Search

By benchmarking with the iteration of drilling technology, fracturing technology and well placement mode for shale oil and gas development in the United States and considering the geological characteristics and development difficulties of shale oil in the Jiyang continental rift lake basin, East China, the development technology system suitable for the geological characteristics of shale oil in continental rift lake basins has been primarily formed through innovation and iteration of the development, drilling and fracturing technologies. The technology system supports the rapid growth of shale oil production and reduces the development investment cost. By comparing it with the shale oil development technology in the United States, the prospect of the shale oil development technology iteration in continental rift lake basins is proposed. It is suggested to continuously strengthen the overall three-dimensional development, improve the precision level of engineering technology, upgrade the engineering technical indicator system, accelerate the intelligent optimization of engineering equipment, explore the application of complex structure wells, form a whole-process integrated quality management system from design to implementation, and constantly innovate the concept and technology of shale oil development, so as to promote the realization of extensive, beneficial and high-quality development of shale oil in continental rift lake basins.

BackgroundTraditional Chinese medicine (TCM) is used to treat mycoplasma pneumonia (MP) in children with favorable treatment outcome in China. In the present study, we evaluated the clinical efficacy of TCM combined with azithromycin (AZM) for the treatment of MP among children, providing high evidence-based reference for clinical treatment.MethodWe retrieved eligible randomized controlled trials (RCTs) from CQVIP, CNKI, WanFang, NSTL, PubMed, Embase, and Embase databases from January 2000 to November 2023. Data extraction and quality assessment of the enrolled studies were independently by two reviewers. Review Manager 5.3 was used for meta-analysis.ResultA total of 51 RCTs involving 5,799 children aged 1–14 enrolled. Meta-analysis demonstrated that TCM combined with AZM improved the cure rate (odds ratio [OR] = 2.34, 95% CI: 2.06 to 2.64) and the effective rate (OR = 5.21, 95% CI: 4.22 to 6.43), shorted the disappearance duration of cough (WMD = −1.62, 95% CI: −1.90 to −1.34), the duration of fever (WMD = −1.62, 95% CI: −1.96 to −1.29), and the disappearance time of lung rales (WMD = −1.15, 95% CI: −1.32 to −0.98), improved CRP levels (WMD = −2.06, 95% CI: −2.57 to −1.55), IL-6 levels (WMD = −1.92,95% CI: −2.51 to −1.34), and TNF-α levels (WMD = −1.59, 95% CI: −2.14 to −1.04), and reduced adverse reactions (OR = 0.37, 95% CI: 0.32 to 0.44).ConclusionTCM combined with AZM in the treatment of MP among children has favorable clinical efficacy and safety.

Lung cystic fibrosis (CF) is a lethal inherited disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, leading to a dysfunctional CFTR protein. Gene therapy offers promise for the treatment of lung CF. However, the development and clinical application of CF gene therapy have long been hampered by the absence of safe and highly efficient delivery vectors. In this work, a novel polymer-based gene replacement treatment approach was developed. A series of poly (β-amino esters) (PAEs) with various topological structures and chemical compositions were screened to create non-viral therapeutic systems for CFTR restoration in lung CF disease. A nanoparticle, formed by the selected highly branched PAE (HPAE) with a CpG-depleted CFTR plasmid, demonstrated CFTR gene expression and biocompatibility in lung epithelial cells, outperforming leading commercial gene transfection reagents such as Lipofectamine 3000 and Xfect. The newly developed gene therapy system successfully restored functional CFTR protein production in lung CF epithelial monolayers. This therapeutic approach holds great potential for use as an efficient and safe non-viral treatment for CF patients.

Abstract Aerogels, as famous lightweight and porous nanomaterials, have attracted considerable attention in various emerging fields in recent decades, however, both low density and weak mechanical performance make their configuration-editing capability challenging. Inspired by folk arts, herein we establish a highly efficient twice-coagulated (TC) strategy to fabricate configuration-editable tough aerogels enabled by transformable gel precursors. As a proof of concept, aramid nanofibers (ANFs) and polyvinyl alcohol (PVA) are selected as the main components of aerogel, among which PVA forms a flexible configuration-editing gel network in the first coagulation process, and ANF forms a configuration-locking gel network in the second coagulation process. TC strategy guarantees the resulting aerogels with both high toughness and feasible configuration editing capability individually or simultaneously. Altogether, the resulting tough aerogels with special configuration through soft to hard modulation provide great opportunities to break through the performance limits of the aerogels and expand application areas of aerogels.

