Genome-wide identification of GA2ox genes family and analysis of PbrGA2ox1-mediated enhanced chlorophyll accumulation by promoting chloroplast development in pear.

BACKGROUND: Chlorophyll (Chl) is an agronomic trait associated with photosynthesis and yield. Gibberellin 2-oxidases (GA2oxs) have previously been shown to be involved in Chl accumulation. However, whether and how the PbrGA2ox proteins (PbrGA2oxs) mediate Chl accumulation in pear (Pyrus spp.) is scarce. RESULTS: Here, we aimed to elucidate the role of the pear GA2ox gene family in Chl accumulation and the related underlying mechanisms. We isolated 13 PbrGA2ox genes (PbrGA2oxs) from the pear database and identified PbrGA2ox1 as a potential regulator of Chl accumulation. We found that transiently overexpressing PbrGA2ox1 in chlorotic pear leaves led to Chl accumulation, and PbrGA2ox1 silencing in normal pear leaves led to Chl degradation, as evident by the regreening and chlorosis phenomenon, respectively. Meanwhile, PbrGA2ox1-overexpressing (OE) tobacco plants discernably exhibited Chl built-up, as evidenced by significantly higher Pn and Fv/Fm. In addition, RNA sequencing (RNA-seq), physiological and biochemical investigations revealed an increase in abscisic acid (ABA), methyl jasmonate (MeJA), and salicylic acid (SA) concentrations and signaling pathways; a marked elevation in reducing and soluble sugar contents; and a marginal decline in the starch and sucrose levels in OE plants. Interestingly, PbrGA2ox1 overexpression did not prominently affect Chl synthesis. However, it indeed facilitated chloroplast development by increasing chloroplast number per cell and compacting the thylakoid granum stacks. These findings might jointly contribute to Chl accumulation in OE plants. CONCLUSION: Overall, our results suggested that GA2oxs accelerate Chl accumulation by stimulating chloroplast development and proved the potential of PbrGA2ox1 as a candidate gene for genetically breeding biofortified pear plants with a higher yield.

BLTSA: pseudotime prediction for single cells by branched local tangent space alignment.

MOTIVATION: The development of single-cell RNA sequencing (scRNA-seq) technology makes it possible to study the cellular dynamic processes such as cell cycle and cell differentiation. Due to the difficulties in generating genuine time-series scRNA-seq data, it is of great importance to computationally infer the pseudotime of the cells along differentiation trajectory based on their gene expression patterns. The existing pseudotime prediction methods often suffer from the high level noise of single-cell data, thus it is still necessary to study the single-cell trajectory inference methods. RESULTS: In this study, we propose a branched local tangent space alignment (BLTSA) method to infer single-cell pseudotime for multi-furcation trajectories. By assuming that single cells are sampled from a low-dimensional self-intersecting manifold, BLTSA first identifies the tip and branching cells in the trajectory based on cells' local Euclidean neighborhoods. Local coordinates within the tangent spaces are then determined by each cell's local neighborhood after clustering all the cells to different branches iteratively. The global coordinates for all the single cells are finally obtained by aligning the local coordinates based on the tangent spaces. We evaluate the performance of BLTSA on four simulation datasets and five real datasets. The experimental results show that BLTSA has obvious advantages over other comparison methods. AVAILABILITY AND IMPLEMENTATION: R codes are available at https://github.com/LiminLi-xjtu/BLTSA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Discovery of digallic acid as XOD/URAT1 dual target inhibitor for the treatment of hyperuricemia.

