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Different from the traditional frequency-mixing technique which employs a contacting transducer, the laser-induced acoustic nonlinear frequency-mixing detection technique utilizes a laser source to instigate crack motion and generate acoustic waves. Thus, apart from the temperature oscillation induced by the pump laser, the "basic temperature" originating from the probe laser can also influence the crack. This additional variable complicates the contact state of the crack, yielding a more diverse range of nonlinear acoustic signal attributes. In light of this, our study enhances the conventional opto-acoustic nonlinear frequency mixing experimental setup by integrating an independent heating laser beam. This modification isolates the impact of the "basic temperature" on crack width while also dialing down the probe laser power to mitigate its thermal effects. To amplify the sensitivity of crack detection, we deliberated on the optimal laser source parameters for this setup. Consequently, our revamped system, paired with fine-tuned parameters, captures nonlinear acoustic signals with an enriched feature set. This investigation can provide support for the non-contact opto-acoustic nonlinear frequency mixing technique in the detection and evaluation of micro-cracks. • A three-beam opto-acoustic nonlinear frequency-mixing technique is proposed. • The addition of the third cw laser enables finer adjustments to the crack. • Richer nonlinear acoustic features are obtained using the proposed technique. [ABSTRACT FROM AUTHOR]

Photo-thermal modulation-based nonlinear opto-acoustic frequency-mixing technique is an effective method for detecting micro-cracks. When using this technique for micro-crack detection, the selection of laser source parameters is particularly crucial. Compared to traditional piezo-transducer-based mixing techniques, the characteristic of using a laser as the detection source is the presence of thermal effects. The thermal effect caused by laser irradiation on the sample surface can not only generate acoustic waves but also affect the crack state, thus influencing nonlinear signals. In this paper, an experimental setup using photo-thermal modulation-based nonlinear opto-acoustic frequency-mixing technique has been set up to investigate the thermal effects of the probe laser source. In addition, a corresponding physical model has been established to discuss the physical mechanisms revealed by the experimental results. This study provides a basis for selecting appropriate probe source parameters and scanning positions of laser sources when detecting micro-cracks using the photo-thermal modulation-based nonlinear opto-acoustic frequency-mixing technique. • The impact of 'basic temperature' of probe laser at f H on crack status is studied. • Established a nonlinear acoustic model of a crack's clapping-closing transition phase. • Verified theoretically the existence of thermal effect of probe laser in experiments. • Described the crack state for optimized nonlinear phenomena generation. [ABSTRACT FROM AUTHOR]

• Trajectory planning to extend the stay of stratospheric airships in an area. • Solved the problem of planning trajectories without endpoints. • Wind potential and position potential are designed for trajectory planning. • A modified rapidly exploring random tree algorithm for station-keeping is proposed. The station-keeping mission is one of the common missions of stratospheric airships. Its movement is sensitive to wind due to the large size and low airspeed of stratospheric airships. When the wind speed exceeds the maximum airspeed of the airship, the airship may fly out of the given mission region. Therefore, station-keeping trajectory planning is a new trajectory planning problem that has never existed before. A rapidly exploring random tree algorithm for station-keeping(RRT-SK) is proposed to solve the trajectory planning problem under multiple constraints of the airship, and an artificial potential field method (APF) considering wind field and relative position is designed as the objective function of the RRT-SK algorithm, both of which form the RRT-SK strategy used for the stratospheric airship station-keeping trajectory planning under multiple constraints. A multidisciplinary model is developed to simulate multiple constraints on the airship flight, including the energy model, thermal model, propulsion model, and kinematic model. The performance of the RRT-SK strategy is demonstrated in this multidisciplinary model with real wind fields. The results show that the multi-constrained station-keeping problem can be solved by the RRT-SK strategy. Compared with the conventional strategy, the RRT-SK strategy can improve the success rate of the airship's 24-h stationing flight and well cope with the impact of wind field changes and stationing area changes. Moreover, the RRT-SK strategy has better advantages in actual long-duration use. [ABSTRACT FROM AUTHOR]

Background and aims: The early diagnosis and intervention of oesophageal squamous cell carcinoma (ESCC) are particularly important because of the lack of effective therapies and poor prognosis. Comprehensive research on early ESCC at the single‐cell level is rare due to the need for fresh and high‐quality specimens obtained from ESD. This study aims to systematically describe the cellular atlas of human intramucosal ESCC. Methods: Five paired samples of intramucosal ESCC, para‐ESCC oesophageal tissues from endoscopically resected specimens and peripheral blood mononuclear cells were adopted for scRNA‐seq analysis. Computational pipeline scMetabolism was applied to quantify the metabolic diversity of single cells. Results: A total of 164 715 cells were profiled. Epithelial cells exhibited high intra‐tumoural heterogeneity and two evolutionary trajectories during ESCC tumorigenesis initiated from proliferative cells, and then through an intermediate state, to two different terminal states of normally differentiated epithelial cells or malignant cells, respectively. The abundance of CD8+ TEXs, Tregs and PD1+CD4+T cells suggested an exhausted and suppressive immune microenvironment. Several genes in immune cells, such as CXCL13, CXCR5 and PADI4, were identified as new biomarkers for poor prognosis. A new subcluster of malignant cells associated with metastasis and angiogenesis that appeared at an early stage compared with progressive ESCC was also identified in this study. Intercellular interaction analysis based on ligand–receptor pairs revealed the subcluster of malignant cells interacting with CAFs via the MDK–NCL pathway, which was verified by cell proliferation assay and IHC. This indicates that the interaction may be an important hallmark in the early change of tumour microenvironment and serves as a sign of CAF activation to stimulate downstream pathways for facilitating tumour invasion. Conclusion: This study demonstrates the changes of cell subsets and transcriptional levels in human intramucosal ESCC, which may provide unique insights into the development of novel biomarkers and potential intervention strategies. [ABSTRACT FROM AUTHOR]

The underlying mechanisms of diseases affecting the central nervous system (CNS) remain unclear, limiting the development of effective therapeutic strategies. Remarkably, cellular senescence, a biological phenomenon observed in cultured fibroblasts in vitro , is a crucial intrinsic mechanism that influences homeostasis of the brain microenvironment and contributes to the onset and progression of CNS diseases. Cellular senescence has been observed in disease models established in vitro and in vivo and in bodily fluids or tissue components from patients with CNS diseases. These findings highlight cellular senescence as a promising target for preventing and treating CNS diseases. Consequently, emerging novel therapies targeting senescent cells have exhibited promising therapeutic effects in preclinical and clinical studies on aging-related diseases. These innovative therapies can potentially delay brain cell loss and functional changes, improve the prognosis of CNS diseases, and provide alternative treatments for patients. In this study, we examined the relevant advancements in this field, particularly focusing on the targeting of senescent cells in the brain for the treatment of chronic neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, and multiple sclerosis) and acute neurotraumatic insults (e.g., ischemic stroke, spinal cord injury, and traumatic brain injury). [Display omitted] • Cellular senescence (CS) is intricately linked with central nervous system (CNS) diseases. • CS is a novel therapeutic target for treating CNS diseases. • Senomorphics and senolytics bring new hope for patients with CNS diseases. • Further exploration of CS-centered research is essential for advancing the treatment of aging-related diseases. [ABSTRACT FROM AUTHOR]

Sensing is one of the important applications of the whispering-gallery-mode (WGM) microresonator. Here we consider a model consisting of two WGM microresonators and one fiber waveguide. We show that the system can be near an exceptional point when the two tapers in the fiber waveguide are coupled to the two microresonators in a way that can lead to an unidirectional coupling. We propose a method to measure the weak coupling strength between the two microresonators. Compared to the conventional method, our method operates near an exceptional point and has the ability to measure smaller coupling strength. • An optical model that can achieve exceptional point. • A method to measure the coupling strength between two microresonators. • The measurable coupling strength can be relatively small. [ABSTRACT FROM AUTHOR]

