0.44, p = 0.009). Conversely, no significant correlation was found between RC and the AVLT-Long Delayed Recall test.ConclusionThis study found that plasma remnant cholesterol was associated with MCI. Further large longitudinal studies are needed in the future to confirm the results and clarify the cause-and-effect relationship.

The improvement of the multi-mode capability of quantum memory can further improve the utilization efficiency of the quantum memory and reduce the requirement of quantum communication for storage units. In this letter, we experimentally investigate the multi-mode light multiplexing storage of orbital angular momentum (OAM) mode based on rubidium vapor, and demultiplexing by a photonic OAM mode splitter which combines a Sagnac loop with two dove prisms. Our results show a mode extinction ratio higher than 80$\%$ at 1 $\mu$s of storage time. Meanwhile, two OAM modes have been multiplexing stored and demultiplexed in our experimental configuration. We believe the experimental scheme may provide a possibility for high channel capacity and multi-mode quantum multiplexed quantum storage based on atomic ensembles.

There is currently no standardized way to determine suitability for extubation of pediatric ICU (PICU) patients, potentially resulting in prolonged duration of mechanical ventilation. We aimed to design and implement a protocol for screening all intubated PICU patients for extubation readiness.We adopted the quality improvement (QI) Model for Improvement with Plan-Do-Study-Act (PDSA) cycles to achieve this aim. This QI project was conducted over 11 months in a multidisciplinary PICU. Outcome measures included the (1) development of a standardized extubation readiness test (ERT) that was acceptable and safe; (2) performance of ERT on80% of all mechanically ventilated subjects; and (3) maintenance or reduction in mechanical ventilation duration, extubation failure (non-elective re-intubation within 48 h of extubation), and need for rescue noninvasive ventilation (NIV). Balancing measures were to ensure (1) no compromise of the subject's clinical status; and (2) acceptability of the ERT workflow by medical, nursing, and respiratory therapist (RT) teams.Four PDSA cycles were necessary to achieve the aims of this study. During the QI period, 438 subjects were admitted to the PICU. The ERT was championed by the RTs who conducted the test during office hours. ERT performance increased from 0% (baseline) to 90% (fourth PDSA cycle). Extubation failure rate after implementing ERT was reduced compared to baseline (4/31 [12.9%] vs 3/127 [2.4%],An acceptable and safe ERT protocol was implemented and found to improve outcomes in PICU subjects on mechanical ventilation.

Acute kidney injury (AKI) is a susceptible factor for chronic kidney disease (CKD). There is still a lack of effective prevention methods in clinical practice. This study investigated the protective effect of the urinary exosomes from premature infants on cisplatin-induced acute kidney injury. Here we isolated exosomes from the fresh urine of premature infants. A C57BL/6 mice model of cisplatin-induced acute kidney injury was given 100 ug urinary exosomes 24 hours after model establishment. The kidneys were collected for pathological examination and the evaluation of renal tubular damage and apoptosis. In the in vitro experiment, human renal cortex/proximal tubular cells (HK-2) were induced by cisplatin to assess the effect of the urine exosomes from premature infants. Exosome microRNA (miRNA) sequencing technology was applied to investigate the miRNAs enriched in exosomes and the dual-luciferase gene reporter system to examine the targeting relationship of the miRNA with target genes. The results indicated that the urinary exosomes could decrease the serum creatinine level and the apoptosis of renal tubular cells, and reduce mice mortality. In addition, miR-30a-5p was the most abundant miRNA in the exosomes. It protected HK-2 cells from cisplatin-induced apoptosis by targeting and down-regulating the mitogen-activated protein kinase 8 (MAPK8). Together, our findings identified that the urinary exosomes derived from premature infants alleviated cisplatin-induced acute kidney injury and inhibited the apoptosis of HK-2 via miR-30a-5p, which could target MAPK8. These findings implied that urinary exosomes from premature infants riched in miR-30a-5p might become a potential treatment for AKI.

