A generic framework for hierarchical de novo protein design.

De novo protein design enables the exploration of novel sequences and structures absent from the natural protein universe. De novo design also stands as a stringent test for our understanding of the underlying physical principles of protein folding and may lead to the development of proteins with unmatched functional characteristics. The first fundamental challenge of de novo design is to devise "designable" structural templates leading to sequences that will adopt the predicted fold. Here, we built on the TopoBuilder (TB) de novo design method, to automatically assemble structural templates with native-like features starting from string descriptors that capture the overall topology of proteins. Our framework eliminates the dependency of hand-crafted and fold-specific rules through an iterative, data-driven approach that extracts geometrical parameters from structural tertiary motifs. We evaluated the TopoBuilder framework by designing sequences for a set of five protein folds and experimental characterization revealed that several sequences were folded and stable in solution. The TopoBuilder de novo design framework will be broadly useful to guide the generation of artificial proteins with customized geometries, enabling the exploration of the protein universe.

Analysis of Carbon Materials with Infrared Photoacoustic Spectroscopy.

Measurement of infrared spectroscopy has emerged as a significant challenge for carbon materials due to the sampling problem. To overcome this issue, in this work, we performed measurements of IR spectra for carbon materials including C60, C70, diamond powders, graphene, and carbon nanotubes (CNTs) using the photoacoustic spectroscopy (PAS) technique; for comparison, the vibrational patterns of these materials were also studied with a conventional transmission method, diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, or Raman spectroscopy. We found that the IR photoacoustic spectroscopy (IR-PAS) scheme worked successfully for these carbon materials, offering advantages in sampling. Interestingly, the profiles of IR-PAS spectra for graphene and CNTs exhibit negative bands using carbon black as the reference; the negative spectral information may provide valuable knowledge about the storage energy, production, structure, defect, or impurity of graphene and CNTs. Thus, this approach may open a new avenue for analyzing carbon materials.

The crosstalk between copper-induced oxidative stress and cuproptosis: a novel potential anticancer paradigm.

Copper is a crucial trace element that plays a role in various pathophysiological processes in the human body. Copper also acts as a transition metal involved in redox reactions, contributing to the generation of reactive oxygen species (ROS). Under prolonged and increased ROS levels, oxidative stress occurs, which has been implicated in different types of regulated cell death. The recent discovery of cuproptosis, a copper-dependent regulated cell death pathway that is distinct from other known regulated cell death forms, has raised interest to researchers in the field of cancer therapy. Herein, the present work aims to outline the current understanding of cuproptosis, with an emphasis on its anticancer activities through the interplay with copper-induced oxidative stress, thereby providing new ideas for therapeutic approaches targeting modes of cell death in the future.

Excavatolide C/cisplatin combination induces antiproliferation and drives apoptosis and DNA damage in bladder cancer cells.

Excavatolide C (EXCC), a marine coral-derived compound, exhibits an antiproliferation effect on bladder cancer cells. The present study evaluated the improvement in the antiproliferation ability of EXCC by co-treatment with cisplatin in bladder cancer cells. EXCC/cisplatin (12.5 and 1 µg/mL) showed higher antiproliferation effects on bladder cancer cells than single treatments (EXCC or cisplatin alone) in the 48 h ATP assay. EXCC/cisplatin also enhanced the increase in subG1, annexin V-mediated apoptosis, and activation of poly (ADP-ribose) polymerase (PARP) and several caspases (caspases 3, 8, and 9) compared to the single treatments. Cellular and mitochondrial oxidative stress was enhanced with EXCC/cisplatin compared to the single treatments according to analyses of reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial membrane potential; in addition, cellular antioxidants, such as glutathione (GSH), and the mRNA expressions of antioxidant signaling genes (catalase and NFE2-like bZIP transcription factor 2) were downregulated. EXCC/cisplatin treatment produced more DNA damage than the single treatments, as indicated by γH2AX and 8-hydroxy-2'-deoxyguanosine levels. Moreover, several DNA repair genes for homologous recombination (HR) and non-homologous end joining (NHEJ) were downregulated in EXCC/cisplatin compared to others. The addition of the GSH precursor N-acetylcysteine, which has ROS scavenging activity, attenuated all EXCC/cisplatin-induced changes. Notably, EXCC/cisplatin showed lower antiproliferation, apoptosis, ROS induction, GSH depletion, and γH2AX DNA damage in normal cells than in bladder cancer cells. Therefore, the co-treatment of EXCC/cisplatin reduces the proliferation of bladder cancer cells via oxidative stress-mediated mechanisms with normal cell safety.

