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Yan Yang,1,* Yiling Wang,1,* Xinran Jiang,1 Jiahao Mi,1 Dizhang Ge,2 Yuna Tong,3 Yuxuan Zhu1,2 1Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China; 2Department of Pharmacy, People’s Hospital of Aba Tibetan and Qiang Autonomous Prefecture, Aba, 624000, People’s Republic of China; 3Department of Nephrology, The Third People’s Hospital of Chengdu, Chongqing Medical University, Chengdu, 610031, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuna Tong; Yuxuan Zhu, Email tongyuna1985@163.com; zhuyuxuan6688@163.comIntroduction: Alzheimer’s disease (AD), a neurodegenerative condition, stands as the most prevalent form of dementia. Its complex pathological mechanisms and the formidable blood-brain barrier (BBB) pose significant challenges to current treatment approaches. Oxidative stress is recognized as a central factor in AD, underscoring the importance of antioxidative strategies in its treatment. In this study, we developed a novel brain-targeted nanoparticle, Ce/Zr-MOF@Cur-Lf, for AD therapy.Methods: Layer-by-layer self-assembly technology was used to prepare Ce/Zr-MOF@Cur-Lf. In addition, the effect on the intracellular reactive oxygen species level, the uptake effect by PC12 and bEnd.3 cells and the in vitro BBB permeation effect were investigated. Finally, the mouse AD model was established by intrahippocampal injection of Aβ1-42, and the in vivo biodistribution, AD therapeutic effect and biosafety of the nanoparticles were researched at the animal level.Results: As anticipated, Ce/Zr-MOF@Cur-Lf demonstrated efficient BBB penetration and uptake by PC12 cells, leading to attenuation of H2O2-induced oxidative damage. Moreover, intravenous administration of Ce/Zr-MOF@Cur-Lf resulted in rapid brain access and improvement of various pathological features of AD, including neuronal damage, amyloid-β deposition, dysregulated central cholinergic system, oxidative stress, and neuroinflammation.Conclusion: Overall, Ce/Zr-MOF@Cur-Lf represents a promising approach for precise brain targeting and multi-target mechanisms in AD therapy, potentially serving as a viable option for future clinical treatment.Keywords: metal-organic frameworks, Alzheimer’s disease, drug delivery, brain targeting, oxidative stress

Yin Li,1,* Manling Jiang,2,3,* Yongqi Wei,1,* Xiang He,2 Guoping Li,2,* Chunlai Lu,1 Di Ge1 1Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, People’s Republic of China; 3State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science & Technology, Taipa, Macao Special Administrative Region of China*These authors contributed equally to this workCorrespondence: Chunlai Lu; Di Ge, Email lu.chunlai@zs-hospital.sh.cn; ge.di@zs-hospital.sh.cnBackground: The pyrimidine salvage pathway plays a critical role in tumor progression and patient outcomes. The roles of pyrimidine salvage pathway-related genes (PSPGs) in cancer, however, are not fully understood. This study aims to depict the characteristics of PSPGs across various cancers.Methods: An integrative pan-cancer analysis of six PSPGs (CDA, UCK1, UCK2, UCKL1, UPP1, and UPP2) was conducted using TCGA data, single-cell RNA sequencing datasets, and patient samples. Single-cell transcriptome analysis and RT-qPCR were used to validate the relation between UPP1 and cytokines. Flow cytometry was performed to validate the role of UPP1 in immune checkpoint regulation. The correlation between UPP1 and tumor associated neutrophils (TAN) were investigated and validated by single-cell transcriptome analysis and tissue microarrays (TMAs).Results: PSPGs showed low mutation rates but significant copy number variations, particularly amplifications in UCKL1, UPP1, and UCK2 across various cancers. DNA methylation patterns varied, with notable negative correlations between methylation and gene expression in UPP1. PSPGs were broadly up-regulated in multiple cancers, with correlations to clinical staging and prognosis. Proteomic data further confirmed these findings. Functional analysis revealed PSPGs’ associations with tumor proliferation, metastasis, and various signaling pathways. UPP1 showed strong correlations with the tumor microenvironment (TME), particularly with cytokines, immune checkpoints, and various immune cells. Single-cell transcriptome analysis confirmed these associations, highlighting UPP1’s influence on cytokine expression and immune checkpoint regulation. In esophageal squamous cell carcinoma (ESCC), UPP1-high tumor cells were significantly associated with immunosuppressive cells in the TME. Spatial analysis using TMAs revealed that UPP1+ tumor cells were predominantly located at the invasive margin and closely associated with neutrophils, correlating with poorer patient prognosis.Conclusion: Our study depicted the multi-dimensional view of PSPGs in cancer, with a particular focus on UPP1’s role in the TME. Targeting UPP1 holds promise as a potential strategy for cancer therapy.Keywords: pyrimidine salvage pathways, UPP1, microenvironment

