A Gut Microbial Mimic that Hijacks Diabetogenic Autoreactivity to Suppress Colitis.

The gut microbiota contributes to the development of normal immunity but, when dysregulated, can promote autoimmunity through various non-antigen-specific effects on pathogenic and regulatory lymphocytes. Here, we show that an integrase expressed by several species of the gut microbial genus Bacteroides encodes a low-avidity mimotope of the pancreatic ß cell autoantigen islet-specific glucose-6-phosphatase-catalytic-subunit-related protein (IGRP206-214). Studies in germ-free mice monocolonized with integrase-competent, integrase-deficient, and integrase-transgenic Bacteroides demonstrate that the microbial epitope promotes the recruitment of diabetogenic CD8+ T cells to the gut. There, these effectors suppress colitis by targeting microbial antigen-loaded, antigen-presenting cells in an integrin ß7-, perforin-, and major histocompatibility complex class I-dependent manner. Like their murine counterparts, human peripheral blood T cells also recognize Bacteroides integrase. These data suggest that gut microbial antigen-specific cytotoxic T cells may have therapeutic value in inflammatory bowel disease and unearth molecular mimicry as a novel mechanism by which the gut microbiota can regulate normal immune homeostasis. PAPERCLIP.

Experimental Investigation of Pore Pressure on Sandy Seabed around Submarine Pipeline under Irregular Wave Loading.

The propagation of shallow-water waves may cause liquefaction of the seabed, thereby reducing its support capacity for pipelines and potentially leading to pipeline settlement or deformation. To ensure the stability of buried pipelines, it is crucial to consider the excess pore pressure induced by irregular waves thoroughly. This paper presents the findings of an experimental study on excess pore pressure caused by irregular waves on a sandy seabed. A series of two-dimensional wave flume experiments investigated the excess pore pressure generated by irregular waves. Based on the experimental results, this study examined the influences of irregular wave characteristics and pipeline proximity on excess pore pressure. Using test data, the signal analysis method was employed to categorize different modes of excess pore-water pressure growth into two types and explore the mechanism underlying pore pressure development under the influence of irregular waves.

Responses of microbial communities subjected to hydrodynamically induced disturbances in an organic contaminated site.

Organic contaminated sites have gained significant attention as a prominent contributor to shallow groundwater contamination. However, limited knowledge exists regarding the impact of hydrodynamic effects on microbially mediated contaminant degradation at such sites. In this study, we investigated the distribution characteristics and community structure of prokaryotic microorganisms at the selected site during both wet and dry seasons, with a particular focus on their environmental adaptations. The results revealed significant seasonal variations (P < 0.05) in the α-diversity of prokaryotes within groundwater. The dry season showed more exclusive OTUs than the wet season. The response of prokaryotic metabolism to organic pollution pressure in different seasons was explored by PICRUSt2, and enzymes associated with the degradation of organic pollutants were identified based on the predicted functions. The results showed that hormesis was considered as an adaptive response of microbial communities under pollution stress. In addition, structural equation models demonstrated that groundwater level fluctuations can, directly and indirectly, affect the abundance and diversity of prokaryotes through other factors such as oxidation reduction potential (ORP), dissolved oxygen (DO), and naphthalene (Nap). Overall, our findings imply that the taxonomic composition and functional properties of prokaryotes in groundwater in organic contaminated sites is influenced by the interaction between seasonal variations and characteristics of organic pollution. The results provide new insights into microbiological processes in groundwater systems in organic contaminated sites.

Zerumbone combined with gefitinib alleviates lung cancer cell growth through the AKT/STAT3/SLC7A11 axis.

