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Abstract Background Definitive concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced, inoperable non-small cell lung cancer (NSCLC). Previous studies have mainly focused on examining local failure and recurrence patterns after surgery and the principles of lymph node metastasis (LNM) in surgical candidates with NSCLC. However, these studies were just only able to guide postoperative radiotherapy (PORT) and the patterns of LNM in patients with resected NSCLC was inadequate to represent that in locally advanced inoperable NSCLC patients for guiding target volume delineation of CCRT. In this study, we aimed to analyze the metastasis regularities and establish the correlations between different lymph node levels in NSCLC patients without any intervention using positron emission tomography/computed tomography (PET/CT) images. Methods Overall, 358 patients with N1–N3 NSCLC admitted in our hospital between 2018 and 2022 were retrospectively analyzed. The diagnosis of metastatic lymph nodes was reviewed and determined using the European Organization for Research and Treatment of Cancer standard and the standardized value of the PET/CT examination. Univariate and multivariate analysis were performed to investigate the correlations between the different levels were evaluated by using of the chi-square test and logistic regression model. Results The lymph nodes with the highest metastasis rates in patients with left lung cancer were in order as follows: 10L, 4L, 5, 4R, and 7; while in those with right lung cancer they were 10R, 4R, 7, 2R, and 1R. Notably, we found left lung patients were more likely to have contralateral hilar, mediastinal and supraclavicular lymph nodes involved, and the right lung group exhibited a higher propensity for ipsilateral mediastinum and supraclavicular lymph node invasion. Furthermore, correlation analysis revealed there were significant correlative patterns in the LNM across different levels. Conclusions This study elucidated the patterns of primary LNM in patients with NSCLC who had not undergone surgery (without any treatment interventions) and the correlations between lymph node levels. These findings were expected to provide useful reference for target volume delineation in definitive concurrent chemoradiotherapy in locally advanced NSCLC patients.

Background: Radiotherapy (RT) for breast cancer (BC) may raise the risk of second primary cancers (SPCs), a relationship inadequately studied. Methods: We analyzed 248268 female BC patients from 9 SEER registries, 1988–2018, identifying SPCs >5 years after initial treatment, comparing SPC risks between RT and non-RT cohorts using Fine-Gray and Poisson regressions. Results: Of all participants, 55.4 % received surgery and RT. The RT group had a higher SPC incidence, with excess incidence significantly dropped from 6.9 % in 1990 to 0.2 % in 2012. The 30-year SPC incidence was 24.69 % in the RT cohort and 18.11 % in the NRT cohort. RT increased the risk of SPCs(HR, 1.29 [95%CI,1.26–1.33]; P

Dispersive soil is a common problem soil in engineering projects, which has the potential risk of causing serious engineering failures. In this paper, calcined waste phosphorus slag (CPS) was chosen to enhance the mechanical properties and reduce soil dispersivity. Dispersive soil samples with 1 % to 10 % CPS content were prepared and cured for 0 to 28 days. The dispersivity identification test was used to assess soil sample dispersivity. The compressive and tensile strength, conductivity, and pH were determined for the soil. Microstructural and mineral composition were analyzed using SEM/EDS, TG/DTG, and XRD analysis. The natural dispersive soil was selected to verify the effect of CPS in improving soil. Experiments show that the CPS inhibits soil dispersivity and converts it into non-dispersive soil. Both compressive and tensile strength increases significantly with the increase in the content of CPS and curing time. The tensile strength of the soil samples cured for 28 days increased by about 76 % and the compressive strength by about 61 % as the mixed content of CPS was increased from 1 % to 10 %. Results show that CPS can improve the strength and modify the dispersivity of soil, its optimal mixing content is 5 %. In addition, using CPS in dispersive soil could also solve the disposal problem of phosphate slag, which is a win-to-win solution.

Background: Extranodal natural killer/T-cell lymphoma (ENKTCL) has a unique treatment principle. However, the optimal combination of drugs along with radiotherapy (RT) is unknown. Design: Retrospective cohort study. Objectives: We screened multiple drug combinations to identify the most efficacious therapeutic combinations. Methods: We reviewed 3105 patients who received 40 chemotherapy regimens with different combinations of 9 drug classes and/or RT. Least absolute shrinkage and selection operator and multivariable Cox regression analyses were used to screen efficacious single drugs and identify optimal combinations for overall survival (OS). Inverse probability of treatment weighting (IPTW) and multivariable analyses were used to compare survival between treatment regimens. Results: Screening and validation revealed RT, asparaginase (ASP), and gemcitabine (GEM) to be the most efficacious single modality/drug. RT remained an important component of first-line treatment, whereas ASP was a fundamental drug of non-anthracycline (ANT)-based regimens. Addition of RT to non-ANT-based or ASP/GEM-based regimens, or addition of an ASP-drug into ANT-based or GEM/platinum-based regimens, improved 5-year OS significantly. Use of ASP/GEM-based regimens was associated with significantly higher 5-year OS (79.9%) compared with ASP/ANT-based (69.2%, p = 0.001), ASP/methotrexate-based (63.5%, p = 0.011), or ASP/not otherwise specified-based (63.2%, p

Background: Acute acquired comitant esotropia (AACE) is a rare subtype of esotropia that occurs after infancy. The exact pathogenesis of AACE remains unknown with aetiologies ranging from benign conditions to serious underlying neurological diseases being reported. Given the elusive characteristic of AACE, diagnostic and management guidelines remain unclear. This systematic review aims to contribute to this field by summarising the risk factors for AACE reported thus far. Methods: A systematic review was conducted with papers found in CINAHL, MEDLINE, Cochrane library, PubMed databases and other sources. Eligible studies investigating the risk factors for, and clinical features of, AACE in children and young adults were critically appraised before relevant data were extracted and discussed via a narrative summary. Results: Twelve studies were included in the final review, of which six and eight papers reported on benign and non-benign risk factors for AACE respectively. Identified benign risk factors varied among studies, while non-benign risk factors were associated with intracranial pathologies, multiple sclerosis and head trauma. Conclusion: Given the low generalisability of study findings, no definitive conclusions can be drawn on the significance of each risk factor on AACE development. Further prospective research with more objective measurements of ‘near work’, larger sample sizes and control groups is required to better ascertain any cause-effect relationship, refine the diagnostic criteria for each AACE subtype and advise on appropriate management guidelines for AACE.

To evaluate the effects of varying proportions of yak meat in feed on the growth of rats and provide a theoretical basis for selecting the optimal feed proportion suitable for rats. This study was designed as a one-variable experiment. Fifty male rats were divided into five groups. The ratios of yak meat to basal feed of rats in four dietary treatment groups were 2:8, 4:6, 6:4, and 8:2, respectively, while those in the control group were only provided a basal diet. In the feeding experiment, the body weights of the rats were recorded on Day 0 and subsequently in the first, second, third, and fourth weeks, along with quantities of feed intake. The body and tail lengths, as well as the waist circumference of the rats, were measured, and blood samples were collected in the fourth week for routine blood and biochemistry investigations. The rats in the 4:6 feed group had the best body condition. They had normal body and tail lengths, smaller waist circumferences, good posture, and were in better overall health than rats in the other groups. The results indicate that the 4:6 diet was optimal for enhancing rats’ growth performance compared to the other diets.

