Revealing synergetic structural activation of a CuAu surface during water-gas shift reaction.

Bimetallic alloy catalysts show strong structural and compositional dependence on their activity, selectivity, and stability. Often referred to as the "synergetic effect" of two metal elements in the alloys, their detailed dynamic information, structurally and chemically, of catalyst surface under reaction conditions remains largely elusive. Here, using aberration-corrected environmental transmission electron microscopy, we visualize the atomic-scale synergetic surface activation of CuAu under a water­gas shift reaction condition. The unique "periodic" structural activation largely determines the dominating reaction pathway, which is related to a possible "carboxyl" reaction route corroborated by density functional theory­based calculation and ab initio molecular dynamics simulation. These results demonstrate how the alloy surface is activated and catalyzes the chemical reaction, which provides insights into catalyst design with atom precision.

Ni and Co Active Site Transition and Competition in Fluorine-Doped NiCo(OH)2 LDH Electrocatalysts for Oxygen Evolution Reaction.

The oxygen evolution reaction (OER) performance of NiCo LDH electrocatalysts can be improved through fluorine doping. The roles of Ni and Co active sites in such catalysts remain ambiguous and controversial. In addressing the issue, this study draws upon the molecular orbital theory and proposes the active center competitive mechanism between Ni and Co. The doped F-atoms can directly impact the valence state of metal atoms or exert an indirect influence through the dehydrogenation, thereby modulating the active center. As the F-atoms are progressively aggregate, the eg orbitals of Ni and Co transition from e2 g to e1 g , and subsequently to e0 g . The corresponding valence state elevates from +2 to +3, and then to +4, signifying an initial increase followed by a subsequent decrease in the electrocatalytic performance. Furthermore, a series of F-NiCo LDH catalysts are synthesized to verify the eg orbital occupancy analysis, and the catalytic OER overpotentials are 303, 243, 240, and 246 mV at the current density of 10 mA cm-2 , respectively, which coincides well with the theoretical prediction. This investigation not only provides novel mechanistic insights into the transition and competition of Ni and Co in F-NiCo LDH catalysts but also establishes a foundation for the design of high-performance catalysts.

Evaluation of the Expansion and Neuronal Differentiation Potency of Cultured Olfactory Epithelium Progenitor Cells from a Rat Model of Depression.

BACKGROUND: Olfactory impairment has been reported in patients with depression and in rodent models of depression. Olfactory epithelium (OE) is the only peripheral neural tissue connected to the brain that has the potential for self-renewal. We hypothesized the olfactory deficit during depression may be related to the dysfunction of OE progenitor cells. The aim of the present study was therefore to evaluate the expansion and neuronal differentiation potency of cultured OE progenitor cells obtained from a rat model of depression. METHODS: Rats were exposed to chronic unpredictable mild stress procedures to establish a depressive-like state. Depressive-like behavior and olfactory sensing function were then evaluated and compared with control rats. Primary OE progenitor cells were cultured in vitro. The proliferation potency and survival of OE progenitor cells were assessed by 5-Ethynyl-2'-deoxyuridine staining and Cell Counting Kit-8 (CCK8), respectively, while cellular apoptosis was measured by flow cytometry. The neuronal differentiation potency of OE progenitor cells was evaluated by measurement of the protein and mRNA level of ß-3 tubulin, a marker of neural cells. mRNA expression associated with neural stemness was examined by quantitative reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Depressive-like rats showed decreased olfactory function. OE progenitor cells from depressive-like rats showed reduced cell proliferation/survival and neuronal differentiation potency. Moreover, OE progenitor cells from depressive-like rats showed decreased expression of mRNA related to neural stemness. CONCLUSIONS: These results indicate the impaired function of OE progenitor cells may contribute to the olfactory deficit observed during depression. The OE may therefore provide a window for the study of depression.

Metabotropic Glutamate Receptor 8 Suppresses M1 Polarization in Microglia by Alleviating Endoplasmic Reticulum Stress and Mitochondrial Dysfunction.

