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AIM: To explore the clinicopathological and immunohistochemistry(IHC)characteristics of meibomian gland carcinoma(MGC).METHODS: Patients who were pathologically diagnosed as MGC from January 1, 2015 to December 31, 2020 in our hospital were enrolled, and their clinicopathological information was retrospectively analyzed. Cancer tissues from all the cases were IHC stained. En Vision two-step method, DAB staining, as well as hematoxylin re-staining were applied in the IHC assay.RESULTS: A total of 50 patients with 21 males and 29 females(1:1.38)were enrolled in the study, ranging from 26 to 80 years old, with a median age of 60 years. The upper eyelid, which was the predilection site, accounting for 66%(33/50). Histopathologically, moderately or poorly differentiated was in the majority(35/50, 70%). The expression rates of IHC parameters of MGC patients were as follows: GATA-3(49/50, 98%), EMA(49/50, 98%), CAM5.2(42/50, 84%), AR(41/50, 82%), MSH2(50/50, 100%), MSH6(50/50, 100%), MLH1(50/50, 100%), PMS2(50/50, 100%), Ki67(positive, 50%-90%). All the patients were followed up for 12 to 72 mo, with 5 cases of recurrence and 0 deaths.CONCLUSION: Pathological diagnosis of MGC should focus on observing cancer cells' cytoplasm to find relevant clues for cortical gland differentiation. Comprehensive analysis of multiple indicators is required when using IHC to assist diagnosis. For most MGC cancer cells, positive expressions of GATA-3, EMA, AR, CAM5.2 and a high Ki67 proliferation index could be always found. In addition, screening for Muir-Torre syndrome related IHC indicators could be also performed in diagnosing MGC simultaneously.

This is an article in the field of mineral processing engineering. For the flotation of sulfide ores whose gangue mineral is serpentine, serpentine can deteriorate the flotation of sulfide ores due to its easy mudification. To solve this problem, 2-hydroxyphosphonoacetic acid (HPAA) was used for the first time in this paper to eliminate the negative effect of serpentine on chalcopyrite flotation. In this article, the effect of HPAA on chalcopyrite/serpentine flotation system and the mechanism of action were investigated by microflotation test, turbidity test, zeta potential test, adsorption amount test and XPS test. The tests showed that serpentine is positively charged and chalcopyrite is negatively charged. Due to the electrostatic attraction, serpentine slime will adsorb on the surface of chalcopyrite, thus inhibiting the flotation of chalcopyrite. After adding HPAA, the flotation recovery of chalcopyrite was increased from 47.85% to 92.44%. The mechanism was that HPAA chemisorbed with Mg2+ of serpentine, which significantly reduced the surface potential of serpentine and caused repulsive effect on mineral particles, thus recovering the floatability of chalcopyrite.

Abstract The American Heart Association has updated its definition of cardiovascular health (CVH) with a new framework known as Life's Essential 8 (LE8). Although gestational CVH assessment has been recommended, its significance based on LE8 for birth outcomes is unknown. We thus evaluated the status of gestational CVH based on LE8 in 3036 pregnant women of the Shanghai Maternal-Child Pairs Cohort and the population of China Maternal Nutrition and Health Sciences Survey, and also examined the association between gestational CVH and child birth outcomes. We found that only a small proportion (12.84%) had high CVH, while 1.98% had low CVH in this cohort study. In adjusted models, a 10-point increase in the gestational CVH score, indicating a more favorable score, was associated with lower neonatal size such as birth weight (β: − 37.05 [95% confidence interval: − 52.93, − 21.16]), birth length (− 0.12[− 0.22, − 0.01]), weight-for-height z-score (− 0.07[− 0.12, − 0.03]), body mass index z-score (− 0.09 [− 0.13, − 0.04]), length-for-age Z-score (− 0.03 [− 0.06, − 0.01]), and weight-for-age z-score (− 0.08 [− 0.12, − 0.05]). Also, a 10-point increase in the gestational CVH score was associated with the lower risk of large for gestational age (LGA) (0.82 [0.73, 0.92]) and macrosomia infant (0.75 [0.64, 0.88]). CVH categories showed similar results. That is, better maternal CVH status in pregnancy was associated with lower neonatal size and lower risks for LGA and macrosomia in newborns.

Purpose: This study aims to translate and culturally adapt the revised The Teachers' Attitudes Towards Inclusion Scale Adjusted (TAISA) into Chinese and to evaluate its reliability and validity among Chinese preservice physical educators. Methodology: The English version of The Teachers' Attitudes Towards Inclusion Scale Adjusted (TAISA) was translated through a rigorous process that included a comprehensive literature review and consultations with subject matter experts. A survey was administered to 500 preservice physical educators in Chongqing. The adapted scale underwent thorough analysis, encompassing demographic frequency analysis, item analysis, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and evaluation of test-retest reliability. Results: The analysis revealed that the Chinese version of The Teacher Attitude toward Inclusive Education Scale for Preservice Physical Educators (TAISA-P) retained the original three-factor structure, comprising positive affect, training and perceived competence, and negative affect. After the removal of four items, the final scale consisted of 17 items, with each dimension containing 5 to 6 items. Factor loadings ranged from 0.442 to 0.705, and the model demonstrated a χ²/df ratio of 1.350, a root mean square error of approximation (RMSEA) of 0.066, a non-normed fit index (NNFI) of 0.825, a comparative fit index (CFI) of 0.946, an incremental fit index (IFI) of 0.948, and a goodness-of-fit index (GFI) of 0.834. The overall internal consistency reliability of TAISA-P was 0.759, with dimension-specific reliabilities of 0.835, 0.790, and 0.779. The test-retest reliability coefficient was 0.743 (P < 0.001). Conclusion: The Teacher Attitude toward Inclusive Education Scale for Preservice Physical Educators (TAISA-P) demonstrates strong reliability and validity, thereby establishing it as a suitable instrument for assessing the attitudes of Chinese preservice physical educators toward inclusive education.

Chirality plays a crucial function in the regulation of normal physiological processes and is widespread in organisms. Chirality can be imparted to nanomaterials, whether they are natural or manmade, through the process of asymmetric assembly and/or grafting of molecular chiral groups or linkers. Chiral inorganic nanomaterials possess unique physical and chemical features that set them apart from regular nanomaterials. They also have the ability to interact with cells and tissues in a specific manner, making them useful in various biomedical applications, particularly in the treatment of tumors. Despite the growing amount of research on chiral inorganic nanomaterials in the tumor microenvironment (TME) and their promising potential applications, there is a lack of literature that comprehensively summarizes the intricate interactions between chiral inorganic nanomaterials and TME. In this review, we introduce the fundamental concept, classification, synthesis methods, and physicochemical features of chiral inorganic nanomaterials. Next, we briefly outline the components of TME, such as T cells, macrophages, dendritic cells, and weak acids, and then discuss the anti-tumor effects of several chiral inorganic nanoparticles targeting these components and their potential for possible application during cancer therapy. Finally, the present challenges faced by chiral inorganic nanomaterials in cancer treatment and their future areas of investigation are disclosed.

Abstract Hepatocellular carcinoma (HCC) genomic research has discovered actionable genetic changes that might guide treatment decisions and clinical trials. Nonetheless, due to a lack of large-scale multicenter clinical validation, these putative targets have not been converted into patient survival advantages. So, it's crucial to ascertain whether genetic analysis is clinically feasible, useful, and whether it can be advantageous for patients. We sequenced tumour tissue and blood samples (as normal controls) from 111 Chinese HCC patients at Qingdao University Hospital using the 508-gene panel and the 688-gene panel, respectively. Approximately 95% of patients had gene variations related to targeted treatment, with 50% having clinically actionable mutations that offered significant information for targeted therapy. Immune cell infiltration was enhanced in individuals with TP53 mutations but decreased in patients with CTNNB1 and KMT2D mutations. More notably, we discovered that SPEN, EPPK1, and BRCA2 mutations were related to decreased median overall survival, although MUC16 mutations were not. Furthermore, we found mutant MUC16 as an independent protective factor for the prognosis of HCC patients after curative hepatectomy. In conclusion, this study connects genetic abnormalities to clinical practice and potentially identifies individuals with poor prognoses who may benefit from targeted treatment or immunotherapy.

