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Background: Acute lung injury (ALI) has received considerable attention in the field of critical care as it can lead to high mortality rates. Polygala tenuifolia, a traditional Chinese medicine with strong expectorant properties, can be used to treat pneumonia. Owing to the complexity of its composition, the main active ingredient is not yet known. Thus, there is a need to identify its constituent compounds and mechanism of action in the treatment of ALI using advanced technological means., Purpose: We investigated the anti-inflammatory mechanism and constituent compounds with regard to the effect of P. tenuifolia Willd. extract (EPT) in lipopolysaccharide (LPS)-induced ALI in vivo and in vitro., Methods: The UHPLC-Q-Exactive Orbitrap MS technology was used to investigate the chemical profile of EPT. Network pharmacology was used to predict the targets and pathways of action of EPT in ALI, and molecular docking was used to validate the binding of polygalacic acid to Toll-like receptor (TLR) 4. The main compounds were determined using LC-MS. A rat model of LPS-induced ALI was established, and THP-1 cells were stimulated with LPS and adenosine triphosphate (ATP) to construct an in vitro model. Pathological changes were observed using hematoxylin and eosin staining, Wright-Giemsa staining, and immunohistochemistry. The expression of inflammatory factors (NE, MPO, Ly-6 G, TNF-α, IL-1β, IL-6, and iNOS) was determined using enzyme-linked immunosorbent assay, real-time fluorescence quantitative polymerase chain reaction, and western blotting. The LPS + ATP-induced inflammation model in THP-1 cells was used to verify the in vivo experimental results., Results: Ninety-nine compounds were identified or tentatively deduced from EPT. Using network pharmacology, we found that TLR4/NF-κB may be a relevant pathway for the prevention and treatment of ALI by EPT. Polygalacic acid in EPT may be a potential active ingredient. EPT could alleviate LPS-induced histopathological lung damage and reduce the wet/dry lung weight ratio in the rat model of ALI. Moreover, EPT decreased the white blood cell and neutrophil counts in the bronchoalveolar lavage fluid and decreased the expression of genes and proteins of relevant inflammatory factors (NE, MPO, Ly-6 G, TNF-α, IL-1β, IL-6, and iNOS) in lung tissues. It also increased the expression of endothelial-type nitric oxide synthase expression. Western blotting confirmed that EPT may affect TLR4/NF-κB and NLRP3 signaling pathways in vivo. Similar results were obtained in THP-1 cells., Conclusion: EPT reduced the release of inflammatory factors by affecting TLR4/NF-κB and NLRP3 signaling pathways, thereby attenuating the inflammatory response of ALI. Polygalacic acid is the likely compounds responsible for these effects., Competing Interests: Declaration of competing interest The authors declare that the publication of this paper has no conflicts of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Rationale: Childhood precocious puberty (CPP) is a common pediatric endocrine disorder with significant associated risks. Zhibai Dihuang pill (ZBDHP), a classic recipe of the Qing dynasty with its efficacy of nourishing yin and clearing heat, can downregulate the expression of ESR1 in the uterus and ovaries, thereby inhibiting CPP. However, as of now, the main active ingredients and pharmacological mechanisms of ZBDHP remain unclear., Methods: A comprehensive approach was proposed using ultra-high-performance liquid chromatography coupled with quadrupole-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS) and network pharmacology to explore the potentially active constituents of ZBDHP and reveal the underlying mechanisms against CPP. Molecular docking was used to verify the possible mechanisms., Results: A total of 214 constituents derived were identified via UHPLC-Q-Exactive Orbitrap-MS, and 12 of them were definitely characterized using reference standards. Subsequently, compounds tetrahydropalmatine, alisol C, 25-anhydroalisol A 11-acetate, hispidone, cavidine, alisol E, melianone, neogitogenin, denudatin B, and 16β-hydroperoxyalisol B with related targets PIK3CA, HSD11B1, CYP19A1, AR, PTGS2, CDK2, NR3C1, MMP2, MMP1, and MAPK1 were regarded as key components and targets for ZBDHP treating CPP using the compound-target-pathway network. Besides, the results revealed that the pathways conduced obviously to therapeutic efficacy, including pathways in cancer, neuroactive ligand-receptor interaction, and cyclic adenosine monophosphate（cAMP） signaling pathways. Molecular docking indicated that PIK3CA, HSD11B1, and CYP19A1 exhibited high affinities to corresponding compounds. Overall, the study determined the multicomponent, multitarget, and multipathway mechanisms of ZBDHP against CPP., Conclusions: This study provided a new method for exploring the chemical constituents and pharmacology mechanism of traditional Chinese medicine., (© 2024 John Wiley & Sons Ltd.)

Topological insulators are characterized by exhibiting an internal insulating state but a surface conductor state, which makes them advantageous for applications in novel devices. However, for most given acoustic topological metamaterials, the operating frequency is relatively fixed and the effect of temperature on their topological properties is rarely considered. Therefore, a temperature-tunable acoustic topological insulator is constructed in this paper. The quadruple degenerate Dirac cone formed at Γ point can be opened by adjusting the temperature, causing topological band inversion between the doubly degenerate dipolar and quadrupole states, and achieving topological phase transition. The evolution of its topological state with temperature is numerically investigated and a novel topological acoustic waveguide is constructed. The switching effect of temperature on the waveguide device is verified by numerical simulation and experiment. Non-contact active modulation of edge states in the structure is achieved by temperature-controlled topological phases, exhibiting acoustic switching effects. This study can provide corresponding references for the intelligent control of acoustic topology in noise, vibration, and other aspects., (© 2024. The Author(s).)

We conducted this meta-analysis to investigate neurological toxicities with poly (ADP-ribose) polymerase inhibitors (PARPis) in cancer patients. Databases were searched for randomized controlled trials (RCTs) from 1 January 2000 to 1 November 2023. Forty-six RCTs and 9529 patients were included. PARPis could increase the risk of all-grade headache [risk ratio (RR), 1.22; 95% confidence intervals (CI), 1.14-1.30; P  < 0.00001], dizziness (RR, 1.40; 95% CI, 1.28-1.53; P  < 0.00001), dysgeusia (RR, 1.93; 95% CI, 1.44-2.60; P  < 0.0001) and insomnia (RR, 1.32; 95% CI, 1.09-1.60; P  < 0.0001) in cancer patients. Headache was the most common neurological toxicity. Niraparib was associated with a higher risk of headache and insomnia, talazoparib with a higher risk of dizziness and rucaparib with a higher risk of dysgeusia. Breast cancer patients receiving PARPis have a higher risk of dysgeusia, while ovarian cancer patients are at an increased risk of insomnia. PARPis may increase the risk of mild to moderate neurological toxicities, but not severe ones.

Processing is an indispensable technology in the preparation of Spirulina platensis (S. platensis). The key odorants in liquids, muds, and powders from S. platensis (NM and GZ) were characterized. A total of 90 odorants were identified and 41 odorants were sniffed with the flavor dilution (FD) factors ranging from 1 to 729. Among them, nonanal, decanal, d-limonene, β-cyclocitral, and β-ionone with FD factors ≥1 were detected in S. platensis during the whole processing stages. In addition, heptanal, (E, E)-2,4-nonadienal, trans-4,5-epoxy-(E)-2-decenal, 1-hepten-3-one, isophorone, 3-ethyl-2,5-dimethylpyrazine, and α-ionone exhibited higher odor activity values in powders; β-myrcene, methional, and S-methyl methanethiosulphonate were key odorants in muds; while trans-3-penten-2-ol was key odorant in liquids. Besides, the GZ-mud presented stronger earthy and fishy odor than NM-mud. S. platensis powders have the stronger grassy odor, roasted odor, and marine odor than S. platensis muds. Overall, drying process promotes the formation of aldehydes, heterocyclic compounds, and terpenoids., 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.)

Modeling user intention with limited evidence in short-term historical sequences is a major challenge in session recommendation. In this domain, research exploration extends from traditional methods to deep learning. However, most of them solely concentrate on the sequential dependence or pairwise relations within the session, disregarding the inherent consistency among items. Additionally, there is a lack of research on context adaptation in session intention learning. To this end, we propose a novel session-based model named C-HAN, which consists of two parallel modules: the context-embedded hypergraph attention network and self-attention. These modules are designed to capture the inherent consistency and sequential dependencies between items. In the hypergraph attention network module, the different types of interaction contexts are introduced to enhance the model's contextual awareness. Finally, the soft-attention mechanism efficiently integrates the two types of information, collaboratively constructing the representation of the session. Experimental validation on three real-world datasets demonstrates the superior performance of C-HAN compared to state-of-the-art methods. The results show that C-HAN achieves an average improvement of 6.55%, 5.91%, and 6.17% over the runner-up baseline method on Precision@K, Recall@K, and MRR evaluation metrics, respectively., (© 2024. The Author(s).)

Double-layer island working face main roadway coal pillars are affected by complex mining stress superposition, when different coal pillar width combinations, the surrounding rock stress field will produce different degrees of regional loading increase effect; the study of the surrounding rock stress field regional superposition loading increase law is meaningful to explaining the failure mode of the roadway and determining the critical control area. This study combines numerical simulation with on-site monitoring and other methods and draws the following conclusions: The superimposed loading increase law ("decreasing" → "increasing") of the abutment pressure and deviatoric stress in the lower coal seam of the double-layer island working face during the mining; the type of the principal stress deflection in the advance working face region; and by obtaining the three types of development morphology of the deviatoric stress peak zone of the roadway and its corresponding nine evolution modes (one type of circular tube → four types of inverse hyperbolic body → four types of hyperbolic body) in the double-layered island working face mining. Indicated the critical reinforcement area corresponding to the main roadway when at different combinations of coal pillar widths; determined the main track roadway protective coal pillars width for 40 m and the shape of the roadway peak deviatoric stress zone is the inverse class hyperbolic body mode; according to the evolution mode of the peak deviatoric stress zone, determined the synergistic failure control program for the asymmetric critical zone of the roadway surrounding rock which is a targeted scientific support method; after the feedback of on-site monitoring and, the support program is reasonable and effective., (© 2024. The Author(s).)

