CCP5 and CCP6 retain CP110 and negatively regulate ciliogenesis.

BACKGROUND: The axonemal microtubules of primary cilium undergo a conserved protein posttranslational modification (PTM) - polyglutamylation. This reversible procedure is processed by tubulin tyrosine ligase-like polyglutamylases to form secondary polyglutamate side chains, which are metabolized by the 6-member cytosolic carboxypeptidase (CCP) family. Although polyglutamylation modifying enzymes have been linked to ciliary architecture and motility, it was unknown whether they also play a role in ciliogenesis. RESULTS: In this study, we found that CCP5 expression is transiently downregulated upon the initiation of ciliogenesis, but recovered after cilia are formed. Overexpression of CCP5 inhibited ciliogenesis, suggesting that a transient downregulation of CCP5 expression is required for ciliation initiation. Interestingly, the inhibitory effect of CCP5 on ciliogenesis does not rely on its enzyme activity. Among other 3 CCP members tested, only CCP6 can similarly suppress ciliogenesis. Using CoIP-MS analysis, we identified a protein that potentially interacts with CCP - CP110, a known negative regulator of ciliogenesis, whose degradation at the distal end of mother centriole permits cilia assembly. We found that both CCP5 and CCP6 can modulate CP110 level. Particularly, CCP5 interacts with CP110 through its N-terminus. Loss of CCP5 or CCP6 led to the disappearance of CP110 at the mother centriole and abnormally increased ciliation in cycling RPE-1 cells. Co-depletion of CCP5 and CCP6 synergized this abnormal ciliation, suggesting their partially overlapped function in suppressing cilia formation in cycling cells. In contrast, co-depletion of the two enzymes did not further increase the length of cilia, although CCP5 and CCP6 differentially regulate polyglutamate side-chain length of ciliary axoneme and both contribute to limiting cilia length, suggesting that they may share a common pathway in cilia length control. Through inducing the overexpression of CCP5 or CCP6 at different stages of ciliogenesis, we further demonstrated that CCP5 or CCP6 inhibited cilia formation before ciliogenesis, while shortened the length of cilia after cilia formation. CONCLUSION: These findings reveal the dual role of CCP5 and CCP6. In addition to regulating cilia length, they also retain CP110 level to suppress cilia formation in cycling cells, pointing to a novel regulatory mechanism for ciliogenesis mediated by demodifying enzymes of a conserved ciliary PTM, polyglutamylation.

Effect of temporary cements and their removal methods on the bond strength of indirect restoration: a systematic review and meta-analysis.

OBJECTIVES: For a conventional indirect restoration, temporary cementation inevitably contaminated collapsed dentin collagen. The purpose of this review was to evaluate the optimal strategy for minimizing its negative effects. MATERIAL AND METHODS: Databases such as PubMed, Web of Science, EMBASE, and the Cochrane Library were searched for in vitro studies, involving the influence of immediate dentin sealing (IDS), different temporary cements, and their removal strategies on dentin bond strength. The meta-analysis used the inverse variance method with effect method of the standardized mean difference and statistical significance at p ≤ 0.05. The I2 value and the Q-test were used to assess the heterogeneity. RESULTS: A total of 14 in vitro trials were subjected to the meta-analysis. Within the study's limitations, we assumed that IDS eliminated the negative effects of temporary bonding, achieving the comparable immediate bond strength with the control (p = 0.46). In contrast, under delayed dentin sealing (DDS), temporary cementation statistically decreased bond strength (p = 0.002). Compared with resin-based and non-eugenol zinc oxide cements, polycarboxylate and calcium hydroxide cements performed better on bond strength with no statistical difference from the control group (p > 0.05). Among the removal methods of temporary cements, the Al2O3 abrasion restored the decreased bond strength (p = 0.07) and performed better than hand instruments alone (p = 0.04), while pumice removal slightly reduced the bond strength in contrast with the control group (p = 0.05, 95% CI = - 1.62 to 0). CONCLUSIONS: The choices of IDS, polycarboxylate and calcium hydroxide temporary cements, Al2O3 abrasion removal method were feasible and efficient to enhance the bond strength. CLINICAL RELEVANCE: It is worthwhile applying IDS technique, polycarboxylate and calcium hydroxide temporary cements during indirect restoration. The Al2O3 abrasion of cleaning dentin can minimize the negative effects of temporary cement.

