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Abstract Background Reproduction in women is at risk due to exposure to chemicals that can disrupt the endocrine system during different windows of sensitivity throughout life. Steroid hormone levels are fundamental for the normal development and function of the human reproductive system, including the ovary. This study aims to elucidate steroidogenesis at different life-stages in human ovaries. Methods We have developed a sensitive and specific LC-MS/MS method for 21 important steroid hormones and measured them at different life stages: in media from cultures of human fetal ovaries collected from elective terminations of normally progressing pregnancy and in media from adult ovaries from Caesarean section patients, and follicular fluid from women undergoing infertility treatment. Statistically significant differences in steroid hormone levels and their ratios were calculated with parametric tests. Principal component analysis (PCA) was applied to explore clustering of the ovarian-derived steroidogenic profiles. Results Comparison of the 21 steroid hormones revealed clear differences between the various ovarian-derived steroid profiles. Interestingly, we found biosynthesis of both canonical and “backdoor” pathway steroid hormones and corticosteroids in first and second trimester fetal and adult ovarian tissue cultures. 17α-estradiol, a less potent naturally occurring isomer of 17β-estradiol, was detected only in follicular fluid. PCA of the ovarian-derived profiles revealed clusters from: adult ovarian tissue cultures with relatively high levels of androgens; first trimester and second trimester fetal ovarian tissue cultures with relatively low estrogen levels; follicular fluid with the lowest androgens, but highest corticosteroid, progestogen and estradiol levels. Furthermore, ratios of specific steroid hormones showed higher estradiol/ testosterone and estrone/androstenedione (indicating higher CYP19A1 activity, p

Objective The COVID-19 pandemic has spurred an increased interest in online healthcare and a surge in usage of online healthcare platforms, leading to a proliferation of user-generated online physician reviews. Yet, distinguishing between genuine and fake reviews poses a significant challenge. This study aims to address the challenges delineated above by developing a reliable and effective fake review detection model leveraging deep learning approaches based on a fake review dataset tailored to the context of Chinese online medical platforms. Methods Inspired by prior research, this paper adopts a crowdsourcing approach to assemble the fake review dataset for Chinese online medical platforms. To develop the fake review detection models, classical machine learning models, along with deep learning models such as Convolutional Neural Network and Bidirectional Encoder Representations from Transformers, were applied. Results Our experimental deep learning model exhibited superior performance in identifying fake reviews on online medical platforms, achieving a precision of 98.36% and an F2-Score of 97.97%. Compared to the traditional machine learning models (i.e., logistic regression, support vector machine, random forest, ridge regression), this represents an 8.16% enhancement in precision and a 7.7% increase in F2-Score. Conclusion Overall, this study provides a valuable contribution toward the development of an effective fake physician review detection model for online medical platforms.

In agricultural ecosystems, incorporation of crop residues has been practiced as a recycling approach for sustaining soil organic matter (SOM) and soil fertility. However, how crop residue amendments in different forms (direct straw return, converted as manure and pyrolyzed as biochar) affect soil organic carbon (SOC) pools and SOM composition is not well known. In this study, a short-term (2015–2019) field experiment in paddy soil was conducted with a one-time maize residue amendment, consistently in a single doses of 10 Mg ha−1 organic carbon (OC) equivalent, in three forms: air-dried straw (CS), cattle manure (CM) and biochar (CB). No residue amendment (CK) was used as control. Topsoil organic matter changes were analysed using 13C isotopic tracing, biomarker analysis, and solid-state 13C nuclear magnetic resonance spectroscopy in combination with soil aggregate density/size fractionation. After four cropping cycles following amendment, SOC content was unchanged under CS and CM but increased by 24% under CB; However, the OC pool ratio of particulate organic matter (POM) to mineral-associated organic matter (MAOM) significantly increased under all amendments compared to CK. The δ13C values indicated that maize-derived OC was preserved the most in the POM within the macroaggregates, particularly under CB. Regarding the molecular composition, all residue amendments increased the abundance ratio of plant- to microbe-derived lipids. Plant-derived lipids were primarily concentrated in macroaggregates, whereas microbial lipids were more prevalent in the silt–clay fractions. Lignin phenols were significantly enriched only in microaggregates under CS relative to CK. Overall, SOM changes in the paddy topsoil following crop residue amendment in different forms were depicted by OC pool redistribution and molecular composition alteration. The study highlighted that biochar amendment, instead of straw or manure, greatly enhanced SOC accumulation by promoting macro-aggregation, which in turn preserved plant-derived carbon through the direct input of the persistent char in a rice paddy.

Abstract Zero thermal expansion (ZTE) alloys with high mechanical response are crucial for their practical usage. Yet, unifying the ZTE behavior and mechanical response in one material is a grand obstacle, especially in multicomponent ZTE alloys. Herein, we report a near isotropic zero thermal expansion (α l = 1.10 × 10−6 K−1, 260–310 K) in the natural heterogeneous LaFe54Co3.5Si3.35 alloy, which exhibits a super-high toughness of 277.8 ± 14.7 J cm−3. Chemical partition, in the dual-phase structure, assumes the role of not only modulating thermal expansion through magnetic interaction but also enhancing mechanical properties via interface bonding. The comprehensive analysis reveals that the hierarchically synergistic enhancement among lattice, phase interface, and heterogeneous structure is significant for strong toughness. Our findings pave the way to tailor thermal expansion and obtain prominent mechanical properties in multicomponent alloys, which is essential to ultra-stable functional materials.

Abstract Laser powder-bed fusion (L-PBF) additive manufacturing presents ample opportunities to produce net-shape parts. The complex laser-powder interactions result in high cooling rates that often lead to unique microstructures and excellent mechanical properties. Refractory high-entropy alloys show great potential for high-temperature applications but are notoriously difficult to process by additive processes due to their sensitivity to cracking and defects, such as un-melted powders and keyholes. Here, we present a method based on a normalized model-based processing diagram to achieve a nearly defect-free TiZrNbTa alloy via in-situ alloying of elemental powders during L-PBF. Compared to its as-cast counterpart, the as-printed TiZrNbTa exhibits comparable mechanical properties but with enhanced elastic isotropy. This method has good potential for other refractory alloy systems based on in-situ alloying of elemental powders, thereby creating new opportunities to rapidly expand the collection of processable refractory materials via L-PBF.

Background & Aims: The functional maturation of the liver largely occurs after birth. In the early stages of life, the liver of a newborn encounters enormous high-fat metabolic stress caused by the consumption of breast milk. It is unclear how the maturing liver adapts to high lipid metabolism. Liver sinusoidal endothelial cells (LSECs) play a fundamental role in establishing liver vasculature and are decorated with many glycoproteins on their surface. The Slc35a1 gene encodes a cytidine-5'-monophosphate (CMP)-sialic acid transporter responsible for transporting CMP-sialic acids between the cytoplasm and the Golgi apparatus for protein sialylation. This study aimed to determine whether endothelial sialylation plays a role in hepatic vasculogenesis and functional maturation. Methods: Endothelial-specific Slc35a1 knockout mice were generated. Liver tissues were collected for histologic analysis, lipidomic profiling, RNA sequencing, confocal immunofluorescence, and immunoblot analyses. Results: Endothelial Slc35a1-deficient mice exhibited excessive neonatal hepatic lipid deposition, severe liver damage, and high mortality. Endothelial deletion of Slc35a1 led to sinusoidal capillarization and disrupted hepatic zonation. Mechanistically, vascular endothelial growth factor receptor 2 (VEGFR2) in LSECs was desialylated and VEGFR2 signaling was enhanced in Slc35a1-deficient mice. Inhibition of VEGFR2 signaling by SU5416 alleviated lipid deposition and restored hepatic vasculature in Slc35a1-deficient mice. Conclusions: Our findings suggest that sialylation of LSECs is critical for maintaining hepatic vascular development and lipid homeostasis. Targeting VEGFR2 signaling may be a new strategy to prevent liver disorders associated with abnormal vasculature and lipid deposition.

