Search

Abstract Aging is characterized by the accumulation of proteins that display amyloid-like behavior. However, the molecular mechanisms by which these proteins arise remain unclear. Here, we demonstrate that amyloid-like proteins are produced in a variety of human cell types, including stem cells, brain organoids and fully differentiated neurons by mistakes that occur in messenger RNA molecules. Some of these mistakes generate mutant proteins already known to cause disease, while others generate proteins that have not been observed before. Moreover, we show that these mistakes increase when cells are exposed to DNA damage, a major hallmark of human aging. When taken together, these experiments suggest a mechanistic link between the normal aging process and age-related diseases.

Objective Many methods of acetabular reconstruction with total hip arthroplasty (THA) for Crowe type II and III adult developmental dysplasia of the hip (DDH) acetabular bone defect have been implemented clinically. However, there was no study comparing the results of integrated acetabular prosthesis (IAP) with bone grafting (BG). This study aims to investigate the efficacy of IAP and BG for acetabular reconstruction in Crowe type II and III DDH. Methods The clinical data of 45 patients with unilateral Crowe type II and III DDH who underwent THA from January 2020 to January 2023 were retrospectively analyzed. The patients were divided into two groups: 25 patients using 3D‐printed IAP (IAP group) and 20 patients using BG (BG group). The operation time and intraoperative blood loss were recorded. The clinical outcomes were assessed by Harris Hip Score (HHS) and full weight‐bearing time. The radiological outcomes were evaluated by the radiological examination. Accordingly, intraoperative and postoperative complications were observed as well. The data between the two groups were compared by independent sample t‐tests and the Mann–Whitney U rank sum test. Results There were no significant differences between the two groups in Harris Hip Score (HHS) (preoperative, 6 months postoperative, and the last follow‐up), leg length discrepancy (LLD), cup inclination, cup anteversion, vertical center of rotation (V‐COR), horizontal center of rotation (H‐COR) (p > 0.05). The mean HHS in the IAP group was higher than in the BG group at 1 and 3 months postoperative (p

Abstract Background An increased incidence of brain abscesses was observed post-COVID-19 pandemic. However, it remains unclear how the COVID-19 pandemic influenced the epidemiology of brain abscesses. This study aimed to investigate changes in the epidemiology of brain abscesses pre- and post-COVID-19 pandemic. Methods A retrospective study of demographic, clinical, radiological, and laboratory characteristics of patients with brain abscesses in Children's Hospital of Soochow University from 2015–2023 was performed. Results A total of 34 patients were admitted to the hospital during the study. The post-COVID-19 cohort had an average of 5.5 cases/year, which is a 129.2% increase compared to the pre-COVID-19 cohort's average of 2.4 cases/year. Additionally, the rates of fever upon admission (86.36% vs 50%, p = 0.04) and experiencing high-grade fever within 6 weeks before admission (40.91% vs 8.33%, p = 0.044) were significantly increased. A potential rise in the rate of intensive care unit admission was observed (36.36% vs 8.33%, p = 0.113). The average value of globulin in the post-COVID cohort was significantly higher compared to the pre-COVID cohort (31.60 ± 5.97 vs 25.50 ± 5.08, p = 0.009). Streptococcal infections were the predominant cause of brain abscesses in both cohorts (40% vs 43.75%, p = 0.57). Conclusions There was a significant increase in the number of brain abscess patients after the COVID-19 pandemic. This underscores the importance of children receiving the streptococcal vaccine.

Abstract Rose is an important ornamental crop cultivated globally for perfume production. However, our understanding of the mechanisms underlying scent production and molecular breeding for fragrance is hindered by the lack of a reference genome for tea roses. We present the first complete telomere-to-telomere (T2T) genome of Rosa gigantea, with high quality (QV > 60), including detailed characterization of the structural features of repetitive regions. The expansion of genes associated with phenylpropanoid biosynthesis may account for the unique tea scent. We uncover the release rhythm of aromatic volatile organic compounds and their gene regulatory networks through comparative genomics and time-ordered gene co-expression networks. Analyzes of eugenol homologs demonstrate how plants attract pollinators using specialized phenylpropanoids in specific tissues. This study highlights the conservation and utilization of genetic diversity from wild endangered species through multi-omics approaches, providing a scientific foundation for enhancing rose fragrance via de novo domestication.

Abstract Background Multi-rooted teeth with extensive dental defects often face challenges in stability and biomechanical failure. High-performance polymer PEEK materials, with properties closer to dentin, show promise in reducing stress concentration and preserving tooth structure. This report aimed to explore the use of a highly retentive polyetheretherketone (PEEK) for manufacturing custom-made split post and core for the restoration of grossly destroyed endodontically treated molars. Clinical considerations A 40-year-old female patient presented with complaints of loss of tooth substance in the posterior mandibular tooth. This case involved the digital design and fabrication of PEEK split post and core to restore multirooted molar with insufficient dental tissue remnants. The restorations were evaluated over a 3-year follow-up using the World Federation criteria (FDI). The restoration was clinically evaluated through intraoral examination, radiographic assessment, and subjective patient satisfaction, and was deemed clinically good according to FDI criteria. Conclusion The outstanding mechanical properties of PEEK, coupled with the structure of the split post, provide an effective treatment option for weakened multirooted teeth. Simultaneously, the restoration configuration effectively addressed the challenge of varying postinsertion directions, and the interlocking mechanism between the primary and auxiliary posts enhanced the stability of the post and core.

Abstract Background Chrysanthemum morifolium ‘HangBaiJu’, a popular medicinal and edible plant, exerts its biological activities primarily through the presence of flavones and caffeoylquinic acids (CQAs). However, the regulatory mechanism of flavone and CQA biosynthesis in the chrysanthemum capitulum remains unclear. Results In this study, the content of flavones and CQAs during the development of chrysanthemum capitulum was determined by HPLC, revealing an accumulation pattern with higher levels at S1 and S2 and a gradual decrease at S3 to S5. Transcriptomic analysis revealed that CmPAL1/2, CmCHS1/2, CmFNS, CmHQT, and CmHCT were key structural genes in flavones and CQAs biosynthesis. Furthermore, weighted gene co-expression correlation network analysis (WGCNA), k-means clustering, correlation analysis and protein interaction prediction were carried out in this study to identify transcription factors (TFs) associated with flavone and CQA biosynthesis, including MYB, bHLH, AP2/ERF, and MADS-box families. The TFs CmERF/PTI6 and CmCMD77 were proposed to act as upstream regulators of CmMYB3 and CmbHLH143, while CmMYB3 and CmbHLH143 might form a complex to directly regulate the structural genes CmPAL1/2, CmCHS1/2, CmFNS, CmHQT, and CmHCT, thereby controlling flavone and CQA biosynthesis. Conclusions Overall, these findings provide initial insights into the TF regulatory network underlying flavones and CQAs accumulation in the chrysanthemum capitulum, which laid a theoretical foundation for the quality improvement of C. morifolium ‘HangBaiJu’ and the high-quality development of the industry.

