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Background: Synovial sarcoma (SS) refers to a malignant soft tissue sarcoma (STS) which often comes about to children and adults and has a poor prognosis in elderly patients. Patients with local lesions can be treated with extensive surgical resection combined with adjuvant or radiotherapy, whereas about half of the cases have recurrent diseases and metastatic lesions, and five-year survival ratio is assessed within the range of 27% - 55% only. Method: We downloaded a set of expression profile data (GSE40021) related to SS metastasis based on the Gene Expression Omnibus (GEO) database, and selected distinctly represented genes (DEGs) related to tumor metastasis. WGCNA was used to emphasize the DEGs related to tumor metastasis, and obtain co-expression modules. Then, the module most related to SS metastasis was screened out. The genes of enriched in this module were analyzed by Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway improvement analysis. Cytoscape software was used for constructing protein-protein interaction (PPI) networks, and screening hub genes were made in virtue of Oncomine analysis. Result: We selected 514 DEGs, consisting of 210 up-regulated genes and 304 down-regulated genes. Through WGCAN, we got seven co-expression modules and the module most related to SS metastasis was turquoise module, which contained 66 genes. Finally, we screened out five hub genes (HJURP, NCAPG, TPX2, CENPA, NDC80) through CytoHubba and Oncomine analysis. Conclusion: In this study, we screened out five hub genes to help clinical diagnosis and serve as the latent purpose of SS treatment.

A major challenge to the treatment of advanced prostate cancer (PCa) is the development of resistance to androgen-deprivation therapy (ADT) and chemotherapy. It is imperative to discover effective therapies to overcome drug resistance and improve clinical outcomes. We have developed a novel class of silicon-containing compounds and evaluated the anticancer activities and mechanism of action using cellular and animal models of drug-resistant PCa. Five organosilicon compounds were evaluated for their anticancer activities in the NCI-60 panel and established drug-resistant PCa cell lines. GH1504 exhibited potent in vitro cytotoxicity in a broad spectrum of human cancer cells, including PCa cells refractory to ADT and chemotherapy. Molecular studies identified several potential targets of GH1504, most notably androgen receptor (AR), AR variant 7 (AR-v7) and survivin. Mechanistically, GH1504 may promote the protein turnover of AR, AR-v7 and survivin, thereby inducing apoptosis in ADT-resistant and chemoresistant PCa cells. Animal studies demonstrated that GH1504 effectively inhibited the in vivo growth of ADT-resistant CWR22Rv1 and chemoresistant C4-2B-TaxR xenografts in subcutaneous and intraosseous models. These preclinical results indicated that GH1504 is a promising lead that can be further developed as a novel therapy for drug-resistant PCa.

Osteosarcoma (OS) is the most common primary bone tumor in children and adolescents. It is an aggressive tumor with a tendency to spread to the lung, which is the most common site of metastasis. Patients with advanced OS with metastases have poor prognoses despite the application of chemotherapy, thus highlighting the need for novel therapeutic targets. The tumor microenvironment (TME) of OS is confirmed to be essential for and supportive of tumor growth and dissemination. The immune component of the OS microenvironment is mainly composed of tumor-associated macrophages (TAMs). In OS, TAMs promote tumor growth and angiogenesis and upregulate the cancer stem cell-like phenotype. However, TAMs inhibit the metastasis of OS. Therefore, much attention has been paid to investigating the mechanism of TAMs in OS development and the progression of immunotherapy for OS. In this article, we aim to summarize the roles of TAMs in OS and the major findings on the application of TAMs in OS treatment.

Aluminum (Al) toxicity is a major constraint for crop growth and production in tropical acidic soils, and organic acids (OAs) play a critical role in mitigating Al toxicity. However, the types of OAs secreted and Al tolerance varies across plants. To better understand the mechanisms that rubber trees use to mitigate Al toxicity, Reyan7-33-97 rubber tree tissue culture saplings were treated with different concentrations of AlCl3 to investigate the secretion of OAs under Al stress, along with the mitigation effects of exogenous OA application. The results showed that the pH value of root exudates was significantly decreased in response to the increase of Al concentration and duration, which resulted in 1.19–2.49 fold increases to total OA levels, particularly oxalic acid as its content was considerately higher than other OAs. When OAs, such as oxalic and malic acids were exogenously applied to Al treatment solutions, the rubber tree chlorophyll content, leaf relative water content and root activity were increased significantly, whereas the Al content in roots and leaves, antioxidant enzyme activities (POD, SOD), MDA and free proline contents decreased significantly in comparison with the Al treatment alone. Oxalic acid was found to be superior to malic acid in alleviating Al toxicity. Taken together, our results demonstrate that root secretion of OAs, particularly oxalic acid, under Al stress is a mechanism for rubber tree Al detoxification.

