Turn-off enzyme activity of histidine-rich peptides for the detection of lysozyme.

An assay that integrates histidine-rich peptides (HisRPs) with high-affinity aptamers was developed enabling the specific and sensitive determination of the target lysozyme. The enzyme-like activity of HisRP is inhibited by its interaction with a target recognized by an aptamer. In the presence of the target, lysozyme molecules progressively assemble on the surface of HisRP in a concentration-dependent manner, resulting in the gradual suppression of enzyme-like activity. This inhibition of HisRP's enzyme-like activity can be visually observed through color changes in the reaction product or quantified using UV-visible absorption spectroscopy. Under optimal conditions, the proposed colorimetric assay for lysozyme had a detection limit as low as 1 nM and exhibited excellent selectivity against other nonspecific interferents. Furthermore, subsequent research validated the practical applicability of the developed colorimetric approach to saliva samples, indicating that the assay holds significant potential for the detection of lysozymes in samples derived from humans.

CDKN2A/B homozygous deletion sensitizes IDH-mutant glioma to CDK4/6 inhibition.

PURPOSE: Treatment paradigms for Isocitrate dehydrogenase (IDH) mutant gliomas are rapidly evolving. While typically indolent and responsive to initial treatment, these tumors invariably recur at higher grade and require salvage treatment. Homozygous deletion of the tumor suppressor gene CDKN2A/B frequently emerges at recurrence in these tumors, driving poor patient outcome. We investigated the effect of CDK-Rb pathway blockade on IDH-mutant glioma growth in vitro and in vivo using CDK4/6 inhibitors (CDKi). EXPERIMENTAL DESIGN: Cell viability, proliferation assays and flow cytometry were used to examine the pharmacologic effect of two distinct CDKis, palbociclib and abemaciclib, in multiple patient-derived IDH-mutant glioma lines. Isogenic models were used to directly investigate the influence of CDKN2A/B status on CDKi sensitivity. Orthotopic xenograft tumor models were used to examine efficacy and tolerability of CDKi in vivo. RESULTS: CDKi treatment leads to decreased cell viability and proliferative capacity in patient-derived IDH-mutant glioma lines, coupled with enrichment of cells in G1 phase. CDKN2A inactivation sensitizes IDH-mutant glioma to CDKi in both endogenous and isogenic models with engineered CDKN2A deletion. CDK4/6 inhibitor administration improves survival in orthotopically implanted IDH-mutant glioma models. CONCLUSIONS: IDH-mutant gliomas with deletion of CDKN2A/B are sensitized to CDK4/6 inhibitors. These results support investigation of the use of these agents in a clinical setting.

Oral post-exercise garlic extract supplementation enhances glycogen replenishment but does not up-regulate mitochondria biogenesis mRNA expression in human-exercised skeletal muscle.

PURPOSE: Garlic extract (GA) is purported to enhance antioxidant and anti-inflammatory activity and glucose regulation in humans. The present study investigated the effects of post-exercise GA supplementation on GLUT4 expression, glycogen replenishment, and the transcript factors involved with mitochondrial biosynthesis in exercised human skeletal muscle. METHODS: The single-blinded crossover counterbalanced study was completed by 12 participants. Participants were randomly divided into either GA (2000 mg of GA) or placebo trials immediately after completing a single bout of cycling exercise at 75% Maximal oxygen uptake (VO2max) for 60 minutes. Participants consumed either GA (2000 mg) or placebo capsules with a high glycemic index carbohydrate meal (2 g carb/body weight) immediately after exercise. Muscle samples were collected at 0-h and 3-h post-exercise. Muscle samples were used to measure glycogen levels, GLUT4 protein expression, as well as transcription factors for glucose uptake, and mitochondria biogenesis. Plasma glucose, insulin, glycerol, non-esterified fatty acid (NEFA) concentrations, and respiratory exchange ratio (RER) were also analyzed during the post-exercise recovery periods. RESULTS: Skeletal muscle glycogen replenishment was significantly elevated during the 3-h recovery period for GA concurrent with no difference in GLUT4 protein expression between the garlic and placebo trials. PGC1-α gene expression was up-regulated for both GA and placebo after exercise (p < 0.05). Transcript factors corresponding to muscle mitochondrial biosynthesis were significantly enhanced under acute garlic supplementation as demonstrated by TFAM and FIS1. However, the gene expression of SIRT1, ERRα, NFR1, NFR2, MFN1, MFN2, OPA1, Beclin-1, DRP1 were not enhanced, nor were there any improvements in GLUT4 expression, following post-exercise garlic supplementation. CONCLUSION: Acute post-exercise garlic supplementation may improve the replenishment of muscle glycogen, but this appears to be unrelated to the gene expression for glucose uptake and mitochondrial biosynthesis in exercised human skeletal muscle.