Abstract The sensory neocortex has been suggested to be a substrate for long-term memory storage, yet which exact single cells could be specific candidates underlying such long-term memory storage remained neither known nor visible for over a century. Here, using a combination of day-by-day two-photon Ca2+ imaging and targeted single-cell loose-patch recording in an auditory associative learning paradigm with composite sounds in male mice, we reveal sparsely distributed neurons in layer 2/3 of auditory cortex emerged step-wise from quiescence into bursting mode, which then invariably expressed holistic information of the learned composite sounds, referred to as holistic bursting (HB) cells. Notably, it was not shuffled populations but the same sparse HB cells that embodied the behavioral relevance of the learned composite sounds, pinpointing HB cells as physiologically-defined single-cell candidates of an engram underlying long-term memory storage in auditory cortex.

The improved electronic conductivity and ion diffusion efficiency of TiO2‐based anode materials have been extensively studied by introducing oxygen vacancies or creating amorphous structure. There has been little exploration of the synergistic effects by combining these two modification strategies into one TiO2‐based matrix. In addition, the structure–activity relationship and energy storage mechanism involved remain to be understood. Herein, a facile one‐step coreduction method is reported to successfully produce the oxygen vacancy‐doped amorphous TiO2 nanoparticles. The oxygen vacancy‐doped amorphous TiO2 anode exhibits significantly enhanced electrochemical activity and high‐rate stability (up to 87 mAh g−1 over 10 000 discharge/charge cycles at a current rate of 100 C). This outstanding electrochemical performance is attributable to the synergistic effects of amorphous structure and oxygen vacancies. Density functional theory calculations reveal the enhanced electronic conductivity and thermodynamically favorable lithium insertion architecture due to the introduction of oxygen vacancy and the construction of the amorphous skeleton. Dynamic analysis indicates that the lithium‐storage mechanism is a hybrid of surface capacitive storage and enhanced diffusion‐controlled ion insertion. This work opens up new pathways in developing novel anode materials for efficient energy storage from the wide spectrum of metal oxides.

Frequent removal and reapplication of wound dressings can cause mechanical disruption to the healing process and significant physical discomfort for patients. In response to this challenge, a dynamic covalent hydrogel has been developed to advance wound care strategies. This system comprises aldehyde functionalized chondroitin sulfate (CS-CHO) and thiolated hyaluronic acid (HA-SH), with the distinct ability to form in situ via thiol–aldehyde addition and dissolve on-demand via the thiol–hemithioacetal exchange reaction. Although rarely reported, the dynamic covalent reaction of thiol–aldehyde addition holds great promise for the preparation of dynamic hydrogels due to its rapid reaction kinetics and easy reversible dissociation. The thiol–aldehyde addition chemistry provides the hydrogel system with highly desirable characteristics of rapid gelation (within seconds), self-healing, and on-demand dissolution (within 30 min). The mechanical and dissolution properties of the hydrogel can be easily tuned by utilizing CS-CHO materials of different aldehyde functional group contents. The chemical structure, rheology, self-healing, swelling profile, degradation rate, and cell biocompatibility of the hydrogels are characterized. The hydrogel possesses excellent biocompatibility and proves to be significant in promoting cell proliferation in vitro when compared to a commercial hydrogel (HyStem® Cell Culture Scaffold Kit). This study introduces the simple fabrication of a new dynamic hydrogel system that can serve as an ideal platform for biomedical applications, particularly in wound care treatments as an on-demand dissolvable wound dressing.

Although biochar application to soils has been found to increase soil quality and crop yield, the biochar dispersion extent and its impacts on native soil organic carbon (SOC) has received relatively little attention. Here, the vertical and lateral migration of fine, intermediate and coarse-sized biochar (

Mixing or regrouping of calves from different pens is a common animal management practice on the farm, which frequently occurs after weaning and has a negative effect on calve welfare. Social integration before regrouping may relieve stresses, but more evidences are needed to verify this hypothesis. The present study aimed to investigate acute physiological and behavioral variations of individually- or group-housed calves after being introduced into a mixed group. A total of 132 postnatal calves were randomly divided into groups of 1, 3, 6 and 12 animals (S, G3, G6, and G12; 6 replicates in each group) until 59 days of age. At 60 days of age, every two replicates from different groups (S, G3, G6 and G12) were introduced in a larger pen which containing 44 of the aboved experimental calves. Before and after regrouping, physiological parameters of stress, including heart rate (HR), saliva cortisol (S-CORT), saliva secretory immunoglobulin A (SIgA), interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) levels, and behavioral responses were recorded. After regrouping, HR and S-CORT increased immediately (P