[Display omitted] • Utilized a flow of hydroxylation and polymerization to assemble NEGSs. • Advanced a heterogeneous PANI@Ni(OH) 2 /NF NEGS without any conductive adhesive. • PANI@Ni(OH) 2 /NF showed a high sensitivity in a wide glucose concentration range. • Set up a general semi-empirical model of current-concentration suitable for NEGSs. • The nonlinear i – c model significantly reduced errors caused by linear fitting. Herein a heterogeneous material PANI@Ni(OH) 2 /NF, hydroxylated nickel foam (NF) modified by polyaniline (PANI), was assembled via an easy-to-operate sequential method. The hydroxylation obviously improves the reaction rate from Ni(II) to Ni (III) and the modification notably decreases the interface resistance. Benefitting from the synergy of Ni(OH) 2 , NF, and PANI, by means of three-segment linear fitting, PANI@Ni(OH) 2 /NF shows a high sensitivity up to 2248.7 μA mM cm−2, a low detection limit of 0.52 μM, and excellent selectivity for glucose sensing when the glucose concentration (c R *) is from 0.001 mM to 16.000 mM. Further, we deduced a general semi-empirical model to describe the relationship between current i (c R *) and c R * , which eliminated the errors near the junction of two adjacent lines obviously and boarded the detection range. By comparing with the multi-segment linear fitting and our previous formula, both the mean d -value of 0.164 mA and the SD of 0.0218 mA obtained from the model are the lowest, respectively. A similar comparison was carried out in literature data, and the results are also satisfactory. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) and its related cardiovascular diseases (CVDs) remain the most frequent cause of morbidity and mortality worldwide. Researches showed that bisphenol A (BPA) exposure might exacerbate AS progression. However, as an analogue of BPA, little is known about the cardiovascular toxicity of bisphenol S (BPS), especially whether BPS exposure has the pro-atherogenic effects in mammals is still unknown. Here, we firstly constructed an apolipoprotein E knockout (ApoE -/- ) mouse model and cultured cells to investigate the risk of BPS on AS and explore the underlying mechanisms. Results showed that prolonged exposure to 50 μg/kg body weight (bw)/day BPS indeed aggravated AS lesions both in the en face aortas and aortic sinuses of ApoE -/- mice. Moreover, BPS were found to be implicated in the AS pathological process: 1) stimulates adhesion molecule expression to promote monocyte-endothelial cells (ECs) adhesion with 3.6 times more than the control group in vivo; 2) increases the distribution of vascular smooth muscle cells (VSMCs) with 9.3 times more than the control group in vivo, possibly through the migration of VSMCs; and 3) induces an inflammatory response by increasing the number of macrophages (MACs), with 3.7 times more than the control group in vivo, and the release of inflammatory mediators. Furthermore, we have identified eight significant AS-related genes induced by BPS, including angiopoietin-like protein 7 (Angptl17) and lipocalin-2 (Lcn2) in ECs; matrix metalloproteinase 9 (Mmp13), secreted phosphoprotein 1 (Spp1), and collagen type II alpha 1 (Col2a1) in VSMCs; and kininogen 1 (Kng1), integrin alpha X (Itgax), and MAC-expressed gene 1 (Mpeg1) in MACs. Overall, this study firstly found BPS exposure could exacerbate mammalian AS and might also provide a theoretical basis for elucidating BPS and its analogues induced AS and related CVDs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the clinical efficacy of roxithromycin combined with azithromycin sequential therapy in the treatment of mycoplasma pneumoniae pneumonia in children., Methods: A retrospective study was conducted on 100 patients with mycoplasma pneumoniae pneumonia admitted to The First Affiliated Hospital of Yangtze University from January 2020 to December 2022. All patients were divided into the observation group (roxithromycin combined with azithromycin sequential therapy) and the control group (azithromycin sequential therapy), with 50 cases in each group. The clinical efficacy, improvement time of clinical symptoms/signs, inflammation indexes, oxidative stress indexes and immune function levels of the two groups were compared. Moreover, the improvement of lung function indexes and the adverse reactions were observed., Results: The overall response rate of the observation group was 96.00%, which was higher than the control group (84.00%) ( p< 0.05). The time of clinical symptoms/signs in the observation group were significantly lower than those in the control group( p< 0.05). After treatment, significant improvements were seen in the levels of CRP, TNF-ɑ, IL-6, GSH-Px, SOD, MDA, CD3 + , CD4 + , CD4 + /CD8 + , IgM, IgG , IgA, FEV 1 , FEV 1 %, FVC and FEV 1 /FVC of the two groups compared with those before treatment ( p< 0.05), and the improvement in the observation group was more obvious than that in the control group( p< 0.05). The overall incidence of adverse reactions in the observation group was 6.00%, which was slightly lower than that in the control group (8.00%) (c²=0.154, P =0.695)., Conclusion: Roxithromycin combined with azithromycin sequential therapy is a safe regimen for the treatment of mycoplasma pneumoniae pneumonia in children., Competing Interests: Declaration of conflicting interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Objective: To analyze the factors affecting the long-term clinical efficacy and quality of life in the treatment of pediatric acute lymphoblastic leukemia (ALL)., Methods: This is a retrospective study. One hundred children with ALL were collected before June, 2018 at The First Affiliated Hospital of Yangtze University and followed up for five years. Not only were their five-years survival rates analyzed, but univariate and multivariate analyses were also performed for factors that might affect their five-year survival rates. The MOS 36-Item Short Form of Health Survey (SF-36) was utilized to investigate the surviving children after five years in order to analyze the factors that may affect the quality of life of the children., Results: The five-years survival rate of one hundred children with ALL after treatment was 91.00% (91/100). Univariate and multivariate Logistic regression analyses were performed on the factors that may affect the long-term efficacy of pediatric ALL. The results showed that white blood cell count at first diagnosis, prednisone response test, treatment compliance and recurrence were independent risk factors for the long-term efficacy of pediatric ALL(p<0.05). The SF-36 survey of 91 surviving children after five years showed that prednisone response test and treatment compliance were independent risk factors affecting the quality of life of pediatric ALL(p<0.05)., Conclusion: In the initial diagnosis of pediatric ALL, sufficient attention and control should be given to the factors that may affect the long-term clinical efficacy and quality of life, and appropriate treatment plans should be adopted. Meanwhile, the treatment compliance of children should be improved during treatment to improve the survival rate and quality of life of pediatric ALL., Competing Interests: Declaration of conflicting interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Background: Acteoside, an active ingredient found in various medicinal herbs, is effective in the treatment of diabetic kidney disease (DKD); however, the intrinsic pharmacological mechanism of action of acteoside in the treatment of DKD remains unclear. This study utilizes a combined approach of network pharmacology and experimental validation to investigate the potential molecular mechanism systematically., Methods: First, acteoside potential targets and DKD-associated targets were aggregated from public databases. Subsequently, utilizing protein-protein interaction (PPI) networks, alongside GO and KEGG pathway enrichment analyses, we established target-pathway networks to identify core potential therapeutic targets and pathways. Further, molecular docking facilitated the confirmation of interactions between acteoside and central targets. Finally, the conjectured molecular mechanisms of acteoside against DKD were verified through experimentation on unilateral nephrectomy combined with streptozotocin (STZ) rat model. The underlying downstream mechanisms were further investigated., Results: Network pharmacology identified 129 potential intersected targets of acteoside for DKD treatment, including targets such as AKT1, TNF, Casp3, MMP9, SRC, IGF1, EGFR, HRAS, CASP8, and MAPK8. Enrichment analyses indicated the PI3K-Akt, MAPK, Metabolic, and Relaxin signaling pathways could be involved in this therapeutic context. Molecular docking revealed high-affinity binding of acteoside to PIK3R1, AKT1, and NF-κB1. In vivo studies validated the therapeutic efficacy of acteoside, demonstrating reduced blood glucose levels, improved serum Scr and BUN levels, decreased 24-hour urinary total protein (P<0.05), alongside mitigated podocyte injury (P<0.05) and ameliorated renal pathological lesions. Furthermore, this finding indicates that acteoside inhibits the expression of pyroptosis markers NLRP3, Caspase-1, IL-1β, and IL-18 through the modulation of the PI3K/AKT/NF-κB pathway., Conclusion: Acteoside demonstrates renoprotective effects in DKD by regulating the PI3K/AKT/NF-κB signaling pathway and alleviating pyroptosis. This study explores the pharmacological mechanism underlying acteoside's efficacy in DKD treatment, providing a foundation for further basic and clinical research., Competing Interests: The authors declared that they have no conflicts of interest in this work., (© 2024 Zhang et al.)