Online Monitoring of Seawater Carbon Dioxide Based on an Infrared Rear Beam Splitter.

The ocean is one of the most extensive ecosystems on Earth and can absorb large amounts of carbon dioxide. Changes in seawater carbon dioxide concentrations are one of the most important factors affecting marine ecosystems. Excess carbon dioxide can lead to ocean acidification, threatening the stability of marine ecosystems and species diversity. Dissolved carbon dioxide detection in seawater has great scientific significance. Conducting online monitoring of seawater carbon dioxide can help to understand the health status of marine ecosystems and to protect marine ecosystems. Current seawater detection equipment is large and costly. This study designed a low-cost infrared carbon dioxide detection system based on molecular theory. Using the HITRAN database, the absorption spectra and coefficients of carbon dioxide molecules under different conditions were calculated and derived, and a wavelength of 2361 cm-1 was selected as the measurement channel for carbon dioxide. In addition, considering the interference effect of direct light, an infrared post-splitting method was proposed to eliminate the interference of light and improve the detection accuracy of the system. The system was designed for the online monitoring of carbon dioxide in seawater, including a peristaltic pump to accelerate gas-liquid separation, an optical path structure, and carbon dioxide concentration inversion. The experimental results showed that the standard deviation of the gas test is 3.05, the standard deviation of the seawater test is 6.04, and the error range is within 20 ppm. The system can be flexibly deployed and has good stability and portability, which can meet the needs of the online monitoring of seawater carbon dioxide concentration.

Visual Gait Analysis Based on UE4.

With the development of artificial intelligence technology, virtual reality technology has been widely used in the medical and entertainment fields, as well as other fields. This study is supported by the 3D modeling platform in UE4 platform technology and designs a 3D pose model based on inertial sensors through blueprint language and C++ programming. It can vividly display changes in gait, as well as changes in angles and displacements of 12 parts such as the big and small legs and arms. It can be used to combine with the module of capturing motion which is based on inertial sensors to display the 3D posture of the human body in real-time and analyze the motion data. Each part of the model contains an independent coordinate system, which can analyze the angle and displacement changes of any part of the model. All joints of the model are interrelated, the motion data can be automatically calibrated and corrected, and errors measured by an inertial sensor can be compensated, so that each joint of the model will not separate from the whole model and there will not occur actions that against the human body's structures, improving the accuracy of the data. The 3D pose model designed in this study can correct motion data in real time and display the human body's motion posture, which has great application prospects in the field of gait analysis.

Association of TyG index with hypertension in Chinese adults: the China Health Examination Collaborative Study (CHEC Study).

BACKGROUND AND OBJECTIVES: We aimed to investigate the association of triglyceride-glucose (TyG) index with hypertension and compare the discriminative power of the TyG index, lipid, glycemic parameters for hypertension using the China Health Examination Collaborative study (CHEC Study). METHODS AND STUDY DESIGN: Data were collected at Ningbo Mingzhou Hospital and Beijing physical examination center from the CHEC Study during 2014 and 2021. Participants with ≥2 medical check-up times were included. The TyG index is the logarithmized product of fasting triglyceride and glucose. Generalised estimation equation (GEE) model was used to evaluate the association between the TyG index, lipid parameters, glycemic parameters and hypertension. Receiver operating characteristic (ROC) analysis was performed to explore the predictive ability of TyG index on hypertension at different years of medical check-up. RESULTS: 112,902 participants with an average age of 42.8 years were recruited in the study, 36,839 participants developed hypertension over the 8-year period. GEE model analysis showed that the ORs with 95% CI of hypertension were 3.35 (3.15-3.57), 1.86 (1.76-1.95), 1.67 (1.58-1.78), 1.45 (1.33-1.58), 1.24 (1.19-1.29), 0.92 (0.86-0.99), and 1.90 (1.83-1.97) in the highest versus lowest quintiles of TyG index, TG/HDL-C ratio, TG, TC, LDL-C, HDL-C and FPG in model 2. The area under the ROC curve of the overall years of medical check-up was signifi-cantly higher than a particular year in predicting hypertension (AUC: 0.883, p < 0.05). CONCLUSIONS: TyG index is associated with hypertension and shows the superior discriminative ability for hypertension compared with lipid and glycemic parameters.

Advanced nitrogen removal performance and microbial community structure of a lab-scale denitrifying filter with in-situ formation of biogenic manganese oxides.