Bili Liu, Dan Ge, Yue Shan, Yanping Li, Juan Lv, Shuzhi Gan Department of Ultrasound, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310007, People’s Republic of ChinaCorrespondence: Bili Liu, Department of Ultrasound, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, No. 453 Stadium Road, Xihu District, Hangzhou, Zhejiang Province, 310007, People’s Republic of China, Tel +86-057185827841, Email lbili_bl1@163.comObjective: Based on the analysis of the images of acromial slide, we explored the application of percutaneous ultrasound-guided subacromial bursography (PUSB) on rotator cuff tear (RCT) in diagnosing elderly patients with shoulder pain.Methods: Eighty-five patients who were clinically diagnosed with RCT and underwent PUSB examination in the department of ultrasound in our hospital were enrolled as the subjects. Independent samples t-test was used to analyze the general characteristics. Based on the gold standard of shoulder arthroscopy, the diagnostic efficacy of ultrasound, magnetic resonance imaging (MRI), and PUSB was evaluated. The sensitivity, specificity, positive and negative predictive values, and accuracy were calculated as well. The consistency of these techniques with shoulder arthroscopy in diagnosing the RCT stage was additionally compared using Kappa test.Results: In patients with large full-thickness RCT, the 100% detection rate was achieved by the techniques of ultrasound, MRI, and PUSB. For patients with small full-thickness RCT, the detection rate of PUSB (100%) was evidently higher than those of ultrasound and MRI. Similar results were shown in the detection rates of patients with bursal-side partial-thickness RCT (90.5%) and articular-side partial-thickness RCT (86.9%). More importantly, the sensitivity, specificity, and accuracy of PUSB in patients with both full-thickness RCT and partial-thickness RCT were significantly better than those of ultrasound and MRI.Conclusion: PUSB has a better efficacy in the detection of RCT than ultrasound and MRI, showing its feasibility as an important imaging method to evaluate the degree of RCT.Keywords: rotator cuff tear, percutaneous ultrasound-guided subacromial bursography, shoulder pain, acromial slide cystography, diagnosis

Yalan Li,1,* Na Li,1,* Jiajing Liu,1 Tieshan Wang,2 Ruijuan Dong,3 Dongyu Ge,3 Guiying Peng1 1Department of Immunology and Microbiology, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Experimental Teaching Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guiying Peng, Email penggy@bucm.edu.cnObjective: Ulcerative colitis (UC) as one of the intractable diseases in gastroenterology seriously threatens human health. Respiratory pathology is a representative extraintestinal manifestation of UC affecting the quality of life of patients. Gegen Qinlian Decoction (GQD) is a classical traditional Chinese medicine prescription for UC or acute lung injury. This study was aimed to reveal the therapeutic effect of GQD on UC and its pulmonary complications and uncover its molecular mechanism mediated by myeloid cells and microbiota.Methods: Mice with DSS-induced colitis were orally administrated with GQD. Overall vital signs were assessed by body weight loss and disease activity index (DAI). Pulmonary general signs were evaluated by pulmonary pathology and lung function. The mechanism of GQD relieving UC was characterized by detecting myeloid cells (neutrophils, macrophages, inflammatory monocytes, and resident monocytes) in colonic and lung tissues, related inflammatory cytokines, as well as the microbiota in bronchoalveolar lavage fluid (BALF) and feces.Results: GQD significantly reduced weight loss, DAI scores, and lung injury but improved the lung function of colitis mice. The DSS-induced colonic and concurrent pulmonary inflammation were also alleviated by GQD, as indicated by the down-regulated expressions of inflammatory cytokines (TNF-α, IL-1β, IL-6, CCR2, and CCL2) and the suppressed recruitment of neutrophils and inflammatory monocytes. Meanwhile, GQD greatly improved intestinal microbiota imbalance by enriching Ruminococcaceae UCG-013 while decreasing Parabacteroides, [Eubacterium]_fissicatena_group, and Akkermansia in the feces of colitis mice. Expectantly, GQD also restored lung microbiota imbalance by clearing excessive Coprococcus 2 and Ochrobactrum in the BALF of colitis mice. Finally, significant correlations appeared between GQD-mediated specific bacteria and inflammatory cytokines or immune cells.Conclusion: GQD could alleviate UC by decreasing excessive inflammatory myeloid cells and cytokines, and reshaping the microbiota between the colon and lung, which contributes to clarifying the mechanism by which GQD ameliorates colitis-associated pulmonary inflammation.Keywords: Gegen Qinlian Decoction, ulcerative colitis, lung and intestinal microbiota, pulmonary inflammation, myeloid cells

