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In recent years, the incidence and mortality rate of cancer is raising worldwide. Traditional approaches for cancer patient management including surgery, chemotherapy, radiotherapy, and targeted therapies provide unsatisfactory results and are often associated with adverse reactions. Over the last few decades, nanotechnology has been a rapidly emerging area of theragnostic in clinical research. It plays a vital role as a bridge between the science and technology of miscellaneous nanoparticles (NPs) and nanomedicine. In general, NPs with a range of sizes of 1–100 nm are thought to be acceptable for cancer medications. NPs may enhance the consistency and solubility of therapeutic drugs to obtain site-specific targeting, controlled release, and safe for healthy organs. NPs have the benefit of pathophysiological properties, enhanced permeability and retention (EPR) effects, and an advantage in cancer targeting. Furthermore, theranostic nanoparticles have been established having incorporated diagnostics and therapy in a single system that might provide more personalized treatment with optimal doses and monitoring the distribution, targeting, and response to therapy by using imaging tools. In this review, we have discussed the classes of nanoparticles, targeting approaches, and implications of NPs for cancer theranostics with recent examples.

Thymopentin (TP5), a clinically used immunomodulatory pentapeptide, can efficiently promote thymocyte differentiation and influence mature T-cell function, thus playing an essential role in the cancer immunotherapy. However, the excellent water solubility and high IC50 of TP5 result in an uncontrolled release behavior, requiring a high loading efficiency to achieve high dosage. Here in, we reported that TP5, combined with specific chemotherapeutic agents, can co-assemble into nanogels due to multiple hydrogen bonding sites. The co-assembly of TP5 with chemotherapeutic agent doxorubicin (DOX) into a carrier-free and injectable chemo-immunotherapy nanogel can enhance the cancer immunity cycle against melanoma metastasis. In this study, the designed nanogel guarantees high drug loading of TP5 and DOX and ensures a site-specific and controlled release of TP5 and DOX with minimal side effects, thus addressing the bottlenecks encountered by current chemo-immunotherapy. Moreover, the released DOX can effectively induce tumor cell apoptosis and immunogenic cell death (ICD) to activate immune initiation. Meanwhile, TP5 can significantly promote the proliferation and differentiation of dendritic cells (DCs) and T lymphocytes to amplify the cancer immunity cycle. As a result, this nanogel shows excellent immunotherapeutic efficacy against melanoma metastasis, as well as an effective strategy for TP5 and DOX application.

N6-methyladenosine (m6A) is a ubiquitous mRNA modification in eukaryotes. m6A occurs through the action of methyltransferases, demethylases, and methylation-binding proteins. m6A methylation of RNA is associated with various neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), depression, cerebral apoplexy, brain injury, epilepsy, cerebral arteriovenous malformations, and glioma. Furthermore, recent studies report that m6A-related drugs have attracted considerable concerns in the therapeutic areas of neurological disorders. Here, we mainly summarized the role of m6A modification in neurological diseases and the therapeutic potential of m6A-related drugs. The aim of this review is expected to be useful to systematically assess m6A as a new potential biomarker and develop innovative modulators of m6A for the amelioration and treatment of neurological disorders.

Seasonal drought events induced by climate change have exacerbated the water deficit in trees. This is particularly pronounced in mature trees with considerable heights and extensive branches, where the long water transport distance leads to a reduction in hydraulic transportation efficiency. Therefore, investigating the water uptake patterns of mature trees is essential to enhance their growth and resilience to climate change. However, previous studies have predominantly focused on trees aged 10–60 years, with limited research on the water uptake patterns of trees over 60 years old. In this study, we employed hydrogen and oxygen stable isotopes coupled with the MixSIAR model to determine the water uptake patterns of mature Quercus aliena var. acuteserrata (40–60 years, 60–90 years, 120–150 years, >150 years) during the growing seasons of 2021 and 2022 in Baotianman Nature Reserve, Henan Province, China. Additionally, we utilized a random forest model to quantify the relative contributions of vegetation (fine root biomass) and soil properties (soil moisture, bulk density, total porosity, field capacity, and soil texture) to the water uptake patterns of Q. aliena. Our findings demonstrate that most mature Q. aliena predominantly extracted deep soil water (60–100 cm) in the early growing season, but shifted towards utilizing shallow soil water (0–40 cm) in the late growing season. The water uptake pattern of mature Q. aliena was primarily regulated by soil moisture. These results reveal that mature Q. aliena trees exhibit a flexible water use strategy, enabling them to cope with seasonal drought by altering the soil depth from which they extract water. In the future, in the process of the cultivation and conservation of mature oak trees, surface soil irrigation can be increased to prevent tree mortality resulting from water deficit during drought conditions.

Background: Mutant analysis remains one of the main genetic tools for characterising unclarified gene functions in plants, especially in non-model plants. Daylily (Hemerocallis spp.) is a popular perennial ornamental plant grown worldwide. Analysis of daylily mutants can enhance understanding of genes regulating the albino phenotype and improve the cultivar quality of daylily. Methods: The natural albino mutant (Alb-⁣/-) was isolated by screening a self-pollinated progeny of daylily cultivar ‘black-eyed stella’. Transmission electron microscopy was used in analysing the structure of plastids between mutant and wild-type seedlings. The content of chlorophyll, carotenoids and chlorophyll precursors in plants was measured by ultraviolet spectrophotometry. RNA sequencing and physiological measurements were performed to explore the association between drought tolerance and mutation. Results: All the seedlings of the daylily albino mutants died spontaneously within fifteen days after germination when grown in soil. The carotenoid and chlorophyll content in the leaves of the mutant plants significantly decreased compared with those of the wild-type control. The mutant plants displayed stunted growth, and their leaves were white or light yellow in color. Abnormal plastids such as those showing endomembrane vesiculation and lacking stacking were discovered in the leaves of mutant plants. Furthermore, genetic analysis revealed that a single recessive nuclear gene mutation led to the albino trait, RNA sequencing and real-time quantitative PCR validation showed extensive differences in gene expression between the mutant plants and the wild-type control, and most of the genes related to chlorophyll metabolism were down-regulated, with foldchange ranging from 0.20–0.49. Additionally, the surviving homozygous plants (Alb+⁣/+), which do not contain this mutation, were also isolated by analysing the phenotype of their self-pollinated progeny. The net photosynthesis rate and light saturation point of Alb+⁣/+ were higher than those of heterozygous (Alb+⁣/-) plants. Additionally, the Alb+⁣/+ plants were more tolerant to drought conditions than the Alb+⁣/- plants, suggesting that a heterozygous Alb- mutation is sufficient to negatively affect photosynthetic efficiency and drought tolerance. Conclusions: The albino mutation negatively affects photosynthetic efficiency and drought tolerance, and homozygous mutation is required for the characteristic albino phenotype. This work highlights the link between albino mutation, photosynthetic pigment metabolism and drought sensitivity in daylily.

Zearalenone (ZEN) is considered one of the most serious mycotoxins contaminating grains and their by-products, causing significant economic losses in the feed and food industries. Biodegradation pathways are currently considered the most efficient solution to remove ZEN contamination from foods. However, low degradation rates and vulnerability to environmental impacts limit the application of biodegradation pathways. Therefore, the main research objective of this article was to screen strains that can efficiently degrade ZEN and survive under harsh conditions. This study successfully isolated a new strain L9 which can efficiently degrade ZEN from 108 food ingredients. The results of sequence alignment showed that L9 is Bacillus velezensis. Meanwhile, we found that the L9 degradation rate reached 91.14% at 24 h and confirmed that the primary degradation mechanism of this strain is biodegradation. The strain exhibits resistance to high temperature, acid, and 0.3% bile salts. The results of whole-genome sequencing analysis showed that, it is possible that the strain encodes the key enzyme, such as chitinase, carboxylesterases, and lactone hydrolase, that work together to degrade ZEN. In addition, 227 unique genes in this strain are primarily involved in its replication, recombination, repair, and protective mechanisms. In summary, we successfully excavated a ZEN-degrading, genetically distinct strain of Bacillus velezensis that provides a solid foundation for the detoxification of feed and food contamination in the natural environment.

