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As characterized by repeated exposure of others’ trauma, vicarious traumatization is a common negative psychological reaction during the COVID-19 pandemic and plays a crucial role in the development of general mental distress. This study aims to identify functional connectome that encodes individual variations of pandemic-related vicarious traumatization and reveal the underlying brain-vicarious traumatization mechanism in predicting general distress. The eligible subjects were 105 general university students (60 females, aged from 19 to 27 years) undergoing brain MRI scanning and baseline behavioral tests (October 2019 to January 2020), whom were re-contacted for COVID-related vicarious traumatization measurement (February to April 2020) and follow-up general distress evaluation (March to April 2021). We applied a connectome-based predictive modeling (CPM) approach to identify the functional connectome supporting vicarious traumatization based on a 268-region-parcellation assigned to network memberships. The CPM analyses showed that only the negative network model stably predicted individuals’ vicarious traumatization scores (q2 = -0.18, MSE = 617, r [predicted, actual] = 0.18, p = 0.024), with the contributing functional connectivity primarily distributed in the fronto-parietal, default mode, medial frontal, salience, and motor network. Furthermore, mediation analysis revealed that vicarious traumatization mediated the influence of brain functional connectome on general distress. Importantly, our results were independent of baseline family socioeconomic status, other stressful life events and general mental health as well as age, sex and head motion. Our study is the first to provide evidence for the functional neural markers of vicarious traumatization and reveal an underlying neuropsychological pathway to predict distress symptoms in which brain functional connectome affects general distress via vicarious traumatization.

To effectively and efficiently control vibrations in steel bridge decks, the flexural wave band gap and vibration attenuation mechanism are studied. The band structures and displacement fields of the eigenmodes at the band gap edges of infinite periodic U-rib stiffened plates are calculated. The calculation method is combining the finite element method with Bloch periodic boundary conditions. A scaled specimen test of a finite periodic U-rib stiffened plate is used to validate the numerical results. A comparison of results confirms that introducing the U-rib allows the periodic U-rib stiffened plates to yield several flexural wave band gaps. In the band gaps, flexural wave propagation is stopped and clear flexural vibration suppression is achieved. Furthermore, the effects of geometric parameters and structural schemes on the flexural wave band gaps are analyzed in detail. Finally, by analyzing a specific case, it is demonstrated that the flexural wave band gaps and vibration attenuation properties can be controlled. This provides a new approach to vibration and noise control in steel bridges.

Human papillomavirus (HPV) vaccines are efficacious against HPV infections and associated lesions in women HPV-naïve at vaccination. However, vaccine efficacy (VE) against oncogenic, high-risk HPV (HR-HPV) types in women infected with any other HR-HPV type at first vaccination (baseline) remains unclear. This post-hoc analysis of a phase II/III study (NCT00779766) evaluated AS04-adjuvanted HPV-16/18 (AS04-HPV-16/18) VE against HR-HPV type infection in 871 Chinese women aged 18–25 years over a 72-month follow-up period. Study participants were DNA-negative at baseline to HR-HPV type(s) considered for VE and DNA-positive to any other HR-HPV type. Initial serostatus was not considered. Baseline DNA prevalence was 14.6% for any HR-HPV type and 10.6% excluding HPV-16/18. In the total vaccinated cohort for efficacy, VE against 6-month and 12-month HPV-16/18 persistent infections (PIs) in women DNA-negative to HPV-16/18 but DNA-positive to any other HR-HPV type at baseline was 100.0% (95% Confidence Interval [CI]: 79.8–100.0) and 100.0% (95%CI: 47.2–100.0), respectively. VE against HPV-16/18 incident infections in women DNA-positive to one vaccine type but DNA-negative to the other one at baseline was 66.8% (95%CI: −18.9–92.5). VE against HPV-31/33/45 incident infections, in women DNA-positive to HPV-16/18 and DNA-negative to the considered HPV type at baseline was 71.0% (95%CI: 27.3–89.8). No HPV-16/18 PIs were observed in vaccinated women with non-vaccine HPV A7/A9 species cervical infection at baseline. These findings indicated that women with existing HR-HPV infection at vaccination might still benefit from the AS04-HPV-16/18 vaccine. However, this potential benefit needs further demonstration in the future.

Geopolymer is a green substitute for Portland cement but has low tensile strength, high brittleness and easy cracking. Therefore, fibers and nanomaterials are used to strengthen and toughen geopolymer composites. The influence of nano-calcium carbonate and PVA fiber on the properties of fresh and hardened geopolymer mortar were studied herein. The hybrid of long and short fibers with small content (0.8 vol.%) is conducive to flowability, while the hybrid with large content (1.6 vol.%) and nano-calcium carbonate is conducive to flowability. The slump flow and flow rate of geopolymer mortars with low fiber factor (product of fiber volume fraction and length-diameter ratio) decrease with the growth in nano-calcium carbonate content. As the PVA fiber factor reaches 464.8%, the slump flow and flow rate values of mortars with 0, 1 wt.% and 2 wt.% nano-calcium carbonate are close to each other. About 450% is the density packing threshold of PVA fiber in geopolymer composites. The combination of 0.8 vol.% 12 mm + 0.4 vol.% 6 mm fiber + 1 wt.% nano-calcium carbonate presents the highest flexural strength and flexural to compressive strength ratio, with a compressive strength of about 36 MPa. The optimal fiber factor range of PVA fiber in cement and geopolymer mortar is about 400% and higher than 600%, respectively. PVA fibers show more effective enhancement of flexural strength and toughness in geopolymer than cement mortar. The ultrasonic wave velocity and apparent density of geopolymer mortar show a downward trend as a whole with the increase in fiber factor. The intensity rise of the hump between 17° and 38° (2 θ) in the XRD pattern is observed. The SEM indicates that the surface of PVA fiber in geopolymer mortar with nano-calcium carbonate is heavily scratched, and the fiber filaments are rolled up, demonstrating improved bonding between PVA fiber and geopolymer mortar.

Three new compounds based on the combination of furoxan (1,2,5-oxadiazole N-oxide) and oxa-[5,5]bicyclic ring were synthesized. Among them, the nitro compound showed satisfactory detonation properties (Dv, 8565 m s−1; P, 31.9 GPa), which is comparable to the performance of RDX (a classic high-energy secondary explosive). Additionally, the introduction of the N-oxide moiety and oxidation of the amino group more effectively improved the oxygen balance and density (d, 1.81 g cm−3; OB%, +2.8%) of the compounds compared to furazan analogues. Combined with good density and oxygen balance as well as moderate sensitivity, this type of furoxan and oxa-[5,5]bicyclic structure will open up a platform for the synthesis and design of new high-energy materials.

Motor current signal analysis is a common method that can be applied to the monitoring and diagnosis of electromechanical equipment. Three-phase unbalance will increase the line power loss and affect the safe operation of power-using equipment. To quickly analyze motor current three-phase unbalance, we propose a method to analyze three-phase unbalance by calculating the coefficient of variation of the three-phase current’s instantaneous frequency and instantaneous amplitude. Simulations were conducted to analyze the effects of amplitude deviation and phase deviation on the coefficient of variation of instantaneous frequency and instantaneous amplitude. The three-phase unbalance with continuous amplitude change was simulated and its instantaneous performance was analyzed. Experiments were conducted to compare and analyze the instantaneous information characteristics of the motor with the continuous changing of three-phase unbalance under different speed conditions. Simulations and experiments show that the proposed method in this paper can analyze three-phase unbalance.