Abstract Oxytocin administration during a trauma analogue has been shown to increase intrusive memories, which are a core symptom of post-traumatic stress disorder (PTSD). However, it is unknown whether oxytocin influences the acquisition or the consolidation of the trauma. The current study investigates the effect of the activation of the oxytocin system during the consolidation of an analogue trauma on the formation of intrusive memories over four consecutive days and whether this effect is influenced by individual neurobiological, genetic, or psychological factors. We conducted a randomized double-blind placebo-controlled study in 217 healthy women. They received either a single dose of intranasal oxytocin (24 IU) or placebo after exposure to a trauma film paradigm, which reliably induces intrusive memories. We used a general random forest to examine a potential heterogeneous treatment effect of oxytocin on the consolidation of intrusive memories. Furthermore, we used a poisson regression to examine whether salivary alpha amylase activity (sAA) as a marker of noradrenergic activity and cortisol response to the film, polygenic risk score (PRS) for psychiatric disorders, and psychological factors influence the number of intrusive memories. We found no significant effect of oxytocin on the formation of intrusive memories (F(2, 543.16) = 0.75, p = 0.51, ηp2 = 0.00) and identified no heterogeneous treatment effect. We replicated previous associations of the PRS for PTSD, sAA and the cortisol response on intrusive memories. We further found a positive association between high trait anxiety and intrusive memories, and a negative association between the emotion regulation strategy reappraisal and intrusive memories. Data of the present study suggest that the consolidation of intrusive memories in women is modulated by genetic, neurobiological and psychological factors, but is not influenced by oxytocin. Trial registration: NCT03875391.

Wind-farm-side modular multilevel converters (WFMMCs) used in modular multilevel converter based high-voltage direct current (MMC-HVDC) transmission systems must be able to control the AC grid voltage in offshore wind farms. Different AC voltage control strategies can significantly affect the dynamic characteristics of WFMMCs. However, existing studies have not provided a general methodology of controller parameter design, and few comparative studies have been conducted on control performance under varying operating conditions as well as the effects of different AC voltage control modes (AVCMs) on the stability of MMC-HVDCs with offshore wind farms. This paper provides a controller parameter design method for AVCMs, which is tested in various operating scenarios. Sequence impedance models of offshore wind farms and WFMMCs under different AVCMs are then developed. The effects of AVCMs on the small-signal stability of the interconnected system are then analyzed and compared using the impedance-based method. Finally, case studies are conducted on a practical MMC-HVDC system with offshore wind farms to verify the theoretical analysis.

Abstract Studying chemosensory processing desires precise chemical cue presentation, behavioral response monitoring, and large-scale neuronal activity recording. Here we present Fish-on-Chips, a set of optofluidic tools for highly-controlled chemical delivery while simultaneously imaging behavioral outputs and whole-brain neuronal activities at cellular resolution in larval zebrafish. These include a fluidics-based swimming arena and an integrated microfluidics-light sheet fluorescence microscopy (µfluidics-LSFM) system, both of which utilize laminar fluid flows to achieve spatiotemporally precise chemical cue presentation. To demonstrate the strengths of the platform, we used the navigation arena to reveal binasal input-dependent behavioral strategies that larval zebrafish adopt to evade cadaverine, a death-associated odor. The µfluidics-LSFM system enables sequential presentation of odor stimuli to individual or both nasal cavities separated by only ~100 µm. This allowed us to uncover brainwide neural representations of cadaverine sensing and binasal input summation in the vertebrate model. Fish-on-Chips is readily generalizable and will empower the investigation of neural coding in the chemical senses.

Abstract Background Joint Awareness is thought to be closely linked to Quality of Life (QoL) for patients undergoing Total Knee Arthroplasty (TKA), yet to date there have been no longitudinal studies to explore how Joint Awareness actually affects QoL. The purpose of this study was therefore to examine the development of Joint Awareness and QoL after TKA as well as the dynamic impact of Joint Awareness on QoL. Methods A total of 342 patients were followed up at 3 months (T1), 6 months (T2), and 12 months (T3) after TKA. Joint Awareness was evaluated using the Forgotten Joint Score-12 (FJS-12), and QoL was measured by SF-36. We used repeated measures analysis of variance to estimate the development of Joint Awareness and QoL and employed a cross-lagged model to examine the dynamic relationship between Joint Awareness and QoL. Results Both Joint Awareness and QoL improved with postoperative time (p

Summary: Neocortical layer 6 (L6) is less understood than other more superficial layers, largely owing to limitations of performing high-resolution investigations in vivo. Here, we show that labeling with the Challenge Virus Standard (CVS) rabies virus strain enables high-quality imaging of L6 neurons by conventional two-photon microscopes. CVS virus injection into the medial geniculate body can selectively label L6 neurons in the auditory cortex. Only three days after injection, dendrites and cell bodies of L6 neurons could be imaged across all cortical layers. Ca2+ imaging in awake mice showed that sound stimulation evokes neuronal responses from cell bodies with minimal contamination from neuropil signals. In addition, dendritic Ca2+ imaging revealed significant responses from spines and trunks across all layers. These results demonstrate a reliable method capable of rapid, high-quality labeling of L6 neurons that can be readily extended to other brain regions.