Abstract Purpose Local primary-recurrence of esophageal squamous cell carcinoma (ESCC) after definitive treatment has the potential for increasing overall survival with re-irradiation (Re-RT), especially with advanced technique. This study aimed to evaluate the efficacy and toxicities of Re-RT using intensity-modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) for local primary-recurrence of ESCC. Materials and methods A total of 130 ESCC patients with local primary-recurrence from Xijing hospital between 2008 and 2021 were enrolled and 30 patients underwent IMRT/VMAT based salvage Re-RT. Cox regression analysis was used to analyze the prognostic factors for overall survival (OS) and after recurrence survival (ARS). The toxicities of 30 patients receiving Re-RT were also assessed. Results The median OS and ARS of the 130 recurrent patients were 21 months (1−164 months) and 6 months (1−142 months). The 1-, 2-, and 3-year OS rates were 81.5%, 39.2%, and 23.8%, respectively. Besides, the 1-, 2-, and 3-year ARS rates were 30.0%, 10%, and 6.2%. Multivariate analysis showed that Re-RT ± chemotherapy (p = 0.043) and chemotherapy alone (p 12 months) and initial radiation dose (> 60 Gy) were significantly associated with improved OS. Radiation esophagitis (Grade 1–2) occurred in 16 patients and myelosuppression (Grade1−2) occurred in 10 patients. Grade 3 toxicities (radiation esophagitis and myelosuppression) were only 13.3%. There were no grade 4 toxicities. Conclusion Our results demonstrated that IMRT/VMAT-based Re-RT was an effective therapeutic option for ESCC patients with local primary-recurrence compared with chemotherapy alone or without any treatment. Re-RT had improved OS but unfavorable ARS.

Abstract Background Filamentous fungi are extensively exploited as important enzyme producers due to the superior secretory capability. However, the complexity of their secretomes greatly impairs the titer and purity of heterologous enzymes. Meanwhile, high-efficient evaluation and production of bulk enzymes, such as biomass-degrading enzymes, necessitate constructing powerful expression systems for bio-refinery applications. Results A novel sucrose-inducible expression system based on the host strain Aspergillus niger ATCC 20611 and the β-fructofuranosidase promoter (PfopA) was constructed. A. niger ATCC 20611 preferentially utilized sucrose for rapid growth and β-fructofuranosidase production. Its secretory background was relatively clean because β-fructofuranosidase, the key enzyme responsible for sucrose utilization, was essentially not secreted into the medium and the extracellular protease activity was low. Furthermore, the PfopA promoter showed a sucrose concentration-dependent induction pattern and was not subject to glucose repression. Moreover, the strength of PfopA was 7.68-fold higher than that of the commonly used glyceraldehyde-3-phosphate dehydrogenase promoter (PgpdA) with enhanced green fluorescence protein (EGFP) as a reporter. Thus, A. niger ATCC 20611 coupled with the PfopA promoter was used as an expression system to express a β-glucosidase gene (bgla) from A. niger C112, allowing the production of β-glucosidase at a titer of 17.84 U/mL. The crude β-glucosidase preparation could remarkably improve glucose yield in the saccharification of pretreated corncob residues when added to the cellulase mixture of Trichoderma reesei QM9414. The efficacy of this expression system was further demonstrated by co-expressing the T. reesei-derived chitinase Chi46 and β-N-acetylglucosaminidase Nag1 to obtain an efficient chitin-degrading enzyme cocktail, which could achieve the production of N-acetyl-D-glucosamine from colloidal chitin with a conversion ratio of 91.83%. Besides, the purity of the above-secreted biomass-degrading enzymes in the crude culture supernatant was over 86%. Conclusions This PfopA-driven expression system expands the genetic toolbox of A. niger and broadens the application field of the traditional fructo-oligosaccharides-producing strain A. niger ATCC 20611, advancing it to become a high-performing enzyme-producing cell factory. In particular, the sucrose-inducible expression system possessed the capacity to produce biomass-degrading enzymes at a high level and evade endogenous protein interference, providing a potential purification-free enzyme production platform for bio-refinery applications.

Abstract This study aimed to investigate the characteristics and prognosis of distant metastasis (DM) after primary treatment for early‐stage extranodal nasal‐type natural killer (NK)/T‐cell lymphoma (ENKTCL). A total of 1619 patients from the China Lymphoma Collaborative Group database were retrospectively reviewed. The cumulative incidence of DM was assessed using Fine and Gray's competing risk analysis. The correlation between DM sites was evaluated using phi coefficients, while DM sites were classified using hierarchical clustering. Regression analysis was used to assess the linear correlation between DM‐free survival (DMFS) and overall survival (OS). The 5‐year cumulative DM rate was 26.2%, with the highest annual hazard rate being in the first year (14.9%). The most frequent DM sites were the skin and soft tissues (SSTs, 32.4%) and distant lymph nodes (LNs, 31.3%). DM sites were categorized into four subgroups of distinct prognosis — distant LN, SST, extracutaneous site, and lymphoma‐associated hemophagocytic lymphohistiocytosis. SST or distant LN, solitary metastasis, and late‐onset DM demonstrated a relatively favorable prognosis. Contemporary chemotherapy significantly decreased DM rates and improved DMFS. Decreased DM rates were further associated with increased OS probabilities. Our findings improve the understanding of the variable clinical behaviors of early‐stage ENKTCL based on four distinct DM sites and thus provide guidance for future therapeutic decisions, metastatic surveillance, and translational trial design.

Purpose: To assess the influence of age as a continuous variable on the prognosis of pT1-2N1 breast cancer and examine its decision-making value for postmastectomy radiotherapy (PMRT). Methods: We retrospectively evaluated 5438 patients with pT1-2N1 breast cancer after mastectomy in 11 hospitals. A multivariable Cox proportional hazards regression model with penalized splines was used to examine the relationship between age and oncologic outcomes. Results: The median follow-up was 67.0 months. After adjustments for confounding characteristics, nonsignificant downward trend in locoregional recurrence (LRR) risk was observed with increasing age (P-non-linear association = 0.640; P-linear association = 0.078). A significant non-linear association was found between age and disease-free survival (DFS) and overall survival (OS) (P-non-linear association 0.05, respectively). The DFS and OS exhibited U-shaped relationships, with the hazard ratios (HRs), reaching a nadir at 50 years old. A decreased risk of LRR with PMRT vs. no PMRT (HR = 0.304, 95% CI: 0.204–0.454) was maintained in all ages. The HR of PMRT vs. no PMRT for DFS and OS gradually increased with age. In patients ≤50 years old, PMRT was independently associated with favorable LRR, DFS, and OS, all P 50 years old, PMRT was independently associated with reduced LRR (P = 0.004), but had no effect on DFS or OS. Conclusions: Age was an independent prognostic factor for pT1-2N1 breast cancer; PMRT provided survival benefits for patients ≤50 years old, but not for patients >50 years old.

The cellular mechanisms mediating norepinephrine (NE) functions in brain to result in behaviors are unknown. We identified the L-type Ca2+ channel (LTCC) CaV1.2 as a principal target for Gq-coupled α1-adrenergic receptors (ARs). α1AR signaling increased LTCC activity in hippocampal neurons. This regulation required protein kinase C (PKC)-mediated activation of the tyrosine kinases Pyk2 and, downstream, Src. Pyk2 and Src were associated with CaV1.2. In model neuroendocrine PC12 cells, stimulation of PKC induced tyrosine phosphorylation of CaV1.2, a modification abrogated by inhibition of Pyk2 and Src. Upregulation of LTCC activity by α1AR and formation of a signaling complex with PKC, Pyk2, and Src suggests that CaV1.2 is a central conduit for signaling by NE. Indeed, a form of hippocampal long-term potentiation (LTP) in young mice requires both the LTCC and α1AR stimulation. Inhibition of Pyk2 and Src blocked this LTP, indicating that enhancement of CaV1.2 activity via α1AR–Pyk2–Src signaling regulates synaptic strength.