Injecting power plant flue gas into a goaf stores CO2 in the flue gas and effectively prevents the spontaneous combustion of the coal remaining in the goaf. Here, we investigated the adsorption behavior of three types of coal at normal temperature and pressure using a self-developed adsorption experimental device. We used a specific surface area and porosity analyzer to study the effects of pore structure, mineral content, and moisture content on CO2 adsorption in coal. Based on the experimental data, we designed a multifactor CO2 adsorption prediction model based on a backpropagation (BP) neural network. The results indicated that the pore size of most micropores in coal was in the range of 0.5–0.7 and 0.8–0.9 nm. The specific surface area and pore volume were positively correlated with the CO2-saturated adsorption capacity, whereas the mean pore diameter, mineral content, and moisture content were inversely associated with the CO2-saturated adsorption amount. The accuracy of the multifactor BP neural network prediction model was satisfactory: the determination coefficients (R2) of the training and test sets were both above 0.98, the root mean square error (RMSE) and mean absolute error (MAE) of the test set were both less than 0.1, and the prediction results satisfied the requirements. To optimize the prediction performance of the model, we used the random forest algorithm to calculate the importance of each factor. The sum of the importance weights of the specific surface area, moisture content, and pore volume was 91.6%, which was much higher than that of the other two factors. Therefore, we constructed an optimization model with specific surface area, moisture content, and pore volume as input variables. The R2 values of the training and test sets in the simplified model were improved compared with those of the multifactor model, the RMSE and MAE were reduced, and the fitting effect was ideal. The prediction model of CO2 adsorption in coal based on the BP neural network can predict the CO2 adsorption capacity of coal under different physical and chemical conditions, thereby providing theoretical support for the application of CO2 storage technology in goafs.

This paper investigates the multiple unmanned aerial vehicle (multi-UAV) cooperative task assignment problem. Specifically, we assign different types of UAVs to accomplish the classification, attack, and verification tasks of targets under resource, precedence, and timing constraints. Due to complex coupling among these tasks, we decompose the considered problem into two subproblems: one with continuous and independent tasks and another with continuous and correlative tasks. To solve them, we first present an adjustable, fully adaptive cross-entropy (AFACE) algorithm based on the cross-entropy (CE) method, which serves as a stepping stone for developing other algorithms. Secondly, to overcome task precedence in the first subproblem, we propose a mutually independent AFACE (MIAFACE) algorithm, which converges faster than the CE method when obtaining the optimal scheme vectors of these continuous and independent tasks. Thirdly, to deal with task coupling in the second subproblem, we present a mutually correlative AFACE (MCAFACE) algorithm to find the optimal scheme vectors of these continuous and correlative tasks, while its computational complexity is inferior to that of the MIAFACE algorithm. Finally, numerical simulations demonstrate that the proposed MIAFACE (MCAFACE, respectively) algorithm consumes less time than the existing algorithms for the continuous and independent (correlative, respectively) task assignment problem.

Organocatalytic atom transfer radical polymerization (O-ATRP) is attractive due to its metal-free nature but catalysts are rarely applied at a low loading. Here the authors introduce a catalyst design logic based on heteroatom-doping of polycyclic arenes, which led to the discovery of oxygen-doped anthanthrene as an organic photoredox catalysts for O-ATRP.

To overcome the shortcoming of conventional transarterial chemoembolization (cTACE) like high systemic release, a novel droplet-based flow-focusing microfluidic device was fabricated and the biocompatible poly(lactic-co-glycolic acid) (PLGA) magnetic drug-eluting beads transarterial chemoembolization (TACE) microspheres with tunable size and shell thickness were prepared via this device. Paclitaxel, as a model active, was loaded through O/O/W emulsion method with high efficiency. The size and the shell thickness vary when adjusting the flow velocity and/or solution concentration, which caters for different clinical requirements to have different drug loading and release behavior. Under the designed experimental conditions, the average diameter of the microspheres is 60 ± 2 μm and the drug loading efficiency has reached 6%. The drug release behavior of the microspheres shows the combination of delayed release and smoothly sustained release profiles and the release kinetics differ within different shell thickness. The microspheres also own the potential of magnetic resonance imaging (MRI) visuality because of the loaded magnetic nanoparticles. The microsphere preparation method and device we proposed are simple, feasible, and effective, which have a good application prospect.

Biodegradable microspheres have been widely used in the field of medicine due to their ability to deliver drug molecules of various properties through multiple pathways and their advantages of low dose and low side effects. Poly (lactic-co-glycolic acid) copolymer (PLGA) is one of the most widely used biodegradable material currently and has good biocompatibility. In application, PLGA with a specific monomer ratio (lactic acid and glycolic acid) can be selected according to the properties of drug molecules and the requirements of the drug release rate. PLGA-based biodegradable microspheres have been studied in the field of drug delivery, including the delivery of various anticancer drugs, protein or peptide drugs, bacterial or viral DNA, etc. This review describes the basic knowledge and current situation of PLGA biodegradable microspheres and discusses the selection of PLGA polymer materials. Then, the preparation methods of PLGA microspheres are introduced, including emulsification, microfluidic technology, electrospray, and spray drying. Finally, this review summarizes the application of PLGA microspheres in drug delivery and the treatment of pulmonary and ocular-related diseases.

Abstract Background Colposcopy diagnosis and directed biopsy are the key components in cervical cancer screening programs. However, their performance is limited by the requirement for experienced colposcopists. This study aimed to develop and validate a Colposcopic Artificial Intelligence Auxiliary Diagnostic System (CAIADS) for grading colposcopic impressions and guiding biopsies. Methods Anonymized digital records of 19,435 patients were obtained from six hospitals across China. These records included colposcopic images, clinical information, and pathological results (gold standard). The data were randomly assigned (7:1:2) to a training and a tuning set for developing CAIADS and to a validation set for evaluating performance. Results The agreement between CAIADS-graded colposcopic impressions and pathology findings was higher than that of colposcopies interpreted by colposcopists (82.2% versus 65.9%, kappa 0.750 versus 0.516, p 0.05). The CAIADS also demonstrated a superior ability in predicting biopsy sites, with a median mean-intersection-over-union (mIoU) of 0.758. Conclusions The CAIADS has potential in assisting beginners and for improving the diagnostic quality of colposcopy and biopsy in the detection of cervical precancer/cancer.

IntroductionAngiogenesis in pituitary tumors is not fully understood, and a better understanding could help inform new pharmacologic therapies, particularly for aggressive pituitary tumors.Materials and Methods219 human pituitary tumors and 12 normal pituitary glands were studied. Angiogenic genes were quantified by an angiogenesis qPCR array and a TaqMan probe-based absolute qPCR. Angiogenesis inhibition in pituitary tumors was evaluated in vitro with the endothelial tube formation assay and in vivo in RbΔ19 mice.Results71 angiogenic genes, 40 of which are known to be involved in sprouting angiogenesis, were differentially expressed in pituitary tumors. Expression of endothelial markers CD31, CD34, and ENG was significantly higher in pituitary tumors, by 5.6, 22.3, and 8.2-fold, respectively, compared to in normal pituitary tissue. There was no significant difference in levels of the lymphatic endothelial marker LYVE1 in pituitary tumors compared with normal pituitary gland tissue. Pituitary tumors also expressed significantly higher levels of angiogenesis growth factors, including VEGFA (4.2-fold), VEGFB (2.2), VEGFC (19.3), PGF (13.4), ANGPT2 (9.2), PDGFA (2.7), PDGFB (10.5) and TGFB1 (3.8) compared to normal pituitary tissue. Expression of VEGFC and PGF was highly correlated with the expression of endothelial markers in tumor samples, including CD31, CD34, and ENG (endoglin, a co-receptor for TGFβ). Furthermore, VEGFR inhibitors inhibited angiogenesis induced by human pituitary tumors and prolonged survival of RbΔ19 mice.ConclusionHuman pituitary tumors are characterized by more active angiogenesis than normal pituitary gland tissue in a manner consistent with sprouting angiogenesis. Angiogenesis in pituitary tumors is regulated mainly by PGF and VEGFC, not VEGFA and VEGFB. Angiogenesis inhibitors, such as the VEGFR2 inhibitor cabozantinib, may merit further investigation as therapies for aggressive human pituitary tumors.