Teachers’ well-being at work is an important indicator of their mental health. Strengths use has been identified as a significant predictor of enhanced well-being at work. However, there is a scarcity of studies that have examined the connection between teachers’ strengths use and well-being at work; thus, its underlying psychological mechanism is unclear. Therefore, this study aimed to explore the association between teachers’ strengths and well-being at work together with the mediating role of basic need satisfaction. A total of 374 university teachers completed a series of questionnaires on strengths use, basic need satisfaction, hedonic well-being, and eudaimonic well-being. The results showed that there were positive correlations between strength use and both types of well-being at work. Moreover, basic need satisfaction mediated the association between strength use and two types of well-being at work. The findings suggest that institutions should prioritize enhancing teachers’ ability to utilize their strengths and foster an environment conducive to such practices, thereby improving their workplace well-being.

The elevational patterns of soil microbial and nematodes diversity (SMND) and the determinants remain controversial. Moreover, how the SMND are modified simultaneously with an elevational gradient has not yet been established. In this study, we investigated the elevational patterns of the SMND and the relative importance among/within tree factors (i.e., tree diversity, identity, and quantity) and environmental factors (i.e., climate and soil) on the SMND. For this purpose, we analyzed datasets from 27 plots across nine elevation bands in the temperate forests of Mt. Gariwang, South Korea. We performed multimodel inference tests and subsequently conducted a variance partitioning to determine the most prominent factors controlling each SMND and compare the relative contribution of the trees and environmental effects. Our results revealed that bacterial and fungal diversity decreased along the elevation gradient. However, nematode diversity did not change significantly, indicating that site-specific environmental conditions may be more influential than the elevation per se. Moreover, this indicates that bacterial diversity was affected by the pH and functional dispersion of the leaf size, and that fungal diversity was governed only by the pH. However, nematode diversity was driven by aboveground biomass, ammonium-nitrogen, and tree size diversity. In summary, the soil microbial diversity was more strongly controlled by the environmental factors, whereas the tree factors were more important for nematodes. Our results show that the elevational patterns and determinants of SMND differed among the taxonomic groups in the common micro-food web. These findings provide new insights into the factors controlling the SMND in a temperate forest and expand the local knowledge of soil biodiversity which is necessary for promoting its mainstreaming. Thus, our results contribute to establishing a basis for more targeted and effective biodiversity conservation and management practices in forest ecosystems.

Optical anisotropy offers a heightened degree of flexibility in shaping optical properties and designing cutting-edge devices. Quasi-one-dimensional Ta2NiS5, with giant optical anisotropy, has been used in the development of new lasers and sensors. In this research endeavor, we successfully acquired the complete dielectric tensor of Ta2NiS5, utilizing the advanced technique of Mueller matrix spectroscopic ellipsometry, enabling a rigorous quantitative assessment of its optical anisotropy. The results indicate that Ta2NiS5 demonstrates giant birefringence and dichroism, with Δnmax = 1.54 and Δkmax = 1.80. This pursuit also delves into the fundamental underpinnings of this optical anisotropy, drawing upon a fusion of first-principles calculations and critical points analysis. The anisotropy of Ta2NiS5 arises from differences in optical transitions in different directions and is shown to be due to van Hove singularities without exciton effects. Its giant optical anisotropy is expected to be useful in the design of novel optical devices, and the revelation of the physical mechanism facilitates the modulation of its optical properties.

Saponins are extracted from different parts of plants such as seeds, roots, stems, and leaves and have a variety of biological activities including immunomodulatory, anti-inflammatory effects, and hypoglycemic properties. They demonstrate inherent low immunogenicity and possess the capacity to effectively regulate both the innate and adaptive immune responses. Plant saponins can promote the growth and development of the body’s immune organs through a variety of signaling pathways, regulate the activity of a variety of immune cells, and increase the secretion of immune-related cytokines and antigen-specific antibodies, thereby exerting the role of immune activity. However, the chemical structure of plant saponins determines its certain hemolytic and cytotoxicity. With the development of science and technology, these disadvantages can be avoided or reduced by certain technical means. In recent years, there has been a significant surge in interest surrounding the investigation of plant saponins as immunomodulators. Consequently, the objective of this review is to thoroughly examine the immunomodulatory properties of plant saponins and elucidate their potential mechanisms, with the intention of offering a valuable point of reference for subsequent research and advancement within this domain.

The Middle and Upper Permian Dalong and Gufeng Formations in South China have recently been considered as potential gas-producing shales. However, their pore structure characteristics remain poorly understood. To investigate the pore structure and fractal characteristics of the pores in these two formations, a suite of shale samples from the Dalong and Gufeng Formations in the western Hubei Province, South China were analyzed by multiple techniques, namely, TOC content, X-ray diffraction (XRD) mineralogy analysis, optical microscopy observations, major elemental analysis, field emission-scanning electron microscopy (FE-SEM), and low-pressure gas adsorption measurements (N2 and CO2). The identified major shale lithofacies include siliceous mudstone, carbonaceous mudstone, argillaceous-siliceous mixed mudstone, and calcareous-siliceous mixed mudstone. SEM images show that the dominant pore types include the pores between brittle minerals, slit-shaped pores between clay sheets, and secondary organic matter (OM) pores within solid bitumen. The pore size distribution is dominated by micropores and mesopores (1, D2) calculated from the nitrogen adsorption data have a range of from 2.489 to 2.772 (D1) and from 2.658 to 2.963 (D2), and are higher in the Gufeng Formation (average TOC = 8.3 wt.%) due to a higher TOC content comparing to the Dalong Formation (average TOC = 6.2 wt.%). The pore development and fractal characteristics are primarily controlled by organic matter (OM), carbonate minerals, and clay minerals for both the Dalong and Gufeng Formations. Shale samples with high TOC content, low carbonate content, and high clay content tend to develop more heterogeneous micropores and mesopores, which is ascribed to the generation of clay-related and OM-hosted pores, along with the destruction of primary pores by pore-filling carbonate cements.

Abstract Secondary epidermoid cyst of the penis is a very rare epidermoid cyst that occurs in the penis. The purpose of this study was to investigate the relationship between the occurrence of secondary epidermoid cyst of penis and circumcision-related factors, and to provide possible reasonable and effective suggestions for circumcision. The data of all patients who visited the clinic for epidermoid cysts of the penis from September 2000 to September 2021 in Xiangya Hospital were collected. A retrospective study was carried out on whether the patients had been circumcised and the surgical method, anesthesia method, cyst location, surgical age, postoperative wound infection, whether they were phimosis patients, and the level of the surgeon. Among the 24 patients followed up, 95.8% had a history of circumcision, and only 4.2% had no history of circumcision, and the more traumatic surgical methods developed secondary epidermoid cyst of the penis after surgery the higher the probability. Injecting anesthesia at the base of the penis increases the chances of developing a secondary epidermoid cyst of the penis. Postoperative secondary epidermoid cyst of the penis were mainly located in the anterior segment and posterior segment, and the anterior segment had a higher proportion, followed by the posterior segment. Secondary epidermoid cyst of the penis occur mainly in adults. Postoperative wound infection accelerates the appearance of secondary epidermoid cyst of the penis. Patients with phimosis have an increased probability of developing secondary epidermoid cysts of the penis after surgery. The incidence of secondary epidermoid cysts and postoperative infection after manual circumcision by the attending physician was higher than that of the chief physician. Circumcision, injection of anesthesia at the base of the penis, ligation of the penis, and postoperative wound infection may be the etiologies and triggers of secondary epidermoid cysts of the penis. Adults and phimosis patients may be high-risk groups. Lower-level surgeons may increase the odds of postoperative secondary epidermoid cysts of the penis, and it is recommended that surgery be performed by a clinically-experienced, higher-level surgeon. The indications for circumcision should be strictly evaluated and the operation should be performed as soon as possible, and the less invasive surgical method and anesthesia method should be selected. Reduce irrelevant operations during surgery and avoid wound infection after surgery.

