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Saline-alkali soils in Xinjiang are extensive and diverse. Reclaiming these soils for agricultural production plays a critical role in safeguarding food security in China. Exploring reclamation technologies that align with the arid environmental nature and modern water-saving irrigation techniques unique in the region is crucial for the sustainable use of these saline-alkali soils. This paper reviews the historical development and effectiveness of various saline-alkali soil management techniques in Xinjiang, based on literature review and quantitative evaluation of available data. We analyze the bottlenecks in managing saline-alkali soils under the constraints of limited water resources, providing insight into comprehensive utilization strategies for saline-alkali soils in the context of new challenges faced by the region. Based on the balance between water and soil resources, as well as the characteristics of secondary soil salinization in irrigated farmland, we propose an integrated ‘prevention, control, and treatment’ strategy for soil management in watersheds and irrigation districts in the region. Our recommendations include determining rational water resource allocation for irrigation and ecological maintenance, identifying effective techniques to desalinate specific soil layers in drip-irrigated farmlands, establishing dynamic monitoring systems to monitor soil salinization, and implementing prevention-control measures tailored to different types of salinized soils in different areas in the region. These provide a guidance for policymaking to improve management and utilization of saline-alkali soils in Xinjiang.

Weihang Yang,1,* Shuang Xia,1,* Liang Li,1,* Jiahao Xu,1,* Hongjian Ji,2,* Wanglin Yao,1 Fengchao Shi1 1Department of Orthopedics, Affiliated Hospital 6 of Nantong University, The Third People’s Hospital of Yancheng, Yancheng, Jiangsu, People’s Republic of China; 2Department of Pharmacy, Jiangsu Vocational College of Medicine, College of Pharmacy, Yancheng, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fengchao Shi; Wanglin Yao, Department of Orthopaedics, Affiliated Hospital 6 of Nantong University, The Third People’s Hospital of Yancheng, Yancheng, Jiangsu, 224000, People’s Republic of China, Tel +86-15189200280 ; +86-15995185295, Email shifengchao1980@126.com; 575733189@qq.comAbstract: This report describes a case of lumbar disc infection potentially induced by acupuncture in a 43-year-old male with a history of back pain. After acupuncture treatment at another hospital, the patient experienced worsened pain. Physical examination revealed tenderness at the upper lumbar intervertebral space and paravertebral percussion pain. Laboratory tests showed no bacterial growth in both aerobic and anaerobic blood cultures after 5 days, but C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were significantly elevated. CT and MRI scans revealed osteolysis of the L2/3 vertebral body and a paraspinal abscess in the left psoas muscle. The patient was treated with intravenous vancomycin (1 g every 12 hours for 4 weeks). After two weeks, CRP normalized, but ESR remained elevated. By week three, CRP increased to 61.19 mg/L, and severe anemia developed. Follow-up MRI indicated worsening of the lumbar infection. A transfusion was performed, and surgery was conducted in the fourth week. Intraoperative findings confirmed methicillin-resistant Staphylococcus aureus (MRSA) as the causative pathogen. Postoperatively, symptoms improved, and inflammatory markers normalized. This case highlights the need for standardized acupuncture practices and prompt surgical intervention in cases of infectious discitis unresponsive to conservative treatment.Keywords: acupuncture, lumbar discitis, methicillin-resistant Staphylococcus aureus, surgical treatment

Chuanchuan Sun,1,2 Xinhai Zhao,1 Xianghong Wang,3 Yeye Yu,1 Heng Shi,4 Jun Tang,5 Shengyun Sun,1 Shiping Zhu1 1Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 2Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 3Department of Endocrinology and Metabolism, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai, People’s Republic of China; 4Department of Gastroenterology, The Central Hospital of Shaoyang, Shaoyang, People’s Republic of China; 5The Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai(Zhuhai Sixth People’s Hospital), Zhuhai, People’s Republic of ChinaCorrespondence: Shengyun Sun; Shiping Zhu, Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinan University, No. 613 Huangpu Avenue West, Tianhe District, Guangzhou, Guangdong Province, 510630, People’s Republic of China, Email shengyunsun2020@163.com; zhushiping@jnu.edu.cnPurpose: This study aimed to examine the impact of APS on acute kidney injury induced by rhabdomyolysis (RIAKI), exploring its association with macrophage M1 polarization and elucidating the underlying mechanisms.Methods: C57BL/6J mice were randomly assigned to one of three groups: a normal control group, a RIAKI model group, and an APS treatment group. Techniques such as flow cytometry and immunofluorescence were employed to demonstrate that APS can inhibit the transition of renal macrophages to the M1 phenotype in RIAKI. Furthermore, the raw264.7 macrophage cell line was chosen and induced into the M1 phenotype to further examine the impact of APS on this model and elucidate the underlying mechanism.Results: Administration of APS led to a significant decrease in UREA levels by 25.2% and CREA levels by 60.9% within the model group. Also, APS exhibited an inhibitory effect on the infiltration of M1 macrophages and the cGAS-STING pathway in kidneys within the RIAKI, subsequently leading to decreased serum concentrations of IL-1β, IL-6 and TNF-α by 44.5%, 12.9%, and 10.3%, respectively, consistent with the results of in vitro experiments. Furthermore, APS exhibited an anti-apoptotic effect on MPC5 cells when co-cultured with M1 macrophages.Conclusion: Astragalus polysaccharide (APS) potentially mitigated rhabdomyolysis-induced renal damage by impeding the M1 polarization of macrophages. This inherent mechanism might involve the suppression of the cGAS-STING pathway activation within macrophages. Furthermore, APS could endow protective effects on podocytes through the inhibition of apoptosis.Keywords: astragalus polysaccharide, macrophages, rhabdomyolysis-induced acute kidney injury, cGAS-STING pathway

Karen G Carrasquillo,1 Kellen Riccobono,1,4 Jennifer Liao,2 Yueming Shi,3 Bita Asghari,1 Daniel Brocks,1 Estelle Crowley,1 Buddika Peiris3 1Department of Ophthalmology, BostonSight, Needham, MA, 02494, USA; 2Specialty and Advanced Care, New England College of Optometry, Boston, MA, 02115, USA; 3Department of Mathematical Sciences, Worcester Polytechnic Institute, Worcester, MA, 01609, USA; 4Currently at: Department of Ophthalmology, Central Texas Eye Center, San Marcos, TX, 78666, USACorrespondence: Karen G Carrasquillo, Department of Ophthalmology, BostonSight, 464 hillside Avenue, Suite 205, Needham, MA, 02494, USA, Tel +1 781-726-7337, Fax +1 781-726-7310, Email kcarrasquillo@bostonsight.orgPurpose: Retrospective study to review scleral lens outcomes in the pediatric population over a 21-year period, at a single clinical center.Results: A total of 209 pediatric eyes (108 males and 101 females), distributed between 97 right and 112 left eyes, of which 147 eyes had ocular surface disease and 62 eyes had irregular cornea/refractive conditions, were treated with scleral lenses over a 21-year period. The mean age at the time of treatment initiation was 10.6 ± 2.6 years and at the time of the last evaluation recorded was 14.7 ± 4.0 years. One hundred and forty-seven eyes (70%) continued to wear scleral lenses at the time of review, with a mean duration of lens wear of 8.2 ± 4.6 years. Sixteen eyes (8%) discontinued lens wear, and of these, challenges with application and removal were the predominant reason for discontinuation. The lens wearing status of forty-six eyes (22%) was unknown. Mean LogMAR visual acuity at presentation for the entire cohort was 0.93 ± 0.74 and improved to 0.43 ± 0.58, p < 0.05 with scleral lens wear. LogMAR visual acuity at the last evaluation recorded was 0.4 ± 0.6, p < 0.05. The mean initial lens diameter of the full study cohort was 17.7 ± 1.2 mm, with a mean increase of 1.3mm (p = 0.0004) over the study period, to end with a mean final diameter of 18.2 ± 1.5 mm, at the time of the last evaluation recorded.Conclusion: Scleral lenses are a viable option for therapeutic and visual rehabilitation applications in the pediatric population for both ocular surface disease and irregular cornea/refractive conditions. Most eyes continued to wear lenses over a 21-year review period. The mean final lens diameter was 18.2mm, suggesting that larger diameters do not appear to be a deterrent or obstacle for successful long-term outcomes in the pediatric population.Keywords: scleral lenses, pediatrics, ocular surface disease, irregular cornea, PROSE

Computational spectrometers utilizing disordered structures have emerged as promising solutions for meeting the imperative demand for integrated spectrometers, offering high performance and improved resilience to fabrication variations and temperature fluctuations. However, the current computational spectrometers are impractical because they rely on a brute-force random design approach for disordered structures. This leads to an uncontrollable, non-reproducible, and suboptimal spectrometer performance. In this study, we revolutionize the existing paradigm by introducing a novel inverse design approach for computational spectrometers. By harnessing the power of inverse design, which has traditionally been applied to optimize single devices with simple performance, we successfully adapted it to optimize a complex system comprising multiple correlated components with intricate spectral responses. This approach can be applied to a wide range of structures. We validated this by realizing a spectrometer utilizing a new type of disordered structure based on interferometric effects that exhibits negligible loss and high sensitivity. For a given structure, our approach yielded a remarkable 12-times improvement in the spectral resolution and a four-fold reduction in the cross-correlation between the filters. The resulting spectrometer demonstrated reliable and reproducible performance with the precise determination of structural parameters.

The Metaverse depicts a parallel digitalized world where virtuality and reality are fused. It has economic and social systems like those in the real world and provides intelligent services and applications. In this paper, we introduce the Metaverse from a new technology perspective, including its essence, corresponding technical framework, and potential technical challenges. Specifically, we analyze the essence of the Metaverse from its etymology and point out breakthroughs promising to be made in time, space, and contents of the Metaverse by citing Maslow's Hierarchy of Needs. Subsequently, we conclude four pillars of the Metaverse, named ubiquitous connections, space convergence, virtuality and reality interaction, and human-centered communication, and establish a corresponding technical framework. Additionally, we envision open issues and challenges of the Metaverse in the technical aspect. The work proposes a new technology perspective of the Metaverse and will provide further guidance for its technology development in the future.© 2022 Published by Elsevier Ltd.

