Search

Background: Tooth-supported surgical guides have demonstrated superior accuracy compared with bone-supported guides. This study aimed to modify the fabrication of tooth-supported guides for compatibility with tumor resection procedures and investigate their accuracy., Methods: Patients with tumors who underwent osteotomy with the assistance of modified tooth- or bone-supported surgical guides were included. Virtual surgical planning (VSP) was employed to align three dimensional (3D) models extracted from intraoperative computed tomography (CT) images. The distances and angular deviations between the actual osteotomy plane and preoperative plane were recorded. A comparative analysis of osteotomy discrepancies between tooth-supported and bone-supported guides, as well as among tooth-supported guides based on CT, cone-beam CT (CBCT), or intraoral scanner (IOS) was conducted. The factors influencing the precision of the guides were analyzed., Results: Sixty patients with 81 resection planes were included in this study. In the tooth-supported group, the mean deviations in the osteotomy plane and angle were 1.39 mm and 4.30°, respectively, whereas those of the bone-supported group were 2.16 mm and 4.95°. In the tooth-supported isotype guide groups, the mean deviations of the osteotomy plane were 1.39 mm, 1.47 mm, 1.23 mm across CT, CBCT, and IOS, respectively. The accuracy of the modified tooth-supported guides remained consistent regardless of number and position of the teeth supporting the guide and location of the osteotomy lines., Conclusions: The findings indicate that the modified tooth-supported surgical guides demonstrated high accuracy in the maxillofacial region, contributing to a reduction in the amount of surgically detached soft tissue., 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 Elsevier Masson SAS. All rights reserved.)

Background: Vascularized bone grafting (VBG) is preferred for mandibular reconstruction post-tumor ablation. Although various bone-free flaps are used, their application is compromised by limitations including insufficient bone volume and poor shape. Here, we report mandibular reconstruction using axial split-step osteotomy with an iliac crest-free flap., Methods: Over December 2018-November 2020, 12 patients underwent mandibular reconstruction via axial split osteotomy using a free iliac-crest flap., Results: The preoperative iliac-crest length was 5.7-9.5 mm (median, 7.5 cm); the mean post-axial split-osteotomy iliac-crest length increased to 9.59 mm (range, 6.34-15.15 mm). All patients presented with initial healing 2 weeks postoperation; good bone healing was achieved in all grafted flaps by the third month of follow-up., Conclusions: We propose a new axial split-step osteotomy technique using free iliac-crest flaps for mandibular reconstruction. We demonstrated this novel technique's reliability for safe and effective bone lengthening and establishing a reliable occlusal relationship., (© 2024 Wiley Periodicals LLC.)

Background: The aim was to analyze the correlation between serum microRNA (miR)-18a level, endothelial function, and prognosis in female coronary heart disease (CHD) patients., Methods: One hundred sixtyfemale patients admitted to our hospital for the first occurrences of chest pain and tightness were divided into CHD and non-CHD groups based on the coronary angiography results. Clinical data, laboratory indexes, serum miR-18a level, and endothelial function [flow-mediated dilation (FMD) function, endothelin 1 (ET-1), and nitric oxide (NO)] were compared., Results: There were no significant differences in clinical data (except CHD family history) between 2 groups. Coronary heart disease group had significantly lower levels of NO and FMD, while significantly higher levels of miR-18a and ET-1 than non-CHD group (P <.05). Pearson correlation showed that serum miR-18a level was positively correlated with ET-1 (r = 0.492, P <.001), and negatively correlated with NO and FMD (r = -0.504, -0.307, P <.001). The receiver operating characteristic) curve showed that the area under the curve of serum miR-18a level in predicting the occurrence of CHD in women was 0.878 (95% CI:  0.828-0.928). Compared with good prognosis group, poor prognosis group had signifi-cantly lower NO, and FMD levels, while higher proportions of acute coronary syndrome, multivessel disease, miR-18a, and ET-1 levels (P <.05)., Conclusion: The expression of serum miR-18a in female CHD patients was high, which was related to endothelial function. The increase in serum miR-18a level was a risk factor for the occurrence of MACE in female CHD patients during follow-up, and the serum miR-18a level could effectively predict the occurrence of CHD in female patients.

Background: Several biallelic truncating and missense variants of the gem nuclear organelle-associated protein 5 (GEMIN5) gene have been reported to cause neurodevelopmental disorders characterized by cerebellar atrophy, intellectual disability, and motor dysfunction. However, the association between biallelic GEMIN5 variants and early-infantile developmental and epileptic encephalopathies (EIDEEs) has not been reported., Purpose: This study aimed to expand the phenotypic spectrum of GEMIN5 and explore the correlations between epilepsy and molecular sub-regional locations., Methods: We performed whole-exome sequencing in two patients with EIDEE with unexplained etiologies. The damaging effects of variants were predicted using multiple in silico tools and modeling. All reported patients with GEMIN5 pathogenic variants and detailed neurological phenotypes were analyzed to evaluate the genotype-phenotype relationship., Results: Novel biallelic GEMIN5 variants were identified in two unrelated female patients with EIDEE, including a frameshift variant (Hg19, chr5:154284147-154284148delCT: NM&#95;015465: c.2551&#95;c.2552delCT: p.(Leu851fs*30)), a nonsense mutation (Hg19, chr5:154299603-154299603delTinsAGA: NM&#95;015465: c.1523delTinsAGA: p.(Leu508*)), and two missense variants (Hg19, chr5:154282663T > A: NM&#95;015465: c.2705T > A: p.(Leu902Gln) and Hg19, chr5:154281002C > G: NM&#95;015465: c.2911C > G: p.(Gln971Glu)), which were inherited from asymptomatic parents and predicted to be damaging or probably damaging using in silico tools. Except p.Leu508*, all these mutations are located in tetratricopeptide repeat (TPR) domain. Our two female patients presented with seizures less than 1 month after birth, followed by clusters of spasms. Brain magnetic resonance imaging suggests dysgenesis of the corpus callosum and cerebellar hypoplasia. Video electroencephalogram showed suppression-bursts. Through a literature review, we found 5 published papers reporting 48 patients with biallelic variants in GEMIN5. Eight of 48 patients have epilepsy, and 5 patients started before 1 year old, which reminds us of the relevance between GEMIN5 variants and EIDEE. Further analysis of the 49 GEMIN5 variants in those 50 patients demonstrated that variants in TPR-like domain or RBS domain were more likely to be associated with epilepsy., Conclusions: We found novel biallelic variants of GEMIN5 in two individuals with EIDEE and expanded the clinical phenotypes of GEMIN5 variants. It is suggested that the GEMIN5 gene should be added to the EIDEE gene panel to aid in the clinical diagnosis of EIDEE and to help determine patient prognosis., (© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Introduction: Curing locally advanced gastric cancer (GC) or gastro-oesophageal junction adenocarcinoma (GEJ) with surgery alone is challenging. Neoadjuvant chemotherapy (NCT) has become the standard treatment for patients with locally advanced GC/GEJ, and SOX is the most common neoadjuvant regimen in China. The generally good tolerability in patients and fruquintinib's low potential for drug-drug interaction suggest that it may be highly suitable for combinations with other antineoplastic therapies. A combination of fruquintinib, S-1 and oxaliplatin can be a promising neoadjuvant treatment for locally advanced GC/GEJ. In this phase II study, we aim to investigate the efficacy and toxicity of fruquintinib plus SOX as neoadjuvant treatment for locally advanced GC/GEJ., Methods and Analysis: The FRUTINEOGA trial is a prospective, multicentre, phase II, single-arm, open-label clinical trial that will enrol 54 patients. Eligible patients will be registered, enrolled and receive 2-4 cycles of fruquintinib plus SOX, after which surgery will be performed and tumour regression will be evaluated. The primary endpoint is the pathological remission rate, and the secondary endpoints are disease-free survival, overall survival, objective response rate, major pathological response rate and R0 resection rate., Ethics and Dissemination: Written informed consent will be required from all patients enrolled, and it will be provided by them. The study protocol received approval from the independent ethical review committee of Guangxi Medical University Cancer Hospital, Wuming Hospital of Guangxi Medical University and Wuzhou Red Cross Hospital, Wuzhou Gongren Hospital (approval number: CS2021(96)). We will submit the finalised paper for publication on completing the analyses. This study will provide valuable insights to clinicians regarding the safety and efficacy of incorporating fruquintinib into SOX as neoadjuvant treatment for locally advanced GC/GEJ. The findings have the potential to inform future research proposals and may guide the use of fruquintinib in the neoadjuvant setting for locally advanced GC/GEJ., Trial Registration Number: NCT05122091., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study investigates the role of Nicotinamide N-methyltransferase (NNMT) in immune infiltration modulation through amino acid metabolism in gastric adenocarcinoma (STAD). Methods: Utilizing data from The Cancer Genome Atlas (TCGA) and validated with clinical samples, we analyzed NNMT expression and its prognostic implications in STAD. Differential amino acid profiles between cancerous and adjacent normal tissues were assessed, along with their associations with NNMT. Results: NNMT exhibits heightened expression in STAD cancer tissues, positively correlating with tumor immune infiltration. Additionally, twenty-eight amino acids display differential expression in gastric tissue, with their metabolic enzymes showing connections to NNMT. Conclusions: Elevated NNMT expression in STAD tissues potentially influences amino acid metabolism, thereby affecting immune infiltration dynamics and tumorigenesis in gastric adenocarcinoma.