Bottom-up de novo design of functional proteins with complex structural features.

De novo protein design has enabled the creation of new protein structures. However, the design of functional proteins has proved challenging, in part due to the difficulty of transplanting structurally complex functional sites to available protein structures. Here, we used a bottom-up approach to build de novo proteins tailored to accommodate structurally complex functional motifs. We applied the bottom-up strategy to successfully design five folds for four distinct binding motifs, including a bifunctionalized protein with two motifs. Crystal structures confirmed the atomic-level accuracy of the computational designs. These de novo proteins were functional as components of biosensors to monitor antibody responses and as orthogonal ligands to modulate synthetic signaling receptors in engineered mammalian cells. Our work demonstrates the potential of bottom-up approaches to accommodate complex structural motifs, which will be essential to endow de novo proteins with elaborate biochemical functions, such as molecular recognition or catalysis.

Adapting the Time-Domain Synthetic Aperture Focusing Technique (T-SAFT) to Laser Ultrasonics for Imaging the Subsurface Defects.

Traditional ultrasonic testing uses a single probe or phased array probe to investigate and visualize defects by adapting certain imaging algorithms. The time-domain synthetic aperture focusing technique (T-SAFT) is an imaging algorithm that employs a single probe to scan along the test specimen in various positions, to generate inspection images with better resolution. Both the T-SAFT and phased array probes are contact methods with limited bandwidth. This work aims to combine the advantages of the T-SAFT and phased array in a noncontact way with the aid of laser ultrasonics. Here, a pulsed laser beam is employed to generate ultrasonic waves in both thermoelastic and ablation regimes, whereas the laser Doppler vibrometer is used to acquire the generated signals. These two lasers are focused on the test specimen and, to avoid the plasma and crater influence in the ablation regime, the transmission beam and reception beam are separated by 5 mm. By moving the test specimen with a step size of 0.5 mm, a 1D linear phased array (41 and 43 elements) with a pitch of 0.5 mm was synthesized, and three side-drilled holes (Ø 8 mm-thermoelastic regime, Ø 10 mm and Ø 2 mm-ablation regime) were introduced for inspection. The A-scan data obtained from these elements were processed via the T-SAFT algorithm to generate the inspection images in various grid sizes. The results showed that the defect reflections obtained in the ablation regime have better visibility than those from the thermoelastic regime. This is due to the high-amplitude signals obtained in the ablation regime, which pave the way for enhancing the pixel intensity of each grid. Moreover, the separation distance (5 mm) does not have any significant effect on the defect location during the reconstruction process.

The Immunological Microenvironment and the Emerging Role of Stem Cells Therapy in Peyronie's Disease: A Systematic Narrative Review.

Current literature has indicated that Peyronie's disease (PD) could be initiated by microtrauma and the subsequent inflammation episodes that follow. PD could be sorted into acute or chronic status, and it can differ when selecting the clinical therapeutics. PD would cause pain and penile deformity to diseased men and impair their erectile function. Occasionally, surgical revision of the penis might be needed to correct the penile curvature. We find that there are limited effective options of intra-lesion injections for the PD plaques. By searching the databases and screening the literature with the PRISMA 2020 guideline, we observed that several preclinical studies that applied stem cell therapy in treating PD were fruitful in the acute phase. Although in the chronic phase of PD, erectile parameters were not significantly improved, and therefore, future studies might be better elevated in certain aspects, such as the sites selected for harvesting stem cells or changing the centrifugation forces. In this review, we concluded the contemporary understanding of inflammatory microenvironments in PD, the stem cell therapy in PD, and our perspectives on future studies. We concluded that there may be great potential in stem cell therapy for treating both acute and chronic phases PD.