Abstract Intracardiac echocardiography (ICE) has been used to guide radio-frequency catheter ablation (RFCA) for better catheter navigation and less radiation exposure in treating atrial fibrillation (AF). This retrospective cohort study enrolled 227 AF patients undergoing ICE- or traditional fluoroscopy (TF)-guided RFCA for AF in a tertiary hospital. ICE was used more often in patients with atrial tachycardia [odds ratio (OR) 3.692, p = 0.062], a higher score of Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly (OR 1.541, p = 0.050), or heart failure (OR 2.098, p = 0.156). Based on the comparisons of 47 propensity score-matched pairs from 156 patients only undergoing pulmonary vein isolation (PVI), patients using ICE exhibited a significantly higher success rate in the first transseptal puncture (100% vs. 87.2%, p = 0.041) and less radiation exposure [utilization of radiographic contrast agent (2.7 ml vs. 6.0 ml, p

Abstract In this paper, river sand, fly ash, modified desulfurization gypsum, an expansion agent, and a water-reducing agent are incorporated into an engineered cementitious composite (ECC) to study the physical and mechanical properties and impermeability of the ECC. The mechanism of PVA fibers is also analyzed. Fiber grating sensing technology is used to monitor the shaft lining in real-time and assess its engineering application effectiveness. The results show that the optimal mix ratio of high-strength ECC is 20% silica fume, 4% desulfurization gypsum, 6% expansion agent, and 1.9% water-reducing agent. When the compressive strength of the ECC exceeds 60 MPa, the ultimate tensile strain reaches 2.84%, the ultimate bending strength reaches 14.06 MPa, and the impermeability grade reaches P8, indicating good flow performance. These properties meet the requirements of actual engineering for ECC strength and durability. The long-term monitoring results of the shaft lining concrete strain are significantly below the early warning value, indicating that shaft lining repair and reinforcement are effective. This study provides a research basis for the application of ECC in shaft lining repair engineering.

Abstract Background Postpartum post-traumatic stress disorder (PTSD) is a debilitating condition that can arise following childbirth. Despite a growing body of research on postpartum mental health, the relationship between social support and postpartum PTSD remains unclear. This study aimed to assess the association between social support and postpartum PTSD. Methods A prospective cohort study was conducted at a tertiary hospital in Guangdong province of China between November 2022 and April 2023. Eligible mothers were assessed for social support using the Social Support Rating Scale (SSRS) at three days postpartum and for PTSD using the Perinatal Post-Traumatic Stress Disorder Questionnaire (PPQ) at 42 days postpartum. The association between social support and postpartum PTSD was analyzed using multiple linear and log-binomial regression, with adjustments for potential confounders. Results Forty-six of 560 (8.2%) mothers developed PTSD within 42 days postpartum. Scores for subjective support (β=-0.319, P

Youshuai Meng,1,&ast; Chuan Chen,1,2,&ast; Ronggui Lin,1,3,&ast; Linlin Zheng,4 Yanying Fan,5 Mengdi Zhang,1 Ziqi Zhang,1 Han Shi,1,3 Xiaohan Zheng,1,3 Junyu Chen,1 Dezhao Chen,1,3 Tianhong Teng,1,3 Bing Chen1 1Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of China; 2Innovation Center for Enzyme Catalysis and Drug Synthesis, School of Pharmacy, Xiamen Medical College, Xiamen, 361023, People’s Republic of China; 3Department of General Surgery/ Department of Obstetrics & Gynecology, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China; 4Department of Oncology, Affiliated Hospital of Putian University, Putian, 351199, People’s Republic of China; 5Fuzhou Children’s Hospital of Fujian Province, Fuzhou, 350005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bing Chen, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of China, Email BingChen_001@126.com, BingChen_001@fjmu.edu.cn Tianhong Teng, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, 350122, People’s Republic of China, Email tianhongteng24@fjmu.edu.cnBackground: The dense and fibrotic nature of the pancreatic tumor microenvironment significantly contributes to tumor invasion and metastasis. This challenging environment acts as a formidable barrier, hindering effective drug penetration and delivery, which ultimately limits the efficacy of conventional cancer treatments. Gold nanoparticles (AuNPs) have emerged as promising nanocarriers to overcome the extracellular matrix barrier; however, their limited targeting precision, poor delivery efficiency, and insufficient photothermal conversion present challenges.Methods: We developed triphenyl phosphonium-functionalized high-branch gold nanoparticles, denoted as Dox@TPAu, to enhance drug delivery and targeting capabilities. The targeted penetration, biopharmaceutical and pharmacokinetic properties of Dox@TPAu were characterized, and the synergistic therapeutic effect was evaluated by the BxPC-3 xenograft tumor mouse model.Results: Dox@TPAu exhibits superior photothermal conversion efficiency (91.0%) alongside a high drug loading efficiency (26%) and effective photo-triggered drug-release potential. This Dox@TPAu drug delivery system adeptly accumulates at tumor sites due to its unique properties, enabling targeted localization within cancer cells and the mitochondria of stromal fibroblasts. This localization disrupts mitochondrial function and transfer—processes crucial for energy production, metabolism, and cell signaling within the tumor microenvironment. Pharmacokinetic analyses revealed an optimal spatiotemporal distribution of Dox@TPAu at the tumor site. This strategic accumulation enables precise disruption of both the physical barrier and cancer cells, enhancing treatment efficacy through near-infrared light-triggered local chemo-photothermal synergistic therapy.Conclusion: Our findings demonstrate that this innovative strategy effectively leverages the unique properties of mitochondria-targeting, virus-like AuNPs for precise and efficient stromal depletion, presenting a promising approach to enhance the efficacy of pancreatic cancer treatment.Keywords: mitochondria-targeting, gold nanoparticle, stromal depletion, chemo-photothermal therapy, pancreatic cancer

Shaoyan Shi, Xuehai Ou, Chao Liu, Rui Li, Qianjin Zheng, Leiming Hu Department of Hand Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an Honghui Hospital North District, Xi’an, Shaanxi, 710000, People’s Republic of ChinaCorrespondence: Leiming Hu, Department of Hand Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an Honghui Hospital North District, Xi’an, Shaanxi, 710000, People’s Republic of China, Email huleiming0506@163.comAbstract: Intervertebral disc degeneration (IDD) is a primary contributor to chronic back pain and disability globally, with current therapeutic approaches often proving inadequate due to the complex nature of its pathophysiology. This review assesses the potential of nanoparticle-driven pharmacotherapies to address the intricate challenges presented by IDD. We initially analyze the primary mechanisms driving IDD, with particular emphasis on mitochondrial dysfunction, oxidative stress, and the inflammatory microenvironment, all of which play pivotal roles in disc degeneration. Then, we evaluate the application of metal-phenolic and catalytic nanodots in targeting mitochondrial defects and alleviating oxidative stress within the degenerative disc environment. Additionally, multifunctional and stimuli-responsive nanoparticles are explored for their capacity to provide precise targeting and controlled therapeutic release, offering improved localization and sustained delivery. Finally, we outline future research directions and identify emerging trends in nanoparticle-based therapies, highlighting their potential to significantly advance IDD treatment by overcoming the limitations of conventional therapeutic modalities and enabling more effective, targeted management strategies.Keywords: nanotechnology, drug delivery, intervertebral disc degeneration, regeneration, therapy

Objective To observe the effects of continuous intravenous infusion of esketamine combined with thoracic paravertebral nerve block (TPVB) on postoperative early sleep, analgesia, and recovery quality in patients undergoing thoracoscopic lobectomy. Methods A total of 76 patients scheduled for elective thoracoscopic lobectomy at Nanjing First Hospital from January 2023 to January 2024 were randomly divided into two groups: the control group (C group) and the esketamine group (E group), with 38 patients in each group. Patients in the E group received intravenous injection of 0.2 mg/kg esketamine during anesthesia induction, followed by a continuous infusion of 0.1 mg·kg-1·h-1 esketamine until the end of the surgery. Patients in the C group received an equal volume of normal saline. Multichannel〖LM〗 sleep monitoring was conducted on the day before surgery, the first day after surgery, and the third day after surgery to assess patients sleep conditions. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality on the same days. Visual Analog Scale (VAS) scores were recorded at 2, 6, 12, 24, and 48 hours postoperatively, along with patient-controlled intravenous analgesia (PCIA) pressing times and rescue analgesia rates within 48 hours after surgery. The Hospital Anxiety and Depression Scale (HADS) was used to assess anxiety (HADS-A) and depression (HADS-D) scores on one day before surgery, the first and third days after surgery. Recovery quality was assessed using the Quality of Recovery-15 (QoR-15) on the first and third days after surgery, and the time of flatus was recorded. Results Compared with the C group, the total sleep time, sleep efficiency index, proportion of rapid eye movement were higher, while PSQI score was lower in the E group on the first and third postoperative days (P

In the field of civil engineering education, accurately evaluating the effectiveness of budget courses is crucial. However, traditional methods of evaluation tend to be cumbersome and subjective. In recent years, machine learning technology has demonstrated immense potential in educational evaluation. Nevertheless, in practical application, the machine learning-based evaluation model for civil engineering budget courses faces the predicament of inadequate evaluation accuracy. To solve this problem, the squirrel search algorithm technology was used to establish support vector machine parameters and create optimization algorithms. The performance of the proposed optimization algorithm was tested, and the results showed that the accuracy of the proposed algorithm was 0.927, which was better than similar prediction algorithms. Then, the empirical analysis of the proposed civil engineering budget course evaluation model showed that student satisfaction and student examination scores had increased to 92 and 94 points, respectively. The above results reveal that the proposed optimization algorithm and course evaluation model have good performance. Therefore, the implementation of the proposed curriculum evaluation method can significantly improve the learning efficiency of students and the teaching quality of civil engineering budgeting methods courses.