Dispositional optimism (hereinafter, optimism), as a vital character strength, reflects the tendency to hold generalized positive expectancies for future outcomes. A great number of studies have consistently shown the importance of optimism to a spectrum of physical and mental health outcomes. However, less attention has been given to the intrinsic neurodevelopmental patterns associated with interindividual differences in optimism. Here, we investigated this important question in a large sample comprising 231 healthy adolescents (16–20 years old) via structural magnetic resonance imaging and behavioral tests. We constructed individual structural covariance networks based on cortical gyrification using a recent novel approach combining probability density estimation and Kullback-Leibler divergence and estimated global (global efficiency, local efficiency and small-worldness) and regional (betweenness centrality) properties of these constructed networks using graph theoretical analysis. Partial correlations adjusted for age, sex and estimated total intracranial volume showed that optimism was positively related to global and local efficiency but not small-worldness. Partial least squares correlations indicated that optimism was positively linked to a pronounced betweenness centrality pattern, in which twelve cognition-, emotion-, and motivation-related regions made robust and reliable contributions. These findings remained basically consistent after additionally controlling for family socioeconomic status and showed significant correlations with optimism scores from 2.5 years before, which replicated the main findings. The current work, for the first time, delineated characteristics of the cortical gyrification covariance network associated with optimism, extending previous neurobiological understandings of optimism, which may navigate the development of interventions on a neural network level aimed at raising optimism.

Resibufogenin (RB) is a major active ingredient in the traditional Chinese medicine Chansu and has garnered considerable attention for its efficacy in the treatment of cancer. However, the anticancer effects and underlying mechanisms of RB on glioblastoma (GBM) remain unknown. Here, we found that RB induced G2/M phase arrest and inhibited invasion in a primary GBM cell line, P3#GBM, and two GBM cell lines, U251 and A172. Subsequently, we demonstrated that RB-induced G2/M phase arrest occurred through downregulation of CDC25C and upregulation of p21, which was caused by activation of the MAPK/ERK pathway, and that RB inhibited GBM invasion by elevating intercellular Ca2+ to suppress the Src/FAK/Paxillin focal adhesion pathway. Intriguingly, we confirmed that upon RB binding to ATP1A1, Na+-K+-ATPase was activated as a receptor and then triggered the intracellular MAPK/ERK pathway and Ca2+-mediated Src/FAK/Paxillin focal adhesion pathway, which led to G2/M phase arrest and inhibited the invasion of GBM cells. Taken together, our findings reveal the antitumor mechanism of RB by targeting the ATP1A1 signaling cascade and two key signaling pathways and highlight the potential of RB as a new class of promising anticancer agents.

ObjectiveMalignant meningioma (MM) is a relatively rare disease with poor survival. Few studies had focused on MM in the elderly population. This study aims to explore the prognostic factors and optimal therapeutic strategy in elderly patients with MM.MethodsWe took advantage of the Surveillance, Epidemiology, and End Results (SEER) database to include 275 adult patients with histologically confirmed MM between 2011 and 2018. The Kaplan–Meier curves were plotted by different covariates to reveal the survival probability. Univariate and multivariable Cox proportional hazard regression analyses were applied to identify prognostic factors for cancer-specific survival (CSS).ResultsThe multivariable analysis in the elderly group revealed that when compared with patients receiving gross total resection (GTR), patients receiving biopsy had significantly worse CSS (HR = 3.72; 95% CI: 1.35–10.21; P = 0.011), whereas patients receiving subtotal resection (STR) had nearly the same CSS (HR = 0.83; 95% CI: 0.37–1.86; P = 0.653). Meanwhile, postoperative radiotherapy (PORT) showed no significant association with CSS in the elderly patient group (HR = 0.94; 95% CI: 0.42–2.12; P = 0.888).ConclusionSurgical resection is recommended for elderly patients with MM in the absence of surgical contraindications, but GTR does not present survival benefit in the elderly patients compared with STR. Additional large-scale clinical studies are needed to explore the survival benefit of PORT applied in patients with MM.

Epigenetic modification of chromatin is involved in non-malignant pituitary neoplasia by causing abnormal expression of tumor suppressors and oncogenes. These changes are potentially reversible, suggesting the possibility of targeting tumor cells by restoring the expression of epigenetically silenced tumor suppressors. The role of the histone deacetylase (HDAC) family in pituitary tumorigenesis is not known. We report that HDAC2 and 3, Class I HDAC members, are highly expressed in clinically non-functioning pituitary adenomas (NFPAs) compared to normal pituitary (NP) samples as determined by RT-PCR and immunohistochemical staining (IHC). Treatment of a human NFPA derived folliculostellate cell line, PDFS, with the HDAC3 inhibitor RGFP966 for 96 hours resulted in inhibition of cell proliferation by 70%. Furthermore, the combination of RGFP966 with a methyltransferase/DNMT inhibitor, 5’-aza-2’-deoxycytidine, led to the restoration of the expression of several tumor suppressor genes, including STAT1, P16, PTEN, and the large non-coding RNA tumor suppressor MEG3, in PDFS cells. Our data support the hypothesis that both histone modification and DNA methylation are involved in the pathogenesis of human NFPAs and suggest that targeting HDACs and DNA methylation can be incorporated into future therapies.

BackgroundLung adenocarcinoma (LUAD) is a fatal malignancy in the world. Growing evidence demonstrated that autophagy-related genes regulated the immune cell infiltration and correlated with the prognosis of LUAD. However, the autophagy-based signature that can predict the prognosis and the efficiency of checkpoint immunotherapy in LUAD patients is yet to be discovered.MethodsWe used conventional autophagy-related genes to screen candidates for signature construction in TCGA cohort and 9 GEO datasets (tumor samples, n=2181; normal samples, n=419). An autophagy-based signature was constructed, its correlation with the prognosis and the immune infiltration of LUAD patients was explored. The prognostic value of the autophagy-based signature was validated in an independent cohort with 70 LUAD patients. Single-cell sequencing data was used to further characterize the various immunological patterns in tumors with different signature levels. Moreover, the predictive value of autophagy-based signature in PD-1 immunotherapy was explored in the IMvigor210 dataset. At last, the protective role of DRAM1 in LUAD was validated by in vitro experiments.ResultsAfter screening autophagy-related gene candidates, a signature composed by CCR2, ITGB1, and DRAM1 was established with the ATscore in each sample. Further analyses showed that the ATscore was significantly associated with immune cell infiltration and low ATscore indicated poor prognosis. Meanwhile, the prognostic value of ATscore was validated in our independent LUAD cohort. GSEA analyses and single-cell sequencing analyses revealed that ATscore was associated with the immunological status of LUAD tumors, and ATscore could predict the efficacy of PD-1 immunotherapy. Moreover, in vitro experiments demonstrated that the inhibition of DRAM1 suppressed the proliferation and migration capacity of LUAD cells.ConclusionOur study identified a new autophagy-based signature that can predict the prognosis of LUAD patients, and this ATscore has potential applicative value in the checkpoint therapy efficiency prediction.

