Search

Lyonia ovalifolia (Wall.) Drude (LO) is mainly distributed in China with health benefits. In this study, LO buds (LOB) were extracted by ultrasonic extraction (UE) with or without ultra-high-pressure (UHP-UE), microwave (MW-UE), subcritical (SC-UE) techniques. The metabolomic result showed that a total of 960 chemical compounds and 117 differential compounds were identified from LOB extracts. The UHP-UE extract was rich in total polyphenol and flavonoid contents, followed by MW-UE, UE and SC-UE extracts, respectively. All LOB extracts increased superoxide dismutase (SOD) and catalase (CAT) activities, and glutathione (GSH) content, decreased reactive oxygen species (ROS) accumulation, levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor -α (TNF-α), and nitric oxide (NO), and alleviated apoptosis in cells. The cellular protective effect was UHP-UE > MW-UE > UE > SC-UE. This study revealed that higher pressure and lower temperature may be key factors for increasing bioactivities of LOB extracts., 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.)

Ethnopharmacological Relevance: Schistosomiasis, caused by infection with organisms of the Schistoma genus, is a parasitic and infectious disease that poses a significant risk to human health. Schistosomiasis has been a widespread issue in China for at least 2000 years. Traditional Chinese medicine (TCM) has a rich history of treating this disease, and the significant theoretical and practical knowledge attained therein may be useful in modern practice., Aim of the Study: To comprehensively review TCM for the treatment of schistosomiasis, summarize the molecular basis, mechanism of action, active ingredients and formulas of TCM, and clarify the value of TCM for expanding drug options for the clinical treatment of schistosomiasis., Materials and Methods: In PubMed, Web of Science, ScienceDirect, Google Scholar and CNKI databases, "Schistosomiasis", "Schistosoma mansoni", "Schistosoma japonicum", "Liver fibrosis" and "Granuloma" were used as the key words. Information related to in vivo animal studies and clinical studies of TCM for the treatment of schistosomiasis in the past 25 years was retrieved, and the inclusion criteria focused on medicinal plants that had a history of use in China., Results: In this study, we collected and organized a large amount of literature on the treatment of schistosomiasis by TCM. TCM exerts therapeutic effects through antischistosomal and immunomodulatory effects, suppresses HSC activation and proliferation, reduces ECM deposition, and inhibits oxidative stress and other activities. The treatment of schistosomiasis by TCM has a unique advantage, especially for the treatment of schistosomal liver fibrosis, and the treatment of schistosomiasis with TCM in combination with praziquantel is superior to monotherapy., Conclusion: Schistosomiasis remains a global public health problem, and TCM has made significant progress in the prevention and treatment of schistosomiasis and is a potential source of drugs for the treatment of schistosomiasis. However, research on drug screening and the mechanism of action of TCM for the treatment of schistosomiasis is lacking, and further studies and research are needed., 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. Published by Elsevier B.V.)

Ethnopharmacological Relevance: Hepatocellular Carcinoma (HCC) is an aggressive killer worldwide with high incidence and mortality. The herb Chloranthus fortunei (A. Gray) Solms-Laub is known as "Si Ji Feng" and is classified as a Feng-type medicine in classic Yao medicines. According to Yao's medical beliefs, Chloranthus fortunei has the functions of dispelling Feng, regulating qi, detoxifying, promoting blood circulation, etc. Folk uses its decoctions to treat stagnant liver conditions, such as liver abscesses, cirrhosis, hepatitis, and liver cancer. However, the bioactivity and mechanisms of Chloranthus fortunei extract against HCC have not been reported., Aim of the Study: To investigate the anti-HCC bioactivity and potential mechanism of the extract of Chloranthus fortunei (CFS)., Materials and Methods: Using 70% ethanol for reflux extraction of CFS resulted in the CFS ethanol extract, followed by sequential extractions with petroleum ether, chloroform, ethyl acetate, and n-butanol, yielding four fractions. The CCK-8 assay was utilized to examine the cytotoxic effects of 4 fractions on MHCC97-H and HepG2 cells, exploring the most effective component, namely petroleum ether extracts of CFS (PECFS). The major active ingredients of PECFS were identified using LC/MS technology, and the impact on cell proliferation and apoptosis in HCC cells was studied. The key genes and proteins in the pathway were validated using RT-PCR and Western blotting. BALB/c nude mice were chosen for tumor xenotransplantation and PECFS therapy. hinders the proliferation of HCC cells and promotes apoptosis., Results: Among the four fractions, it was found that PECFS have the highest antiproliferative activity against MHCC97-H and HepG2 cells (IC 50  = 13.86, 10.55 μg/mL), with sesquiterpene compounds being the primary active constituents. The antiproliferative activity of PECFS on HCC cells was linked to the inhibition of cell cloning, invasion, and metastasis abilities, as well as the arrest of the cell cycle at the G2/M phase. Additionally, exerts pro-apoptotic effects on HCC cells by upregulating the pro-apoptotic protein Bax, downregulating the anti-apoptotic protein Bcl-2, and activating the expression of the Caspase family. Moreover, protein and m-RNA expression data showed that PECFS inhibits HCC cell proliferation and promotes apoptosis by regulating the PI3K/AKT/mTOR pathway. Besides, after PECFS treatment, tumor growth in nude mice was suppressed., Conclusion: PECFS can inhibit the viability of HCC cells by acting on the PI3K/AKT/mTOR pathway, demonstrating anti-tumor potential. This study's findings suggest that PECFS may represent a promising source of novel agents for liver cancer treatment, providing scientific evidence for the traditional application of CFS in treating HCC., 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 B.V. All rights reserved.)

Ethnopharmacological Relevance: Rhapontici Radix ethanol extract (RRE) is derived from the dried root of Rhaponticum uniflorum (L.) DC belonging to the Asteraceae family. RRE exhibits significant anti-inflammatory and antioxidant properties; however, the potential of RRE in mastitis treatment requires further investigation., Aim of This Study: This research was performed to examine the protective properties of RRE against mastitis and the mechanisms underlying the effects of RRE., Material and Methods: RRE components were analyzed by HPLC-MS/MS and DPPH methods. Isochlorogenic acid B (ICAB) was obtained commercially. MTT assay was utilized to assess RRE or ICAB cytotoxicity in bovine mammary alveolar (MAC-T) cells. Immunohistochemistry were used to investigate the pathological alterations in mammary tissue. The protein levels of inflammatory cytokines and mediators were analyzed using ELISA, and the expression of MAPK and NF-κB signaling pathways, as well as p65 nuclear translocation, were analyzed through Western blotting and immunofluorescence techniques, respectively. Target proteins of RRE were screened by RNA-seq and tandem mass tag analyses. Protein interaction was revealed and confirmed using co-immunoprecipitation and CRISPR/Cas9-based knockdown and overexpression of target genes., Results: ICAB was revealed as one of the main components in RRE, and it was responsible for 84.33% of RRE radical scavenging activity. Both RRE and ICAB mitigated the infiltration of T lymphocytes in the mammary glands of mice, leading to decreased levels of inflammatory mediators (COX-2 and iNOS) and cytokines (TNF-α, IL-6, and IL-1β) in lipopolysaccharide (LPS)-induced MAC-T cells. Furthermore, RRE and ICAB suppressed the LPS-induced phosphorylation of NF-κB inhibitor and p65, thereby impeding p65 nuclear translocation in mouse mammary glands and MAC-T cells. In addition, RRE and ICAB attenuated the LPS-triggered activation of c-Jun N-terminal kinase 1/2, p38, and extracellular regulated protein kinase 1/2. Importantly, co-treated with LPS and ICAB in MAC-T cells, an upregulation of G-protein coupled receptor 161 (GPR161) and transmembrane protein 59 (TMEM59) was observed; the interact between TMEM59 and was found, leading to inhibition of NF-κB activity and inflammatory cytokine production., Conclusion: ICAB is a prominent antioxidant in RRE. RRE and ICAB reduce mammary inflammation via MAPK and NF-κB pathways and the interaction between TMEM59 and GPR161 mediates the control of ICAB in NF-κB signaling., 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 B.V. All rights reserved.)