Abstract Background Antimicrobial resistance (AMR) is one of the top ten global public health challenges. However, given the lack of a comprehensive assessment of worldwide AMR status, our objective is to develop a One Health-based system-wide evaluation tool on global AMR. Methods We have further developed the three-hierarchical Global One Health Index (GOHI)-AMR indicator scheme, which consists of five key indicators, 17 indicators, and 49 sub-indicators, by incorporating 146 countries’ data from diverse authoritative databases, including WHO's Global Antimicrobial Resistance and Use Surveillance System (GLASS) and the European CDC. We investigated the overall- or sub-rankings of GOHI-AMR at the international/regional/national levels for data preprocessing and score calculation utilizing the existing GOHI methodology. Additionally, a correlation analysis was conducted between the GOHI-AMR and other socioeconomic factors. Results The average GOHI-AMR score for 146 countries is 38.45. As expected, high-income countries (HICs) outperform the other three income groups on overall rankings and all five key indicators of GOHI-AMR, whereas low-income countries unexpectedly outperform upper-middle-income countries and lower-middle-income countries on the antibiotics-resistant key indicator (ARR) and ARR-subordinate indicators, including carbapenem-, β-lactam-, and quinolone resistance, and even HICs on aminoglycoside resistance. There were no significant differences among the four groups on the environmental-monitoring indicator (P > 0.05). GOHI-AMR was positively correlated with gross domestic product, life expectancy, and AMR-related publications, but negatively with natural growth rate and chronic respiratory disease. In contrast to Cyprus, the remarkably lower prevalence of "ESKAPE pathogens" in high-scoring Sweden and Denmark highlights Europe's huge gaps. China and Russia outperformed the other three BRICS countries on all key indicators, particularly India's ARR and Brazil's AMR laboratory network and coordination capacity. Furthermore, significant internal disparities in carbapenem-resistant Klebsiella pneumoniae (CRKP) and methicillin-resistant Staphylococcus aureus (MRSA) prevalence were observed between China and the USA, with MRSA prevalence both gradually declining, whereas CRKP prevalence has been declining in the USA but increasing in China, consistent with higher carbapenems-related indicator’ performance in USA. Conclusions GOHI-AMR is the most comprehensive tool currently available for the assessment of AMR status worldwide. We discovered unique features impacting AMR in each country and offered precise recommendations to improve the capacity to tackle AMR in low-ranking countries. Graphical Abstract

Abstract Urethral stricture is related to scar tissue fibrosis, but its pathogenesis is still unclear. This study aims to explore the regulatory mechanism of circular RNA (circRNA) in the occurrence and development of urethral stricture. CircRNA microarray was employed to analyze circRNA expression profiles between human urethral scar tissue and normal urethral tissue. The results of circRNA microarray showed that there were 296 differentially expressed genes between urethral scar tissue and normal urethral tissue. The enrichment analysis of Kyoto encyclopedia of genes and genomes showed that these circRNAs were significantly correlated with ECM–receptor interaction. The first nine differentially expressed circRNA were selected to predict the circRNA–miRNA network. RT-qPCR results showed that circ_0047339 was upregulated considerably in urethral scar tissue. Urethral scar fibroblasts were isolated from human urethral scar tissue and cultured in vitro. After silencing circ_0047339, the proliferation of urethral scar cells decreased significantly, and the expressions of Collagen I (COL-1) and α-smooth muscle actin (α-SMA) also reduced. As a competing endogenous RNA, circ_0047339 could increase the expression of TSP-1 by competitively binding miR-4691-5p. In addition, miR-4691-5p mimic transfection could inhibit the proliferation of urethral scar fibroblasts and the presentation of thrombospondin-1 (TSP-1), α-SMA and COL-1, while circ_0047339 overexpression eliminated this inhibition. Our results showed that circ_0047339 might promote the growth and fibrosis of urethral scar fibroblasts through miR-4691-5p/TSP-1 axis, thus promoting the development of urethral stricture.

In the period of historic intersection of energy revolution, a new round of technological revolution and industrial transformation, unprecedented opportunities and challenges are appearing in the development of urban gas industry. Herein, the development history of urban gas industry was reviewed briefly, four major development trends of industry future were analyzed and summarized, and the pain spots of the industry were pointed out, including the insufficient industry intelligence, the incomplete safety system and the inadequate depth of low-carbon energy transformation layout. In addition, an overall logical block diagram was constructed based on the key technologies of intelligent gas. Meanwhile, the key problems in the construction of perception layer, transmission layer and application layer were analyzed. Moreover, focusing on the key technologies of gas safety, the concept of building a safety management system of urban gas based on integrity management was proposed, coring at the establishment of a digital model for the gas transportation and distribution system and the construction of a failure database. Furthermore, the development approach for constructing a "near-zero carbon"energy ecological network of urban gas was put forward based on gas decarbonisation. Finally, the economic and safety problems faced by the technologies such as efficient utilization of natural gas and hydrogen mixing in natural gas pipelines were emphatically analyzed, and accordingly, appreciate solutions were developed.

Xylooligosaccharides (XOS) are mainly derived from lignocellulosic materials, such as rice husk, corn cobs, straw, wheat bran, wheat straw and other grain by-products. XOS have become one of the functional oligosaccharides of great concern at home and abroad due to their beneficial functional properties, such as low calorie, high stability, poor digestibility and high performance in proliferating probiotics. At present, the XOS extraction methods from grain byproducts mainly include autohydrolysis, acidolysis and enzymolysis. Among them, autohydrolysis has high requirements for equipment for achieving higher extraction rate and higher purity of products; and acidolysis can cause environmental pollution due to the usage of harmful reagents. Enzymolysis is the most common method for the production of XOS because of its high convenience, high efficiency and no pollution; and the widely used enzyme is the xylanase from Aspergillus niger. Current researches have showed that XOS can be utilized by probiotics such as Bifidobacteria and Lactobacillus to exert prebiotic effects, such as optimizing intestinal flora, promoting intestinal health, improving intestinal barrier, enhancing immune function, improving antioxidant capacity and so on. However, XOS extracted from the grain by-products contain a large amount of impurities, which limits their industrial application and makes it difficult to control the product quality. Therefore, XOS refining, separation and purification has become the key to their subsequent industrial application. This paper reviewed the current status of XOS extraction technologies from various grain by-products, and also summarized the prebiotic effect of XOS to provide reference for industrial production of XOS and its wide application in prebiotics market, thereby facilitating utilization and development of grain byproducts.

Iron widely exists in minerals and food, and has an essential role in human health. A major iron-regulating peptide hormone, hepcidin, maintains the balance of iron metabolism. The association between serum iron, hepcidin levels, and stroke risk is still under ongoing research. In this meta-analysis, Random‐effects meta‐analysis revealed that stroke patients had significantly higher serum iron and hepcidin levels compared with HC subjects. Further analysis of serum hepcidin levels in different degrees of stroke and its relation to prognosis revealed that hepcidin level is also associated with the degrees and prognosis of stroke. Finally, the role of iron overload in the mechanism of stroke development and the effect and mechanism of iron chelator intervention in stroke were also reviewed. Overall, the findings indicate that stroke patients had higher serum iron and hepcidin levels compared with healthy subjects, and their changes were associated with the severity and prognosis of stroke.