Abstract Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution (SCRaMbLE) is a promising tool to study genomic rearrangements. However, the potential of SCRaMbLE to study genomic rearrangements is currently hindered, because a strain containing all 16 synthetic chromosomes is not yet available. Here, we construct SparLox83R, a yeast strain containing 83 loxPsym sites distributed across all 16 chromosomes. SCRaMbLE of SparLox83R produces versatile genome-wide genomic rearrangements, including inter-chromosomal events. Moreover, when combined with synthetic chromosomes, SCRaMbLE of hetero-diploids with SparLox83R leads to increased diversity of genomic rearrangements and relatively faster evolution of traits compared to hetero-diploids only with wild-type chromosomes. Analysis of the SCRaMbLEd strain with increased tolerance to nocodazole demonstrates that genomic rearrangements can perturb the transcriptome and 3D genome structure and consequently impact phenotypes. In summary, a genome with sparsely distributed loxPsym sites can serve as a powerful tool for studying the consequence of genomic rearrangements and accelerating strain engineering in Saccharomyces cerevisiae.

Abstract Layered metal oxides are promising cathode materials for sodium-ion batteries (SIBs) due to their high theoretical specific capacity and wide Na+ diffusion channels. However, the irreversible phase transitions and cationic/anionic redoxes cause fast capacity decay. Herein, P2-type Na0.67Mg0.1Mn0.8Fe0.1O2 (NMMF-1) cathode material with moderate active Fe3+ doping has been designed for sodium storage. Uneven Mn3+/Mn4+distribution is observed in NMMF-1 and the introduction of Fe3+ is beneficial for reducing the Mn3+ contents both at the surface and in the bulk to alleviate the Jahn–Teller effect. The moderate Fe3+/Fe4+ redox can realize the best tradeoff between capacity and cyclability. Therefore, the NMMF-1 demonstrates a high capacity (174.7 mAh g−1 at 20 mA g−1) and improved cyclability (78.5% over 100 cycles) in a wide-voltage range of 1.5–4.5 V (vs. Na+/Na). In-situ X-ray diffraction reveals a complete solid-solution reaction with a small volume change of 1.7% during charge/discharge processes and the charge compensation is disclosed in detail. This study will provide new insights into designing high-capacity and stable layered oxide cathode materials for SIBs.

Abstract Li‐rich Mn‐based layered oxides (LLO) hold great promise as cathode materials for lithium‐ion batteries (LIBs) due to their unique oxygen redox (OR) chemistry, which enables additional capacity. However, the LLOs face challenges related to the instability of their OR process due to the weak transition metal (TM)‐oxygen bond, leading to oxygen loss and irreversible phase transition that results in severe capacity and voltage decay. Herein, a synergistic electronic regulation strategy of surface and interior structures to enhance oxygen stability is proposed. In the interior of the materials, the local electrons around TM and O atoms may be delocalized by surrounding Mo atoms, facilitating the formation of stronger TM─O bonds at high voltages. Besides, on the surface, the highly reactive O atoms with lone pairs of electrons are passivated by additional TM atoms, which provides a more stable TM─O framework. Hence, this strategy stabilizes the oxygen and hinders TM migration, which enhances the reversibility in structural evolution, leading to increased capacity and voltage retention. This work presents an efficient approach to enhance the performance of LLOs through surface‐to‐interior electronic structure modulation, while also contributing to a deeper understanding of their redox reaction.

ObjectiveTo visualize and analyze the literature related to sciatic nerve injury treatment from January 2019 to December 2023, and summarize the current status, hotspots, and development trends of research in this field.MethodsUsing CiteSpace and VOSviewer software, we searched the Web of Science database for literature related to the treatment of sciatic nerve injury. Then we analyzed and plotted visualization maps to show the number of publications, countries, institutions, authors, keywords, references, and journals.ResultsA total of 2,653 articles were included in the English database. The annual number of publications exceeded 230, and the citation frequency increased yearly. The United States and China were identified as high-influence nations in this field. Nantong University was the leading institution in terms of close cooperation among institutions. The authors Wang Yu had the highest number of publications and were highly influential in this field. Keyword analysis and reference Burst revealed a research focus on nerve regeneration and neuropathic pain, which involve regenerative medicine and neural tissue engineering. Chronic pain resulting from sciatic nerve injury often manifests alongside anxiety, depression, cognitive-behavioral disorders, and other issues. Interventions such as stem cells, electrical stimulation, electroacupuncture, total joint replacement, pharmacological interventions, gene therapy, nerve conduits, chitosan scaffolds, and exercise promote nerve repair and alleviate pain. Schwann cells have been the focus of much attention in nerve repair and regeneration. Improving the outcome of sciatic nerve injury is a current research challenge and focus in this field. Based on keyword Burst, nerve conduits and grafts may become a potential research hotspot in the treatment of sciatic nerve injury.ConclusionThis visual analysis summarizes research trends and developments of sciatic nerve injury treatment and predicts potential research frontiers and hot directions.

Exposure to persistent organic pollutants (POPs), such as dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs), has historically been linked to population collapses in wildlife. Despite international regulations, these legacy chemicals are still currently detected in women of reproductive age, and their levels correlate with reduced ovarian reserve, longer time-to-pregnancy, and higher risk of infertility. However, the specific modes of action underlying these associations remain unclear. Here, we examined the effects of five commonly occurring POPs − hexachlorobenzene (HCB), p,p'-dichlorodiphenyldichloroethylene (DDE), 2,3,3′,4,4′,5-hexachlorobiphenyl (PCB156), 2,2′,3,4,4′,5,5′-heptachlorobiphenyl (PCB180), perfluorooctane sulfonate (PFOS) − and their mixture on human ovaries in vitro. We exposed human ovarian cancer cell lines COV434, KGN, and PA1 as well as primary ovarian cells for 24 h, and ovarian tissue containing unilaminar follicles for 6 days. RNA-sequencing of samples exposed to concentrations covering epidemiologically relevant levels revealed significant gene expression changes related to central energy metabolism in the exposed cells, indicating glycolysis, oxidative phosphorylation, fatty acid metabolism, and reactive oxygen species as potential shared targets of POP exposures in ovarian cells. Alpha-enolase (ENO1), lactate dehydrogenase A (LDHA), cytochrome C oxidase subunit 4I1 (COX4I1), ATP synthase F1 subunit alpha (ATP5A), and glutathione peroxidase 4 (GPX4) were validated as targets through qPCR in additional cell culture experiments in KGN. In ovarian tissue cultures, we observed significant effects of exposure on follicle growth and atresia as well as protein expression. All POP exposures, except PCB180, decreased unilaminar follicle proportion and increased follicle atresia. Immunostaining confirmed altered expression of LDHA, ATP5A, and GPX4 in the exposed tissues. Moreover, POP exposures modified ATP production in KGN and tissue culture. In conclusion, our results demonstrate the disruption of cellular energy metabolism as a novel mode of action underlying POP-mediated interference of follicle growth in human ovaries.

Abstract The genome of an organism is inherited from its ancestor and continues to evolve over time, however, the extent to which the current version could be altered remains unknown. To probe the genome plasticity of Saccharomyces cerevisiae, here we replace the native left arm of chromosome XII (chrXIIL) with a linear artificial chromosome harboring small sets of reconstructed genes. We find that as few as 12 genes are sufficient for cell viability, whereas 25 genes are required to recover the partial fitness defects observed in the 12-gene strain. Next, we demonstrate that these genes can be reconstructed individually using synthetic regulatory sequences and recoded open-reading frames with a “one-amino-acid-one-codon” strategy to remain functional. Finally, a synthetic neochromsome with the reconstructed genes is assembled which could substitute chrXIIL for viability. Together, our work not only highlights the high plasticity of yeast genome, but also illustrates the possibility of making functional eukaryotic chromosomes from entirely artificial sequences.