Background and Purpose: Salivary gland cancers (SGCs) are hard to treat when inoperable, and sole brachytherapy appears to be a promising therapeutic strategy. This study aimed to evaluate the effectiveness, safety, and capability of pain palliation using sole brachytherapy for inoperable, recurrent, and irradiated SGCs., Materials and Methods: Patients with inoperable SGCs treated using sole brachytherapy at Peking University School and Hospital of Stomatology were retrospectively included. Patients were divided into primary and recurrent groups and irradiated and non-irradiated groups. Local control (LC), overall survival (OS), radiation-relevant toxicities, and Visual Analogue Scale (VAS) score for pain, were recorded and evaluated., Results: A total of 176 patients from 2006 to 2020 were included. The 5-year LC rate was 48.6 %; for the primary, recurrent, non-irradiated and irradiated groups, the rates were 72.6 %, 39.5 %, 56.8 %, and 34.5 %, respectively. The 5-year OS rates was 52.6 %; for the primary, recurrent, non-irradiated, and irradiated groups, the rates were 62.9 %, 48.6 %, 58.9 %, and 42.3 %, respectively. The mean ± standard deviation of posttreatment VAS score of pain was 2.154 ± 2.989, which was significantly decreased from the score of 6.923 ± 2.280 prior to brachytherapy. Skin hyperpigmentation, mucositis, and dysphagia were the most frequently reported adverse events., Conclusions: Brachytherapy as a sole modality, was retrospectively proven effective and safe in the management of inoperable SGCs and was beneficial in multiple irradiation and pain control., 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 Elsevier B.V. All rights reserved.)

Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a devastating urological chronic pelvic pain condition. In search of a potential treatment, we investigated the effect of emodin on IC/BPS inflammation and fibrosis, and explore the potential mechanism., Methods: An experimental model of interstitial cystitis was induced by cyclophosphamide, and human bladder smooth muscle cells were treated with lipopolysaccharide to establish the cell model in vitro. In both models, inflammation- and fibrosis-related indexes were measured after emodin administration. Furthermore, the specific antagonists were used to dig for the mechanisms underlying the response to emodin treatment., Results: Emodin significantly ameliorated management of cystitis, reduced the amount of inflammatory cytokines (tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1β, interleukin-8, and interleukin-6) in models, as well as reducing the synthesis of fibrosis marker including collagen1, collagen3, vimentin, fibronectin and α-smooth muscle actin. Further mechanism studies demonstrated that emodin inhibited inflammatory reaction and fibrosis through blocking lysine-specific demethylase 6B (JMJD3) expression via JAK/STAT, NF-κB and TGF-β/SMAD pathways., Conclusions: Our study reveals the critical role of emodin-JMJD3 signaling in interstitial cystitis by regulating inflammation, fibrosis, and extracellular matrix deposition in cells and tissues, and these findings provide an avenue for effective treatment of patients with cystitis.

Photon-counting LiDAR encounters interference from background noise in remote target detection, and the statistical detection of the accumulation of multiple pulses is necessary to eliminate the uncertainty of responses from the Geiger-mode avalanche photodiode (Gm-APD). The cumulative number of statistical detections is difficult to select due to the lack of effective evaluation of the influence of the background noise. In this work, a statistical detection signal evaluation method based on photon statistical entropy (PSE) is proposed by developing the detection process of the Gm-APD as an information transmission model. A prediction model for estimating the number of cumulative pulses required for high-accuracy ranging with the background noise is then established. The simulation analysis shows that the proposed PSE is more sensitive to the noise compared with the signal-to-noise ratio evaluation, and a minimum PSE exists to ensure all the range detections with background noise are close to the true range with a low and stable range error. The experiments demonstrate that the prediction model provides a reliable estimation of the number of required cumulative pulses in various noise conditions. With the estimated number of cumulative pulses, when the signal photons are less than 0.1 per pulse, the range accuracy of 4.1 cm and 5.3 cm are obtained under the background noise of 7.6 MHz and 5.1 MHz, respectively.

