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Introduction: The aim of this study was to evaluate the association of peripheral eosinophil (EOS) count with disease activity and kidney outcomes in lupus nephritis (LN) patients. Methods: A total of 453 hospitalized and biopsy-proven LN patients at our hospital from 2006 to 2013 were enrolled, of which 388 patients had repeated measurements of EOS. Relationships were explored between average EOS and disease activity at baseline, using the systemic lupus erythematosus disease activity (SLEDAI) and activity index (AI) on kidney biopsy. Follow-up data were available through December 2016. The primary outcome measure was a composite of doubling of serum creatinine and end-stage kidney disease after a median follow-up of 51 months. Results: The mean age of the enrolled 388 LN patients was 33.1 ± 10.8 years old, and 335 (86%) were female. The median average peripheral EOS count was 0.033 (0.015–0.057) ×109/L. Mean AI and SLEDAI score were 6.8 ± 2.5 and 14.9 ± 5.4, respectively. Logistic regression models showed that decreased average EOS was independently associated with higher AI (≥6) and higher SLEDAI (≥15) (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.90–0.97; and OR 0.96, 95% CI: 0.93–0.99, respectively). There was a parabolic relationship between average EOS and the primary outcome, with hazard ratio (HR) > 1 for both levels ≤0.033 and >0.16 × 109/L. Conclusion: Lower EOS count was independently associated with severe disease activity and kidney progression in LN.

A highly soluble benzodithiophene-derived building block is used for constructing high-performance donor–acceptor alternating wide bandgap copolymers with a power conversion efficiency of 15.77%.

Background Peritoneal dialysis (PD) patients have a high risk of abnormal glucose and lipids metabolism. Objective We investigated the effects of baseline fasting plasma glucose (FPG) as well as its interaction with lipid profiles on all-cause and cardiovascular disease (CVD) cause-specific mortality in PD patients. Methods A total of 1995 PD patients were enrolled. Kaplan–Meier survival curves and Cox regression models were performed to assess the association of FPG levels with mortality in PD patients. Results During a median (25th–75th quartile) follow-up period of 48.1 (21.8–77.9) months, 567 (28.4%) patients died, including 282 (14.1%) CVD deaths. Kaplan–Meier survival curves showed that all-cause and CVD cause-specific mortality increased significantly with elevated baseline FPG levels (Log-rank tests: both P-values Conclusion The significant interaction effect between baseline FPG and LDL-C on all-cause mortality showed that, for PD patients with LDL-C ≥3.37 mmol/L, higher FPG levels (≥7.0 mmol/L) were significantly associated with an increased risk of all-cause mortality and need more intensive management of their FPG by clinicians in the future.

Cellulose/collagen composites have been widely used in biomedicine and tissue engineering. Interfacial interactions are crucial in determining the final properties of cellulose/collagen composite. Molecular dynamics simulations were carried out to gain insights into the interactions between cellulose and collagen. It has been found that the structure of collagen remained intact during adsorption. The results derived from umbrella sampling showed that (110) and ([Formula: see text]) faces exhibited the strongest affinity with collagen (100) face came the second and (010) the last, which could be attributed to the surface roughness and hydrogen-bonding linkers involved water molecules. Cellulose planes with flat surfaces and the capability to form hydrogen-bonding linkers produce stronger affinity with collagen. The occupancy of hydrogen bonds formed between cellulose and collagen was low and not significantly contributive to the binding affinity. These findings provided insights into the interactions between cellulose and collagen at the molecular level, which may guide the design and fabrication of cellulose/collagen composites.