Coal mine conveyor belt and other low-speed large torque system, the torque density and torque stability of the motor requirements are higher, permanent magnet / magnet reluctance hybrid rotor double stator synchronous motor (PM/MRHRDSSM) is just adapted to this requirement, however, the traditional close winding single inverter vector control system control PM/MRHRDSSM provides large torque ripple, high speed fluctuation and large total harmonic distortion (THD) of the current, difficult to be used in actual production and life, this paper proposes a large torque open winding-permanent magnet / magnet reluctance hybrid rotor double stator synchronous motor(OW-PM/MRHRDSSM) based on SVPWM dual inverter control strategy, and analysis of open winding double inverter structure, and its voltage vector mathematical model, using the existing two-level inverter as a basis, the bilateral inverter separately discussed its role and control method, as well as the decomposition method of synthetic voltage vector and the inverter device in the small sector on-time, the end of this paper through simulation to compare the traditional close winding single inverter vector control system control PM/MRHRDSSM and the large torque OW-PM/MRHRDSSM based on SVPWM dual inverter control strategy to prove the effectiveness of the proposed method in reducing torque ripple, speed fluctuation and THD of current during motor operation.

Abstract To improve the toughness and strength of ceramsite concrete, this study employed three different types of fibers to enhance its performance. It prepared 8 sets of specimens, conducted stress-strain curve and static strength tests, and calculated various performance parameters. Through analysis of the economic performance and failure modes, it is found that high-toughness polypropylene fibers and steel fibers significantly enhanced both the strength and toughness of ceramsite concrete, while carbon fibers, although capable of increasing strength, do not improve toughness. Specifically, high-toughness polypropylene (HTPP) fibers and steel fibers increased the strength of ceramsite concrete by 32.8% and 49.0%, respectively, resulting in corresponding improvements in strength-to-weight ratio by 33.0% and 39.8%. While the toughness index Wcu 0.85 increased by 20.0% and 85.1%, respectively, Wcu 0.5 increased by 29.0% and 257.6%. The failure mode exhibited ductile fracture. Additionally, HTPP fibers were more cost-effective in increasing the strength and toughness of ceramsite concrete. Finally, based on SEM test results, we explained the mechanisms through which the three types of fibers enhance the performance of ceramsite concrete from the perspective of fibers surface characteristics. These research findings provide theoretical support for the optimization design of ceramsite concrete and are of significant importance for its application as a structural material.

Abstract We present a versatile platform for label-free magnetic separation of plasma, tailored to accommodate diverse environments. This innovative device utilizes an advanced long-short alternating double Halbach magnetic array, specifically engineered for optimal magnetic separation. The array’s adaptability allows for seamless integration with separation channels of varying sizes, enabling static separation of whole blood. The platform has a highly flexible processing throughput, spanning from 100 μL to 3 mL per separation cycle without sacrificing separation efficiency. A key aspect of this device is its power-free operation throughout the separation process, obviating the complexity of conventional separation devices. Its effectiveness is demonstrated by the extraction of 40 μL of plasma from 100 μL of rat whole blood within 8 min. The separated plasma proved effective for subsequent analysis of antibody concentration and size in the separated plasma for pharmacokinetic investigations, yielding results on par with those obtained via centrifugation. Furthermore, the device’s high-throughput capability was validated using human whole blood, achieving 3 mL of plasma separation in just 1 min. In a follow-up study on COVID-19 IgG antibody detection, the results matched those from centrifugation. The device demonstrates a separation efficiency of 99.9% for cells larger than 1 μm in both rat and human blood samples, with a plasma recovery rate of 72.7%. In summary, our magnetic separation device facilitates rapid plasma extraction from whole blood, with a capacity of up to 3 mL per minute in human blood, without compromising subsequent plasma-based analyses, thereby highlighting its broad applicability across diverse settings.

Abstract Adult Schistosoma produces a large number of eggs that play essential roles in host pathology and disease dissemination. Consequently, understanding the mechanisms of sexual maturation and egg production may open a new avenue for controlling schistosomiasis. Here, we describe that Bantam miRNA and miR-1989 regulate Wnt signaling pathway by targeting Frizzled-5/7/9, which is involved in ovarian development and oviposition. Additionally, Frizzled-7 could cooperate with SjRho to maintain normal ovarian development and egg productions and SjRho may interact with Hsp60 to potentially support Frizzled-7 trafficking and signaling. Further in vivo inhibition of SjRho in mice model infected with Schistosoma results in a remarkable decrease in worm burden and egg productions. Our findings not only broaden the functions of Bantam miRNA and miR-1989 as well as Wnt signaling pathway, but also imply that interruption of Bantam/miR-1989-Frizzled-5/7/9-SjRho axis may serve as effective targets against schistosomiasis.

Quantitative assessment of the first acidity constant (pKa) for BFC (27.6 in CH3CN) and FIC (27.8 in CH3CN) shows the methylene protons to be significantly more acidic than those in related cyclopentadiene (32 in CH3CN), indene (34 in CH3CN), or fluorene (37 in CH3CN) and comparable to the methine of 9-perfluorophenylfluorene (28.14 in CH3CN). This work reports quantitative pKa values of BFC and FIC, places those values in a broadened context of CpH-cognate hydrocarbon acidity and presents a Clar–Loschmidt graph perspective to help understand the “surprises”.

Yue Yang,1,&ast; Jinjie Shi,2,&ast; Jiming Yu,3,&ast; Xin Zhao,1 Ke Zhu,1 Shen Wang,4 Xinwen Zhang,1 Xieyu Zhang,1 Guangcheng Wei,1 Wei Cao1 1Rheumatology Department, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Graduate School, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3The Second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 4Orthopedics Department, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Cao, Wangjing Hospital of China Academy of Chinese Medical Sciences, 6 South Central Road, Chaoyang District, Beijing, 100102, People’s Republic of China, Email academic_caowei66@163.comAbstract: Lactic acid (LA) is an essential glycolytic metabolite and energy source in the body, which is present in high levels in the synovial fluid of patients with rheumatoid arthritis (RA) and is a reliable indicator for identifying inflammatory arthritis. LA not only acts as an inflammatory amplifier in RA, recent studies have found that novel posttranslational modification (PTM) lactylation mediated by LA may also play a key role in RA. Single-cell sequencing showed that the RA lactylation score of patients with RA was significantly increased, and core lactylation-promoting genes, including NDUFB3, NGLY1, and other genes, were found to be potential biomarkers of RA. More studies have shown that lactylation can regulate genes in various cells, such as fibroblast-like synoviocytes (FLSs) and macrophages, thus playing a special role in the development and occurrence of autoimmune diseases, neurological diseases, and cancer diseases. In this paper, we review the research on lactylation in RA-related cells and mechanisms and bring new insights into the pathogenesis, diagnosis, and treatment of RA.Keywords: lactic acid, lactylation, posttranslational modification, rheumatoid arthritis

Liu Shi,1,&ast; Youxin Liao,2,&ast; Yue Chen3 1Department of Critical Care Medicine, Jiangjin Central Hospital, Chongqing, 402260, People’s Republic of China; 2Department of Medical Administration, Jiangjin Central Hospital, Chongqing, 402260, People’s Republic of China; 3Department of Oncology, Jiangjin Central Hospital, Chongqing, 402260, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue Chen, Department of Oncology, Jiangjin Central Hospital, No. 725, Jiangzhou Road, Dingshan Street, Jiangjin District, Chongqing, 402260, People’s Republic of China, Tel +86-15823491696, Email wenlinlin0606@163.comObjective: To analyze the independent associations of the Kidney Failure Risk Equation (KFRE) and neutrophil gelatinase-associated lipocalin (NGAL) with end-stage renal disease (ESRD) among patients with chronic kidney disease (CKD) stages 3– 5 in China and evaluate their predictive values for ESRD.Patients and Methods: A total of 716 patients with CKD stages 3– 5 at the time of the initial renal medicine referral were retrospectively enrolled, and the study outcome was the observed incidence of ESRD at 2 years after the initial referral. Baseline characteristics were collected, and relevant laboratory indexes, including neutrophil gelatinase-associated lipocalin (NGAL), were detected. The binary logistic regression model was used to analyze the independent associations, and the receiver operating characteristic (ROC) curve was used to assess the predictive values.Results: The 2-year incidence of ESRD was 20.5% (147/716). The 4-variable KFRE, 8-variable KFRE and NGAL were independently associated with ESRD after adjusting for potential confounding factors. The AUCs of the 4-variable KFRE, 8-variable KFRE and NGAL for predicting ESRD among patients with CKD stages 3– 5 were 0.711 [standard error (SE): 0.026, 95% confidence interval (CI): 0.662– 0.761], 0.725 (SE: 0.025, 95% CI: 0.677– 0.774) and 0.736 (SE: 0.024, 95% CI: 0.686– 0.785), respectively. The AUC of the 4-variable KFRE plus NGAL was significantly higher than those of the 4-variable KFRE and NGAL alone (0.900 vs 0.711, Z = 6.297, P < 0.001; 0.900 vs 0.736, Z = 5.795, P < 0.001), and the AUC of the 8-variable KFRE plus NGAL was also significantly higher than those of the 8-variable KFRE and NGAL alone (0.911 vs 0.725, Z = 6.491, P < 0.001; 0.911 vs 0.736, Z = 6.298, P < 0.001).Conclusion: The KFRE was able to independently predict progression of CKD stage 3– 5 to ESRD in Chinese population. The addition of NGAL to the KFRE was able to elevate the predictive value when applied in predicting 2-year ESRD.Keywords: chronic kidney disease, end-stage renal disease, kidney failure risk equation, neutrophil gelatinase-associated lipocalin