Yongan Wang,1,* Na Li,1,* Qiuyi Li,1 Zirui Liu,1 Yalan Li,1 Jingwei Kong,1 Ruijuan Dong,2 Dongyu Ge,2 Jie Li,3 Guiying Peng1 1Department of Immunology and Microbiology, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Experimental Teaching Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Respiratory Medicine, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guiying Peng; Jie Li Email penggy@bucm.edu.cn; lijie2007@126.comPurpose: Chronic obstructive pulmonary disease (COPD), a prevalent obstructive airway disease, has become the third most common cause of death globally. Xuanbai Chengqi decoction (XBCQ) is a traditional Chinese medicine prescription for the acute exacerbation of COPD. Here, we aimed to reveal the therapeutic effects of XBCQ administration and its molecular mechanisms mediated by Th17/Treg balance and gut microbiota.Methods: We determined the counts of Th17 and Treg cells in the serum of 15 COPD and 10 healthy subjects. Then, cigarette smoke extract-induced COPD mice were gavaged with low, middle, and high doses of XBCQ, respectively. Weight loss, pulmonary function and inflammation, Th17/Treg ratio, and gut microbiota were measured to evaluate the efficacy of XBCQ on COPD.Results: COPD patients had a higher Th17/Treg ratio in the serum than healthy controls, which was consistent with the results in the lung and colon of COPD mice. The middle dose of XBCQ (M-XBCQ) significantly decreased the weight loss and improved the pulmonary function (FEV0.2/FVC) in COPD mice. Moreover, M-XBCQ alleviated lung inflammation by rectifying the Th17/Treg imbalance, reducing the expressions of TNF-α, IL-1β, and MMP-9, and suppressing inflammatory cells infiltration. Meanwhile, M-XBCQ greatly improved the microbial homeostasis in COPD mice by accumulating probiotic Gordonibacter and Akkermansia but inhibiting the growth of pathogenic Streptococcus, which showed significant correlations with pulmonary injury.Conclusion: Oral M-XBCQ could alleviate COPD exacerbations by reshaping the gut microbiota and improving the Th17/Treg balance, which aids in elucidating the mechanism through which XBCQ as a therapy for COPD.Keywords: XBCQ, COPD, intestinal microbiota, Th17/Treg, pulmonary inflammation

Jie Tang,1 Liqun Zhu,1 Yuejiao Huang,2,3 Lixiang Yang,4 Dangen Ge,5 Zhengyu Hu,6 Chun Wang1 1Department of Oncology, Liyang People’s Hospital, Liyang, 213300, People’s Republic of China; 2Medical School, Nantong University, Nantong, 226019, People’s Republic of China; 3Department of Medical Oncology, Affiliated Tumor Hospital of Nantong University, Nantong, 226399, People’s Republic of China; 4Department of Neurosurgery, Affiliated Zhongda Hospital of Southeast University, Nanjing, 210009, People’s Republic of China; 5Department of Pharmacy, Liyang People’s Hospital, Liyang, 213300, People’s Republic of China; 6Department of General Surgery, Shanghai Tenth People’s Hospital, Affiliated to Tongji University School of Medicine, Shanghai, 200072, People’s Republic of ChinaCorrespondence: Chun WangDepartment of Oncology, Liyang People’s Hospital, 70 Jianshe Road, Liyang, Jiangsu, 213300, People’s Republic of ChinaEmail zlkwangchun@163.comObjective: Anal canal cancer is a rare malignancy with increasing incidence in recent times. This study aimed to develop two nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with anal canal cancer.Methods: Information of patients with anal canal cancer from 2004 to 2015 was extracted from the surveillance, epidemiology, and end results (SEER) database. Cox analysis was used to select the risk factors for prognosis, and nomograms were constructed using the R software. The C-index, area under the curve (AUC) of time-dependent receiver operating characteristic (ROC) curves, calibration plot and decision curve analysis (DCA) were used to assess the clinical utility of the nomograms.Results: A total of 2458 patients with malignant tumours of the anal canal were screened out. Sex, age, marital status, histological type, grade, tumour size, AJCC stage, SEER stage and chemotherapy were independent