PAICS/DYRK3 Multienzyme Interactions as Coregulators of Purinosome Formation and Metabolism on Radioresistance in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a prevalent type of oral cancer. While therapeutic innovations have made strides, radioresistance persists as a significant hindrance in OSCC treatment. Despite identifying numerous targets that could potentially suppress the oncogenic attributes of OSCC, the exploration of oncogenic protein kinases for cancer therapy remains limited. Consequently, the functions of many kinase proteins in OSCC continue to be largely undetermined. In this research, we aim to disclose protein kinases that target OSCC and elaborate their roles and molecular mechanisms. Through the examination of the kinome library of radiotherapy-resistant/sensitive OSCC cell lines (HN12 and SAS), we identified a key gene, the tyrosine phosphorylation-regulated kinase 3 (DYRK3), a member of the DYRK family. We developed an in vitro cell model, composed of radiation-resistant OSCC, to scrutinize the clinical implications and contributions of DYRK3 and phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthase (PAICS) signaling in OSCC. This investigation involves bioinformatics and human tissue arrays. We seek to comprehend the role of DYRK3 and PAICS signaling in the development of OSCC and its resistance to radiotherapy. Various in vitro assays are utilized to reveal the essential molecular mechanism behind radiotherapy resistance in connection with the DYRK3 and PAICS interaction. In our study, we quantified the concentrations of DYRK3 and PAICS proteins and tracked the expression levels of key pluripotency markers, particularly PPAT. Furthermore, we extended our investigation to include an analysis of Glut-1, a gene recognized for its linkage to radioresistance in oral squamous cell carcinoma (OSCC). Furthermore, we conducted an in vivo study to affirm the impact of DYRK3 and PAICS on tumor growth and radiotherapy resistance, focusing particularly on the role of DYRK3 in the radiotherapy resistance pathway. This focus leads us to identify new therapeutic agents that can combat radiotherapy resistance by inhibiting DYRK3 (GSK-626616). Our in vitro models showed that inhibiting PAICS disrupts purinosome formation and influences the survival rate of radiation-resistant OSCC cell lines. These outcomes underscore the pivotal role of the DYRK3/PAICS axis in directing OSCC radiotherapy resistance pathways and, as a result, influencing OSCC progression or therapy resistance. Our findings also reveal a significant correlation between DYRK3 expression and the PAICS enzyme in OSCC radiotherapy resistance.

[Revising the Taiwan Code of Ethics for Nurses].

BACKGROUND: The 2005 revision of the code of ethics for nurses has been in effect in Taiwan for more than 17 years. Although this code has been smoothly implemented during this time, changing social expectations and ethical perspectives, advancements in science and technology, and the evolution of the nurse-patient relationship suggest this code should be once again be updated. PURPOSE: This study was conducted to suggest revisions to the Taiwan code of ethics for nurses necessary to meet current needs and address social and medical care environment trends. METHODS: A multivariate research approach was adopted. The classification of the code of ethics for nurses norms in six international nursing organizations and evidence-based ethical and philosophical thinking literature were referenced, with the main notification demands incorporated into the Ministry of Health and Welfare's Nursing Workplace Controversy Reporting Platform. After drafting the aspects and provisions of Taiwan code of ethics for nurses norms, expert review procedures such as focus groups, Delphi expert consensus, and public forums were conducted. RESULTS: After three expert focus group discussion rounds, a structured questionnaire was completed, and 50 Delphi experts in six fields completed the online questionnaire. After the second consensus round, the importance and clarity of the 47 ethical code provisions in the four aspects were determined with 100% and 99.8% agreement reached, indicating no significant difference in scores between the multidisciplinary expert group and the ethical code. The resulting revision proposed for the Taiwan code of ethics for nurses includes: nursing staff and care recipients (14 provisions), nursing staff and practice (13 provisions), nursing staff and the profession (10 provisions), and nursing staff and society (10 provisions). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: In terms of education, the revised Taiwan code of ethics for nurses should be integrated into the nursing education curriculum of nursing colleges and used as teaching material for the continuing education of nurses. In terms of policy, these norms should be included as evaluation benchmarks and inspection items for hospitals. In addition, the attention and support of senior managers in institutions must be secured and a handling protocol for moral dilemma cases and related consultation mechanisms must be established. Nursing supervisors should be guided to develop the ability to address these dilemmas to help foster a positive workplace and a respectful team atmosphere. All professional groups should participate actively in promoting issues related to nursing ethics, organize seminars and continuing education activities, and make the revised Taiwan code of ethics for nurses and learning cases available online for reference by nursing staff nationwide.

Boosting subdominant neutralizing antibody responses with a computationally designed epitope-focused immunogen.