Abstract Chronic wounds are a major complication in patients with diabetes. Here, we identify a therapeutic circRNA and load it into small extracellular vesicles (sEVs) to treat diabetic wounds in preclinical models. We show that circCDK13 can stimulate the proliferation and migration of human dermal fibroblasts and human epidermal keratinocytes by interacting with insulin-like growth factor 2 mRNA binding protein 3 in an N6-Methyladenosine-dependent manner to enhance CD44 and c-MYC expression. We engineered sEVs that overexpress circCDK13 and show that local subcutaneous injection into male db/db diabetic mouse wounds and wounds of streptozotocin-induced type I male diabetic rats could accelerate wound healing and skin appendage regeneration. Our study demonstrates that the delivery of circCDK13 in sEVs may present an option for diabetic wound treatment.

Extrachromosomal circular DNA (eccDNA), a chromosome-independent circular DNA, has garnered significant attention due to its widespread distribution and intricate biogenesis in carcinoma. Existing research findings propose that multiple eccDNAs contribute to drug resistance in cancer treatments through complex and interrelated regulatory mechanisms. The unique structure and genetic properties of eccDNA increase tumor heterogeneity. This increased diversity is a result of eccDNA's ability to stimulate oncogene remodeling and participate in anomalous splicing processes through chimeric cyclization and the reintegration of loop DNA back into the linear genome. Such actions promote oncogene amplification and silencing. eccDNA orchestrates protein interactions and modulates protein degradation by acting as a regulatory messenger. Moreover, it plays a pivotal role in modeling the tumor microenvironment and intensifying the stemness characteristics of tumor cells. This review presented detailed information about the biogenesis, distinguishing features, and functions of eccDNA, emphasized the role and mechanisms of eccDNA during cancer treatment, and further proposed the great potential of eccDNA in inspiring novel strategies for precision cancer therapy and facilitating the discovery of prognostic biomarkers for cancer.

In the reform of medical laboratory courses, innovative teaching methods and the development of a teaching assessment system are crucial. However, in past practices, assessments have encountered some issues: a greater emphasis on recording outcomes, neglecting supervision of the process; a focus on summarizing writing, overlooking the importance of analysis and improvement. In the teaching process of Jilin University’s Oncological Rehabilitation Experimental Teaching Demonstration Center, the Peer-Assisted Learning (PAL) model is employed to enhance students’ learning approaches. The innovative incorporation of Direct Observation of Procedural Skills (DOPS) and Mini-Clinical Evaluation Exercise (Mini-CEX) facilitates effective assessment and feedback. The combination of these reform measures not only addresses issues in experimental teaching but also enhances the internalization of students’ knowledge and skills. In this study, we applied the evaluation systems of Direct Observation of Procedural Skills and Mini-Clinical Evaluation Exercise (Mini-CEX) to the comprehensive laboratory course in oncological rehabilitation. We utilized questionnaires to assess the impact of these reforms on students, aiming to evaluate the effectiveness of the course modifications. Statistical analysis of the data revealed a high level of student approval and a strong willingness to learn under the new evaluation system. Compared to traditional teaching methods, the introduction of DOPS and Mini-CEX significantly enhanced students’ overall competencies and improved the quality of the oncological rehabilitation course. Our approach represents an innovative reform, suggesting that incorporating DOPS and Mini-CEX into teaching could provide a widely applicable and promising new educational method. This paper explores and systematically elaborates on the reform and practice of the teaching model and formative assessment in the comprehensive laboratory course of oncological rehabilitation.

Abstract Gamma‐aminobutyric acid (GABA) is involved in the signal transduction and metabolism of various substances in plants. Its in vivo detection in plants is of great importance for understanding its physiological role. In this study, an ultrasensitive electrochemical immunosensor is developed for in vivo detecting GABA in plants based on screen printed electrode (SPE) electrode. Gold nanoparticles (Au NP) was electrodeposited on the SPE to improve the conductivity of the electrode. Nanocomposite of ferrocene‐Carboxylated graphene oxide‐carboxylated multi‐walled carbon nanotubes (Fc‐GO‐MWCNT) was fabricated on the electrode to improve the electrochemical properties of the sensor, and Fc was used to generate electrochemical signals. Then polydopamine (PDA) was electropolymerized on the electrode to improve the electrochemical activity of the sensor and increase the loading amount of GABA antibody. The as‐prepared immunosensor shows the widest detection range of 10 fM to 10 mM, and lowest detection limit of 1.9 fM (S/N=3) for GABA. This immunosensor was applied for in vivo detecting GABA in the cucumber leaves under salt stress. Our sensor is the first electrochemical immunosensor for in vivo detecting GABA in plant. It proposes a new strategy for the development of immunosensor for in vivo detection of biomolecules in plants.

Indirect evaporative cooling (IEC), which utilizes natural cooling sources, is an advanced and promising technology to reduce the energy consumption of cooling systems in a data center (DC). This study presents a model of an IEC air-conditioning unit in a DC using TRNSYS simulation software validated using actual operational data to investigate the adaptability of IEC units in data centers located in regions with varying humidity levels, providing a reference for their application and promotion in DCs. Based on this premise, the authors analyzed the meteorological characteristics of Urumqi (a dry region), Beijing (a region with medium humidity), and Shanghai (a region with high humidity), which are representative cities in different humidity zones. The analysis identified the annual operating hours of the unit’s three operation modes, including fresh-air indirect heat transfer (FAIHT), IEC, and hybrid. Simultaneously, the authors conducted a simulation of the unit’s yearly energy consumption and determined time change curves for annual energy consumption, hourly coefficient of performance (COP) throughout the year, and mechanical cooling in various locations. The results indicate that IEC air-conditioning systems are highly effective in promoting the efficiency of data centers in various humidity regions. Dry locations demonstrate the greatest adaptability, followed by regions with medium humidity and, finally, regions with high humidity. The findings indicate that IEC units provide significant energy efficiency and cost-effectiveness when deployed in typical urban DCs across various humidity zones in China. The average annual power-usage effectiveness (PUE) of each city’s DC utilizing the unit is less than 1.3, and the unit’s annual operational cost savings exceed 30%.

Leakage problems occur from time to time due to the large number of equipment and complex processes during oil and gas production and transportation. The traditional detection methods highly depend on manpower with large workload and are prone to missed and false alarms, which seriously affects the efficiency and safety of oil and gas production and transportation. With the continuous improvement of information technology and the rapid advancement of artificial intelligence (AI), the research on leakage detection technology based on AI methods has attracted more and more attention. This paper discusses the application scenarios of an AI agent based on the recently emerged large language model (LLM) technology in oil and gas production leakage detection: (1) Compared with the traditional leakage detection methods, this paper innovatively employs a combination of AI-based diagnostics and infrared temperature measurement technologies to develop a specialized small model for oil and gas leakage detection, which has been proven to significantly improve the accuracy of detecting industrial venting events in natural gas valve chambers; (2) By employing retrieval-augmented generation (RAG) technology, a knowledge vector library is constructed, utilizing a series of leakage-related documents, assisting the LLM to carry out knowledge questioning and inference. Compared with the traditional SimBERT, the accuracy can be improved by about 15% in the Q&A search ability test. The correct rate is about 70% higher than the SimBERT in the Chinese complex reasoning quiz. Also, it can still remain stable under high load conditions, with the interruption rate of retrieval closing to zero. (3) By combining the specialized small model and the knowledge Q&A tool, the natural gas valve chambers’ leakage detection AI agent based on the open-source LLM model was designed and developed, which preliminarily achieved the leakage detection based on the specialized small model, and the automatic processing of the retrieval reasoning process based on the knowledge Q&A tool and the intelligent generation of corresponding leakage disposal scheme. The effectiveness of the method has been verified by actual project data. This article conducts preliminary explorations into the in-depth applications of AI agents based on LLMs in the oil and gas energy industry, demonstrating certain positive outcomes.