BACKGROUND AND PURPOSE To compare and characterize metabolic features of high- and low-grade glioma tumors using 68 Ga-PSMA-617 and 18 F-FDG positron emission tomography/computed tomography (PET/CT). METHODS Thirty patients who underwent both 68 Ga-PSMA-617 and 18 F-FDG PET/CT over 2 consecutive days and then underwent surgical treatment were retrospectively identified. All tumors were diagnosed histologically. This report includes 16 high-grade glioma (HGG) and 14 low-grade glioma (LGG) tumors. Standard uptake value (SUV) and target to nontarget (T/NT) were quantitatively investigated through the entire tumor region. Statistical analyses were performed using area under the curve (AUC) and comparison of two means. RESULTS SUVmax and SUVmean were the most effective (AUC, 0.96 and 0.94 for PSMA PET; AUC, 0.79 and 0.74 for FDG PET, respectively) for differentiating HGGs from LGGs. These methods distinguished between HGG and LGG effectively (PSMA PET: SUVmax , 5.766 ± 3.945 vs. 0.7364 ± 0.5295, p < 0.0001; SUVmean , 1.666 ± 1.680 and 0.1514 ± 0.1534, p < 0.0001, respectively) (FDG PET: SUVmax , 11.67 ± 3.639 and 9.118 ± 6.612; SUVmean , 5.648 ± 2.114 and 4.435 ± 2.872; p = 0.0083, 0.0262, respectively). The Youden index for SUVmax and SUVmean of 68 Ga-PSMA-617 and 18 F-FDG were 0.82 and 0.79 and 0.54 and 0.61, separately. T/NTmax was helpful for visual inspection of 68 Ga-PSMA-617-PET images (T/NTmax : 1.291 ± 0.9553 in grade II, 5.25 ± 2.435 in grade III, and 13.61 ± 13.84 in grade IV). T/NTmax differed significantly between LGG and HGG and between subtypes of LGG. CONCLUSION PET/CT with 68 Ga-PSMA-617 and 18 F-FDG may help distinguish between HGG and LGG, and 68 Ga-PSMA-617 PET/CT is superior to18 F-FDG in differentiating HGG and LGG.

BACKGROUND Gastrointestinal stromal tumor (GIST) usually originates in the stomach, followed by the small intestine, rectum, and other parts of the gastrointestinal tract. The most common sites of metastasis are the liver and peritoneum, whereas spinal metastases from GIST are extremely rare. CASE SUMMARY We found a case of GIST with the first presentation of multilevel spinal metastases involving the thoracic and lumbar vertebrae. A 61-year-old Chinese man presented to our clinic because of pain in his lower back and hip for 10 d without cause. Subsequently, computed tomography (CT) and magnetic resonance imaging (MRI) revealed abnormal signals in the vertebral appendages of T12 and L4 accompanied by spinal canal stenosis, which was considered as tumor metastasis. As there were no metastases to vital organs, posterior thoracic and lumbar spinal decompression + adnexal mass resection + pedicle internal fixation was adopted to achieve local cure and prevent nerve compression. The results of histopathological studies were consistent with the metastasis of GIST. No local recurrence or new metastases were found at the 6-mo follow-up at the surgical site. The patient has no neurological symptoms at present. It is worth mentioning that a rectal mass was found and surgically removed 1 mo after the patient was discharged from hospital, and the pathological diagnosis of the mass was GIST. CONCLUSION By reviewing 26 previously reported cases of spinal metastasis in GIST, it was found that spinal metastasis of GIST has become more common in recent years, so the possibility of early spinal metastasis should be recognized. CT and MRI are of great value in the diagnosis of spinal metastatic tumors, and pathological biopsy is the gold standard for the diagnosis of metastatic tumors. It is safe and feasible to treat isolated spinal metastasis in GIST by excising metastatic masses, decompressing the spinal canal, and stabilizing the spine.

Objective This retrospective study was purposed to evaluate epidemiological, clinical, and 3D radiological features of supernumerary teeth (ST) in a non-syndromic Chinese children and adolescent dental population. Materials and methods Original cone-beam CT (CBCT) data from 18,861 patients aged from 6 to 17 years with dental maxillofacial diseases treated in a Chinese dental hospital from June 2012 to December 2018 were utilized to screen patients with ST. Diagnosis and characterizations of ST were analyzed by CBCT coupled with 3D reconstruction. All relevant epidemiological, clinical, and radiographic details about ST were collected and statistically analyzed. Results Among total 18,861 patients, 2,768 ST were identified in 1984 subjects with a prevalence of 10.52% and a male:female ratio of 1.86:1. Majority of ST were single, conical, inverted, impacted, and located in maxilla anterior region. ST-associated complications mainly included malposition, rotation, and impaction of adjacent teeth, which were notably associated with morphology and position of ST. Conclusion The prevalence of ST in Chinese children and adolescent dental population was 10.52% and tended to present as single, conical, inverted, and impacted, which resulted in abnormalities of neighboring teeth. Our outcomes are beneficial for clinicians to more comprehensively understand the incidence, characterization, and clinical treatment planning of ST in dental children and adolescents.

