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Abstract Background Nitrogen (N) deposition has become a major driving factor affecting the balance of terrestrial ecosystems, changing the soil environment, element balance and species coexistence relationships, driving changes in biodiversity and ecosystem structure and function. Human-induced nitrogen input leads to a high NH4 +/ NO3 - ratio in soil. However, relatively few studies have investigated the effects of different nitrogen sources on forest plant-microbial symbionts. In this study, the effects of four nitrogen sources, N free, NH4Cl, L-glutamic acid, and Na(NO3)2 (N-, NH4 +-N, Org-N, and NO3 --N) on four fungal species, Suillus granulatus (Sg), Pisolithus tinctorius (Pt), Pleotrichocladium opacum (Po), and Pseudopyrenochaeta sp. (Ps), which were isolated from the roots of Pinus tabulaeformis, were studied in vitro. The effects of inoculation with the four fungi on the growth performance, nutrient uptake and nitrogen metabolism-related enzymes of Pinus tabuliformis under different nitrogen source conditions were subsequently studied. Results The biomass and N concentration of the Sg and Po strains were the highest under the NO3 --N treatment, while the biomass and N concentration of the Pt and Ps strains were significantly greater under the NH4 +-N and NO3 --N treatments than under the Org-N and N- treatments. All four fungi could effectively colonize the roots of P. tabuliformis and formed a symbiotic relationship with it. Under all nitrogen conditions, the inoculation of the four fungi had positive effects on the growth, root development and nutrient concentration of the P. tabuliformis seedlings. Under the Org-N and NO3 --N treatments, the nitrate reductase (NR) activity of the inoculated plants was significantly greater than that of the noninoculated control (CK) plants. Under all nitrogen conditions, the glutamine synthetase (GS) activity of the inoculated plants was significantly greater than that of the CK plants. Conclusions The four fungi can establish good symbiotic relationships with P. tabuliformis seedlings and promote their growth and development under different nitrogen source treatments.

Summary: Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne phlebovirus that causes viral hemorrhagic fever. Pandemic concerns have arisen due to the increased human-to-human transmission and high mortality rate, highlighting the urgent need for specific therapeutics. Methods: Our observational study characterized the memory B cell response to natural SFTSV infection in four survivors. Monoclonal antibodies (mAbs) targeting the SFTSV glycoprotein N (Gn) were isolated and tested for in vitro neutralizing activities and effects on virus binding. Structural analysis was performed to identify neutralizing epitopes recognized by the mAbs. Prophylactical and therapeutical protections were evaluated using a lethal SFTSV infection model. Findings: The selected mAbs exhibiting neutralizing activity primarily originate from the IGHV5-51 and IGHV3-30 germlines and target four distinct antigenic sites on SFTSV Gn. These elite mAbs effectively blocked the interaction between Gn and the cell receptor, preventing infections from five phylogenetically distinct SFTSV clades. Structural analysis revealed a novel neutralizing epitope located within SFTSV Gn domain I recognized by the elite mAbs. In mice of lethal infections with different SFTSV strains, administering a low dose of elite mAbs significantly improved survival rates in both prophylactic and therapeutic settings. Interpretation: This study identifies potent broadly neutralizing antibodies that holds promise for use in humans against SFTSV infection and highlights inhibition of receptor binding as a crucial mechanism for effective antibody-mediated neutralization against phleboviruses. Funding: The National Key Research and Development Plan of China (2018YFE0200401, 2022YFC2303300), National Natural Science Foundation of China (81825019), China Postdoctoral Science Foundation (2023M741824).

Abstract The expression dysregulation of microRNAs (miRNA) has been widely reported during cancer development, however, the underling mechanism remains largely unanswered. In the present work, we performed a systematic integrative study for genome-wide DNA methylation, copy number variation and miRNA expression data to identify mechanisms underlying miRNA dysregulation in lower grade glioma. We identify 719 miRNAs whose expression was associated with alterations of copy number variation or promoter methylation. Integrative multi-omics analysis revealed four subtypes with differing prognoses. These glioma subtypes exhibited distinct immune-related characteristics as well as clinical and genetic features. By construction of a miRNA regulatory network, we identified candidate miRNAs associated with immune evasion and response to immunotherapy. Finally, eight prognosis related miRNAs were validated to promote cell migration, invasion and proliferation through in vitro experiments. Our study reveals the crosstalk among DNA methylation, copy number variation and miRNA expression for immune regulation in glioma, and could have important implications for patient stratification and development of biomarkers for immunotherapy approaches.

