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Purpose: This meta-analysis was carried out to evaluate the clinical effectiveness of rotator cuff repair surgery in treating rotator cuff tears in individuals with mild glenohumeral osteoarthritis (GHOA)., Methods: A computer-based search was conducted across multiple databases including PubMed, Embase, Web of Science, and Cochrane Library using the keywords "Shoulder Joints", "Osteoarthrosis", and "rotator cuff". Only studies focusing on patients with GHOA who underwent rotator cuff repair were considered for inclusion. The pertinent data was extracted and assessed for heterogeneity., Results: A total of 5 studies involving 924 patients were included in the meta-analysis. The treatment outcomes of patients with rotator cuff tears accompanied by mild GHOA and those with simple rotator cuff tears after rotator cuff repair were comparable in terms of retear(OR: 1.24; 95% CI 0.82-1.89; P = 0.31). The postoperative functional scores: the VAS score (MD: 0.14; 95% CI -0.19-0.47; P = 0.41)、ASES score (MD: -0.33; 95% CI -1.64-0.99)were similar between the two groups. Subgroup analysis of rotator cuff tears(small to moderate, MD: 0.85; 95%CI -0.65-2.39; p = 0.28; large to massive, MD: -1.94; 95% CI -8.45-4.58; P = 0.56), showed no difference in postoperative ASES scores between the two groups. Constant score (MD:-3.20; 95% CI -6.33-0.08; P = 0.04), external rotation (ER) in Range of motion (ROM) (MD: -4.42; 95% CI -6.72-2.13; P = 0.0002) and forward flexion (FF) in ROM(MD: -4.22; 95% CI -8.28-0.15; P = 0.04) were superior in patients with simple rotator cuff tears compared to those with rotator cuff tears accompanied by GHOA., Conclusion: Patients with rotator cuff tears and mild GHOA can achieve shoulder joint restoration after shoulder cuff repair surgery, and there is only a certain difference in postoperative Constant Score and ROM between these two groups., Trial Registration: PROSPERO registration CRD42024565212., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Fang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Predictive, preventive, and personalized medicine (PPPM/3PM) is a strategy aimed at improving the prognosis of cancer, and programmed cell death (PCD) is increasingly recognized as a potential target in cancer therapy and prognosis. However, a PCD-based predictive model for serous ovarian carcinoma (SOC) is lacking. In the present study, we aimed to establish a cell death index (CDI)-based model using PCD-related genes., Methods: We included 1254 genes from 12 PCD patterns in our analysis. Differentially expressed genes (DEGs) from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were screened. Subsequently, 14 PCD-related genes were included in the PCD-gene-based CDI model. Genomics, single-cell transcriptomes, bulk transcriptomes, spatial transcriptomes, and clinical information from TCGA-OV, GSE26193, GSE63885, and GSE140082 were collected and analyzed to verify the prediction model., Results: The CDI was recognized as an independent prognostic risk factor for patients with SOC. Patients with SOC and a high CDI had lower survival rates and poorer prognoses than those with a low CDI. Specific clinical parameters and the CDI were combined to establish a nomogram that accurately assessed patient survival. We used the PCD-genes model to observe differences between high and low CDI groups. The results showed that patients with SOC and a high CDI showed immunosuppression and hardly benefited from immunotherapy; therefore, trametinib_1372 and BMS-754807 may be potential therapeutic agents for these patients., Conclusions: The CDI-based model, which was established using 14 PCD-related genes, accurately predicted the tumor microenvironment, immunotherapy response, and drug sensitivity of patients with SOC. Thus this model may help improve the diagnostic and therapeutic efficacy of PPPM., Competing Interests: Declarations. Ethics approval and consent to participate: The TCGA and GEO databases are publicly available. Users can download the data for free for research purposes and publish related articles. The authors declare no ethical issues or conflicts of interest. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

This research provides an important approach for low-nitrogen wastewater treatment through anaerobic ammonium oxidation (Anammox), and Anammox granule sludge (AnGS) in the Upflow. Blanket Filter Anammox (UBFA) system through shortening the hydraulic retention time was successfully cultivated. The percentage of medium granules (1.0-2.0 mm) with the highest Anammox activity increased from 0 to 28.5%, and the proportion of flocs (0-200 μm) reduced from 84.5% to 17.6%. Through the multidimensional analysis of AnGS, the relationship between AnGS and EPS secretion, low SVI, high PN/PS, multiple filamentous bacteria, and AnAOB were explored. Microelectrode tracing tests demonstrated that the main anammox reaction active layer was 0-1500 μm, and the highest activity was observed at 200-400 μm, whereas denitrification activity and N 2 O production were mainly distributed in the granules deep layer of 1500-2500 μm. The research showed that Candidatus Brocadia and Candidatus Kuenenia were the predominant anammox species in the UBFA system, while the abundance of AnAOB was higher in medium granules., Competing Interests: Declarations.  Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: Cognitive frailty refers to the coexistence of physical frailty and cognitive impairment in older adults, without a concurrent diagnosis of Alzheimer's disease or other dementias. This review aims to evaluate the prevalence of CF subtypes and identify influencing factors among Chinese older adults., Methods: The following databases were searched: PubMed/Medline, Embase, Cochrane Library, WOS, PsycINFO and CNKI et al (1 January 2001 to 20 October 2022). The risk of bias was assessed using the Agency for Healthcare Research and Quality Evidence-based Practice Center Methods Guide. Stata 17.0 software was used to pool the prevalence of cognitive frailty, and the pooled odds ratio and 95% CI of the influencing factors were calculated., Results: The meta-analysis (56 studies and 80,320 participants) revealed the following prevalence rates: CF (18.9%), reversible CF (19.5%), potentially reversible CF (17.5%), CF in community-dwelling older adults (14.3%), CF in nursing homes (22.7%) and CF in older inpatients (25.2%). Influential factors identified included age, gender, education, nutrition, depression, exercise, sleep and comorbidity., Conclusions: The prevalence of CF among Chinese older adults is notably high, and it probably underestimates the prevalence of reversible cognitive frailty. It is crucial to encourage adherence to healthy behaviours, as it can effectively reduce and delay the onset of cognitive frailty., (© 2024 John Wiley & Sons Australia, Ltd.)