Background: The prognostic value of histomorphologic regression in primary gastric and gastroesophageal cancers (GC/GEJ) has been previously established, however, the impact of lymph node (LN) regression on survival still remains unclear., Methods: A prospectively maintained database was reviewed to identify cT4N+ gastric and gastroesophageal cancers (GC/GEJ) after NAC (neoadjuvant chemotherapy). Patients were categorized into two groups based on LN status: cN+/ypN0 (downstaged N0) and cN+/ypN+ (persistent N+), long-term survival were analyzed using Kaplan-Meier survival estimates., Results: In total, 125 patients with cT4N+ GC/GEJ underwent NAC followed by surgery were enrolled. A total of 39 patients (31.2%) had cN+/ypN0 (ypN0) disease, 86 patients (68.8%) had cN+/ypN+ (ypN+) disease. Prognosis in ypN+ patients was significantly worse than those in ypN0 group for 3- and 5-year overall survival (OS) (p < 0.05). The 3-year OS was 83%, 44% in ypN0 and ypN+ group, respectively. The 5-year OS was 75%, 35% in ypN0 and ypN+ group, respectively. Multivariable analysis suggested that multivisceral resection (hazard ratio [HR] = 0.33, 95% confidence interval [CI]: 0.14-0.76, p = 0.009), and ypN+ (HR = 3.42, 95% CI: 1.15-10.13, p =0.027) were independent prognostic factors for OS., Conclusion: Nodal downstaging is an important hallmark representing the effectiveness of NAC for GC/GEJ, and it positively impacts on survival of these patients., (© 2022 Wiley Periodicals LLC.)

X-linked juvenile retinoschisis (XLRS), caused by the mutation of RS1 gene, is one of the most common causes of macular degeneration for male adolescents. The mutations and clinical manifestations of the disease are diverse. Neither the relationship between the genotypes and phenotypes, nor the radical treatment like gene therapy has been found by now. Retrospective studies have shown that carbonic anhydrase inhibitors can help reduce cysts. However, the specifically pharmacological mechanism remains unknown. Here, we culture induced pluripotent stem cells by drawing peripheral blood from a patient with XLRS, which are supposed to facilitate related researches., 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 © 2022. Published by Elsevier B.V.)

Brachytherapy has the advantages of being minimally invasive and highly conformal, and it achieves good results in head and neck tumors. To precisely implant the radioactive seeds according to the preplan in deep head and neck regions, the surgical navigation is applied. This study aims to explore the clinical application and accuracy of imaging-based surgical navigation-guided 125I interstitial brachytherapy in terms of seed position. We included 41 patients with tumors in deep head and neck regions. The brachytherapy treatment plan was designed, and the preplanned data were transferred to the navigation system. Needle implantation and seed delivery were performed under surgical navigation system guidance with or without the combination of individual template. The treatment accuracy was evaluated by comparing seed cluster locations between the preoperative treatment plan and the postoperative treatment outcome. A total of 2879 seeds were delivered. The range, mean and median distances between the geometric centers of the preoperative seed point clusters and the postoperative seed point clusters were 0.8-10.5 mm, 4.5 ± 2.3 mm and 4.1 mm, respectively. The differences between preoperative and postoperative volumes of the minimum bounding box of seed point clusters were nonsignificant. In conclusion, the imaging-based surgical navigation system is a promising clinical tool to provide the preplanned data for interstitial brachytherapy intraoperatively, and it is feasible and accurate for the real-time guidance of needle implantation and seed delivery in deep head and neck regions., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Gastric cancer (GC) is one of the most common gastrointestinal malignancies. Ferroptosis is a new type of peroxidation-driven and iron-dependent cell death. However, the biological functions and exact regulatory mechanisms of ferroptosis in GC remain elusive. Here, we performed RNAi and gene transfection, cell viability assay, lipid peroxidation assay, reactive oxygen species (ROS) assay, glutathione assay, qRT-PCR, Western blotting, and transmission electron microscopy (TEM) to study ferroptosis in gastric cancer. The results revealed that silencing latent transforming growth factor β binding proteins (LTBP2) can significantly inhibit GC cell proliferation and decrease cellular GSH levels, reduce GPX4 activity, and increase ROS generation and malondialdehyde (MDA) levels, leading to ferroptosis in GC cells. In addition, we demonstrate that suppression of LTBP2 could regulate the p62-Keap1-Nrf2 pathway, thereby downregulating the GPX4 and xCT expression and upregulating the PTGS2 and 4HNE expression. Our findings described a new role of LTBP2 in regulating ferroptosis, which heralds the prospect of ferroptosis-mediated cancer therapy., Competing Interests: The authors report no conflicts of interest in this work., (Copyright © 2022 TingAn Wang et al.)

Oral cancer is a common malignant tumor in the maxillofacial region. Surgical resection is the preferred treatment, but the severe functional impairment after surgery forces us to look for noninvasive treatments. As a promising noninvasive treatment method, photodynamic therapy (PDT) has received widespread attention in the field of cancer therapy, but the inefficient uptake capacity of tumor cells and the damage repair mechanisms limit the actual therapeutic effect. The establishment of a targeted therapy function and autophagy inhibition strategy is considered to be an important way to further enhance the effect of PDT. Based on this, we developed the biomimetic nanomaterial PCN-CQ@CCM. The metal-organic framework material PCN-224 was used as a carrier to load the autophagy inhibitor chloroquine (CQ) and it was coated onto the surface with isolated oral squamous cell carcinoma (OSCC) cell membranes. Owing to the immune evasion and homologous targeting ability of the biomimetic functionalized surface, PCN-CQ@CCM can escape macrophage phagocytosis and homologously adhere to tumor cells, enhancing the retention and uptake of nanomaterials in the tumor microenvironment. After being activated with a 660 nm laser, the generated reactive oxygen species (ROS) triggered the apoptosis pathway, as assessed by mitochondrial damage, and the released CQ further aggravated the ROS lethal pathway by effectively inhibiting the protective autophagic flux. Therefore, PCN-CQ@CCM achieves the precise synergy of PDT and autophagy inhibition through the biomimetic homologous targeting method, and the highly effective tumor suppression effect expands the field of vision for the noninvasive diagnosis and treatment of oral cancer.

Theranostic systems that permit both diagnosis and treatment in vivo are highly appealing means by which to meet the demands of precision medicine. However, most such systems remain subject to issues related to complex molecular design and synthesis, potential toxicity, and possible photoactivity changes. Herein, a novel supramolecular theranostic strategy involving biomarker protein activation (BPA) and a host-guest strategy is proposed. To exemplify BPA, a facile "one-for-all" nanotheranostic agent for both albumin detection and cancer treatment is demonstrated, which utilizes a nanoparticulate heavy-atom-free BODIPY dye derivative (B4 NPs). The fluorescence and photoactivity of BODIPY dyes are completely suppressed by aggregation-induced self-quenching in the nanoparticulate state. However, a Balb/c nude mouse model is used to confirm that following the disassembly of injected B4 NPs, BODIPY specifically binds albumin in vivo, accompanied by significantly enhanced biocompatibility and photothermal conversion efficiency. More importantly, this supramolecular host-guest BPA strategy enables the resultant nanoplatform to act as a facile and efficient strategy for photodynamic and photothermal immunotherapy., (© 2022 Wiley-VCH GmbH.)