Background and Aims. Mean platelet volume to platelet count ratio (MPV/PC) has been found to be an independent risk factor for mortality in various diseases, including cardiovascular disease, cancer, and hemodialysis. We aimed to evaluate the association between MPV/PC and all-cause and cardiovascular (CV) mortality in peritoneal dialysis (PD) patients. Methods and Results. We conducted a retrospective cohort study at a single center and enrolled 1473 PD patients who were catheterized at our PD center from January 1, 2006, to December 31, 2013. All patients were divided into four groups according to the quartiles of baseline MPV/PC levels and followed up until December 31, 2018. A total of 453 patients died, and 221 deaths were caused by cardiovascular disease during a median follow-up time of 48.0 (21.9-82.2) months. There was a significant interaction by age of association between MPV/PC level and all-cause mortality ( P = 0.009 ), and multivariate Cox regression analysis showed that higher MPV/PC level was related to a decreased risk of all-cause and CV mortality in PD patients aged < 60 years ( HR = 0.62 , 95 % CI = 0.40 − 0.96 , P = 0.032 ; HR = 0.49 , 95 % CI = 0.26 − 0.93 , P = 0.029 , respectively), rather than in patients aged ≥ 60 years ( HR = 1.37 , 95 % CI = 0.84 − 2.22 , P = 0.208 ; HR = 1.50 , 95 % CI = 0.77 − 2.92 , P = 0.237 , respectively). Conclusion. Our results indicated that low MPV/PC level was an independent risk factor for all-cause and CV mortality in PD patients aged less than 60 years.

Perovskite light-emitting diodes (PeLEDs) show great potential in display and lighting because of their tunable wavelength, narrow emission bandwidths, and high color purity. Currently, the external quantum efficiency (EQE) of red and green PeLEDs has reached23%. However, yellow PeLEDs are still rarely reported because of phase separation in mixed-halide perovskites and the coexistence of multiple phases in quasi-two-dimensional (quasi-2D) perovskites L

Circular RNAs (circRNAs) are stable and prevalent RNAs in eukaryotic cells that arise from back-splicing. Synthetic circRNAs and some endogenous circRNAs can encode proteins, raising the promise of circRNA as a platform for gene expression. In this study, we developed a systematic approach for rapid assembly and testing of features that affect protein production from synthetic circRNAs. To maximize circRNA translation, we optimized five elements: vector topology, 5′ and 3′ untranslated regions, internal ribosome entry sites and synthetic aptamers recruiting translation initiation machinery. Together, these design principles improve circRNA protein yields by several hundred-fold, provide increased translation over messenger RNA in vitro, provide more durable translation in vivo and are generalizable across multiple transgenes.

Circular RNAs (circRNAs) are a class of RNAs commonly found across eukaryotes and viruses, characterized by their resistance to exonuclease-mediated degradation. Their superior stability compared to linear RNAs, combined with previous work showing that engineered circRNAs serve as efficient protein translation templates, make circRNA a promising candidate for RNA medicine. Here, we systematically examine the adjuvant activity, route of administration, and antigen-specific immunity of circRNA vaccination in mice. Potent circRNA adjuvant activity is associated with RNA uptake and activation of myeloid cells in the draining lymph nodes and transient cytokine release. Immunization of mice with engineered circRNA encoding a protein antigen delivered by a charge-altering releasable transporter induced innate activation of dendritic cells, robust antigen-specific CD8 T cell responses in lymph nodes and tissues, and strong antitumor efficacy as a therapeutic cancer vaccine. These results highlight the potential utility of circRNA vaccines for stimulating potent innate and T cell responses in tissues.

Background: Psychotic depression (PD) and schizophrenia (SCZ) are disorders with shared symptoms but unique causes, development, and treatments. Identifying them based on symptoms is difficult, requiring deeper comprehension of cognitive and neural mechanisms for accurate diagnosis and treatment. Aim: This study aims to compare cognitive impairments and brain functional activities in PD and SCZ, in order to identify unique features of each disorder. Methods: We studied 42 PD and 30 SCZ patients using RBANS and rs-fMRI. We computed ReHo values from the rs-fMRI data and compared RBANS scores between groups. We also investigated the correlation between cognition and brain function using Pearson analysis. Results: (1) SC group had lower RBANS scores than PD group in all test sections; (2) Left precuneus had significant ReHo difference between PD and SC groups, with SCZ group showing significantly increased ReHo (p < 0.05); (3) Negative correlation found between visuospatial construction score, delayed memory score and ReHo value of left precuneus by Pearson correlation analysis. conclusion: Cognitive impairment is more severe in SCZ than PD. Elevated left precuneus activity distinguishes PD from SCZ and relates to cognitive deficits in both, offering neuroimaging evidence for differential diagnosis and insight into cognitive impairment pathology.