Fungal diseases form perforated disease spots in tobacco plants, resulting in a decline in tobacco yield and quality. The present study investigated the antagonistic effect of Bacillus subtilis CTXW 7-6-2 against Rhizoctonia solani , its ability to promote the growth of tobacco seedlings, and the expression of disease resistance-related genes for efficient and eco-friendly plant disease control. Our results showed that CTXW 7-6-2 had the most vigorous growth after being cultured for 96 h, and its rate of inhibition of R. solani growth in vitro was 94.02%. The volatile compounds produced by CTXW 7-6-2 inhibited the growth of R. solani significantly (by 96.62%). The fungal growthinhibition rate of the B. subtilis CTXW 7-6-2 broth obtained after high-temperature and no-high-temperature sterile fermentation was low, at 50.88% and 54.63%, respectively. The lipopeptides extracted from the B. subtilis CTXW 7-6-2 fermentation broth showed a 74.88% fungal growth inhibition rate at a concentration of 100 mg/l. Scanning and transmission electron microscopy showed some organelle structural abnormalities, collapse, shrinkage, blurring, and dissolution in the R. solani mycelia. In addition, CTXW 7-6-2 increased tobacco seedling growth and improved leaf and root weight compared to the control. After CTXW 7-6-2 inoculation, tobacco leaves showed the upregulation of the PDF1.2 , PPO , and PAL genes, which are closely related to target spot disease resistance. In conclusion, B. subtilis CTXW 7-6-2 may be an efficient biological control agent in tobacco agriculture and enhance plant growth potential., (© 2024 Ning Huang et al., published by Sciendo.)

Introduction: Ubiquitination is a crucial biological mechanism in humans, essential for regulating vital biological processes, and has been recognized as a promising focus for cancer therapy. Our objective in this research was to discover potential enzymes associated with ubiquitination that may serve as therapeutic targets for individuals with esophageal carcinoma (ESCA)., Methods: To identify genes linked to the prognosis of ESCA, we examined mRNA sequencing data from patients with ESCA in the TCGA database. Further investigation into the role of the candidate gene in ESCA was conducted through bioinformatic analyses. Subsequently, we carried out biological assays to assess its impact on ESCA development., Results: Through univariate Cox regression analysis, we identified Ubiquitin Conjugating Enzyme E2 B (UBE2B) as a potential gene associated with the prognosis of ESCA. UBE2B exhibited significant upregulation and was found to be correlated with survival outcomes in ESCA as well as other cancer types. Additionally, UBE2B was observed to be involved in various biological pathways linked to the development of ESCA, including TNF-a signaling via NF-κB, epithelial-mesenchymal transition, inflammatory response, and hypoxia. Moreover, immune-related pathways like B cell activation (GO: 0042113), B cell receptor signaling pathway (GO: 0050853) and B cell mediated immunity (GO:0019724) were also involved. It was found that high expression of UBE2B was correlated with the increase of several kinds of T cells (CD8 T cells, Th1 cells) and macrophages, while effector memory T cell (Tem) and Th17 cells decreased. Furthermore, UBE2B showed potential as a prognostic biomarker for ESCA, displaying high sensitivity and specificity. Notably, proliferation and migration in ESCA cells were effectively suppressed when the expression of UBE2B was knocked down., Conclusions: To summarize, this study has made a discovery regarding the importance of gaining new insights into the role of UBE2B in ESCA. UBE2B might be an oncogene with good ability in predicting and diagnosing ESCA. Consequently, this discovery highlights the feasibility of targeting UBE2B as a viable approach for treating patients with ESCA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ding, Xu, Ding, Wu, Liu, Zhang, Chen, Zhang and Zhou.)

