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Cui-Ping Li,1,* Lei Li,2,* Lin-Ming Su,3,* Shu-Sheng Zhu,4 Meng-Jie Li5 1Department of Pathology, Renmin Hospital of Qingxian, Cangzhou, People’s Republic of China; 2Department of the First Surgery, Wuhan Jin-Yin-Tan Hospital, Wuhan, People’s Republic of China; 3Department of Radiology, Renmin Hospital of Qingxian, Cangzhou, People’s Republic of China; 4Department of Thoracic Surgery, Taizhou Hospital of Traditional Chinese Medicine, Taizhou, People’s Republic of China; 5Department of Respiratory Oncology, Renmin Hospital of Qingxian, Cangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shu-Sheng Zhu; Meng-Jie Li, Email lwb421223@163.com; lmjnkdf@163.comAbstract: Schwannomas are benign slow-growing tumors arising from the embryonic neural crest cells of the nerve sheaths of peripheral and cranial nerves, and they are a rare type of soft tissue mass that is usually always solitary. Generally, it grows in the head, neck, and flexor portions of the limbs, where many nerves are located. Schwannomas of the lung are extremely rare. Fewer than ten cases of schwannomas in this organ region have been reported in the existing literature. In this case report, a 40-year-old male non-smoker was hospitalized with occasional chest pain. His chest computed tomographic scan revealed a 3.8 cm space occupying lesion in the upper lobe of the right lung. This lesion has clear boundaries and uneven internal density. And it was concluded as a benign lesion possibility, it is preferred to be considered as a haematoma. This space occupying lesion was eventually confirmed as a schwannoma by needle biopsy tissues. Due to the presence in rare locations, such as the lung, the clinical presentation of this space occupying lesion is non-specific, making diagnosis difficult. The data presented in this case report can help clinicians to obtain information on the identification of this disease, which highlighted lung schwannoma as a differential diagnosis for patients with intermittent pain. It can also alert clinicians and radiologists to observe every detail of the radiology imaging findings.Keywords: diagnosis, schwannoma, lung cancer, thoracic radiology, solitary pulmonary nodule

Yin Dong,1,* Ming-Jing Li,2,* Yan-Zhu Hong,3 Wen-Jie Li4 1Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 4Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan-Zhu Hong, Xiamen University, No. 422, Siming South Road, Siming District, Xiamen, Fujian, 361005, People’s Republic of China, Tel +86 13671617025, Email hongyanzhu2020@sina.com Wen-Jie Li, Shanghai University of Traditional Chinese Medicine, No. 1200 Cai-lun Road, Pudong District, Shanghai, 201203, People’s Republic of China, Tel +86 15397687742, Email liwenjie@shutcm.edu.cnAbstract: Dysmenorrhea, classified as primary dysmenorrhea and secondary dysmenorrhea, is a common gynecological symptom that seriously affects female daily life. At present, studies on dysmenorrhea are numerous and complex. To better reflect the trend and innovative progress of dysmenorrhea-related research, this study screened papers on the Web of Science from January 1, 1992, to December 31, 2022. A total of 1012 papers were selected and analyzed for their affiliated countries, institutions, authors, keywords, etc. China is the country with the most academic output, Beijing University of Traditional Chinese Medicine is the most influential institution, and Yang Jie, from Chengdu University of Traditional Chinese Medicine, China, is the scholar with the most papers. We consider that the current research focus is on pathogenesis, treatment, epidemiology, and self-management. With increasing research on functional connectivity between dysmenorrhea and various brain regions, functional connectivity has gradually become the forefront of research. We hope our study can promote the further study of dysmenorrhea.Keywords: pathogenesis, treatment, management, traditional Chinese medicine

Wan-Ling Liu,1– 4,* Yong-Qu Zhang,1– 5,* Xiang-Jie Luo,6 Yuan-Yuan Zhu,1– 4 Liang Song,7 Zi-He Ming,1– 4 Li-Xin Zhang,1– 4 Meng-Jun Li,1– 4 Rui-Chan Lv,8 Guo-Jun Zhang,1– 4,9,* Min Chen2– 4,* 1Department of Breast-Thyroid-Surgery and Cancer Center, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 2Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer, Xiang’an Hospital of Xiamen University, Xiamen, People’s Republic of China; 3Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, Xiamen, People’s Republic of China; 4Xiamen Research Center of Clinical Medicine in Breast & Thyroid Cancers, Xiamen, People’s Republic of China; 5Department of Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, People’s Republic of China; 6College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, People’s Republic of China; 7Xiamen Institute of Rare Earth Materials, Haixi Institute, Chinese Academy of Sciences and Technology University, Xiamen, People’s Republic of China; 8Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi’an, Shanxi, People’s Republic of China; 9Cancer Research Center, School of Medicine, Xiamen University, Xiamen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Min Chen; Guo-Jun Zhang, Email mchen@xah.xmu.edu.cn; gjzhang@xah.xmu.edu.cnBackground: Durable responses to immune-checkpoint blocking therapy (ICT) targeting programmed cell death protein-1/ligand-1 (PD-1/PD-L1) have improved outcomes for patients with triple negative breast cancer (TNBC). Unfortunately, only 19– 23% of patients benefit from ICT. Hence, non-invasive strategies evaluating responses to therapy and selecting patients who will benefit from ICT are critical issues for TNBC immunotherapy.Methods: We developed a novel nanoparticle-Atezolizumab (NPs-Ate) consisting of indocyanine green (ICG), gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA), human serum albumin (HSA), and Atezolizumab. The efficiency of Gd-DTPA linking was verified using mass spectrometry, and the size of NPs-Ate was characterized using Nano-flow cytometry. The synthesized NPs-Ate were evaluated for fluorescence stability, penetration depth, and target specificity. TNBC cell lines and tumor-bearing mice models were used to identify the feasibility of this dual-modal second near-infrared/magnetic resonance imaging (NIR-II/MRI) system. Additionally, ICT combination with chemotherapy or radiotherapy in TNBC tumor-bearing mice models were used to assess dynamic changes of PD-L1 and predicted therapeutic responses with NPs-Ate.Results: Atezolizumab, a monoclonal antibody, was successfully labeled with ICG and Gd-DTPA to generate NPs-Ate. This demonstrated strong fluorescence signals in our NIR-II imaging system, and relaxivity (γ 1) of 9.77 mM− 1 s− 1. In tumor-bearing mice, the NIR-II imaging signal background ratio (SBR) reached its peak of 11.51 at 36 hours, while the MRI imaging SBR reached its highest as 1.95 after 12 hours of tracer injection. NPs-Ate specifically targets cells and tumors expressing PD-L1, enabling monitoring of PD-L1 status during immunotherapy. Combining therapies led to inhibited tumor growth, prolonged survival, and increased PD-L1 expression, effectively monitored using the non-invasive NPs-Ate imaging system.Conclusion: The NIR-II/MRI NPs-Ate effectively reflected PD-L1 status during immunotherapy. Real-time and non-invasive immunotherapy and response/prognosis monitoring under NIR-II/MRI imaging guidance in TNBC is a promising and innovative technology with potential for extensive clinical applications in the future.Keywords: dual-modal imaging, triple-negative breast cancer, immune-checkpoint blocking therapy, programmed cell death protein ligand-1, monitoring therapeutic response