Abstract Background The gastrointestinal (GI) tract is the second most frequent extranasal involvement site for ENKTL. This study aimed to explore the clinicopathological features, treatment models, survival outcomes, and prognosis of gastrointestinal ENKTL (GI‐ENKTL). Methods The clinical data of GI‐ENKTL patients were extracted from the China Lymphoma Collaborative Group (CLCG) database and were analyzed retrospectively. Results A total of 30 patients were enrolled, with a male/female ratio of 4:1 and a median age of 42 years. Twenty‐nine patients received chemotherapy, of whom 15 patients received asparaginase‐based (ASP‐based) regimens. Moreover, seven received surgery and three received radiotherapy. The overall response an d complete remission rates were 50.0% and 30.0% for the whole cohort, 50.0% and 37.5% for patients treated with ASP‐based regimens, and 50.0% and 25.0% for those treated with non‐ASP‐based regimens, respectively. The median follow‐up was 12.9 months and the 1‐year overall survival rate was 40.0% for the whole cohort. For those patients in an early stage, ASP‐based regimens resulted in a superior 1‐year progression‐free survival rate compared to non‐ASP‐based regimens (100.0% vs. 36.0%, p = .07). However, ASP‐based regimens did not improve survival in patients at an advanced stage. Conclusion GI‐ENKTL still has a poor prognosis, even in the era of modern asparaginase‐based treatment strategies.

Cellulose degradation results from the synergistic effect of different enzymes, but which enzyme is involved in the initial stage of cellulose degradation is still not well understood. Cellobiohydrolase 2 (CBH2) attached to the conidial surface is possibly associated with the initial stage. However, its specific mechanism is still incompletely known. This study explored the potential role of CBH2 in initiating cellulose degradation using a constitutive overexpression strategy. First, the CBH2-overexpression Trichoderma reesei strains Qgc2–5 and Qrc2–40 were constructed using the constitutive promoters Pgpd1 and PrpS30, respectively. It was found that cbh2 was expressed at a high level under the glucose conditions and was significantly higher than that of the parental strain QM9414 at the early stage of 29 h when cellulose was used as the carbon source. Particularly, the constitutive overexpression of cbh2 caused the strong expression of major cellulase-encoding genes (cbh1, eg1, and eg2) and the rapid decomposition of cellulosic material. Meanwhile, the scanning electron microscope showed that the groove-like structure of the cellulose surface was eroded seriously owing to CBH2 overexpression, which caused the cellulose surface to be smooth. These results showed that the overexpression of CHB2 caused the major cellulase enzymes to be expressed and contributed to cellulose degradation, showing the potential role of CBH2 in the initial stage of the cellulose hydrolytic process.

The standard of care for locally advanced cervical cancer is concurrent chemoradiotherapy, which is associated with significant toxicity, especially hematologic toxicity. To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing neutropenia during radical chemoradiotherapy for cervical cancer, 40 patients receiving prophylaxis from February 2018 to July 2019 were randomly divided into two arms in a 1:1 ratio. Patients in the study arm (N = 21) received PEG-rhG-CSF, while patients in the control arm (N = 19) received short-acting rhG-CSF. The primary endpoint was the incidence of grade 3–4 neutropenia, and the secondary endpoints were the incidence of febrile neutropenia, chemotherapy delay, and radiotherapy interruption. In addition, dynamic changes in absolute neutrophil count during radical chemoradiotherapy and adverse events were compared between the two groups. There were 0 and 4 cycles of grade 3–4 neutropenia in the PEG-rhG-CSF and rhG-CSF groups, respectively. The incidence of neutropenia of all grades was lower in patients on PEG-rhG-CSF than on rhG-CSF [24.05% (19/79) vs. 56.94% (41/72); p < 0.001]. No patient developed neutropenic fever. The lowest values of neutropenia during concurrent chemoradiotherapy cycles were 2.73 ± 1.02 and 1.91 ± 0.79 × 10 9/ml in the PEG-rhG-CSF and rhG-CSF groups, respectively (p < 0.001). In the PEG-rhG-CSF and rhG-CSF groups, 0 and 8 (11.11%) cycles of chemotherapy were delayed due to neutropenia, respectively (p = 0.01). There was no delay of radiotherapy by more than one week in either group. Prophylactic use of PEG-rhG-CSF during chemoradiotherapy for cervical cancer can effectively prevent neutropenia and associated adverse events. PEG-rhG-CSF may be an effective strategy to provide uninterrupted radical chemoradiotherapy for cervical cancer.

Survival from extranodal nasal-type NK/T-cell lymphoma (ENKTCL) has substantially improved over the last decade. However, there is little consensus as to whether a population of patients with ENKTCL can be considered “cured” of the disease. We aimed to evaluate the statistical “cure” of ENKTCL in the modern treatment era. This retrospective multicentric study reviewed the clinical data of 1,955 patients with ENKTCL treated with non-anthracycline-based chemotherapy and/or radiotherapy in the China Lymphoma Collaborative Group multicenter database between 2008 and 2016. A non-mixture cure model with incorporation of background mortality was fitted to estimate cure fractions, median survival times and cure time points. The relative survival curves attained plateau for the entire cohort and most subsets, indicating that the notion of cure was robust. The overall cure fraction was 71.9%. The median survival was 1.1 years in uncured patients. The cure time was 4.5 years, indicating that beyond this time, mortality in ENKTCL patients was statistically equivalent to that in the general population. Cure probability was associated with B symptoms, stage, performance status, lactate dehydrogenase, primary tumor invasion, and primary upper aerodigestive tract site. Elderly patients (>60 years) had a similar cure fraction to that of younger patients. The 5-year overall survival rate correlated well with the cure fraction across risk-stratified groups. Thus, statistical cure is possible in ENKTCL patients receiving current treatment strategies. Overall probability of cure is favorable, though it is affected by the presence of risk factors. These findings have a high potential impact on clinical practice and patients’ perspective.

Objective: To clarify the effect of postmastectomy radiotherapy (PMRT) on pT1-2N1 breast cancer patients with different molecular subtypes. Methods: We retrospectively analyzed the data of 5442 patients with pT1-2N1 breast cancer treated using modified radical mastectomy in 11 hospitals in China. Univariate, multivariate, and propensity score matching (PSM) analyses were used to evaluate the effect of PMRT on locoregional recurrence (LRR). Results: With a median follow-up duration of 63.8 months, the 5-year LRR rates were 4.0% and 7.7% among patients treated with and without PMRT, respectively (p

Myeloperoxidase is an important inflammatory factor in the myeloid system, primarily expressed in neutrophils and microglia. Myeloperoxidase and its active products participate in the occurrence and development of hemorrhagic and ischemic stroke, including damage to the blood-brain barrier and brain. As a specific inflammatory marker, myeloperoxidase can be used in the evaluation of vascular disease occurrence and development in stroke, and a large amount of experimental and clinical data has indicated that the inhibition or lack of myeloperoxidase has positive impacts on stroke prognosis. Many studies have also shown that there is a correlation between the overexpression of myeloperoxidase and the risk of stroke. The occurrence of stroke not only refers to the first occurrence but also includes recurrence. Therefore, myeloperoxidase is significant for the clinical evaluation and prognosis of stroke. This paper reviews the potential role played by myeloperoxidase in the development of vascular injury and secondary brain injury after stroke and explores the effects of inhibiting myeloperoxidase on stroke prognosis. This paper also analyzes the significance of myeloperoxidase etiology in the occurrence and development of stroke and discusses whether myeloperoxidase can be used as a target for the treatment and prediction of stroke.