Geopolymer concrete (GPC) is a promising alternative to Ordinary Portland cement concrete (OPC), with great potential in reducing carbon emissions and energy consumption. However, current mix proportion designs overlook the recyclability for future applications. This study aims to explore the recyclability of GPC in freeze-thaw environment. Different precursors (fly ash, metakaolin, red mud, and slag) were used to prepare GPC with the comparable strength level. To enhance the frost resistance of GPC, slag was implemented to replace 40 % of the precursors. After 350 rapid freeze-thaw cycles, the GPC specimens were crushed and screened to obtain recycled geopolymer coarse aggregates (RGA), and the physical properties of RGA were investigated. The results showed GPC demonstrated excellent frost resistance, withstanding up to 350 freeze-thaw cycles, except for fly ash-based GPC which failed after 150 cycles. After 350 freeze-thaw cycles, metakaolin-based, red mud-based and slag-based GPC still met the requirements of 50 years’ service life in cold regions. The physical properties of RGA recycled from the GPC could meet the quality standards for Class II recycled aggregate, highlighting the promising recyclability of GPC in freeze-thaw environment. It was worth noting that the quality of recycled aggregate depended on the performance of the parent concrete.

Objective This scoping review and meta-analysis aimed to map the evidence regarding prognostic factors in Chinese patients with immunoglobulin light chain (AL) amyloidosis and to identify current research gaps.Methods We searched EMBASE, PubMed, and CNKI databases from their inception to 15 September 2021. All studies investigated the association between any prognostic factor and target outcomes, including overall survival (OS), progression-free survival (PFS), and end-stage renal disease (ESRD) in Chinese patients with AL amyloidosis.Results This scoping review included 52 studies, of which 44 with 6,432 patients contributed to the multivariate prognostic analysis. Multivariate analysis identified a total of 106 factors that correlated with OS, 16 factors with PFS, and 18 factors with ESRD. Five prognostic factors were significantly associated with PFS, and 11 prognostic factors were significantly associated with ESRD. Meta-analysis was only available for prognostic factors without heterogeneous cutoff values, for which hazard ratios (HRs) and their 95% confidence intervals (CIs) were reported. Meta-analysis showed that bone marrow plasma cells (BMCs) (HR: 1.96, 95% CI: 1.21–3.19, p

BackgroundDrought constitutes a major abiotic stress factor adversely affecting plant growth and productivity. Plant-microbe symbiotic associations have evolved regulatory mechanisms to adapt to environmental stress conditions. However, the interactive effects of different fungi on host growth and stress tolerance under drought conditions remain unclear.ObjectiveThis study explored the effects of varying polyethylene glycol (PEG-6000) concentrations (0%, 15%, 25%, and 35%) on the growth and physiological responses of two ectomycorrhizal fungi (Suillus granulatus (Sg) and Pisolithus tinctorius (Pt)) and two dark septate endophytes (Pleotrichocladium opacum (Po) and Pseudopyrenochaeta sp. (Ps)) isolated from the root system of Pinus tabuliformis. Specifically, the study aimed to evaluate six inoculation treatments, including no inoculation (CK), single inoculations with Sg, Pt, Po, Ps, and a mixed inoculation (Sg: Pt : Po: Ps = 1:1:1:1), on the growth and physiological characteristics of P. tabuliformis seedlings under different water regimes: well-watered at 70% ± 5%, light drought at 50% ± 5%, and severe drought at 30% ± 5% of the maximum field water holding capacity.ResultsAll four fungi exhibited the capacity to cope with drought stress by enhancing antioxidant activities and regulating osmotic balance. Upon successful root colonization, they increased plant height, shoot biomass, root biomass, total biomass, and mycorrhizal growth response in P. tabuliformis seedlings. Under drought stress conditions, fungal inoculation improved seedling drought resistance by increasing superoxide dismutase and catalase activities, free proline and soluble protein contents, and promoting nitrogen and phosphorus uptake. Notably, mixed inoculation treatments significantly enhanced antioxidant capacity, osmotic adjustment, and nutrient acquisition abilities, leading to superior growth promotion effects under drought stress compared to single inoculation treatments.ConclusionAll four fungi tolerated PEG-induced drought stress, with increased antioxidant enzyme activities and osmotic adjustment substances and they promoted the growth and enhanced drought resistance of P. tabuliformis seedlings.