Background/aim Chemoresistance is a major obstacle in the treatment of prostate cancer (PCa). It is imperative to develop novel strategies for overcoming chemoresistance and improving clinical outcomes. We evaluated the in vitro activity and mechanism of action of dihydroergocristine (DHECS), an ergot alkaloid approved for the treatment of dementia, in PCa cells. Materials and methods The in vitro effects of DHECS on PCa cell cycle and viability were determined by flow cytometry and colorimetric assay. The effects of DHECS on PCa cell signaling were evaluated by quantitative PCR, western blot analysis and reporter assay. Results DHECS was effective in inducing cell cycle arrest and apoptosis in human PCa cells. Of particular interest, DHECS demonstrated high potency against chemoresistant PCa cells. At the molecular level, DHECS affected multiple factors implicated in the regulation of cancer cell cycle and programmed cell death, including p53, mouse double minute 2 homolog (MDM2), retinoblastoma protein (RB), p21, E2F transcription factor 1 (E2F1), survivin, myeloid cell leukemia 1 (Mcl-1) and poly ADP ribose polymerase (PARP). Furthermore, DHECS may function through dopamine receptor-mediated effects on 5'-AMP-activated protein kinase (AMPK) and nuclear factor kappa B (NF-ĸB). Conclusion DHECS has the potential to be repurposed as a novel anticancer agent for the management of chemoresistant PCa.

Objective Hepcidin deficiency is known to cause body iron accumulation and bone microarchitecture defects, but the exact underlying mechanisms of hepcidin deficiency-induced bone loss remain unclear. Our objective was to understand the molecular mechanism of hepcidin deficiency-induced bone loss. Methods The bone phenotypes of wild type (WT) and hepcidin knockout (Hepcidin-KO) mice were measured by microcomputed tomography. The osteoclastic marker of the bone was measured by tartrate-resistant acid phosphatase staining. The osteoblastic marker of the bone was measured by immunostaining of osteocalcin. Primary osteoblastic and osteoclastic differentiation was performed using bone marrow cells. The mature osteoclast was determined by tartrate-resistant acid phosphatase staining, pit formation assay and relative gene expression. The mature osteoblast was determined by alkaline phosphatase activity, alkaline phosphatase staining, Alizarin Red staining and relative gene expression. The protein expression of β-catenin, TCF4/TCF7L2 and Forkhead box O3a (FOXO3a) was measured by Western blot and their combination by co-immunoprecipitation. In vivo study was performed by tail vein administration of FOXO3a-RNAi using an adeno-associated virus in Hepcidin-KO mice. Results We found that Hepcidin-KO mice exhibited iron accumulation and bone loss compared with WT mice. The osteoclastic differentiation of bone marrow-derived macrophages from Hepcidin-KO mice was not significantly different from that of bone marrow–derived macrophages from WT mice. However, the osteoblastic differentiation of bone marrow–derived mesenchymal stem cells from Hepcidin-KO mice was obviously decreased compared with that of bone marrow–derived mesenchymal stem cells from WT mice. Furthermore, it was confirmed in this study that upon hepcidin deficiency, β-catenin, TCF4/TCF7L2 and FOXO3a expression in bone tissues was not altered, but β-catenin combination with TCF4/TCF7L2 was strongly inhibited by β-catenin combination with FOXO3a, indicating that the canonical Wnt/β-catenin pathway was affected. Tail vein administration of FOXO3a-RNAi using an adeno-associated virus in Hepcidin-KO mice resulted in bone mass recovery. Conclusion These findings suggested that hepcidin deficiency might cause bone loss by interfering with the canonical Wnt/β-catenin pathway via FOXO3a, and FOXO3a inhibition would be a possible approach to treat hepcidin deficiency-induced bone loss. The translational potential of this article Hepcidin deficiency, as well as iron accumulation, has been considered as a risk factor for osteoporosis. For this kind of osteoporosis, inhibition of FOXO3a either by neutralized antibody or AAV-mediated RNAi, represents an effective and promising method.

Human copper transporter 1 (CTR1) has been proven to be overexpressed in many types of cancer cells, and copper (II)-64 chloride (64CuCl2) has been used as an effective tracer for positron emission tomography (PET) imaging in tumor-bearing animal models. Thus, this study aimed to investigate the potential application of 64CuCl2 in PET imaging of lung cancer through targeting CTR1. The expression of CTR1 in a series of lung cancer cell lines was identified by quantitative real-time polymerase chain reaction (Q-PCR), western blot, enzyme-linked immunosorbnent assay (ELISA), and immunofluorescent staining. Then in vitro cell uptake assay of 64CuCl2 was investigated in human lung cancer cell lines with different levels of CTR1 expression. Small animal PET imaging and quantitative analysis were performed in human lung cancer tumor-bearing mice after intravenous injection of 64CuCl2, respectively. The CTR1 expression in multiple human lung cancer cells was identified and confirmed, and H1299 cell lines with high CTR1 expression, H460 with moderate CTR1, and H1703 with low CTR1 were selected for further experiments. In vitro cellular uptake assay displayed that the 64CuCl2 uptake by these three kinds of cells was positively correlated with their CTR1 expressed levels. The blocking experiments testified the specificity of 64CuCl2 to target CTR1. Moreover, small animal PET imaging and quantitative results showed that 64CuCl2 accumulation in H1299, H460, and H1703 tumor-bearing mice were consistent with CTR1 levels and cell uptake experiments. The expression of CTR1 in human lung cancer xenograft model could be successfully visualized by 64CuCl2 PET examination. With the expected growth of PET/CT examination to be an essential strategy in clinical lung cancer management, 64CuCl2 has the potential to be a promising PET imaging agent of lung cancer.