Advanced nitrogen removal faces the challenges of high operational cost resulted from the additional carbon source and secondary pollution caused by inaccurate carbon source dosage in municipal wastewater. To address these problems, a novel carbon source was developed, which was the oxidation products of refractory organic matters in the secondary effluent of municipal wastewater treatment plant (MWWTP) by in-situ generated biogenic manganese oxides (BMOs) in the denitrifying filter. In the steady phase, the effluent chemical oxygen demand (CODcr), NO3--N and total nitrogen (TN) in the denitrifying filter 2# with BMOs was 11.27, 9.03 and 10.36 mg/L, and the corresponding removal efficiency was 54.79%, 51.85% and 48.03%, respectively, which was significantly higher than those in the control denitrifying filter 1# that the removal efficiency of CODcr, NO3--N and TN was only 32.30%, 28.58% and 29.36%, respectively. Kinds of denitrifying bacteria (Candidatus Competibacter, Defluviicoccus, Dechloromonas, Candidatus Competibacter, Dechloromonas, Pseudomonas, Thauera, Acinetobacter, Denitratisoma, Anaerolineae and Denitratisoma) and anammox bacteria (Pirellula, Gemmata, Anammoximicrobium and Brocadia) were identified in the denitrifying filters 1# and 2#, which explained why the actual CODcr consumption (1.55 and 1.44 mg) of reducing 1 mg NO3--N was much lower than the theoretical CODcr consumption. While manganese oxidizing bacteria (MnOB, Bacillus, Crenothrix and Pedomicrobium) was only identified in the denitrifying filter 2#. This novel technology presented the advantages of no additional carbon source, low operational cost and no secondary pollution. Therefore, the novel technology has superlative application value and broad application prospect.

miR-486 improves fibrotic activity in myocardial infarction by targeting SRSF3/p21-Mediated cardiac myofibroblast senescence.

The regulation of fibrotic activities is key to improving pathological remodelling post-myocardial infarction (MI). Currently, in the clinic, safe and curative therapies for cardiac fibrosis and improvement of the pathological fibrotic environment, scar formation and pathological remodelling post-MI are lacking. Previous studies have shown that miR-486 is involved in the regulation of fibrosis. However, it is still unclear how miR-486 functions in post-MI regeneration. Here, we first demonstrated that miR-486 targeting SRSF3/p21 mediates the senescence of cardiac myofibroblasts to improve their fibrotic activity, which benefits the regeneration of MI by limiting scar size and post-MI remodelling. miR-486-targeted silencing has high potential as a novel target to improve fibrotic activity, cardiac fibrosis and pathological remodelling.

LncRNA GUARDIN suppresses cellular senescence through a LRP130-PGC1α-FOXO4-p21-dependent signaling axis.

The long noncoding RNA GUARDIN functions to protect genome stability. Inhibiting GUARDIN expression can alter cell fate decisions toward senescence or apoptosis, but the underlying molecular signals are unknown. Here, we show that GUARDIN is an essential component of a transcriptional repressor complex involving LRP130 and PGC1α. GUARDIN acts as a scaffold to stabilize LRP130/PGC1α heterodimers and their occupancy at the FOXO4 promotor. Destabilizing this complex by silencing of GUARDIN, LRP130, or PGC1α leads to increased expression of FOXO4 and upregulation of its target gene p21, thereby driving cells into senescence. We also found that GUARDIN expression was induced by rapamycin, an agent that suppresses cell senescence. FOS-like antigen 2 (FOSL2) acts as a transcriptional repressor of GUARDIN, and lower FOSL2 levels in response to rapamycin correlate with increased levels of GUARDIN. Together, these results demonstrate that GUARDIN inhibits p21-dependent senescence through a LRP130-PGC1α-FOXO4 signaling axis, and moreover, GUARDIN contributes to the anti-aging activities of rapamycin.

The Impact of Quarantine and Medical Resources on the Control of COVID-19 in Wuhan based on a Household Model.

