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Flavin-dependent halogenase (FDH) is highly prized in pharmaceutical and chemical industries for its exceptional capacity to produce halogenated aromatic compounds with precise regioselectivity. This study has devised a multi-enzyme self-assembly strategy to construct an effective and reliable in vitro coenzyme cycling system tailored for FDHs. Initially, tri-enzyme self-assembling nanoclusters (TESNCs) were developed, comprising glucose dehydrogenase (GDH), flavin reductase (FR) and FDH. The TESNCs exhibited enhanced thermal stability and conversion efficiency compared to free triple enzyme mixtures during the conversion of L-Trp to 6-Cl-L-Trp, resulting in a 2.1-fold increase in yield. Subsequently, an ordered co-immobilization of GDH, FR, and FDH was established, further amplifying the stability and catalytic efficiency of the FDH coenzyme cycle system. Compared to the free TESNCs, the immobilized TESNCs demonstrated a 4.2-fold increase in catalytic efficiency in a 5 mL reaction system. This research provides an effective strategy for developing a robust and efficient coenzyme recycling system for FDHs., (© 2024 Wiley Periodicals LLC.)

Silicosis is a systemic disease with predominantly diffuse fibrosis of the lungs due to prolonged inhalation of free SiO 2 dust during the manufacturing process, for which there is no effective treatment. In this study, we used a combined epigenetic and transcriptomic approach to reveal the chromatin-opening features of silicosis and identify the key transcription factor activator protein 1 (AP-1) that responds to silicosis fibrosis. Therapeutic administration of an AP-1 inhibitor inhibits the PI3K/AKT signaling pathway, reduces fibrosis marker proteins, and significantly ameliorates lung fibrosis in a mouse model of silicosis. In addition, it was observed that the expression of Jun and JunB was significantly up-regulated in a TGF-β1-induced in vitro transdifferentiation model of NIH/3T3 cells, and Co-IP confirmed that a protein complex could be formed between Jun and JunB. Mechanistically, silencing of Jun and JunB expression reversed the activation of the PI3K/AKT signaling pathway and the upregulation of fibrosis marker proteins in NIH/3 T3 cells after TGF-β1 stimulation. Taken together, Jun/JunB is expected to be a potential therapeutic target for silicosis fibrosis., Competing Interests: Declaration of competing interest The authors report no conflicts of interest in this work. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, based on the self-assembly strategy, we fused CipA with carbonyl reductase LXCAR S154Y derived from Leifsonia xyli by gene coding, and successfully performed the carrier-free immobilization of LXCAR S154Y . The immobilized enzyme was then characterized using scanning electron microscope (SEM), dynamic light scattering (DLS) and fourier transform infrared spectroscopy (FTIR). Compared with the free enzyme, the immobilized LXCAR S154Y exhibited a 2.3-fold improvement in the catalytic efficiency k cat /k m for the synthesis of a chiral pharmaceutical intermediate (R)-3,5-bis(trifluoromethyl)phenyl ethanol ((R)-BTPE) by reducing 3,5-bis(trifluoromethyl)acetophenone (BTAP). Moreover, the immobilized enzyme showed the enhanced stability while maintaining over 61 % relative activity after 18 cycles of batch reaction. Further, when CipA-fused carbonyl reductase was employed for (R)-BTPE production in a continuous flow reaction, almost complete yield (97.0 %) was achieved within 7 h at 2 M (512.3 g/L) of BTAP concentration, with a space-time yield of 1717.1 g·L -1 ·d -1 . Notably, we observed the retention of cofactor NADH by CipA-based enzyme aggregates, resulting in a higher total turnover number (TTN) of 4815 to facilitate this bioreductive process. This research developed a concise strategy for efficient preparation of chiral intermediate with cofactor self-sufficiency via continuous flow biocatalysis, and the relevant mechanism was also explored., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Prolonged exposure to free silica leads to the development of silicosis, wherein activated fibroblasts play a pivotal role in its pathogenesis and progression. Fibroblast Activation Protein (FAP), as a biomarker for activated fibroblasts, its expression pattern and role in key aspects of silicosis pathogenesis remain unclear. This study elucidated the expression pattern and function of FAP through population-based epidemiological investigations, establishment of mouse models of silicosis, and in vitro cellular models. Results indicated a significant elevation of FAP in plasma from silicosis patients and lung tissues from mouse models of silicosis. In the cellular model, we observed a sharp increase in FAP expression early in the differentiation process, which remained high expression. Inhibition of FAP suppressed fibroblast differentiation, while overexpression of FAP produced the opposite effect. Moreover, fibroblast-derived FAP can alter the phenotype and function of neighboring macrophages. In summary, we revealed a high expression pattern of FAP in silicosis and its potential mechanistic role in fibrosis, suggesting FAP as a potential therapeutic target for silicosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Silicosis is a progressive interstitial lung disease characterized by diffuse pulmonary fibrosis. The transdifferentiation of lung fibroblasts into myofibroblasts is a key cellular event driving the progression of silicosis fibrosis. Recent studies have shown that PD-L1 expression is significantly upregulated in activated fibroblasts, and PD-L1 plays a crucial role in mediating fibroblast transdifferentiation. This study aims to elucidate the molecular mechanisms regulating PD-L1 expression in fibroblasts and analyze the functional significance of PD-L1 upregulation in fibroblast activity and silicosis fibrosis. In this research, an in vitro model of TGF-β1-induced NIH-3 T3 fibroblast transdifferentiation was established. Small molecule inhibitors, siRNA, and plasmids were used to interfere with the PI3K/AKT/mTOR signaling pathway and PD-L1 expression. It was found that TGF-β1 stimulation increased PD-L1 expression in fibroblasts, while blocking the PI3K/AKT/mTOR pathway inhibited this upregulation. Knockdown of PD-L1 significantly inhibited fibroblast transdifferentiation and impeded TGF-β1-induced activation of the PI3K/AKT/mTOR pathway, whereas PD-L1 overexpression had the opposite effect. Additionally, PD-L1 protein in fibroblasts undergoes ubiquitin-proteasome-mediated degradation, negatively regulating PD-L1 upregulation. In vivo, adeno-associated virus was used to specifically knockdown PD-L1 in mouse lung fibroblasts, resulting in significantly reduced lung tissue damage and fibrosis in silicosis mice. This effect was associated with the involvement of the PI3K/AKT/mTOR pathway. In summary, PD-L1 expression in fibroblasts is upregulated during transdifferentiation, a process regulated by the PI3K/AKT/mTOR pathway. Upregulated PD-L1 enhances PI3K/AKT/mTOR signaling through positive feedback, sustaining fibroblast activation. Ubiquitin-proteasome-mediated protein degradation may serve as a negative feedback mechanism maintaining PD-L1 homeostasis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Morphological novelties, or key innovations, are instrumental to the diversification of the organisms. In plants, one such innovation is the evolution of zygomorphic flowers, which is thought to promote outcrossing and increase flower morphological diversity. We isolated three allelic mutants from two Mimulus species displaying altered floral symmetry and identified the causal gene as the ortholog of Arabidopsis BLADE-ON-PETIOLE . We found that MlBOP and MlCYC2A physically interact and this BOP-CYC interaction module is highly conserved across the angiosperms. Furthermore, MlBOP self-ubiquitinates and suppresses MlCYC2A self-activation. MlCYC2A, in turn, impedes MlBOP ubiquitination. Thus, this molecular tug-of-war between MlBOP and MlCYC2A fine-tunes the expression of MlCYC2A , contributing to the formation of bilateral symmetry in flowers, a key trait in angiosperm evolution.