Ginseng Radix et Rhizoma Rubra (Panax ginseng C.A. Mey, Hongshen, in Chinese) and Ophiopogonis Radix (Ophiopogon japonicus (L.f) Ker-Gawl., Maidong, in Chinese) are traditional Chinese herbal pairs, which were clinically employed to enhance the immune system of cancer patients. This study employed the pharmacokinetic and pharmacodynamic (PK–PD) spectrum-effect association model to investigate the antitumor active substances of P. ginseng and O. japonicus (PG–OJ). The metabolic processes of 20 major bioactive components were analyzed using Ultra-Performance Liquid Chromatography–Mass Spectrometry/Mass Spectrometry (UPLC–MS/MS) in the lung tissue of tumor-bearing mice treated with PG–OJ. The ELISA method was employed to detect the levels of TGF-β1, TNF-α, and IFN-γ in the lung tissue of mice at various time points, and to analyze their changes after drug administration. The results showed that all components presented a multiple peaks absorption pattern within 0.083 to 24 h post-drug administration. The tumor inhibition rate of tumor and repair rate of IFN-γ, TNF-α, and TGF-β1 all increased, indicating a positive therapeutic effect of PG–OJ on A549 tumor-bearing mice. Finally, a PK–PD model based on the GBDT algorithm was developed for the first time to speculate that Methylophiopogonanone A, Methylophiopogonanone B, Ginsenoside Rb1, and Notoginsenoside R1 are the main active components in PG–OJ for lung cancer treatment.

Driven by practical conundrums that users often face in maximizing (e-)dictionaries as a companion resource, this article revisits and redefines ecolexicography as a new paradigm that situates compilers and users in a relational dynamic. Drawing insights from ecolinguistics and cognitive studies, it appeals for rethinking the compiler–user relationship and placing dictionaries in a distributed cognitive system. A multidimensional framework of ecolexicography is proposed, consisting of a micro-level and a macro-level. To the micro-level, both symbolic and cognitive dimensions are added: (1) the dictionary can be symbolically viewed as a semantic and semiotic ecology; (2) dialogicality should be highlighted as an essential aspect of e-dictionary compilation/ design, and distributed cognition can be emancipatory for rethinking dictionary use. The macrolevel concerns the obligations of lexicographers as committed to three interrelated ecologies or ecosystems: language, socio-culture and nature. Transdisciplinary in nature, ecolexicography involves a holistic, systematic and integrative methodology to nourish lexicographical practice and research. Corpus-based Frame Analysis is introduced to identify ecologically destructive frames and ideologies so that the dictionary discourse could be reframed. The study upgrades our understanding of the ontological, epistemological and methodological aspects related to ecolexicography, serving as a call for philosophical reflections on metalexicography. It is also expected to create an opportunity for lexicographers to examine problems with (e-)dictionaries in a new light and dialogue about how to find solutions.

Brain-wide axonal projections of single neurons have been extensively reconstructed without any functional characterization. The authors present a method that allows for developing a precise one-to-one map of both projection patterns and functional features of single neurons in mice.

Existing research on syntactic complexity tends to examine diversity and complexity embedded in grammatical employments which may well be witnessed in formulations of different syntactic structures. Conceivably, the subject syntactic complexity seems to be exercised mostly by non-native speakers and writers. The present study employs pseudo-longitudinal data: essays written by undergraduate students in different levels collected at the same time. Hence, it aims at investigating the mechanism involved in the L2 production of L2 learners in terms of syntactic complexity by analyzing a corpus of non-native English-speaking learners. The research inquiry is mainly focused on investigation of significant differences in terms of syntactic complexity between writing of Japanese university students and that of native speakers, probing further into the particular dimension and level of difference. The study also traces marked variations in syntactic complexity employed by Japanese university students in different grades. Nagoya Interlanguage Corpus of English (NICE) developed by Sugiura in 2015 was employed to conduct the entire research proceedings. The corpus of the subject study comprises 339 essays written by L2 EFL learners studying in a Japanese university employing a judicious selection of quantitative measures of syntactic complexity. The results exhibited a considerable statistical difference between the writing of Japanese learners and native English writers. The findings of this study provide meaningful pedagogical implications for English teachers and textbook compilers. Japanese university students in higher grades are found to be employing more complicated and diverse syntactic structures. Conforming to the already conducted research studies with almost similar objectives, this study demonstrates the significance of using both general and more particular complexity metrics to assess syntactic development in L2.