This study investigated cold plasmas for multiple biological applications. Our previous work has found dielectric barrier discharge plasma improves chicken sperm quality. The number of Sertoli cells (SCs) decides spermatogenesis. However, whether cold plasma can regulate SC proliferation remains unclear. This study explored the effects of cold plasma on immature chicken SC proliferation and the regulation mechanism. Results showed that cold plasma exposure at 2.4 W for 30 s twice with an interval of 6 h produced (P

The salinization of several hundred million hectares of land poses a serious threat to global food security and biodiversity. Biochar and wood vinegar amendment has been suggested as a possible way to promote plant productivity and improve soil qualities, whereas less emphasis has been placed on the application of biochar in saline−alkaline soils to increase plant productivity. Herein, the single and composite application of sawdust biochar, wood vinegar, and acid-modified biochar on the restoration of coastal saline−alkali soil and plant growth of strawberry seedlings was investigated. Proximate and ultimate analyses and different characterization techniques such as FTIR and scanning electron microscopy were applied to study the physicochemical characteristics of raw and modified biochar. A pot experiment was conducted to explore the effects of different soil additives on soil properties and strawberry growth. Our results revealed that acid-modified biochar shows the most significant promoting effect on strawberry growth, which could increase the weight gain rate, root length, root specific surface area, and root volume of strawberry seedlings by 41.2%, 18.9%, 23.0%, and 34.7%, respectively. Moreover, the application of acid-modified biochar can effectively alleviate soil salinization by reducing soil pH (7.65) and CEC (19.5 cmol/kg). Furthermore, the addition of biochar can significantly improve the community structure of microorganisms (Proteobacteria) and increase the content of bacteria related to soil nutrient cycling (Pseudomonadaceae and Sphingomonadaceae). Preliminary findings from this study suggested that acid-modified biochar is a potentially effective means of preventing soil salinization and increasing economic crop yields.

BackgroundLung cancer is the leading malignant disease and cause of cancer-related death worldwide. Most patients with lung cancer had insignificant early symptoms so that most of them were diagnosed at an advanced stage. In addition to factors such as smoking, pollution, lung microbiome and its metabolites play vital roles in the development of lung cancer. However, the interaction between lung microbiota and carcinogenesis is lack of systematically characterized and controversial. Therefore, the purpose of this study was to excavate the features of the lung microbiota and metabolites in patients and verify potential biomarkers for lung cancer diagnosis.MethodsLung tissue flushing solutions and bronchoalveolar lavage fluid samples came from patients with lung cancer and non-lung cancer. The composition and variations of the microbiota and metabolites in samples were explored using muti-omics technologies including 16S rRNA amplicon sequencing, metagenomics and metabolomics.ResultsThe metabolomics analysis indicated that 40 different metabolites, such as 9,10-DHOME, sphingosine, and cysteinyl-valine, were statistically significant between two groups (VIP > 1 and P < 0.05). These metabolites were significantly enriched into 11 signal pathways including sphingolipid, autophagy and apoptosis signaling pathway (P < 0.05). The analysis of lung microbiota showed that significant changes reflected the decrease of microbial diversity, changes of distribution of microbial taxa, and variability of the correlation networks of lung microbiota in lung cancer patients. In particular, we found that oral commensal microbiota and multiple probiotics might be connected with the occurrence and progression of lung cancer. Moreover, our study found 3 metabolites and 9 species with significantly differences, which might be regarded as the potential clinical diagnostic markers associated with lung cancer.ConclusionsLung microbiota and metabolites might play important roles in the pathogenesis of lung cancer, and the altered metabolites and microbiota might have the potential to be clinical diagnostic markers and therapeutic targets associated with lung cancer.

Abstract Background Cranial nerve (CN) palsy due to cancer involvement has been considered as an unfavorable prognostic factor for patients with nasopharyngeal carcinoma (NPC). We assessed the role of IMRT based treatment on the recovery of CN palsy and investigated the prognostic value of complete recovery of CN palsy. Methods A total of 115 NPC patients with cancer-related CN palsy were included in the study. We referred CTCAE version 5.0 to evaluate the grade of CN palsy. Results All patients with grade 1 CN palsy recovered completely during the 2 years of follow-up after definite treatment. Most grade 2 palsy could change gradually to grade 1 palsy or complete recovery during 2 years of follow-up. Patients with more than 2 symptoms of CN palsy had poor 3-year disease-free survival (DFS) than these with 1 or 2 symptoms (60.3% vs. 84.9%, HR 0.25, 95% CI 0.07–0.89, P = 0.001). There were no significant differences for PFS, OS, DMFS and LRFS between patients with complete recovery and non-complete recovery from CN palsy after receiving IMRT based comprehensive treatment. Conclusions IMRT based comprehensive treatment could effectively promote the recovery of tumor-related CN palsy for NPC patient. More than 2 symptoms of CN palsy was a poor prognostic factor for DFS of NPC patients. The prognostic role of complete recovery of CN palsy was not identified in our study.

Abstract. Objective:. Laboratory diagnosis of neurosyphilis (NS) remains a great challenge. This study was the aimed to identify miRNA candidates as biomarkers to distinguish between NS, non-neurosyphilis, and healthy controls (HCs). Methods:. We analyzed miRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from six patients with NS, eight patients with secondary syphilis (SS), and five HCs using microarray technology. The differentially expressed miRNAs were validated in 33 NS samples, 31 SS samples, and 30 HC samples using TaqMan miRNA real-time qPCR (qRT-PCR). Results:. Thirty-nine miRNAs were differentially expressed in SS and NS patients compared with HCs. Thirteen miRNAs were randomly selected to validate their expression levels in the same samples used in microarray assay by qRT-PCR. All miRNAs were upregulated in SS and NS samples compared with HC. qRT-PCR analysis of the expression of the 13 miRNAs in a second cohort (76 samples) showed that the average expression levels of nine miRNAs were higher in SS than in NS (SS: 0.185, NS: 0.136, P=3.8E-10), while the expressions of the other four miRNAs were lower in SS than in NS (SS: 0.000757, NS: 0.000873, P=0.022). ROC curve analysis of the 13 miRNAs showed the area under the curve value to be 1.00 for distinguishing SS patients from HCs, 1.00 for distinguishing NS patients from HCs, 1.00 for distinguishing SS and NS patients from HCs, and 0.968 for distinguishing NS from SS patients. Conclusion:. The present study is the first one that identified differentially expressed miRNAs in PBMCs from patients with NS. Our results suggest that the 13 candidate miRNAs in PBMCs may be novel noninvasive biomarkers for NS diagnosis.

ObjectiveTo propose a new definition of partial remission (PR) for patients with type 1 diabetes (T1D) of all-ages using insulin dose and glycated albumin (GA), and find the optimal cut-off values for stimulated C-peptide to diagnose PR in different age-groups.Research Design and MethodsPatients with newly diagnosed T1D (n=301) were included. GA/insulin dose was used to diagnose PR, and insulin dose-adjusted glycated albumin (IDAGA) was proposed to facilitate clinical application. The optimal diagnostic levels of IDAGA and stimulated C-peptide were determined in different age-groups (≤ 12y, 12-18y and ≥ 18y). Furthermore, the diagnostic consistency between different PR definitions was studied.ResultsGA≤ 23%/insulin dose ≤ 0.5u/kg/day was used to define PR, and IDAGA (GA (%) + 40 * insulin dose(u/kg/day)) ≤ 40 was feasible in all age-groups. Whereas, the optimal diagnostic level showed difference for stimulated C-peptide (265.5, 449.3 and 241.1 pmol/L for the ≤ 12y, 12-18y and ≥ 18y age-group, respectively). About 40% of patients met the PR definition by stimulated C-peptide but not GA/insulin dose or IDAGA, who showed dyslipidemia and higher insulin resistance.ConclusionsA new definition of the PR phase is proposed using GA/insulin dose, and the calculated IDAGA≤ 40 applies to all age-groups. The stimulated C-peptide to diagnose PR is the highest in the 12-18y age-group, which reflects the effect of puberty on metabolism. For patients with insulin resistance, it is not recommended to use stimulated C-peptide alone to diagnose PR.

