RNA Polymerase Subunits and Ribosomal Proteins: An Overview and Their Genetic Impact on Complex Human Traits.

Accurate gene expression is fundamental for sustaining life, enabling adaptive responses to routine tasks and management of urgent cellular environments. RNA polymerases (RNAP I, RNAP II, and RNAP III) and ribosomal proteins (RPs) play pivotal roles in the precise synthesis of proteins from DNA sequences. In this review, we briefly examined the structure and function of their constituent proteins and explored to characterize these proteins and the genes encoding them, particularly in terms of their expression quantitative trait loci (eQTL) associated with complex human traits. We gathered a comprehensive set of 4007 genome-wide association study (GWAS) signal-eQTL pairs, aligning GWAS Catalog signals with eQTLs across various tissues for the genes involved. These pairs spanned 16 experimental factor ontology (EFO) parent terms defined in European Bioinformatics Institute (EBI). A substantial majority (83.4%) of the pairs were attributed to the genes encoding RPs, especially RPS26 (32.9%). This large proportion was consistent across all tissues (15.5~81.9%), underscoring its extensive impact on complex human traits. Notably, these proportions of EFO terms differed significantly (p < 0.0031) from those for RNAPs. Brain-specific pairs for POLR3H, a component of RNAP III, were implicated in neurological disorders. The largest number of pairs in RNAP I was found for POLR1H, encoding RPA12, a built-in transcription factor essential for high transcriptional efficiency of RNAP I. RNAP II-related pairs were less abundant, with unique structural organization featuring minimal subunits for flexible transcription of a diverse range of genes with customized dissociable subunits. For instance, RPB4 encoded by POLR2D, the RNAP II gene with the most pairs, forms its dissociable stalk module with RPB7. This study provides insightful genetic characteristics of RPs and RNAPs, with a priority emphasis on RPS26, POLR1H, POLR2D, and POLR3H, for future studies on the impact of individual genetic variation on complex human traits.

Development of cooking method for senior-friendly food using fruits suitable for older adults with masticatory dysfunction.

BACKGROUND/OBJECTIVES: The purpose of this study was to establish a fruit-cooking method suitable for older adults with masticatory dysfunction. MATERIALS/METHODS: Five types of fruits were selected to make fruit jelly and puree: apple, sweet persimmon, mandarin, Korean melon, and watermelon. Recipes were selected based on the Korean Industrial Standard (KS) for senior-friendly foods (KS H 4897), which classifies foods into 3 levels (L1-L3) based on their hardness and viscosity. RESULTS: In South Korea, senior-friendly foods are classified into 3 stages based on their hardness. Stage 1 is for foods that are able to eat with teeth (hardness greater than 50,000 N and less than 500,000 N), Stage 2 is for foods that are able to eat with gums (hardness greater than 20,000 N and less than 50,000 N), and Stage 3 is for foods that are able to eat with the tongue (hardness less than 20,000 N). As a result of measuring the hardness by varying the shape of the fruit, it was found that nearly all fruits could be eaten fresh by chewing with the teeth (L1) but did not meet the KS for mastication using the gums (L2) or tongue (L3), so the cooking method was selected as fruit jelly and fruit puree. Only sweet persimmon, which had a hardness of 61,624-496,393 N, was not suitable for consumption in fresh fruit, unprocessed form. Based on their hardness measurements, fruit jellies (27,869 to 36,343 N) and fruit purees (315 to 1,156 N) met the L2 and L3 requirements, respectively. The viscosity results of all fruit purees met the L3 requirement. CONCLUSION: These results offer a simple cooking method to prepare texture-modified fruits suitable for safe consumption by older adults living with masticatory difficulties in general households and nursing facilities.

Classification of thermal environment control indicators according to the thermal sensitivity of office occupants.