Abstract This study aimed to develop and validate a predictive model to determine the risk of in-hospital mortality in patients with acute paraquat poisoning. This retrospective observational cohort study included 724 patients with acute paraquat poisoning whose clinical data were collected within 24 h of admission. The primary outcome was in-hospital mortality. Patients were randomly divided into training and validation cohorts (7/3 ratio). In the training cohort, the least absolute shrinkage and selection operator regression models were used for data dimension reduction and feature selection. Multivariate logistic regression was used to generate a predictive nomogram for in-hospital mortality. The prediction model was assessed for both the training and validation cohorts. In the training cohort, decreased level of consciousness (Glasgow Coma Scale score

AbstractBackground Amyloid light chain (AL) amyloidosis is the most common systemic amyloidosis. The objective of this scoping review was to map the available literature on the diagnosis of AL amyloidosis in China.Materials and Methods The published academic papers related to the diagnosis of AL amyloidosis were screened from 1 January 2000 to 15 September 2021. Chinese patients who have suspected AL amyloidosis were included. The included studies were categorized into accuracy studies and descriptive studies based on if the studies supplied the diagnostic accuracy data or not. The information on the diagnostic methods reported by included studies was synthesized.Results Forty-three articles were included for the final scoping review, with 31 belonging to descriptive studies and 12 having information on diagnostic accuracy. Although cardiac involvement was second top in Chinese patients with AL amyloidosis, a cardiac biopsy was rare. Next, we found light chain classification and monoclonal (M-) protein identification were essential methods for the diagnosis of AL amyloidosis in China. In addition, some combined tests (e.g. immunohistochemistry and serum free light chain, immunohistochemistry and immunofixation electrophoresis, and serum free light chain and immunofixation electrophoresis) can increase the sensitivity of the diagnosis. Finally, several adjuvant methods (e.g. Imaging, N-terminal-pro hormone BNP, and brain natriuretic peptide test) were important for AL amyloidosis diagnosis.Conclusion This scoping review details the characteristics and results of the recently published studies on diagnosing AL Amyloidosis in China. Biopsy is the most important method for AL Amyloidosis diagnosis in China. In addition, combined tests and some adjuvant methods played essential roles in the diagnosis. Further research is required to determine an acceptable and feasible diagnostic algorithm after symptom onset. REGISTRATION: INPLASY2022100096KEY MESSAGESThis scoping review details the characteristics and results of the recently published studies on diagnosing Amyloid light chain (AL) Amyloidosis in China.Biopsy is the most important method for AL Amyloidosis diagnosis in China.Combined tests and some adjuvant methods played essential roles in the diagnosis.

Abstract Albeit the majority of eukaryotic genomes can be pervasively transcribed to a diverse population of lncRNAs and various subtypes of lncRNA are discovered. However, the genome‐wide study of miRNA‐derived lncRNAs is still lacking. Here, it is reported that over 800 miRNA gene‐originated lncRNAs (molncRNAs) are generated from miRNA loci. One of them, molnc‐301b from miR‐301b and miR‐130b, functions as an “RNA decoy” to facilitate dissociation of the chromatin remodeling protein SMARCA5 from chromatin and thereby sequester transcription and mRNA translation. Specifically, molnc‐301b attenuates erythropoiesis by mitigating the transcription of erythropoietic and translation‐associated genes, such as GATA1 and FOS. In addition, a useful and powerful CRISPR screen platform to characterize the biological functions of molncRNAs at large‐scale and single‐cell levels is established and 29 functional molncRNAs in hematopoietic cells are identified. Collectively, the focus is on miRNA‐derived lncRNAs, deciphering their landscape during normal hematopoiesis, and comprehensively evaluating their potential roles.