Ethnopharmacological Relevance: Cistanche deserticola is a kind of parasitic plant living in the roots of desert trees. It is a rare Chinese medicine, which has the effect of tonifying kidney Yang, benefiting essence and blood and moistening the intestinal tract. Cistache deserticola phenylethanoid glycoside (PGS), an active component found in Cistanche deserticola Ma, have potential kidney tonifying, intellectual enhancing, and neuroprotective effects. Cistanche total glycoside capsule has been marketed to treat vascular dementia disease., Aim of the Study: To identify the potential renal, intellectual enhancing and neuroprotective effects of PGS and explore the exact targets and mechanisms of PGS., Materials and Methods: This study systematically investigated the four types of pathways leading to ferroptosis through transcriptome, metabolome, ultrastructure and molecular biology techniques and explored the molecular mechanism by which multiple PGS targets and pathways synergistically exert neuroprotective effects on hypoxia., Results: PGS alleviated learning and memory dysfunction and pathological injury in mice exposed to hypobaric hypoxia by attenuating hypobaric hypoxia-induced hippocampal histopathological damage, impairing blood‒brain barrier integrity, increasing oxidative stress levels, and increasing the expression of cognitive proteins. PGS reduced the formation of lipid peroxides and improved ferroptosis by upregulating the GPX-4/SCL7A311 axis and downregulating the ACSL4/LPCAT3/LOX axis. PGS also reduced ferroptosis by facilitating cellular Fe 2+ efflux and regulating mitochondrial Fe 2+ transport and effectively antagonized cell ferroptosis induced by erastin (a ferroptosis inducer)., Conclusions: This study demonstrated the mechanism by which PGS prevents hypobaric hypoxic nerve injury through four types of ferroptosis pathways, achieved neuroprotective effects and alleviated learning and memory dysfunction in hypobaric hypoxia mice. This study provides a theoretical basis for the development and application of PGS., 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 B.V. All rights reserved.)

Atomically precise supported nanocluster catalysts (APSNCs), which feature exact atomic composition, well-defined structures, and unique catalytic properties, offer an exceptional platform for understanding the structure-performance relationship at the atomic level. However, fabricating APSNCs with precisely controlled and uniform metal atom numbers, as well as maintaining a stable structure, remains a significant challenge due to uncontrollable dispersion and easy aggregation during synthetic and catalytic processes. Herein, we developed an effective ligand engineering strategy to construct a Pt 6 nanocluster catalyst stabilized on oxidized carbon nanotubes (Pt 6 /OCNT). The structural analysis revealed that Pt 6 nanoclusters in Pt 6 /OCNT were fully exposed and exhibited a planar structure. Furthermore, the obtained Pt 6 /OCNT exhibited outstanding acidic HOR performances with a high mass activity of 18.37 A ⋅ mg pt -1 along with excellent stability during a 24 h constant operation and good CO tolerance, surpassing those of the commercial Pt/C. Density functional theory (DFT) calculations demonstrated that the unique geometric and electronic structures of Pt 6 nanoclusters on OCNT altered the hydrogen adsorption energies on catalytic sites and thus lowered the HOR theoretical overpotential. This work presents a new prospect for designing and synthesizing advanced APSNCs for efficient energy electrocatalysis., (© 2024 Wiley-VCH GmbH.)

Background and Aim: Phoenixin (PNX), a newly discovered neuropeptide associated with reproduction, has been speculated to be involved in precocious puberty. Therefore, we assessed serum PNX levels in girls with precocious puberty., Methods: Serum phoenixin-14 (PNX-14) and phoenixin-20 (PNX-20) levels were determined in girls with central precocious puberty (CPP) and premature thelarche (PT) and in healthy controls (n = 58 per group). Spearman's correlation was used to analyze the correlations between variables. Receiver operating characteristic curves were used to evaluate the performance of PNX for the diagnosis of CPP. Significant predictors of serum PNX levels were determined using least absolute shrinkage and selection operator regression and multiple linear regression analyses., Results: Serum PNX-14 and PNX-20 levels were significantly higher in girls with CPP than in the controls; however, no significant differences in serum PNX-14 and PNX-20 levels were observed between girls with PT and the controls. PNX-20 levels were positively correlated with basal luteinizing hormone (LH) levels, peak LH levels, the peak LH to follicle-stimulating hormone (FSH) ratio, and estradiol levels. No significant correlation was observed between PNX-14 levels and any of these parameters. Multivariate linear regression analysis revealed that PNX-20 levels exhibited the strongest correlation with peak LH/FSH values. The areas under the curve (AUCs) of PNX-14 and PNX-20 for predicting CPP were 0.628 (cut-off value, 100.12 pg/mL; sensitivity, 44.6%; specificity, 77.6%) and 0.775 (cut-off value, 360.03 pg/mL; sensitivity, 66.5%; specificity, 79.3%), respectively. When these two indicators were combined, the AUC was 0.785., Conclusions: Serum PNX levels may be associated with precocious puberty in girls and can be used as an auxiliary CPP indicator. However, given the low sensitivity and specificity of PNX, it should not be used as a single diagnostic indicator of CPP., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Organophosphate esters (OPEs) have proven to be pervasive in aquatic environments globally. However, understanding their partitioning behavior and mechanisms at the sediment-water interface remains limited. This study elucidated the spatial heterogeneity, interfacial exchange, and diffusion mechanisms of 14 OPEs (∑ 14 OPEs) from river to coastal aquatic system. The transport tendencies of OPEs at the sediment-water interface were quantitatively assessed using fugacity methods. The total ∑ 14 OPEs concentrations in water and sediments ranged from 154 ng/L to 528 ng/L and 2.41 ng/g dry weight (dw) to 230 ng/g dw, respectively. This result indicated a descending spatial tendency with moderate variability. OPE distribution was primarily influenced by temperature, pH, and dissolved oxygen levels. As the carbon atom number increased, alkyl and chlorinated OPEs transitioned from diffusion towards the aqueous phase to equilibrium. In contrast, aryl OPEs and triphenylphosphine oxide, which had equivalent carbon atom counts, maintained equilibrium throughout. Diffusion trends of individual OPE congener at the sediment-water interface varied at the same total organic carbon contents (f oc ). As the f oc increased, the fugacity fraction values for all OPE homologs showed a declining trend. The distinct molecular structure of each OPE monomer might lead to unique diffusive behaviors at the sediment-water interface. Higher soot carbon content had a more pronounced effect on the distribution patterns of OPEs. The sediment-water distribution of OPEs was primarily influenced by total organic carbon, sediment particle size, dry density, and moisture content. OPEs displayed the highest sensitivity to fluctuations in ammonium and dissolved organic carbon. This study holds significant scientific and theoretical implications for elucidating the interfacial transport and driving forces of OPEs and comprehending their fate and endogenous release in aquatic ecosystems., 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.)

The Ecological Security Pattern (ESP) has emerged as a prominent area of focus in global ecosystem research, offering valuable scientific insights for reconciling ecological preservation with economic progress. Understanding the differences among different approaches to constructing ESP serves as a fundamental step in ensuring its efficacy. However, there has been a scarcity of studies that quantitatively assess the disparities in the effectiveness of various ESP construction methods. This study focuses on the West Liaohe River Basin as its research subject. Leveraging remote sensing data alongside county-level statistical information, the study employs three distinct ecological source identification methodologies to establish ESP frameworks. Subsequently, it analyzes the discrepancies in ecological protection outcomes across different ESP construction methods under varying future development scenarios. The findings reveal that the ESP centered around ecosystem services emerges as particularly suited for diverse development scenarios, consistently yielding optimal ecological protection outcomes. Our research not only furnishes a theoretical foundation and practical guidance for ESP development in the West Liaohe River Basin but also offers methodological insights transferrable to other regions., 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.)

Microplastic (MP) pollution can exert significant pressure on soil ecosystems, however, the interactive effects of MPs on soil bacterial, fungal and protist communities remains poorly understood. Soil macrofauna, such as earthworms, can be directly affected by MPs, potentially leading to a range of feedbacks on the soil microbial community. To address this, we conducted a microcosm experiment to examine the effects of conventional (i.e., polyethylene, polystyrene) and biodegradable MPs (i.e. PBAT, polylactic acid) on the structure of the soil bacterial, fungal, and protist communities in the presence or absence of earthworms. We found that MP contamination negatively affected the diversity and composition of soil microbial and protist communities, with smaller-sized conventional MPs having the most pronounced effects. For example, compared with the unamended control, small-sized polyethylene MPs both significantly reduced the Shannon diversity of soil bacteria, fungi, and protist by 4.3 %, 37.0 %, and 9.1 %, respectively. Biodegradable MPs increased negative correlations among bacteria, fungi, and protists. However, earthworms mitigated these effects, enhancing the diversity and altering the composition of these communities. They also increased the niche width and stability of the soil microbial food web network. Our study indicated that earthworms help attenuate the response of soil microorganisms to MPs stress by influencing the diversity and composition of soil microorganisms and soil physicochemical properties and underscores the importance of considering macrofauna in MPs research., 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.)