The control that have the greatest influence on comfortable in the office occupants are the heating, ventilation, and air conditioning (HVAC) system operation and the thermal environment. However, comfortable HVAC operation is difficult in the office space characterized by a recommended standard thermal environment or a centralized HVAC system. To consider the occupant's thermal comfort to the greatest possible extent, must establish a method to quantify the variables related to the occupant's thermal comfort. This study aims to group occupants in Thermal sensation vote (TSV) clusters and perform sensitivity analysis (SA) on the relationship between thermal environmental factors in an office building and each cluster's TSV to establish the typology of the control indicators for each cluster. A total of 10 field experiments were conducted in the same office. This field study was carried out 2022. The indoor thermal environmental parameters, the subjective evaluation of the thermal comfort of the resident and the operation pattern of the heating system were monitored at the same time. A total of 4,200 datasets related to indoor thermal environmental parameters and a total of 1,680 datasets related to occupants' thermal comfort were collected and analyzed. The results of this study show that people have different levels of adaptability and sensitivity to a given thermal environment. This study founded distinguishable similarities in their thermal sensation traits and grouped similar TSV values into five clusters that responded differently to the same thermal environment. Each cluster showed different TSV and Thermal comfort vote (TCV) patterns, which allowed us to classify the groups that had sensitive responses to the thermal environment and those that did not. This study was determined different control indicators and guidelines for the divided groups according to thermal sensitivity.

Fibular free flap with proximal perforator skin paddle due to aberrant anatomy - a case report.

BACKGROUND: The fibular free flap is considered one of the most valuable options for mandible reconstruction. A perforator flap has gained widespread acceptance in oral and maxillofacial reconstruction. Typically, the fibula flap is obtained primarily with the distal perforator due to its reliable blood supply, with less attention given to the proximal perforators during the harvesting process. Normally, the distal perforator of the fibula exhibits stability and shows limited anatomical variations. However, there have been reported cases in which the distal perforator is absent. At times, these vascular abnormalities remain undetectable through Doppler examination or preoperative angiography evaluation. Therefore, this case details the experience of encountering the rare event of vascular abnormality in oral cancer surgery. CASE PRESENTATION: This article reports the case of a patient who presented with a congenital absence of the distal perforator in the peroneal artery, attributed to a vascular abnormality. Additionally, we provide a review of the concept of utilizing the proximal perforator as an alternative approach in the flap harvesting process. CONCLUSIONS: While the distal perforator of the peroneal artery is typically utilized for fibula free flap procedures, surgeons must remain cognizant of the potential for its absence due to aberrant anatomy. Recognizing an alternative approach in such cases can be pivotal for precise surgical planning and favorable outcomes in oral and maxillofacial reconstruction.

Irregularity of instantaneous gamma frequency in the motor control network characterize visuomotor and proprioceptive information processing.

Objective.The study aims to characterize movements with different sensory goals, by contrasting the neural activity involved in processing proprioceptive and visuo-motor information. To accomplish this, we have developed a new methodology that utilizes the irregularity of the instantaneous gamma frequency parameter for characterization.Approach.In this study, eight essential tremor patients undergoing an awake deep brain stimulation implantation surgery repetitively touched the clinician's finger (forward visually-guided/FV movement) and then one's own chin (backward proprioceptively-guided/BP movement). Neural electrocorticographic recordings from the motor (M1), somatosensory (S1), and posterior parietal cortex (PPC) were obtained and band-pass filtered in the gamma range (30-80 Hz). The irregularity of the inter-event intervals (IEI; inverse of instantaneous gamma frequency) were examined as: (1) auto-information of the IEI time series and (2) correlation between the amplitude and its proceeding IEI. We further explored the network connectivity after segmenting the FV and BP movements by periods of accelerating and decelerating forces, and applying the IEI parameter to transfer entropy methods.Main results.Conceptualizing that the irregularity in IEI reflects active new information processing, we found the highest irregularity in M1 during BP movement, highest in PPC during FV movement, and the lowest during rest at all sites. Also, connectivity was the strongest from S1 to M1 and from S1 to PPC during FV movement with accelerating force and weakest during rest.Significance. We introduce a novel methodology that utilize the instantaneous gamma frequency (i.e. IEI) parameter in characterizing goal-oriented movements with different sensory goals, and demonstrate its use to inform the directional connectivity within the motor cortical network. This method successfully characterizes different movement types, while providing interpretations to the sensory-motor integration processes.

Comparison of genetic variations between high- and low-risk Listeria monocytogenes isolates using whole-genome de novo sequencing.