Meng-Jie Li,1,* Jun Wei,2,* Guo-Ping Ai,3,* Ying Liu,4 Jian Zhu4 1Department of Respiratory Oncology, Renmin Hospital of Qingxian, Cangzhou, 062650, People’s Republic of China; 2Department of the First Surgery, Wuhan Jin-Yin-Tan Hospital, Wuhan, 430011, People’s Republic of China; 3Department of Radiology, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan, 430070, People’s Republic of China; 4Department of Thoracic Cardiovascular Surgery, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan, 430070, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Zhu; Ying Liu, Department of Thoracic Cardiovascular Surgery, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan, 430070, People’s Republic of China, Tel +86-13871166489, Fax +86-27-50772388, Email zhujian0718@163.com; xxwkly@163.comIntroduction: Molecular targeted therapy has shown certain therapeutic effects on various cancer types, especially lung cancer. Here, we report a case of a patient with unresectable non-small cell lung cancer (NSCLC) with bone metastases and metastatic lesions that disappeared after molecular targeted therapy.Patient Information: A 49-year-old male patient’s chest CT scan showed a patchy, slightly high-density shadow on the upper lobe of the left lung with an unclear boundary. The multiple thoracic vertebrae, 4th lumbar vertebrae, multiple ribs, right sacroiliac joint, right hip joint, right inferior ramus of pubis, left middle and upper femur, and right proximal radial bone showed nodular and slightly high-density shadows.Interventions: The patient was not considered eligible for tumor resection due to his metastatic lesions. A resected lymph node biopsy was performed. The pathologic findings suggested lung adenocarcinoma, and the gene detection results indicated NM-005228:exon19:c.2235– 2249del:p. GLu746-Ala750del (15.31%), NM-005228:exon20:c. G2356A: p. V786M (1.67%). The patient received the icotinib hydrochloride molecular targeted therapy.Outcomes: After two months of treatment, pulmonary nodules were basically absent on chest CT scan re-examination. After nine months of treatment, no obvious abnormalities in the thoracic vertebral bone were found on 99mTc-MDP bone scan and CT scan re-examination. No obvious structural abnormalities, such as enlarged lymph nodes, could be found by ultrasound re-examination, and the patient remained alive without recurrence at the five-year follow-up.Conclusion: This case report may provide a clue for the future development of molecular targeted therapy for lung cancer. It will allow surgeons to collaborate with oncologists and raise awareness of the benefit of the multidisciplinary approach to the diagnosis and treatment of cancer. Moreover, our results will help patients to fully understand the effect of nonsurgical treatments and improve confidence in the diagnosis and treatment of advanced lung cancer.Keywords: bone metastases, lung cancer, molecular targeted therapy, gene therapy

Lei Li,1,* Meng-Jie Li,2,* Liu Sun,3,* Yuan-Liang Jiang,4 Jian Zhu5 1Department of the First Surgery, Wuhan Jin-Yin-Tan Hospital, Wuhan, 430011, People’s Republic of China; 2Department of Respiratory Oncology, Renmin Hospital of Qingxian, Cangzhou, 062650, People’s Republic of China; 3Department of Otolaryngology-Head and Neck Surgery, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan, 430070, People’s Republic of China; 4Department of Radiology, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan, 430070, People’s Republic of China; 5Department of Thoracic Cardiovascular Surgery, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan, 430070, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Zhu; Yuan-Liang Jiang, General Hospital of Central Theater Command of the People’s Liberation Army, 627#, Wuluo Road, Wuchangqu, Wuhan, Hubei, 430070, People’s Republic of China, Tel +86-13871166489, Fax +86-27-50772388, Email zhujian0718@163.com; whzyyjyl@126.comAbstract: Foreign body aspiration (FBA) occurs less frequently in adults than in children. Case reports of FBAs occurring in adults after lung surgery are not found in the literature, and this particular condition is often misdiagnosed. We report a case in which the patient was diagnosed after various events. A 56-year-old female patient had undergone robotic-assisted resection of the right upper lobe. The patient recovered well after the operation, with a slight irritant dry cough. Chest computed tomography (CT) examination of the patient showed no obvious abnormality early postoperatively. However, she developed intermittent cough and hemoptysis at six months. Repeat chest CT showed a soft tissue shadow near the bronchus in the lower lobe of the right lung. Cancer recurrence, surgery-related foreign body residue, lymphoid reactive hyperplasia, or other reasons was considered. Further examination revealed a piece of watermelon seed shell blocking the bronchial opening of the lower lung. This case highlights the importance of medical history, careful physical examination and fiberoptic bronchoscopic examination after lung cancer surgery due to lung cancer recurrence risk or FBA.Keywords: foreign body aspiration, cancer recurrence, fiberoptic bronchoscopy, diagnosis

Bo Yang,1– 3,* Lin-Lin Ji,1,2,* Hong-Liang Xu,1,* Xiao-Ping Li,3 Hong-Gang Zhou,4 Ting Xiao,4 Xiao-He Li,4 Zhou-Yong Gao,1,2 Jian-Zhong Li,5 Wei-Dong Zhang,3 Guang-Shun Wang,1 Ming-Jiang Li3 1Department of Thoracic Surgery, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Tianjin, 301800, People’s Republic of China; 2State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing, 102206, People’s Republic of China; 3Department of Thoracic Surgery, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, 300192, People’s Republic of China; 4State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key, Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300353, People’s Republic of China; 5Department of Thoracic Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guang-Shun WangDepartment of Thoracic Surgery, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Tianjin, 301800, People’s Republic of ChinaEmail wgs@bddhospital.comMing-Jiang LiDepartment of Thoracic Surgery, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, 300192, People’s Republic of ChinaEmail mingjiangli@nankai.edu.cnBackground: Zc3h12d is a negative regulator which plays a crucial role in immune modulation. However, the role of zc3h12d in lung adenocarcinoma (LUAD) remains unclear. We aim to explore the prognostic of zc3h12d and investigate the relationship between zc3h12d expression and immune infiltration in LUAD.Methods: TIMER site was used to analyze the expression of zc3h12d in LUAD. The zc3h12d protein levels in patient tissue samples were detected by immunohistochemistry staining assays. Meanwhile, based on UALCAN database and samples’ data from our cohort, we explored the relationship of clinicopathological features and zc3h12d expression to determine the clinical effect of zc3h12d in LUAD. Several databases including GEPIA, Kaplan–Meier plotter and our samples’ data were used to explore the prognostic value of zc3h12d in LUAD. Cox regression analysis was established to further evaluate the prognostic value of zc3h12d in LUAD. In addition, zc3h12d promoter methylation was analyzed by UALCAN database. Genetic alteration analysis was observed in the cBioPortal web. GO and KEGG analyses were conducted to elucidate the underlying mechanisms. Finally, the correlation between zc3h12d and tumor-infiltrating immune cells in LUAD was investigated by TIMER database. The B cells level was investigated by flow cytometry analysis of peripheral blood from our LUAD cohort.Results: Zc3h12d expression was significantly higher in LUAD, compared with adjacent normal tissues. The clinical data from the UALCAN database demonstrated that zc3h12d expression was closely related with cancer stage and nodal metastasis. However, patient sample detection revealed that zc3h12d expression was closely related to pathological N (p = 0.0431) and grade (p = 0.004). Moreover, low zc3h12d expression was associated with poorer overall survival in LUAD. We analyzed the methylation level of zc3h12d in LUAD and found that the methylation levels of zc3h12d promoter in LUAD were significantly reduced. In addition, zc3h12d genetic alterations, including deep deletion, could be found in LUAD. GO and KEGG pathway analysis results indicated that zc3h12d has a certain value in immune infiltration. We investigated the expression of zc3h12d in tumor-immune interactions. It was found that zc3h12d might be associated with the immune infiltration and markers of infiltrating immune cells of LUAD. The results of patient sample detection confirmed that B cells level was significantly lower in the patients with low zc3h12d expression than those in the patients with high zc3h12d expression.Conclusion: zc3h12d might be considered as a potential biomarker for determining prognosis and immune-related therapeutic target in LUAD.Keywords: zc3h12d, lung adenocarcinoma, hypomethylation, tumor microenvironment, prognosis