Objective: Obstructive sleep apnoea (OSA) is positively associated with cardiovascular diseases, and continuous positive airway pressure (CPAP) is a common treatment for such patients. This study aimed to explore the impact of CPAP on cardiovascular outcomes and prognosis in patients with OSA., Methods: A search was conducted in the PubMed, Embase and CENTRAL databases for relevant studies published up to March 2024. Two independent reviewers screened the studies based on inclusion and exclusion criteria, and data were synthesised using RevMan 5.3 software. Heterogeneity was assessed using the Cochran Q test and the I 2 statistic., Results: A total of 10 randomised controlled trials and 3 observational studies, comprising 13,832 patients, were included. Compared with standard treatment, the use of CPAP did not significantly reduce the risk of major adverse cardiovascular events (MACE) (risk ratio [RR]: 0.73, 95% confidence interval [CI]: 0.52-1.03; p = 0.07; I 2  = 66%), all-cause mortality (RR: 0.92, 95% CI: 0.72-1.16; p = 0.48; I 2  = 0%), cardiovascular mortality (RR: 0.63, 95% CI: 0.33-1.19; p = 0.15; I 2  = 70%) or non-cardiovascular mortality (RR: 0.81, 95% CI: 0.57-1.15; p = 0.23; I 2  = 0%). Similarly, there were no significant differences in the incidence of myocardial infarction, stroke, hospitalisation due to unstable angina or heart failure or atrial fibrillation among those using CPAP. However, when CPAP adherence was ≥ 4 h, CPAP significantly reduced the risk of MACE and cardiovascular mortality., Conclusion: Although CPAP's cardiovascular benefits in patients with OSA are not confirmed, it may be that bias risks, CPAP adherence and characteristics of the study population may attenuate the perceived benefits of CPAP. Further research is needed to optimise CPAP therapy., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Rationale: Himalayan marmot oil (SPO) has been used for pharmaceutical purposes for centuries, but its composition is still unclear. The bioactivity of SPO highly depends on the techniques used for its processing. This study focused on the comprehensive lipidomics of SPO, especially on the ones derived from dry rendering, wet rendering, cold pressing, and ultrasound-assisted solvent extraction., Methods: We performed lipid profiling of SPO acquired by different extraction methods using ultrahigh-performance liquid chromatography Q-Exactive Orbitrap mass spectrometry, and 17 classes of lipids (2 BMPs, 12 LysoPCs, 9 LysoPEs, 41 PCs, 24 PEs, 23 Plasmenyl-PCs, 10 Plasmenyl-PEs, 10 MGs, 63 DGs, 187 TGs, 2 MGDGs, 3 Cer[NDS]s, 22 Cer[NS]s, 2 GlcCer[NS]s, 14 SMs, 14 CEs, and 6 AcylCarnitines) were characterized., Results: Fifty-five lipids were differentially altered (VIP > 1.5, p < 0.05) between the extraction techniques, which can be used as potential biomarkers to differentiate SPO extracted by various methods. Additionally, the contents of oleic acid and arachidic acid were abundant in all samples that may suggest their medicinal values and are conducive to in-depth research., Conclusions: These findings reveal the alterations of lipid profile and free fatty acid composition in SPO obtained with different extraction methods, providing a theoretical foundation for investigating its important components as functional factors in medicines and cosmetics., (© 2024 John Wiley & Sons Ltd.)

Novel and covert fluorescence is quite desirable for fluorescent anticounterfeiting application. Here, Cs 2 InCl 5 ·H 2 O/Sb and Cs 2 NaInCl 6 /Sb with high photoluminescence quantum yields (PLQYs) of 99.61 and 99.9%, respectively, were achieved. Considering the excellent optical performances together with the high similarity of the two crystal structures, we tried to realize the crystal structure transition from Cs 2 InCl 5 ·H 2 O/Sb to Cs 2 NaInCl 6 /Sb by an ion-exchange method. It was well done by just adding the NaCl precursor with different concentrations in the Cs 2 InCl 5 ·H 2 O/Sb product. Interestingly, a gradual color change from yellow to orange, warm white, white, cool white, and blue was achieved in the process of crystal structure transition. The energy-transfer dynamic models of Cs 2 InCl 5 ·H 2 O/Sb, the white product, and Cs 2 NaInCl 6 /Sb were identified. The chemical reaction and UV fluorescence properties made it possible for application in chemical and fluorescent double-modal anticounterfeiting and highly decreased the possibility of being cracked and copied. Especially, when salt for daily cooking was used to replace NaCl, a similar phenomenon happened as that of the 99.9% NaCl precursor, which made it easy to be applicated. The combination of chemical and optical verifications provides two levels of security and unbreakable encryption. The results demonstrate that the transition from Cs 2 InCl 5 ·H 2 O/Sb to Cs 2 NaInCl 6 /Sb is highly promising in fluorescent anticounterfeiting application.

A purified polysaccharide with a galactose backbone (SPR-1, Mw 3,622 Da) was isolated from processed Polygonati Rhizoma with black beans (PRWB) and characterized its chemical properties. The backbone of SPR-1 consisted of [(4)-β-D-Gal p -(1] 9  → 4,6)-β-D-Gal p -(1 → 4)-α-D-Gal p A-(1 → 4)-α-D-Gal p A-(1 → 4)-α-D-Glc p -(1 → 4,6)-α-D-Glc p -(1 → 4)-α/β-D-Glc p , with a branch chain of R 1 : β-D-Gal p -(1 → 3)-β-D-Gal p -(1→ connected to the →4,6)-β-D-Gal p -(1→ via O-6, and a branch chain of R 2 : α-D-Glc p -(1 → 6)-α-D-Glc p -(1→ connected to the →4,6)-α-D-Glc p -(1→ via O-6. Immunomodulatory assays showed that the SPR-1 significantly activated macrophages, and increased secretion of NO and cytokines (i.e., IL-1β and TNF-α), as well as promoted the phagocytic activities of cells. Furthermore, isothermal titration calorimetry (ITC) analysis and molecular docking results indicated high-affinity binding between SPR-1 and MD2 with the equilibrium dissociation constant ( K D ) of 18.8 μM. It was suggested that SPR-1 activated the immune response through Toll-like receptor 4 (TLR4) signaling and downstream responses. Our research demonstrated that the SPR-1 has a promising candidate from PRWB for the TLR4 agonist to induce immune response, and also provided an easily accessible way that can be used for PR deep processing., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Authors.)

Tilianin and linarin, two rare glycosylated flavonoids in the aromatic endangered medicinal plant Nardostachys jatamansi (D.on)DC., play an important role in the fields of medicine, cosmetics, food and dye industries. However, there remains a lack of comprehensive understanding regarding their biosynthetic pathway. In this study, the phytochemical investigation of N. jatamansi resulted in the isolation of linarin. With help of AlphaFold2 to cluster the entire glycosyltransferase family based on predicted structure similarities, we successfully identified a flavonoid glycosyltransferase NjUGT73B1, which could efficiently catalyze the glucosylation of acacetin at 7-OH to produce tilianin, also the key precursor in the biosynthesis of linarin. Additionally, NjUGT73B1 displayed a high degree of substrate promiscuity, enabling glucosylation at 7-OH of many flavonoids. Molecular modeling and site-directed mutagenesis revealed that H19, H21, H370, F126, and F127 play the crucial roles in the glycosylation ability of NjUGT73B1. Notably, comparation with the wild NjUGT73B1, mutant H19K led to a 50% increase in the activity of producing tilianin from acacetin., 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.)

The non-thermal and thermal effects on aroma of sea buckthorn juice have rarely been investigated. In this study, 57 odor compounds were identified in fresh sea buckthorn juice (FSBJ), high pressure processing sea buckthorn juice (HSBJ), and pasteurized sea buckthorn juice (PSBJ), including 29 esters, 8 aldehydes, 1 ketone, 5 alcohols, 5 acids, 6 terpenoids, and 3 others. Ethyl 2-methylbutanoate, ethyl 3-methylbutanoate, ethyl hexanoate, and ethyl 2-hydroxy-3-methylbutanoate with flavor dilution factors ranging from 729 to 59,049 contributed to the fruity odors of FSBJ and HSBJ. Besides, the formation of off-odor compounds including hexanal, nonanal, furfural, 3-methylbutanoic acid, and dimethyl disulfide with odor activity values ≥ 1, imparts fatty, roasted, sweaty, and cooked odor in PSBJ. The variations of vitamin C and reducing sugar are significantly associated with changes in odor-active compounds during pasteurized processing. These findings provide new insights that high pressure processing minimizes the adverse effects of pasteurization., 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.)