Background:The neuropeptide galanin has been shown to exhibit anticonvulsant effects in animal models. However, only a few studies have attempted to identify the galanin receptor subtype (s) involved in this effect. In the present study, the expression of galanin and that of its receptors in a rat model of temporal lobe epilepsy was studied to reveal the epileptogenesis-related alterations.Methods:Pilocarpine-inducted status epilepticus (SE) rat model was used for temporal lobe epilepsy. Galanin and galanin receptor mRNA was detected by Real-time polymerase chain reaction in dorsal hippocampus of rats at three different time points following SE: at the acute phase (24h), latent period (7 days), and chronic epileptic period (8 weeks). Using immunohistochemistry, galanin positive fibers and bodies were also observed.Results:In the acute seizure phase, a significant up-regulation of the galanin mRNA was observed in the hippocampus. Meanwhile, galanin-positive cells appeared, while galanin-positive fibers disappeared in the hilus of the dentate gyrus, stratum radiatum of CA1, and stratum lucidum of CA3, indicating an increase in galanin synthesis and release during the acute seizure phase. The gene expression analysis also indicated a significant increase in the transcription of galanin receptors GalR1 and GalR3 24h after SE. The increased levels of GalR1 mRNA were also observed in the latent and chronic epileptic periods.Conclusion:In general, these data suggest that adaptive changes occur in the galanin system during epileptogenesis that may affect its antiepileptic effects. Furthermore, these changes should be taken into account when attempting to pharmacologically modulate this system.

Abstract How wind generates ocean surface waves is a classic fluid mechanics problem, and it is commonly believed that the resonance mechanism between wind and surface waves, first proposed by Phillips in 1957, is responsible for the early stages of wind-wave generation. However, there has not been any conclusive study to fully validate this theory. We present the results of a combined theoretical and computational study of the initial response of a calm water surface to turbulent wind and an analysis in terms of the Phillips theory on wind-wave generation. We address a nascent stage of wind-wave generation after the sudden impact of a turbulent wind on a calm water surface but before the initial stage described by Phillips. We show that in such nascent stage, the wave energy grows over time following a quartic law. We provide direct numerical evidence of the resonance mechanism during the initial stage and clarify its role in the formation of the heterogeneous wave energy distribution in the spectral space.

The hydrothermal dolomitization, facilitated by basement fault activities, had an important impact on the Permian Maokou Formation dolomite in the Sichuan Basin, which experienced complex diagenesis and presented strong reservoir heterogeneity. The source and age of diagenetic fluids in this succession remain controversial. In this study, various analyses were implemented on samples collected from outcrops and wells near the No. 15 fault in the eastern Sichuan Basin to reconstruct the multi-stage fluid activity and analyze the impact on reservoir development, including petrology, micro-domain isotopes, rare earth elements, homogenization temperature of fluid inclusions, and Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) U-Pb dating. The homogenization temperature of primary brine inclusions in fine-grained matrix dolomite and saddle dolomite is concentrated between 100 and 150 °C, which indicates that the impacts of abnormally high temperatures of other geological bodies. The δ13C and δ18O value and low 87Sr/86Sr value indicate that the diagenetic fluid of fine-grained matrix dolomite is mainly Permian seawater. The U-Pb ages of fine-grained matrix dolomite are ~260 Ma, which coincides with the age of the main magmatism of Emeishan Large Igneous Province (ELIP), and hydrothermal fluid provided a favorable high-temperature environment in the penecontemporaneous stage. While highly radiogenic 87Sr/86Sr compositions suggests those of saddle dolomite, the high-temperature Sr-rich formation fluid. The U-Pb ages of saddle dolomite are 245–250 Ma, which coincides with the age of the 255~251 Ma magmatism of ELIP. This indicates that those should be the diagenetic products of the ELIP hydrothermal fluid in the shallow burial stage. The U-Pb age of coarse-grained calcite is 190–220 Ma, and it should be the diagenetic product of the deep burial stage. Brine inclusions associated with primary methane inclusions were developed in coarse-grained calcite, with a homogenization temperature range of 140.8–199.8 °C, which indicates that the formation fluid activities were related to hydrocarbon charging. The Permian Maokou Formation dolomite was firstly formed in the penecontemporaneous shallow burial stage, and then it was subjected to further hydrothermal dolomitization due to the basement faulting and the abnormally high heat flow during the active period of ELIP. Hydrothermal dolomitization contributed to the formation and maintenance of intercrystalline and dissolution pores, whereas it also formed saddle dolomite to fill the pores, and reduce the pore space. The influence of deep fluid activities on reservoir evolution is further distinguished.

Over the past 35 years, studies conducted worldwide have revealed a threefold increase in the incidence of thyroid cancer. Strain elastography is a new imaging technique to identify benign and malignant thyroid nodules due to its sensitivity to tissue stiffness. However, there are certain limitations of this technique, particularly in terms of standardization of the compression process, evaluation of results and several assumptions used in commercial strain elastography modes for the purpose of simplifying imaging analysis. In this work, we propose a novel conditional generative adversarial network (TSE-GAN) for automatically generating thyroid strain elastograms, which adopts a global-to-local architecture to improve the ability of extracting multi-scale features and develops an adaptive deformable U-net structure in the sub-generator to apply effective deformation. Furthermore, we introduce a Lab-based loss function to induce the networks to generate realistic thyroid elastograms that conform to the probability distribution of the target domain. Qualitative and quantitative assessments are conducted on a clinical dataset provided by Shanghai Sixth People’s Hospital. Experimental results demonstrate that thyroid elastograms generated by the proposed TSE-GAN outperform state-of-the-art image translation methods in meeting the needs of clinical diagnostic applications and providing practical value.

In this study, we evaluate the “propose-review” framework for the mitigation of bias in machine classification. The framework considers Bob, who aims to protect sensitive dimensions from discrimination, and Alice, who sends proposals to Bob for using his data to construct a target classifier. The goal is to minimize discrimination in Bob’s protected dimension while preserving the desired separating capability of Alice’s classifier. The method does not assume predefined bias terms, does not anchor on specific fairness metrics, and is independent of Alice’s classifier choice. We consider that data attributes have different concentrations of the latent bias axes; assessing attributes’ concentrations in the ruled bias hyperspace helps identify bias-prone attributes and inform bias-mitigating data transforms. To this end, we assess attributes’ contribution to the separating capability of Bob’s conceptual classifier. We then compute the pairwise distances between attributes, and by applying multidimensional scaling to the distance matrix, we infer the axes of bias and establish a bias-attribute mapping. Bias mitigation is achieved by greedily applying appropriate data transforms to bias-prone attributes. The method works desirably across 21 classifiers and 7 datasets, bringing about substantial bias reduction under different choices of the protected dimension and the fairness metric. Compared to adversarial debiasing, the method better exploits the fairness-utility trade-off in machine classification.

Abstract Neuroinflammation manifests following injury to the central nervous system (CNS) and M1/M2 polarization of microglia is closely associated with the development of this neuroinflammation. In this study, multiple databases were used to collect targets regarding luteolin and microglia polarization. After obtaining a common target, a protein–protein interaction (PPI) network was created and further analysis was performed to obtain the core network. Molecular docking of the core network with luteolin after gene enrichment analysis. In vitro experiments were used to examine the polarization of microglia and the expression of related target proteins. A total of 77 common targets were obtained, and the core network obtained by further analysis contained 38 proteins. GO and KEGG analyses revealed that luteolin affects microglia polarization in regulation of inflammatory response as well as the interleukin (IL)-17 and tumor necrosis factor (TNF) signaling pathways. Through in vitro experiments, we confirmed that the use of luteolin reduced the expression of inducible nitric oxide synthase (iNOS), IL-6, TNF-α, p-NFκBIA (p-IκB-α), p-NFκB p65, and MMP9, while upregulating the expression of Arg-1 and IL-10. This study reveals various potential mechanisms by which luteolin induces M2 polarization in microglia to inhibit the neuroinflammatory response.