prognostic factors for OS, whereas sex, age, race, histological type, grade, tumour size, AJCC stage, SEER stage and radiotherapy were independent prognostic factors for CSS. In the training cohort, the C-index value for OS nomogram was 0.73 (95% CI, 0.69– 0.77), and the AUC values that predicted the 1-, 3- and 5-year survival rates were 0.764, 0.758 and 0.760, respectively, whereas the C-index value for CSS nomogram model was 0.74 (95% CI, 0.69– 0.79), and the AUC values were 0.763, 0.769 and 0.763, respectively. The calibration plot and DCA curves demonstrated good prediction performance of the model in both the training and validation cohorts.Conclusion: The established nomogram is a visualisation tool that can effectively predict the OS and CSS of patients with anal canal cancer.Keywords: anal canal cancer, cancer specific survival, nomogram, overall survival, prognosis

Panghua Ding,1,* Jiajing Liu,2,* Qiuyi Li,2 Qiongqiong Lu,3 Junxiang Li,3 Rui Shi,3 Lei Shi,2 Tangyou Mao,3 Dongyu Ge,4 HaiJun Niu,5 Guiying Peng,2 Zhibin Wang3 1Department of Graduate School, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Immunology and Microbiology, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Gastroenterology, Dong Fang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Experimental Teaching Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5Anhui Joyfar Pharmaceutical Research Institute Co. Ltd, Hefei, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guiying Peng; Zhibin Wang Email penggy@bucm.edu.cn; wangsanger@126.comBackground: Hudi enteric-coated capsule (HDC) is a Chinese medicine prescribed to treat ulcerative colitis (UC). However, its anti-inflammatory active ingredients and mechanisms remain unknown. This study aimed to investigate the active components of HDC and explore its potential mechanisms against UC by integrating network pharmacology and experimental verification.Methods: A DSS-induced colitis murine model was established to validate the efficacy of HDC by detecting disease activity index (DAI) and histopathological changes. Network pharmacological analysis was performed to identify the active compounds and core targets of HDC for the treatment of UC. The main compounds in HDC were identified by high-performance liquid chromatography. The relative expressions of HDC’s core targets were also determined in vivo. Finally, molecular docking was applied to model the interaction between HDC and target proteins.Results: In an in vivo experiment, HDC, especially the middle-dose HDC, effectively reduced clinical symptoms of UC, including weight loss, bloody stool, and colon shortening. Besides, the severity of colitis was considerably suppressed by HDC as evidenced by reduced DAI scores. A total of 118 active compounds and 69 candidate targets from HDC closely related to UC progression were identified via network pharmacology. Enrichment analysis revealed that the key targets of HDC correlated with the expressions of PTGS2, TNF-α, IL-6, and IL-1β. Meanwhile, these cytokines were enriched in various biological processes through the IL-17/JAK2/STAT3 signaling pathway. The middle-dose HDC contributed more to ameliorating DSS-induced colitis through this signaling pathway than other dosages. Nine components binding to JAK2, STAT3, IL-17 and IL-6 were identified by molecular docking, confirming again the inhibition effects of HDC on the IL-17/JAK2/STAT3 signaling pathway.Conclusion: The HDC treatment, particularly the middle-dose, exerted an anti-UC effect in a multi-component, multi-target, and multi-mechanism manner, especially inhibiting the IL-17/JAK2/STAT3 signaling pathway to downregulate the secretion of proinflammatory cytokines.Keywords: Hudi enteric-coated capsule, ulcerative colitis, network pharmacology, IL-17/JAK2/STAT3 pathway

Di Mei,1,&ast; Xiaolong Guo,2,&ast; Yirong Wang,1 Xiaofei Huang,1 Li Guo,1 Pengfei Zou,3 Delong Ge,1 Xinxin Wang,1 Wenhui Lee,4 Tongyi Sun,1 Zhiqin Gao,1 Yuanyuan Gao3 1School of Life Science and Technology, Shandong Key Laboratory of Proteins and Peptides Pharmaceutical Engineering, Shandong Universities Key Laboratory of Biopharmaceuticals, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China; 2School of Basic Medicine, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China; 3School of Pharmacy, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China; 4Key Laboratory of Animal Models and Human Disease Mechanism, Institute of Zoology, Kunming, Yunnan, 650233, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiqin GaoSchool of Life Science and Technology, Shandong Key Laboratory of Proteins and Peptides Pharmaceutical