Xujun Feng,1,2,&ast; Yuan Shi,1,&ast; Ye Zhang,1 Fei Lei,1 Rong Ren,1 Xiangdong Tang1 1Sleep Medicine Center, Department of Respiratory and Critical Care Medicine, Mental Health Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rong Ren; Xiangdong Tang, Department of Respiratory and Critical Care Medicine, Sleep Medicine Center, Mental Health Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China, Tel +86-28-85422733, Email 498880651@qq.com; 2372564613@qq.comStudy Objectives: This study aimed to evaluate the test-retest reliability of the Epworth Sleepiness Scale (ESS) in patients with untreated obstructive sleep apnea (OSA) and investigate the effects of different follow-up techniques and various factors on ESS score discrepancies.Methods: This study prospectively enrolled participants diagnosed with OSA at West China Hospital of Sichuan University from October 2022 to May 2023. Each participant completed a polysomnography (PSG) and the Chinese version of the ESS. Initial ESS evaluations were performed before the PSG and were reassessed either face-to-face or on telephone within a week. Analysis involved Bland-Altman plots, the intraclass correlation coefficient (ICC), and calculation of mean differences.Results: We included 382 patients with untreated OSA, averaging 43.52 years old, with a mean body mass index (BMI) of 26.54 kg/m2 and an average apnea-hypopnea index (AHI) of 47.93 events/hour. The ICC was recorded at 0.820. The signed difference in ESS scores from baseline to follow-up was 1.68 ± 2.93 overall. In OSA patients with a BMI > 28, the difference was 2.39 ± 3.46, while in those with an AHI ≥ 30, it was 1.77 ± 3.27.Conclusion: This study underscores the significance of repeated ESS testing to improve the reliability of sleepiness evaluations in patients with OSA. Further studies should aim to confirm these findings in a broader demographic and develop refined methods for more precise sleepiness assessments among different OSA groups.Keywords: Epworth Sleepiness Scale, obstructive sleep apnea, test-retest reliability

Chen-Ming Tang,1,2,&ast; Yuan-Chuan Chen,1,2,&ast; Yu-Cheng Huang,1,2 Yuan Meng,1,2 Jing-Chun Xia,1,2 Jian Pang,1,2 Ying Shi1,2 1Shi’s Center of Orthopedics and Traumatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Institute of Traumatology & Orthopedics, Shanghai Academy of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Pang; Ying Shi, Shi’s Center of Orthopedics and Traumatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China, Email pangjian@shutcm.edu.cn; shiying1974@126.comPurpose: This trial aimed to investigate the efficacy of Migu capsules in treating osteoporotic low back pain.Patients and Methods: In this single-center trial, we randomly assigned patients with osteoporotic low back pain that had lasted for 3 months in a 1:1 ratio to receive Migu capsules alongside Caltrate D in treatment group or to receive Caltrate D only in control group, both for 48 weeks. The primary outcome measure was the intensity of low back pain on a visual analog scale at 24 weeks after enrollment. Secondary outcome measures included the Roland-Morris Disability Questionnaire (RMDQ), bone turnover markers, and bone mineral density.Results: A total of 100 patients were enrolled, with 50 in each group. At baseline, the mean score for low back pain intensity was 6.2 in the treatment group and 6.1 in the control group. The primary outcome of the low back pain intensity score at 24 weeks was 2.9 in the treatment group and 4.7 in the control group (adjusted mean difference, − 1.8; 95% confidence interval, − 2.3 to − 1.4; P< 0.001). Secondary outcomes including the score on RMDQ and pain at 48 weeks were in the same direction as the primary outcome. Compared to the control group, the treatment group only showed a difference in bone density after continuous intervention for 48 weeks (P< 0.05). Three patients experienced a mild adverse event associated with the intake of Migu capsules.Conclusion: Migu capsules can alleviate bone pain and reduce functional disabilities caused by osteoporotic lower back pain.Keywords: osteoporotic low back pain, traditional Chinese medicine, osteoporosis, low back pain, Migu capsules

Blasting excavation and cavity filling are the core means of filling mining in underground metal mine. As the core load-bearing unit of cavity, the backfill is inevitably subjected to the blasting dynamic load perturbation of adjacent ore body, which in turn induces some structural changes in the internal structure of matrix and affects its re-bearing capacity and stability, which is related to the safety of mine production. Therefore, in this paper, the dynamic damage filling body considering the magnitude of impact amplitude is prepared based on the split Hopkinson press bar system (SHPB), and the simulation of filling body blasting disturbance is realized. The mesoscopic structural response characteristics of the filling body under dynamic loading are investigated, the mechanical behavior and crack extension mechanism of the dynamically damaged filling body are revealed, and the instability over-warning of the dynamically damaged filling body is realized. The results show that: the degradation of meso-structure of the dynamically damaged filling body increases with the increase of impact amplitude, corresponding to the increase of porosity by 34.48%, the decrease of wave velocity by 44.48%, and the intensification of the initial damage degree. With the increased impact amplitude, the uniaxial compressive strength and elastic modulus of the dynamically damaged filling body show a three-stage trend of slow decrease, then rapid decrease and then slow decrease, with the maximum decrease rate of 54.15% and 69.02%, respectively. Meanwhile, the compaction stage of the stress-strain curve of the dynamically damaged filling body is significantly prolonged with the increase of the damage degree. The peak strain increases by 78.35%, and the filling body changes from brittle ductile to ductile. The characteristic parameters of acoustic emission (AE) are closely related to the rupture behavior of the filling body. Due to the difference in the initial damage degree, the rate, number and scale of cracks sprouting, expanding and propagating within the matrix of the dynamically damaged filling body are significantly different. The activity and sparsity of the AE signal initially decrease, then increase, and finally decrease again with the increase in impact amplitude. The AE ib value exhibits a pattern of “fluctuating increase”, “sharp decrease”, and “large fluctuation”. As the impact amplitude increases, there is an increase in the area of sharp decline in AE ib values and a shift to the pre-peak stage. The area of sharp decline in ib value is judged to be the precursor information of instability, and the dynamic damage filling body reaches the critical value of instability at a smaller stress. Increasing the impact amplitude has no significant effect on the failure mode of the dynamically damaged filling body, but the area of the surface collapse zone is increased and the degree of failure is significantly enhanced.

【Objective】Common optical switches are usually polarization sensitive or have complex structures, the article proposes a 2×2 microfluidic optical switch.【Methods】The optical switch proposed in this article employs a waveguide structure. It utilizes microfluidic driving technology based on magnetic fluids, along with trace amounts of liquid and air, to achieve optical path selection and switching functions for the optical switch. The transmission characteristics of optical switch are studied and discussed, and the structure of optical switch is optimized.【Results】The results show that the insertion losses at two output ports of optical switch are 0.42 and 0.20 dB, and the crosstalk are -24.13 and -42.63 dB, respectively.【Conclusion】The proposed 2×2 microfluidic optical switch has simple structure and is not sensitive to polarization. It also has lower insertion loss and crosstalk than common optical switches. It can be used as the switching core for building Optical Cross Connect (OXC) equipment to realize the fault protection function of the optical network.

Yuchen Dai,1 Kaikai Shi,1 Qingren Liu,2 Changli Shen,3 Xinjian Lu,1 Xiaodong Qiu,1 Jie Sun1 1Department of Anesthesiology & Key Laboratory of Clinical Science and Research, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Anesthesiology, Xishan People’s Hospital of Wuxi City, Wuxi, Jiangsu, People’s Republic of China; 3Department of Anesthesiology, Xinxiang Central Hospital, Xinxiang, Henan, People’s Republic of ChinaCorrespondence: Jie Sun; Xiaodong Qiu, Department of Anesthesiology & Key Laboratory of Clinical Science and Research, Zhongda Hospital, Southeast University, No. 87 Dingjiaqiao, Nanjing City, 210009, Jiangsu Province, People’s Republic of China, Email dgsunjie@hotmail.com; qxdong@hotmail.comPurpose: This study aimed to investigate the relationship between intraoperative sleep spindle activity and postoperative sleep disturbance (PSD) in elderly orthopedic surgery patients.Patients and Methods: In this prospective observational cohort study, we collected intraoperative electroencephalography (EEG) data from 212 elderly patients undergoing orthopedic surgery from May 2023 to December 2023. We used the Athens Insomnia Scale to assess sleep quality on postoperative day (POD) 1 and POD 3 and analyzed the correlation between intraoperative sleep spindle activity and PSD through logistic regression.Results: The incidence of PSD was 65.6% on POD 1 and 41.9% on POD 3. On the first day, there were no significant differences in intraoperative sleep spindle characteristics between PSD and non-postoperative sleep disturbance (non-PSD) patients. However, by the third day, PSD patients showed lower sigma power compared to non-PSD patients, as well as lower spindle density in the bilateral frontopolar (Fp1/Fp2) and bilateral temporal (F7/F8) channels, with shorter average spindle duration (P < 0.05). Multivariate logistic regression analysis suggested that the average spindle density in F7/F8 channels (OR 0.543, 95% CI 0.375– 0.786; P = 0.001) was an independent risk factor for PSD on POD 3. Furthermore, Mini-Mental State Examination (MMSE) could independently predict PSD on POD 1 (OR 0.806, 95% CI 0.656– 0.991; P = 0.041) and POD 3 (OR 0.701, 95% CI 0.562– 0.875; P = 0.002). Pain on movement and at rest were independently associated with PSD on POD 1 (OR 1.480, 95% CI 1.200– 1.824; P < 0.001) and POD 3 (OR 1.848, 95% CI 1.166– 2.927; P = 0.009), respectively.Conclusion: Intraoperative mean spindle density in the F7/F8 channels was an independent risk factor for PSD on POD 3 in elderly patients undergoing orthopedic surgery. MMSE and postoperative pain also independently increased the risk of PSD.Keywords: postoperative sleep disturbance, sleep spindle, electroencephalography spectrum, elderly patients, orthopedic surgery