BACKGROUND: Microglia-mediated neuroinflammation is a hallmark of neurodegeneration. Metabotropic glutamate receptor 8 (GRM8) has been reported to promote neuronal survival in neurodegenerative diseases, yet the effect of GRM8 on neuroinflammation is still unclear. Calcium overload-induced endoplasmic reticulum (ER)-mitochondrial miscommunication has been reported to trigger neuroinflammation in the brain. The aim of this study was to investigate putative anti-inflammatory effects of GRM8 in microglia, specifically focusing on its role in calcium overload-induced ER stress and mitochondrial dysfunction. METHODS: BV2 microglial cells were pretreated with GRM8 agonist prior to lipopolysaccharide administration. Pro-inflammatory cytokine levels and the microglial polarization state in BV2 cells were then quantified. Cellular apoptosis and the viability of neuron-like PC12 cells co-cultured with BV2 cells were examined using flow cytometry and a Cell Counting Kit-8, respectively. The concentration of cAMP, inositol-1,4,5-triphosphate receptor (IP3R)-dependent calcium release, ER Ca2+ concentration, mitochondrial function as reflected by reactive oxygen species levels, ATP production, mitochondrial membrane potential, expression of ER stress-sensing protein, and phosphorylation of the nuclear factor kappa B (NF-κB) p65 subunit were also quantified in BV2 cells. RESULTS: GRM8 activation inhibited pro-inflammatory cytokine release and shifted microglia polarization towards an anti-inflammatory-like phenotype in BV2 cells, as well as promoting neuron-like PC12 cell survival when co-cultured with BV2 cells. Mechanistically, microglial GRM8 activation significantly inhibited cAMP production, thereby desensitizing the IP3R located within the ER. This process markedly limited IP3R-dependent calcium release, thus restoring mitochondrial function while inhibiting ER stress and subsequently deactivating NF-κB signaling. CONCLUSIONS: Our results indicate that GRM8 activation can protect against microglia-mediated neuroinflammation by attenuating ER stress and mitochondrial dysfunction, and that IP3R-mediated calcium signaling may play a vital role in this process. GRM8 may thus be a potential target for limiting neuroinflammation.

Fruit and Vegetable Consumption, Food Acquisition Behavior, and Food Insecurity Before and After the COVID-19 Vaccine Rollout.

OBJECTIVES: To assess changes in food acquisition behavior, food insecurity, and dietary behavior and identify factors associated with fruit and vegetable (FV) consumption during the transitional period (before and after the initial vaccine rollout for all adults) of the COVID-19 pandemic. DESIGN: Successive independent samples design. Online surveys were conducted from October 2020 to February 2021 (time 1, before the vaccine rollout) and from October 2021 to December 2021 (time 2, after the vaccine rollout). Descriptive analysis examined changes in food sources, food security, and daily FV consumption in cup equivalents (CEs) from time 1 to time 2. A multivariable logistic regression analysis examined factors associated with FV consumption. SETTING: The Capital Region of New York State. PARTICIPANTS: 1553 adults 18 years of age and older. MAIN OUTCOME MEASURE: Meeting the 2020-2025 MyPlate daily FV consumption recommendations. RESULTS: There were statistically significant (P < .05) increases in the use of supermarkets, eat-in restaurants, farmers' markets, and convenience stores from time 1 to time 2. Food insecurity (40.1% vs 39.4%) and FV consumption (2.6 CE vs 2.4 CE) slightly declined but not significantly. Home food procurement such as gardening and foraging (OR, 1.61; 95% CI, 1.08-2.37) and shopping at food co-op/health food stores (OR, 1.64; 95% CI, 1.07-2.49) were significantly associated with the FV outcome, and these relationships were not modified by food security status. CONCLUSIONS: The present study highlights the importance of food sources in understanding adult dietary behavior during the transitional period of the pandemic. Continuing efforts to monitor access to food sources, food insecurity, and dietary behavior are warranted as various COVID-related emergency food assistance measures have expired.

Interface-Compatible Gel-Polymer Electrolyte Enabled by NaF-Solubility-Regulation toward All-Climate Solid-State Sodium Batteries.