Sulfide is a well-known environmental pollutant that can have detrimental effects on most organisms. However, few metazoans living in sulfide-rich environments have developed mechanisms to tolerate and adapt to sulfide stress. Epigenetic mechanisms, including DNA methylation, have been shown to play a vital role in environmental stress adaptation. Nevertheless, the precise function of DNA methylation in biological sulfide adaptation remains unclear. Urechis unicinctus, a benthic organism inhabiting sulfide-rich intertidal environments, is an ideal model organism for studying adaptation to sulfide environments. In this study, we conducted a comprehensive analysis of the DNA methylome and transcriptome of U. unicinctus after exposure to 50 μM sulfide. The results revealed dynamic changes in the DNA methylation (5-methylcytosine) landscape in response to sulfide stress, with U. unicinctus exhibiting elevated DNA methylation levels following stress exposure. Integrating differentially expressed genes (DEGs) and differentially methylated regions (DMRs), we identified a crucial role of gene body methylation in predicting gene expression. Furthermore, using a DNA methyltransferase inhibitor, we validated the involvement of DNA methylation in the sulfide stress response and the gene regulatory network influenced by DNA methylation. The results indicated that by modulating DNA methylation levels during sulfide stress, the expression of glutathione S-transferase, glutamyl aminopeptidase, and cytochrome c oxidase could be up-regulated, thereby facilitating the metabolism and detoxification of exogenous sulfides. Moreover, DNA methylation was found to regulate and enhance the oxidative phosphorylation pathway, including NADH dehydrogenase, isocitrate dehydrogenase, and ATP synthase. Additionally, DNA methylation influenced the regulation of Cytochrome P450 and macrophage migration inhibitory factor, both of which are closely associated with oxidative stress and stress resistance. Our findings not only emphasize the role of DNA methylation in sulfide adaptation but also provide novel insights into the potential mechanisms through which marine organisms adapt to environmental changes., 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.)

Objective: To investigate the distribution characteristics of intestinal flora in patients with obstructive sleep apnoea hypopnea syndrome (OSAHS) of different severities and the relationship between different intestinal flora and sleep structure disorder, hypoxemia and obesity., Methods: A total of 25 healthy volunteers and 80 patients with OSAHS were enrolled in this study. The control group was healthy, and the experimental group comprised patients with OSAHS. The apnoea-hypopnea index (AHI), minimum saturation of peripheral oxygen (SpO 2min ), mean saturation of peripheral oxygen, body mass index, maximum apnoea time and other indicators were collected in clinical practice. The patients with OSAHS were divided into 20 mild and 42 moderate OSAHS cases, as well as 18 patients with severe OSAHS according to the AHI classification. Bioinformatics-related statistics were analysed using the QIIME2 software, and clinical data were analysed with the SPSS 22.0 software., Results: The changes in microbial alpha diversity in the intestinal flora of patients with OSAHS showed that richness, diversity and evenness decreased, but the beta diversity did not change significantly. The Thermus Anoxybacillus, Anaerofustis, Blautia, Sediminibacterium, Ralstonia, Pelomonas, Ochrobactrum, Thermus Sediminibacterium, Ralstonia, Coccidia, Cyanobacteria, Anoxic bacilli and Anaerobes were negatively correlated with AHI (r = -0.38, -0.36, -0.35, -0.33, -0.31, -0.29, -0.22, -0.18) and positively correlated with SpO 2 min (r =0.38, 0.2, 0.25, 0.22, 0.24, 0.11, 0.23, 0.15)., Conclusion: Some bacteria showed a significant correlation with clinical sleep monitoring data, which provides a possibility for the assessment of disease risk, but the mechanisms of their actions in the intestinal tract are not clear at present. Further research and observations are needed., (© 2024. The Author(s).)

Polygonatum cyrtonema Hua (PCH), as an important economic crop, is used as raw industrial materials and traditional Chinese medicine. There are significant variations in the quality of PCH from different geographical origins. It can be due to the change of the endophytic fungi and soil microbial communities of PCH. Therefore, the aim of this study is to investigate the composition and functional prediction of the main microbial communities in the rhizomes and soil of PCH and explore their impact on medicinal quality. High-throughput sequencing techniques targeting ITS and 16S rDNA were employed to compare the structure and biodiversity differences of endophytic fungi in the rhizomes and soil microbial communities of PCH from 12 different locations in Sichuan and Guangxi province. Heatmap analysis was used for comprehensive statistics and visualization of the richness of rhizome and soil microbial communities from all locations. Venn analysis was conducted to determine the total number of shared fungi between rhizomes and soil, and GraphPad Prism analysis was employed to predict and compare the microbial communities related to phenotypes at the genus level in Sichuan and Guangxi. Tax4Fun and Fungild were used for metabolic function prediction of microbial communities in the rhizomes and soil of PCH. The results revealed the identification of 19,387 bacterial amplicon sequence variants (ASVs) in the rhizomes and 37,990 bacterial ASVs in the soil, with 6,889 shared bacterial ASVs. In addition, 2,948 fungal ASVs were identified in the rhizomes and 8,868 in the soil, with 1,893 shared fungal ASVs. Microbial sequencing results indicated that the fungal communities between soil and rhizomes were mainly composed of Ascomycota and Basidiomycota , while bacterial communities included Proteobacteria , Acidobacteria , Bacteroidota , Gammatimonadota , and Firmicutes . Dominant bacterial groups such as Nitrospira , Acidibacter , and fungal groups including Mortierella , Ceratobasidium , and Fusarium were identified as potential contributors to the observed traits. In the top 15 microbial genera, both Sichuan and Guangxi contain 15 bacterial genera, but there are differences in their abundance. Guangxi has three unique fungal genera, including the genera Scleroderma , Russula , and Gliocladiopsis . On the other hand, Sichuan has the unique fungal genus Chamaeota . The correlation analysis between the microbiota and the chemical content from 12 different collecting spots was performed by GraphPad Prism. Burkholderia-Caballeronia-Paraburkholderia , Acidibacter , and Amycolatopsis show an inverse proportionality to total polysaccharides and saponins, while Enterobacter shows a direct proportionality to total polysaccharides and inverse proportionality to saponins. The metabolism pathways show a significant positive correlation with PCH polysaccharides and saponins. This study provide new insights into the mechanisms underlying the quality differences between the two major indigenous areas., 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 © 2024 Yang, Yang, Wulu, Wang, Jin, Yan and Zhang.)

Ethnopharmacological Relevance: Gentiana species, known as the traditional Tibetan medicine "Bangjian," have been integral to clinical practice for millennia. Despite their longstanding use, our understanding of the variation in chemical constituents and bioactive effects among different species is limited., Aim of the Study: In the present study, we aimed to assess the differences in chemical profiles and bioactivities among four Gentiana species (G. veitchiorum, G. trichotoma, G. crassuloides, and G. squarrosa) and explore potential bioactive markers., Materials and Methods: The chemical composition of the four Gentiana species was analyzed using UPLC-QE-Orbitrap-MS. The antioxidant activity of the extracts was compared through DPPH, ABTS, and reducing power assays. The anti-inflammatory activity was evaluated by measuring the inhibitory effects on lipopolysaccharide-induced secretion of nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) by RAW264.7 macrophages. Additionally, compounds strongly correlated with anti-inflammatory and antioxidant activities were identified through spectrum-effect relationship analysis., Results: A total of 50 compounds were identified across the four Gentiana species. In vitro antioxidant assays demonstrated DPPH and ABTS scavenging abilities and reducing power within the concentration range of 62.5-2000 μg/mL. All four species inhibited the production of NO, IL-6, and TNF-α in RAW264.7 cells. Spectrum-effect relationship analysis revealed that gentiascabraside A, gentiatibetine, tachioside, lutonarin, and isotachioside were associated with the highest antioxidant activity; and swertiamarin, tarennoside, eleganoside C, and alpigenoside were associated with the highest anti-inflammatory activity., Conclusions: This study presents, for the first time, the chemical profiles and bioactivities of G. trichotoma, G. crassuloides, and G. squarrosa, which were comprehensively compared with those of G. veitchiorum. The findings provide novel insights to understand the traditional use and/or expand the current use of Gentiana species. Additionally, this research highlights the potential of Gentiana species as natural sources of antioxidants and anti-inflammatory agents, suggesting promising applications in tea production or medicinal contexts in the near future., Competing Interests: Declaration of competing interest The authors have declared no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To investigate the correlation between the levels of serum lipopolysaccharide (LPS), nuclear factor erythroid 2-related factor 2 (Nrf2), haem oxygenase 1 (HO-1) and cognitive impairment in patients with obstructive sleep apnoea (OSA)., Methods: Serum LPS, Nrf2, HO-1 levels and cognitive impairment were measured using the Montreal Cognitive Assessment (MoCA) score in 56 patients in the "severe" group, 67 patients in the "mild-to-moderate" group and 100 healthy people in the "control" group. The differences in general conditions and serological indexes between the three groups were compared, the correlation between the MoCA scores and the serological indexes was explored and the independent predictors of the MoCA scores were analysed., Results: Serum LPS, Nrf2 and HO-1 levels were higher in the severe group than in the mild-to-moderate group and the control group ( p < 0.05). A total of 71 patients with OSA had combined cognitive impairment, accounting for 57.7%, and the MoCA scores were lower in the severe group than in the mild-to-moderate group and the control group ( p = 0.018). Serum LPS, Nrf2 and HO-1 levels were significantly higher in the severe group and mild-to-moderate group than in the control group ( p < 0.05) and were negatively correlated with the MoCA scores. Lipopolysaccharide ( p < 0.001) and HO-1 ( p = 0.002) could be considered independent predictors of the MoCA score., Conclusion: Serum LPS and HO-1 levels are closely related to cognitive impairment in patients with OSA and have potential clinical value in the diagnosis., Competing Interests: The authors declare that they have no competing interests., (© 2024 Feng et al.)