Abstract Immune evasion is one of the critical hallmarks of malignant tumors, especially non-small cell lung cancer (NSCLC). Emerging findings have illustrated the roles of N6-methyladenosine (m6A) on NSCLC immune evasion. Here, this study investigated the function and underlying mechanism of m6A reader YTH domain family protein 3 (YTHDF3) on NSCLC immune evasion. YTHDF3 was found to be highly expressed in NSCLC tissue and act as an independent prognostic factor for overall survival. Functionally, up-regulation of YTHDF3 impaired the CD8+ T antitumor activity to deteriorate NSCLC immune evasion, while YTHDF3 silencing recovered the CD8+ T antitumor activity to inhibit immune evasion. Besides, YTHDF3 up-regulation reduced the apoptosis of NSCLC cells. Mechanistically, PD-L1 acted as the downstream target for YTHDF3, and YTHDF3 could upregulate the transcription stability of PD-L1 mRNA. Overall, YTHDF3 targeted PD-L1 to promote NSCLC immune evasion partially through escaping effector cell cytotoxicity CD8+ T mediated killing and antitumor immunity. In summary, this study provides an essential insight for m6A modification on CD8+ T cell-mediated antitumor immunity in NSCLC, which might inspire an innovation for lung cancer tumor immunotherapy.

Abstract Enhancing the quality and safety of exported agricultural products and improving export competitiveness is the key to establishing enhanced competitive advantages in agricultural products, developing a trade powerhouse and realising high-quality development of agriculture. This paper uses the data of Chinese listed companies and Chinese Customs from 2007 to 2016 to discuss the effect and mechanism of digital transformation of enterprises on the quality and safety level of export agricultural products by using the staggered differential method. The study shows that (1) Enterprise digital transformation effectively improves the quality and safety of exported agricultural products, and this result holds after endogeneity, placebo and multiple robustness tests; (2) Heterogeneity analyses reveal that the quality and safety effect of enterprise digital transformation is greater for exporting to developed countries’ markets, non-state-owned enterprises and enterprises in the eastern region, in addition to bulk agricultural products and consumer-oriented agricultural products; (3) Mechanism analyses shows that enterprise digital transformation raises the quality and safety of exported agricultural products through technological innovation, product tracing, information sharing and quality assurance effects.

Abstract Background Increased level of serum cholic acid (CA) is often accompanied with decreased CYP2E1 expression in hepatocellular carcinoma (HCC) patients. However, the roles of CA and CYP2E1 in hepatocarcinogenesis have not been elucidated. This study aimed to investigate the roles and the underlying mechanisms of CYP2E1 and CA in HCC cell growth. Methods The proteomic analysis of liver tumors from DEN-induced male SD rats with CA administration was used to reveal the changes of protein expression in the CA treated group. The growth of CA-treated HCC cells was examined by colony formation assays. Autophagic flux was assessed with immunofluorescence and confocal microscopy. Western blot analysis was used to examine the expression of CYP2E1, mTOR, AKT, p62, and LC3II/I. A xenograft tumor model in nude mice was used to examine the role of CYP2E1 in CA-induced hepatocellular carcinogenesis. The samples from HCC patients were used to evaluate the clinical value of CYP2E1 expression. Results CA treatment significantly increased the growth of HCC cells and promoted xenograft tumors accompanied by a decrease of CYP2E1 expression. Further studies revealed that both in vitro and in vivo, upregulated CYP2E1 expression inhibited the growth of HCC cells, blocked autophagic flux, decreased AKT phosphorylation, and increased mTOR phosphorylation. CYP2E1 was involved in CA-activated autophagy through the AKT/mTOR signaling. Finally, decreased CYP2E1 expression was observed in the tumor tissues of HCC patients and its expression level in tumors was negatively correlated with the serum level of total bile acids (TBA) and gamma-glutamyltransferase (GGT). Conclusions CYP2E1 downregulation contributes to CA-induced HCC development presumably through autophagy regulation. Thus, CYP2E1 may serve as a potential target for HCC drug development.

ObjectiveEarly detection and prediction of Alzheimer's Disease are paramount for elucidating neurodegenerative processes and enhancing cognitive resilience. Structural Magnetic Resonance Imaging (sMRI) provides insights into brain morphology, while resting-state Magnetoencephalography (rsMEG) elucidates functional aspects. However, inherent disparities between these multimodal neuroimaging modalities pose challenges to the effective integration of multimodal features.ApproachTo address these challenges, we propose a deep learning-based multimodal classification framework for Alzheimer's disease, which harnesses the fusion of pivotal features from sMRI and rsMEG to augment classification precision. Utilizing the BioFIND dataset, classification trials were conducted on 163 Mild Cognitive Impairment cases and 144 cognitively Healthy Controls.ResultsThe study findings demonstrate that the InterFusion method, combining sMRI and rsMEG data, achieved a classification accuracy of 0.827. This accuracy significantly surpassed the accuracies obtained by rsMEG only at 0.710 and sMRI only at 0.749. Moreover, the evaluation of different fusion techniques revealed that InterFusion outperformed both EarlyFusion with an accuracy of 0.756 and LateFusion with an accuracy of 0.801. Additionally, the study delved deeper into the role of different frequency band features of rsMEG in fusion by analyzing six frequency bands, thus expanding the diagnostic scope.DiscussionThese results highlight the value of integrating resting-state rsMEG and sMRI data in the early diagnosis of Alzheimer's disease, demonstrating significant potential in the field of neuroscience diagnostics.

The Ordovician carbonate reservoirs in the Tarim Basin are hotspots for oil and gas exploration in recent years. However, due to the lack of effective paleo-geothermometers in carbonate formations, thermal history studies have been greatly restricted. In this study, we reconstructed thermal history of Ordovician carbonate intervals in Tarim Basin by applying clumped isotopes, equivalent vitrinite reflectance ( R equ ) and zircon (U–Th)/He ages as thermal indicators. The modeled results indicated that there are three phases of heat flow evolution in the Shuntuoguole low-uplift. (a) The gradual cooling stage during Ordovician-carboniferous. The heat flow is gradually decreasing during this period. (b) Rapidly raised stage in the early Permian period. The heat flow in Shunbei and Shuntuo area are raised rapidly during this period and the maximum is 51–65 mW/m 2 , but the SN3 well in Shunnan area increased slightly and the heat flow values of other single wells were still relatively stable. (c) The decline stage since Middle Permian. The tectonic activity is relatively stable and the geothermal heat flow is gradually reduced during this period, but the heat flow in Shunnan area is higher than the Shunbei and Shuntuo areas. Due to the control of thermal evolution, the dissolution of the Ordovician carbonate reservoir in Shuntuoguole area occurred earlier than the formation of large quantities of hydrocarbon materials, and the improvement of reservoir physical properties provided sufficient conditions for the late oil and gas filling, which was conducive to the preservation of large oil and gas reservoirs.