Gel-polymer electrolyte (GPE) is a pragmatic choice for high-safety sodium batteries but still plagued by interfacial compatibility with both cathode and anode simultaneously. Here, salt-in-polymer fibers with NaF salt inlaid in polylactide (PLA) fiber network was fabricated via electrospinning and subsequent in situ forming gel-polymer electrolyte in liquid electrolytes. The obtained PLA-NaF GPE achieves a high ion conductivity (2.50×10-3 S cm-1) and large Na+ transference number (0.75) at ambient temperature. Notably, the dissolution of NaF salt occupies solvents leading to concentrated-electrolyte environment, which facilitates aggregates with increased anionic coordination (anion/Na+ >1). Aggregates with higher HOMO realize the preferential oxidation on the cathode so that inorganic-rich and stable CEI covers cathode' surface, preventing particles' breakage and showing good compatibility with different cathodes (Na3V2(PO4)3, Na2+2xFe2-x(SO4)3, Na0.72Ni0.32Mn0.68O2, NaTi2(PO4)3). While, passivated Na anode induced by the lower LUMO of aggregates, and the lower surface tension between Na anode and PLA-NaF GPE interface, leading to the dendrites-free Na anode. As a result, the assembled Na || Na3V2(PO4)3 cells display excellent electrochemical performance at all-climate conditions.

Reductive Competition Effect-Derived Solid Electrolyte Interphase with Evenly Scattered Inorganics Enabling Ultrahigh Rate and Long-Life Span Sodium Metal Batteries.

Constructing an inorganic-rich and robust solid electrolyte interphase (SEI) is one of the crucial approaches to improving the electrochemical performance of sodium metal batteries (SMBs). However, the low conductivity and distribution of common inorganics in SEI disturb Na+ diffusion and induce nonuniform sodium deposition. Here, we construct a unique SEI with evenly scattered high-conductivity inorganics by introducing a self-sacrifice LiTFSI into the sodium salt-base carbonate electrolyte. The reductive competition effect between LiTFSI and FEC facilitates the formation of the SEI with evenly scattered inorganics. In which the high-conductive Li3N and inorganics provide fast ions transport domains and high-flux nucleation sites for Na+, thus conducive to rapid sodium deposition at a high rate. Therefore, the SEI derived from LiTFSI and FEC enables the Na∥Na3V2(PO4)3 cell to show 89.15% capacity retention (87.62 mA h g-1) at an ultrahigh rate of 60 C after 10,000 cycles, while the cell without LiTFSI delivers only 48.44% capacity retention even after 8000 cycles. Moreover, the Na∥Na3V2(PO4)3 pouch cell with the special SEI presents a stable capacity retention of 92.05% at 10 C after 2000 cycles. This unique SEI design elucidates a new strategy to propel SMBs to operate under extreme high-rate conditions.

Exploring the Depth-Dependent Microviscosity inside a Micelle Using Butterfly-Motion-Based Fluorescent Probes.

The viscosity distribution of micellar interiors from the very center to the outer surface is dramatically varied, which has been distinguished in theoretical models, yet it remains highly challenging to quantify this issue experimentally. Herein, a series of fluorophore-substituted surfactants DPAC-Fn (n = 3, 5, 7, 9, 11, 13, and 15) are developed by functionalizing the different alkyl-trimethylammonium bromides with the butterfly motion-based viscosity sensor, N,N'-diphenyl-dihydrodibenzo[a,c]phenazine (DPAC). The immersion depth of DPAC units of DPAC-Fn in cetrimonium bromide (C16TAB) micelles depends on the alkyl chain lengths n. From deep (n = 15) to shallow (n = 3), DPAC-Fn in C16TAB micelles exhibits efficient viscosity-sensitive dynamic multicolor emissions. With external standards for quantification, the viscosity distribution inside a C16TAB micelle with the size of ∼4 nm is changed seriously from high viscosity (∼190 Pa s) in the core center to low viscosity (∼1 Pa s) near the outer surface. This work provides a tailored approach for powerful micelle tools to explore the depth-dependent microviscosity of micellar interiors.

Prognostic significance of the systemic inflammation response index in gastrointestinal malignancy patients: a pooled analysis of 10,091 participants.

