Cathelicidin Antimicrobial Peptide Acts as a Tumor Suppressor in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is associated with high rates of metastasis and recurrence, and is one of the most common causes of cancer-associated death worldwide. This study examined the protein changes within circulating exosomes in patients with HCC against those in healthy people using isobaric tags for a relative or absolute quantitation (iTRAQ)-based quantitative proteomics analysis. The protein levels of von Willebrand factor (VWF), cathelicidin antimicrobial peptide (CAMP), and proteasome subunit beta type-2 (PSMB2) were altered in HCC. The increased levels of VWF and PSMB2 but decreased CAMP levels in the serum of patients with HCC were validated by enzyme-linked immunosorbent assays. The level of CAMP (the only cathelicidin found in humans) also decreased in the circulating exosomes and buffy coat of the HCC patients. The serum with reduced levels of CAMP protein in the HCC patients increased the cell proliferation of Huh-7 cells; this effect was reduced following the addition of CAMP protein. The depletion of CAMP proteins in the serum of healthy people enhances the cell proliferation of Huh-7 cells. In addition, supplementation with synthetic CAMP reduces cell proliferation in a dose-dependent manner and significantly delays G1-S transition in Huh-7 cells. This implies that CAMP may act as a tumor suppressor in HCC.

Mechanism and evolutionary analysis of Yarrowia lipolytica CA20 capable of producing erythritol with a high yield based on comparative genomics.

Combined mutagenesis is widely applied for the breeding of robust Yarrowia lipolytica used in the production of erythritol. However, the changes of genome after mutagenesis remains unclear. This study aimed to unravel the mechanism involved in the improved erythritol synthesis of CA20 and the evolutionary relationship between different Y. lipolytica by comparative genomics analysis. The results showed that the genome size of Y. lipolytica CA20 was 20,420,510 bp, with a GC content of 48.97%. There were 6330 CDS and 649 ncRNA (non-coding RNA) in CA20 genome. Average nucleotide identity (ANI) analysis showed that CA20 genome possessed high similarity (ANI > 99.50%) with other Y. lipolytica strains, while phylogenetic analysis displayed that CA20 was classified together with Y. lipolytica IBT 446 and Y. lipolytica H222. CA20 shared 5342 core orthologous genes with the 8 strains while harbored 65 specific genes that mainly participated in the substrate and protein transport processes. CA20 contained 166 genes coding for carbohydrate-active enzymes (CAZymes), which was more than that found in other strains (108－137). Notably, 4, 2, and 13 different enzymes belonging to glycoside hydrolases (GHs), glycosyltransferases (GTs), and carbohydrate esterases (CEs), respectively, were only found in CA20. The enzymes involved in the metabolic pathway of erythritol were highly conserved in Y. lipolytica, except for transaldolase (TAL1). In addition, the titer and productivity of erythritol by CA20 were 190.97 g/L and 1.33 g/L/h, respectively, which were significantly higher than that of WT5 wherein 128.61 g/L and 0.92 g/L/h were obtained (P< 0.001). Five frameshift mutation genes and 15 genes harboring nonsynonymous mutation were found in CA20 compared with that of WT5. Most of these genes were involved in the cell division, cell wall synthesis, protein synthesis, and protein homeostasis maintenance. These findings suggested that the genome of Y. lipolytica is conserved during evolution, and the variance of living environment is one important factor leading to genome divergence. The varied number of CAZymes existed in Y. lipolytica is one factor that contributes to the performance difference. The increased synthesis of erythritol by Y. lipolytica CA20 is correlated with the improvement of the stability of cell structure and internal environment. The results of this study provide a basis for the directional breeding of robust strains used in erythritol production.

Visualizing moiré ferroelectricity via plasmons and nano-photocurrent in graphene/twisted-WSe2 structures.