The investigation of lunar soil encompasses extensive periods, employs many improvement methods, and has generated several simulants. The improvement of lunar soil has recently garnered growing interest as an aspect of In-Situ Resource Utilization (ISRU) for regolith. It is crucial to clarify the challenges of utilizing lunar soil as a planting substrate to develop more effective techniques. This review presents a comprehensive analysis of research on improving lunar soil properties, highlights the disparities in mineral composition between real lunar soil (also called regolith) and simulated lunar soil, then details their deficiencies as planting substrates. Following an investigation of existing improvement methods, a dilemma of metals、salt precipitation and high pH caused by adding organic matter alone was noted, while the function of microbes (bacteria, algae, and lichens) in improvement processes was assessed. Finally, we present a perspective on future the lunar soil plantable research development based on the Bioregenerative Life Support System (BLSS). This review aims to promote the engineering application of lunar soil improvements and sustainable development. We hope that one day, regolith will enable plants to flourish on the Moon., 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. Published by Elsevier B.V.)

China is experiencing large-scale rural-urban migration and rapid urbanization, which have had significant impact on terrestrial carbon sink. However, the impact of rural-urban migration and its accompanying urban expansion on the carbon sink is unclear. Based on multisource remote sensing product data for 2000-2020, the soil microbial respiration equation, relative contribution rate, and threshold analysis, we explored the impact of rural depopulation on the carbon sink and its threshold. The results revealed that the proportion of the rural population in China decreased from 63.91 % in 2000 to 36.11 % in 2020. Human pressure decreased by 1.82% in rural depopulation areas, which promoted vegetation restoration in rural areas (+8.45 %) and increased the carbon sink capacity. The net primary productivity (NPP) and net ecosystem productivity (NEP) of the vegetation in the rural areas increased at rates of 2.95 g C m -2  yr -1 and 2.44 g C m -2  yr -1 . Strong rural depopulation enhanced the carbon sequestration potential, and the NEP was 1.5 times higher in areas with sharp rural depopulation than in areas with mild rural depopulation. In addition, the rural depopulation was accompanied by urban expansion, and there was a positive correlation between the comprehensive urbanization level (CUL) and NEP in 75.29 % of urban areas. In the urban areas, the vegetation index increased by 88.42 %, and the urban green space partially compensated for the loss of carbon sink caused by urban expansion, with a growth rate of 4.96 g C m -2  yr -1 . Changes in rural population have a nonlinear impact on the NEP. When the rural population exceeds 545.686 people/km 2 , an increase in the rural population will have a positive impact on the NEP. Our research shows that rural depopulation offers a potential opportunity to restore natural ecosystems and thus increase the carbon sequestration capacity., 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 article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Biochar and organic fertilizer are commonly used to maintain soil health and sustainable agroecosystems, and the alternate wet-dry management of soil moisture in dry direct-seeded paddy fields can complicate the effects of biochar and organic fertilizer on soil microhabitats. Therefore, this study used chicken manure organic fertilizer to replace some of the inorganic fertilizer and applied biochar to explore the ability of biochar and organic fertilizer to regulate the functions of the soil microhabitat in dry direct-seeded paddy fields. The coupling effect of organic fertilizer and biochar increased the diversity and richness of soil bacteria but had no significant effect on soil fungi. Biochar and organic fertilizer affected the distribution and composition of soil bacteria and fungi, and the total number of soil bacteria and fungi increased by 1365 and -71 (5 t/hm 2 biochar and no organic fertilizer), 660 and 79 (10 t/hm 2 biochar and no organic fertilizer), 3121 and 7 (no biochar and 20 % organic fertilizer substitution), 1873 and -72 (5 t/hm 2 biochar and 20 % organic fertilizer substitution), and -544 and -65 (10 t/hm 2 biochar and 20 % organic fertilizer substitution), respectively, compared with that of the control treatment. Compared with the application of biochar alone, the coupling effect of biochar and organic fertilizer increased the average degree (0.95 and 0.16), links (190 and 32), and ratio of fungal positive links (1.651 %), and decreased the modularity (0.034 and 0.052) and ratio of bacterial positive links (6.482 %) of bacterial and fungal networks. In addition, the coupling effect resulted in a more complex association between soil microbial diversity and richness and microbial ecological functions. Random forest predictions indicated that, organic fertilizer as a random factor, changes in the abundance of bacterial Bacteroidetes and Nitrospirae and fungal Monoblepharomycota were the main factors driving the differences in soil microbial ecological functions., 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.)

To understand the microbial diversity and community composition within the main constructive tree species, Picea crassifolia, Betula platyphylla, and Pinus tabuliformis, in Helan Mountain and their response to changes in soil physicochemical factors, a high throughput sequencing technology was used to analyze the bacterial and fungal diversity and community structure. RDA (Redundancy Analysis) and Pearson correlation analysis were used to explore the influence of soil physicochemical factors on microbial community construction, and co-occurrence network analysis was conducted on the microbial communities. The results showed that the fungal and bacterial diversity was highest in B. platyphylla, and lowest in P. crassifolia. Additionally, the fungal/bacterial richness was greatest in the rhizosphere soils of P. tabuliformis and B. platyphylla. RDA and Pearson correlation analysis revealed that NN (nitrate nitrogen) and AP (available phosphorus) were the main determining factors of the bacterial community, while NN and SOC (soil water content) were the main determining factors of the fungal community. Pearson correlation analysis between soil physicochemical factors and the alpha diversity of the microbial communities revealed a significant positive correlation between pH and the bacterial and fungal diversity, while SOC, TN (total nitrogen), AP, and AN (available nitrogen) were significantly negatively correlated with the bacterial and fungal diversity. Co-occurrence network analysis revealed that the soil bacterial communities exhibit richer network nodes, edges, greater diversity, and greater network connectivity. Indicating that bacterial communities exhibit more complex and stable interaction patterns in soil. This study reveals the complex interactive relationship between microbial communities and soil physicochemical factors in forest ecosystems. By analyzing the response of rhizosphere microbial communities of major tree species in Helan Mountain to nutrient dynamics and pH changes, we can deepen our understanding of the role of microorganisms in regulating ecosystem functions and provide theoretical basis for soil improvement and ecological restoration strategies., (© 2024. The Author(s).)

Key Message: A plant growth regulator, 5-aminolevulinic acid, enhanced the saline-alkali tolerance via photosynthetic, oxidative-reduction, and glutathione metabolism pathways in pepper seedlings. Saline-alkali stress is a prominent environmental problem, hindering growth and development of pepper. 5-Aminolevulinic acid (ALA) application effectively improves plant growth status under various abiotic stresses. Here, we evaluated morphological, physiological, and transcriptomic differences in saline-alkali-stressed pepper seedlings after ALA application to explore the impact of ALA on saline-alkali stress. The results indicated that saline-alkali stress inhibited plant growth, decreased biomass and photosynthesis, altered the osmolyte content and antioxidant system, and increased reactive oxygen species (ROS) accumulation and proline content in pepper seedlings. Conversely, the application of exogenous ALA alleviated this damage by increasing the photosynthetic rate, osmolyte content, antioxidant enzyme activity, and antioxidants, including superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase, and reducing glutathione to reduce ROS accumulation and malonaldehyde content. Moreover, the transcriptomic analysis revealed the differentially expressed genes were mainly associated with photosynthesis, oxidation-reduction process, and glutathione metabolism in saline-alkali stress + ALA treatment compared to saline-alkali treatment. Among them, the change in expression level in CaGST, CaGR, and CaGPX was close to the variation of corresponding enzyme activity. Collectively, our findings revealed the alleviating effect of ALA on saline-alkali stress in pepper seedlings, broadening the application of ALA and providing a feasible strategy for utilize saline-alkali soil., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Severe fever with thrombocytopenia syndrome (SFTS) is caused by the SFTS virus (SFTSV) with high morbidity and mortality. The major immunodominant region of SFTSV surface glycoprotein (G) remains unclear. In this study, we constructed adenovirus type 5 (Ad5) vectored vaccine candidates expressing different regions of SFTSV G (Gn, Gc and Gn-Gc) and evaluated their immunogenicity and protective efficacy in mice. In wild-type mice, compared with Ad5-Gc or Ad5-Gn-Gc, Ad5-Gn recruited/activated more dendritic cells and B cells in lymph nodes or peripheral blood, causing Th1-/Th2-mediated responses in splenocytes and triggered a greater level of SFTSV-neutralizing antibodies. In IFNAR Ab-treated mice, immunization of Ad5-Gn exhibited better protection against SFTSV challenge than Ad5-Gc or Ad5-Gn-Gc. Furthermore, passive immunization revealed complete protective immunity of Gn-specific serum rather than Gc. Collectively, our data demonstrated that Gn is the immunodominant fragment of SFTSV G and could be a potential candidate for SFTSV vaccine development., (© 2024. The Author(s).)