Low temperatures pose a significant threat to plant growth and development. Studies have shown that aquaporins (AQPs), as the main functional proteins on the cell membrane regulating water ingress and egress, play a vital role in maintaining dynamic water balance when plants face cold stress. Catalpa bungei, an important timber and ornamental tree species, has its cultivation range significantly limited by its poor cold tolerance. However, no study has been found aiming to identify its aquaporin gene family. This study aims to fill this gap using two C. bungei cultivars with differing cold tolerance as experimental material: “Qiuza 1”, which is less cold-tolerant, and “Qiuza 2”, which is more cold-tolerant. The plants were subjected to low-temperature stress at 4 °C for 24 h. Using high-throughput molecular sequencing technology, a transcriptome sequencing of the leaves was performed at 0, 6, 12, and 18 h of cold stress. Fifteen candidate aquaporin genes in C. bungei (CbAQP) were identified. Phylogenetic analysis showed that the CbAQP gene family is divided into five subfamilies: 5 PIPs, 4 TIPs, 3 NIPs, 2 SIPs, and 1 XIP. By analyzing AQPs related to cold stress in other plants and the expression patterns of CbAQP genes, 12 CbAQP genes related to cold stress were identified. The genes that responded positively include CbPIP2;5, CbPIP1;2, CbTIP4;1, and CbNIP2;1. The results provide a foundation for further analysis of the biological functions of candidate CbAQP genes related to cold tolerance and offer theoretical support for improving seedling quality, cold-resistant genetic breeding, and expanding its distribution range.

Global epidemics, wars, and lack of resources pose threats to society and the tertiary industry. After the world went through a period of de-globalization for a short period of time since the year 2019, the Global tourism industry suffers a fatal blow. The main objective of this paper is to evaluate the economic vulnerability of a specialized tourism city Dali (a typical tourism city in China) and propose risk avoidance strategies for its sustainable tourism development. This paper establishes a vulnerability assessment model from the aspects of sensitivity and responding capacity by using the set pair analysis (SPA) model to evaluate the economic vulnerability of Dali. The obstacle evaluation model and the entropy value method were used to analyze its obstacle factors. This research employs the National Economic and Social Development Statistics as its primary data source, augmented by the Statistical Yearbook and Yearbooks from different years. The results show that the change of the vulnerability of Dali's tourism economic system is relatively stable, but in general the vulnerability is at a high level in most years. According to the analysis of obstacle factors, the ratio of tourist arrivals to local population, Elasticity coefficient of tourism to industrial growth and National economy (GDP) output value are the main obstacles to reduce the vulnerability of Dali's tourism economy.

In practical engineering, the total vertical stress in the soil layer is not constant due to stress diffusion, and varies with time and depth. Therefore, the purpose of this paper is to investigate the effect of stress diffusion on the two-dimensional (2D) plane strain consolidation properties of unsaturated soils when the stress varies with time and depth. A series of semi-analytical solutions in terms of excess pore air and water pressures and settlement for 2D plane strain consolidation of unsaturated soils can be derived with the joint use of Laplace transform and Fourier sine series expansion. Then, the inverse Laplace transform of the semi-analytical solution is given in the time domain using a self-programmed code based on Crump's method. The reliability of the obtained solutions is proved by the degeneration. Finally, the 2D plots of excess pore pressures and the curves of settlement varying with time, considering different physical parameters of unsaturated soil stratum and depth-dependent stress, are depicted and analyzed to study the 2D plane strain consolidation properties of unsaturated soils subjected to the depth-dependent stress.

Technological advancements, particularly in the field of artificial intelligence (AI) have played an increasingly important role in transforming education. More recently, ground-breaking AI applications like ChatGPT have demonstrated the potential to bring radical changes to the educational landscape due to their capability to understand complex questions, generate plausible responses and human-like writing, and assist with the completion of complex tasks. However, ChatGPT has limitations in the quality of its output, such as the inclusion of inaccurate, fabricated and biased information and the lack of critical thinking and in-depth understanding. The combinations of these capabilities and limitations along with external factors (e.g., the growing demand for personalized learning support, the irresponsible and unethical use of AI) presents a range of opportunities and challenges to the potential use of ChatGPT in education. This paper presents a thorough SWOT (strength, weakness, opportunity, threat) analysis of ChatGPT, based on which we propose how ChatGPT can be properly integrated into teaching and learning practice to harness its potential in education.

AimTo develop and internally validate a novel predictive model for SDHB mutations in pheochromocytomas and retroperitoneal paragangliomas (PPGLs).MethodsClinical data of patients with PPGLs who presented to Peking Union Medical College Hospital from 2013 to 2022 and underwent genetic testing were retrospectively collected. Variables were screened by backward stepwise and clinical significance and were used to construct multivariable logistic models in 50 newly generated datasets after the multiple imputation. Bootstrapping was used for internal validation. A corresponding nomogram was generated based on the model. Sensitivity analyses were also performed.ResultsA total of 556 patients with PPGLs were included, of which 99 had a germline SDHB mutation. The prediction model revealed that younger age of onset [Odds ratio (OR): 0.93, 95% CI: 0.91-0.95], synchronous metastasis (OR: 6.43, 95% CI: 2.62-15.80), multiple lesion (OR: 0.22, 95% CI: 0.09-0.54), retroperitoneal origin (OR: 5.72, 95% CI: 3.13-10.47), negative 131I-meta-iodobenzylguanidine (MIBG) (OR: 0.34, 95% CI: 0.15-0.73), positive octreotide scintigraphy (OR: 3.24, 95% CI: 1.25-8.43), elevated 24h urinary dopamine (DA) (OR: 1.72, 95% CI: 0.93-3.17), NE secretory type (OR: 2.83, 95% CI: 1.22- 6.59), normal secretory function (OR: 3.04, 95% CI: 1.04-8.85) and larger tumor size (OR: 1.09, 95% CI: 0.99-1.20) were predictors of SDHB mutations in PPGLs, and showed good and stable predictive performance with a mean area under the ROC curve (AUC) of 0.865 and coefficient of variation of 2.2%.ConclusionsThis study provided a novel and useful tool for predicting SDHB mutations by integrating easily obtained clinical data. It may help clinicians select suitable genetic testing methods and make appropriate clinical decisions for these high-risk patients.