Zerumbone had been verified as a potential anti-cancer agent. Our research aimed to investigate the effect of zerumbone combined with gefitinib in lung cancer. Human pulmonary alveolar epithelial cells (HPAEpiC), A549, and H460 cell lines were used to detect the efficacy of zerumbone. BALB/c nude mice were randomly divided into five groups, including model, gefitinib (Gef, 10 mg/kg), low dose zerumbone (L-Zer, 20 mg/kg), high dose zerumbone (H-Zer, 40 mg/kg), and H-Zer + Gef groups, and the tumor growth in each group was monitored. TdT-mediated dUTP Nick-End Labeling (TUNEL) was used to detect cell apoptosis. Immunohistochemistry (IHC), immunofluorescence, and western blot were used to analyze the protein expressions in tumor tissues. Glutathione (GSH) and malondialdehyde (MAD) were detected by special kits. Zerumbone inhibited the proliferation of lung cancer cells in vitro. Tumor volume and weight were reduced after gefitinib or zerumbone treatment. Gefitinib and zerumbone treatment significantly promoted the apoptosis of tumor cells. The expression of Bcl-2, Bax, and P53 proteins confirmed cell apoptosis. IHC results indicated that zerumbone and gefitinib treatment decreased tumor angiogenesis. Consistent with this result, the expression of EGFR, VEGFR2, and Ki-67 proteins decreased, while the expression of angiostatin and endostatin proteins increased. Interestingly, zerumbone treatment increased the level of MDA while decreasing GSH. Next, the levels of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) decreased after zerumbone and gefitinib treatment. Our study suggested that zerumbone combined with gefitinib could effectively inhibit lung cancer for multi-model therapies, including the inhibition of tumor growth, angiogenesis, induce cell apoptosis, and ferroptosis.

Shaping the concentration of petroleum hydrocarbon pollution in soil: A machine learning and resistivity-based prediction method.

A new method relying on machine learning and resistivity to predict concentrations of petroleum hydrocarbon pollution in soil was proposed as a means of investigation and monitoring. Currently, determining pollutant concentrations in soil is primarily achieved through costly sampling and testing of numerous borehole samples, which carries the risk of further contamination by penetrating the aquifer. Additionally, conventional petroleum hydrocarbon geophysical surveys struggle to establish a correlation between survey results and pollutant concentration. To overcome these limitations, three machine learning models (KNN, RF, and XGBOOST) were combined with the geoelectrical method to predict petroleum hydrocarbon concentrations in the source area. The results demonstrate that the resistivity-based prediction method utilizing machine learning is effective, as validated by R-squared values of 0.91 and 0.94 for the test and validation sets, respectively, and a root mean squared error of 0.19. Furthermore, this study confirmed the feasibility of the approach using actual site data, along with a discussion of its advantages and limitations, establishing it as an inexpensive option to investigate and monitor changes in petroleum hydrocarbon concentration in soil.

Expanding antigen-specific regulatory networks to treat autoimmunity.

Regulatory T cells hold promise as targets for therapeutic intervention in autoimmunity, but approaches capable of expanding antigen-specific regulatory T cells in vivo are currently not available. Here we show that systemic delivery of nanoparticles coated with autoimmune-disease-relevant peptides bound to major histocompatibility complex class II (pMHCII) molecules triggers the generation and expansion of antigen-specific regulatory CD4(+) T cell type 1 (TR1)-like cells in different mouse models, including mice humanized with lymphocytes from patients, leading to resolution of established autoimmune phenomena. Ten pMHCII-based nanomedicines show similar biological effects, regardless of genetic background, prevalence of the cognate T-cell population or MHC restriction. These nanomedicines promote the differentiation of disease-primed autoreactive T cells into TR1-like cells, which in turn suppress autoantigen-loaded antigen-presenting cells and drive the differentiation of cognate B cells into disease-suppressing regulatory B cells, without compromising systemic immunity. pMHCII-based nanomedicines thus represent a new class of drugs, potentially useful for treating a broad spectrum of autoimmune conditions in a disease-specific manner.

Lower urinary tract symptoms in an elderly women caused by degeneration of the pubic symphysis.

