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Background: Several studies have suggested that snoring is associated with an increased risk of stroke; however, the results are inconsistent. We aim to conduct a systematic review and meta-analysis of observational studies assessing the association between snoring and the risk of stroke in adults.Methods: We searched PubMed for relevant studies. A random-effect model was adopted to summary relative risks (RRs), and forest plots from a cumulative meta-analysis method were used for a better presentation of how the pooled RRs changed as updated evidence accumulated.Results: The literature search yielded 16 articles that met our inclusion criteria, and a total of 3,598 stroke patients and 145,901 participants were finally included in our analysis. A consistent trend toward association was found after the initial discovery, and the summary analysis indicated that snoring is associated with a 46% (RR, 1.46; 95%CI, 1.29–1.63; p < 0.001) increased risk of stroke.Conclusions: Snoring is associated with a significantly increased risk for stroke, up to 46%. The importance of the current study lies in that we provide an imputes to take a more active approach against the increased risk of stroke in snorers.

This paper studies the data-based polyhedron model and its application in uncertain linear optimization of engineering structures, especially in the absence of information either on probabilistic properties or about membership functions in the fussy sets-based approach, in which situation it is more appropriate to quantify the uncertainties by convex polyhedra. Firstly, we introduce the uncertainty quantification method of the convex polyhedron approach and the model modification method by Chebyshev inequality. Secondly, the characteristics of the optimal solution of convex polyhedron linear programming are investigated. Then the vertex solution of convex polyhedron linear programming is presented and proven. Next, the application of convex polyhedron linear programming in the static load-bearing capacity problem is introduced. Finally, the effectiveness of the vertex solution is verified by an example of the plane truss bearing problem, and the efficiency is verified by a load-bearing problem of stiffened composite plates.

The campaign life of a blast furnace is largely limited by the erosion state of its hearth section. Therefore, the study of hearth erosion is important for blast furnace ironmaking. In this study, the hearth erosion of the WISCO No. 1 blast furnace was investigated in combination with the numerical analysis of the iron flow and heat transfer in the hearth. The distributions of the wall shear stress and the temperature in the hearth were simulated and the hearth sections with high erosion risk were discussed. The hearth lining with higher shear stress is generally located near the taphole region and the 1423 K isotherm is totally located inside the hearth lining structure, with a deeper position in the central part of the hearth bottom. Based on the measurement data from the hearth damage investigation, the erosion state of the hearth bottom and the lower part of the hearth sidewall is more serious. The erosion line at the hearth bottom showed a typical “pot-bottom” shaped contour and for the hearth corner section, the average erosion depth was about 1/3 of the total wall thickness. The empirical expressions between the hearth erosion depth and the wall shear stress and the temperature were established. Moreover, the effects of key iron tapping factors on the wall shear stress and the effect of the hearth’s refractory structure on the heat transfer in the hearth are respectively discussed, aiming to provide more suggestions for hearth protection.

With the development of science and technology, photocatalytic technology is of great interest. Nanosized photocatalysts are easy to agglomerate in an aqueous solution, which is unfavorable for recycling. Therefore, hydrogel-based photocatalytic composites were born. Compared with other photocatalytic carriers, hydrogels have a three-dimensional network structure, high water absorption, and a controllable shape. Meanwhile, the high permeability of these composites is an effective way to promote photocatalysis technology by inhibiting nanoparticle photo corrosion, while significantly ensuring the catalytic activity of the photocatalysts. With the growing energy crisis and limited reserves of traditional energy sources such as oil, the attention of researchers was drawn to natural polymers. Like almost all abundant natural polymer compounds in the world, cellulose has the advantages of non-toxicity, degradability, and biocompatibility. It is used as a class of reproducible crude material for the preparation of hydrogel photocatalytic composites. The network structure and high hydroxyl active sites of cellulose-based hydrogels improve the adsorption performance of catalysts and avoid nanoparticle collisions, indirectly enhancing their photocatalytic performance. In this paper, we sum up the current research progress of cellulose-based hydrogels. After briefly discussing the properties and preparation methods of cellulose and its descendant hydrogels, we explore the effects of hydrogels on photocatalytic properties. Next, the cellulose-based hydrogel photocatalytic composites are classified according to the type of catalyst, and the research progress in different fields is reviewed. Finally, the challenges they will face are summarized, and the development trends are prospected.