Bitter taste receptors (TAS2Rs) Tas2r108 gene possesses a high abundance in mouse kidney; however, the biological functions of Tas2r108 encoded receptor TAS2Rs member 4 (TAS2R4) are still unknown. In the present study, we found that mouse TAS2R4 (mTAS2R4) signaling was inactivated in chronic high glucose-stimulated mouse podocyte cell line MPC, evidenced by the decreased protein expressions of mTAS2R4 and phospholipase C β2 (PLCβ2), a key downstream molecule of mTAS2R4 signaling. Nonetheless, agonism of mTAS2R4 by quinine recovered mTAS2R4 and PLCβ2 levels, and increased podocyte cell viability as well as protein expressions of ZO-1 and nephrin, biomarkers of podocyte slit diaphragm, in high glucose-cultured MPC cells. However, blockage of mTAS2R4 signaling with mTAS2R4 blockers γ-aminobutyric acid and abscisic acid, a Gβγ inhibitor Gallein, or a PLCβ2 inhibitor U73122 all abolished the effects of quinine on NLRP3 inflammasome and p-NF-κB p65 as well as the functional podocyte proteins in MPC cells in a high glucose condition. Furthermore, knockdown of mTAS2R4 with lentivirus-carrying Tas2r108 shRNA also ablated the effect of quinine on the key molecules of the above inflammatory signalings and podocyte functions in high glucose-cultured MPC cells. In summary, we demonstrated that activation of TAS2R4 signaling alleviated the podocyte injury caused by chronic high glucose, and inhibition of NF-κB p65 and NLRP3 inflammasome mediated the protective effects of TAS2R4 activation on podocytes. Moreover, activation of TAS2R4 signaling could be an important strategy for prevention and treatment of diabetic kidney disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

It has been well documented that mutations in coding DNA or cis-regulatory elements underlie natural phenotypic variation in many organisms. However, the development of sophisticated functional tools in recent years in a wide range of traditionally non-model systems have revealed many 'unusual suspects' in the molecular bases of phenotypic evolution, including upstream open reading frames (uORFs), cryptic splice sites, and small RNAs. Furthermore, large-scale genome sequencing, especially long-read sequencing, has identified a cornucopia of structural variation underlying phenotypic divergence and elucidated the composition of supergenes that control complex multi-trait polymorphisms. In this review article we highlight recent studies that demonstrate this great diversity of molecular mechanisms producing adaptive genetic variation and the panoply of evolutionary paths leading to the 'grandeur of life'., Competing Interests: Declaration of interests The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The emergence of novel traits is often preceded by a potentiation phase, when all the genetic components necessary for producing the trait are assembled. However, elucidating these potentiating factors is challenging. We have previously shown that an anthocyanin-activating R2R3-MYB, STRIPY, triggers the emergence of a distinct foliar pigmentation pattern in the monkeyflower Mimulus verbenaceus. Here, using forward and reverse genetics approaches, we identify three potentiating factors that pattern STRIPY expression: MvHY5, a master regulator of light signaling that activates STRIPY and is expressed throughout the leaf, and two leaf developmental regulators, MvALOG1 and MvTCP5, that are expressed in opposing gradients along the leaf proximodistal axis and negatively regulate STRIPY. These results provide strong empirical evidence that phenotypic novelties can be potentiated through incorporation into preexisting genetic regulatory networks and highlight the importance of positional information in patterning the novel foliar stripe., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Silicosis is one of the most common and severe types of pneumoconiosis and is characterized by lung dysfunction, persistent lung inflammation, pulmonary nodule formation, and irreversible pulmonary fibrosis. The transdifferentiation of fibroblasts into myofibroblasts is one of the main reasons for the exacerbation of silicosis. However, the underlying mechanism of transcription factors regulating silicosis fibrosis has not been clarified. The aim of this study was to investigate the potential mechanism of transcription factor FOXF1 in fibroblast transdifferentiation in silica-induced pulmonary fibrosis. Therefore, a silicosis mouse model was established, and we found that FOXF1 expression level was significantly down-regulated in the silicosis group, and after overexpression of FOXF1 by adeno-associated virus (AAV), FOXF1 expression level was up-regulated, and silicosis fibrosis was alleviated. In order to further explore the specific regulatory mechanism of FOXF1 in silicosis, we established a fibroblasts transdifferentiation model induced by TGF-β in vitro. In the model, the expression levels of SMAD2/3 and P-SMAD2/3 were up-regulated, but the expression levels of SMAD2/3 and P-SMAD2/3 were down-regulated, inhibiting transdifferentiation and accumulation of extracellular matrix after the overexpressed FOXF1 plasmid was constructed. However, after silencing FOXF1, the expression levels of SMAD2/3 and P-SMAD2/3 were further up-regulated, aggravating transdifferentiation and accumulation of extracellular matrix. These results indicate that the activation of FOXF1 in fibroblasts can slow down the progression of silicosis fibrosis by inhibiting TGF-β/SMAD2/3 classical pathway, which provides a new idea for further exploration of silicosis treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Although overexposure to manganese (Mn) is known to cause neurotoxic damage, effective exposure markers for assessing Mn loading in Mn-exposed workers are lacking. Here, we construct a Mn-exposed rat model to perform correlation analysis between Mn-induced neurological damage and Mn levels in various biological samples. We combine this analysis with epidemiological investigation to assess whether Mn concentrations in red blood cells (MnRBCs) and urine (MnU) can be used as valid exposure markers. The results show that Mn exposure resulted in neurotoxic damage in rats and that MnRBCs correlated well with neurological damage, showing potential as a novel Mn exposure biomarker. These findings provide a basis for health monitoring of Mn-exposed workers and the development of more appropriate biological exposure limits., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Long-term exposure to inhalable silica particles may lead to severe systemic pulmonary disease, such as silicosis. Exosomes have been demonstrated to dominate the pathogenesis of silicosis, but the underlying mechanisms remain unclear. Therefore, this study aimed to explore the roles of exosomes by transmitting miR-107, which has been linked to the toxic pulmonary effects of silica particles. We found that miR-107, miR-122-5p, miR-125a-5p, miR-126-5p, and miR-335-5p were elevated in exosomes extracted from the serum of patients with silicosis. Notably, an increase in miR-107 in serum exosomes and lung tissue was observed in the experimental silicosis mouse model, while the inhibition of miR-107 reduced pulmonary fibrosis. Moreover, exosomes helped the migration of miR-107 from macrophages to lung fibroblasts, triggering the transdifferentiation of cell phenotypes. Further experiments demonstrated that miR-107 targets CDK6 and suppresses the expression of retinoblastoma protein phosphorylation and E2F1, resulting in cell-cycle arrest. Overall, micron-grade silica particles induced lung fibrosis through exosomal miR-107 negatively regulating the cell cycle signaling pathway. These findings may open a new avenue for understanding how silicosis is regulated by exosome-mediated cell-to-cell communication and suggest the prospect of exosomes as therapeutic targets., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this paper, the workability, mechanical, ion leaching, and drying shrinkage properties of alkali-activated concrete with recycled coarse and fine aggregates were studied, and the pore structure and micro-morphology of different alkali-activated recycled aggregate concretes (AARACs) were characterized by using the mercury intrusion method and scanning electron microscopy, respectively. The experimental results showed that with the increase in the replacement rate of the recycled fine aggregate (RFA), the flowability showed a decreasing trend. Adding a certain amount of RFA improves the mechanical properties of the AARAC. The compressive strength at a curing age of 28 days was 65.3 MPa with 70 wt% RFA replacement. When the replacement rate of the RFA was 100 wt%, the maximum splitting tensile strength (4.5 MPa) was obtained at a curing age of 7 days. However, the addition of the RFA had little effect on the flexural strength of the AARAC. As an extension of the curing age, the splitting tensile strength, flexural strength, tension-to-compression ratio, and flexure-to-compression ratio all showed an increasing trend at first and then a decreasing trend. At a curing age of 7 days, the tension-to-compression ratio and flexure-to-compression ratio were both high (except for those of R100), indicating that the ductility and toughness of the specimen were improved. The addition of the RFA increased the drying shrinkage of the AARAC. At a curing age of 120 days, compared to the specimen without the RFA, the drying shrinkage rate of the specimen with the addition of 70 wt% RFA increased by 34.15%. As the curing age increased, the microstructure of the reaction products became denser, but the proportion of large-diameter pores increased. This study evaluated the application of RFA in AARAC. The experimental results showed that the RFA-based AARAC had acceptable mechanical and durability properties., Competing Interests: The authors declare no conflict of interest.