BACKGROUND: Lower urinary tract symptoms are very common in elderly women, and transvaginal delivery and multiple deliveries have been confirmed to be risk factors. Transvaginal delivery and multiple deliveries may lead to an increase in pubic symphysis degeneration. CASE PRESENTATION: A 79-year-old woman consulted a urologist because of worsening lower urinary tract symptoms such as frequent urination and urodynia. Color ultrasound and cystoscopy suggested the possibility of a bladder mass. A lump on the anterior wall of the bladder was observed although the surface mucosa was normal. Physical examination showed obvious tenderness in the posterior area of the pubic symphysis. Further urological computed tomography (CT) and pelvic magnetic resonance imaging (MRI) showed a nodular bony protuberance in the posterior part of the pubic symphysis, which was more obvious than before, with compression changes near the anterior wall of bladder. Open pelvic surgery showed that nodular bone tissue originating from the pubic symphysis significantly oppressed the anterior wall of the bladder behind the pubic symphysis. After resection of the nodule, the lower urinary tract symptoms were relieved significantly. CONCLUSIONS: Pubic symphysis degeneration caused by transvaginal delivery may be an important cause of lower urinary tract symptoms in women. Pelvic CT or MRI is necessary to diagnosis this condition.

Spatial distribution model of DEHP contamination categories in soil based on Bi-LSTM and sparse sampling.

Soil pollution is a serious threat to human life and development. Different remedial measures are applied to soils with different levels of contamination. The degree of soil contamination in different areas is generally evaluated and categorised based on the analysis of samples. Regional soil sampling sites are generally sparse because of the cost of sampling and other factors, which makes it difficult to accurately assess the extent of regional soil contamination. In this study, a spatial classification model was established for the Di(2-ethylhexyl) phthalate (DEHP) pollution level using a Bi-directional Long Short-Term Memory (Bi-LSTM) neural network considering that the sampling information gradually diminishes with increasing distance between the sampling and prediction points. In this study, a method is proposed for the prediction of the spatial distribution of soil pollution categories based on sparse samples. We also established a model for the spatial distribution of organic pollution categories. The analysis of an actual contaminated area shows that the DEHP concentrations at different locations can be effectively predicted with the proposed method by categorising the contamination levels of specific DEHP samples. The results show that the method can be used to classify the degree of light/severe DEHP contamination. The results are in good agreement with the actual situation, verifying the validity of the method. This method is important for the rapid assessment of the spatial distribution of soil contamination levels based on sparse sampling.

Experimental investigation of solute transport across transition interface of porous media under reversible flow directions.

Understanding solute transport through macroscopic interfaces is essential to understand the effects of geological heterogeneity on contaminant transport in porous media. Studies of solute transport in compartmental porous media have noted the asymmetry of breakthroughs (BTCs) in solute movement across material interfaces, indicating the presence of discontinuous concentration that makes solute transport directionally dependent. Transition interfaces are more common in nature than sharp interfaces. To understand solute transport across transition interfaces, well-controlled laboratory experiments were performed. A numerical model was also built to understand mass accumulation and concentration discontinuity through transition as well as sharp interfaces. We conclude that directionally dependent asymmetry of BTCs was found with both sharp and transition interfaces. The asymmetry of BTCs was more pronounced at a transition interface than at a sharp interface. The mobile and immobile (MIM) model can better capture the directionally dependent transport of solutes through a sharp/transition interface than the advection-dispersion equation (ADE). The mobile water partition coefficient (ß) and mass transfer coefficient (ω) in MIM were lager in the direction from fine sand to coarse sand (F-C). The time difference between tracer replace and tracer input is greater in the presence of an interface, especially transition interfaces. Even at small Reynolds numbers (1 × 10-4 to 0.116), solute transport across a discontinuous interface under reversible flow directions is most likely dominated by convective dispersion rather than an assumed diffusion process.

Detection of nucleotides in hydrated ssDNA via 2D h-BN nanopore with ionic-liquid/salt-water interface.

