The aim is to explore the relation between inflammation‐associated factors and in‐hospital mortality and investigate which factor is an independent predictor of in‐hospital death in patients with ...coronavirus disease‐2019. This study included patients with coronavirus disease‐2019, who were hospitalized between February 9, 2020, and March 30, 2020. Univariate Cox regression analysis and least absolute shrinkage and selection operator regression (LASSO) were used to select variables. Multivariate Cox regression analysis was applied to identify independent risk factors in coronavirus disease‐2019. A total of 1135 patients were analyzed during the study period. A total of 35 variables were considered to be risk factors after the univariate regression analysis of the clinical characteristics and laboratory parameters (p < .05), and LASSO regression analysis screened out seven risk factors for further study. The six independent risk factors revealed by multivariate Cox regression were myoglobin (HR, 5.353; 95% CI, 2.633–10.882; p < .001), C‐reactive protein (HR, 2.063; 95% CI, 1.036–4.109; p = .039), neutrophil count (HR, 2.015; 95% CI, 1.154–3.518; p = .014), interleukin 6 (Il‐6; HR, 9.753; 95% CI, 2.952–32.218; p < .001), age (HR, 2.016; 95% CI, 1.077–3.773; p = .028), and international normalized ratio (HR, 2.595; 95% CI, 1.412–4.769; p = .002). Our results suggested that inflammation‐associated factors were significantly associated with in‐hospital mortality in coronavirus disease‐2019 patients. C‐reactive protein, neutrophil count, and interleukin 6 were independent factors for predicting in‐hospital mortality and had a better independent predictive ability. We believe these findings may allow early identification of the patients at high risk for death, and can also assist in better management of these patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Testicular cancer is the most common solid malignancy among young men. We downloaded data of testicular cancer patients from The Cancer Genome Atlas database to find novel genes in the testicular ...cancer microenviroment based on ESTIMATE algorithm‐derived immune scores. A total of 156 cases of testicular cancer were included in this study and 165 cases of normal testicular tissues were used. We divided the testicular cancer patients into high‐ and low‐score groups based on their immune scores. We identified 1,226 differentially expressed genes (fold change > 2, false discovery rate < 0.05), including 688 downregulated genes and 538 upregulated genes, between these two groups. The top Gene Ontology terms were involved in the immune response‐regulating cell surface receptor signaling pathway, immune response‐activating cell surface receptor signaling pathway, external side of the plasma membrane, and receptor ligand activity. By performing the Kyoto Encyclopedia of Genes and Genomes analysis, we demonstrated that cAMP signaling pathway was highly enriched among these differentially expressed genes. High expression of LINC01564, LINC02208, ODAM, RNA5SP111, and RNU6‐196P were found to be associated with poor overall survival. The expression of genes was further validated by the Human Protein Atlas and only ALB and IFNG were demonstrated to be differentially expressed between testis tissue and testicular cancer tissue.
Testicular cancer is the most common solid malignancy among young men. We used the ESTIMATE algorithm to calculate immune scores and obtain several novel genes associated with testicular cancer microenvironment. Two genes were validated by the Human Protein Atlas database to be differentially expressed between testis tissue and testicular cancer tissues. These findings would contribute greatly to the understanding of the potential mechanism of testicular cancer.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Despite intensive research in surface enhanced Raman spectroscopy (SERS), the influence mechanism of chemical effects on Raman signals remains elusive. Here, we investigate such chemical effects ...through tip‐enhanced Raman spectroscopy (TERS) of a single planar ZnPc molecule with varying but controlled contact environments. TERS signals are found dramatically enhanced upon making a tip–molecule point contact. A combined physico‐chemical mechanism is proposed to explain such an enhancement via the generation of a ground‐state charge‐transfer induced vertical Raman polarizability that is further enhanced by the strong vertical plasmonic field in the nanocavity. In contrast, TERS signals from ZnPc chemisorbed flatly on substrates are found strongly quenched, which is rationalized by the Raman polarizability screening effect induced by interfacial dynamic charge transfer. Our results provide deep insights into the understanding of the chemical effects in TERS/SERS enhancement and quenching.
We find that the tip‐molecule point contact can dramatically increase the molecular tip‐enhanced Raman spectroscopy (TERS) signal via a combined physico‐chemical mechanism induced by the ground‐state charge transfer (GSCT). In contrast, the TERS signal from a planar molecule chemisorbed flatly on the silver substrate is significantly quenched, mainly due to the polarizability screening induced by the interfacial dynamic charge transfer (IDCT).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background and Aims
Heparin‐binding epidermal growth factor (HB‐EGF), a member of the epidermal growth factor family, plays a pivotal role in the progression of several malignancies, but its role and ...regulatory mechanisms in hepatocellular carcinoma (HCC) remain obscure. Here, we report that transmembrane protease serine 4 (TMPRSS4) significantly enhanced the expression and proteolytic cleavage of HB‐EGF to promote angiogenesis and HCC progression.