With the development of power electronic technology, adding bidirectional DC/DC to the DC side of the motor controller has become an effective way to broaden the speed of motors. However, the motor drive system integrated with bidirectional DC/DC increases the switching loss and current harmonics of the inverter. Therefore, in this paper, a method based on fixed space vector pulse width modulation (SVPWM) modulation index and voltage instruction compensation are proposed, In this method, by considering the back electromotive force of the motor and the security margin of the weak magnetic region, the output voltage command amplitude of the current loop and the limit value of the inverter output is judged, and the optimal inverter input voltage is obtained, which effectively reduces the switching loss of the inverter, broadens the high efficient area of motor operation, and improves the efficiency of the controller. At the same time, the standardized benchmark composed of motor parameters is used to per-nit the permanent magnet synchronous motor (PMSM) mathematical model, which is helpful for the derivation of the formula and dramatically simplifies the calculation amount of the microcontroller. Moreover, the simulation and experimental results prove the effectiveness and feasibility of the algorithm.

Tumors are a serious threat to human health, and tumor treatments have continued to evolve from chemotherapy to targeted therapy, immunotherapy, and individualized immunotherapy. Tumor cells have many mutations that cause the production of neoantigens, which are unique to tumor cells. Tumor neoantigen vaccines can effectively activate the body’s immune system to kill tumor cells, making individualized immunotherapy based on tumor neoantigens a new direction for the development of personalized immunotherapy for tumors. This technique is unique in that it can kill cancer cells without damaging healthy tissues, it can target and attack tumors in any part of the body, it has minimal toxicity, and it is effective for almost all forms of cancer, allowing immune cells to “remember” cancer cells to prevent tumor recurrence. Tumor neoantigen vaccines are not only therapeutic but may also exert a preventive effect in high-risk groups. This therapy may also be applied to other diseases that can produce neoantigens, including infectious diseases, which increases the potential for broad application.

DAHP synthase catalyzes the first step in the shikimate pathway, deriving the biosynthesis of aromatic amino acids (Trp, Phe and Tyr), phenazine-1-carboxamide, folic acid, and ubiquinone in Pseudomonas chlororaphis. In this study, we identified and characterized one DAHP synthase encoding gene phzC, which differs from the reported DAHP synthase encoding genes aroF, aroG and aroH in E. coli. PhzC accounts for approximately 90% of the total DAHP synthase activities in P. chlororaphis HT66 and plays the most critical role in four DAHP synthases in the shikimate pathway. Inactivation of phzC resulted in the reduction of PCN production by more than 90%, while the absence of genes aroF, aroG and aroH reduced PCN yield by less than 15%, and the production of PCN was restored after the complementation of gene phzC. Moreover, the results showed that phzC in P. chlororaphis HT66 is not sensitive to feedback inhibition. This study demonstrated that gene phzC is essential for PCN biosynthesis. The expression level of both phzC and phzE genes are not inhibited in feedback by PCN production due to the absence of a loop region required for allosteric control reaction. This study highlighted the importance of PhzC and applying P. chlororaphis for shikimate pathway-derived high-value biological production.

