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Abstract The application of biochar to soil is widely recognized as a promising strategy for enhancing the accumulation and stability of soil organic carbon (SOC), which is crucial in mitigating climate change. However, the influence of interactions between plants and biochar on soil microbial communities and their involvement in SOC mineralization and stability remains unclear. This understanding is essential for optimizing carbon (C) sequestration in systems involving plants, soil, and biochar. In this study, employing a 13C natural abundance approach, we investigated the effect of biochar on the maize rhizosphere priming effect (RPE) in paddy soil. We also examined alterations in microbial communities and functional genes related to C degradation and fixation. Over the 99 days of maize growth, biochar application increased RPE and total SOC while decreasing dissolved organic C. It also elevated soil pH, resulting in shifts in fungal and bacterial community structure, favoring oligotrophic species. Fungal and bacterial assemblies were dominated by deterministic and stochastic processes, respectively. While the abundance of fungal guilds varied irregularly, bacterial guilds were uniformly enriched under biochar-plant interactions. Functional traits such as ecoenzymatic activities, bacterial guilds, and functional genes predominantly affected RPE under biochar application. Bacterial functional genes associated with C degradation and fixation were concurrently enhanced with biochar application. Our results indicate that interactions between plants and biochar can enhance native SOC mineralization and accumulation in a short timeframe by modulating functional traits of soil microorganisms, particularly the bacterial community involved in C degradation and fixation. Graphical Abstract

Muscle is one of the important quality of fish. However, there is still a lack of sufficient understanding of the mechanism of muscle growth regulation in fish. In this study, the expression patterns of 10 reported muscle development related genes are analyzed in zebrafish during growth or under water flow stress. Myogenic regulatory factors (MyoD, MyoG, MRF4), myostatin regulatory genes (Mstna, Mstnb) and myoblast development-related genes (Pax7, Prmt5, Desmin, MYHC) are significantly increased expression at somite stage and muscle effect stage embryos in zebrafish. The mRNA levels of the muscle development related genes are up-regulated in 7-day fries and 30-day juvenile of zebrafish. And there are differences in the expression levels of seven muscle development related genes (MyoD, Myf5, MyoG, Mstna, Mstnb, Desmin, MYHC) between the large and small individuals of 20-day-old zebrafish. Results indicated that short-term water flow stressing can promote zebrafish muscle growth, while prolonged water flow stress may lead to motor fatigue and affect growth in zebrafish. This research provides a foundation for further exploration of the growth regulation mechanism in fish, and is helpful on fish farming.

Abstract The occurrence of diabetic nephropathy (DN) and diabetic retinopathy (DR) are closely associated in patients with diabetes. However, the cellular and molecular linkage of DN and DR has not been elucidated, and further revelations are needed to improve mutual prognostic decisions and management. Here, we generate and integrate single-cell RNA sequencing profiles of kidney and retina to explore the cellular and molecular association of kidney and retina in both physiological and pathological conditions. We find renal mesangial cells and retinal pericytes share molecular features and undergo similar molecular transitions under diabetes. Furthermore, we uncover that chemokine regulation shared by the two cell types is critical for the co-occurrence of DN and DR, and the chemokine score can be used for the prognosis of DN complicated with DR. These findings shed light on the mechanism of the co-occurrence of DN and DR and could improve the prevention and treatments of diabetic microvascular complications.

Abstract The perinatal period occurring immediately before and after birth is critical for cardiomyocytes because they must change rapidly to accommodate the switch from fetal to neonatal circulation after birth. This transition is a well-orchestrated process, and any perturbation leads to unhealthy cardiomyocytes and heart disease. Despite its importance, little is known about how this transition is regulated and controlled. Here, by mapping the genome-wide chromatin accessibility, transcription-centered long-range chromatin interactions and gene expression in cardiomyocytes undergoing perinatal transition, we discovered two key transcription factors, MEF2 and AP1, that are crucial for driving the phenotypic changes within the perinatal window. Thousands of dynamic regulatory elements were found in perinatal cardiomyocytes and we show these elements mediated the transcriptional reprogramming through an elegant chromatin high-order architecture. We recompiled transcriptional program of induced stem cell-derived cardiomyocytes according to our discovered network, and they showed adult cardiomyocyte-like electrophysiological expression. Our work provides a comprehensive regulatory resource of cardiomyocytes perinatal reprogramming, and aids the gap-filling of cardiac translational research.