In order to understand how Wuhan curbed the COVID-19 outbreak in 2020, we build a network transmission model of 123 dimensions incorporating the impact of quarantine and medical resources as well as household transmission. Using our new model, the final infection size of Wuhan is predicted to be 50,662 (95%CI: 46,234, 55,493), and the epidemic would last until April 25 (95%CI: April 23, April 29), which are consistent with the actual situation. It is shown that quarantining close contacts greatly reduces the final size and shorten the epidemic duration. The opening of Fangcang shelter hospitals reduces the final size by about 17,000. Had the number of hospital beds been sufficient when the lockdown started, the number of deaths would have been reduced by at least 54.26%. We also investigate the distribution of infectious individuals in unquarantined households of different sizes. The high-risk households are those with size from two to four before the peak time, while the households with only one member have the highest risk after the peak time. Our findings provide a reference for the prevention, mitigation and control of COVID-19 in other cities of the world.

Potential Genes Associated with COVID-19 and Comorbidity.

Hypertension, diabetes mellitus, and coronary artery disease are common comorbidities and dangerous factors for infection and serious COVID-19. Polymorphisms in genes associated with comorbidities may help observe susceptibility and disease severity variation. However, specific genetic factors and the extent to which they can explain variation in susceptibility of severity are unclear. Therefore, we evaluated candidate genes associated with COVID-19 and hypertension, diabetes mellitus, and coronary artery disease. In particular, we performed searches against OMIM, NCBI, and other databases, protein-protein interaction network construction, and GO and KEGG pathway enrichment analyses. Results showed that the associated overlapping genes were TLR4, NLRP3, MBL2, IL6, IL1RN, IL1B, CX3CR1, CCR5, AGT, ACE, and F2. GO and KEGG analyses yielded 302 GO terms (q < 0.05) and 29 signaling pathways (q < 0.05), respectively, mainly including coronavirus disease-COVID-19 and cytokine-cytokine receptor interaction. IL6 and AGT were central in the PPI, with 8 and 5 connections, respectively. In this study, we identified 11 genes associated with both COVID-19 and three comorbidities that may contribute to infection and disease severity. The key genes IL6 and AGT are involved in regulating immune response, cytokine activity, and viral infection. Therefore, RAAS inhibitors, AGT antisense nucleotides, cytokine inhibitors, vitamin D, fenofibrate, and vaccines regulating non-immune and immune factors could be potential strategies to prevent and cure COVID-19. The study provides a basis for further investigation of genes and pathways with predictive value for the risk of infection and prognosis and could help guide drug and vaccine development to improve treatment efficacy and the development of personalised treatments, especially for COVID-19 individuals with common comorbidities.

Farnesoid X receptor (FXR) agonists induce hepatocellular apoptosis and impair hepatic functions via FXR/SHP pathway.

Farnesoid X receptor (FXR) plays an indispensable role in liver homeostasis and has been a promising drug target for hepatic diseases. However, the concerns of undesired biological actions limit the clinical applications of FXR agonists. To reveal the intrinsic mechanism of FXR agonist-induce hepatotoxicity, two typical FXR agonists with different structures (obeticholic acid (OCA) and Px-102) were investigated in the present study. By detecting MMP, ROS, and ATP and analyzing the fate of cells, we found that both OCA and Px-102 reduced the mitochondrial function of hepatocytes and promoted cell apoptosis. Gene ablation or inhibition of FXR or SHP ameliorated the cytotoxicities of OCA and Px-102, which indicated the adverse actions of FXR/SHP activation including down-regulation of phosphorylation of PI3K/AKT and functional hepatic genes. The dose-related injurious effects of OCA (10 mg/kg and 30 mg/kg) and Px-102 (5 mg/kg and 15 mg/kg) on the liver were confirmed on a high-fat diet mouse model. The decrease of hepatocyte-specific genes and augmenter of liver regeneration in the liver caused by OCA or Px-102 suggested an imbalance of liver regeneration and a disruption of hepatic functions. Exploration of intestinally biased FXR agonists or combination of FXR agonist with apoptosis inhibitor may be more beneficial strategies for liver diseases.

Extracting clinical named entity for pituitary adenomas from Chinese electronic medical records.