Development of a vaccine that can elicit robust HIV specific antibody responses in the mucosal compartments is desired for effective prevention of HIV via sexual transmission. However, the current mucosal vaccines have either poor immunogenicity when administered orally or invite safety concerns when administered intranasally. Sublingual immunization has received more attention in recent years based on its efficiency in inducing systemic and mucosal immune responses in both mucosal and extra-mucosal tissues. To facilitate the transport of the immunogen across the sub-mucosal epithelial barrier, we found that CD91, the receptor of C1q, is prevalently expressed in the sublingual mucosal lining, and thus, a modified chimeric C1q surface conjugated CD40L/HIV VLP was generated. The ability of this chimeric C1q/CD40L/HIV VLP to bind, cross the epithelial layer, access and activate the sub-mucosal layer dendritic cells (DCs), and ultimately induce enhanced mucosal and systemic immune responses against HIV is evaluated in this study. We found that C1q/CD40L/HIV VLPs have enhanced binding, increased transport across the epithelial layer, and upregulate DC activation markers as compared to CD40L/HIV VLPs alone. Mice immunized with C1q/CD40L/HIV VLPs by sublingual administration showed higher levels of IgA salivary antibodies against both HIV Gag and Env than mice immunized with CD40L/HIV VLPs. Moreover, sublingual immunization with C1q/CD40L/HIV VLPs induced more Env- and Gag-specific IFN-γ producing T cells than the CD40L/HIV VLPs group. Interestingly, C1q/CD40L/HIV VLP immunization can also induce more mucosal homing T cells than that in CD40L/HIV VLP group. Our data suggest that incorporation of C1q to CD40L/HIV VLPs is a promising novel strategy and that the sublingual immunization can be a favorite immunization route for HIV mucosal vaccines.

We previously reported a new polymer, lactic-co-glycolic acid-polyethylenimine (LGA-PEI), as an improved nanoparticle (NP) delivery for therapeutic nucleic acids (TNAs). Here, we further developed two antibody (Ab)-conjugated LGA-PEI NP technologies for active-targeting delivery of TNAs. LGA-PEI was covalently conjugated with a single-chain variable fragment antibody (scFv) against mesothelin (MSLN), a biomarker for pancreatic cancer (PC), or a special Ab fragment crystallizable region-binding peptide (FcBP), which binds to any full Ab (IgG). TNAs used in the current study included tumor suppressor microRNA mimics (miR-198 and miR-520h) and non-coding RNA X-inactive specific transcript (XIST) fragments; green fluorescence protein gene (GFP plasmid DNA) was also used as an example of plasmid DNA. MSLN scFv-LGA-PEI NPs with TNAs significantly improved their binding and internalization in PC cells with high expression of MSLN in vitro and in vivo. Anti-epidermal growth factor receptor (EGFR) monoclonal Ab (Cetuximab) binding to FcBP-LGA-PEI showed active-targeting delivery of TNAs to EGFR-expressing PC cells.

Guertu virus (GTV) is a tick-borne phleboviruses (TBPVs) which belongs to the genus Banyangvirus in the family of Phenuiviridae. In vitro and in vivo studies of GTV demonstrated that it was able to infect animal and human cell lines and could cause pathological lesions in mice. Glycoproteins (GP, including Gn and Gc) on the surface of Guertu virus (GTV) could bind to receptors on host cells and induce protective immunity in the host, but knowledge is now lacking on the information of B cell epitopes (BCEs) present on GTV-GP protein. The aim of this study was to identify all BCEs on Gn of the GTV DXM strain using rabbit pAbs against GTV-Gn. Seven fine BCEs and two antigenic peptides (APs) from nine reactive 16mer-peptides were identified, which are EGn1 (2PIICEGLTHS11), EGn2 (135CSQDSGT141), EGn3 (165IP EDVF170), EGn4 (169VFQEL K174), EGn5 (187IDGILFN193), EGn6 (223QTKWIQ228), EGn7 (237CHKDGIGPC245), AP-8 (299GVRVRPKCYGFSRMMA314) and AP-9 (355CASH FCSSAESGKKNT370), of which six of mapped BCEs were recognized by the IgG-positive sheep serum obtained from sheep GTV-infected naturally. Multiple sequence alignments (MSA) based on each mapped BCE motif identified that the most of identified BCEs and APs are highly conserved among 10 SFTSV strains from different countries and lineages that share relatively close evolutionary relationships with GTV. The fine epitope mapping of the GTV-Gn would provide basic data with which to explore the GTV-Gn antigen structure and pathogenic mechanisms, and it could lay the foundation for the design and development of a GTV multi-epitope peptide vaccine and detection antigen.