Throughout the last several decades, vaccination has been key to prevent and eradicate infectious diseases. However, many pathogens (e.g., respiratory syncytial virus [RSV], influenza, dengue, and others) have resisted vaccine development efforts, largely because of the failure to induce potent antibody responses targeting conserved epitopes. Deep profiling of human B cells often reveals potent neutralizing antibodies that emerge from natural infection, but these specificities are generally subdominant (i.e., are present in low titers). A major challenge for next-generation vaccines is to overcome established immunodominance hierarchies and focus antibody responses on crucial neutralization epitopes. Here, we show that a computationally designed epitope-focused immunogen presenting a single RSV neutralization epitope elicits superior epitope-specific responses compared to the viral fusion protein. In addition, the epitope-focused immunogen efficiently boosts antibodies targeting the palivizumab epitope, resulting in enhanced neutralization. Overall, we show that epitope-focused immunogens can boost subdominant neutralizing antibody responses in vivo and reshape established antibody hierarchies.

Hymenobacter piscis sp. nov., isolated from a fish pond.

Bacterial strain NST-14T, isolated from a freshwater fish pond in Taiwan, was characterized using a polyphasic taxonomy approach. The strain was Gram-stain-negative, strictly aerobic, non-motile, rod-shaped and formed pink colonies. Optimal growth occurred at 30 °C, pH 7 and in the absence of NaCl. Phylogenetic analyses based on 16S rRNA gene sequences and coding sequences of 92 protein clusters indicated that strain NST-14T formed a phylogenetic lineage in the genus Hymenobacter. Analysis of 16S rRNA gene sequences showed that strain NST-14T had the highest similarity to Hymenobacter actinosclerus CCUG 39621T (97.7%), Hymenobacter amundsenii P5136T (97.3%) and Hymenobacter humicola P6312T (96.9%). Strain NST-14T showed 75.1-85.3 % average nucleotide identity, 73.7-89.8 % average amino acid identity and 14.5-26.0 % digital DNA-DNA hybridization with the type strains of other closely related Hymenobacter species. Strain NST-14T contained iso-C15 : 0, C16 : 1 ω5c and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) as the predominant fatty acids. The major hydroxyl fatty acids were iso-C17 : 0 3-OH and iso-C15 : 0 3-OH. The polar lipids were phosphatidylethanolamine, one unidentified glycolipid, four unidentified aminophospholipids, one unidentified aminolipid, two unidentified phospholipids and three unidentified lipids. The major polyamine was homospermidine. The major isoprenoid quinone was MK-7. The DNA G+C content of the genomic DNA was 62.4 mol%. Differential phenotypic properties, together with the phylogenetic inference, demonstrate that strain NST-14T should be classified as a novel species of the genus Hymenobacter, for which the name Hymenobacter piscis sp. nov. is proposed. The type strain is NST-14T (=BCRC 81249T=LMG 31686T).

Taiwanese dermatological association consensus for the definition, classification, diagnosis, and management of urticaria: A 2021 update.

Urticaria is a prevalent disease with substantial physical, psychological, and economic impacts. With the advent of understandings of the disease and the emerging evidence of treatments, the international guidelines for treating urticaria have been updated in recent years. In order to update the 2014 edition of the Taiwanese Dermatological Association (TDA) consensus of urticaria, a total of 17 dermatologists with extensive experience in urticaria management were invited to and attended the TDA consensus meetings. All the specific aspects of the content were approved by at least 75% of the experts in attendance. Comparing to the former edition, several substantial modifications were made. For diagnosis, D-dimer was added as the recommended routine test in patients with chronic spontaneous urticaria. For pharmacological management, treatment suggestions were simplified. The approved-dosed, the up-dosed second-generation antihistamines, omalizumab, and cyclosporine were listed as the first-line to the fourth-line treatment, respectively. In addition, the management for patients of special considerations, such as the elderly, children, and pregnant women, were all discussed and mentioned in the consensus. We hope the updated TDA consensus can serve as a reference for all physicians and can help the physicians providing up-to-dated managements for these patients.

Inter-spike mitochondrial Ca2+ release enhances high frequency synaptic transmission.