Few studies were performed on the impact of exposure to gaseous pollutants on the risk of knee osteoarthritis (KOA). We conducted this study to analyze the association between short-term exposure to gaseous pollutants and the risk of hospitalizations for KOA. A total of 2952 KOA hospitalizations derived from two hospitals in Hefei, and the relationship between gaseous pollutants and KOA hospitalizations was analyzed by a distributed lag non-linear model combined with a generalized linear model. We found that the decreased risk of hospitalizations for KOA were both related to exposure to NO 2 (RR = 0.993, lag19 day) and O 3 (RR = 0.984, lag0 day), while exposure to CO could increase the risk of hospitalizations for KOA (RR = 1.076, lag2 day). Stratified analyses suggested that the KOA patients < 65 years were more susceptible to O 3 exposure, and the female, male, patients ≥ 65 years, and patients < 65 years were both more sensitive to CO exposure. Our findings demonstrated that exposure to NO 2 , O 3 resulted in a decreased risk for KOA hospitalizations, and CO exposure might increase the risk of KOA hospitalizations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Peroxisome proliferator-activated receptor alpha (PPARα) activation-induced hepatomegaly is accompanied by hepatocyte hypertrophy around the central vein (CV) area and hepatocyte proliferation around the portal vein (PV) area. However, the molecular mechanisms underlying this spatial change of hepatocytes remains unclear. In this study, we examined the characteristics and possible reasons for the zonation distinction of hypertrophy and proliferation during PPARα activation-induced mouse liver enlargement. Mice were injected with corn oil or a typical mouse PPARα agonist WY-14643 (100 mg·kg -1 ·d -1 , i.p.) for 1, 2, 3, 5 or 10 days. At each time point, the mice were sacrificed after the final dose, and liver tissues and serum were harvested for analysis. We showed that PPARα activation induced zonal changes in hepatocyte hypertrophy and proliferation in the mice. In order to determine the zonal expression of proteins related to hepatocyte hypertrophy and proliferation in PPARα-induced liver enlargement, we performed digitonin liver perfusion to separately destroy the hepatocytes around the CV or PV areas, and found that PPARα activation-induced increase magnitude of its downstream targets such as cytochrome P450 (CYP) 4 A and acyl-coenzyme A oxidase 1 (ACOX1) levels around the CV area were higher compared with those around the PV area. Upregulation of proliferation-related proteins such as cell nuclear antigen (PCNA) and cyclin A1 (CCNA1) after WY-14643-induced PPARα activation mainly occurred around the PV area. This study reveals that the zonal expression of PPARα targets and proliferation-related proteins is responsible for the spatial change of hepatocyte hypertrophy and proliferation after PPARα activation. These findings provide a new insight into the understanding of PPARα activation-induced liver enlargement and regeneration., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Cardiac hypertrophy, a kind of cardiomyopathic abnormality, might trigger heart contractile and diastolic dysfunction, and even heart failure. Currently, bisphenols (BPs) including bisphenol A (BPA), and its alternatives bisphenol AF (BPAF), bisphenol F (BPF) and bisphenol S (BPS) are ubiquitously applied in various products and potentially possess high cardiovascular risks for humans. However, the substantial experimental evidences of BPs on heart function, and their structure-related effects on cardiomyocyte hypertrophy are still urgently needed. DNA methylation, a typical epigenetics, play key roles in BPs-induced transcription dysregulation, thereby affecting human health including cardiovascular system. Thus, in this study, we performed RNA-seq and reduced representation bisulfite sequencing (RRBS) to profile the landscapes of BPs-induced cardiotoxicity and to determine the key roles of DNA methylation in the transcription. Further, the capabilities of three BPA analogues, together with BPA, in impacting heart function and changing DNA methylation and transcription were compared. We concluded that similar to BPA, BPAF, BPF and BPS exposure deteriorated heart function in a mouse model, and induced cardiomyocyte hypertrophy in a H9c2 cell line. BPAF, BPF and BPS all played BPA-like roles in both transcriptive and methylated hierarchies. Moreover, we validated the expression levels of four cardiomyocyte hypertrophy related candidate genes, Psmc1, Piptnm2, Maz and Dusp18, which were all upregulated and with DNA hypomethylation. The findings on the induction of BPA analogues on cardiomyocyte hypertrophy and DNA methylation revealed their potential detrimental risks in heart function of humans., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: To determine the reproducibility of measuring the gross total volume (GTV) of primary rectal tumor with manual and semi-automatic delineation on the diffusion-weighted image (DWI), examine the consistency of using the same delineation method on DWI images with different high b-values, and find the optimal delineation method to measure the GTV of rectal cancer., Methods: 41 patients who completed rectal MR examinations in our hospital from January 2020 to June 2020 were prospectively enrolled in this study. The post-operative pathology confirmed the lesions were rectal adenocarcinoma. The patients included 28 males and 13 females, with an average age of (63.3 ± 10.6) years old. Two radiologists used LIFEx software to manually delineate the lesion layer by layer on the DWI images (b=1000 s/mm 2 and 1500 s/mm 2 ) and used 10% to 90% of the highest signal intensity as thresholds to semi-automatically delineate the lesion and measure the GTV. After one month, Radiologist 1 performed the same delineation work again to obtain the corresponding GTV., Results: The inter- and intra-observer interclass correlation coefficients (ICC) of measuring GTV using semi-automatic delineation with 30% to 90% as thresholds were all >0.900. There was a positive correlation between manual delineation and semi-automatic delineation with 10% to 50% thresholds (P < 0.05). However, the manual delineation was not correlated with the semi-automatic delineation with 60%, 70%, 80%, and 90% thresholds. On the DWI images with b=1000 s/mm 2 and 1500 s/mm 2 , the 95% limit of agreement (LOA%) of measuring GTV using semi-automatic delineation with 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, and 90% thresholds were -41.2~67.4, -17.8~51.5, -16.1~49.3, -26.2~50.1, -42.3~57.6, -57.1~65.4, -67.3~66.5, -101.6~91.1, -129.4~136.0, and -15.3~33.0, respectively. The time required for GTV measurement by semi-automatic delineation was significantly shorter than that of manual delineation (12.9 ± 3.6s vs 40.2 ± 13.1s)., Conclusions: The semi-automatic delineation of rectal cancer GTV with 30% threshold had high repeatability and consistency, and it was positively correlated with the GTV measured by manual delineation. Therefore, the semi-automatic delineation with 30% threshold could be a simple and feasible method for measuring rectal cancer GTV., 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 © 2023 Qiu, Zhou, Li, Zhang, Wang and Yang.)

Electromagnetically induced transparency (EIT) and absorption (EIA) are two phenomena that can be observed in whispering-gallery-mode (WGM) optical microresonators. Transition from EIT to EIA has potential applications in optical switching, filtering and sensing. In this paper an observation of the transition from EIT to EIA in a single WGM microresonator is presented. A fiber taper is used to couple light into and out of a sausage-like microresonator (SLM) that contains two coupled optical modes with significantly different quality factors. By stretching the SLM axially the resonance frequencies of the two coupled modes are tuned to the same, a transition from EIT to EIA is then observed in the transmission spectra when the fiber taper is moved closer to the SLM. It is the special spatial distribution of the optical modes of the SLM that provide a theoretical basis for the observation.

The design simulation and fabrication results of a bandpass filter based on micro-electro-mechanical system (MEMS) switches are presented in this paper. The MEMS filter element consists of a MEMS capacitance switch and two resonant rings that are fixed onto coplanar waveguide lines through anchor points. The micromachine characteristics of the filter could be optimized to change the center frequency from 8.5 to 12 GHz by improving the geometrical parameters; other electrical parameters of the filter, such as stopband rejection, insertion loss, and return loss at each center frequency, were simulated and calculated. In order to evaluate the MEMS filter design methodology, a filter working at 10.5 GHz fabricated with an aluminum top electrode was used, and it displayed a low insertion loss of 1.12 dB and a high stopband rejection of 28.3 dB. Compared with the simulation results, these proposed filter showed better electrical performance. Our results demonstrated that the filter with the integrated RF MEMS switch not only provides the benefit of reduced size compared with a traditional filter, but also improves stopband rejection, insertion loss, and return loss.

Objectives: To study the clinical features of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection., Methods: A retrospective analysis was performed on the medical data of 201 children with coronavirus disease 2019 (COVID-19) who were hospitalized and diagnosed with SARS-CoV-2 Omicron variant infection in Quanzhou First Hospital from March 14 to April 7, 2022. Among the 201 children, there were 34 children with asymptomatic infection and 167 with symptomatic infection. The two groups were compared in terms of clinical features, results of experimental examinations, and outcome., Results: Of all the 201 children, 161 (80.1%) had a history of exposure to COVID-19 patients and 132 (65.7%) had a history of COVID-19 vaccination. Among the 167 children with symptomatic infections, 151 had mild COVID-19 and 16 had common COVID-19, with no severe infection or death. Among the 101 children who underwent chest CT examination, 16 had ground glass changes and 20 had nodular or linear opacities. The mean time to nucleic acid clearance was (14±4) days for the 201 children with Omicron variant infection, and the symptomatic infection group had a significantly longer time than the asymptomatic infection group [(15±4) days vs (11±4) days, P <0.05]. The group vaccinated with one or two doses of COVID-19 vaccine had a significantly higher positive rate of IgG than the group without vaccination ( P <0.05). The proportions of children with increased blood lymphocyte count in the symptomatic infection group was significantly lower than that in the asymptomatic infection group ( P <0.05). Compared with the asymptomatic infection group, the symptomatic infection group had significantly higher proportions of children with increased interleukin-6, increased fibrinogen, and increased D-dimer ( P <0.05)., Conclusions: Most of the children with Omicron variant infection have clinical symptoms, which are generally mild. The children with symptomatic infection are often accompanied by decreased or normal blood lymphocyte count and increased levels of interleukin-6, fibrinogen, and D-dimer, with a relatively long time to nucleic acid clearance. Some of them had ground glass changes on chest CT.