Ferroelectricity, a spontaneous and reversible electric polarization, is found in certain classes of van der Waals (vdW) materials. The discovery of ferroelectricity in twisted vdW layers provides new opportunities to engineer spatially dependent electric and optical properties associated with the configuration of moiré superlattice domains and the network of domain walls. Here, we employ near-field infrared nano-imaging and nano-photocurrent measurements to study ferroelectricity in minimally twisted WSe2. The ferroelectric domains are visualized through the imaging of the plasmonic response in a graphene monolayer adjacent to the moiré WSe2 bilayers. Specifically, we find that the ferroelectric polarization in moiré domains is imprinted on the plasmonic response of the graphene. Complementary nano-photocurrent measurements demonstrate that the optoelectronic properties of graphene are also modulated by the proximal ferroelectric domains. Our approach represents an alternative strategy for studying moiré ferroelectricity at native length scales and opens promising prospects for (opto)electronic devices.

Enhancing the Photoelectrochemical Performance of a Nanoporous Silicon Photocathode through Electroless Nickel Deposition.

Renewable energy sources, particularly solar energy, are key to our efforts to decarbonize. This study investigates the photoelectrochemical (PEC) behavior of nanoporous silicon (NPSi) and its Ni-coated hybrid system. The methods involve the application of a Ni coating to NPSi, a process aimed at augmenting catalytic activity, light absorption, and carrier transport. Scanning electron microscopy was used to analyze the morphological changes on NPSi surfaces due to the Ni coating. Results demonstrate that the Ni coating creates unique structures on NPSi surfaces, with peak PEC performance observed at 15 min of coating time and 60 °C. These conditions were found to promote electron-hole pair separation and uniform Ni coverage. A continuous 50-min white light illumination experiment confirmed stable PEC fluctuations, showing the interplay of NPSi's characteristics and Ni's catalytic effect. This study provides practical guidance for the design of efficient water-splitting catalysts, contributing to the broader field of renewable energy conversion.

Exploring the Regulatory Role of XIST-microRNAs/mRNA Network in Circulating CD4+ T Cells of Hepatocellular Carcinoma Patients.

Hepatocellular carcinoma (HCC) is one of the most common cancers and the main cause of cancer-related death globally. Immune dysregulation of CD4+ T cells has been identified to play a role in the development of HCC. Nevertheless, the underlying molecular pathways of CD4+ T cells in HCC are not completely known. Thus, a better understanding of the dysregulation of the lncRNA-miRNA/mRNA network may yield novel insights into the etiology or progression of HCC. In this study, circulating CD4+ T cells were isolated from the whole blood of 10 healthy controls and 10 HCC patients for the next-generation sequencing of the expression of lncRNAs, miRNAs, and mRNAs. Our data showed that there were different expressions of 34 transcripts (2 lncRNAs, XISTs, and MIR222HGs; 29 mRNAs; and 3 other types of RNA) and 13 miRNAs in the circulating CD4+ T cells of HCC patients. The expression of lncRNA-XIST-related miRNAs and their target mRNAs was confirmed using real-time quantitative polymerase chain reaction (qPCR) on samples from 100 healthy controls and 60 HCC patients. The lncRNA-miRNA/mRNA regulation network was created using interaction data generated from ENCORI and revealed there are positive correlations in the infiltration of total CD4+ T cells, particularly resting memory CD4+ T cells, and negative correlations in the infiltration of Th1 CD4+ T cells.

Conjugated topological cavity-states in one-dimensional photonic systems and bio-sensing applications.

Traditional photonic systems are endowed with brand new properties owing to the addition of topological physics with light. A conjugated topological cavity-states (CTCS) in one-dimensional photonic systems is presented, which has not only robust light transport but also ultra-high performances, such as high quality factor (high-Q) and perfect transmission. This extraordinary CTCS can address the bottleneck of typical topological photonic systems, which can only achieve robust light transport without maintaining high performance. Furthermore, the CTCS is especially suitable for bio-photonic sensing with high resolution requirements. An ultra-sensitivity of 2000 nm/RIU and a high-Q of 109 for detecting the concentration of SARS-CoV-2 S-glycoprotein solution are obtained. Notably, the CTCS not only opens new possibilities for advanced photonics but also paves the way for high performance in topological photonic devices.

Deciphering the Divergent Gene Expression Landscapes of m6A/m5C/m1A Methylation Regulators in Hepatocellular Carcinoma Through Single-Cell and Bulk RNA Transcriptomic Analysis.