In this study, genetic variations and characteristics of Listeria monocytogenes isolates from enoki mushrooms (23), smoked ducks (7), and processed ground meat products (30) were examined with respect to hemolysis, virulence genes, growth patterns, and heat resistance. The isolates that showed the highest pathogenicity and the lowest pathogenicity were analyzed to obtain the whole-genome sequence, and the sequences were further analyzed to identify genetic variations in virulence, low-temperature growth-related, and heat resistance-related factors. All isolates had ß-hemolysis and virulence genes (actA, hlyA, inlA, inlB, and plcB). At low temperatures, isolates with high growth (L. monocytogenes strains SMFM 201803 SD 1-1, SMFM 201803 SD 4-2, and SMFM 201804 SD 5-3) and low growth (L. monocytogenes strains SMFM 2019-FV43, SMFM 2019-FV42, and SMFM 2020-BT30) were selected. Among them, L. monocytogenes SMFM 201804 SD 5-3 showed the highest resistance at 60°C and 70°C. The strains SMFM 201804 SD 5-3 (high-risk) and SMFM 2019-FV43 (low-risk) harbored 45 virulence genes; 41 single nucleotide variants (SNVs) were identified between these two isolates. A comparison of 26 genes related to low-temperature growth revealed 18 SNVs between these two isolates; a comparison of the 21 genes related to heat resistance revealed 16 SNVs. These results indicate that the differences in the pathogenicity of L. monocytogenes SMFM 201804 SD 5-3 and L. monocytogenes SMFM 2019-FV43 are associated with the SNVs identified in virulence genes, low-temperature growth-related genes, and heat resistance-related genes.

Cystic lesion between a deciduous tooth and the succeeding permanent tooth: a retrospective analysis of 87 cases.

Objectives: The purpose of this study is to investigate the characteristics of dentigerous and radicular cysts that occur between deciduous and succeeding permanent teeth and to propose considerations for differential diagnosis of cysts at the treatment planning stage in the outpatient clinic. Materials and Methods: A total of 87 patients with a cystic lesion located between a deciduous tooth and the succeeding permanent tooth participated in the study. Twelve variables were analyzed to diagnose such a cyst. For data analysis, Fisher's exact test was used to determine the statistical significance of the variables. Results: Of the total 87 patients who participated in this study, 69 were diagnosed with dentigerous cysts and 18 were diagnosed with radicular cysts. Seven of the 12 differential factors analyzed in this study were statistically significant: age, location, symptoms, dental caries, endodontic treatment, delayed eruption, and size. Conclusion: Several criteria can be considered for diagnosis of dentigerous cysts or radicular cysts. Age, location, presence of symptoms and dental caries, previous endodontic treatment, cystic size, and delayed eruption of impacted permanent teeth are reliable factors that should be considered when diagnosing dentigerous and radicular cysts.

Systemic TM4SF5 overexpression in ApcMin/+ mice promotes hepatic portal hypertension associated with fibrosis.

Mutation of the gene for adenomatous polyposis coli (APC), as seen in ApcMin/+ mice, leads to intestinal adenomas and carcinomas via stabilization of ß-catenin. Transmembrane 4 L six family member 5 (TM4SF5) is involved in the development of non-alcoholic fatty liver disease, fibrosis, and cancer. However, the functional linkage between TM4SF5 and APC or ß-catenin has not been investigated for pathological outcomes. After interbreeding ApcMin/+ with TM4SF5-overexpressing transgenic (TgTM4SF5) mice, we explored pathological outcomes in the intestines and livers of the offspring. The intestines of 26-week-old dual-transgenic mice (ApcMin/+:TgTM4SF5) had intramucosal adenocarcinomas beyond the single-crypt adenomas in ApcMin/+ mice. Additional TM4SF5 overexpression increased the stabilization of ß-catenin via reduced glycogen synthase kinase 3ß (GSK3ß) phosphorylation on Ser9. Additionally, the livers of the dualtransgenic mice showed distinct sinusoidal dilatation and features of hepatic portal hypertension associated with fibrosis, more than did the relatively normal livers in ApcMin/+ mice. Interestingly, TM4SF5 overexpression in the liver was positively linked to increased GSK3ß phosphorylation (opposite to that seen in the colon), ß-catenin level, and extracellular matrix (ECM) protein expression, indicating fibrotic phenotypes. Consistent with these results, 78-week-old TgTM4SF5 mice similarly had sinusoidal dilatation, immune cell infiltration, and fibrosis. Altogether, systemic overexpression of TM4SF5 aggravates pathological abnormalities in both the colon and the liver. [BMB Reports 2022; 55(12): 609-614].