Astrocytic Ca2+ transients are essential for astrocyte integration into neural circuits. These Ca2+ transients are primarily sequestered in subcellular domains, including primary branches, branchlets and leaflets, and endfeet. In previous studies, it suggests that aging causes functional defects in astrocytes. Until now, it was unclear whether and how aging affects astrocytic Ca2+ transients at subcellular domains. In this study, we combined a genetically encoded Ca2+ sensor (GCaMP6f) and in vivo two-photon Ca2+ imaging to determine changes in Ca2+ transients within astrocytic subcellular domains during brain aging. We showed that aging increased Ca2+ transients in astrocytic primary branches, higher-order branchlets, and terminal leaflets. However, Ca2+ transients decreased within astrocytic endfeet during brain aging, which could be caused by the decreased expressions of Aquaporin-4 (AQP4). In addition, aging-induced changes of Ca2+ transient types were heterogeneous within astrocytic subcellular domains. These results demonstrate that the astrocytic Ca2+ transients within subcellular domains are affected by aging differently. This finding contributes to a better understanding of the physiological role of astrocytes in aging-induced neural circuit degeneration.

This study explores the impact of customers’ value co-creation behavior on their experiences with and loyalty to P2P accommodations. We propose a theoretical model integrating two lines of tourism research: customer value co-creation and customer experience. To extract the dimensions of customer experience and test the proposed model, 34 in-depth interviews were conducted along with a survey of Chinese Airbnb users. Structural equation modeling and mediation analysis were implemented to assess relationships involving customers’ value co-creation behavior, experience, and loyalty. Results indicate that customer citizenship behavior directly influences loyalty. In particular, relationships involving customers’ participation behavior and citizenship behavior with loyalty are both mediated by customer experience. Relevant implications and future research opportunities are discussed.

Highly branched poly(β-amino ester) (HPAE) has become one of the most promising non-viral gene delivery vector candidates. When compared to other gene delivery vectors, HPAE has a broad molecular weight distribution (MWD). Despite significant efforts to optimize HPAE targeting enhanced gene delivery, the effect of different molecular weight (MW) components on transfection has rarely been studied. In this work, a new structural optimization strategy was proposed targeting enhanced HPAE gene transfection. A series of HPAE with different MW components was obtained through a stepwise precipitation approach and applied to plasmid DNA delivery. It was demonstrated that the removal of small MW components from the original HPAE structure could significantly enhance its transfection performance (e.g., GFP expression increased 7 folds at w/w of 10/1). The universality of this strategy was proven by extending it to varying HPAE systems with different MWs and different branching degrees, where the transfection performance exhibited an even magnitude enhancement after removing small MW portions. This work opened a new avenue for developing high-efficiency HPAE gene delivery vectors and provided new insights into the understanding of the HPAE structure–property relationship, which would facilitate the translation of HPAEs in gene therapy clinical applications.

Variation and evolution of DNA methylation during maize domestication remain largely unknown. Here, the authors generate genome and methylome sequencing data as well as HiChIP-based interactome data to investigate the adaptive and phenotypic consequences of methylation variations in maize.

Nucleosome turnover concomitant with incorporation of the histone variant H3.3 is a hallmark of regulatory regions in the animal genome. Here, the authors demonstrate that fast histone turnover and H3.3 incorporation defines a dynamic heterochromatin state in pluripotent stem cells.

Using a combination of two-photon imaging and single-cell electrophysiology, the authors discover that associative learning induces the emergence of a unique subset of neurons in the auditory cortex, exhibiting high-rate bursting responses to the learned complex sounds but not to any of the constituents.

Recently, small-signal stability of the modular multilevel converter (MMC) based high-voltage direct current (HVDC) transmission for wind farm integration has attracted great attentions. The impedance-based frequency-domain method is an effective tool for such studies, in which the accuracy of the impedance model is of significant importance. Currently, the decoupled single-input single-output (SISO) sequence impedance of the MMC-HVDC system with wind farm is commonly used due to the simplicity in stability analysis. However, since both the MMC and wind farm exhibit frequency coupling behaviors, the decoupled SISO sequence impedance model may lead to inaccurate stability conclusion under certain conditions. In order to improve the model accuracy, based on the harmonic state-space (HSS) modeling approach, this paper proposes a generalized multi-input multi-output (MIMO) sequence impedance model of the MMC-wind farm system. The proposed MIMO impedance model can effectively capture the frequency couplings in the interconnected system, based on which the coupling mechanism of multi-frequency components within the MMC is then revealed. To facilitate the interconnection analysis, the model truncation criteria is proposed and validated by comparing the accuracy of the MIMO model with different truncated dimensions. In addition, this paper considers the internal impedance network of the wind farm when developing the aggregated wind farm impedance model for interaction stability analysis. Finally, the proposed MIMO sequence impedance model is applied to accurately predict the instability of the MMC-HVDC connected wind farm system.