Engineering, Shandong Universities Key Laboratory of Biopharmaceuticals, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of ChinaTel +86 5368462066Email zhiqingao2013@163.comYuanyuan GaoSchool of Pharmacy, Weifang Medical University, Baotong Road, Weifang, Shandong Province, 261053, People’s Republic of ChinaTel +86 536 846 2067Email yyg20062006@126.comBackground: The treatment of Staphylococcus aureus (S. aureus)-infected wounds is difficult. It causes extreme pain to tens of thousands of patients and increases the cost of medical care. The antimicrobial peptide OH-CATH30 (OH30) has a good killing activity against S. aureus and can play a role in accelerating wound healing and immune regulation. Therefore, it shows great potential for wound healing.Purpose: The aim of this study was to overcome the short half-life and easy enzymolysis of OH30 by using graphene oxide conjugated with polyethylene glycol to load OH30 (denoted as PGO-OH30), as well as to evaluate its effect on wounds infected by S. aureus.Methods: PGO-OH30 nanoparticles were prepared by π–π conjugation and characterized. Their cell cytotoxicity, cell migration, infectious full-thickness dermotomy models, and histopathology were evaluated.Results: Characterization and cytotoxicity experiments revealed that the PGO-OH30 drug-delivery system had good biocompatibility and excellent drug-delivery ability. Cell-migration experiments showed that PGO-OH30 could promote the migration of human immortalized keratinocytes (HaCaT) cells compared with the control group (P< 0.05). In a mouse model of skin wound infection, PGO-OH30 accelerated skin-wound healing and reduced the amount of S. aureus in wounds compared with the control group (P< 0.05). In particular, on day 7, the number of S. aureus was 100 times lower in the PGO-OH30 group than in the control group.Conclusion: The PGO-OH30 drug-delivery system had good biocompatibility and excellent drug-delivery ability, indicating its good therapeutic effect on a skin wound-infection model.Keywords: OH-CATH30, bacterial infection, graphene oxide, skin wound

Hao-cheng Zheng,1,* Yong-an Wang,1,* Zi-rui Liu,1 Ya-lan Li,1 Jing-wei Kong,1 Dong-yu Ge,2 Gui-ying Peng1 1Department of Immunology and Microbiology, School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China; 2Experimental Teaching Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gui-ying PengBeijing University of Chinese Medicine, No. 11, East Road North Ring 3rd, Chao-Yang District, Beijing 100029, People’s Republic of ChinaTel +86-010-53912169Email penggy@bucm.edu.cnObjective: In China, lamb and fish are well-known triggers for an asthma attack. Our investigation aims at assessing whether the long-term intake of lamb meat or Basa fish would aggravate pulmonary inflammation as well as exploring changes in the intestinal microbiota and immune cells in asthmatic mice.Materials and Methods: The murine asthmatic model was established by intraperitoneal injection of ovalbumin (OVA) plus aluminum on day 0 and 14 and nebulization of OVA from day 21 to 27. Lamb meat or fish was administered to asthmatic mice by oral gavage from day 0 to 27.Results: Our results showed that long-term consumption of lamb meat or Basa fish in asthmatic mice increased the number of inflammatory cells in bronchoalveolar lavage fluid (BALF), enhanced levels of IL-5, IL-13 in BALF and total IgE in serum, aggravated pulmonary inflammatory cell infiltration and mucus secretion. Long-term oral lamb enhanced the proportion of type 2 innate lymphoid cells (ILC2) from small intestine while it inhibited that of Treg from lung in asthmatic mice. Oral fish showed no remarkable effect on that of ILC2 from lung and small intestine but inhibited that of intestinal Treg in asthmatic mice. What’s more, the chao-1 and observed species richness as well as PD whole tree diversity increased in asthmatic mice while these increments were inhibited after lamb treatment. PCA analysis indicated that there were significant differences in the bacterial community composition after lamb or fish treatment in asthmatic mice. Both lamb and fish treatment enhanced the abundance of colonic Alistipes in asthmatic mice.Conclusion: Collectively, long-term intake of lamb or fish shapes colonic bacterial communities and aggravates pulmonary inflammation in asthmatic mice, which provides reasonable food guidance for asthmatic patients.Keywords: asthma, intestinal microbiota, lamb, fish, ILC2, Treg