Immunoglobulin light chain (AL) amyloidosis is the most common type of systemic amyloidosis in China and is associated with increased morbidity and a poor prognosis. However, the clinical characteristics of Chinese patients with AL amyloidosis have not been systematically investigated. This scoping review aimed to summarize the available literature regarding the clinical characteristics of patients with AL amyloidosis and identify potential knowledge gaps. We searched three electronic databases from inception to 7 February 2021. PICOS (Patient, Intervention, Comparison, Outcome and Study) design structure was used to formulate the data extraction. All statistical calculations and analyses were performed with R (version 3.6.0). Sixty-seven articles with 5022 patients were included. Results suggest Chinese patients were younger (57 years) at the time of diagnosis when compared with other patient populations and were predominantly male (61.2%). The time interval from the onset of symptoms to diagnosis was between 6 and 12 months. It was found that 41.1% of Chinese patients with AL amyloidosis were diagnosed with an advanced stage III disease when diagnosed, and 20.2% had a concurrent disease. The most involved organs were the kidneys (84.3%) and the heart (62.5%). In conclusion, our study shows some similarities and differences with other studies on the clinical characteristics of Chinese patients with AL amyloidosis, including the age at diagnosis, Mayo stage, and organ involvement. However, a nationwide epidemiological investigation is still needed to provide a comprehensive overview of this patient population in China.

Abstract Background Intravenous daratumumab (DARA IV) has been increasingly used in the treatment of amyloid light-chain (AL) amyloidosis. However, the outcomes for patients administered with DARA IV have not been aggregated. The objective of this systematic review and meta-analysis was to investigate the efficacy and safety of DARA IV for AL amyloidosis. Methods We searched Medline, EMBASE, Cochrane Library and Web of Science up to 17 June 2021. Response rates and survival rates, and the corresponding 95% confidence intervals (CIs) were pooled and calculated using a fixed-effects model. Results Thirty studies (5 cohort studies and 25 single-arm studies) with 997 patients were included. In patients receiving DARA IV-based treatments, very good partial response or better response rate, complete response rate, very good partial response rate, partial response rate and overall response rate were 66% (95% CI, 62–69%), 30% (95% CI, 23–36%), 40% (95% CI, 33–46%), 17% (95% CI, 14–21%), and 77% (95% CI, 73–80%), respectively. Cardiac and renal responses were 41% (95% CI, 34–49%) and 43% (95% CI, 32–54%), respectively. 58% (95% CI, 49–66%) of patients achieved PFS one year or longer. 2.5% (range, 1–10.0%) of patients experienced grade 3 or 4 adverse events, of which the most common adverse event was lymphocytopenia (range, 13.6–25.0%). Conclusion This study supports the efficacy and safety of DARA IV for the treatment of patients with AL amyloidosis.

DC high current measurement is one of the important supporting technologies of the power system. As an emerging current sensing technology, tunnel magnetoresistance (TMR) has attracted more and more attention due to its advantages of high sensitivity and good linearity. But the TMR sensor is not suitable for high current measurement, and its accuracy can be further improved. Aiming at these problems, this paper proposes a TMR array with a circular skeleton coil for high current measurement. Eight TMR chips are evenly installed on the circular skeleton coil to measure the magnetic field generated by the primary current carrying conductor, and the output of the feedback amplifier generates a compensation current to the feedback winding to generate a compensation magnetic field, so that the magnetic flux in the sensor is almost zero. The circular structure can reduce measurement errors caused by wire offset and external interference. Since there is no iron core, the nonlinear errors are also avoided. Simultaneously, the feedback loop designed based on zero magnetic flux principle can reduce the hysteresis error and expand the measurement range, making the sensor suitable for DC high current measurement. This paper proposes a new TMR array current sensor model, builds a prototype and compares it with a closed-loop TMR current sensor with an iron core. Experimental results proved that the TMR array sensor’s DC measurement error could be lower than 0.01%, compared to 0.32% of the closed-loop current sensor. Moreover, the proposed current sensor consistently has higher measurement accuracy in the full range of primary current.