A lower connection to nature is related to lower mental health benefits from nature contact.

Increasing evidence demonstrates the psychological benefits of nature contact. However, the evidence is often established at the population level, and the individual differences in the psychological benefits gained from nature are considered negligible variations. In this study, we performed a cross-sectional online survey in Brisbane and Sydney, Australia, from April 15th and May 15th, 2021 around one year after the first covid-19 pandemic lockdowns. The results show that individuals with a stronger connection to nature are linked with a lower level of stress and anxiety with increased frequency in public greenspace visits, while such an association is less clear for individuals with a weaker connection to nature. We also find that, through the answer to an open-ended question, individuals with a lower connection to nature tend to mention nature-related words less as the reason for visiting greenspace. This indicates that a person's connection to nature is linked with how they interact with nature and thus might determine whether and how much psychological benefit a person gains from experiencing nature.

Blocking pathogenic Leptospira invasion with aptamer molecules targeting outer membrane LipL32 protein.

This study aimed to develop aptamers targeting LipL32, a most abundant lipoprotein in pathogenic Leptospira, to hinder bacterial invasion. The objectives were to identify high-affinity aptamers through SELEX and evaluate their specificity and inhibitory effects. SELEX was employed to generate LipL32 aptamers (L32APs) over 15 rounds of selection. L32APs' binding affinity and specificity for pathogenic Leptospira were assessed. Their ability to inhibit LipL32-ECM interaction and Leptospira invasion was investigated. Animal studies were conducted to evaluate the impact of L32AP treatment on survival rates, Leptospira colonization, and kidney damage. Three L32APs with strong binding affinity were identified. They selectively detected pathogenic Leptospira, sparing non-pathogenic strains. L32APs inhibited LipL32-ECM interaction and Leptospira invasion. In animal studies, L32AP administration significantly improved survival rates, reduced Leptospira colonies, and mitigated kidney damage compared to infection alone. This pioneering research developed functional aptamers targeting pathogenic Leptospira. The identified L32APs exhibited high affinity, pathogen selectivity, and inhibition of invasion and ECM interaction. L32AP treatment showed promising results, enhancing survival rates and reducing Leptospira colonization and kidney damage. These findings demonstrate the potential of aptamers to impede pathogenic Leptospira invasion and aid in recovery from Leptospira-induced kidney injury (190 words).

What is the meta-analytic evidence for life-history trade-offs at the genetic level?

Understanding the evolutionary mechanisms underlying the maintenance of individual differences in behavior and physiology is a fundamental goal in ecology and evolution. The pace-of-life syndrome hypothesis is often invoked to explain the maintenance of such within-population variation. This hypothesis predicts that behavioral traits are part of a suite of correlated traits that collectively determine an individual's propensity to prioritize reproduction or survival. A key assumption of this hypothesis is that these traits are underpinned by genetic trade-offs among life-history traits: genetic variants that increase fertility, reproduction and growth might also reduce lifespan. We performed a systematic literature review and meta-analysis to summarize the evidence for the existence of genetic trade-offs between five key life-history traits: survival, growth rate, body size, maturation rate, and fertility. Counter to our predictions, we found an overall positive genetic correlation between survival and other life-history traits and no evidence for any genetic correlations between the non-survival life-history traits. This finding was generally consistent across pairs of life-history traits, sexes, life stages, lab vs. field studies, and narrow- vs. broad-sense correlation estimates. Our study highlights that genetic trade-offs may not be as common, or at least not as easily quantifiable, in animals as often assumed.

Garlic supplementation attenuates cycling exercise-induced oxidative inflammation but fails to improve time trial performance in healthy adults.