As the most frequent genetic alteration in cancer, more than half of human cancers have p53 mutations that cause transcriptional inactivation. However, how p53 modulates the immune landscape to create a niche for immune escape remains elusive. We found that cancer stem cells (CSCs) established an interleukin-34 (IL-34)-orchestrated niche to promote tumorigenesis in p53-inactivated liver cancer. Mechanistically, we discovered that Il34 is a gene transcriptionally repressed by p53, and p53 loss resulted in IL-34 secretion by CSCs. IL-34 induced CD36-mediated elevations in fatty acid oxidative metabolism to drive M2-like polarization of foam-like tumor-associated macrophages (TAMs). These IL-34-orchestrated TAMs suppressed CD8 + T cell-mediated antitumor immunity to promote immune escape. Blockade of the IL-34-CD36 axis elicited antitumor immunity and synergized with anti-PD-1 immunotherapy, leading to a complete response. Our findings reveal the underlying mechanism of p53 modulation of the tumor immune microenvironment and provide a potential target for immunotherapy of cancer with p53 inactivation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Thio-benzothioxanthene imide (BTXI) exhibits long excited state lifetime ( τ T = 17.7 μs) and high ISC efficiency ( Φ Δ = 97%). For the first time, BTXI derivatives were used as photosensitizers for triplet-triplet annihilation upconversion, achieving the highest efficiency of 13.8%. In addition, thio-BTXI derivatives were used as photoinitiators for photopolymerization, resulting in a series of green light-activated radical polymerization systems.

Lung adenocarcinoma (LUAD) generally presents as an immunosuppressive microenvironment. The characteristics of cell-to-cell communication in the LUAD microenvironment has been unclear. In this study, the LUAD bulk RNA-seq data and single-cell RNA-seq data were retrieved from public dataset. Differential expression genes (DEGs) between LUAD tumor and adjacent non-tumor tissues were calculated by limma algorithm, and then detected by PPI, KEGG, and GO analysis. Cell-cell interactions were explored using the single-cell RNA-seq data. Finally, the first 15 CytoHubba genes were used to establish related pathways and these pathways were used to characterize the immune-related ligands and their receptors in LUAD. Our analyses showed that monocytes or macrophages interact with tissue stem cells and NK cells via SPP1 signaling pathway and tissue stem cells interact with T and B cells via CXCL signaling pathway in different states. Hub genes of SPP1 participated in SPP1 signaling pathway, which was negatively correlated with CD4+ T cell and CD8+ T cell. The expression of SPP1 in LUAD tumor tissues was negatively correlated with the prognosis. While CXCL12 participated in CXCL signaling pathway, which was positively correlated with CD4+ T cell and CD8+ T cell. The role of CXCL12 in LUAD tumor tissues exhibits an opposite effect to that of SPP1. This study reveals that tumor-associated monocytes or macrophages may affect tumor progression. Moreover, the SPP1 and CXCL12 may be the critic genes of cell-to-cell communication in LUAD, and targeting these pathways may provide a new molecular mechanism for the treatment of LUAD., (© 2024 Wiley Periodicals LLC.)

Background: Lipid metabolism disorders are associated with degeneration of multiple tissues and organs, but the mechanism of crosstalk between lipid metabolism disorder and intervertebral disc degeneration (IDD) has not been fully elucidated. In this study we aim to investigate the regulatory mechanism of abnormal signal of lipid metabolism disorder on intervertebral disc endplate chondrocyte (EPC) senescence and calcification., Methods: Human intervertebral disc cartilage endplate tissue, cell model and rat hyperlipemia model were performed in this study. Histology and immunohistochemistry were used to human EPC tissue detection. TMT-labelled quantitative proteomics was used to detect differential proteins, and MRI, micro-CT, safranin green staining and immunofluorescence were performed to observe the morphology and degeneration of rat tail intervertebral discs. Flow cytometry, senescence-associated β-galactosidase staining, alizarin red staining, alkaline phosphatase staining, DCFH-DA fluorescent probe, and western blot were performed to detect the expression of EPC cell senescence, senescence-associated secretory phenotype, calcification-related proteins and the activation of cell senescence-related signaling pathways., Results: Our study found that the highly expressed oxidized low-density lipoprotein (ox-LDL) and Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) in human degenerative EPC was associated with hyperlipidemia (HLP). TMT-labelled quantitative proteomics revealed enriched pathways such as cell cycle regulation, endochondral bone morphogenesis and inflammation. The rat model revealed that HLP could induce ox-LDL, LOX-1, senescence and calcification markers high expression in EPC. Moreover, we demonstrated that ox-LDL-induced EPCs senescence and calcification were dependent on the LOX-1 receptor, and the ROS/P38-MAPK/NF-κB signaling pathway was implicated in the regulation of senescence induced by ox-LDL/LOX-1 in cell model., Conclusions: So our study revealed that ox-LDL/LOX-1-induced EPCs senescence and calcification through ROS/P38-MAPK/NF-κB signaling pathway, providing information on understanding the link between lipid metabolism disorders and IDD., (© 2024. The Author(s).)

Background: Acute myeloid leukemia (AML) is characterized by high heterogeneity, poor long-term survival, and a propensity for relapse. Exceptional efficacy in treating recurrent or refractory B-lymphoid malignancies has been demonstrated by Chimeric antigen receptor T cells (CAR-T cells). Given the therapeutic potential of targeting both CD33 and C-type lectin-like molecule-1 (CLL1) in AML, the development of a dual-targeting CD33-CLL1 CAR-T cells assumes significant importance., Materials and Methods: The expressions of CD33 and CLL-1 antigens in peripheral blood cells and bone marrow cells from AML patients was assessed. Subsequently, a Chimeric Antigen Receptor (CAR) incorporating a dual-specific single-chain variable fragment targeting CLL1 and CD33 (CD33-CLL1-CAR-T) was engineered. The anti-tumor efficacy and potential side effects of CD33-CLL1-CAR-T cells were comprehensively investigated in both in vitro and in vivo settings., Results: The constructed tandem CD33-CLL1 CAR-T exhibited potent cytotoxicity against leukemia cell lines and human primary AML cells in vitro. Co-cultivation of AML blasts with CD33-CLL1-CAR-T cells resulted in effective proliferation and the secretion of substantial quantities of GM-CSF and IFN-γ. Importantly, the impact of CD33-CLL1-CAR-T cells on normal hematopoietic stem cells was minimal, ensuring safety in vivo mouse models. Notably, significant anti-leukemic activity was observed in the mouse model, with CD33-CLL1-CAR-T cells leading to tumor eradication and prolonged survival., Discussion: The tandem CD33-CLL1 CAR-T cells not only efficiently eliminated AML blasts but also exhibited low cytotoxicity toward normal hematopoietic stem cells (HSCs). These findings underscore the potential clinical applicability of the tandem CD33-CLL1 CAR-T cells as an effective and safe treatment strategy for AML, representing a noteworthy advancement in the field of CAR-T cells therapy.

Neuroblastoma (NB) is one of the most common childhood malignancies. Sixty percent of patients present with widely disseminated clinical signs at diagnosis and exhibit poor outcomes. However, the molecular mechanisms triggering NB metastasis remain largely uncharacterized. In this study, we generated a transcriptomic atlas of 15 447 NB cells from eight NB samples, including paired samples of primary tumors and bone marrow metastases. We used time-resolved analysis to chart the evolutionary trajectory of NB cells from the primary tumor to the metastases in the same patient and identified a common 'starter' subpopulation that initiates tumor development and metastasis. The 'starter' population exhibited high expression levels of multiple cell cycle-related genes, indicating the important role of cell cycle upregulation in NB tumor progression. In addition, our evolutionary trajectory analysis demonstrated the involvement of partial epithelial-to-mesenchymal transition (p-EMT) along the metastatic route from the primary site to the bone marrow. Our study provides insights into the program driving NB metastasis and presents a signature of metastasis-initiating cells as an independent prognostic indicator and potential therapeutic target to inhibit the initiation of NB metastasis., (© 2024. Higher Education Press.)