Abstract Background Cellular RNA-binding proteins (RBPs) have multiple roles in post-transcriptional control, and some are shown to bind DNA. However, the global localization and the general chromatin-binding ability of RBPs are not well-characterized and remain undefined in hematopoietic cells. Results We first provide a full view of RBPs’ distribution pattern in the nucleus and screen for chromatin-enriched RBPs (Che-RBPs) in different human cells. Subsequently, by generating ChIP-seq, CLIP-seq, and RNA-seq datasets and conducting combined analysis, the transcriptional regulatory potentials of certain hematopoietic Che-RBPs are predicted. From this analysis, quaking (QKI5) emerges as a potential transcriptional activator during monocytic differentiation. QKI5 is over-represented in gene promoter regions, independent of RNA or transcription factors. Furthermore, DNA-bound QKI5 activates the transcription of several critical monocytic differentiation-associated genes, including CXCL2, IL16, and PTPN6. Finally, we show that the differentiation-promoting activity of QKI5 is largely dependent on CXCL2, irrespective of its RNA-binding capacity. Conclusions Our study indicates that Che-RBPs are versatile factors that orchestrate gene expression in different cellular contexts, and identifies QKI5, a classic RBP regulating RNA processing, as a novel transcriptional activator during monocytic differentiation.

Nitrogen (N) availability is significant in different ecosystems, but the response of forest plant-microbial symbionts to global N deposition remains largely unexplored. In this study, the effects of different N concentration levels on four types of fungi, Suillus granulatus (Sg), Pisolithus tinctorius (Pt), Pleotrichocladium opacum (Po), and Pseudopyrenochaeta sp. (Ps), isolated from the roots of Pinus tabulaeformis were investigated in vitro. Then, the effects of the fungi on the growth performance, nutrient uptake, and rhizosphere soil microbial community structure of P. tabulaeformis under different N addition conditions (0, 40, and 80 kg hm−2 year−1) were examined. The biomass and phytohormone contents of the Sg, Pt and Po strains increased with increasing N concentration, while those of the Ps strain first increased and then decreased. All four fungal strains could effectively colonize the plant roots and form a strain-dependent symbiosis with P. tabulaeformis. Although the effects depended on the fungal species, the growth and root development of inoculated seedlings were higher than those of uninoculated seedlings under N deficiency and normal N supply conditions. However, these positive effects disappeared and even became negative under high N supply conditions. The inoculation of the four fungal strains also showed significant positive effects on the shoot and root nutrient contents of P. tabulaeformis. Fungal inoculation significantly increased different microbial groups and the total soil microorganisms but decreased the microbial diversity under N deficiency stress. In summary, exogenous symbiotic fungal inoculations could increase the growth performance of P. tabulaeformis under N deficiency and normal N supply conditions, but the effects were negative under excessive N addition.

In this paper, a new feedback-added pseudoinverse-type balanced minimization (FPBM) scheme is proposed and studied for the kinematic control of redundant robot manipulators. Such a scheme is designed by combining the minimum acceleration norm (MAN) solution and the weighted minimum velocity norm (WMVN) solution and by introducing the feedback. With the MAN and WMVN combination, the proposed FPBM scheme can not only remedy the phenomena of high velocity and acceleration but also generate a near-zero velocity after task execution. With the feedback introduction, the proposed FPBM scheme can guarantee a nondivergent end-effector tracking error. Based on a four-link robot manipulator, the simulation results are presented to show the effectiveness of the proposed FPBM scheme.