Pneumoconiosis is one of the most serious occupational diseases worldwide. Silicosis due to prolonged inhalation of free silica dust during occupational activities is one of the main types. Cuproptosis is a newly discovered mode of programmed cell death characterized by the accumulation of free copper in the cell, which ultimately leads to cell death. Increased copper in the serum of silicosis patients, suggests that the development of silicosis is accompanied by changes in copper metabolism, but whether cuproptosis is involved in the progression of silicosis is actually to be determined. To test this hypothesis, we screened the genetic changes in patients with idiopathic fibrosis by bioinformatics methods and predicted and functionally annotated the cuproptosis-related genes among them. Subsequently, we established a mouse silicosis model and detected the concentration of copper ions and the activity of ceruloplasmin (CP) in serum, as well as changes of the concentration of copper and cuproptosis related genes in mouse lung tissues. We identified 9 cuproptosis-related genes among the differential genes in patients with IPF at different times and the tissue-specific expression levels of ferredoxin 1 (FDX1) and Lipoyl synthase (LIAS) proteins. Furthermore, serum CP activity and copper ion levels in silicosis mice were elevated on days 7th and 56th after silica exposure. The expression of CP in mouse lung tissue elevated at all stages after silica exposure. The mRNA level of FDX1 decreased on days 7th and 56th, and the protein level remained in accordance with the mRNA level on day 56th. LIAS and Dihydrolipoamide dehydrogenase (DLD) levels were downregulated at all times after silica exposure. In addition, Heatshockprotein70 (HSP70) expression was increased on day 56. In brief, our results demonstrate that there may be cellular cuproptosis during the development of experimental silicosis in mice and show synchronization with enhanced copper loading in mice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Whether and how tumor intrinsic signature determines macrophage-elicited metastasis remain elusive. Here, we show, in detailed studies of data regarding 7,477 patients of 20 types of human cancers, that only 13.8% ± 2.6%/27.9% ± 3.03% of patients with high macrophage infiltration index exhibit early recurrence/vascular invasion. In parallel, although macrophages enhance the motility of various hepatoma cells, their enhancement intensity is significantly heterogeneous. We identify that the expression of malignant Dicer, a ribonuclease that cleaves miRNA precursors into mature miRNAs, determines macrophage-elicited metastasis. Mechanistically, the downregulation of Dicer in cancer cells leads to defects in miRNome targeting NF-κB signaling, which in turn enhances the ability of cancer cells to respond to macrophage-related inflammatory signals and ultimately promotes metastasis. Importantly, transporting miR-26b-5p, the most potential miRNA targeting NF-κB signaling in hepatocellular carcinoma, can effectively reverse macrophage-elicited metastasis of hepatoma in vivo. Our results provide insights into the crosstalk between Dicer-elicited miRNome and cancer immune microenvironments and suggest that strategies to remodel malignant cell miRNome may overcome pro-tumorigenic activities of inflammatory cells., Competing Interests: Declaration of interests The authors disclose no competing interests., (Copyright © 2024 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

The halogenase-based catalysis is one of the most environmentally friendly methods for the synthesis of halogenated products, among which flavin-dependent halogenases (FDHs) have attracted great interest as one of the most promising biocatalysts due to the remarkable site-selectivity and wide substrate range. However, the complexity of constructing the NAD + -NADH-FAD-FADH 2 bicoenzyme cycle system has affected the engineering applications of FDHs. In this work, a coenzyme self-sufficient tri-enzyme fusion was constructed and successfully applied to the continuous halogenation of L-tryptophan. SpFDH was firstly identified derived from Streptomyces pratensis, a highly selective halogenase capable of generating 6-chloro-tryptophan from tryptophan. Then, using gene fusion technology, SpFDH was fused with glucose dehydrogenase (GDH) and flavin reductase (FR) to form a tri-enzyme fusion, which increased the yield by 1.46-fold and making the coenzymes self-sufficient. For more efficient halogenation of L-tryptophan, a continuous halogenation bioprocess of L-tryptophan was developed by immobilizing the tri-enzyme fusion and attaching it to a continuous catalytic device, which resulted in a reaction yield of 97.6% after 12 h reaction. An FDH from S. pratensis was successfully applied in the halogenation and our study provides a concise strategy for the preparation of halogenated tryptophan mediated by multienzyme cascade catalysis., (© 2024 Wiley‐VCH GmbH.)

Manganese is essential trace elements, to participate in the body a variety of biochemical reactions, has important physiological functions, such as stimulate the immune cell proliferation, strengthen the cellular immunity, etc. However, excessive manganese exposure can cause damage to multiple systems of the body.The immune system is extremely vulnerable to external toxicants, however manganese research on the immune system are inadequate and biomarkers are lacking. Therefore, here we applied a manganese-exposed rat model to make preliminary observations on the immunotoxic effects of manganese. We found that manganese exposure inhibited humoral immune function in rats by decreasing peripheral blood IgG (ImmunoglobulinG, IgG), IgM (ImmunoglobulinM, IgM) and complement C3 levels; It also regulates rat cellular immune activity by influencing peripheral blood, spleen, and thymus T cell numbers and immune organ ICs (Immune Checkpoints, ICs) and cytokine expression. Furthermore, it was revealed that the impact of manganese exposure on the immune function of rats exhibited a correlation with both the dosage and duration of exposure. Notably, prolonged exposure to high doses of manganese had the most pronounced influence on rat immune function, primarily manifesting as immunosuppression.The above findings suggest that manganese exposure leads to impaired immune function and related changes in immune indicators, or may provide clues for the discovery of its biomarkers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

ω-Transaminase (ω-TA) is a promising biocatalyst for the synthesis of chiral amines. In this study, a ω-TA derived from Vitreoscilla stercoraria DSM 513 (VsTA) was heterologous expressed in recombinant E. coli cells and applied to reduce 4'-(trifluoromethyl)acetophenone (TAP) to (S)-1-[4-(trifluoromethyl)phenyl]ethylamine ((S)-TPE), a pharmaceutical intermediate of chiral amine. Aimed to a more efficient synthesis of (S)-TPE, VsTA was further engineered via a semi-rational strategy. Compared to wild-type VsTA, the obtained R411A variant exhibited 2.39 times higher activity towards TAP and enhanced catalytic activities towards other prochiral aromatic ketones. Additionally, better thermal stability for R411A variant was observed with 25.4% and 16.3% increase in half-life at 30 °C and 40 °C, respectively. Structure-guided analysis revealed that the activity improvement of R411A variant was attributed to the introduction of residue A411, which is responsible for the increase in the hydrophobicity of substrate tunnel and the alleviation of steric hindrance, thereby facilitating the accessibility of hydrophobic substrate TAP to the active center of VsTA. This study provides an efficient strategy for the engineering of ω-TA based on semi-rational approach and has the potential for the molecular modification of other biocatalysts., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cement-based material encapsulation is a method of encapsulating electronic devices in highly thermally conductive cement-based materials to improve the heat dissipation performance of electronic components. In the field of construction, a thermoelectric generator (TEG) encapsulated with cement-based materials used in the building envelope has significant potential for waste heat energy recovery. The purpose of this study was to investigate the effect of cement-based materials integrated with aluminum heatsinks on the heat dissipation of the TEG composite structure. In this work, three types of thermoelectric work units encapsulated with cement paste were proposed. Moreover, we explored the effect of encapsulated structure, heat dissipation area, the height of thermoelectric single leg, and heat input temperature on maintaining the temperature difference between the two sides of the thermoelectric single leg with COMSOL Multiphysics. The numerical simulation results showed that under the conditions of a heat source temperature of 313.15 K and ambient temperature of 298.15 K, the temperature difference between the two sides of the internal thermoelectric single leg of Type-III can maintain a stable temperature difference of 7.77 K, which is 32.14% higher than that of Type-I and Type-II (5.88 K), and increased by 26.82% in the actual experiment. This work provides a reference for the selection and application of TEG composite structures of cement-based materials combined with aluminum heatsinks.