Qintai Yang,1 Hui Li,2,* Weijun Wu,2,* Xuekun Huang,1 Bo Tu,2 Yukun Ma,2 Huiyi Deng,1 Meijiao Li,1 Hongfeng He,2 Can Li,2 Yongqi Yang2 1Department of Otorhinolaryngology – Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Otorhinolaryngology – Head and Neck Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: The effect of continuous positive airway pressure (CPAP) on nasal symptoms in patients with obstructive sleep apnea–hypopnea syndrome (OSAHS) remains controversial. In addition, possible mechanism(s) remains unclear. Objective: To examine whether CPAP contributes to the onset and exacerbation of allergic rhinitis (AR) in OSAHS patients based on patient-reported changes in nasal symptoms with and without CPAP therapy and the detection of house dust mites (HDMs) in CPAP filters and household environments. Materials and methods: In a cohort of OSAHS patients, 350 patients who were undergoing CPAP therapy and 100 patients who declined CPAP therapy were retrospectively analyzed. These patients were contacted by telephone and asked to compare their nasal symptoms before and after CPAP therapy. HDMs in air conditioner and CPAP device filters and in household dust samples were detected using enzyme-linked immunosorbent assays. Results: The prevalence of AR was higher in the CPAP group vs the non-CPAP group (15.8% vs 7.0%, respectively; P = 0.025). The onset of AR among the OSAHS patients with no previous history of AR significantly increased within the first year of CPAP therapy compared with the control group (5.7% vs 0%, respectively; P = 0.031). Meanwhile, the patients with a history of AR were more likely to experience exacerbated rhinitis symptoms within the second year of treatment compared with the control group (7.5% vs 0%, respectively; P = 0.005). There was no significant difference in HDM concentrations between the CPAP and air conditioner filters, yet the concentrations in both the filters were higher than the concentrations in the bedroom dust samples (all P < 0.05). Conclusion: CPAP is associated with the onset and exacerbation of AR in OSAHS patients. Long-term exposure to high concentrations of HDM allergens may be a significant factor. Keywords: obstructive sleep apnea–hypopnea syndrome, continuous positive airway pressure, allergic rhinitis, house dust mites, allergens

Objective: To study the anatomical and biomechanical features of sacral pedicle and lateral mass so as to provide reference for clinical screw fixation technology of sacral pedicle and lateral mass.Methods: A total of 60 adult patients'spiral CT images of the sacrum and coccyx were selected randomly. The entry points of sacral pedicle and lateral mass screws were determined, and the screw trajectory was measured using the three dimensional reconstruction method. Meanwhile, the gross anatomy was scrutinized in 15 adult cadaver specimens to determine the sacral pedicle and lateral mass screw entry points. The length, width and angle of sacral pedicle and lateral mass screw trajectory were measured. Eight of 15 cadaver specimens were selected to test the maximal extraction force of sacral pedicle and lateral mass screws. The clinical data of 15 cases treated by pedicle and lateral mass screw technology were collected and analyzed.Results: The diameter and length of S(1)-S(5) sacral pedicle and lateral mass screw trajectory were regular, with about 20 degree inclination angle. The S(1) pedicle screw entry point was located at the intersection point of the basal lateral part of articular process and median line of transverse process, and no significant difference was found for the maximal extraction force between pedicle and lateral mass screws (P larger than 0.05). The entry points of S(2)-S(5) pedicle screws were located at the intersection point of the line connecting adjacent posterior sacral foramina and median line of the transverse process. The lateral mass screw entry point of S(2)-S(5) was on the median side of intersection point between median line of the transverse process and lateral sacral crest. The maximal extraction force of pedicle screws was significantly greater than that of lateral mass screws (P less than 0.05).Conclusion: Both the sacral pedicle and the lateral mass screw fixation techniques can offer effective fixation and reconstruction for fracture of the sacrum and coccyx, but pedicle screw fixation may be more convenient, safe and reliable than lateral mass screw fixation. [ABSTRACT FROM AUTHOR]

Unraveling the causal variants from genome wide association studies (GWASs) is pivotal for understanding genetic underpinnings of complex traits and diseases. Despite continuous efforts, tools to refine and prioritize GWAS signals need enhancement to address the direct causal implications of genetic variations. To overcome challenges related to statistical fine-mapping in identifying causal variants, CAUSALdb has been updated with novel features and comprehensive datasets, morphing into CAUSALdb2. This expanded repository integrates 15 057 updated GWAS summary statistics across 10 839 unique traits and implements both LD-based and LD-free fine-mapping approaches, including innovative applications of approximate Bayes Factor and SuSiE. Additionally, by incorporating larger LD reference panels such as TOPMED and UK Biobank, and integrating functional annotations via PolyFun, CAUSALdb2 enhances the accuracy and context of fine-mapping results. The database now supports interrogation of additional causal signals and offers sophisticated visualizations to aid researchers in deciphering complex genetic architectures. By facilitating a deeper and more precise characterisation of causal variants, CAUSALdb2 serves as a crucial tool for advancing the genetic analysis of complex diseases. Available freely, CAUSALdb2 continues to set benchmarks in the post-GWAS era, fostering the development of targeted diagnostics and therapeutics derived from responsible genetic research. Explore these advancements at http://mulinlab.org/causaldb., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Transcriptome-wide association study (TWAS) has successfully identified numerous complex disease susceptibility genes in the post-genome-wide association study (GWAS) era. Over the past 3 years, the focus of TWAS algorithms has shifted from merely identifying associations to understanding how single nucleotide polymorphisms (SNPs) regulate gene expression, with a growing emphasis on incorporating fine-mapping techniques. Additionally, the rapid increase in GWAS summary statistics, driven largely by the UK Biobank and other consortia, has made it essential to update our webTWAS resource. To address these challenges and meet the growing needs of researchers, we developed webTWAS 2.0, an updated platform for identifying susceptibility genes for human complex diseases using TWAS. Additionally, webTWAS 2.0 provides an online TWAS analysis tool that simplifies conducting TWAS analyses. The updated resource includes 7247 GWAS summary statistics covering 1588 complex human diseases from 192 publications. It also incorporates multiple TWAS methods, such as sTF-TWAS, 3'aTWAS and GIFT, along with an updated interactive visualization tool that allows users to easily explore significant associations across different methods. Other upgrades include a personalized online analysis tool for user-submitted GWAS data and a refined search function that makes it easier to identify relevant associations and meet diverse user needs more efficiently. webTWAS 2.0 is freely accessible at http://www.webtwas.net., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: In the United States, most (~ 70%) annual newly diagnosed HIV infections are among substance-using sexual minority men (SMM) and gender minority transgender women (trans women). Trans women and SMM are more likely to report or be diagnosed with a substance use disorder (SUD) than their cisgender or heterosexual counterparts and the presence of an SUD substantially increases the risk of HIV infection in both groups. Although Pre-Exposure Prophylaxis (PrEP) is highly effective, initiation, adherence, and persistence are exclusively behavioral outcomes; thus, the biomedical benefits of PrEP are abrogated by substance use. SUD is also associated with reduced quality-of-life, and increased overdose deaths, utilization of high-cost healthcare services, engagement in a street economy, and cycles of incarceration., Objective: To determine the optimal (considering efficacy and cost-effectiveness) strategy for advancement along the PrEP Care Continuum among trans women and SMM with an SUD., Methods: This study will implement a randomized controlled trial, evaluating two Stepped Care approaches involving A.S.K.-PrEP vs. standard of care (SOC) to determine optimal intervention strategies for trans women and SMM with an SUD (N = 250; n = 83 trans women; n = 167 SMM) for advancement along the PrEP Care Continuum. Participants will be randomized (3:1) to Stepped Care (n = 187) or SOC (n = 63). Participants in the Stepped Care arm will be assessed at 3-months for intervention response; responders will be maintained in A.S.K.-PrEP, while non-responders will receive added attention to their SUD via Contingency Management (CM). Non-responders will be re-randomized (1:1) to either (a) receive A.S.K.-PrEP + CM, or (b) shift the primary focus to their SUD (CM alone)., Results: Recruitment and enrollment began in May 2023. Recruitment will span approximately 36 months. Data collection, including all follow-up assessments, is expected to be completed in April 2027., Discussion: Trans women and SMM with an SUD have the two highest HIV prevalence rates in the United States, which underscores the urgent need for effective measures to develop scalable behavioral interventions that can encourage advancement along the PrEP Care Continuum. To improve public health, researchers must identify scalable and cost-effective behavioral interventions to promote PrEP initiation, adherence, and persistence among trans women and SMM who use substances., Trial Registration: This trial has been registered at ClinicalTrials.gov under the number NCT05934877., (© 2024. The Author(s).)