Introduction: RNA modifications mediated by the m6A, m1A, and m5C regulatory genes are crucial for the progression of malignancy. This study aimed to explore the expression of regulator genes for m6A/m5C/m1A methylation at the single-cell level and to validate their expression in cancerous and adjacent para-cancerous liver tissues of adult patients with HCC who underwent tumor resection. Methods: The bulk sequencing from The Cancer Genome Atlas (TCGA) database and the single-cell RNA sequencing (scRNA-seq) data obtained from the Gene Expression Omnibus (GEO) database were used to identify the dysregulated m6A/m5C/m1A genes for hepatocellular carcinoma (HCC). A real-time polymerase chain reaction (real-time PCR) was used to measure the expression of dysregulated m6A/m5C/m1A genes in collected human HCC tissues and compared with adjacent para-cancerous liver tissues. Immune cell infiltration with these significantly expressed methylation-related genes was evaluated using Timer2.0. Results: A discrepancy in m6A/m5C/m1A gene expression was observed between bulk sequencing and scRNA-seq. The clustered heatmap of the scRNA-seq-identified dysregulated m6A/m5C/m1A genes in TCGA cohort revealed heterogeneous expression of these methylation regulators within the cancer, whereas their expression in the adjacent liver tissues was more homogeneous. The real-time PCR validated the significant overexpression of DNMT1, NSUN5, TRMT6, IGF2BP1, and IGFBP3, which were identified using scRNA-seq, and IGFBP2, which was identified using bulk sequencing. These dysregulated methylation genes are mainly correlated with the infiltration of natural killer cells. Discussion: This study suggests that cellular diversity inside tumors contributes to the discrepancy in the expression of methylation regulator genes between traditional bulk sequencing and scRNA-seq. This study identified five regulatory genes that will be the focus of further studies regarding the function of m6A/m5C/m1A in HCC.

Gene therapy with a synthetic adeno-associated viral vector improves audiovestibular phenotypes in Pjvk-mutant mice.

Recessive PJVK mutations that cause a deficiency of pejvakin, a protein expressed in both sensory hair cells and first-order neurons of the inner ear, are an important cause of hereditary hearing impairment. Patients with PJVK mutations garner limited benefits from cochlear implantation; thus, alternative biological therapies may be required to address this clinical difficulty. The synthetic adeno-associated viral vector Anc80L65, with its wide tropism and high transduction efficiency in various inner ear cells, may provide a solution. We delivered the PJVK transgene to the inner ear of Pjvk mutant mice using the synthetic Anc80L65 vector. We observed robust exogenous pejvakin expression in the hair cells and neurons of the cochlea and vestibular organs. Subsequent morphologic and audiologic studies demonstrated significant restoration of spiral ganglion neuron density and hair cells in the cochlea, along with partial recovery of sensorineural hearing impairment. In addition, we observed a recovery of vestibular ganglion neurons and balance function to WT levels. Our study demonstrates the utility of Anc80L65-mediated gene delivery in Pjvk mutant mice and provides insights into the potential of gene therapy for PJVK-related inner ear deficits.

The Network of miRNA-mRNA Interactions in Circulating T Cells of Patients Following Major Trauma - A Pilot Study.

Purpose: Following major trauma, genes involved in adaptive immunity are downregulated, which accompanies the upregulation of genes involved in systemic inflammatory responses. This study investigated microRNA (miRNA)-mRNA interactome dysregulation in circulating T cells of patients with major trauma. Patients and Methods: This study included adult trauma patients who had an injury severity score ≥16 and required ventilator support for more than 48 h in the intensive care unit. Next-generation sequencing was used to profile the miRNAs and mRNAs expressed in CD3+ T cells isolated from patient blood samples collected during the injury and recovery stages. Results: In the 26 studied patients, 9 miRNAs (hsa-miR-16-2-3p, hsa-miR-16-5p, hsa-miR-185-5p, hsa-miR-192-5p, hsa-miR-197-3p, hsa-miR-23a-3p, hsa-miR-26b-5p, hsa-miR-223-3p, and hsa-miR-485-5p) were significantly upregulated, while 58 mRNAs were significantly downregulated in T cells following major trauma. A network consisting of 8 miRNAs and 22 mRNAs interactions was revealed by miRWalk, with three miRNAs (hsa-miR-185-5p, hsa-miR-197-3p, and hsa-miR-485-5p) acting as hub genes that regulate the network. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested that "chemokine signaling pathway" was the predominant pathway. Conclusion: The study revealed a miRNA-mRNA interactome consisting of 8 miRNAs and 22 mRNAs that are predominantly involved in chemokine signaling in circulating T cells of patients following major trauma.