Background: The breakthrough development of novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines and oral antivirals have played a critical role in curtailing the spread of the pandemic and dramatically reducing the morbidity and mortality rates among those infected. Among these oral antivirals, nirmatrelvir/ritonavir (NR) has been repurposed successfully for use against coronavirus disease-2019 (COVID-19) and is now readily available on the market with promising therapeutic effects. The availability of convenient and effective NR treatments for COVID-19 greatly mitigates the severity of the epidemic and contributes to an early end to the pandemic. Furthermore, certain patient subgroups, specifically those with rheumatic disease (RD) who are currently undergoing intensive immunodeficiency and/or immunosuppressive treatments, continue to be vulnerable and at a higher risk of experiencing severe consequences from COVID-19. Additionally, it has also been observed that NR exhibited prevalent drug-drug interactions of clinical significance, and more instances of COVID-19 rebound were being recognized with increasing frequency.Methods: A retrospective cohort study was conducted on a real-world RD population who were infected with SARS-CoV-2 and treated with NR. The time of symptom resolution, length of hospitalization, and response rate were assessed. Results were compared among the standard regimen and non-standard regimen groups, early NR regimen and late NR regimen groups, and the NR indication regimen and NR non-indication regimen groups. During the course, all grades of adverse drug reactions (ADRs) directly associated with NR administration and associated with drug-drug interactions (DDIs) were also monitored.Results: A total of 32 patients with RD, who were infected with SARS-CoV-2 and received NR, were retrospectively identified and divided into different groups. We found that the standard regimen group and the early NR regimen group had a shorter median time of symptom resolution compared to the control group [9.0 (interquartile range [IQR], 8.3-11.3) vs. 21.5 (IQR16.0-24.0) days, p < 0.001 and 9.0 (IQR 8.3-11.3) vs. 23.0 (IQR 18.0-24.0) days, p = 0.0]. We further found that even if the NR administration time exceeds 5 days, patients with RD who receive the NR indication regimen can still derive certain benefits from it. The proportion of patients who showed symptom improvement was higher in the NR indication regimen compared to the NR non-indication regimen group (n = 13/17 vs. 3/6, 76.5% vs. 50.0%) at the end of follow-up, and there was a statistical difference (p = 0.0) in the response rate of patients between the two groups. We also analyzed the effect of comorbidities on patient response rates and found that the percentage of patients who showed symptom improvement was higher in the group with 5 days may also mitigate progression to severe disease and is a viable strategy. Our results highlight the importance of early utilization and/or NR indication, which may yield clinical advantages for patients with RD infected with SARS-CoV-2.

Introduction: Ticagrelor is extensively utilized for the treatment of acute coronary syndromes (ACS), but its platelet aggregation inhibitory effects can potentially result in tissue bleeding, posing a serious risk to patients’ lives.Methods: In this study, we developed highly sensitive full length anti-ticagrelor Quenchbodies (Q-bodies) for fast monitoring of ticagrelor both in solution and serum for the first time. Ticagrelor coupled with N- hydroxysuccinimide (Ticagrelor-NHS) ester was also designed and synthesized for interaction and biological activity detection.Results: Both ATTO-labeled MEDI2452 (2452A) Q-body and TAMRA-labeled IgG 152 (152T) Q-body demonstrated efficient detection of ticagrelor and its active metabolite (TAM). The 2452A Q-body exhibited a broader detection range, while the 152T Q-body displayed a lower limit of detection (LOD). Under physiological conditions (Ticagrelor:TAM, 3:1), the concentration of ticagrelor was further measured, yielding LOD values of 4.65 pg/mL and 2.75 pg/mL for the two Q-bodies, with half-maximal effect concentrations of 8.15 ng/mL and 3.0 ng/mL, respectively.Discussion: Compared with traditional liquid chromatography-mass spectrometry (LC-MS) methods, anti-ticagrelor Q-bodies have higher sensitivity and detection speed. It enabled the completion of analysis within 3 min, facilitating rapid preoperative detection of blood drug concentration in ACS to determine the feasibility of surgery and mitigate the risk of intraoperative and postoperative hemorrhage. The swift detection of ticagrelor holds promise for enhancing individualized drug administration, preventing adverse reactions, and providing preoperative guidance.

A prevailing challenge when testing chemicals for their potential to cause female reproductive toxicity is the lack of appropriate toxicological test methods. We hypothesized that starting a 28-day in vivo toxicity study already at weaning, instead of in adulthood, would increase the sensitivity to detect endocrine disruptors due to the possibility of including assessment of pubertal onset. We compared the sensitivity of two rat studies using pubertal or adult exposure. We exposed the rats to two well-known human endocrine disruptors, the estrogen diethylstilbestrol (DES; 0.003, 0.012, 0.048 mg/kg bw/day) and the steroid synthesis inhibitor ketoconazole (KTZ; 3, 12, 48 mg/kg bw/day). Specifically, we addressed the impact on established endocrine-sensitive endpoints including day of vaginal opening (VO), estrous cyclicity, weights of reproductive organs and ovarian histology. After 28 days of exposure, starting either at weaning or at 9 weeks of age, DES exposure altered estrous cyclicity, reduced ovary weight as well as number of antral follicles and corpora lutea. By starting exposure at weaning, we could detect advanced day of VO in DES-exposed animals despite a lower body weight. Some endpoints were affected mainly with adult exposure, as DES increased liver weights in adulthood only. For KTZ, no effects were seen on time of VO, but adrenal and liver weights were increased in both exposure scenarios, and adult KTZ exposure also stimulated ovarian follicle growth. At first glance, this would indicate that a pubertal exposure scenario would be preferrable as timing of VO may serve as sensitive indicator of endocrine disruption by estrogenic mode of action. However, a higher sensitivity for other endocrine targets may be seen starting exposure in adulthood. Overall, starting a 28-day study at weaning with inclusion of VO assessment would mainly be recommended for substances showing estrogenic potential e.g., in vitro, whereas for other substances an adult exposure scenario may be recommended.

The aim of this scoping review was to critically review and synthesize the evidence concerning the relationship between traumatic peripheral lesions and cognitive impairments. Five electronic databases (Medline, Cinahl, Psycinfo, Embase, and Cochrane Library) were searched in their entirety using the two key words “cognition” and “trauma”. An additional manual search was conducted. All inclusion criteria comprised English language, an assessment of cognition, and the study participants experienced acute peripheral lesion or physical trauma and were aged between 18 and 65 years. The articles were screened for eligibility by two independent reviewers. Disagreements were resolved by discussion or consensus with a third author. A total of 11737 records were identified, of which 10 met the inclusion criteria. Whiplash injury, brachial plexus injury, soft tissue injury around the cervical spine, and fracture were found to be associated with cognitive impairments. The earliest cognitive assessment time point was one-month post injury, while the latest counterpart was 444 months. Cognition was assessed using 20 unique instruments, targeting nine distinct cognitive domains. An overall positive association was found between traumatic peripheral lesions and cognitive impairments. Therefore, further longitudinal research is needed to monitor the changes in cognitive functions post physical trauma.

Electroencephalography (EEG) signals from each channel mainly reflect activities of the brain region close to the channel position, and the activities cooperated by various brain regions are response to the emotion-induced stimuli. In this paper, temporal, spatial and connective features are extracted from EEG signals gotten around the head, and used for emotion recognition via a proposed model, spatial-temporal-connective muti-scale convolutional neural network (STC-CNN). The channel-to-channel connectivity is gotten to describe brain region-to-region cooperation under emotion stimuli. The model obtained an average accuracy of 96.79% and 96.89% in classifying the two emotional dimensions of valence and arousal.

While transmon is the most widely used superconducting qubit, the search for alternative qubit designs with improved characteristic is ongoing. Hyyppä et al. demonstrate a novel superconducting qubit, the unimon, that combines high anharmonicity and protection against low-frequency charge noise and flux noise.

This paper studied the influence of salt concentration on the volatile flavor compounds during the fermentation of Northeast farmhouse soybean paste. HS-SPME-GC-MS combined with electronic nose technology were used to analyze the changes of volatile flavor substances and flavor characteristics of soybean paste with different salt concentrations (8%, 10%, 12%) during the fermentation process (0, 30, 60 d). The differences between samples were statistically analyzed through PCA and cluster analysis. The results of HS-SPME-GC-MS showed that there were 2 flavors with OAV≥0.1 at 0 days of fermentation. At the time of 30 days, 8%, 10% and 12% salt concentration samples of flavor substances with OAV≥0.1 increased to 12, 8 and 8, respectively. At the time of 60 days, 8%, 10% and 12% salt concentration samples of the flavor substances with OAV≥0.1 increased to 19, 11 and 10, respectively. And the OAV values of most flavor substances decreased with the increase of salt concentration. This indicated that salt concentration affected the type and content of volatile flavor compounds. The results of the electronic nose showed that the increase in salt concentration would promote the production of organic sulfur compounds and inhibit the production of alkanes, alcohols and hydride compounds. With the extension of the fermentation time, the methyl, alcohol, aldehyde and ketone compounds in the soybean paste would gradually increase, while the ammonia, short-chain alkanes and organic sulfides would gradually decrease. The results of PCA and cluster analysis showed that the difference between samples with different salt concentrations fermented for 0 days was very small, and with the extension of the fermentation time, the difference between the soybean paste with different salt concentrations would become more and more significant. To sum up, the salt concentration has a significant effect on the volatile flavor components in the Northeast farmhouse soybean paste.