Accomplishing slow translocation speed with high sensitivity has been the most critical mission for solid-state nanopore (SSN) device to electrically detect nucleobases in ssDNA. In this study, a method to detect nucleobases of ssDNA using a 2D SSN is introduced by considerably reducing the translocation speed and effectively increasing its sensitivity. The ultra-thin titanium dioxide coated hexagonal boron nitride nanopore was fabricated, along with an ionic-liquid 1-butyl-3-methylimidazolium hexafluorophosphate/2.0 M KCl aqueous (cis/trans) interface, for increasing both the spatial and the temporal resolutions. As the ssDNA molecules entered the nanopore, a brief surge of electrical conductivity occurred, which was followed by multiple resistive pulses from nucleobases during the translocation of ssDNA and another brief current surge flagging the exit of the molecule. The continuous detection of nucleobases using a 2D SSN device is a novel achievement: the water molecules bound to ssDNA increased the molecular conductivity and amplified electrical signals during the translocation. Along with the experiment, computational simulations using COMSOL Multiphysics are presented to explain the pivotal role of water molecules bound to ssDNA to detect nucleobases using a 2D SSN.

MicroRNA-4429 suppresses proliferation of prostate cancer cells by targeting distal-less homeobox 1 and inactivating the Wnt/ß-catenin pathway.

BACKGROUND: Emerging evidence suggests that microRNAs (miRNAs) play multiple roles in human cancers through regulating mRNAs and distinct pathways. This paper focused on the functions of miR-4429 in prostate cancer (PCa) progression and the molecules involved. METHODS: Expression of miR-4429 in PCa tissues and cells was determined. Upregulation of miR-4429 was introduced in PCa cells to examine its role in the malignant behaviors of cells. The putative target mRNA of miR-4429 involved in PCa progression was predicted from a bioinformatic system and validated through luciferase assays. Overexpression of distal-less homeobox 1 (DLX1) was further induced in cells to validate its implication in miR-4429-mediated events. The activity of Wnt/ß-catenin pathway was determined. RESULTS: miR-4429 was poorly expressed in PCa tissues and cells. Artificial upregulation of miR-4429 significantly reduced proliferation, growth, invasion, migration and resistance to death of cancer cells and inactivated the Wnt/ß-catenin pathway. DLX1 mRNA was found as a target of miR-4429. Upregulation of DLX1 restored the malignant behaviors of PCa cells which were initially suppressed by miR-4429, and it activated the Wnt/ß-catenin pathway. CONCLUSION: Our study highlights that miR-4429 inhibits the growth of PCa cells by down-regulating DLX1 and inactivating the Wnt/ß-catenin pathway. This finding may offer novel insights into PCa treatment.

Controllable Ferromagnetism in Super-tetragonal PbTiO3 through Strain Engineering.

The coupling strain in nanoscale systems can achieve control of the physical properties in functional materials, such as ferromagnets, ferroelectrics, and superconductors. Here, we directly demonstrate the atomic-scale structure of super-tetragonal PbTiO3 nanocomposite epitaxial thin films, including the extraordinary coupling of strain transition and the existence of the oxygen vacancies. Large strain gradients, both longitudinal and transverse (∼3 × 107 m-1), have been observed. The original non-magnetic ferroelectric composites notably evoke ferromagnetic properties, derived from the combination of Ti3+ and oxygen vacancies. The saturation ferromagnetic moment can be controlled by the strain of both the interphase and substrate, optimized to a high value of ∼55 emu/cc in 10-nm thick nanocomposite epitaxial thin films on the LaAlO3 substrate. Strain engineering provides a route to explore multiferroic systems in conventional non-magnetic ferroelectric oxides and to create functional data storage devices from both ferroelectrics and ferromagnetics.

A conjunctive management framework for the optimal design of pumping and injection strategies to mitigate seawater intrusion.