Comparing Outcomes between Major Trauma Patients Transferred from a Different Hospital and Patients Transported Directly to Trauma Centers: A Retrospective Analysis with Propensity Score Matching Analysis.

This study aimed to explore differences in outcomes between these major trauma patients who were transferred and those directly transported to trauma centers. The medical information and outcome of 5,341 major trauma patients with an injury severity score (ISS) ≥ 16 who were hospitalized for treatment between January 1, 2009, and December 31, 2019, were collected from the Trauma Registry System of the hospital. There were 2,386 patients who were transferred (transfer group) and 2,955 patients transported directly to trauma centers first (direct group). Regarding the outcomes, there was no significant difference in the mortality rate between patients in the transfer group and the direct group (11.1% vs. 10.5%, respectively, p=0.527). However, the patients in the transfer group had a longer hospital stay (16.8 days vs. 14.3 days, respectively, p < 0.001) and higher incidence of intensive care unit (ICU) admission (74.9% vs. 70.5%, respectively, p < 0.001) than those patients in the direct group. Similar results were observed in the selected 2,139 pairs of propensity score-matched patient populations, who did not present with significant differences in sex, age, comorbidities, trauma mechanisms, and ISS. This study revealed no significant difference in the mortality rate between the two groups of major trauma patients. However, the transferred patients had significantly longer hospital stays and higher rates of ICU admission than patients directly transported to trauma centers.

Regular Exercise and Weight-Control Behavior Are Protective Factors against Osteoporosis for General Population: A Propensity Score-Matched Analysis from Taiwan Biobank Participants.

The rising prevalence of osteoporosis, which can lead to osteoporotic fractures, increases morbidity, mortality, and socioeconomic burden. Multiple factors influencing bone mass have already been identified. The aim of this study was to investigate whether exercise habits and weight-control behaviors can lower the incidence of osteoporosis in the general population. This retrospective study recruited all participants aged 35-70 years who underwent dual-energy X-ray absorptiometry (DXA) from Taiwan Biobank (TWB). The final analysis consisted of 3320 eligible participants divided into two groups; demographic characteristics, prevalence of clinical symptoms, comorbidities, and daily behavior were collected using a self-reported questionnaire. After propensity score matching with a 1:1 ratio, 1107 out of 2214 individuals were classified into the osteoporosis group. Age, body fat rate, body shape, diabetes mellitus, and social status were found to affect the incidence of osteoporosis. Subjects with a habit of regular exercise and weight-control behavior showed decreased odds of osteoporosis. (odds ratio: 0.709 and 0.753, 95% confidence interval: 0.599-0.839 and 0.636-0.890). In the general population, regular exercise or weight-control behavior lowers the incidence of osteoporosis.

Disparity of Hepatocellular Carcinoma in Tumor Microenvironment-Related Genes and Infiltrating Immune Cells between Asian and Non-Asian Populations.

Hepatocellular carcinoma (HCC) is the most common cause of primary liver cancer deaths worldwide. The major risk factors for liver cancer development are cirrhosis, hepatitis B virus (HBV), hepatitis C virus (HCV) infection, and chronic alcohol abuse. HCC displays heterogeneity in terms of biology, etiology, and epidemiology. In Southeast Asia and Africa, chronic HBV infection is a major risk factor for HCC, whereas chronic HCV infection is a risk factor for HCC in western countries and Japan. Environmental and genetic conditions also play a role in the regional and temporal variations in the incidence of HCC. In this study, we used the ESTIMATE (ESTIMATE, Estimation of stromal and immune cells in malignant tumor tissues using expression data) algorithm and the CIBERSOFT tool to analyze gene expression profiles and infiltrating immune cells in HCC between Asian and non-Asian patients. The results showed that stromal and immune scores were dependent on overall survival (OS) in non-Asian patients but not in Asian patients. Kaplan-Meier survival analysis revealed four differentially expressed genes (DEGs) that were significantly associated with OS in non-Asian patients only. CIBERSORT (CIBERSORT, Cell type identification by estimating relative subsets of known RNA transcripts) analysis indicated that the composition of infiltrating immune cells was significantly different between Asian and non-Asian patients. By parsing the subclasses of HCC, the ability to predict prognosis and guide therapeutic targets for potentially actionable HCC may be improved.