OBJECTIVE: Pituitary adenomas are the most common type of pituitary disorders, which usually occur in young adults and often affect the patient's physical development, labor capacity and fertility. Clinical free texts noted in electronic medical records (EMRs) of pituitary adenomas patients contain abundant diagnosis and treatment information. However, this information has not been well utilized because of the challenge to extract information from unstructured clinical texts. This study aims to enable machines to intelligently process clinical information, and automatically extract clinical named entity for pituitary adenomas from Chinese EMRs. METHODS: The clinical corpus used in this study was from one pituitary adenomas neurosurgery treatment center of a 3A hospital in China. Four types of fine-grained texts of clinical records were selected, which included notes from present illness, past medical history, case characteristics and family history of 500 pituitary adenoma inpatients. The dictionary-based matching, conditional random fields (CRF), bidirectional long short-term memory with CRF (BiLSTM-CRF), and bidirectional encoder representations from transformers with BiLSTM-CRF (BERT-BiLSTM-CRF) were used to extract clinical entities from a Chinese EMRs corpus. A comprehensive dictionary was constructed based on open source vocabularies and a domain dictionary for pituitary adenomas to conduct the dictionary-based matching method. We selected features such as part of speech, radical, document type, and the position of characters to train the CRF-based model. Random character embeddings and the character embeddings pretrained by BERT were used respectively as the input features for the BiLSTM-CRF model and the BERT-BiLSTM-CRF model. Both strict metric and relaxed metric were used to evaluate the performance of these methods. RESULTS: Experimental results demonstrated that the deep learning and other machine learning methods were able to automatically extract clinical named entities, including symptoms, body regions, diseases, family histories, surgeries, medications, and disease courses of pituitary adenomas from Chinese EMRs. With regard to overall performance, BERT-BiLSTM-CRF has the highest strict F1 value of 91.27% and the highest relaxed F1 value of 95.57% respectively. Additional evaluations showed that BERT-BiLSTM-CRF performed best in almost all entity recognition except surgery and disease course. BiLSTM-CRF performed best in disease course entity recognition, and performed as well as the CRF model for part of speech, radical and document type features, with both strict and relaxed F1 value reaching 96.48%. The CRF model with part of speech, radical and document type features performed best in surgery entity recognition with relaxed F1 value of 95.29%. CONCLUSIONS: In this study, we conducted four entity recognition methods for pituitary adenomas based on Chinese EMRs. It demonstrates that the deep learning methods can effectively extract various types of clinical entities with satisfying performance. This study contributed to the clinical named entity extraction from Chinese neurosurgical EMRs. The findings could also assist in information extraction in other Chinese medical texts.

The Second Class of Tetrahydrofolate (THF-II) Riboswitches Recognizes the Tetrahydrofolic Acid Ligand via Local Conformation Changes.

Riboswitches are regulatory noncoding RNAs found in bacteria, fungi and plants, that modulate gene expressions through structural changes in response to ligand binding. Understanding how ligands interact with riboswitches in solution can shed light on the molecular mechanisms of this ancient regulators. Previous studies showed that riboswitches undergo global conformation changes in response to ligand binding to relay information. Here, we report conformation switching models of the recently discovered tetrahydrofolic acid-responsive second class of tetrahydrofolate (THF-II) riboswitches in response to ligand binding. Using a combination of selective 2'-hydroxyl acylation, analyzed by primer extension (SHAPE) assay, 3D modeling and small-angle X-ray scattering (SAXS), we found that the ligand specifically recognizes and reshapes the THF-II riboswitch loop regions, but does not affect the stability of the P3 helix. Our results show that the THF-II riboswitch undergoes only local conformation changes in response to ligand binding, rearranging the Loop1-P3-Loop2 region and rotating Loop1 from a ~120° angle to a ~75° angle. This distinct conformation changes suggest a unique regulatory mechanism of the THF-II riboswitch, previously unseen in other riboswitches. Our findings may contribute to the fields of RNA sensors and drug design.

Interaction Structure and Affinity of Zwitterionic Amino Acids with Important Metal Cations (Cd2+, Cu2+, Fe3+, Hg2+, Mn2+, Ni2+ and Zn2+) in Aqueous Solution: A Theoretical Study.

Heavy metals are non-biodegradable and carcinogenic pollutants with great bio-accumulation potential. Their ubiquitous occurrence in water and soils has caused serious environmental concerns. Effective strategies that can eliminate the heavy metal pollution are urgently needed. Here the adsorption potential of seven heavy metal cations (Cd2+, Cu2+, Fe3+, Hg2+, Mn2+, Ni2+ and Zn2+) with 20 amino acids was systematically investigated with Density Functional Theory method. The binding energies calculated at B3LYP-D3/def2TZVP level showed that the contribution order of amino acid side chains to the binding affinity was carboxyl > benzene ring > hydroxyl > sulfhydryl > amino group. The affinity order was inversely proportional to the radius and charge transfer of heavy metal cations, approximately following the order of: Ni2+ > Fe3+ > Cu2+ > Hg2+ > Zn2+ > Cd2+ > Mn2+. Compared to the gas-phase in other researches, the water environment has a significant influence on structures and binding energies of the heavy metal and amino acid binary complexes. Collectively, the present results will provide a basis for the design of a chelating agent (e.g., adding carboxyl or a benzene ring) to effectively remove heavy metals from the environment.