Dan Ge,1,2,* Qiqi Du,1,2,* Bingqing Ran,1,2 Xingyu Liu,1,2 Xin Wang,1,2 Xuehu Ma,1 Fang Cheng,1,3 Bingbing Sun1,21State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, People’s Republic of China; 2Department of Chemical Engineering, Dalian University of Technology, Dalian 116024, People’s Republic of China; 3Department of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian 116024, People’s Republic of China*These authors contributed equally to this work Abstract: Engineered nanomaterials (ENMs) have been widely used in various fields due to their novel physicochemical properties. However, the use of ENMs has led to an increased exposure in humans, and the safety of ENMs has attracted much attention. It is universally acknowledged that ENMs could enter the human body via different routes, eg, inhalation, skin contact, and intravenous injection. Studies have proven that ENMs can cross or bypass the blood–brain barrier and then access the central nervous system and cause neurotoxicity. Until now, diverse in vivo and in vitro models have been developed to evaluate the neurotoxicity of ENMs, and oxidative stress, inflammation, DNA damage, and cell death have been identified as being involved. However, due to various physicochemical properties of ENMs and diverse study models in existing studies, it remains challenging to establish the structure-activity relationship of nanomaterials in neurotoxicity. In this paper, we aimed to review current studies on ENM-induced neurotoxicity, with an emphasis on the molecular and cellular mechanisms involved. We hope to provide a rational material design strategy for ENMs when they are applied in biomedical or other engineering applications.Keywords: engineered nanomaterials, neurotoxicity, oxidative stress, inflammation, DNA damage, cell death

The Ethnic Density hypothesis posits that living around others from similar ethnic backgrounds reduces the risk of adverse mental health outcomes such as depression. Contrary to this hypothesis, previous work has shown that Hispanic ethnic density is cross-sectionally associated with increased depressive symptom severity among patients hospitalized with an acute coronary syndrome (ACS; myocardial infarction or unstable angina pectoris). To date, no study has examined the prospective association of Hispanic ethnic density on long-term depressive symptom severity following an acute medical event. We prospectively assessed the impact of Hispanic ethnic density on depressive symptoms, 1-year following an ACS event, among Hispanic adult patients. We tested the non-linear association between ethnic density and depressive symptoms to account for inconsistent findings on the ethnic density hypothesis. At the time of an index ACS event (i.e., baseline, N = 326) and 1-year later (N = 252), Hispanic patients from the Prescription Usage, Lifestyle, and Stress Evaluation prospective cohort study completed the Beck Depression Inventory as a measure of depressive symptom severity. Hispanic ethnic density was defined by the percentage of Hispanic residents within each patient's census tract using data extracted from the American Community Survey Census (2010-2013). Covariates included baseline demographic factors (age, gender, English fluency, education, nativity status), cardiovascular factors (Charlson comorbidity index, left ventricular ejection fraction, Global Registry of Acute Coronary Events 6-month prognostic risk score), and neighborhood factors (residential density, income, and percentage of households receiving public assistance). In an adjusted multivariable linear regression analysis there was a significant curvilinear association between Hispanic ethnic density and depressive symptom severity at 1 year. As Hispanic ethnic density increased from low to moderate density, there was an increase in depressive symptoms, but depressive symptoms slightly declined in census tracts with the highest density of Hispanics. Furthermore, gender significantly moderated the relation between Hispanic ethnic density and 1-year depressive symptom severity, such that Hispanic ethnic density was significantly associated with increased depressive symptom severity for female Hispanic patients with ACS, but not for male Hispanic patients. Previous research suggests that ethnic density may be protective against depression in Hispanic enclaves; however, our findings suggest a non-linear ethnic density effect and an overall more complex association between ethnic density and depression. These data add to a growing body of literature on the effects of sociodemographic and contextual factors on health., Author(s): Ellen-ge D. Denton[sup.1] , Jonathan A. Shaffer[sup.2] , Carmela Alcantara[sup.3] , Esteban Cadermil[sup.4] Author Affiliations: (1) Department of Psychology, City University of New York College of Staten Island, 2800 [...]