Background: We performed a meta-analysis to investigate the association of the systemic inflammation response index (SIRI) with long-term survival outcomes in patients with gastrointestinal malignancy. Methods: PubMed, Web of Science and Embase were searched for relevant studies evaluating the prognostic significance of the SIRI in gastrointestinal malignancies until May 2023. Results: 30 studies with 10,091 patients were included. The pooled results identified that patients in the high SIRI group had a worse overall survival and disease-free survival, which was observed across various tumor types, tumor stages and primary treatments. Conclusion: An elevated SIRI is negatively associated with worse survival outcomes of gastrointestinal malignancy patients and can be used as a risk stratification index for gastrointestinal malignancies.

Enhanced recovery after gynecological surgery: A meta-analysis of randomized controlled trials.

Enhanced recovery after surgery protocol is a multidisciplinary and multimodal approach designed to improve perioperative outcomes for patients. This meta-analysis aimed to identify and elaborate on the efficacy of this protocol in women undergoing gynecologic surgery. Four databases were searched for randomized controlled trials from inception to December 2021. A total of 14 studies met the inclusion criteria and were analyzed. There was a significant reduction in the length of stay, the time to first flatus and first defecation, complications, and readmission rates in patients undergoing enhanced recovery after surgery when compared to routine care. The rate of discharge on the first postoperative day significantly increased in patients from the enhanced recovery group. There was no significant difference in the surgery time and blood loss. In conclusion, the enhanced recovery after surgery protocol might have a positive effect on patients undergoing gynecologic surgery. However, there is still heterogeneity between the included studies, and we need more research to draw reliable conclusions that enhanced recovery after surgery is favorable.

Operando High-Valence Cr-Modified NiFe Hydroxides for Water Oxidation.

High-valence metal-doped multimetal (oxy)hydroxides outperform noble metal electrocatalysts for the oxygen evolution reaction (OER) owing to the modified energetics between 3d metals and high-valence dopants. However, the rational design of sufficient and subtle modulators is still challenging. With a multimetal layered double hydroxide (LDH) as the OER catalyst, this study introduces a series of operando high-valence dopants (Cr, Ru, Ce, and V), which can restrict the 3+ valence states in the LDH template to prevent phase separation and operando transfer to the >3+ valence states for sufficient electronic interaction during the OER process. Through density functional theory simulations, ultrathin Cr-doped NiFe (NiFeCr) LDH is synthesized with strong electronic interaction between Cr dopants and NiFe bimetallic sites, evidenced by X-ray absorption spectroscopy. The resulting NiFeCr-LDH catalyzes the OER with ultralow overpotentials of 189 and 284 mV, obtaining current densities of 10 and 1000 mA cm-2 , respectively. Further, a NiFeCr-LDH anode is coupled in the anion exchange membrane electrolyzers to promote alkaline water splitting and CO2 -to-CO electrolysis, which achieves low full cell voltages at high current densities.

A Multifunctional Microspheric Soil Conditioner Based on Chitosan-Grafted Poly(acrylamide-co-acrylic acid)/Biochar.

A multifunctional microspheric soil conditioner based on chitosan-grafted poly(acrylamide-co-acrylic acid)/biochar [CS-g-P(AM-co-AA)/BC] was prepared. First, the P(AM-co-AA) was synthesized and successfully grafted onto CS, and the three-dimensional network structure of microspheres was formed with N,N-methylenebis(acrylamide) as the cross-linking agent according to the inverse suspension polymerization method. Meanwhile, BC and urea were encapsulated into the body of microspheres during the polymerization. The structure of the microspheres was analyzed by Fourier transform infrared spectroscopy, polarized optical microscopy, and scanning electron microscopy, and the mechanism of adsorption of Cu2+ on the microspheres was investigated by X-ray photoelectron spectroscopy. Furthermore, the experimental results demonstrated the excellent water absorption and retention capabilities of microspheres, and the release rate of urea was dramatically reduced. Importantly, the introduction of BC significantly enhanced the adsorption performance of the microspheres with respect to heavy metal ions. Consequently, the multifunctional soil conditioner held promise for use in soil improvement and agricultural production.