This study was aimed to delineate the prevalence, clinical, and 3-dimentional radiographic characteristics of adult supernumerary teeth (ST found) in a Chinese non-syndromic, dental population. Medical records and cone beam computed tomography (CBCT) images were utilized to identify adult patients with ST in a tertiary referral dental hospital between June 2012 and December 2018. CBCT scan coupled with 3-dimentional reconstruction was used to characterize the detailed location, morphology, orientation of ST, and their relationship with adjacent teeth and neighboring structures. All relevant information regarding age and gender of patients, morphology, and 3-dimentional topography of ST as well as ST-associated complications were recorded and statistically analyzed. A total number of 1149 ST was identified in 921 eligible patients screened from 60,104 subjects with the prevalence of 1.5%. Male patients outnumbered females with a gender ratio of 1.76:1. The majority of ST was single, located in the maxilla, especially the maxillary central incisor region. Most ST were conical shape, inverted orientation, and impacted. ST-associated complications including impaction or root resorption of adjacent teeth, and cystic/tumor-like lesions were totally found in 13% ST and significantly associated with location, orientation, and morphology of ST. Most ST in Chinese adults were conical, inverted, impacted, and located in the maxillary central incisor region, and associated with various complications. Our findings offer valuable information concerning the prevalence, clinical, and radiographic characteristics of ST in non-syndromic Chinese adults. These findings are beneficial for clinicians to comprehensively understand the incidence, pathogenesis, and clinical management of ST.

Magnetic hyperthermia (MH) has been introduced clinically as an alternative approach for the focal treatment of tumors. MH utilizes the heat generated by the magnetic nanoparticles (MNPs) when subjected to an alternating magnetic field (AMF). It has become an important topic in the nanomedical field due to their multitudes of advantages towards effective antitumor therapy such as high biosafety, deep tissue penetration, and targeted selective tumor killing. However, in order for MH to progress and to realize its paramount potential as an alternative choice for cancer treatment, tremendous challenges have to be overcome. Thus, the efficiency of MH therapy needs enhancement. In its recent 60-year of history, the field of MH has focused primarily on heating using MNPs for therapeutic applications. Increasing the thermal conversion efficiency of MNPs is the fundamental strategy for improving therapeutic efficacy. Recently, emerging experimental evidence indicates that MNPs-MH produces nano-scale heat effects without macroscopic temperature rise. A deep understanding of the effect of this localized induction heat for the destruction of subcellular/cellular structures further supports the efficacy of MH in improving therapeutic therapy. In this review, the currently available strategies for improving the antitumor therapeutic efficacy of MNPs-MH will be discussed. Firstly, the recent advancements in engineering MNP size, composition, shape, and surface to significantly improve their energy dissipation rates will be explored. Secondly, the latest studies depicting the effect of local induction heat for selectively disrupting cells/intracellular structures will be examined. Thirdly, strategies to enhance the therapeutics by combining MH therapy with chemotherapy, radiotherapy, immunotherapy, photothermal/photodynamic therapy (PDT), and gene therapy will be reviewed. Lastly, the prospect and significant challenges in MH-based antitumor therapy will be discussed. This review is to provide a comprehensive understanding of MH for improving antitumor therapeutic efficacy, which would be of utmost benefit towards guiding the users and for the future development of MNPs-MH towards successful application in medicine.

In this study, a magnetothermodynamic (MTD) therapy is introduced as an efficient systemic cancer treatment, by combining the magnetothermal effect and the reactive oxygen species (ROS)-related immunologic effect, in order to overcome the obstacle of limited therapeutic efficacy in current magnetothermal therapy (MTT). This approach was achieved by the development of an elaborate ferrimagnetic vortex-domain iron oxide nanoring and graphene oxide (FVIOs-GO) hybrid nanoparticle as the efficient MTD agent. Such a FVIOs-GO nanoplatform was shown to have high thermal conversion efficiency, and it was further proved to generate a significantly amplified ROS level under an alternating magnetic field (AMF). Both in vitro and in vivo results revealed that amplified ROS generation was the dominant factor in provoking a strong immune response at a physiological tolerable temperature below 40 °C in a hypoxic tumor microenvironment. This was supported by the exposure of calreticulin (CRT) on 83% of the 4T1 breast cancer cell surface, direct promotion of macrophage polarization to pro-inflammatory M1 phenotypes, and further elevation of tumor-infiltrating T lymphocytes. As a result of the dual action of magnetothermal effect and ROS-related immunologic effect, impressive in vivo systemic therapeutic efficacy was attained at a low dosage of 3 mg Fe/kg with two AMF treatments, as compared to that of MTT (high dosage of 6-18 mg/kg under four to eight AMF treatments). The MTD therapy reported here has highlighted the inadequacy of conventional MTT that solely relies on the heating effect of the MNPs. Thus, by employing a ROS-mediated immunologic effect, future cancer magnetotherapies can be designed with greatly improved antitumor capabilities.