The development of XOD/URAT1 dual target inhibitors has emerged as a promising therapeutic strategy for the management of hyperuricemia. Here, through virtual screening, we have identified digallic acid as a novel dual target inhibitor of XOD/URAT1 and subsequently evaluated its pharmacological properties, pharmacokinetics, and toxicities. Digallic acid inhibited URAT1 with an IC50 of 5.34 ± 0.65 µM, which is less potent than benzbromarone (2.01 ± 0.36 µM) but more potent than lesinurad (10.36 ± 1.23 µM). Docking and mutation analysis indicated that residues S35, F241 and R477 of URAT1 confer a high affinity for digallic acid. Digallic acid inhibited XOD with an IC50 of 1.04 ± 0.23 µM. Its metabolic product, gallic acid, inhibited XOD with an IC50 of 0.91 ± 0.14 µM. Enzyme kinetic studies indicated that both digallic acid and gallic acid act as mixed-type XOD inhibitors. It shares the same binding mode as digallic acid, and residues E802, R880, F914, T1010, N768 and F1009 contribute to their high affinity. The anion group (carboxyl) of digallic acid contribute significantly to its inhibition activity on both XOD and URAT1 as indicated by docking analysis. Remarkably, at a dosage of 10 mg/kg in vivo, digallic acid exhibited a stronger urate-lowering and uricosuric effect compared to the positive drug benzbromarone and lesinurad. Pharmacokinetic study indicated that digallic acid can be hydrolyzed into gallic acid in vivo and has a t1/2 of 0.77 ± 0.10 h. Further toxicity evaluation indicated that digallic acid exhibited no obvious renal toxicity, as reflected by CCK-8, biochemical analysis (CR and BUN) and HE examination. The findings of our study can provide valuable insights for the development of XOD/URAT1 dual target inhibitors, and digallic acid deserves further investigation as a potential anti-hyperuricemic drug.

Ecological and health risk assessments of heavy metals and their accumulation in a peanut-soil system.

Heavy metals pollution is a notable threat to environment and human health. This study evaluated the potential ecological and health risks of heavy metals (Cu, Cr, Cd, Pb, Zn, Ni, and As) and their accumulation in a peanut-soil system based on 34 soil and peanut kernel paired samples across China. Soil As and Cd posed the greatest pollution risk with 47.1% and 17.6% of soil samples exceeding the risk screen levels, respectively, with 26.5% and 20.6% of the soil sites at relatively strong potential ecological risk level, respectively, and with the geo-accumulation levels at several soil sites in the uncontaminated to moderately contaminated categories. About 35.29% and 2.94% of soil sites were moderately and severely polluted based on Nemerow comprehensive pollution index, respectively, and a total of 32.4% of samples were at moderate ecological hazard level based on comprehensive potential ecological risk index values. The Cd, Cr, Ni, and Cu contents exceeded the standard in 11.76, 8.82, 11.76 and 5.88% of the peanut kernel samples, respectively. Soil metals posed more health risks to children than adults in the order As > Ni > Cr > Cu > Pb > Zn > Cd for non-carcinogenic health risks and Ni > Cr â‰« Cd > As > Pb for carcinogenic health risks. The soil As non-cancer risk index for children was greater than the permitted limits at 14 sites, and soil Ni and Cr posed the greatest carcinogenic risk to adults and children at many soil sites. The metals in peanut did not pose a non-carcinogenic risk according to standard. Peanut kernels had strong enrichment ability for Cd with an average bio-concentration factor (BCF) of 1.62. Soil metals contents and significant soil properties accounted for 35-74% of the variation in the BCF values of metals based on empirical prediction models.

A gut microbial metabolite cocktail fights against obesity through modulating the gut microbiota and hepatic leptin signaling.