Digestive tract cancers are among the most common malignancies worldwide and have high incidence and mortality rates. Thus, the discovery of more effective diagnostic and therapeutic targets is urgently required. The development of technologies to accurately detect RNA modification has led to the identification of numerous RNA chemical modifications in humans (epitranscriptomics) that are involved in the occurrence and development of digestive tract cancers. RNA modifications can cooperatively regulate gene expression to facilitate normal physiological functions of the digestive system. However, the dysfunction of relevant RNA-modifying enzymes ("writers," "erasers," and "readers") can lead to the development of digestive tract cancers. Consequently, targeting dysregulated enzyme activity could represent a potent therapeutic strategy for the treatment of digestive tract cancers. In this review, we summarize the most widely studied roles and mechanisms of RNA modifications (m 6 A, m 1 A, m 5 C, m 7 G, A-to-I editing, pseudouridine [Ψ]) in relation to digestive tract cancers, highlight the crosstalk between RNA modifications, and discuss their roles in the interactions between the digestive system and microbiota during carcinogenesis. The clinical significance of novel therapeutic methods based on RNA-modifying enzymes is also discussed. This review will help guide future research into digestive tract cancers that are resistant to current therapeutics., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Chronic graft-versus-host disease (cGVHD) is the most common long-term complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The patients with pulmonary cGVHD in particular have a very poor prognosis. NK cells are the first reconstituted lymphocyte subset after allo-HSCT; however, the impact of reconstituted NK cells on cGVHD is unclear. Here, we found allogeneic recipients showed obvious pulmonary cGVHD. Surprisingly, deletion of reconstituted NK cells resulted in maximal relief of pulmonary cGVHD. Mechanistically, reconstituted NK cells with donor profiles modulated the pulmonary inflammatory microenvironment to trigger cGVHD. Reconstituted NK cells secreted IFN-γ and TNF-α to induce CXCL10 production by epithelial cells, which recruited macrophages and CD4 + T cells to the lungs. Then macrophages and CD4 + T cells were activated by the inflammatory microenvironment, thereby mediating lung injury. Through assessment of differences in cellular energy, we found that CD74 + NK cells with high mitochondrial potential and pro-inflammatory activity triggered pulmonary cGVHD. Furthermore, targeted elimination of CD74 + NK cells using the anti-CD74 antibody significantly alleviated pulmonary cGVHD but preserved the CD74 - NK cells to exert graft-versus-leukemia (GVL) effects. Data from human samples corroborated our findings in mouse models. Collectively, our results reveal that reconstituted CD74 + NK cells trigger pulmonary cGVHD and suggest that administration of CD74 antibody was a potential therapeutic for patients with cGVHD., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Studies have highlighted a possible crosstalk between the pathogeneses of COVID-19 and systemic lupus erythematosus (SLE); however, the interactive mechanisms remain unclear. We aimed to elucidate the impact of COVID-19 on SLE using clinical information and the underlying mechanisms of both diseases., Methods: RNA-seq datasets were used to identify shared hub gene signatures between COVID-19 and SLE, while genome-wide association study datasets were used to delineate the interaction mechanisms of the key signaling pathways. Finally, single-cell RNA-seq datasets were used to determine the primary target cells expressing the shared hub genes and key signaling pathways., Results: COVID-19 may affect patients with SLE through hematologic involvement and exacerbated inflammatory responses. We identified 14 shared hub genes between COVID-19 and SLE that were significantly associated with interferon (IFN)-I/II. We also screened and obtained four core transcription factors related to these hub genes, confirming the regulatory role of the IFN-I/II-mediated Janus kinase/signal transducers and activators of transcription (JAK-STAT) signaling pathway on these hub genes. Further, SLE and COVID-19 can interact via IFN-I/II and IFN-I/II receptors, promoting the levels of monokines, including interleukin (IL)-6/10, tumor necrosis factor-α, and IFN-γ, and elevating the incidence rate and risk of cytokine release syndrome. Therefore, in SLE and COVID-19, both hub genes and core TFs are enriched within monocytes/macrophages., Conclusions: The interaction between SLE and COVID-19 promotes the activation of the IFN-I/II-triggered JAK-STAT signaling pathway in monocytes/macrophages. These findings provide a new direction and rationale for diagnosing and treating patients with SLE-COVID-19 comorbidity., (© 2024. The Author(s).)

Layered metal-halide perovskites, or two-dimensional perovskites, can be synthesized in solution, and their optical and electronic properties can be tuned by changing their composition. We report a molecular templating method that restricted crystal growth along all crystallographic directions except for [110] and promoted one-dimensional growth. Our approach is widely applicable to synthesize a range of high-quality layered perovskite nanowires with large aspect ratios and tunable organic-inorganic chemical compositions. These nanowires form exceptionally well-defined and flexible cavities that exhibited a wide range of unusual optical properties beyond those of conventional perovskite nanowires. We observed anisotropic emission polarization, low-loss waveguiding (below 3 decibels per millimeter), and efficient low-threshold light amplification (below 20 microjoules per square centimeter).