Paper, a low-cost and eco-friendly substrate, can be used to prepare flexible electronic devices by resorting to surface modification technology. In this study, we investigated the surface modification of paper substrates, including those that were uncoated or coated with traditional mineral coatings, to analyze the enhancements to surface flatness and water resistance using a UV curing varnish layer. Furthermore, we explored the formation of perovskite films on the surface-modified paper substrates utilizing a PEO-doped perovskite precursor solution in ambient air, and the surface morphology, crystallinity, photoluminescence properties, and absorption properties of the prepared perovskite films were discussed accordingly. Considering the nontransparent feature of paper-based substrates, the inverted perovskite light-emitting device was finally assembled by transfer printing a transparent PEDOT:PSS layer as a top electrode. The conductive and optical properties of the electrode layer were thus analyzed as well. It is found that the surface modification of paper substrates via printing the UV curing varnish can illustrate significant improvements, such as pore-filling on the surface, a more than 10-fold reduction in roughness, and downward penetration. Moreover, prepared perovskite films on the surface-modified coated paper exhibit superior enhancements, including photoluminescence, higher crystallinity, and surface roughness and porosity. Devices fabricated on the surface-modified substrates are less susceptible to short-circuiting. The electroluminescence improved on the surface-modified coated paper substrate is 2.16 times higher than the prepared device on the surface-modified base paper substrate and even 3.23 times higher than on the PET substrate. Therefore, it is quite feasible to fabricate a perovskite light-emitting device on the modified surface of a paper substrate by using a printed UV curing varnish layer, which is expected to be a promising coating to polish the paper surface in the preparation of electroluminescent devices.

Background Recently studies had showed that the amygdala may take part in the cognitive impairment in schizophrenia (SC). However, the mechanism is still unclear, so we explored the relationship between the amygdala resting state magnetic resonance imaging (rsMRI) signal and cognitive function, to provide a reference for the follow-up study. Methods We collected 59 drug-naïve SCs and 46 healthy controls (HCs) from the Third People’s Hospital of Foshan. The rsMRI technique and automatic segmentation tool were used to extract the volume and functional indicators of the SC’s amygdala. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of the disease, and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognitive function. Pearson correlation analysis was used to compare the relationship between the structural and functional indicators of the amygdala and PANSS and RBANS. Results (1) There was no significant difference between SC and HC in age, gender and years of education. Compared with HC, the PANSS score of SC increased and the RBANS score decreased significantly. Meanwhile, the left amygdala volume decreased (t=-3.675, p L=3.916, p R=3.131, p = 0.002). (2) The volumes of the left amygdala were negatively correlated with the PANSS score (rL=-0.243, p = 0.039). While the FALFF values of the bilateral amygdala were positively correlated with the PANSS score (rL=0.257, p = 0.026; rR=0.259, p = 0.026). Bilateral amygdala volumes and FALFF values were positively correlated (rL=0.445, p R=0.326, p = 0.006) and negatively correlated with RBANS score (rL=-0.284, p = 0.014; rR=-0.272, p = 0.020), respectively. Conclusion The abnormal volume and function of the amygdala play important roles in the disease process of SC, and are closely related to cognitive impairment.