Carbon Nanotubes/Polydopamine/ZSM-5 Composite Soil Conditioner with Good Controlled Release and Adsorption Properties.

Currently, the excessive application of fertilizers and the random discharge of waste water, waste gas, and residues have led to more and more serious soil pollution problems. Zeolite is the most promising material for preparing a green and environmentally friendly soil conditioner. Herein, the carbon nanotubes/polydopamine/ZSM-5 composite soil conditioner was prepared by a facile two-step method, and it was used to release fulvic acid and adsorb methylene blue to improve the environment. The cumulative release rate of the composite soil conditioner was 52% within 430 h for fulvic acid, which had a good sustained release effect and could be sustained-released in different acid-based surroundings. In addition, it showed a good adsorption capacity of methylene blue, and it is about 80.02 mg/g which was about six times higher than that of ZSM-5. It was beneficial for the adsorption of methylene blue in a neutral environment. Finally, it could promote the growth of brassica chinensis and maize, and the promotion effect was 60 and 35%, respectively. Therefore, the carbon nanotubes/polydopamine/ZSM-5 composite soil conditioner is a green and efficient material, which provides a new strategy to solve the problem of soil pollution.

Aminated Multiwalled Carbon Nanotube-Doped Magnetic Flower-like WSe2 Nanosheets for Efficient Adsorption in Acidic Wastewater.

The water body environment is related to ecological and human health. Adsorption is an effective means to remove pollutants from water bodies. Currently, the common adsorbents suffer from disadvantages such as structural instability and poor adsorption performance under acidic conditions, which not only affect the adsorption efficiency but also cause secondary pollution of water bodies. In this study, a novel aminated multiwalled carbon nanotube-doped flower-like nanocomposite was designed, where the anionic or neutral groups were protonated under acidic conditions, and it displayed a higher adsorption capacity for dyes by ion exchange, represented by methylene blue (MB) and rhodamine B (RB). WSe2 in the composite increases its adsorption sites. The adsorption efficiency of pollutants in acidic wastewater was enhanced while avoiding secondary contamination. The synthesized composites showed maximum adsorptions of 27.55 and 27.47 mg/g for MB and RB, respectively. The current work offers a novel approach to treating acidic wastewater.

Patients with degenerative cervical myelopathy exhibit neurophysiological improvement upon extension and flexion: a retrospective cohort study with a minimum 1-year follow-up.

BACKGROUND: Cervical extension and flexion are presumably harmful to patients with degenerative cervical myelopathy (DCM) because they worsen medullary compression visible on dynamic magnetic resonance imaging (MRI). Dynamic somatosensory evoked potentials (SSEPs) are an objective tool to measure the electrophysiological function of the spinal cord at different neck positions. In contrast to previous hypotheses, a considerable proportion of patients with DCM present improved SSEPs upon extension and flexion compared to a neutral position. METHODS: Patients with DCM who underwent preoperative dynamic SSEP examinations and subsequent decompression surgeries between 2015 and 2019 were retrospectively evaluated. We compared extension and flexion SSEPs with neutral SSEPs in each patient and classified them into extension-improved (EI) or extension-nonimproved (EN) and flexion-improved (FI) or flexion-nonimproved (FN) groups. Preoperative clinical evaluations, decompression surgical methods and one-year follow-up clinical data were recorded. Cervical spondylolisthesis and cervical alignment types were evaluated on plain cervical lateral radiographs. The number of stenotic segments, Mühle stenosis grade and disc degeneration stage of the most severe segment, and presence of ligamentum flavum hypertrophy and intramedullary T2 weighted imaging (T2WI) hyperintensity were evaluated on lateral and axial MRI. Data were compared between the EN and EN groups or FI and FN groups with T-tests, chi-square tests or Kruskal-Wallis tests. Prediction criteria were determined with logistic regression analyses. RESULTS: Forty-nine patients were included, and 9 (18.4%) and 11 (22.4%) showed improved extension and flexion SSEPs compared to their own neutral SSEPs, respectively. Interestingly, EI or FI patients had significantly better one-year postoperative mJOA recoveries than EN or FN patients (T-test, P < 0.001). Moreover, the disease duration (T-test, P = 0.024), involved segment number (Kruskal-Wallis test, P < 0.001), and cervical alignment type (chi-square test, P = 0.005) varied significantly between the EI and EN groups. The FI group presented a significantly higher Mühle stenosis grade than the FN group (Kruskal-Wallis test, P = 0.038). Furthermore, ≤ 2 involved segments and straight or sigmoid cervical alignment were significant criteria predicting improved extension SSEPs (probability: 85.7%), while Mühle stenosis Grade 3 and disease duration ≤6 months were significant criteria predicting improved flexion SSEPs (probability: 85.7%). CONCLUSIONS: Our findings provide evidence for neurophysiological improvement in patients with DCM at extension and flexion and its significance in predicting prognoses. Moreover, certain clinical and radiographic criteria may help predict neurophysiological improvement upon extension or flexion. TRIAL REGISTRATION: " [2020]151 ". Retrospectively registered on April 30, 2020.