Lithium-sulfur batteries promise high energy density, but polysulfide shuttling acts as a major stumbling block toward practical development. Here, a redox-active interlayer is proposed to confine polysulfides, increase the cell capacity and improve cell cycle life.

We address the problem of data augmentation in a rotating turbulence set-up, a paradigmatic challenge in geophysical applications. The goal is to reconstruct information in two-dimensional (2D) cuts of the three-dimensional flow fields, imagining spatial gaps present within each 2D observed slice. We evaluate the effectiveness of different data-driven tools, based on diffusion models (DMs), a state-of-the-art generative machine learning protocol, and generative adversarial networks (GANs), previously considered as the best-performing method both in terms of point-wise reconstruction and the statistical properties of the inferred velocity fields. We focus on two different DMs recently proposed in the specialized literature: (i) RePaint, based on a heuristic strategy to guide an unconditional DM for flow generation by using partial measurements data, and (ii) Palette, a conditional DM trained for the reconstruction task with paired measured and missing data. Systematic comparison shows that (i) DMs outperform the GAN in terms of the mean squared error and/or the statistical accuracy; (ii) Palette DM emerges as the most promising tool in terms of both point-wise and statistical metrics. An important property of DMs is their capacity for probabilistic reconstructions, providing a range of predictions based on the same measurements, enabling uncertainty quantification and risk assessment.

A gas turbine cooling system is a typical multivariable, strongly coupled, nonlinear system; however, the randomness and large disturbances make it difficult to control the variables precisely. In order to solve the problem of precise process control for multi-input and multi-output coupled systems with flow, pressure, and temperature, this article conducts the following research: (1) Designing a secondary circuit for waste hot water and establishing a water-circulating gas turbine cooling system to improve the efficiency of waste heat utilization. (2) Identifying the coupled system model and establishing a mathematical model of the coupling relationship based on the characteristic data of input and output signals in the gas turbine cooling system. (3) Designing a coupled-system decoupling compensator to weaken the relationships between variables, realizing the decoupling between coupled variables. (4) An Opposition-based Learning Jumping Spider Optimization Algorithm is proposed to be combined with the PID control algorithm, and the parameters of the PID controller are adjusted to solve the intelligent control problems of heat exchanger water inlet flow rate, pressure, and temperature in the gas turbine cooling system. After simulation verification, the gas turbine cooling system based on an Opposition-based Learning Jumping Spider Optimization Algorithm can realize the constant inlet flow rate, with an error of no more than 1 m3/h, constant inlet water temperature, with an error of no more than 0.2 °C, and constant main-pipe pressure, with an error of no more than 0.01 MPa. Experimental results show that a gas turbine cooling system based on the Opposition-based Learning Jumping Spider Optimization Algorithm can accurately realize the internal variable controls. At the same time, it can provide a reference for decoupling problems in strongly coupled systems, the controller parameter optimization problems, and process control problems in complex systems.

Localized turbulence is common in geophysical flows, where the roles of rotation and stratification are paramount. In this study, we investigate the evolution of a stratified turbulent cloud under rotation. Recognizing that a turbulent cloud is composed of vortices of varying scales and shapes, we start our investigation with a single eddy using analytical solutions derived from a linearized system. Compared to an eddy under pure rotation, the stratified eddy shows the physical manifestation of a known potential vorticity mode, appearing as a static stable vortex. In addition, the expected shift from inertial waves to inertial-gravity waves is observed. In our numerical simulations of the turbulent cloud, carried out at a constant Rossby number over a range of Froude numbers, stratification causes columnar structures to deviate from vertical alignment. This deviation increases with increasing stratification, slowing the expansion rate of the cloud. The observed characteristics of these columnar structures are consistent with the predictions of linear theory, particularly in their tilt angles and vertical growth rates, suggesting a significant influence of inertial-gravity waves. Using Lagrangian particle tracking, we have identified regions where wave activity dominates over turbulence. In scenarios of milder stratification, these inertial-gravity waves are responsible for a significant energy transfer away from the turbulent cloud, a phenomenon that attenuates with increasing stratification.

Abstract Background Human endogenous retroviruses (HERVs) result from ancestral infections caused by exogenous retroviruses that became incorporated into the germline DNA and evolutionarily fixed in the human genome. HERVs can be transmitted vertically in a Mendelian fashion and be stably maintained in the human genome, of which they are estimated to comprise approximately 8%. HERV-K (HML1-10) transcription has been confirmed to be associated with a variety of diseases, such as breast cancer, lung cancer, prostate cancer, melanoma, rheumatoid arthritis, and amyotrophic lateral sclerosis. However, the poor characterization of HML-9 prevents a detailed understanding of the regulation of the expression of this family in humans and its impact on the host genome. In light of this, a precise and updated HERV-K HML-9 genomic map is urgently needed to better evaluate the role of these elements in human health. Results We report a comprehensive analysis of the presence and distribution of HERV-K HML-9 elements within the human genome, with a detailed characterization of the structural and phylogenetic properties of the group. A total of 23 proviruses and 47 solo LTR elements were characterized, with a detailed description of the provirus structure, integration time, potential regulated genes, transcription factor binding sites (TFBS), and primer binding site (PBS) features. The integration time results showed that the HML-9 elements found in the human genome integrated into the primate lineage between 17.5 and 48.5 million years ago (mya). Conclusion The results provide a clear characterization of HML-9 and a comprehensive background for subsequent functional studies.

The Dahuoluo pill (DHLP) is a classic Chinese patent medicine used to treat rheumatoid arthritis and other conditions. However, there has been no research on the chemical components of DHLP and the mechanisms by which it ameliorates rheumatoid arthritis. Hence, we analysed the chemical components of DHLP and the DHLP components absorbed in blood by using ultraperformance liquid chromatography-Q-exactive-orbitrap-mass spectrometry. We then used network pharmacology to predict the underlying mechanisms by which DHLP ameliorates rheumatoid arthritis. We identified 153 chemical compounds from DHLP, together with 27 prototype components absorbed in blood. We selected 48 of these compounds as potential active ingredients to explore the mechanism. These compounds are related to 88 significant pathways, which are linked to 18 core targets. This study preliminarily reveals the potential mechanisms by which DHLP ameliorates rheumatoid arthritis and provides a basis for further evaluation of the drug’s efficacy.

Long persistent luminescence of Gd3+ is reported and a possible mechanism of the trivalent lanthanides’ persistent luminescence in wide bandgap hosts is proposed.

Abstract Defect extremal surface is defined by extremizing the Ryu-Takayanagi formula corrected by the quantum defect theory. This is interesting when the AdS bulk contains a defect brane (or string). We introduce a defect extremal surface formula for reflected entropy, which is a mixed state generalization of entanglement entropy measure. Based on a decomposition procedure of an AdS bulk with a brane, we demonstrate the equivalence between defect extremal surface formula and island formula for reflected entropy in AdS3/BCFT2. We also compute the evolution of reflected entropy in evaporating black hole model and find that defect extremal surface formula agrees with island formula.