Coastal aquifer management (CAM) considering conjunctive optimization of pumping and injection system for seawater intrusion (SI) mitigation poses significant decision-making challenges. CAM needs to pose multiple objectives and massive decision variables to explore tradeoff strategies between the conflicting resources, economic, and environmental requirements. Here, we investigate a joint artificial injection scheme for ameliorating SI by establishing an evolutionary multi-objective decision-making framework that combines simulation-optimization (S-O) modelling with a cost-benefit analysis, and demonstrate the framework on a large-scale CAM case in Baldwin County, Alabama. First, a SI numerical model, using SEAWAT, was configured to predict the vulnerable region as an SI encroachment area with the scenarios of minimum and maximum pumping capacity. As a result, a smaller number of candidate sites were selected in the SI encroachment area for implementing groundwater injection to avoid the computationally infeasible SI optimization with an inordinate number of injection related decision variables. Second, the effective S-O methodology of niched Pareto tabu search combined with a genetic algorithm (NPTSGA), which considers the moving-well option, was applied to discover optimal pumping/injection (P/I) strategies (including P/I rates and injection well locations) between three conflicting management objectives under complicated SI constraints. Third, for practical operation of the P/I schemes, a cost-benefit analysis provides judgment criteria to allow decision-makers to implement more sustainable P/I strategies to capture the different realistic preferences. The implementation of three extreme optimization solutions for the case study indicates that, compared to the initial unoptimized scheme, a maximum increase of a factor of 3 in groundwater extraction rates, a maximum reduction of 17% in extent of SI, and a maximum 82.3 million US dollars in comprehensive benefits are specifically achieved by conjunctive P/I optimization. The robustness in the decision alternatives attributed to the uncertainty in physical parameters of hydraulic conductivity was discovered through global sensitivity analysis. The proposed framework provides a decision support system for multi-objective CAM with combined pumping control and engineering measures for SI mitigation.

Strong Second Harmonic Generation in a Tungsten Bronze Oxide by Enhancing Local Structural Distortion.

To discover the nonlinear optical (NLO) materials with strong second harmonic generation (SHG), the design of NLO-active molecular units with large polarization is considered as a common strategy. Herein, we propose that the local structural distortion induced with vacancies, apart from the NLO-active units, can be employed to improve the NLO effect in solids as well. Accordingly, a new tungsten bronze (TB) oxide, Pb2(Pb0.15Li0.7□0.15)Nb5O15 (□ representing vacancies), is successfully designed and prepared, which exhibits a strong SHG response of 39 times that of KH2PO4. The detailed analysis reveals that the local structural distortions enhanced by the vacancies in PLN strengthen the local dipole moments of neighboring NbO6 octahedra, and thus significantly prompt the SHG effect. Moreover, a series of new TB compounds with large NLO effects are discovered by this molecular design strategy, which are perspectives for new NLO materials synthesis.

Intravenous dexmedetomidine versus tramadol for treatment of shivering after spinal anesthesia: a meta-analysis of randomized controlled trials.

BACKGROUND: Shivering is a frequent complication after spinal anesthesia. Increasing studies have compared the effect of intravenous dexmedetomidine and intravenous tramadol on shivering after spinal anesthesia, hence we performed a meta-analysis of randomized controlled trials to compare dexmedetomidine with tramadol on the treatment of post-spinal anesthesia shivering. METHODS: PubMed, Embase, Cochrane library, Web of Science and Google Scholar were searched to find the eligible studies comparing the effect of dexmedetomidine and tramadol on the treatment of shivering after spinal anesthesia. Mean difference (MD) or risk ratio (RR) along with 95% confidence interval (CI) was used to analyze the outcomes. I2 test was conducted to assess the heterogeneity of the included trials. We utilized Review Manager 5.3 to perform statistical analyses. RESULTS: Thirteen randomized controlled trials including 864 subjects were included. Dexmedetomidine had higher effective rate of shivering control (RR =1.03; 95%CI [1.01, 1.06], P = 0.01, I2 = 14%), shorter time to cease shivering (MD = -2.14; 95%CI [- 2.79, - 1.49], P < 0.00001, I2 = 98%), lower recurrent rate of shivering (RR = 0.45; 95%CI [0.27, 0.73], P = 0.001, I2 = 0%), lower incidences of nausea (RR = 0.10; 95%CI [0.05, 0.19], P < 0.00001, I2 = 48%), and vomiting (RR = 0.13; 95%CI [0.06, 0.30], P < 0.00001, I2 = 0%), higher incidence of sedation (RR = 2.48; 95%CI [1.32, 4.65], P = 0.005, I2 = 82%), hypotension (RR = 2.50; 95%CI [1.24, 5.03], P = 0.01, I2 = 0%) and bradycardia (RR = 4.78; 95%CI [1.76, 13.00], P = 0.002, I2 = 0%), compared with tramadol. CONCLUSIONS: Dexmedetomidine is superior to tramadol for shivering treatment, due to higher effective rate of shivering control, earlier onset of action and lesser recurrence of shivering with higher incidence of sedation and lower incidences of nausea and vomiting. However, dexmedetomidine is also associated with higher incidences of hypotension and bradycardia than tramadol.