Background: Neer type II/bilateral distal clavicular fracture is an extremely rare injury combination, with few cases having been reported., Case Presentation: This paper reports a case of polytrauma in a 16-year-old female following a road traffic accident. The radiographs revealed distal fractures of the bilateral clavicles (Neer type II), and an open reduction and internal fixation procedure was performed. Initially, the distal fracture of the right clavicle was fixed with a six-hole hook plate before the fracture of the left clavicle was fixed using a pre-contoured lateral locking plate following reduction. At the two-year follow-up, the patient had an excellent constant score in terms of the bilateral shoulder joints., Conclusion: It is important to achieve stability and to aim for excellence in terms of full shoulder function in this rare combination injury.

Pregnane X receptor (PXR) is highly expressed in the liver and plays a pivotal role in xenobiotic and endobiotic metabolism. We previously reported that PXR activation by its specific mouse agonist pregnenolone 16α-carbonitrile (PCN) significantly induces liver enlargement and lipid accumulation. However, the effect of long-term PCN treatment on PXR and mouse liver is still unknown. This study aimed to explore the influence of long-term administration of PCN on mouse liver and hepatic lipid homeostasis. Male C57BL/6 mice were injected intraperitoneally with PCN (100 mg/kg once a week) for 42 weeks. Serum and liver samples were collected for biochemical and histological analysis. PXR activation was investigated by Western blot. Ultra-high-performance liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (UHPLC-ESI-HRMS)-based lipidomics analysis was performed to explore the change in different lipid categories. The results showed that long-term treatment with PCN significantly promoted hepatomegaly without hepatocyte proliferation and enlargement. Long-term treatment with PCN did not upregulate PXR target proteins in mice, and there was no significant upregulation of CYP3A11, CYP2B10, UGT1A1, MRP2, or MRP4. Lipidomics analysis showed obvious hepatic lipid accumulation in the PCN-treated mice, and the most significant change was found in triglycerides (TGs). Additionally, long-term treatment with PCN had no risk for carcinogenesis. These findings demonstrated that long-term PCN treatment induces hepatomegaly and lipid accumulation without hepatocyte proliferation or enlargement., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Monoclonal antibodies represent important weapons in our arsenal to against the COVID-19 pandemic. However, this potential is severely limited by the time-consuming process of developing effective antibodies and the relative high cost of manufacturing. Herein, we present a rapid and cost-effective lipid nanoparticle (LNP) encapsulated-mRNA platform for in vivo delivery of SARS-CoV-2 neutralization antibodies. Two mRNAs encoding the light and heavy chains of a potent SARS-CoV-2 neutralizing antibody HB27, which is currently being evaluated in clinical trials, were encapsulated into clinical grade LNP formulations (named as mRNA-HB27-LNP). In vivo characterization demonstrated that intravenous administration of mRNA-HB27-LNP in mice resulted in a longer circulating half-life compared with the original HB27 antibody in protein format. More importantly, a single prophylactic administration of mRNA-HB27-LNP provided protection against SARS-CoV-2 challenge in mice at 1, 7 and even 63 days post administration. In a close contact transmission model, prophylactic administration of mRNA-HB27-LNP prevented SARS-CoV-2 infection between hamsters in a dose-dependent manner. Overall, our results demonstrate a superior long-term protection against SARS-CoV-2 conferred by a single administration of this unique mRNA antibody, highlighting the potential of this universal platform for antibody-based disease prevention and therapy against COVID-19 as well as a variety of other infectious diseases., (© 2022. The Author(s).)

Background: Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD)., Methods: This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18-59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 μg, 10 μg, 15 μg, 20 μg, and 25 μg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212)., Findings: Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 μg group, 13 [65%] of 20 in the 10 μg group, 17 [85%] of 20 in the 15 μg group, 19 [95%] of 20 in the 20 μg group, 16 [100%] of 16 in the 25 μg group; p<0·0001). The incidence of grade 3 systemic adverse events were none (0%) of 20 in the 5 μg group, three (15%) of 20 in the 10 μg group, six (30%) of 20 in the 15 μg group, seven (35%) of 20 in the 20 μg group, five (31%) of 16 in the 25 μg group, and none (0%) of 20 in the placebo group (p=0·0013). As expected, the majority of fever resolved in the first 2 days after vaccination for all groups. The incidence of solicited systemic adverse events was similar after administration of ARCoV as a first or second vaccination. Humoral immune responses including anti-RBD IgG and neutralising antibodies increased significantly 7 days after the second dose and peaked between 14 and 28 days thereafter. Specific T-cell response peaked between 7 and 14 days after full vaccination. 15 μg induced the highest titre of neutralising antibodies, which was about twofold more than the antibody titre of convalescent patients with COVID-19., Interpretation: ARCoV was safe and well tolerated at all five doses. The acceptable safety profile, together with the induction of strong humoral and cellular immune responses, support further clinical testing of ARCoV at a large scale., Funding: National Key Research and Development Project of China, Academy of Medical Sciences China, National Natural Science Foundation China, and Chinese Academy of Medical Sciences., Competing Interests: C-FQ and BY are co-inventors on pending patent applications related to the ARCoV mRNA vaccine. LW is an employee of Suzhou Abogen Biosciences. S-YY and ZH are employees of Walvax. All other authors declare no competing interests., (© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.)

Alleviating odontoblast inflammation is crucial to control the progression of pulpitis. Mitochondrial DNA (mtDNA) is a vital driver of inflammation when it leaks from mitochondria of inflamed odontoblasts into the cytosol. Bacteria-induced inflammation leads to a novel type of cell death named pyroptosis. The canonical pyroptosis is a gasdermin (GSDM)-dependent cytolytic programmed cell death characterized by cell swelling and pore formation in the plasma membrane. To date, whether odontoblast cytosolic mtDNA regulates dental pulp inflammation through the canonical pyroptosis pathway remains to be elucidated. In this study, high gasdermin D (GSDMD) expression was detected in human pulpitis. We found that LPS stimulation of mDPC6T cells promoted BAX translocation from the cytosol to the mitochondrial membrane, leading to mtDNA release. Moreover, overexpression of isolated mtDNA induced death in a large number of mDPC6T cells, which had the typical appearance of pyroptotic cells. Secretion of the inflammatory cytokines CXCL10 and IFN-β was also induced by mtDNA. These results suggest that cytosolic mtDNA participates in the regulation of odontoblast inflammation through GSDMD-mediated pyroptosis in vitro. Interestingly, after overexpression of mtDNA, the expression of inflammatory cytokines CXCL10 and IFN-β was increased and not decreased in GSDMD knockdown mDPC6T cells. We further proposed a novel model in which STING-dependent inflammation in odontoblast-like cell is a compensatory mechanism to control GSDMD-mediated pyroptosis, jointly promoting the immune inflammatory response of odontoblasts. Collectively, these findings provide the first demonstration of the role of the mtDNA-GSDMD-STING in controlling odontoblast inflammation and a detailed description of the underlying interconnected relationship., (© 2021. The Author(s).)

There is an urgent need for animal models to study SARS-CoV-2 pathogenicity. Here, we generate and characterize a novel mouse-adapted SARS-CoV-2 strain, MASCp36, that causes severe respiratory symptoms, and mortality. Our model exhibits age- and gender-related mortality akin to severe COVID-19. Deep sequencing identified three amino acid substitutions, N501Y, Q493H, and K417N, at the receptor binding domain (RBD) of MASCp36, during in vivo passaging. All three RBD mutations significantly enhance binding affinity to its endogenous receptor, ACE2. Cryo-electron microscopy analysis of human ACE2 (hACE2), or mouse ACE2 (mACE2), in complex with the RBD of MASCp36, at 3.1 to 3.7 Å resolution, reveals the molecular basis for the receptor-binding switch. N501Y and Q493H enhance the binding affinity to hACE2, whereas triple mutations at N501Y/Q493H/K417N decrease affinity and reduce infectivity of MASCp36. Our study provides a platform for studying SARS-CoV-2 pathogenesis, and unveils the molecular mechanism for its rapid adaptation and evolution., (© 2021. The Author(s).)