Purpose: Retinal neovascularization poses heightened risks of vision loss and blindness. Despite its clinical significance, the molecular mechanisms underlying the pathogenesis of retinal neovascularization remain elusive. This study utilized single-cell multiomics profiling in an oxygen-induced retinopathy (OIR) model to comprehensively investigate the intricate molecular landscape of retinal neovascularization., Methods: Mice were exposed to hyperoxia to induce the OIR model, and retinas were isolated for nucleus isolation. The cellular landscape of the single-nucleus suspensions was extensively characterized through single-cell multiomics sequencing. Single-cell data were integrated with genome-wide association study (GWAS) data to identify correlations between ocular cell types and diabetic retinopathy. Cell communication analysis among cells was conducted to unravel crucial ligand-receptor signals. Trajectory analysis and dynamic characterization of Müller cells were performed, followed by integration with human retinal data for pathway analysis., Results: The multiomics dataset revealed six major ocular cell classes, with Müller cells/astrocytes showing significant associations with proliferative diabetic retinopathy (PDR). Cell communication analysis highlighted pathways that are associated with vascular proliferation and neurodevelopment, such as Vegfa-Vegfr2, Igf1-Igf1r, Nrxn3-Nlgn1, and Efna5-Epha4. Trajectory analysis identified a subset of Müller cells expressing genes linked to photoreceptor degeneration. Multiomics data integration further unveiled positively regulated genes in OIR Müller cells/astrocytes associated with axon development and neurotransmitter transmission., Conclusions: This study significantly advances our understanding of the intricate cellular and molecular mechanisms underlying retinal neovascularization, emphasizing the pivotal role of Müller cells. The identified pathways provide valuable insights into potential therapeutic targets for PDR, offering promising directions for further research and clinical interventions.

Introduction: Anemia may contribute significantly to the onset of Parkinson's disease (PD). Current research on the association between anemia and PD risk is inconclusive, and the relationships between anemia-related blood cell indices and PD incidence require further clarification. This study aims to investigate the relationships between anemia, blood cell indicators, and PD risk using a thorough prospective cohort study., Methods: We used data from the UK Biobank, a prospective cohort study of 502,649 participants, and ultimately, 365,982 participants were included in the analysis. Cox proportional hazards models were utilized to adjust for confounding factors, aiming to thoroughly explore the associations between anemia and blood cell indices with the risk of incident PD. The interaction between anemia and Polygenic Risk Score (PRS) for PD was also examined. Linear regression and mediation analyses assessed potential mechanisms driven by brain structures, including grey matter volume., Results: During a median follow-up of 14.24 years, 2513 participants were diagnosed with PD. Anemia considerably increased PD risk (hazard ratio [HR] 1.98, 95 % confidence interval [CI]: 1.81-2.18, P < 0.001) after adjustments. Those with high PRS for anemia had an 83 % higher PD incidence compared to low PRS participants. Sensitivity analyses confirmed result robustness. Linear regression showed that anemia correlated with grey matter volumes and most white matter tracts. Furthermore, mediation analyses identified that the volume of grey matter in Thalamus mediates the relationship between anemia and PD risk., Conclusion: In summary, we consider there to be a substantial correlation between anemia and increased PD risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Cancer cells metastatic to the leptomeninges encounter a metabolically-challenging extreme microenvironment. To understand adaptations to this space, we subjected leptomeningeal-metastatic (LeptoM) mouse breast and lung cancers isolated from either the leptomeninges or orthotopic primary sites to ATAC-and RNA-sequencing. When inhabiting the leptomeninges, the LeptoM cells demonstrated transcription downstream of retinoid-X-receptors (RXRs). We found evidence of local retinoic acid (RA) generation in both human leptomeningeal metastasis and mouse models in the form of elevated spinal fluid retinol and expression of RA-generating dehydrogenases within the leptomeningeal microenvironment. Stimulating LeptoM cells with RA induced expression of transcripts encoding de novo fatty acid synthesis pathway enzymes in vitro . In vivo , while deletion of Stra6 did not alter cancer cell leptomeningeal growth, knockout of Rxra/b/g interrupted cancer cell lipid biosynthesis and arrested cancer growth. These observations illustrate a mechanism whereby metastatic cancer cells awake locally-generated developmental cues for metabolically reprograming, suggesting novel therapeutic approaches.

Covalent organic frameworks are a type of crystalline porous materials that linked through covalent bond, and they have numerous potential applications in adsorption, separation, catalysis, and more. However, there are rarely relevant reported on photochromism. Fortunately, a hydrazone-linked DBTB-DETH-COF is rapidly generated through ultrasound method. The DBTB-DETH-COF is found to exhibit reversible photochromism (at least 50 cycles) from yellow to olive in the presence of light and air, and subsequently back to the original color upon heating. In addition, the structure of DBTB-DETH-COF remains unchanged after 15 days of light illumination. Furthermore, the reason of photochromic process is discussed by electron paramagnetic resonance, X-ray photoelectron spectroscopy, electrochemistry characterizations and transient absorption measurements. The reversible photochromic DBTB-DETH-COF can be used as anti-counterfeiting ink and optical switch in the presence of air. This work expands a stable organic photochromic material and broadens the applications of COFs., (© 2024. The Author(s).)

The heavy metal cadmium (Cd) is a toxic and bioaccumulative metal that can be enriched in the tissues and organs of living organisms through the digestive tract. However, more research is needed to determine whether food-sourced Cd affects the homeostasis of host gut microflora. In this study, the snail Bradybaena ravida (Benson) was used as a model organism fed with mulberry leaves spiked with different concentrations of Cd (0, 0.052, 0.71, and 1.94 mg kg -1 ). By combining 16S rRNA high-throughput sequencing with biochemical characterization, it was found that there were increases in the overall microbial diversity and abundances of pathogenic bacteria such as Corynebacterium, Enterococcus, Aeromonas, and Rickettsia in the gut of B. ravida after exposure to Cd. However, the abundances of potential Cd-resistant microbes in the host's gut, including Sphingobacterium, Lactococcus, and Chryseobacterium, decreased with increasing Cd concentrations in the mulberry leaves. In addition, there was a significant reduction in activities of energy, nutrient metabolism, and antioxidant enzymes for gut microbiota of snails treated with high concentrations of Cd compared to those with low ones. These findings highlight the interaction of snail gut microbiota with Cd exposure, indicating the potential role of terrestrial animal gut microbiota in environmental monitoring through rapid recognition and response to environmental pollution., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: This study aimed to investigate whether flow fluid shear stress (FFSS)-mediated signal transduction affects the function of Piezo1 ion channel in chondrocyte and to further explore the role of mechanical overloading in development of temporomandibular joint osteoarthritis (TMJ OA)., Methods: Immunohistochemical staining was used to determine the expression of Piezo1 in TMJ OA tissue collected from rat unilateral anterior crossbite (UAC) models. Chondrocytes harvested from normal adult SD rats were treated with FFSS (0, 4, 8, 12 dyn/cm 2 ) in vitro. Immunofluorescent staining, real-time polymerase chain reaction, western blotting, flow cytometry and phalloidin assay were performed to detect the changes of cellular morphology as well as the expression of Piezo1 and certain pro-inflammatory and degradative factors in chondrocyte., Results: Immunohistochemical analysis revealed that significantly increased Piezo1 expression was associated with UAC stimulation (p < .05). As applied FFSS escalated (4, 8 and 12 dyn/cm 2 ), the expression levels of Piezo1, ADAMTS-5, MMP-13 and Col-X gradually increased, compared with the non-FFSS group (p < .05). Administering Piezo1 ion channel inhibitor to chondrocytes beforehand, it was observed that expression of ADAMTS-5, MMP-13 and Col-X was substantially decreased following FFSS treatment (p < .05) and the effect of cytoskeletal thinning was counteracted. The activated Piezo1 ion channel enhanced intracellular Ca 2+ excess in chondrocytes during abnormal mechanical stimulation and the increased intracellular Ca 2+ thinned the cytoskeleton of F-actin., Conclusions: Mechanical overloading activates Piezo1 ion channel to promote pro-inflammation and degradation and to increase Ca 2+ concentration in chondrocyte, which may eventually result in TMJ OA., (© 2024 John Wiley & Sons Ltd.)