Abstract Background This study aimed to determine the effect of type 2 diabetes mellitus (T2DM) on overall survival (OS) of patients with stage IIIB–IV non‐small cell lung cancer (NSCLC). Methods We retrospectively analyzed patients with stage IIIB–IV NSCLC from January 2015 to December 2018 in the Department of Oncology at the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine. Kaplan–Meier plots, log‐rank tests, and Cox proportional hazards regression models were used to describe the effect of T2DM on the OS of patients with stage IIIB–IV NSCLC. Results This study collected data on 76 patients with NSCLC and T2DM (group A) and 214 NSCLC patients without T2DM (group B). After propensity score matching (PSM) analysis, 74 patients were included in each group. The mean OS of all patients was 17 months (range, 11–31 months). The mean OS of group A was 15 months (range, 8–25 months) and the mean OS of group B was 20 months (range, 14–39 months). The mean OS of group B was longer than group A, and the difference was statistically significant. Univariate analysis of the clinical data showed that T2DM and complications were significantly correlated with the prognosis of patients with stage IIIB‐IV NSCLC (p = 0.003 and p = 0.034). Multivariate Cox model analysis showed that T2DM and complications were independent prognostic factors for patients with stage IIIB–IV NSCLC (p = 0.002 and p = 0.024, respectively). Conclusion Stage IIIB–IV NSCLC patients without T2DM have an increased OS compared to patients with stage IIIB–IV NSCLE and T2DM.

The heterogeneity of cell-of-origin for papillary renal cell carcinoma (pRCC) remains unknown. Here, with single-cell ATAC-seq from normal human kidney cells and ATACseq profiles from pRCC samples, the authors show that pRCC can originate from kidney collecting duct principal cells and this subtype is associated with advanced pRCC.

Wang et al. use several genome-wide approaches to investigate glucocorticoid receptor (GR) action in a podocyte cell line model. They conclude that direct GR bindings are enriched at super enhancers, highlighting a strategy potentially used by GR to regulate transcription through super-enhancers and long-range interactions.

Abstract Background Cell type-specific transcriptional programming results from the combinatorial interplay between the repertoire of active regulatory elements. Disease-associated variants disrupt such programming, leading to altered expression of downstream regulated genes and the onset of pathological states. However, due to the non-linear regulatory properties of non-coding elements such as enhancers, which can activate transcription at long distances and in a non-directional way, the identification of causal variants and their target genes remains challenging. Here, we provide a multi-omics analysis to identify regulatory elements associated with functional kidney disease variants, and downstream regulated genes. Results In order to understand the genetic risk of kidney diseases, we generated a comprehensive dataset of the chromatin landscape of human kidney tubule cells, including transcription-centered 3D chromatin organization, histone modifications distribution and transcriptome with HiChIP, ChIP-seq and RNA-seq. We identified genome-wide functional elements and thousands of interactions between the distal elements and target genes. The results revealed that risk variants for renal tumor and chronic kidney disease were enriched in kidney tubule cells. We further pinpointed the target genes for the variants and validated two target genes by CRISPR/Cas9 genome editing techniques in zebrafish, demonstrating that SLC34A1 and MTX1 were indispensable genes to maintain kidney function. Conclusions Our results provide a valuable multi-omics resource on the chromatin landscape of human kidney tubule cells and establish a bioinformatic pipeline in dissecting functions of kidney disease-associated variants based on cell type-specific epigenome.