Anisotropic structures exist in almost all living organisms to endow them with superior properties and physiological functionalities. However, conventional artificial materials possess unordered isotropic structures, resulting in limited functions and applications. The development of anisotropic structures on carbohydrates is reported to have an impact on their properties and applications. In this review, various alignment strategies for carbohydrates (i.e., cellulose, chitin and alginate) from bottom-up to top-down strategies are discussed, including the rapidly developed innovative technologies such as shear-induced orientation through extrusion-based 3D/4D printing, magnetic-assisted alignment, and electric-induced alignment. The unique properties and wide applications of anisotropic carbohydrate materials across different fields, from biomedical, biosensors, smart actuators, soft conductive materials, to thermal management are also summarized. Finally, recommendations on the selection of fabrication strategies are given. The major challenge lies in the construction of long-range hierarchical alignment with high orientation degree and precise control over complicated architectures. With the future development of hierarchical alignment strategies, alignment control techniques, and alignment mechanism elucidation, the potential of anisotropic carbohydrate materials for scalable manufacture and clinical applications will be fully realized., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Reducing the south and reinforcing the north method (RSRN) has a positive effect on atherosclerosis disease. However, there is a lack of objective standards based on the quantification of 4 diagnostic methods in evaluating the improvement or effectiveness of the treatment. This study aimed to explore the quantitative evaluation of the therapeutic effect of RSRN on postmenopausal atherosclerosis based on the 4 diagnostic methods. The observational prospective cohort study was conducted at Longhua hospital Shanghai University of traditional Chinese medicine. According to the inclusion criteria, 96 patients (disease group) and 38 healthy cases (control group) were selected, the pulse parameters were compared between the 2 groups to demonstrate the reliability and success of the disease model. Then 4 diagnostic information before and after RSRN treatment were collected and statistical analyzed by 1-way analysis of variance (ANOVA) (with Bonferroni correction). Furthermore, social network analysis was used to analyze the changes of symptoms, tongue, pulse, and complexion characteristics before and after treatment. There was a significant difference in pulse parameters between the disease group and the control group. The pulse parameters t1, h3, h3/h1, h4/h1, S, As, and w values in disease group were higher than those in control group, while the h5, h5/h1, and Ad values were lower than those in control group (P < .05). After the treatment of RSRN, the clinical symptoms of patients were greatly improved. The facial color indexes L, a, b values of the disease group at week 6 were different from those at week 0 (P < .05). The overall brightness and chroma of the patient's facial color were significantly improved. The patients had virtual string pulse at week 0, and mainly string I and string II at week 7. The pulse parameters t1, t5, w, w/t, h1, h5, h3/h1, and h5/h1 values at week 7 were different from those at weeks 0, 1, 2 (P < .05); the tongue image was mainly red and crimson, peeling or greasy fur at week 0, while at weeks 6, 7, mainly light red, or thin white tongue. The RSRN method can regulate the complexion, tongue and pulse condition, clinical symptoms of postmenopausal atherosclerosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Larval settlement and metamorphosis represent critical events in the life history of marine benthic animals. Myoinhibitory peptide (MIP) plays a pivotal role in larval settlement of marine invertebrates. However, the molecular mechanisms of MIP involved in this process are not well understood., Results: In this study, we evaluated the effects of thirteen MIP mature peptides on triggering the larval settlement of Urechis unicinctus (Xenopneusta, Urechidae), and determined that MIP2 was the principal neuropeptide. Transcriptomic analysis was employed to identify differentially expressed genes (DEGs) between the MIP2-treated larvae and normal early-segmentation larvae. Both cAMP and calcium signaling pathways were enriched in the DEGs of the MIP2-treated larvae, and two neuropeptide receptor genes (Spr, Fmrfar) were up-regulated in the MIP2-treated larvae. The activation of the SPR-cAMP pathway by MIP2 was experimentally validated in HEK293T cells. Furthermore, fourteen cilia-related genes, including Tctex1d2, Cfap45, Ift43, Ift74, Ift22, Cav1 and Mns1, etc. exhibited down-regulated expression in the MIP2-treated larvae. Whole-mount in situ hybridization identified two selected ciliary genes, Tctex1d2 and Cfap45, were specially expressed in circumoral ciliary cells of the early-segmentation larvae. Knocking down Tctex1d2 mRNA levels by in vivo RNA interference significantly increased the larval settlement rate., Conclusion: Our findings suggest that MIP2 inhibits the function of the cilia-related genes, such as Tctex1d2, through the SPR-cAMP-PKA pathway, thereby inducing larval settlement in U. unicinctus. The study contributes important data to the understanding of neuropeptide regulation in larval settlement., (© 2024. The Author(s).)

Steroidal alkaloids are the main bioactive components of the bulbs of Fritillaria, which have been used as traditional Chinese medicine, known as "Beimu", for the treatment of cough for thousands of years in China. Cough and dyspnea are the most common symptoms observed in patients with pulmonary fibrosis. However, the antifibrotic activity of steroidal alkaloids has not been reported yet. In this study, two previously unreported cevanine-type steroidal alkaloids (1 and 2), four previously undescribed cevanine-type alkaloid glycosides (3-6), and 19 known steroidal alkaloids (7-25) were isolated from the bulbs of Fritillaria unibracteata var. wabuensis. The structures of these compounds were elucidated by comprehensive HRESIMS and NMR spectroscopic data analysis, as well as DP4+ NMR calculations. The biological evaluation showed that compounds 2, 7-10, 14, 15, and 17 downregulated fibrotic markers induced by transforming growth factor-β (TGF-β) in MRC-5 cells. Moreover, compounds 14 and 17 dose dependently inhibited TGF-β-induced epithelial-mesenchymal transition in A549 cells, alleviated TGF-β-induced migration and proliferation of fibroblasts, and decreased the expression of fibrotic markers, fibronectin, and N-cadherin in TGF-β-induced MRC-5 cells. The research showed the potential of cevanine-type alkaloids as a class of natural antifibrotic agents., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, author-ship, and/or publication of this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Iron is an essential cofactor in the fundamental metabolic pathways of organisms. Moderate iron intake can enhance animal growth performance, while iron overload increases the risk of pathogen infection. Although the impact of iron on the pathogen-host relationship has been confirmed in higher vertebrates, research in fish is extremely limited. The effects and mechanisms of different levels of iron exposure on the infection of Aeromonas hydrophila in largemouth bass (Micropterus salmoides) remain unclear. In this study, experimental diets were prepared by adding 0, 800, 1600, and 3200 mg/kg of FeSO 4 ∙7H 2 O to the basal feed, and the impact of a 56-day feeding period on the mortality rate of largemouth bass infected with A. hydrophila was analyzed. Additionally, the relationships between mortality rate and tissue iron content, immune regulation, oxidative stress, iron homeostasis, gut microbiota, and tissue morphology were investigated. The results showed that the survival rate of largemouth bass infected with A. hydrophila decreased with increasing iron exposure levels. Excessive dietary iron intake significantly increased iron deposition in the tissues of largemouth bass, reduced the expression and activity of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, increased the content of lipid peroxidation product malondialdehyde, and thereby induced oxidative stress. Excessive iron supplementation could influence the immune response of largemouth bass by upregulating the expression of pro-inflammatory cytokines in the intestine and liver, while downregulating the expression of anti-inflammatory cytokines. Additionally, excessive iron intake could also affect iron metabolism by inducing the expression of hepcidin, disrupt intestinal homeostasis by interfering with the composition and function of the gut microbiota, and induce damage in the intestinal and hepatic tissues. These research findings provide a partial theoretical basis for deciphering the molecular mechanisms underlying the influence of excessive iron exposure on the susceptibility of largemouth bass to pathogenic bacteria., Competing Interests: Declaration of competing interest The authors claim no competing financial interests in this study., (Copyright © 2024. Published by Elsevier Ltd.)

Background and Aim: Both intestinal symptoms and comorbidities exist in irritable bowel syndrome (IBS) patients and influence their quality of life (QOL). More research is needed to determine how these variables impact the QOL of IBS patients. This study aimed to determine which specific factors had a higher influence on QOL and to further compare the effects of intestinal symptoms and comorbidities on QOL., Methods: IBS patients were recruited from six tertiary hospitals in different regions of China. QOL, gastrointestinal symptoms, and comorbidities were assessed by different scales. Correlation analysis, multiple linear regression, and mediation model were used for statistics., Results: Four hundred fifty-three IBS patients (39.7% women, mean age 45 years) were included and no significant differences in QOL were found across demographic characteristics. Abnormal defecation ( r  = -0.398), fatigue ( r  = -0.266), and weakness ( r  = -0.286) were found to show higher correlation with QOL. More than 40% of IBS patients were found to suffer from varying degrees of anxiety or depression, and anxiety ( r  = -0.564) and depression ( r  = -0.411) were significantly negatively correlated with QOL ( P  < 0.001). Psychological factors showed the strongest impact ( β'  = -0.451) and play a strong mediating role in the impact of physiological symptoms on QOL. Anxiety was found to be the strongest factor ( β'  = -0.421)., Conclusion: Compared with other symptoms, psychological symptoms, particularly anxiety, are more common and have a more negative influence on QOL. The QOL of IBS patients is also significantly impacted by abnormal defecation, abdominal distension, and systemic extraintestinal somatic symptoms. In the treatment of IBS patients with unhealthy mental status, psychotherapy might be prioritized., (© 2024 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Arginine vasopressin (AVP) is a key contributor to heart failure (HF), but the underlying mechanisms remain unclear. In the present study, a mouse model of HF and human cardiomyocyte (HCM) cells treated with dDAVP are generated in vivo and in vitro , respectively. Hematoxylin and eosin (HE) staining is used to evaluate the morphological changes in the myocardial tissues. A colorimetric method is used to measure the iron concentration, Fe 2+ concentration and malondialdehyde (MDA) level. Western blot analysis is used to examine the protein levels of the V1a receptor (V1aR), calcineurin (CaN), nuclear factor of activated T cells isoform C3 (NFATC3), glutathione peroxidase 4 (GPX4) and acyl-CoA synthase long chain family member 4 (ACSL4). Immunoprecipitation (IP) and luciferase reporter assays are performed to determine the interaction between NFATC3 and ACSL4. Both in vivo and in vitro experiments reveal that the V1aR-CaN-NFATC3 signaling pathway and ferroptosis are upregulated in HFs, which are verified by the elevated protein levels of V1aR, CaN, NFATC3 and ACSL4; reduced GPX4 protein level; and enhanced Fe 2+ and MDA levels. We further find that inhibiting NFATC3 by suppressing the V1aR/CaN/NFATC3 pathway via V1aR/CaN inhibitors or sh-NFATC3 not only alleviates HF but also inhibits AVP-induced ferroptosis. Mechanistically, sh-NFATC3 significantly reverses the increase in AVP-induced ACSL4 protein level, Fe 2+ concentration, and MDA level by directly interacting with ACSL4. Our results demonstrate that AVP enhances ACSL4 expression by activating the V1aR/CaN/NFATC3 pathway to induce ferroptosis, thus contributing to HF. This study may lead to the proposal of a novel therapeutic strategy for HF.