Increased Angiogenesis by Exosomes Secreted by Adipose-Derived Stem Cells upon Lipopolysaccharide Stimulation.

Exosomes secreted by adipose-derived stem cells (ADSCs) enhance angiogenesis and wound healing. However, in clinical settings, wounds may be infected by various bacteria or pathogens. We investigated whether human ADSCs stimulated with lipopolysaccharide (LPS) secrete exosomes (ADSC-LPS-exo) that augment the angiogenesis of human umbilical vein endothelial cells (HUVECs). ExoQuick-TC exosome precipitation solution was used to purify exosomes from human ADSC culture media in the presence or absence of 1 µg/mL LPS treatment for 24 h. The uptake of ADSC-LPS-exo significantly induced the activation of cAMP response element binding protein (CREB), activating protein 1 (AP-1), and nuclear factor-κB (NF-κB) signaling pathways and increased the migration of and tube formation in HUVECs. RNA interference with CREB, AP-1, or NF-κB1 significantly reduced the migration of and tube formation in HUVECs treated with ADSC-LPS-exo. An experiment with an antibody array for 25 angiogenesis-related proteins revealed that only interleukin-8 expression was significantly upregulated in HUVECs treated with ADSC-LPS-exo. In addition, proteomic analysis revealed that eukaryotic translation initiation factor 4E, amyloid beta A4 protein, integrin beta-1, and ras-related C3 botulinum toxin substrate 1 may be potential candidates involved in ADSC-LPS-exo-mediated enhanced angiogenesis.

Geriatric Nutritional Risk Index as a Prognostic Factor for Mortality in Elderly Patients with Moderate to Severe Traumatic Brain Injuries.

BACKGROUND: The Geriatric Nutritional Risk Index (GNRI) is a simple and objective screening tool for clinicians to screen patients' nutritional status based on serum albumin level and their weight and height. The original study had divided patients based on GNRI into quartiles of nutritional risk for death: a no-risk group (GNRI >98), a low-risk group (GNRI 92-98), a moderate-risk group (GNRI 82 to <92), and a major-risk group (GNRI <82). Given that the patients generally sustained traumatic brain injury (TBI) in an acute condition, the study aimed to explore whether GNRI presents a prognostic value for the mortality outcome of these patients. METHODS: From January 1, 2009, to December 31, 2019, 581 elderly patients with moderate to severe TBI, which was defined as sustaining a head Abbreviated Injury Scale ≥3, was included in the study population. The collected data included age, sex, body mass index, serum albumin levels at admission, preexisting comorbidities, Glasgow Coma Scale, and Injury Severity Score. The primary outcome in the comparison was in-hospital mortality. RESULTS: Multivariate logistic regression analysis revealed that GNRI, ESRD, and ISS were significant independent risk factors for mortality in patients with moderate to severe TBI. When subgrouping the study population into four nutritional risk categories according to the quartile deviation as Q1 (GNRI <85, n = 145), Q2 (GNRI 85 to <93.8 n = 145), Q3 (GNRI 93.8 to 103, n = 145), and Q4 (GNRI >103, n = 146), Q1 patients had a significantly longer LOS in hospital (25.2 days vs 18.6 days, respectively; p = 0.004) and higher mortality rate (28.3% vs 11.7%, respectively; p < 0.001) than Q4 patients. The mortality rate was significantly higher in Q1 patients than in Q4 patients (OR, 2.8; 95% CI, 1.14-6.78; p = 0.021). CONCLUSION: This study revealed that the GNRI is a significant independent risk factor and a promising simple assessment tool for mortality in elderly patients with moderate to severe TBI.

Reply to Comment on Tsai, Y.-C., et al. Association of Stress-Induced Hyperglycemia and Diabetic Hyperglycemia with Mortality in Patients with Traumatic Brain Injury: Analysis of a Propensity Score-Matched Population. Int. J. Environ. Res. Public Health 2020, 17, 4266.