Zheng-lun Lin,1– 3,&ast; Li Liu,4,&ast; Kai Shi,1– 3 Tian-jie Chen,1– 3 Lin-ming Chen,1– 3 Hong-da Cai1– 3 1Department of Anesthesiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, People’s Republic of China; 2Department of Anesthesiology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 3Institute of Anesthesiology, Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 4Department of Anesthesiology, Fuzhou Traditional Chinese Medicine Hospital, Fujian University of Traditional Chinese Medicine, Fuzhou, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong-da Cai, Email caihd2000@163.comObjective: To evaluate the effect of intravenous lidocaine injection on the half-maximum effective concentration (EC50) of remifentanil in preventing cough due to tracheal extubation in female patients undergoing thyroid surgery by Dixon’s sequential method.Methods: A total of 50 female patients underwent elective thyroidectomy were randomly divided into two groups of a 1:1 ratio. Group L (lidocaine group) was given intravenous lidocaine (1.5 mg/kg) and then continuous infusion (2 mg/kg/h) until the end of surgery. Group C (control group) received 0.9% sodium chloride solution infusion in the same way. The primary outcome was effective concentration EC50 of remifentanil in preventing cough due to tracheal extubation in female patients undergoing thyroid surgery. The secondary outcomes were as follows: mean arterial pressure (MAP), oxygen saturation (SpO2), heart rate (HR), PetCO2 and respiratory rate at the time of tracheal extubation. The incidence of postoperative nausea and vomiting, and symptoms associated with lidocaine toxicity.Results: Finally, 44 subjects completed the study. The EC50 values of remifentanil calculated using probit regression were 1.40 ng/mL (95% CI, 1.15– 1.65 ng/mL) in Group C and 0.83 ng/mL (95% CI, 0.58– 1.08 ng/mL) in Group L. A lower concentration of remifentanil can inhibit the cough reaction during intravenous lidocaine infusion. PetCO2 in the lidocaine group was lower than that in the control group (Z=− 2.162, P < 0.05). The respiratory rate of the lidocaine group after extubation was higher than that of the control group (Z=− 3.287, P < 0.05).Conclusion: Intravenous injection of lidocaine can reduce the effective concentration EC50 of remifentanil in preventing tracheal extubation cough in female patients undergoing thyroid surgery.Keywords: lidocaine, thyroid surgery, remifentanil, extubation cough

Hua Fan,&ast; Ruile Shen,&ast; Junqiang Yan,&ast; Yongjie Bai, Qizhi Fu, Xiaofei Shi, Ganqin Du, Dongmei Wang The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, 471003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ganqin Du; Dongmei Wang, Email dgq99@163.com; wdmzgadyx@163.comAbstract: This review elucidates the pivotal role of pyroptosis, triggered by gut microbiota, in the development of multiple sclerosis (MS), emphasizing its significance within the gut-brain axis. Our comprehensive analysis of recent literature reveals how dysbiosis in the gut microbiota of MS patients—characterized by reduced microbial diversity and shifts in bacterial populations—profoundly impacts immune regulation and the integrity of the central nervous system (CNS). Pyroptosis, an inflammatory form of programmed cell death, significantly exacerbates MS by promoting the release of inflammatory cytokines and causing substantial damage to CNS tissues. The gut microbiota facilitates this detrimental process through metabolites such as short-chain fatty acids and neuroactive compounds, or self-structural products like lipopolysaccharides (LPS), which modulate immune responses and influence neuronal survival. This review highlights the potential of modulating gut microbiota to regulate pyroptosis, thereby suggesting that targeting this pathway could be a promising therapeutic strategy to mitigate inflammatory responses and preserve neuronal integrity in patients with MS.Keywords: multiple sclerosis, gut microbiota, pyroptosis, gut-brain axis, neuroinflammation, therapeutic targets

Tianfeng Zhao,1 Zhuo Xu,2 Min Xu,2 Yubin Lai,2 Xiaodong Chen,2 Zhaohui Shi3,4 1Department of Otolaryngology-Head and Neck Surgery, General Hospital of Southern Theatre Command, Guangzhou, People’s Republic of China; 2Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital, Air Force Military Medical University, Xi’an, People’s Republic of China; 3Department of Otolaryngology, Shenzhen Longgang Otolaryngology Hospital & Shenzhen Otolaryngology Research Institute, Shenzhen, People’s Republic of China; 4Department of Otolaryngology-Head and Neck Surgery, Naso-Orbital-Maxilla and Skull Base Center, Department of Allergy, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Zhaohui Shi, Department of Otorhinolaryngology-Head and Neck Surgery, Naso-Orbital-Maxilla and Skull Base Center, Department of Allergy, Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong, 510630, People’s Republic of China, Tel +86-20-85253333, Fax +86-20-85253336, Email shizhh35@mail.sysu.edu.cnObjective: This study aims to summarize the clinical characteristics of skull base osteoradionecrosis (ORN) with the internal carotid artery (ICA) involvement and to distill the key surgical techniques that can enhance the protective measures for ICA.Methods: We conducted a retrospective, observational study over a six-year period from February 2017 to May 2023. We included patients who were diagnosed with osteoradionecrosis with invasion of the internal carotid artery and collected their demographic information, pathology results, complication rates, ect. The goal was the alleviated rate after the surgery and the anatomic consideration during the surgery. We compared the verbal rating score (VRS) of headache pre- and post-operation by the Wilcoxon rank-sum test.Results: A retrospective analysis was conducted on 19 patients diagnosed with ORN, with a mean age of 53.73 yr (range, 32– 68 yr). Among them, 17 patients (89.47%) were nasopharyngeal carcinoma (NPC), 1 patient (5.23%) was squamous cell carcinoma of the sphenoid sinus, and 1 patient (5.23%) had adenoid cystic carcinoma. After the surgery, 1 fatality occurred within 2 months, which was attributed to a severe parapharyngeal space infection.1 patient succumbed to ICA rupture two days post-operation. Additionally, 1 patient experienced ORN recurrence 2 years after the initial surgery. The mean follow-up period for the study was 37.47 mo (range 2 − 77 mo). The alleviation rate was 89.4%. The results revealed a significant decrease in VRS after the surgery (Z=− 3.921, P=0.000). Finally, we summarized clinical evidences of ICA involvement, such as the formation of pseudoaneurysm.Conclusion: A four-quadrant division of SBORN as a standardized and systematic approach is meaningful to guide surgical intervention for osteoradionecrosis. There are relevant clinical and imaging evidences that can predict the rupture of ICA.Keywords: skull base osteoradionecrosis, skull base debridement surgery, endonasal endoscopic approach

Yi Liu,1,2 Changqing He,1 Quanhai Zhong,3 Xianbao Shi,4 Hongyan Li,1 Gaoge Fu,1 Lixuan Guo,1 Churong Zhao,1 Lei Tian,1 Xin Li,1 Xue Jiao,1 Lina Shan1 1Department of Respiratory Disease, The First Affiliated Hospital, Jinzhou Medical University, Jinzhou, 121000, People’s Republic of China; 2Department of Critical Care Medicine, Panzhihua Central Hospital, Panzhihua, 61700, People’s Republic of China; 3Clinical Drug Laboratory, People’s Hospital of Yichun City, Yichun, Jiangxi, 336000, People’s Republic of China; 4Department of Pharmacy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, People’s Republic of ChinaCorrespondence: Lina Shan, Email shanlina321@163.comIntroduction: Pulmonary hypertension (PH) is a progressive and life-threatening condition. Recent research has demonstrated that exosomes derived from mesenchymal stem cells (MSC) exhibit significant therapeutic potential in the treatment of PH. The composition of these exosomes is often substantially influenced by the characteristics of their parental cells. This study aimed to identify an intervention strategy to enhance the efficacy of mesenchymal stem cell exosomes in treating PH.Methods: Exosomes were isolated from control MSC and tadalafil-pretreated MSCs. In vitro and in vivo studies were conducted.Results: MSCTAD-Exo attenuated macrophage inflammation and improved endothelial cell (EC) apoptosis while also reducing pulmonary arterial pressure in a hypoxia-induced rat model. Furthermore, MSC exosomes can mitigate hypoxia-induced proliferation and migration of smooth muscle cells (SMC) by influencing the secretion of endothelial exosomes. MiR-29a-3p has been identified as a crucial mediator in this process, with its expression regulated by cAMP responsive element binding protein 1 (CREB1). MiR-29a-3p exerts anti-inflammatory effects by modulating the expression of ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2). Notably, the anti-inflammatory and anti-vascular remodeling activities of exosomes were diminished following the depletion of MiR-29a-3p.Discussion: MSC treated with tadalafil can secrete better exosomes. MSCTAD-Exo may enhance anti-inflammatory and anti-vascular remodeling properties by upregulating mir-29a-3p expression, providing a novel idea for PH therapy. Future studies could explore the clinical application of this finding. Keywords: exosome, tadalafil, hypoxia pulmonary hypertension, mesenchymal stem cell, miR-29a-3p

Lei Yin,1– 3,&ast; Lixin Mao,4,&ast; Rui Yin,5,&ast; Chengxun Lv,1,&ast; Xiaokai Shi,4 Chuang Yue,4 Yin Chen,4 Chao Lu,4 Zonglin Wu,1 Kai Xu,4 Wei Cao4 1Department of Urology, Shidong Hospital, Yangpu District, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai, 200438, People’s Republic of China; 2Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 3Department of Urology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201999, People’s Republic of China; 4Department of Urology, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, 213000, People’s Republic of China; 5Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250012, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Xu; Wei Cao, Email jssqxk@126.com; weicao_czey@163.comPurpose: Emerging literature links the role of the renin-angiotensin-aldosterone system (RAAS) to the progression of cancers. However, the function of RAAS has not been verified in Clear-cell renal cell carcinoma (ccRCC).Methods: ACE expression in ccRCC tissues was determined using RT-PCR, Western blot, and immunohistochemistry staining. The clinical significance of ACE was evaluated through Cox regression analysis. To assess the impact of ACE expression on ccRCC cell growth, metastasis, and glucose activity, CCK-8 assays, transwell assays, Seahorse detection, and xenograft models were utilized. The mechanisms of ACE and its upstream and downstream regulatory factors were investigated using RNA-seq, chromatin immunoprecipitation (ChIP), and luciferase reporter assays.Results: RAAS-related gene Angiotensin-Converting Enzyme (ACE) was significantly under expressed in ccRCC cells and tissues. High ACE expression was positively associated with a favorable prognosis in ccRCC patients. Functional studies showed that ACE overexpression suppressed ccRCC cell line OS-RC-2 and A498 growth, metastasis, and glycolysis activities, while its knockdown had the opposite effect. Mechanistically, ACE inhibited ccRCC progression and epithelial-mesenchymal transition (EMT) by disrupting the AKT-FOXO1 signaling pathway. Furthermore, we provide evidence that ACE could enhance everolimus (approved agent for ccRCC) antitumor effect and ACE expression is transcriptionally regulated by ZBTB26.Conclusion: Our findings investigated the roles and mechanisms of ACE in ccRCC. ACE inhibits the growth and metastasis of ccRCC cells in vitro and in vivo by promoting FOXO1 expression, which is the downstream target of PI3K-AKT pathway. Thus, this research suggests that ACE may be a promising target for new therapeutic strategy in ccRCC. Keywords: ACE, AKT, FOXO1, clear-cell renal cell carcinoma, everolimus