ABSTRACT: The microbiomes of the reproductive tract play a crucial role in the egg production and quality and reproductive health of laying hens. Speckled eggs are characterized by shells with brown spots of varying sizes and commonly produced by brown-shelled laying hens. Speckles reduce the economic value of eggs. However, the relationship between oviduct and cloacal microbiomes and the presence of speckled eggs in laying hens remains unclear. In this study, we collected samples from the reproductive tracts (uterus, vagina, and cloaca) of hens laying speckled eggs and those laying normal eggs and compared their microbial structures and relative abundances through 16S rRNA sequencing. We found that the microbial community structure in the reproductive tracts of the hens laying speckled eggs was similar to that in the reproductive tracts of the hens laying normal eggs; however, the relative abundances of Clostridium in the uterus and Turicibacter and Gallibacterium in the vagina of the hens from the speckled group (7.27%, 6.83% and 0.10%, respectively) were significantly higher than those in the normal group (2.00%, 0% and 0%, respectively [P < 0.05]). Additionally, 8, 24, and 11 bacterial taxa in the uterus, vagina, and cloaca were different between the groups of hens laying speckled and normal eggs. At the same time, Clostridium in the uterus may be associated with eggshell speckles. However, further investigations are necessary to understand the functions of these microbiota in the reproductive tracts of laying hens. This study provides novel insights into methods for reducing the occurrence of speckled eggs in laying hens.

Abstract Most deaths in breast cancer patients are attributed to metastasis, and lung metastasis is associated with a particularly poor prognosis; therefore it is imperative to identify potential target for intervention. The transforming growth factor‐β (TGF‐β) pathway plays a vital role in breast cancer metastasis, in which Smad3 is the key mediator and performs specific functions by binding with different cofactors. However, Smad3 cofactors involved in lung metastasis have not yet been identified. This study first establishes the interactome of Smad3 in breast cancer cells and identifies ZNF8 as a novel Smad3 cofactor. Furthermore, the results reveal that ZNF8 is closely associated with breast cancer lung metastasis prognosis, and specifically facilitates TGF‐β pathway‐mediated breast cancer lung metastasis by participating in multiple processes. Mechanistically, ZNF8 binds with Smad3 to enhance the H3K4me3 modification and promote the expression of lung metastasis signature genes by recruiting SMYD3. SMYD3 inhibition by BCI121 effectively prevents ZNF8‐mediated lung metastasis. Overall, the study identifies a novel cofactor of TGF‐β/Smad3 that promotes lung metastasis in breast cancer and introduces potential therapeutic strategies for the early management of breast cancer lung metastasis.

Expandable shape‐morphing hydrogels that ensure prolonged site residence, have tailored mechanical integrity and tunability, are biocompatible to minimize side effects and can release drugs over an extended time remain challenging to achieve. Herein, a new class of enzyme‐triggered bovine serum albumin and polyethylene glycol diacrylate hybrid hydrogels is presented, contributing to advancements in controlled drug‐model release and actuation. These hydrogels combine the intrinsic properties of proteins with the resilience of synthetic polymers, offering a versatile application platform. Central to our research is the trypsin‐induced simultaneous functionality of controlled drug model release and dynamic shape changes under physiological trypsin concentrations (0.01% w/v). These hydrogels display tailored mechanical and physical properties and microstructure, which are crucial for biomedical devices, soft robotics, and tissue engineering applications. Additionally, the hydrogels effectively control the release of fluorescein isothiocyanate, a model drug, indicating their potential for highly targeted drug delivery, particularly in the gastrointestinal tract. The study also highlights the significant effect of shape‐morphing on drug release rates under physiological trypsin concentrations. These findings suggest that enzyme‐responsive hybrid protein‐polymer hydrogel actuators with tailored mechanical and physical properties can enhance the precision of drug delivery in biomedical applications.

The connections between cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) is critical in cancer initiation, progression, metastasis, and therapy resistance, making it a focal point in cancer theragnosis. This review provides a panorama of associations and regulation pathways between CSCs and EMT, highlighting their significance in cancer. The molecular mechanisms underlined EMT are thoroughly explored, including the involvement of key transcription factors and signaling pathways. In addition, the roles of CSCs and EMT in tumor biology and therapy resistance, is further examined in this review. The clinical implications of CSCs-EMT interplay are explored, including identifying mesenchymal-state CSC subpopulations using advanced research methods and developing targeted therapies such as inhibitors and combination treatments. Overall, understanding the reciprocal relationship between EMT and CSCs holds excellent potential for informing the development of personalized therapies and ultimately improving patient outcomes.

Background and objectivesGeographical variation existed in the incidences of Guillain-Barré syndrome (GBS), but no national population-based study has evaluated the incidences of GBS in China. This study aimed to estimate the incidence of GBS in urban China and evaluate the worldwide variation in the incidence of GBS.MethodsFirstly, we did a population-based study to calculate the incidence of GBS in urban China based on the National Urban Medical Insurance database from 2013 to 2017. To identify GBS cases, natural language processing was used first for handling the lengthy and unstructured diagnostic information and then checked by prestigious neurologists. Secondly, a systematic review and meta-analysis were performed to analyze the incidence of GBS worldwide. Up to July 4, 2022, Medline, Embase, and Web of Science were retrieved to identify the population-based studies regarding the incidence of GBS. The basic information and the statistics regarding incidence were extracted. Quality assessment considered sample representativeness, condition assessment, and statistical methods.ResultsA total of 1.44 billion person-years in insurance data was covered, with 3,534 GBS cases identified. The annual incidences of GBS in urban China between 2013 and 2017 ranged from 0.41 (95% CI: 0.27 to 0.58) to 0.58 (95% CI: 0.38 to 0.82) per 100,000 person-years. The incidence was the highest in Northwest China and the lowest in Northeast China. The meta-analysis included 122 articles. The quality assessment showed that the quality scores of 43.3% of studies were ≥ 0.75 (the total score is 1). The global incidence of GBS was 1.12 (95% CI: 0.98 to 1.27) per 100,000 person-years. The incidences in West Europe, South Asia, and North Europe were higher, while the incidences in Australia and New Zealand, Southeast Asia, and North Africa were lower. The incidence of enteric infections was positively associated with the incidence of GBS (coefficient=0.0000185, P=0.007). The incidence in Europe, Australia, and America rose significantly from 1960 to 2020 (coefficient=0.01, t=2.52, P=0.015).DiscussionThere is a clear regional variation of the GBS incidence at both national and global levels. Careful control of enteric infections should be conducted to reduce the disease burden.

Summary: Energy crops play a vital role in meeting future energy and chemical demands while addressing climate change. However, the idealization of low-carbon workflows and careful consideration of cost-benefit equations are crucial for their more sustainable implementation. Here, we propose tobacco as a promising energy crop because of its exceptional water solubility, mainly attributed to a high proportion of water-soluble carbohydrates and nitrogen, less lignocellulose, and the presence of acids. We then designed a strategy that maximizes biomass conversion into bio-based products while minimizing energy and material inputs. By autoclaving tobacco leaves in water, we obtained a nutrient-rich medium capable of supporting the growth of microorganisms and the production of bioproducts without the need for extensive pretreatment, hydrolysis, or additional supplements. Additionally, cultivating tobacco on barren lands can generate sufficient biomass to produce approximately 573 billion gallons of ethanol per year. This approach also leads to a reduction of greenhouse gas emissions by approximately 76% compared to traditional corn stover during biorefinery processes. Therefore, our study presents a novel and direct strategy that could significantly contribute to the goal of reducing carbon emissions and global sustainable development compared to traditional methods.