Spores are essential for the long-term survival of many diverse organisms, due to their roles in reproduction and stress resistance. In the environmental human fungal pathogen, Cryptococcus , basidiospores are robust cells with the ability to cause disease in animal models of infection. Here we describe methods for producing and purifying Cryptococcus basidiospores in quantities sufficient for large-scale analyses. The production of high numbers of pure spores has facilitated the development of new assays, including quantitative germination assays, and enabled transcriptomic, proteomic, and virulence studies, leading to discoveries of behaviors and properties unique to spores and spore-mediated disease.

ARR3 has been associated with X-linked, female-limited, high myopia. However, using exome sequencing (ES), we identified the first high myopia case with hemizygous ARR3 -related mutation in a male patient in a Southern Chinese family. This novel truncated mutation ( ARR3 : c.569C>G, p.S190*) co-segregated with the disease phenotype in affected family members and demonstrated that high myopia caused by ARR3 is not X-linked, female-limited, where a complicated X-linked inheritance pattern may exist. Thus, our case expanded the variant spectrum in ARR3 and provided additional information for genetic counseling, prenatal testing, and diagnosis. Moreover, we characterized the nonsense-mediated decay of the ARR3 mutant mRNA and discussed the possible underlying pathogenic mechanisms., Competing Interests: Author VZ is employed by the company AmCare Genomics Laboratory. Author MH is employed by the company Aegicare (Sheznzhen) Technology Co., Ltd. The remaining 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 © 2021 Yuan, Yan, Luo, Huang, Tan, Zhang, Zhang, Lan, Hu, Guo, Huang and Zeng.)

X-linked juvenile retinoschisis (XLRS) is an inherited disease characterized by splitting within inner retinal layers and impaired vision, which begins in childhood and occurs mostly in males. Peripheral blood mononuclear cells (PBMCs) were isolated from a seven-year-old boy carrying a hemizygous mutation in RS1 gene, and were reprogrammed into human induced pluripotent stem cells (iPSCs) using non-integrative episomal vectors. The cell line, ZOCi003-A, had normal karyotype, expressed pluripotency markers, and could differentiate into three germ layers in vivo. This IPSC line may be used for studying the molecular basis of XLRS and selecting potential therapeutic targets and drugs., 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 © 2021. Published by Elsevier B.V.)

Objective: This study aimed to investigate the predictive value of pulse oximetry plethysmography (POP) for the return of spontaneous circulation (ROSC) in cardiac arrest (CA) patients., Methods: This was a multicenter, observational, prospective cohort study of patients hospitalized with cardiac arrest at 14 teaching hospitals cross China from December 2013 through November 2014. The study endpoint was ROSC, defined as the restoration of a palpable pulse and an autonomous cardiac rhythm lasting for at least 20 minutes after the completion or cessation of CPR., Results: 150 out-of-hospital cardiac arrest (OHCA) patients and 291 in-hospital cardiac arrest (IHCA) patients were enrolled prospectively. ROSC was achieved in 20 (13.3%) and 64 (22.0%) patients in these cohorts, respectively. In patients with complete end-tidal carbon dioxide (ETCO 2 ) and POP data, patients with ROSC had significantly higher levels of POP area under the curve (AUCp), wave amplitude (Amp) and ETCO 2 level during CPR than those without ROSC (all p < 0.05). Pairwise comparison of receiver operating characteristic (ROC) curve analysis indicated no significant difference was observed between ETCO 2 and Amp (p = 0.204) or AUCp (p = 0.588) during the first two minutes of resuscitation., Conclusion: POP may be a novel and effective method for predicting ROSC during resuscitation, with a prognostic value similar to ETCO 2 at early stage., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Photon counting lidar for long-range detection faces the problem of declining ranging performance caused by background noise. Current anti-noise methods are not robust enough in the case of weak signal and strong background noise, resulting in poor ranging error. In this work, based on the characteristics of the uncertainty of echo signal and noise in photon counting lidar, an entropy-based anti-noise method is proposed to reduce the ranging error under high background noise. Firstly, the photon counting entropy, which is considered as the feature to distinguish signal from noise, is defined to quantify the uncertainty of fluctuation among photon events responding to the Geiger mode avalanche photodiode. Then, the photon counting entropy is combined with a windowing operation to enhance the difference between signal and noise, so as to mitigate the effect of background noise and estimate the time of flight of the laser pulses. Simulation and experimental analysis show that the proposed method improves the anti-noise performance well, and experimental results demonstrate that the proposed method effectively mitigates the effect of background noise to reduce ranging error despite high background noise.

There is a critical need for new antifungal drugs; however, the lack of available fungus-specific targets is a major hurdle in the development of antifungal therapeutics. Spore germination is a differentiation process absent in humans that could harbor uncharacterized fungus-specific targets. To capitalize on this possibility, we developed novel phenotypic assays to identify and characterize inhibitors of spore germination of the human fungal pathogen Cryptococcus. Using these assays, we carried out a high-throughput screen of ∼75,000 drug-like small molecules and identified and characterized 191 novel inhibitors of spore germination, many of which also inhibited yeast replication and demonstrated low cytotoxicity against mammalian cells. Using an automated, microscopy-based, quantitative germination assay (QGA), we discovered that germinating spore populations can exhibit unique phenotypes in response to chemical inhibitors. Through the characterization of these spore population dynamics in the presence of the newly identified inhibitors, we classified 6 distinct phenotypes based on differences in germination synchronicity, germination rates, and overall population behavior. Similar chemical phenotypes were induced by inhibitors that targeted the same cellular function or had shared substructures. Leveraging these features, we used QGAs to identify outliers among compounds that fell into similar structural groups and thus refined relevant structural moieties, facilitating target identification. This approach led to the identification of complex II of the electron transport chain as the putative target of a promising structural cluster of germination inhibitory compounds. These inhibitors showed high potency against Cryptococcus spore germination while maintaining low cytotoxicity against mammalian cells, making them prime candidates for development into novel antifungal therapeutics. IMPORTANCE Fungal pathogens cause 1.5 million deaths annually, and there is a critical need for new antifungal drugs. However, humans and fungi are very similar on a molecular level, and so many drugs that kill fungi also damage human cells, leading to extreme side effects, including death. The lack of fungus-specific targets is a major hurdle in the development of antifungal therapeutics. Spore germination is a process absent in humans that could harbor fungus-specific targets. To capitalize on this possibility, we developed new assays to identify and characterize inhibitors of spore germination of the human fungal pathogen Cryptococcus. Using these assays, we identified and characterized 191 novel inhibitors of spore germination. These inhibitors showed high potency against Cryptococcus spore germination while maintaining low cytotoxicity against mammalian cells, making them prime candidates for development into novel antifungal therapeutics.