Risk factors of lymph node metastasis in the splenic hilum of gastric cancer patients: a meta-analysis.

BACKGROUND: The issue of whether or not splenic hilum lymph nodes (SHLN) should be excised in radical gastrectomy with D2 lymph node dissection remains controversial. In this study, we identified the clinicopathological features in patients with gastric cancer that could serve as predictive risk factors of SHLN metastasis. METHODS: We searched Medline, Embase, PubMed, and Web of Science databases from inception to May 2020 and consulted the related references. Overall, 15 articles evaluating a total of 4377 patients were included for study. The odds ratios (OR) of each risk factor and corresponding 95% confidence intervals (CI) were determined using the Revman 5.3 software. RESULTS: Our meta-analysis revealed tumor size greater than 5 cm (p < 0.01), tumor localization in the greater curvature (p < 0.01), diffuse type (Lauren's classification) (p < 0.01), Borrmann types 3-4 (p < 0.01), poor differentiation and undifferentiation (p < 0.01), depth of invasion T3-T4 (p < 0.01), number of lymph node metastases N2-N3 (p < 0.01), distant metastasis M1 (p < 0.01), TNM stages 3-4 (p < 0.01), vascular invasion (p = 0.01), and lymphatic invasion (p < 0.01) as potential risk factors of SHLN metastasis. Moreover, positivity of Nos. 1, 2, 3, 4sa, 4sb, 4d, 6, 7, 9, 11, and 16 lymph nodes for metastasis was strongly associated with SHLN metastasis. CONCLUSIONS: Tumor size, tumor location, Lauren's diffuse type, Borrmann type, degree of differentiation, T stage, N stage, M stage, TNM stage, vascular invasion, lymphatic infiltration, and other positive lymph nodes are risk factors for SHLN metastasis.

Intravenous dexmedetomidine versus intravenous clonidine for post spinal anesthesia shivering: a meta-analysis of randomized controlled trials.

BACKGROUND: Dexmedetomidine and clonidine are the most extensively studied drugs for shivering treatment, because α2-adrenergic agonists can reduce the shivering threshold. The objective of this meta-analysis was to compare the efficacy and complications of dexmedetomidine with those of clonidine, when used for control of post spinal anesthesia shivering. METHODS: Electronic databases were searched for randomized controlled trials (RCT) comparing the effect of dexmedetomidine versus clonidine for control of post spinal anesthesia shivering. The endpoints were effective rate of shivering treatment, time to cease shivering, recurrent rate of shivering and complications. RESULTS: Six studies comprising 340 adult patients were included in this meta-analysis. Dexmedetomidine had higher effective rate of shivering treatment (odds ratio [OR]: 4.11, 95% confidence interval (CI): [1.53, 11.07], P = 0.005), shorter time to cease shivering (Mean differences (MD)=-1.91; 95% CI [-3.66, -0.15], P = 0.03), lower recurrent rate of shivering (OR = 0.30; 95% CI [0.12, 0.75], P = 0.01), compared to clonidine. Dexmedetomidine had a lower rate of hypotension and higher incidence of sedation than clonidine. CONCLUSIONS: Dexmedetomidine is superior to clonidine when used for shivering treatment after spinal anesthesia, because of higher incidence of effective rate and sedation, faster control of shivering, lower incidence of recurrent rate and hypotention.

Ganoderma triterpenoids attenuate tumour angiogenesis in lung cancer tumour-bearing nude mice.