Anomaly detection is a common analytical task aimed at identifying rare cases that differ from the majority of typical cases in a dataset. In the management of photovoltaic (PV) power generation systems, it is essential for electric power companies to effectively detect anomalies in PV sequence data, as this helps operators and experts understand and interpret anomalies within PV arrays when making response decisions. However, traditional methods that rely on manual labor and regular data collection are difficult to monitor in real time, resulting in delays in fault detection and localization. Traditional machine learning algorithms are slow and cumbersome in processing data, which affects the operational safety of PV plants. In this paper, we propose a visual analytic approach for detecting and exploring anomalous sequences in a PV sequence dataset via sequence learning. We first compare the sequences with their reconstructions through an unsupervised anomaly detection algorithm (Long Short-Term Memory) based on AutoEncoders to identify anomalies. To further enhance the accuracy of anomaly detection, we integrate the artificial intelligence of things (AIoT) technology with a strict time synchronization data collection and real-time processing algorithm. This integration ensures that data from multiple sensors are synchronized and processed in real time. Then, we analyze the characteristics of the anomalies based on the visual comparison of different PV sequences and explore the potential correlation factors to analyze the possible causes of the anomalies. Case studies based on authentic enterprise datasets demonstrate the effectiveness of our method in the anomaly detection and exploration of PV sequence data.

Nymphaea colorata, valued for its diverse flower colors and attractive shapes, is a popular ornamental aquatic plant. Anthocyanins provide color to flowers, and their biosynthesis is regulated by the R2R3-MYB transcription factor. In this study, we identified and analyzed the R2R3-MYB genes in N. colorata, focusing on their structure, evolution, expression patterns, regulatory mechanisms, and biological functions. We also investigated the role of the NcMYB25 gene in anthocyanin biosynthesis. There were 59 R2R3-MYB genes in N. colorata, distributed across 14 chromosomes. Among these, 14 genes were involved in segmental duplications and 6 in tandem duplications. Multiple R2R3-MYB transcription factors appeared to play a role in biological processes in N. colorata, including NcMYB48 in flavonoid synthesis, NcMYB33 in lignin synthesis, NcMYB23 in cold stress response, and NcMYB54 in osmotic stress response. Additionally, we identified 92 miRNAs in N. colorata, with 43 interacting with 35 R2R3-MYB genes. The NcMYB25 protein is localized in the nucleus and possesses transcriptional activation activity. Overexpression of the NcMYB25 gene in an apple pericarp resulted in anthocyanin accumulation. These findings provide insight into the evolutionary trajectory of the R2R3-MYB genes in N. colorata and highlight the regulatory function of the NcMYB25 gene in anthocyanin biosynthesis.

Immunostimulatory antibody conjugates (ISACs) as a promising new generation of targeted therapeutic antibody-drug conjugates (ADCs), that not only activate innate immunity but also stimulate adaptive immunity, providing a dual therapeutic effect to eliminate tumor cells. However, several ISACs are still in the early stages of clinical development or have already failed. Therefore, it is crucial to design ISACs more effectively to overcome their limitations, including high toxicity, strong immunogenicity, long development time, and poor pharmacokinetics. This review aims to summarize the composition and function of ISACs, incorporating current design considerations and ongoing clinical trials. Additionally, the review delves into the current issues with ISACs and potential solutions, such as adjusting the drug-antibody ratio (DAR) to improve the bioavailability of ISACs. By leveraging the affinity and bioavailability-enhancing properties of bispecific antibodies, the utility between antibodies and immunostimulatory agents can be balanced. Commonly used immunostimulatory agents may induce systemic immune reactions, and BTK (Bruton's tyrosine kinase) inhibitors can regulate immunogenicity. Finally, the concept of grafting ADC's therapeutic principles is simple, but the combination of payload, linker, and targeted functional molecules is not a simple permutation and combination problem. The development of conjugate drugs faces more complex pharmacological and toxicological issues. Standing on the shoulders of ADC, the development and application scenarios of ISAC are endowed with broader space.

Purpose: To investigate the effects of accommodation on the geometrical parameters of human lens. Methods: Eight databases from inception to November 2023 were used for the literature search: CNKI, CBM, VIP, Wan-Fang, PubMed, Web of Science, EMBASE, and the Cochrane Library. The Methodological Index for Non-randomized Studies was used to assess the risk of bias. The PRISMA were followed and the following outcomes were taken into consideration: lens diameter (LD), lens thickness (LT), anterior curvature radius (ACR), posterior curvature radius (PCR), lens center position (LCP), and total cross-sectional area (TCSA). This systematic review was registered on an international platform for registered systematic reviews and meta-analysis (INPLASY202260085). Results: A total of 19 studies were included. LT increased by 0.04 mm/D (18 studies; 95% confidence interval [CI], 0.03–0.06; I2 = 96.6%; P

Abstract Delayed wound healing is a major complication of diabetes, and is associated with impaired cellular functions. Current treatments are unsatisfactory. Based on the previous reports on microRNA expression in small extracellular vesicles (sEVs), miR‐17‐5p‐engineered sEVs (sEVs17‐OE) and encapsulated them in gelatin methacryloyl (GelMA) hydrogel for diabetic wounds treatment are fabricated. SEVs17‐OE are successfully fabricated with a 16‐fold increase in miR‐17‐5p expression. SEVs17‐OE inhibited senescence and promoted the proliferation, migration, and tube formation of high glucose‐induced human umbilical vein endothelial cells (HG‐HUVECs). Additionally, sEVs17‐OE also performs a promotive effect on high glucose‐induced human dermal fibroblasts (HG‐HDFs). Mechanism analysis showed the expressions of p21 and phosphatase and tensin homolog (PTEN), as the target genes of miR‐17‐5p, are downregulated significantly by sEVs17‐OE. Accordingly, the downstream genes and pathways of p21 and PTEN, are activated. Next, sEVs17‐OE are loaded in GelMA hydrogel to fabricate a novel bioactive wound dressing and to evaluate their effects on diabetic wound healing. Gel‐sEVs17‐OE effectively accelerated wound healing by promoting angiogenesis and collagen deposition. The cellular mechanism may be associated with local cell proliferation. Therefore, a novel bioactive wound dressing by loading sEVs17‐OE in GelMA hydrogel, offering an option for chronic wound management is successfully fabricated.

Abstract The overcrowding of scenic spots not only threatens tourists’ safety but also affects the travel experience. Traditional methods for addressing tourist overload have involved limited access and guided evacuation. While limited access has been effective, it often results in a diminished tourist experience. Moreover, the existing guided evacuation rarely considers the impact on tourists’ experience, resulting in a low willingness to cooperate and making it difficult to estimate evacuation effort efficiency. To solve these problems, this paper proposed a tourist evacuation route recommendation algorithm based on a graph neural network considering the similarity of tourism styles (PER-GCN) and designed a visualization system to simulate and analyse evacuation efficiency. First, the interaction matrix of tourists and scenic spots was constructed using graph mining to extract the high-order interaction information. In the output layer, the similarity between scenic spots and tourism styles was calculated to further improve the accuracy of scenic spot recommendations. Second, due to route complexity and the real-time carrying capacity of scenic spots, the researchers optimized the evacuation routes. Finally, taking the West Lake spot as the case study, the effectiveness of PER-GCN was verified. Additionally, a visualization system was designed to monitor tourist flow in real time and analyse tourist portraits according to the clustering results of scenic spot styles. In addition, the evacuation efficiency of scenic spots was analysed by adjusting the parameters of tourists’ willingness to cooperate, evacuation batch, and the weight of route complexity and scenic spot carrying capacity.