Background and Aims: A 12-week placebo-controlled, sequential parallel Accelerated Development of Additive Pharmacotherapy Treatment for Methamphetamine Use Disorder (ADAPT-2) trial evaluated the effects of extended-release injectable naltrexone plus extended-release oral bupropion (NTX + BUPN) on methamphetamine (MA) use over two stages. This study reports on the previously unpublished stage 2 MA use in participants randomized at stage 1 to receive NTX + BUPN through both stages compared with those assigned to placebo., Design: This is a secondary analysis of the US National Institute on Drug Abuse (NIDA) ADAPT-2 network trial., Setting: The parent ADAPT-2 trial was carried out across multiple NIDA Clinical Trials Network (CTN) sites in the United States., Participants: This analysis includes 403 people with MA use disorder who participated in the ADAPT-2 CTN trial., Intervention and Comparator: NTX + BUPN was compared with placebo over the course of the trial., Measurement: MA use was measured by urine drug screens conducted twice weekly for 12 weeks, then once in week 13 and once in week 16 post-treatment follow-up., Findings: Participants on NTX + BUPN in stage 1 showed an additional 9.2% increase [95% confidence interval (CI), 0.09%-17.9%, P = 0.038] during stage 2 in their probability of testing negative for MA, with a total increase of 27.1% (95% CI, 13.2%-41.1%, P < 0.001) over the full 12 weeks of treatment. In contrast, participants on placebo in both stages increased in probability of testing MA-negative by a total of 11.4% (95% CI, 4.1%-18.6%, P = 0.002) over all 12 weeks. The 12-week increase among participants on NTX + BUPN was significantly greater-by 15.8% (95% CI, 4.5%-27.0%, P = 0.006)-than the increase among those on placebo., Conclusion: For people with methamphetamine (MA) use disorder receiving treatment with extended-release injectable naltrexone plus extended-release oral bupropion (NTX + BUPN), continued treatment with NTX + BUPN after 6 weeks is associated with additional reductions in MA use up to 12 weeks., (© 2024 Society for the Study of Addiction.)

Introduction: An early evaluating system for autism spectrum disorder (ASD) severity is crucial. Questionnaire survey is challenging for accurately assessing the severity levels for ASD in children., Methods: Offspring with ASD-like phenotypes were induced by treating pregnant mice with Poly (I:C) at GD12.5 and the placentae corresponding to the offspring were obtained by caesarean. The autism severity composite score (ASCS) for offspring was calculated through behavioral tests. HE staining and immunohistochemistry were used to observe the morphology of placenta. Candidate biomarkers were identified by weighted protein co-expression network analysis (WPCNA) combined with machine learning and further validated by ELISA. Sperman's was used to analyze the correlation between biomarkers and metabolome., Results: The placental weight and mean vascular area of male offspring with ASD-like phenotypes were significantly decreased compared with typical mice. According to the WPCNA, four modules were identified and significantly correlated with ASCS of offspring. Two biomarkers (ASPG and DAD1) with high correlation with ASCS in offspring were identified., Discussion: VEGF pathway may contribute to sexual dimorphism in placental morphology within mice with ASD-like phenotypes in term. The placental ASPG and DAD1 levels could reflect ASD-like symptom severity levels in male/female mice offspring., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A smartphone-assisted electrochemiluminescence (ECL) strategy based on Ru(bpy) 2 (L) 4+ as chromophores confined with metal - organic frameworks (Ru(bpy) 2 (L) 4+ @MOF-5) for the signal-amplified detection of miRNA-21 was developed. We synthesized a derivative of tris(2,2'-bipyridyl)ruthenium(II) complex (Ru(bpy) 2 (L) 4+ ) with high charges, which can be loaded into the MOF-5 by strong electrostatic interaction to prevent from leakage. In addition, nucleic acid cycle amplification was used to quench the signal of Ru(bpy) 2 (L) 4+ @MOF-5 by ferrocene. This method was applied to detect the concentration of miRNA-21 ranging from 1.0 × 10 -14 -1.0 × 10 -9 M with a low LOD of 7.2 fM. This work demonstrated the construction of a signal quenching strategy ECL biosensor for miRNA using Ru(bpy) 2 (L) 4+ @MOF-5 systems and its application in smartphone-assisted ECL detection., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Myocardial fibrosis, a hallmark of heart disease, is closely associated with macrophages, yet the genetic pathophysiology remains incompletely understood. In this study, we utilized integrated single-cell transcriptomics and bulk RNA-seq analysis to investigate the relationship between macrophages and myocardial fibrosis across omics integration., Methods: We examined and curated existing single-cell data from dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), myocardial infarction (MI), and heart failure (HF), and analyzed the integrated data using cell communication, transcription factor identification, high dimensional weighted gene co-expression network analysis (hdWGCNA), and functional enrichment to elucidate the drivers of macrophage polarization and the macrophage-to-myofibroblast transition (MMT). Additionally, we assessed the accuracy of single-cell data from the perspective of driving factors, cell typing, anti-fibrosis performance of left ventricular assist device (LVAD). Candidate drugs were screened using L1000FWD., Results: All four heart diseases exhibit myocardial fibrosis, with only MI showing an increase in macrophage proportions. Macrophages participate in myocardial fibrosis through various fibrogenic molecules, especially evident in DCM and MI. Abnormal RNA metabolism and dysregulated transcription are significant drivers of macrophage-mediated fibrosis. Furthermore, profibrotic macrophages exhibit M1 polarization and increased MMT. In HF patients, those responding to LVAD therapy showed a significant decrease in driver gene expression, M1 polarization, and MMT. Drug repurposing identified cinobufagin as a potential therapeutic agent., Conclusion: Using integrated single-cell transcriptomics, we identified the drivers of macrophage-mediated myocardial fibrosis in four heart diseases and confirmed the therapeutic effect of LVAD on improving HF with single-cell accuracy, providing novel insights into the diagnosis and treatment of myocardial fibrosis., (© 2024. The Author(s).)

Introduction: Hybrid rice demonstrated superior performance in enhancing yield and efficiency in rice production compared to inbred rice. Nevertheless, the underlying mechanism responsible for the increased yield and efficiency of hybrid rice in South China's double-cropping rice region remains understudied., Methods: Field experiments over two consecutive years were conducted. Firstly, yield variations among 20 inbred and 15 hybrid rice cultivars prevalent in South China's double-cropping rice system were examined. Secondly, selecting representative hybrid and inbred rice cultivars with significant yield disparities were carried out on further analyzing dry-matter production, source-sink relationships, and nutrient absorption and utilization in both rice types., Results: Hybrid rice displayed an average grain yield of 8.07 and 7.22 t hm -2 in the early and late seasons, respectively, which corresponds to a 12.29% and 13.75% increase over inbred rice with statistically significant differences. In comparison to inbred rice, hybrid rice exhibited enhanced nitrogen concentration in leaves at the heading stage (15.48-16.20%), post-heading dry matter accumulation (52.62-73.21%), post-heading dry matter conversion rate (29.23-34.12%), and harvest index (17.31-18.37%). Additionally, grain nitrogen and phosphorus uptake in hybrid rice increased by 11.88-22.50% and 16.38-19.90%. Hybrid rice mainly improved post-heading nitrogen and phosphorus uptake and transport, while not total nitrogen and phosphorus uptake. Internal nitrogen and phosphorus use efficiency enhanced by 9.83%-14.31% and 10.15%-13.66%, respectively. Post-heading dry matter accumulation, harvest index, grain nitrogen and phosphorus uptake, and internal nitrogen and phosphorus use efficiency exhibited significant positive linear correlations with grain yield., Discussion: The period from heading to maturity is critical for enhancing hybrid rice yield and efficiency. Improving photosynthetic capacity during this period and promoting nutrient transport to grains serve as crucial pathways for increasing grain yield and efficiency. This study is of great significance for further improvement grain yield and breeding rice cultivars with high-yield and high nutrients use efficiency for South China's double-cropped rice system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fu, Lu, Zhong, Liang, Pan, Liu, Hu, Hu, Li, Wang, Ye, Yin, Huang and Huang.)