Dysbiosis of gut microbiota has been implicated in the pathogenesis of hypertension. A definite relationship between gut microbiota and hypertension remains intriguing. Here, we show that the Sacha inchi (Plukenetia volubilis L.) shell extract (SISE) intervention significantly reduced systolic blood pressures in spontaneous hypertensive rats (SHR), attenuated the oxidative damage and modulated plasma calcium homeostasis and left ventricular hypertrophy in both SHR and high-salt diet Wistar-Kyoto rats. SISE reshaped the gut microbiome and metabolome, particularly by improving the prevalence of Roseburia and dihydrofolic acid levels in the gut. Transcriptome analyses showed that the protective effects of SISE were accompanied by the modulation of renal molecular pathways, beneficial for cardiovascular functions such as the L-type voltage-dependent calcium channel (LTCC), a key regulator of calcium signaling. Overall, the results have shown that dietary SISE can alleviate hypertension regulating the gut microbiota, and Ca2+ signaling might be a potential target for spontaneous hypertension.

Metabolic dysfunction (MD) is a major health problem threatening the life quality of menopausal women. Saffron has been widely used in herb prescriptions for treating menopausal syndrome. However, the pharmacological effects and mechanisms of saffron are poorly understood. Here, we investigated the effect of crocin, the major ingredient of saffron and its active metabolite in blood, crocetin, on MD and lipid metabolism in ovariectomized (OVX) mice and 3T3-L1 adipocytes. The present study showed that intragastric treatment of crocin prevented weight gain, fat accumulation, and insulin resistance in OVX mice by increasing energy expenditure and fat oxidation. Mechanistically, crocin influenced adipose tissue homeostasis by regulating adipogenic and lipolytic factors, which was strongly associated with the restoration of the downregulated ERβ function in white adipose tissue (WAT). In vitro, crocetin facilitated lipid metabolism in an ERβ-dependent manner. Our results demonstrated the beneficial effects of crocetin/crocin-mediated intervention against metabolic dysfunction, revealing a prospective therapeutic application in menopausal women.

Skeletal muscle regeneration requires extracellular matrix (ECM) remodeling, including an acute and transient breakdown of collagen that produces gelatin. Although the physiological function of this process is unclear, it has inspired the application of gelatin to injured skeletal muscle for a potential pro-regenerative effect. Here, we investigated a bi-phasic effect of gelatin in skeletal muscle regeneration, mediated by the hormetic effects of reactive oxygen species (ROS). Low-dose gelatin stimulated ROS production from NADPH oxidase 2 (NOX2) and simultaneously upregulated the antioxidant system for cellular defense, reminiscent of the adaptive compensatory process during mild stress. This response triggered the release of the myokine IL-6, which stimulates myogenesis and facilitates muscle regeneration. By contrast, high-dose gelatin stimulated ROS overproduction from NOX2 and the mitochondrial chain complex, and ROS accumulation by suppressing the antioxidant system, triggering the release of TNFα, which inhibits myogenesis and regeneration. Our results have revealed a bi-phasic role of gelatin in regulating skeletal muscle repair mediated by intracellular ROS, the antioxidant system and cytokine (IL-6 and TNFα) signaling., Summary: Application of high- and low-dose gelatin to skeletal muscle revealed a bi-phasic role of gelatin in regulating skeletal muscle repair, which has translational implications for regenerative medicine.

Background: Social media is used as a new channel for health information. In China, the official WeChat account is becoming the most popular platform for health information dissemination, which has created a good opportunity for the Centers for Disease Control and Prevention to facilitate health information online to improve emergency public health literacy.Methods: Data were collected from the Guangzhou CDC i-Health official WeChat account between April 1, 2018 and April 30, 2019. Descriptive analysis was performed for basic information about the followers and posts of the official WeChat account. Multiple logistic regression analysis was used to analyze the association among various factors of posts on engagement of followers of the official WeChat account.Results: Among 187,033 followers, the total numbers of post views, shares, likes, add to favorites, and comments for 213 posts were 1,147,308, 8,4671, and 5,535, respectively. Engagement of followers peaked on the dissemination date and gradually declined. The main post topics were health education posts and original posts. In the multiple logistic regression model, the number of post views was found to be significantly associated with infectious disease posts (AOR: 3.20, 95% CI: 1.16–8.81), original posts (AOR: 10.20, 95% CI: 1.17–89.28), and posts with title-reflected content (AOR: 2.93, 95% CI: 1.16–8.81).Conclusion: Our findings facilitate the government to formulate better strategies and improve the effectiveness of public information dissemination.