Screening for high-risk human papillomavirus (HPV) infection is one of the most important preventative measures for cervical cancer. However, fast, convenient, and low-cost HPV detection remains challenging, especially in resource-limited settings. Here, we report a portable all-in-one device (PAD) for point-of-care testing (POCT) for HPV16 and HPV18 DNA in cervical swabs. The PAD was engineered to integrate modules for extraction-free sample lysis, loop-mediated isothermal amplification (LAMP) with lyophilized reagent beads, and real-time colorimetric signal sensing into a single miniaturized device, considerably shortening the sample-to-result time to 15 min. The precision liquid handling in the completely sealed microfluidic chip is achieved by a uniquely designed pressure-balanced automatic liquid flow mechanism, thereby eliminating the need for manual manipulation of liquids and thus the risk of biohazards. The PAD employs an improved real-time colorimetric LAMP (rcLAMP) assay with a limit of detection (LOD) of 1 copy/μL, enabled by enhanced assay chemistry to maximize the reaction kinetics. To validate this device for clinical application, we tested 206 clinical cervical swab samples and obtained a sensitivity of 92.1% and a specificity of 99.0%. This custom PAD enabled by microfluidic and electronic engineering techniques can be configured for the simultaneous detection of HPV16 and HPV18 or other pathogens in point-of-care applications., 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.)

Millettia speciosa Champ. (MSCP) enjoys widespread recognition for its culinary and medicinal attributes. Despite the extensive history of MSCP cultivation, the disparities in quality and bioactivity between wild and cultivated varieties have remained unexplored. In this study, 20 wild and cultivated MSCP samples were collected from different regions in China. We embarked on a comprehensive investigation of the chemical constituents found in both wild and cultivated MSCP utilizing UHPLC-Q-Exactive Orbitrap-MS technology and multivariate analysis such as principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). In total, 62 chemical components were unequivocally identified or tentatively characterized. Via the multivariate statistical analysis, we successfully pinpointed nine compounds with the potential to serve as chemical markers, enabling the differentiation between wild and cultivated MSCP varieties. Moreover, both genotypes exhibited substantial antioxidant and anti-fatigue properties. The bioactivities of wild MSCP were marginally higher when compared to their cultivated counterparts. This study illuminates the impressive antioxidant and anti-fatigue potential present in both wild and cultivated MSCP genotypes, further augmenting the allure of this species and opening new avenues for the economic valorization of MSCP. Hence, this study provides a valuable method for the identification and quality control of MSCP and a method in chemistry and pharmacology to assess an alternative possibility for cultivated MSCP.

Rapid non-destructive testing technologies are effectively used to analyze and evaluate the linoleic acid content while processing fresh meat products. In current study, hyperspectral imaging (HSI) technology was combined with deep learning optimization algorithm to model and analyze the linoleic acid content in 252 mixed red meat samples. A comparative study was conducted by experimenting mixed sample data preprocessing methods and feature wavelength extraction methods depending on the distribution of linoleic acid content. Initially, convolutional neural network Bi-directional long short-term memory (CNN-Bi-LSTM) model was constructed to reduce the loss of the fully connected layer extracted feature information and optimize the prediction effect. In addition, the prediction process of overfitting phenomenon in the CNN-Bi-LSTM model was also targeted. The Bayesian-CNN-Bi-LSTM (Bayes-CNN-Bi-LSTM) model was proposed to improve the linoleic acid prediction in red meat through iterative optimization of Gaussian process acceleration function. Results showed that best preprocessing effect was achieved by using the detrending algorithm, while 11 feature wavelengths extracted by variable combination population analysis (VCPA) method effectively contained characteristic group information of linoleic acid. The Bi-directional LSTM (Bi-LSTM) model combined with the feature extraction data set of VCPA method predicted 0.860 Rp 2 value of linoleic acid content in red meat. The CNN-Bi-LSTM model achieved an Rp 2 of 0.889, and the optimized Bayes-CNN-Bi-LSTM model was constructed to achieve the best prediction with an Rp 2 of 0.909. This study provided a reference for the rapid synchronous detection of mixed sample indicators, and a theoretical basis for the development of hyperspectral on-line detection equipment.

Objective: This study aims to evaluate the efficacy and safety of using a strip-shaped cymba conchae orthosis for the nonsurgical correction of complex auricular deformities., Methods: Clinical data were collected from 2020 to 2021 for 6 patients who underwent correction using a strip-shaped cymba conchae orthosis. The indications, corrective effects, and complications associated with use of the orthosis were analyzed., Results: There were four indications for treatment: cryptotia with helix adhesion; cryptotia with grade I microtia; cryptotia with excessive helix thickness; and auricular deformity beyond the treatment time window (≥6 months). Excellent corrective effects were observed in all 6 patients. Complications occurred in one patient, who recovered after symptomatic treatment., Conclusion: The use of a strip-shaped cymba conchae orthosis alone or combined with a U-shaped helix orthosis presents a feasible approach for correcting complex auricular deformities or deformities beyond the treatment time window in pediatric patients., Competing Interests: The authors have no conflicts of interest to disclose., (© [copyright 2023] PLA General Hospital Department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd.)

Oligosaccharide-containing macromolecular bio adhesives are emerging as highly promising eco-friendly materials to enhance the cytocompatibility of viscous hydrogels for wound healing applications. In our prior research, we extensively elucidated the properties of branch-structure fructo-oligosaccharides derived from Polygonatum Cyrtonema Hua (referred to as PCOS). However, the characteristics of hydrogels based on fructo-oligosaccharides remain to be fully explored. In present work, we developed an injectable, PCOS/carboxymethyl cellulose (CMC) hydrogel which is a dual ion-physical cross-linked hydrogel that can be considered as a potential diabetic wound dressing. The tests showed that the optimal ratios for hydrogel preparation were 2 % CBM 940 (Carbomer 940), 5 % CMC and 10 % PCOS. The resultant hydrogel was formulated into composite hydrogels that were then used for the treatment of full-thickness excisional wounds in a db/db diabetic mouse model. Wound closure and histological evaluation confirmed its beneficial effect on wound healing. Further morphological analysis through scanning electron microscopy images revealed a porous hydrogel structure, while Fourier-transform infrared spectroscopy provided structural insights on the crosslinking reaction. Physicochemical properties of the hybrid hydrogels determined by rheological properties, thermogravimetric, water loss rate, et al., indicated that the double crosslinking PCOS/CMC hybrid hydrogel showed enhanced dynamic mechanical properties and water retention capacity compared to the CMC cellulose matrix hydrogels. Thus, this novel PCOS-hybrid hydrogel exhibited good dissolvability and injectable properties, which was proved to facilitate for the diabetic wound healing both in vitro and in vivo test and holds a potential clinical application in the wound healing., 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. Published by Elsevier B.V.)

Objectives: Enhanced external counterpulsation (EECP) is an effective and noninvasive treatment for patients with refractory angina and chronic heart failure. However, previous studies evaluating the influence of EECP on endothelial function showed inconsistent results. This systematic review and meta-analysis was conducted to evaluate the effects of EECP on endothelial function measured by brachial artery flow-mediated dilation (FMD)., Design: PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases were searched for randomized controlled trials comparing the influence of EECP versus usual care on FMD in adult population. A random-effects model incorporating the potential influence of heterogeneity was used to pool the results., Results: Nineteen studies with 1647 patients were included in the meta-analysis. Compared with usual care or conventional therapy, additional treatment with EECP for 3-7 weeks was associated with a significantly improved FMD (mean difference [ MD ]: 1.96%, 95% confidence interval [CI]: 1.57-2.36, p  < 0.001, I 2 = 52%). Subgroup analysis showed consistent results in patients with coronary artery disease and in patients with other diseases ( p for subgroup difference = 0.21). Results of meta-regression analysis showed that the mean baseline FMD level was positively correlated with the influence of EECP on FMD (coefficient = 0.42, p  < 0.001). Results of subgroup analysis suggested that the increment of FMD following EECP was larger in patients with baseline FMD ≥ 5% ( MD : 2.69, 95% CI: 2.27-3.10, p  < 0.001; I 2 = 15%) compared to those with baseline FMD < 5% ( MD : 1.49, 95% CI: 1.13-1.85, p  < 0.001; I 2 = 0%; p for subgroup difference < 0.001)., Conclusions: EECP may be effective in improving endothelial function measured by FMD.