BACKGROUND: Excessive body weight and obesity elevate the risk of chronic non-communicable diseases. The judicious application of the gut microbiome, encompassing both microorganisms and their derived compounds, holds considerable promise in the treatment of obesity. RESULTS: In this study, we showed that a cocktail of gut microbiota-derived metabolites, comprising indole 3-propionic acid (IPA), sodium butyrate (SB) and valeric acid (VA), alleviated various symptoms of obesity in both male and female mice subjected to a high-fat diet (HFD). The 16S ribosomal RNA (rRNA) sequencing revealed that administering the cocktail via oral gavage retained the gut microbiota composition in obese mice. Fecal microbiota transplantation using cocktail-treated mice as donors mitigated the obesity phenotype of HFD-fed mice. Transcriptomic sequencing analysis showed that the cocktail preserved the gene expression profile of hepatic tissues in obese mice, especially up-regulated the expression level of leptin receptor. Gene delivery via in vivo fluid dynamics further validated that the anti-obesity efficacy of the cocktail was dependent on leptin signaling at least partly. The cocktail also inhibited the expression of appetite stimulators in hypothalamus. Together, the metabolite cocktail combated adiposity by retaining the gut microbiota configuration and activating the hepatic leptin signaling pathway. CONCLUSIONS: Our findings provide a sophisticated regulatory network between the gut microbiome and host, and highlight a cocktail of gut microbiota-derived metabolites, including IPA, SB, and VA, might be a prospective intervention for anti-obesity in a preclinical setting. © 2024 Society of Chemical Industry.

Study on the enhancement of citric acid chemical leaching of contaminated soil by modified nano zero-valent iron.

This study aimed to evaluate the effect of modified nanoscale zero-valent iron (SAS-nZVI) on chemical leaching of lead and cadmium composite contaminated soil by citric acid (CA). The synthesized SAS-nZVI was used as a leaching aid to improve the removal rate of soil heavy metals (HMs) by CA chemical leaching. The effects of various factors such as SAS-nZVI dosage, elution temperature and elution time were studied. At the same time, the effect of chemical leaching on the basic physical and chemical properties of soil and the morphology of HMs was evaluated. The results show that when the SAS-nZVI dosage is 2.0 g/L, the leaching temperature is 25 °C, and the leaching time is 720 min, the maximum removal rates of Pb and Cd in the soil are 77.64% and 97.15% respectively. The experimental results were evaluated using elution and desorption kinetic models (Elovich model, double constant model, diffusion model). The elution and desorption process of Pb and Cd in soil by SAS-nZVI-CA fitted well with the double-constant model, indicating that the desorption kinetic process of Pb and Cd is a heterogeneous diffusion process, and the elution process is controlled by diffusion factors. After leaching with SAS-nZVI-CA, the physical and chemical properties of the soil changed little, the mobility and toxicity of HMs in the soil were reduced, and the HMs content in the leaching waste liquid was reduced. It can be concluded that SAS-nZVI enhances the efficiency of CA in extracting Pb and Cd from soil, minimizes soil damage resulting from chemical leaching technology, and alleviates the challenges associated with treating leaching waste liquid.

Transcriptome and miRNAome analysis reveals components regulating tissue differentiation of bamboo shoots.

Primary thickening determines bamboo yield and wood property. However, little is known about the regulatory networks involved in this process. This study identified a total of 58,652 genes and 150 miRNAs via transcriptome and small RNA sequencing using the underground thickening shoot samples of wild-type (WT) Moso bamboo (Phyllostachys edulis) and a thick wall (TW) variant (P. edulis "Pachyloen") at five developmental stages (WTS1/TWS1-WTS5/TWS5). A total of 14,029 (65.17%) differentially expressed genes and 68 (45.33%) differentially expressed miRNAs were identified from the WT, TW, and WTTW groups. The first two groups were composed of four pairwise combinations, each between two successive stages (WTS2/TWS2_versus_WTS1/TWS1, WTS3/TWS3_versus_WTS2/TWS2, WTS4/TWS4_versus_WTS3/TWS3, and WTS5/TWS5_versus_WTS4/TWS4), and the WTTW group was composed of five combinations, each between two relative stages (TWS1-5_versus_WTS1-5). Additionally, among the phytohormones, zeatin showed more remarkable changes in concentrations than indole-3-acetic acid, gibberellic acid, and abscisic acid throughout the five stages in the WT and the TW groups. Moreover, 125 cleavage sites were identified for 387 miRNA-mRNA pairs via degradome sequencing (P < 0.05). The dual-luciferase reporter assay confirmed that 13 miRNAs bound to 12 targets. Fluorescence in situ hybridization localized miR166 and miR160 in the shoot apical meristem and the procambium of Moso bamboo shoots at the S1 stage. Thus, primary thickening is a complex process regulated by miRNA-gene-phytohormone networks, and the miRNAome and transcriptome dynamics regulate phenotypic plasticity. These findings provide insights into the molecular mechanisms underlying wood formation and properties and propose targets for bamboo breeding.