KEY POINTS: Presynaptic mitochondria not only absorb but also release Ca2+ during high frequency stimulation (HFS) when presynaptic [Ca2+ ] is kept low (<500 nm) by high cytosolic Ca2+ buffer or strong plasma membrane calcium clearance mechanisms under physiological external [Ca2+ ]. Mitochondrial Ca2+ release (MCR) does not alter the global presynaptic Ca2+ transients. MCR during HFS enhances short-term facilitation and steady state excitatory postsynaptic currents by increasing vesicular release probability. The intra-train MCR may provide residual calcium at interspike intervals, and thus support high frequency neurotransmission at central glutamatergic synapses. ABSTRACT: Emerging evidence indicates that mitochondrial Ca2+ buffering contributes to local regulation of synaptic transmission. It is unknown, however, whether mitochondrial Ca2+ release (MCR) occurs during high frequency synaptic transmission. Confirming the previous notion that 2 µm tetraphenylphosphonium (TPP+ ) is a specific inhibitor of the mitochondrial Na+ /Ca2+ exchanger (mNCX), we studied the role of MCR via mNCX in short-term plasticity during high frequency stimulation (HFS) at the calyx of Held synapse of the rat. TPP+ reduced short-term facilitation (STF) and steady state excitatory postsynaptic currents during HFS at mature calyx synapses under physiological extracellular [Ca2+ ] ([Ca2+ ]o  = 1.2 mm), but not at immature calyx or at 2 mm [Ca2+ ]o . The inhibitory effects of TPP+ were stronger at synapses with morphologically complex calyces harbouring many swellings and at 32°C than at simple calyx synapses and at room temperature. These effects of TPP+ on STF were well correlated with those on the presynaptic mitochondrial [Ca2+ ] build-up during HFS. Mitochondrial [Ca2+ ] during HFS was increased by TPP+ at mature calyces under 1.2 mm [Ca2+ ]o , and further enhanced at 32°C, but not under 2 mm [Ca2+ ]o or at immature calyces. The close correlation of the effects of TPP+ on mitochondrial [Ca2+ ] with those on STF suggests that mNCX contributes to STF at the calyx of Held synapses. The intra-train MCR enhanced vesicular release probability without altering global presynaptic [Ca2+ ]. Our results suggest that MCR during HFS elevates local [Ca2+ ] near synaptic sites at interspike intervals to enhance STF and to support stable synaptic transmission under physiological [Ca2+ ]o .

Neurodevelopmental and transcriptomic effects of CRISPR/Cas9-induced somatic orco mutation in honey bees.

In insects, odorant receptors facilitate olfactory communication and require the functionality of the highly conserved co-receptor gene orco. Genome editing studies in a few species of ants and moths have revealed that orco can also have a neurodevelopmental function, in addition to its canonical role in adult olfaction, discovered first in Drosophila melanogaster. To extend this analysis, we determined whether orco mutations also affect the development of the adult brain of the honey bee Apis mellifera, an important model system for social behavior and chemical communication. We used CRISPR/Cas9 to knock out orco and examined anatomical and molecular consequences. To increase efficiency, we coupled embryo microinjection with a laboratory egg collection and in vitro rearing system. This new workflow advances genomic engineering technologies in honey bees by overcoming restrictions associated with field studies. We used Sanger sequencing to quickly select individuals with complete orco knockout for neuroanatomical analyses and later validated and described the mutations with amplicon sequencing. Mutant bees had significantly fewer glomeruli, smaller total volume of all the glomeruli, and higher mean individual glomerulus volume in the antennal lobe compared to wild-type controls. RNA-Sequencing revealed that orco knockout also caused differential expression of hundreds of genes in the antenna, including genes related to neural development and genes encoding odorant receptors. The expression of other types of chemoreceptor genes was generally unaffected, reflecting specificity of CRISPR activity in this study. These results suggest that neurodevelopmental effects of orco are related to specific insect life histories.

Postnatal maturation of glutamate clearance and release kinetics at the rat and mouse calyx of Held synapses.

Although calyx of Held synapses undergo dramatic changes around the hearing onset, previous in vivo studies suggest that the calyx synapses undergo further post-hearing maturation process. While developmental changes over the hearing onset have been extensively studied, this post-hearing maturation process remained relatively little investigated. Because of post-hearing maturation, previous results from studies around hearing onset and studies of post-hearing calyx synapses are somewhat inconsistent. Here, we characterized the post-hearing maturation of calyx synapses with regard to in vitro electrophysiological properties in rats and mice. We found that parameters for residual glutamate in the cleft during a train, EPSC kinetics, and vesicle pool size became close to a full mature level by P14, but they further matured until P16 in the rats. Consistently, the phasic and slow EPSCs evoked by action potential trains at P16 calyx synapses were not different from those at P18 or P25 under physiological extracellular [Ca2+ ]o (1.2 mM). In contrast, the parameters for residual current and EPSC kinetics displayed drastic changes until P16 in mice, and slow EPSCs during the train further decreased between P16 and P18, suggesting that maturation of calyx synapses progresses at least up to P16 in rats and P18 in mice.