Ischemic stroke (IS) is the second leading cause of death and disability in the world. Pyroptosis, a form of programmed cell death initiated by caspases, participates in the occurrence and development of IS. Because it can increase cell membrane permeability, mediate the release of inflammatory factors, and aggravate inflammation, inhibiting this process can significantly reduce the pathological injury of IS. The nucleotide binding oligomerization domain-like receptor family pyrin domain protein 3 (NLRP3) is a multiprotein complex whose activation is the core link of pyroptosis. In recent years, studies have reported that traditional Chinese medicine (TCM) could regulate pyroptosis mediated by NLRP3 inflammasome through multi-channel and multi-target networks and thus exert the effect against IS. This article reviews 107 papers published in recent years in PubMed, Chinese National Knowledge Infrastructure (CNKI), and WanFang Data in recent years. It has found that the activation factors of NLRP3 inflammasome include ROS, mitochondrial dysfunction, K+, Ca2+, lysosome rupture, and trans-Golgi breakdown. TLR4/NF-κB/NLRP3, ROS/TXNIP/NLRP3, AMPK/Nrf2/NLRP3, DRP1/NLRP3, TAK1/JNK/NLRP3 signaling pathways regulate the initiation and assembly of the NLRP3 inflammasome, subsequently induce pyroptosis, affecting the occurrence and development of IS. TCM can affect the above signaling pathways and regulate the pyroptosis mediated by NLRP3 inflammasome, so as to play a protective role against IS, which provides a new entry point for discussing the pathological mechanism of IS and a theoretical basis for developing TCM treasure house.

Abstract Triple‐negative breast cancer (TNBC) is a highly lethal malignancy with limited therapy options. TWIST1, a key transcriptional factor of epithelial‐mesenchymal transition (EMT), contributes to self‐renewal of cancer stem‐like cells (CSCs), chemo‐resistance, metastasis, and TNBC‐related death. However, the mechanism by which TWIST1 is deregulated in TNBC remains elusive. Here, USP29 is identified as a bona fide deubiquitinase of TWIST1. The deubiquitination of TWIST1 catalyzed by USP29 is required for its stabilization and subsequent EMT and CSC functions in TNBC, thereby conferring chemotherapeutic resistance and metastasis. Furthermore, the results unexpectedly reveal that CDK1 functions as the direct USP29 activator. Mechanistically, CDK1‐mediated phosphorylation of USP29 is essential for its deubiquitinase activity toward TWIST1 and TWIST1 driven‐malignant phenotypes in TNBC, which could be markedly mitigated by the genetic ablation or pharmacological inhibition of CDK1. Moreover, the histological analyses show that CDK1 and USP29 are highly upregulated in TNBC samples, which positively correlate with the expression of TWIST1. Taken together, the findings reveal a previously unrecognized tumor‐promoting function and clinical significance of the CDK1‐USP29 axis through stabilizing TWIST1 and provide the preclinical evidence that targeting this axis is an appealing therapeutic strategy to conquer chemo‐resistance and metastasis in TNBC.

Skin and soft tissue diffusion metastasis (also known as occult cancer) is rare in renal cell carcinoma (RCC). Here, we report an extremely rare case of a 67-year-old male patient with occult primary RCC who developed metastases to the gums, skin, and diffuse soft tissue. The primary renal lesion was missed by computed tomography (CT), ultrasound, and 18F-fluorodeoxyglucose positron emission tomography (PET)/CT, and the diagnosis was confirmed by biopsy of gums and subcutaneous nodules. Subsequent enhanced CT revealed a lesion in the left kidney. The patient had progression-free survival of 16 months after treatment with axitinib and pembrolizumab. Pseudoprogression and tumor heterogeneity pose major challenges in the evaluation of immunotherapy. PET/CT is indispensable especially for cases with multiple metastases, widespread distribution of lesions, and major heterogeneity. In this case, the total lesion glycolysis was calculated by PET/CT and was used to evaluate systemic tumor load before and after immunotherapy, which was calculated as the product of the metabolic tumor volume and the mean standardized uptake value of the target lesion, which increased the accuracy of assessing diffuse lesions. Total lesion glycolysis can be used as a new method to quantitatively evaluate the efficacy of immunotherapy.

Potato is one of the world’s most important food crops, with a time-consuming breeding process. In this study, we performed a genome-wide association (GWAS) analysis of the two important traits of potato tuber shape and eye depth, using the tetraploid potato genome (2n=4x=48) as a reference. A total of 370 potatoes were divided into three subgroups based on the principal component analysis and evolutionary tree analysis. The genetic diversity within subgroups is low (5.18×10-5, 4.36×10-5 and 4.24×10-5). Genome-wide linkage disequilibrium (LD) analysis showed that their LD is about 60 Kb. GWAS analysis identified that 146 significant single nucleotide polymorphism (SNP) loci at Chr01A1:34.44−35.25 Mb and Chr02A1:28.35−28.54 Mb regions are significantly associated with potato tuber shape, and that three candidate genes that might be related to potato tuber traits, PLATZ transcription factor, UTP-glucose-1-phosphate uridylyltransferase and FAR1 DNA-binding domain, are in the association region of Chr02A1. GWAS analysis identified 53 significant SNP loci at Chr05A2: 49.644-50.146 Mb and Chr06A2: 25.866-26.384 Mb regions with robust associations with potato tuber eye depth. Hydrolase and methyltransferases are present in the association region of Chr05A2, and three CYPs are present in the association region of Chr06A2. Our findings suggested that these genes are closely associated with potato tuber shape and eye depth. Our study identified molecular markers and candidate genes for improving tetraploid potato tuber shape and eye depth and provided ideas and insights for tetraploid potato breeding.

IntroductionThe food-borne Gram-negative bacterial pathogen Campylobacter jejuni may cause the acute enterocolitis syndrome campylobacteriosis in infected humans. Given that human C. jejuni infections are rising globally which hold also true for resistance rates against antibiotic compounds such as macrolides and fluoroquinolones frequently prescribed for the treatment of severe infectious enteritis, novel antibiotics-independent therapeutic strategies are needed. Distinct organic acids are well known for their health-beneficial including anti-microbial and immunomodulatory properties. In our present study, we investigated potential pathogen-lowering and anti-inflammatory effects of benzoic acid, butyric acid, caprylic acid, and sorbic acid either alone or in combination during acute murine campylobacteriosis.MethodsTherefore, secondary abiotic IL-10–/– mice were perorally infected with C. jejuni strain 81–176 and subjected to a 4-day-course of respective organic acid treatment.Results and discussionOn day 6 post-infection, mice from the combination cohort displayed slightly lower pathogen loads in the duodenum, but neither in the stomach, ileum nor large intestine. Remarkably, the clinical outcome of C. jejuni induced acute enterocolitis was significantly improved after combined organic acid treatment when compared to the placebo control group. In support, the combinatory organic acid treatment dampened both, macroscopic and microscopic inflammatory sequelae of C. jejuni infection as indicated by less colonic shrinkage and less pronounced histopathological including apoptotic epithelial cell changes in the colon on day 6 post-infection. Furthermore, mice from the combination as compared to placebo cohort exhibited lower numbers of innate and adaptive immune cells such as neutrophilic granulocytes, macrophages, monocytes, and T lymphocytes in their colonic mucosa and lamina propria, respectively, which also held true for pro-inflammatory cytokine secretion in the large intestines and mesenteric lymph nodes. Notably, the anti-inflammatory effects were not restricted to the intestinal tract, but could also be observed systemically given pro-inflammatory mediator concentrations in C. jejuni infected mice from the combination organic acid treatment that were comparable to basal values. In conclusion, our in vivo study provides first evidence that an oral application of distinct organic acids in combination exhibits pronounced anti-inflammatory effects and hence, constitutes a promising novel antibiotics-independent therapeutic strategy in the combat of acute campylobacteriosis.

Recent large datasets measuring the gene expression of millions of possible gene promoter sequences provide a resource to design and train optimized deep neural network architectures to predict expression from sequences. High predictive performance due to the modeling of dependencies within and between regulatory sequences is an enabler for biological discoveries in gene regulation through model interpretation techniques. To understand the regulatory code that delineates gene expression, we have designed a novel deep-learning model (CRMnet) to predict gene expression in Saccharomyces cerevisiae. Our model outperforms the current benchmark models and achieves a Pearson correlation coefficient of 0.971 and a mean squared error of 3.200. Interpretation of informative genomic regions determined from model saliency maps, and overlapping the saliency maps with known yeast motifs, supports that our model can successfully locate the binding sites of transcription factors that actively modulate gene expression. We compare our model's training times on a large compute cluster with GPUs and Google TPUs to indicate practical training times on similar datasets.