Clinical trials of EGFR inhibitors in combination with gemcitabine for the treatment of pancreatic ductal adenocarcinoma (PDAC) have generated mixed results partially due to the poorly defined effectiveness of EGFR inhibitors in PDAC. Here, we studied a panel of PDAC cell lines to compare the IC50s of the EGFR inhibitors gefitinib and cetuximab. We found that gefitinib induced biphasic inhibition in over 50% of PDAC cells, with the initial growth inhibition occurring at nanomolar concentrations and a second growth inhibition occurring outside the clinical range. In contrast to gefitinib, cetuximab produced a single phase growth inhibition in a subset of PDAC cells. Using this sensitivity data, we screened for correlations between cell morphology proteins and EGFR ligands to EGFR inhibitor sensitivity, and found that mesothelin and the EGFR ligand TGF-α have a strong correlation to gefitinib and cetuximab sensitivity. Analysis of downstream signaling pathways indicated that plc-γ1 and c-myc were consistently inhibited by EGFR inhibitor treatment in sensitive cell lines. While an inconsistent additive effect was observed with either cetuximab or gefitinib in combination with gemcitabine, the cell pathway data indicated consistent ERK activation, leading us to pursue EGFR inhibitors in combination with trametinib, a MEK1/2 inhibitor. Both cetuximab and gefitinib in combination with trametinib produced an additive effect in all EGFR sensitive cell lines. Our results indicate that mesothelin and TGF-α can predict PDAC sensitivity to EGFR inhibitors and a combination of EGFR inhibitors with trametinib could be a novel effective treatment for PDAC.

Studies have shown that blockade of CTLA-4 promoted the expansion of germinal center B-cells in viral infection or immunization with model antigens. Few studies have evaluated the immunological consequences of CTLA-4 blockade during immunization against relevant vaccine candidates. Here, we investigated the effects of CTLA-4 blockade on HIV virus-like particles (VLPs) vaccination in a C57BL/6J mouse model. We found that CTLA-4 blockade during HIV VLP immunization resulted in increased CD4+ T-cell activation, promoted the expansion of HIV envelope (Env)-specific follicular helper T cell (Tfh) cells, and significantly increased HIV Gag- and Env-specific IgG with higher avidity and antibody-dependent cellular cytotoxicity (ADCC) capabilities. Furthermore, after only a single immunization, CTLA-4 blockade accelerated T-cell dependent IgG class switching and the induction of significantly high serum levels of the B-cell survival factor, A proliferation-inducing ligand (APRIL). Although no significant increase in neutralizing antibodies was observed, increased levels of class-switched Env- and Gag-specific IgG are indicative of increased polyclonal B-cell activation, which demonstrated the ability to mediate and enhance ADCC in this study. Altogether, our findings show that CTLA-4 blockade can increase the levels of HIV antigen-specific B-cell and antigen-specific Tfh cell activity and impact humoral immune responses when combined with a clinically relevant HIV VLP-based vaccine.