Abstract Background Sexual compulsivity (SC) and its relationship with unprotected intercourse (UI) have long been an intriguing topic, but its existential meaning in the management of public health or, more precisely, sexually transmitted infections (STIs) has rarely been studied to date. This study examines whether SC plays a role in UI among sexually active STI patients. Method A cross-sectional study was conducted in two sexual transmitted disease (STD) clinicals of Shanghai Skin Diseases Hospital in Shanghai. Totally 664 sexually active STI patients were included. Results The ages of the 664 participants ranged from 18 to 76 years, with 58.73% between 26 and 40 years old. 449 (191 male and 258 female) reported had UI during the past 6 months. Although the only statistically significant difference (p

Abstract Background Glioma stem cells (GSCs) are glioma cells with stemness and are responsible for a variety of malignant behaviors of glioma. Evidence has shown that signals from tumor microenvironment (TME) enhance stemness of glioma cells. However, identification of the signaling molecules and underlying mechanisms has not been completely elucidated. Methods Human samples and glioma cell lines were cultured in vitro to determine the effects of adenovirus (ADV) infection by sphere formation, RT-qPCR, western blotting, FACS and immunofluorescence. For in vivo analysis, mouse intracranial tumor model was applied. Bioinformatics analysis, gene knockdown by siRNA, RT-qPCR and western blotting were applied for further mechanistic studies. Results Infection of patient-derived glioma cells with ADV increases the formation of tumor spheres. ADV infection upregulated stem cell markers and in turn promoted the capacities of self-renewal and multi-lineage differentiation of the infected tumor spheres. These ADV infected tumor spheres had stronger potential to form xenograft tumors in immune-compromised mice. GSCs formation could be promoted by ADV infection via TLR9, because TLR9 was upregulated after ADV infection, and knockdown of TLR9 reduced ADV-induced GSCs. Consistently, MYD88, as well as total STAT3 and phosphorylated (p-)STAT3, were also upregulated in ADV-induced GSCs. Knockdown of MYD88 or pharmaceutical inhibition of STAT3 attenuated stemness of ADV-induced GSCs. Moreover, we found that ADV infection upregulated lncRNA NEAT1. Knockdown of NEAT1 impaired stemness of ADV-induced GSCs. Lastly, HMGB1, a damage associated molecular pattern (DAMP) that triggers TLR signaling, also upregulated stemness markers in glioma cells. Conclusion ADV, which has been developed as vectors for gene therapy and oncolytic virus, promotes the formation of GSCs via TLR9/NEAT1/STAT3 signaling. Video abstract

ABSTRACT Treponema pallidum can invade any organ, and T. pallidum DNA can be detected in various tissues and fluids. However, the knowledge of the presence and loads of T. pallidum DNA in urine is limited. For this study, we enrolled 208 syphilis patients (34 primary syphilis, 61 secondary syphilis, 68 latent syphilis, and 45 symptomatic neurosyphilis) and collected urine and plasma samples from them. polA and Tpp47 genes were amplified in urine supernatant, urine sediment, and plasma using nested PCR and droplet digital PCR assays. The detection rates were 14.9% (31 of 208) and 24.2% (50 of 207) in urine supernatant and sediment, respectively (P = 0.017). The detection rates of T. pallidum DNA in urine sediment were 47.1, 47.5, 4.4, and 4.5% for primary, secondary, latent, and symptomatic neurosyphilis, respectively. After treatment, T. pallidum DNA in urine in 20 syphilis patients turned negative. Loads of T. pallidum DNA in urine sediment were significantly higher than those in plasma and urine supernatant (both P

ObjectiveThe study aims to investigate if a relationship exists between vaginal doses and vaginal stenosis (VS) using posterior–inferior border of symphysis (PIBS) points and the International Commission on Radiation Units-Rectum (ICRU-R) point evaluation system for definitive radio(chemo)therapy in locally advanced cervical cancer.Methods and MaterialsFrom a vaginal dose study in China, 351 patients were prospectively assessed. For every reference point of the PIBS system and ICRU-R point was calculated for all BT and summed with EBRT. Pearson’s chi-square test and Student’s unpaired t-test compared variables with and without vaginal stenosis (VS) G ≥2. The risk factors were assessed for VS G ≥2 in multi- and univariate analyses through Cox proportional hazards model followed by a dose–effect curve construction. The VS morbidity rate was compared via the log-rank test using the median vaginal reference length (VRL).ResultsThe patients (38-month median follow-up) had 21.3% three-year actuarial estimate for VS G ≥2. Compared to G 4.6 cm, the 3-year actuarial estimate was 12.8% vs. 29.6% for VRL ≤4.6 cm. According to the model curve, the risks were 21, 30, and 39% at 75, 85, and 95 Gy, respectively (ICRU-R point dose).ConclusionsPIBS system point doses correlated with late vaginal toxicity. VRL combined with both EBRT and BT dose to the ICRU-R point contribute to VS risk.

Thiazolidinedione (TZD) is an oral anti-diabetic drug that exhibits some side effects on the male reproductive system by interfering with the steroidogenesis and androgenic activity and also shows anti-proliferative effect on several cell types. This study investigated the effect of TZD on immature chicken Sertoli cell (SC) proliferation and the potential mechanism by which 17β-estradiol regulated this process. Chicken SC viability was investigated under different treatment concentration and time of TZD. 17β-estradiol (0.001 μM, 24 h) was added to analyze its effects on TZD-mediated cell viability, cell metabolic activity, cell growth, cell cycle progression, reactive oxygen species (ROS) level, antioxidant enzyme activity, mitochondria activity, oxygen consumption rate, adenosine triphosphate (ATP) level, and mitochondrial respiratory chain enzyme activity, adiponectin expression and several cell proliferation-related genes mRNA and protein levels. We performed the microRNA (miRNA) array to find TZD-induced differentially expressed miRNAs and validated whether miR-1577 can target on adiponectin via the dual luciferase reporter assay, as well as verified the effect of adiponectin addition with different concentrations on the SC viability. Further, SCs were transfected with miR-1577 agomir (a double-stranded synthetic miRNA mimic) in the presence or absence of TZD and antagomir (a single-stranded synthetic miRNA inhibitor) in the presence or absence of 17β-estradiol to analyze whether miR-1577 was involved in TZD-mediated SC proliferation and whether 17β-estradiol regulated this process. Results showed that TZD significantly inhibited SC viability, cell metabolic activity, cell growth, and cell cycle progression, while increased adiponectin level and ROS generation. TZD-treated SCs presented decreases of antioxidant enzyme activity, mitochondria activity, basal and maximal respiration, ATP production and level, mitochondrial respiratory chain enzyme activity, and mRNA and protein expressions of several cell proliferation-related genes, as well as the significant alteration of miRNA expressions (a total number of 55 miRNAs were up-regulated whereas 53 miRNAs down-regulated). Whereas, 17β-estradiol played a positive role in chicken SC proliferation and rescued the damage of TZD on SC proliferation by up-regulating miR-1577 expression whose target gene was validated to be the adiponectin. In addition, exogenous adiponectin (more than 1 μg/ml) treatment exhibited a significant inhibition on the SC viability. Transfection of miR-1577 agomir promoted the SC proliferation via down-expressed adiponectin, and increased the mitochondrial function and cell proliferation-related gene expression, while TZD weakened the positive effect of miR-1577 agomir on SCs. On the other hand, transfection of miR-1577 antagomir inhibited SC proliferation by producing the opposite effects on above parameters, while 17β-estradiol attenuated the negative effect of miR-1577 antagomir on SCs. These findings suggest down-expressed miR-1577 is involved in the regulation of TZD-inhibited SC proliferation through increasing adiponectin level, and this damage of TZD on the immature chicken SC proliferation can be ameliorated by appropriate dose of exogenous 17β-estradiol treatment. This study provides an insight into the cytoprotective effect of 17β-estradiol on TZD-damaged SC proliferation and may suggest a potential strategy for reducing the risk of SC dysfunction caused by the abuse of TZD.