Background: Cold‐inducible RNA‐binding protein (CIRBP) is associated with cell stress. However, its upstream regulatory factors are still largely unknown. Objectives: This study investigated whether CIRBP expression was regulated by transforming growth factor beta (TGF‐β) during the process of heat‐induced testicular damage. Materials and Methods: Ten male adult ICR mice were allocated to heat treatment (scrotal hyperthermia at 43 °C for 30 min, n = 5) and control group (n = 5); CIRBP and TGF‐β1, TGF‐β2, and TGF‐β3 expression levels in the testis in mRNA and protein were analyzed. Then, we conducted in vivo and in vitro studies to investigate the regulatory effects of TGF‐β on CIRBP. In the in vivo study, male adult ICR mice were subjected to testicular hyperthermia followed by a local testicular injection of TGF‐β antagonist (non‐selective TGF‐β I/II receptor inhibitor, 5 μg or 10 μg). In the in vitro study, GC2‐spd cells were cultured under 43 °C for 30 min or with different TGF‐β isoforms (10 ng/mL), and CIRBP expression levels in the testis and GC2‐spd cells were analyzed 24 and 48 h, respectively, after treatment. Results: As a result, heat treatment significantly downregulated the relative CIRBP mRNA and protein expression (p = 0.006 and 0.011), and significantly upregulated TGF‐β2 and TGF‐β3 expression levels (p = 0.022 and 0.04, for mRNA, and p = 0.001 for both protein levels). Local testicular injection of 10 μg TGF‐β antagonist significantly attenuated heat‐induced histological damage to the testes and CIRBP downregulation (p = 0.038). Furthermore, TGF‐β2 and TGF‐β3 significantly downregulated CIRBP mRNA and protein expression in GC2‐spd cells (all p < 0.01), exerting a similar effect to heat treatment. Discussion and Conclusion: Our in vivo and in vitro experiments demonstrated that heat‐induced CIRBP downregulation in the testes was mediated by the upregulation of TGF‐β. Further studies are needed to clarify the molecular mechanisms underlying these processes. [ABSTRACT FROM AUTHOR]

Abstract Atherosclerosis is a maladaptive chronic inflammatory disease, which remains the leading cause of death worldwide. The NLRP3 inflammasome constitutes a major driver of atherosclerosis, yet the mechanism of action is poorly understood. Mitochondrial dysfunction is essential for NLRP3 inflammasome activation. However, whether activated NLRP3 inflammasome exacerbates mitochondrial dysfunction remains to be further elucidated. Herein, we sought to address these issues applying VX765, a well-established inhibitor of caspase 1. VX765 robustly restrains caspase 1-mediated interleukin-1β production and gasdermin D processing. Our study assigned VX765 a novel role in antagonizing NLRP3 inflammasome assembly and activation. VX765 mitigates mitochondrial damage induced by activated NLRP3 inflammasome, as evidenced by decreased mitochondrial ROS production and cytosolic release of mitochondrial DNA. VX765 blunts caspase 1-dependent cleavage and promotes mitochondrial recruitment and phosphorylation of Parkin, a key mitophagy regulator. Functionally, VX765 facilitates mitophagy, efferocytosis and M2 polarization of macrophages. It also impedes foam cell formation, migration and pyroptosis of macrophages. VX765 boosts autophagy, promotes efferocytosis, and alleviates vascular inflammation and atherosclerosis in both ApoE −/− and Ldlr −/− mice. However, these effects of VX765 were abrogated upon ablation of Nlrp3 in ApoE −/− mice. This work provides mechanistic insights into NLRP3 inflammasome assembly and this inflammasome in dictating atherosclerosis. This study highlights that manipulation of caspase 1 paves a new avenue to treatment of atherosclerotic cardiovascular disease.

Abstract Background The transtheoretical model of intentional health behavior change categorizes people into experiencing five stages in understanding the process of initiating and maintaining effective stress management (i.e., engagement in any form of healthy activity that is practiced for at least 20 min per day). The first purpose of this study was to observe whether any cases would disclose stage misclassification over one month. The second was to examine whether different model's variables are associated with the stage transitions for effective stress management at different stages. Methods Data from 946 Chinese students and workers were subjected to analyses. This study is a part of a larger, longitudinal web-based study in which three surveys were conducted in March, April, and September 2014. This study analyzes the data of demographic variables, perceived stress, stages of change, processes of change, pros, cons, and self-efficacy at the point of the first survey and stages of change at the point of the second survey. Results Of 144 participants who progressed from the pre-Action stages to the post-Action stages, 44 then progressed to Maintenance (practicing effective stress management for six months or longer). These patterns could not technically occur, and thus, these participants were excluded from the following analyses. Data from the remaining 902 participants were subject to a series of logistic regression analyses. Generally, the model’s variables failed to predict the stage transitions. Exceptions were found that higher experiential processes (the cognitive activities required to progress through stages) and lower self-efficacy (the confidence that one can engage in effective stress management despite barriers to it) predicted the forward and backward stage transitions from Precontemplation (with no intention to initiate effective stress management in the next six months) and Action/Maintenance (practicing effective stress management). Conclusions Evidence of stage misclassification indicated the limitations of the model’s stage classification. Experiential processes and self-efficacy as predictors at different stages were in line with the model’s assumption that different variables are assumed to be predictors of stage transitions at different stages, partially supporting the utility of the stage classification.

Abstract. Background:. Keloids are benign fibrous growths that are caused by excessive tissue build-up. Severe keloids exert more significant effects on patients’ quality of life than do mild keloids. We aimed to identify factors associated with the progression from mild keloids to severe keloids, as distinct from those associated with the formation of keloids. Methods:. In this retrospective case-control study, 251 patients diagnosed with keloids at West China Hospital between November 2018 and April 2021 were grouped according to the severity of lesions (mild [n = 162] or severe [n = 89]). We collected their basic characteristics, living habits, incomes, comorbidities, and keloid characteristics from Electronic Medical Records in the hospital and the patients’ interviews. Conditional multivariable regression was performed to identify the independent risk factors for the progression of keloids. Results:. Eighty-nine patients (35.5%) were classified as having severe keloids. We found the distribution of severe keloids varied with sex, age, excessive scrubbing of keloids, family income, the comorbidity of rheumatism, disease duration, characteristics of the location, location in sites of high-stretch tension, the severity and frequency of pain, the severity of pruritus, and infection. Multivariable analysis revealed significant associations between severe keloids and infection (odds ratio [OR], 3.55; P = 0.005), excessive scrubbing of keloids (OR, 8.65; P = 0.001), low or middle family income (OR, 13.44; P = 0.021), comorbidity of rheumatism (OR, 18.97; P = 0.021), multiple keloids located at multiple sites (OR, 3.18; P = 0.033), and disease duration > 15 years (OR, 2.98; P = 0.046). Conclusion:. Doctors should implement more active and thorough measures to minimize the progression of mild keloids in patients who have any of the following risk factors: infection, excessive scrubbing of keloids, low or middle family income, comorbidity of rheumatism, multiple keloids located at multiple sites, and disease duration > 15 years.

Sepsis-induced acute kidney injury (AKI) is one of the important causes of increased mortality in sepsis patients. Long non-coding RNA (lncRNA) is believed to play a vital function in the progression of AKI. However, the mechanism of nuclear enriched abundant transcript 1 (NEAT1) has not been fully elucidated. NEAT1 was overexpressed and miR-22-3p was underexpressed in sepsis patients and lipopolysaccharide (LPS)-induced AKI cell models. Knockdown of NEAT1 could promote viability and suppress apoptosis and the inflammatory response in LPS-induced HK2 cells. MiR-22-3p could be sponged by NEAT1, and its inhibitor reversed the inhibition effect of NEAT1 silencing on LPS-induced HK2 cell injury. CXCL12 could be targeted by miR-22-3p, and its overexpression reversed the suppression effect of miR-22-3p on LPS-induced HK2 cell injury. Silenced NEAT1 could restrain the activity of the NF-B signaling pathway, and miR-22-3p inhibitor or CXCL12 overexpression could reverse this effect. In addition, NEAT1 knockdown alleviated the inflammation response of cecal ligation and puncture (CLP) mouse models. In summary, our data showed that NEAT1 promoted LPS-induced HK2 cell injury via regulating the miR-22-3p/CXCL12/NF-B signaling pathway, suggesting that NEAT1 knockdown might be a potential pathway for alleviating sepsis-induced AKI.