Background Chimeric antigen receptor- T (CAR-T) cell therapy is an efficient therapeutic strategy for specific hematological malignancies. However, positive outcomes of this novel therapy in treating solid tumors are restricted by the immunosuppressive tumor microenvironment (TME), wherein, checkpoint molecular programmed death-1 (PD-1)/PD-L1 signaling directly inhibits T-cell responses. Although checkpoint immunotherapy succeeds in increasing the number of T cells produced to control tumor growth, the desired effect is mitigated by the action of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) present in the TME. Previous studies have confirmed that targeting triggering-receptor-expressed on myeloid cells 2 (TREM2) on TAMs and MDSCs enhances the outcomes of anti-PD-1 immunotherapy. Methods Therefore, we constructed carcinoembryonic antigen (CEA)-specific CAR-T cells for colorectal cancer (CRC)-specific antigens with autocrine PD-1-TREM2 single-chain variable fragment (scFv) to target the PD-1/PD-L1 pathway, MDSCs and TAMs. Results We found that the PD-1-TREM2-targeting scFv inhibited the activation of the PD-1/PD-L1 pathway. In addition, these secreted scFvs blocked the binding of ligands to TREM2 receptors present on MDSCs and TAMs, reduced the proportion of MDSCs and TAMs, and enhanced T-cell effector function, thereby mitigating immune resistance in the TME. Meanwhile, the scFv secreted by CAR-T cells remained localized within tumors and exhibited an extended half-life. Conclusions The PD-1-TREM2 scFv-secreting CAR-T cells exhibited substantially potent anti-tumor effects, evidenced by highly effective elimination of tumors compared to that achieved with PD-1 scFv-secreting CAR-T therapy in a subcutaneous CRC mouse model. Together, these results indicate that PD-1-TREM2 scFv-secreting CAR-T cells have strong potential as an effective therapy for CRC.

Background Non-small cell lung cancer (NSCLC) is a worldwide health threat with high annual morbidity and mortality. Chemotherapeutic drugs such as paclitaxel (PTX) have been widely applied clinically. However, systemic toxicity due to the non-specific circulation of PTX often leads to multi-organ damage, including to the liver and kidney. Thus, it is necessary to develop a novel strategy to enhance the targeted antitumor effects of PTX. Methods Here, we engineered exosomes derived from T cells expressing the chimeric antigen receptor (CAR-Exos), which targeted mesothelin (MSLN)-expressing Lewis lung cancer (MSLN-LLC) through the anti-MSLN single-chain variable fragment (scFv) of CAR-Exos. PTX was encapsulated into CAR-Exos (PTX@CAR-Exos) and administered via inhalation to an orthotopic lung cancer mouse model. Results Inhaled PTX@CAR-Exos accumulated within the tumor area, reduced tumor size, and prolonged survival with little toxicity. In addition, PTX@CAR-Exos reprogrammed the tumor microenvironment and reversed the immunosuppression, which was attributed to infiltrating CD8+ T cells and elevated IFN-γ and TNF-α levels. Conclusions Our study provides a nanovesicle-based delivery platform to promote the efficacy of chemotherapeutic drugs with fewer side effects. This novel strategy may ameliorate the present obstacles to the clinical treatment of lung cancer.

In order to extend the duration of the electrolyte solution in which copper granules recovered from waste printed circuit board are refined through electrolysis to obtain copper with high purity and which is contaminated by the accumulation of metallic impurities along with the refinery of waste printed circuit board, the leaching and electrowinning processes are used to pretreat the copper granules. The effects of impurities of copper granules as well as H2SO4 mole ratio, leaching temperature, liquid to solid ratio, and operation time on the removing efficiencies of Zn, Sn, Fe, and Al, were studied. The results showed that more than 95% of impurities can be removed when the mole ratio of impurities to H2SO4 was 1:4, the temperature was 70°C, the liquid-solid ratio was 20 mL/g, along with the leaching time of 180 min. After 1440 min electrolysis of the pretreated granules with the electric current density of 40 mA/cm2, the purity of refined copper maintained at 99% in contrast with 95% which copper granules are without pretreatment. The maximal concentration of the accumulated ions of impurities is less than 60 mg/L, which suggests the sulfuric acidic pretreatment is a promising approach to increase the duration of the electrolyte solution.

