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Abstract Skin wound infection has become a notable medical threat. Herein, the polysaccharide-based injectable hydrogels with multifunctionality were developed by a simple and fast gelation process not only to inactivate bacteria but also to accelerate bacteria-infected wound healing. Sodium nitroprusside (SNP) loaded PCN-224 nanoparticles were introduced into the polymer matrix formed by the dynamic and reversible coordinate bonds between Ag+ with carboxyl and amino or hydroxyl groups on carboxymethyl chitosan (CMCS), hydrogen bonds and electrostatic interactions in the polymer to fabricate SNP@PCN@Gel hydrogels. SNP@PCN@Gel displayed interconnected porous structure, excellent self-healing capacity, low cytotoxicity, good blood compatibility, and robust antibacterial activity. SNP@PCN@Gel could produce reactive oxygen species (ROS) and NO along with Fe2+, and showed long-term sustained release of Ag+, thereby effectively killing bacteria by synergistic photothermal (hyperthermia), photodynamic (ROS), chemodynamic (Fenton reaction), gas (NO) and ion (Ag+ and -NH3 + in CMCS) therapy. Remarkably, the hydrogels significantly promoted granulation tissue formation, reepithelization, collagen deposition and angiogenesis as well as wound contraction in bacteria-infected wound healing. Taken together, the strategy represented a general method to engineer the unprecedented photoactivatable “all-in-one” hydrogels with enhanced antibacterial activity and paved a new way for development of antibiotic alternatives and wound dressing. Graphical abstract

A novel strategy of not only stimulating the immune cycle but also modulating the immunosuppressive tumor microenvironment is of vital importance to efficient cancer immunotherapy. Here, a new type of spatiotemporal biomimetic “Gemini nanoimmunoregulators” was engineered to activate robust systemic photoimmunotherapy by integrating the triple-punch of amplified immunogenic cell death (ICD), tumor-associated macrophages (TAMs) phenotype reprogramming and programmed cell death ligand 1 (PD-L1) degradation. The “Gemini nanoimmunoregulators” PM@RM-T7 and PR@RM-M2 were constructed by taking the biocompatible mesoporous polydopamine (mPDA) as nanovectors to deliver metformin (Met) and toll-like receptor 7/8 agonist resiquimod (R848) to cancer cells and TAMs by specific biorecognition via wrapping of red blood cell membrane (RM) inlaid with T7 or M2 peptides. mPDA/Met@RM-T7 (abbreviated as PM@RM-T7) was constructed to elicit an amplified in situ ICD effect through the targeted PTT and effectively stimulated the anticancer immunity. Meanwhile, PD-L1 on the remaining cancer cells was degraded by the burst metformin to prevent immune evasion. Subsequently, mPDA/R848@RM-M2 (abbreviated as PR@RM-M2) specifically recognized TAMs and reset the phenotype from M2 to M1 state, thus disrupting the immunosuppressive microenvironment and further boosting the function of cytotoxic T lymphocytes. This pair of sister nanoimmunoregulators cooperatively orchestrated the comprehensive anticancer activity, which remarkably inhibited the growth of primary and distant 4T1 tumors and prevented malignant metastasis. This study highlights the spatiotemporal cooperative modalities using multiple nanomedicines and provides a new paradigm for efficient cancer immunotherapy against metastatic-prone tumors.