AC-PCoA: Adjustment for confounding factors using principal coordinate analysis.

Confounding factors exist widely in various biological data owing to technical variations, population structures and experimental conditions. Such factors may mask the true signals and lead to spurious associations in the respective biological data, making it necessary to adjust confounding factors accordingly. However, existing confounder correction methods were mainly developed based on the original data or the pairwise Euclidean distance, either one of which is inadequate for analyzing different types of data, such as sequencing data. In this work, we proposed a method called Adjustment for Confounding factors using Principal Coordinate Analysis, or AC-PCoA, which reduces data dimension and extracts the information from different distance measures using principal coordinate analysis, and adjusts confounding factors across multiple datasets by minimizing the associations between lower-dimensional representations and confounding variables. Application of the proposed method was further extended to classification and prediction. We demonstrated the efficacy of AC-PCoA on three simulated datasets and five real datasets. Compared to the existing methods, AC-PCoA shows better results in visualization, statistical testing, clustering, and classification.

Pharmacological evaluation of a novel skeleton compound isobavachin (4',7-dihydroxy-8-prenylflavanone) as a hypouricemic agent: Dual actions of URAT1/GLUT9 and xanthine oxidase inhibitory activity.

Previously we discovered a novel natural scaffold compound, isobavachin (4', 7-dihydroxy-8-prenylflavanone), as a potent URAT1 inhibitor by shape and structure based on a virtue screening approach. In this study, further urate-lowering mechanism, pharmacokinetics and toxicities of isobavachin were conducted. Isobavachin inhibited URAT1 with an IC50 value of 0.24 ± 0.06 µM, and residues S35, F365, I481 and R477 of URAT1 contributed to high affinity for isobavachin. Isobavachin also inhibited glucose transporter 9 (GLUT9), another pivotal urate reabsorption transporter, with an IC50 value of 1.12 ± 0.26 µM. Molecular docking and MMGBSA results indicated that isobavachin might compete residues R171, L75 and N333 with uric acid, which leads to inhibition of uric acid transport of GLUT9. Isobavachin weakly inhibited urate secretion transporters OAT1 with an IC50 value of 4.38 ± 1.27 µM, OAT3 with an IC50 of 3.64 ± 0.62 µM, and ABCG2 with an IC50 of 10.45 ± 2.17 µM. Isobavachin also inhibited xanthine oxidase (XOD) activity in vitro with an IC50 value of 14.43 ± 3.56 µM, and inhibited the hepatic XOD activities at 5-20 mg/kg in vivo. Docking and MMGBSA analysis indicated that isobavachin might bind to the Mo-Pt catalyze center of XOD, which leads to inhibition of uric acid production. In vivo, isobavachin exhibited powerful urate-lowering and uricosuric effects at 5-20 mg/kg compared with the positive drugs morin (20 mg/kg) and RDEA3170 (10 mg/kg). Safety assessments revealed that isobavachin was safe and had no obvious toxicities. Isobavachin has little cell toxicity in HK2 cells as indicated by the MTT assay. In vivo, after treatment with 50 mg/kg isobavachin for 14 days, isobavachin had little renal toxicity, as revealed by serum CR/BUN levels, and no hepatotoxicity as revealed by ALT/AST levels. Further HE examination also suggests that isobavachin has no obvious kidney/liver damage. A pharmacokinetic study in SD rats indicated isobavachin had lower bioavailability (12.84 ± 5.13 %) but long half-time (7.04 ± 2.68 h) to maintain a continuous plasma concentration. Collectively, these results indicate that isobavachin deserves further investigation as a candidate anti-hyperuricemic drug with a novel mechanism of action: selective urate reabsorption inhibitor (URAT1/GLUT9) with a moderate inhibitory effect on XOD.

