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Objectives: Bone and joint infections (BJI) pose formidable challenges in orthopaedics due to antibiotic resistance and the complexities of biofilm, complicating treatment. This comprehensive exploration addresses the intricate challenges posed by BJI and highlights the significant role of phage therapy as a non-antibiotic strategy. Methods: BJI, which encompass prosthetic joint infections, osteomyelitis, and purulent arthritis, are exacerbated by biofilm formation on bone and implant surfaces, hindering treatment efficacy. Gram-negative bacterial infections, characterized by elevated antibiotic resistance, further contribute to the clinical challenge. Amidst this therapeutic challenge, phage therapy emerges as a potential strategy, showing unique characteristics such as strict host specificity and biofilm disruption capabilities. Results: The review unveils the dynamics of phages, including their origins, lifecycle outcomes, and genomic characteristics. Animal studies, in vitro investigations, and clinical research provide compelling evidence of the efficacy of phages in treating Staphylococcus aureus infections, particularly in osteomyelitis cases. Phage lysins exhibit biofilm-disrupting capabilities, offering a meaningful method for addressing BJI. Recent statistical analyses reveal high clinical relief rates and a favourable safety profile for phage therapy. Conclusions: Despite its promise, phage therapy encounters limitations, including a narrow host range and potential immunogenicity. The comprehensive analysis navigates these challenges and charts the future of phage therapy, emphasizing standardization, pharmacokinetics, and global collaboration. Anticipated strides in phage engineering and combination therapy hold promise for combating antibiotic-resistant BJI.

Pleurotus pulmonarius, commonly known as the mini oyster mushroom, is highly esteemed for its crisp texture and umami flavor. Limited genetic diversity among P. pulmonarius cultivars raises concerns regarding its sustainable industrial production. To delve into the maternal genetic diversity of the principal P. pulmonarius cultivars, 36 cultivars and five wild isolates were subjected to de novo sequencing and assembly to generate high-quality mitogenome sequences. The P. pulmonarius mitogenomes had lengths ranging from 69,096 to 72,905 base pairs. The mitogenome sizes of P. pulmonarius and those of other mushroom species in the Pleurotus genus showed a significant positive correlation with the counts of LAGLIDAG and GIY-YIG homing endonucleases encoded by intronic open reading frames. A comparison of gene arrangements revealed an inversion of a fragment containing atp9-nad3-nad2 between P. pulmonarius and P. ostreatus. The mitogenomes of P. pulmonarius were clustered into three distinct clades, two of which were crowded with commercial cultivars. Clade I, all of which possess an inserted dpo gene, shared a maternal origin linked to an ancestral cultivar from Taiwan. Primers were designed to target the dpo gene, potentially safeguarding intellectual property rights. The wild isolates in Clade III exhibited more divergent mitogenomes, rendering them valuable for breeding.

Food security is a matter of great importance for the nation. The high-quality development of the grain industry is the key to maintaining national food security, and new quality productivity is an important driving force for achieving high-quality development of the grain industry. This article has systematically reviews the existing research on agricultural new quality productivity. It aimed to analyze the formation mechanism of new quality productive forces from a theoretical perspective, and defined the basic connotation of new quality productive forces in the food industry. It explained the typical characteristics of new quality productivity in the grain industry from three levels: high technology, high efficiency, and high quality. From a practical perspective, this article pointed out the current challenges faced by the development of new quality productivity in China's grain industry, including insufficient technological level, severe resource and environmental constraints, prominent quality and safety issues, and a shortage of professional and technical talents. Corresponding suggestions of implementation paths have been proposed, including strengthening technological innovation and application, optimizing various resource allocation, strengthening quality and safety supervision, and emphasizing talent cultivation and introduction, to promote the sustainable, healthy, and high-quality development of the grain industry.

Abstract Background Deep partial-thickness burns have a significant impact on both the physical and mental health of patients. Our previous study demonstrated human Umbilical Cord Mesenchymal stem cells (hUCMSCs) could enhance the healing of severe burns in small animal burn models, such as rats. Furthermore, our team has developed a deep partial-thickness burn model in Bama miniature pigs, which can be utilized for assessing drug efficacy in preclinical trials for wound healing. Therefore, this study further determine the optimal dosage of hUCMSCs in future clinical practice by comparing the efficacy of low-to-high doses of hUCMSCs on deep partial-thickness burn wounds in Bama miniature pigs. Materials and methods The male Bama miniature pigs (N = 8, weight: 23–28 kg and length: 71–75 cm) were used to establish deep partial-thickness burn models, which used a continuous pressure of 1 kg and contact times of 35 s by the invented electronic burn instrument at 100℃ to prepare 10 round burn wounds with diameter of 5 cm according to our previous report. And then, 0 × 10^7, 1 × 10^7, 2 × 10^7, 5 × 10^7 and 1 × 10^8 doses of hUCMSCs were respectively injected into burn wounds of their corresponding groups. After treatment for 7, 14 and 21 days, the burned wound tissues were obtained for histological evaluation, including HE staining for histopathological changes, immunohistochemistry for neutrophil (MPO+) infiltration and microvessel (CD31+) quantity, as well as Masson staining for collagen deposition. The levels of inflammatory factors TNF-α, IL-1β, IL-10 and angiogenesis factors angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), as well as collagen type-I/type-III of the wound tissues were quantified by ELISA. Results All of doses hUCMSCs can significantly increase wound healing rate and shorten healing time of the deep partial-thickness burn pigs in a dose-dependent manner. Furthermore, all of doses hUCMSCs can significantly promote epithelialization and decreased inflammatory reaction of wound, including infiltration of inflammatory cells and levels inflammatory factors. Meanwhile, the amounts of microvessel were increased in all of doses hUCMSCs group than those in the burn group. Furthermore, the collagen structure was disordered and partially necrotized, and ratios of collagen type-I and type-III were significantly decreased in burn group (4:1 in normal skin tissue), and those of all hUCMSCs groups were significantly improved in a dose-dependent manner. In a word, 1 × 10^8 dose of hUCMSCs could regenerate the deep partial-thickness burn wounds most efficaciously compared to other dosages groups and the burn group. Conclusion This regenerative cell therapy study using hUCMSCs demonstrates the best efficacy toward a high dose, that is dose of 1 × 10^8 of hUCMSCs was used as a reference therapeutic dose for treating 20 cm2 deep partial-thickness burns wound in future clinical practice. Graphical abstract

In order to screen the active ingredients of Qinbai Qingfei Concentrated Pill (QQCP) on treating pneumonia contributed by Pheretima, the extracts of QQCP with and without Pheretima were detected by ultra-high performance liquid chromatography/quadrupole-exactive Orbitrap mass spectrometry (UHPLC/Q-Exactive Orbitrap MS) after conducting the cell anti-inflammatory experiment. Compound Discoverer (CD) software was used to screen the differential ions, and the differential components were identified according to MS2 spectra and standards. Further, the active ingredients and targets were predicted by carrying out network pharmacology of differential components treating pneumonia. At last, active ingredients which were identified by standards and their corresponding targets were verified by molecular docking and real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-qPCR). The results of cell anti-inflammatory experiments showed that QQCP can exert anti-inflammatory activity by decreasing the expression of IL6, IL-1b, CXCL2 and CXCR2. After detecting the extracts of QQCP by applying UHPLC/Q-Exactive Orbitrap MS, a total of 15 components are identified on the basis of their retention time, MS/MS spectra as well as standards. After that, there are 7 components connecting and 22 core targets obtained by applying networkpharmacology. After verified by molecular docking and RT-qPCR, α-linolenic acid and adenosine are considered as the active components of QQCP treating pneumonia. This study develops a method of UHPLC/Q-Exactive Orbitrap MS uniting network pharmacology to screen the contributing active components from one medicine in Chinese medicine compounds, which provides a new idea for the study on active components of Chinese medicine compounds.