Abstract Work zones have critical effects on traffic safety and efficiency. Previous researchers have developed lots of merge strategies to regulate drivers’ behaviours, which can be divided into early merge and late merge. As a special kind of late merge, signal‐based merge strategy was proposed in recent years to reduce traffic conflicts and increase throughput at bottlenecks. Although traffic signal has been confirmed to improve the traffic in work zone areas effectively, the existing strategy still has limitations that require further improvements. In this research, an improved signal‐based merge (IM) strategy was proposed to fulfil the research gaps. The strategy included a calculation method of green time considering the relationship between arrival traffic and the bottleneck's capacity and a dynamic signal‐phase conversion method. Based on the Cellular Automata simulation, the effectiveness of the IM strategy was verified through parameter sensitive analysis and comparative study with the existing merge strategies. The results showed that the IM strategy could lead to greater throughputs, lower traffic delays, less aggressive merge and more balanced queue length. Furthermore, the IM strategy also showed great stability in response to the changes of parameters and the imbalance of arrival traffic. Overall, the proposed IM strategy is considered more effective in improving the traffic management in work zone areas and is feasible to be applied in practice.

Here, the effects of compatibilization and clay nanoparticles on the gas permeability of nanocomposites of poly-lactic acid (PLA)/thermoplastic starch (TPS)/nanoclay were discussed. TPS and compatibilized PLA/TPS were tailored in the first step. The starch with D-sorbitol as a plasticizer was mingled through the internal mixer. Afterward, the maleination method was utilized on PLA to ameliorate the compatibilization of PLA and TPS. In this regard, maleic anhydrate (MA) has been grafted on PLA in the presence of L101 as a peroxide initiator via melt mixing to obtain PLA-g-MA. The optimum content of PLA-g-MA was about 4 phr, confirmed by DMTA and SEM. Noteworthy, the presence of PLA-g-MA has moderately improved the oxygen barrier. Then, the nanocomposites of PLA and TPS containing 1% of Cloisite-30B as well as the optimum compatibilizer (4phr), were produced by melt mixing in the masterbatch module leading to the formation of an extraordinary well-dispersed structure according to XRD patterns. The mixing order controlled the localization of nanosheets. It was concluded that the inclusion of 1% nanoclay in the PLA phase reduces the oxygen permeability by 55% compared to the pristine blend due to the tortuosity effect of nanosheets that are appropriately dispersed in the matrix.

The tumor microenvironment plays a critical role in tumor progression and immune regulation. As one of the most important components of the tumor microenvironment, macrophages have become a new therapeutic target for inhibiting tumor progression. Despite the well-documented anticancer activity of cucurbitacin I, its effect on macrophages remains unclear. In this study, we established a coculture system of macrophages and cancer cells under hypoxic conditions to simulate the tumor-promoting environment mediated by M2-like macrophages. We determined whether cucurbitacin I modulates M2-like polarization in macrophages in vitro and conducted RNA sequencing to identify gene expression changes induced by cucurbitacin I in macrophages. The results indicated a remarkable inhibition of the M2-like polarization phenotype in macrophages following treatment with cucurbitacin I, which was accompanied by the significant downregulation of heme oxygenase-1. Moreover, we found that cucurbitacin I-treated macrophages reduced the migration of cancer cells by inhibiting the M2 polarization in vitro. These findings highlight the potential of cucurbitacin I as a therapeutic agent that targets M2-like macrophages to inhibit cancer cell metastasis. Our study provides novel insights into the intricate interplay among macrophage polarization, cucurbitacin I, and heme oxygenase-1, thereby opening new avenues for cancer treatment.

Phase transition behaviors of poly(N-isopropylacrylamide) nanogels with different compositions induced by (−)-epigallocatechin-3-gallate (EGCG) and ethyl gallate (EG) has been investigated systematically. Monodisperse poly(N-isopropylacrylamide-co-N-hydroxymethyl acrylamide) (P(NIPAM-co-NMAM)) and poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) (P(NIPAM-co-HEMA)) nanogels with different feeding monomer ratios were prepared by emulsion polymerization. P(NIPAM-co-NMAM) nanogels exhibit rapid isothermal phase transition behavior in EGCG solutions with low concentration (10−3 mol/L) in less than 10 minutes. The thermosensitive phase transition behaviors of nanogels are affected not only by the copolymerized monomers but also by the concentrations of EGCG and EG in aqueous solutions. Nanogels remain in a shrunken state and do not exhibit thermosensitive phase transition behaviors in EGCG solutions (≥5 mmol/L), whereas they display thermo-responsive phase transition behaviors in EG solutions. The volume phase transition temperature (VPTT) shifts to lower temperatures with increasing EG concentration. The diameters of P(NIPAM-co-NMAM) nanogels decrease with increasing EG concentration at temperatures between 29 and 33 °C. In contrast, the diameters of P(NIPAM-co-HEMA) nanogels increase with increasing EGCG concentration at temperatures between 37 and 45 °C. The results demonstrate the potential of nanogels for simple detection of EG and EGCG concentrations in aqueous solutions over a wide temperature range, and EGCG can serve as a signal for the burst-release of drugs from the P(NIPAM-co-NMAM)-based carriers at physiological temperature.

The mining environment of thin coal seam working faces is generally harsh, the labor intensity is high, and the production efficiency is low. Previous studies have shown that thin coal seam mining finds it difficult to follow machines, does not have complete sets of equipment, has a low degree of automation, and has difficult system co-control, which easily causes production safety accidents. In order to effectively solve the problems existing in thin coal seam mining, Binhu Coal Mine has established intelligent fully mechanized mining and actively explored automatic coal cutting, automatic support following, and intelligent control. The combination of an SAC electro-hydraulic control system and SAP pumping station control system has been applied in 16,108 intelligent fully mechanized coal mining faces, which realizes the automatic following of underground support and the control of adjacent support, partition support, and group operation; the automatic coal cutting of the shearer is realized by editing the automatic coal-cutting state of the shearer and adjusting the automatic parameters. A centralized control center is set up, which realizes the remote control and one-button start–stop of working face equipment. Through a comparative analysis of 16,108 intelligent fully mechanized mining faces and traditional fully mechanized mining faces, it is found that intelligent fully mechanized mining faces have obvious advantages in terms of equipment maintenance, equipment operation mode, and working face efficiency, which improve the equipment and technical mining level of thin coal seam. The application of intelligent mining in Binhu Coal Mine has a great and far-reaching impact on the development of thin coal seam mining technology in China.

Various studies have shown that the cell-cycle-related regulatory proteins UBE2C, PLK1, and BIRC5 promote cell proliferation and migration in different types of cancer. However, there is a lack of in-depth and systematic research on the mechanism of these three as therapeutic targets. In this study, we found a positive correlation between the expression of UBE2C and PLK1/BIRC5 in the Cancer Genome Atlas (TCGA) database, revealing a potential combination therapy candidate for pan-cancer. Quantitative real-time PCR (qRT-PCR), Western blotting (WB), cell phenotype detection, and RNA-seq techniques were used to evidence the effectiveness of the combination candidate. We found that combined interference of UBE2C with PLK1 and UBE2C with BIRC5 affected metabolic pathways by significantly downregulating the mRNA expression of IDH1 and ACLY, which was related to the synthesis of acetyl-CoA. By combining the PLK1 inhibitor volasertib and the ACLY inhibitor bempedoic acid, it showed a higher synergistic inhibition of cell viability and higher synergy scores in seven cell lines, compared with those of other combination treatments. Our study reveals the potential mechanisms through which cell-cycle-related genes regulate metabolism and proposes a potential combined targeted therapy for patients with higher PLK1 and ACLY expression in pan-cancer.