Extracting drug-drug interactions from no-blinding texts using key semantic sentences and GHM loss.

The extraction of drug-drug interactions (DDIs) is an important task in the field of biomedical research, which can reduce unexpected health risks during patient treatment. Previous work indicates that methods using external drug information have a much higher performance than those methods not using it. However, the use of external drug information is time-consuming and resource-costly. In this work, we propose a novel method for extracting DDIs which does not use external drug information, but still achieves comparable performance. First, we no longer convert the drug name to standard tokens such as DRUG0, the method commonly used in previous research. Instead, full drug names with drug entity marking are input to BioBERT, allowing us to enhance the selected drug entity pair. Second, we adopt the Key Semantic Sentence approach to emphasize the words closely related to the DDI relation of the selected drug pair. After the above steps, the misclassification of similar instances which are created from the same sentence but corresponding to different pairs of drug entities can be significantly reduced. Then, we employ the Gradient Harmonizing Mechanism (GHM) loss to reduce the weight of mislabeled instances and easy-to-classify instances, both of which can lead to poor performance in DDI extraction. Overall, we demonstrate in this work that it is better not to use drug blinding with BioBERT, and show that GHM performs better than Cross-Entropy loss if the proportion of label noise is less than 30%. The proposed model achieves state-of-the-art results with an F1-score of 84.13% on the DDIExtraction 2013 corpus (a standard English DDI corpus), which fills the performance gap (4%) between methods that rely on and do not rely on external drug information.

Improved Wearable Devices for Dietary Assessment Using a New Camera System.

An unhealthy diet is strongly linked to obesity and numerous chronic diseases. Currently, over two-thirds of American adults are overweight or obese. Although dietary assessment helps people improve nutrition and lifestyle, traditional methods for dietary assessment depend on self-report, which is inaccurate and often biased. In recent years, as electronics, information, and artificial intelligence (AI) technologies advanced rapidly, image-based objective dietary assessment using wearable electronic devices has become a powerful approach. However, research in this field has been focused on the developments of advanced algorithms to process image data. Few reports exist on the study of device hardware for the particular purpose of dietary assessment. In this work, we demonstrate that, with the current hardware design, there is a considerable risk of missing important dietary data owing to the common use of rectangular image screen and fixed camera orientation. We then present two designs of a new camera system to reduce data loss by generating circular images using rectangular image sensor chips. We also present a mechanical design that allows the camera orientation to be adjusted, adapting to differences among device wearers, such as gender, body height, and so on. Finally, we discuss the pros and cons of rectangular versus circular images with respect to information preservation and data processing using AI algorithms.

In Operando Identification of In Situ Formed Metalloid Zincδ+ Active Sites for Highly Efficient Electrocatalyzed Carbon Dioxide Reduction.