Purpose Extradomain B of fibronectin (EDB-FN) is a promising diagnostic and therapeutic biomarker for thyroid cancer (TC). Here, we identified a high-affinity EDB-FN targeted peptide named EDBp, and developed three EDBp-based probes, Cy5-EDBp, [18F]-EDBp and [177Lu]-EDBp the surgical navigation, radionuclide imaging and therapy of TC. Methods Based on the previously identified EDB-FN targeted peptide ZD2, the optimized EDB-FN targeted peptide EDBp was identified by using the alanine scan strategy. Three EDBp-based probes, Cy5-EDBp, [18F]-EDBp and [177Lu]-EDBp, were developed for fluorescence imaging, positron emission tomography (PET) imaging and radiotherapy in TC tumor-bearing mice, respectively. Additionally, [18F]-EDBp was evaluated in two TC patients. Results The binding affinity of EDBp to the EDB fragment protein (Kd = 14.4 ± 1.4 nM, n = 3) was approximately 336-fold greater than that of the ZD2 (Kd = 4839.7 ± 361.7 nM, n = 3). Fluorescence imaging with Cy5-EDBp facilitated the complete removal of TC tumors. [18F]-EDBp PET imaging clearly delineated TC tumors, with high tumor uptake (16.43 ± 1.008%ID/g, n = 6, at 1 h postinjection). Radiotherapy with [177Lu]-EDBp inhibited tumor growth and prolonged survival in TC tumor-bearing mice (survival time of different treatment groups: Saline vs. EDBp vs. ABRAXANE vs. [177Lu]-EDBp = 8 d vs. 8 d vs. 11.67 d vs. 22.33 d, ***p 18F]-EDBp demonstrated that it had specific targeting properties (SUVmax value of 3.6) and safety. Conclusion Cy5-EDBp, [18F]-EDBp and [177Lu]-EDBp are promising candidates for the surgical navigation, radionuclide imaging and radionuclide therapy of TC, respectively.

BackgroundMassive amounts of data are produced by combining next-generation sequencing (NGS) with complex biochemistry techniques to characterize regulatory genomics profiles, such as protein-DNA interaction and chromatin accessibility. Interpretation of such high-throughput data typically requires different computation methods. However, existing tools are usually developed for a specific task, which makes it challenging to analyze the data in an integrative manner.ResultsWe here describe the Regulatory Genomics Toolbox (RGT), a computational library for the integrative analysis of regulatory genomics data. RGT provides different functionalities to handle genomic signals and regions. Based on that, we developed several tools to perform distinct downstream analyses, including the prediction of transcription factor binding sites using ATAC-seq data, identification of differential peaks from ChIP-seq data, and detection of triple helix mediated RNA and DNA interactions, visualization, and finding an association between distinct regulatory factors.ConclusionWe present here RGT; a framework to facilitate the customization of computational methods to analyze genomic data for specific regulatory genomics problems. RGT is a comprehensive and flexible Python package for analyzing high throughput regulatory genomics data and is available at:https://github.com/CostaLab/reg-gen. The documentation is available at:https://reg-gen.readthedocs.io

Electrochromic devices (ECDs) are in high demand for many applications; however, there is no ideal method to achieve the full recycling of the substrate and the functional layer in ECDs. Currently, it is still challenging to access ECDs with excellent electrochromic property, good degradability, and facile recycling capability. In this study, high-performance ECDs are successfully fabricated by using poly(3,4-ethylene dioxythiophene):poly(styrenesulfonate) as the functional layer and transparent gelatin film (TGF) derived from pigskin as the substrate. Compared with PET films or PET-based ECDs, the optical transmittance of TGF and the coloration efficiency of our ECDs could be increased by 3.2 and 41.4%, respectively, showing a great potential to replace conventional plastic-based ECDs. Furthermore, the TGF not only showed good biodegradability but also could be regenerated via a simple process without the loss of desirable properties. In addition, the functional layer and substrate can be easily separated in water due to the adjusted interactions of the interface and the unique property of gelatin, which may open a new path for fabricating green electronics.