To rapidly evaluate the quality of complex herbal preparations, a new strategy was proposed based on multi-color scale and efficacy-oriented high-performance thin-layer chromatography (HPTLC) characteristic fingerprint combined with chemometric method. Firstly, effective components were screened through high-performance liquid chromatography with ultraviolet detection and evaporative light-scattering (HPLC-UV-ELSD), using multi-wavelength fusion combined with network pharmacology and molecular docking techniques. Subsequently, guided by the effective components, the targeted HPTLC characteristic fingerprint was established by multi-color scale scanning. Finally, combined with the chemometric method, the consistency of the preparation quality was evaluated, the marker components leading to quality differences were screened, and the quality control limit was established. Sanwujiao Pills (SWJPs) is a herbal preparation composed of six herbs for treating rheumatoid arthritis (RA). Through this strategy, four HPTLC characteristic fingerprints were established, they were derived from five herbs and guided by eight effective components in SWJPs. Through similarity, clustering heatmap, principal component analysis (PCA), and orthogonal partial least squares discriminant analysis (OPLS-DA), the quality distinctions among the 12 batches of SWJPs were determined. These batches were categorized into two groups based on their production time, and eight components affecting the quality of the preparation were identified. Meanwhile, the quality control threshold for SWJPs was determined based on Hotelling's T 2 and DModX methods. This strategy aims to rapidly evaluate the quality of complex herbal preparations by HPTLC and extends the application of HPTLC fingerprint chromatography for identifying herbal medicine species and activity-related quality detection. The proposed strategy is also helpful for the quality control of other complex herbal preparations., Competing Interests: Liqin ZHOU, Hongfang YANG, Mingshun ZHAO are the employees of Yunnan Jinwu Black Medicine Pharmaceutical Co. Ltd. who donated Sanwujiao Pill samples for this research, but had no role in the data acquisition, statistical analysis and writing of this article. The other 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 The Authors.)

Background: Mediastinal neoplasms are typical thoracic diseases with increasing incidence in the general global population and can lead to poor prognosis. In clinical practice, the mediastinum's complex anatomic structures and intertype confusion among different mediastinal neoplasm pathologies severely hinder accurate diagnosis. To solve these difficulties, we organised a multicentre national collaboration on the basis of privacy-secured federated learning and developed CAIMEN, an efficient chest CT-based artificial intelligence (AI) mediastinal neoplasm diagnosis system., Methods: In this multicentre cohort study, 7825 mediastinal neoplasm cases and 796 normal controls were collected from 24 centres in China to develop CAIMEN. We further enhanced CAIMEN with several novel algorithms in a multiview, knowledge-transferred, multilevel decision-making pattern. CAIMEN was tested by internal (929 cases at 15 centres), external (1216 cases at five centres and a real-world cohort of 11 162 cases), and human-AI (60 positive cases from four centres and radiologists from 15 institutions) test sets to evaluate its detection, segmentation, and classification performance., Findings: In the external test experiments, the area under the receiver operating characteristic curve for detecting mediastinal neoplasms of CAIMEN was 0·973 (95% CI 0·969-0·977). In the real-world cohort, CAIMEN detected 13 false-negative cases confirmed by radiologists. The dice score for segmenting mediastinal neoplasms of CAIMEN was 0·765 (0·738-0·792). The mediastinal neoplasm classification top-1 and top-3 accuracy of CAIMEN were 0·523 (0·497-0·554) and 0·799 (0·778-0·822), respectively. In the human-AI test experiments, CAIMEN outperformed clinicians with top-1 and top-3 accuracy of 0·500 (0·383-0·633) and 0·800 (0·700-0·900), respectively. Meanwhile, with assistance from the computer aided diagnosis software based on CAIMEN, the 46 clinicians improved their average top-1 accuracy by 19·1% (0·345-0·411) and top-3 accuracy by 13·0% (0·545-0·616)., Interpretation: For mediastinal neoplasms, CAIMEN can produce high diagnostic accuracy and assist the diagnosis of human experts, showing its potential for clinical practice., Funding: National Key R&D Program of China, National Natural Science Foundation of China, and Beijing Natural Science Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Rolling treatments have been identified as a promising fabrication and deformation processing technique for graphene/metal composites with high performance. However, it is still a challenge to choose appropriate rolling parameters to achieve high strength, ductility and electrical conductivity of the composite simultaneously. In this study, graphene/Cu composites were prepared with an in situ growth method and rolling treatment. The effects of rolling deformation and temperature on the microstructural evolution of graphene and Cu grains, interface bonding between graphene and the matrix, mechanical and electrical properties were systemically investigated. The cold-rolled composite with 85% deformation displayed a maximum ultimate strength of 548 MPa, a high elongation of 8.8% and a good electrical conductivity of 86.2% IACS. This is attributed to oriented graphene arrangement and matrix grain refinement. Our research provides a comprehensive understanding for the rolling behavior of graphene/Cu composites, and can promote the development of graphene-based composites with high performance.

Ototoxic drugs such as aminoglycoside antibiotics and cisplatin (CDDP) can cause sensorineural hearing loss (SNHL), which is closely related to oxidative stress and the acidification of the inner ear microenvironment. Effective treatment of SNHL often requires multifaceted approach due to the complex pathology, and drug combination therapy is expected to be at the forefront of modern hearing loss treatment. Here, space-station-like composite nanoparticles (CCC@mPP NPs) with pH/oxidation dual responsiveness and multidrug simultaneous delivery capability were constructed and then loaded with various drugs including panax notoginseng saponins (PNS), tanshinone IIA (TSIIA), and ammonia borane (AB) to provide robust protection against SNHL. Molecular dynamics simulation revealed that carboxymethyl chitosan/calcium carbonate-chitosan (CCC) NPs and monomethoxy poly(ethylene glycol)-PLGA (mPP) NPs can rendezvous and dock primarily by hydrogen bonding, and electrostatic forces may be involved. Moreover, CCC@mPP NPs crossed the round window membrane (RWM) and entered the inner ear through endocytosis and paracellular pathway. The docking state was basically maintained during this process, which created favorable conditions for multidrug delivery. This nanosystem was highly sensitive to pH and reactive oxygen species (ROS) changes, as evidenced by the restricted release of payload at alkaline condition (pH 7.4) without ROS, while significantly promoting the release in acidic condition (pH 5.0 and 6.0) with ROS. TSIIA/PNS/AB-loaded CCC@mPP NPs almost completely preserved the hair cells and remained the hearing threshold shift within normal limits in aminoglycoside- or CDDP-treated guinea pigs. Further experiments demonstrated that the protective mechanisms of TSIIA/PNS/AB-loaded CCC@mPP NPs involved direct and indirect scavenging of excessive ROS, and reduced release of pro-inflammatory cytokines. Both in vitro and in vivo experiments showed the high biocompatibility of the composite NPs, even after long-term administration. Collectively, this work suggests that composite NPs is an ideal multi-drug-delivery vehicle and open new avenues for inner ear disease therapies.

A weldable Al-Mg-Zn-Sc alloy was produced using vacuum induction melting and an argon-protected casting method to achieve high strength and ductility, and the effects of heat treatment on the microstructure evolution and mechanical properties of Al-Mg-Zn-Sc alloys were comparatively investigated. The results reveal that fine equiaxed grains with an average grain size of 40 μm in an as-cast Al-Mg-Zn-Sc alloy change little after heat treatments, bringing about a grain-boundary strengthening of 46.1 MPa. The coarse T-Mg 32 (Al, Zn) 49 phases at grain boundaries are completely dissolved into the matrix through solid-solution treatment, and T-Mg 32 (Al, Zn) 49 with diameters ranging from 10 to 25 nm and Al 3 Sc with diameters ranging from 5 to 20 nm gradually precipitate during the artificial aging process. The Mg solid solubility is 4.67% in the as-cast Al-Mg-Zn-Sc alloy, and it increased to 5.33% after solid-solution treatment and dramatically decreased to 4.15% after post-aging treatment. The contributions of solid-solution strengthening to as-cast, post-solid-solution and post-aging Al-Mg-Zn-Sc alloys are 78.2 MPa, 85.4 MPa and 72.3 MPa, respectively. The precipitation strengthening of the post-aging alloy is 49.7 MPa, which is an increase of 21% in comparison to that of both as-cast and post-solid-solution alloys. The alloy achieves an optimal tensile strength of 355.3 MPa, yield strength of 175 MPa and elongation of 22% after undergoing solid-solution treatment.

Hearing loss is mainly due to outer hair cell (OHC) damage in three cochlear turns. Local administration via the round window membrane (RWM) has considerable otological clinical potential in bypassing the blood-labyrinth barrier. However, insufficient drug distribution in the apical and middle cochlear turns results in unsatisfactory efficacy. We functionalized poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) with targeting peptide A665, which specifically bound to prestin, a protein uniquely expressed in OHCs. The modification facilitated the cellular uptake and RWM permeability of NPs. Notably, the guide of A665 towards OHCs enabled more NPs perfusion in the apical and middle cochlear turns without decreasing accumulation in the basal cochlear turn. Subsequently, curcumin (CUR), an appealing anti-ototoxic drug, was encapsulated in NPs. In aminoglycoside-treated guinea pigs with the worst hearing level, CUR/A665-PLGA NPs, with superior performance to CUR/PLGA NPs, almost completely preserved the OHCs in three cochlear turns. The lack of increased low-frequencies hearing thresholds further confirmed that the delivery system with prestin affinity mediated cochlear distribution rearrangement. Good inner ear biocompatibility and little or no embryonic zebrafish toxicity were observed throughout the treatment. Overall, A665-PLGA NPs act as desirable tools with sufficient inner ear delivery for improved efficacy against severe hearing loss., (Copyright © 2023. Published by Elsevier B.V.)