Objective. This study aimed to analyze changes in occupational stress in new nurses during the first year of employment. Methods. A prospective longitudinal study was conducted from 2020 to 2021 using one questionnaire four times on 127 newly employed nurses in a tertiary general teaching hospital in the province of Fujian. Results. The results showed that new nurses had moderate to high levels of stress in all four stages, with the highest stress level at 4 and 8 months of employment and the lowest stress level at 12 months; the differences in stress scores at different time points were statistically significant (p

Lipid metabolism plays a basic role in renal physiology, especially in tubules. Hypoxia and hypoxia-induced factor (HIF) activation are common in renal diseases; however, the relationship between HIF and tubular lipid metabolism is poorly understood. Using prolyl hydroxylase inhibitor roxadustat (FG-4592), we verified and further explored the relationship between sustained HIF1α activation and lipid accumulation in cultured tubular cells. A transcriptome and chromatin immunoprecipitation sequencing analysis revealed that HIF1α directly regulates the expression of a number of genes possibly affecting lipid metabolism, including those associated with mitochondrial function. HIF1α activation suppressed fatty acid (FA) mobilization from lipid droplets (LDs) and extracellular FA uptake. Moreover, HIF1α decreased FA oxidation and ATP production. A lipidomics analysis showed that FG-4592 caused strong triglyceride (TG) accumulation and increased some types of phospholipids with polyunsaturated fatty acyl (PUFA) chains, as well as several proinflammatory lipids. Nevertheless, the overall FA level was maintained. Thus, our study indicated that HIF1α reduced the FA supply and utilization and reconstructed the composition of lipids in tubules, which is likely a part of hypoxic adaptation but could also be involved in pathological processes in the kidney.

Abstract Rationale Our pilot study suggested that noninvasive ventilation (NIV) reduced the need for intubation compared with conventional administration of oxygen on patients with “early” stage of mild acute respiratory distress syndrome (ARDS, PaO2/FIO2 between 200 and 300). Objectives To evaluate whether early NIV can reduce the need for invasive ventilation in patients with pneumonia-induced early mild ARDS. Methods Prospective, multicenter, randomized controlled trial (RCT) of NIV compared with conventional administration of oxygen through a Venturi mask. Primary outcome included the numbers of patients who met the intubation criteria. Results Two hundred subjects were randomized to NIV (n = 102) or control (n = 98) groups from 21 centers. Baseline characteristics were similar in the two groups. In the NIV group, PaO2/FIO2 became significantly higher than in the control group at 2 h after randomization and remained stable for the first 72 h. NIV did not decrease the proportion of patients requiring intubation than in the control group (11/102 vs. 9/98, 10.8% vs. 9.2%, p = 0.706). The ICU mortality was similar in the two groups (7/102 vs. 7/98, 4.9% vs. 3.1%, p = 0.721). Multivariate analysis showed minute ventilation greater than 11 L/min at 48 h was the independent risk factor for NIV failure (OR, 1.176 [95% CI, 1.005–1.379], p = 0.043). Conclusions Treatment with NIV did not reduce the need for intubation among patients with pneumonia-induced early mild ARDS, despite the improved PaO2/FIO2 observed with NIV compared with standard oxygen therapy. High minute ventilation may predict NIV failure. Trial registration NCT01581229. Registered 19 April 2012

Pesticides and pharmaceuticals are widely used in modern life and are discharged into wastewater after usage. However, a large number of transformation products (TPs) are formed through abiotic (hydrolysis/photolysis, etc.) and biotic (aerobic/anaerobic degradation by micro-organisms) wastewater treatment processes, and the structure and potential risk of TPs are still unclear. In this study, a suspect and non-target screening was performed to monitor these chemicals with HPLC-QTOF-MS. We identified 60 parent compounds by suspect screening in three Chinese wastewater treatment plants with the commercial database of pesticides and pharmaceuticals, and they were confirmed by authentic standards. Then, suspect and non-target screening strategies based on the predicted diagnostic fragment ions were used to screen TPs of the 60 parent compounds. We tentatively identified 50 TPs and confirmed thirteen of them with authentic standards. Among 13 quantified TPs, about 40% of them showed higher concentration than their parent compounds in effluent. Especially, cloquintocet, as a TP of cloquintocet-mexyl, had a concentration ratio TP/parent = 14,809 in effluent. Twenty-five TPs had higher predicted toxicity than the corresponding parent compounds by calculating their LC50 values towards aquatic organisms using toxicity prediction software. Twenty identified TPs were firstly reported in this study. These results indicate the importance of TP analysis in environmental monitoring in wastewater. Keywords: Non-target screening, Transformation products, Toxicity, Wastewater, QTOF-MS