Abstract The cooled mid-wave infrared biomimetic compound eye camera has wide range of applications, such as industrial inspection, military project, and security. Due to the low resolution of individual eyes and the large field view of the imaging system, existing motion target enhancement and detection algorithms cannot effectively detect all potential targets. To address this issue, we propose an improved elementary motion detector model that combines a double-layer ON_OFF channel and a cross-type computational architecture, which is able to suppress a stationary background and enhance moving targets. In order to further reduce the missed detection, we designed the spatial and temporal consistency detection methods of the compound eye structure, which further improved the accuracy and stability of the detection results. The experimental results show that our method can fully utilize the features of the image and can be applied to the enhancement and detection of moving objects in complex scenes, and the detection efficiency is significantly improved.

Abstract Background The benefits of low-pressure laparoscopic cholecystectomy (LPLC) in patients with cardiopulmonary comorbidities remain unclear. This study aimed to explore the feasibility and pulmonary effects of LPLC in patients with cardiopulmonary comorbidities. Methods This was a multicenter, parallel, double-blind, randomized controlled trial. Eligible patients included patients with cardiac or pulmonary comorbidities, who were randomly assigned (1:1) to undergo LPLC (10 mmHg) or standard-pressure laparoscopic cholecystectomy (SPLC) (14 mmHg). The primary outcome was postoperative partial pressure of carbon dioxide (CO2). Surgical safety variables, patient recovery, pulmonary function parameters, and surgeon comfort were also compared between groups. Results This study enrolled 144 participants, with 124 participants extracted for the final analysis (62 in LPLC and 62 in SPLC group, respectively). The median postoperative PaCO2 was similar in the LPLC (43.3 mmHg) and SPLC (43.0 mmHg) groups (p = 0.988). Pulmonary parameters including postoperative pH, PaCO2, HCO3, and lactate levels were similar between the two groups. Postoperative base excess was significantly higher in the LPLC group (− 0.6 mmol/L [− 6.9 ~ 7.5] vs. −1.9 mmol/L [− 6.6 ~ 5.4]; p = 0.031). There was no between-group difference regarding intraabdominal operative time, rate of intraoperative bile spillage, blood loss, surgeon comfort during surgery, and conversion rate. Moreover, postoperative major complication rates, the median time to the first flatus, postoperative hospital stay, or mean postoperative visual analog scale score for pain were similar in both groups. Conclusions This study found no reduction of partial pressure of CO2 with LPLC compared with SPLC for patients with cardiopulmonary comorbidities. LPLC with a pneumoperitoneum pressure of 10 mmHg may be safe and feasible for these patients when performed by experienced surgeons, although it does not improve pulmonary parameters. Registration The trial is retrospectively registered at ClinicalTrials.gov (NCT04670952) on December 17, 2020.

Abstract Background Fetal growth monitoring is important for twin pregnancies. However, there has been no clinically validated tool for monitoring fetal growth of twin pregnancies in China. This study aims to develop and validate a chorionicity-specific growth chart of ultrasound estimated fetal weight (EFW) for Chinese twin pregnancies. Methods This retrospective cohort study included all twin pregnancies who delivered two live fetuses with gestational age ≥ 34 weeks without severe obstetric complications at a tertiary hospital from January 2007 to March 2021. The participants were divided into a development set (delivered in or before December 2017) and a validation set (delivered in or after January 2018). Chorionicity-specific growth charts were created using the generalized additive models for location, scale, and shape (GAMLSS) based on the development set. The fetuses from the validation set were classified into three groups based on the last EFW: small-for-gestational-age (SGA) indicated by both the newly established twin charts and the Hadlock singleton chart currently used for twin pregnancies in China, suspected SGA indicated by only the singleton chart, and no SGA indicated by either chart. The incidence of neonatal outcomes among the three groups was then compared accordingly, including intensive care unit (NICU) stay length, respiratory diseases, and neurological disorders. Results The development set included 883 twin pregnancies and a total of 6374 EFW measurements between 16 and 38 weeks of gestation, and the validation set included 801 twin pregnancies and 7630 EFW measurements. In the development set, monochorionic diamniotic (MCDA) twins had a significantly lower EFW compared to dichorionic diamniotic (DCDA) twins beginning at 26 weeks, with the difference gradually increasing thereafter, supporting the establishment of chorionicity-specific growth charts. Of the 1,602 twin neonates in the validation set, 103 (6.4%) were classified into the SGA group, 164 (10.2%) into the suspected SGA group, and 1335 (83.3%) into the no SGA group. The incidence of respiratory diseases and neurological disorders was comparable between the suspected SGA group and the no SGA group, but apparently higher in the SGA group. Meanwhile, NICU stay lengths were consistently longer for twins in the SGA group compared to the no SGA group (difference: 0.57, 95% CI: 0.31–0.83), with no significant differences observed between the suspected SGA and no SGA groups. Conclusions The fetal growth trajectories differed by chorionicity, with a lower EFW for MCDA twins beginning at 26 weeks. The establishment of chorionicity-specific growth chart could reduce overdiagnosis of SGA and improve fetal growth monitoring of twin pregnancies.

To determine invasive group A Streptococcus trends in Canada, we characterized emm1 isolates collected during 2018–2023. The percentage of hypervirulent M1UK lineage isolates increased significantly, from 22.1% in 2018 to 60.2% in 2023. Genomic analysis identified geographically and temporally associated clusters and genes associated with virulent bacteriophage acquisition.

To achieve carbon neutrality for China, the transmission mechanism, path, diffusion effect,and allocation of Emission Reduction Targets (ERT) among industries must be investigated. Setting short-term ERT will create a reverse pressure mechanism for the industry's carbon reduction, ensuring the achievement of carbon emission control target. However, few studies have explored how to influence the entire system by controlling key industries from the perspective of network control. Therefore, this study investigates Inter-industry Carbon Emission Transfer (ICET) in China from 1997 to 2017,and found that ICET can achieve fair distribution of ERT. Inspired by the controllability theory of complex networks to integrate the driving factors, the transmission paths, diffusion effects, and allocation of ERT into a unified analytical framework. Then, breaking the traditional top-down hierarchical decomposition mechanism and transforming it into a bottom-up target forcing mechanism, a decomposition algorithm for the total control target was proposed.The results reveal that ICET accounts for the majority of carbon emission. The characteristics of network structure have a significant impact on the ICET.Different industries have varying control capabilities. Compared with industry-wide control, target control on the Minimum Control Industry Set (MCMCS) has a slightly worse emission reduction effect, but the economic loss is smaller, making it an effective policy choice.

Abstract Objective Chemotherapy during pregnancy has a certain risk of causing a series of complications, such as miscarriage, premature birth, or fetal growth restriction, although the relationship between these complications and chemotherapy is currently unclear. This experiment focuses on the possible damage mechanism of the chemotherapeutic drug paclitaxel on placental trophoblast cells, and explores whether chemotherapy can affect pregnancy outcomes by directly damaging placental tissue. Methods This study explored the mechanism of paclitaxel induced damage on placental trophoblast cell lines JEG-3 and BEWO through immunofluorescence staining, Western blot experiments, cell flow cytometry, Seahorese cell metabolism experiments, and mouse modeling verification. Results The experiment found that paclitaxel could induce JEG-3 and BEWO cells to produce reactive oxygen species (ROS), and elevate the ratio of Bax/Bcl-2 expression. Besides, paclitaxel mediated the reduction of mitochondrial membrane potential in JEG-3 and BEWO cells, causing damage and leading to mitochondrial autophagy and the occurrence of unfolded protein response. Paclitaxel inhibited the glycolysis rate of JEG-3 and BEWO cells, and leaded to impaired mitochondrial function, including decreased basal respiratory values, decreased respiratory reserve capacity, and proton leakage. In pregnant mice with tumor modeling, paclitaxel could cause DNA damage in placental tissue cells, and might lead to apoptosis of chemotherapy mice placental tissue cells and impairment of normal physiological functions. Conclusion Paclitaxel may directly or indirectly affect the normal physiological functions of placental trophoblast cells, including energy metabolism and protein synthesis dysfunction, which may be related to the adverse pregnancy outcomes caused by paclitaxel chemotherapy.