Motor Signatures in Digitized Cognitive and Memory Tests Enhances Characterization of Parkinson's Disease.

Although interest in using wearable sensors to characterize movement disorders is growing, there is a lack of methodology for developing clinically interpretable biomarkers. Such digital biomarkers would provide a more objective diagnosis, capturing finer degrees of motor deficits, while retaining the information of traditional clinical tests. We aim at digitizing traditional tests of cognitive and memory performance to derive motor biometrics of pen-strokes and voice, thereby complementing clinical tests with objective criteria, while enhancing the overall characterization of Parkinson's disease (PD). 35 participants including patients with PD, healthy young and age-matched controls performed a series of drawing and memory tasks, while their pen movement and voice were digitized. We examined the moment-to-moment variability of time series reflecting the pen speed and voice amplitude. The stochastic signatures of the fluctuations in pen drawing speed and voice amplitude of patients with PD show a higher signal-to-noise ratio compared to those of neurotypical controls. It appears that contact motions of the pen strokes on a tablet evoke sensory feedback for more immediate and predictable control in PD, while voice amplitude loses its neurotypical richness. We offer new standardized data types and analytics to discover the hidden motor aspects within the cognitive and memory clinical assays.

Cemento-osseous dysplasia: clinical presentation and symptoms.

Objectives: The purpose of this study was to evaluate risk factors and symptoms in cemento-osseous dysplasia (COD) patients. Materials and Methods: In this study, 62 patients who were diagnosed histologically with COD were investigated from 2010 to 2020 at the author's institution. We compared clinical and radiological characteristics of symptomatic and asymptomatic patients. The factors were sex, age, lesion size, site, radiologic stage of lesion, apical involvement, sign of infection, and history of tooth extraction. Statistical analysis was performed using Fisher's exact test and the chi-square test. Results: COD was more prevalent in female patients. With the exception of three cases, all were focal COD. The majority of patients presented with symptoms when the lesion was smaller than 1.5 cm in size. Symptoms were observed when the apex of the tooth was included in the lesion or there was a local infection around the lesion. The history of tooth extraction and previous endodontic treatment were evaluated, and history was not a significant predictor for the onset of symptoms. Conclusion: In this study, risk factors associated with symptomatic patients were size of lesion, apical involvement, and local infection.

Toward interpretable digital biomarkers of walking and reaching in Parkinson's disease.

Multimodal digital data registered with wearable biosensors have emerged as highly complementary of clinical pencil-and-paper criteria, offering new insights in ways to detect and diagnose various aspects of Parkinson's disease (PD). A pressing question is how to combine both the clinical knowledge of PD and the new technology to create interpretable digital biomarkers easily obtainable with off-the-shelf technology. Several challenges concerning disparity in biophysical units, anatomical differences across participants, sensor positioning, and sampling resolution are addressed in this work, along with identification of optimal parameters to automatically differentiate patients with PD from controls. We combine data from a multitude of biosensors registering signals from the central (electroencephalography) and peripheral (magnetometry, kinematics) nervous systems, inclusive of the autonomic nervous system (electrocardiogram), as the participants perform natural tasks requiring different levels of intentional planning and automatic control. We find that magnetometer data during walking, across a variety of amplitude and timing signals, provide optimal separation of PD from neurotypical controls. We conclude that using multimodal signals within the context of actions that bear different levels of intent, can be revealing of features of PD that would scape the naked eye. Further, we add that clinical criteria combined with such optimal digital parameter spaces offer a far more complete picture of PD than using either one of these pieces of data alone.

MG1141A as a Highly Potent Monoclonal Neutralizing Antibody Against SARS-CoV-2 Variants.

Since the coronavirus disease outbreak in 2019, several antibody therapeutics have been developed to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Antibody therapeutics are effective in neutralizing the virus and reducing hospitalization in patients with mild and moderate infections. These therapeutics target the spike protein of SARS-CoV-2; however, emerging mutations in this protein reduce their efficiency. In this study, we developed a universal SARS-CoV-2 neutralizing antibody. We generated a humanized monoclonal antibody, MG1141A, against the receptor-binding domain of the spike protein through traditional mouse immunization. We confirmed that MG1141A could effectively neutralize live viruses, with an EC50 of 92 pM, and that it exhibited effective Fc-mediated functions. Additionally, it retained its neutralizing activity against the alpha (UK), beta (South Africa), and gamma (Brazil) variants of SARS-CoV-2. Taken together, our study contributes to the development of a novel antibody therapeutic approach, which can effectively combat emerging SARS-CoV-2 mutations.