The booming photothermal therapy (PTT) has achieved great progress in non-invasive oncotherapy, and paves a novel way for clinical oncotherapy. Of note, mild temperature PTT (mPTT) of 42–45 °C could avoid treatment bottleneck of the traditional PTT, including nonspecific injury to normal tissues, vasculature and host antitumor immunity. However, cancer cells can resist mPTT via heat shock response and autophagy, thus leading to insufficient mPTT monotherapy to ablate tumor. To overcome the deficient antitumor efficacy caused by thermo-resistance of cancer cells and mono mPTT, synergistic therapies towards cancer cells have been conducted with mPTT. This review summarizes the recent advances in nanomedicine-potentiated mPTT for cancer treatment, including strategies for enhanced single-mode mPTT and mPTT plus synergistic therapies. Moreover, challenges and prospects for clinical translation of nanomedicine-potentiated mPTT are discussed.

Understanding fine root morphology is crucial to uncover water and nutrient acquisition and transposition of fine roots. However, there is still a lack of knowledge regarding how the soil environment affects the fine root morphology of various root orders in the stable forest ecosystem. Therefore, this experiment assessed the response strategies of fine root morphology (first- to fifth -order fine roots) in four different soil environments. The results showed that fine root morphology was related to soil environment, and there were significant differences in specific root length (SRL), specific surface area (SRA), diameter (D), and root tissue density (RTD) of first- and second -order fine roots. Soil total nitrogen (TN), alkaline nitrogen (AN) and available phosphorus (AP) were positively correlated with SRL and SRA and negatively correlated with D and RTD. Soil moisture (SW) was positively correlated with the D and RTD of first- and second-order fine roots and negatively correlated with the SRL and SRA. Soil temperature (ST), organic carbon (OC), soil bulk density (SBD) and soil porosity (SP) were not significantly correlated with the D, SRL, SRA, and RTD of the first- and second -order fine roots. AN was positively correlated with SRL and SRA and negatively correlated with both D and RTD in the first- and second -order fine roots, and the correlation coefficient was very significant. Therefore, we finally concluded that soil AN was the most critical factor affecting root D, SRL, SRA and RTD of fine roots, and mainly affected the morphology of first- and second -order fine roots. In conclusion, our research provides support for understanding the relationship between fine root morphology and soil environment, and indicates that soil nutrient gradient forms good root morphology at intraspecific scale.

Abstract Interface engineering in electrode materials is an attractive strategy for enhancing charge storage, enabling fast kinetics, and improving cycling stability for energy storage systems. Nevertheless, the performance improvement is usually ambiguously ascribed to the “synergetic effect”, the fundamental understanding toward the effect of the interface at molecular level in composite materials remains elusive. In this work, a well‐defined nanoscale MoS2/TiO2 interface is rationally designed by immobilizing TiO2 nanocrystals on MoS2 nanosheets. The role of heterostructure interface between TiO2 and MoS2 by operando synchrotron X‐ray diffraction (sXRD), solid‐state nuclear magnetic resonance, and density functional theory calculations is investigated. It is found that the existence of a hetero‐interfacial electric field can promote charge transfer kinetics. Based on operando sXRD, it is revealed that the heterostructure follows a solid‐solution reaction mechanism with small volume changes during cycling. As such, the electrode demonstrates ultrafast Na+ ions storage of 300 mAh g−1 at 10 A g−1 and excellent reversible capacity of 540 mAh g−1 at 0.2 A g−1. This work provides significant insights into understanding of heterostructure interface at molecular level, which suggests new strategies for creating unconventional nanocomposite electrode materials for energy storage systems.

The HIV-1 Rev response element (RRE) is a cis-acting RNA element that facilitates the nuclear export of mRNA-containing introns by binding specifically to the Rev protein, enabling a critical step in the viral replication cycle. This study aims to determine the subtype-specific loci of HIV-1 subtype B RRE circulating in China and to analyze their effects on Rev-RRE function and HIV-1 replication. We amplified 71 HIV-1 subtype B RRE full-length sequences from the HIV patients’ blood samples collected in China, analyzed the subtype-specific loci on them by comparing them with subtype B in the United States, and predicted their RNA secondary structures. Rev-RRE activity assay was used to test the binding activity of Rev and different RREs. Infectious clones were mutated to test the effect of the subtype-specific loci on replication capacity. In this study, two sites were determined to be the subtype-specific loci of HIV-1 subtype B RRE circulating in China. Both site 186 and site 56-57insAAC can significantly increase the viral mRNA transcription and Rev-RRE activity, but only the site 186 can significantly improve viral replication ability. Collectively, the subtype-specific loci of subtype B RRE circulating in China have a significant effect on the Rev-RRE activity and viral replication. This study investigates the subtype-specific loci of RRE, which are unique to retroviruses and essential for viral replication, and will help to explore the reasons why subtype B circulating in China is more widespread and persistent than American subtype B in China at the genetic level, and will provide theoretical support for the development of more inclusive detection and treatment methods for subtype B circulating in China. At the same time, it will also provide insight into the impact of different subtype HIV-1 genetic characteristics on viral replication.

ContextTumor-associated cutaneous vascular disorder induced by PPGL was extremely rare, and the cutaneous manifestations could disappear after removal of the tumors. However, the definite pathological diagnosis and the potential mechanism remained unidentified. We presented a severe cutaneous vascular lesion manifested as diffuse erythema with ulceration and necrosis over the limbs in a female patient with metastatic paraganglioma. Skin biopsy was performed on her for defining the pathological diagnosis and potential mechanism. The patient was diagnosed as vascular disease according to the obvious angioectasia in dermis on cutaneous pathology, which might be caused by PPGL-induced hypercoagulability. We used the antiplatelet therapy with aspirin to treat the PPGL-associated cutaneous vascular disease for the first time, and the cutaneous lesions were relieved and healed gradually, further supporting the diagnosis of vascular disease.ConclusionFor metastatic PPGL patients like the case we reported, the definite diagnosis by skin biopsy and the early antiplatelet therapy might be effective to the cutaneous lesions caused by the hypercoagulable state of PPGL.

The natural regeneration of seedlings is a key factor for forest succession. Nevertheless, studies explaining the mechanism of growth and biomass allocation in regenerated seedlings after disturbance are lacking. Therefore, we measured the growth, biomass accumulation, and biomass allocation in current-age seedlings of Pinus massoniana after selective logging (logging of competitive trees, LCT; logging of inferior trees, LIT; and unlogged control, CK), and established structural equation models (SEMs) among the spatial structure characteristic indexes of the stand, environmental factors, and biomass allocation in different organs. As compared to the CK, the mingling index (M), uniform angle index (W), opening degree (O), soil organic carbon (SOC), available nitrogen (SAN), available phosphorus (SAP), available potassium (SAK), and bulk density (SBD) significantly increased (p < 0.05), while the competition index (CI) and neighborhood comparison (U) significantly decreased after logging (p < 0.05). After the LCT, seedling branch biomass improved, with an increase in the ground-diameter, crown-root ratio, and seedling quality index. More biomass was allocated to foliage and roots by an increase in the height and height-diameter ratio under the LIT. In the CK, increasing stem biomass helped the seedlings absorb and utilize more light. The Pearson correlation coefficient showed that biomass allocation to organs was independent, and seedlings adopted the strategies of heterogeneous adaptation and growth, thereby resulting in the separation of the allocation patterns among the organs. As per the redundancy analysis (RDA), CI was the main factor in biomass allocation. Environmental factors had direct effects on biomass allocation to organs, while the stand spatial structure characteristic indexes had indirect effects on biomass allocation based on SEMs. In summary, the LCT had significant, albeit indirect, effects on SOC, SAN, and SBD by reducing the CI for the regeneration and growth of seedlings in the stand, which was of great significance to the sustainable development of the forest stand of P. massoniana.