Abstract Background The integration of 7 Tesla (7T) magnetic resonance imaging (MRI) with advanced multimodal artificial intelligence (AI) models represents a promising frontier in neuroimaging. The superior spatial resolution of 7TMRI provides detailed visualizations of brain structure, which are crucial forunderstanding complex central nervous system diseases and tumors. Concurrently, the application of multimodal AI to medical images enables interactive imaging‐based diagnostic conversation. Methods In this paper, we systematically investigate the capacity and feasibility of applying the existing advanced multimodal AI model ChatGPT‐4V to 7T MRI under the context of brain tumors. First, we test whether ChatGPT‐4V has knowledge about 7T MRI, and whether it can differentiate 7T MRI from 3T MRI. In addition, we explore whether ChatGPT‐4V can recognize different 7T MRI modalities and whether it can correctly offer diagnosis of tumors based on single or multiple modality 7T MRI. Results ChatGPT‐4V exhibited accuracy of 84.4% in 3T‐vs‐7T differentiation and accuracy of 78.9% in 7T modality recognition. Meanwhile, in a human evaluation with three clinical experts, ChatGPT obtained average scores of 9.27/20 in single modality‐based diagnosis and 21.25/25 in multiple modality‐based diagnosis. Our study indicates that single‐modality diagnosis and the interpretability of diagnostic decisions in clinical practice should be enhanced when ChatGPT‐4V is applied to 7T data. Conclusions In general, our analysis suggests that such integration has promise as a tool to improve the workflow of diagnostics in neurology, with a potentially transformative impact in the fields of medical image analysis and patient management.

Background: To explore whether IgG4 is involved in the pathogenesis of IgG4 HT. Methods: Serum TgAb IgG4 and TPOAb IgG4 were measured in IgG4 HT and non-IgG4 HT. C1q, mannose-binding lectin (MBL), Bb, C3d, C4d, and membrane attack complex (MAC) in thyroid tissues from IgG4 HT, non-IgG4 HT, and controls were examined by immunohistochemistry. We assessed IgG4 and MAC deposition in mouse thyroid by immunohistochemistry after injecting purified IgG4 into mice. The glycosylation patterns of TgAb IgG4 from IgG4 HT were identified by MALDI-TOF-MS. The ability of IgG4 to bind to MBL before and after deglycosylation was assessed by ELISA. MBL and MAC fluorescence were detected in thyrocytes after the addition of IgG4 or deglycosylated IgG4. Results: Serum TgAb IgG4 and TPOAb IgG4 levels were significantly higher in the IgG4 HT group. MBL, Bb, C3d, C4d, and MAC levels were significantly higher in the thyroid tissues of IgG4 HT than in non-IgG4 HT (all P < 0.001). IgG4 colocalized with MBL by immunofluorescence. In mice, follicular cell structure disruption was observed after the injection of IgG4 from IgG4 HT, as well as the colocalization of IgG4 with MAC. High levels of TgAb IgG4 glycosylation patterns, including monogalactose glycan (G1F), galactose-deficient glycan (G0F), and high-mannose glycan (M5), were detected in IgG4 HT. After deglycosylation, IgG4 reduced its ability to bind to MBL, and there was low MBL and MAC activation in thyrocytes. Conclusion: High levels of IgG4 glycosylation patterns, including G1F, G0F, and M5, may activate the complement lectin pathway, thereby participating in the pathogenesis of IgG4 HT.

Abstract Type I interferon (IFN-I) plays a crucial role in the antiviral immune response and inflammatory autoimmune diseases by inducing the expression of IFN-stimulated genes (ISGs). Hence, the regulation of ISG expression is fundamental for maintaining immune homeostasis. In this study, we found that PCGF3 negatively regulates the antiviral response by suppressing the expression of ISGs. The deficiency of PCGF3 in innate immune cells results in an augmented expression of ISGs in response to IFN-I stimulation. Mechanistically, PCGF3 is recruited to interferon-stimulated response elements (ISREs) region in an IFN-dependent way, precluding STAT1 from binding to the ISG promoter and diminishing ISRE activity. Additionally, we observed a negative correlation between decreased PCGF3 expression and elevated ISG expression in peripheral blood mononuclear cells (PBMCs) of patients with dermatomyositis (DM). Our findings clarified the epigenetic regulatory role of PCGF3 in inhibiting the excessive expression of ISGs induced by IFN-I under pathological circumstances.

Phase Change Material-based Battery Thermal Management System (PCM-based BTMS) has become a current research hotspot due to its high efficiency, thermal stability, and compactness. Regrettably, most existing research on PCM-based BTMS neglects the existence of mechanical vibrations, despite the inevitable involvement of such vibrations in the operating conditions of BTMS in electric vehicles. Therefore, in this study, a PCM-based BTMS is applied to a 6-cell lithium-ion battery (LIB) module, and then numerical simulation is employed to comprehensively evaluate the BTMS's performance in the existence of mechanical vibration. The findings indicate that, under mechanical vibration condition, mechanical vibration's influence on the performance of the BTMS is negligible at lower discharge rates, but becomes significant when the discharge rate surpasses a certain threshold, particularly at extremely fast discharge level, resulting in a decrease of 2.28 K in the LIB module’s maximum temperature and a more uniform temperature distribution upon completion of an 8 C discharge in contrast to its stationary equivalent. Furthermore, mechanical vibration only effectively enhances the BTMS’s thermal absorption capability when the PCM thickness surpasses a certain value, and this vibration also improves the capability of the BTMS to achieve uniform temperature distribution in the LIB module, especially for larger PCM thicknesses. Lastly, the BTMS's performance is able to strengthened by raising vibrational amplitude, but the impact is negligible when the amplitude is equal to or greater than 50 mm, and the thermal absorption capability of the BTMS can be augmented by raising the vibrational frequency, but there exists an enhancement limit. This work promotes the use of PCM-based BTMS in real-world applications and contributes to the advancement of LIB towards higher discharge rates.

In traditional crop genetics research, protein-coding genes have always been the primary focus. However, recent scientific advances have revealed the critical role of non-coding genetic resources in regulating key agronomic traits such as crop yield, quality, and resistance. These non-coding genetic resources include regulatory non-coding RNAs, constitutive non-coding RNAs, non-coding regions of genes, nucleic acid aptamers, and small peptides derived from non-coding sequences. They play crucial roles in gene expression regulation, cellular metabolism, genome stability, and biotechnological applications. The rapid development of high-throughput sequencing technologies, bioinformatics, and functional genomics has provided technical support for the systematic discovery and functional study of these non-coding genetic resources. In the field of crop breeding, the precise regulatory features of non-coding genetic elements offer new strategies for improving agronomic traits, surpassing the limitations of traditional protein-coding gene research. These studies not only reveal the diverse functions and refined regulatory mechanisms of non-coding sequences in controlling complex crop traits but also demonstrate immense application potential. This paper comprehensively reviews the progress in research on non-coding genetic resources in regulating agronomic traits, systematically categorizing these elements and examining their origins and evolutionary background. It discusses in detail the regulatory mechanisms and networks through which these non-coding elements influence critical agronomic traits in crops. Finally, the article explores the potential applications of non-coding genetic resources in crop breeding and presents future directions for their development in genetic improvement. By systematically summarizing current research findings, this review aims to provide a solid theoretical foundation for future studies and promote the innovative application of non-coding genetic resources in crop genetic improvement.