Objective: This study aimed to develop an individual WeChat Mini Program to provide pharmaceutical care to better manage cancer pain patients and to evaluate its feasibility and the differences in analgesic efficacy, medication adherence and safety versus conventional pharmacy interventions., Methods: In this parallel randomized clinical trial, 42 cancer pain patients were equally allocated into the experimental group and the control group. The experimental group received individualized pharmaceutical care based on the "Yao Nin You Wo" WeChat Mini Program, while the control group received conventional care during the 4-week period. Main outcomes contained pain scores, medication adherence, incidences and relief rates of breakthrough pain, and incidences of adverse events. Relief rates of pain were also calculated according to pain scores., Results: At the beginning of intervention, none of the pain scores and medication adherence showed relevant differences between the two groups (all P  > .05). After intervention, the experimental group had significantly lower pain scores compared to the control group ( P  = .003). Breakthrough pain of both groups was alleviate; not only the incidence of breakthrough pain considerably was lower at 4 weeks than at baseline, but the relief rate of breakthrough in the experimental group was higher than that in the control group. Compared with the control group, the medication adherence rate of the experimental group was significantly improved ( P  = .02). Types of adverse events that happened in experimental and groups were similar, but the total incidence of adverse events in the experimental group was lower than that in the control group., Conclusions: WeChat Mini Program is a useful and facilitative tool with the potential to improve cancer pain self-management ability in discharged patients. In addition, pharmacists could play a key role through the Mini Program to connect with patients successfully by providing personalized pharmaceutical services., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Integrin alpha L (ITGAL), a member of the integrin family, is associated with carcinogenesis and immune regulation. However, the biological functions of ITGAL in lung adenocarcinoma (LUAD) remain poorly understood. In this study, we utilized the TCGA dataset to analyse ITGAL mRNA expression in LUAD and examined its correlation with clinical prognosis. Three-dimensional (3D) Matrigel culture, 5-bromodeoxyuridine (BrdU) ELISA, wound-healing migration and cell adherence assays were used to demonstrate the potential role of ITGAL in LUAD progression. Additionally, we analysed single-cell sequencing data of LUAD to determine the expression and biological function of ITGAL. Our research revealed that the expression of ITGAL in LUAD samples is an independent predictor of prognosis. Patients with high expression of ITGAL had significantly better overall survival (OS), progression-free survival (PFS) and disease-specific survival (DSS) compared to the low-expression group. Meanwhile, the expression of ITGAL suppressed malignant progression in LUAD cells. Functional enrichment analyses showed that ITGAL was significantly correlated with cell immune response and immune checkpoint, consistent with the analysis of single-cell sequencing in paired samples of normal and tumour. Furthermore, we confirmed that ITGAL expression affect the tumour microenvironment (TME) through regulation of the expression of cytokines in NK cells of LUAD. In summary, ITGAL is a prognostic biomarker for LUAD patients, and it repressed malignant progression in LUAD cells. Moreover, ITGAL expression also enhanced the effect of immunotherapy and may be an important target in LUAD therapy., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Current literatures suggest a growing body of evidence highlighting the pivotal role of Immunogenic Cell Death (ICD) in multiple tumor types. Nevertheless, the potential and mechanisms of ICD in diffuse large B-cell lymphoma (DLBCL) remain inadequately studied. To address this gap, our current study aims to examine the impact of ICD on DLBCL and identify a corresponding gene signature in DLBC. Using the expression profiles of ICD-associated genes, the gene expression omnibus (GEO) samples were segregated into ICD-high and ICD-low subtypes utilizing non-negative matrix factorization clustering. Next, univariate and LASSO Cox regression analyses were employed to establish the ICD-related gene signature. Subsequently, the CIBERSORT tool, ssGSEA, and ESTIMATE algorithm were utilized to examine the association between the signature and tumor immune microenvironment of DLBC. Finally, the oncoPredict algorithm was implemented to evaluate the drug sensitivity prediction of DLBCL patients. These findings suggest that the immune microenvironment of the ICD-high group with a poor prognosis was significantly suppressed. An 8-gene ICD-related signature was identified and validated to prognosticate and evaluate the tumor immune microenvironment in DLBCL. Similarly, the high-risk group exhibited a worse prognosis compared to the low-risk group, and the immune function was considerably suppressed. Moreover, the results of oncoPredict algorithm indicated that patients in the high-risk group exhibited higher sensitivity to Cisplatin, Cytarabine, Epirubicin, Oxaliplatin, and Vincristine with low IC50. In conclusion, the present study provides novel insights into the role of ICD in DLBCL by identifying a new biomarker for the disease and may have implications for the development of immune-targeted therapies for the tumor., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: This study explored promising prognostic and immune therapeutic candidate biomarkers for OC and determined the expression, prognostic value, and immune effects of UCHL3., Methods: UCHL3 expression and clinical data were investigated using bioinformatic analysis. CCK8 and transwell assays were conducted to evaluate the impact of UCHL3 on proliferation and migration, and the effects of UCHL3 were further validated in a mouse model. Univariate and least absolute shrinkage and selection operator regression analyses were performed to construct a novel UCHL3-related prognostic risk model. Gene set enrichment analysis (GSEA) and immune analysis were performed to identify the significantly involved functions of UCHL3. Finally, bioinformatic analysis and immunohistochemistry were performed to explore the effect of UCHL3 on chemotherapy., Results: UCHL3 expression was upregulated and associated with worse overall survival (OS) in OC. UCHL3 depletion repressed cell proliferation and migration both in vitro and in vivo. Furthermore, 237 genes were differentially expressed between the high and low UCHL3 expression groups. Subsequently, a UCHL3-related prognostic signature was built based on six prognostic genes (PI3, TFAP2B, MUC7, PSMA2, PIK3C2G, and NME1). Independent prognostic analysis suggested that age, tumor mutational burden, and RiskScore can be used as independent prognostic factors. The immune infiltration analysis and GSEA suggested that UCHL3 expression was related to the immune response. In addition, UCHL3 expression was higher in platinum-resistant OC patients than in platinum-sensitive patients. UCHL3 overexpression was associated with poorer OS., Conclusion: UCHL3 overexpression contributes to aggressive progression, poor survival, and chemoresistance in OC. Therefore, UCHL3 may be a candidate prognostic biomarker and potential target for controlling progression and platinum resistance in OC., Competing Interests: Declaration of competing interest 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To compare the clinical efficacy and safety of first-line treatments for advanced unresectable oesophageal squamous cell cancer., Materials and Methods: A systematic review and network meta-analysis was carried out by retrieving and retaining relevant literature from databases. The studies were randomised controlled trials comparing first-line treatments for advanced unresectable oesophageal squamous cell cancer. A Bayesian network meta-analysis was used to assess clinical outcomes., Results: Nine studies including 4499 patients receiving first-line treatments were analysed. For all populations, toripalimab plus chemotherapy tended to provide the best overall survival (hazard ratio 0.58, 95% confidence intervals 0.43-0.78) and sintilimab plus chemotherapy provided the best progression-free survival (0.56, 0.46-0.68). Nivolumab plus chemotherapy presented the best objective response rate (odds ratio 2.45, 1.78-3.42) and camrelizumab plus chemotherapy (0.47, 0.29-0.74) appeared to be the safest. Sintilimab plus chemotherapy (0.55, 0.40-0.75) and nivolumab (0.54, 0.37-0.80) plus chemotherapy had the best overall survival in programmed death ligand 1 (PD-L1) tumour proportion score <1% and ≥1% subgroups. Toripalimab plus chemotherapy (0.61, 0.40-0.93) and pembrolizumab (0.57, 0.43-0.75) were the best in overall survival in combined positive score <10 and ≥10 subgroups, respectively. Toripalimab plus chemotherapy showed the best overall survival in the Asian group; pembrolizumab presented better overall survival in the Asian population than the non-Asian group., Conclusion: Most immunotherapy combined with chemotherapy showed superior clinical benefits and sintilimab plus chemotherapy, toripalimab plus chemotherapy and tislelizumab plus chemotherapy had better comprehensive clinical efficacy. PD-L1 expression detection and ethnicity differences are still of great significance and most suitable regimens varied from each subgroup., (Copyright © 2023. Published by Elsevier Ltd.)