Abstract To investigate the risk factors for new renal scarring (NRS) in children with vesicoureteral reflux (VUR) receiving continuous antibiotic prophylaxis (CAP). This was a single-center cohort study. The clinical data of 140 children with grade I–V VUR receiving CAP were analyzed. In this study, exposure variables were sex, younger age at the initial diagnosis of UTI ≤ 12 months, the occurrence of breakthrough urinary tract infection (BT-UTI), high-grade VUR, bilateral VUR, etiology, presence of renal scarring at the initial diagnosis and ultrasound abnormalities. The outcome was NRS. A total of 140 children were included in the risk factor analysis of NRS, 73 of whom experienced NRS, an incidence rate of 52.14%. Multivariate Cox regression suggested that the presence of renal function impairment after the initial diagnosis of UTI (OR 3.411, 95% CI 1.5751–6.646) and the occurrence of BT-UTI while receiving CAP (OR 1.995, 95% CI 1.089–2.958) were independent risk factors for NRS. Multivariate Cox regression showed that high-grade VUR had no significant effects on NRS (OR 0.940, 95% CI 0.462–1.912, P = 0.864). No significant difference was identified in multivariate Cox regression analysis in the IV–V group (vs I–III group) (OR 0.960, 95% CI 0.565–1.633, P = 0.960). Renal function impairment after the initial diagnosis of UTI and the occurrence of BT-UTI while receiving CAP were independent risk factors for NRS. Neither univariate analysis nor multivariate analysis found a correlation between VUR grade and NRS.

Drilling into fractured formations can easily lead to mud loss, which significantly affects drilling efficiency and increases drilling costs. In high-temperature and high-pressure environments, changes in mud properties render mud loss more uncontrollable. On the basis of a mud performance test in a high-temperature and high-pressure environment, and considering the time-varying characteristics of wellbore temperature and pressure and the distribution law of fracture temperature and pressure, a coupling model of temperature and pressure in the wellbore and fracture was established in this study. The developed model was solved numerically using the finite difference approximation, and the characteristics of the mud loss were analyzed. The effects of geothermal gradient, fracture parameters (fracture width, fracture length, and deformation capacity), mud properties (viscosity, yield value, and specific heat capacity), and operating conditions on mud loss were investigated. The model was validated using field measurement-while-drilling tool data of the LD1 well in the South China Sea. The results show that the average errors between the calculated temperature and pressure results of the numerical model and the actual data are 2.45% and 0.57%, respectively, which proves that the model has high accuracy in the prediction of the bottom hole temperature and pressure. A comparison of the predicted data of mud loss with the actual measured data indicates that the average error of the mud leakage model is 4.23%. This also demonstrates that the model has a high accuracy in predicting mud loss. In addition, the results show that the mud performance changes significantly under high-temperature and high-pressure conditions, which has a significant influence on mud loss. The geothermal gradient affected the mud properties and thus significantly affected the mud loss characteristics. The larger the mud pumping rate, the larger the bottomhole pressure difference and the more serious the mud loss. Blindly increasing mud viscosity is not advisable because it may lead to more serious losses. With an increase in the mud yield value, the mud flow resistance in the fractures can be significantly increased to inhibit mud loss. The larger the mud-specific heat capacity, the less mud loss is affected by the temperature. With an increase in the fracture width, the degree of mud loss gradually decreased. The larger the fracture length and deformation capacity, the more serious the mud loss. The fracture length and width could be inverted using the developed model.

Introduction: As signal molecules in aerobic organisms, locally accumulated ROS have been reported to balance cell division and differentiation in the root meristem. Protein posttranslational modifications such as lysine acetylation play critical roles in controlling a variety of cellular processes. However, the mechanism by which ROS regulate root development is unknown. In addition, how protein lysine acetylation is regulated and whether cellular ROS levels affect protein lysine acetylation remain unclear. Objectives: We aimed to elucidate the relationship between ROS and protein acetylation by exploring a rice mutant plant that displays a decreased level of ROS in postembryonic crown root (CR) cells and severe defects in CR development. Methods: First, proteomic analysis was used to find candidate proteins responsible for the decrease of ROS detected in the wox11 mutant. Then, biochemical, molecular, and genetic analyses were used to study WOX11-regulated genes involved in ROS homeostasis. Finally, acetylproteomic analysis of wild type and wox11 roots treated with or without potassium iodide (KI) and hydrogen peroxide (H2O2) was used to study the effects of ROS on protein acetylation in rice CR cells. Results: We demonstrated that WOX11 was required to maintain ROS homeostasis by upregulating peroxidase genes in the crown root meristem. Acetylproteomic analysis revealed that WOX11-dependent hydrogen peroxide (H2O2) levels in CR cells promoted lysine acetylation of many non-histone proteins enriched for nitrogen metabolism and peptide/protein synthesis pathways. Further analysis revealed that the redox state affected histone deacetylases (HDACs) activity, which was likely related to the high levels of protein lysine acetylation in CR cells. Conclusion: WOX11-controlled ROS level in CR meristem cells is required for protein lysine acetylation which represents a mechanism of ROS-promoted CR development in rice.