OBJECTIVE: As an important anatomic factor in the process of lumbar disc herniation (LDH), the correlation between end plate sagittal morphology and intervertebral disc degeneration (IDD) is unclear. Moreover, research on imaging data of lumbar end plate in patients with LDH is still insufficient. Our study aimed to observe the morphological change of the lower lumbar end plate (L3-S1) in patients with LDH on magnetic resonance imaging (MRI) and analyze its correlation with the degree of IDD. MATERIALS AND METHODS: A total of 116 patients were included in the study. Based on their MRI, we divided end plates into three types (concave, flat, and irregular), assigned intervertebral discs with Grade I–V given 1–5 points successively according to the Pfirrmann system, and determined whether there was Modic change of each end plate. The correlation between the morphology of the end plate and the degree of IDD was analyzed. Results: There was an excellent interobserver agreement for each item we analyzed (interclass correlation coefficient >0.75). Concave end plate appeared most frequently (187, 53.7%) and was mainly distributed in L3/4 and L4/5, whereas irregular end plate was the least common type (54, 15.5%) and mainly concentrated in L5/S1. The IDD degree of the corresponding disc increased gradually from concave (3.27 ± 0.81) to irregular end plates (4.25 ± 0.79) (P < 0.05). Irregular end plates were more likely to have Modic changes than concave and flat end plates (P < 0.05). Conclusion: The sagittal morphology of the lower lumbar end plate is related to modic changes and degree of IDD (based on the Pfirrmann grading system) in patients with LDH, and the concave end plate mostly reflects a lower degree of lumbar disc degeneration, which has substantial clinical significance.

Abstract Background The potential effects of global warming on soil fungal communities and their functions remain uncertain. To address this issue, we investigated the effects of 3-year simulated field warming on the community and function of fungi in a temperate steppe of Inner Mongolia, northern China. Methods The diversity and structure of the fungal community were measured by high-throughput sequencing. The functionality of fungal communities was identified by comparison with the ITS reference database. Results Our results showed that warming did not affect the diversity of fungi, but significantly increased the complexity of the fungal community, with fungal taxa more closely associating with each other. We observed that plant pathogens and arbuscular mycorrhizal fungi were the most abundant functional groups. Meanwhile, warming significantly decreased the relative abundance of animal pathogens. Conclusions Warming significantly increased the complexity of the fungal community, with soil pH being the main factor affecting soil fungal function. Our findings emphasize that the response of the fungal community and its functional groups to warming has significant implications for ecosystem biogeochemical cycling.

Abstract Hemolysis drives susceptibility to lung injury and predicts poor outcomes in diseases, such as malaria and sickle cell disease (SCD). However, the underlying pathological mechanism remains elusive. Here, we report that major facilitator superfamily domain containing 7 C (MFSD7C) protects the lung from hemolytic-induced damage by preventing ferroptosis. Mechanistically, MFSD7C deficiency in HuLEC-5A cells leads to mitochondrial dysfunction, lipid remodeling and dysregulation of ACSL4 and GPX4, thereby enhancing lipid peroxidation and promoting ferroptosis. Furthermore, systemic administration of MFSD7C mRNA-loaded nanoparticles effectively prevents lung injury in hemolytic mice, such as HbSS-Townes mice and PHZ-challenged 7 C−/− mice. These findings present the detailed link between hemolytic complications and ferroptosis, providing potential therapeutic targets for patients with hemolytic disorders.

Abstract We study that the different-mode (waveguide-connected) power splitter [(W)PS] can provide different-mode testing points for the optical testing. With the PS or WPS providing two different-mode testing points, the measured insertion losses (ILs) of the three-channel and dual-mode waveguide crossing (WC) for both the fundamental transverse electric (TE0) and TE1 modes are less than 1.8 dB or 1.9 dB from 1540 nm to 1560 nm. At the same time, the crosstalks (CTs) are lower than −17.4 dB or −18.2 dB. The consistent test results indicate the accuracy of the (W)PS-based testing circuit. Additionally, combining the tunable tap couplers, the (W)PS can provide multiple testing points with different modes and different transmittances.

In recent years, exopoly saccharides (EPS) produced by microorganisms have garnered attention due to their functional properties such as improving food quality, regulating intestinal microbiota, antioxidative effects, anticancer properties, immunoprevention, and treatment of cardiovascular diseases. Currently, research on microbial EPS (extracellular polymeric substances) in China is still in its early stages and requires further exploration. This paper comprehensively reviewed the latest advancements in the classification, biosynthesis, structural modification, functional properties, and applications of EPS produced by microorganisms both domestically and internationally. This study also focused on analyzing the biosynthetic pathways and structural features of different types of EPS, as well as the strategies for functional modification through physical, chemical, and biological methods. The aim is to provide new references and guidance for research and development in relevant fields, thereby promoting the application and industrialization of EPS in the food, pharmaceutical, and industrial sectors.

Abstract Breast cancer ranks as one of the most common malignancies among women, with its prognosis and therapeutic efficacy heavily influenced by factors associated with the tumor cell biology, particularly the tumor microenvironment (TME). The diverse elements of the TME are engaged in dynamic bidirectional signaling interactions with various pathways, which together dictate the growth, invasiveness, and metastatic potential of breast cancer. The Hedgehog (Hh) signaling pathway, first identified in Drosophila, has been established as playing a critical role in human development and disease. Notably, the dysregulation of the Hh pathway is recognized as a major driver in the initiation, progression, and metastasis of breast cancer. Consequently, elucidating the mechanisms by which the Hh pathway interacts with the distinct components of the breast cancer TME is essential for comprehensively evaluating the link between Hh pathway activation and breast cancer risk. This understanding is also imperative for devising novel targeted therapeutic strategies and preventive measures against breast cancer. In this review, we delineate the current understanding of the impact of Hh pathway perturbations on the breast cancer TME, including the intricate and complex network of intersecting signaling cascades. Additionally, we focus on the therapeutic promise and clinical challenges of Hh pathway inhibitors that target the TME, providing insights into their potential clinical utility and the obstacles that must be overcome to harness their full therapeutic potential.

Abstract Background Cardiac etiologies arrest accounts for almost half of all in-hospital cardiac arrest (IHCA), and previous studies have shown that the location of IHCA is an important factor affecting patient outcomes. The aim was to compare the characteristics, causes and outcomes of cardiovascular disease in patients suffering IHCA from different departments of Fuwai hospital in Beijing, China. Methods We included patients who were resuscitated after IHCA at Fuwai hospital between March 2017 and August 2022. We categorized the departments where cardiac arrest occurred as cardiac surgical or non-surgical units. Independent predictors of in-hospital survival were assessed by logistic regression. Results A total of 119 patients with IHCA were analysed, 58 (48.7%) patients with cardiac arrest were in non-surgical units, and 61 (51.3%) were in cardiac surgical units. In non-surgical units, acute myocardial infarction/cardiogenic shock (48.3%) was the main cause of IHCA. Cardiac arrest in cardiac surgical units occurred mainly in patients who were planning or had undergone complex aortic replacement (32.8%). Shockable rhythms (ventricular fibrillation/ventricular tachycardia) were observed in approximately one-third of all initial rhythms in both units. Patients who suffered cardiac arrest in cardiac surgical units were more likely to return to spontaneous circulation (59.0% vs. 24.1%) and survive to hospital discharge (40.0% vs. 10.2%). On multivariable regression analysis, IHCA in cardiac surgical units (OR 5.39, 95% CI 1.90-15.26) and a shorter duration of resuscitation efforts (≤ 30 min) (OR 6.76, 95% CI 2.27–20.09) were associated with greater survival rate at discharge. Conclusion IHCA occurring in cardiac surgical units and a duration of resuscitation efforts less than 30 min were associated with potentially increased rates of survival to discharge.

Abstract In metazoans mitochondrial DNA (mtDNA) or retrotransposon cDNA released to cytoplasm are degraded by nucleases to prevent sterile inflammation. It remains unknown whether degradation of these DNA also prevents nuclear genome instability. We used an amplicon sequencing-based method in yeast enabling analysis of millions of DSB repair products. In non-dividing stationary phase cells, Pol4-mediated non-homologous end-joining increases, resulting in frequent insertions of 1–3 nucleotides, and insertions of mtDNA (NUMTs) or retrotransposon cDNA. Yeast EndoG (Nuc1) nuclease limits insertion of cDNA and transfer of very long mtDNA ( >10 kb) to the nucleus, where it forms unstable circles, while promoting the formation of short NUMTs (~45–200 bp). Nuc1 also regulates transfer of extranuclear DNA to nucleus in aging or meiosis. We propose that Nuc1 preserves genome stability by degrading retrotransposon cDNA and long mtDNA, while short NUMTs originate from incompletely degraded mtDNA. This work suggests that nucleases eliminating extranuclear DNA preserve genome stability.