Transition metal hydroxides are a kind of promising electrode material in electrochemical energy storage, but the poor conductivity limits their application. Lanthanides are good proton conductors and can usually improve the intrinsic conductivity of other materials. By integrating the merits of lanthanide elements and transition metal hydroxide, we designed lanthanum oxide nickel hydroxide composites (LONH) with unique ultrathin triangle nanosheet morphology via a controllable synthetic strategy for high-performance supercapacitors. When the LONH is used as positive electrode material in aqueous asymmetric supercapacitor, it reveals an energy density (107.8 W h kg−1 at 800 W kg−1), rate performance (86.9% retention at 4 kW kg−1) and outstanding cycle stability (more than 90% retention after 3,000 cycles). This work confirms that compositing La2O3 and Ni(OH)2 can significantly improve the supercapacitor performance of both pristine La2O3 and transition metal hydroxide composites. We hope this work would offer a good prospect for developing other lanthanide-transition metal hydroxide composites as an attractive class of electrode materials in electrochemical energy storage.

PurposeTo accurately stratify nasopharyngeal carcinoma (NPC) patients who were benefit from induction chemotherapy (IC) followed by chemoradiotherapy (CCRT), we established residual volume of lymph nodes during chemoradiotherapy based nomogram to predict survival for NPC patients.MethodsCox regression analysis were used to evaluate predictive effects of tumor volume parameters. Multivariate Cox regression analysis was used to identify the prognostic factors, and nomogram models were developed to predict survival of NPC patients receiving IC followed by CCRT.ResultsCompared with other tumor volumetric parameters, midRT GTVnd was the best predictive factor for OS (HR: 1.043, 95%CI: 1.031-1.055), PFS (HR: 1.040, 95%CI: 1.030- 1.051), and DMFS (HR: 1.046, 95%CI: 1.034 – 1.059) according to the HR of Cox regression analysis. Based on multivariate analysis, three nomograms included midRT GTVnd were constructed to predict 4-year survival. The C-index of nomograms for each survival endpoints were as follow (training cohort vs. validation cohort): 0.746 vs. 0.731 for OS; 0.747 vs. 0.735 for PFS; 0.768 vs. 0.729 for DMFS, respectively. AUC showed a good discriminative ability. Calibration curves demonstrated a consistence between actual results and predictions. Decision curve analysis (DCA) showed that the nomograms had better clinical predictive effects than current TNM staging system.ConclusionWe identified the best volumetric indicator associated with prognosis was the residual volume of lymph nodes at the fourth week of chemoradiotherapy for patients receiving IC followed by CCRT. We developed and validated three nomograms to predict specific probability of 4-year OS, PFS and DMFS for NPC patient receiving IC followed by CCRT.

Olfactory ensheathing cells (OECs) are promising seed cells for nerve regeneration. However, their application is limited by the hypoxic environment usually present at the site of injury. Exosomes derived from human umbilical cord mesenchymal stem cells have the potential to regulate the pathological processes that occur in response to hypoxia. The ability of OECs to migrate is unknown, especially in hypoxic conditions, and the effect of OECs combined with exosomes on peripheral nerve repair is not clear. Better understanding of these issues will enable the potential of OECs for the treatment of nerve injury to be addressed. In this study, OECs were acquired from the olfactory bulb of Sprague Dawley rats. Human umbilical cord mesenchymal stem cell-derived exosomes (0–400 μg/mL) were cultured with OECs for 12–48 hours. After culture with 400 μg/mL exosomes for 24 hours, the viability and proliferation of OECs were significantly increased. We observed changes to OECs subjected to hypoxia for 24 hours and treatment with exosomes. Exosomes significantly promoted the survival and migration of OECs in hypoxic conditions, and effectively increased brain-derived neurotrophic factor gene expression, protein levels and secretion. Finally, using a 12 mm left sciatic nerve defect rat model, we confirmed that OECs and exosomes can synergistically promote motor and sensory function of the injured sciatic nerve. These findings show that application of OECs and exosomes can promote nerve regeneration and functional recovery. This study was approved by the Institutional Ethical Committee of the Air Force Medical University, China (approval No. IACUC-20181004) on October 7, 2018; and collection and use of human umbilical cord specimens was approved by the Ethics Committee of the Linyi People’s Hospital, China (approval No. 30054) on May 20, 2019.

Abstract Background The posterior-inferior border of symphysis (PIBS) point system is a novel vaginal dose-reporting method and is a simple and reliable method proposed by the Medical University of Vienna proposed for both external-beam radiotherapy (EBRT) and brachytherapy (BT). In this multicenter study, we sought to first evaluate the vaginal radiation dose in Chinese cervical cancer patients according to the PIBS point system and then to analyze the factors influencing the dose distribution. Methods We collected data from the medical records of 936 cervical cancer patients who underwent concurrent radiochemotherapy at 13 different institutions in China. Radiation doses at points A, PIBS+ 2 cm, PIBS and PIBS-2 cm, International Commission on Radiation Units (ICRU)-R and ICRU-B were measured. Results The median total doses in EQD2α/β = 3 at points PIBS+ 2 cm, PIBS and PIBS-2 cm were 82.5 (52.7–392.1) Gy, 56.2 (51.4–82.1) Gy and 2.6 (0.9–7.4) Gy, respectively. The median total doses in EQD2α/β = 3 at ICRU-R and ICRU-B were 77.5 (54.8–132.4) Gy and 79.9 (60.7–133.7) Gy, respectively. The mean vaginal reference length (VRL) was 4.6 ± 1.0 cm (median, 4.5 cm). In patients with VRL ≤4.5 cm, the mean total doses in EQD2α/β = 3 at points PIBS+ 2 cm, PIBS and PIBS-2 cm were 128.5, 60.7 and 0.8 Gy, respectively. In patients with VRL > 4.5 cm, the mean total doses at these three points were 68.9, 0.5 and 54.5 Gy, respectively. Classification of patients revealed significant differences (P

Abstract Background Incubating birds must balance the conflict between thermal needs of the developing embryos and their self-maintenance needs for energy. The Chinese Grouse (Tetrastes sewerzowi) lives in high mountain conifer forests and faces energy stress, cold environment, and predation pressure. Females might adjust incubation rhythm to adapt to these constraints. Methods Two methods were used to investigate egg laying and incubation pattern of the Chinese Grouse; 25 nests were monitored by data loggers and 12 nests by infrared video cameras. Results Female Chinese Grouses usually laid an egg every 2 days. The incubation period was 28–31 days. Overall incubation constancy for Chinese Grouse was 93%. The females took 5.0 recesses per day and 34% of all 1696 recesses were taken in the crepuscular period. The average recess duration was 20.3 min. Females took more and shorter recesses in the latter part of incubation. The females who allocated more time to foraging had a higher reproductive success. Conclusions Probably due to its high egg/body mass ratio, the Chinese Grouse has a long laying interval of 49 h. We suggest that, due to energy stress, females have relatively more recesses and they increase the number of recesses as incubation progresses. To compensate for the embryos’ thermal needs, they extend the incubation period and shorten the recess duration in this cold environment.