Cartilage tissue has a relatively low regenerative capacity which leads to a need for disease‐modifying active pharmaceutical ingredients (APIs) which can stimulate its regeneration and more urgently, effective ways of introducing APIs into the cartilage defects. Herein, an integrated system is proposed in which a hyaluronic acid (HA)‐based injectable hydrogel scaffold is embedded with API‐loaded poly(d,l‐lactide‐co‐glycolide) microspheres (PLGA MPs). This new injectable drug delivery system can successfully deliver APIs locally, increase drug retention time, and promote endogenous cartilage regeneration. In this study, resveratrol (RSV), a small hydrophobic compound is introduced as the selected API. PLGAs with differing copolymer ratios and endgroups are evaluated to study their effects on particle formation, RSV encapsulation, and drug release kinetics. This system is optimized as a 1 month sustained release formulation. In addition, the long‐acting chondrogenic induction of the RSV‐loaded system is evaluated by coculturing with cartilage‐derived progenitor cells in vitro. PLGA–RSV MPs stimulated the expression of cartilage‐related genes and the production of the cartilage‐specific extracellular matrix. This integrated system shows great potential as an injectable formulation for long‐acting chondrogenesis and endogenous cartilage tissue regeneration.

Although hematopoietic stem cell transplantation (HCT) is the only curative treatment for acute myeloid leukemia (AML), it is associated with significant treatment related morbidity and mortality. There is great need for predictive biomarkers associated with overall survival (OS) and clinical outcomes. We hypothesized that circulating metabolic, inflammatory, and immune molecules have potential as predictive biomarkers for AML patients who receive HCT treatment. This retrospective study was designed with an exploratory approach to comprehensively characterize immune, inflammatory, and metabolomic biomarkers. We identified patients with AML who underwent HCT and had existing baseline plasma samples. Using those samples (n = 34), we studied 65 blood based metabolomic and 61 immune/inflammatory related biomarkers, comparing patients with either long-term OS (≥ 3 years) or short-term OS (OS ≤ 1 years). We also compared the immune/inflammatory response and metabolomic biomarkers in younger vs. older AML patients (≤30 years vs. ≥ 55 years old). In addition, the biomarker profiles were analyzed for their association with clinical outcomes, namely OS, chronic graft versus host disease (cGVHD), acute graft versus host disease (aGVHD), infection and relapse. Several baseline biomarkers were elevated in older versus younger patients, and baseline levels were lower for three markers (IL13, SAA, CRP) in patients with OS ≥ 3 years. We also identified immune/inflammatory response markers associated with aGVHD (IL-9, Eotaxin-3), cGVHD (Flt-1), infection (D-dimer), or relapse (IL-17D, bFGF, Eotaxin-3). Evaluation of metabolic markers demonstrated higher baseline levels of medium- and long-chain acylcarnitines (AC) in older patients, association with aGVHD (lactate, long-chain AC), and cGVHD (medium-chain AC). These differentially expressed profiles merit further evaluation as predictive biomarkers.

Many polymeric gene delivery nano-vectors with hyperbranched structures have been demonstrated to be superior to their linear counterparts. The higher delivery efficacy is commonly attributed to the abundant terminal groups of branched polymers, which play critical roles in cargo entrapment, material-cell interaction, and endosome escape. Hyperbranched poly(β-amino ester)s (HPAEs) have developed as a class of safe and efficient gene delivery vectors. Although numerous research has been conducted to optimise the HPAE structure for gene delivery, the effect of the secondary amine residue on its backbone monomer, which is considered the non-ideal termination, has never been optimised. In this work, the effect of the non-ideal termination was carefully evaluated. Moreover, a series of HPAEs with only ideal terminations were synthesised by adjusting the backbone synthesis strategy to further explore the merits of hyperbranched structures. The HPAE obtained from modified synthesis methods exhibited more than twice the amounts of the ideal terminal groups compared to the conventional ones, determined by NMR. Their transfection performance enhanced significantly, where the optimal HPAE candidates developed in this study outperformed leading commercial benchmarks for DNA delivery, including Lipofectamine 3000, jetPEI, and jetOPTIMUS.

Abstract. Background:. The development of auditory and speech perception ability of children with hearing loss is affected by many factors after they undergo cochlear implantation (CI). Age at CI (CI age) appears to play an important role among these factors. This study aimed to evaluate the development of auditory and speech perception ability and explore the impact of CI age on children with pre-lingual deafness present before 3 years of age. Methods:. Two hundred and seventy-eight children with pre-lingual deafness (176 boys and 102 girls) were included in this study, and the CI age ranged from 6 to 36 months (mean age, 19 months). Categorical auditory performance (CAP) was assessed to evaluate auditory ability, and the speech intelligibility rating was used to evaluate speech intelligibility. The evaluations were performed before CI and 1, 3, 6, 12, 18, 24, 36, 48, and 60 months after CI. Results:. The auditory ability of the pre-lingually hearing-impaired children showed the fastest development within 6 months after CI (k = 0.524, t = 30.992, P 0.05). The optimal cutoff age for CI was 15 months. Conclusions:. Within 5 years after CI, the auditory and speech ability of young hearing-impaired children continuously improved, although speech development lagged behind that of hearing. An earlier CI age is recommended; the optimal cutoff age for CI is at 15 months.