Nectar guide trichomes play crucial ecological roles in bee-pollinated flowers, as they serve as footholds and guides for foraging bees to access the floral rewards. However, the genetic basis of natural variation in nectar guide trichomes among species remains poorly understood. In this study, we performed genetic analysis of nectar guide trichome variation between two closely related monkeyflower (Mimulus) species, the bumblebee-pollinated Mimulus lewisii and self-pollinated M. parishii. We demonstrate that a MIXTA-like R2R3-MYB gene, GUIDELESS, is a major contributor to the nectar guide trichome length variation between the two species. The short-haired M. parishii carries a recessive allele due to non-synonymous substitutions in a highly conserved motif among MIXTA-like MYB proteins. Furthermore, our results suggest that besides GUIDELESS, additional loci encoding repressors of trichome elongation also contribute to the transition from bumblebee-pollination to selfing. Taken together, these results suggest that during a pollination syndrome switch, changes in seemingly complex traits such as nectar guide trichomes could have a relatively simple genetic basis, involving just a few genes of large effects., (© 2024. The Author(s).)

Polycyclic aromatic hydrocarbons (PAHs), which are a wide range of environmental toxicants, may act on humans through inhalation, ingestion, and skin contact, resulting in a range of toxic reactions. Epidemiological studies showed that long-term exposure to PAHs in the occupational and living environment results in a substantial rise in the incidence rate of many cancers in the population, so the prevention and treatment of these diseases have become a major worldwide public health problem. N6-methyladenosine (m6A) modification greatly affects the metabolism of RNA and is implicated in the etiopathogenesis of many kinds of diseases. In addition, m6A-binding proteins have an important role in disease development. The abnormal expression of these can cause the malignant proliferation, migration, invasion, and metastasis of cancers. Furthermore, a growing number of studies revealed that environmental toxicants are one of the cancer risk factors and are related to m6A modifications. Exposure to environmental toxicants can alter the methylation level of m6A and the expression of the m6A-binding protein, thus promoting the occurrence and development of cancers through diverse mechanisms. m6A may serve as a biomarker for early environmental exposure. Through the study of m6A, we can find the health injury early, thus providing a new sight for preventing and curing environmental health-related diseases., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Waste dolomite powder (WDP) is a byproduct obtained from dolomite quarries during the preparation of dolomite products. To study the re-utilisation of WDP, an eco-friendly cement-based material was prepared using WDP as a micro-aggregate. The effects of WDP on the early hydration process, microscale characteristics, and life-cycle assessment of cement paste are discussed in this study. The isothermal calorimetry results showed that the incorporating WDP in cement paste accelerated the early hydration process of cement according to the degree of reaction. In this case, the setting time of the cement pastes with WDP was shortened, and the early compressive strength was significantly improved. The results of X-ray diffraction and scanning electron microscopy analysis at early curing ages (1 and 3 d) showed changes in the peak intensity of ettringite and portlandite and a denser microstructure. Mercury intrusion porosimetry tests showed that the middle and large capillary pores were refined by the nucleation and filling effects of WDP. Based on environmental and economic evaluations, the utilisation of WDP reduced energy consumption, CO 2 emissions, and economic costs. Compared to the sample without WDP, the energy consumption, CO 2 emissions, and economic cost indices were 42 %, 42.69 %, and 39.4 % lower, respectively. Our results may provide valuable references for the re-utilisation of WDP in low-carbonation cement-based materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Until now, the specific pathogenesis of silicosis is not clear. Exosomal miRNAs, as a newly discovered intercellular communication medium, play an important role in many diseases. Our previous research found that serum exosomal miR125a-5p was increased in silicosis patients by miRNAs high-throughput sequencing. TRAF6, is a target gene of miR125a-5p, which is involved in T-cell differentiation. Furthermore, results from animal study indicate that knockdown of miR-125a-5p can regulate T lymphocyte subsets and significantly reduce pulmonary fibrosis by targeting TRAF6. However, the level of serum exosomal miR125a-5p in silicosis patients has not been reported, the role of macrophages-secreted exosomal miR-125a-5p in regulating T cell differentiation to promote fibroblast transdifferentiation (FMT) remains unknown. In this study, the levels of serum exosomal miR125a-5p and serum TGF-β1, IL-17A, IL-4 cytokines in silicosis patients were elevated, with the progression of silicosis, the level of serum exosomal miR125a-5p and serum IL-4 were increased; thus, the serum level of IFN-γ was negatively correlated with the progression of silicosis. In vitro, the levels of miR125a-5p in macrophages, exosomes, and T cells stimulated by silica were significantly increased. When the mimic was transfected into T cells, which directly suppressed TRAF6 and caused the imbalance of T cells differentiation, induced FMT. To sum up, these results indicate that exosomal miR-125a-5p may by targeting TRAF6 of T cells, induces the activation and apoptosis of T cells and the remodeling of Th1/Th2 and Th17/Tregs distribution, ultimately promotes FMT. Suggesting that exosomal miR-125a-5p may be a potential therapeutic target for silicosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Mn (Manganese, Mn) is an essential trace element involved in various biological processes such as the regulation of immune, nervous and digestive system functions. However, excessive Mn exposure can lead to immune damage. Occupational workers in cement and ferroalloy manufacturing and other related industries are exposed to low levels of Mn for a long time. Mn exposure is one of the important occupational hazards, but the research on the effect of Mn on the immune system of the occupational population is not complete, and there is no reliable biomarker. Therefore, this study aimed to evaluate the immunotoxicity of Mn from the soluble immune checkpoint TIM-3 (T-cell immunoglobulin and mucin containing protein 3, TIM-3) and complement C3. A total of 144 Mn-exposed workers were recruited from a bus manufacturing company and a railroad company in Henan Province. An inductively coupled plasma mass spectrometer was used to detect the concentration of RBC Mn (Red blood cell Mn, RBC Mn), and ELISA kits were used to detect serum complement C3 and TIM-3. Finally, the subjects were statistically analyzed by dividing them into low and high Mn groups based on the median RBC Mn concentration. We found that Mn exposure resulted in elevated serum TIM-3 expression and decreased complement C3 expression in workers; that serum TIM-3 and complement C3 expression showed a dose-response relationship with RBC Mn; and that the mediating effect of complement C3 between RBC Mn and TIM-3 was found to be significant. The above findings indicate that this study has a preliminary understanding of the effect of Mn exposure on the immune system of the occupational population exposed to Mn, and complement C3 and TIM-3 may be biomarkers of Mn exposure, which may provide clues for the prevention and control of Mn occupational hazards., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Qi, Si, Jin, Guo, Xia, He, Deng, Deng, Yao and Hao.)