Metastatic osteosarcoma is a commonly seen malignant tumor in adolescents, with a five year survival rate of approximately 20% and a lack of treatment options. Osteosarcoma cancer stem cells are considered to be important drivers of the metastasis of osteosarcoma, and therefore their clearance is considered a promising strategy for treating metastatic osteosarcoma. In the relevant literature, retinoic acid (ATRA) is considered effective for eliminating osteosarcoma stem cells, but it has some inherent disadvantages, including poor solubility, difficulty in entering cells, and structural instability. Tetrahedral framework nucleic acids (tFNAs) are a type of nanoparticles that can carry small-molecule drugs into cells to exert therapeutic effects. Therefore, we designed and synthesized a nanoparticle named T-ATRA by using tFNAs to load ATRA and studied its effect in a nude mouse model. T-ATRA is more effective than ATRA in the clearance of osteosarcoma stem cells and in inhibiting osteosarcoma cell metastasis via the Wnt signaling pathway, thus prolonging the survival time of nude mice with osteosarcoma.

Background: Hexaconazole, thifluzamide, difenoconazole and azoxystrobin are widely used fungicides for the control of Rhizoctonia solani in China. However, few studies have assessed the sensitivity and resistance risk of R. solani to these four fungicides., Results: The sensitivities of 126 R. solani isolates to hexaconazole, thifluzamide, difenoconazole and azoxystrobin were determined, with average half maximal effective concentration (EC 50 ) values of 0.0386, 0.0659, 0.663 and 1.508 μg mL -1 , respectively. Field resistance monitoring of the four fungicides showed that the three isolates had moderate resistance to difenoconazole. Resistant mutants to the four fungicides were obtained by fungicide adaptation, and resistance could be stably inherited by most mutants. Compared with those of the parent isolates, the biological characteristics of hexaconazole-resistant mutants exhibited enhanced or similar compound fitness index (CFI), whereas most of the other mutants displayed reduced or comparable CFI. There was evidence of positive cross-resistance between hexaconazole and difenoconazole. In the presence of fungicides, the expression of the CYP51 genes in hexaconazole- and difenoconazole-resistant mutants significantly increased, the expression of SDH genes in thifluzamide-resistant mutants significantly decreased, and the expression of the Cyt b gene in azoxystrobin-resistant mutants did not significantly change., Conclusion: Based on these data, we speculated that R. solani had a low-to-medium resistance risk to four fungicides. The change of target gene expression may be one of the reasons for fungicide resistance in R. solani. This study provides a theoretical basis for monitoring resistance emergence and developing resistance management strategies to control R. solani. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: Normal tissue and immune organ protection are critical parts of the tumor radiation therapy process. Radiation-induced immune organ damage (RIOD) causes several side reactions by increasing oxidative stress and inflammatory responses, resulting in unsatisfactory curability in tumor radiation therapy. The aim of this study was to develop a novel and efficient anti irradiation nanoparticle and explore its mechanism of protecting splenic tissue from radiation in mice., Methods: Nanoparticles of triphenylphosphine cation NIT radicals (NPs-TPP-NIT) were prepared and used to protect the spleens of mice irradiated with X-rays. Splenic tissue histopathology and hematological parameters were investigated to evaluate the protective effect of NPs-TPP-NIT against X-ray radiation. Proteomics was used to identify differentially expressed proteins related to inflammatory factor regulation. In addition, in vitro and in vivo experiments were performed to assess the impact of NPs-TPP-NIT on radiation therapy., Results: NPs-TPP-NIT increased superoxide dismutase, catalase, and glutathione peroxidase activity and decreased malondialdehyde levels and reactive oxygen species generation in the spleens of mice after exposure to 6.0 Gy X-ray radiation. Moreover, NPs-TPP-NIT inhibited cell apoptosis, blocked the activation of cleaved cysteine aspartic acid-specific protease/proteinase, upregulated the expression of Bcl-2, and downregulated that of Bax. We confirmed that NPs-TPP-NIT prevented the IKK/IκB/NF-κB activation induced by ionizing radiation, thereby alleviating radiation-induced splenic inflammatory damage. In addition, when used during radiotherapy for tumors in mice, NPs-TPP-NIT exhibited no significant toxicity and conferred no significant tumor protective effects., Conclusions: NPs-TPP-NIT prevented activation of IKK/IκB/NF-κB signaling, reduced secretion of pro-inflammatory factors, and promoted production of anti-inflammatory factors in the spleen, which exhibited radiation-induced damage repair capability without diminishing the therapeutic effect of radiation therapy. It suggests that NPs-TPP-NIT serve as a potential radioprotective drug to shelter immune organs from radiation-induced damage., (© 2024. The Author(s).)

Microplastics and antibiotics are emerging contaminants in agricultural soil that can have negative effects on crops. However, limited research has been conducted on the effects of the polypropylene (PP) microplastic and sulfamethoxazole (SMX) co-exposure on crops, specifically regarding the impact of PP microplastics on SMX uptake and transport in crops. In this study, hydroponic experiments were carried out using lettuce (Lactuca sativa L.), PP microplastics (1.0 g L -1 ), and SMX (0.5 mg L -1 or 2.5 mg L -1 ) to investigate the individual and co-exposure effects of PP microplastics and SMX on Lettuce growth, explore the uptake and translocation of SMX in lettuce and elucidate the underlying mechanism of PP microplastic impact on SMX uptake. Results demonstrated that co-exposure to 1.0 g L -1 of PP microplastics and 0.5 mg L -1 of SMX resulted in an enhanced toxic effect. However, no intensified toxic effect on the lettuce was observed when 1.0 g L -1 PP microplastics were added in the presence of 2.5 mg L -1 SMX, indicating that the SMX dominated the toxic effect on lettuce at high concentrations. Additionally, the study found that the water absorption process controlled by the aquaporin and transpiration contributed to the uptake and translocation of SMX in lettuce. When exposed to PP microplastics, no impact was observed on the aquaporin contents of the lettuce while the transpiration rate was significantly decreased by 31.6 % - 44.2 % resulting from microplastics adhered to the root surface. Therefore, in the presence of 2.5 mg L -1 SMX, the SMX uptake in the lettuce root was inhibited by 35.9 % (P < 0.05) when exposed to 1.0 g L -1 PP microplastic. This work deepens our understanding of the behaviour of microplastics and antibiotics in the terrestrial environment., 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.)

China is a major cycling nation with nearly 400 million bicycles, significantly alleviating urban traffic congestion. However, safety concerns are prominent, with approximately 35% of cyclists forming groups with family, friends, or colleagues, exerting a significant impact on the traffic system. This study focuses on group cycling, employing urban cycling experiments, GPS trajectory tracking, and eye-tracking to analyze the visual search, and cycling control of both groups and individuals. Findings reveal that group cyclists tend to focus more on companions, leading to a dispersed gaze pattern compared to individual riders who focus more on the direct path and surroundings. Group riders also exhibit shorter fixation times on traffic signs, potentially indicating decreased attention to traffic regulations. Despite similar lateral position deviation, group cyclists exhibit higher steering entropy, indicating greater variability in their steering choices. Additionally, group riders demonstrate varied passing times, suggesting a collective advantage in navigating complex traffic conditions. This study enhances our understanding of bicycles within traffic dynamics, offering valuable insights for traffic management systems., 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. Published by Elsevier Ltd.)

Background: Subarachnoid hemorrhage (SAH) is a life -threatening cerebrovascular disease, where early brain injury (EBI) stands as a primary contributor to mortality and unfavorable patient outcomes. Neuronal ferroptosis emerges as a key pathological mechanism underlying EBI in SAH. Targeting ferroptosis for therapeutic intervention in SAH holds significant promise as a treatment strategy., Methods: SAH model was induced via intravascular puncture and quantitatively assessed the presence of neuronal ferroptosis in the early phase of SAH using FJC staining, Prussian blue staining, as well as malondialdehyde (MDA) and glutathione (GSH) measurements. Hyaluronic acid-coated ursolic acid nanoparticles (HA-PEG-UA NPs) were prepared using the solvent evaporation method. We investigated the in vivo distribution of HA-PEG-UA NPs in SAH model through IVIS and fluorescence observation, and examined their impact on short-term neurological function and cortical neurological injury. Finally, we assessed the effect of UA on the Nrf-2/SLC7A11/GPX4 axis via Western Blot analysis., Results: We successfully developed self-assembled UA NPs with hyaluronic acid to target the increased CD44 expression in the SAH-afflicted brain. The resulting HA-PEG-UA NPs facilitated delivery and enrichment of UA within the SAH-affected region. The targeted delivery of UA to the SAH region can effectively inhibit neuronal ferroptosis, improve neurological deficits, and prognosis in mice. Its mechanism of action is associated with the activation of the Nrf-2/SLC7A11/GPX4 signaling pathway., Conclusions: Brain-targeted HA-PEG-UA NPs was successfully developed and hold the potential to enhance SAH prognosis by limiting neuronal ferroptosis via modulation of the Nrf-2/SLC7A11/GPX4 signal., (© 2024. The Author(s).)