Therapeutics delivery by using non-viral vectors presents several challenges in the design of an appropriate polymeric structure. Here, the authors report a series of highly branched, biodegradable polymers which show high transfection efficiency in human multipotent adipose derived stem cells and primary astrocytes.

BackgroundAllogeneic hematopoietic stem cell transplantation (HCT) is an often curative intent treatment, however it is associated with significant gastrointestinal (GI) toxicity and treatment related mortality. Graft-versus-host disease is a significant contributor to transplant-related mortality. We performed a phase 2 trial of the somatostatin analog pasireotide to prevent gastrointestinal toxicity and GVHD after myeloablative allogeneic HCT.MethodsPatients received 0.9mg pasireotide every 12 hours from the day prior to conditioning through day +4 after HCT (or a maximum of 14 days). The primary outcomes were grade 3-4 gastrointestinal toxicity through day 30 and acute GVHD. Secondary outcomes were chronic GVHD, overall survival and relapse free survival at one year. Stool and blood samples were collected from before and after HCT for analyses of stool microbiome, local inflammatory markers, and systemic inflammatory and metabolic markers. Results were compared with matched controls.ResultsTwenty-six patients received pasireotide and were compared to 52 matched contemporaneous controls using a 1-2 match. Grade 3-4 GI toxicity occurred in 21 (81%) patients who received pasireotide and 35 (67%) controls (p = 0.33). Acute GVHD occurred in 15 (58%) patients in the pasireotide group and 28 (54%) controls (p = 0.94). Chronic GVHD occurred in 16 patients in the pasireotide group (64%) versus 22 patients in the control group (42%) (p = 0.12). Overall survival at 1 year in the pasireotide group was 63% (95% CI: 47%,86%) versus 82% (95% CI: 72%, 93%) in controls (log-rank p = 0.006). Relapse-free survival rate at one year was 40% (95% CI: 25%, 65%) in the pasireotide group versus 78% (95% CI: 68%, 91%) in controls (log-rank p = 0.002). After controlling for the effect of relevant covariates, patients in the pasireotide group had attenuated post-HCT loss of microbial diversity. Analysis of systemic inflammatory markers and metabolomics demonstrated feasibility of such analyses in patients undergoing allogeneic HCT. Baseline level and pre-to-post transplant changes in several inflammatory markers (including MIP1a, MIP1b, TNFa, IL8Pro, and IL6) correlated with likelihood of survival.ConclusionsPasireotide did not prevent gastrointestinal toxicity or acute GVHD compared to contemporaneous controls. Pasireotide was associated with numerically higher chronic GVHD and significantly decreased OS and RFS compared to contemporaneous controls. Pasireotide may provide a locally protective effect in the stool microbiome and in local inflammation as measured by stool calprotectin, stool beta-defensin, and stool diversity index.

Reducing the capacitance of the sub-modules (SMs) and handling dc short-circuit faults are critical for the economical and reliable operation of modular multilevel converters (MMCs) in high-voltage direct current (HVDC) transmission systems. To deal with these issues, the optimized design and control for the hybrid MMC are proposed in this paper. First, the capacitor voltage fluctuations of the hybrid MMC with second-order circulating current and third-order common-mode voltage injection are analyzed. On this basis, the modulation index, required number of half-bridge SMs and full-bridge SMs, and SM capacitances are optimally designed with consideration of the operation constraints of the hybrid MMC, respectively. Further, an optimized control strategy is proposed to ensure the stable operation of the converter and to provide good dynamic performance. The capacitance requirements of the hybrid MMC with optimized design can be reduced to about 38% of those of the hybrid MMC with conventional design. The correctness of the theoretical analysis and the effectiveness of the proposed optimized design and the control strategy have been validated by the simulation and experimental results.