VSIR is a critical immunomodulatory receptor that inhibits T cell effector function and maintains peripheral tolerance. However, the mechanism by which VSIR participates in tumor immunity in the pan-cancer tumor microenvironment remains unclear. This study systematically explored the prognostic and immune profile of VSIR in the tumor microenvironment of 33 cancers. We compared the expression patterns and molecular features of VSIR in the normal and cancer samples both from the public databases and tumor chips. VSIR level was significantly related to patients’ prognosis and could be a promising predictor in many tumor types, such as GBM, KIRC, SKCM, READ, and PRAD. Elevated VSIR was closely correlated with infiltrated inflammatory cells, neoantigens expression, MSI, TMB, and classical immune checkpoints in the tumor microenvironment. Enrichment signaling pathways analysis indicated VSIR was involved in several immune-related pathways such as activation, proliferation, and migration of fibroblast, T cell, mast cell, macrophages, and foam cell. In addition, VSIR was found to widely express on cancer cells, fibroblasts, macrophages, and T cells in many tumor types based on the single-cell sequencing analysis and co-express with M2 macrophage markers CD68, CD163 based on the immunofluorescence staining. Finally, we predicted the sensitive drugs targeting VSIR and the immunotherapeutic value of VSIR. In sum, VSIR levels strongly correlated with the clinical outcome and tumor immunity in multiple cancer types. Therefore, therapeutic strategies targeting VSIR in the tumor microenvironment may be valuable tools for cancer immunotherapy.

CD147 plays an important role in promoting tumor proliferation and inhibiting cancer cell apoptosis in the tumor microenvironment. However, the mechanisms by which CD147 is involved in tumorigenesis remains unclear. This study systematically analyzed the prognostic value and immune characteristics of CD147 in 31 cancer types. The expression levels and mutant landscapes of CD147 in pan-cancer were explored. The Kaplan-Meier (KM) analysis was applied to analyze the prognostic value of CD147. The immune characteristics of CD147 in the tumor microenvironment were evaluated via TIMER 2.0 and R package (immunedeconv). We also explored the expression of CD147 on tumor cells and stromal cells through Gene Set Variation Analysis and single-cell sequencing analysis. The co-expression of CD147 and macrophage markers CD68 and CD163 in pan-cancer was detected using multiplex immunofluorescence staining on tissue microarrays. CD147 was found to be overexpressed in almost all cancer types, which was related to poor outcome. CD147 expression exhibited a strong association with immune infiltrates, immune checkpoint molecules, and neoantigen levels in the tumor microenvironment. In addition, CD147 was expressed on various cell types in the tumor microenvironment, including tumor cells, macrophages, T cells, monocytes, fibroblasts, etc. Furthermore, multiplex immunofluorescence revealed the co-expression pattern of CD147 and macrophage markers CD68 and CD163 in many tumor types. Finally, the immunotherapy response and sensitive small molecule drugs based on CD147 expression were predicted. In sum, CD147 has a significant relationship with the clinical outcome and immune infiltrates in multiple cancer types. Inhibiting the CD147-dependent signaling pathways might be a promising therapeutic strategy for tumor immunotherapy.

A luminescent Si nanocrystal (SiNC) thin film with photoluminescence quantum yield (PLQY) > 70% was made by using hydrogen silsesquioxane (HSQ), followed by long-time high-pressure hydrogenation. A net optical gain of 524 ± 21 cm−1 was obtained by means of variable stripe length-shifting excitation spot (VSL-SES). A rectangularly shaped SiO2 Fabry-Perot (F-P) cavity with size of 1.5 μm (width) × 0.7 μm (height) × 2000 μm (length) was made on top of the SiNC thin film. The waveguide F-P device was pumped with a 400 nm femtosecond pulsed laser. A threshold behavior of the light emission intensity as a function of the pumping power was observed. Other lasing characteristics including spectral narrowing, polarization of the emission, and small emission angle were also observed beyond the threshold pumping power.

Natural rivers have always been invaded by multiple pollutants discharged by anthropogenic activities, inducing physiochemical and biological changes to waterbodies. However, the effects of different types of anthropogenic disturbances and natural wetlands on water quality and bacterial communities in black-odor rivers remain largely unknown. In this study, 13 water quality parameters at 48 sampling sites along the typical contaminated Jishan River were selected to evaluate water quality through water quality index (WQI). The analysis of microbial community composition and its correlation with water quality of different disturbances (industrial effluent, aquacultural wastewater, domestic sewage, confluences, dam and wetlands) were further conducted. The results revealed that water quality parameters had significant spatial heterogeneity in water samples of different disturbed sites, and the different types of disturbances shaped the abundance and distribution of bacterial communities. Among these disturbances, dam altered the hydrological and hydraulic conditions of this river, leading to the worst water quality, with the fermentative microorganism Lactococcus becoming the dominant genus. Natural wetlands surrounding the terminus of this river had recuperative functions and could restore water quality and microbial community. The WQI values 38.08–63.46 were rated as “low” or “moderate” and primarily affected by excessive nutrient contaminates, such as nitrogen, phosphorus, and organic matter. Random forest analysis revealed that the biomarkers for water quality were C39, Trichococcus, norank_f_norank_o_Chloroplast, and unclassified_f_Enterobacteriaceae. This study not only facilitated a more comprehensive understanding about the correlation between water quality and bacterial communities of river ecosystem but also provided theoretical support for ecological restoration and governmental regulation of the water ecosystem.

Abstract Background It is widely acknowledged that HPV prophylactic vaccine could prevent new infections and their associated lesions among women who are predominantly HPV-naive at vaccination. Yet there still remains uncertainty about whether HPV vaccination could benefit to individuals who have undergone surgery for cervical disease. Methods This post-hoc analysis intends to focus on intent-to-treat participants who underwent excision treatment at baseline and the follow-up period in a phase II/III, double-blind, randomized trial ( ClinicalTrials.gov , number NCT00779766 ) conducted in Jiangsu province, China. We evaluate the impact of HPV vaccination on preventing women from subsequent infection and cervical lesions (LSIL+ and CIN2+) after excision treatment. Results One hundred sixty-eight (vaccine, n = 87; placebo, n = 81) performed excisional treatment in this clinical trial. We observed a significant effect of vaccination on acquiring 14 high-risk HPV (HR-HPV) infection after treatment (vaccine efficacy: 27.0%; 95% CI 4.9, 44.0%). The vaccine efficacy against new infections after treatment for 14 HR-HPV infection was estimated as 32.0% (95%CI 1.8, 52.8%), and was 41.2% (95%CI -162.7, 86.8%) for HPV16/18 infection. The accumulative clearance rates of the vaccine group and placebo group were 88.9 and 81.6% for HPV16/18 infection (P = 0.345), 63.4, 48.7% for 14 HR-HPV infection (P = 0.062), respectively. No significant difference was observed on the persistent rate of HPV16/18, 14 HR-HPV infection and occurrence rate of LSIL+ between the two groups. Conclusions No significant evidence from this study showed that HPV-16/18 AS04-adjuvanted vaccine could lead to viral faster clearance or have any effect on the rates of persistent infection among women who had excision treatment. However, the vaccine may still benefit post-treatment women with “primary prophylactic” effect. Further research is required in clarifying the effect of using the prophylactic HPV vaccine as therapeutic agents. Trial registration ClinicalTrials.gov identifier: NCT00779766 . Date and status of trial registration: October 24, 2008. Completed; Has Results.