Approach and Results
A mechanistic analysis revealed that TMPRSS4 not only increased the transcriptional and translational levels of HB‐EGF precursor, but also promoted its proteolytic cleavage by enhancing matrix metallopeptidase 9 expression through the EGF receptor/Akt/mammalian target of rapamycin/ hypoxia‐inducible factor 1 α signaling pathway. In addition, HB‐EGF promoted HCC proliferation and invasion by the EGF receptor/phosphoinositide 3‐kinase/Akt signaling pathway. The level of HB‐EGF in clinical samples of serum or HCC tissues from patients with HCC was positively correlated with the expression of TMPRSS4 and the microvessel density, and was identified as a prognostic factor for overall survival and recurrence‐free survival, which suggests that HB‐EGF can serve as a potential therapeutic target for HCC. More importantly, we provide a demonstration that treatment with the HB‐EGF inhibitor cross‐reacting material 197 alone or in combination with sorafenib can significantly suppress angiogenesis and HCC progression.
Conclusions
HB‐EGF can be regulated by TMPRSS4 to promote HCC proliferation, invasion, and angiogenesis, and the combination of the HB‐EGF inhibitor cross‐reacting material 197 with sorafenib might be used for individualized treatment of HCC.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background and Aim
The purpose of the present study was to evaluate the effect of direct‐acting antivirals (DAAs) therapy on the clinical outcomes of hepatitis C virus (HCV) patients with ...hepatocellular carcinoma (HCC).
Methods
We searched multiple electronic databases from database inception to June 14, 2021. Meta‐analyses were performed separately for HCC recurrence and overall survival (OS).
Results
A total of 23 studies were identified for the primary analysis. Compared with no intervention, pooled data showed significant benefit from DAAs therapy in reducing recurrence (adjusted HR = 0.55, 95% CI 0.41–0.74, P < 0.001; I2 = 66.6%, P < 0.001) and improving OS (adjusted HR = 0.36, 95% CI 0.16–0.83, P = 0.017; I2 = 90.7%, P < 0.001) of HCV‐related HCC patients. Compared with non‐responders, patients with sustained virologic response (SVR) had greater benefit from DAAs therapy in reducing recurrence (HR = 0.37, 95% CI 0.16–0.84, P = 0.017; I2 = 58.8%, P = 0.088) and improving OS (HR = 0.17; 95% CI 0.06–0.50; P = 0.001; I2 = 56.4%, P = 0.130). Though DAAs did not show significant advantages over IFN in reducing recurrence (adjusted HR = 0.96, 95% CI 0.72–1.28, P = 0.784; I2 = 0.0%, P = 0.805), there seems to be a trend toward OS benefit from DAAs therapy (adjusted HR = 0.11, 95% CI 0.01–1.19, P = 0.059).
Conclusion
DAAs therapy can prevent recurrence and improve OS of HCV‐related HCC patients, especially for patients with SVR. Further prospective randomized controlled trial is warranted to validate these results.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
In nanostructure assemblies, the superposition of current paths forms microscopic electric circuits, and different circuit networks produce varying results, particularly when utilized as transistor ...channels for computing applications. However, the intricate nature of assembly networks and the winding paths of commensurate currents hinder standard circuit modeling. Inspired by the quantum collapse of superposition states for information decoding in quantum circuits, the implementation of analogous current path collapse to facilitate the detection of microscopic circuits by modifying their network topology is explored. Here, the superposition and collapse of current paths in gate‐all‐around polysilicon nanosheet arrays are demonstrated to enrich the computational resources within transistors by engineering the channel length and quantity. Switching the ferroelectric polarization of Hf0.5Zr0.5O2 gate dielectric, which drives these transistors out‐of‐equilibrium, decodes the output polymorphism through circuit topological modifications. Furthermore, a protocol for the single‐electron readout of ferroelectric polarization is presented with tailoring the channel coherence. The introduction of lateral path superposition results into intriguing metal‐to‐insulator transitions due to transient behavior of ferroelectric switching. This ability to adjust the current networks within transistors and their interaction with ferroelectric polarization in polycrystalline nanostructures lays the groundwork for generating diverse current characteristics as potential physical databases for optimization‐based computing.
Superposition and collapse of nanostructured in‐transistor current networks are demonstrated to be read and decoded by quantum tunneling and ferroelectric switching in gate‐all‐around polysilicon nanosheet arrays and planar‐gated nanofilms. The drain current output is therefore endowed with polymorphism due to the interplay of the polysilicon and Hf0.5Zr0.5O2 nanostructures.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective
This study aimed to identify risk factors for intracranial aneurysms (IAs) recurrence and establish a predictive model to aid evaluation.
Methods
A total of 302 patients with 312 IAs ...undergoing coil embolization between September 2017 and October 2022 were divided into two groups based on digital subtraction angiography follow-up. Clinical characteristics, operation-related factors, and morphologies were measured. Cox proportional hazard regression was used to identify the risk factors. Hazard ratios (HRs) were used to score points, and a predictive model was established. The test cohorts consisted of 51 IAs. Receiver operating characteristic curves were generated to determine the cutoff values and area under the curves (AUCs). A Delong test was performed to compare the AUCs.