We proposed and demonstrated a high sensitivity temperature sensor in an avoided-crossing-based selective-filling photonic crystal fiber (SFPCF) which was designed by selectively filling two symmetrical air holes around the fiber core of an index-guiding PCF with a kind of high index liquid. The avoided-crossing effect caused by the resonant couplings rather than the crossings between the two-high-index-rod modes and the fundamental mode results in unique birefringence characteristics. The temperature response of the modal phase and group birefringence were both calculated in detail. And the phase and group birefringence are highly sensitive to temperature. Then, the transmission characteristics of a Sagnac interferometer (SI) based on the SFPCF were discussed both in theory and in experiments. The experimental results present that the weak mode couplings have no influence on the transmission spectrum of the SFPCF based SI. The interference dips at different wavelengths present distinctive transmission and temperature characteristics. In experiment, the highest temperature sensitivity of -6.9 nm/°C at 36.5°C was achieved.

Background: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are common in patients with underlying moderate to severe COPD and are associated with increased health and economic burden. International and Chinese guidelines recommend using glucocorticoids for the management of AECOPD because glucocorticoid therapy has been shown to benefit clinical outcomes. However, only scant data are available for current status of glucocorticoid therapy in hospitalized AECOPD patients in China. The aim of the study was to identify current use of glucocorticoids for the treatment of AECOPD in China. Methods: This retrospective, multicenter, noninterventional study evaluated the treatment pattern of AECOPD in patients hospitalized from January 2014 to September 2014 at 43 sites (41 tertiary hospitals and two secondary hospitals) in China. The endpoints of the study were the percentage of patients receiving glucocorticoids by different routes of administration, doses and duration, mortality, and the mean length of hospitalization. Results: A total of 4569 patients (90.17%) received glucocorticoids for AECOPD treatment. A combination of nebulized and systemic route was most frequently used (40.51%), followed by using nebulized route alone (38.00%), systemic route alone (15.45%), and inhaled route other than nebulization (6.04%). Furthermore, the most commonly prescribed glucocorticoids of the nebulized, intravenous, inhaled (other than nebulized) and oral route was budesonide (69.4%), methylprednisolone sodium succinate (45.31%), fluticasone propionate (19.54%), and prednisone acetate (11.90%), respectively. The in-hospital mortality rate was 1.24% and the mean length of hospitalization was 12.22 ± 6.20 days (± SD). Conclusions: Our study was the first study of the treatment pattern of glucocorticoids in the management of hospitalized AECOPD patients in China. Data indicates that there is a gap in the implementation of international guidelines for the treatment of AECOPD in China. Further studies are warranted to clarify the appropriate glucocorticoids strategy for the management of AECOPD to determine the optimal route of administration, dose and duration, and resulting clinical outcomes.

Pharmacological treatment of recombinant growth differentiation factor 15 (GDF15) proteins reduces body weight in obese rodents and primates. Paradoxically, circulating GDF15 levels are increased in obesity. To investigate the role of endogenous GDF15 in obesity development, we put GDF15 knockout mice and wildtype controls on high fat diet for the mice to develop diet-induced obesity. Compared to wildtype animals, GDF15 knockout mice were more prone to high fat diet-induced obesity. Male knockout mice showed worse glucose tolerance, lower locomotor activity and lower metabolic rate than wildtype mice. Additionally, GDF15 deficiency increased occurrences of high fat diet-induced skin lesions. Our data suggests that endogenous GDF15 has a protective role in obesity development and lack of GDF15 aggravates the progression of obesity and associated pathological conditions. Elevated GDF15 levels in obesity may have resulted from a response to overcome GDF15 resistance.