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies, whose initiation and development are driven by alterations in driver genes. In this study, we identified four driver genes (TP53, PTEN, CTNNB1, and KRAS) that show a high frequency of somatic mutations or copy number variations (CNVs) in patients with HCC. Four different spontaneous HCC mouse models were constructed to screen for changes in various kinase signaling pathways. The sgTrp53 + sgPten tumor upregulated mTOR and noncanonical nuclear factor-κB signaling, which was shown to be strongly inhibited by rapamycin (an mTOR inhibitor) in vitro and in vivo. The JAK-signal transducer and activator of transcription (STAT) signaling was activated in Ctnnb1 mut  + sgPten tumor, the proliferation of which was strongly inhibited by napabucasin (a STAT3 inhibitor). Additionally, mTOR, cytoskeleton, and AMPK signaling were upregulated while rapamycin and ezrin inhibitors exerted potent antiproliferative effects in sgPten + Kras G12D tumor. We found that JAK-STAT, MAPK, and cytoskeleton signaling were activated in sgTrp53 + Kras G12D tumor and the combination of sorafenib and napabucasin led to the complete inhibition of tumor growth in vivo. In patients with HCC who had the same molecular classification as our mouse models, the downstream signaling pathway landscapes associated with genomic alterations were identical. Our research provides novel targeted therapeutic options for the clinical treatment of HCC, based on the presence of specific genetic alterations within the tumor., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

The switch from anchorage-dependent to anchorage-independent growth is essential for epithelial metastasis. The underlying mechanism, however, is not fully understood. In this study, we identified growth factor independent-1 (GFI1), a transcription factor that drives the transition from adherent endothelial cells to suspended hematopoietic cells during hematopoiesis, as a critical regulator of anchorage independence in lung cancer cells. GFI1 elevated the numbers of circulating and lung-infiltrating tumor cells in xenograft models and predicted poor prognosis of patients with lung cancer. Mechanistically, GFI1 inhibited the expression of multiple adhesion molecules and facilitated substrate detachment. Concomitantly, GFI1 reconfigured the chromatin structure of the RASGRP2 gene and increased its expression, causing Rap1 activation and subsequent sustained ERK activation upon detachment, and this led to ERK signaling dependency in tumor cells. Our studies unveiled a mechanism by which carcinoma cells hijacked a hematopoietic factor to gain anchorage independence and suggested that the intervention of ERK signaling may suppress metastasis and improve the therapeutic outcome of patients with GFI1-positive lung cancer.

CD49a + natural killer (NK) cells play a critical role in promoting fetal development and maintaining immune tolerance at the maternal-fetal interface during the early stages of pregnancy. However, given their residency in human tissue, thorough studies and clinical applications are difficult to perform. It is still unclear as to how functional human CD49a + NK cells can be induced to benefit pregnancy outcomes. In this study, we established three no-feeder cell induction systems to induce human CD49a + NK cells from umbilical cord blood hematopoietic stem cells (HSCs), bone marrow HSCs, and peripheral blood NK cells in vitro . These induced NK cells (iNKs) from three cell induction systems display high levels of CD49a, CD9, CD39, CD151 expression, low levels of CD16 expression, and no obvious cytotoxic capability. They are phenotypically and functionally similar to decidual NK cells. Furthermore, these iNKs display a high expression of growth-promoting factors and proangiogenic factors and can promote fetal growth and improve uterine artery blood flow in a murine pregnancy model in vivo . This research demonstrates the ability of human-induced CD49a + NK cells to promote fetal growth via three cell induction systems, which could eventually be used to treat patients experiencing adverse pregnancy outcomes., 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 © 2022 Du, Zhu, Jiao, Nian, Zhang, Zhou, Zheng, Tong, Wei and Fu.)

Purpose: Ongoing clinical trials show limited efficacy for Chimeric antigen receptor (CAR) T treatment for acute myeloid leukemia (AML). The aim of this study was to identify potential causes of the reported limited efficacy from CAR-T therapies against AML., Experimental Design: We generated CAR-T cells targeting Epithelial cell adhesion molecule (EpCAM) and evaluated their killing activity against AML cells. We examined the impacts of modulating mTORC1 and mTORC2 signaling in CAR-T cells in terms of CXCR4 levels. We examined the effects of a rapamycin pretreatment of EpCAM CAR-T cells (during ex vivo expansion) and assessed the in vivo antitumor efficacy of rapamycin-pretreated EpCAM CAR-T cells (including CXCR4 knockdown cells) and CD33 CAR-T cells in leukemia xenograft mouse models., Results: EpCAM CAR-T exhibited killing activity against AML cells but failed to eliminate AML cells in bone marrow. Subsequent investigations revealed that aberrantly activated mTORC1 signaling in CAR-T cells results in decreased bone marrow infiltration and decreased the levels of the rapamycin target CXCR4. Attenuating mTORC1 activity with the rapamycin pretreatment increased the capacity of CAR-T cells to infiltrate bone marrow and enhanced the extent of bone marrow AML cell elimination in leukemia xenograft mouse models. CXCR4 knockdown experiments showed that CXCR4 contributes to the enhanced bone marrow infiltration capacity of EpCAM CAR-T cells and the observed reduction in bone marrow AML cells., Conclusions: Our study reveals a potential cause for the limited efficacy of CAR-T reported from current AML clinical trials and illustrates an easy-to-implement pretreatment strategy, which enhances the anti-AML efficacy of CAR-T cells. See related commentary by Maiti and Daver, p. 5739 ., (©2021 The Authors; Published by the American Association for Cancer Research.)

Osteoblast-induced bone formation and osteoclast-regulated bone resorption are the essential events contributing to bone homeostasis. It is critical to investigate the underlying molecular mechanisms. In this study, we explored the effects of receptor-interacting serine-threonine kinases (RIPKs) on osteoclastogenesis and bone loss in vitro and in vivo. We found that both RIPK1 and RIPK3 expression levels were highly up-regulated during osteoclastogenesis. Inhibiting RIPK1 and RIPK3 by their inhibitors Necrostatin-1 (Nec-1) and GSK-872, respectively, showed effective activities against osteoclast differentiation and bone resorption induced by receptor activator of nuclear factor-κB ligand (Rankl). Osteoclast-specific gene expression levels were also impeded by RIPK1/RIPK3 blockage in a time-dependent manner. Subsequently, we found that the pyrin domain-containing protein 3 (NLRP3) inflammasome stimulated by Rankl during osteoclastogenesis was greatly inhibited by Nec-1 and GSK-872. Additionally, reducing RIPK1/RIPK3 overtly reduced the activation of NF-κB (p65) and mitogen-activated protein kinases (MAPKs) signaling during Rankl-induced osteoclast formation. Notably, adenovirus-regulated NLRP3 over-expression significantly abrogated the inhibitory effects of Nec-1 and GSK-872 on NF-κB and MAPKs signaling pathways, as well as the osteoclastogenesis. Finally, the in vivo studies indicated that suppressing RIPK1/RIPK3 could effectively ameliorate ovariectomy (OVX)-induced bone loss in mice through repressing osteoclastogenesis, as proved by the clearly down-regulated number of osteoclasts via histological staining. In conclusion, our study elucidated that restraining RIPK1/RIPK3 could hinder osteoclastogenesis and attenuate bone loss through suppressing NLRP3-dependent NF-κB and MAPKs signaling pathways. Therefore, targeting RIPK1/RIPK3 signaling might be a potential therapeutic strategy to develop effective treatments against osteoclast-related bone lytic diseases., (Copyright © 2020. Published by Elsevier Inc.)