Electrochemical CO2 -to-CO conversion provides a possible way to address problems associated with the greenhouse effect; however, developing low-cost electrocatalysts to mediate high-efficiency CO2 reduction remains a challenge on account of the limited understanding of the nature of the real active sites. Herein, we reveal the Znδ+ metalloid sites as the real active sites of stable nonstoichiometric ZnOx structure derived from Zn2 P2 O7 through operando X-ray absorption fine structure analysis in conjunction with evolutionary-algorithm-based global optimization. Furthermore, theoretical and experimental results demonstrated that Znδ+ metalloid active sites could facilitate the activation of CO2 and the hydrogenation of *CO2 , thus accelerating the CO2 -to-CO conversion. Our work establishes a critical fundamental understanding of the origin of the real active center in the zinc-based electrocatalysts for CO2 reduction reaction.

Development and clinical validation of a novel 9-gene prognostic model based on multi-omics in pancreatic adenocarcinoma.

The prognoses of patients with pancreatic adenocarcinoma (PAAD) remain poor due to the lack of biomarkers for early diagnosis and effective prognosis prediction. RNA sequencing, single nucleotide polymorphism, and copy number variation data were downloaded from The Cancer Genome Atlas (TCGA). Univariate Cox regression was used to identify prognosis-related genes. GISTIC 2.0 was used to identify significantly amplified or deleted genes, and Mutsig 2.0 was used to analyze the mutation data. The Lasso method was used to construct a risk prediction model. The Rms package was used to evaluate the overall predictive performance of the signature. Finally, Western blot and polymerase chain reaction were performed to evaluate gene expression. A total of 54 candidate genes were obtained after integrating the genomic mutated genes and prognosis-related genes. The Lasso method was used to ascertain 9 characteristic genes, including UNC13B, TSPYL4, MICAL1, KLHDC7B, KLHL32, AIM1, ARHGAP18, DCBLD1, and CACNA2D4. The 9-gene signature model was able to help stratify samples at risk in the training and external validation cohorts. In addition, the overall predictive performance of our model was found to be superior to that of other models. KLHDC7B, AIM1, DCBLD1, TSPYL4, and MICAL1 were significantly highly expressed in tumor tissues compared to normal tissues. ARHGAP18 and CACNA2D4 had no difference in expression between tumor and normal tissues. UNC13B and KLHL32 expression in the normal group was higher than in the tumor group. The 9-gene signature constructed in this study can be used as a novel prognostic marker to predict the survival of patients with pancreatic adenocarcinoma.

MTIF2 impairs 5 fluorouracil-mediated immunogenic cell death in hepatocellular carcinoma in vivo: Molecular mechanisms and therapeutic significance.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality; it has been reported that immune cell infiltration is a prognosis factor. Here we identified genes that associated with tumor immune cell infiltrate; the underlying mechanism was verified by in vivo and in vitro experiment. In this study, Weighted correlation network analysis (WGCNA) and CIBERSORT tool were used to identify MTIF2 as the hub tumor immune infiltrating gene in HCC. To investigate the underlying role played by MTIF2, MTIF2 was knocked down by transfection of shRNA targeting MTIF2, CCK8, and EdU incorporation assay was used to evaluate the effect of MTIF2 on proliferation, wound heal assay and transwell assay was used to confirm its effect on cell migration. Ecto-calreticulin on the cell surface was evaluated by flow cytometry, ATP, and HMGB1 secretion were tested to the investigated effect of MTIF2 on the immunogenic cell death (ICD) process. We found that down-regulation of MTIF2 impaired proliferation and migration capacity of HCC cells, chemoresistance to 5-Fluorouracil (5-FU) weakened after MTIF2 was knocked down. Reduced release of damage-associated molecular patterns (DAMP) was observed after MTIF2 was overexpressed, which subsequently impaired dendritic cell (DC) maturation and proliferation of CD8 + T cells. Mechanically, the co-IP experiment confirmed that MTIF2 could interact with AIFM1, prevents AIFM1 induced transcription of caspase3, and finally suppress apoptosis. In vivo experiment also used to confirm our previously conclusion, our result indicated that MTIF2 overexpression suppresses tumor apoptosis and immune cell activity in the 5-FU therapy in vivo model, by suppression maturation of tumor-infiltrated DC. Collectively, our study confirmed that MTIF2 impair drug-induced immunogenic cell death in hepatocellular carcinoma cells.