The compatibility of aircraft landing gear and pavement is of great significance to the ground motion ability of aircraft. In this paper, the landing gear load and tire load distribution under different working conditions for a large aircraft are calculated by using the Portland Cement Association method based on Westgard laminate theory and the United States Army Corps of Engineers method based on California bearing ratio（CBR）. The influence of the landing conditions, ground mobility, tire number, tire deflation and track widths on the aircraft classification number（ACN）is analyzed. The aircraft float-ability under rigid and flexible pavement is analyzed. Results show that the increased tire load and uneven load distribution caused by vertical overload and tire deflation can weaken the float-ability of aircraft to varying degrees, especially during turning and landing conditions with tail sinking, therefore, which need to be limited. Increasing the number of tires and the distance between them can improve the float-ability, but the structural design, strength margin and other factors should also be taken into consideration to optimize the design of trolley type landing gear.

Background: The reproducibility of positron emission tomography (PET) radiomics features is affected by several factors, such as scanning equipment, drug metabolism time and reconstruction algorithm. We aimed to explore the role of 3D local binary pattern (LBP)-based texture in increasing the accuracy and reproducibility of PET radiomics for predicting pelvic lymph node metastasis (PLNM) in patients with cervical cancer. Methods: We retrospectively analysed data from 177 patients with cervical squamous cell carcinoma. They underwent 18F-fluorodeoxyglucose (18F-FDG)whole-body PET/computed tomography (PET/CT), followed by pelvic 18F-FDG PET/magnetic resonance imaging (PET/MR). We selected reproducible and informative PET radiomics features using Lin's concordance correlation coefficient, least absolute shrinkage and selection operator algorithm, and established 4 models, PET/CT, PET/CT-fusion, PET/MR and PET/MR-fusion, using the logistic regression algorithm. We performed receiver operating characteristic (ROC) curve analysis to evaluate the models in the training data set (65 patients who underwent radical hysterectomy and pelvic lymph node dissection) and test data set (112 patients who received concurrent chemoradiotherapy or no treatment). The DeLong test was used for pairwise comparison of the ROC curves among the models. Results: The distribution of age, squamous cell carcinoma (SCC), International Federation of Gynaecology and Obstetrics stage and PLNM between the training and test data sets were different (P < 0.05). The LBP-transformed radiomics features (50/379) had higher reproducibility than the original radiomics features (9/107). Accuracy of each model in predicting PLNM was as follows: training data set: PET/CT = PET/CT-fusion = PET/MR-fusion (0.848) and test data set: PET/CT = PET/CT-fusion (0.985) > PET/MR = PET/MR-fusion (0.954). There was no statistical difference between the ROC curve of PET/CT and PET/MR models in both data sets (P > 0.05). Conclusions: The LBP-transformed radiomics features based on PET images could increase the accuracy and reproducibility of PET radiomics in predicting pelvic lymph node metastasis in cervical cancer to allow the model to be generalised for clinical use across multiple centres.

Objective To study the RHD genotyping of primary screening RhD negative population in Beijing, and analyze the serological characteristics of different genotypes and the distribution of Rh phenotypes. Methods From August 2022 to January 2024, 204 RhD negative samples in our hospital were initially screened by microplate or microcolumn agglutination method. RhD antigen phenotype was identified by saline tube method, and RhD negative confirmation test was performed by microcolumn gel-indirect antiglobulin technology.RHD genotyping was performed by polymerasing chain reaction-sequence specific primmer (PCR-SSP) method and sequencing technology, and the phenotypic frequency and gene frequency were calculated. Results The distribution of Rh serologic phenotypes in 204 RhD negative samples were 112 cases of ccee (54.90%) > 73 cases of Ccee (35.78%) > 9 cases of CCee (4.41%) > 6 cases of ccEe (2.94%) > 4 cases of CcEe (1.96%). A total of 7 RHD genotypes were detected in this study, including 129 cases of RHD* 01N.01 (63.24%), 44 cases of RHD* 01EL.01 (21.57%), 26 cases of RHD* 01N.03 (12.75%), 2 cases of RHD* 01N.16 (0.98%), 1 case of RHD* 06.03.01 (0.49%), 1 case of weak RHD* 15 (0.49%) and 1 case of RHD* 13.01/RHD* 01N.01 (0.49%). The frequency and phenotype distribution of Rh blood group antigen gene were consistent with Hardy-Weinberg equilibrium (P>0.05). Conclusion The RHD gene is polymorphic in the primary screening RhD negative population in Beijing, and the most common RhD negative genotype is RHD* 01N.01, and the RHD variant is RHD* 01EL.01.This study may provide data to support the clinical implementation of genotype-matched blood transfusions.

Abstract Background Thromboelastography (TEG) is a widely utilized clinical testing method for real‐time monitoring of platelet function and the thrombosis process. Lipid metabolism disorders are crucial risk factors for thrombosis. The lipid metabolism characteristics of hamsters resemble those of humans more closely than mice and rats, and their relatively large blood volume makes them suitable for studying the mechanisms of thrombosis related to plasma lipid mechanisms. Whole blood samples from golden Syrian hamsters and healthy humans were obtained following standard clinical procedures. TEG was employed to evaluate coagulation factor function, fibrinogen (Fib) function, platelet function, and the fibrinolytic system. Methods The whole blood from hamster or healthy human was isolated following the clinical procedure, and TEG was employed to evaluate the coagulation factor function, Fib function, platelet function, and fibrinolytic system. Coagulation analysis used ACLTOP750 automatic coagulation analysis pipeline. Blood routine testing used XN‐2000 automatic blood analyzer. Results TEG parameters revealed that hamsters exhibited stronger coagulation factor function than humans (reaction time [R], p = 0.0117), with stronger Fib function (alpha angle, p

Abstract Clear cell renal cell carcinoma (ccRCC) demonstrates enhanced glycolysis, critically contributing to tumor development. Programmed death-ligand 1 (PD-L1) aids tumor cells in evading T-cell-mediated immune surveillance. Yet, the specific mechanism by which glycolysis influences PD-L1 expression in ccRCC is not fully understood. Our research identified that the glycolysis-related gene (GRG) HK3 has a unique correlation with PD-L1 expression. HK3 has been identified as a key regulator of O-GlcNAcylation in ccRCC. O-GlcNAcylation exists on the serine 900 (Ser900) site of EP300 and can enhance its stability and oncogenic activity by preventing ubiquitination. Stably expressed EP300 works together with TFAP2A as a co-transcription factor to promote PD-L1 transcription and as an acetyltransferase to stabilize PD-L1 protein. Furthermore, ccRCC exhibits interactive dynamics with tumor-associated macrophages (TAMs). The uridine 5′-diphospho-N-acetylglucosamine (UDP-GlcNAc), which serves as a critical substrate for the O-GlcNAcylation process, facilitates TAMs polarization. In ccRCC cells, HK3 expression is influenced by IL-10 secreted by M2 TAMs. Our study elucidates that HK3-mediated O-GlcNAcylation of EP300 is involved in tumor immune evasion. This finding suggests potential strategies to enhance the efficacy of immune checkpoint blockade therapy.