ABSTRACT: In the late growth stage of commercial Pekin ducks, a significant increase in feed intake and a decline in body weight gain have been observed, leading to impaired feed conversion efficiency. To address this issue, we investigated alterations in production performance, blood biochemical indices, ileum tissue architecture, and microbial community structure in Pekin ducks. The primary objective was to provide robust data supporting the improvement of meat duck production efficiency during the late growth stage (28–42-days-old). Forty 28-day-old Pekin ducks were randomly assigned to 8 replicates, with five ducks per replicate. The rearing period lasted 14 days, with feed and water provided ad libitum. Our findings indicated a significant increase in Pekin duck body and heart weights with advancing age (P < 0.05). Moreover, serum antioxidant enzyme and high-density lipoprotein concentrations significantly increased, whereas triglyceride levels decreased (P < 0.05). Notably, the height of the ileal villi was significantly reduced (P < 0.05). The microbial community structure of the ileum exhibited significant changes as ducks aged, accompanied by a substantial increase in microbial flora diversity, particularly with the formation of more tightly connected microbial network modules. Time-dependent enrichment was observed in microbial gene functions related to energy metabolism pathways. At the genus level, Sphingomonas and Subdoligranulum have emerged as crucial players in microbial differential functional pathways and network formation. These bacteria likely serve as the key driving factors in the dynamic microbial changes that occur in Pekin ducks over time. Overall, our findings suggest a potential decline in the absorption function of the small intestine and fat deposition performance of Pekin ducks during later growth stages, which may be attributed to the maturation and proliferation of the gut microbial community.

As the most prevalent and reversible internal epigenetic modification in eukaryotic mRNAs, N6-methyladenosine (m6A) post-transcriptionally regulates the processing and metabolism of mRNAs involved in diverse biological processes. m6A modification is regulated by m6A writers, erasers, and readers. Emerging evidence suggests that m6A modification plays essential roles in modulating the cell-fate transition of embryonic stem cells. Mechanistic investigation of embryonic stem cell maintenance and differentiation is critical for understanding early embryonic development, which is also the premise for the application of embryonic stem cells in regenerative medicine. This review highlights the current knowledge of m6A modification and its essential regulatory contribution to the cell fate transition of mouse and human embryonic stem cells.

To solve the sand problem during the depressurization of methane hydrate (MH), we proposed a method to build a porous grout body with sufficient permeability and strength around the wellbore through inhibitor pre-injection and grouting, and verified its effectiveness and potential in our previous research using artificial cores created with silica sand and alternative hydrates such as TBAB- hydrate and iso-butane hydrate. However, all of the artificial cores mentioned above were created with high homogeneity, injected, cured, and had their physical properties measured in the vertical direction, which differs from real reservoir conditions. To investigate the effects of grouting in a more realistic fluid flow, we conducted further experiments using horizontal 1D cores, 1D cubic models, and a 2D cross-sectional model mimicking the near wellbore. These experiments revealed that (1) the generated gas somewhat suppressed the effects of grouting as in the case of previous experiments, and (2) grouted reservoirs would be heterogenous and anisotropic due to the fluid densities and the distribution of grout particles and turbidite sediments, but sufficient permeability and satisfactory strength could still be attained. The above series of experiments demonstrated that our method has the potential to effectively produce actual MH, preventing sand problems even in heterogeneous and anisotropic grouted reservoirs.

Abstract A key strategy for designing environmental barrier coatings is to incorporate multiple rare-earth (RE) components into β- and γ-RE2Si2O7 to achieve multifunctional performance optimization. However, the polymorphic phase presents significant challenges for the design of multicomponent RE disilicates. Here, employing decision fusion, a machine learning (ML) method is crafted to identify multicomponent RE disilicates, showcasing notable accuracy in prediction. The well-trained ML models evaluated the phase formation capability of 117 (RE10.25RE20.25Yb0.25Lu0.25)2Si2O7 and (RE11/6RE21/6RE31/6Gd1/6Yb1/6Lu1/6)2Si2O7, which are unreported in experiments and validated by first-principles calculations. Utilizing model visualization, essential factors governing the formation of (RE10.25RE20.25Yb0.25Lu0.25)2Si2O7 are pinpointed, including the average radius of RE3+ and variations in different RE3+ combinations. On the other hand, (RE11/6RE21/6RE31/6Gd1/6Yb1/6Lu1/6)2Si2O7 must take into account the average mass and the electronegativity deviation of RE3+. This work combines material-oriented ML methods with formation mechanisms of multicomponent RE disilicates, enabling the efficient design of superior materials with exceptional properties for the application of environmental barrier coatings.

Abstract The use of robots to augment human capabilities and assist in work has long been an aspiration. Robotics has been developing since the 1960s when the first industrial robot was introduced. As technology has advanced, robotic-assisted surgery has shown numerous advantages, including more precision, efficiency, minimal invasiveness, and safety than is possible with conventional techniques, which are research hotspots and cutting-edge trends. This article reviewed the history of medical robot development and seminal research papers about current research progress. Taking the autonomous dental implant robotic system as an example, the advantages and prospects of medical robotic systems would be discussed which would provide a reference for future research.

Abstract Linear ubiquitination catalyzed by HOIL-1-interacting protein (HOIP), the key component of the linear ubiquitination assembly complex, plays fundamental roles in tissue homeostasis by executing domain-specific regulatory functions. However, a proteome-wide analysis of the domain-specific interactome of HOIP across tissues is lacking. Here, we present a comprehensive mass spectrometry-based interactome profiling of four HOIP domains in nine mouse tissues. The interaction dataset provides a high-quality HOIP interactome resource with an average of approximately 90 interactors for each bait per tissue. HOIP tissue interactome presents a systematic understanding of linear ubiquitination functions in each tissue and also shows associations of tissue functions to genetic diseases. HOIP domain interactome characterizes a set of previously undefined linear ubiquitinated substrates and elucidates the cross-talk among HOIP domains in physiological and pathological processes. Moreover, we show that linear ubiquitination of Integrin-linked protein kinase (ILK) decreases focal adhesion formation and promotes the detachment of Shigella flexneri-infected cells. Meanwhile, Hoip deficiency decreases the linear ubiquitination of Smad ubiquitination regulatory factor 1 (SMURF1) and enhances its E3 activity, finally causing a reduced bone mass phenotype in mice. Overall, our work expands the knowledge of HOIP-interacting proteins and provides a platform for further discovery of linear ubiquitination functions in tissue homeostasis.

Abstract Coherent beam combination offers a solution to the challenges associated with the power handling capacity of individual fibres, however, the combined intensity profile strongly depends on the relative phase of each fibre. Optimal combination necessitates precise control over the phase of each fibre channel, however, determining the required phase compensations is challenging because phase information is typically not available. Additionally, the presence of continuously varying phase noise in fibre laser systems means that a single-step and high-speed correction process is required. In this work, we use a spatial light modulator to demonstrate coherent combination in a seven-beam system. Deep learning is used to identify the relative phase offsets for each beam directly from the combined intensity pattern, allowing real-time correction. Furthermore, we demonstrate that the deep learning agent can calculate the phase corrections needed to achieve user-specified target intensity profiles thus simultaneously achieving both beam combination and beam shaping.