Abstract Ferroptosis is a recently discovered distinct type of regulated cell death caused by the accumulation of lipid-based ROS. Metabolism and expression of specific genes affect the occurrence of ferroptosis, making it a promising therapeutic target to manage cancer. Here, we describe the current status of ferroptosis studies in breast cancer and trace the key regulators of ferroptosis back to previous studies. We also compare ferroptosis to common regulated cell death patterns and discuss the sensitivity to ferroptosis in different subtypes of breast cancer. We propose that viewing ferroptosis-related studies from a historical angle will accelerate the development of ferroptosis-based biomarkers and therapeutic strategies in breast cancer.

Atomic structure of alkali metal is difficult to be revealed at room temperature because of the chemical reactivity and irradiation sensitivity. Here the authors show that electron beam-induced in situ growth of alkali metals enables the investigation of atomic structure and growth kinetics at high spatiotemporal resolution.

At this stage,the Internet of things (IoT) customer business is developing rapidly.The management problems of weak customer operation ability have gradually exposed in the IoT industry,resulting in the low AP (analytical processing) value of customers,the low profitability and high operating cost.Therefore,it is urgent to enhance the massive data analysis capabilities of the IoT to provide data guidance for business development.To improve the customer value,big data technology,multi-dimensional analysis technology and massive query technology were used to make portraits of IoT enterprise customers,and realize the construction of the customer data platform with refined and efficient operation services.It was introduced how to construct the data operation platform from the aspect of technology implementation.

The Internet of Radio-Light (IoRL) is a cutting-edge system paradigm to enable seamless 5G service provision in indoor environments, such as homes, hospitals, and museums. The system draws on innovative architectural structure that sits on the synergy between the Radio Access Network (RAN) technologies of millimeter Wave communications (mmWave) and Visible Light Communications (VLC) for improving network throughput, latency, and coverage compared to existing efforts. The aim of this paper is to introduce the IoRL system architecture and present the key technologies and techniques utilised at each layer of the system. Special emphasis is given in detailing the IoRL physical layer (Layer 1) and Medium Access Control layer (MAC, Layer 2) by means of describing their unique design characteristics and interfaces as well as the robust IoRL methods of improving the estimation accuracy of user positioning relying on uplink mmWave and downlink VLC measurements.

The robust reconstruction of the reference signal is one of the key technologies in passive radars. This paper investigates the reference signal reconstruction problem for digital television terrestrial multimedia broadcasting (DTMB)-based passive radar. The conventional digital signal processing for the DTMB signal is usually based on the assumption of the equal bandwidth sampling (EBS) in which the sampling rate is equal to the nominal bandwidth 7.56 MHz defined in the DTMB standard. But we reveal that the high-frequency subcarriers of the DTMB signal are aliased under the EBS, which will degrade the reconstruction performance. Thus we suggest the oversampling approach for the DTMB-based passive radar. The least squares (LS) channel estimation under oversampling is thoroughly analyzed. Moreover to solve the problem that the LS algorithm cannot estimate the time-domain response of the channel under oversampling, we propose two modified LS channel estimation algorithms, namely the Tikhonov regularization LS and reduced rank approximation LS. The advantages of the reference signal reconstruction under oversampling over that under EBS are validated by both the simulation and field experimental data.

Digital signage is an important outdoor advertising medium in cities. However, advertising on digital signage often lacks pertinence. Thus, it is important to introduce an accurate digital signage audience classification method to facilitate targeted advertising. In this study, a multi-label classification model based on a backpropagation (BP) neural network and the Huff model, referred to as the Huff-BP model, is proposed to investigate digital signage audience classification. A case study is performed on outdoor digital signage within the 6th Ring Road in Beijing, China, and economic census, population census, average housing price, social media check-in and the centrality of traffic networks as research data. The data are divided into 100 × 100-1,000 × 1,000 m normal grids. Multi-label classification modelling factors for various grid scales are constructed. The BP neural network classification algorithm is improved to solve the multilabel classification problem. In addition, an improved Huff model is used to calculate the digital signage influence values between each grid cell and integrated into the improved BP neural network to classify modelling factors at various scales. Finally, four metrics are used to examine the effectiveness of the proposed model. The results show that the Huff-BP-based multi-label classification model achieves relatively good classification results, and the digital signage audiences are mainly concentrated within the 4th Ring Road and near the 5th Ring Road.

Abstract Purpose To evaluate the method and effectiveness of transcatheter arterial chemoembolization (TACE) combined with simultaneous DynaCT-guided Microwave ablation (MWA) for the treatment of small hepatocellular carcinoma (SHCC). Materials and methods From June 2015 to May 2017, a total of 28 consecutive patients with SHCC received single treatment of TACE and 23 subjects received a combination treatment of TACE with simultaneous DynaCT-guided MWA. Following 1 month of treatment, the tumor response was assessed using the mRECIST criteria and the outcomes were analyzed including intervention-associated complications, changes in liver function, imaging response, and progression-free survival (PFS). Results The technical success rate was 100%. The rates of CR (65%) in the combined TACE and MWA group were higher than those of the TACE group (46%). The rate of common adverse events, such as liver abscess, spontaneous bacterial peritonitis and liver dysfunction, in the combined TACE and MWA group (56%) was comparable to the corresponding rate of the TACE group (P > 0.411). The median and mean PFS of the TACE group were significantly lower than those of the combined TACE and MWA group (19.00 months vs. 29.00 months, 21.076 months vs. 24.693 months, p = 0.019, log-rank test). Conclusion Stereotactic DynaCT-guided MWA is a safe and effective method for the treatment of SHCC, which usually provides an effective tumor puncture path, notably for lesions that cannot be detected following TACE. Overall, the data suggested that this treatment method could improve the clinical outcome of patients with SHCC.

An interacting multiple model based on unscented Kalman filter (IMM-UKF) is widely applied to positioning and tracking targets in various tracking scenarios. At the same time, visible light positioning (VLP) is developing rapidly due to the low cost and accuracy. Therefore, indoor positioning and tracking based on VLP combined with the IMM-UKF has attracted considerable interest. However, existing algorithms work on the assumption that the light-emitting diodes used for tracking are all point light sources, which ignores the geometry of these transmitters and results in low tracking accuracy. To overcome this problem, this paper proposes an innovative tracking algorithm based on VLP. This algorithm considers the shapes of the lights in combination with existing tracking algorithms, such as IMM-UKF. Simulation results show that in a standard Gaussian noise environment, the larger the transmitter is, the more meaningful the proposed algorithm is.

RNA interference (RNAi) is a widely used technique for gene function researches and recently pest controls. It had been applied in emerald ash borer (EAB Agrilus planipennis) larvae and adults, and achieved significant interference effects, whether by ingesting or microinjecting. Feeding in the phloem and cambial regions, the larvae of A. planipennis are difficult to be controlled by conventional insecticides, so adult stage is the critical stage for EAB control. However, the target genes of adult stage of A. planipennis need to be further screened. Here, we preliminarily screened five potential target genes of vision and olfaction for RNAi in A. planipennis. Three odorant binding proteins (OBPs) and three opsins, which expressed significantly different between newly emerged and sexually mature EABs (OBP5, OBP7, OBP10, LW opsin 1 and UV opsin 2) or highly in sexually mature male EAB (UV opsin 3), were selected as targets to design primers for gene silencing. After dsRNA injection, the gene expression levels were determined by real-time quantitative PCR. We found that the expression levels of five genes were significantly down-regulated, during the 4 days after dsRNA injection. Among these genes, the expression of LW opsin 1 was down-regulated the most, causing a reduction of 99.1% compared with the control treated with EGFP dsRNA, followed by UV opsin 3 (97.4%), UV opsin 2 (97.0%), OBP7 (96.2%), and OBP10 (88.7%). This study provides a basis for further RNAi-based new controlling method development of A. planipennis at adult stage.