Qingli Li,1,2 Mark J Lambrechts,1 Qiuyang Zhang,1 Sen Liu,1 Dongxia Ge,1 Rutie Yin,2 Mingrong Xi,2 Zongbing You1 1Departments of Structural and Cellular Biology and Orthopaedic Surgery, Tulane Cancer Center and Louisiana Cancer Research Consortium, Tulane Center for Stem Cell Research and Regenerative Medicine, and Tulane Center for Aging, Tulane University Health Sciences Center, New Orleans, LA, USA; 2Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China Abstract: Glycine is a nonessential amino acid that is reversibly converted from serine intracellularly by serine hydroxymethyltransferase. Glyphosate and its degradation product, aminomethylphosphonic acid (AMPA), are analogs to glycine, thus they may inhibit serine hydroxymethyltransferase to decrease intracellular glycine synthesis. In this study, we found that glyphosate and AMPA inhibited cell growth in eight human cancer cell lines but not in two immortalized human normal prostatic epithelial cell lines. AMPA arrested C4-2B and PC-3 cancer cells in the G1/G0 phase and inhibited entry into the S phase of the cell cycle. AMPA also promoted apoptosis in C4-2B and PC-3 cancer cell lines. AMPA upregulated p53 and p21 protein levels as well as procaspase 9 protein levels in C4-2B cells, whereas it downregulated cyclin D3 protein levels. AMPA also activated caspase 3 and induced cleavage of poly (adenosine diphosphate [ADP]-ribose) polymerase. This study provides the first evidence that glyphosate and AMPA can inhibit proliferation and promote apoptosis of cancer cells but not normal cells, suggesting that they have potentials to be developed into a new anticancer therapy. Keywords: serine hydroxymethyltransferase, prostate cancer, apoptosis

INTRODUCTION: Linezolid is a synthetic oxazolidinone antimicrobial drug with a broad spectrum and a unique mechanism of inhibiting resistant pathogenic strains, and it was approved by the Food and Drug Administration (FDA) in April 2000. Several different systemic side effects were reported after the use of this medication. In this article, we report a case in which a syndrome of inappropriate antidiuretic hormone (SIADH) was developed after linezolid treatment was started. CASE PRESENTATION: We present the case of a 79-year-old woman who developed severe hyponatremia during linezolid treatment (0.6 g i.v. q12 h) after undergoing hemiarthroplasty for left femoral neck fracture. The patient's baseline serum sodium upon admission (138 mmol/L) decreased to 118 mmol/L, urine sodium was 102 mmol/L, plasma osmolality was 248 mOsm/kg and urine osmolarity was 310 mOsm/kg at day 4, thus a diagnosis of SIADH was made. The patient was not taking any other medication known to cause SIADH, and she did not present a comorbidity that could explain her condition. Her serum sodium increased to 135 and 137 mmol/L, respectively, 11 and 12 days after cessation of linezolid, strongly suggesting that SIADH was the cause in this case. CONCLUSIONS: This is the fourth case of linezolid-induced SIADH. A thorough workup was essential for the diagnosis to correctly differentiate between SIADH and other causes of hyponatremia, which helped us properly conducting follow-up treatments. SIADH is a rare but serious side effect of linezolid, and practicing physicians should be aware of this complication. It is necessary to periodically monitor the serum sodium. [ABSTRACT FROM AUTHOR]