Abstract: Even though the pectoralis major myocutaneous flap (PMMF) still has an important role in the free flaps ear, it is reported to have drawbacks such as the limited cephalad extension and high incidence of total or partial flap necrosis. Various modifications have been attempted to augment the limited cephalad extension and a stable blood supply.The aim of this study is to describe a modified design of the skin paddle and preparation of the PMMF, to achieve stable blood circulation and sufficient pedicle length. The priority skin paddle is the medial part for its stable blood supply, and the lateral margin should be adjusted as needed. During the harvesting, the lateral thoracic artery (LTA) is preserved to protect the perforating branches, and the anterior sheath of the rectus abdominis muscle is used as a suture margin to prevent damage of the thin muscle of the PMMF. The skin paddles in this study are larger than those previously reported. All of the 21 patients in our study, the skin paddles show complete survival with no partial necrosis of skin paddle, fistula, or wound dehiscence.It is worthwhile to consider and preserve the LTA as a major contributor to a lateral and distal PMMF. This study would be useful in future and preparation of the PMMF in head and neck reconstruction., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by Mutaz B. Habal, MD.)

Background: Tissue inhibitor of metalloproteinases (TIMP) gene family, including TIMP1 , TIMP2 , TIMP3 and TIMP4 , was found to be correlated with serval cancers. Still the diagnostic and prognostic study of it in gastric cancer (GC) have few reports. Methods and materials: In this study, the gene expression and clinical data were acquired from the Cancer Gene Atlas (TCGA), function enrichment was used by several databases for verifying known function. Operating characteristic (ROC) curves with area under the curve (AUC) used to assess diagnostic value. Survival analysis and joint-effects survival analysis was performed by the Kaplan-Meier curve. The results were adjusted by cox-regression model. Nomogram is used to directly predict the survival rate for individual GC patient. The potential mechanism for diagnostic and prognostic value was assessed by gene set enrichment analysis (GSEA). Further functions of gene were verified by cell proliferation, migration and invasion assays in human gastric cancer cell line. Results: TIMP1 was expressed in GC tissue was higher than normal gastric tissue. TIMP3 and TIMP4 have expressed in normal gastric tissue were higher than GC tissue. TIMP1 , TIMP3 and TIMP4 have potential diagnostic value (AUC=0.842, 0.729, 0.786 respectively; all P<0.01). Low expression of TIMP2 and TIMP3 associated with favorable overall survival (all P<0.05). TIMP2 and TIMP3 , which had significantly affection of prognosis were found having some function such as tRNA processing, cell cycle pathway ncRNA processing. The silencing of TIMP3 could inhibit the migration and invasion of gastric cancer cell. Conclusion: We analyzed the TIMP gene family in GC, and the prognostic and diagnostic value. TIMP1 and TIMP2 could be used as diagnostic biomarkers in GC. TIMP2 and TIMP3 could be used as potential biomarkers for GC's prognosis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Susceptibility to idiopathic generalized epilepsy-15 (EIG15) is an autosomal dominant seizure disorder characterized by onset of variable types of seizures in the first decade, caused by heterozygous mutations in the RORB gene encoding the retinoid-related orphan receptor β. We established an induced pluripotent stem cell (iPSC) line from PBMCs collected from a five-year-old female patient with EIG15, via reprogramming with OCT3/4, SOX2, KLF4, and c-MYC. Upon careful examination, the iPSCs stably expressed pluripotent genes, maintained a normal karyotype, and had full potential for three-germ layer differentiation., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: To describe a technique in which the anterior jugular vein is preserved in the infrahyoid myocutaneous flap (IHMCF) to augment skin paddle venous drainage., Methods: From April 2018 to December 2019, 14 patients with primary oral cancer underwent radical resection and IHMCF reconstruction. Three-dimensional reconstruction of the anterior jugular vein was used to assess the venous drainage of the skin paddle preoperatively. The anterior jugular vein was preserved during dissection of the flap. Healing of the recipient and donor sites was observed., Results: Total flap necrosis occurred in one patient and marginal skin paddle necrosis occurred in one patient. No flap complications occurred in the other 12 patients., Conclusion: This new approach to augment venous drainage of the IHMCF appears to be effective for decreasing risk of flap necrosis., (© 2020 Wiley Periodicals LLC.)

As a kind of noncoding RNAs, microRNAs (miRNAs) play important roles in disease pathogenesis by regulating gene expression. However, the molecular mechanism of miRNAs in osteoporosis remains largely unknown. In the present study, we aim to explore the genome-wide miRNAs expression profile and the regulatory mechanism of miR-205-5p in osteoporosis. A total of 72 differentially expressed miRNAs were identified in osteoporosis via microarray technology and bioinformatics analysis. We focused on one of the abnormally expressed miRNAs, miR-205-5p, which was previously unknown in osteoporosis. Quantitative real-time polymerase chain reaction (qRT-PCR) results showed that miR-205-5p was upregulated in osteoporosis samples and its expression was gradually decreased during osteogenic differentiation. Besides, miR-205-5p overexpression could inhibit the activity of osteoblast markers, including collagen, type I, α 1 (COL1A1) and alkaline phosphatase (ALP) while miR-205-5p inhibition showed the opposite results. Moreover, bioinformatics analysis identified the potential targets of miR-205-5p, including runt-related transcription factor 2 (RUNX2), SMAD1 and BCL6, etc. The dual-luciferase reporter assay confirmed RUNX2 was directly targeted by miR-205-5p. Furthermore, the rescue experiments showed that RUNX2 overexpression could significantly weaken the effect of miR-205-5p on osteoblast markers, indicating that miR-205-5p may inhibit osteogenic differentiation by targeting RUNX2., (© 2019 Wiley Periodicals, Inc.)

The bacterial microbiota in the gut varies among species, as well as with habitat, diet, age, and other factors. Intestinal microbiota homeostasis allows a host to adjust metabolic and immune performances in response to environmental changes. Therefore, potential implications of the gut microbiota in sustaining the health of the host have gained increasing attention in the field of endangered animal conservation. However, the effect of host intraspecies genetic variation on the gut microbiota is unknown. Moreover, little is known about the complexity of the gut mycobiota. Tigers are listed as endangered species, raising worldwide concern. Potential influences of subspecies, diet, and age on the gut microbiota in tigers were investigated in this study to provide a better understanding of the response of the tiger gut microbiota to external changes. The results revealed that the impacts of the factors listed above on gut bacterial and fungal communities are versatile. Host intraspecies genetic variation significantly impacted only fungal alpha diversity of the gut microbiota. Differences in diet, on the other hand, had a significant impact on alpha diversity of the gut microbiota, but exerted different effects on beta diversity of gut bacterial and fungal communities. Host age had no significant impact on the diversity of the gut fungal communities, but significantly impacted beta diversity of gut bacterial communities. This comprehensive study of tiger gut microbiota is an essential reference for tiger conservation when considering feeding and management strategies, and will contribute to a better understanding of the mycobiota in wildlife., (© 2020 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)

Armadillo gene subfamily members (ARMCX1-6) are well-known to regulate protein-protein interaction involved in nuclear transport, cellular connection, and transcription activation. Moreover, ARMCX signals on cell pathways also implicated in carcinogenesis and tumor progression. However, little is known about the associations of the ARMCX subfamily members with gastric carcinoma. This study investigated the prognostic value of ARMCX subfamily mRNA expression levels with the prognosis of gastric carcinoma (GC). We retrieved the data of a total of 351 GC patients from TCGA database. Survival and gene set enrichment analyses were employed to explore the predictive value and underlying mechanism of ARMCX genes in GC. The multivariate survival analysis revealed that individually low expressions of ARMCX1 (adjusted P = 0.006, HR = 0.620, CI = 0.440 - 0.874) and ARMCX2 (adjusted P = 0.005, HR = 0.610, 95%CI = 0.432-0.861) were related to preferable overall survival (OS). The joint-effects analysis shown that combinations of low level expression of ARMCX1 and ARMCX2 were correlated with favorable OS (adjusted P = 0.003, HR = 0.563, 95%CI = 0.384-0.825). ARMCX1 and ARMCX2 were implicated in WNT and NF-kappaB pathways, and biological processes including cell cycle, apoptosis, RNA modification, DNA replication, and damage response. Our results suggest that mRNA expression levels of ARMCX subfamily are potential prognostic markers of GC., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 TingAn Wang et al.)