Increasing evidence has demonstrated that RING finger (RNF) proteins played a vital role in cellular and physiological processes and various diseases. However, the function of RNF proteins in low-grade glioma (LGG) remains unknown. In this study, 138 RNF family members revealed their role in LGG. The TCGA database was used as the training cohort; two CGGA databases and GSE108474 were selected as external validation cohorts. Patients were grouped into cluster 1 and cluster 2, both in the training and validation cohorts, using consensus clustering analysis. The prognosis of patients in cluster 1 is significantly better than that in cluster 2. Meanwhile, biofunction prediction was further introduced to explore the potential mechanisms that led to differences in survival outcomes. Patients in Cluster 2 showed more complicated immunocytes infiltration and highly immunosuppressive features than cluster 1. Enrichment pathways such as negative regulation of mast cell activation, DNA replication, mismatch repair, Th17 cell differentiation, antigen processing and presentation, dendritic cell antigen processing and presentation, dendritic cell differentiation were also enriched in cluster 2 patients. For the last, the main contributors were distinguished by employing a machine learning algorithm. A lot of targeted and small molecule drugs that are sensitive to patients in cluster 2 were predicted. Importantly, we discovered TRIM8, DTX2, and TRAF5 as the most vital contributors from the RNF family, which were related to immune infiltration in LGG tumor immune landscape. In this study, we demonstrated the predicted role of RNF proteins in LGG. In addition, we found out three markers among RNF proteins that are closely related to the immune aspects of LGG, which might serve as novel therapeutic targets for immunotherapy in the future.

Background: The pathophysiological mechanisms underlying postoperative cognitive dysfunction (POCD) remain unclear over the years. Neuroinflammation caused by surgery has been recognized as an important element in the development of POCD. Many studies also suggest that the vagus nerve plays an important role in transmitting peripheral injury signals to the central nervous system (CNS) and the resultant neuroinflammation. Previously, we have demonstrated that brain mast cells (BMCs), as the “first responders”, play a vital role in neuroinflammation and POCD. However, how the vagus nerve communicates with BMCs in POCD has not yet been clarified.Methods: In the current study, we highlighted the role of the vagus nerve as a conduction highway in surgery-induced neuroinflammation for the first time. In our model, we tested if mice underwent unilateral cervical vagotomy (VGX) had less neuroinflammation compared to the shams after laparotomy (LP) at an early stage. To further investigate the roles of mast cells and glutamate in the process, we employed KitW-sh mice and primary bone marrow-derived MCs to verify the glutamate-NR2B axis on MCs once again.Results: Our results demonstrated that there were higher levels of glutamate and BMCs activation as early as 4 h after LP. Meanwhile, vagotomy could partially block the increases and reduce neuroinflammation caused by peripheral inflammation during the acute phase. Excitingly, inhibition of NR2B receptor and knockout of mast cells can attenuateneuroinflammation induced by glutamate.Conclusion: Taken together, our findings indicate that the vagus is a high-speed pathway in the transmission of peripheral inflammation to the CNS. Activation of BMCs triggered a neuroinflammatory cascade. Inhibition of NR2B receptor on BMCs can reduce glutamate-induced BMCs activation, neuroinflammation, and memory impairment, suggesting a novel treatment strategy for POCD.

Lower-grade glioma (LGG) is one of the most common primary tumor types in adults. The chemokine-like factor (CKLF)-like Marvel transmembrane domain-containing (CMTM) family is widely expressed in the immune system and can modulate tumor progression. However, the role of the CMTM family in LGG remains unknown. A total of 508 LGG patients from The Cancer Genome Atlas (TCGA) database were used as a training cohort, and 155 LGG patients from the Chinese Glioma Genome Atlas (CGGA) array database, 142 LGG patients from the CGGA RNA-sequencing database, and 168 LGG patients from the GSE108474 database were used as the validation cohorts. Patients were subdivided into two groups using consensus clustering. The ENET algorithm was applied to build a scoring model based on the cluster model. Finally, ESTIMATE, CIBERSORT, and xCell algorithms were performed to define the tumor immune landscape. The expression levels of the CMTM family genes were associated with glioma grades and isocitrate dehydrogenase (IDH) status. Patients in cluster 2 and the high-risk score group exhibited a poor prognosis and were enriched with higher grade, wild-type IDH (IDH-WT), 1p19q non-codeletion, MGMT promoter unmethylation, and IDH-WT subtype. Patients in cluster 1 and low-risk score group were associated with high tumor purity and reduced immune cell infiltration. Enrichment pathways analysis indicated that several essential pathways involved in tumor progression were associated with the expression of CMTM family genes. Importantly, PD-1, PD-L1, and PD-L2 expression levels were increased in cluster 2 and high-risk groups. Therefore, the CMTM family contributes to LGG progression through modulating tumor immune landscape.

Gliomas are malignant tumors that originate from the central nervous system. The aldehyde dehydrogenase family has been documented to affect cancer progression; however, its role in gliomas remains largely unexplored. Bulk RNA-seq analysis and single-cell RNA-Seq analysis were performed to explore the role of the aldehyde dehydrogenases family in gliomas. Training cohort contained The Cancer Genome Atlas data, while data from Chinese Glioma Genome Atlas and Gene Expression Omnibus were set as validation cohorts. Our scoring system based on the aldehyde dehydrogenases family suggested that high-scoring samples were associated with worse survival outcomes. The enrichment score of pathways were calculated by AUCell to substantiate the biofunction prediction results that the aldehyde dehydrogenases family affected glioma progression by modulating tumor cell proliferation, migration, and immune landscape. Tumor immune landscape was mapped from high-scoring samples. Moreover, ALDH3B1 and ALDH16A1, two main contributors of the scoring system, could affect glioblastoma cell proliferation and migration by inducing cell-cycle arrest and the epithelial-mesenchymal transition. Taken together, the aldehyde dehydrogenases family could play a significant role in the tumor immune landscape and could be used to predict patient prognosis. ALDH3B1 and ALDH16A1 could influence tumor cell proliferation and migration.

Gliomas are aggressive tumors in the central nervous system and glioblastoma is the most malignant type. Ferroptosis is a programmed cell death that can modulate tumor resistance to therapy and the components of tumor microenvironment. However, the relationship between ferroptosis, tumor immune landscape, and glioblastoma progression is still elusive. In this work, data from bulk RNA-seq analysis, single cell RNA-seq analysis, and our own data (the Xiangya cohort) are integrated to reveal their relationships. A scoring system is constructed according to ferroptosis related gene expression, and high scoring samples resistant to ferroptosis and show worse survival outcome than low scoring samples. Notably, most of the high scoring samples are aggressive glioblastoma subtype, mesenchymal, and classical, by calculating RNA velocity. Cross-talk between high scoring glioblastoma cells and immunocytes are explored by R package ‘celltalker’. Ligand–receptor pairs like the TRAIL or TWEAK signaling pathway are identified as novel bridges implying how ferroptosis modulate immunocytes’ function and shape tumor microenvironment. Critically, potential drugs target to high scoring samples are predicted, namely, SNX2112, AZ628, and bortezomib and five compounds from the CellMiner database. Taken together, ferroptosis associates with glioblastoma aggressiveness, cross-talk with immunocytes and offer novel chemotherapy strategy.