Assessment soil cadmium and copper toxicity on barley growth and the influencing soil properties in subtropical agricultural soils.

Evaluation joint cadmium (Cd) and copper (Cu) phytotoxicity in wide range of subtropical agricultural soils is highly vital for phytoremediation of soils contaminated with Cd and Cu. In this study, barley root elongation assays were performed in 30 representative soils in response to single and combined Cd and Cu inhibition. The single Cd caused nearly 50% inhibition of barley root elongation, and Cu induced more than 50% inhibition in most soils. Mixed Cd + Cu caused significant inhibition on barley growth with average relative root elongation values of 20.0% and 30.4% in soil with a pH < 7 and pH > 7, respectively. An antagonistic interaction was evaluated in combined Cd + Cu toxicity, which was strong in soils containing low soluble Cu and Cd contents. Soil pH was the controlling factor in predicting single and mixed Cd and Cu phytotoxicity, which could explain 44% and 46% variation of single Cd and Cu toxicity, respectively. Soil organic carbon and effective cation exchange capacity were another important factor positively influencing metal toxicity, which further improved empirical prediction models accuracy, with determined coefficient (r2) values of 0.44-0.84. These results provide a theoretical basis for soils Cd and Cu pollution control.

Comparison of Proximal Anti-Rotation Intramedullary Nail and Femoral Head Replacement for the Treatment of Femoral Intertrochanteric Fractures in Elderly Patients.

Objective: To compare and analyze the effects of proximal femoral nail anti-rotation (PFNA) and femoral head replacement in treating elderly patients with femoral intertrochanteric fracture. Methods: A retrospective analysis was performed on clinical data of elderly patients with femoral intertrochanteric fractures from February 2019 to February 2021 in the hospital. Patients were divided into a control group (PFNA) and a study group (femoral head replacement) based on surgical methods after propensity score matching. Perioperative indicators, hematocrit (HCT), hemoglobin (Hb), hip function, and complications one year after surgery were compared between the two groups after excluding confounding factors. Result: Both groups had complete follow-ups without any cases lost. The study group had longer surgical time, higher intraoperative blood loss, and greater postoperative drainage volume compared to the control group, while the hospital stay and weight-bearing starting time were shorter in the study group (P < .05). There were statistically significant differences in HCT and Hb after surgery between the two groups (P < .05). One year after surgery, the excellent and good rate of hip function was 90.28% in the study group and 76.39% in the control group (P < .05). The total incidence rate of postoperative early complications was higher in the study group, while the total incidence rate of late postoperative complications was lower in the study group compared to the control group (P < .05). Conclusion: PFNA and femoral head replacement have their respective advantages in treating elderly patients with femoral intertrochanteric fractures. PFNA causes less trauma to patients but has poorer postoperative hip function recovery, while femoral head replacement causes greater trauma to patients but has better postoperative hip function recovery. Therefore, the appropriate surgical method can be selected based on the patient's specific conditions.

Degradation of 2,4-DCP by immobilized laccase on modified biochar carrier.