This research produced five hybrid-bonded fiber-reinforced plastic (HB-FRP)-reinforced beam specimens, and different fatigue load amplitudes were used as parameter variables for the fatigue performance tests of the FRP–concrete interface. The results show that FRP sliding with the number of cycles can be roughly divided into fatigue initiation stage, fatigue development stage, and fatigue damage stage, and finally, because the load is too large and friction, pin, and bonding cannot provide a greater inhibition effect, FRP adhesive length is not enough to withstand the stripping load and failure. FRP slip increases with increasing fatigue load amplitude for the same number of fatigue cycles; for the specimens with fatigue damage, the interfacial stiffness of FRP–concrete decreases with the increase in the number of cyclic, and the rate of stiffness damage at the FRP–concrete interface accelerates with increasing fatigue load amplitude. For fatigue load magnitudes higher than 0.6, the slopes of fatigue bond–slip curves decrease with the increase in the number of cycles. When the fatigue load magnitude is lower than 0.4, the slope of the fatigue bond–slip curve increases with the number of cycles and is close to the slope of the monotonically loaded curve. Due to the difference in load class, the bond strength of HB-F-1 continues to decrease with the increase in fatigue times, decreasing by 26% after 100 fatigue cycles and decreasing to 7.33 MPa after 5000 fatigue cycles. The bond strength of the sample HB-F-2 first increased and then decreased with the increase in fatigue times. After 10,000 fatigue cycles, the bond strength decreased by 8%, and at 11,133,300 fatigue breaks, the bond strength of the sample HB-F-3 continued to increase with the increase in fatigue times. At 2 million fatigue load cycles, the bond strength increased to 7 MPa, far from reaching the peak strength. The empirical formulas for the fatigue life curve of HB-FRP-reinforced specimens under single steel fasteners are proposed.

miRNAs have been shown to be involved in the regulation of a variety of physiological and pathological processes, but their use in the treatment of diseases is still limited due to their instability. Biomimetic nanomaterials combine nanomaterials with cellular components that are readily modifiable and biocompatible, making them an emerging miRNA delivery vehicle. In this study, adipose-derived MSC membranes were wrapped around PLGA-PEI loaded with miR-21 through co-extrusion and later transplanted into C57BL/6 mice wounds. The wound-healing rate, epithelialization, angiogenesis, and collagen deposition were assessed after treatment and corroborated in vitro. Our study demonstrated that m/NP/miR-21 can promote wound healing in terms of epithelialization, dermal reconstruction, and neovascularization, and it can regulate the corresponding functions of keratinocytes, fibroblasts, and vascular endothelial cells. m/NP/miR-21 can inhibit the expression of PTEN, a gene downstream of miR-21, and increase the phosphorylation activation of AKT, which can then regulate the functions of fibroblasts. In conclusion, this provides a new approach to therapy for skin wounds using microRNA transporters and biomimetic nanoparticles.

Abstract Background and Aim Adequate bowel preparation is essential for colonoscopy, which is important for detecting colon polyps and preventing colorectal cancer. Linaclotide is approved for irritable bowel syndrome with predominant constipation (IBS‐C) symptoms. The main objective of this study was to explore the quality of bowel preparation by low‐volume compound polyethylene glycol (PEG) combined with linaclotide. Methods A total of 266 patients who underwent colonoscopy in Shangrao People's Hospital from June 2021 to June 2022 were randomized to 1 of 3 split PEG regimens: 4LPEG, 2LPEG, and 2LPEG + L (linaclotide). The primary end point was adequate bowel preparation (Boston Bowel Preparation Scale [BBPS] total score of ≥6, with each of three colonic segments subscores ≥2). Secondary outcomes were polyp detection rates and the incidence of adverse reactions. Results Over 12 months, 266 subjects were randomized into 2LPEG (n = 12), 4LPEG (n = 112), or 2LPEG + L (n = 142). There were no significant differences between the 4LPEG and 2LPEG + L groups in achieving adequate bowel preparation (P > 0.05). The mean BBPS score of the total colon, left hemi‐colon, right hemi‐colon, and transverse in the 2LPEG + L group was higher than that in the 2LPEG group (P

Neutrophil extracellular traps (NETs) have been considered a significant unfavorable factor for wound healing in diabetes, but the mechanisms remain unclear. The therapeutic application of small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) has received considerable attention for their properties. Hypoxic preconditioning is reported to enhance the therapeutic potential of MSC-derived sEVs in regenerative medicine. Therefore, the aim of this study is to illustrate the detailed mechanism of NETs in impairment of diabetic wound healing and develop a promising NET-targeting treatment based on hypoxic pretreated MSC-derived sEVs (Hypo-sEVs). Excessive NETs were found in diabetic wounds and in high glucose (HG)-induced neutrophils. Further research showed that high concentration of NETs impaired the function of fibroblasts through activating endoplasmic reticulum (ER) stress. Hypo-sEVs efficiently promoted diabetic wound healing and reduced the excessive NET formation by transferring miR-17–5p. Bioinformatic analysis and RNA interference experiment revealed that miR-17–5p in Hypo-sEVs obstructed the NET formation by targeting TLR4/ROS/MAPK pathway. Additionally, miR-17–5p overexpression decreased NET formation and overcame NET-induced impairment in fibroblasts, similar to the effects of Hypo-sEVs. Overall, we identify a previously unrecognized NET-related mechanism in diabetic wounds and provide a promising NET-targeting strategy for wound treatment.

Fungal infections have become clinically challenging owing to the emergence of drug resistance in invasive fungi and the rapid increase in the number of novel pathogens. The development of drug resistance further restricts the use of antifungal agents. Therefore, there is an urgent need to identify alternative treatments for Cryptococcus neoformans (C. neoformans). Disulfiram (DSF) has a good human safety profile and promising applications as an antiviral, antifungal, antiparasitic, and anticancer agent. However, the effect of DSF on Cryptococcus is yet to be thoroughly investigated. This study investigated the antifungal effects and the mechanism of action of DSF against C. neoformans to provide a new theoretical foundation for the treatment of Cryptococcal infections. In vitro studies demonstrated that DSF inhibited Cryptococcus growth at minimum inhibitory concentrations (MICs) ranging from 1.0 to 8.0 μg/mL. Combined antifungal effects have been observed for DSF with 5-fluorocytosine, amphotericin B, terbinafine, or ketoconazole. DSF exerts significant protective effects and synergistic effects combined with 5-FU for Galleria mellonella infected with C. neoformans. Mechanistic investigations showed that DSF dose-dependently inhibited melanin, urease, acetaldehyde dehydrogenase, capsule and biofilm viability of C. neoformans. Further studies indicated that DSF affected C. neoformans by interfering with multiple biological pathways, including replication, metabolism, membrane transport, and biological enzyme activity. Potentially essential targets of these pathways include acetaldehyde dehydrogenase, catalase, ATP-binding cassette transporter (ABC transporter), and iron-sulfur cluster transporter. These findings provide novel insights into the application of DSF and contribute to the understanding of its mechanisms of action in C. neoformans.