ObjectiveThe purpose of this study was to screen active components and molecular targets of nine prescriptions recommended by the National Health Commission (NHC) of China by network pharmacology, and to explore the potential mechanism of the core active components against COVID-19 with molecular docking.MethodsDifferentially expressed genes of lung adenocarcinoma (LUAD) screened by edgeR analysis were overlapped with immune-related genes in MMPORT and COVID-19-related genes in GeneCards. The overlapped genes were also COVID-19 immune-related genes in LUAD. TCMSP platform was used to identify active ingredients of the prescription, potential targets were identified by the UniProt database, and the cross genes with COVID-19 immune-related genes in LUAD were used to construct a Chinese Medicine-Logy-immune target network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the target genes of each prescription. Finally, the key active components were selected for molecular docking simulation with ACE2.ResultsWe obtained 15 overlapping immunization target genes from FPQXZ, HSYFZ, HSZFZ, and QFPDT, 16 overlapping immunization target genes from QYLFZ, SDYFZ, SRYFZ, and YDBFZ, and 17 overlapping immunization target genes from QYLXZ. ADRB2, FOS, HMOX1, ICAM1, IL6, JUN, NFKBIA, and STAT1 also had the highest-ranked therapeutic targets for 9 prescriptions, and their expressions were positively correlated with TME-related stromal score, immune score, and ESTIMATE score. Among 9 compounds with the highest frequency of occurrence in the 9 prescriptions, baicalein had the highest ACE2 binding affinity and can be well-combined into the active pocket of ACE2 It is stabilized by forming hydrogen bonds with ASN290 and ILE291 in ACE2 and hydrophobic interaction with PHE438, ILE291, and PRO415.ConclusionThe nine Chinese medicine prescriptions may play an anti-SARS-CoV-2 role via regulating viral transcription and immune function through multi-component, multi-target, and multi-pathway.

Hypoxia and angiogenesis are the leading causes of tumor progression, and their strong correlation has been discovered in many cancers. However, their collective function’s prognostic and biological roles were not reported in gastric cancer. Hence, we aimed to investigate the effects of hypoxia and angiogenesis on gastric cancer via sequencing data. This study used weighted gene coexpression network analysis and random forest regression to build a hypoxia-angiogenesis-related model (HARM) via the TCGA-STAD lncRNA data. It estimated the HARM’s correlation with clinical features and its accuracy for survival prediction. Sequential functional analyses were conducted to investigate its biological role, and we next sought the immune landscape status and immunological function variation by ESTIMATE score calculation and GSVA, respectively. Seven different algorithms were conducted to assess the immunocyte infiltration, and TIDE score and immune checkpoint levels were compared between the high- and low-HARM groups. As a result, we found that HARM predicted patient survival with high accuracy and was correlated with higher stages of gastric cancer. Various cancer-associated pathways and macrophage-related regulations were upregulated in the high-HRAM group. The high-HARM group harbored higher immune levels, and M2 macrophages and cancer-associated fibroblasts were particularly highly unfiltered. Furthermore, globally upregulated immune checkpoints and higher TIDE scores were observed in the high-HARM group. Finally, we filtered eight drugs with lower IC50 in the high-HARM group as potential drugs for the HARM-targeted therapy. We believe this study opens up novel perspectives into the interaction between hypoxia-angiogenesis and immunosuppression and will provide novel insights for gastric cancer immunotherapy.

Oil shale is a crucial unconventional energy source to supplement conventional oil and gas. The oil shale in the Maoming Basin of China has excellent resource potential. In this study, through systematic geochemical testing, the industrial quality and geochemical characteristics of oil shale are revealed, and the hydrocarbon generation potential of oil shale, the parent rock type, and the tectonic setting of the source area are discussed. It is comprehensively assessed that Maoming oil shale has a medium-oil yield (avg. 6.71%) with high ash content (avg. 76.1%), a high calorific value (avg. 7.16 M J/kg), and ultra-low sulfur (avg. 0.54%). The mineralogical compositions primarily consist of clay minerals and quartz, and barely pyrite. Maoming oil shale is in an immature evolution stage, with high TOC and I-II1 kerogen type, and could be considered an excellent hydrocarbon source rock. The chemical index of alteration (CIA), the index of chemical variability (ICV), and the Th/U ratio indicate that the Maoming oil shale parent rock area is strongly weathered. Multitudinous geochemical diagrams also show that the oil shale was mainly derived from Late Cretaceous felsic volcanic rock and the granite zone, and the tectonic setting was a continental island arc environment related to the active continental margin. This is consistent with the tectonic history of southern China in the Late Cretaceous.

Abstract Background Posterior percutaneous endoscopic lumbar discectomy (PELD) has become a preferred procedure for the treatment of simple lumbar disc herniation (LDH) but has rarely been reported for distant upward migration. The purpose of this research was to investigate the feasibility, safety, clinical efficacy and technical points of posterior PELD combined with the vertical anchoring technique (VAT) for the treatment of LDH with distant upward migration. Methods Thirteen patients with distant upward migrated LDH who underwent posterior PELD combined with the VAT from March 2016 to May 2018 were selected. Among these cases, the herniated disc was located at L3/4 in 2 patients, L4/5 in 9 patients and L5/S1 in 2 patients. The operative time, length of hospital stay and postoperative complications were recorded. The visual analogue score (VAS), Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) scores and modified MacNab criteria were used to assess surgical efficacy. Results All 13 patients underwent successful surgery. We compared the VAS, ODI and JOA scores before and after surgery. The differences were statistically significant (P

Aberrant methylation has been regarded as a hallmark of cancer. 5-hydroxymethylcytosine (5hmC) is recently identified as the ten-eleven translocase (ten-eleven translocase)-mediated oxidized form of 5-methylcytosine, which plays a substantial role in DNA demethylation. Cell-free DNA has been introduced as a promising tool in the liquid biopsy of cancer. There are increasing evidence indicating that 5hmC in cell-free DNA play an active role during carcinogenesis. However, it remains unclear whether 5hmC could surpass classical markers in cancer detection, treatment, and prognosis. Here, we systematically reviewed the recent advances in the clinic and basic research of DNA 5-hydroxymethylation in cancer, especially in cell-free DNA. We further discuss the mechanisms underlying aberrant 5hmC patterns and carcinogenesis. Synergistically, 5-hydroxymethylation may act as a promising biomarker, unleashing great potential in early cancer detection, prognosis, and therapeutic strategies in precision oncology.

DNA methylation patterns are essential in understanding carcinogenesis. However, the relationship between DNA methylation and the immune process has not been clearly established—this study aimed at elucidating the interaction between glioma and DNA methylation, consolidating glioma classification and prognosis. A total of 2,483 immune-related genes and 24,556 corresponding immune-related methylation probes were identified. From the Cancer Genome Atlas (TCGA) glioma cohort, a total of 683 methylation samples were stratified into two different clusters using unsupervised clustering, and eight types of other cancer samples from the TCGA database were shown to exhibit excellent distributions. A total of 3,562 differentially methylated probes (DMPs) were selected and used for machine learning. A five-probe signature was established to evaluate the prognosis of glioma as well as the potential benefits of radiotherapy and Procarbazine, CCNU, Vincristine (PCV) treatment. Other prognostic clinical models, such as nomogram and decision tree, were also evaluated. Our findings confirmed the interactions between immune-related methylation patterns and glioma. This novel approach for cancer molecular characterization and prognosis should be validated in further studies.