Background: Mitochondrial DNA (mtDNA) is a vital driver of inflammation when it leaks from damaged mitochondria into the cytosol. mtDNA stress may contribute to cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway activation in infectious diseases. Odontoblasts are the first cells challenged by cariogenic bacteria and involved in maintenance of the pulp immune and inflammatory responses to dentine-invading pathogens. In this study, we investigated that mtDNA as an important inflammatory driver participated in defending against bacterial invasion via cGAS-STING pathway in odontoblasts., Methods: The normal tissues, caries tissues and pulpitis tissues were measured by western blotting and immunohistochemical staining. Pulpitis model was built in vitro to evaluated the effect of the cGAS-STING pathway in odontoblast-like cell line (mDPC6T) under inflammation. Western blot and real-time PCR were performed to detect the expression of cGAS-STING pathway and pro-inflammatory cytokines. The mitochondrial function was evaluated reactive oxygen species (ROS) generated by mitochondria using MitoSOX Red dye staining. Cytosolic DNA was assessed by immunofluorescent staining and real-time PCR in mDPC6T cells after LPS stimulation. Furthermore, mDPC6T cells were treated with ethidium bromide (EtBr) to deplete mtDNA or transfected with isolated mtDNA. The expression of cGAS-STING pathway and pro-inflammatory cytokines were measured., Results: The high expression of cGAS and STING in caries and pulpitis tissues in patients, which was associated with inflammatory progression. The cGAS-STING pathway was activated in inflamed mDPC6T. STING knockdown inhibited the nuclear import of p65 and IRF3 and restricted the secretion of the inflammatory cytokines CXCL10 and IL-6 induced by LPS. LPS caused mitochondrial damage in mDPC6T, which promoted mtDNA leakage into the cytosol. Depletion of mtDNA inhibited the cGAS-STING pathway and nuclear translocation of p65 and IRF3. Moreover, repletion of mtDNA rescued the inflammatory response, which was inhibited by STING knockdown., Conclusion: Our study systematically identified a novel mechanism of LPS-induced odontoblast inflammation, which involved mtDNA leakage from damaged mitochondria into the cytosol stimulating the cGAS-STING pathway and the inflammatory cytokines IL-6 and CXCL10 secretion. The mtDNA-cGAS-STING axis could be a potent therapeutic target to prevent severe bacterial inflammation in pulpitis. Video Abstract.

We examined the effects of a combination of slow-release urea (PCU) and common urea (PU) applied at different soil depths (0-30 cm soil layer) on inorganic nitrogen content, enzyme activity, and crop yield during two years (2017-2018) in a field experiment. There were eight treatments: CK (without N fertilizer); PU 1 (common urea applied at 5-10 cm deep soil layer); PU 2 (common urea applied at 5-10 cm deep soil layer, 60% seed fertilizer + 40% topdressing); PU 3 (20% common urea at 5-10 cm soil depth, 30% common urea at 15-20 cm soil depth, 50% common urea at 25-30 cm soil depth); PCU 1 (20% total nitrogen application rate at 5-10 cm soil depth, 30% total nitrogen application rate at 15-20 cm soil depth, 50% total nitrogen application rate at 25-30 cm soil depth), the N fertilizer at 5-10 cm was common urea, but, at 15-20 and 25-30 cm, it was a combination of PCU and PU at ratios of 3:7 and 3:7; PCU 2 was as PCU 1 but the ratio of PCU and PU was 5:5 at 15-20 cm and 5:5 at 25-30 cm; in PCU 3 , the ratio of PCU and PU was 3:7 at 15-20 cm and 5:5 at 25-30 cm; in PCU 4 , the ratio of PCU and PU was 5:5 at 15-20 cm and 3:7 at 25-30 cm. The results showed that PU 1 could meet nitrogen demand at the 0-10 cm layer in the early growth stage compared with CK. PU 2 and PU 3 could meet nitrogen demand for 10-30 cm soil layer in the early stage of maize development. The combined application of slow release urea and common urea could meet nitrogen demand for the whole growth period of maize. In the filling and maturing period, combined application of slow release and common urea significantly increased not only NO 3 - -N, NH 4 + -N, and alkali-hydrolyzed nitrogen contents but also urease and protease activities in the 10-20 cm and 20-30 cm soil layers compared with PU 1 -PU 3 . Compared with PU 3 , maize yield increased by 2.3%-24.6% and 1.3%-16.5% in the PCU 1 -PCU 4 treatments in 2017 and 2018, respectively. PCU 4 had the highest yield, with 13899 and 12439 kg·hm -2 , respectively. Therefore, the combined application of slow-release and common urea at different soil layers could meet nitrogen demand in the early growth stage of maize and increase the content of inorganic nitrogen and enzyme activities in the 10-30 cm soil layers in the later growth period, which promoted the growth and increased the yield of maize. Among all the treatments PCU 4 treatment was the most effective.

Freshwater aquatic ecosystems are important sources of greenhouse gases, such as CO 2 . However, few studies have presented data on the greenhouse gas flux from coastal aquaculture ponds. Diffusion models are important tools for estimating the CO 2 exchange flux across the water-air interface of aquatic ecosystems. Several different parameterized means were selected to estimate the CO 2 gas exchange rate ( k x ) and CO 2 diffusive flux across the water-air interface of shrimp ponds in the Minjiang River Estuary. The results indicated that:① the CO 2 gas exchange rate and diffusive flux over the culture period all presented significant temporal variation. This variation showed a dynamic trend:October > September > November > July > August and November > July > August > September > October. ② Wind speed, k x , CO 2 concentration, pH, DOC concentration, and Chl-a concentration were important factors affecting the temporal variation of CO 2 diffusive flux. ③ There were differences in the estimated value of CO 2 diffusive flux across the water-air interface of the culture ponds in the Minjiang River Estuary among different parameterized approaches ( P <0.01). This indicates that the model method has some uncertainties in estimating the CO 2 diffusive flux in culture ponds. Our results suggest that the models RC01 and CW03 are more suitable methods for estimating the CO 2 diffusive flux at the water-air interface of estuarine reclaimed aquaculture ponds in the Minjiang River Estuary, after comprehensive analysis of the water environment and the different estimation results.

This study aims to validate our hypothesis that acid-sensing ion channels (ASICs) may contribute to the symptom of pain in patients with chronic prostatitis (CP). We first established a CP rat model, then isolated the L5-S2 spinal dorsal horn neurons for further studies. ASIC1a was knocked down and its effects on the expression of neurogenic inflammation-related factors in the dorsal horn neurons of rat spinal cord were evaluated. The effect of ASIC1a on the Ca 2+ ion concentration in the dorsal horn neurons of rat spinal cord was measured by the intracellular calcium ([Ca 2+ ]i) intensity. The effect of ASIC1a on the p38/mitogen-activated protein kinase (MAPK) signaling pathway was also determined. ASIC1a was significantly upregulated in the CP rat model as compared with control rats. Acid-induced ASIC1a expression increased [Ca 2+ ]i intensity in the dorsal horn neurons of rat spinal cord. ASIC1a also increased the levels of neurogenic inflammation-related factors and p-p38 expression in the acid-treated dorsal horn neurons. Notably, ASIC1a knockdown significantly decreased the expression of pro-inflammatory cytokines. Furthermore, the levels of p-p38 and pro-inflammatory cytokines in acid-treated dorsal horn neurons were significantly decreased in the presence of PcTx-1, BAPTA-AM, or SB203580. Our results showed that ASIC1a may contribute to the symptom of pain in patients with CP, at least partially, by regulating the p38/MAPK signaling pathway.