Abstract Background PHD-finger domain protein 5A (PHF5A) is a highly conserved small transcriptional regulator also involved in pre-mRNA splicing; however, its biological functions and molecular mechanisms in non-small cell lung cancer (NSCLC) have not yet been investigated. The purpose of this study was to determine the functional relevance and therapeutic potential of PHF5A in lung adenocarcinoma (LAC). Methods The expression of PHF5A in LAC tissues and adjacent non-tumor (ANT) tissues was investigated using immunohistochemistry of a tissue microarray, qRT-PCR, western blot and bioinformatics. The function of PHF5A was determined using several in vitro assays and also in vivo assay by lentiviral vector-mediated PHF5A depletion in LAC cell lines. Results PHF5A was highly upregulated in LAC tissues compared with the ANT counterparts, and closely associated with tumor progression and poor patient prognosis. These results were further confirmed by findings of the TCGA database. Moreover, functional studies demonstrated that PHF5A knockdown not only resulted in reduced cell proliferation, increased cell apoptosis, and cell cycle arrest, but also suppressed migration and invasion in LAC cells. PHF5A silencing was also found to inhibit LAC tumor growth in nude mice. Microarray and bioinformatics analyses revealed that PHF5A depletion led to dysregulation of multiple tumor signaling pathways; selected factors in key signaling pathways were verified in vitro. Conclusions The data suggest for the first time that PHF5A is an oncoprotein that contributes to LAC progression by regulating multiple signaling pathways, and may constitute a prognostic factor and potential new therapeutic target in NSCLC.

BACKGROUND: In addition to SARS associated coronaviruses, 4 non-SARS related human coronaviruses (HCoVs) are recognized as common respiratory pathogens. The etiology and clinical impact of HCoVs in Chinese adults with acute upper respiratory tract infection (URTI) needs to be characterized systematically by molecular detection with excellent sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we detected 4 non-SARS related HCoV species by real-time RT-PCR in 981 nasopharyngeal swabs collected from March 2009 to February 2011. All specimens were also tested for the presence of other common respiratory viruses and newly identified viruses, human metapneumovirus (hMPV) and human bocavirus (HBoV). 157 of the 981 (16.0%) nasopharyngeal swabs were positive for HCoVs. The species detected were 229E (96 cases, 9.8%), OC43 (42 cases, 4.3%), HKU1 (16 cases, 1.6%) and NL63 (11 cases, 1.1%). HCoV-229E was circulated in 21 of the 24 months of surveillance. The detection rates for both OC43 and NL63 were showed significantly year-to-year variation between 2009/10 and 2010/11, respectively (P

Acute pancreatitis (AP) with sepsis is a severe and potentially fatal complication. Current predictive systems for identifying high-risk sepsis in AP patients often lack specificity and timeliness, resulting in delays in diagnosis and intervention. This study retrospectively collected data from emergency departments in three tertiary comprehensive hospitals to develop a machine learning (ML) model for the rapid identification of high-risk sepsis in patients with AP. Patients were randomly divided into training and testing datasets (7:3 ratio). In the training dataset, we employed 10 ML algorithms to analyze bedside parameters of patients with AP upon admission. The 10-fold cross-validation was used to find the best parameter and model. The model was then applied to the testing dataset without modifying the model parameters to obtain unbiased classification performance. The performance of the ML model was assessed using the receiver operating characteristic curve (ROC) and compared to scoring systems using the DeLong test. In this study, 771 AP patients were assessed. During hospitalization, 559 patients were diagnosed with sepsis within the first 24 hours, while 212 were not. A Random Forest (RF) model containing 8 features demonstrated the highest area under the curve (AUC) on the cross-validation dataset (AUC: 0.877, accuracy: 0.772), with the AUC of 0.947 and accuracy of 0.836 on the testing dataset. Compared to the Acute Physiology and Chronic Health Evaluation II (AUC 0.708), quick Sequential Organ Failure Assessment (AUC 0.672), and Bedside Index of Severity in Acute Pancreatitis (AUC 0.680), the RF model showed superior performance in predicting sepsis occurrence in patients with AP. This study constructed and validated ML models for the early prediction of sepsis in patients with AP. The RF model provides clinicians with a rapid and useful tool to guide the level of patient care and implement early intervention strategies. [ABSTRACT FROM AUTHOR]