Plant-based diagnosis is one of the most important methods to determine nitrogen (N) content of crops. Our objective was to establish the relationship between soil-plant analysis development (SPAD) values and N nutrition index (NNI) during the three developmental stages of rice and apply the SPAD meter as diagnostic tools for predicting grain yield response to N fertilization. We determined the SPAD values of four uppermost fully expanded leaves of two rice cultivars at six N fertilization levels at three growth stages and examined the relationship between SPAD values and NNI. The critical N concentration (Nc) was 5.31 W–0.5 in Xiushui63, and 5.38 W–0.49 in Hang43, where W is the total shoot biomass. The correlation between SPAD value and NNI varied with the leaf position, developmental stage, and variety. The lower leaf appeared to be more sensitive to the N level than the upper leaf in the response of biomass, and could be more suitable as a test sample for N status diagnosis, especially in the booting and heading stage. The dependence of grain yield on SPAD values of the fourth fully expanded leaf (L4) was significant at booting stage (R2L4 = 0.82** in 2011, R2L4 = 0.72** in 2012). Ratio of SPAD values of L4 to that in the N-saturated plot (RSPAD) (R2L4 = 0.92** in 2011, R2L4 = 0.77** in 2012) and NNI (R2 = 0.96** in 2011, R2 = 0.86** in 2012) at booting stage demonstrated a closer relationship with grain yield.

We will study the existence of constant sign solutions for the second-order m-point boundary-value problem $$displaylines{ u''(t)+f(t,u(t))=0,quad tin(0,1),cr u(0)=0, quad u(1)=sum^{m-2}_{i=1}alpha_i u(eta_i), }$$ where $mgeq3$, $eta_iin(0,1)$ and $alpha_i>0$ for $i=1,dots,m-2$, with $sum^{m-2}_{i=1}alpha_i

A Soil-Plant Analysis Development (SPAD) chlorophyll meter can be used as a simple tool for evaluating N concentration of the leaf and investigating the combined effects of nitrogen rate and leaf age on N distribution. We conducted experiments in a paddy field over two consecutive years (2008-2009) using rice plants treated with six different N application levels. N distribution pattern was determined by SPAD readings based on the temporal dynamics of N concentrations in individual leaves. At 62 days after transplantation (DAT) in 2008 and DAT 60 in 2009, leaf SPAD readings increased from the upper to lower in the rice canopy that received N levels of 150 to 375 kg ha(-1)The differences in SPAD readings between the upper and lower leaf were larger under higher N application rates. However, as plants grew, this atypical distribution of SPAD readings in canopy leaf quickly reversed to the general order. In addition, temporal dynamics of the leaf SPAD readings (N concentrations) were fitted to a piecewise function. In our model, changes in leaf SPAD readings were divided into three stages: growth, functioning, and senescence periods. The leaf growth period lasted approximately 6 days, and cumulative growing days were not affected by N application rates. The leaf functioning period was represented with a relatively stable SPAD reading related to N application rate, and cumulative growing days were extended with increasing N application rates. A quadratic equation was utilized to describe the relationship between SPAD readings and leaf age during the leaf senescence period. The rate of decrease in SPAD readings increased with the age of leaves, but the rate was slowed by N application. As leaves in the lower canopy were physiologically older than leaves in the upper canopy, the rate of decrease in SPAD readings was faster in the lower leaves.