Carbon supplementation strategies still have certain practical application constraints. Zn/Fe-based metal-organic frameworks (MOFs) nanoparticles that which are not toxic to Scenedesmus obliquus were successfully introduced into microalgal solutions to overcome low CO 2 solubility. The maximum specific surface area of MOFs reached 342.94 m 2 ·g -1 at a Zn/Fe molar ratio of 10/1. Under the optimal MOFs concentrations of 2.5 mg·L -1 , the conversion of inorganic carbon increased by 2.6-fold. When S. obliquuswas cultured in a MOFs-modified medium with 1.50 % CO 2 at 25 °C, the CO 2 mass transfer coefficient and mixing time reached 9.01 × 10 -3 min -1 and 55 s, respectively. The maximum chlorophyll-a content, biomass productivity, and CO 2 fixation efficiency reached 32.57 mg·L -1 , 0.240 g·L -1 ·d -1 and 21.6 %, respectively. Enriching CO 2 for ribulose-1,5-bisphosphate carboxylase/oxygenase carboxylation by MOFs may be the key to improving the photosynthetic efficiency of microalgae. This strategy could serve as a reference for improving the microalgal CO 2 fixation efficiency., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Terrestrial animal intestines are hotspots for the enrichment of micro/nano plastics (M/NPs) and antibiotic-resistant genes (ARGs). However, little is known about the further impact of M/NPs on the spread of ARGs in animal guts. This study investigates the role of M/NPs (polystyrene) with varying particle sizes (0.082, 42, and 182 μm), concentrations (10 and 100 mg/L), and exposure durations (4 and 16 days) in the ARGs dissemination via conjugation in the edible snail (Achatina fulica) gut. Combination of qPCR with 16S rRNA-based sequencing, we found that PS exposure caused intestinal cell impairment and shifts in the gut microbial community of snails. Conjugation rate increased with PS particle sizes in the snail gut. After 4 days of exposure, significantly higher conjugation rates were observed in the gut exposed to 100 mg/L PS compared to 10 mg/L, however, this trend reversed after 16 days. Consistently, the abundances of conjugation relevant genes trfA and trbB shared similar trends to the conjugation ratios in the snail gut after PS exposure. Transconjugant diversity was much lower in 10 mg/L PS groups than in 100 mg/L PS treatments. Therefore, this study suggests that the presence of M/NPs would complicate management of ARG spread. The selection pressure exerted by M/NPs may sustain or even amplify the spread of ARGs in the gut of terrestrial animals even in the absence of antibiotics. It highlights the necessity of avoiding M/NPs intake as a part of comprehensive strategy for cubing ARG dissemination in the gut of animals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

This study investigated the possible interaction between gut flora and miRNAs and the effect of both on anxiety disorders. The model group was induced with chronic restraint stress (CRS) and each group was tested for anxiety-like behaviour by open field test and elevated plus maze test. Meanwhile, the gut flora was analysed by 16S rRNA high-throughput sequencing. The miRNAs in hippocampus were analysed by high-throughput sequencing, and the key miRNAs were obtained by using the method of bioinformatics analysis. PCR was used to verify the significantly related key miRNAs. Spearman correlation analysis was used to explore the correlation between behaviour, key miRNAs and differential gut microbiota. The 16S rRNA high-throughput sequencing result showed that the gut flora was dysregulated in the model group. In particular, Verrucomicrobia, Akkermansia, Anaerostipes, Ralstonia, Burkholderia and Anaeroplasma were correlated with behaviour. The results of miRNA high-throughput sequencing analysis and bioinformatics analysis showed that 7 key miRNAs influenced the pathogenesis of anxiety, and qRT-PCR results were consistent with the high-throughput sequencing results. Mmu-miR-543-3p and mmu-miR-26a-5p were positively correlated with Verrucomicrobia, Akkermansia and Anaerostipes. Therefore, we infer that chronic stress caused the decrease of Akkermansia abundance, which may aggravate the decrease of mmu-miR-543-3p and mmu-miR-26a-5p expression, leading to the increase of SLC1A2 expression. In conclusion, gut flora has played an important influence on anxiety with changes in miRNAs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is a neurodegenerative disorder frequently accompanied by neuroinflammation and oxidative stress. The medicine and food homology (MFH) has shown potential for treating neuroinflammation and oxidative stress. This study aimed to provide a safe and efficient therapy for AD based on MFH. In this study, we develop a MFH formula consisting of egg yolk oil, perilla seed oil, raphani seed oil, cinnamon oil, and noni puree (EPRCN). To evaluate the ameliorative effects of EPRCN on AD-related symptoms, a mouse model of AD was constructed using intraperitoneal injection of scopolamine in ICR mice. Experimental results demonstrated that EPRCN supplement restored behavioral deficits and suppressed neuroinflammation and oxidative stress in the hippocampus of scopolamine-induced mice. An in vitro study was then performed using induction of Aβ (25-35) in glial (BV-2 and SW-1783) and neuron (SH-SY5Y) cell lines to examine the improvement mechanism of EPRCN on cognitive deficits. Multi-omics and in vitro studies demonstrated that these changes were driven by the anandamide (AEA)-Trpv1-Nrf2 pathway, which was inhibited by AM404 (an AEA inhibitor), AMG9810 (a Trpv1 inhibitor), and BT (an Nrf2 inhibitor). Consequently, EPRCN is an effective therapy on preventing cognitive deficits in mouse models of AD. In contrast to donepezil, EPRCN exhibits a novel modes action for ameliorating neuroinflammation. The mechanism of EPRCN on preventing cognitive deficits is mediated by improving neuroinflammation and oxidative stress via activating the AEA-Trpv1-Nrf2 pathway., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

We administered a questionnaire to participants who received different vaccination regimens to evaluate the effectiveness of Ad5-vectored COVID-19 vaccines. The results showed that administration of intramuscular Ad5-nCoV provided 21.32% more protection against SARS-CoV-2 infection than that of the inactivated COVID-19 vaccine in people who had received only one type of COVID-19 vaccine. Furthermore, aerosolized Ad5-nCoV exhibited good protection, whether it was administered as a homologous booster to people vaccinated with the intramuscular Ad5-nCoV or as a heterologous booster to people vaccinated with inactivated COVID-19 vaccines. Our research indicates that Ad5-nCoV is an effective booster. This finding supports the future selection of COVID-19 immunization strategies.

In patients with liver cirrhosis, approximately one-third experience pigmented cholelithiasis. In parallel to this, cirrhotics consequently encounter a greater prevalence of acute cholecystitis. Traditionally, the definitive treatment for acute cholecystitis in non-cirrhotic patients is cholecystectomy. However, decompensated cirrhosis and portal hypertension pose a surgical challenge, as these comorbidities increase the risk of postoperative complications such as bleeding, infection, and multi-organ failure. Therefore, it is of utmost importance to consider patient risk factors, anatomy, and acuity of patient cholecystitis on an individual basis and develop a surgical (or non-surgical) plan that minimizes risk to patients with decompensated cirrhosis and portal hypertension. We present the management strategies of a case of a 50-year-old male who presents with a history of decompensated liver cirrhosis and portal hypertension complicated by acute cholecystitis. Upon initial presentation, he was critically ill, and a percutaneous cholecystostomy tube was placed for management and the patient was instructed to follow up in the clinic. Then, the patient later returned to the emergency department with a fever, UTI, and sepsis. At that time, his cholecystostomy tube continued to have bilious drainage and he had tenderness in the right upper quadrant. The decision was made to proceed with surgery. Because of his significant comorbid conditions and underlying cirrhosis, surgery posed an increased risk. For this patient, it was especially important to evaluate the risk of complications and the decision of open vs laparoscopic cholecystectomy. In this patient, robotic-assisted laparoscopic cholecystectomy was eventually performed. Due to the patient's hepatomegaly, splenomegaly, and portal hypertension, special consideration was needed for trocar placement. In this case, we aim to exemplify that is of utmost importance to consider patient anatomy by using imaging and marking organ borders to inform trocar placement as part of the surgical approach., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Li et al.)