Background and ObjectivesTo establish a prognostic stratification nomogram for T1–2 breast cancer with 1–3 positive lymph nodes to determine which patients can benefit from postmastectomy radiotherapy (PMRT).MethodsA population-based study was conducted utilizing data collected from the Surveillance, Epidemiology, and End Results database. Chi-square test or Fisher exact test was used to compare the distribution of characteristics. Cox analysis identified significant prognostic factors for survival. A prognostic stratification model was constructed by R software. Propensity score matching was applied to balance characteristics between PMRT cohort and control cohort. Kaplan-Meier method was performed to evaluate the performance of stratification and the benefits of PMRT in the total population and three risk groups.ResultsThe overall performance of the nomogram was good (3-year, 5-year, 10-year AUC were 0.75, 0.72 and 0.67, respectively). The nomogram was performed to excellently distinguish low-risk, moderate-risk, and high-risk groups with 10-year overall survival (OS) of 86.9%, 73.7%, and 62.7%, respectively (P

Collagens from marine animals are an important component of marine organic nitrogen. Collagenase-producing bacteria and their collagenases play important roles in collagen degradation and organic nitrogen recycling in the ocean. However, only a few collagenase-producing marine bacteria have been so far discovered. Here, we reported the isolation and characterization of a collagenase-secreting bacterium, designated strain SM1988T, isolated from a green alga Codium fragile sample. Strain SM1988T is a Gram-negative, aerobic, oxidase-, and catalase-positive, unipolar flagellated, and rod-shaped bacterium capable of hydrolyzing casein, gelatin and collagens. Phylogenetic analysis revealed that strain SM1988T formed a distinct phylogenetic lineage along with known genera within the family Pseudoalteromonadaceae, with 16S rRNA gene sequence similarity being less than 93.3% to all known species in the family. Based on the phylogenetic, genomic, chemotaxonomic and phenotypic data, strain SM1988T was considered to represent a novel species in a novel genus in the family Pseudoalteromonadaceae, for which the name Flocculibacter collagenilyticus gen. nov., sp. nov. is proposed, with the type strain being SM1988T (= MCCC 1K04279T = KCTC 72761T). Strain SM1988T showed a high production of extracellular collagenases, which had high activity against both bovine collagen and codfish collagen. Biochemical tests combined with genome and secretome analyses indicated that the collagenases secreted by strain SM1988T are serine proteases from the MEROPS S8 family. These data suggest that strain SM1988T acts as an important player in marine collagen degradation and recycling and may have a promising potential in collagen resource utilization.

Patients with advanced-stage natural killer/T-cell lymphoma (NKTCL) usually have a poor prognosis. However, there is limited data of comprehensive analysis on this particular patient population due to the rarity of the disease. The present study aimed to investigate the treatment models, survival outcomes, and prognosis of advanced-stage NKTCL. Data from 336 patients with advanced-stage NKTCL diagnosed between 2006 and 2015 in the China Lymphoma Collaborative Group database were retrospectively analyzed. The median age was 42 years and the male/female ratio was 2.4:1. About 97% of patients had stage IV disease and 77% had >1 extranodal involvement site. All patients received chemotherapy, with the most common option being asparaginase (Asp)-containing regimens (n=146; 43.5%). Among 286 patients with available response data, the overall response rate (ORR) was 57.3% with a complete remission (CR) rate of 35.7%. Asp-containing regimens led to better ORRs (86/132, 65.2% vs. 54/113, 47.8%, P = 0.006) and CR rates (60/132, 45.5% vs. 27/113, 23.9%, P < 0.001) than non-Asp-containing regimens. The expected 5-year progression-free survival (PFS) and overall survival (OS) rates were 22.6 and 32.0%, respectively, for the whole cohort. Compared to non-Asp-containing chemotherapy, Asp-containing chemotherapy improved 5-year PFS (34.2 vs. 17.1%, P < 0.001) and OS (45.3 vs. 27.8%, P < 0.001). A trend toward improvement in OS was observed when gemcitabine was added to Asp-containing chemotherapies. Moreover, those undergoing autologous hematopoietic stem cell transplantation had prolonged survival time. In conclusion, Asp-containing chemotherapy could improve the prognosis of advanced-stage NKTCL, and refinement of treatment models is warranted in the future.

The aim of this study was to investigate the role of high mobility group protein-1 (HMGB1) in the proliferation and migration of lung cancer cells. CCK-8 assays and colony formation assays were used to evaluate the effect of HMGB1 regulation on cancer cell viability and colony formation. Trans-well assays and wound healing assays were also performed. Our data showed that HMGB1 is upregulated in clinical lung cancer tissues compared with non-cancer tissues, and it is differentially expressed in lung cancer cell lines. The knockdown of HMGB1 in A549 lung cancer cells significantly reduced cell proliferation, viability and motility. In contrast, overexpression of HMGB1 in lung cancer H1299 cells significantly increased cell viability and motility. Western blotting showed that HMGB1 could promote epithelial-mesenchymal transition. The Wnt/β-catenin pathway was activated after overexpression of HMGB1 in H1299 cells, while it was inactivated by knocking down HMGB1 in A549 cells. These data suggest that HMGB1 promotes the proliferation and migration of lung cancer cells in vitro . The carcinogenic behavior of HMGB1 can be achieved by activating the Wnt/β-catenin pathway.

Purpose: The purpose of this study was to investigate the production of IL-27 p28 and EBI3 in the ocular inflammatory sites, and the role of IL-27 signaling in a model of HSV-1 induced herpetic stromal keratitis (HSK). Methods: The BALB/c mice were injected intraperitoneally (24 h before infection) with anti-IL-27 antibody or IgG antibody as control, infected with HSV-1 via corneal scarification, and then injected intraperitoneally with anti-IL-27 antibody or IgG antibody at 1, 3, and 5 days postinfection. Slit lamp and histopathology were used to assess disease outcome. The levels of IL-27 p28 and EBI3 in corneas were determined by western blotting and immunofluorescence. Furthermore, viral titers were determined, and immune cell infiltrates were collected and analyzed by flow cytometry. Results: We found that the levels of IL-27 p28 and EBI3 in corneas were elevated significantly at the peak of HSK, and both of them were expressed simultaneously in the epithelium, stroma, and endothelium of corneas. In the group of anti-IL-27 treatment, the severity of the corneal lesion and CD4+ T cells infiltration were significantly decreased, and the percentage of CD4+ Foxp3+ Tregs was upregulated markedly in the spleen, DLNs and cornea of HSK mice compared to IgG treatment. Conclusion: These results provided evidence that IL-27 as a pathogenic pro-inflammatory cytokine controlled CD4+ Foxp3+ Tregs production in HSK, which ultimately resulted in promoting the progression of HSK and poor prognosis.