Mollusca represents one of the ancient bilaterian groups with high morphological diversity, while the formation mechanisms of the precursors of all germ cells, primordial germ cells (PGCs), have not yet been clarified in mollusks. PRDI-BF1 and RIZ homology domain-containing proteins (PRDMs) are a group of transcriptional repressors, and PRDM1 (also known as BLIMP1) and PRDM14 have been reported to be essential for the formation of PGCs. In the present study, we performed a genome-wide retrieval in Mulinia lateralis and identified 11 putative PRDMs, all of which possessed an N-terminal PR domain. Expressional profiles revealed that all these prdm genes showed specifically high expression levels in the given stages, implying that all PRDMs played important roles during early development stages. Specifically, Ml-prdm1 was highly expressed at the gastrula stage, the key period when PGCs arise, and was specifically localized in the cytoplasm of two or three cells of blastula, gastrula, or trochophore larvae, matching the typical characteristics of PGCs. These results suggested that Ml-prdm1 -positive cells may be PGCs and that Ml-prdm1 could be a candidate marker for tracing the formation of PGCs in M. lateralis . In addition, the expression profiles of Ml-prdm14 hinted that it may not be associated with PGCs of M. lateralis . The present study provides insights into the evolution of the PRDM family in mollusks and offers a better understanding of the formation of PGCs in mollusks.

During the early development of marine invertebrates, planktic larvae usually occur, and their body surfaces often form specific types of cilia that are involved in locomotion and feeding. The echiuran worm Urechis unicinctus sequentially undergoes the formation and disappearance of different types of body surface cilia during embryonic and larval development. The morphological characteristics and molecular mechanisms involved in the process remain unclear. In this study, we found that body surface cilia in U. unicinctus embryos and larvae can be distinguished into four types: body surface short cilia, apical tufts, circumoral cilia and telotrochs. Further, distribution and genesis of the body surface cilia were characterized using light microscope and electron microscope. To better understand the molecular mechanism during ciliogenesis, we revealed the embryonic and larval transcriptome profile of the key stages of ciliogenesis in U. unicinctus using RNA-Seq technology. A total of 29,158 differentially expressed genes (DEGs) were obtained from 24 cDNA libraries by RNA-Seq. KEGG pathway enrichment results showed that Notch, Wnt and Ca 2+ signaling pathways were significantly enriched during the occurrence of apical tufts and circumoral cilia. Furthermore, all DEGs were classified according to their expression pattern, and DEGs with similar expression pattern were grouped into a module. All DEG co-expression modules were correlated with traits (body surface short cilia, apical tufts, circumoral cilia and telotrochs) by WGCNA, the results showed DEGs were divided into 13 modules by gene expression patterns and that the genes in No. 7, No. 8 and No. 10 modules were to be highly correlated with the occurrence of apical tufts, circumoral cilia and telotrochs. The top 10 hub genes in the above three modules were identified to be highly correlated with ciliogenesis, including the reported cilium-related gene Cnbd2 and unreported cilium-related candidate genes FAM181B , Capsl , Chst3 , TMIE and Innexin . Notably, Innexin was included in the top10 hub genes of the two modules (No. 7 and No. 8), suggesting that Innexin may play an important role in U. unicinctus apical tufts, circumoral cilia and telotrochs genesis. This study revealed the characteristics of ciliogenesis on the body surface of U. unicinctus embryos and larvae, providing basic data for exploring the molecular mechanism of ciliogenesis on the body surface.

Three-dimensional porous network encapsulation strategy is an effective means to obtain composite phase-change materials (PCMs) with high heat storage capacity and enhanced thermal conductivity. Herein, macroporous reduced graphene oxide (rGO) aerogels with adjustable pore size are prepared by the emulsion template method and hydrothermal reduction process. Further, the shape-stabilized rGO-aerogel-based composite PCMs are constructed after the combination of 3D porous rGO supports and paraffin wax (PW) through vacuum melting infiltration. By regulating the pore structure of the rGO aerogel network, the rGO-based composite PCMs achieve excellent energy storage properties with a phase-change enthalpy of 179.94 J/g for the loading amount of 95.61 wt% and an obvious enhancement in thermal conductivity of 0.412 W/m -1 ·K -1 , which is 54.89% higher than pristine PW and enduring thermal cycling stability. The obtained macroporous rGO-aerogel-based composite PCMs with high thermal storage and heat transfer performance effectively broaden the application of PCMs in the field of thermal energy storage.

Toll-like receptors (TLR) are an important class of pattern recognition receptors involved in innate immunity that recognize pathogen-associated and damage-associated molecular patterns. Although the role of TLRs in immunity has been extensively studied, a systematic investigation of their function in environmental adaptation is still in its infancy. In this study, a genome-wide search was conducted to systematically investigate TLR family members of Urechis unicinctus, a typical benthic organism in intertidal mudflats. A total of 28 TLR genes were identified in the U. unicinctus genome, and their fundamental physiological and biochemical properties were characterized. Gene copy number analysis among species in different habitats indicated that TLR family gene expansion may be probably related with benthic environmental adaptation. To further investigate the expression patterns of TLR members under environmental stress, transcriptome data was analyzed from different developmental stages and the hindgut under sulfide stress. Transcriptome analysis of different developmental stages showed that most TLR genes were highly expressed during a key period of benthic environment adaptation (worm-shaped larva). Transcriptome analysis of the hindgut under sulfide stress showed that the expression of 12 TLR members was significantly induced under sulfide stress. These results indicate that the regulation of TLR gene expression may be probably involved in the adaptation of U. unicinctus to the benthic intertidal zone environment. Taken together, this study may lay the foundation for future functional analysis of the specific role of TLRs in host immune responses against sulfide exposure and benthic environmental stress in annelid., 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. Published by Elsevier B.V.)

Graphene, with its two linearly dispersing Dirac points with opposite windings, is the minimal topological nodal configuration in the hexagonal Brillouin zone. Topological semimetals with higher-order nodes beyond the Dirac points have recently attracted considerable interest due to their rich chiral physics and their potential for the design of next-generation integrated devices. Here we report the experimental realization of the topological semimetal with quadratic nodes in a photonic microring lattice. Our structure hosts a robust second-order node at the center of the Brillouin zone and two Dirac points at the Brillouin zone boundary-the second minimal configuration, next to graphene, that satisfies the Nielsen-Ninomiya theorem. The symmetry-protected quadratic nodal point, together with the Dirac points, leads to the coexistence of massive and massless components in a hybrid chiral particle. This gives rise to unique transport properties, which we demonstrate by directly imaging simultaneous Klein and anti-Klein tunnelling in the microring lattice., (© 2023. The Author(s).)

Objectives: Linezolid-resistant Staphylococcus capitis (LRSC) has become a new challenge for clinical anti-infective therapy. The present study aimed to investigate the trends of LRSC prevalence in a tertiary hospital of China 2017-2020. The resistance mechanisms, virulence genes, biofilm formation, and mass spectrometric characteristics of LRSC isolates were also analysed., Methods: This study retrospectively analysed the antibiotic resistance trends of coagulase negative staphylococci (CoNS) isolated from clinical samples collected between 2017-2020. Antimicrobial resistance profiles were tested by micro-broth dilution and the E-test method. Antimicrobial resistance genes and virulence genes were detected by polymerase chain reaction, and dru-typing sequences were obtained by Sanger sequencing. Crystal violet staining in 96-well plates was used to detect biofilm formation ability. Mass spectrometric characterization of LRSC was analysed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) coupled with ClinProTools., Results: The linezolid resistance rate in 3575 CoNS clinical strains was 1.6%, wherein the great majority of was LRSC (91.1%, n = 51/56), with a resistant rate of 15.5% (n = 51/328) in all S. capitis isolates. In this study, 48 out of the 51 LRSC strains and 54 of 277 linezolid-susceptible S. capitis (LSSC) strains were enrolled. G2576T, C2104T, T2130A, C2163T, and T2319C mutations in the 23S rRNA V region and acquisition of cfr were the main linezolid resistant mechanisms in LRSC. The biofilm-forming ability of LRSC was more potent than LSSC, with a higher detection rate of bap (P < 0.05). Eleven mass spectrometric peaks of interest were identified by using MALDI-TOF MS and ClinProTools, which were differently distributed between LRSC and LSSC strains, with the area under the receiver operating characteristic curve of more than 0.8, especially for 5465.37 m/z., Conclusions: Linezolid resistance was mediated by mutations in the 23S rRNA V region and presence of the cfr gene in LRSC strains. LRSC strains have stronger biofilm-forming ability than LSSC strains, which maybe associated with the adhesion-related gene of bap. Further, linezolid-resistant and linezolid-susceptible S. capitis could be rapidly identified with mass spectrometric characterization. To the best of our knowledge, this study is the first to document the biofilm formation ability of LRSC and the potential usefulness of MALDI-TOF MS for the discrimination of LRSC and LSSC., (Copyright © 2023. Published by Elsevier Ltd.)