Abstract [Objective] The study aims to investigate the effects of different light exposure durations and intensities on the sugar, acid, and flavonoid contents of Cerasus humilis fruits, and to provide a reference for further exploration of the molecular mechanisms underlying the influence of light exposure on fruit quality. [Methods] The C. humilis varieties ‘Nongda 6’ and ‘Nongda 7’ were used as experimental materials. Fruit bags with three different light transmission rates (30%, 55%, and 100%) were applied during fruit enlargement period and color conversion period, respectively, and measured the fruit mass and titratable acid, soluble solid, and flavonoid content. [Results] (1) The single fruit mass and soluble solid content of both varieties were lower during fruit enlargement period than during color conversion period, and both were decreased gradually with increasing light-blocking rate of fruit bags. (2) The titratable acid content of ‘Nongda 6’ was significantly reduced under bagging treatment, and the higher the light-blocking rate of the fruit bag and the longer the bagging time, the more pronounced the reduction in acidity. In contrast, the titratable acid content of ‘Nongda 7’ was less affected. (3) The flavonoid content of bagged ‘Nongda 6’ was higher than the control, increasing first and then decreasing with the increase in lightblocking rate of the fruit bag, and the content during fruit enlargement period was higher than that during color conversion period. The flavonoid content of bagged ‘Nongda 7’ was significantly higher than the control only at a 30% light-blocking rate, and the content during fruit enlargement period was significantly lower than during color conversion period. [Conclusion] Bagging can effectively improve the sugar, acid, and flavonoid content of C. humilis fruits. Furthermore, bagging during fruit enlargement period is suitable for ‘Nongda 6’, while bagging during color conversion period is more effective for ‘Nongda 7’. Both varieties show the best overall improvement in sugar, acid, and flavonoid content with a 55% light-blocking rate of the fruit bag.

Abstract Tumor neovascularization is essential for the growth, invasion, and metastasis of tumors. Recent studies have highlighted the significant role of N6-methyladenosine (m6A) modification in regulating these processes. This review explores the mechanisms by which m6A influences tumor neovascularization, focusing on its impact on angiogenesis and vasculogenic mimicry (VM). We discuss the roles of m6A writers, erasers, and readers in modulating the stability and translation of angiogenic factors like vascular endothelial growth factor (VEGF), and their involvement in key signaling pathways such as PI3K/AKT, MAPK, and Hippo. Additionally, we outline the role of m6A in vascular-immune crosstalk. Finally, we discuss the current development of m6A inhibitors and their potential applications, along with the contribution of m6A to anti-angiogenic therapy resistance. Highlighting the therapeutic potential of targeting m6A regulators, this review provides novel insights into anti-angiogenic strategies and underscores the need for further research to fully exploit m6A modulation in cancer treatment. By understanding the intricate role of m6A in tumor neovascularization, we can develop more effective therapeutic approaches to inhibit tumor growth and overcome treatment resistance. Targeting m6A offers a novel approach to interfere with the tumor’s ability to manipulate its microenvironment, enhancing the efficacy of existing treatments and providing new avenues for combating cancer progression.

Abstract Accurate cannulation of the adrenal vein is challenging during adrenal venous sampling (AVS) because of the variations in adrenal vein anatomy. This study aimed to investigate the adrenal venous morphology in Chinese and improve the success rate of AVS. A total of 221 participants with primary aldosteronism (PA) who underwent AVS were enrolled. Compare the morphology among subgroups divided according to sex, body mass index (BMI), and with or without adenoma. The success rate of right, left, and bilateral AVS was 98.60%, 97.20%, and 96.85%, respectively. The triangular pattern was the most common (39.37%) on the right side, while the glandlike pattern (70.14%) on the left. The proportion of adrenal venous morphology varies among patients with different sexes (χ2 = 21.335, P

Introduction: Whole-genome duplication (WGD) is one of the most sudden and dramatic events rarely reported in invertebrates, but its occurrence can lead to physiological, morphological, and behavioral diversification. WGD has also never been reported in barnacles, which is one of the most unique groups of crustaceans with extremely speciallized morphology (calcareous shells) and habits (intertidal sessile lifestyle). Objectives: To investigate whether WGD has occurred in barnacles and examine its potential role in driving the adaptive evolution and diversification of barnacles. Methods: Based on a newly sequenced and assembled chromosome-level barnacle genome, a novel WGD event has been identified in barnacles through a comprehensive analysis of interchromosomal synteny, the Hox gene cluster, and synonymous substitution distribution. Results: We provide ample evidences for WGD in the barnacle genomes. Comparative genomic analysis indicates that this WGD event predates the divergence of Thoracicalcarea, occurring more than 247 million years ago. The retained ohnologs from the WGD are primarily enriched in various pathways related to environmental information processing, shedding light on the adaptive evolution and diversification of intertidal sessile lifestyle. In addition, transcriptomic analyses show that most of these ohnologs were differentially expressed following the ebb of tide. And the cytochrome P450 ohnologs with differential expression patterns are subject to subfunctionalization and/or neofunctionalization for intertidal adaptation. Besides WGD, parallel evolution underlying intertidal adaptation has also occurred in barnacles. Conclusion: This study revealed an ancient WGD event in the barnacle genomes, which is potentially associated with the origin and diversification of thoracican barnacles, and may have contributed to the adaptive evolution of their intertidal sessile lifestyle.

In order to meet the power source requirements of C-band linear accelerators for industrial applications, a C-band high power klystron operating at a frequency of 5 712 MHz was developed. For this klystron, the development objective of the output power is no less than 3.5 MW and the efficiency is no less than 35%. During the entire design process, the output power was optimized to over 4 MW and the power efficiency over 40% to compensate for the disadvantage effects caused by manufacturing and testing errors in the development processes. Firstly, the electron optics system with a Pierce gun and a combination of five forward and one reverse focusing coils was designed. The Pierce gun with a perveance of 2 μP was adopted and the beam voltage and current were chosen as 120 kV and 83.3 A. By iteratively calculating the structure of the electron gun with EGUN code and optimizing the magnetic field between the electron gun and the beam-wave interaction section, the final electron beam pass rate reaches 100% and the fluctuation of the beam envelop is only 4.8%. Secondly, the efficiency optimization and PIC simulation of the beam-wave interaction section were carried out using the one dimensional AJDISK code, 1.5 dimensional KlyC code and three dimensional CST code. The scheme of six resonant cavities was ultimately determined and the basic cavity parameters were optimized based on the principles of stagger tuning. The simulation results of different codes all indicate that the efficiency can reach above 46.5%, and the output power can all reach above 4.650 MW. And the influence of frequency errors and output external quality factor on efficiency was also analyzed to guide the manufacturing process. After that, the mechanical structure of cavities was designed and all cavities were manufactured with oxygen free copper. The cold test and tuning of all cavities were carried out and the frequency error is mostly within the range of ±5 MHz, which basically does not affect the output power. Finally, the electron gun, the beam-wave interaction section and the collector were welded together. And the high power test was conducted immediately after the first high power C-band klystron protype was completed. When the electron gun operates at the voltage of 115 kV and current of 79.6 A, the klystron peak output power reaches 3.52 MW, the gain reaches 45.5 dB and the efficiency reaches about 38.5%. The high power test results show that this C-band high power klystron achieves the expected development goals.

Objective To investigate the clinical efficacy of preoperative therapeutic plasma exchange(TPE) in preventing acute rejection after ABO incompatible kidney transplantation(ABOi-KT). Methods Nine patients with ABOi-KT who were admitted to the renal transplant department of our hospital from April 2022 to April 2024 were retrospectively analyzed. They received a total of 28 TPEs before kidney transplantation, and the treatment plan was summarized as follows: The proportion of the substitute fluid, as well as the frequency and volume of TPE were determined based on the patient′s ABO blood group system antibody titer, gender, height, weight, hematocrit and other indicators upon admission. The patient′s relevant laboratory indicators, including hemoglobin, platelets, leukocytes, coagulation function, total protein, albumin, globulin, A/G, creatinine and urea nitrogen upon admission and after TPE were monitored and statistically analyzed. After transplantation, changes in renal function indicators such as ABO blood group system antibody titers, creatinine and urinary excretion were observed, and clinical symptoms of acute rejection, such as swelling, pain and edema in the transplanted kidney area were observed. Results Nine ABOi-KT patients had an average of about 3 TPEs before transplantation surgery, with an average total volume of approximately 2 500 mL to 3 500 mL per TPE, or approximately about 1.01 to 1.16 plasma volume (PV). After multiple TPEs, pre-transplantation antibody titers decreased by an average of 3 times compared to before TPE. There were no statistically significant differences in Hb, PLT, PT, PTA, INR, TBil, ALB, Cr and BUN (P>0.05), while statistically significant differences were found in WBC, APTT, Fbg, TP, GLB and A/G (P