Soaring bird migration often relies on suitable terrain and airflow; therefore, route selection is vital for successful migration. While age and experience have been identified as key factor influencing migration route selection among soaring raptors in the African-Eurasian Flyway, how they shape the migration route of soaring raptors in East Asia is still largely unknown. In this study, we investigated potential variations in the routes and timing in autumn migration of juvenile and older soaring birds, using count data of Greater Spotted Eagles (Clanga clanga) from two coastal sites and two inland sites in China. From 2020 to 2023, we recorded a total of 340 individuals, with the highest site averaging over 90 individuals per autumn, making it one of the world’s top single-season counts and thus a globally important site for this species. We found that 82% and 61% records from coastal sites were juveniles, significantly higher than inland sites (15% and 24%). Juveniles at all four sites exhibited markedly earlier median passage time than non-juveniles, with brief overlapping in their main migration periods. Both coastal sites are located on the tip of peninsulas stretching southwest, requiring long overwater flights if crossing the Bohai Bay or Beibu Gulf, which would be energetically demanding and increase mortality risk. Experienced individuals may have learned to avoid such terrain and subsequent detour, while juveniles are more prone to enter these peninsulas due to lack of experience and opportunities for social learning, or following other raptor species that are more capable of powered flight. Our findings highlight the importance of age and experience in migration route selection of large soaring birds.

How does foreign aid affect recipient countries’ labor institutions? Extant empirical evidence is sparse due to ambiguous theoretical predictions and potential endogeneity issues. This study uses data detailing aid flow and institutional functions to mitigate such inconclusiveness and displays originality by constructing a concise theoretical framework in which foreign aid contributes to the improvement of the labor institutions in recipient countries through two mechanisms—economic growth purpose and expected aid attraction. The findings indicate that only aid to enhance local economic growth provides incentives to change domestic labor markets. Such effects have a more crucial influence on labor institutions of minimum wage, collective bargaining rights, and working hours than those related to hiring and firing regulations, mandated costs for worker dismissal, and conscription. For comparison with the actual aid level, we construct forecasted proxies to capture exogenous fluctuations in aid, determining that domestic labor markets can also change via a novel mechanism, as the recipient voluntarily mimics the funder’s labor policies in anticipation of receiving future aid, with exact amounts derived from the noninstitutional characteristics of pairs of bilateral recipient and giver economies. Therefore, we provide policy implications for the aid giver on how to secure a continued and increased aid flow and for the aid receivers on which aspects of reforming measures are most effective in enhancing the labor market regulations.

China's rural revitalization strategy has expanded non-agricultural employment opportunities for rural residents. This has directly raised farmers' incomes and household expenditures, which in turn has contributed to the upgrading of industrial structure. Using provincial data for 2012-2021, our study investigates how this employment transition affects industrial development. The effect of rural residents' consumption expenditures on this relationship is also explored through a linkage model to help measure the extent of the impact. This study further explores the regional differences in this effect and its robustness. The findings suggest that non-farm employment significantly contributes to industrial structural upgrading. However, this effect is not consistent across regions. Moreover, rural residents' consumption plays a pivotal role in this relationship. Governments should therefore encourage more non-farm jobs, stimulate domestic demand and use rural consumption as a key growth catalyst, especially after the demographic dividend disappears. It is also important to take into account regional nuances in policy formulation and make adjustments to cater for these differences to prevent any potential imbalances.

Carbon risk may have potential influences on the green transition of enterprises. This paper thoroughly investigates the effect and mechanism of carbon risk on the transition towards sustainability. We use quantitative regression models and a panel of Chinese manufactural listed companies from 2011-2020. There is strong evidence manifesting that the effect of carbon risk on corporate green transition is positive and statistically significant. The green transition is marked by the overall encouragement of exploratory, exploitable, autonomous, and collaborative green innovation. The mechanism test indicates that the enhancement of internal R&D transformation and the pressure of external stakeholders are two fundamental pathways by which carbon risk influences the green transition. Additional examination reveals that the beneficial impact is particularly noticeable for companies that have limited capital intensity, minimal governmental assistance, reduced financial limitations, and are state-owned enterprises. These results are robust to resolve the problem of endogeneity by means of instrumental variables, Heckman two-step, placebo test, propensity score matching and difference-in-difference ways. Against the background of carbon neutrality, it is of great significance to examine the relationship between carbon risk and corporate green transition. The conclusion complements the knowledge of carbon risk and green transition, as well as provides theoretical insights and practical enlightenment for the green transition of manufacturing enterprises in emerging economies.

In this paper, the basic framework of data mining is first proposed, and the data mining model based on the ID3 algorithm decision tree is constructed by analyzing the information gain of the attributes to divide each subset recursively, and the model is utilized to mine the data related to the teaching of practical application of English in the university effectively. Then, the attributes of support, confidence, and interest from the Apriori rule association algorithm are utilized to measure students’ evaluation of English teaching. Finally, the applicability of this paper’s algorithm was evaluated by indicators such as classification accuracy and computing speed, and the effectiveness of the English practical application integrated teaching system was verified in terms of the dimensions of students’ English literacy, learning interest, and classroom problems. The results show that the mean values of students’ English basic knowledge, English application ability, English core skills, and English awareness attitude are 4.02, 4.15, 4.06, and 3.99, respectively, and the students’ learning interest has been improved by at least 50%, indicating that the teaching effect is good.

Aim: This is a Chinese population-based study aimed to determine the causes and clinical features of drug-induced liver injury (DILI) from traditional Chinese medicines (TCMs) and current Western medicines (WMs) and identify the risk factors of drug-induced liver failure (DILF) and chronic DILI for early recognition and better management. Methods: The medical records of patients who were diagnosed with DILI for at least six-month follow-up between January 2018 to December 2020 were reviewed and investigated. The risk factors of DILF and chronic DILI were identified by univariate and multivariate logistic regression analysis. Results: TCMs (47.5%) including herbal medicine (83.0% in TCM-induced DILI) and some Chinese patent drugs were the leading cause of DILI in the present study. Cholestatic type was more associated with severe and chronic DILI. Pre-existing gallbladder disease, initial total bilirubin (TBIL), initial prothrombin time (PT), initial antinuclear antibodies (ANA), and clinical classification are independent risk factors for DILF. Prolonged T0.5AST and T0.5GGT were independent risk factors for chronic DILI [area under the curve (AUC) = 0.812, 95% confidence interval (CI): 0.748–0.876, P < 0.001] with cut-off values of 8.5 days and 29.5 days, respectively. Conclusions: TCMs especially herbal medicine were the leading causes of DILI, and the risk of developing severe DILI was associated with pre-existing gallbladder disease, clinical classification, initial TBIL, PT, and ANA. T0.5AST and T0.5GGT might serve as indicators for chronicity.

Proso millet (Panicum miliaceum L.) is resilient to abiotic stress, especially to drought. However, the mechanisms by which its roots adapt and tolerate salt stress are obscure. In this study, to clarify the molecular mechanism of proso millet in response to drought stress, the physiological indexes and transcriptome in the root of seedlings of the proso millet cultivar ‘Yumi 2’ were analyzed at 0, 0.5, 1.0, 1.5, and 3.0 h of stimulated drought stress by using 20% PEG-6000 and after 24 h of rehydration. The results showed that the SOD activity, POD activity, soluble protein content, MDA, and O2−· content of ‘Yumi 2’ increased with the time of drought stress, but rapidly decreased after rehydration. Here, 130.46 Gb of clean data from 18 samples were obtained, and the Q30 value of each sample exceeded 92%. Compared with 0 h, the number of differentially expressed genes (DEGs) reached the maximum of 16,105 after 3 h of drought, including 9153 upregulated DEGs and 6952 downregulated DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that upregulated DEGs were mainly involved in ATP binding, nucleus, protein serine/threonine phosphatase activity, MAPK signaling pathway–plant, plant–pathogen interactions, and plant hormone signal transduction under drought stress, while downregulated DEGs were mainly involved in metal ion binding, transmembrane transporter activity, and phenylpropanoid biosynthesis. Additionally, 1441 TFs screened from DEGs were clustered into 64 TF families, such as AP2/ERF-ERF, bHLH, WRKY, NAC, MYB, and bZIP TF families. Genes related to physiological traits were closely related to starch and sucrose metabolism, phenylpropanoid biosynthesis, glutathione metabolism, and plant hormone signal transduction. In conclusion, the active oxygen metabolism system and the soluble protein of proso millet root could be regulated by the activity of protein serine/threonine phosphatase. AP2/ERF-ERF, bHLH, WRKY, NAC, MYB, and bZIP TF families were found to be closely associated with drought tolerance in proso millet root. This study will provide data to support a subsequent study on the function of the drought tolerance gene in proso millet.