Abstract COVID‐19 is currently pandemic and the detection of SARS‐CoV‐2 variants in wastewater is causing widespread concern. Herein, cold atmospheric plasma (CAP) is proposed as a novel wastewater disinfection technology that effectively inactivates SARS‐CoV‐2 transcription‐ and replication‐competent virus‐like particles, coronavirus GX_P2V, pseudotyped SARS‐CoV‐2 variants, and porcine epidemic diarrhoea virus in a large volume of water within 180 s (inhibition rate > 99%). Further, CAP disinfection did not adversely affect the viability of various human cell lines. It is identified that CAP produced peroxynitrite (ONOO−), ozone (O3), superoxide anion radicals (O2−), and hydrogen peroxide (H2O2) as the major active substances for coronavirus disinfection. Investigation of the mechanism showed that active substances not only reacted with the coronavirus spike protein and affected its infectivity, but also destroyed the nucleocapsid protein and genome, thus affecting virus replication. This method provides an efficient and environmentally friendly strategy for the elimination of SARS‐CoV‐2 and other coronaviruses from wastewater.

Abdominal Aortic Aneurysm (AAA) is a disease characterized by localized dilation of the abdominal aorta, involving multiple factors in its occurrence and development, ultimately leading to vessel rupture and severe bleeding. AAA has a high mortality rate, and there is a lack of targeted therapeutic drugs. Epigenetic regulation plays a crucial role in AAA, and the treatment of AAA in the epigenetic field may involve a series of related genes and pathways. Abnormal expression of these genes may be a key factor in the occurrence of the disease and could potentially serve as promising therapeutic targets. Understanding the epigenetic regulation of AAA is of significant importance in revealing the mechanisms underlying the disease and identifying new therapeutic targets. This knowledge can contribute to offering AAA patients better clinical treatment options beyond surgery. This review systematically explores various aspects of epigenetic regulation in AAA, including DNA methylation, histone modification, non-coding RNA, and RNA modification. The analysis of the roles of these regulatory mechanisms, along with the identification of relevant genes and pathways associated with AAA, is discussed comprehensively. Additionally, a comprehensive discussion is provided on existing treatment strategies and prospects for epigenetics-based treatments, offering insights for future clinical interventions.

Abstract The low-frequency oscillation (LFO) has occurred in the train–network system due to the introduction of the power electronics of the trains. The modeling and analyzing method in current researches based on electrified railway unilateral power supply system are not suitable for the LFO analysis in a bilateral power supply system, where the trains are supplied by two traction substations. In this work, based on the single-input and single-output impedance model of China CRH5 trains, the node admittance matrices of the train–network system both in unilateral and bilateral power supply modes are established, including three-phase power grid, traction transformers and traction network. Then the modal analysis is used to study the oscillation modes and propagation characteristics of the unilateral and bilateral power supply systems. Moreover, the influence of the equivalent inductance of the power grid, the length of the transmission line, and the length of the traction network are analyzed on the critical oscillation mode of the bilateral power supply system. Finally, the theoretical analysis results are verified by the time-domain simulation model in MATLAB/Simulink.

ObjectivesThis paper focuses on parametric modeling of a typical butt joint and establishes a finite element model with uncertain geometry of the weld seam, aiming to investigate the stress concentration factor Kt at the weld toe of the butt joint with uncertain weld seam geometry and analyze its distribution characteristics.MethodsFirstly, the mesh size and element type used in the past were improved, and the influence of different types of elements and mesh sizes on Kt is studied through finite element mesh sensitivity analysis. Nodal stresses are extracted along the welding direction of the butt joint, and the location of maximum stress concentration at the weld toe is determined by plotting the stress distribution. Then, the uncertainty of the weld seam geometry is accurately reflected by introducing control points to describe the variation of the weld seam geometry. Combined with the distribution pattern of the actual measured weld seam geometry data, a large amount of weld seam geometry parameter data are randomly sampled. Finally, Kt is calculated based on the notch stress method and its distribution was statistically analyzed to explore the distribution pattern of Kt when there is uncertainty in the weld seam geometry parameters of the butt joint. ResultsThe results show that the distribution of Kt follows a normal distribution. ConclusionsExploring the stress distribution of welding toes has great significance for analyzing fatigue strength and improving the prediction accuracy of fatigue life.

Abstract Electrochemical carbon dioxide reduction reaction using sustainable energy is a promising approach of synthesizing chemicals and fuels, yet is highly energy intensive. The oxygen evolution reaction is particularly problematic, which is kinetically sluggish and causes anodic carbon loss. In this context, we couple CO2 electrolysis with hydrogen oxidation reaction in a single electrochemical cell. A Ni(OH)2/NiOOH mediator is used to fully suppress the anodic carbon loss and hydrogen oxidation catalyst poisoning by migrated reaction products. This cell is highly flexible in producing either gaseous (CO) or soluble (formate) products with high selectivity (up to 95.3%) and stability (>100 h) at voltages below 0.9 V (50 mA cm−2). Importantly, thanks to the “transferred” oxygen evolution reaction to a water electrolyzer with thermodynamically and kinetically favored reaction conditions, the total polarization loss and energy consumption of our H2-integrated CO2 reduction reaction, including those for hydrogen generation, are reduced up to 22% and 42%, respectively. This work demonstrates the opportunity of combining CO2 electrolysis with the hydrogen economy, paving the way to the possible integration of various emerging energy conversion and storage approaches for improved energy/cost effectiveness.

Despite the existence of audio description (AD) in China from 2005, little is known about how AD is conducted in China due to the scarcity of studies on this subject. This article, based on semi-structured interviews with six Chinese AD providers from Shanghai, Wuxi, and Guangzhou, aims to narrow this knowledge gap and present how AD is performed in Mainland China, as seen by some of the key agents involved. The interviews were conducted between April 30 and July 13, 2020, through voice calls on WeChat. Results can be grouped under the following three topics: the current state of AD in China, how AD is conducted in China, and the feasibility of AD translation from Spanish into Chinese. This study has reached two main conclusions. First, AD in China is, now, full of opportunities and challenges, with the copyright issue as its main problem and the objectivity versus subjectivity dichotomy as one of the most debatable concerns in the scriptwriting process. Second, almost all the interviewees showed a positive attitude towards the proposal of AD translation to promote this service in China, in our particular case from Spanish into Chinese.

Abstract Background Gray mold and anthracnose are the main factors affecting strawberry quality and yield. Accurate and rapid early disease identification is of great significance to achieve precise targeted spraying to avoid large-scale spread of diseases and improve strawberry yield and quality. However, the characteristics between early disease infected and healthy leaves are very similar, making the early identification of strawberry gray mold and anthracnose still a challenge. Results Based on hyperspectral imaging technology, this study explored the potential of combining spectral fingerprint features and vegetation indices (VIs) for early detection (24-h infected) of strawberry leaves diseases. The competitive adaptive reweighted sampling (CARS) algorithm and ReliefF algorithm were used for the extraction of spectral fingerprint features and VIs, respectively. Three machine learning models, Backpropagation Neural Network (BPNN), Support Vector Machine (SVM) and Random Forest (RF), were developed for the early identification of strawberry gray mold and anthracnose, using spectral fingerprint, VIs and their combined features as inputs respectively. The results showed that the combination of spectral fingerprint features and VIs had better recognition accuracy compared with individual features as inputs, and the accuracies of the three classifiers (BPNN, SVM and RF) were 97.78%, 94.44%, and 93.33%, respectively, which indicate that the fusion features approach proposed in this study can effectively improve the early detection performance of strawberry leaves diseases. Conclusions This study provided an accurate, rapid, and nondestructive recognition of strawberry gray mold and anthracnose disease in early stage.