Background: Scrub typhus was epidemic in the western Pacific Ocean area and East Asia, scrub typhus epidemic in densely populated areas in southern China. To better understand the association between meteorological variables, Southern Oscillation Index (SOI), and scrub typhus incidence in Guangzhou was benefit to the control and prevention.Methodology/Principal Findings: We collected weekly data for scrub typhus cases and meteorological variables in Guangzhou, and Southern Oscillation Index from 2006 to 2018, and used the distributed lag non-linear models to evaluate the relationships between meteorological variables, SOI and scrub typhus. The median value of each variable was set as the reference. The high-risk occupations were farmer (51.10%), house worker (17.51%), and retiree (6.29%). The non-linear relationships were observed with different lag weeks. For example, when the mean temperature was 27.7°C with1-week lag, the relative risk (RR) was highest as 1.08 (95% CI: 1.01–1.17). The risk was the highest when the relative humidity was 92.0% with 9-week lag, with the RR of 1.10 (95% CI: 1.02–1.19). For aggregate rainfall, the highest RR was 1.06 (95% CI: 1.03–1.11), when it was 83.0 mm with 4-week lag. When the SOI was 19 with 11-week lag, the highest RR was 1.06 (95% CI: 1.01–1.12). Most of the extreme effects of SOI and meteorological factors on scrub typical cases were statistically significant.Conclusion/Significance: The high-risk occupations of scrub typhus in Guangzhou were farmer, house worker, and retiree. Meteorological factors and SOI played an important role in scrub typhus occurrence in Guangzhou. Non-linear relationships were observed in almost all the variables in our study. Approximately, mean temperature, and relative humidity positively correlated to the incidence of scrub typhus, on the contrary to atmospheric pressure and weekly temperature range (WTR). Aggregate rainfall and wind velocity showed an inverse-U curve, whereas the SOI appeared the bimodal distribution. These findings can be helpful to facilitate the development of the early warning system to prevent the scrub typhus.

Though a definitive link between small colony variants (SCVs) and implant-related staphylococcal infections has been well-established, the specific underlying mechanism remains an ill-explored field. The present study analyzes the role SCVs play in catheter infection by performing genomic and metabolic analyses, as well as analyzing biofilm formation and impacts of glycine on growth and peptidoglycan-linking rate, on a clinically typical Staphylococcus epidermidis case harboring stable SCV, normal counterpart (NC) and nonstable SCV. Our findings reveal that S. epidermidis stable SCV carries mutations involved in various metabolic processes. Metabolome analyses demonstrate that two biosynthetic pathways are apparently disturbed in SCV. One is glycine biosynthesis, which contributes to remarkable glycine shortage, and supplementation of glycine restores growth and peptidoglycan-linking rate of SCV. The other is overflow of pyruvic acid and acetyl-CoA, leading to excessive acetate. SCV demonstrates higher biofilm-forming ability due to rapid autolysis and subsequent eDNA release. Despite a remarkable decline in cell viability, SCV can facilitate in vitro biofilm formation and in vivo survival of NC when co-infected with its normal counterparts. This work illustrates an intriguing strategy utilized by a glycine-auxotrophic clinical S. epidermidis SCV isolate to facilitate biofilm-related infections, and casts a new light on the role of SCV in persistent infections., Liu et al. investigate the mechanism for small colony variant (SCV) formation in Staphylococcus epidermidis and following genomic and metabolomic analysis, implicate a frame-shift mutation in glycine production as a potential cause of SCV formation. The authors also examine the effect of eDNA production and biofilm formation.

Objectives Avian influenza viruses (AIVs) poise significant risk to human health and the poultry industry. We evaluated the transmission risk along the poultry supply chain. Methods During October 2015 and July 2016, four rounds of cross-sectional surveys were performed to characterize AIV spread in farms, transport vehicles, slaughterhouses, wholesale and retail live poultry markets (LPMs). Poultry cloacal and oral swabs, environmental swabs, bioaerosol samples and human sera were collected. Poultry and environmental samples were tested for AIVs by rRT-PCR, further subtyped by next generation sequencing. Previous human H9N2 infections were identified by hemagglutination inhibition and microneutralization tests. Logistic regression was fitted to compare AIV transmission risk in different settings. Results AIVs was detected in 23.9% (424/1771) of the poultry and environmental samples. AIV detection rates in farms, transport vehicles, wholesale and retail LPMs were 4.5%, 11.1%, 30.3% and 51.2%, respectively. 5.2%, 8.3% and 12.8% of the poultry workers were seropositive in farms, wholesale and retail LPMs, respectively. The regression analysis showed that virus detection and transmission risk to human increased progressively along the poultry supply chain. Conclusions Strengthening control measures at every level along the poultry supply chain, using a one health approach, is crucial to control AIV circulation.

Mitochondrial redox homeostasis, the balance between reactive oxygen species and antioxidants such as glutathione, plays critical roles in many biological processes, including biosynthesis and apoptosis, and thus is a potential target for cancer treatment. Here, we report a mitochondrial oxidative stress amplifier, MitoCAT-g, which consists of carbon-dot-supported atomically dispersed gold (CAT-g) with further surface modifications of triphenylphosphine and cinnamaldehyde. We find that the MitoCAT-g particles specifically target mitochondria and deplete mitochondrial glutathione with atomic economy, thus amplifying the reactive oxygen species damage caused by cinnamaldehyde and finally leading to apoptosis in cancer cells. We show that imaging-guided interventional injection of these particles potently inhibits tumour growth in subcutaneous and orthotopic patient-derived xenograft hepatocellular carcinoma models without adverse effects. Our study demonstrates that MitoCAT-g amplifies the oxidative stress in mitochondria and suppresses tumour growth in vivo, representing a promising agent for anticancer applications.