Item does not contain fulltext Adult kidney organoids have been described as strictly tubular epithelia and termed tubuloids. While the cellular origin of tubuloids has remained elusive, here we report that they originate from a distinct CD24(+) epithelial subpopulation. Long-term-cultured CD24(+) cell-derived tubuloids represent a functional human kidney tubule. We show that kidney tubuloids can be used to model the most common inherited kidney disease, namely autosomal dominant polycystic kidney disease (ADPKD), reconstituting the phenotypic hallmark of this disease with cyst formation. Single-cell RNA sequencing of CRISPR-Cas9 gene-edited PKD1- and PKD2-knockout tubuloids and human ADPKD and control tissue shows similarities in upregulation of disease-driving genes. Furthermore, in a proof of concept, we demonstrate that tolvaptan, the only approved drug for ADPKD, has a significant effect on cyst size in tubuloids but no effect on a pluripotent stem cell-derived model. Thus, tubuloids are derived from a tubular epithelial subpopulation and represent an advanced system for ADPKD disease modeling.

A super-hydrophobic paper-based flexible sensor was developed and proven to be able to work under water without encapsulation.

AlN-doped SiC nanocrystalline ceramics were prepared by ball milling and reactive liquid-phase spark plasma sintering (SPS), using Si, C and AlN powders as raw materials. The oxidation behavior of the ceramics was studied. The AlN-doped SiC ceramics exhibited excellent oxidation resistance at 1773 K for 50 h and the parabolic rate constant was 0.004 mg2 cm−4 h−1. Compared with SiC ceramics, AlN-doped SiC ceramics could inhibit the crystallization of silica, prevent the grain growth of cristobalite and ensure the integrity of oxide scale by healing the possible cracks during the oxidation process, resulting in the improved oxidation resistance.

Purpose To characterize the diagnostic performance of [18F]FDG dose de-escalation with shortened acquisition times using total-body PET/CT in pediatric tumor imaging in terms of the subjective image quality and quantification of tracer uptake. Methods In this single-center prospective study, 31 pediatric oncology patients under 14 years old were enrolled and underwent total-body PET/CT using the uEXPLORER PET/CT scanner. All patients were randomly assigned to one of four [18F]FDG dose groups: full-dose (3.7 MBq/kg), 1/2-dose (1.9 MBq/kg), 1/3-dose (1.2 MBq/kg), and 1/4-dose (0.9 MBq/kg). Images with a shortened acquisition time frame (20 min, 12 min, 10 min, 8 min, 6 min, 5 min, 4 min, 3 min, 2 min, 1.5 min, 1 min, and 0.5 min) were reconstructed for each study, with the 20-min images as controls for each dose group. Semiquantitative uptake metrics were assessed using region-of-interest (ROI) analysis of healthy liver and suspected lesions. The subjective analysis was performed using 5-point Likert scales. Suspected major lesions and microlesions were recorded, while 3-point Likert scales were used for diagnostic confidence. Results With shortened acquisition times, the liver maximum standard uptake value (SUVmax) and standard deviation (SD) increased in each dose group. The signal-to-noise ratio (SNR) was significantly reduced with shortened acquisition time, while the lesion SUVmax and tumor-to-background ratio (TBR) showed no significant deviation. A decent subjective image quality score could be achieved in the full-, 1/2-, 1/3-, and 1/4-dose groups with at least 2-min, 4-min, 6-min, and 8-min acquisitions, respectively, where great overall image quality and brain delineation (scored 5.0) and superior organ boundaries and image noise (scored over 4.0) could be achieved, and all suspicious lesions found in 20-min images were detectable with high diagnostic confidence. Conclusions The regimen of full-dose [18F] FDG with a 2-min scan, 1/2-dose with a 4-min scan, 1/3-dose with a 6-min scan, and 1/4-dose with an 8-min scan using total-body PET/CT can provide great image qualities, can maintain a desired diagnostic performance and is feasible for pediatric oncological clinical applications. Trial registration: ChiCTR2000036334. Registered 22 August 2020.