Coreopsis tinctoria Nutt. is an important medicinal plant in traditional Uyghur medicine. The skin-lightening potential of the flower has been recognized recently; however, the active compounds responsible for that are not clear. In this work, tyrosinase, a target protein for regulating melanin synthesis, was immobilized on the Whatman paper for the first time to screen skin-lightening compounds present in the flower. Quercetagetin-7- O -glucoside ( 1 ), marein ( 2 ), and okanin ( 3 ) were found to be the enzyme inhibitors. The IC 50 values of quercetagetin-7- O -glucoside ( 1 ) and okanin ( 3 ) were 79.06 ± 1.08 μM and 30.25 ± 1.11 μM, respectively, which is smaller than 100.21 ± 0.11 μM of the positive control kojic acid. Enzyme kinetic analysis and molecular docking were carried out to investigate their inhibition mechanism. Although marein ( 2 ) showed a weak inhibition effect in vitro, it inhibited the intracellular tyrosinase activity and diminished melanin production in melanoma B16 cells as did the other two inhibitors. The paper-based ligand fishing method developed in this work makes it effective to quickly screen tyrosinase inhibitors from natural products. This is the first report on the tyrosinase inhibitory effect of those three compounds, showing the promising potential of Coreopsis tinctoria for the development of herbal skin-lightening products.

Diabetes, a prevalent chronic condition, significantly increases the risk of mortality from COVID-19, yet the underlying mechanisms remain elusive. Emerging evidence implicates Cathepsin L (CTSL) in diabetic complications, including nephropathy and retinopathy. Our previous research identified CTSL as a pivotal protease promoting SARS-CoV-2 infection. Here, we demonstrate elevated blood CTSL levels in individuals with diabetes, facilitating SARS-CoV-2 infection. Chronic hyperglycemia correlates positively with CTSL concentration and activity in diabetic patients, while acute hyperglycemia augments CTSL activity in healthy individuals. In vitro studies reveal high glucose, but not insulin, promotes SARS-CoV-2 infection in wild-type cells, with CTSL knockout cells displaying reduced susceptibility. Utilizing lung tissue samples from diabetic and non-diabetic patients, alongside Lepr db/db mice and Lepr db/+ mice, we illustrate increased CTSL activity in both humans and mice under diabetic conditions. Mechanistically, high glucose levels promote CTSL maturation and translocation from the endoplasmic reticulum (ER) to the lysosome via the ER-Golgi-lysosome axis. Our findings underscore the pivotal role of hyperglycemia-induced CTSL maturation in diabetic comorbidities and complications., Competing Interests: QH, MZ, ML, XL, JJ, YF, LZ, WH, FY, JY No competing interests declared, (© 2024, He, Zhao et al.)

The MYB(v-myb avian myeloblastosis viral oncogene homolog) family of transcription factors is the largest class of genes among higher plant transcription factors, which can be divided into four subfamilies, with the R2R3-MYB being the most common subfamily type. R2R3-MYB transcription factors are widely involved in the regulation of organ development and secondary metabolite biosynthesis in plants. To investigate the role of R2R3-MYB family transcription factors in the synthesis of flavonoids and glandular trichome development in Artemisia argyi, this study screened and identified 92 R2R3-MYB transcription factors based on the whole genome data of A. argyi, and predicted their potential functions based on bioinformatics. The results showed that the amino acid lengths of the 92 transcription factors ranged from 168 to 547 aa, with relative molecular weights ranging from 19. 6 to 60. 5 kDa, all of which were hydrophilic proteins. Subcellular localization analysis showed that 89 AaMYB proteins were located in the nucleus, while three proteins were simultaneously located in the nucleus and cytoplasm. According to the classification of Arabidopsis R2R3-MYB family, the 92 A. argyi R2R3-MYB proteins were divided into 26 subfamilies, with similar gene structures within the same subfamily.Cis-acting element prediction results showed that light-responsive elements, methyl jasmonate elements, and abscisic acid elements were widely distributed in the promoter regions of R2R3-MYB genes. Transcriptome expression analysis results showed that the expression of AaMYB60, AaMYB63, and AaMYB86 in leaves was higher than that in stems and roots, indicating that these three transcription factors mainly function in leaves. Additionally, five candidate R2R3-MYB transcription factors involved in A. argyi flavonoid biosynthesis or glandular trichome development were selected through phylogenetic analysis. This study provides important genetic resources for the breeding of superior varieties and germplasm innovation of A. argyi in the future.

Tibetan strawberry ( Fragaria nubicola ) is a wild medicinal and edible plant in Tibet possessing various health benefits such as neuroprotection and anti-oxidation. However, there has been little study reported on its chemical constituents. To investigate the inhibitors of monoamine oxidase B (MAO-B) in Tibetan strawberry, we immobilized the enzyme onto cellulose filter paper for the first time to develop a new screening method. Two known glycosides (compounds 1 and 2 ) and one new iridoid glucoside (Compound 3 ) were fished out by this method, which was found to effectively inhibit MAO-B with IC 50 values of 16.95 ± 0.93, 24.69 ± 0.20, and 46.77 ± 0.78 μM, respectively. Molecular docking and kinetic analysis were performed to reveal the inhibition mechanism of these compounds. Furthermore, compound 1 exhibited neuroprotective effects against 6-OHDA-induced injury on PC12 cells. The developed method exhibits the advantages of rapidness and effectiveness in screening of MAO-B inhibitors from complex herbal extracts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of Interest No conflict of interest exits in the submission of this manuscript. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, nor under consideration for publication elsewhere, in whole or in part.

The pursuit of effective treatments for brain tumors has increasingly focused on the promising area of nanoparticle-enhanced radiotherapy (NERT). This review elucidates the context and significance of NERT, with a particular emphasis on its application in brain tumor therapy-a field where traditional treatments often encounter obstacles due to the blood-brain barrier (BBB) and tumor cells' inherent resistance. The aims of this review include synthesizing recent advancements, analyzing action mechanisms, and assessing the clinical potential and challenges associated with nanoparticle (NP) use in radiotherapy enhancement. Preliminary preclinical studies have established a foundation for NERT, demonstrating that nanoparticles (NPs) can serve as radiosensitizers, thereby intensifying radiotherapy's efficacy. Investigations into various NP types, such as metallic, magnetic, and polymeric, have each unveiled distinct interactions with ionizing radiation, leading to an augmented destruction of tumor cells. These interactions, encompassing physical dose enhancement and biological and chemical radio sensitization, are crucial to the NERT strategy. Although clinical studies are in their early phases, initial trials have shown promising results in terms of tumor response rates and survival, albeit with mindful consideration of toxicity profiles. This review examines pivotal studies affirming NERT's efficacy and safety. NPs have the potential to revolutionize radiotherapy by overcoming challenges in targeted delivery, reducing off-target effects, and harmonizing with other modalities. Future directions include refining NP formulations, personalizing therapies, and navigating regulatory pathways. NERT holds promise to transform brain tumor treatment and provide hope for patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Li, Liang, Sun, Shao, Hu and Xing.)