Rape straw was used as the raw material for the biochar in this study, which was then changed using acid, alkali, and magnetic techniques. The laccase was attached using the adsorptions-crosslinking process, and the three modified biochars served as the carriers. The ideal circumstances for laccase immobilization were explored, and both biochar and immobilized laccase's characteristics were examined. The removal of 2,4-dichlorophenol (2,4-DCP) by immobilized laccase from modified biochar and its degradation products were researched. The main conclusions are as follows: the optimal concentration of glutaraldehyde (GLU) was 4%, and the pH was four, and the enzyme dosage was 1.75 mg/mL for the immobilized laccase of acid-modified biochar (SBC@LAC). The optimal concentration of GLU was 5%; the pH was four, and the enzyme dosage was 2 mg/mL for immobilized laccase from alkali-modified biochar (JBC@LAC). The optimal concentration of GLU was 5%; the pH was four, and the enzyme dosage was 1.75 mg/mL for immobilized laccase from magnetically modified biochar (CBC@LAC). SEM images could show the changes in the surface morphology of biochar caused by three modification methods. The BET results demonstrated that acid and magnetic modification increased the specific surface area of biochar, and alkali modification mainly expanded the pore size of biochar. FT-IR and XRD showed that modification and laccase loading had little effect on the structure of biochar. The stability of immobilized laccase was better than that of free laccase in acid-base, heat, and storage. Among the three modified biochar immobilized laccases, JBC@LAC showed the best acid-base stability and thermal stability, and the relative enzyme activity changed the least when pH and temperature conditions changed. The storage stability of SBC@LAC is the best. After 30 days of storage, the relative enzyme activity is still 83%. The removal rates of 2,4-DCP were 57, 99, and 63%, respectively, by SBC@LAC, JBC@LAC, and CBC@LAC. After five reuses, the removal rates of 2,4-DCP by SBC@LAC, JBC@LAC and CBC@LAC were 26, 42, and 27%, respectively. The intermediate products of 2,4-DCP degradation by immobilized laccase were p-phenol, p-benzoquinone and maleic acid.

Nickel-Catalyzed Suzuki Coupling of Phenols Enabled by SuFEx of Tosyl Fluoride.

A practical and efficient Suzuki coupling of phenols has been developed by using trans-NiCl(o-Tol)(PCy3)2/2PCy3 as a catalyst in the presence of tosyl fluoride as an activator. The key for the direct use of phenols lies in the compatibility of the nickel catalyst with tosyl fluoride (TsF) and its sulfur(VI) fluoride exchange (SuFEx) with CAr-OH. Water has been found to improve the one-pot process remarkably. The steric and electronic effects and the functional group compatibility of the one-pot Suzuki coupling of phenols appear to be comparable to the conventional one of pre-prepared aryl tosylates. A series of electronically and sterically various biaryls could be obtained in good to excellent yields by using 3-10 mol% loading of the nickel catalyst. The applications of this one-pot procedure in chemoselective derivatization of complex molecules have been demonstrated in 3-phenylation of estradiol and estrone.

In Situ N, O Co-Doped Nanoporous Carbon Derived from Mixed Egg and Rice Waste as Green Supercapacitor.

The conversion of nitrogen-oxygen-rich biomass wastes into heteroatomic co-doped nanostructured carbons used as energy storage materials has received widespread attention. In this study, an in situ nitrogen-oxygen co-doped porous carbon was prepared for supercapacitor applications via a two-step method of pre-carbonization and pyrolytic activation using mixed egg yolk/white and rice waste. The optimal sample (YPAC-1) was found to have a 3D honeycomb structure composed of abundant micropores and mesopores with a high specific surface area of 1572.1 m2 g-1, which provided abundant storage space and a wide transport path for electrolyte ions. Notably, the specific capacitance of the constructed three-electrode system was as high as 446.22 F g-1 at a current density of 1 A g-1 and remained above 50% at 10 A g-1. The capacitance retention was 82.26% after up to 10,000 cycles. The symmetrical capacitor based on YPAC-1 with a two-electrode structure exhibited an energy density of 8.3 Wh kg-1 when the power density was 136 W kg-1. These results indicate that porous carbon materials prepared from mixed protein and carbohydrate waste have promising applications in the field of supercapacitors.

Ion exchange synthesis of copper-based hydroxyapatite for the catalytic degradation of phenol.