Objective: To identify Streptococcus mutans (S. mutans) in carious patients' saliva using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and to establish a faster and more accurate method to identify S. mutans., Methods: In this study, a total of 90 carious patients from Department of Endodontics of Peking University School of Stomatology were recruited. All these patients' saliva was collected. After extracting the protein of the samples, they were identified by MALDI-TOF MS. The composite profile was analyzed using BioExplorer 1.0 software. The scores ≥ 25 were considered as S. mutans, whereas the scores <25 were as considered as non S. mutans. Finally, these results were compared with 16S rDNA sequencing to figure out the sensitivity and concordance rate, respectively., Results: The sensitivity of MALDI-TOF MS was 96.0%, and the concordance rate compared with 16S rDNA sequencing was as high as 98.7%., Conclusion: MALDI-TOF MS is high throughput, rapid and easy to perform in comparison to other conventional methods. It has a high sensivity and concordance rate. Thus, MALDI-TOF MS can serve as an effective tool for identification of S. mutans.

Whether the assessment results of Contingent Valuation Method (CVM) have temporal stability is an important issue in examining the reliability of CVM findings, and also, is critical to decide whether CVM can be applied to evaluate the ecosystem services value in China. Taking the ecological restoration along the Caohejing River in Shanghai as a case, three CVM survey schemes with one month apart and two years apart were designed. Then, 426, 498, and 200 questionnaires in these surveys were comparatively analyzed, respectively. The mean values of the willingness to pay (WTP) from the three surveys were 14. 2, 14. 1, and 18. 0 RMB, and the median values were 5, 5, and 10 RMB, respectively. With the comparison of the WTP distribution and the main statistics, the analysis of the factors affecting the WTP, and the test of the significances of temporal variables, it was found that the CVM results from the surveys with one-month apart had temporal stability, while those from the surveys with two years apart presented definite difference.

Objective: To access the prevalence of menopause-like symptoms, and their related factors in old and middle-aged males in the area of Hefei., Methods: This study included 1 026 males aged over 45 years that came to the clinic for health examination. We collected their personal data, and evaluated their general health status and the results of the questionnaire investigation using the Aging Males' Symptoms (AMS) scale., Results: The total incidence of menopause-like symptoms was 64.7% among the old and middle-aged males in Hefei area, of which 58.1% were mild, 30.9% moderate and 11.0% severe. The average AMS score was 31.2 +/- 6.8, in which the scores on psychological, physical and sexual function symptoms were 8.3 +/- 2.1, 12.4 +/- 4.8 and 9.3 +/- 4.5, respectively. Sexual function symptoms were increased significantly with the increase of age (P < 0.05), but psychological and physical symptoms showed no obvious correlation with age (P > 0.05). The main risk factors of menopause-like symptoms included age, smoking, diabetes, cardiovascular diseases, and obesity, but physical exercise was an important protective factor against them., Conclusion: With the increase of age, the prevalence of male menopause-like symptoms rises and sexual function declines gradually, but psychological and physical scores are not affected significantly. Age, general health status and lifestyle are closely associated with the prevalence of menopause-like symptoms among old and middle-aged males.

We present a system for vectorizing 2D raster format cartoon animations. The output animations are visually flicker free, smaller in file size, and easy to edit. We identify decorative lines separately from colored regions. We use an accurate and semantically meaningful image decomposition algorithm, supporting an arbitrary color model for each region. To ensure temporal coherence in the output, we reconstruct a universal background for all frames and separately extract foreground regions. Simple user-assistance is required to complete the background. Each region and decorative line is vectorized and stored together with their motions from frame to frame. The contributions of this paper are: 1) the new trapped-ball segmentation method, which is fast, supports nonuniformly colored regions, and allows robust region segmentation even in the presence of imperfectly linked region edges, 2) the separate handling of decorative lines as special objects during image decomposition, avoiding results containing multiple short, thin oversegmented regions, and 3) extraction of a single patch-based background for all frames, which provides a basis for consistent, flicker-free animations.

Objective: To compare the therapeutic efficacies and toxicities of single-agent docetaxel or docetaxel plus platinum combination agent in patients with advanced non-small cell lung cancer (NSCLC) so as to provide rationales for standard second-line chemotherapy., Methods: The clinical data from 152 patients with NSCLC who were admitted into Chest Hospital Affiliated to Shanghai Jiaotong University, from January 2004 to May 2008 were retrospectively analyzed. Forty patients were treated with single-agent docetaxel (single-agent group, 16 and 24 patients with stages IIIb and IV disease respectively; 32 patients with PS score 0-1 before treatment and 8 patients with PS score 2 before treatment), and 112 patients were treated with docetaxel plus platinum combination agent (combination group, 29 and 83 patients with stage IIIb and IV disease respectively; 98 patients with PS score 0-1 before treatment and 14 patients with PS score 2 before treatment). Primary end point was overall survival (OS), and secondary end point were progression-free survival time (PFS), disease control rate (DCR), one-year survival, and drug toxicity. Survival analysis was evaluated by Kaplan-Meier. Single factor analysis and Cox regression model were done to analyze the relationship between the influencing factors and the prognosis of disease., Results: The median PFS of the single-agent group was 3.0 months, significantly shorter than that of the combination group (4.2 months, P = 0.048). However, no statistical differences were found in OS, DCR or one-year survival between the two groups (all P > 0.05). The most common grade 3 to 4 toxicities were leukopenia (32.5% for single-agent group, and 56.2% for combination group, P = 0.000), and gastro-intestinal toxicity (0 for single-agent group, and 4.5% for combination group, P = 0.000). Single factor analysis showed that the factors including radiotherapeutic history, operative history, PS score before treatment, clinical stage, and response to second-line treatment influenced the prognosis of NSCLC (all P < 0.05). Cox regression analysis demonstrated operative history (HR = 0.428, 95% CI: 0.261-0.701), PS score before treatment (HR = 1.919, 95% CI: 0.999-3.685), clinical stage (HR = 2.297, 95% CI: 1.427-3.696) and response to second-line treatment (HR = 0.318, 95% CI: 0.177-0.571) had effects on survival., Conclusions: To those well-selected patients, docetaxel plus platinum combination agent as the second-line treatment of advanced NSCLC significantly prolongs the progression-free survival. But such a regimen is more toxic and does not improve the response rate and overall survival.

Objective: To observe the therapeutic effect and influential factors of strong stimulation of acupoints around eyes by reducing method of twisting the needle for treatment of adolescent myopia, and to compare the different curative effects of both weak and strong stimulus intensities and wearing glasses in daytime., Methods: According to the principle of knowing and permission, the patients were divided into a strong stimulation group (60 cases, 120 eyes), a weak stimulation group (60 cases, 120 eyes) and a wearing glasses group (60 cases, 120 eyes). Both the strong stimulation group and the weak stimulation group were treated by reducing method of twisting the needle, with Cuanzhu (BL 2), Yuyao (EX-HN 4), Sizhukong (TE 23), Sibai (ST 2) and Taiyang (EX-HN 5) selected. Each acupoint was twisted 360 and 90 times per min for the strong stimulation group, and 90 degrees and 60 times per min for the weak stimulation group; the wearing glasses group were not treated with acupuncture, but with wearing glasses in daytime., Results: After treatment with the reducing method of twisting the needle, the vision improved (P < 0.01), with more obviously increased in the strong stimulation group than the weak stimulation group (P < 0.01), and there was no significant change of vision in the wearing glasses group. The age and the myopic degree of the patient before treatment were closely related with the change of vision after treatment (P < 0.01)., Conclusion: The reducing method of twisting the needle has a definite clinical therapeutic effect on adolescent myopia; strong stimulation has a better effect than the weak one; the age and the myopic degree of the patient possibly influence the therapeutic effect.