For more than 20 years, disaster dynamic monitoring and early warning have achieved orderly and sustainable development in China, forming a systematic academic research system and top-down policy design, which are inseparable from the research of China’s scientific community and the promotion of government departments. In the past, most of the research on dynamic disaster monitoring and early warning focused on specific research in a certain field, scene, and discipline, while a few studies focused on research review or policy analysis, and few studies combined macro and meso research reviews in academia with national policy analysis for comparative analysis. It is necessary and urgent to explore the interaction between scholars’ research and policy deployment, which can bring theoretical contributions and policy references to the top-down design, implementation promotion, and academic research of China’s dynamic disaster monitoring and early warning. Based on 608 international research articles on dynamic disaster monitoring and early warning published by Chinese scholars from 2000–2021 and 187 national policy documents published during this period, this paper conducts a comparative analysis between the knowledge maps of international research hotspots and the co-occurrence maps of policy keywords on dynamic disaster monitoring and early warning. The research shows that in the stage of initial development (2000–2007), international research articles are few and focused, and research hotspots are somewhat alienated from policy keywords. In the stage of rising development (2008–2015), after the Wenchuan earthquake, research hotspots are closely related to policy keywords, mainly in the fields of geology, engineering disasters, meteorological disasters, natural disasters, etc. Meanwhile, research hotspots also focus on cutting-edge technologies and theories, while national-level policy keywords focus more on overall governance and macro promotion, but the two are gradually closely integrated. In the stage of rapid development (2016–2021), with the continuous attention and policy promotion of the national government, the establishment of the Ministry of Emergency Management, and the gradual establishment and improvement of the disaster early warning and monitoring system, research hotspots and policy keywords are integrated and overlapped with each other, realizing the organic linkage and mutual promotion between academic research and political deployment. The motivation, innovation, integration, and transformation of dynamic disaster monitoring and early warning are promoted by both policy and academic research. The institutions that issue policies at the national level include the State Council and relevant departments, the Ministry of Emergency Management, the Ministry of Water Resources, and other national ministries and commissions. The leading affiliated institutions of scholars’ international research include China University of Mining and Technology, Chinese Academy of Sciences, Wuhan University, Shandong University of Science and Technology, and other institutions. The disciplines involved are mainly multidisciplinary geosciences, environmental sciences, electrical and electronic engineering, remote sensing, etc. It is worth noting that in the past two to three years, research and policies focusing on COVID-19, public health, epidemic prevention, environmental governance, and emergency management have gradually increased.

Nephronophthisis type 12 (NPHP 12) is a rare cilia-related cystic kidney disease, caused by TTC21B mutation, mainly involving the kidneys, which generally occurs in children. Our study aimed to illustrate its clinical, pathological and genetic characteristics by reporting an adult-onset case of NPHP 12 caused by a single heterozygous nonsense mutation of TTC21B confirmed by renal histology and whole exome sequencing and reviewing related literature with a comparative analysis of the clinical features of each case. It will further increase the recognition of this rare kidney genetic disease, which sometimes can manifest as an adult disease.A 33-years-old man showed a chronic disease course, and he exhibited slight renal dysfunction (CKD stage 3, eGFR = 49 ml/[min* 1.73 m2]) with renal tubular proteinuria, without any extrarenal manifestations, congenital malformation history of kidney disease, or family hereditary disease. Renal histological findings showed substantial interstitial fibrosis with some irregular and tortuous tubules with complex branches and segmental thickening and splitting of the tubular basement membrane. The patient was diagnosed with chronic interstitial nephritis for an unknown reason clinically. Further genetic analysis revealed a single heterozygous nonsense mutation in the TTC21B gene and NPHP 12 was diagnosed finally.A single heterozygous mutation in the TTC21B gene may cause atypical NPHP12, which had a relatively later onset and milder clinical symptoms without developmental abnormalities. Therefore, for unexplained adult-onset chronic interstitial nephritis with unusual changes of renal tubules and interstitial fibrosis, even without a clear history of hereditary kidney disease, genetic testing is still recommended. The correct diagnosis of this rare adult-onset hereditary nephropathy can avoid unnecessary treatment.