Objective To explore the prognostic impact and clinical application value of therapeutic plasma exchange(TPE) intervention timing and liver injury periodization in patients with exertional heat stroke(EHS). Methods Data of 127 EHS patients from the First Medical Center of the General Hospital of the People′s Liberation Army from January 2011 to December 2023 were collected, then divided into the death group and the survival group based on therapeutic outcomes and into 5 stages according to the dynamic changes of ALT, AST, TBIL and DBIL. According to propensity score matching analysis, 11 patients in the survival group and 12 patients in the death group were included in the statistical analysis, and 20 of them were treated with TPE. The changes in indicators and clinical outcomes before and after TPE were observed, in order to evaluate the impact of intervention timing on prognosis. Results Among the 23 patients, 14 had no liver injury or could progress to the repair phase, resulting in 3 deaths(with the mortality rate of 21.43%), while 9 patients failed to progress to the repair phase, resulting in 9 deaths(with the mortality rate of 100%), with significant differences(P

Objective To review the occurrence of allergic reactions during therapeutic plasma exchange (TPE) and to explore the risk factors of TPE allergic reactions. Methods The clinical data of 929 patients treated with TPE using plasma components by the Department of Transfusion Medicine in our medical center from 2018 to 2023 were collected. The influencing factors of allergic reactions were analyzed by univariate analysis, and the independent risk factors of allergic reactions were analyzed by logistic multivariate regression analysis. Results A total of 4 071 TPEs were performed in 929 patients.Among them, 198 patients (21.31%) experienced 349 times (8.57%) of allergic reactions, with the incidence of grade Ⅰ, Ⅱ and Ⅲ allergic reactions of 16.33%, 81.38% and 2.29%, respectively, and no deaths. The univariate analysis showed that the patient′s age, allergy history, diagnosis of immune-related diseases, ICU admission, plasma consumption, total blood volume, maximum blood flow rate and combined use of albumin were related to the occurrence of allergic reactions (P

Abstract Background Lupus nephritis (LN) is the most common cause of kidney injury in systemic lupus erythematosus (SLE) patients and is associated with increased mortality. DNA methylation, one of the most important epigenetic modifications, has been reported as a key player in the pathogenesis of SLE. Hence, our article aimed to explore DNA methylation in CD4+ T cells from LNs to identify additional potential biomarkers and pathogenic genes involved in the progression of LN. Methods Our study enrolled 46 SLE patients with or without kidney injury and 23 healthy controls from 2019 to 2022. CD4+ T cells were sorted for DNA methylation genotyping and RNA-seq. Through bioinformatics analysis, we identified the significant differentially methylated CpG positions (DMPs) only in the LN group and validated them by Bisulfite PCR. Integration analysis was used to screen for differentially methylated and expressed genes that might be involved in the progression of LN, and the results were analyzed via cell experiments and flow cytometry. Results We identified 243 hypomethylated sites and 778 hypermethylated sites only in the LN cohort. Three of these DMPs, cg08332381, cg03297029, and cg16797344, were validated by Bisulfite PCR and could be potential biomarkers for LN. Integrated analysis revealed that the expression of BCL2L14 and IFI27 was regulated by DNA methylation, which was validated by azacytidine (5-aza) treatment. The overexpression of BCL2L14 in CD4+ T cells might induce renal fibrosis and inflammation by regulating the differentiation and function of Tfh cells. Conclusion Our study identified novel aberrant DMPs in CD4+ T cells only in LN patients and DNA methylation-regulated genes that could be potential LN biomarkers. BCL2L14 is likely involved in the progression of LN and might be a treatment target.

Abstract To successfully market to automotive parts customers in the Industrial Internet era, parts agents need to perform effective customer analysis and management. Dynamic customer segmentation is an effective analytical tool that helps parts agents identify different customer groups. RFM model and time series clustering algorithms are commonly used analytical methods in dynamic customer segmentation. The original RFM model suffers from the problems of R index randomness and ignoring customers’ perceived value. For most existing studies on dynamic customer segmentation, time series clustering techniques largely focus on univariate clustering, with less research on multivariate clustering. To solve the above problems, this paper proposes a dynamic customer segmentation approach by combining LRFMS and multivariate time series clustering. Firstly, this method represents each customer behavior as a time series sequence of the Length, Recency, Frequency, Monetary and Satisfaction variables. And then, we apply a multi-dimensional time series clustering algorithm based on three distance measurement methods called DTW-D, SBD, and CID to carry out customer segmentation. Finally, an empirical study and comparative analyses are conducted using customer transaction data of parts agents to verify the effectiveness of the approach. Additionally, a detailed analysis of different customer groups is made, and corresponding marketing suggestions are provided.

Abstract Increasing prevalence of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) constitutes an emerging water safety issue globally. However, the effectiveness of current water treatment techniques in the control of ARGs dissemination remains controversial. Here, we develop a dual-zone strategy based on piezoelectric membrane filtration to efficiently eliminate waterborne antibiotic resistance. Following complete ARB inactivation and effective ARGs reduction in the retentate near the membrane surface (zone 1), a subsequent trans-membrane process (zone 2) further promotes ARGs elimination in the permeate, due to boosted interactions between ARGs and reactive oxygen species (ROS) generated from piezoelectric peroxymonosulfate activation and minimized ROS competition from inactivated ARB within piezocatalytic channels. The abundance of ARGs was largely reduced to ~1.0 × 103 copies·mL−1 in the permeate from ~5.0 × 106 copies·mL−1 in the feed solution. The singlet oxygen (1O2) is demonstrated to be primarily responsible for ARB inactivation, while 1O2, hydroxyl radical (•OH), sulfate radical (SO4 ·−) and superoxide radical (·O2 −) can all participate in ARGs degradation. Our work demonstrates that the piezoelectric membrane-based dual-zone strategy has great potential to control the risk of ARGs dissemination.

Abstract Using a symmetry-preserving formulation of a vector $$\,\times \,$$ × vector contact interaction (SCI) and treating the proton as a quark + interacting-diquark bound state, whose structure is obtained by solving a Poincaré-covariant Faddeev equation, we provide a comprehensive, coherent set of predictions for unpolarised and polarised proton parton distribution functions (DFs): valence, glue, and four-flavour separated sea. The results enable many themes to be addressed, including: the asymmetry of antimatter in the proton; the neutron:proton structure function ratio; helicity retention in hard scattering processes; the charm quark momentum fraction; the sign and size of the polarised gluon DF; and the origin of the proton spin. In all cases where sound analyses of data are available, SCI predictions are semiquantitatively in agreement with the results. Those mismatches which exist are typically attributable to the momentum-independence of the underlying interaction. Judiciously interpreted, the SCI delivers a sound and insightful explanation of proton structure as expressed in DFs.

Pseudomyxoma peritonei (PMP) is an indolent malignant syndrome. The standard treatment for PMP is cytoreductive surgery combined with intraperitoneal hyperthermic chemotherapy (CRS + HIPEC). However, the high recurrence rate and latent clinical symptoms and signs are major obstacles to further improving clinical outcomes. Moreover, patients in advanced stages receive little benefit from CRS + HIPEC due to widespread intraperitoneal metastases. Another challenge in PMP treatment involves the progressive sclerosis of PMP cell-secreted mucus, which is often increased due to activating mutations in the gene coding for guanine nucleotide-binding protein alpha subunit ( GNAS ). Consequently, the development of other PMP therapies is urgently needed. Several immune-related therapies have shown promise, including the use of bacterium-derived non-specific immunogenic agents, radio-immunotherapeutic agents, and tumor cell-derived neoantigens, but a well-recognized immunotherapy has not been established. In this review the roles of GNAS mutations in the promotion of mucin secretion and disease development are discussed. In addition, the immunologic features of the PMP microenvironment and immune-associated treatments are discussed to summarize the current understanding of key features of the disease and to facilitate the development of immunotherapies.