Developing multifunctional theranostic nanoplatforms with high tumor therapeutic efficacy is the focus area of nanomedicine. In this study, we have designed Fe3O4–Pd Janus nanoparticles (JNPs) with dual-mode magnetic resonance imaging/photoacoustic (MRI/PA) imaging properties for magnetic-photo hyperthermia and chemodynamic therapy simultaneously. Due to the magnetic-photothermal properties of Fe3O4 nanoparticles and plasmonic photothermia effect of Pd nanosheets, the combined Fe3O4–Pd JNPs can achieve synergistic heating effects of 1 + 1 > 2. It is demonstrated that Fe3O4–Pd JNPs reached a higher temperature enhancement under alternating magnetic field (AMF) plus laser irradiation than the corresponding individual modality (only AMF or laser irradiation alone for Fe3O4–Pd JNPs) or the sum of two individual modalities. Besides amplified magnetic-photo heating, Fe3O4–Pd JNPs also enhanced ROS generation due to the interface synergistic effect in producing hydroxyl radicals (˙OH), which is realized by Fe3O4 nanoparticle-based Fenton reaction and Pd nanosheet-based catalytic properties in the presence of H2O2 in an acidic environment. Remarkably, the ROS level could be further elevated under external AMF plus laser irradiation. The in vivo anti-tumor effect of Fe3O4–Pd JNPs was evaluated on a 4T1 orthotopic mouse breast cancer model. The results showed that Fe3O4–Pd JNPs enable complete tumor inhibition without appreciable adverse effects under AMF plus laser irradiation, guided by MRI/PA dual-mode imaging with a high spatial resolution and accuracy. This study provides an alternative way for cancer therapy by on-demand design of high-performance theranostic nanoplatforms according to the characteristics of the tumor microenvironment and the intriguing physiochemical properties of inorganic nanomaterials.

Background Evaluation of the clinical efficacy of percutaneous pedicle screw fixation (PPSF) combined with percutaneous vertebroplasty (PVP) in the treatment of thoracic and lumbar metastatic tumor.Methods 20 patients with thoracic and lumbar metastatic tumor were treated with PPSF combined with PVP and followed up 6–25 months. Using the visual analog scale (VAS) and the Barthel Index of Activities of Daily Living (BIADL) to evaluate pain intensity and quality of life before surgery and at 7 days, 3 months, 6 months after treatment.Results In this study, a total of 20 patients were followed up for 6–25 months (mean time was 14.10 months). The VAS scores of all patients were significantly decreased, while the BIADL scores were significantly increased. No patients suffered from complications such as infection, pedicle screw loosening or PMMA oozing. Spine stability was observed in all the surviving patients during the follow-up.Conclusions PPSF combined with PVP is a potentially viable treatment for thoracolumbar metastases in patients with poor systemic condition or patients who refuse to undergo a conventional open procedure such as en bloc corpectomy, and in the presence of vertebral instability or pathological fracture without significant spinal compression.

Apolipoprotein E e4 allele (APOE4) is a minor allele of the APOE gene associated with a higher risk for Alzheimer's Disease (AD) and Vascular Dementia (VD). While lipid deposition and chronic inflammation in glia are the commonalities between atherosclerosis, VD, and AD. Hence, we presented an iPSC line of an AD male donor suffering from Cerebrovascular Atherosclerosis with APOE-e4/e4 alleles background. Furthermore, we differentiated the iPSCs into astrocyte to explore pathogenesis in APOE4 related dementia. The characterized iPSC line expressed typical pluripotency markers and showed differentiation potential and normal karyotype.

Objective: The purpose of this study was to explore the value of 18F-FDG PET/CT in monitoring the disease activity and predicting the prognosis of the Adult-onset Still's disease (AOSD).Methods: We retrospectively analyzed the electronic medical records of 45 AOSD patients who underwent 18F-FDG PET/CT in the Second Xiangya Hospital. PET/CT imaging and clinical information were retrospectively reviewed and analyzed. 18F-FDG uptake was assessed by measuring standard uptake value (SUV) in the spleen, liver, bone marrow, and lymph nodes. The spleen-to-liver ratio of the SUVmax (SLRmax) and SUVmean (SLRmean), the bone-to-liver ratio of the SUVmax (BLRmax), and SUVmean (BLRmean), and the lymph nodes-to-liver ratio of the SUVmax (LyLRmax) were calculated. Clinical and laboratory information were collected and evaluated for association with metabolic parameters of 18F-FDG PET/CT. The influencing factors for recurrence within 1 year were analyzed to determine whether 18F-FDG PET/CT can predict the prognosis of AOSD patients.Results: Elevated 18F-FDG uptake could be observed in bone marrow, spleen, and lymph nodes of AOSD patients. Correlation analysis between 18F-FDG uptake of organs and laboratory examinations showed that SLRmean positively correlated with LDH, AST, ferritin, and the systemic score (r = 0.572, 0.353, 0.586, and 0.424, P < 0.05). The SLRmean had the highest correlation with ferritin (r = 0586, P < 0.001). All metabolic parameters in spleen, including SUVmax, SUVmean, SLRmax, and SLRmean, are positively correlated with LDH level (r = 0.405, 0.539, 0.481, and 0.572, P < 0.05). Bone marrow SUVmax, BLRmax, and BLRmean were correlated with C-reactive protein (CRP) level (r = 0.395, 0.437, and 0.469, P < 0.05). Analysis of the influencing factors of recurrence within 1 year showed that the spleen SUVmax, spleen SUVmean, SLRmax, SLRmean, ferritin, and the systemic score of the recurrence group was significantly higher than the non-recurrence group (P < 0.05). The SLRmean cutoff of 1.66 with a sensitivity of 72.7% and specificity of 80.0% had the highest performance in predicting recurrence.Conclusion: The glucose metabolism of the liver, spleen, and bone marrow of AOSD patients were correlated with laboratory inflammatory indicators and system score, suggesting that 18F-FDG PET/CT could be applied to evaluate disease activity. Moreover, spleen 18F-FDG uptake may be a potential biomarker for predicting clinical prognosis of AOSD patients.