TM4SF5-mediated liver malignancy involves NK cell exhaustion-like phenotypes.

Aberrant extracellular matrix and immune cell alterations within the tumor microenvironment promote the pathological progression of liver carcinogenesis. Although transmembrane 4 L six family member 5 (TM4SF5) is involved in liver fibrosis and cancer, its mechanism avoiding immune surveillance during carcinogenesis remains unknown. We investigated how TM4SF5-mediated signaling caused immune evasion using in vitro primary cells and in vivo liver tissues from genetic or chemically induced mouse models. TM4SF5-transgenic and diethylnitrosamine (DEN)-induced liver cancer mouse models exhibited fibrotic and cancerous livers, respectively, with enhanced TM4SF5, pY705STAT3, collagen I, and laminin γ2 levels. These TM4SF5-mediated effects were abolished by TM4SF5 inhibitor, 4'-(p-toluenesulfonylamido)-4-hydroxychalcone (TSAHC). TM4SF5-dependent tumorigenesis involved natural killer (NK) cell exhaustion-like phenotypes including the reduction of NK cell number or function, which were blocked with TSAHC treatment. TM4SF5 expression in cancer cells downregulated stimulatory ligands and receptors for NK cell cytotoxicity, including SLAMF6, SLAMF7, MICA/B, and others. TM4SF5 suppression or inhibition reduced STAT3 signaling activity and recovered the receptor levels and NK cell surveillance, leading to reduced fibrotic and cancerous phenotypes, and longer survival. Altogether, these findings suggest that TM4SF5-mediated STAT3 activity for extracellular matrix modulation is involved in the progression of liver disease to HCC and that TM4SF5 appears to suppress NK cells during liver carcinogenesis.

Sensory Attributes of Buckwheat Jelly (Memilmuk) with Mung Bean Starch Added to Improve Texture and Taste.

Buckwheat contains more essential proteins, dietary fiber, vitamins, minerals, and diverse phytochemicals than wheat and rice. The aims of this study are to develop the descriptive sensory attributes and evaluate the consumer acceptability of six buckwheat jellies (memilmuk) with added mung bean starch and to analyze the relationship between their descriptive sensory attributes and consumer acceptability. Statistical analyses were performed by one-way analysis of variance (ANOVA), principal component analysis (PCA), and partial least squares regression (PLSR). A total of 18 sensory attributes of buckwheat jelly, including appearance (brown, brightness, and roughness), odor/aroma (soymilk smell, grain smell, red bean porridge smell, and buckwheat tea smell), flavor or taste (savory flavor, plain taste, buckwheat taste, sweet taste, salty taste, and umami), and texture (squashed, dry, smooth, elasticity and stickiness) were developed. Consumer acceptability tests of six buckwheat jellies were conducted by 93 consumers evaluating for color, smell, savory taste, aftertaste, harmony with the sauce, overall liking, and would recommend or try again. Buckwheat jelly with 25% of mung bean starch (BJ_916) was the most favorable jelly sample among the six samples. All attributes except color, smell, and the savory taste of samples showed a significant difference (p < 0.001). BJ_916 showed a close relationship with a grain smell, elasticity, red bean porridge smell, and sweet taste of descriptive attributes and also all attributes of consumer acceptability. The determination of sensory attributes and consumer acceptability of buckwheat jelly will help to improve sensory characteristics to fulfill consumer needs and desires. Furthermore, this current study will help facilitate the expansion of the buckwheat consumption market.

Optimal time lags from causal prediction model help stratify and forecast nervous system pathology.