Abstract Background The prognosis of advanced gastric cancer (AGC) is relatively poor, and long-term survival depends on timely intervention. Currently, predicting survival rates remains a hot topic. The application of radiomics and immunohistochemistry-related techniques in cancer research is increasingly widespread. However, their integration for predicting long-term survival in AGC patients has not been fully explored. Methods We Collected 150 patients diagnosed with AGC at the Affiliated Zhongshan Hospital of Dalian University who underwent radical surgery between 2015 and 2019. Following strict inclusion and exclusion criteria, 90 patients were included in the analysis. We Collected postoperative pathological specimens from enrolled patients, analyzed the expression levels of MAOA using immunohistochemical techniques, and quantified these levels as the MAOAHScore. Obtained plain abdominal CT images from patients, delineated the region of interest at the L3 vertebral body level, and extracted radiomics features. Lasso Cox regression was used to select significant features to establish a radionics risk score, convert it into a categorical variable named risk, and use Cox regression to identify independent predictive factors for constructing a clinical prediction model. ROC, DCA, and calibration curves validated the model’s performance. Results The enrolled patients had an average age of 65.71 years, including 70 males and 20 females. Multivariate Cox regression analysis revealed that risk (P = 0.001, HR = 3.303), MAOAHScore (P = 0.043, HR = 2.055), and TNM stage (P = 0.047, HR = 2.273) emerged as independent prognostic risk factors for 3-year overall survival (OS) and The Similar results were found in the analysis of 3-year disease-specific survival (DSS). The nomogram developed could predict 3-year OS and DSS rates, with areas under the ROC curve (AUCs) of 0.81 and 0.797, respectively. Joint calibration and decision curve analyses (DCA) confirmed the nomogram’s good predictive performance and clinical utility. Conclusion Integrating immunohistochemistry and muscle fat features provides a more accurate prediction of long-term survival in gastric cancer patients. This study offers new perspectives and methods for a deeper understanding of survival prediction in AGC.

Abstract Background “Multidisciplinary fast-track” (MFT) care can accelerate recovery and improve prognosis after surgery, but whether it is effective in older people after hip fracture surgery is unclear. Methods We retrospectively compared one-year all-cause mortality between hip fracture patients at least 80 years old at our institution who underwent hip fracture surgery between January 2014 and December 2018 and who then received MFT or conventional care. Multivariable regression was used to assess the association between MFT care and mortality after adjustment for confounders. Results The final analysis included 247 patients who received MFT care and 438 who received conventional orthopedic care. The MFT group showed significantly lower one-year mortality (8.9% vs. 14.4%, P = 0.037). Log-rank testing of Kaplan-Meier survival curves confirmed the survival advantage. However, the two groups did not differ significantly in rates of mortality during hospitalization or at 30 or 90 days after surgery. Regression analysis confirmed that MFT care was associated with lower risk of one-year mortality (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.281–0.788, P = 0.04), and the survival benefit was confirmed in subgroups of patients with anemia (HR 0.453, 95% CI 0.268–0.767, P = 0.003) and patients with American Society of Anesthesiologists grade III (HR 0.202, 95% CI 0.08–0.51, P = 0.001). Conclusions MFT care can reduce one-year mortality among hip fracture patients at least 80 years old. This finding should be verified and extended in multi-center randomized controlled trials.

Abstract Ovarian fibrosis, characterized by the excessive proliferation of ovarian fibroblasts and the accumulation of extracellular matrix (ECM), serves as one of the primary causes of ovarian dysfunction. Despite the critical role of ovarian fibrosis in maintaining the normal physiological function of the mammalian ovaries, research on this condition has been greatly underestimated, which leads to a lack of clinical treatment options for ovarian dysfunction caused by fibrosis. This review synthesizes recent research on the molecular mechanisms of ovarian fibrosis, encompassing TGF-β, extracellular matrix, inflammation, and other profibrotic factors contributing to abnormal ovarian fibrosis. Additionally, we summarize current treatment approaches for ovarian dysfunction targeting ovarian fibrosis, including antifibrotic drugs, stem cell transplantation, and exosomal therapies. The purpose of this review is to summarize the research progress on ovarian fibrosis and to propose potential therapeutic strategies targeting ovarian fibrosis for the treatment of ovarian dysfunction.

To determine the relationship of hemodialysis access with vital sign variability and hemodialysis-related headache (HRH). Adult outpatients receiving maintenance hemodialysis (MHD) were prospectively recruited, and 12 consecutive dialysis sessions were monitored. Intradialysis (hour-to-hour) and interdialysis (dialysis day-to-day) vital sign variabilities were assessed via three metrics: the difference between the maximum and minimum values, average real variability (ARV), and residuals. Multivariate logistic regression analysis was used to explore the factors triggering HRH. A total of 91 Chinese MHD patients (60.4% male) aged 58.5 ± 17.2 years were included, with 59 patients using radiocephalic arteriovenous fistulas (RCAVFs) and 32 patients using tunneled cuffed catheters (TCCs) for dialysis. The median dialysis vintage was 26.8 (12.0–44.7) months. Compared with the RCAVF group, the TCC group had significantly greater urea reduction (71.1 ± 9.3% vs. 61.7 ± 10.5%, p

Magnetite (Fe3O4) particles have been widely reported to enhance the anammox's activity in anammox granular sludge (AnGS), yet the underlying mechanisms remain unclear. This study demonstrates that both Fe3O4 microparticles (MPs) and nanoparticles (NPs) at a dosage of 200 mg Fe3O4/L significantly increased the specific anammox activity (SAA) of AnGS. Additionally, the transcriptional activities of the hzs and hdh genes involved in the anammox process, as well as the heme c content in AnGS, were also notably enhanced. Notably, Fe3O4 NPs were more effective than MPs in boosting anammox activity within AnGS. Mechanistically, Fe3O4 MPs released free iron, which anammox bacteria utilized to promote the synthesis of key enzymes, thereby enhancing their activity. Compared to MPs, Fe3O4 NPs not only elevated the synthesis of these key enzymes to a higher level but also induced a nanofluids effect on the surface of AnGS, improving substrate permeability and accessibility to intragranular anammox bacteria. Moreover, the nanofluids effect was identified as the primary mechanism through which Fe3O4 NPs enhanced anammox activity within AnGS. These findings provide new insights into the effects of nanoparticles on granular sludge systems, extending beyond AnGS.

ABSTRACTInfectious spleen and kidney necrosis virus (ISKNV), a member of the genus Megalocytivirus in the family Iridoviridae, can infect over 50 fish species and cause significant economic losses in Asia. Our previous study showed that hypoxia triggers the hypoxia-inducible factor pathway (HIF-pathway), leading to increased replication of ISKNV through promoting the upregulation of viral hypoxic response genes like orf077r. This study delved into the molecular mechanism of how ISKNV manipulates the HIF-pathway to enhance its replication. In vitro and in vivo experiments confirmed that ISKNV infection activated the HIF-pathway, which in turn promoted ISKNV replication. These findings suggest that ISKNV actively manipulates the HIF-pathway. Co-immunoprecipitation experiments revealed that the ISKNV-encoded protein VP077R interacts with the Von Hippel−Lindau (VHL) protein at the HIF-binding region, competitively inhibiting the interaction of HIF-1α with VHL. This prevents HIF degradation and activates the HIF-pathway. Furthermore, VP077R interacts with factor-inhibiting HIF (FIH), recruiting FIH and S-phase kinase-associated protein 1 (Skp1) to form an FIH – VP077R – Skp1 complex. This complex promotes FIH protein degradation via ubiquitination, further activating the HIF-pathway. These findings indicated that ISKNV takes over the HIF-pathway by releasing two “brakes” on this pathway (VHL and FIH) via VP077R, facilitating virus replication. We speculate that hypoxia initiates a positive feedback loop between ISKNV VP077R and the HIF pathway, leading to the outbreak of ISKNV disease. This work offers valuable insights into the complex interactions between the environment, host, and virus.