With the rapid increase of downward pressure on China’s economy, the stability of the property market, as an important part of the economic transformation process, also has a far-reaching impact on enterprises’ R&D investment. We select the data of Chinese large and medium-sized industrial enterprises from 1998 to 2015 as our research sample and propose a new combination measurement model based on closeness degree to measure the real estate bubble level in China accurately. The structural vector autoregressive (SVAR) theory is utilized to empirically test the dynamic relationship between the real estate bubble, corporate liquidity, and R&D investment. The results indicate that the real estate bubble level in China is increasing, and a certain risk of deviating from the safety interval in the future exists; The rapid expansion of the real estate bubble has a continuing negative impact on corporate R&D investment, that is, its "credit mitigation effect" is much smaller than the "capital relocation effect," and industrial enterprises will fall into the so-called "low-tech lock-in" state. In other words, to a certain extent, the development of this kind of real estate bubble will not be conducive to the transformation and upgradation of enterprises and long-term economic growth.

OBJECTIVE: To determine the duration of SARS-CoV-2 persistence in quarantine hotel environments. METHODS: 39 Patients confirmed by RT-PCR were included. We collected clinical features, laboratory test results, smear sample information, and quarantine room information. Genome sequencing and phylogenetic analysis were conducted. We analyzed the factors associated with environmental contamination. RESULT: Among 39 COVID-19 cases, 10 were asymptomatic and 37 were imported from aboard. We collected 271 swab samples from environmental surfaces related to observational patients. Eighteen swab samples from seven patients were positive. The highest contamination rates occurred on cups (100%), followed by hand sink (12.82%), toilet seat and flush (7.89%), telephone (5.56%), bedside table (5.56%), and floor drain (5.41%). The results showed that environmental surface contamination was associated with the clinical cycle threshold values for patients (P = 0.01) and the sampling interval time after the cases left their rooms (P = 0.03). The duration of environmental surface contamination was associated with the wet status of the sampling site (P = 0.01). CONCLUSION: Our findings showed that environmental contamination might be attributed to the viral load in the respiratory tracts of patients and the sampling interval time after the cases left their rooms. Moist surfaces were more vulnerable to remaining SARS-CoV-2 RNA-positive. Our study highlights the importance of implementing strict chemical disinfection strategies in quarantine rooms.

The global increase of community-associated (CA) infections with methicillin-resistant Staphylococcus aureus (MRSA) is a major healthcare problem. Although sequence type (ST) 398 MRSA was first described as a livestock-associated (LA) lineage, human-adapted MRSA (HO-MRSA) ST398 without livestock contact has subsequently been reported from China in our previous study and other later research. The proportion of ST398 HO-MRSA has also remarkably increased in recent years in China. Based on 3878 S. aureus isolates that were collected in a general hospital between 2008 and 2018, we identified 56 ST398 HO-MRSA isolates. The four early appearing isolates of them have been sequenced by whole-genome sequencing (WGS) in our previous study. Here, by usage of WGS on the later-appearing 52 isolates and analyzing the phylogenetic dynamics of the linage, we found that 50 isolates clustered together with the former 4 isolates, making it a main clade out of MSSA clones and other MRSA clones, although ST398 HO-MRSA evolved with multiple origins. Drug resistance and virulence gene analysis based on the WGS data demonstrated that ST398 HO-MRSA main clade exhibited a similar pattern in both parts. Furthermore, they all carried a conserved variant of prophage 3 to guarantee virulence and a short SCCmec type V element of class D to maintain considerable lower methicillin resistance. Further phenotypical research verified that the epidemic HO-MRSA ST398 displayed enhanced biofilm formation ability when keeping high virulence. The dual advantages of virulence and biofilm formation in the HO-MRSA ST398 subtype promote their fitness in the community and even in the healthcare environment, which poses a serious threat in clinical S. aureus infections. Therefore, further surveillance is required to prevent and control the problematic public health impact of HO-MRSA ST398 in the future.