Background: Patients undergoing surgical resection of hepatocellular carcinoma (HCC) are at risk of recurrence; however, the underlying mechanism remains poorly understood., Methods: Through the analysis of gene expression profiles in tumour and matched normal tissues from patients with hepatocellular carcinoma (HCC), we identified differences in interleukin-11 (IL-11) expression. Further, we used genetic mouse, orthotopic tumour, chemically induced, and orthotopic allograft models to study the correlation between IL-11 and postsurgical recurrence. Additionally, we conducted a series of experiments, including histology and immunohistochemistry analysis, three-dimensional culture, immunofluorescence, western blotting, enzyme-linked immunosorbent assay (ELISA) and flow cytometry to investigate the role of IL-11-signal transducer and activator of transcription 3 (STAT3) signaling in HCC recurrence., Findings: We demonstrate that IL-11 levels increase after surgery, triggering HCC outgrowth. Accordingly, pharmacological blocking of IL-11-STAT3 signaling in model systems significantly alleviates tumour cell proliferation and suppresses postsurgical recurrence of HCC tumours., Interpretation: These data demonstrate that IL-11 has a central role in postsurgical HCC recurrence, and that inhibition of IL-11-STAT3 signaling is a potential therapeutic strategy to prevent recurrence. FUND: Natural Science Foundation of China., (Copyright © 2019. Published by Elsevier B.V.)

Background: Laparoscopic Kasai portoenterostomy (LKPE) is generally regarded to have a poorer outcome for surgical treatment of uncorrectable biliary atresia. We herein described our initial experience of some modifications to make LKPE easier in the treatment of type III biliary atresia (BA)., Methods: During the period July 2012-October 2016, a total of 25 infants with type III BA were treated with a modified LKPE technique. A percutaneous suture was introduced just below the xiphoid process to snare the round ligament and retract the liver; other percutaneous stay sutures were then introduced to the fundus and neck of the gallbladder to elevate the liver and expose the porta hepatis. In 15 cases, part of the hepatic lobus quadratus was removed laparoscopically to expose the porta hepatis. The two elastic rubber bands were put around the portal vein and hepatic artery, and the porta hepatis was exposed by stretching the two rubber bands laterally to facilitate laparoscopic portoenterostomy., Results: Patients were divided into two groups according to their ages at operation: group I: age between 30 and 75 days (n = 18), and group II: age between 76 and 85 days (n = 8). There were no operative deaths, but two patients died of repeated cholangitis and liver failure. Blood loss during operation was minimal and no blood transfusions were required. Operating times varied from 210 to 270 min (mean 232.4 ± 19.0 min). Among the two groups, there were no differences in blood loss (P > 0.05), but there were differences in operating time (P < 0.05). All patients survived the surgery without any intraoperative complications, and the median follow-up time was 25.3 months. Total bilirubin dropped to normal in 18 patients with an additional 5 patients showing a significant overall drop after surgery., Conclusions: With the original concepts of Kasai portoenterostomy, perfect laparoscopic skills and some key modifications to expose the porta hepatis, our LKPE can be performed safely and successfully with improved outcome for infants with type III BA., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Our previous study explored the roles of microRNA-424 (miR-424) in the development of endometrial carcinoma (EC) and analyzed the miR-424/E2F7 axis in EC cell growth. In this study, we investigated the status of miR-424 in human endometrial cancer tissues, which were collected from a cohort of Zunyi patients. We found that the expression level of miR-424 was associated with clinical tumor stage, cell differentiation, lymph node metastasis and cell migration ability. Cell function experiments demonstrated that miR-424 overexpression suppressed the invasion and migration abilities of endometrial carcinoma cells in vitro . Bioinformatic predictions and dual-luciferase reporter assays suggested E2F6 as a possible target of miR-424. RT-PCR and western blot assays demonstrated that miR-424 transfection reduced the expression level of E2F6, while inhibiting miR-424 with ASO-miR-424 (antisense oligonucleotides of miR-424) increased the expression level of E2F6. Cell function experiments indicated that E2F6 transfection rescued the EC cell phenotype induced by miR-424. In addition, we also found that E2F6 negatively regulated miR-424 expression in EC cells. In summary, our results demonstrated that the miR-424/E2F6 feedback loop modulates cell invasion, migration and EMT in EC and that the miR-424/E2Fs regulation network may serve as a new and potentially important therapeutic target in EC., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Obesity is characterized by aberrant fat accumulation. However, the intracellular signaling pathway that senses dietary fat and leads to fat storage remains elusive. Here, we have observed that the levels of histone deacetylase 6 (HDAC6) and the related family member HDAC10 are markedly reduced in adipose tissues of obese animals and humans. Mice with adipocyte-specific depletion of Hdac6 exhibited increased fat accumulation and reduced insulin sensitivity. In normal adipocytes, we found that reversal of P300/CBP-associated factor-induced (PCAF-induced) acetylation at K56 on cell death-inducing DFFA-like effector C (CIDEC, also known as FSP27) critically regulated lipid droplet fusion and lipid storage. Importantly, HDAC6 deacetylates CIDEC, leading to destabilization and reduced lipid droplet fusion. Accordingly, we observed elevated levels of CIDEC and its acetylated form in HDAC-deficient adipocytes as well as the adipose tissue of obese animals and humans. Fatty acids (FAs) prevented CIDEC deacetylation by promoting the dissociation of CIDEC from HDAC6, which resulted in increased association of CIDEC with PCAF on the endoplasmic reticulum. Control of CIDEC acetylation required the conversion of FAs to triacylglycerols. Thus, we have revealed a signaling axis that is involved in the coordination of nutrient availability, protein acetylation, and cellular lipid metabolic responses.