Yun Wu,1 Huixin Shi,1 Wei Li,1 Yijun An,1 Yuhan Shao,1 Xia Rao,1 Nicholas R Waterfield,2 Wei Wang,3 Guowei Yang1 1Beijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Warwick Medical School, Warwick University, Coventry, UK; 3Department of Respiratory Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Yun Wu; Guowei Yang, Beijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, 95 Yong’an Road, Xi Cheng District, Beijing, 100050, People’s Republic of China, Tel +86-10-63139853 ; +86-10-63139130, Email wuyun@ccmu.edu.com; yangguowei@hotmail.comPurpose: Pneumocystis jirovecii pneumonia (PJP) shows a high fatality rate in non-HIV patients. However, there are limited data on P. jirovecii drug resistance-related gene mutations in these patients. This study aimed to describe the prevalence of mutations in the dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes of P. jirovecii in non-HIV patients in China, providing a reference for drug usage.Methods: We analyzed the polymorphisms of DHPS and DHFR genes from 45 non-HIV patients in China, including P. jirovecii infection (n = 14) and P. jirovecii colonization (n = 31). This analysis also considered clinical characteristics, P. jirovecii burden, treatment response, and prognosis.Results: Compared to the P. jirovecii colonization, P. jirovecii infection had significantly altered blood indicators (GR%, LY%, HGB, TP, ALB, CRP, P< 0.05) with higher P. jirovecii burden (P< 0.05) and worse prognosis (P< 0.05). Additionally, patients with P. jirovecii infection were more susceptible to infections, such as the Epstein-Barr virus, Cytomegalovirus, Mycoplasma and Klebsiella pneumoniae. Although no known drug-resistance mutations were detected in the DHPS gene in this study, 10 nonsynonymous mutations were identified. Furthermore, 10 nonsynonymous and 2 synonymous mutations were found in the DHFR gene. However, these mutations were not associated with a worse prognosis.Conclusion: Our results implied that TMP-SMX prophylaxis is still recommended for PJP in high-risk non-HIV patients in China.Keywords: Pneumocystis jirovecii pneumonia, mutation, drug resistance, prognosis, non-HIV

Jianhua Wu,1,2 Yisha Wu,1 Peng Jin,3 Xiaoxue Zi,3 Yuzhu Wan,1 Kaiyue Sun,1,4 Li Shi,1,3 Deyun Wang5 1Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Otolaryngology Head and Neck Surgery, Binzhou People’s Hospital, Binzhou, Shandong, People’s Republic of China; 3Department of Otolaryngology, The Second Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 4Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 5Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeCorrespondence: Li Shi, Department of Otolaryngology, The Second Hospital of Shandong University, Jinan, Shandong, 250033, People’s Republic of China, Tel +86 0531 83086278, Fax +86 0531 83086279, Email shili126@sina.com Kaiyue Sun, Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250022, People’s Republic of China, Tel +86 0531 83086277, Fax +86 0531 83086279, Email 18354159626@163.comBackground: Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNA molecules in eukaryotes, involved in many essential biological processes. However, their role in allergic rhinitis (AR) has not been extensively studied.Methods: The expression levels of hsa_circRNA_100791 were measured using qRT-PCR in peripheral blood mononuclear cells (PBMCs) and nasal mucosa from AR patients. The biological function of hsa_circRNA_100791 in AR was investigated through RNA-seq and a series of in vitro experiments. Western blotting, luciferase reporter assays, and rescue experiments were conducted to elucidate the molecular mechanisms underlying hsa_circRNA_100791. Additionally, a mouse model was used to assess the functional role of hsa_circRNA_100791 in vivo.Results: Upregulation of hsa_circRNA_100791 was observed in both PBMCs and nasal mucosa of AR patients. In vitro, increased expression of hsa_circRNA_100791 promoted the production of pro-inflammatory mediators (IL-1β, IL-4, IL-5, IL-6, IL-8, IL-13, IL-17, IL-18, IL-33, TNF-α, and NF-κB) and inhibited IL-2 and IFN-γ. Conversely, knockdown of hsa_circRNA_100791 both in vitro and in vivo alleviated AR symptoms, reduced pro-inflammatory mediators, and enhanced IL-2 and IFN-γ levels. Mechanistically, we found hsa_circRNA_100791 contributing to the pathological processes of AR, which upregulate TRIM13 via sponging miR-487b-5p.Conclusion: Our study demonstrated that hsa_circRNA_100791 mitigates the inhibitory effect of miR-487b-5p on Trim13 by directly binding to miR-487b-5p. This interaction regulates the expression of inflammatory factors and facilitates AR. Thus, hsa_circRNA_100791 could be a promising new therapeutic target for AR.Keywords: allergic rhinitis, hsa_circ_100791, miR-487b-5p, Trim13, diagnosis, inflammation, NF-κB

Sitong Guo,1,2 Songze Wang,2,3 Chunli Chen,2 Xiaojin He,4 Bentao Yang,5 Zhiqin Huang,2 Jianmin Ma,2 Jitong Shi,2 Libin Jiang,2 Fred Kuanfu Chen6– 8 1Department of Ophthalmology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China; 2Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University; Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, 100730, People’s Republic of China; 3Beijing FengTai You’anmen Hospital, Beijing, People’s Republic of China; 4Department of Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People’s Republic of China; 5Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People’s Republic of China; 6Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, WA, Australia; 7Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, VIC, Australia; 8Department of Ophthalmology, Royal Perth Hospital, Perth, WA, AustraliaCorrespondence: Libin Jiang, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University; Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, 100730, People’s Republic of China, Email jlbjlb@sina.comPurpose: Orbital inflammatory myofibroblastic tumors (IMTs) are a rare tumor with intermediate biological potential. We analyzed a series of orbital IMTs to determine their unique features.Methods: Records from patients with pathologically confirmed IMT at Beijing Tongren Hospital, Capital Medical University, between January 2004 and August 2022, were reviewed for their ocular presentation and treatment outcomes.Results: Thirteen cases of primary orbital IMT with positive anaplastic lymphoma kinase on fluorescent in situ hybridization were included. These consists of five men and eight women with an age of onset ranged from 2 to 54 years. Nearly half of the primary orbital IMTs displayed local invasion into the maxillary sinus, ethmoid sinus, and pterygopalatine fossa. On magnetic resonance imaging, orbital IMT usually appeared as an ill-defined, oval, irregular, or diffuse mass with heterogeneous signals. Nearly half (46.2%) of these lesions caused bone destruction, and 31% developed recurrence, which was more likely to occur in lesions involving multiple tissues (50%). All cases of recurrence occurred within five months after the first surgery. No patient developed distant metastases.Conclusion: Orbital IMT is rare and prone to local invasion and recurrence. The histology and behavior of orbital IMT requires further investigation.Keywords: inflammatory myofibroblastic tumor, orbit, MRI, pathologic, prognosis

Ziyao Zheng,1 Liyuan Ke,1 Shumin Ye,1 Peiying Shi,2 Hong Yao1,3 1Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of China; 2Department of Traditional Chinese Medicine Resource and Bee Products, College of Animal Sciences (College of Bee Science), Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China; 3Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, Fujian Medical University, Fuzhou, 350122, People’s Republic of ChinaCorrespondence: Peiying Shi; Hong Yao, Email peiyshi@126.com; yauhung@126.com, hongyao@mail.fjmu.edu.cnAbstract: Cryptotanshinone (CTS) is an important active ingredient of Salvia miltiorrhiza Bge. In recent years, its remarkable pharmacological effects have triggered extensive and in-depth studies. The aim of this study is to retrieve the latest research progress on CTS and provide prospects for future research. The selection of literature for inclusion, data extraction and methodological quality assessment were discussed. Studies included (1) physicochemical and ADME/Tox properties, (2) pharmacological effects and mechanism, (3) conclusion and bioinformatics analysis. A total of 915 titles and abstracts were screened, resulting in 184 papers used in this review; CTS has shown therapeutic effects on a variety of diseases by modulating multiple molecular pathways. For example, CTS primarily targets NF-κB pathway and MAPK pathway to have a therapeutic role in cardiovascular diseases; in cancer, CTS shows superior efficacy through the PI3K/Akt/mTOR pathway and the JAK/STAT pathway; CTS act on the Nrf2/HO-1 pathway to combat neurological diseases. In addition, key targets of CTS were predicted by bioinformatics analysis, referring to disease ontology (DO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analysis, with R Studio; AKT1, MAPK1, STAT3, P53 and EGFR are predicted to be the key targets of CTS against diseases. The key proteins were then docked by Autodock software to preliminarily assess their binding activities. This review provided new insights into research of CTS and its potential applications in the future, and especially the targets and directly binding modes for CTS are waiting to be investigated. Keywords: cryptotanshinone, pharmacological effects, molecular mechanism, bioinformatics analysis

Purpose. To quantitatively investigate the reflectivity and structure of the outer retinal layers in children with hyperopic anisometropic amblyopia by using swept-source optical coherence tomography (SS-OCT). Methods: Seventy-eight patients with amblyopia and 64 age-matched children with normal vision were included in this study. All participants underwent SS-OCT and detailed ophthalmic examinations. Longitudinal reflectance profile measurements were measured using Image J. The reflectivity of outer retinal layers was measured at the three selected positions: subfovea, 1 mm nasal to the fovea, and 1 mm temporal to the fovea. The reflectivity ratios were calculated by outer retinal layers divided by the nuclear layer (ONL) for normalization. Photoreceptor outer segment layer thickness was also measured. The results were compared between the amblyopia and normal controls. The possible effects of age, sex, and axial length on results were adjusted by generalized estimating equations. Results: Photoreceptor outer segment layer thickness was significantly greater in amblyopic eyes than in normal control eyes at all three regions (18.41 ± 1.83 vs. 16.84 ± 1.39, P < 0.001 at the fovea; 14.78 ± 1.34 vs. 14.19 ± 1.40, P = 0.030 at 1 mm nasal to the foveal; 14.92 ± 1.48 vs. 14.41 ± 1.32, P = 0.049 at 1 mm temporal to the fovea). The reflectivity ratio of outer segment/ONL was higher only at 1 mm nasal to the fovea (2.94 ± 0.61 vs. 2.70 ± 0.42, P = 0.02). Subfoveal OS thickness was positively correlated with choroidal thickness (r = 0.248, P = 0.018) but was not correlated with spherical equivalent, age, axial length, or logMAR visual acuity. Conclusion: Quantitative measurement of SS-OCT images revealed greater photoreceptor outer segments in both eyes of children with amblyopia than in normal control eyes. A thicker OS thickness is somehow related to amblyopia, and this may be a new useful diagnostic parameter for amblyopia.