The correlation between crystal chemistry characteristics and dispersion performance of Ca-montmorillonite with different layer charge density was studied. The four kinds of purified montmorillonite were characterized by XRD, XRF, FTIR, SEM, TEM, BET, TG-DTG, Zeta potential, and Molecular dynamics simulation (MD). The XRD analysis results show that the d _(001) value of the four kinds of Ca-montmorillonite are 1.51 nm, 1.51 nm, 1.53 nm, and 1.50 nm, respectively, and the calculation results of layer charge density show that the semi-unit cell charge density are 0.38, 0.53, 0.61, and 0.69, respectively. The charge density is positively correlated with the mass content of MgO. The FTIR analysis results show that with the increase of layer charge density, the couple vibration wave number of Si–O–Mg and Mg–O move towards the high frequency region, from 464.70 cm ^−1 to 466.36 cm ^−1 and from 517.12 cm ^−1 to 520.41 cm ^−1 . The SEM analysis results show that the higher layer charge density of montmorillonite, the worse exfoliation between layers and the thicker layer thickness, The images of TEM show that montmorillonites are mainly composed of a clearly layered structure. The results of BET show that with the increase of charge density, the BET surface area, micropore area and total pore volume gradually increase from 32.69 m ^2 g ^−1 to 64.50 m ^2 g ^−1 , from 4.87 m ^2 g ^−1 to 18.24 m ^2 g ^−1 , and from 0.06 cm ^3 g ^−1 to 0.12 cm ^3 g ^−1 , respectively, while PSDs and pore diameter decrease from 7.88 nm to 1.74 nm, and from 7.65 nm to 5.47 nm. The results of TG and DTG show that with the increase of charge density, the removal temperature of free water and inter-layer water increase from 80 °C to 100 °C and 139 °C to 155 °C, respectively. The simulation results of MD show that with the increase of layer charge density, the number of hydrogen bonds increase from 186 to 271 and the adsorption energy increases from −1467.11 to −1874.32 kcal mol ^−1 . The particle size increases from 701 nm(Mt1) to 1576 nm(Mt4) with the layer charge density, and the absolute value of Zeta potential, colloidal value and expansion capacity of montmorillonites suspension decrease with the increase of the layer charge density, which further indicates that the dispersion of montmorillonites decrease with the increase of layer charge density.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen that causes severe disease in humans. CCHFV is widely distributed in more than 30 countries and distinct regions, which means that it poses a serious threat to human health. The nucleocapsid protein (NP) encoded by the CCHFV S gene is the primary detectable antigen in infected cells, which makes it an important viral antigen and a clinical diagnostic target. In this study, the modified biosynthetic peptide (BSP) method was used to identify the fine epitopes on the N- and C- terminals of NP from the CCHFV YL04057 strain using rabbit antiserum against CCHFV-NP. Nine epitopes were identified: E1a (178NLILNRGG185), E1b (184GGDENP189), E2 (352PLKWGKK358), E3 (363FADDS367), E4 (399NPDDAA404), E5a (447DIVASEHL454), E5b (452EHLLHQSL459), E6 (464SPFQNAY470) and E7 (475NATSANII482). Western blotting analysis showed that each epitope interacted with the positive serum of sheep that had been naturally infected with CCHFV. Amino acid sequence alignment between each epitope and their homologous proteins showed that they were almost 100% conserved among 12 CCHFV sequences from different lineages, except for epitopes E1a, E1b and E2. Three-dimensional structural modeling analysis showed that all identified epitopes were located on the surface of the NP "head" domain. This study identified fine epitopes on the N- and C- terminals of NP, which will increase the understanding of the structure and function of NP, and it could lay the foundation for the design and development of a CCHFV multi-epitope peptide vaccine and detection antigen.

BackgroundSeveral studies have suggested that cytomegalovirus infection is likely associated with an increased relative risk of cardiovascular disease (CVD); however, the results are inconsistent. We aimed to provide a systematic review and meta‐analysis of community‐based prospective studies assessing the association between cytomegalovirus infection and relative risk of CVD. Methods and ResultsWe searched Medline and EMBASE to retrieve prospective studies that reported risk estimates of the association between cytomegalovirus infection and relative risk of CVD. The search yielded 10 articles including a total of 34 564 participants and 4789 CVD patients. Overall, exposure to cytomegalovirus infection was associated with a 22% (relative risk: 1.22, 95% CI: 1.07–1.38, P=0.002) increased relative risk of future CVD. We estimated that 13.4% of CVD incidence could be attributable to cytomegalovirus infection. ConclusionsIn conclusion, cytomegalovirus infection is associated with a significantly increased relative risk of CVD.