Abstract Fungal pathogens typically use secreted effector proteins to suppress host immune activators to facilitate invasion. However, there is rarely evidence supporting the idea that fungal secretory proteins contribute to pathogenesis by transactivating host genes that suppress defense. We previously found that pathogen Magnaporthe oryzae induces rice Bsr-d1 to facilitate infection and hypothesized that a fungal effector mediates this induction. Here, we report that MoSPAB1 secreted by M. oryzae directly binds to the Bsr-d1 promoter to induce its expression, facilitating pathogenesis. Amino acids 103-123 of MoSPAB1 are required for its binding to the Bsr-d1 promoter. Both MoSPAB1 and rice MYBS1 compete for binding to the Bsr-d1 promoter to regulate Bsr-d1 expression. Furthermore, MoSPAB1 homologues are highly conserved among fungi. In particular, Colletotrichum fructicola CfSPAB1 and Colletotrichum sublineola CsSPAB1 activate kiwifruit AcBsr-d1 and sorghum SbBsr-d1 respectively, to facilitate pathogenesis. Taken together, our findings reveal a conserved module that may be widely utilized by fungi to enhance pathogenesis.

Abstract Osmotic energy generation with reverse electrodialysis through membranes provides a worldwide free energy resource. Photo-driven proton transport in photosynthesis supplies basal energy for plants and living organisms on the planet. Here, we utilized aramid nanofiber (ANF) semiconductor-based membranes to enable light-driven proton transport for osmotic energy generation. Under unilateral illumination, the light-driven proton transport system converted light energy into electrical energy and showed wavelength- and intensity-dependent transmembrane potentials and currents. Interestingly, the synergistic effects of simultaneous illumination and pressure provided a five-fold increase in the voltage and a three-fold increase in the current relative to pressure alone. Density functional theory calculations and spectroscopic measurements demonstrated that the ANF and photoinduced electrons enabled proton transport during illumination and generated a transmembrane potential and current. The light-driven proton transport system supports the development of devices with flexible and stable ANF membranes.

Shared energy storage system provides an attractive solution to the high configuration cost and low utilization rate of multi-microgrid energy storage system. In this paper, an electricity-heat integrated energy storage supplier (EHIESS) containing electricity and heat storage devices is proposed to provide shared energy storage services for multi-microgrid system in order to realize mutual profits for different subjects. To this end, electric boiler (EB) is introduced into EHIESS to realize the electricity-heat coupling of EHIESS and improve the energy utilization rate of electricity and heat storage equipment. Secondly, due to the problem of the uncertainty in user-side operation of multi-microgrid system, a price-based demand response (DR) mechanism is proposed to further optimize the resource allocation of shared electricity and heat energy storage devices. On this basis, a bi-level optimization model considering the capacity configuration of EHIESS and the optimal scheduling of multi-microgrid system is proposed, with the objectives of maximizing the profits of energy storage suppliers in upper-level and minimizing the operation costs of the multi-microgrid system in lower-level, and solved based on the Karush-Kuhn-Tucker (KKT) condition and Big-M method. The simulation results show that in case of demand response, the total operation cost of multi-microgrid system and the total operation profit of EHIESS are 51,687.73 and 11,983.88 CNY, respectively; and the corresponding electricity storage unit capacity is 9730.80 kWh. The proposed model realizes the mutual profits of EHIESS and multi-microgrid system.

Plant-derived medicinal materials have significant potential and promising applications in wound healing and skin regeneration. This study aims to develop a plant-based extract hydrogel from Bletilla striata (Thunb.Reichb.f.), specifically a glucosyloxybenzyl 2-isobutylmalates extract (B), and characterize its potential effects on wound healing. We synthesized the hydrogel using carbomer (C), glycerol (G), and triethanolamine (T) as the matrix, incorporating B into the hydrogel base, and evaluated its physical and chemical properties. In vitro tests assessed the biocompatibility of the glucosyloxybenzyl 2-isobutylmalates-carbomer-glycerol-triethanolamine (B-CGT) hydrogel and its effects on cell proliferation, migration, and adhesion. Animal model experiments evaluated its potential to promote wound healing. The results showed that the prepared B-CGT hydrogel possessed a good three-dimensional network structure and stability, demonstrating significant free radical scavenging capacity in antioxidant tests. In cell experiments, the B-CGT hydrogel exhibited no potential cytotoxicity and showed good hemocompatibility and promotion of cell proliferation. Animal experiments indicated that wounds treated with the B-CGT hydrogel healed significantly faster, with improved formation of new epithelial tissue and collagen. This study suggests that the developed B-CGT hydrogel is a promising candidate for wound dressings, with excellent physicochemical properties and controlled drug release capabilities, effectively promoting the wound healing process.

The coating effect of 1,2-bis(triethoxysilyl)ethane (BTES) on carbonyl iron particles (CIPs) was enhanced by etching with hydrochloric acid (HCl) of various concentrations, and magnetorheological fluids (MRFs) with significantly improved dispersion stability were obtained. The microstructures, coating effect, and magnetism of CIPs were examined using scanning electron microscopy (SEM), automatic surface and porosity analysis (BTE), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and a vibrating sample magnetometer (VSM), respectively. Furthermore, the rheological properties and dispersion stability of the MRFs were assessed by a rotating rheometer and a Turbiscan Tower. The results show that as the HCl concentration increased, nanopores appeared on CIPs and then disappeared, and the specific surface area of the particles increased and then decreased. When the concentration of HCl was 0.50 mol/L, the number of nanopores and the specific surface area of particles changed sharply. Not only that, the coated mass of BTES increased greatly and the saturation magnetization of particles decreased sharply. As the coated mass increased, without a magnetic field, the viscosity and shear stress of the MRFs increased, especially when the coated mass was more than 2.45 wt.%; while under a magnetic field, the viscosity and shear stress decreased, and the sedimentation rate of the MRFs decreased from 0.13 to 0.01 mm/h. By controlling the concentration of HCl for etching, the coating effect of CIPs was greatly enhanced, and thus an MRF with superior shear stress and excellent dispersion stability was obtained, which is significant in basic research and MRF-related applications.

Abstract The CRISPR‐Cas system, initially for DNA‐level gene editing and transcription regulation, has expanded to RNA targeting with the Cas13d family, notably the RfxCas13d. This advancement allows for mRNA targeting with high specificity, particularly after catalytic inactivation, broadening the exploration of translation regulation. This study introduces a CRISPR‐dCas13d‐eIF4G fusion module, combining dCas13d with the eIF4G translation regulatory element, enhancing target mRNA translation levels. This module, using specially designed sgRNAs, selectively boosts protein translation in targeted tissue cells without altering transcription, leading to notable protein expression upregulation. This system is applied to a kidney stone disease model, focusing on ferroptosis‐linked GPX4 gene regulation. By targeting GPX4 with sgRNAs, its protein expression is upregulated in human renal cells and mouse kidney tissue, countering ferroptosis and resisting calcium oxalate‐induced cell damage, hence mitigating stone formation. This study evidences the CRISPR‐dCas13d‐eIF4G system's efficacy in eukaryotic cells, presenting a novel protein translation research approach and potential kidney stone disease treatment advancements.