Taking the roadway peripheral rock anchoring unit as the research object, the rock compression test containing the anchor solid was carried out to analyze the influence of the degree of peripheral rock fragmentation and the anchor support method on the mechanical properties of the rock body. The test results showed that the smaller the size of the structural surface, the more a greater number of anchor rods were needed, which in turn provided better support. With the increase in the size of the structural surface, the uniaxial compressive strength and modulus of elasticity of the specimen showed a gradual decrease. Numerical tests of the uniaxial compression of rock containing cohesive units showed that the deformation of the specimen near the anchor bar was significantly reduced, while the main rupture surface was blocked, and an obvious reinforcement zone was formed near the anchor bar. Under the double-anchor condition, the anchor tension stress was more obvious, the reinforcement zone was wider, and the rock rupture surface was strongly blocked, all of which made its reinforcement effect the more obvious. This double-anchor condition showed that the anchoring effect of the anchor rods on the specimens was reflected in two aspects of reinforcement and crack stopping. The denser the anchor rods, the wider the reinforcement zone and hence the more likely that the superposition effect will occur, which allowed the anchor rods to play a greater supporting role in stabilizing the rock. The research results can provide a theoretical basis for the design of anchor support and early warning prediction of destabilization damage in the fractured surrounding rock of coal mine roadways.

The Arctic stratospheric ozone depletion event in spring 2020 was the most severe compared with previous years. We retrieved the critical indicator ozone vertical column density (VCD) using zenith scattered light differential optical absorption spectroscopy (ZSL-DOAS) from March 2017 to September 2021 in Ny-Ålesund, Svalbard, Norway. The average ozone VCD over Ny-Ålesund between 18 March and 18 April 2020 was approximately 274.8 Dobson units (DU), which was only 64.7 ± 0.1% of that recorded in other years (2017, 2018, 2019, and 2021). The daily peak difference was 195.7 DU during this period. The retrieved daily averages of ozone VCDs were compared with satellite observations from the Global Ozone Monitoring Experiment-2 (GOME-2), a Brewer spectrophotometer, and a Système d’Analyze par Observation Zénithale (SAOZ) spectrometer at Ny-Ålesund. As determined using the empirical cumulative density function, ozone VCDs from the ZSL-DOAS dataset were strongly correlated with data from the GOME-2 and SAOZ at lower and higher values, and ozone VCDs from the Brewer instrument were overestimated. The resulting Pearson correlation coefficients were relatively high at 0.97, 0.87, and 0.91, respectively. In addition, the relative deviations were 2.3%, 3.1%, and 3.5%, respectively. Sounding and ERA5 data indicated that severe ozone depletion occurred between mid-March and mid-April 2020 in the 16–20 km altitude range over Ny-Ålesund, which was strongly associated with the overall persistently low temperatures in the winter of 2019/2020. Using ZSL-DOAS observations, we obtained ozone VCDs and provided evidence for the unprecedented ozone depletion during the Arctic spring of 2020. This is essential for the study of polar ozone changes and their effect on climate change and ecological conditions.

A recombinant inbred line population including 371 lines was developed by a high kernel number per spike (KNPS) genotype T1208 and a low KNPS genotype Chuannong18 (CN18). A genetic linkage map consisting of 11,583 markers was constructed by the Wheat55K SNP Array. The quantitative trait loci (QTLs) related to KNPS were detected in three years. Eight, twenty-seven, and four QTLs were identified using the ICIM-BIP, ICIM-MET, and ICIM-EPI methods, respectively. One QTL, QKnps.sau-2D.1, which was mapped on chromosome 2D, can explain 18.10% of the phenotypic variation (PVE) on average and be considered a major and stable QTL for KNPS. This QTL was located in a 0.89 Mb interval on chromosome 2D and flanked by the markers AX-109283238 and AX-111606890. Moreover, KASP-AX-111462389, a Kompetitive Allele-Specific PCR (KASP) marker which closely linked to QKnps.sau-2D.1, was designed. The genetic effect of QKnps.sau-2D.1 on KNPS was successfully confirmed in two RIL populations. The results also showed that the significant increase of KNPS and 1000-kernel weight (TKW) was caused by QKnps.sau-2D.1 overcoming the disadvantage due to the decrease of spike number (SN) and finally lead to a significant increase of grain yield. In addition, within the interval in which QKnps.sau-2D.1 is located in Chinese Spring reference genomes, only fifteen genes were found, and two genes that might associate with KNPS were identified. QKnps.sau-2D.1 may provide a new resource for the high-yield breeding of wheat in the future.

Abstract Scanning Electron Microscope/Focused Ion Beam (SEM/FIB) system has become valuable and popular tool for the analysis of biological materials such as dentine structures. According to physiological and anatomical studies, dentine structures are a complicated system containing collagen fibers, nanocrystalline hydroxyapatite, and numerous networks of tubular pores. During a routine FIB milling process, collagen fibers and other organic structures are vaporized, which increases the number of pores on the milled surface of the dentine. This causes the final cross-section to be more porous than the pristine sample. Unfortunately, little attention has been paid to the collagen fiber loss and how to preserve them during a FIB milling process. In this work, we present a novel and simple approach to preserve the organic portions of the dentine structure through metal staining. By using this method, the porosity of the dentine structure after the FIB milling process is significantly reduced similar to the pristine sample. This indicates that the organic portion of the dentine structure is well protected by the metal staining. This approach enables the SEM/FIB system to generate super-high quality SEM images with less ion beam damage; and the SEM images can better reflect the original condition of the dentine structure. Further, serial energy-dispersive X-ray spectroscopy (EDS) mapping of the stained dentine structure is achieved without an additional metal coating; and three-dimensional (3-D) elemental mapping of an occluded dentine is achieved with a significantly reduced data acquisition time.

Objective: To study the changes of physicochemical properties in Shuidouchi before and after fermentation, and to preliminarily explore the inhibitory effect of its extracts on castration-resistant prostate cancer cells (CRPC). Methods: Shuidouchi was fermented using three high-yielding protease strains. With reference to the national standard methods, contents ofamino nitrogen, total acid, pH, reducing sugar and soybean isoflavones in Shuidouchi before and after fermentation were tested, and total phenol and flavonoids were examined by chemical method. And the antioxidant capacity of Shuidouchi extracts was also determined. Finally, the inhibitory effect of Shuidouchi extracts fermented with the optimal strain was observed. Results: Fermented by high-yielding protease strains，the contents of amino nitrogen, reducing sugar, isoflavone and antioxidant capacity of soybean were all improved compared with steamed soybean, among which B19 strain fermented Shuidouchi had the best effect. And the extract of Shuidouchi fermented by B19 strain could selectively kill CRPC cells and promote their apoptosis, and inhibit the secretion of prostate-specific antigen (PSA), androgen (T) and dihydrotestosterone (DHT). Conclusion: Fermentation by high-yielding protease strains of Shuidouchi can change the physicochemical properties, and enhance its nutritional activities. Moreover, the extract of Shuidouchi fermented with B19 strain has an inhibitory effect on CRPC cells. This study provides data references and theoretical support for the research and development of health functional foods related to Shuidouchi.

With the rapid increase in the penetration rate of renewable energy, the power quality of grid-connected wind farm is deteriorated seriously with power fluctuation and point of common coupling (PCC) voltage instability. The conventional solution is to use the energy storage device and the reactive power compensation apparatus to adjust separately, which complicates the system structure. Besides, an active power filter is needed additionally when harmonic pollution caused by local nonlinear load is serious. To solve these problems, this paper investigates the modular multilevel converter-based battery energy storage system (MMC-BESS), which can realize fluctuating power suppression, PCC voltage regulation, and harmonic mitigation simultaneously in grid-connected wind farm. Firstly, the topology and energy flow of MMC-BESS have been studied. Then, three-layer balance control of the state of charge (SOC) is proposed, which is essential to maintaining the normal operation of the device. Finally, the overall control of MMC-BESS applied in the grid-connected wind farm is given. Plenty of experimental results are obtained from a downscaled MMC-BESS prototype, which validate the effectiveness of the proposed control strategy.