Within the effective Lagrangian approach, we carry out a unified study of the J/ψ(ψ′)→VP, J/ψ→Pγ and relevant radiative decays of light-flavor hadrons. A large amount of experimental data, including the various decay widths and electromagnetic form factors, is fitted to constrain the numerous hadron couplings. Relative strengths between the strong and electromagnetic interactions are revealed in the J/ψ→VP and ψ′→VP processes. The effect from the strong interaction is found to dominate in the J/ψ→ρπ decay, while the electromagnetic interaction turns out to be the dominant effect in ψ′→ρπ decay, which provides an explanation to the ρπ puzzle. For the J/ψ→K*K¯+K¯*K and ψ′→K*K¯+K¯*K, the former process is dominated by the strong interactions, and the effects from the electromagnetic parts are found to be comparable with those of strong interactions in the latter process. Different SU(3) breaking effects from the electromagnetic parts appear in the charged and neutral channels for the ψ′→K*K¯+K¯*K processes explain the rather different ratios between B(ψ′→K*+K−+K*−K+)/B(J/ψ→K*+K−+K*−K+) and B(ψ′→K*0K¯0+K¯*0K0)/B(J/ψ→K*0K¯0+K¯*0K0).

Objective: To analyze the nutritional status of primary school children in Furong District of Changsha from 2019 to 2020. Methods: The physical examination data of students from 35 primary schools (grade 1-6) in Furong District of Changsha in Hunan Provincial People’s Hospital from September 2019 to October 2020 were analyzed retrospectively. General information of all children was collected for statistical analysis of malnutrition among children of different gender and age groups. Result: The overnutrition rate was 32.73% in 2020. This was 7.42% higher than 25.31% in 2019. The undernourishment rate was 4.70% in 2020. This was 3.94% lower than 8.64% in 2019. In 2019 and 2022, the obesity and overweight rates of boys were higher than those of girls (both P < 0.05). The rates of growth retardation (0.36%, 0.37%) for boys were higher than those for girls (0.27%, 0.24%). The rates of mild wasting (4.31%, 2.36%) were lower than those for girls (4.00%, 2.39%) in 2020 and 2019. The rates of moderate and severe wasting (4.06%, 1.98%) were higher than those for girls (2.75%, 1.47%). In 2020, the undernourishment rate for boys decreased by 4.02% compared to 2019. The undernourishment rate for girls decreased by 2.91% compared to 2019. The growth retardation rate for boys increased by 0.01% compared to 2019. The growth retardation rate for girls decreased by 0.03% compared to 2019. The mild wasting rate for boys decreased by 1.95% as compared to 2019. The mild wasting rate for girls decreased by 1.61% as compared to 2019. The moderate to severe emaciation rate in boys was 2.08% lower in 2020 than in 2019 and 1.28% lower in girls than in 2019. The malnutrition rates of children aged 6-11 decreased by 4.20%, 4.85%, 3.83%, 9.45%, 6.65%, and 6.45% in 2020 compared with that of 2019. Conclusion: Compared to 2019, the primary school students in Furong District had abnormal nutritional status in 2020. It is necessary to strengthen the management of children’s health care to ensure the healthy growth of children.

Multilingual pretrained language models (mPLMs) have shown their effectiveness in multilingual word alignment induction. However, these methods usually start from mBERT or XLM-R. In this paper, we investigate whether multilingual sentence Transformer LaBSE is a strong multilingual word aligner. This idea is non-trivial as LaBSE is trained to learn language-agnostic sentence-level embeddings, while the alignment extraction task requires the more fine-grained word-level embeddings to be language-agnostic. We demonstrate that the vanilla LaBSE outperforms other mPLMs currently used in the alignment task, and then propose to finetune LaBSE on parallel corpus for further improvement. Experiment results on seven language pairs show that our best aligner outperforms previous state-of-the-art models of all varieties. In addition, our aligner supports different language pairs in a single model, and even achieves new state-of-the-art on zero-shot language pairs that does not appear in the finetuning process., Published at Findings of EMNLP 2022