Chronic prostatitis (CP) is a common disease among adult men. It can result in male infertility mainly by alternating the semen quality, volume, pH, component, viscosity and liquefaction. There seems to be a strong association between CP and semen delayed liquefaction. Researches on the mechanism of semen delayed liquefaction resulting from CP mainly focus on the proteolytic ferment, plasminogen activator, prostate acid phosphatase, tissue factor, lack of zinc, and pH. This article briefly reviews the progress in these aspects.

Background & Objective: It had been observed that BRM-SJS had antitumor effect in our clinical practice. This study was designed to investigate the antitumor activity of BRM-SJS, and mechanism of its action., Methods: In vitro antitumor experiments with MTT method, meanwhile cell morphology, flow cytometry, and agarose gel electrophoresis were performed for determining apoptosis in several tumor cell lines., Results: BRM-SJS had antitumor effects on human Suzhou human glioma (SHG-44), breast carcinoma (MCF-7), and human pancreas carcinoma (PANC1) in vitro, the IC50 values of BRM-SJS were 0. 299 mg/ml, 1.853 mg/ml and 9.416 mg/ml respectively. At the 2. 5 mg of BRM-SJS on SHG-44 and MCF-7, marked morphological changes, including cell shrinkage and condensation of chromosomes, were observed with electric microscope. The increase of apoptosis in SHG-44 and MCF-7 cells treated with BRM-SJS extracts 0.625 -2.5 mg for 14 -48 h was observed by Annexin-V/PI flow cytometry analysis. Agarose gel electrophoresis of DNA from SHG-44 and MCF-7 cells treated with BRM-SJS extracts 1.25 -5 mg for 24 h or 48 h showed marked DNA Ladder pattern., Conclusion: Antitumor activity of BRM-SJS may be related with inducement of apoptosis of tumor cells.

Objective: To explore the insulin resistance and first-phase insulin secretion of beta-cells in normal persons, obese persons with normal glucose tolerance, obese persons with impaired glucose tolerance (IGT) and obese persons with type 2 diabetes (T2DM)., Methods: 75 g oral glucose tolerance test (OGTT) and Bergman's minimal model method of frequently sampled intravenous glucose tolerance test (FSIGTT) with reduced sample number (n = 12) were performed on a total of 151 subjects, 29 normal controls (control group), 44 obese persons with normal glucose tolerance (obesity group), 36 obese persons with IGT (IGT group), and 42 T2DMT patients (T2DM group) to determine the acute insulin response to glucose (AIRg), insulin sensitivity index (S(I)), and glucose effectiveness (S(G)). The disposition index (DI, AIRg X S(I)) was calculated to determine whether AIRg was adequate to compensate for insulin resistance., Results: The S(I) value of the control group was significantly higher than those of the obesity, IGT, and T2DM groups (all P < 0.01), without significant difference among the latter three groups. The S(G) value of the control group was not significantly different from that of the obesity group, but significantly higher than those of the IGT and T2DM groups (both P < 0.01), without significant difference any 2 groups from the latter two groups. The AIRg of the normal group was similar to that of the IGT group (2.61 mU x L(-1) x min(-1) +/- 0.13 mU.L(-1) x min(-1) vs 2.56 mU x L(-1) x min(-1) +/- 0.25 mU x L(-1) x min(-1)), and significantly lower than that of the obesity group (3.02 mU x L(-1) x min(-1) +/- 0.27 mU x L(-1) x min(-1), P < 0.01) and higher than that of the T2DM group (1.54 mU x L(-1) x min(-1) +/- 0.55 mU x L(-1) x min(-1), P < 0.01). The value of DI was gradually decreased from the sequence of the groups of control, obesity, IGT, and T2DM (3.16 +/- 0.31, 2.65 +/- 0.50, 1.67 +/- 0.54), with significant differences between any two groups (all P < 0.01). Multiple regression analyses with S(I) and AIRg as dependent variables showed that S(I) was negatively correlated with BMI, 2 h glucose level in OGTT, 2 h insulin, triglyceride, and cholesterol (r(2) = 0.589, P < 0.001), and AIRg was positively correlated with BMI, S(G), fasting insulin, and 2 h insulin level and negatively correlated with 2 h glucose, and age (r(2) = 0.515, P < 0.001)., Conclusion: Obese patients with different glucose tolerance have similar degrees of insulin resistance. Acute insulin response is increased in obesity group to compensate for the insulin resistance. Although the acute insulin response in the IGT group is similar to that in the control group, however, the compensation of islet beta cells in the IGT group is significantly decreased as compared with that in the obesity group, leading to glucose intolerance. There is a severe deficiency of acute insulin response to glucose in T2DM group.

Objective: To investigate the relationship among fasting serum free fatty acid (FFA), insulin sensitivity index (ISI), serum triglyceride (TG) and total cholesterol (TC) levels in subjects with different body mass index (BMI) and glucose tolerance by using Bergman's minimodel method., Methods: 26 normal control subjects, 39 obese subjects, 25 impaired glucose tolerance (IGT) subjects and 21 patients with newly diagnosed type 2 diabetes mellitus (DM) were recruited into this study. Serum FFA level was measured with radioimmunoassay and ISI was obtained by using Bergman's minimal model method., Results: (1) In the four groups, serum FFA concentration of the control group was significantly lower than that of the other three groups, although there was no difference among the latter three. (2) ISI level of the control group was significantly higher than that of other three groups, while there was no difference among the latter three. (3) After adjusting with BMI, there was still significant difference in serum FFA levels between the control and the other three groups. (4) ISI, HOMAIR, BMI, waist hip ratio (WHR) and TG were all related to the concentration of serum FFA (r = -0.454, 0.213, 0.241, 0.336 and 0.414 respectively, P < 0.01, < 0.05, < 0.05, < 0.01 and < 0.01 respectively), while age, sex and serum TC levels were not related with serum FFA. (5) According to multivariate stepwise regression, ISI, BMI and TG were the major determinant factors for FFA (R(2) = 0.109, 0.212, 0.156, P < 0.001)., Conclusions: Besides BMI, ISI and serum TG level are the major determinant factors that affect the concentration of serum FFA. As compared with the simple index HOMAIR, ISI level was more significantly related with serum FFA concentration. FFA levels are significantly different in various glucose tolerant states even after adjusting with BMI. FFA levels were obviously higher in subjects with IGT or type 2 diabetes mellitus.

Objective: To determine the relationship between a single point mutation in RET proto-oncogene and the occurrence of multiple endocrine neoplasia type 2B (MEN-2B) in a Chinese pedigree., Methods: We used the methods of polymerase chain reaction (PCR), reverse transcriptase polymerase chain reaction (RT-PCR) and direct gene sequencing of PCR products by an automated DNA sequencer to scan the entire exon 16 of RET proto-oncogene in the tumor (c)DNA from one patient with MEN-2B and the leukocyte DNA from this patient and both of his parents., Results: We found the same mutation Met(ATG)-->Thr(ACG) at codon 918 in exon 16 of RET proto-oncogene in both the tumor (c)DNA and leukocyte DNA of the MEN-2B patient in the form of homozygous missense mutation, but there was no corresponding mutation in leukocytes DNA of his parents., Conclusion: We propose that in Chinese population, the point mutation M918T is also associated with the onset of MEN-2B and this case of MEN-2B is sporadic. Thus it may provide a genetic basis for the early diagnosis and treatment of patients suffering from MEN-2B and their at-risk family members in Chinese population.