Abstract Multiple small- to middle-scale cities, mostly located in northern China, became epidemic hotspots during the second wave of the spread of COVID-19 in early 2021. Despite qualitative discussions of potential social-economic causes, it remains unclear how this unordinary pattern could be substantiated with quantitative explanations. Through the development of an urban epidemic hazard index (EpiRank) for Chinese prefectural districts, we came up with a mathematical explanation for this phenomenon. The index is constructed via epidemic simulations on a multi-layer transportation network interconnecting local SEIR transmission dynamics, which characterizes intra- and inter-city population flow with a granular mathematical description. Essentially, we argue that these highlighted small towns possess greater epidemic hazards due to the combined effect of large local population and small inter-city transportation. The ratio of total population to population outflow could serve as an alternative city-specific indicator of such hazards, but its effectiveness is not as good as EpiRank, where contributions from other cities in determining a specific city’s epidemic hazard are captured via the network approach. Population alone and city GDP are not valid signals for this indication. The proposed index is applicable to different epidemic settings and can be useful for the risk assessment and response planning of urban epidemic hazards in China. The model framework is modularized and the analysis can be extended to other nations.

Migraine is a common clinical disabling disease that seriously affects the patient's health, and there are many adverse reactions associated with the drugs that treat it. Chuanxiong Chatiao granules (CXCT) have the effect of dispersing wind and relieving pain, and are often used to treat migraine. At present, the potential compounds and mechanism of CXCT in the treatment of migraine are unclear. In this study, a total of 119 components of CXCT were identified, based on UHPLC-QE-Orbitrap-MS, which preliminarily characterized the potential compounds of CXCT, and Schrodinger software was used to carry out molecular docking between these 119 components and migraine targets. The first 30 components with low binding energy were selected and entered on the Swisstarget website to predict targets, resulting in 318 treating targets being obtained by intersection of the components with the disease targets. Cytoscape software was used to construct the ''compounds-targets-disease'' network, and 124 related pathways were obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. It was predicted that CXCT could play a role in the treatment of migraine by regulating neurotransmitter transmission, inflammation, angiogenesis, vasomotor, immunity and other pathways.

ABSTRACT The long terminal repeats (LTRs) of human endogenous retroviruses (HERVs) are distributed throughout the human genome and provide favorable conditions to regulate the expression of their adjacent genes. HML-2 is the most biologically active subgroup of the HERV-K family, and expression of its members has been associated with many cancer types. The LTRs of HML-2 have been classified into three subgroups (LTR5A, LTR5B, and LTR5Hs) based on phylogenetic analyses. The current study aimed to explore the LTR transcriptional activity differences among the three subtypes and further explore the underlying factors. A total of 43 LTR5A elements, 62 LTR5B elements, and 194 LTR5Hs elements were selected. A phylogenetic tree showed that the LTR5Hs group was clearly separated from the LTR5A and LTR5B groups. A luciferase reporter assay indicated that LTR5Hs had the strongest promoter activity, followed by LTR5A and LTR5B. To investigate the underlying factors, LTR5Hs was divided into 4 sections, and the homologous fragments in LTR5B were replaced successively. Replacement of the third section (−263 to 0) significantly increased LTR5B activity. Subsequent mutation experiments revealed that the increased transcriptional activity was induced by the TATA box and the two p53 binding sites within the section. Further interference with TP53 significantly decreased LTR5Hs transcriptional activity. Chromatin immunoprecipitation (ChIP) and CUT&Tag experiments finally confirmed the direct binding of the p53 protein with the two LTR5Hs p53 binding sites. Overall, the two p53 binding sites in the third section (−263 to 0) of LTR5Hs were revealed to play critical roles in the difference in transcriptional activity among the three subtypes. IMPORTANCE Human endogenous retroviruses (HERVs) were integrated into the human genome in ancient times and have been coevolving with the host. Since the Human Genome Project, HERVs have attracted increasing attention. Many studies have focused on their characterization, evolution, and biological function. In particular, the expression of HERV-K has been associated with many diseases, such as germ cell tumors, neurotoxicity, ovarian cancer, prostate cancer, and melanoma. Indeed, two HML-2-produced proteins, Np9 and Rec, are associated with certain cancers. However, their roles in these disease associations remain unclear. The current work focused on subgroup HML-2 of HERV-K, which is recognized as the most biologically active subgroup, and aimed to explore the mechanistic basis of transcriptional activity. The results revealed that p53 deeply determined the activity of HML-2 LTR5Hs. p53 is a rather important tumor suppressor protein. It can regulate the expression of genes related to cell cycle arrest, organic processes, and apoptosis in response to cellular stress and is critical for the control of homeostasis. Previous ChIP and expression studies of individual genes suggested that p53 sites in HERV LTRs may be part of the p53 transcription program and directly regulate p53 target genes in a species-specific manner. However, the exact function of p53 in the regulation of HERV LTR expression is largely elusive. Our results clearly demonstrated the interaction between LTR5Hs of HML-2 and p53. They are of great significance for the future comprehensive study of the physiological and pathological functions of LTRs of HERVs.

Fine root anatomy plays an important role in understanding the relationship between fine root function and soil environment. However, in different soil environments, the variation of fine root anatomical structure in different root sequences is not well studied. We measured the soil conditions and anatomical structure characteristics (root diameter, cortical tissue, vascular tissue and xylem) of fine roots of Cupressus funebris in four experimental sites, and analyzed each level of fine roots separately. We link these data to understand the relationship between fine root anatomy and soil conditions. We found that the anatomical structure of fine roots is closely related to soil environmental factors. The fine roots of lower root order are mainly affected by soil nutrients. Among them, the cortical tissue of first-order fine roots was positively correlated with potassium and phosphorus, but negatively correlated with nitrogen, while second- and third-order fine roots was positively correlated with soil total potassium and negatively correlated with nitrogen and phosphorus. For the fine roots of high root order, the cortical tissue disappeared, and the secondary vascular tissue was mainly affected by soil moisture. In addition, we also found that the division of fine root functional groups is not fixed. On the one hand, the function of third-order fine roots will slip. For example, the decrease of soil moisture will promote the transformation of third-order fine roots into transport roots, and the reduction of nitrogen will promote the transformation of third-order fine roots into absorption roots to fix nitrogen. This transformation strategy can effectively prevent the restriction of soil nutrients on plant growth. On the other hand, with the change of habitat, the first- and second-order fine roots are still the absorbing root, and the fourth- and fifth-order fine roots are still the transport root, but the efficiency of absorption and transport will be affected. In conclusion, our findings emphasize the fine roots in different soil environment to show high levels of plasticity, shows that fine root anatomical structure changes may make plants, and reveals that the fine is just order of reaction and its mechanism in the soil environment.

Tremors affect pediatric and adult populations, with roughly 3% of people worldwide experiencing essential tremors. Treatments include medication, deep brain stimulation, occupational/physical therapy, or adaptive equipment. This unblinded experimental pre-test–post-test study was performed (April–September 2021) at Children’s Health of Orange County, evaluating the effectiveness of Move-D, a novel orthotic brace, on pediatric tremors. Ten participants (14–19 years old) experiencing upper extremity tremors (5 essential, 2 dystonic, 1 coarse, 1 postural, and 1 unspecified) were enrolled. Participants completed a usability survey and performance was measured utilizing the Bruininks–Oseretsky Test of Motor Proficiency, second edition, with and without the brace, using one-sided t-tests of mean differences. Move-D improved age-equivalent scores for fine motor precision by 20.5 months and upper limb coordination by 15.1 months. Manual coordination percentile rankings increased by 2.9%. Manual dexterity performance was unaffected. The usability survey revealed that 7/10 participants agreed or strongly agreed that they could move their arm freely while wearing the brace, the brace reduced their tremors, and they felt comfortable wearing the brace at home. Through standardized testing and findings from the usability survey, Move-D showed an improvement of functional abilities in a pediatric population with tremors.