Traditional clinical approaches diagnose disorders of the nervous system using standardized observational criteria. Although aiming for homogeneity of symptoms, this method often results in highly heterogeneous disorders. A standing question thus is how to automatically stratify a given random cohort of the population, such that treatment can be better tailored to each cluster's symptoms, and severity of any given group forecasted to provide neuroprotective therapies. In this work we introduce new methods to automatically stratify a random cohort of the population composed of healthy controls of different ages and patients with different disorders of the nervous systems. Using a simple walking task and measuring micro-fluctuations in their biorhythmic motions, we combine non-linear causal network connectivity analyses in the temporal and frequency domains with stochastic mapping. The methods define a new type of internal motor timings. These are amenable to create personalized clinical interventions tailored to self-emerging clusters signaling fundamentally different types of gait pathologies. We frame our results using the principle of reafference and operationalize them using causal prediction, thus renovating the theory of internal models for the study of neuromotor control.

Idiopathic bone cavity: clinical and radiological features of 90 retrospective cases and surgical treatment.

OBJECTIVES: The purpose of this study was to evaluate the clinical and radiographic characteristics of idiopathic bone cavity (IBC) to determine the effect of surgical intervention on the process of healing. MATERIALS AND METHODS: All cases diagnosed with IBC during the period of 2011 to 2020 at our Department of Oral and Maxillofacial Surgery were searched. Ninety cases were retrieved. The features evaluated were sex, age, contour of the lesion, number of teeth involved, site, history of trauma, and postoperative healing pattern. The significance of differences was assessed by Mann-Whitney U test and chi-square test. RESULTS: The female:male ratio showed no predilection toward either sex (0.9:0.8). The mean age of the collected sample was 22.05±14.38 years, and the age ranged from 10 to 58 years. All cases presented in the mandible and showed well-circumscribed radiolucency. Margins were either scalloped or round in shape, and the size varied from one tooth to six teeth involvement. Seventy cases involved three or fewer roots. Three cases showed bilateral lesion. Four cases had a history of trauma at the area of the lesion. Fifty-one cases were followed for six months after surgery, and all showed increased bone density at the lesion. CONCLUSION: There is no definitive radiological or clinical feature of IBC. Considering the diversity of clinical and radiological features, such a diagnosis relies primarily on surgical findings of an empty bone cavity with no epithelial lining. Our data suggest that surgical intervention be the first choice of treatment as opposed to observation.

Microfluidic valvular chips and a numerical lymphatic vessel model for the study of lymph transport characteristics.

Lymph transport inside lymphatic vessels is highly complex and not yet fully understood. So far, a consensus has not been reached among existing analytical models on how spatiotemporal coordination of contracting adjacent lymphangions affects lymph transport. To understand complex lymph transport, we created a novel microfluidic valvular chip with flexible bicuspid valves and segmental pneumatic pumps based on a microfluidic device with an inside 3D structure made of hydrogels. Inside the chip, water moved unidirectionally when the microfluidic channel was locally compressed, with its velocity profile closely resembling the waveform of lymph observed in vivo. Furthermore, for a systematic and mechanistic study, we constructed a numerical model based on fluid-structure interaction and validated the model via demonstration of similarities in water transport characteristics between the model and the chip. Using this model, we examined various mechanical and time-dependent parameters, such as period, phase delay, sequence, and strength of contractions, valve compliance, fluid viscosity, and pressure differences, for their effects on water transport. Although our model is simplified, it enabled a parametric study that helped clarify the mechano-temporal correlations between compressions of adjacent chambers via transmissions of hydrodynamic forces, which regulate complex lymph transport. Moreover, our chip demonstrated technical advances that enable unidirectional discrete movement of fluid in the picoliter range by phenumatic pumping. The velocity profile is also similar to the pulse waveform of arteries under pathological conditions such as increased aortic stiffness, allowing our chip to be used for in vitro mechanobiology studies of endothelial cells.

Personalized Biometrics of Physical Pain Agree with Psychophysics by Participants with Sensory over Responsivity.

The study of pain requires a balance between subjective methods that rely on self-reports and complementary objective biometrics that ascertain physical signals associated with subjective accounts. There are at present no objective scales that enable the personalized assessment of pain, as most work involving electrophysiology rely on summary statistics from a priori theoretical population assumptions. Along these lines, recent work has provided evidence of differences in pain sensations between participants with Sensory Over Responsivity (SOR) and controls. While these analyses are useful to understand pain across groups, there remains a need to quantify individual differences more precisely in a personalized manner. Here we offer new methods to characterize pain using the moment-by-moment standardized fluctuations in EEG brain activity centrally reflecting the person's experiencing temperature-based stimulation at the periphery. This type of gross data is often disregarded as noise, yet here we show its utility to characterize the lingering sensation of discomfort raising to the level of pain, individually, for each participant. We show fundamental differences between the SOR group in relation to controls and provide an objective account of pain congruent with the subjective self-reported data. This offers the potential to build a standardized scale useful to profile pain levels in a personalized manner across the general population.