DKK1 suppresses WWP2 to enhance bortezomib resistance in multiple myeloma via regulating GLI2 ubiquitination.

Bortezomib-based chemotherapy represents the most prevalent regimens for multiple myeloma (MM), whereas acquired drug resistance remains a major obstacle. Myeloma cells often produce excessive amount of dickkopf-1 (DKK1), giving rise to myeloma bone disease. However, it remains obscure about the effects and mechanisms of DKK1 in the progression and bortezomib responsiveness of MM cells. In the current study, we found WWP2, an E3 ubiquitin-protein ligase, was downregulated in the bortezomib-resistant cells along with high expression of DKK1. Further investigation revealed that WWP2 was a direct target of Wnt/ß-catenin signaling pathway, and DKK1 suppressed the expression of WWP2 via canonical Wnt signaling. We further identified that WWP2 mediated the ubiquitination and degradation of GLI2, a main transcriptional factor of the Hedgehog (Hh) pathway. Therefore, DKK1-induced WWP2 downregulation improved GLI2 stability and activation of Hh signaling pathway, contributing to the resistance to bortezomib of MM cells. Clinical data also validated that WWP2 expression was associated with the treatment response and clinic outcomes of MM patients. WWP2 overexpression restricted MM progression and enhanced cell sensitivity to bortezomib treatment in vitro and in vivo. Taken together, our findings demonstrate that DKK1 facilitates the generation of bortezomib resistance in MM via downregulating WWP2 and activating Hh pathway. Thus, the manipulation of DKK1-WWP2-GLI2 axis might sensitize myeloma cells to proteasome inhibitors.

Cobalt chloride-simulated hypoxia elongates primary cilia in immortalized human retina pigment epithelial-1 cells.

Primary cilia are microtubule-based organelles that are involved in sensing micro-environmental cues and regulating cellular homeostasis via triggering signaling cascades. Hypoxia is one of the most common environmental stresses that organ and tissue cells may often encounter during embryogenesis, cell differentiation, infection, inflammation, injury, cerebral and cardiac ischemia, or tumorigenesis. Although hypoxia has been reported to promote or inhibit primary ciliogenesis in different tissues or cultured cell lines, the role of hypoxia in ciliogenesis is controversial and still unclear. Here we investigated the primary cilia change under cobalt chloride (CoCl2)-simulated hypoxia in immortalized human retina pigment epithelial-1 (hTERT RPE-1) cells. We found CoCl2 treatment elongated primary cilia in a time- and dose-dependent manner. The prolonged cilia recovered back to near normal length when CoCl2 was washed out from the cell culture medium. Under CoCl2-simulated hypoxia, the protein expression levels of HIF-1/2α and acetylated-α-tubulin (cilia marker) were increased, while the protein expression level of Rabaptin-5 is decreased during hypoxia. Taken together, our results suggest that hypoxia may elongate primary cilia by downregulating Rabaptin-5 involved endocytosis. The coordination between endocytosis and ciliogenesis may be utilized by cells to adapt to hypoxia.

An easy-to-operate web-based calculator for predicting the progression of chronic kidney disease.

BACKGROUND: This study aimed to establish and validate an easy-to-operate novel scoring system based on simple and readily available clinical indices for predicting the progression of chronic kidney disease (CKD). METHODS: We retrospectively evaluated 1045 eligible CKD patients from a publicly available database. Factors included in the model were determined by univariate and multiple Cox proportional hazard analyses based on the training set. RESULTS: Independent prognostic factors including etiology, hemoglobin level, creatinine level, proteinuria, and urinary protein/creatinine ratio were determined and contained in the model. The model showed good calibration and discrimination. The area under the curve (AUC) values generated to predict 1-, 2-, and 3-year progression-free survival in the training set were 0.947, 0.931, and 0.939, respectively. In the validation set, the model still revealed excellent calibration and discrimination, and the AUC values generated to predict 1-, 2-, and 3-year progression-free survival were 0.948, 0.933, and 0.915, respectively. In addition, decision curve analysis demonstrated that the model was clinically beneficial. Moreover, to visualize the prediction results, we established a web-based calculator ( https://ncutool.shinyapps.io/CKDprogression/ ). CONCLUSION: An easy-to-operate model based on five relevant factors was developed and validated as a conventional tool to assist doctors with clinical decision-making and personalized treatment.