The evolution of genomic incompatibilities causing postzygotic barriers to hybridization is a key step in species divergence. Incompatibilities take 2 general forms-structural divergence between chromosomes leading to severe hybrid sterility in F1 hybrids and epistatic interactions between genes causing reduced fitness of hybrid gametes or zygotes (Dobzhansky-Muller incompatibilities). Despite substantial recent progress in understanding the molecular mechanisms and evolutionary origins of both types of incompatibility, how each behaves across multiple generations of hybridization remains relatively unexplored. Here, we use genetic mapping in F2 and recombinant inbred line (RIL) hybrid populations between the phenotypically divergent but naturally hybridizing monkeyflowers Mimulus cardinalis and M. parishii to characterize the genetic basis of hybrid incompatibility and examine its changing effects over multiple generations of experimental hybridization. In F2s, we found severe hybrid pollen inviability (<50% reduction vs parental genotypes) and pseudolinkage caused by a reciprocal translocation between Chromosomes 6 and 7 in the parental species. RILs retained excess heterozygosity around the translocation breakpoints, which caused substantial pollen inviability when interstitial crossovers had not created compatible heterokaryotypic configurations. Strong transmission ratio distortion and interchromosomal linkage disequilibrium in both F2s and RILs identified a novel 2-locus genic incompatibility causing sex-independent gametophytic (haploid) lethality. The latter interaction eliminated 3 of the expected 9 F2 genotypic classes via F1 gamete loss without detectable effects on the pollen number or viability of F2 double heterozygotes. Along with the mapping of numerous milder incompatibilities, these key findings illuminate the complex genetics of plant hybrid breakdown and are an important step toward understanding the genomic consequences of natural hybridization in this model system., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The shortage of natural aggregate poses challenges and offers new opportunities for the construction industry. Under this background, the emergence of recycled aggregates sheds new lights on building aggregate. In this study, a green ultra-high performance geopolymer concrete (UHPGC) containing recycled fine aggregate (RFA) was prepared. To assess the feasibility of RFA and reveal the reaction mechanism of UHPGC, the reaction process, mechanical properties, freeze-thaw resistance and microstructure were systematically studied. The heat evolution results indicate that the control of reaction process could be achieved by adjusting the precursor component. A compact microstructure with extremely low porosity could be formed in the UHPGC specimens, which contributes to their good mechanical properties and freeze-thaw resistance. Good compatibility in the interface transition zone between fiber, paste and RFA could be observed, indicating great potential in the manufacture of UHPGC by alkali-activation technology. A considerable environmental benefit could be obtained in UHPGC when compared to ordinary ultra-high performance concrete (UHPC). This study is expected to offer more insights into the application of recycled aggregate and the manufacture of green UHPC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Cardiac valve calcification (CVC) is associated with adverse cardiovascular events. We studied the risk factors of CVC in maintenance hemodialysis (MHD) patients and the value of serum β2-microglobulin (β2-MG) levels in predicting the incidence of CVC. β2-MG is a middle molecular weight toxin. In recent years, researchers found that elevated blood β2-MG was associated with coronary, thoracic, and abdominal aortic calcifications with significant correlations. β2-MG has been emerging as a strong biomarker for cardiovascular mortality in uremic patients but its role in CVC is not well studied. This study looked specifically at CVC occurrence in relation to β2-MG for MHD patients., Methods: Patients who underwent MHD for more than 3 months in the First People's Hospital of Nantong City from November 2012 to November 2019 with complete available data were included in the study. The patients were divided into the CVC group and the non-CVC group. The general information and clinical laboratory indicators of the patients were collected in a retrospective manner. We analyzed the risk factors for developing CVC in MHD patients using binary logistic regression method. Receiver operating characteristic (ROC) curves were used to calculate the cut-off value of β2-MG for predicting CVC. The decision tree (DT) method was used to classify and explore the probability of CVC in patients with MHD., Results: The β2-MG in the CVC group was significantly higher than that in the non-CVC group ( t =6.750, P<0.001). Multivariate binary logistic regression analysis showed that gender, age, serum β2-MG, and hemodialysis (HD) adequacy (Kt/V urea) were independent risk factors for CVC in MHD patients. ROC analysis showed that a β2-MG value of 25 µg/L was the best cut-off point for predicting CVC in MHD patients. According to binary logistic regression analysis, the β2-MG ≥25 µg/L group was 3.39 times more likely to develop CVC than the β2-MG <25 µg/L group [odds ratio (OR), 3.39; 95% confidence interval (CI), 1.63-7.06; P=0.001]. The DT model determined that serum β2-MG ≥25 µg/L and age >69 years were important determinants for predicting CVC in MHD patients., Conclusions: Serum β2-MG in MHD patients has a positive correlation with the severity and occurrence of CVC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1185/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Idiopathic pulmonary fibrosis (IPF) is a devastating and progressive pulmonary disease which is characterized by epithelial cell damage and extracellular collagen deposition. To date, the therapeutic options for IPF are still very limited, so the relevant mechanisms need to be explored. Heat shock protein 70 (HSP70), which has protective versus antitumor effects on cells under stress, is a member of the heat shock protein family. In the current study, qRT-PCR, western blotting, immunofluorescence staining, and migration assays were used to explore the Epithelial-mesenchymal transition (EMT) process in BEAS-2B cells. Moreover, the role of GGA in the process of pulmonary fibrosis was detected by HE, Masson staining, pulmonary function test and immunohistochemistry in C57BL/6 mice. Our results indicated that GGA, as an inducer of HSP70, enhanced the transformation of BEAS-2B cells from epithelial to mesenchymal cells through the NF-κB/NOX4/ROS (reactive oxygen species) signalling pathway and could significantly reduce apoptosis of BEAS-2B cells induced by TGF-β1(Transforming growth factor β1) in vitro. In vivo studies demonstrated that HSP70-inducing drugs, such as GGA, attenuated pulmonary fibrosis progression induced by bleomycin (BLM). Collectively, these results suggested that overexpression of HSP70 attenuated pulmonary fibrosis induced by BLM in C57BL/6 mice and EMT process induced by TGF-β1 through NF-κB/NOX4/ROS pathway in vitro. Thus, HSP70 might be a potential therapeutic strategy for human lung fibrosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Fibrosis is a response to ongoing cellular injury, disruption, and tissue remodeling, the pathogenesis of which is unknown, and is characterized by extracellular matrix deposition. The antifibrotic effect of Geranylgeranylacetone (GGA), as an inducer of Heat shock protein 70 (HSP70), in liver, kidney and pulmonary fibrosis has been supported by multiple preclinical evidence. However, despite advances in our understanding, the precise roles of HSP70 in fibrosis require further investigation. The purpose of this study was to investigate whether GGA could participate in the progression of pulmonary fibrosis in mice through apoptosis, oxidative stress and inflammation., Methods and Results: B-cell lymphoma-2(Bcl-2) and Bcl2-Associated X (Bax) are two proteins related to apoptosis. Anti-apoptotic factor Bcl-2 and pro-apoptotic factor Bax are often involved in the apoptotic process in the form of dimer. Immunofluorescence and Western blot results showed that bleomycin (BLM) and transforming growth factor-β (TGF-β) inhibited Bcl-2 expression and promoted Bax expression in vitro and in vivo, respectively. In contrast, GGA treatment reverses this change. Reactive oxygen species (ROS), Malondialdehyde (MDA) and superoxide dismutase (SOD) are markers of oxidative stress, which often reflect oxidative injury of cells. The detection of ROS, MDA and SOD expression showed that TGF-β and BLM treatment could significantly promote oxidative stress, while GGA treatment could alleviate oxidative stress damage. In addition, BLM significantly elevated Tumor necrosis factor-α(TNF-α), Interleukin1β (IL-1β) and Interleukin 6 (IL-6), while scutellarin reversed the above alterations except for that of GGA., Results: Taken together, GGA suppressed apoptotic, oxidative stress and inflammation in BLM-induced pulmonary fibrosis., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Studies have documented that utilizing peer feedback can enhance students' English academic writing skills. Little is known, however, about the effects of incorporating peer feedback to enhance English as a second language (L2) medical students' academic writing performance., Methods: This longitudinal interventional study examines Chinese medical students' English academic writing skills development via peer feedback in four parallel classes over an 18-week semester between the experimental and control groups (n = 124)., Results: Significant increases in the experimental group's performance in the post-test were found after 18-week instructions (pre- vs. post-test: overall score, p < .001; task response, p < .001; coherence and cohesion, p < .001; lexical resource, p < .001; grammatical range and accuracy, p < .001), and the effects were retained in the delayed post-test 6 weeks later (post- vs. delayed post-test: overall score, p = .561; task response, p = .585; coherence and cohesion, p = .533; lexical resource, p = .796; grammatical range and accuracy, p = .670). Little improvement was found in the control group in the post-test (pre- vs. post-test: overall score, p = .213; task response, p = .275; coherence and cohesion, p = .383; lexical resource, p = .367; grammatical range and accuracy, p = .180) or the delayed post-test (post- vs. delayed post-test: overall score, p = .835; task response, p = .742; coherence and cohesion, p = .901; lexical resource, p = .897; grammatical range and accuracy, p = .695). Between-group comparisons indicate that the experimental group outperformed the control group in the post- and the delayed post-tests, as shown in their overall score and scores on the four components., Conclusions: Incorporating peer feedback into process-oriented medical English writing classroom teaching can effectively enhance Chinese medical students' English academic writing skills over time, while the traditional product-oriented writing instructions had little help in improving Chinese medical students' academic writing skills. This longitudinal intervention study develops our understanding of the effectiveness of peer feedback in L2 academic writing pedagogy. It offers instructional implications for L2 writing teachers to teach English academic writing among medical students in China and beyond. Limitations and suggestions for future studies are discussed., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Coke oven emissions (COEs) exposure leads to oxidative stress, an imbalance between oxidant production and antioxidant defence in the body, which then leads to shortened relative telomere length (RTL) and reduced mitochondrial DNA copy number (mtDNAcn), ultimately leading to ageing and disease. By analysing the relationship among COEs, oxidative stress, RTL and mtDNAcn, we investigated the chain-mediating effects of oxidative stress and telomeres on mitochondrial damage and mitochondria on telomere damage in coke oven workers. A total of 779 subjects were included in the study. Cumulative COEs exposure concentrations were estimated, and the RTL and mtDNAcn of peripheral blood leukocytes were measured using real-time fluorescence quantitative PCR. Total antioxidant capacity (T-AOC) was measured to reflect the level of oxidative stress. The data were statistically analysed using SPSS 21.0 software and discussed using mediation effect analysis. After adjusting for age, sex, smoking, drinking and BMI, generalised linear model revealed dose-response associations between COEs and T-AOC, RTL and mtDNAcn, respectively. (P trend < 0.05). The results of chain-mediating effect showed that the proportion of the chain-mediating effect of "CED-COEs→T-AOC→ RTL→mtDNAcn" was 0.82% (β = -0.0005, 95% CI = [-0.0012, -0.0001]), and the proportion of the chain-mediating effect of "CED-COEs→T-AOC→ mtDNAcn → RTL ″ was 2.64% (β = -0.0013, 95% CI = [-0.0025, -0.0004]). After oxidative stress is induced by COEs, mitochondria and telomeres may interact with each other while leading further to potential bodily damage. This study provides clues to explore the association between mitochondria and telomeres., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Long-term inhalation of silica particles in the workplace causes silicosis, which is incurable and seriously endangers the health of workers. It is believed that silicosis is caused by an imbalance of the pulmonary immune microenvironment, in which pulmonary phagocytes play a crucial role. As an emerging immunomodulatory factor, it is unclear whether T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) participate in silicosis by modulating pulmonary phagocytes function. The purpose of this study was to investigate the dynamic changes of the TIM-3 in pulmonary macrophages, dendritic cells (DCs), and monocytes during the development of silicosis in mice. The plasma levels of soluble TIM-3 in silicosis patients were also examined. Flow cytometry was used to identify alveolar macrophages (AMs), interstitial macrophages (IMs), CD11b + DC, CD103 + DC, Ly6C + , and Ly6C - monocytes in mouse lung tissues, and further analyses were conducted on the expression of TIM-3. Results showed that soluble TIM-3 was significantly elevated in plasma of silicosis patients, and the level of which was higher in stage II and III patients than that in stage I. In silicosis mice, the protein and mRNA levels of TIM-3 and Galectin9 were significantly upregulated in lung tissues. Specific to pulmonary phagocytes, silica exposure affected TIM-3 expression in a cell-specific and dynamic manner. In macrophages, TIM-3 expression upregulated in AM after 28 days and 56 days of silica instillation, while the expression of TIM-3 in IM decreased at all observation time points. In DCs, silica exposure only caused a decrease of TIM-3 expression in CD11b + DCs. In monocytes, TIM-3 dynamics in Ly6C + and Ly6C - monocytes were generally consistent during silicosis development, which significant decrease after 7 and 28 days of silica exposure. In conclusion, TIM-3 may mediate the development of silicosis by regulating pulmonary phagocytes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Histone deacetylase 3 (HDAC3) restores chromatin nucleosomes to a transcriptional repression state, thereby inhibiting gene expression. Studies have found that HDAC3 expression is upregulated in a variety of pathological states of the central nervous system and related to its neurotoxicity. However, the role of HDAC3 in surgical brain injury (SBI) has not been thoroughly explored., Objective: To observe the role of HDAC3 in SBI and the outcome of SBI after its suppression., Methods: Rat SBI model was used, and intraperitoneal injection of RGFP966 (HDAC3 specific inhibitor) was used to detect the changes of HDAC3 expression and neuronal apoptosis indexes in the surrounding cortex of SBI rats, and the cerebral edema and neurological outcome of rats were observed., Results: The expression of HDAC3 in the peripheral cortex of SBI rats was increased, and RGFP966 inhibited the upregulation of HDAC3 and saved the nerve cells around the damaged area. In addition, RGFP966 increased the expression of anti-oxidative stress proteins such as heme oxygenase-1 (HO-1) and superoxide dismutase 2 (SOD2). At the same time, the expression of apoptotic marker protein cleaved-caspase-3 (cle-caspase-3) was decreased, while the expression level of apoptotic protective marker protein B-cell lymphoma 2 (Bcl-2) was increased. In addition, this research demonstrated that in the RGFP966 rat SBI model, the expression level of antioxidant modifier nuclear factor-erythroid 2-related factor 2 (Nrf2) was increased., Conclusion: RGFP966 might activate HDAC3/Nrf2 signaling pathway by inhibiting HDAC3, regulated oxidative stress and nerve cell apoptosis induced by SBI in rat SBI model, reduced brain edema, and had a protective effect on nerve injury. It might be a potential target of SBI pathology., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Background: Syringo-subarachnoid shunt (SSS) is often considered a rescue procedure or a second-line treatment option for syringomyelia. However, the clinical efficacy of SSS in treating this condition remains controversial., Objective: To evaluate the long-term outcome of the SSS and its relationship with the syrinx area, as well as to investigate the factors that influence the prognosis., Methods: This retrospective study included twenty-seven consecutive patients who underwent SSS between 2014 and 2020. The study evaluated several independent variables such as age, sex, duration of progressive symptoms, morphological characteristics of the syrinx, changes in the syrinx area, and Chiari malformation. The long-term follow-up (>2 years) Japanese Orthopaedic Association (JOA) score was used to assess neurological function and outcome. Statistical analysis was performed using a stepwise logistic regression test., Results: All patients were followed up for an average of 48.6 ± 14.8(26.8 to 78.0) months. Follow-up magnetic resonance imaging showed syrinx collapse to different degrees occurred in 96.3% (26 of 27) patients. The JOA score was improvedinonly6patients (22.2%), remained stable in 5 patients (18.5%),and deteriorated in 16 patients(59.3%).A logistic regression test showed that the tension syrinx (odds ratio 0.111) and early shunting intervention (odds ratio 0.138) were favorable independent prognostic factors., Conclusions: It is important to note that the shrinkage of the syrinx does not necessarily translate to an improvement in clinical outcomes. Therefore, the decision to perform SSS should be made with caution and considered as a last resort., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