Background: The role and mechanism of hsa&#95;circRNA&#95;104433 in gastric cancer (GC) are further elucidated., Materials and Methods: CircRNA&#95;104433 was selected by circRNA microarrays and GEO database. qRT-PCR was used to analyze the expression of circRNA&#95;104433 in GC. The role of circRNA&#95;104433 in GC cells was evaluated based on cell cycle progression, cell proliferation, cell apoptosis, and tumor xenograft experiment assay. To explore the mechanisms of circRNA&#95;104433 in GC TCGA database, STRING version, qRT-PCR and luciferase assay were performed. Furthermore, the prognostic value of CDC25A in GC was determined based on the GEO database., Results: The level of circRNA&#95;104433 showed upregulation in GC tissues, and the expression of it showed a positive correlation with the degree of differentiation and the size of the tumor. Knockdown of circRNA&#95;104433 inhibited cell cycle transition, and cell proliferation, while promoted cell apoptosis in GC. CircRNA&#95;104433 directly binds to miR-497-5p, which directly regulates CDC25A. The median survival period of GC patients with high expression levels of CDC25A was 21.3 months, which was shorter than those with low group expression of CDC25A (35.9 months). The cell cycle proteins CDK1, CDK2, CCNB1, PKMYT1, CDC20, CHEK1 and CDC25A were coexpressed with CDC25A., Conclusion: These findings suggested that knockdown of circRNA&#95;104433 expression suppressed tumor development in GC., Competing Interests: The authors declare that they have no competing interests in this work., (© 2020 Wei et al.)

Spores are required for long-term survival of many organisms, including most fungi. For the majority of fatal human fungal pathogens, spore germination is the key process required to initiate vegetative growth and ultimately cause disease. Because germination is required for pathogenesis, the process could hold fungal-specific targets for new antifungal drug development. Compounds that inhibit germination could be developed into high efficacy, low-toxicity drugs for use in the prevention and/or treatment of fungal spore-mediated diseases. To identify drugs with the ability to inhibit pathogenic fungal spore germination, we developed a novel luciferase-based germination assay, using spores of the meningitis-causing yeast Cryptococcus. We screened the L1300 Selleck Library of FDA-approved drugs and identified 27 that inhibit germination. Of these, 22 inhibited both germination and yeast growth, and 21 have not been previously indicated for use in the treatment of fungal diseases. We quantitated the inhibition phenotypes of 10 specific germination/growth inhibitors in detail and tested one drug, the antiparasitic compound pentamidine, in our mouse intranasal model of cryptococcal infection. We discovered that pentamidine was effective at reducing lung fungal burdens when used in either prophylaxis (before infection) or treatment (after establishing an infection). Due to its efficacy in vivo and low intranasal toxicity, pentamidine is a lead candidate for repurposing for broader use as an antigerminant to prevent spore-mediated disease in immunocompromised patients. Not only does pentamidine provide an opportunity for prophylaxis against fungal spores, but it also provides proof of concept for targeting pathogenic spore germination for antifungal drug development., (Copyright © 2019 American Society for Microbiology.)

Adrenergic receptor α1 (ADRA1) subfamily members, including ADRA1A, ADRA1B and ADRA1D, are understood to participate in cardiac disease and benign prostatic hyperplasia. In addition, adrenergic signals in cell pathways can promote the development of cancer. However, little is understood regarding the associations between ADRA1 subfamily members and gastric carcinoma (GC). The present study investigated the prognostic value of the ADRA1 subfamily genes in GC. Data from a total of 379 patients with GC were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. Kaplan-Meier analysis and Cox regression analysis were used to determine associations with overall survival (OS) and to evaluate the median survival time using hazard ratios (HRs) and 95% confidence intervals (CIs). Multivariate survival analysis revealed that low expression levels of ADRA1A (HR, 0.595; 95% CI, 0.426-0.831; adjusted P=0.002) ADRA1B (HR, 0.576; 95% CI, 0.412-0.805; adjusted P=0.001) and ADRA1D (HR, 0.559; 95% CI, 0.398-0.787; adjusted P=0.001) were associated with a favourable OS. Joint-effects analysis demonstrated that combinations of low expression levels of ARDA1A, ARDA1B and ARDA1D were significantly associated with a favourable OS. Overall, the current results suggested that the mRNA expression levels of ARDA1 subfamily members may serve as potential prognostic markers for GC.

Background: Cohort studies have shown that neoadjuvant chemotherapy (NAC) is not associated with increased risk of postoperative complications and mortality as compared to upfront surgery (SURG)., Objective: The aim of this study was to compare postoperative morbidity and mortality after NAC with SURG., Patients and Methods: Patients who underwent gastrectomy with D2 lymphadenectomy for advanced gastric cancer (GC) between 2010 and 2017 were selected. The impact of neoadjuvant chemotherapy on surgical safety was investigated by using propensity score matching., Results: Three hundred and seventy-seven patients were included. After propensity score matching, 86 patients in each group were matched. The percentage of patients with one or more complications was 10.5% in NAC group and 15.1% in SURG group ( P =0.361), there was no mortality developed in either group. The total blood loss was significantly more in the NAC group than that in the SURG group (320.79 vs 243.37 ml, P <0.04). In univariate and multivariate of the matched cohort, sex, age (<70), BMI (<24), ASA grade, surgical procedure (open vs laparoscopy), gastrectomy extent, cTNM and Charlson index comorbidity were not associated with postoperative complications (all P >0.05)., Conclusion: This study showed that postoperative morbidity and mortality were similar for NAC group and SURG group., Competing Interests: The authors report no conflicts of interest in this work.

Aim: To investigate the postoperative morbidity and mortality for neoadjuvant chemotherapy (NAC) plus surgery compared with surgery alone., Methods: PubMed and Embase were searched to capture the incidence of any postoperative complications, pulmonary complications, anastomotic leakage, surgical site infections, and postoperative mortality in randomized clinical trials comparing NAC plus surgery with surgery alone. The meta-analyses were performed with a random effects model., Results: Nine relevant studies were included. Comparing NAC with surgery alone, there were no increases in any postoperative complications, pulmonary complications, anastomotic leakage, surgical site infections, or postoperative mortality attributable to NAC. Sensitivity analysis suggested a possible increased risk of any postoperative complications compared with surgery alone: the risk difference 0.056 (95% confidence interval -0.032 to 0.145). Severe complications such as anastomotic leakage and pulmonary complications were similar in the 2 groups., Conclusions: NAC for gastric cancer does not increase the risk of postoperative morbidity and mortality compared with surgery alone.