Ma Huang,&ast; Xinxin Liu,&ast; Yingcong Ren,&ast; Qianxia Huang, Yuanzhi Shi, Ping Yuan, Miao Chen Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi City, Gui Zhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Miao Chen, Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi City, Gui Zhou, People’s Republic of China, Email chenmiao64@163.comAbstract: In intensive care units, acute lung injury (ALI) is a syndrome that is frequently encountered. It is associated with a high rate of morbidity and mortality. Despite the extensive research conducted by the medical community on its treatment, no specific effective drugs have been identified. Quercetin is a natural flavonoid with many biological activities and pharmacological effects. Research indicates that Quercetin can modulate various targets and signaling pathways, inhibiting oxidative stress, inflammatory responses, ferroptosis, apoptosis, fibrosis, and bacterial and viral infections in ALI. This regulation suggests its potential therapeutic application for the condition. Currently, there is no comprehensive review addressing the application of Quercetin in the treatment of ALI. This paper begins with a classification of ALI, followed by a detailed summary of the mechanisms through which Quercetin may treat ALI to evaluate its potential as a novel therapeutic option. Keywords: quercetin, acute lung injury, treatment, oxidative stress, inflammation

Jiahui Shi,1 Shuangwei Li,1 Langping Yi,1 Minghuang Gao,1 Jiaying Cai,1 Cong Yang,1 Yujie Ma,1 Yousheng Mo,2 Qi Wang1 1Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 2Department of Hepatology, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Yousheng Mo; Qi Wang, Email 378480308@qq.com; wangqi@gzucm.edu.cnIntroduction: Acute kidney injury (AKI) is characterized by a significant reduction in kidney function and the accumulation of metabolites such as Creatinine (CRE) and Blood Urea Nitrogen (BUN). Levistolide A (LA), an active component of Ligusticum chuanxiong, offers multiple therapeutic benefits, including cardiovascular and neuroprotection, antitumor and analgesic effects, as well as anti-inflammatory, antioxidant, antifibrotic, and proapoptotic actions. However, the underlying mechanism of LA in treating AKI has not been fully elucidated.Methods: In this study, we established a glycerol-induced AKI model in mice to evaluate the protective effects of LA. Renal function was assessed by measuring levels of CRE and BUN. Histological analyses were performed to evaluate kidney tissue damage. Additionally, oxidative stress markers, apoptosis indicators, inflammatory cell infiltration, and inflammatory mediator levels were assessed. The involvement of the TLR-4/NF-κB signaling pathway was investigated through molecular assays.Results: LA treatment significantly ameliorated glycerol-induced AKI in mice, evidenced by reduced levels of CRE and BUN. Histological examination revealed decreased renal tissue damage in LA-treated groups. LA exerted antioxidant effects by increasing the levels of Glutathione (GSH) and Superoxide Dismutase (SOD), while reducing Reactive Oxygen Species (ROS) accumulation. Apoptosis in renal tissues was attenuated, as indicated by decreased caspase-3 activation. Furthermore, LA reduced the infiltration of inflammatory cells and the release of inflammatory mediators such as TNF-α and IL-6. Mechanistically, LA suppressed the inflammatory response by inhibiting the TLR-4/NF-κB signaling pathway, as demonstrated by reduced NF-κB activation and decreased expression of TLR-4.Conclusion: Levistolide A mitigates acute kidney injury through its antioxidative properties and modulation of the TLR-4/NF-κB signaling pathway. These findings provide valuable insights into the therapeutic potential of LA for AKI treatment and lay the groundwork for further mechanistic studies.Keywords: acute kidney injury, levistolide A, TLR-4/NF-&Kgr;b, inflammatory response, antioxidant effect

Jie Li,1,&ast; Wenyang Ma,1,&ast; Wuzhuang Tang,1 Kaixuan Yang,2 Hongqiu Gu,2 Junfeng Shi,1 Feng Chen,1 Chenhan Xu,1 Shiyuan Gu,1 Yongjun Wang2,3 1Department of Neurology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiyuan Gu; Yongjun Wang, Email shiyuan1178@hotmail.com; yongjunwang@ncrcnd.org.cnBackground and Objective: Raised serum glucose-phosphate ratio on admission is associated with severity and poor outcome of aneurysmal subarachnoid hemorrhage and severe traumatic brain injury. However, its role in acute ischemic stroke (AIS) remains still unknown. Therefore, this prospective study aimed to investigate the association between admission serum glucose-phosphate ratio and the severity and 1-year clinical outcome of AIS.Methods: All the patients with AIS were enrolled from the Third China National Stroke Registry III. Participants were classified into four groups according to quartiles of admission serum glucose-phosphate ratio levels. Multiple regression models and restricted cubic splines were performed to evaluate the association between serum glucose-phosphate ratio and the severity and 1-year outcome of patients with AIS.Results: Among the 5,541 participants, the mean age was 62.3 years, and 69.4% patients were men. As the quartiles of admission serum glucose-phosphate ratio increased, the median NIHSS score raised, the percentage of moderate and severe stroke elevated, and rates of poor functional outcomes and recurrent stroke raised at one-year follow-up. After adjusting conventional risk factors, the highest admission serum glucose-phosphate ratio-level quartile group showed an association of poor functional outcome and stroke recurrence [OR (95% CI): 1.67 (1.28, 2.17) and HR (95% CI): 1.44 (1.08, 1.92), respectively], relative to the lowest group. Restricted cubic splines showed no significant nonlinear relationship between serum glucose-phosphate ratio and adverse outcomes of AIS.Conclusion: Admission serum glucose-phosphate ratio may be a potential blood biomarker for reflecting stroke severity, predicting poor functional outcomes, and stroke recurrence.Keywords: serum glucose-phosphate ratio, acute ischemic stroke, outcome, severity, blood biomarker

Abstract The gig economy, fundamentally relying on the digital economy, is often celebrated for its potential to expand employment opportunities and close gender wage gaps. However, research on its gender impacts in China, the largest developing country with a rapidly expanding gig sector, is notably lacking. Employing discrimination theory, the findings challenge the prevailing optimistic view on the role of the gig economy. Utilising the China Labour Dynamics Survey data from 2014, 2016, and 2018, and applying the Bourguignon, Fournier, and Gurgand model to correct selection bias, this study reveals that, digitalisation has exacerbated gender wage gaps, with the wage growth of female gig workers significantly lagging behind their male counterparts, especially among married and older cohorts. Adopting the Neumark decomposition, the analysis confirms that discrimination largely accounts for this gap. This study uses Generalised Propensity Score Matching as robustness test and concludes with policy recommendations.

Abstract Mitogen-activated protein kinase (MAPK) cascades are evolutionarily conserved in both plants and animals and play critical roles in activating innate immunity to defend against various pathogens. However, the role of MAPK cascades in positively regulating or enhancing viral infections in plants is unclear. In this study, we investigate the involvement of MAPK cascades in infection by the positive-strand RNA virus tomato chlorosis virus (ToCV). Our findings reveal that ToCV infection activates MAPK cascades, promoting virus spread within plants. Specifically, ToCV P7, a pathogenicity determinant protein, localizes to the plasma membrane and recruits NbMPK3/6 from the nucleus. Subsequently, P7 is directly phosphorylated on serine 59 by NbMPK3/6. Phosphorylated P7 interacts with NbREM1.1 and inhibits its ability to induce callose deposition at plasmodesmata. These results demonstrate that NbMPK3/6 directly phosphorylate ToCV P7, modulating antiviral defence mechanisms by downregulating callose deposition at plasmodesmata and thereby enhancing ToCV transmission in N. benthamiana. This study sheds light on the intricate arms race between host defence and viral counter-defence strategies.

Abstract Extracellular vesicles (EVs) are known to mediate cell communications and shape tumor microenvironment. Compared to the well-studied small EVs, the function of large microvesicles (MVs) during tumorigenesis is poorly understood. Here we show the proteome of MVs in Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC), and identify olfactomedin 4 (OLFM4) is induced by EBV infection and secreted via MVs to promote tumor progression through Hippo signaling. Specifically, OLFM4 is a target gene of the cGAS-STING pathway, and EBV infection activates cGAS-STING pathway and increases OLFM4 expression. Moreover, MV-carried OLFM4 binds with the extracellular cadherin domain of FAT1, thereby impairing its intracellular interaction with MST1 and leading to YAP activation in recipient cells. Together, our study not only reveals a regulatory mechanism though which viral infection is coupled via MVs with intercellular control of the Hippo signaling, but also highlights the OLFM4-Hippo axis as a therapeutic target for EBV-associated cancers.