H3 K27-altered diffuse midline glioma is a highly lethal pediatric-type tumor without efficacious treatments. Recent findings have highlighted the heterogeneity among diffuse midline gliomas with different locations and ages. Compared to tumors located in the brain stem and thalamus, the molecular and clinicopathological features of H3 K27-altered spinal cord glioma are still largely elusive, thus hindering the accurate management of patients. Here we aimed to characterize the clinicopathological and molecular features of H3 K27M-mutant spinal cord glioma in 77 consecutive cases. We found that the H3 K27M-mutant spinal cord glioma, with a median age of 35 years old, had a significantly better prognosis than H3 K27M-mutant brain tumors. We noticed a molecular heterogeneity of H3 K27M-mutant spinal cord astrocytoma via targeted sequencing with 34 cases. TP53 mutation which occurred in 58.8% of cases is mutually exclusive with PPM1D (26%) and NF1 (44%) mutations. The TP53-mutant cases had a significantly higher number of copy number variants (CNV) and a marginally higher proportion of pediatric patients (age at diagnosis <18 years old, p = 0.056). Cox regression and Kaplan-Meier curve analysis showed that the higher number of CNV events (≥3), chromosome (Chr) 9p deletion, Chr 10p deletion, ATRX mutation, CDK6 amplification, and retinoblastoma protein (RB) pathway alteration are associated with worse survival. Cox regression analysis with clinicopathological features showed that glioblastoma histological type and a high Ki-67 index (>10%) are associated with a worse prognosis. Interestingly, the histological type, an independent prognostic factor in multivariate Cox regression, can also stratify molecular features of H3 K27M-mutant spinal cord glioma, including the RB pathway, KRAS/PI3K pathway, and chromosome arms CNV. In conclusion, although all H3 K27M-mutant spinal cord diffuse glioma were diagnosed as WHO Grade 4, the histological type, molecular features representing chromatin instability, and molecular alterations associated with accelerated cell proliferative activity should not be ignored in clinical management., (© 2023 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)