Ferromanganese nodules are an important mineral resource in the seafloor; however, the genetic mechanism is still unknown. The biomineralization of microorganisms appears to promote ferromanganese nodule formation. To investigate the possible mechanism of microbial–ferromanganese nodule interaction, to test the possibility of marine microorganisms as deposition template for ferromanganese nodules minerals, the interactions between Jeotgalibacillus campisalis strain CW126-A03 and ferromanganese nodules were studied. The results showed that strain CW126-A03 increased ion concentrations of Fe, Mn, and other metal elements in solutions at first. Then, metal ions were accumulated on the cells’ surface and formed ultra-micro sized mineral particles, even crystalline minerals. Strain CW126-A03 appeared to release major elements in ferromanganese nodules, and the cell surface may be a nucleation site for mineral precipitation. This finding highlights the potentially important role of biologically induced mineralization (BIM) in ferromanganese nodule formation. This BIM hypothesis provides another perspective for understanding ferromanganese nodules’ genetic mechanism, indicating the potential of microorganisms in nodule formation.

The new generation Geometrical Product Specifications require consideration of the effects of measurement uncertainty in the product inspection. This study estimated the measurement results and the uncertainty by integrating the statistical production information into the product detection results to rationally and fairly narrow the uncertainty area of qualification determination. Based on the Bayesian information fusion and statistical inference principle, the model of uncertainty evaluation is established. The Bayesian information fusion model integrated measuring information with manufacturing information was built, with which the uncertainty of product inspection was reappraised based on posteriori distribution function. The validity of the proposed method and theory was demonstrated by the example analysis.

The product inspection process with measurement uncertainty as a quality indicator is researched. Based on the product quality control information and the design and processing precision, the relationship between the misjudgement probability and measurement uncertainty of conformance testing is established. In view of the limitation of uncertainty evaluation based on the single piece in product inspection, the method for evaluating uncertainty fusing multiple product measurement information in a fully integrated batch is proposed. The uncertainty components caused by the measurement repeatability and reproducibility of the whole test work are evaluated based on the conjugate Bayesian estimation method. The test results show that there is a certain false positive rate in the whole test of the product under the condition of uncertainty. Research results show that the misjudgement probability caused by the measurement uncertainty cannot be ignored. In the product test, batch detection information should be fully integrated to improve the representation of uncertainty evaluation results.

Soybean is an important crop that is grown worldwide. Flowering time is a critical agricultural trait determining successful reproduction and yields. For plants, light and temperature are important environmental factors that regulate flowering time. Soybean is a typical short-day (SD) plant, and many studies have elucidated the fine-scale mechanisms of how soybean responds to photoperiod. Low temperature can delay the flowering time of soybean, but little is known about the detailed mechanism of how temperature affects soybean flowering. In this study, we isolated GmFLC-like from soybean, which belongs to the FLOWERING LOCUS C clade of the MADS-box family and is intensely expressed in soybean leaves. Heterologous expression of GmFLC-like results in a delayed-flowering phenotype in Arabidopsis. Additional experiments revealed that GmFLC-like is involved in long-term low temperature-triggered late flowering by inhibiting FT gene expression. In addition, yeast one-hybrid, dual-luciferase reporter assay, and electrophoretic mobility shift assay revealed that the GmFLC-like protein could directly repress the expression of FT2a by physically interacting with its promoter region. Taken together, our results revealed that GmFLC-like functions as a floral repressor involved in flowering time during treatments with various low temperature durations. As the only the FLC gene in soybean, GmFLC-like was meaningfully retained in the soybean genome over the course of evolution, and this gene may play an important role in delaying flowering time and providing protective mechanisms against sporadic and extremely low temperatures.

Background: Despite their ubiquitous use and several safety incidents involving cosmetics for children in China, there is little research on adverse reactions to cosmetics in children. Objectives: We assessed the cosmetic adverse reactions (CARs) reports submitted to the Chongqing Drug Administration in China for children, to understand the characteristics of CARs in a pediatric population and determine whether useful insights can be derived. Methods: We extracted the data file of the Chongqing Drug Administration's cosmetic adverse events reporting system from 2017 to 2021, and screened the information of people under the age of 18 years for analysis. Results: A total of 589 children were reported; of them, 475 female children and 114 male children, aged 1-17 years, and 89.6% were diagnosed with cosmetic contact dermatitis. Itching and burning were the most prominent symptoms and accounted for 83.4% and 40.2%, respectively. The most frequently reported clinical sign was erythema (73.3%) followed by papule (37.9%). The face is the most vulnerable location to lesions, accounting for 80.8% of all areas, with girls having a significantly higher rate of facial and scalp damage than boys. The majority of the CARs were reported with cream, lotion, and toner for the skin (45.9%) and facial or body cleansing products (15.4%), and most of these products were purchased from authoritative shops. Conclusion: Although adults are the main group of people who use cosmetics, due to the special physiological structure of children, the safety of children's cosmetics should be given more attention. In addition, pediatricians and dermatologists should be active in submitting reports of adverse cosmetic events and encouraging consumers to do so likewise in situations in which a product adversely affects a child's health. [ABSTRACT FROM AUTHOR]