Hydroxyapatite (HAP) is a material renowned for its exceptional capabilities in adsorbing and exchanging heavy metal ions, making it a widely employed substance within the environmental domain. This study aims to present a novel material, namely copper-HAP (Cu-HAP), which was synthesized via an ion exchange method. The resulting material underwent comprehensive characterization using scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and Brunauer-Emmett-Teller (BET) analysis. Subsequently, based on the principle of the Fenton-like oxidation reaction, the material was used for the degradation of phenol. The outcomes of the investigation revealed that the optimal preparation conditions for the catalyst were achieved at a temperature of 40 °C, a pH value of 5, and a relative dosage of Cu-HAP at 100 mg/g. Under the reaction conditions of a catalyst dosage of 2 g/L, a 30% hydrogen peroxide concentration of 30 mM, a phenol concentration of 20 mg/L, a pH value of 6, a temperature of 40 °C, and the degradation rate of phenol impressively reached 98.12%. Furthermore, the degradation rate remained at 42.31% even after five consecutive cycles, indicating the promising potential of Cu-HAP in the treatment of recalcitrant organic compounds within this field.

Study on the removal of Pb(II) from water by coated sulfur-modified nanoscale zero-valent iron.

Being prepared by a liquid-phase reduction method, sulfur-modified nanoscale zero-valent iron (S-nZVI) was then coated with sodium alginate (SA) to form gel beads (SAS-nZVI) which are capable of removing Pb(II) from water. SAS-nZVI was characterized by SEM, EDS, FTIR, XRD, and BET, and its removal effect on Pb(II) in water, including the effects of pH, adsorbent dosage, shaking time, and initial concentration of lead, was also studied. The results demonstrated that the maximum removal efficiency of Pb(II) by SAS-nZVI was 97.89%, and the maximum uptake was 246.40 mg/g. In the Pb(II) removal behavior study, the pseudo-second-order kinetic model and the Langmuir isotherm model were found to fit the adsorption process well. SAS-nZVI was easier to recycle from the reaction system, and the removal efficiency of SAS-nZVI to Pb(II) in water was still able to reach 82.75% after five cycles. Therefore, this study suggests that SAS-nZVI has a high removal capacity for Pb(II) and great potential in water pollution treatment.

Long-term safety of infants from mothers with chronic hepatitis B treated with tenofovir disoproxil in China.

OBJECTIVE: The physical and neuromental development of infants remains uncertain after fetal exposure to tenofovir disoproxil fumarate (TDF) for the prevention of mother-to-child transmission of HBV. We aimed to investigate the safety of TDF therapy during the third trimester of pregnancy. DESIGN: Infants from a previous randomised controlled trial were recruited for our long-term follow-up (LTFU) study. Mothers with chronic hepatitis B were randomised to receive TDF therapy or no treatment during the third trimester. Infants' physical growth or malformation, bone mineral density (BMD) and neurodevelopment, as assessed using Bayley-III assessment, were examined at 192 weeks of age. RESULTS: Of 180 eligible infants, 176/180 (98%) were enrolled and 145/176 (82%) completed the LTFU (control group: 75; TDF-treated group: 70). In the TDF-treated group, the mean duration of fetal exposure to TDF was 8.57±0.53 weeks. Congenital malformation rates were similar between the two groups at week 192. The mean body weight of boys in the control and TDF-treated groups was significantly higher (19.84±3.46 kg vs. 18.47±2.34 kg; p=0.03) and within the normal range (18.48±2.35 kg vs. 17.80±2.50 kg; p=0.07), respectively, when compared with the national standard. Other prespecified outcomes (head circumference, height, BMD, and cognitive, motor, social-emotional, and adaptive behaviour measurements) were all comparable between the groups. CONCLUSION: Infants with fetal exposure to TDF had normal physical growth, BMD and neurodevelopment at week 192. Our findings provide evidence on the long-term safety of infants after fetal exposure to maternal TDF therapy for preventing hepatitis B transmission. TRIAL REGISTRATION NUMBER: NCT01488526.

CALLR: a semi-supervised cell-type annotation method for single-cell RNA sequencing data.