Purpose: Myxopapillary ependymoma (MPE) was classified as grade 2 tumor in the 2021 World Health Organization central nervous system classification because of its high recurrence probability. This study aimed to investigate predictive factors and management of tumor recurrence., Methods: Seventy-two patients with spinal MPE underwent initial surgical treatment at our hospital between 2011 and 2021. Kaplan-Meier curves and Cox regression were used to analyze the correlation between clinical variables and progression-free survival (PFS)., Results: The median age at diagnosis was 33.5 years (range 8-60 years). Twenty-one patients (29.2%) had preoperative spinal drop metastases. Gross total resection (GTR) was performed in 37 patients (51.4%). The median follow-up was 7.2 years, and the follow-up rate was 88.9% (64 of 72 cases). Twelve of the 64 patients (18.9%) relapsed, and preoperative drop metastasis occurred in 7 patients (58.3%). The estimated 5-year and 10-year PFS rates were 82% and 77%, respectively. Univariate analysis showed that GTR was associated with improved PFS (hazard ratio [HR] 0.149, p = 0.014), while preoperative drop metastasis (HR 3.648, p = 0.027) and tumor involvement sacrococcygeal region (HR 7.563, p = 0.003) were associated with tumor recurrence. Adjuvant radiotherapy (RT) was significantly associated with improved PFS in patients with preoperative drop metastasis (p = 0.039)., Conclusion: Complete surgical resection under the premise of protecting neurological function is an important factor in reducing spinal MPE recurrence. Adjuvant RT is recommended when the tumor invades the capsule with preoperative drop metastasis or adhesion to the nerve and cannot reach GTR., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The water-cement ratio (w/c) has a significant effect on the strength of recycled concrete. In this study, considering the effects of water/cement ratio, strength, and water content of recycled aggregates, two kinds of pulse sequences of low-field nuclear magnetic resonance (LF-NMR) were applied to investigate the water migration behavior between simulated recycled aggregates (SRA) and water or fresh mortar. Three sets of concrete strength tests were designed and the results were used to verify the findings of LF-NMR imaging tests. The results showed that the depth of water migration in the SRA increases with time: at first the change rate is rapid, then slows down, and eventually tends to remain stable. When the SRA is in contact with fresh mortar with low w/c, no water migration occurs because the hydration of the cement in the mixture consumes a large amount of water, resulting in the inability of water to migrate into the SRA through capillary pressure. For the recycled aggregate concrete with high strength, the addition of extra water will increase the effective w/c and reduce the compressive strength of the concrete.

Objective: The study aimed to estimate the benchmark dose (BMD) of coke oven emissions (COEs) exposure based on mitochondrial damage with the mitochondrial DNA copy number (mtDNAcn) as a biomarker., Methods: A total of 782 subjects were recruited, including 238 controls and 544 exposed workers. The mtDNAcn of peripheral leukocytes was detected through the real-time fluorescence-based quantitative polymerase chain reaction. Three BMD approaches were used to calculate the BMD of COEs exposure based on the mitochondrial damage and its 95% confidence lower limit (BMDL)., Results: The mtDNAcn of the exposure group was lower than that of the control group (0.60 ± 0.29 vs. 1.03 ± 0.31; P < 0.001). A dose-response relationship was shown between the mtDNAcn damage and COEs. Using the Benchmark Dose Software, the occupational exposure limits (OELs) for COEs exposure in males was 0.00190 mg/m 3 . The OELs for COEs exposure using the BBMD were 0.00170 mg/m 3 for the total population, 0.00158 mg/m 3 for males, and 0.00174 mg/m 3 for females. In possible risk obtained from animal studies (PROAST), the OELs of the total population, males, and females were 0.00184, 0.00178, and 0.00192 mg/m 3 , respectively., Conclusion: Based on our conservative estimate, the BMDL of mitochondrial damage caused by COEs is 0.002 mg/m 3 . This value will provide a benchmark for determining possible OELs., (Copyright © 2023 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Background: Silica-induced pulmonary fibrosis (silicosis) is a diffuse interstitial fibrotic disease characterized by the massive deposition of extracellular matrix in lung tissue. Fibroblast to myofibroblast differentiation is crucial for the disease progression. Inhibiting myofibroblast differentiation may be an effective way for pulmonary fibrosis treatment., Methods: The experiments were conducted in TGF-β treated human lung fibroblasts to induce myofibroblast differentiation in vitro and silica treated mice to induce pulmonary fibrosis in vivo., Results: By quantitative mass spectrometry, we revealed that proteins involved in mitochondrial folate metabolism were specifically upregulated during myofibroblast differentiation following TGF-β stimulation. The expression level of proteins in mitochondrial folate pathway, MTHFD2 and SLC25A32, negatively regulated myofibroblast differentiation. Moreover, plasma folate concentration was significantly reduced in patients and mice with silicosis. Folate supplementation elevated the expression of MTHFD2 and SLC25A32, alleviated oxidative stress and effectively suppressed myofibroblast differentiation and silica-induced pulmonary fibrosis in mice., Conclusion: Our study suggests that mitochondrial folate pathway regulates myofibroblast differentiation and could serve as a potential target for ameliorating silica-induced pulmonary fibrosis., (© 2023. The Author(s).)

Background: Early childhood is a critical stage for the prevention of dental caries. The prevalence of caries in preschool children is still high in Taiwan, where National Health Insurance covers 99% of the population. The effort to improve the oral health of preschool children should be based on conceptual model that encompasses more than individual-level factors. This study input nationwide survey data in a conceptual model to evaluate the effects of comprehensive factors related to the high prevalence of caries in preschool children., Methods: This observation study examined factors related to the oral health of preschool children by employing a comprehensive multilevel model to analyse nationally representative data from the Taiwan Oral Health Survey of Preschool Children (TOHPC) 2017-2018. Individual-level, family-level and community-level contextual effects were evaluated through multilevel analysis in this study. The proportional change in variance (PCV) was used to compare the multilevel model with the null model and individual-level, family-level, and community-level context effects., Results: The estimated deft index for preschool children was 1.34 (1.22-1.47) at age 3, 2.20 (2.08-2.32) at age 4, and 3.05 (2.93-3.18) at age 5. The overall prevalence of caries in preschool children in Taiwan was 34.27% (30.76%, 37.78%) at age 3, 51.67% (48.99%, 54.35%) at age 4, and 62.05% (59.66%, 64.44%) at age 5. The model that included the individual-, family-, and community-context levels exhibited the highest reduction of variance (PCV = 53.98%). The PCV was further reduced to 35.61% when only the level of accessibility to dental services for individuals, families, and the community was considered. For the model in which no community-context cofactors were considered and the model considering only the individual level, the PCVs were 20.37% and 5.52%, respectively., Conclusions: Our findings indicate the key components that affect oral health in preschool children and can serve as a reference for policy makers. The most notable finding of this study is that to improve the oral health of preschool children, community-level factors should be targeted. To rely solely on dentists for leading oral health education programs for children is impractical and inefficient. Training more professional oral health educators to provide additional community-based oral health promotion campaigns is critical. We suggest training more professional oral health educators to provide more community-based oral health promotion campaigns., (© 2023. The Author(s).)