Rubus idaeus is a pivotal cultivated species of raspberry known for its attractive color, distinct flavor, and numerous health benefits. It can be used in pharmaceutical, cosmetics, agriculture and food industries not only as fresh but also as a processed product. Nowadays due to climatic changes, genetic diversity of cultivars has decreased dramatically. However, until now, the status of wild R. idaeus resources in China have not been exploited. In this study, we investigated the resources of wild R. idaeus in China to secure its future potential and sustainability. The MaxEnt model was used to predict R. idaeus suitable habitats and spatial distribution patterns for current and future climate scenarios, based on wild domestic geographic distribution data, current and future climate variables, and topographic variables. The results showed that, mean temperature of the coldest quarter (bio11), precipitation of the coldest quarter (bio19), precipitation of the warmest quarter (bio18), and temperature seasonality (bio4) were crucial factors affecting the distribution of R. idaeus. Presently, the suitable habitats were mainly distributed in the north of China including Xinjiang, Inner Mongolia, Gansu, Ningxia, Shaanxi, Shanxi, Hebei, Beijing, Liaoning, Jilin, Heilongjiang. According to our results, in 2050s, the total suitable habitat area of R. idaeus will increase under SSP1-2.6 and then will be decreased with climate change, while in the 2090s, the total suitable habitat area will continue to decrease. From the present to the 2090s, the centroid distribution of R. idaeus in China will shift towards the east and the species will always be present in Inner Mongolia. Our results provide wild resource information and theoretical reference for the protection and rational utilization of R. idaeus., (© 2024. The Author(s).)

The controlled synthesis of recyclable hematite in the leaching solution of secondary zinc oxide powder is an urgent problem in the chemical industry and metallurgy fields. In this paper, the effects of the temperature, agitation speed, and seed addition on the contents of iron, sulfur, potassium, sodium, and zinc in the iron removal residues, as well as the iron concentration in the supernatant after iron removal were systematically studied. In addition to the temperature control already reported, we found that the agitation speed can also control the transformation between jarosite and hematite phases. The content of jarosite in the residues can be effectively controlled by adjusting the agitation speed, thereby significantly improving the quality of hematite product, as indicated by SEM-EDS and XRD results. Under temperature of 185 °C, an agitation speed of 500 rpm, and a seed addition of 15 g/L, the iron, sulfur and zinc contents in the filter residues and the iron concentration in the supernatant were 59%, 3.22%, 0.92%, and 4.182 g/L, respectively. Kinetic studies show that the rapid oxidation kinetics is not conducive to the formation of high-quality hematite products. These results can directly guide the process of transformation of harmful jarosite into recyclable hematite from the leaching solution of secondary zinc oxide powder, which is of great practical significance for the controlled and waste-free removal of iron from aqueous solutions in the chemical industry and metallurgy fields., (© 2024. The Author(s).)

Background: Docetaxel (DTX) resistance attenuates anti-tumor effects of DTX on prostate cancer (mCRPC) and drug resistance was related to Treg expansion in tumors. ZNF667-AS1 played a suppressing role in various tumors and tumor-derived exosomes carry lncRNAs to participate in tumor progression. Here, the effects of ZNF667-AS1 on malignant characteristics and DTX resistance in PC and the effect and its underlying molecular mechanism of tumor-derived exosomes carrying ZNF667-AS1 on Treg expansion were investigated., Methods: The identification of exosomes were determined using TEM, NTA and western blot. The abundance of genes and proteins were evaluated using IHC, RT-qPCR, western blot and FISH. Malignant phenotypes of PC cells were evaluated by means of Edu, scratch test, transwell, CCK-8 and flow cytometry. The percentage of CD4 + CD25 + Foxp 3+ Tregs was detected using flow cytometry. The location of ZNF667-AS1 was detected using nuclear-cytoplasmic fractionation. The co-location of ZNF667-AS1 and U2AF1 protein was detected using IF-FISH assay. The interactions among ZNF667-AS1, TGFBR1 and U2AF1 were verified using RNA pull-down, RIP and dual luciferase activity., Results: ZNF667-AS1 expression in PC samples was lowered, which was negatively relative to poor prognosis and DTX resistance. ZNF667-AS1 overexpression inhibited malignant phenotypes of PC cells, tumor growth and DTX resistance. Besides, DTX resistant cell-derived exosomes expressed lower ZNF667-AS1 expression. Exosomes carrying exogenously high ZNF667-AS1 expression derived PC cells or serum of mice suppressed Treg expansion. On the mechanism, ZNF667-AS1 interacted with U2AF1 to destabilize TGFBR1 mRNA and reduce TGFBR1 expression in CD4 + T cells., Conclusion: ZNF667-AS1 suppressed cell growth of PC cells, tumor growth of mice and DTX resistance to PC cells and exogenously high ZNF667-AS1 expression in tumor-derived exosomes destabilized TGFBR1 mRNA and reduce TGFBR1 expression through interacting with U2AF1, thus resulting in attenuated Treg expansion, which was related to DTX resistance., (© 2024. The Author(s).)

Background: Pine wilt disease (PWD), caused by the pinewood nematode Bursaphelenchus xylophilus, poses a significant threat to global forestry, resulting in extensive economic and ecological damage. Traditional trunk injection agents (TIAs) are limited by environmental factors, such as high winter temperatures and vigorous resin flow, particularly in southern China. This study aimed to develop an ordinary temperature trunk injection agent (OTTIA) for year-round application and to evaluate its performance under high-temperature conditions in comparison to commercial TIAs., Results: Extensive laboratory and field tests identified N,N-Dimethylformamide (DMF) and benzyl acetate as optimal solvents and Tween-40 as an effective emulsifier for the OTTIA formulation. The new agent was fully absorbed by Pinus massoniana within 3 h at temperatures exceeding 30 °C, outperforming existing commercial agents. Treated trees maintained comparable emamectin benzoate (EB) levels but achieved lower LC 90 lethal concentration values (27.65 mg L -1 ), indicating greater efficacy. The OTTIA provided protection against PWD for ≤360 days postinjection., Conclusion: The development of OTTIA marks a significant advancement in PWD management, offering an effective solution for high-temperature regions and potentially transforming year-round treatment strategies. The results highlight the critical role of optimizing solvent and emulsifier combinations to enhance the efficacy and application of trunk injection agents, contributing to sustainable forest management and improved protection against PWD. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Maximizing the molecular information density requires simultaneously functionalizing distinct monomers and their coupling connections. However, current synthesis generally focuses on distinct monomers rather than coupling reactions because the multistep reactions significantly escalate the synthetic complexity in an exponential increase. Here, we report the two-dimensional nanoarchitectures (2DNs) of end-on oligomers, with versatile molecular structures and negative differential resistance (NDR), synthesized by programmed and surface-initiated step electrosynthesis based on the simultaneous utilization of six reactions including cross- and homocouplings. The resulting vertically end-on oligomers, with similar values in thickness and molecular length, as crystalline 2DNs, exhibit subnanometer uniformity, ultrahigh compressive modulus of 40 GPa, and low-bias NDR at 0.13 V with an ultralow power consumption of down to 0.05 nW/μm 2 . This highly controlled electrosynthesis provides a unique dimension to enhance the structural diversity of molecular 2D nanomaterials for high-density and low-power consumption electronics.