In order to optimize the ventilation effect of ammonia leakage in the refrigeration machinery room, a food processing enterprise is selected as the subject investigated. The velocity and concentration field distribution during the process of ammonia leakage are discussed through simulation of refrigeration machinery room using CFD software. The ventilation system of the room is optimized in three aspects which are named air distribution, ventilation volume and discharge outlet. The influence of the ammonia alarm system through ventilation is also analyzed. The results show that it will be better to set the discharge outlet at the top of the plant than at the side of the wall, and the smaller of the distance between the air outlet and the ammonia gathering area, the better of the effect of ventilation will be. The air flow can be improved and the vortex flow can be reduced if the ventilation volume, the number of air vents and the exhaust velocity are reasonably arranged. Not only the function of the alarm could be ensured, but also the scope of the detection area could be enlarged if the detectors are set on the ceiling of the refrigeration units or the ammonia storage vessel.

Confined space is a special working place. To ensure the safety, the forced ventilation must be carried out before entering the confined space. In this paper, ventilation process in municipal heating confine space is simulated by CFD numerical simulation method, and the distribution of temperature, oxygen and carbon dioxide in municipal heating confined space during ventilation process is studied. The simulation results show that the airflow and temperature are obviously stratified in vertical direction during the ventilation. The temperature is low and the airflow velocity is high at the bottom part of the tunnel. While the temperature is high and the airflow velocity is low at the top of the tunnel. By contrast, recovery of the oxygen and carbon dioxide content is relatively faster at the bottom than it at the top. When the ventilation volume flow rates are 6000 m3·h−1, 8000 m3·h−1, 10000 m3·h−1, 12000 m3·h−1, and 14000 m3·h−1 respectively, the time when the temperature reach stable and gas fraction return to normal are 45 minutes, 32 minutes, 22 minutes, 15 minutes, 10 minutes respectively.

The existence of high-frequency components in common-mode (CM) current would reduce the stability of a non-isolated PV grid-connected system. It has great impacts on the output power quality when the generated power from PV is low. The method of single CM inner loop in suppressing the high-frequency components has poor effect. Based on the CM equivalent circuit model and the cause analysis of the CM current, a novel dual CM inner loops method is proposed to restrain the high-frequency components in CM current. This method not only meets the grid connection demand of CM current, but also overcomes the high frequency resonant problem. Furthermore, the high-frequency components in CM current from the outer parasitic circuit are substantially reduced. Finally, the proposed method is verified by simulation and experimental results.

Aminoglycoside antibiotics such as gentamicin could cause ototoxicity in mammalians, by inducing oxidative stress and apoptosis in sensory hair cells of the cochlea. Sodium hydrosulfide (NaHS) is reported to alleviate oxidative stress and apoptosis, but its role in protecting aminoglycoside-induced hearing loss is unclear. In this study, we investigated the anti-oxidant and anti-apoptosis effect of NaHS in in vitro cultured House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and isolated mouse cochlea. Results from cultured HEI-OC1 cells and cochlea consistently indicated that NaHS exhibited protective effects from gentamicin-induced ototoxicity, evident by maintained cell viability, hair cell number and cochlear morphology, reduced reactive oxygen species production and mitochondrial depolarization, as well as apoptosis activation of the intrinsic pathway. Moreover, in the isolated cochlear culture, NaHS was also demonstrated to protect the explant from gentamicin-induced mechanotransduction loss. Our study using multiple in vitro models revealed for the first time, the potential of NaHS as a therapeutic agent in protecting against aminoglycoside-induced hearing loss.