Abstract The transient receptor potential melastatin (TRPM) channel family has been previously implicated in various diseases, including those related to temperature sensing, cardiovascular health, and neurodegeneration. Nowadays, increasing evidence indicates that TRPM family members also play significant roles in various types of cancers, exhibiting both pro- and anti-tumorigenic functions. They are involved in tumor cell proliferation, survival, invasion, and metastasis, serving as potential diagnostic and prognostic biomarkers for cancer. This paper begins by describing the structure and physiological functions of the TRPM family members. It then outlines their roles in several common malignancies, including pancreatic, prostate, colorectal, breast, brain cancer, and melanoma. Subsequently, we focused on investigating the specific mechanisms by which TRPM family members are involved in tumorigenesis and development from both the tumor microenvironment (TME) and intracellular signaling. TRPM channels not only transmit signals from the TME to regulate tumor cell functions, but also mediate extracellular matrix remodeling, which is conducive to the malignant transformation of tumor cells. Importantly, TRPM channels depend on the regulation of the inflow of various ions in cells, and participate in key signaling pathways involved in tumor progression, such as Wnt/β-catenin, MAPK, PI3K/AKT, p53, and autophagy. Finally, we summarize the current strategies and challenges of targeting TRPM channels in tumor treatment, and discuss the feasibility of combining targeted TRPM channel drugs with cancer immunotherapy.

Abstract Information security plays an important role in every aspect of life to protect data from stealing and deciphering. However, most of the previously reported works were based on pure algorithm layer or pure physical layer encryptions, which have certain limitations in security. In this paper, a nondeterministic message encryption communication scheme is proposed based on a spin-space-frequency multiplexing metasurface (SSFMM), which integrates both algorithmic and physical layer encryptions, and can also produce multiple different ciphertexts for the same message to prevent the message from being cracked through frequency analysis, thus greatly enhancing the security of the information. To be specific, an SSFMM is first designed as a physical-layer meta-key, which can generate eight independent dot matrix holograms with different spin, space, and frequency characteristics. The target message is then encrypted based on these dot matrix holograms combined with algorithmic operations, and the encrypted message is converted into a quick response (QR) code for easy sending to the target users. Once the target user gets that QR code, he/she can scan it to obtain the encryption information, and then recover the target message according to the pre-agreed encryption protocol combined with the eight dot matrix holograms of SSFMM. Finally, the feasibility of the proposed encryption scheme was experimentally validated at the microwave frequency band.

Abstract Purpose This multicenter qualitative study aimed to explore the perceptions of clinicians and research ethics boards (REBs) regarding ethical issues in Investigator Initiated Trials (IITs). Methods Between February and April 2024, semi-structured interviews were conducted with 27 participants from 15 tertiary hospitals, including clinical doctors and members of REBs. Responses were grouped and analyzed using a descriptive phenomenological approach. Results Clinicians expressed challenges in navigating the formal review process due to limited access to information and unclear guidelines. Academic review highlighted a deficiency in research literacy among clinical investigators, leading to flawed study design. Ethical review revealed concerns about inadequate ethical awareness among clinicians, resulting in failed ethical approvals. Moreover, delays in review processes and resource shortages were noted, hindering the efficient conduct of IITs. Conclusion The findings underscore the need for comprehensive training programs to enhance clinicians’ research literacy and ethical awareness. Establishing a comprehensive system to support IITs, including enhanced guidance and support from REBs, is essential to ensure the quality and integrity of IITs in China.

Xiaowen Han,1 Ruiling Xu,1 Yang Xia,2 Ying Liu,3 Shan Chen,3 Mingsong Shi,1 Zhiyan Zou,1 Yuanyuan Liang,1 Tingting Chen,1 Yufeng Tang,4 Wei Tang,3 Xiaoan Li,1,5 Liangxue Zhou2,6,7 1NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China; 2Department of Neurosurgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China; 3Institute of Materials, China Academy of Engineering Physics, Jiangyou, 621907, People’s Republic of China; 4Department of Neurology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China; 5Department of Gastroenterology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China; 6Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 7Department of Neurosurgery, the Fifth People’s Hospital of Ningxia, Shizuishan, Ningxia, 753000, People’s Republic of ChinaCorrespondence: Xiaoan Li; Liangxue Zhou, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China, Email lixiaoan@sc-mch.cn; liangxue_zhou@126.comPurpose: Skin radiation damage is a prevalent form of tissue injury encountered during radiotherapy, radiation accidents, and occupational exposure. The only clinically approved radioprotective agent, amifostine, is associated with numerous side effects, underscoring the urgent need for the development of safe and effective radioprotective agents. Natural products with reductive properties possess high antioxidant activity and biocompatibility, but their low bioavailability limits their radioprotective efficacy and clinical application. To address this, we utilized epigallocatechin gallate (EGCG) as a model compound and employed nanotechnology to enhance cellular uptake of natural compounds, thereby improving their free radical scavenging capabilities.Methods: EGCG nanoparticles (EGCG NPs) with robust intracellular reactive oxygen species (ROS) scavenging ability were prepared via self-assembly. The morphology, size distribution, and antioxidant capacity of EGCG NPs were characterized. Cytocompatibility, intracellular ROS levels and DNA damage, cell migration and immune response of EGCG NPs to macrophages were tested in vitro. The in vivo radiation protection and biocompatibility of EGCG NPs were assessed in murine model.Results: The EGCG NPs was successfully prepared and compared to free EGCG, EGCG NPs demonstrated better cellular uptake, significantly enhancing their biocompatibility, intracellular ROS scavenging capacity, and ability to mitigate DNA damage. Furthermore, EGCG NPs facilitated fibroblast proliferation and migration, while inhibiting the polarization of macrophages towards the M1 phenotype in vitro. In animal levels, EGCG NPs exhibited markedly improved radioprotective efficacy over free EGCG, effectively reducing skin edema and ulceration, alleviating pathological conditions such as interstitial edema, dermal fluid accumulation, and inflammatory infiltration, decreasing the duration of skin injury, and promoting wound healing.Conclusion: This work offers novel insights into the therapeutic application of EGCG NPs as a potential alternative for skin radioprotection and provides a powerful approach for developing radioprotective agents derived from natural products. Keywords: radiation-induced skin injury, nanoparticles, free radicals scavenging, radioprotection

Abstract Collaborative transmission, comprising multiple devices owned by a single user, is progressively evolving into an essential strategy to meet the stringent demands of burgeoning collaborative scenarios in 5G‐advanced and 6G networks. This paper proposes three novel use cases for device collaboration, namely data duplication, data splitting and wireless backup, to address these requirements. To provide dynamic and efficient collaboration, both non‐transparent mode via the medium access control layer collaboration and transparent mode via the physical layer collaboration are proposed. The paper further introduces a comprehensive design framework including protocol stack design, user equipment capability reporting, user equipment pairing, scheduling mechanism and transmission mechanism for different collaborative use cases with different collaborative modes. Evaluation outcomes reveal that the recommended methods could decrease the resources consumed for data duplication while increasing the user perceived throughput for data duplication and data splitting. The proposed methods also augment transmission reliability for both data duplication and wireless backup.

The Hefang crucian carp (HFJ) derived from Carassius cuvieri (♀) × C. auratus red var. (♂) and the crucian carp-like homodiploid fish (NCRC) derived from Cyprinus carpio (♀) × Megalobrama amblycephala (♂) are important germplasm resources of crucian carp. To investigate the population characteristics and reveal the current genetic situations of these hybrid varieties, we sequenced one nuclear molecular marker transferrin (Tf) among six Carassius populations, which included two hybrid varieties (HFJ and NCRC), one laboratory variety (red crucian carp, RCC) and three wild populations. A total of 166 distinct Tf alleles (A1∼A166) were identified, with sequence lengths ranging from 1145 bp to 1244 bp. Unexpectedly, the nucleotide diversity of Tf alleles in cultured populations (HFJ, NCRC, and RCC) exceeded that of wild populations. The phylogenetic reconstruction analysis results showed that HFJ and C. cuvieri were closely related, but they could not be separated from C. auratus. Besides, while most Tf alleles of NCRC and other Carassius populations were intermixed in five clades, two Tf alleles, together with Cy. carpio, formed a distinct monophyletic clade. Moreover, network and genetic structure analyses failed to distinguish between wild and cultured populations. Although AMOVA analysis based on Tf alleles indicated genetic differentiation among all six populations, the majority of the genetic variation (92.00 %) was observed within populations. Furthermore, the population dynamics analysis suggested that these populations have maintained relative stability in recent history. Therefore, the elevated nucleotide diversity of Tf alleles in cultured populations, the ambiguous population structure, and the limited genetic divergence among the six Carassius populations highlighted the hybrid genetic characteristics of HFJ and NCRC. These findings, based on Tf alleles, differ from the results obtained using mitochondrial gene markers, providing an alternative perspective for germplasm evaluation of hybrid varieties and crucian carp breeding.

The artificial breeding of carp existed in China 8000 years ago. The breeding of carp played an important role in ancient Chinese history, and it still played a crucial role in modern aquaculture. The output of carp in China is very high, accounting for 8.42 % of the total output of freshwater products in 2023, ranking fifth in the total output of freshwater aquaculture fish. At the same time, carp is also the fish species with the highest number of new varieties bred in China. With the advent of the genomics era, breeding technologies have also made progress. This paper reviews the history and current status of carp farming, the germplasm resources of carp, and the application of fish genetic breeding technology in the germplasm innovation of carp.

Infected bone defect is a formidable clinical challenge. Conventional approaches to prevention and treatment for infected bone defects are unsatisfactory. The key elements of the treatment are bone defect reconstruction, anti-infection, and osteogenesis. Conventional treatment methods remain unsatisfactory owing to the absence of composite integrating materials with anti-infective, and osteogenic activities as well as proper mechanical strength at the same time. In this study, we fabricated a vancomycin-encapsulated hydrogel with bacteria-responsive release properties combined with a shaved porous (submicron-micron) three-dimensional-printed Ti6Al4V implant. The implant surface, modified with submicron-sized pores through microarc oxidation (MAO), showed enhanced osteogenic activity and integrated well with the hydrogel drug release system, enabling sustained vancomycin release. In vitro experiments underscored the commendable antibacterial ability, biosafety, and osteoinductive potential. Effective antibacterial and osteogenic abilities of the implant were further demonstrated in vivo in infected rabbit bone defects. These results showed that the vancomycin-encapsulated hydrogel-loaded microarc-oxidized 3D-printed porous Ti6Al4V can repair the infected bone defects with satisfactory anti-infection and osseointegration effects.