Purpose: Bisphosphonates are pivotal in managing bone tumors by inhibiting bone resorption. This study investigates the therapeutic potential of [ 177 Lu]Lu-P15-073, a novel bisphosphonate, for radioligand therapy (RLT) in bone metastases., Methods: Ten patients (age 35 to 75) with confirmed bone metastases underwent therapy with a single dose of [ 177 Lu]Lu-P15-073 (1,225 ± 84 MBq, or 33 ± 2 mCi). Prior to treatment, bone metastases were verified via [ 99m Tc]Tc-MDP bone scans. Serial planar whole-body scans monitored biodistribution over a 14-day period. Dosimetry was assessed for major organs and tumor lesions, while safety was evaluated through blood biomarkers and pain scores., Results: Serial planar whole-body scans demonstrated rapid and substantial accumulation of [ 177 Lu]Lu-P15-073 in bone metastases, with minimal uptake in blood and other organs. The absorbed dose in the critical organ, red marrow, was measured at (0.034 ± 0.010 mSv/MBq), with a notably low normalized effective dose (0.013 ± 0.005 mSv/MBq) compared to other 177 Lu-labeled bisphosphonates. Persistent high uptake in bone metastases was observed, resulting in elevated tumor doses (median 3.12 Gy/GBq). Patients exhibited favorable tolerance to [ 177 Lu]Lu-P15-073 therapy, with no new instances of side effects. Additionally, 87.5% (7/8) of patients experienced a significant reduction in pain scale (numerical rating scale, NRS, from 5.1 ± 2.3 to 3.0 ± 1.8). The tumor-background ratio (TBRmean) of [ 99m Tc]Tc-MDP correlated significantly with [ 177 Lu]Lu-P15-073 uptake (P < 0.01), indicating its potential for prediction of absorbed dose., Conclusions: This study demonstrates the safety, dosimetry, and efficacy of a single therapeutic dose of [ 177 Lu]Lu-P15-073 in bone metastases. The treatment was well-tolerated with no severe adverse events. These findings suggest that [ 177 Lu]Lu-P15-073 holds promise as a novel RLT agent for bone metastases., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Depression is recognized globally as one of the most intractable diseases, and its complexity and diversity make treatment extremely challenging. Acupuncture has demonstrated beneficial effects in various psychiatric disorders. However, the underlying mechanisms of acupuncture's antidepressant action, particularly in depression, remain elusive. Therefore, this study aimed to investigate the effects of acupuncture on chronic unpredictability stress (CUMS)-induced depressive symptoms in rats and to further elucidate its underlying molecular mechanisms. All rats were exposed to CUMS of two stressors every day for 28 days, except for the control group. One hour before CUMS, rats were given a treatment with acupuncture, electroacupuncture, sham-acupuncture, or fluoxetine (2.1 mg/kg). Behavioral tests and biological detection methods were conducted in sequence to evaluate depression-like phenotype in rats. The findings of this study demonstrate that acupuncture therapy effectively ameliorated depression-like behavior induced by CUMS in rats. Additionally, acupuncture exerted a restorative effect on the alterations induced by CUMS in the levels of malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF), cyclic AMP response element-binding protein (CREB), postsynaptic density95 (PSD95), gamma-aminobutyric acid (GABA), and acetylcholine (ACh). Additionally, our findings indicate that acupuncture also modulates the ERK and Caspase-3 apoptotic pathways in the hippocampus of CUMS rats. This study suggests that acupuncture may play a potential preventive role by regulating hippocampal neuroinflammatory response, levels of oxidative stress, apoptotic processes, and enhancing synaptic plasticity., (© 2024. The Author(s).)

PROteolysis TArgeting Chimeras (PROTACs) have been considered the next blockbuster therapies. However, due to their inherent limitations, the efficacy of PROTACs is frequently impaired by limited tissue penetration and particularly insufficient cellular internalization into their action sites. Herein, based on the ultra-pH-sensitive and enzyme-sensitive nanotechnology, a type of polymer PROTAC conjugated and pH/cathepsin B sequential responsive nanoparticles (PSRNs) are deliberately designed, following the construction of the PROTAC for Cyclin-dependent kinase 4 and 6 (CDK4/6). Colorectal cancer (CRC) which hardly responds to many treatments even immune checkpoint blockades was selected as the tumor model in this study. As a result, PSRNs were found to maintain nanostructure (40 nm) in circulation and efficiently accumulated in tumors via enhanced permeation and retention effect. Then, they were dissociated into unimers (<10 nm) in response to an acidic tumor microenvironment, facilitating tumor penetration and cellular internalization. Eventually, the CDK4/6 degrading PROTACs were released intracellularly following the cleavage of cathepsin B. Importantly, PSRNs led to the enhanced degradation of target protein in vitro and in vivo. The degradation of CDK4/6 also augmented the efficacy of immune checkpoint blockades, through the upregulation of programmed cell death-ligand 1 (PD-L1) expression in cancer cells and the suppression of regulatory T cells cell proliferation in tumor microenvironment. By combination with α-PD-1, an enhanced anti-tumor outcome is well achieved in CT26 tumor model. Overall, our study verifies the significance of precise intracellular delivery of PROTACs and introduces a promising therapeutic strategy for the targeted combination treatment of CRC., (© 2024. The Author(s).)

Nearly all antitumor drugs can benefit greatly from effective tumor-targeted delivery for improved therapeutic efficacy and reduced toxic side effects. However, the vast majority of tumor-targeting ligands can only target specific tumor cells that highly express the corresponding receptors and thus are only applicable to limited tumor types. Heptamethine cyanines with medium cyclohexene and medium Cl atoms, such as IR780 and IR808, have shown an unusual ability to indiscriminately accumulate into virtually all tumor types. In this study, IR808 was conjugated with DSPE-mPEG 2000 -NH 2 , and the resultant DSPE-PEG 2000 -IR808 (DP-IR808) in combination with TPGS successfully encapsulated paclitaxel (PTX) and immunomodulator R848 into nanoparticles with a small particle size of 150.20 nm, negative charge of -16.50 mV, rod-like morphology, and PTX loading content of 31.6%. The obtained DP-IR808@PTX-R848 NPs rapidly accumulated in 4T1 tumors with a tumor/liver fluorescence ratio of 1.71, and it demonstrated a significant photothermal effect and could be directly used for NIR imaging. The DP-IR808@PTX-R848 NPs achieved a high tumor inhibition rate of 94%, a mean survival time of >90 d, and a tumor-free survival percentage of 57%. To the best of our knowledge, this was the first time that nanoparticles were modified with heptamethylcyanine molecules. The nanoparticles system based on DSPE-PEG-IR808, which integrates tumor-targeted drug delivery, in vivo infrared imaging and photothermal therapy, is expected to become a versatile drug-delivery platform for tumor therapy.

Despite the considerable achievements of antibodies targeting PD-1/PD-L1 in cancer immunotherapy, limitations in antitumor immune response and pharmacokinetics hinder their clinical adoption. Small molecules toward PD-L1 degradation signifies an innovative avenue to modulate PD-1/PD-L1 axis. Herein, we unveil a comprehensive engineering involving the development of new PD-L1 degraders based on the berberine (BBR) and palmatine (PMT) bioactive frameworks and explore their translational potential for cancer immunotherapy using a peptide-drug conjugate strategy. Chemical modifications at the O-9 position of PMT dramatically enhance the PD-L1 degradation capacity. Further conjugation of PMT degraders with an anti-PD-L1 peptide featuring disulfide linkers enables efficient GSH-specific prodrug activation, yielding synergistic immunotherapeutic benefits through both external PD-L1 blockade and internal PD-L1 degradation mechanisms. This work elucidates the compelling charm of the discovery and application of PD-L1 degraders, offering solutions to the challenges in advancing cancer immunotherapy in widespread clinics.

In recent years, organic electrochemical transistors (OECTs) have attracted widespread attention due to their significant advantages such as low-voltage operation, biocompatibility, and compatibility with flexible substrates. Organic photoelectrochemical transistors (OPECTs) are OECTs with photoresponse capabilities that achieve photoresponse and signal amplification in a single device, demonstrating tremendous potential in multifunctional optoelectronic devices. In this mini-review, we briefly introduce the channel materials and operation mechanisms of OECTs/OPECTs. Then different types of OPECTs are discussed depending on their device-architecture-related photoresponse generation. Following this, we summarize recent advances in OPECT applications across various fields including biomedical sciences, optoelectronics, and sensor technologies. Finally, we outline the current challenges and explore future research prospects, aiming at extending their further development and applications.

Messenger RNA (mRNA)-based therapeutics have emerged as a promising modality for various clinical applications, necessitating robust methods for mRNA quantification. This biodistribution study compares the performance of branched DNA and reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) assays for measuring lipid nanoparticle-encapsulated mRNA. Following intravenous administration of nascent peptide imaging luciferase mRNA (1 mg/kg) to rats, mRNA levels in various tissues and serum were quantified using both assays. Statistical analyses, including Bland-Altman, Deming regression and Passing-Bablok regression, were employed to assess method comparability and reproducibility. The results indicated that mRNA pharmacokinetics measured by branched DNA and RT-qPCR were largely consistent across tissues, with RT-qPCR showing greater reproducibility across multiple laboratories. RT-qPCR also demonstrated a wider dynamic range and higher sensitivity, making it a more versatile option for large-scale studies. Despite some differences in data due to tissue types and timepoints, both methods provided comparable pharmacokinetic profiles for mRNA quantification. This study underscores the importance of selecting an appropriate quantification method based on study requirements and highlights RT-qPCR's adaptability for multisite research, especially for the clinical development of mRNA-based therapeutics.