Political risk, one of the most significant uncertainty shocks, affects firms’ future attitudes toward risks and plays a crucial role in their decision making. A stock price crash risk is a classical topic in financial markets; therefore, this paper probes the relationship between firm-level political risk and stock price crash risk based on a sample of Chinese listed firms from 2011 to 2020. This paper collects the MD&A textual material of Chinese listed firms and calculates the firm-level political risk of Chinese listed firms. Our results show that a firm’s stock price crash risk is positively associated with its firm-level political risk exposure. Our findings hold after conducting various robustness tests, including instrument variable regression and altering the measurement of stock price crash risk. Further discussion reveals that political involvement mitigates the positive effect of firm-level political risk on the risk of a stock price jump.

Abstract Using a clustering algorithm based on cloud‐to‐ground (CG) lighting data, 72,974 thunderstorms were identified and tracked in the middle reaches of the Yangtze River Basin from May to September of 2016–2020. Thunderstorms predominantly occur in the southeast region and move to the northeast at a speed of 16–64 km/hr. Most thunderstorms have short durations (98.3%, ≤3 hr) and low CG flash frequencies (90.0%, ≤64). Thunderstorms with longer durations are mainly triggered near the mountains and tend to occur (end) earlier (later) in the afternoon (evening). The peak composite reflectivity (CR) corresponding to CG flashes from all thunderstorms is 50 dBZ. Approximately 70% (20%) of CG flashes occur in convective (stratiform) areas. The first CG flash of a thunderstorm tends to occur in convective areas with a higher CR than that of the last CG flash. The average and maximum CRs of CG flashes increase significantly with thunderstorm duration.

Abstract This is the protocol for an evidence and gap map. The objectives are as follows: To map available randomized control trials, economic evaluations, and systematic reviews that assess the effectiveness and cost‐effectiveness of non‐pharmacological interventions for older people with a diagnosis of depression and identify any existing gaps in the evidence that can inform future research.

Abstract Diabetic wounds have imposed a significant burden on both patients and society with prolonged healing processes hindered by dysfunctional skin repair cells. Small extracellular vesicles (sEVs), as the important media for intercellular communications, show promising therapeutic potential in treating diabetic wounds by restoring cellular functions. However, low yields and limited bio‐function of sEVs greatly challenge their large‐scale clinical use. Here, we briefly overview the biogenesis and cellular uptake of sEVs, emphasize current advances in improving the yields of sEVs and optimizing the function of sEVs with engineering approaches, and summarize the applications of engineered sEVs in diabetic wound treatment. Furthermore, the undissolved issues during the clinical transformation of engineered sEVs are also discussed. This critical review aims to provide meaningful guidance for future applications of engineered sEVs in the management of diabetic wounds.

Green mold disease, caused by Trichoderma spp., is one of the most devastating diseases of mushrooms in China. The application of fungicides remains one of the important control methods among the integrated pest management tools for disease management in mushroom farms. This study aimed to identify Trichoderma spp., isolated from G. sichuanense fruiting bodies displaying green mold symptoms collected from mushroom farms in Zhejiang, Hubei, and Jilin Province, China, and evaluate their in vitro sensitivity to six fungicides. A total of 47 isolates were obtained and classified into nine Trichoderma spp. namely, T. asperellum, T. citrinoviride, T. ganodermatiderum, T. guizhouense, T. hamatum, T. harzianum, T. koningiopsis, T. paratroviride, and T. virens, through morphological characteristics and phylogenetic analysis of concatenated sequences of translation elongation factor 1-alpha (TEF) and DNA-dependent RNA polymerase II subunit (RPB2) genes. The pathogenicity test was repeated two times, and re-isolation of the nine Trichoderma spp. from the fruiting bodies of G. sichuanense fulfilled Koch’s postulates. Prochloraz manganese showed the best performance against most species. This research contributes to our understanding of green mold disease, reveals the phylogenetic relationships among Trichoderma species, and expands our knowledge of Trichoderma species diversity associated with green mold disease in G. sichuanense.

Nymphaea atrans belongs to the subgenus Anecphya and displays varied flower colors over successive days. Because of its excellent ornamental characteristics, this species is widely cultivated in waterscape gardens worldwide. Here, we have sequenced the complete chloroplast genome of N. atrans. The whole genome size is 160,990 bp in length with four subregions: large and small single-copy regions of 90,879 and 19,699 bp, respectively, separated by a pair of inverted repeat regions of 25,206 bp each. A total of 126 genes were annotated, including 82 coding genes, eight ribosomal RNAs, and 36 transfer RNAs. The total GC content of the complete genome was 39%. Phylogenetic analysis showed that N. atrans was closely related to N. immutabilis. In this study, we have provided the chloroplast genome of N. atrans as a valuable resource for further phylogenetic analysis of Nymphaea species.

ObjectiveTo analyze the association of maternal psychological resilience during pregnancy with parent-child interaction in early infancy and the mediating and moderating effect of postpartum depressive symptoms on the association. MethodsThe study was conducted during April 2016 – June 2020 among 3 429 mother-infant dyads recruited from the participants of Shanghai Maternal-Child Pairs Cohort. Baseline survey on the mothers was carried out at 12 – 14 weeks′ gestation with a self-administered questionnaire. Maternal psychological resilience during pregnancy was evaluated using the Resilience Scale for Adult (RSA). During follow-ups two months after delivery, postpartum depressive symptoms of the mothers was assessed with the Edinburgh Postnatal Depression Scale (EPDS) and parent-child interaction was estimated by main caregivers of the infants using a self-designed questionnaire under the guidance of community physicians. Unconditional binary logistic regression model was adopted to analyze the effect of maternal higher resilience on insufficient parent-child interaction in early infancy; causal mediation and stratified analysis were used to analyze the mediating and moderating effects of maternal postpartum depressive symptoms on the effect of maternal psychological resilience. ResultsOf the mothers, 1 738 (50.69%) and 1 691 (49.31%) were assessed as having high and low psychological resilience. Compared to the mothers with low resilience, the mothers with high resilience reported significantly higher proportion of with high socioeconomic status (56.24% vs. 36.94%) but lower proportions of aged < 25 years at the delivery (9.23% vs. 16.46%), tobacco exposure in first trimester (14.84% vs. 19.33%) and postpartum depressive symptoms (17.86% vs. 22.90%) (all P < 0.001). Unconditional binary logistic regression analysis showed that the mothers with high resilience were at a lower risk of insufficient parent-child interaction in early infancy than those with low resilience (adjusted odds ratio [aOR] = 0.75, 95% confidence interval [95% CI]: 0.63 – 0.89) after adjusting main confounders. The results of the causal mediation analysis revealed that high maternal resilience could play a protective role on insufficient parent-child interaction by reducing postpartum depressive symptoms, with a percentage mediated (PM) of 7.19% (ORnature indirect effect = 0.97, 95% CI: 0.95 – 0.99). Compared to the mothers with high resilience and without postpartum depressive symptoms, the mothers with only low resilience or postpartum depressive symptoms were at increased risk of insufficient parent-child interaction, with the aORs (95% CI) of 1.29 (1.06 – 1.56) or 1.45 (1.08 – 1.97); the increased risk was much higher (aOR = 2.20, 95% CI: 1.71 – 2.85) for the mothers with both low resilience and postpartum depressive symptoms. ConclusionHigh maternal resilience during pregnancy has a protective effect on insufficient parent-child interaction in early infancy, and postpartum depressive symptoms plays both mediating and moderating effect on the effect of maternal resilience.