Abstract Horizontal wells with a slim hole (HW‐SH), characterized by high productivity, high environmental protection, and low cost are gradually being introduced into oil and gas extraction processes in high‐temperature and high‐pressure formations. However, the HW‐SH annulus is narrow, and the distributions of temperature and pressure in the wellbore are very different from those of conventional horizontal wells. Furthermore, the mud properties change under the influence of high temperature and pressure. In this study, a numerical model of the transient temperature‐pressure coupling field in an HW‐SH wellbore was developed based on high‐temperature and high‐pressure performance tests of mud, combined with the characteristics of a narrow annulus in HW‐SH. Subsequently, the effects of the ground temperature gradient, displacement, drill pipe speed, annulus size, and joint size on the temperature‐pressure coupling field were analyzed. Measured data from the HW‐SH drilled in the Mahu field in China were used to validate the developed model. The results showed that the ground temperature had a significant effect on the mud density and rheological properties. As the temperature increased, the mud density decreased, and its rheological properties improved. Although pressure also has a large effect on density, it has a negligible effect on the rheological properties of the mud. The coupled temperature‐pressure field model for HW‐SH considering the effects of the temperature and narrow annulus can predict the annulus temperature and pressure with an accuracy of up to 97%. The ground temperature gradient has the greatest influence on the HW‐SH annular temperature, larger than that of the displacement. In addition, the annular size, rotation speed of the drill pipe, and joint size have almost no influence on the annular temperature. Compared to those of conventional horizontal wells, the rotational speed, annulus size, and joint size of the HW‐SH have a greater impact on the annulus pressure.

The borehole breathing observed when drilling into natural fractured formations is often erroneously identified as leakage or kick. The main reason for this phenomenon is that the fractures around the well have opened and closed after being affected by the wellbore pressure fluctuations. In this paper, a three-dimensional geological model is established for simulating fractured borehole breathing based on the Cohesive unit method, and the full three-dimensional simulation of fractured borehole breathing is realized for the first time. Based on this model, this paper studies the dynamic response characteristics of the fractured borehole breathing mechanism in detail, and analyzes a variety of parameters that may affect borehole breathing. The research results show that: increasing the viscosity of drilling fluid can effectively inhibit the occurrence of borehole breathing and extend its duration; formation elastic modulus is inversely correlated with borehole breathing; borehole breathing is not sensitive to changes in formation Poisson’s ratio and porosity; horizontal geostress affects the severity of borehole breathing by determining the reopening pressure of the fracture; changes in the original width of the fracture will not affect the total volume of backflow, but will affect the amount of mud lost in the early stage.

Abstract The Yinggehai Basin (YGH) in the South China Sea is a Cenozoic, high‐temperature, and high‐pressure basin. Exploration and development of natural gas resources in the YGH show that owing to the diapir structures make the formation pressure system is complex, overpressure characteristics are obvious, prediction is difficult, and spatial distribution is irregular, which severely restricts the development of natural gas. To evaluate the influence of diapir structures on the formation and distribution of overpressure, we compared and analyzed the ancient and modern geothermal temperatures, organic matter maturity, clay mineral evolution, burial depth, and pressure coefficient in the diapir and nondiapir zones of the YGH. The results showed that of the diapir structures in the YGH occurred in the following order: Uplift–spiking–piercing–depositing. The Dongfang area is dominated by low‐amplitude turtle‐back diapir structures with weak energy, whereas the Ledong area is dominated by high‐amplitude spiked diapir structures with strong energy, both of which pressurize the upper formation. The Changnan area is dominated by high‐amplitude pierced/depositing diapirs with strong energy, which can relieve pressure. The influence of the diapir and its associated structures on the formation of overpressure can be attributed to the transport of the diapir body and the associated fault‐fracture system and the local thermal effect caused by the upwelling of hot fluids. Under the influence of the diapir structure, the overpressure top surface of the basin was shallower. According to the degree of influence and intensity of the diapir structure, variations in formation pressure coefficient with depth can be divided into four evolution modes: constant pressure, slow pressurization, “Z” pressurization, and “S” pressurization types. This study provides some guidance and references for the identification and accurate prediction of the overpressure formation mechanism in basins containing diapirs, and helps in formulating efficient drilling and production plans.