Stress tolerance in apple (Malus domestica) can be improved by grafting to a stress-tolerant rootstock, such as 'SH6' (Malus honanensis × M. domestica 'Ralls Genet'). However, the mechanisms of stress tolerance in this rootstock are unclear. In Arabidopsis (Arabidopsis thaliana), the transcription factor ZINC FINGER OF ARABIDOPSIS THALIANA 10 is a key component of plant tolerance to multiple abiotic stresses and positively regulates antioxidant enzymes. However, how reactive oxygen species are eliminated upon activation of ZINC FINGER OF ARABIDOPSIS THALIANA 10 in response to abiotic stress remains elusive. Here, we report that MhZAT10 in the rootstock SH6 directly activates the transcription of three genes encoding the antioxidant enzymes MANGANESE SUPEROXIDE DISMUTASE 1 (MhMSD1), ASCORBATE PEROXIDASE 3A (MhAPX3a) and CATALASE 1 (MhCAT1) by binding to their promoters. Heterologous expression in Arabidopsis protoplasts showed that MhMSD1, MhAPX3a and MhCAT1 localize in multiple subcellular compartments. Overexpressing MhMSD1, MhAPX3a or MhCAT1 in SH6 fruit calli resulted in higher superoxide dismutase, ascorbate peroxidase and catalase enzyme activities in their respective overexpressing calli than in those overexpressing MhZAT10. Notably, the calli overexpressing MhZAT10 exhibited better growth and lower reactive oxygen species levels under simulated osmotic stress. Apple SH6 plants overexpressing MhZAT10 in their roots via Agrobacterium rhizogenes-mediated transformation also showed enhanced tolerance to osmotic stress, with higher leaf photosynthetic capacity, relative water content in roots and antioxidant enzyme activity, as well as less reactive oxygen species accumulation. Overall, our study demonstrates that the transcription factor MhZAT10 synergistically regulates the transcription of multiple antioxidant-related genes and elevates reactive oxygen species detoxification., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The co-occurrence and familial clustering of neurodevelopmental disorders and immune disorders suggest shared genetic risk factors. Based on genome-wide association summary statistics from five neurodevelopmental disorders and four immune disorders, we conducted genome-wide, local genetic correlation and polygenic overlap analysis. We further performed a cross-trait GWAS meta-analysis. Pleotropic loci shared between the two categories of diseases were mapped to candidate genes using multiple algorithms and approaches. Significant genetic correlations were observed between neurodevelopmental disorders and immune disorders, including both positive and negative correlations. Neurodevelopmental disorders exhibited higher polygenicity compared to immune disorders. Around 50%-90% of genetic variants of the immune disorders were shared with neurodevelopmental disorders. The cross-trait meta-analysis revealed 154 genome-wide significant loci, including 8 novel pleiotropic loci. Significant associations were observed for 30 loci with both types of diseases. Pathway analysis on the candidate genes at these loci revealed common pathways shared by the two types of diseases, including neural signaling, inflammatory response, and PI3K-Akt signaling pathway. In addition, 26 of the 30 lead SNPs were associated with blood cell traits. Neurodevelopmental disorders exhibit complex polygenic architecture, with a subset of individuals being at a heightened genetic risk for both neurodevelopmental and immune disorders. The identification of pleiotropic loci has important implications for exploring opportunities for drug repurposing, enabling more accurate patient stratification, and advancing genomics-informed precision in the medical field of neurodevelopmental disorders., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ZD and NW are employees of Mills Institute for Personalized Cancer Care, Fynn Biotechnologies Ltd., Jinan, China. All other authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Type 2 diabetes(T2DM) is a metabolic disorder marked by glucose toxicity, lipotoxicity, insulin resistance, and other pathological manifestations, representing a pressing global health concern. Obesity stands out as a pivotal risk factor for T2DM development. When combined with T2DM, obesity exacerbates insulin resistance and metabolic abnormalities. The disturbance in the inflammatory microenvironmental balance between adipose and pancreatic islet tissue emerges as a significant contributor to obese with T2DM development. Macrophages play a crucial role in maintaining immune homeostasis and responding to inflammation in adipose and pancreatic islet tissue. Individuals with obese with T2DM exhibit an imbalanced M1/M2 macrophage polarization, contributing to the progression of glycolipid metabolism abnormalities. Hence, restoring the equilibrium of macrophage polarization becomes imperative for obese with T2DM treatment. Scientific researchers have demonstrated that traditional Chinese medicine(TCM) therapies can effectively modulate macrophage polarization, offering a viable approach for treating obese with T2DM. In light of the existing evidence, this study systematically reviewed the research progress of TCM targeting the balance of M1/M2 macrophage polarization to ameliorate obese with T2DM, so as to furnish evidence supporting the clinical diagnosis and treatment of obese with T2DM with TCM while also contributing to the exploration of the biological basis of obese with T2DM.

Background: Inflammatory processes could potentially impact both mood and suicide risk, however, the relationship between cytokines and suicidal ideation remains unclear. This study aimed to investigate the association between plasma levels of cytokines and suicidal ideation in population with major depressive disorders (MDD)., Methods: A cross-sectional study was performed to assess the peripheral plasma levels of interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-10 and tumor necrosis factor-α (TNF-α) in 88 Chinese Han first-episode drug-naïve MDD patients. Suicidal ideation in the past week were identified using the Beck Scale for Suicide Ideation-Chinese Version (BSI-CV). The Hamilton Depression Rating Scale-17 (HAMD-17), the Hamilton Anxiety Rating Scale-14 (HAMA-14) and the Childhood Trauma Questionnaire (CTQ) was used to assess depression, anxiety and childhood trauma. Multivariable logistic regression models were used to estimate the association between cytokines and suicidal ideation. Interaction and stratified analyses were conducted according to age, sex, marital status, education, smoking status, BMI and physical activity., Results: Among the 88 participants, 42 individuals (47.7%) reported suicidal ideation within the past week. In the fully adjusted model, a statistically significant trend was observed in the association between IL-2 level and suicidal ideation (OR: 1.40, 95% CI: 1.00-1.97). The stratified analysis showed a statistically significant association between IL-6 level and suicidal ideation among younger people (OR: 1.17, 95% CI: 1.01-1.36) and a significant positive association between IL-8 (OR: 1.59, 95% CI: 1.03-2.44) and IL-10 (OR: 2.51, 95% CI: 1.27-4.96) levels and suicide ideation among higher educated populations., Limitations: The cross-sectional design, residual confounding effects and small sample size CONCLUSION: Our findings indicate a significant positive association between plasma IL-2 level and suicidal ideation in MDD patients. IL-2 has the potential to be a biomarker of suicidal ideation in patients with depression., Competing Interests: Declaration of Competing Interest All the authors declared that there is no conflict of interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Neutral aqueous organic redox flow batteries (AORFBs) hold the potential to facilitate the transition of renewable energy sources from auxiliary to primary energy, the commercial production of anolyte materials still suffers from insufficient performance of high-concentration and the high cost of the preparation problem. To overcome these challenges, this study provides a hydrothermal synthesis methodology and introduces the charged functional groups into hydrophobic naphthalene diimide cores, and prepares a series of high-performance naphthalene diimide anolytes. Under the synergistic effect of π-π stacking and H-bonding networks, the naphthalene diimide exhibits excellent structural stability and the highest water solubility (1.85 M for dex-NDI) reported to date. By employing the hydrothermal method, low-cost naphthalene diimides are successfully synthesized on a hundred-gram scale of $0.16 g -1 ($2.43 Ah -1 ), which is also the lowest price reported to date. The constructed full battery achieves a high electron concentration of 2.4 M, a high capacity of 54.4 Ah L -1 , and a power density of 318 mW cm -2 with no significant capacity decay observed during long-duration cycling. These findings provide crucial support for the commercialization of AORFBs and pave the way for revolutionary developments in neutral AORFBs., (© 2024 Wiley-VCH GmbH.)

Lymphoma-associated hemophagocytic syndrome is aggressive with rapid progression, particularly in NK/T cell lymphoma. The MINE regimen is a salvage treatment for aggressive non-Hodgkin lymphoma. In our center, the modified MINE regimen was applied to treat three patients with hemophagocytic syndrome secondary to aggressive NK cell leukemia and T-cell lymphoma. The modified MINE regimen showed good efficacy against NK/T cell lymphoma, control of the inflammatory state of secondary hemophagocytic syndrome, and good tolerability.