Rhodobacter amnigenus sp. nov. and Rhodobacter ruber sp. nov., isolated from freshwater habitats.

Two bacterial strains, designated HSP-20T and CCP-1T, isolated from freshwater habitats in Taiwan, were characterized by polyphasic taxonomy. Both strains were Gram-stain-negative, aerobic, non-motile and rod-shaped. Cells of strains HSP-20T and CCP-1T formed pink and dark red coloured colonies, respectively. Both strains contained bacteriochlorophyll a, and showed optimum growth under anaerobic conditions by photoheterotrophy, but no growth by photoautotrophy. Phylogenetic analyses based on 16S rRNA gene and whole-genome sequences indicated that both strains belonged to the genus Rhodobacter. Analysis of 16S rRNA gene sequences showed that strains HSP-20T and CCP-1T shared 98.3 % sequence similarity and were closely related to Rhodobacter tardus CYK-10T (96.0 %) and Rhodobacter flagellatus SYSU G03088T (96.0 %), respectively. Both strains shared common chemotaxonomic characteristics including Q-10 as the major isoprenoid quinone, C18 : 1 ω7c as the predominant fatty acid, and phosphatidylethanolamine, phosphatidylglycerol and phosphatidylcholine as the main polar lipids. The DNA G+C content of both strains was 66.2 mol%. The average nucleotide identity, average amino acid identity and digital DNA-DNA hybridization values between these two novel isolates and their closest relatives were below the cut-off values of 95-96, 90 and 70 %, respectively, used for species demarcation. On the basis of phenotypic and genotypic properties and phylogenetic inference, both strains should be classified as novel species within the genus Rhodobacter, for which the names Rhodobacter amnigenus sp. nov. (=BCRC 81193T=LMG 31334T) and Rhodobacter ruber sp. nov. (=BCRC 81189T=LMG 31335T) are proposed.

Higher serum homocysteine level and frequency of hyperhomocysteinemia in carcinoembryonic antigen-positive or squamous cell carcinoma-antigen-positive oral leukoplakia patients.

BACKGROUND/PURPOSE: Our previous study found significantly lower serum hematinic levels and higher serum homocysteine level as well as higher frequencies of serum hematinic deficiencies and hyperhomocysteinemia in oral leukoplakia (OL) patients than in healthy control subjects. This study evaluated whether carcinoembryonic antigen (CEA)-positive or squamous cell carcinoma-antigen (SCC-Ag)-positive OL patients had significantly lower serum hematinic levels and higher serum homocysteine level as well as significantly higher frequencies of hematinic deficiencies and hyperhomocysteinemia than CEA-negative or SCC-Ag-negative OL patients or healthy control subjects. METHODS: The complete blood count, serum iron, vitamin B12, folic acid, and homocysteine levels in 184 OL patients including 85 CEA-positive, 99 CEA-negative, 25 SCC-Ag-positive, and 159 SCC-Ag-negative OL patients and in 184 age- and sex-matched healthy control subjects were measured and compared. RESULTS: We found that the 85 CEA-positive or 25 SCC-Ag-positive OL patients had a significantly lower mean serum folic acid level and a significantly higher mean serum homocysteine level as well as significantly higher frequencies of serum folic acid deficiency and hyperhomocysteinemia than 184 healthy control subjects. Moreover, the 25 SCC-Ag-positive OL patients had a significantly higher mean serum homocysteine level than the 159 SCC-Ag-negative OL patients. The 85 CEA-positive OL patients had a higher mean serum homocysteine level and a higher frequency of hyperhomocysteinemia than 99 CEA-negative OL patients (marginally significant, P = 0.060). CONCLUSION: CEA-positive or SCC-Ag-positive OL patients tend to have a higher mean serum homocysteine level and a higher frequency of hyperhomocysteinemia than CEA-negative or SCC-Ag-negative OL patients, respectively.

Serum levels and positive rates of tumor biomarkers in oral precancer patients.