Pulmonary challenge with the ubiquitous fungus Cryptococcus neoformans results in allergic airway inflammation (AAI) characterized by robust recruitment of eosinophils and T cells producing type 2 cytokines to the lungs. Previous studies have demonstrated a critical role for Nuclear Factor Kappa B (NF-κB) activation within lung epithelial cells (LECs) in driving AAI in response to protein allergens, yet the role of LEC-intrinsic NF-κB in promoting AAI following exposure to C. neoformans is poorly understood. To investigate the role of LEC-intrinsic NF-κB in promoting AAI following C. neoformans challenge, we used IKK ∆ LEC mice, which lack canonical NF-κB activation specifically within LECs. IKK ∆ LEC and littermate control mice were intranasally challenged with 10 6 CFU of C. neoformans strain 52D, and lung tissues were collected at 7, 14 and 21 days post infection to assess the development of AAI. Notably, the absence of epithelial NF-κB signalling did not affect the magnitude or kinetics of lung eosinophilia when compared with the response in wild-type control mice. The total numbers of lung T cells producing the type 2 cytokines interleukin-5 and interleukin-13 were also unchanged in IKK ∆ LEC mice. Furthermore, IKK ∆ LEC mice showed no defect in the recruitment of protective interferon-γ-producing CD4 T cells to the lungs, fungal clearance, or host survival compared with control mice. Immunofluorescence imaging surprisingly revealed no evidence of nuclear localization of NF-κB in LECs in response to C. neoformans challenge, indicating that NF-κB is not activated within these cells. Taken together, these data strongly suggest that NF-κB signalling within LECs does not promote AAI observed in response to C. neoformans., (© 2017 John Wiley & Sons Ltd.)

Background: Previous clinical trials have demonstrated the diagnostic accuracy of magnifying narrow-band (ME-NBI) for gastric cancerous lesions, but the results are inconsistent. The purpose of this meta-analysis is to investigate the accuracy of ME-NBI in distinguishing between cancerous and noncancerous gastric lesions., Methods: Systematic literature searches were conducted until October 2016 in PubMed, Embase by 2 independent reviewers. Meta-analysis was performed to calculate the pooled sensitivity, specificity. Two authors independently evaluated studies for inclusion, rated methodological quality, and abstracted relevant data. Meta-analytic method was used to construct summary receiver operating characteristic curves, and pooled sensitivity, specificity were calculated., Results: Nine studies enrolling 5398 lesions were included. The pooled sensitivity, specificity were 88% (95% confidence interval [CI]: 78-93%), 96% (95% CI: 91-98%), respectively. The area under the curve (AUC) was 0.97. There was a large heterogeneity between the included studies. Studies with lesions ≤ 10 mm still had a high pooled sensitivity of 81% (95% CI: 73-90%) and specificity of 97% (95% CI: 95-100%). Studies which analyzed resected specimens had a sensitivity of 91% (95 CI: 82-99%) and specificity of 88% (95% CI: 83-94%), and studies which analyzed biopsied specimens had a sensitivity of 85% (95 CI: 74-96%) and specificity of 99% (95% CI: 98-99%)., Conclusions: ME-NBI is highly accurate and consistent to distinguish between gastric cancerous and noncancerous lesions.

Sporulation is a strategy widely utilized by a wide variety of organisms to adapt to changes in their individual environmental niches and survive in time and/or space until they encounter conditions acceptable for vegetative growth. The spores produced by bacteria have been the subjects of extensive studies, and several systems such as Bacillus subtilis have provided ample opportunities to understand the molecular basis of spore biogenesis and germination. In contrast, the spores of other microbes, such as fungi, are relatively poorly understood. Studies of sporulation in model systems such as Saccharomyces cerevisiae and Aspergillus nidulans have established a basis for investigating eukaryotic spores, but very little is known at the molecular level about how spores function. This is especially true among the spores of human fungal pathogens such as the most common cause of fatal fungal disease, Cryptococcus neoformans. Recent proteomic studies are helping to determine the molecular mechanisms by which pathogenic fungal spores are formed, persist and germinate into actively growing agents of human disease.

Invasive fungal diseases are generally difficult to treat and often fatal. The therapeutic agents available to treat fungi are limited, and there is a critical need for new agents to combat these deadly infections. Antifungal compound development has been hindered by the challenge of creating agents that are highly active against fungal pathogens but not toxic to the host. Host defense peptides (HDPs) are produced by eukaryotes as a component of the innate immune response to pathogens and have served as inspiration for the development of many new antibacterial compounds. HDP mimics, however, have largely failed to exhibit potent and selective antifungal activity. Here, we present an HDP-like nylon-3 copolymer that is effective against diverse fungi while displaying only mild to moderate toxicity toward mammalian cells. This polymer is active on its own and in synergy with existing antifungal drugs against multiple species of Candida and Cryptococcus , reaching levels of efficacy comparable to those of the clinical agents amphotericin B and fluconazole in some cases. In addition, the polymer acts synergistically with azoles against different species of Aspergillus , including some azole-resistant strains. These findings indicate that nylon-3 polymers are a promising lead for development of new antifungal therapeutic strategies., (Copyright © 2017 American Society for Microbiology.)

Objectives: To explore the functional effects of miR-1284 on gastric cancer cells., Results: Overexpression of miR-1284 significantly reduced SGC-7901 cell proliferation, but improved apoptosis. However, miR-1284 suppression displayed the inversed impacts. Furthermore, the protein levels of p27, Bax, procaspase-3 and active caspase-3 were up-regulated by miR-1284 overexpression, but were down-regulated by miR-1284 suppression. The level of Bcl-2 was down-regulated by miR-1284 overexpression, while it was up-regulated by miR-1284 suppression. The level of p21 was unaffected., Conclusion: These results suggest that miR-1284 overexpression might be a suppressor for gastric cancer via controlling of cell proliferation and apoptosis.