Background. We aimed to characterize patterns of differences in heart graft failure rates by recipient sex, accounting for modifying effects of donor sex and recipient age. Methods. We evaluated 69 246 first heart transplant recipients (1988–2019; Scientific Registry of Transplant Recipients). We used multivariable time-varying Cox models, considering recipient sex by donor sex by recipient age interaction and adjusting for potential confounders. Using the hazard ratio (HR) from the models and a fixed profile of recipient and donor characteristics, we also compared fitted absolute failure rates by recipient sex. Results. Among recipients of male donors, female recipients of all ages had higher failure rates than males (0–12 y: HR 1.36 (95% confidence interval [CI], 1.03-1.81); 13–24 y: 1.43 [1.09-1.88]; 25–44 y: 1.22 [0.95-1.57]; ≥45 y: 1.16 [1.06-1.27]); differences were statistically significant in all age intervals except 25–44 y. When the donor was male, 13 to 24-y-olds showed the largest absolute difference in fitted absolute failure rates, with rates higher by 11.3 failures per 1000 person-y in female than male recipients. Among recipients of female donors, there were no statistically significant differences in graft failure rates between female and male heart recipients of any age. Although point estimates suggested higher failure rates in female than male recipients

Existing therapeutic strategies for gliomas are restricted; hence, exploration for novel diagnostic indicator and treatment is essential. Here, we performed bioinformatic analyses for TNFSF13 (also known as APRIL), a proliferation-inducing ligand of the tumor necrosis factor (TNF) superfamily, aiming to assess its potential for predicting glioma patient’s prognosis and targeted therapy. TNFSF13 expression was upregulated in the increase of tumor grades based on Xiangya cohort. In high TNFSF13 gliomas, somatic mutation was proved to correlate with amplification of EGFR and deletion of CDKN2A; while mutation of IDH1 was more frequently observed in low TNFSF13 group. We also confirmed the positive correlation between TNFSF13 and infiltrating immune and stromal cells in glioma microenvironment. Further, TNFSF13 was found to be involved in immunosuppression via diverse immunoregulation pathways and was associated with other immune checkpoints and inflammation. Single-cell sequencing revealed an abundant expression of TNFSF13 in neoplastic cells and M2 macrophages, which TNFSF13 might potentially regulate the cell communication via IL-8, C3, and CD44. Lastly, TNFSF13 mediated the activities of transcription factors including FOXO3, MEIS2, and IRF8. Our analyses demonstrated the relevance between TNFSF13 and glioma progress and indicated the potential of TNFSF13 as a novel diagnostic onco-inflammatory biomarker and immunotherapy target of gliomas.

Human pituitary adenomas are one of the most common intracranial neoplasms. Although most of these tumors are benign and can be treated medically or by transsphenoidal surgery, a subset of these tumors are fast-growing, aggressive, recur, and remain a therapeutic dilemma. Because antibodies against immune checkpoint receptors PD-1 and CLTA-4 are now routinely used for cancer treatment, we quantified the expression of mRNA coding for PD-1, CLTA-4, and their ligands, PD-L1, PD-L2, CD80, and CD86 in human pituitary adenomas and normal pituitary glands, with the ultimate goal of exploiting immune checkpoint therapy in aggressive pituitary adenomas. Aggressive pituitary adenomas demonstrated an increased expression of PD-L2, CD80, and CD86 in compared to that of normal human pituitary glands. Furthermore, aggressive pituitary tumors demonstrated significantly higher levels of CD80 and CD86 compared to non-aggressive tumors. Our results establish a rationale for studying a potential role for immune checkpoint inhibition therapy in the treatment of pituitary adenomas.

Under the background of global climate change, the impact from drought on the ecosystem exhibits the characteristics of complexity and multi-process, especially for the main component, which is the grassland ecosystem of the overall ecosystem. Identifying past droughts and predicting future ones is vital in limiting their effects. However, the random and non-linear nature of drought variables makes accurate drought prediction still a challenging scientific problem. In this study, the boundaries, Land Surface Temperature (LST) and Enhanced Vegetation Index (EVI) of Asian Grassland Ecosystem (AGE) were obtained by Google Earth Engine (GEE), which were used to construct LST-EVI feature spaces to calculate the dry-wet edge fitting equations and Temperature Vegetation Drought Index (TVDI). Mann–Kendall test and Sen trend degrees were further used to analyze the drought trend of AGE. The results showed that there were obvious spatial differences in the wet and dry conditions of AGE, which showed that the TVDI increased from east to west and from north to south, with humid areas mainly concentrated in northern Asia and severe drought areas concentrated in southern Asia. From 2010 to 2018, the area of humid areas and severe drought areas of AGE decreased, and some humid areas changed to normal areas or even drought areas, while the drought in severe drought areas was alleviated. The results of the Sen trend test further show that the aggravating trend of drought in severe drought areas of South Asia is relatively low, and some areas show a trend of changing to humidity. However, there is an obvious aggravating trend of drought in humid areas or low drought areas of South Asia, these areas should also be the focus areas for drought prevention in the future. This study identified the spatio-temporal distribution characteristics and evaluated the evolution trend of the drought of AGE, which is of great significance to the management and prevention of drought of AGE.

Gliomas are a type of malignant central nervous system tumor with poor prognosis. Molecular biomarkers of gliomas can predict glioma patient’s clinical outcome, but their limitations are also emerging. C-X-C motif chemokine ligand family plays a critical role in shaping tumor immune landscape and modulating tumor progression, but its role in gliomas is elusive. In this work, samples of TCGA were treated as the training cohort, and as for validation cohort, two CGGA datasets, four datasets from GEO database, and our own clinical samples were enrolled. Consensus clustering analysis was first introduced to classify samples based on CXCL expression profile, and the support vector machine was applied to construct the cluster model in validation cohort based on training cohort. Next, the elastic net analysis was applied to calculate the risk score of each sample based on CXCL expression. High-risk samples associated with more malignant clinical features, worse survival outcome, and more complicated immune landscape than low-risk samples. Besides, higher immune checkpoint gene expression was also noticed in high-risk samples, suggesting CXCL may participate in tumor evasion from immune surveillance. Notably, high-risk samples also manifested higher chemotherapy resistance than low-risk samples. Therefore, we predicted potential compounds that target high-risk samples. Two novel drugs, LCL-161 and ADZ5582, were firstly identified as gliomas’ potential compounds, and five compounds from PubChem database were filtered out. Taken together, we constructed a prognostic model based on CXCL expression, and predicted that CXCL may affect tumor progression by modulating tumor immune landscape and tumor immune escape. Novel potential compounds were also proposed, which may improve malignant glioma prognosis.

Summary: Garnet-type solid electrolytes have attracted extensive attention for solid-state lithium (Li) batteries. However, the high processing temperature of up to 1,200°C limits large-scale production. Here, we report a simple approach to reduce the sintering temperature by using a conformal nanoscale amorphous alumina coating. The ceramic sintered at 980°C shows a high room temperature ionic conductivity of 0.13 mS cm−1. It reveals that the second phases segregated at grain boundaries are ionically conductive but electronically blocking, which can block electronic conduction and improve mechanical property. The Li symmetry cells indicate a long-term 2,500-cycle life and a high critical current density of 0.52 mA cm−2. The garnet electrolyte enables the high-voltage cells using Li1.2Ni0.2Mn0.6O2 to deliver a high specific capacity of 248 mAh g−1 at 0.05 C. This work provides a new clue for lowering sintering temperature for garnet electrolytes, which can extend to other ceramics toward practical applications.