CONTEXT: Ganoderma lucidum (Leyss. ex Fr.) Karst. (Polyporaceae) triterpenoids (GLTs), the main components and bioactive metabolites of G. lucidum, have antitumour activity. OBJECTIVE: We investigated the effects of GLTs in lung cancer tumour-bearing nude mice and their potential mechanism. MATERIALS AND METHODS: Forty BALB/c nude mice were randomly divided into four groups: saline control, GLT (1 g/kg/day), gefitinib (GEF, 15 mg/kg/day), and GLT (1 g/kg/day) + GEF (15 mg/kg/day) for 14 days. Cell viability was conducted using the Cell Counting Kit-8 assay. The tumour volume, inhibition rate, histopathological, microvessel density (MVD), mRNAs, and proteins were determined. RESULTS: GLTs inhibited the cell viability of A549 cells with an IC50 value of 14.38 ± 0.29 mg/L, while the IC50 value of GEF was 10.26 ± 0.47 µmol/L. The tumour inhibition rate in the GLT + GEF group (51.54%) was significantly decreased relative to the saline control… group (p < 0.05). The MVD in the GLT + GEF group (2.9 ± 0.7) was significantly decreased than that in the saline control group (12.8 ± 1.4, p < 0.05). The angiostatin, endostatin, and Bax protein expression in the GLT, GEF, and GLT + GEF groups were significantly increased compared to those in the saline control group, while the VEGFR2 and Bcl-2 protein expression were decreased. DISCUSSION AND CONCLUSIONS: Our study provided evidence that GLT and GEF combination therapy may be a promising candidate for the treatment of lung cancer and as an experimental basis for clinical treatment.

[Application of the Green Model to lifestyle intervention in male sterility patients].

OBJECTIVE: To evaluate the application of the Green Model to lifestyle intervention in male infertility patients. METHODS: A total of 120 male infertility patients treated from October 2018 to January 2019 were equally randomized into a control and an observation group, the former given conventional nursing and the latter Green Model intervention in addition. Comparisons were made between the two groups of patients in their satisfaction with nursing intervention, scores on lifestyle knowledge, beliefs and behaviors, and compliance with the healthy lifestyle. RESULTS: The patients in the observation group showed a dramatically higher satisfaction with the nursing intervention than the controls (96.67% vs 75.00%, P < 0.01) as well as higher scores on lifestyle knowledge (8.92 ± 1.08 vs 5.89 ± 1.99, P < 0.05), beliefs (8.78 ± 0.68 vs 5.98 ± 1.50, P < 0.05) and behaviors (19.32 ± 1.12 vs 13.88 ± 2.11, P < 0.05) and their compliance with the healthy lifestyle (61.67% vs 38.33, P < 0.05). CONCLUSIONS: Green Model intervention can help male infertility patients to obtain correct lifestyle cognition, beliefs and behaviors, promote their compliance with the healthy lifestyle and improve their satisfaction with nursing intervention.

Reversal of autoimmunity by boosting memory-like autoregulatory T cells.

Blunting autoreactivity without compromising immunity remains an elusive goal in the treatment of autoimmunity. We show that progression to autoimmune diabetes results in the conversion of naive low-avidity autoreactive CD8(+) T cells into memory-like autoregulatory cells that can be expanded in vivo with nanoparticles coated with disease-relevant peptide-major histocompatibility complexes (pMHC-NP). Treatment of NOD mice with monospecific pMHC-NPs expanded cognate autoregulatory T cells, suppressed the recruitment of noncognate specificities, prevented disease in prediabetic mice, and restored normoglycemia in diabetic animals. pMHC-NP therapy was inconsequential in mice engineered to bear an immune system unresponsive to the corresponding epitope, owing to absence of epitope-experienced autoregulatory T cells. pMHC-NP-expanded autoregulatory T cells suppressed local presentation of autoantigens in an interferon-gamma-, indoleamine 2,3-dioxygenase-, and perforin-dependent manner. Nanoparticles coated with human diabetes-relevant pHLA complexes restored normoglycemia in a humanized model of diabetes. These observations expose a paradigm in the pathogenesis of autoimmunity amenable for therapeutic intervention.