Protein neddylation is catalyzed by a neddylation activating enzyme (NAE, E1), an E2 conjugating enzyme, and an E3 ligase. In various types of human cancers, the neddylation pathway is abnormally activated. Our previous study validated that the neddylation E2 UBE2F is a promising therapeutic target in lung cancer. Although the NAE inhibitor MLN4924/pevonedistat is currently under clinical investigation as an anti-cancer agent, there are no small molecules available that selectively target UBE2F. Here, we report, for the first time, the discovery, via structure-based virtual screen and chemical optimization, of such a small molecule, designated as HA-9104. HA-9104 binds to UBE2F, reduces its protein levels, and consequently inhibits cullin-5 neddylation. Blockage of cullin-5 neddylation inactivates cullin-RING ligase-5 (CRL5) activity, leading to accumulation of the CRL5 substrate, NOXA, to induce apoptosis. Moreover, HA-9104 appears to form the DNA adduct via its 7-azaindole group to induce DNA damage and G2/M arrest. Biologically, HA-9104 effectively suppresses the growth and survival of lung cancer cells and confers radiosensitization in both in vitro cell culture and in vivo xenograft tumor models. In summary, we discovered a small molecule, designated HA-9104, that targets the UBE2F-CRL5 axis with anti-cancer activity alone or in combination with radiation.

We have theoretically investigated the reflectance spectrums of the U-shape nanohole symmetry and asymmetric structure. It is shown that light can be perfectly confined in the photonic crystal slab at a given incident angle. Also, we studied the influence of U-shape nanohole size on reflectance spectrum and Q-factor of both at-Γ bound states in the continuum (BIC) and off-Γ BIC with the nanohole shape in symmetrical and asymmetrical cases. For a U-shape nanohole symmetry structure, it is shown that at-Γ BIC is dependent on the nanohole size. The Q-factor of the nanoholes structure at off-Γ BIC can reach the order of 106. The obtained results provide useful guidelines for practical implementations of biosensing, perfect filters and waveguides.

Xu Zhao,1,&ast; Jitao Zhang,1,&ast; Wenjuan Zhang,2 Ruping Dai,1 Junmei Xu,1 Zhijian Li,1 Lin Yang1 1Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Yang; Zhijian LiDepartment of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of ChinaFax +86 73185295970; Fax +86 73185295970Email linyang@csu.edu.cn; lizhijian@csu.edu.cnBackground: Bone morphogenetic protein-4 (BMP4) has been identified as an inflammation regulator in the diseases of arteries and other organs. However, the relationship between circulating BMP4 and perioperative inflammation remains unclear.Patients and Methods: Forty patients undergoing lobectomy were randomly allocated into the Control group (not receiving flurbiprofen) and the Flurb group (received 100mg flurbiprofen during surgery). Arterial blood was obtained before surgery (T1), at the end of surgery (T2), and 24 hours after surgery (T3) to test the plasma concentrations of BMP4, its antagonist Noggin, interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-10. The relationship between BMP4 and other variables and the effects of flurbiprofen on BMP4 changes were investigated.Results: A total of 35 patients were included. Circulating BMP4 was positively correlated with IL-1β (P< 0.01, r=0.575) and TNF-α (P< 0.01, r=0.491), negatively correlated with IL-10 (P< 0.01, r=− 0.675), but not correlated with Noggin. The plasma concentrations of BMP4, IL-1β, and TNF-α increased at T2 (P< 0.01, compared with T1) and decreased at T3 (P< 0.05, compared with T2). BMP4 concentrations at T3 were significantly higher than at T1 in the Control group (P< 0.05), while showing no significant difference in the Flurb group. However, in the Flurb group, the relative changes of BMP4 and IL-1β at T2 and T3 were significantly lower than those in the Control group.Conclusion: Circulating BMP4 was elevated during surgery and highly correlated with inflammation cytokines. The elevation of BMP4 and inflammatory cytokines could be alleviated by flurbiprofen, indicating that BMP4 may exert pro-inflammatory properties via cyclooxygenase-II signaling pathways.Keywords: bone morphogenetic protein-4, Noggin, inflammation, non-steroidal anti-inflammatory drugs, perioperative, cyclooxygenase-II