Abstract Sand deposition in the wellbore is one of the most common problems in oil–gas and hydrate exploitation work. A detailed understanding of the migration characteristics of the sand bed and accurate prediction of the starting velocity of the sand bed are key aspects of effective sand carrying. Therefore, this study conducted a large‐scale outdoor gas–water–sand three‐phase flow experiment. The effects of critical factors such as flow pattern, sand size, sand bed height, and pipe inclination angle on sand bed startup velocity and migration were studied experimentally. The experimental results indicated that during the startup process of the sand bed, sand particles exhibited three states: rolling, jumping, and suspension. During the experiment, the sand bed morphology included a static bed, rolling bed, jumping bed, and suspension bed. Compared to a stratified flow, intermittent flow and agitated flow were more beneficial for the startup velocity of sand beds. An increase in pipe inclination also reduced the starting velocity of the sand bed. With an increase in sand size, the startup velocity of the sand bed increased correspondingly. However, there was no significant influence on the migration morphology of the sand bed. Additionally, the greater the thickness of the sand bed, the lower the starting velocity of the sand bed. Based on the stress states of sand grains, in combination with experimental data, this study used least‐squares estimation to establish a prediction model for the startup velocity of sand beds. The model prediction results were in good agreement with the experimental data. This study will provide a basis for predicting the startup velocity of sand beds during the gas–liquid two‐phase sand‐carrying process.

Abstract Formation pressure is the most fundamental data in oil and gas drilling and production; it has an important position in the entire cycle of oil and gas extraction. However, most current prediction methods are limited to parametric methods with fixed models; such that the accuracy does not meet requirements. This is especially true for deeper layers of marine sedimentary basins where the safety density window is extremely narrow. In this study, we propose a novel method to predict pore pressure using machine learning techniques. For the first time, the effective stress (direct output variable) was accurately predicted by a combination of four input variables (2900 sets of data, of which 90% is the training subset and 10% is the testing subset), including longitudinal velocity, porosity, mud content, and density. As such, an accurate prediction of the formation pressure was achieved based on the effective stress theorem. The performance of machine learning techniques was verified by comparing and analyzing the prediction results with traditional parametric single and multivariate models; whereby the best algorithm was chosen by structural optimization and comparative analysis of five algorithms (multilayer perceptron neural network, radial basis neural network, support vector machine, random forest, and gradient boosting machine). Compared with the methods based on parametric one‐dimensional and multivariate models, the machine learning‐based method was determined to possess high accuracy, adequate self‐adaptation, and high fault tolerance (D2 = 0.9981, RMSE = 0.00718 g/cm3). Moreover, the multilayer perceptual neural network algorithm outperformed other machine learning algorithms in terms of goodness of fit, generalization, and prediction accuracy, with D2 = 0.9981 and RMSE = 0.00709 g/cm3. The formation pressure prediction model developed in this study is not affected by the mechanical depositional environment and is applicable to sandy mudstone formations, such that it can be a useful and highly accurate alternative to the traditional formation pressure prediction methods with fixed parameter forms.