BACKGROUND/PURPOSE: Several previous studies have reported higher serum tumor marker levels in patients with oral or head and neck squamous cell carcinomas. This study evaluated whether 232 patients with oral precancerous lesions (oral precancer patients) had significantly higher serum carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), and ferritin levels than healthy control subjects. METHODS: The serum CEA, SCC-Ag, and ferritin levels in 232 oral precancer patients and 187 healthy control subjects were measured and compared. Patients with serum CEA level ≥3 ng/mL, SCC-Ag level ≥2 ng/mL, and ferritin level ≥250 ng/mL were scored as serum positive for CEA, SCC-Ag, and ferritin, respectively. RESULTS: We found significantly higher mean serum CEA, SCC-Ag, and ferritin levels in 232 oral precancer patients than in 187 healthy control subjects (all P-values < 0.05). Moreover, 232 oral precancer patients had significantly higher serum positive rates of CEA (47.4%), SCC-Ag (13.8%), and ferritin (52.2%) than 187 healthy control subjects (all P-values < 0.05). Of the 232 oral precancer patients, 121 (52.1%), 56 (24.1%), and 10 (4.3%) had serum positivities of one, two, or three tumor markers including CEA, SCC-Ag, and ferritin, respectively. CONCLUSION: There are significantly higher mean serum CEA, SCC-Ag, and ferritin levels and significantly higher serum positive rates of CEA, SCC-Ag, and ferritin in oral precancer patients than in healthy control subjects. The serum CEA, SCC-Ag, and ferritin levels are of diagnostic value and may be potential tumor markers for the screening of oral precancer patients.

Anemia, hematinic deficiencies, and hyperhomocysteinemia in gastric parietal cell antibody-positive and -negative burning mouth syndrome patients.

BACKGROUND/PURPOSE: Our previous study found the serum gastric parietal cell antibody (GPCA) positivity in 12.3% of burning mouth syndrome (BMS) patients. This study assessed whether GPCA-positive BMS (GPCA+BMS) patients had significantly higher frequencies of macrocytosis, anemia, hematinic deficiencies, and hyperhomocysteinemia than healthy control subjects or GPCA-negative BMS (GPCA-BMS) patients. METHODS: The mean corpuscular volume, blood hemoglobin (Hb), and serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels were measured and compared between any two of three groups of 109 GPCA+BMS patients, 775 GPCA-BMS patients, and 442 healthy control subjects. RESULTS: We found that 109 GPCA+BMS patients had significantly higher frequencies of macrocytosis, blood Hb and serum iron and vitamin B12 deficiencies, and hyperhomocysteinemia than 442 healthy control subjects (all P-values < 0.001) and significantly higher frequencies of macrocytosis, blood Hb and serum vitamin B12 deficiencies, and hyperhomocysteinemia than 775 GPCA-BMS patients (all P-values < 0.01). Moreover, 775 GPCA-BMS patients had significantly higher frequencies of macrocytosis, blood Hb and serum iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia than 442 healthy control subjects (all P-values < 0.005). Pernicious anemia (45.5%) and normocytic anemia (24.2%) were the two most common types of anemia in 33 anemic GPCA+BMS patients. Moreover, normocytic anemia (61.3%), thalassemia trait-induced anemia (15.5%), and iron deficiency anemia (14.1%) were the three most common types of anemia in 142 anemic GPCA-BMS patients. CONCLUSION: GPCA+BMS patients have significantly higher frequencies of macrocytosis, blood Hb and serum vitamin B12 deficiencies, and hyperhomocysteinemia than healthy control subjects or GPCA-BMS patients.

An Optimization-Based Orchestrator for Resource Access and Operation Management in Sliced 5G Core Networks.

Network slicing is a promising technology that network operators can deploy the services by slices with heterogeneous quality of service (QoS) requirements. However, an orchestrator for network operation with efficient slice resource provisioning algorithms is essential. This work stands on Internet service provider (ISP) to design an orchestrator analyzing the critical influencing factors, namely access control, scheduling, and resource migration, to systematically evolve a sustainable network. The scalability and flexibility of resources are jointly considered. The resource management problem is formulated as a mixed-integer programming (MIP) problem. A solution approach based on Lagrangian relaxation (LR) is proposed for the orchestrator to make decisions to satisfy the high QoS applications. It can investigate the resources required for access control within a cost-efficient resource pool and consider allocating or migrating resources efficiently in each network slice. For high system utilization, the proposed mechanisms are modeled in a pay-as-you-go manner. Furthermore, the experiment results show that the proposed strategies perform the near-optimal system revenue to meet the QoS requirement by making decisions.