Crimean-Congo hemorrhagic fever (CCHF), a severe viral disease known to have occurred in over 30 countries and distinct regions, is caused by the tick-borne CCHF virus (CCHFV). Nucleocapsid protein (NP), which is encoded by the S gene, is the primary antigen detectable in infected cells. The goal of the present study was to map the minimal motifs of B-cell epitopes (BCEs) on NP. Five precise BCEs (E1, 247FDEAKK252; E2a, 254VEAL257; E2b, 258NGYLNKH264; E3, 267EVDKA271; and E4, 274DSMITN279) identified through the use of rabbit antiserum, and one BCE (E5, 258NGYL261) recognized using a mouse monoclonal antibody, were confirmed to be within the central region of NP and were partially represented among the predicted epitopes. Notably, the five BCEs identified using the rabbit sera were able to react with positive serum mixtures from five sheep which had been infected naturally with CCHFV. The multiple sequence alignment (MSA) revealed high conservation of the identified BCEs among ten CCHFV strains from different areas. Interestingly, the identified BCEs with only one residue variation can apparently be recognized by the positive sera of sheep naturally infected with CCHFV. Computer-generated three-dimensional structural models indicated that all the antigenic motifs are located on the surface of the NP stalk domain. This report represents the first identification and mapping of the minimal BCEs of CCHFV-NP along with an analysis of their primary and structural properties. Our identification of the minimal linear BCEs of CCHFV-NP may provide fundamental data for developing rapid diagnostic reagents and illuminating the pathogenic mechanism of CCHFV.

Tissue-resident memory T cells (TRM) are a specialized subset of long-lived memory T cells that reside in peripheral tissues. However, the impact of TRM-related immunosurveillance on the tumor-immune microenvironment (TIME) and tumor progression across various non-small-cell lung cancer (NSCLC) patient populations is yet to be elucidated. Our comprehensive analysis of multiple independent single-cell and bulk RNA-seq datasets of patient NSCLC samples generated reliable, unique TRM signatures, through which we inferred the abundance of TRM in NSCLC. We discovered that TRM abundance is consistently positively correlated with CD4+ T helper 1 cells, M1 macrophages, and resting dendritic cells in the TIME. In addition, TRM signatures are strongly associated with immune checkpoint and stimulatory genes and the prognosis of NSCLC patients. A TRM-based machine learning model to predict patient survival was validated and an 18-gene risk score was further developed to effectively stratify patients into low-risk and high-risk categories, wherein patients with high-risk scores had significantly lower overall survival than patients with low-risk. The prognostic value of the risk score was independently validated by the Cancer Genome Atlas Program (TCGA) dataset and multiple independent NSCLC patient datasets. Notably, low-risk NSCLC patients with higher TRM infiltration exhibited enhanced T-cell immunity, nature killer cell activation, and other TIME immune responses related pathways, indicating a more active immune profile benefitting from immunotherapy. However, the TRM signature revealed low TRM abundance and a lack of prognostic association among lung squamous cell carcinoma patients in contrast to adenocarcinoma, indicating that the two NSCLC subtypes are driven by distinct TIMEs. Altogether, this study provides valuable insights into the complex interactions between TRM and TIME and their impact on NSCLC patient prognosis. The development of a simplified 18-gene risk score provides a practical prognostic marker for risk stratification. [ABSTRACT FROM AUTHOR]

Temperature stress affect a stress response of aquatic animals including physiological metabolism, immune defense and other metabolic processes, damaged their immune response even cause dead. In this study, the physiological and histological changes of Procambarus clarkii under the high temperature (30°C) and the low temperature (10°C) stress were investigated. With the increase of temperature, the pyruvate kinase activity in the hepatopancreas and gill tissues of crayfish was gradually increased, and the fatty acid synthase activity at 10°C and 30°C were significantly lower than the control group of 25°C. Furthermore, lysozyme, catalase and superoxide dismutase in 10 °C and 30 °C were significantly lower than that of 25 °C. ELISA revealed that HSP90 activities was enhanced with the increasing temperature in hepatopancreas after 36h of treatment. HE sections showed that high temperature stress or hypothermia caused deformation of R cells (storage cells), rupture of B cells (secretory cells), and partial rupture of the basement membrane (BM) in hepatopancreas, as well as the deformation of epithelial cells and respiratory epithelial cells of BM in gill tissues. While the temperature stress (30°C and 10°C treatment) caused the deformation of epithelial cells and respiratory epithelial cells, making rupture of the BM, comparing with the group at 25°C. The study provides the data about the response of crayfish to temperature stress at the molecular level, and benefit to develop the strategy to defend the damage in the crayfish aquaculture caused by the temperature neither in the different regions nor in the different season. [ABSTRACT FROM AUTHOR]