Due to the absence of effective control measures, tea leaf spot, caused by Lasiodiplodia theobromae, can seriously reduce the production and quality of tea leaves. Analysis of the relationship between messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) of tea could help to prevent and control the disease. In this current study, high-performance sequencing of mRNA and lncRNA from tea leaves during infection by L. theobromae was conducted using the Illumina HiSeq 4000 platform. Of the differentially expressed mRNAs, 2,503 or 5,278 were significantly up- or down regulated, respectively, in challenged leaves relative to unchallenged leaves. Differentially expressed lncRNAs were also analyzed at the level of genes for the above two treatments. The numbers of significantly up- or downregulated lncRNAs were 3,403 or 1,477, respectively. Functional analysis of mRNA revealed that L. theobromae challenge can induce the upregulation of the genes of seven transmembrane MLO family protein -3, -6, -11, major allergen Pru ar 1, and so on. In total, 176 differentially expressed lncRNAs occurred in response to L. theobromae challenge as a result of cis regulation, with 146 differentially expressed mRNAs. At the biological process of defense response, the glycosyl hydrolase 9A1 gene was cis regulated by the differentially expressed lncRNA. The expression profiling and association studies of the tea host infected by L. theobromae will provide a resource for future research into host–pathogen interactions and disease resistance.[Figure: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

This study reports the clinical manifestations, genetics, and efficacy of treatment with the efficacy of recombinant human granulocyte macrophage colony-stimulating factor (rhGM-GSF) of a 2-year-old female patient with severe congenital neutropenia (SCN) type 7 (SCN7) caused by novel biallelic mutations in the colony-stimulating factor 3 receptor (CSF3R) gene. Genetic diagnosis of the patient was performed by whole-exome and Sanger sequencing. Expression of the CSF3R gene in the peripheral neutrophils of the patient was detected by real-time PCR and Western blotting. The patient presented with recurrent suppurative tonsillitis and decreased absolute neutrophil count A). The patient's neutrophils had lower CSF3R mRNA and protein levels than those of the parents. Low-dose rhGM-CSF (3 μg/kg/day once a week) prevented recurrent infection in the patient. These results demonstrate that the clinical manifestations of SCN7 with biallelic CSF3R mutations and downregulated CSF3R can be effectively treated with rhGM-CSF.

Gray blight disease is one of the most destructive diseases of tea plants and occurs widely in the tea-growing areas of the world. It is caused by several fungal phytopathogens, of which Pseudopestalotiopsis camelliae-sinensis is the main pathogen in China. The environmentally friendly antimicrobial, phenazine-1-carboxylic acid (PCA), a metabolite of the natural soil-borne bacteria Pseudomonas spp., can inhibit a range of fungal crop diseases. In this study, we determined that PCA was active against Ps. camelliae-sinensis in vitro. We studied the mode of action of PCA on hyphae using a microscopic investigation, transcriptomics, biochemical methods, and molecular docking. The results of scanning and transmission electron microscopy indicated that PCA caused developmental deformity of mycelia and organelle damage, and it significantly decreased the accumulation of exopolysaccharides on the hyphal surface. The transcriptome revealed that 1705 and 1683 differentially expressed genes of Ps. camelliae-sinensis treated with PCA were up-regulated or down-regulated, respectively, with genes associated with ribosome biogenesis, oxidative phosphorylation, and encoding various proteins of N-glycan biosynthesis being significantly up-regulated. Up-regulation of nine genes related to N-glycan biosynthesis of Ps. camelliae-sinensis in response to PCA treatment was confirmed by reverse transcription qPCR. The enzymatic activity of catalase and superoxide dismutase of hyphae was significantly decreased by PCA treatment. Our results indicated that exposure to PCA resulted in expression changes in oxidoreductase genes, accumulation of reactive oxygen species, and decreased activity of catalase, with concomitant damage to the fungal cell membrane and cell wall.