DNA methylation indicates the individual’s aging, so-called Epigenetic clocks, which will improve the research and diagnosis of aging diseases by investigating the correlation between methylation loci and human aging. Although this discovery has inspired many researchers to develop traditional computational methods to quantify the correlation and predict the chronological age, the performance bottleneck delayed access to the practical application. Since artificial intelligence technology brought great opportunities in research, we proposed a perceptron model integrating a channel attention mechanism named PerSEClock. The model was trained on 24,516 CpG loci that can utilize the samples from all types of methylation identification platforms and tested on 15 independent datasets against seven methylation-based age prediction methods. PerSEClock demonstrated the ability to assign varying weights to different CpG loci. This feature allows the model to enhance the weight of age-related loci while reducing the weight of irrelevant loci. The method is free to use for academics at www.dnamclock.com/#/original.

Prevalent neurological disorders such as Alzheimer’s disease, Parkinson’s disease, and stroke are increasingly becoming a global burden as society ages. It is well-known that degeneration and loss of neurons are the fundamental underlying processes, but there are still no effective therapies for these neurological diseases. In recent years, plenty of studies have focused on the pharmacology and feasibility of natural products as new strategies for the development of drugs that target neurological disorders. Antrodia camphorata has become one of the most promising candidates, and the crude extracts and some active metabolites of it have been reported to play various pharmacological activities to alleviate neurological symptoms at cellular and molecular levels. This review highlights the current evidence of Antrodia camphorata against neurological disorders, including safety evaluation, metabolism, blood-brain barrier penetration, neuroprotective activities, and the potential on regulating the gut-microbiome-brain axis. Furthermore, potential strategies to resolve problematic issues identified in previous studies are also discussed. We aim to provide an overview for the ongoing development and utilization of Antrodia camphorata in cerebral neuropathology.

Abstract The incidences of periodontitis and osteoporosis are rising worldwide. Observational studies have shown that periodontitis is associated with increased risk of osteoporosis. We performed a Mendelian randomization (MR) study to genetically investigate the causality of periodontitis on osteoporosis. We explored the causal effect of periodontitis on osteoporosis by MR analysis. A total of 9 single nucleotide polymorphisms (SNP) were related to periodontitis. The primary approach in this MR analysis was the inverse variance-weighted (IVW) method. Simple median, weighted median, and penalized weighted median were used to analyze sensitivity. The fixed-effect IVW model and random-effect IVW model showed no significant causal effect of genetically predicted periodontitis on the risk of osteoporosis (OR=1.032; 95%CI: 0.923-1.153; P=0.574; OR=1.032; 95%CI: 0.920-1.158; P=0.588, respectively). Similar results were observed in simple mode (OR=1.031; 95%CI: 0.780-1.361, P=0.835), weighted mode (OR=1.120; 95%CI: 0.944-1.328, P=0.229), simple median (OR=1.003; 95%CI: 0.839-1.197, P=0.977), weighted median (OR=1.078; 95%CI: 0.921-1.262, P=0.346), penalized weight median (OR 1.078; 95%CI: 0.919-1.264, P=0.351), and MR-Egger method (OR=1.360; 95%CI: 0.998-1.853, P=0.092). There was no heterogeneity in the IVW and MR-Egger analyses (Q=7.454, P=0.489 and Q=3.901, P=0.791, respectively). MR-Egger regression revealed no evidence of a pleiotropic influence through genetic variants (intercept: -0.004; P=0.101). The leave-one-out sensitivity analysis indicated no driven influence of any individual SNP on the association between periodontitis and osteoporosis. The Mendelian randomization analysis did not show a significant detrimental effect of periodontitis on the risk of osteoporosis.

Abstract Background Fringe is a glycosyltransferase involved in tumor occurrence and metastasis. However, a comprehensive analysis of the Fringe family members lunatic fringe (LFNG), manic fringe (MFNG), radical fringe (RFNG) in human cancers is lacking. Methods In this study, we performed a pan-cancer analysis of Fringe family members in 33 cancer types with transcriptomic, genomic, methylation data from The Cancer Genome Atlas (TCGA) project. The correlation between Fringe family member expression and patient overall survival, copy number variation, methylation, Gene Ontology enrichment, and tumor-infiltrating lymphocytes (TILs) was investigated by using multiple databases, such as cBioPortal, Human Protein Atlas, GeneCards, STRING, MSigDB, TISIDB, and TIMER2. In vitro experiments and immunohistochemical assays were performed to validate our findings. Results High expression levels of LFNG, MFNG, RFNG were closely associated with poor overall survival in multiple cancers, particularly in pancreatic adenocarcinoma (PAAD), uveal melanoma (UVM), and brain lower-grade glioma (LGG). Copy number variation analysis revealed that diploid and gain mutations of LFNG was significantly increased in PAAD and stomach adenocarcinoma (STAD), and significantly associated with the methylation levels in promoter regions. Significant differential genes between high and low expression groups of these Fringe family members were found to be consistently enriched in immune response and T cell activation pathway, extracellular matrix adhesion pathway, RNA splicing and ion transport pathways. Correlation between the abundance of tumor-infiltrating lymphocytes (TILs) and LFNG, MFNG, and RFNG expression showed that high LFNG expression was associated with lower TIL levels, particularly in PAAD. In vitro experiment by using pancreatic cancer PANC1 cells showed that LFNG overexpression promoted cell proliferation and invasion. Immunohistochemical assay in 90 PAAD patients verified the expression level of LFNG and its relationship with the prognosis. Conclusions Our study provides a relatively comprehensive understanding of the expression, mutation, copy number, promoter methylation level changes along with prognosis values of LFNG, MFNG, and RFNG in different tumors. High LFNG expression may serve as a poor prognosis molecular marker for PAAD.

Abstract Background Endometrial carcinoma (EC) is the second most common gynecological malignancy, and the differences between different pathological types are not entirely clear. Here, we retrospectively collected eligible EC patients to explore their differences regarding clinical characteristics and prognosis. Methods Five hundred seventy EC patients from the First Affiliated Hospital of Zhengzhou University were included. Prognostic factors were measured using the univariate/multivariate Cox models. Overall survival (OS) and progression-free survival (PFS) were the primary and secondary endpoints, respectively. Results In total, 396 patients with uterine endometrioid carcinoma (UEC), 106 patients with uterine serous carcinoma (USC), 34 patients with uterine mixed carcinoma (UMC), and 34 patients with uterine clear cell carcinoma (UCCC) were included. Comparison of baseline characteristics revealed patients diagnosed with UEC were younger, had more early clinical stage, and had lower incidence of menopause and lymph node metastasis. Compared to UEC, other pathological EC obtained more unfavorable OS (UCCC: HR = 12.944, 95%CI = 4.231–39.599, P