Thank you for Eduardo Mekitarian Filho's appreciation of our work on the study of stress-induced hyperglycemia (SIH) and diabetic hyperglycemia (DH) in patients with traumatic brain injuries [...].

Dual functional modes for nanostructured p-Cu2O/n-Si heterojunction photodiodes.

Many applications require a photodetector (PD) with multiple functional modes. This study demonstrates a dual functional PD with a simple structure that uses a nanostructured p-Cu2O/n-Si heterojunction. This device features a self-powering characteristic for an open-circuit voltage (V oc) of 0.5 V and exhibits an external quantum efficiency (EQE) of 3780% at a reverse bias of -5 V. There is a high EQE at low reverse-bias because trapped holes cause charge to be injected from the electrode. The nanostructured p-Cu2O/n-Si heterojunction also has a high response speed (<10 ms) in the self-powered mode because there is a built-in potential within p-n junction. This study shows that a nanostructured p-Cu2O/n-Si heterojunction acts as a self-powered PD for reducing power consumption and as a photomultiplication (PM)-type PD with high internal gain.

Geriatric Nutritional Risk Index as a Screening Tool to Identify Patients with Malnutrition at a High Risk of In-Hospital Mortality among Elderly Patients with Femoral Fractures-A Retrospective Study in a Level I Trauma Center.

BACKGROUND: Malnutrition is frequently underdiagnosed in geriatric patients and is considered to be a contributing factor for worse outcomes during hospitalization. In addition, elderly patients who undergo trauma are often malnourished at the time of incurring fractures. The geriatric nutritional risk index (GNRI), calculated based on the serum albumin level and the ratio of present body weight to ideal body weight, was proposed for the assessment of the nutritional status of elderly patients with various illnesses. This study aimed to investigate whether the GNRI has a prognostic value that links the nutritional status and mortality outcomes of elderly patients who have previously undergone trauma with femoral fractures. METHODS: From January 1, 2009 to December 31, 2019, a total of 678 elderly patients with femoral fractures were categorized into four nutritional risk groups: a major-risk group (GNRI <82; group 1, n = 127), moderate-risk group (GNRI 82- <92; group 2, n = 179), low-risk group (GNRI 92-98; group 3, n = 123), and no-risk group (GNRI >98; group 4, n = 249). To minimize the confounding effects of sex, age, preexisting comorbidities, and injury severity of patients on outcome measurements, propensity score-matched patient cohorts were created to assess the impact of patients being in different nutritional risk groups on the in-hospital mortality outcomes against the no-risk group. RESULTS: The patients in groups 1-3 were significantly older and presented a significantly lower body mass index and lower serum albumin levels than those in group 4. Compared with patients in group 4 (3.6%), a significantly higher mortality rate was found in the patients in group 1 (17.3%, p < 0.001), but not in those in group 2 (6.7%) or group 3 (2.4%). The study of propensity score-matched patient cohorts provided similar results; group 1 patients had significantly higher odds of mortality than group 4 patients (odds ratio, 6.3; 95% confidence interval, 1.34-29.37; p = 0.009), but there were no significant differences in mortality risks among patients in groups 2 and 3 compared with those in group 4. CONCLUSIONS: This preliminary study suggested that the GNRI may be used as a screening tool to identify patients with malnutrition at a high risk of mortality among elderly patients with femoral fractures. A prospective study is needed to validate the suggestion.

High-performance metal-semiconductor-metal ZnSnO UV photodetector via controlling the nanocluster size.

Solution processing of amorphous oxide semiconductors (AOS) is used for electronic and optoelectronic applications. However, the device performance is much lower than that for a device that is fabricated using vacuum processing. This study uses acetylacetone (acac) as an additive in the precursor solution to reduce the nanocluster size in a ZnSnO (ZTO) film. A metal-semiconductor-metal (MSM)-type UV photodetector (PD) is fabricated using as-prepared ZTO film. ZTO film that features a smaller nanocluster size, so more oxygen vacancies are induced, which produces more electrons and the photocurrent is increased. The surface at the metal/semiconductor interface is smoother so there is greater contact with fewer interface states and the dark current is decreased. An extremely high photo-to-dark current ratio (PDCR) of 1314 is achieved for a solution-processed ZTO MSM-type PD.