Results
Diameter maximum (D max) (
p
< 0.001, HR = 1.221), Raymond-Roy occlusion classification (RROC) II or III (
p
= 0.004, HR = 2.852), and ruptured status (
p
< 0.001, HR = 7.782) were independent risk factors for the recurrence of IAs. A predictive model was established: D max + 2
*
RROC (II or III; yes = 1, no = 0) + 6
*
ruptured status (yes = 1; no = 0). The AUC of the predictive model (0.818) was significantly higher than those of D max (0.704), RROC (II or III) (0.645), and rupture status (0.683), respectively (Delong test,
p
< 0.05). The cutoff values of the predictive model and D max were 9.75 points and 6.65 mm, respectively.
Conclusion
The D max, RROC (II or III), and ruptured status could independently predict the recurrence of IAs after coil embolization. Our model could aid in practical evaluations.
Although solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have been successfully used as drug delivery systems for about 30 years, the usage of these nanoparticles as ...food-grade nanovehicles for nutraceuticals or bioactive compounds has been, relatively speaking, scarcely investigated. With fast-increasing interest in the incorporation of a wide range of bioactives in food formulations, as well as health awareness of consumers, there has been a renewed urge for the development of food-compatible SLNs and/or NLCs as nanovehicles for improving water dispersibility, stability, bioavailability, and bioactivities of many lipophilic nutraceuticals or poorly soluble bioactives. In this review, the development of food-grade SLNs and NLCs, as well as their utilization as nanosized delivery systems for lipophilic or hydrophobic nutraceuticals, was comprehensively reviewed. First, the structural composition and preparation methods of food-grade SLNs and NLCs were simply summarized. Next, some key issues about the usage of such nanoparticles as oral nanovehicles, e.g., incorporation and release of bioactives, oxidative stability, lipid digestion and absorption, and intestinal transport, were critically discussed. Then, recent advances in the utilization of SLNs and NLCs as nanovehicles for encapsulation and delivery of different liposoluble or poorly soluble nutraceuticals or bioactives were comprehensively reviewed. The performance of such nanoparticles as nanovehicles for improving stability, bioavailability, and bioactivities of curcuminoids (and curcumin in particular) was also highlighted. Lastly, some strategies to improve the oral bioavailability and delivery of loaded nutraceuticals in such nanoparticles were presented. The review will be relevant, providing state-of-the-art knowledge about the development of food-grade lipid-based nanovehicles for improving the stability and bioavailability of many nutraceuticals.
Olfactory disturbance is one of the main symptoms of coronavirus disease-2019 (COVID-19). Various olfactory disorders caused by viral infections are treated with nasal corticosteroids. This study ...aimed to evaluate the safety and efficacy of nasal corticosteroids in the treatment of olfactory disorders caused by the severe acute respiratory syndrome coronavirus 2.
We searched the Web of Science, Embase, PubMed, and Cochrane Library databases for clinical trials of nasal corticosteroids for treating COVID-19 olfactory dysfunction.
We assessed the effect of nasal corticosteroids on olfactory function in COVID-19-affected individuals using a Meta-analysis of published studies, considering the number of patients who fully recovered from olfactory dysfunction, olfactory scores following treatment, and olfactory recovery time.
Seven studies involving 930 patients were analyzed. The Meta-analysis results revealed that the olfactory score of the experimental group was 1.40 points higher than that of the control group (standardized mean difference MD: 1.40, 95% confidence interval 95% CI: 0.34-2.47, P < .00001). However, the differences in the outcomes of cure rate (risk ratio: 1.18, 95% CI: 0.89-1.69, P = .21) and recovery time (MD: -1.78, 95% CI: -7.36 to 3.81, P = .53) were not statistically significant. Only 1 study reported adverse effects of nasal steroid treatment, namely tension, anger, and stomach irritation.
Although nasal steroid therapy does not result in significant adverse effects, it proves ineffective in the treatment of COVID-19 olfactory dysfunction.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Prostate cancer is a major cause of death in males. Cyproterone acetate (CPA), the steroidal anti-androgen for part of androgen deprivation therapy, may block the androgen-receptor interaction and ...then reduce serum testosterone through its weak anti-gonadotropic action. In addition to CPA inducing hepatitis, CPA is known to cause liver tumors in rats also. Aryl hydrocarbon receptor (AhR) is a cytoplasmic receptor and regulates multiple physiological functions. CYP1A1 is an AhR-targeted gene. We found that CPA induced CYP1A1 expression, transcriptional activity of the aryl hydrocarbon response element (AHRE), and the nuclear localization of AhR in mouse Hepa-1c1c7 cells. However, CPA suppressed CYP1A1 mRNA expression and the transcriptional activity of AHRE in human HepG2 and MCF7 cells, and also decreased AhR ligand-induced CYP1A1 protein expression and transcriptional activity of AHRE in HepG2 cells. In summary, CPA is an AhR agonist in mouse cells, but an AhR antagonist in human cells. Accordingly, CPA potentially plays a role as an endocrine disruptor of the AhR. This study helps us to understand why CPA induces acute hepatitis, gene mutation, and many other side effects. In addition, it may trigger further studies investigating the relationships between CPA, glucocorticoid receptor and castration-resistant prostate cancer in the future.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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