Abstract Unhealable diabetic wounds need to be addressed with the help of newer, more efficacious strategies. Exosomes combined with biomaterials for sustained delivery of therapeutic agents are expected to bring new hope for chronic wound treatment. Here, the engineered exosomes modified for efficiently loading miR146a and attaching to silk fibroin patch (SFP) were demonstrated to promote diabetic wound healing. Silk fibroin binding peptide (SFBP) was screened through phage display, and SFBP-Gluc-MS2 (SGM) and pac-miR146a-pac fusion protein were constructed. The designed exosomes (SGM-Exos, miR146a-Exos, and SGM-miR146a-Exos) were isolated from the engineered placental mesenchymal stem cells (PMSCs) transduced with SGM or/and pac-miR146a-pac protein. Gluc signals indicated SGM-Exo@SFP markedly increased the binding rate and the stability of SGM-Exo. Moreover, the loading efficiency of miR146a in SGM-miR146a-Exos was ten-fold higher than that in miR146a-Exos. Superior to untreated, SGM-miR146a-Exo-only treated, and SFP-only treated groups, SGM-miR146a-Exo@SFP drived wound healing associated with less inflammation, collagen deposition, and neovascularization. The transcriptomics analysis suggested anti-inflammatory and regenerative effects with SGM-miR146a-Exo@SFP treatment. Here, we show efficient exosome@biomaterial-based miRNA delivery systems for regenerative medicine and tissue engineering.

In the fixed prosthesis process dental prosthesis treatment, the dentist needs to conceive the morphology of the tooth preparation and make numerous micro-adjustments by manual operation. This study aims to establish a digital design system for accurate designing of veneer preparation and study the trajectory planning of the robot-assisted preparation. According to the standard operation requirements, the projection line segmentation method based on point drawing is proposed for interactive selection to ensure the margin smoothness of the preparation area. The preparation depth is parameterized, and the foldback point correction method based on secondary segmentation is used for repairing the offset preparation area to ensure surface smoothness. The fenestration preparation model was obtained in the digital interactive design software. The model is divided into two feature areas which are interpolated by the B-spline curve and NURBS surface, respectively. The isoparametric curve method is used to plan the preparation trajectory. The experimental and theoretical values of the target feature points from the X, Y and Z coordinate directions were also calculated and analyzed. The experiment is carried out by the physical prototype of the tooth preparation robot. The maximum error of the feature points on the preparation are 0.180 mm, 0.104 mm and 0.142 mm in X, Y and Z directions, respectively. The confidence interval of the system error is stable within 0.30 mm. The error of the feature points verifies the feasibility of the digital interactive design system and the correctness of the trajectory planning of tooth veneer preparation. The system could have the potential to assist dentists in the precise design of the veneer preparation, improve the processing efficiency and ensure the effect of tooth veneer prosthesis.

RISC-V is an open-source and royalty-free instruction set architecture (ISA), which opens up a new era of processor innovation. RISC-V has the characteristics of modularization and extensibility, and explicitly supports domain-specific custom extensions. Nowadays, RISC-V is a popular ISA for embedded processors. However, there is still a gap between the capabilities of RISC-V and the requirements of various emerging computing scenarios (e.g., artificial intelligence, cloud computing). Recently, the RISC-V standards organization has continuously introduced new ISA extensions to meet the needs of advanced computing. There are also a variety of novel research proposed customized extensions of RISC-V for certain scenarios. As far as we know, there is a lack of a survey to systematically present the research progress of RISC-V ISA extensions. The goal of this paper is to provide a comprehensive survey on existing works about RISC-V ISA extensions. First, the application scenarios of RISC-V are introduced, and the requirements for ISA extensions are analyzed. Then, we survey the progress of official RISC-V ISA extension specification and recent research on RISC-V ISA extension. Finally, we highlight some possible future research opportunities on the RISC-V ISA extension.

Abstract Background Multiple perioperative inflammatory markers are considered important factors affecting the long-term survival of esophageal cancer (EC) patients. Hematological parameters, whether single or combined, have high predictive value. Aim To investigate the inflammatory status of patients with preoperative EC using blood inflammatory markers, and to establish and validate competing risk nomogram prediction models for overall survival (OS) and progression-free survival (PFS) in EC patients. Methods A total of 508 EC patients who received radical surgery (RS) treatment in The First Affiliated Hospital of Zhengzhou University from August 5, 2013, to May 1, 2019, were enrolled and randomly divided into a training cohort (356 cases) and a validation cohort (152 cases). We performed least absolute shrinkage and selection operator (LASSO)-univariate Cox- multivariate Cox regression analyses to establish nomogram models. The index of concordance (C-index), time-dependent receiver operating characteristic (ROC) curves, time-dependent area under curve (AUC) and calibration curves were used to evaluate the discrimination and calibration of the nomograms, and decision curve analysis (DCA) was used to evaluate the net benefit of the nomograms. The relative integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were calculated to evaluate the improvement in predictive accuracy of our new model compared with the AJCC staging system and another traditional model. Finally, the relationship between systemic inflammatory response markers and prognostic survival was explored according to risk plot, time-dependent AUC, Kaplan–Meier and restricted cubic spline (RCS). Results Based on the multivariate analysis for overall survival (OS) in the training cohort, nomograms with 10 variables, including the aggregate index of systemic inflammation (AISI) and lymphocyte-to-monocyte ratio (LMR), were established. Time-dependent ROC, time-dependent AUC, calibration curves, and DCA showed that the 1-, 3-, and 5 year OS and PFS probabilities predicted by the nomograms were consistent with the actual observations. The C-index, NRI, and IDI of the nomograms showed better performance than the AJCC staging system and another prediction model. Moreover, risk plot, time-dependent AUC, and Kaplan–Meier showed that higher AISI scores and lower LMR were associated with poorer prognosis, and there was a nonlinear relationship between them and survival risk. Conclusion AISI and LMR are easy to obtain, reproducible and minimally invasive prognostic tools that can be used as markers to guide the clinical treatment and prognosis of patients with EC.

Abstract Breast cancer (BC) cell lines are useful experimental models to understand cancer biology. Yet, their relevance to modelling cancer remains unclear. To better understand the tumour-modelling efficacy of cell lines, we performed RNA-seq analyses on a combined dataset of 2D and 3D cultures of tumourigenic MCF7 and non-tumourigenic MCF10A. To our knowledge, this was the first RNA-seq dataset comprising of 2D and 3D cultures of MCF7 and MCF10A within the same experiment, which facilitates the elucidation of differences between MCF7 and MCF10A across culture types. We compared the genes and gene sets distinguishing MCF7 from MCF10A against separate RNA-seq analyses of clinical luminal A (LumA) and normal samples from the TCGA-BRCA dataset. Among the 1031 cancer-related genes distinguishing LumA from normal samples, only 5.1% and 15.7% of these genes also distinguished MCF7 from MCF10A in 2D and 3D cultures respectively, suggesting that different genes drive cancer-related differences in cell lines compared to clinical BC. Unlike LumA tumours which showed increased nuclear division-related gene expression compared to normal tissue, nuclear division-related gene expression in MCF7 was similar to MCF10A. Moreover, although LumA tumours had similar cell adhesion-related gene expression compared to normal tissues, MCF7 showed reduced cell adhesion-related gene expression compared to MCF10A. These findings suggest that MCF7 and MCF10A cell lines were limited in their ability to model cancer-related processes in clinical LumA tumours.