Objective: To study the preparation and cytocompatibility of bone tissue engineering scaffolds by combining low temperature three dimensional (3D) printing and vacuum freeze-drying techniques., Methods: Collagen (COL) and silk fibroin (SF) were manufactured from fresh bovine tendon and silkworm silk. SolidWorks2014 was adopted to design bone tissue engineering scaffold models with the size of 9 mm x 9 mm x 3 mm and pore diameter of 500 μm. According to the behavior of composite materials that low temperature 3D printing equipment required, COL, SF, and nano-hydroxyapatite (nHA) at a ratio of 9 : 3 : 2 and low temperature 3D printing in combination with vacuum freeze-drying techniques were accepted to build COL/SF/nHA composite scaffolds. Gross observation and scanning electron microscope (SEM) were applied to observe the morphology and surface structures of composite scaffolds. Meanwhile, compression displacement, compression stress, and elasticity modulus were measured by mechanics machine to analyze mechanical properties of composite scaffolds. The growth and proliferation of MC3T3-E1 cells were evaluated using SEM, inverted microscope, and MTT assay after cultured for 1, 7, 14, and 21 days on the composite scaffolds. The RT-PCR and Western blot techniques were adopted to detect the gene and protein expressions of COL I, alkaline phosphatase (ALP), and osteocalcin (OCN) in MC3T3-E1 cells after 21 days., Results: COL/SF/nHA composite scaffolds were successfully prepared by low temperature 3D printing technology and vacuum freeze-drying techniques; the SEM results showed that the bionic bone scaffolds were 3D polyporous structures with macropores and micropores. The mechanical performance showed that the elasticity modulus was (344.783 07 ± 40.728 55) kPa; compression displacement was (0.958 41 ± 0.000 84) mm; and compression stress was (0.062 15 ± 0.007 15) MPa. The results of inverted microscope, SEM, and MTT method showed that a large number of cells adhered to the surface with full extension and good cells growth inside the macropores, which demonstrated a satisfactory proliferation rate of the MC3T3-E1 cells on the composite scaffolds. The RT-PCR and Western blot electrophoresis revealed gene expressions and protein synthesis of COL I, ALP, and OCN in MC3T3-E1 cells., Conclusion: Low temperature 3D printing in combination with vacuum freeze-drying techniques could realize multi-aperture coexisted bionic bone tissue engineering scaffolds and control the microstructures of composite scaffolds precisely that possess good cytocompatibility. It was expected to be a bone defect repair material, which lays a foundation for further research of bone defect.

Introduction: In this study, the silk fibroin blended constructs were produced, scaffold performances of different kinds of scaffold were analyzed, and the better type for tissue engineering was optimized., Methods: The silk fibroin/collagen (SF/C) and silk fibroin/chitosan (SF/CS) were made using a freeze-drying technique, porosity, water absorption expansion rate, mechanical properties and pore size of different scaffold was detected. Bone marrow mesenchymal stem cells (BMSCs) of 4-week-old male Wistar rats were separated by density gradient centrifugation, third generation BMSCs were seeded onto scaffolds, cultured 14 days, proliferation and metabolize of cells were detected in different time using the thiazolyl blue tetrazolium bromide (MTT) assay method, and cell morphology and distribution were observed by histological analysis and scanning electron microscopy (SEM)., Results: Porosity, water absorption expansion rate and Young's modulus of SF/C were significantly higher than SF/CS (p < 0.05); pore size of SF/C and SF/CS was 103 ± 12 and 76 ± 11 μm and had no significant differences between two types (p > 0.05); MTT results showed that the metabolism of cells in the SF/C was better than SF/CS; after cultivation for 14 days, in the inner zone of scaffolds, cells staining were little or absent from SF/CS, lots of cells staining were existing in SF/C; pore size was consistent, holes communicated with each other better, stem cells grew well inside the scaffolds, extended fully and secreted much extracellular matrix under SEM in SF/C scaffold; internal structure of SF/CS was disorder, holes size were not consistent, and did not communicated with each other and cells were partly dead., Conclusion: Compared with SF/CS, SF/C scaffold showed better porosity, water absorption expansion rate, elasticity modulus and pore size, cells grow well inside the scaffolds, and was more suitable for tissue engineering.

Objective: To prepare composite scaffold of different quality ratio of silk fibroin to collagen, analyze the scaffold performance, and optimize the quality ratio for chondrocyte tissue engineering., Methods: The silk fibroin/collagen composite scaffold was made using a freeze-drying technique in different quality ratios of silk fibroin to collagen: 4:2 (group A), 4:4 (group B), and 4:8 (group C). The porosity, water absorption expansion rate, mechanical properties, and pore size of composite scaffold were detected. The bone marrow mesenchymal stem cells (BMSCs) were isolated from 4-week-old male Wistar rats by density gradient centrifugation, and the third generation BMSCs were seeded onto the scaffolds at 2 x 10(7) cells/ mL density, and were cultured for 14 days. The cell proliferation was detected using MTT assay at 1, 3, 5, 7, 9, 11, and 13 days, the cell morphology and distribution were observed by HE staining and scanning electron microscopy (SEM)., Results: The porosity of groups A, B, and C was 94.6% ± 1.6%, 80.6% ± 1.1%, and 60.6% ± 1.0% respectively; and significant differences were found between group A and groups B and C, and between group B and group C (P < 0.05). The water absorption expansion rates of groups A, B, and C were 1 523.7% ± 186.6%, 1 091.0% ± 151.6%, and 659.6% ± 161.4% respectively, showing no significant difference among 3 groups (F = 6.67, P = 0.08). The elasticity modulus of groups A, B, and C were (23.1 ± 2.5), (25.1 ± 2.3), and (29.8 ± 2.6) kPa respectively, showing no significant difference among 3 groups (F=2.00, P=0.28). The pore size of groups A, B, and C was (103 ± 12), (80 ± 15), and (60 ± 16) µm respectively, showing no significant difference among 3 groups (F = 2.22, P = 0.26). MTT results showed that the cell proliferation in the group A at 7, 9, 11, and 13 days were better than those in groups B and C (P < 0.05); at 14 days after cultivation, even pore size, good intercommunicating of holes, and good cells growth on the scaffolds with full extension and more extracellular matrix were seen under SEM in group A, but small pore size, poor intercommunicating of holes and poor cell growth on the scaffolds in groups B and C. HE staining and SEM results showed thatthe cells on the scaffold in group A was obviously more than those in groups B and C., Conclusion: The scaffold prepared in a quality ratio 4 : of silk fibroin to collagen has better porosity, water absorption expansion rate, elasticity modulus, and pore size, on which the cells can grow well, so it is more suitable for cartilage tissue engineering.

To determine whether PKH26 labeling affects the morphologies, phenotypes, proliferation, and secretion abilities of human umbilical mesenchymal stromal cells (HUMSCs) were investigated. Isolated HUMSCs were labeled with PKH26, and cell morphology was observed under microscope. Cell cycle, apoptotic cell death, expression of PKH26, and the proliferation rate were evaluated. Additionally, fluorescence intensity of PKH26 labeling at different passage times was quantified. There were no detectable differences in cell morphology, cell growth, and proliferation rate after PKH26 labeling. In addition, fluorescence intensity of PKH26 labeling was gradually reduced with increase of the passage times. The PKH26 labeling disappeared after passage six times. In summary, PKH26 labeling is a safe and effective way to label live HUMSCs.