This study is the first to extract and characterize pectin from citrus physiological premature fruit drop. The extraction yield of pectin reached 4.4 % by acid hydrolysis method. The degree of methoxy-esterification (DM) of citrus physiological premature fruit drop pectin (CPDP) was 15.27 %, indicating it was low-methoxylated pectin (LMP). The monosaccharide composition and molar mass test results showed CPDP was a highly branched macromolecular polysaccharide (β: 0.02, Mw: 2.006 × 10 5  g/mol) with rich rhamnogalacturonan I domain (50.40 %) and long arabinose and galactose side chain (32.02 %). Based on the fact that CPDP is LMP, Ca 2+ was used to induce CPDP to form gels. Textural and rheological tests showed that the gel strength and storage modulus of CPDP were higher than commercial citrus pectin (CP) used in this paper due to the lower DM and rich neutral sugar side chains of CPDP. Scanning electron microscope (SEM) results showed CPDP had stable gel network structure., Competing Interests: Declaration of competing interest We declare that there are no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper We declare that this manuscript or part of its content is not submitted elsewhere, nor is it under consideration for submission elsewhere., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Processing of Chinese herbal medicines (CHMs) is a traditional pharmaceutical technology in Chinese medicine. Traditionally, proper processing of CHMs is necessary to meet the specific clinical requirements of different syndromes. Processing with black bean juice is considered one of the most important techniques in traditional Chinese pharmaceutical technology. Despite the long-standing practice of processing Polygonatum cyrtonema Hua (PCH), there is little research on the changes in chemical constituents and bioactivity before and after processing. This study investigated the influence of black bean juice processing on the chemical composition and bioactivity of PCH. The results revealed significant changes in both composition and contents during processing. Saccharide and saponin content significantly increased after processing. Moreover, the processed samples exhibited considerably stronger DPPH and ABTS radical scavenging capacity, as well as FRAP-reducing capacity, compared to the raw samples. The IC 50 values for DPPH were 1.0 ± 0.12 mg/mL and 0.65 ± 0.10 mg/mL for the raw and processed samples, respectively. For ABTS, the IC 50 values were 0.65 ± 0.07 mg/mL and 0.25 ± 0.04 mg/mL, respectively. Additionally, the processed sample demonstrated significantly higher inhibitory activity against α-glucosidase and α-amylase (IC 50 = 1.29 ± 0.12 mg/mL and 0.48 ± 0.04 mg/mL) compared to the raw sample (IC 50 = 5.58 ± 0.22 mg/mL and 0.80 ± 0.09 mg/mL). These findings underscore the significance of black bean processing in enhancing the properties of PCH and lay the foundation for its further development as a functional food. The study elucidates the role of black bean processing in PCH and offers valuable insights for its application.

Ischemic insult stimulates proliferation of neural stem cells (NSCs) in the subventricular zone (SVZ) after stroke. However, only a fraction of NSC-derived neuroblasts from SVZ migrate toward poststroke brain region. We have previously reported that direct-current stimulation guides NSC migration toward the cathode in vitro. Accordingly, we set up a new method of transcranial direct-current stimulation (tDCS), in which the cathodal electrode is placed on the ischemic hemisphere and anodal electrode on the contralateral hemisphere of rats subjected to ischemia-reperfusion injury. We show that the application of this bilateral tDCS (BtDCS) promotes the migration of NSC-derived neuroblasts from SVZ toward the cathode direction into poststroke striatum. Reversing the position of the electrodes blocks the effect of BtDCS on the migration of neuroblasts from SVZ. BtDCS protects against neuronal death and improves the functional recovery of stroke animals. Thus, the migration of NSC-derived neuroblasts from SVZ toward poststroke brain region contributes to the effect of BtDCS against ischemia-induced neuronal death, supporting a potential development of noninvasive BtDCS as an endogenous neurogenesis-based stroke therapy., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. FASEB BioAdvances published by Wiley Periodicals LLC on behalf of The Federation of American Societies for Experimental Biology.)

Background: Real-time quantitative PCR (RT-qPCR) is a crucial and widely used method for gene expression analysis. Selecting suitable reference genes is extremely important for the accuracy of RT-qPCR results. Commonly used reference genes are not always stable in various organisms or under different environmental conditions. With the increasing application of high-throughput sequencing, transcriptome analysis has become an effective method for identifying novel stable reference genes., Results: In this study, we identified candidate reference genes based on transcriptome data covering embryos and larvae of early development, normal adult tissues, and the hindgut under sulfide stress using the coefficient of variation (CV) method in the echiuran Urechis unicinctus, resulting in 6834 (15.82%), 7110 (16.85%) and 13880 (35.87%) candidate reference genes, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the candidate reference genes were significantly enriched in cellular metabolic process, protein metabolic process and ribosome in early development and normal adult tissues as well as in cellular localization and endocytosis in the hindgut under sulfide stress. Subsequently, ten genes including five new candidate reference genes and five commonly used reference genes, were validated by RT-qPCR. The expression stability of the ten genes was analyzed using four methods (geNorm, NormFinder, BestKeeper, and ∆Ct). The comprehensive results indicated that the new candidate reference genes were more stable than most commonly used reference genes. The commonly used ACTB was the most unstable gene. The candidate reference genes STX12, EHMT1, and LYAG were the most stable genes in early development, normal adult tissues, and hindgut under sulfide stress, respectively. The log 2 (TPM) of the transcriptome data was significantly negatively correlated with the Ct values of RT-qPCR (Ct =  - 0.5405 log 2 (TPM) + 34.51), which made it possible to estimate the Ct value before RT-qPCR using transcriptome data., Conclusion: Our study is the first to select reference genes for RT-qPCR from transcriptome data in Echiura and provides important information for future gene expression studies in U. unicinctus., (© 2023. The Author(s).)

ConspectusWell-controlled olefin insertion is critical for achieving catalytic and productive bulk and fine-chemical synthesis. Developing efficient and selective methods for meeting diverse insertion demands is extremely noteworthy, as it supports numerous transformations. The challenges are related to improving catalyst performance and selectivity control and uniting previously unreactive substrate pairs to achieve higher molecular structural complexity and utility. Nickel catalysts have received persistent attention in higher substituted olefin synthesis and polymerization, and numerous new strategies have been established to fulfill the ever-changing demands. This Account focuses on the recent progress based on N-heterocyclic carbene (NHC) ligands and nickel catalysts in our laboratory in using simple terminal olefins as olefin donors or acceptors.It begins with a brief history of olefin codimerization and the major advances in hydrovinylation achieved by other research groups using ethylene as an olefin donor. It then describes problems related to the reductive elimination that can occur when both the hydrometalated alkene and NHC are on the catalyst. It emphasizes the impact of NHC catalyst generation methods on the competing reactivity. Next, it explains the principal challenges and great opportunities in using our method (with α-olefins as olefin donors and alkenyl sources) to replace intermolecular reductive hydroalkenylation reactions (which require rare and more expensive alkenyl halides and boronic acids as reactants, alongside a stoichiometric amount of metallic reagents). The Account then illustrates the potential uses of our method for solving challenging organic synthesis problems using tailor-made (NHC)Ni(II) catalysts to allow redox-neutral catalytic cycles based on high chemo- and regioselective cross-insertion controls. It shows that upon optimal steric and electronic cooperation between the NHC, olefin donor, and olefin acceptor, regiodivergent insertion and convergent synthesis can be achieved easily.In the course of our work, we uncovered several unique insights into regulating (anti-)Markovnikov hydronickelation, carbonickelation, hydrocarbonation, ring closure, 1,3-allyl shift, isomerization, and catalyst regeneration under green, neutral, and mild-temperature conditions. These insights are also outlined here, along with theoretical calculations that offer additional understandings of the insertion reactivity and selectivity differences observed between the NHC and the highly related phosphorus-based Ni(II) hydride-catalyzed cross-hydroalkenylation and cycloisomerization systems.Compared to traditional olefin and cyclic structure synthesis technology, such as olefin cross-metathesis, enyne cyclization, and cross-coupling reactions, the new catalyst systems often offer previously inaccessible product structural characteristics, substrate scope, and outcomes. In particular, the method is effective for the catalytic synthesis of unsymmetrical and functionalized 1,1-disubstituted olefins (a.k.a. gem -olefins), 1,4-dienes (a.k.a. skipped dienes), conjugated dienes, endo- and exocyclic olefins, fused and spiro rings, and aromatic products. These syntheses are variously achieved by cross-hydroalkenylation, insertion-induced rearrangement, cycloadditions, and other approaches inspired by our investigations and detailed in this Account. Cross-hydroalkenylation can be achieved with high enantioselectivity by application of carefully designed and structurally flexible C 1 and C 2 chiral NHC ligands, yielding a pool of chiral branched alkenes and 1,4-dienes directly from simple chemical feedstocks used in industry. This Account will draw further attention to green alkenylation and the related development of redox-neutral catalytic cycles.

Background: Despite years of public cardiopulmonary resuscitation (CPR) training efforts, the training rate and survival following out-of-hospital cardiac arrest (OHCA) have increased modestly in China. Access is imperative to increase the public CPR training rate, which is determined by both demand- (e.g., the lay public) and supply-side (e.g., CPR trainers) factors. We aimed to explore the demand and supply determinants of access to CPR training for the lay public in China., Methods: Qualitative semi-structured interviews were conducted with 77 laypeople (demand side) and eight key stakeholders from CPR training institutions (supply side) in Shanghai, China. The interview guide was informed by Levesque et al. healthcare access framework. Data were transcribed, quantified, described, and analyzed through thematic content analysis., Results: On the demand side, the laypeople's ability to perceive their need and willingness for CPR training was strong. However, they failed to access CPR training mainly due to the lack of information on where to get trained. Overestimation of skills, optimism bias, and misconceptions impeded laypeople from attending training. On the supply side, trainers were able to meet the needs of the trainees with existing resources, but they relied on participants who actively sought out and registered for training and lacked an understanding of the needs of the public for marketing and encouraging participation in the training., Conclusion: Insufficient information and lack of initiative on the demand side, lack of motivation, and understanding of public needs on the supply side all contributed to the persistently low CPR training rate in China. Suppliers should integrate resources, take the initiative to increase the CPR training rate, innovate training modes, expand correct publicity, and establish whole-process management of training programs., Competing Interests: LZ receives funding from the Laerdal Foundation. AB receives funding for research related to OHCA and CPR from the Laerdal Foundation and the National Institutes of Health's National Heart Lung and Blood Institute, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. SK, TB, and HM are employees of Laerdal Medical, but they have no conflict of interest. The remaining 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 Dong, Kong, Xu, Ho, Blewer, Birkenes, Myklebust, Zheng, Li, Zheng, Zhang and Zhang.)