Constant pH molecular dynamics of porcine circovirus 2 capsid protein reveals a mechanism for capsid assembly.

Spatiotemporal regulation of viral capsid assembly ensures the selection of the viral genome for encapsidation. The porcine circovirus 2 is the smallest autonomously replicating pathogenic virus, yet how PCV2 capsid assembly is regulated to occur within the nucleus remains unknown. We report that pure PCV2 capsid proteins, in the absence of nucleic acids, require acidic conditions to assemble into empty capsids in vitro. By employing constant pH replica exchange molecular dynamics, we unveil the atomistic mechanism of pH-dependency for capsid assembly. The results show that an appropriate protonation configuration for a cluster of acidic amino acids is necessary to appropriately position the GH-loop for driving the capsid assembly. We demonstrate that assembly is prohibited at neutral pH because deprotonation of these residues results in their electrostatic repulsion, shifting the GH-loop to a position incompatible with capsid assembly. We propose that encapsulation of nucleic acids overcomes this repulsion to suitably position the GH-loop. Our findings provide the first atomic resolution mechanism of capsid assembly regulation. These findings are useful for the development of therapeutics that inhibit PCV2 self-assembly.

Near-Null Magnetic Field Suppresses Fruit Growth in Arabidopsis.

We previously found that a near-null magnetic field affected reproductive growth in Arabidopsis under white light. To test whether the effect of a near-null magnetic field on fruit growth of Arabidopsis is related to cryptochrome, we grew wild-type Arabidopsis and cryptochrome double mutant, cry1/cry2, in a near-null magnetic field under blue light. We found that fruit growth of wild-type Arabidopsis instead of the cry1/cry2 mutant was suppressed by the near-null magnetic field. Furthermore, gibberellin (GA) levels of GA4 , GA9 , GA34 , and GA51 in fruits of wild-type plants in the near-null magnetic fields were significantly lower than local geomagnetic field controls. However, in cry1/cry2 mutants, levels of the four detected GAs in fruits in the near-null magnetic fields did not differ significantly from controls. Expressions of GA20-oxidase (GA20ox) genes (GA20ox1 and GA20ox2) and GA3-oxidase (GA3ox) genes (GA3ox1 and GA3ox3) in fruits of wild-type plants rather than cry1/cry2 mutants were downregulated by the near-null magnetic field. In contrast, expressions of GA2-oxidase (GA2ox) genes and GA signaling genes were not affected by the near-null magnetic field. These results indicate that suppression of fruit growth by the near-null magnetic field is mediated by cryptochrome and that GAs are involved in the regulation of fruit growth by the near-null magnetic field. © 2021 Bioelectromagnetics Society.

Restoration priority assessment of coal mining brownfields from the perspective of enhancing the connectivity of green infrastructure networks.

Integration of mining brownfields into green infrastructure(GI) planning has been widely recognized as a sustainable developmentstrategy. The key is to locate the spatial priority areas for brownfieldrestoration that would provide the greatest enhancement of themultifunctionality of the GI network. At the regional scale, a wellconnectedGI network can help maximize the benefits that it generates andachieve greater multifunctionality. In this paper, an approach forassessing the restoration priority of brownfields is proposed from the perspective of enhancing the structural connectivity of GI network. Itcan also be used as an assistance tool for planning GI networks at theregional level. The Least Cost Path (LCP) model is adopted for mapping corridors among GI patches on the basis of a resistance map composed by considering the naturalness of land covers, the riparian corridor, and disturbance of roads. Taking Fenhe River Basin (in China) as an example, three factors are jointly considered in the priority assessment of brownfields restoration: their potential contribution as corridors, their importance as stepping stones, and their resistance values. Then, we divided the brownfields into groups indicating the level of priority for restoration. The results show that 67% of the brownfields are of high or very high priority for restoration (mainly located in the north), and less than 10% area is recognized as very low or low priority. Our proposed approach could be a valuable tool for providing a macro-scale assessment of restoration priorities of brownfields for enhancing the GI network connectivity, and giving instructions for on-site redevelopment.