Strains from a collection of Drosophila GFP protein trap lines express GFP in the normal tissues where the endogenous protein is present. This collection can be used to screen for proteins distributed in the nucleus in a non-uniform pattern.We analyzed four lines that show peripheral or punctate nuclear staining. One of these lines affects an uncharacterized gene named CG11138. The CG11138 protein shows a punctate distribution in the nuclear periphery similar to that of Drosophila insulator proteins but does not co-localize with known insulators. Interestingly, mutations in Lamin proteins result in alterations in CG11138 localization, suggesting that this protein may be a novel component of the nuclear lamina. A second line affects the Decondensation factor 31 (Df31) gene, which encodes a protein with a unique nuclear distribution that appears to segment the nucleus into four different compartments. The X-chromosome of males is confined to one of these compartments. We also find that Drosophila Nucleoplasmin (dNlp) is present in regions of active transcription. Heat shock leads to loss of dNlp from previously transcribed regions of polytene chromosome without redistribution to the heat shock genes. Analysis of Stonewall (Stwl), a protein previously found to be necessary for the maintenance of germline stem cells, shows that Stwl is present in a punctate pattern in the nucleus that partially overlaps with that of known insulator proteins. Finally we show that Stwl, dNlp, and Df31 form part of a highly interactive network. The properties of other components of this network may help understand the role of these proteins in nuclear biology.These results establish screening of GFP protein trap alleles as a strategy to identify factors with novel cellular functions. Information gained from the analysis of CG11138 Stwl, dNlp, and Df31 sets the stage for future studies of these proteins.

Etiologic diagnoses of lower respiratory tract infections (LRTI) have been relying primarily on bacterial cultures that often fail to return useful results in time. Although DNA-based assays are more sensitive than bacterial cultures in detecting pathogens, the molecular results are often inconsistent and challenged by doubts on false positives, such as those due to system- and environment-derived contaminations. Here we report a nationwide cohort study on 2986 suspected LRTI patients across P. R. China. We compared the performance of a DNA-based assay qLAMP (quantitative Loop-mediated isothermal AMPlification) with that of standard bacterial cultures in detecting a panel of eight common respiratory bacterial pathogens from sputum samples. Our qLAMP assay detects the panel of pathogens in 1047(69.28%) patients from 1533 qualified patients at the end. We found that the bacterial titer quantified based on qLAMP is a predictor of probability that the bacterium in the sample can be detected in culture assay. The relatedness of the two assays fits a logistic regression curve. We used a piecewise linear function to define breakpoints where latent pathogen abruptly change its competitive relationship with others in the panel. These breakpoints, where pathogens start to propagate abnormally, are used as cutoffs to eliminate the influence of contaminations from normal flora. With help of the cutoffs derived from statistical analysis, we are able to identify causative pathogens in 750 (48.92%) patients from qualified patients. In conclusion, qLAMP is a reliable method in quantifying bacterial titer. Despite the fact that there are always latent bacteria contaminated in sputum samples, we can identify causative pathogens based on cutoffs derived from statistical analysis of competitive relationship.ClinicalTrials.gov NCT00567827.

The spread and removal of pollution sources, namely, cough-released droplets in three different areas (front, middle, and rear areas) of a fully-loaded passenger car in a high-speed train under different fresh air flow volume were studied using computational fluid dynamics (CFD) method. In addition, the structure of indoor flow fields was also analysed. The results show that the large eddies are more stable and flow faster in the air supply under Mode 2 (fresh air volume: 2200m³/h) compared to Mode 1 (fresh air volume: 1100m³/h). By analysing the spreading process of droplets sprayed at different locations in the passenger car and with different particle sizes, the removal trends for droplets are found to be similar under the two air supply modes. However, when increasing the fresh air flow volume, the droplets in the middle and front areas of the passenger car are removed faster. When the droplets had dispersed for 60s, Mode 2 exhibited a removal rate approximately 1%-3% higher than Mode 1 for small and medium-sized droplets with diameters of 10 and 50 µm.While those in the rear area, the situation is reversed, with Mode 1 slightly surpassing Mode 2 by 1%-3%. For large droplets with a diameter of 100 µm, both modes achieved a removal rate of over 96% in all three regions at the 60 s. The results can provide guidance for air supply modes of passenger cars of high-speed trains, thus suppressing the spread of virus-carrying droplets and reducing the risk of viral infection among passengers. [ABSTRACT FROM AUTHOR]