As a powerful eukaryotic expression vector, the baculovirus expression vector system (BEVS) is widely applied to the production of heterogeneous proteins for research and pharmaceutical purposes, while optimization of BEVS remains a work in progress for membrane or secreted protein expression. In this study, the impact of the signal peptide (SP) derived from Bombyx mori nucleopolyhedrovirus (BmNPV) GP64 protein on protein expression, secretion, and the endoplasmic reticulum-associated degradation (ERAD) pathway were investigated in BmN cells and BEVS. Transient expression studies in BmN cells revealed that SP alters the localization and expression levels of recombinant proteins, reducing intracellular accumulation while enhancing secretion efficiency. Quantitative analysis demonstrated that SP-mediated secretion was markedly higher compared to controls, albeit with lower total expression levels. Further exploration into SP-mediated ERAD pathway activation showed increased expression of BiP and other ERAD-associated genes (PDI, UFD1, S1P, and ASK1), correlating with higher SP-driven protein expression levels. RNA interference (RNAi) experiments elucidated that knockdown of ERAD-associated genes enhances both the secretion efficiency of SP-guided proteins and the infectivity of BmNPV. Particularly, interference with BiP demonstrated the most pronounced effect on protein secretion enhancement. Viral infection experiments further supported these findings, showing upregulated ERAD-associated genes during BmNPV infection, indicating their role in viral protein processing and infectivity. In conclusion, this study elucidates the complex interplay between SP-mediated protein secretion, ERAD pathway activation, and viral infectivity in BmNPV-infected cells. These insights suggest strategies for optimizing recombinant protein production and viral protein processing in baculovirus expression systems, with potential implications for biotechnological and biomedical applications. Further research could refine our understanding and manipulation of protein secretion pathways in insect cell-based expression systems., (© 2024. The Author(s).)

Sodium-ion batteries hold great promise as next-generation energy storage systems. However, the high instability of the electrode/electrolyte interphase during cycling has seriously hindered the development of SIBs. In particular, an unstable cathode-electrolyte interphase (CEI) leads to successive electrolyte side reactions, transition metal leaching and rapid capacity decay, which tends to be exacerbated under high-voltage conditions. Therefore, constructing dense and stable CEIs are crucial for high-performance SIBs. This work reports localized high-concentration electrolyte by incorporating a highly oxidation-resistant sulfolane solvent with non-solvent diluent 1H, 1H, 5H-octafluoropentyl-1, 1, 2, 2-tetrafluoroethyl ether, which exhibited excellent oxidative stability and was able to form thin, dense and homogeneous CEI. The excellent CEI enabled the O3-type layered oxide cathode NaNi 1/3 Mn 1/3 Fe 1/3 O 2 (NaNMF) to achieve stable cycling, with a capacity retention of 79.48% after 300 cycles at 1 C and 81.15% after 400 cycles at 2 C with a high charging voltage of 4.2 V. In addition, its nonflammable nature enhances the safety of SIBs. This work provides a viable pathway for the application of sulfolane-based electrolytes on SIBs and the design of next-generation high-voltage electrolytes., (© 2024. The Author(s).)

Hole transport materials (HTMs) are essential for improving the stability and efficiency of perovskite solar cells (PSCs). In this study, we have designed and synthesized a novel organic small molecule HTM, cor-(DPA)5, characterized by a bowl-shaped core with symmetric five diphenylamine groups. Compared to already-known HTMs, the bowl-shaped and relatively compact structure of cor-(DPA)5 facilitates intermolecular π-π interactions, promotes film formations, and enhances charge transport. Consequently, the cor-[DPA(2)]5 HTM exhibits high charge mobility, exceptional hydrophobicity, and a significantly elevated glass transition temperature. Superior to previously reported HTMs such as spiro-OMeTAD and cor-OMePTPA, our newly synthesized cor-(DPA)5 HTM is free from any ionic dopants. As a result, the dopant-free cor-[DPA(2)]5-based PSC demonstrates an impressive efficiency of 24.01%, and exhibits outstanding operational stability. It retains 96% after continuous exposure to 1 sun irradiation for 800 hours under MPP (maximum power point) tracking in ambient air. These findings present a structurally compact novel HTM and exemplify a new approach to the molecular design of HTM for the development of stable and effective PSCs., (© 2024 Wiley‐VCH GmbH.)

Objective . In magneto-acousto-electrical tomography (MAET), linearly frequency-modulated (LFM) signal stimulation uses much lower peak voltage than the spike pulse stimulation, lengthening the operation life of the transducer. However, due to the uneven frequency responses of the transducer, the low-noise amplifier (LNA), and the bandpass filter (BPF), MAET using LFM signal stimulation suffers from longitudinal resolution loss. In this paper, frequency response compensated linearly frequency-modulated (FRC-LFM) signal stimulation is investigated to resolve the problem. Approach . The physical model of measurement of the frequency responses of the transducer and the cascading module of the detection electrodes, the LNA, and the BPF is constructed. The frequency responses are approximated by fitting a curve to the measurement data. The frequency response compensation function is set to the reciprocal of the product of the frequency responses. The digital FRC-LFM signal is generated in MATLAB and converted to analog signal through an arbitrary waveform generator. Two groups of MAET experiments are designed to confirm the performance of the FRC-LFM signal stimulation. Pure agar phantom with rectangular through-holes and agar phantom with pork tissue inclusion serve as the samples. Main results . The pulse-compressed magneto-acousto-electrical signal obtained using FRC-LFM stimulation has narrower main-lobe than that obtained using LFM excitation, although the signal to noise pulse interference ratio of the former is little lower than that of the latter, which is due to the limitation of the power amplifier. FRC-LFM also proves to be an effective method to utilize the frequency outside the working band of the transducer in MAET. Significance . The method in this study compensates for the longitudinal resolution loss due to the uneven frequency responses. Combining with high-capability power amplifier and high-performance LNA, the MAET using FRC-LFM signal stimulation can potentially achieve high longitudinal resolution and high sensitivity, advancing MAET toward the clinical application., (© 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Freeze-thaw (FT) cycle would greatly influence the fate of plastic particles (one of emerging contaminants with great concerns) in soils, yet its impacts and mechanisms remain unclear. The vertical migration/release behaviors of plastic particles (with diameters of 0.2 μm and 1 μm) in two natural soils and one model soil (i.e. quartz sand) without/with FT treatments (1 and 3 cycles) were examined. Owing to the presence of Fe/Al oxide minerals, finer pore structure, and uneven surfaces of natural soils, the breakthrough ratio of plastics in two natural soils was over 25% lower than in quartz sand. However, regardless of porous media type, FT processes (increasing cycles) significantly promoted the remobilization of plastics initially retained in three media during the subsequent water flushing processes. Via theoretical calculation, tracer experiments, and visible chamber experiments, the mechanisms driving plastics release from natural soils subjected to FT treatments during the water elution processes were determined to be different from those from pure quartz sand. The change of sand local configuration (the rearrangement of local sand pore spaces) during FT process mainly drove to plastics released from quartz sand columns. While the alteration in local soil configuration, the formation of preferential pathways, and increased release of soil particles contributed to plastics remobilization from soil columns subjected to FT. Clearly, FT processes significantly increased the vertical migration of plastics in soils potentially to groundwater, enhancing environmental risks of plastics., 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. ☐ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024. Published by Elsevier Ltd.)

Antibiotics are of emerging concern due to their widespread use, lack of adequate treatment, and for their potential to threaten human health and the environment. Here, a facile fabrication approach for synthesizing ZnO/CuO-bentonite composites was investigated via carbon-bed pyrolysis of bentonite followed by ZnO/CuO co-precipitation. Sorbents were synthesized using a range of bentonite pyrolysis temperatures, metal oxide contents, and ZnO:CuO mass ratios. The ZnO/CuO-bentonite composites exhibited diverse functional groups, excellent mesoporosity, and high specific surface area (135.0 m 2  g -1 , four times that of pyrolyzed bentonite-only control). Ciprofloxacin removal was maximized at a bentonite pyrolysis temperature of 450 °C, a total metal oxide content of 25 %, and a Zn/Cu ratio between 95:5 and 93:7, and this material had an observed experimental CIP adsorption of 451 mg g -1 and a calculated maximum adsorption capacity of 1249.3 mg g -1 . This excellent CIP sorption ability was attributed to its abundant surface active sites and multiple sorption mechanisms, including hydrogen-bond interaction, ion exchange, and electrostatic interaction. These results illustrate that ZnO/CuO-bentonite composite sorbents have excellent potential for use in environmental remediation and water treatment applications., (Copyright © 2024. Published by Elsevier B.V.)