【Objective】To carry out cross breeding of high-quality Hybrid Cymbidium by using Hybrid Cymbidium germplasm resources, observe the performance of main target traits of offspring, and obtain new Hybrid Cymbidium varieties that meet the requirements of target traits.【Method】With Cymbidium sinense Yunv and C. lancifolium Wen Yin-1 as parents, conventional hybridization and seed culture of Hybrid Cymbidium were carried out. The characters of hybrid offspring were investigated and analyzed, and compared with their parents and control varieties Moye Amethyst.【Result】A new excellent Hybrid Cymbidium variety Yuqinglan was bred through the mixed selection breeding program. The collective hybrid was registered in the British Royal Horticultural Society under the name of Cymbidium SCAU Love Song. The results of variety comparison and many years of multi-point experiments show that Yuqinglan has compact plant type, erect leaves, erect inflorescences, 9.5 flowers on average, yellow white flowers with light fragrance, 5.6 cm in horizontal diameter and 5.9 cm in vertical diameter. It is cultivated in simple greenhouses in Guangzhou, and starts to flower in late December. Its single flower life is 30 days, and its ornamental period is 50 days. It is different from its parents in plant type, leaf type, and flower type, and its ornamental period is better than their parents, and it is more ornamental and disease resistant than the control Moye Amethyst, and it also has the characteristics of continuous flowering and forming flower lateral branches, which is the first report on orchids.【Conclusion】The new excellent Hybrid Cymbidium variety Yuqinglan, which has been bred through cross breeding and innovative improvement methods, has good characters and strong ornamental ability, and has broad prospects for popularization and application.

Study on the mineral processing of a high sulfur lead-zinc ore in Yunnan Province were conducted. Grades of lead, zinc and silver were 2.98%, 2.79% and 114.95 g/t, respectively. Ore was ground to -0.074 mm 76.19% and under the condition of selective flotation process, the combined reagents ZnSO4 and Na2CO3 used as the depressant and HQ-Pb and HQ-Zn were used as a novel galena and sphalerite collector. From the results of closed circuit tests, the lead concentrate, containing 56.62% Pb and 1915.38 g/t Ag, was produced, at recovery of 82.36% Pb and 73.44% Ag. And zinc concentrate of 45.92% Zn and 171.38 g/t Ag, was obtained, at recovery of 82.29% Zn and 7.58% Ag.

Abstract Background Cervical squamous cell carcinoma (CESC) is the most common histological type of cervical cancer which is the major cause of death in women worldwide. Although squamous cell carcinoma antigen (SCC-Ag) is widely used to detect CESC, it is not sensitive and specific enough to predict the disease. Methods We investigated serum CXC motif chemokine 10 (CXCL10) as potential diagnostic biomarker in detecting CESC in this study. Serum levels of CXCL10 and SCC-Ag were measured by ELISA or automated immunoassay in 345 participants, including 189 patients with different stages of CESC, 75 patients with cervical intraepithelial neoplasia, and 81 healthy individuals. Performances of CXCL10 and SCC-Ag as single biomarkers were analyzed by the ROC curves. The changes of serum levels of CXCL10 and SCC-Ag in 10 longitudinal followed-up CESC patients with partial response (PR) during chemoradiotherapy or chemotherapy were evaluated. Results The two markers showed similar diagnostic capacity in distinguishing both CESC early stage from healthy controls (AUCCXCL10 = 0.740, AUCSCC-Ag = 0.710) and all CESC from healthy controls (AUCCXCL10 = 0.775, AUCSCC-Ag =0.793). Moreover, CXCL10 showed ability in distinguishing cervical intraepithelial neoplasia from healthy control (AUCCXCL10 = 0.727) and cervical cancer SCC-Ag-negative from healthy control. (AUCCXCL10 = 0.739). The combination of CXCL10 and SCC-Ag displayed significant improvement of AUCs than individual SCC-Ag or CXCL10 in the analysis groups (healthy vs all cervical cancer, healthy vs cervical cancer early stage). The AUCs were improved to 0.877 (AUCSCC-Ag = 0.793, P

Introduction: Methamphetamine (METH) abuse by pregnant drug addicts causes toxic effects on fetal neurodevelopment; however, the mechanism underlying such effect of METH is poorly understood.Methods: In the present study, we applied three-dimensional (3D) neurospheres derived from the embryonic rat hippocampal tissue to investigate the effect of METH on neurodevelopment. Through the combination of whole genome transcriptional analyses, the involved cell signalings were identified and investigated.Results: We found that METH treatment for 24 h significantly and concentration-dependently reduced the size of neurospheres. Analyses of genome-wide transcriptomic profiles found that those down-regulated differentially expressed genes (DEGs) upon METH exposure were remarkably enriched in the cell cycle progression. By measuring the cell cycle and the expression of cell cycle-related checkpoint proteins, we found that METH exposure significantly elevated the percentage of G0/G1 phase and decreased the levels of the proteins involved in the G1/S transition, indicating G0/G1 cell cycle arrest. Furthermore, during the early neurodevelopment stage of neurospheres, METH caused aberrant cell differentiation both in the neurons and astrocytes, and attenuated migration ability of neurospheres accompanied by increased oxidative stress and apoptosis.Conclusion: Our findings reveal that METH induces an aberrant cell cycle arrest and neuronal differentiation, impairing the coordination of migration and differentiation of neurospheres.

Background: Pulmonary fibrosis (PF) is a terminal pathological change in a variety of lung diseases characterized by excessive deposition of extracellular matrix, for which effective treatment is lacking. Tangeretin (Tan), a flavonoid derived from citrus, has been shown to have a wide range of pharmacological effects. This study aimed to investigate the role and potential mechanisms of Tan on pulmonary fibrosis.Methods: A model of pulmonary fibrosis was established by administering bleomycin through tracheal drip, followed by administering Tan or pirfenidone through gavage. HE and Masson staining were employed to assess the extent of pulmonary fibrosis. Subsequently, Western blot, enzyme-linked immunosorbent assay (ELISA), RNA sequencing, and immunohistochemistry techniques were employed to uncover the protective mechanism of Tan in PF mice. Furthermore, A549 cells were stimulated with TGF-β1 to induce epithelial-mesenchymal transition (EMT) and demonstrate the effectiveness of Tan in mitigating PF.Results: Tan significantly ameliorated bleomycin-induced pulmonary fibrosis, improved fibrotic pathological changes, and collagen deposition in the lungs, and reduced lung inflammation and oxidative stress. The KEGG pathway enrichment analysis revealed a higher number of enriched genes in the PI3K/Akt pathway. Additionally, Tan can inhibit the EMT process related to pulmonary fibrosis.Conclusion: Taken together, the above research results indicate that Tan suppresses inflammation, oxidative stress, and EMT in BLM-induced pulmonary fibrosis via the PI3K/Akt pathway and is a potential agent for the treatment of pulmonary fibrosis.

Nuclear Factor Y (NF-Y) is a class of heterotrimeric transcription factors composed of three subunits: NF-A, NF-YB, and NF-YC. NF-YC family members play crucial roles in various developmental processes, particularly in the regulation of flowering time. However, their functions in petunia remain poorly understood. In this study, we isolated four PhNF-YC genes from petunia and confirmed their subcellular localization in both the nucleus and cytoplasm. We analyzed the transcript abundance of all four PhNF-YC genes and found that PhNF-YC2 and PhNF-YC4 were highly expressed in apical buds and leaves, with their transcript levels decreasing before flower bud differentiation. Silencing PhNF-YC2 using VIGS resulted in a delayed flowering time and reduced chlorophyll content, while PhNF-YC4-silenced plants only exhibited a delayed flowering time. Furthermore, we detected the transcript abundance of flowering-related genes involved in different signaling pathways and found that PhCO, PhGI, PhFBP21, PhGA20ox4, and PhSPL9b were regulated by both PhNF-YC2 and PhNF-YC4. Additionally, the transcript abundance of PhSPL2, PhSPL3, and PhSPL4 increased only in PhNF-YC2-silenced plants. Overall, these results provide evidence that PhNF-YC2 and PhNF-YC4 negatively regulate flowering time in petunia by modulating a series of flowering-related genes.