MOTIVATION: Single-cell RNA sequencing (scRNA-seq) technology has been widely applied to capture the heterogeneity of different cell types within complex tissues. An essential step in scRNA-seq data analysis is the annotation of cell types. Traditional cell-type annotation is mainly clustering the cells first, and then using the aggregated cluster-level expression profiles and the marker genes to label each cluster. Such methods are greatly dependent on the clustering results, which are insufficient for accurate annotation. RESULTS: In this article, we propose a semi-supervised learning method for cell-type annotation called CALLR. It combines unsupervised learning represented by the graph Laplacian matrix constructed from all the cells and supervised learning using sparse logistic regression. By alternately updating the cell clusters and annotation labels, high annotation accuracy can be achieved. The model is formulated as an optimization problem, and a computationally efficient algorithm is developed to solve it. Experiments on 10 real datasets show that CALLR outperforms the compared (semi-)supervised learning methods, and the popular clustering methods. AVAILABILITY AND IMPLEMENTATION: The implementation of CALLR is available at https://github.com/MathSZhang/CALLR. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Caloric restriction alleviates radiation injuries in a sex-dependent fashion.

Safe and effective regimens are still needed given the risk of radiation toxicity from iatrogenic irradiation. The gut microbiota plays an important role in radiation damage. Diet has emerged as a key determinant of the intestinal microbiome signature and function. In this report, we investigated whether a 30% caloric restriction (CR) diet may ameliorate radiation enteritis and hematopoietic toxicity. Experimental mice were either fed ad libitum (AL) or subjected to CR preconditioning for 10 days and then exposed to total body irradiation (TBI) or total abdominal irradiation (TAI). Gross examinations showed that short-term CR pretreatment restored hematogenic organs and improved the intestinal architecture in both male and female mice. Intriguingly, CR preconditioning mitigated radiation-induced systemic and enteric inflammation in female mice, while gut barrier function improved in irradiated males. 16S rRNA high-throughput sequencing showed that the frequency of pro-inflammatory microbes, including Helicobacter and Desulfovibrionaceae, was reduced in female mice after 10 days of CR preconditioning, while an enrichment of short-chain fatty acid (SCFA)-producing bacteria, such as Faecalibaculum, Clostridiales, and Lactobacillus, was observed in males. Using fecal microbiota transplantation (FMT) or antibiotic administration to alter the gut microbiota counteracted the short-term CR-elicited radiation tolerance of both male and female mice, further indicating that the radioprotection of a 30% CR diet depends on altering the gut microbiota. Together, our findings provide new insights into CR in clinical applications and indicate that a short-term CR diet prior to radiation modulates sex-specific gut microbiota configurations, protecting male and female mice against the side effects caused by radiation challenge.

Sparse logistic regression revealed the associations between HBV PreS quasispecies and hepatocellular carcinoma.

BACKGROUND: Chronic infection with hepatitis B virus (HBV) has been proved highly associated with the development of hepatocellular carcinoma (HCC). AIMS: The purpose of the study is to investigate the association between HBV preS region quasispecies and HCC development, as well as to develop HCC diagnosis model using HBV preS region quasispecies. METHODS: A total of 104 chronic hepatitis B (CHB) patients and 117 HBV-related HCC patients were enrolled. HBV preS region was sequenced using next generation sequencing (NGS) and the nucleotide entropy was calculated for quasispecies evaluation. Sparse logistic regression (SLR) was used to predict HCC development and prediction performances were evaluated using receiver operating characteristic curves. RESULTS: Entropy of HBV preS1, preS2 regions and several nucleotide points showed significant divergence between CHB and HCC patients. Using SLR, the classification of HCC/CHB groups achieved a mean area under the receiver operating characteristic curve (AUC) of 0.883 in the training data and 0.795 in the test data. The prediction model was also validated by a completely independent dataset from Hong Kong. The 10 selected nucleotide positions showed significantly different entropy between CHB and HCC patients. The HBV quasispecies also classified three clinical parameters, including HBeAg, HBVDNA, and Alkaline phosphatase (ALP) with the AUC value greater than 0.6 in the test data. CONCLUSIONS: Using NGS and SLR, the association between HBV preS region nucleotide entropy and HCC development was validated in our study and this could promote the understanding of HCC progression mechanism.