Monoacylglycerol lipases (MGLs) are present in all domains of life. However, reports on bacterial MGLs are still limited. Until now, reported bacterial MGLs are all thermophilic/mesophilic enzymes from warm terrestrial environments or deep-sea hydrothermal vent, and none of them originates from marine environments vastly subject to low temperature, high salts, and oligotrophy. Here, we characterized a novel MGL, GnMgl, from the marine cold-adapted and halophilic bacterium Glaciecola nitratireducens FR1064T. GnMgl shares quite low sequence similarities with characterized MGLs (lower than 31%). GnMgl and most of its bacterial homologs harbor a catalytic Ser residue located in the conserved C(A/S)HSMG motif rather than in the typical GxSxG motif reported on other MGLs, suggesting that GnMgl-like enzymes might be different from reported MGLs in catalysis. Phylogenetic analysis suggested that GnMgl and its bacterial homologs are clustered as a separate group in the monoglyceridelipase_lysophospholipase family of the Hydrolase_4 superfamily. Recombinant GnMgl has no lysophospholipase activity but could hydrolyze saturated (C12:0-C16:0) and unsaturated (C18:1 and C18:2) MGs and short-chain triacylglycerols, displaying distinct substrate selectivity from those of reported bacterial MGLs. The substrate preference of GnMgl, predicted to be a membrane protein, correlates to the most abundant fatty acids within the strain FR1064T, suggesting the role of GnMgl in the lipid catabolism in this marine bacterium. In addition, different from known bacterial MGLs that are all thermostable enzymes, GnMgl is a cold-adapted enzyme, with the maximum activity at 30°C and retaining 30% activity at 0°C. GnMgl is also a halotolerant enzyme with full activity in 3.5M NaCl. The cold-adapted and salt-tolerant characteristics of GnMgl may help its source strain FR1064T adapt to the cold and saline marine environment. Moreover, homologs to GnMgl are found to be abundant in various marine bacteria, implying their important physiological role in these marine bacteria. Our results on GnMgl shed light on marine MGLs.

Abstract is missing (Short communication)

BACKGROUND:Prompt therapy with high-dose intravenous benzylpenicillin for a prolonged period is critical for neurosyphilis patients to avoid irreversible sequelae. However, life-threatening neutropenia has been reported as a complication of prolonged therapy with high doses of benzylpenicillin when treating other diseases. This study aimed to investigate the incidence, presentation, management and prognosis of benzylpenicillin-induced neutropenia in treating neurosyphilis based on a large sample of syphilis patients in Shanghai. METHODOLOGY/PRINCIPAL FINDINGS:Between 1st January 2013 and 31st December 2015, 1367 patients with neurosyphilis were treated with benzylpenicillin, 578 of whom were eligible for recruitment to this study. Among patients without medical co-morbidities, the total incidence of benzylpenicillin-induced neutropenia and severe neutropenia was 2.42% (95% CI: 1.38-4.13%) and 0.35% (95% CI: 0.06-1.39%), respectively. The treatment duration before onset of neutropenia ranged from 10 to 14 days, with a total cumulative dose of between 240 and 324 megaunits of benzylpenicillin. Neutropenia was accompanied by symptoms of chills and fever (5 patients), fatigue (2 patients), cough (1 patient), sore throat (1 patient), diarrhea (1 patient) and erythematous rash (1 patient). The severity of neutropenia was not associated with age, gender or type of neurosyphilis (p>0.05). Neutropenia, even when severe, was often tolerated and normalized within one week. A more serious neutropenia did not occur when reinstituting benzylpenicillin in patients with mild or moderate neutropenia nor when ceftriaxone was used three months after patients had previously experienced severe neutropenia. CONCLUSIONS/SIGNIFICANCE:Benzylpenicillin-induced neutropenia was uncommon in our cohort of patients. Continuation of therapy was possible with intensive surveillance for those with mild or moderate neutropenia. For severe neutropenia, it is not essential to aggressively use hematopoietic growth factors or broad-spectrum antibiotics for patients in good physical condition after withdrawing anti-neurosyphilis regimen. We did not see an exacerbation of neutropenia in patients with the readministration of benzylpenicillin.

Background: Mitogen-activated protein kinase (MAPK) signaling pathway plays an important role in response to viral infection. The aim of this study was to explore the function and mechanism of MAPK signaling pathway in enterovirus 71 (EV71) infection of human rhabdomyosarcoma (RD) cells. Methods: Apoptosis of RD cells was observed using annexin V-FITC/PI binding assay under a fluorescence microscope. Cellular RNA was extracted and transcribed to cDNA. The expressions of 56 genes of MAPK signaling pathway in EV71-infected RD cells at 8 h and 20 h after infection were analyzed by PCR array. The levels of IL-2, IL-4, IL-10, and TNF-α in the supernatant of RD cells infected with EV71 at different time points were measured by ELISA. Results: The viability of RD cells decreased obviously within 48 h after EV71 infection. Compared with the control group, EV71 infection resulted in the significantly enhanced releases of IL-2, IL-4, IL-10 and TNF-α from infected RD cells (p

Although some alginate lyases have been isolated from marine bacteria, alginate lyases-excreting bacteria from the Arctic alga have not yet been investigated. Here, the diversity of the bacteria associated with the brown alga Laminaria from the Arctic Ocean was investigated for the first time. Sixty five strains belonging to nine genera were recovered from six Laminaria samples, in which Psychrobacter (33/65), Psychromonas (10/65) and Polaribacter (8/65) were the predominant groups. Moreover, 21 alginate lyase-excreting strains were further screened from these Laminaria-associated bacteria. These alginate lyase-excreting strains belong to five genera. Psychromonas (8/21), Psedoalteromonas (6/21) and Polaribacter (4/21) are the predominant genera, and Psychrobacter, Winogradskyella, Psychromonas and Polaribacter were first found to produce alginate lyases. The optimal temperatures for the growth and algiante lyase production of many strains were as low as 10–20 °C, indicating that they are psychrophilic bacteria. The alginate lyases produced by 11 strains showed the highest activity at 20–30 °C, indicating that these enzymes are cold-adapted enzymes. Some strians showed high levels of extracellular alginate lyase activity around 200 U/mL. These results suggest that these algiante lyase-excreting bacteria from the Arctic alga are good materials for studying bacterial cold-adapted alginate lyases.

Polydatin and resveratrol, as major active components in Polygonum cuspidatum, have anti-inflammatory, antioxidant and antitumor functions. However, the effect and mechanism of polydatin and resveratrol on enterovirus 71 (EV71) have not been reported. In this study, resveratrol revealed strong antiviral activity on EV71, while polydatin had weak effect. Neither polydatin nor resveratrol exhibited influence on viral attachment. Resveratrol could effectively inhibit the synthesis of EV71/VP1 and the phosphorylation of IKKα, IKKβ, IKKγ, IKBα, NF-κB p50 and NF-κB p65, respectively. Meanwhile, the remarkably increased secretion of IL-6 and TNF-α in EV71-infected rhabdosarcoma (RD) cells could be blocked by resveratrol. These results demonstrated that resveratrol inhibited EV71 replication and cytokine secretion in EV71-infected RD cells through blocking IKKs/NF-κB signaling pathway. Thus, resveratrol may have potent antiviral effect on EV71 infection.

In cancer biology, cells and molecules that form the fundamental components of the tumor microenvironment play a major role in tumor initiation, and progression as well as responses to therapy. Therapeutic approaches that would enable and harness the immune system to target tumor cells mark the future of anticancer therapy as it could induce an immunological memory specific to the tumor type and further enhance tumor regression and relapse-free survival in cancer patients. Gastric cancer is one of the leading causes of cancer-related mortalities that has a modest survival benefit from existing treatment options. The advent of immunotherapy presents us with new approaches in gastric cancer treatment where adaptive cell therapies, cancer vaccines, and antibody therapies have all been used with promising outcomes. In this paper, we review the current advances and prospects in the gastric cancer immunotherapy. Special focus is laid on new strategies and clinical trials that attempt to enhance the efficacy of various immunotherapeutic modalities in gastric cancer.