Differential TM4SF5-mediated SIRT1 modulation and metabolic signaling in nonalcoholic steatohepatitis progression.

Nonalcoholic fatty liver disease is a chronic condition involving steatosis, steatohepatitis and fibrosis, and its progression remains unclear. Although the tetraspanin transmembrane 4 L six family member 5 (TM4SF5) is involved in hepatic fibrosis and cancer, its role in nonalcoholic steatohepatitis (NASH) progression is unknown. We investigated the contribution of TM4SF5 to liver pathology using transgenic and KO mice, diet- or drug-treated mice, in vitro primary cells, and in human tissue. TM4SF5-overexpressing mice exhibited nonalcoholic steatosis and NASH in an age-dependent manner. Initially, TM4SF5-positive hepatocytes and liver tissue exhibited lipid accumulation, decreased Sirtuin 1 (SIRT1), increased sterol regulatory-element binding proteins (SREBPs) and inactive STAT3 via suppressor of cytokine signaling (SOCS)1/3 upregulation. In older mice, TM4SF5 promoted inflammatory factor induction, SIRT1 expression and STAT3 activity, but did not change SOCS or SREBP levels, leading to active STAT3-mediated ECM production for NASH progression. A TM4SF5-associated increase in chemokines promoted SIRT1 expression and progression to NASH with fibrosis. Suppression of the chemokine CCL20 reduced immune cell infiltration and ECM production. Liver tissue from high-fat diet- or CCl4 -treated mice and human patients exhibited TM4SF5-dependent steatotic or steatohepatitic livers with links between TM4SF5-mediated SIRT1 modulation and SREBP or SOCS/STAT3 signaling axes. TM4SF5-mediated STAT3 activation in fibrotic NASH livers increased collagen I and laminin γ2. Both collagen I α1 and laminin γ2 suppression resulted in reduced SIRT1 and active STAT3, but no change in SREBP1 or SOCS, and abolished CCl4 -mediated mouse liver damage. TM4SF5-mediated signaling pathways that involve SIRT1, SREBPs and SOCS/STAT3 promoted progression to NASH. Therefore, TM4SF5 and its downstream effectors may be promising therapeutic targets to treat nonalcoholic fatty liver disease. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Trends and Dietary Assessment According to Fruit and Vegetable Intake in Korean Elderly People: Analysis Based on the Korea National Health and Nutrition Examination Survey 1998, 2008, and 2018.

The study aimed to examine the 20-year trends in fruit and non-starch/unsalted vegetable intake among the Korean elderly aged 65 years or older based on the Korea National Health and Nutrition Examination Survey (KNHANES) data. A total of 3722 elderly citizens aged 65 years or older who participated in the dietary survey (24-h recall of dietary intake) of the 1998, 2008, and 2018 NHANES were selected as the subjects of this study. Fruit and non-starchy/unsalted vegetable intake increased by approximately 86.53 g over the past 20 years, from 268.27 g in 1998 to 355.8 g in 2018. In particular, 65-74-year-olds had an increased intake by approximately 130.38 g over the past 20 years, from 277.34 g in 1998 to 407.72 g in 2018. In addition, snacks intake significantly increased over the past 20 years (p for trend < 0.001). Intake according to daily meal cooking location increased by approximately 130 g over the past 20 years, from 64.50 g in 1998 to 123.39 g in 2008, and to 198.01 g in 2018. The annual proportion of the total elderly population who meet the amount of vegetable food intake recommended by the World Health Organization (WHO)/World Cancer Research Fund (WCRF) (400 g or more fruits and non-starchy vegetables) increased by approximately 11.28%p (percentage points) over the past 20 years, from 21.78% in 1998 to 24.63% in 2008, and to 33.06% in 2018. The results of this study suggest that more fundamental measures are required to increase the fruit and non-starchy vegetable intake among the elderly. Furthermore, it is thought that the results of this study can be used as basic data in establishing dietary policy. In addition, it is thought that it can be used in developing nutrition education and dietary guidelines for enhancing fruit and vegetable intake.