A camera with an image sensor is an important alternative device to a photodiode-based receiver of visible-light communication in outdoor scenarios. The intrinsic color separation capability of a camera qualifies color shift keying (CSK) modulation as an intuitive solution to enhance the achievable data rate. The symbol error rate (SER) of CSK modulation is considerably important to system design and performance evaluation, and has not been extensively investigated for outdoor optical camera communication systems from the viewpoint of camera-based channel and image processing-based demodulation. In this study, a two-level channel model is proposed to characterize CSK transmission in a single pixel and in the entire image. A general framework of SER analysis for arbitrary CSK constellations was proposed by directly calculating the upper bounds from the empirical distribution of the noise light in the CIE 1931 color space. Through numerical simulations, the influence of the image detector on CSK demodulation was evaluated. The results indicated that an accurate target region is important for maintaining the SER, and an enlarged target region is beneficial when the maximum ratio combination and selective combination algorithms are used in pixel combination.

Abstract The Hunga Tonga‐Hunga Ha'apai (HTHH) eruption on 15 January 2022 was one of the most explosive volcanic events of the 21st century so far. According to satellite‐based measurements, 0.4 Tg of sulfur dioxide (SO2) was injected into the stratosphere during the eruption. By using observations and model simulations, here we investigate changes in the chemical compositions of the stratosphere 1 year after the HTHH eruption and examine the key physical and chemical processes that influence the ozone (O3) concentrations. Injected SO2 was oxidized into sulfate during the first 2 months, and transported from the tropics to the Antarctic by the Brewer‐Dobson circulation within 1 year. In mid‐to‐low latitudes, enhanced sulfate aerosol increased O3 concentrations in the middle stratosphere but declined in the lower stratosphere. In addition to the chemical processes, sulfate aerosols also reduced polar low‐stratospheric O3 concentrations through enhanced Antarctic upwelling anomalies.

Introduction: Hyperlipidemia is a common metabolic disorder with presence of excess fat or lipids in the blood, may induce liver injury, oxidative stress and inflammatory. Xuezhiping capsule (XZP) is a famous Chinese patent medicine clinically used for anti-hyperlipidemia. However, the regulation mechanism of XZP on hyperlipidemia has not been elucidated so far.Methods: This study aimed to explore the effects of XZP on hypolipidemic, antioxidant and anti-inflammatory effects, and the potential mechanism by a combination of untargeted metabolomics and 16S rRNA sequencing.Results: The results indicated that XZP reduced the level of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), increased the level of high density liptein cholesterol (HDL-C), alleviated excessive accumulation of lipid droplets in liver. Biochemical indexes of liver function including gamma glutamyl transferase (GGT) and glutamic oxaloacetic transaminase (GOT) in liver were remarkably decreased. Meanwhile, XZP increased the level of oxidative stress biochemical indexes including superoxide dismutase (SOD) and glutathione (GSH). In addition, XZP increased the level of peroxisome proliferators-activated receptors α (PPARα), acetyl CoA carboxylase 1 (ACOX1) and cholesterol 7-alpha hydroxylase (CYP7A1) in liver, and improved lipid metabolism in serum, liver and fecal lipid metabolism. XZP increased diversity index and the ratio of Firmicutes and Bacteroidetes, regulated seventeen genera, and illustrated strong correlations with liver lipid metabolism and phenotypic indicators.Discussion: These findings suggest that XZP reduced blood lipid and liver lipid, protected liver function, anti inflammation and anti-oxidation, ameliorate lipid metabolic disorders by modulating alpha linolenic acid and linoleic acid metabolism, bile acid metabolism, arachidonic acid metabolism, and regulated gut microbiota composition of high-fat diet (HFD) hamsters.

Mycoplankton play a key role in aquatic microbial food webs and nutrient cycling. However, the environmental factors that affect their composition and trophic modes in coastal water remain unclear. In this study, we used fungal metabarcoding to characterize seasonal mycoplanktonic communities in the surface water of the Maowei Sea. Dothideomycetes and Sordariomycetes were the dominant classes in the Maowei Sea. Random forest modeling analyses suggested that Ochroconis, Rhodotorula, Perenniporia and Derxomyces were the best seasonal bioindicators of environmental changes. Spearman’s correlation analysis showed that TOC (total organic carbon) is the main factor affecting mycoplanktonic bioindicators. Through FUNGuild analysis, we classified mycoplankton in the Maowei Sea into eight trophic modes and found that saprotrophs were the most abundant. Random forest analysis and Spearman’s correlation indicated that the mycoplankton trophic modes could reflect environmental changes in the Maowei Sea and were mainly influenced by dissolved inorganic phosphorus (DIP), dissolved oxygen (DO), and total organic carbon (TOC). Mycoplanktonic alpha and beta diversities significantly varied in different seasons (p

Abstract A novel localized surface plasmon resonance (LSPR) system based on the coupling of gold nanomushrooms (AuNMs) and gold nanoparticles (AuNPs) is developed to enable a significant plasmonic resonant shift. The AuNP size, surface chemistry, and concentration are characterized to maximize the LSPR effect. A 31 nm redshift is achieved when the AuNMs are saturated by the AuNPs. This giant redshift also increases the full width of the spectrum and is explained by the 3D finite‐difference time‐domain (FDTD) calculation. In addition, this LSPR substrate is packaged in a microfluidic cell and integrated with a CRISPR‐Cas13a RNA detection assay for the detection of the SARS‐CoV‐2 RNA targets. Once activated by the target, the AuNPs are cleaved from linker probes and randomly deposited on the AuNM substrate, demonstrating a large redshift. The novel LSPR chip using AuNP as an indicator is simple, specific, isothermal, and label‐free; and thus, provides a new opportunity to achieve the next generation multiplexing and sensitive molecular diagnostic system.

Introduction: Epimedium, a traditional Chinese medicine (TCM) commonly used in ancient and modern China, is one of the traditional Chinese medicines clinically used to treat kidney yang deficiency syndrome (KYDS). There are differences in the efficacy of Epimedium before and after processing, and the effect of warming the kidney and enhancing yang is significantly enhanced after heating with suet oil. However, the active compounds, corresponding targets, metabolic pathways, and synergistic mechanism of frying Epimedium in suet oil to promote yang, remain unclear.Methods: Herein, a strategy based on comprehensive GC-TOF/MS metabolomics and network pharmacology analysis was used to construct an “active compounds-targets-metabolic pathways” network to identify the active compounds, targets and metabolic pathways involved. Subsequently, the targets in kidney tissue were further validated by real-time quantitative polymerase chain reaction (RT-qPCR). Histopathological analysis with physical and biochemical parameters were performed.Results: Fifteen biomarkers from urine and plasma, involving five known metabolic pathways related to kidney yang deficiency were screened. The network pharmacology results showed 37 active compounds (13 from Epimedium and 24 from suet oil), 159 targets, and 267 pathways with significant correlation. Importantly, integrated metabolomics and network pharmacologic analysis revealed 13 active compounds (nine from Epimedium and four from suet oil), 7 corresponding targets (ALDH2, ARG2, GSTA3, GSTM1, GSTM2, HPGDS, and NOS2), two metabolic pathways (glutathione metabolism, arginine and proline metabolism), and two biomarkers (Ornithine and 5-Oxoproline) associated with improved kidney yang deficiency by Epimedium fried with suet oil.Discussion: These finds may elucidate the underlying mechanism of yang enhancement via kidney warming effects. Our study indicated that the mechanism of action mainly involved oxidative stress and amino acid metabolism. Here, we demonstrated the novel strategies of integrating metabolomics and network pharmacology in exploring of the mechanisms of traditional Chinese medicines.