This study evaluated the effects of BTEX exposure on oxidative stress; it analyzed the correlation between oxidative stress and peripheral blood counts and estimated the benchmark dose (BMD) of BTEX compounds. This study recruited 247 exposed workers and 256 controls; physical examination data were collected and serum oxidative stress levels were measured. Relationships between BTEX exposure and biomarkers were analyzed using Mann-Whitney U, generalized linear model, and chi-square trend tests. Environmental Protection Agency Benchmark Dose Software was used to calculate the BMD and lower confidence limit of the BMD (BMDL) for BTEX exposure. The total antioxidant capacity (T-AOC) correlated positively with peripheral blood counts, and negatively with the cumulative exposure dose. On using T-AOC as the outcome variable, the estimated BMD and BMDL for BTEX exposure were 3.57 mg/m 3 and 2.20 mg/m 3 , respectively. Based on T-AOC, the calculated occupational exposure limit of BTEX was 0.055 mg/m 3 ., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Abstract: Blast lung injuries (BLIs) are frequent because of industrial accidents and terrorist groups. Bone marrow mesenchymal stem cells (BMSCs) and exosomes derived from BMSCs (BMSCs-Exo) have become a hot topic in modern biology because of their significance in damage healing, immune regulation, and gene therapy. The aim of this study is to investigate the effect of BMSCs and BMSCs-Exo on BLI in rats caused by gas explosion. Here, BMSCs and BMSCs-Exo were transplanted into BLI rats via tail vein and then evaluated pathological alterations, oxidative stress, apoptosis, autophagy, and pyroptosis in the lung tissue. Through histopathology and changes in malondialdehyde (MDA) and superoxide dismutase (SOD) contents, we discovered that oxidative stress and inflammatory infiltration in the lungs were significantly reduced by BMSCs and BMSCs-Exo. After treatment with BMSCs and BMSCs-Exo, apoptosis-related proteins, such as cleaved caspase-3 and Bax, were significantly decreased, and the ratio of Bcl-2/Bax was significantly increased; the level of pyroptosis-associated proteins, including NLRP3, GSDMD-N, cleaved caspase-1, IL-1β, and IL-18, were decreased; autophagy-related proteins, beclin-1 and LC3, were downregulated while P62 was upregulated; the number of autophagosomes was decreased. In summary, BMSCs and BMSCs-Exo attenuate BLI caused by gas explosion, which may be associated with apoptosis, aberrant autophagy, and pyroptosis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by the Shock Society.)

Fibrosis is a pathological tissue repair activity in which many myofibroblasts are activated and extracellular matrix are excessively accumulated, leading to the formation of permanent scars and finally organ failure. A variety of organs, including the lung, liver, kidney, heart, and skin, can undergo fibrosis under the stimulation of various exogenous or endogenous pathogenic factors. At present, the pathogenesis of fibrosis is still not fully elucidated, but it is known that the immune system plays a key role in the initiation and progression of fibrosis. Immune checkpoint molecules are key regulators to maintain immune tolerance and homeostasis, among which the programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) axis has attracted much attention. The exciting achievements of tumor immunotherapy targeting PD-1/PD-L1 provide new insights into its use as a therapeutic target for other diseases. In recent years, the role of PD-1/PD-L1 axis in fibrosis has been preliminarily explored, further confirming the close relationship among PD-1/PD-L1 signaling, immune regulation, and fibrosis. This review discusses the structure, expression, function, and regulatory mechanism of PD-1 and PD-L1, and summarizes the research progress of PD-1/PD-L1 signaling in fibrotic diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Qu, Hao and Yao.)

The colonization and expansion of plants on land is considered one of the most profound ecological revolutions, yet the precise timing remains controversial. Because land vegetation can enhance weathering intensity and affect terrigenous input to the ocean, changes in terrestrial plant biomass with distinct negative Δ 199 Hg and Δ 200 Hg signatures may overwrite the positive Hg isotope signatures commonly found in marine sediments. By investigating secular Hg isotopic variations in the Paleozoic marine sediments from South China and peripheral paleocontinents, we highlight distinct negative excursions in both Δ 199 Hg and Δ 200 Hg at Stage level starting in the early Silurian and again in the Carboniferous. These geochemical signatures were driven by increased terrestrial contribution of Hg due to the rapid expansion of vascular plants. These excursions broadly coincide with rising atmospheric oxygen concentrations and global cooling. Therefore, vascular plants were widely distributed on land during the Ordovician-Silurian transition (~444 million years), long before the earliest reported vascular plant fossil, Cooksonia (~430 million years).

Beetle daisies evolved floral spots that mimic female bee flies to entice mate-seeking males for pollination. A new study shows that these deceptive spots emerged through stepwise co-option of multiple genetic elements, shedding light on the origin of complex phenotypic novelties., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Lung cancer is the leading cause of cancer-related deaths globally. Early detection of lung cancer can lead to more effective treatment and improved survival. Circulatory abnormal cells (CACs) with specific chromosomal variation may be used to diagnose lung cancer and to differentiate benign from malignant nodules. The value of CAC in precancer diagnosis, however, remains controversial. In this study, a systematic review and meta-analysis are conducted to clarify the diagnostic value of CAC in early-stage lung cancer. A systematic literature search was conducted using the following medical topic title terms and text-free words: "circulating genetically abnormal cells", "CACs", "liquid biopsy", "early lung cancer", "non-small cell lung cancer", "diagnostic accuracy", "sensitivity" and "specificity" in Science Direct, CNKI and Wanfang databases, respectively. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and area under the curve were analyzed by STATA15.0 (MP) software. Deek funnel plots were used to assess potential publication bias. Heterogeneity was tested using the I2 statistic and the Cochrane Q test. 7 major studies were included in this meta-analysis, and a total of 53728 participants were analyzed. In the diagnosis of early lung cancer, CAC had pooled sensitivity, specificity, and receiver operating characteristics of 0.80 (95% CI: 0.73-0.86), 0.85 (95% CI: 0.69-0.94), and 0.87 (95% CI: 0.84-0.90). The combined positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and diagnostic score were 23.36 (95% CI: 7.33-74.46), 5.42 (95% CI: 2.37-12.43), 0.23 (95% CI: 0.16-0.35) and 3.15 (95% CI: 1.99-4.31) respectively. Publication bias was not detected. The CAC is effective at detecting lung cancer in its early stages., Competing Interests: None., (AJCR Copyright © 2023.)

Aim: The main objective of this study was to explore the value of the discharged case fatality rate (DCFR) in estimating the severity and epidemic trend of COVID-19 in China., Subjects and Methods: Epidemiological data on COVID-19 in China and Hubei Province were obtained from the National Health Commission of the People's Republic of China from January 20, 2020, to March 31, 2020. The number of daily new confirmed cases, daily confirmed deaths, daily recovered cases, the proportion of daily deaths and total deaths of discharged cases were collected, and the total discharge case fatality rate (tDCFR), daily discharge case fatality rate (dDCFR), and stage-discharge case fatality rate (sDCFR) were calculated. We used the R software (version 3.6.3, R core team) to apply a trimmed exact linear time method to search for changes in the mean and variance of dDCFR in order to estimate the pandemic phase from dDCFR., Results: The tDCFR of COVID-19 in China was 4.16% until March 31, 2020. According to the pattern of dDCFR, the pandemic was divided into four phases: the transmission phase (from January 20 to February 2), the epidemic phase (from February 3 to February 14), the decline phase (from February 15 to February 22), and the sporadic phase (from February 23 to March 31). The sDCFR for these four phases was 43.18% (CI 39.82-46.54%), 13.23% (CI 12.52-13.94%), 5.86% (CI 5.49-6.22%), and 1.61% (CI 1.50-1.72%), respectively., Conclusion: DCFR has great value in assessing the severity and epidemic trend of COVID-19., Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-023-01895-4., Competing Interests: Conflicts of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

In this study, SrGe 4 O 9 :Mn 4+ red phosphors for plant illumination were prepared using a high-temperature solid-phase method. The samples were characterized and analyzed by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), fluorescence spectroscopy, and other techniques. The phase structure, apparent morphology, and luminescence properties of the SrGe 4 O 9 :Mn 4+ red phosphors were investigated. The results indicated that the dopant Mn 4+ was incorporated into the matrix structure by substituting some Ge 4+ ions without any changes in the crystal structure of the SrGe 4 O 9 matrix. The samples comprised micron-scale particles and exhibited high purity and uniform distribution of elements. The SrGe 4 O 9 :Mn 4+ phosphors exhibited relatively strong red light emission at 660 nm under the excitation of a 430-nm blue light, and the luminescence intensity was the highest when the Mn 4+ doping amount was 1%. Proper doping of Ti 4+ or Sn 4+ could effectively improve the luminescence intensity of the SrGe 4 O 9 :Mn 4+ phosphors. The light-emitting diode (LED) device packaging showed that the SrGe 4 O 9 :Mn 4+ red phosphors could be used for plant growth illumination., (© 2023 John Wiley & Sons Ltd.)