The lithium-sulfur (Li-S) battery with an ultrahigh theoretical energy density has emerged as a promising rechargeable battery system. However, the practical applications of Li-S batteries are severely plagued by the sluggish reaction kinetics of sulfur species and notorious shuttling of soluble lithium polysulfides (LiPSs) intermediates that result in low sulfur utilization. The introduction of functional layers on separators has been considered as an effective strategy to improve the sulfur utilization in Li-S batteries by achieving effective regulation of LiPSs. Herein, a promising self-assembly strategy is proposed to achieve the low-cost fabrication of hollow and hierarchically porous Fe _3 O _4 nanospheres (p-Fe _3 O _4 -NSs) assembled by numerous extremely-small primary nanocrystals as building blocks. The rationally-designed p-Fe _3 O _4 -NSs are utilized as a multifunctional layer on the separator with highly efficient trapping and conversion features toward LiPSs. Results demonstrate that the nanostructured p-Fe _3 O _4 -NSs provide chemical adsorption toward LiPSs and kinetically promote the mutual transformation between LiPSs and Li _2 S _2 /Li _2 S during cycling, thus inhibiting the LiPSs shuttling and boosting the redox reaction kinetics via a chemisorption-catalytic conversion mechanism. The enhanced wettability of the p-Fe _3 O _4 -NSs-based separator with the electrolyte enables fast transportation of lithium ions. Benefitting from these alluring properties, the functionalized separator with p-Fe _3 O _4 -NSs endows the battery with an admirable rate performance of 877 mAh g ^−1 at 2 C, an ultra-durable cycling performance of up to 2176 cycles at 1 C, and a promising areal capacity of 4.55 mAh cm ^−2 under high-sulfur-loading and lean-electrolyte conditions (4.29 mg cm ^−2 , electrolyte/ratio: 8 µ l mg ^−1 ). This study will offer fresh insights on the rational design and low-cost fabrication of multifunctional separator to strengthen electrochemical reaction kinetics by regulating LiPSs conversion for developing efficient and long-life Li-S batteries.

Plants are subjected to various environmental stresses throughout their life cycle. Reactive oxygen species (ROS) play important roles in maintaining normal plant growth, and improving their tolerance to stress. This review describes the production and removal of ROS in plants, summarizes recent progress in understanding the role of ROS during plant vegetative apical meristem development, organogenesis, and abiotic stress responses, and some novel findings in recent years are discussed. More importantly, interplay between ROS and epigenetic modifications in regulating gene expression is specifically discussed. To summarize, plants integrate ROS with genetic, epigenetic, hormones and external signals to promote development and environmental adaptation.

As a novel brominated flame retardant, 1,2-dibromo-4-(1,2-dibromoethyl) cyclohexane (TBECH) has been detected in a variety of environmental media and organisms, but studies on its toxic effect is quite scarce. In this work, the selective accumulation of four TBECH diastereomers (α-, β-, γ- and δ-TBECH) in soil by earthworm ( Eisenia fetida) was studied. The effect of TBECH exposure on the growth of earthworm ( Eisenia fetida), the free radical levels, malondialdehyde (MDA) and phosphorylated histone (γ-H2AX) contents, and antioxidant enzyme activities in earthworms were investigated. The results showed that the enrichment of TBECH by earthworms was diastereomer-specific, with the biological soil accumulation factor (BSAF) of γ-TBECH higher than that of other diastereomers. When exposed to low TBECH concentrations (50 -200 mg·kg-1 ), the average body weight and mortality of earthworms were not significantly different from the blank group. When exposed to high TBECH concentrations (≥400 mg·kg-1 ), the average body weight decreased with the increases of exposure concentration, and the mortality increased. During TBECH exposure, the content of MDA and γ-H2AX in earthworms increased significantly. The activity of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and glutathione S-transferases (GSTs) was significantly induced at 50 mg·kg-1 exposed concentration, while decreased with increasing exposure time and concentrations at 100 - 600 mg·kg-1 . The level of free radicals in earthworms was measured by electron spin resonance combined with secondary radical capture technology. It was found that TBECH exposure could induce the production of a large number of hydroxyl radicals in earthworms, and there was a significant positive correlation between the level of hydroxyl radicals and the content of MDA, which indicated that the oxidative damage caused by inducing a large number of hydroxyl radicals in earthworms is an important reason for the toxicity of TBECH to earthworms. The above research results revealed the enrichment ability of TBECH by Eisenia fetidaand the toxic effect of TBECH on Eisenia fetida, which provided the basis for the ecological health risk assess- ment of TBECH. [ABSTRACT FROM AUTHOR]