Despite the lack of resources and materials, there has been an increasing demand for acute neurologic care owing to the heavy burden of neurocritical illness in most developing countries, including China, where the morbidity and mortality of severe neurologic and neurosurgical disorders remains high. Neurointensive care units did not start appearing in China until the late 1980s. Although great progress has been made over the past 2 decades in the establishment of equipped neurocritical care centers, advancements in medical infrastructure, streamlining of resident training programs, and implementation of multidisciplinary care teams, there remain areas that warrant improvement to care for our growing patient population. Here we review and discuss the history, present state, and future of neurocritical care in the People's Republic of China., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cryptococcal meningoencephalitis is a fungal infection that predominantly affects immunocompromised patients and is uniformly fatal if left untreated. Timely diagnosis is difficult, and screening or prophylactic measures have generally not been successful. Thus, we need a better understanding of early, asymptomatic pathogenesis. Inhaled cryptococci must survive the host immune response, escape the lung, and persist within the bloodstream in order to reach and invade the brain. Here we took advantage of the zebrafish larval infection model to assess the process of cryptococcal infection and disease development sequentially in a single host. Using yeast or spores as infecting particles, we discovered that both cell types survived and replicated intracellularly and that both ultimately established a sustained, low-level fungemia. We propose that the establishment and maintenance of this sustained fungemia is an important stage of disease progression that has been difficult to study in other model systems. Our data suggest that sustained fungemia resulted from a pattern of repeated escape from, and reuptake by, macrophages, but endothelial cells were also seen to play a role as a niche for cryptococcal survival. Circulating yeast collected preferentially in the brain vasculature and eventually invaded the central nervous system (CNS). As suggested previously in a mouse model, we show here that neutrophils can play a valuable role in limiting the sustained fungemia, which can lead to meningoencephalitis. This early stage of pathogenesis-a balanced interaction between cryptococcal cells, macrophages, endothelial cells, and neutrophils-could represent a window for timely detection and intervention strategies for cryptococcal meningoencephalitis., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Gastric cancer is a prevalent disease causing a high annual death rate worldwide. Recent studies suggest the pivotal regulatory role of microRNAs in gastric cancer and the aberrant expression of microRNA-141 (miR-141) in gastric cancer cells. This study aims to explore the role and possible mechanism of miR-141 in gastric cancer prognosis and cell proliferation. A total of 30 gastric cancer patients were recruited for miR-141 level detection and a follow up of 115 weeks. Human adenocarcinoma cell line AGS was transfected with miR-141 mimic or inhibitor for cell viability, colony formation and cell cycle assays. A gastric cancer mouse model was constructed by implantation of transfected AGS cells. Insulin-like growth factor 1 receptor (IGF1R) was overexpressed in AGS cells to investigate miR-141 mechanism. Results showed that miR-141 was significantly down-regulated in gastric cancer tissue (P < 0.001). The patients with lower miR-141 levels exhibited poorer prognosis. miR-141 inhibited AGS cell viability (P < 0.01), colony formation (P < 0.01) and cell cycle (P < 0.05), and the mice implanted with miR-141 mimic cells showed an obvious smaller tumor size (P < 0.01), suggesting the anti-proliferative role of miR-141. Both the phosphorylated and total IGF1R protein levels were inhibited by miR-141, while IGF1R overexpression reversed the effects of miR-141 in AGS cell proliferation. These results indicate the potential roles of miR-141 as a prognostic factor and as a therapeutic alternative for gastric cancer. Its mechanism may be associated with IGF1R, and further research is necessary for more detail information.

Spores are an essential cell type required for long-term survival across diverse organisms in the tree of life and are a hallmark of fungal reproduction, persistence, and dispersal. Among human fungal pathogens, spores are presumed infectious particles, but relatively little is known about this robust cell type. Here we used the meningitis-causing fungus Cryptococcus neoformans to determine the roles of spore-resident proteins in spore biology. Using highly sensitive nanoscale liquid chromatography/mass spectrometry, we compared the proteomes of spores and vegetative cells (yeast) and identified eighteen proteins specifically enriched in spores. The genes encoding these proteins were deleted, and the resulting strains were evaluated for discernable phenotypes. We hypothesized that spore-enriched proteins would be preferentially involved in spore-specific processes such as dormancy, stress resistance, and germination. Surprisingly, however, the majority of the mutants harbored defects in sexual development, the process by which spores are formed. One mutant in the cohort was defective in the spore-specific process of germination, showing a delay specifically in the initiation of vegetative growth. Thus, by using this in-depth proteomics approach as a screening tool for cell type-specific proteins and combining it with molecular genetics, we successfully identified the first germination factor in C. neoformans. We also identified numerous proteins with previously unknown functions in both sexual development and spore composition. Our findings provide the first insights into the basic protein components of infectious spores and reveal unexpected molecular connections between infectious particle production and spore composition in a pathogenic eukaryote.

Among pathogenic environmental fungi, spores are thought to be infectious particles that germinate in the host to cause disease. The meningoencephalitis-causing yeast Cryptococcus neoformans is found ubiquitously in the environment and sporulates in response to nutrient limitation. While the yeast form has been studied extensively, relatively little is known about spore biogenesis, and spore germination has never been evaluated at the molecular level. Using genome transcript analysis of spores and molecular genetic approaches, we discovered that trehalose homeostasis plays a key role in regulating sporulation of C. neoformans, is required for full spore viability, and influences virulence. Specifically, we found that genes involved in trehalose metabolism, including a previously uncharacterized secreted trehalase (NTH2), are highly overrepresented in dormant spores. Deletion of the two predicted trehalases in the C. neoformans genome, NTH1 and NTH2, resulted in severe defects in spore production, a decrease in spore germination, and an increase in the production of alternative developmental structures. This shift in cell types suggests that trehalose levels modulate cell fate decisions during sexual development. We also discovered that deletion of the NTH2 trehalase results in hypervirulence in a murine model of infection. Taken together, these data show that the metabolic adaptations that allow this fungus to proliferate ubiquitously in the environment play unexpected roles in virulence in the mammalian host and highlight the complex interplay among the processes of metabolism, development, and pathogenesis., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Background: Little is known about the optimal cut-off point of fasting plasma glucose for the diagnosis of gestational diabetes mellitus for pregnant Chinese women. This study investigates the relationship between gestational fasting plasma glucose and several variables: neonatal birth weight, prenatal blood pressure and dystocia rate of pregnant women. In this study, we hoped to provide a useful tool to screen gestational diabetes mellitus in pregnant Chinese women., Methods: For 1058 pregnant women enrolled in our hospital at pregnancy weeks 22-30, fasting plasma glucose, neonatal birth weight and prenatal blood pressure, as well as dystocia conditions, were examined. We analysed the correlations between the following: gestational fasting plasma glucose and neonatal birth weight; prenatal blood pressure and gestational fasting plasma glucose as well as dystocia rate and gestational fasting plasma glucose group., Results: A modest correlation was observed between gestational fasting plasma glucose and neonatal birth weight (r = 0.093, p = 0.003). The macrosomia rate was smallest when the gestational fasting plasma glucose was in the range 3.51-5.5 mmol/L. Prenatal blood pressure increased linearly with increasing gestational fasting plasma glucose (p = 0.000). There was a significant difference between the dystocia rates in different fasting plasma glucose groups (chi-squared = 13.015, p = 0.043). The results showed that the dystocia rate significantly increased when gestational fasting plasma glucose was >4.9 mmol/L; p = 0.03, OR = 2.156 (95% CI, 1.077-4.318)., Conclusion: We suggest that the optimal range of gestational fasting plasma glucose for pregnant Chinese women is in the range 3.5-4.9 mmol/L., (Copyright © 2014 John Wiley & Sons, Ltd.)