Chemotherapy has become an emerging strategy to activate cytotoxic T cell responses by inducing immunogenic cell death (ICD), but the level of antitumor immunity induced by chemotherapeutic agents, such as oxaliplatin (OXA), is limited due to inadequate tumor antigen presentation and T cell activation. Inducing autophagic cell death (ACD) promotes the release of tumor antigen and the recruitment of dendritic cells, therefore strengthening antitumor immune responses. Here we simultaneously activate ICD and ACD with tumor targeting micelle to achieve enhanced antitumor chemo-immunotherapy. A self-delivery micelle is formulated by conjugating OXA prodrug with tocopherol succinate (TOS) as a hydrophobic segment and further encapsulates autophagy activator SMER28 to afford TOPR/SMER28, which specifically targets αvβ3 on tumor cells with c(RGDfK). Upon cellular internalization, OXA is released from the prodrug in response to the high concentration of reduced glutathione (GSH) in tumor cells, triggering ICD and releasing associated molecular patterns (DAMPs) signaling molecules to stimulate immunity. Meanwhile, SMER28 over-activates autophagy to induce autophagic cell death, which further leads to the maturation of dendritic cells and ultimately activates anti-tumor immune response. In the 4T1 tumor-bearing mice, the combination of OXA and SMER28 effectively inhibits tumor growth and activates antitumor immune responses. The tumor targeted micelle releases OXA and SMER28 in an on-demand profile and strengthens tumor chemo-immunotherapy by synergizing ICD and ACD, providing an alternative for antitumor immunotherapy. STATEMENT OF SIGNIFICANCE: Chemotherapy induces immunogenic cell death (ICD) to activate anti-tumor immunity. However, the efficacy is limited by low levels of antigen presentation and T cell activation. To strengthen the antitumor immune responses induced by ICD, we first combine autophagic cell death (ACD) with ICD by formulating a glutathione-responsive oxaliplatin prodrug micelle co-encapsulating the autophagy activator SMER28. The activated autophagic level by SMER28 enhances the release of antigen and the recruitment of APCs, and ultimately bolsters T cell-mediated antitumor immune responses. We provide a potential strategy to amplify antitumor immune effects by combining autophagy activation with chemotherapy., 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. Published by Elsevier Ltd.)

Two new paraherquamides (PHQs) namely aculeaquamides B and C (1 and 2), along with four known PHQs (3-6), were isolated from the co-culture of marine fungus Aspergillus aculeatinus WHUF0198 and mangrove-associated fungus Penicillium sp. DM27. Compound 1 represents the first PHQ derivative featuring an uncommon 7/6/5/5/6/5 hexacyclic system. The structures of the isolated compounds were elucidated based on exhaustive NMR spectroscopy measurement and HRESIMS data. The absolute configurations of new compounds were determined by TDDFT-ECD calculations. Compound 3 demonstrated suppression of AngII-induced cardiac hypertrophy while exhibiting relatively low cardiomyocyte toxicity., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

DNA deamination occurs constantly in a cell and causes DNA damage. As this damage can be deleterious, organisms have evolved many systems to eliminate it, such as endonuclease V (Endo V). DUF99 family protein contains a domain of unknown function similar to Endo V, but had not been experimentally characterized to date. Here, we show that DUF99 family proteins cleave the 3'-side of deoxyuridine (dU) on DNA substrates. Based on phylogenetic analysis, we designated this new protein family as Endonuclease dU (Endo&#95;dU). We also observed that Endo&#95;dU coding gene frequently colocalizes with that for uracil-DNA glycosylase (UDG) in halophilic archaea, and we further performed gene knockout of Endo&#95;dU gene on Haloferax volcanii. The transcription level of UDG gene on Endo&#95;dU knockout strain was increased when induced by sodium bisulfite. Thus, we hypothesize that Endo&#95;dU establishes a new endonuclease family with broad phylogenetic distribution and may participate in DNA repair., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Despite the optimisation of the zero-COVID policy in late 2022, there was a subsequent increase noted in the number of respiratory syncytial virus (RSV) cases in Northern China. In this study, we investigated and characterised the dynamics of this surge at the genomic level in Beijing, China., Methods: Patients with acute respiratory tract infections (ARTIs) were enrolled from 35 sentinel hospitals in Beijing, China. Epidemiological investigations, G gene amplification, and whole-genome sequencing were performed, followed by epidemiological analysis, imported clade detection, and mutation identification. We also combined global data to illustrate the biological and epidemiological characteristics of the emerging clades., Results: A total of 60,423 patients with ARTIs were recruited between January 2015 and January 2024. The RSV peak observed in the winter of 2023 was the highest in the past 9 years. Two novel imported clades, A.D.5.2 and B.D.E.1, were detected for the first time in China. This surge was mainly driven by B.D.E.1, which exhibited a significantly higher proportion of older individuals both in Beijing and globally. Seven non-synonymous mutations in B.D.E.1 were found in Beijing. B.D.E.1 had more sites suffering from positive selection than its parent., Conclusions: The novel imported clade B.D.E.1 accelerated an unprecedented RSV surge in Beijing, presenting noteworthy epidemiological and biological characteristics. Continuous RSV genome monitoring has important implications for RSV outbreak identification, genetic diversity tracking, vaccine development, and strategy implementation., 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. Published by Elsevier Ltd.)

The root of Stemona tuberosa Lour has been used to treat tuberculosis, scabies, and eczema. Polysaccharides are among its main bioactive ingredients. A low-molecular-weight (1819 Da) polysaccharide (SPS2-A) was obtained from the root of S. tuberosa Lour by optimizing three-phase partitioning, purified using an ion chromatography column, and its effects and mechanisms were investigated. Structural analysis revealed that SPS2-A contained arabinose, galactose (Gal), glucose (Glc), xylose, and mannose. The SPS2-A backbone structure comprised sugar residues →4)-α-D-Glcp-(1→, →4)-α-D-Galp-(1→, and →4,6)-β-D-Galp-(1→, while the side chain primarily comprised α-D-Glcp-(1 → connected to the O-6 position of the residue →4,6)-β-D-Galp-(1→. In vitro, SPS2-A downregulated the expression of interleukin-6 in lipopolysaccharide-induced RAW264.7 macrophages. In vivo, SPS2-A significantly downregulated the expression of myeloperoxidase, interleukin-6, interleukin-1β, and tumor necrosis factor-α in bronchoalveolar lavage fluid and lung tissue. Western blotting analysis indicated that SPS2-A reduced lung inflammation in mice with sepsis-induced acute lung injury by activating the nuclear factor κB pathway. These results suggest that SPS2-A is a potential anti-inflammatory candidate for the treatment of sepsis-induced acute lung injury., 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. Published by Elsevier B.V.)

Scope: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that can lead to insulin resistance (IR) and dysregulation of glucose metabolism, resulting in an imbalance in the endometrial environment, which is unfavorable for embryo implantation of PCOS. This study aims to investigate whether nicotinamide mononucleotide (NMN) improves the stability of the endometrium in a rat model of PCOS and identifies whether it is related to reduce IR and increase glycolysis levels and its potential signaling pathway., Methods and Results: Female Sprague-Dawley (SD) rats are fed letrozole and a high-fat diet (HFD) to form the PCOS model, then the model rats are treated with or without NMN. It randomly divided into control, PCOS, and PCOS-NMN groups according to the feeding and treating method. Compared with the PCOS group, the regular estrous cycles are restored, the serum androgen (p<0.01) and fasting insulin levels (p<0.05) are reduced, and endometrial morphology (p<0.05) is improved in NMN-PCOS group. Furthermore, NMN inhibits endometrial cell apoptosis, improves endometrial decidualization transition, reduces IR, restores the expression of glycolysis rate-limiting enzymes, and activates the PI3K/AKT pathway in the uterus., Conclusions: These results suggest that NMN enhances endometrial tissue homeostasis by decreasing uterine IR and regulating the glycolysis through the PI3K/AKT pathway., (© 2024 Wiley‐VCH GmbH.)