Adipocytes are among the most important cells for energy storage, metabolism and balance in mammals. Dysfunctional adipocytes are closely associated with type 2 diabetes and obesity, and thus with insulin resistance and inflammation. Recent studies show that endoplasmic reticulum (ER) stress may be responsible for obesity-induced insulin resistance. In this study, we investigated an ER-associated degradation-related protein in adipocytes, namely osteosarcoma amplified 9 (OS-9), a protein that is reported to have lectin activity and to be involved in ER quality control. We found that OS-9 is expressed at high levels in both types of fat tissues - brown and white adipose tissues - and we examined the subcellular localization of OS-9 in 3T3-L1 adipocytes. Furthermore, we observed that the expression levels of the OS-9 protein gradually increased as 3T3-L1 adipocytes differentiated. Most notably, we found that the depletion of this protein influences adipocyte differentiation and lipid storage, although the mechanism behind this is unclear.

The fat-specific protein 27 (Fsp27), a protein localized to lipid droplets (LDs), plays an important role in controlling lipid storage and mitochondrial activity in adipocytes. Fsp27-null mice display increased energy expenditure and are resistant to high fat diet-induced obesity and diabetes. However, little is known about how the Fsp27 protein is regulated. Here, we show that Fsp27 stability is controlled by the ubiquitin-dependent proteasomal degradation pathway in adipocytes. The ubiquitination of Fsp27 is regulated by three lysine residues located in the C-terminal region. Substitution of these lysine residues with alanines greatly increased Fsp27 stability and enhanced lipid storage in adipocytes. Furthermore, Fsp27 was stabilized and rapidly accumulated following treatment with beta-agonists that induce lipolysis and fatty acid re-esterification in adipocytes. More importantly, Fsp27 stabilization was dependent on triacylglycerol synthesis and LD formation, because knockdown of diacylglycerol acyltransferase in adipocytes significantly reduced Fsp27 accumulation in adipocytes. Finally, we observed that increased Fsp27 during beta-agonist treatment preferentially associated with LDs. Taken together, our data revealed that Fsp27 can be stabilized by free fatty acid availability, triacylglycerol synthesis, and LD formation. The stabilization of Fsp27 when free fatty acids are abundant further enhances lipid storage, providing positive feedback to regulate lipid storage in adipocytes.

We comparatively assessed the in vivo efficacy of artemether, artesunate, praziquantel and tribendimidine against different stages of Clonorchis sinensis. Rats were infected with 40-50 C. sinensis metacercariae, and drugs were administered singly by the oral route at different dosages. Rats were dissected 2-4 weeks post-treatment and C. sinensis trematodes were removed from the liver and bile ducts and counted. We used a negative binomial regression model to test the effect of drug and dosage in terms of worm burden reduction. Single 150 mg/kg oral doses of artesunate, artemether, tribendimidine and praziquantel, administered to rats infected with adult C. sinensis, resulted in mean worm burden reductions of 100, 100, 89.5 and 80.7%, respectively (all P<0.001). Halving the dose to 75 mg/kg still resulted in highly significant worm burden reductions for artesunate, artemether and tribendimidine (71.4-100%), but not for praziquantel (20.7%). In the juvenile infection model, a single 150 mg/kg oral dose of tribendimidine and praziquantel resulted in mean worm burden reductions of 99.1 and 90.0%, respectively, whereas considerably lower reductions were observed for artemether (59.2%) and artesunate (57.6%) when used at the same single dose. The in vivo results presented here with the artemisinins and tribendimidine provide further data for clinical investigations to assess the safety and efficacy of these drugs in clonorchiasis patients.

In China, traffic-related injuries are often treated as transportation issues, called 'accidents'. The objectives of the research are to analyse traffic injury patterns, estimate costs of traffic injuries and provide evidence to develop effective prevention strategies. There were over 1 500 deaths due to traffic-related injuries annually in Shanghai from 1987 to 2003, and it is rising year by year with the rate of growth in motorization. The rates of annual increase are 3.59% in fatalities (from 7.78 to 14.18 per 100000 population) and 10.46% in non-fatalities (from 53.93 to 264.98 per 100000 population) respectively during the period. The analysis of the geographic information system showed that the geographic distribution of traffic injuries in the countryside regions of Shanghai had the highest rates. Labour force groups represented the majority of fatalities (70.97%) and serious traffic injuries (90.51%). The mortality rates were 18.40 per 100000 population and 10.02 per 100000 population in 45-65 year age group and 15-44 year age group respectively; the morbidity rates of serious traffic injuries were 121.60 per 100000 population and 70.46 per 100000 population in the same groups respectively. And females generally showed a lower incidence than males. In general, fatalities and injuries were higher for drivers, bicyclists and pedestrians. Among road traffic injury-related fatalities, 66.8% were attributed to head injuries. Of those with fatal head injuries, bicyclists accounted for 29.8% of the total; pedestrians accounted for 28.3%; motorcyclists accounted for 25.5%. Total traffic injury cost was estimated at least US $645989580 in Shanghai in 2003. Good injury intervention programmes need to be done as soon as possible to effectively reduce traffic injury burden in Shanghai, China.

Paragonimiasis in Yongjia County, Zhejiang Province, China, has been of such public health concern that a specialized Institute for Paragonimiasis Control has been established there. The study reported here involved both parasitological research on Paragonimus westermani in the endemic areas and a clinical analysis of 94 cases of paragonimiasis. Eggs were found in sputum, feces and brain tissue in 45 cases. Twenty patients, 19 of whom where children under 10 years of age, showed hepatic injury. Treatment with praziquantel or bithionol had satisfactory results in all cases. Dimensions of the parasite eggs, metacercariae from freshwater crabs and adult flukes suggested that the form of P. westermani in Yongjia is the 'small type': a suggestion supported by karyotypic studies on gonad cells from adult flukes collected from experimentally infected animals as all were found to be diploid. In conclusion, the 'small type' or diploid form of P. westermani is the cause of paragonimiasis pulmonary symptoms in Yongjia.

The hypertensive rat model was made by chronic stress of electric foot-shocks and noises. On such hypertensive rats, when anesthetized with urethane and chloralose, the electroacupuncture (EA) to bilateral "Zusanli (st.36)" acupoints for 20 min, could result in a depressor (including both systolic and diastolic pressure) and bradycardiac response as well as an attenuation in the maximum of left ventricular pressure, end diastolic pressure and +/-dp/dt. In power spectrum analysis of heart rate variability aspect, EA could increase all total variance, very low frequency component, low frequency component and the ratio of low frequency component and high frequency component. When EA with microinjection of N(omega) - Nitro- L-Arginine , a blocker of the formation of nitric oxide, into the ventral periaqueductal gray matter (vPAG), the above effects of EA were abolished or reduced significantly. The results suggest that the depressor effect of EA on stress-induced hypertensive rats might be mediated by nitric oxide in the vPAG due to activation of sympathetic inhibitory system and by attenuated cardiac activities.