Abstract Triterpenoids, as the main active ingredient of Ganoderma lucidum fermented extract, exert multiple pharmacological activities, including immunomodulatory properties. Our study aimed to reveal the pharmacological effects and potential mechanisms of Ganoderic acid C2 (GAC) against cyclophosphamide (CY)-associated immunosuppression. Target genes were collected from several public databases, including the DisGeNET, Comparative Toxicogenomics Database, GeneCards, and PharmMapper. STRING database was used to construct the protein–protein interaction of network. Subsequently, molecular docking was carried out to visualize the protein-GAC interactions. Experimental validations, including ELISA and qRT-PCR were performed to confirm the pharmacological activities of GAC on CY-induced immunosuppression model. A total of 56 GAC-related targets were identified to be closely associated with CY-induced immunosuppression. Enrichment analyses results revealed that these targets were mainly involved in immune and inflammatory response-related pathways. STAT3 and TNF were identified as the core targets of GAC. Molecular docking indicated that GAC combined well with STAT3 and TNF protein. In addition, animal experiments indicated that GAC improved immunity as well as STAT3 and TNF genes expression in CY-induced immunosuppression, which further verified the prediction through bioinformatics analysis and molecular docking. We successfully revealed the potential therapeutics mechanisms underlying the effect of GAC against CY-induced immunosuppression based on the combination of bioinformatics analysis, molecular docking, and animal experiments. Our findings lay a theoretical foundation for the in-depth development and utilization of Ganoderma lucidum fermentation product in the future, and also provide theoretical guidance for the development of innovative drugs that assist in improving immunity.

Abstract Improving the quality of agricultural exports and increasing value–added trade is crucial for shaping new competitive advantages of agricultural exports, building a strong trading nation and achieving high–quality agricultural development. This study constructed a multi–time point difference–in–differences model to empirically test the effect and mechanism of the mutual recognition of geographical indications (GIs) between China and the European Union (EU) on the quality upgrading of China’s exported agricultural products from 2000 to 2016 based on theoretical analysis of the effect mechanism of GIs on agricultural product exports. The study determined that mutual GI recognition between China and the EU has effectively improved the quality of agricultural exports, with a greater effect on upgrading the quality of products from countries with high GIs endowment, quality frontier and large and medium–sized enterprises and labour–intensive products. The mechanism analysis revealed that mutual GI recognition between China and the EU can improve the quality of agricultural exports through specialisation agglomeration and cost-saving effects on the supply side and domestic demand upgrading and product recognition effects on the demand side. This study has important implications for further enriching quality improvement theory regarding agricultural products and presents a new approach for enhancing the quality improvement path of exported agricultural products that lack supply–side resources.

Abstract Background Genetic and lifestyle factors both contribute to the pathogenesis of bladder cancer, but the extent to which the increased genetic risk can be mitigated by adhering to a healthy lifestyle remains unclear. We aimed to investigate the association of combined lifestyle factors with bladder cancer risk within genetic risk groups. Methods We conducted a prospective study of 375 998 unrelated participants of European ancestry with genotype and lifestyle data and free of cancer from the UK biobank. We generated a polygenic risk score (PRS) using 16 single nucleotide polymorphisms and a healthy lifestyle score based on body weight, smoking status, physical activity, and diet. Cox models were fitted to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of genetic and lifestyle factors on bladder cancer. Results During a median follow-up of 11.8 years, 880 participants developed bladder cancer. Compared with those with low PRS, participants with intermediate and high PRS had a higher risk of bladder cancer (HR 1.29, 95% CI 1.07–1.56; HR 1.63, 95% CI 1.32–2.02, respectively). An optimal lifestyle was associated with an approximately 50% lower risk of bladder cancer than a poor lifestyle across all genetic strata. Participants with a high genetic risk and a poor lifestyle had 3.6-fold elevated risk of bladder cancer compared with those with a low genetic risk and an optimal lifestyle (HR 3.63, 95% CI 2.23 –5.91). Conclusions Adhering to a healthy lifestyle could substantially reduce the bladder cancer risk across all genetic strata, even for high-genetic risk individuals. For all populations, adopting an intermediate lifestyle is more beneficial than a poor one, and adhering to an optimal lifestyle is the ideal effective strategy for bladder cancer prevention.

Background: Inguinal hernia is a common condition; however, irreducible inguinal hernias are rare. In this retrospective study, two laparoscopic procedures for irreducible inguinal hernia were compared. Materials and methods: The study cohort comprised 88 patients who had undergone laparoscopic repair of primary irreducible inguinal hernias between 1 June 2011 and 31 December 2019. The patients were retrospectively divided into Hybrid (Group H) and Standard Transabdominal Preperitoneal (TAPP) Groups (Group S). Patient characteristics, hernia details, and intraoperative and postoperative complications were compared between study groups. Results: There were no significant differences between the two groups in baseline characteristics, including age, sex, body mass index, hernia type, operation time, hospital stay, cost, and duration of follow-up. No recurrence or surgical site infection occurred in either group. There were no significant differences between the two groups in incidence of spermatic vessel injury (0% vs. 2.04%, P = 0.370), vas deferens injury (0% vs. 6.12%, P = 0.116), epigastric vessels injury (0% vs. 4.08%, P = 0.202), scrotal hematoma (7.69% vs. 2.04%, P = 0.206), dysuria (5.13% vs. 8.16%, P = 0.575), fever (17.95% vs. 16.32%, P = 0.841), seroma (25.64% vs. 32.65%, P = 0.474), chronic pain (0% vs. 2.04%, P = 0.370), sensation of a foreign body (2.56% vs. 2.04%, P = 0.870), or pain on ejaculation (0% vs. 2.04%, P = 0.370). The incidence of acute pain was higher in Group H than in Group S (43.59% vs. 8.16%, P = 0.000). Conclusion: The hybrid TAPP procedure is a safe and feasible means of treating irreducible inguinal hernias. Though it is associated with a higher incidence of postoperative acute pain than the standard TAPP procedure, it may have advantages in avoiding injuries to the vas deferens and spermatic vessels.

The study of thermal history of sedimentary basins is very important for oil-gas accumulation analysis and has decisive influence on oil and gas exploration and oil-gas resource evaluation. However, it is difficult to reconstruct the thermal history of carbonate strata in marine basins due to the lack of effective palaeo-thermometer. The carbonate cluster isotope is an index that can indicate the formation temperature of carbonate rock. It records temperature information in chemical bond through conjugated 13C-18O, and temperature information is revealed through changes in the abundance of conjugated 13C-18O, namely, the abundance of carbonate clumped isotope (Δ47) is closely related to the evolution of strata temperature. This paper reviews the application of carbonate clumped isotope palaeo-thermometer and discusses the existing problems and future development direction based on the basic principle and methods of carbonate clumped isotope thermometry and thermal history reconstruction, and combined with the case studies of thermal history reconstruction in marine basins in recent years. As a new palaeo-thermometer, carbonate clumped isotope shows great potential in the thermal history reconstruction of carbonate strata. Previous studies show that the maximum paleotemperature of the Bird Spring Formation in Arrow Canyon, Nevada, USA is about 175 ℃, and the maximum burial temperature of Permian Maokou Formation in the Sichuan Basin is 213-225 ℃. There is an abnormal high temperature of above 160 ℃ in the Ordovician strata of the Tarim Basin due to the Permian magmatic activity. We believe that the carbonate clumped isotope is still insufficient in the reconstruction of thermal history due to the immaturity of thermal evolution models, the recrystallization, and the change of burial temperature. Thus, we suggest that combining the carbonate clumped isotope, U-Pb dating, and other palaeo-thermometers to accurately reconstruct the thermal history of carbonate strata will be the future development direction.