BACKGROUND: Garlic extract has been shown to enhance antioxidant and anti-inflammation activities in humans. The present study investigated the effects of garlic supplementation on 40-km cycling time trial performance, exercise-induced oxidative stress, and inflammatory responses in healthy adults. METHODS: Eleven healthy males were recruited to perform this single-blind crossover study. Participants were randomly assigned to either garlic (garlic extracts 1000 mg/d for 4 weeks) or placebo trials. Following 4-wks of supplementation, participants performed a 40-km cycling challenge. Total cycling performance time and respiratory exchange ratio (RER) were recorded. Blood samples were collected every 10 km to determine exercise-induced oxidative stress, inflammation, and muscle damage. RESULTS: The 40-km cycling time trial performance was not improved following 4 weeks of garlic supplementation. However, 4-wk garlic supplementation significantly increased whole-body antioxidant capacity (total antioxidant capacity, TAC), and subsequently attenuated MDA, TNF-α, and LDH during the 40-km cycling exercise period (p < 0.05). There were no significant differences among the blood biomarkers glucose, NEFA, IL-6, UA, and CK respectively. The respiratory exchange ratio was similar between garlic and placebo trials. CONCLUSION: Four-week oral garlic supplementation attenuates exercise-induced oxidative inflammation and muscle damage during a 40-km bout of cycling. However, it appeared that 4-wk oral garlic had no ergogenic effect on cycling performance in healthy males.

Nature experience from yards provide an important space for mental health during Covid-19.

Urban dwellers' use of public and private green spaces may have changed during the early years of the Covid-19 pandemic due to movement restriction. A survey was deployed in Brisbane and Sydney, Australia 1 year after the start of Covid-19 restrictions (April 2021) to explore relationships of mental health and wellbeing to different patterns of private yard versus public green space visitation. More frequent yard use during the initial year of Covid-19 was correlated with lower stress, depression, and anxiety and higher wellbeing. However, greater duration of yard visits (week prior to survey) was associated with higher stress, anxiety, and depression scores, potentially because individuals may seek to use nature spaces immediately available for emotional regulation during difficult times. The results highlight the importance of yards for mental health and wellbeing during the Covid-19 pandemic and that relationships between nature interaction and mental health may be context and timeframe dependent.

Visiting Urban Green Space and Orientation to Nature Is Associated with Better Wellbeing during COVID-19.

The COVID-19 pandemic has severely challenged mental health and wellbeing. However, research has consistently reinforced the value of spending time in green space for better health and wellbeing outcomes. Factors such as an individual's nature orientation, used to describe one's affinity to nature, may influence an individual's green space visitation behaviour, and thus influence the wellbeing benefits gained. An online survey in Brisbane and Sydney, Australia (n = 2084), deployed during the COVID-19 pandemic (April 2021), explores if nature experiences and nature orientation are positively associated with personal wellbeing and if increased amounts of nature experiences are associated with improvement in wellbeing in the first year of the COVID-19 pandemic. We found that both yard and public green space visitation, as well as nature orientation scores, were correlated with high personal wellbeing scores, and individuals who spent more time in green space compared to the previous year also experienced a positive change in their health and wellbeing. Consistently, people with stronger nature orientations are also more likely to experience positive change. We also found that age was positively correlated to a perceived improvement in wellbeing over the year, and income was negatively correlated with a decreased change in wellbeing over the year, supporting other COVID-19 research that has shown that the effects of COVID-19 lifestyle changes were structurally unequal, with financially more established individuals experiencing better wellbeing. Such results highlight that spending time in nature and having high nature orientation are important for gaining those important health and wellbeing benefits and may provide a buffer for wellbeing during stressful periods of life that go beyond sociodemographic factors.

A knowledge elicitation approach to traffic accident analysis in open data: comparing periods before and after the Covid-19 outbreak.

Extracting knowledge from open data of traffic accidents has been attracting increasing attention to policymakers responsible for road safety. This article presents a knowledge elicitation approach to exploring the determinants of traffic accidents from open government data of an urban area in Taiwan. The collected open dataset contains 34 decisional attributes and one predictive attribute (i.e., type of injury, including head, breast, leg), and 47,974 cases. Prediction models using a classification-oriented mechanism and generated rules that considered datasets from before (B-dataset; 30,116 cases) and after (A-dataset; 17,868 cases) beginning to combat the Covid-19 pandemic in an urban area of Taiwan were compared. The findings showed that prediction accuracy was acceptable but not high, at 70.73% for B-dataset and 74.77% for A-dataset. Determinants in the human and vehicle categories revealed higher classification ranks than those in the temporal and environment categories. Traffic accidents involving motorcycles were 5.13% higher in A-dataset, whereas those involving cars were 4.11% lower. Injury on leg or foot was 3.46% higher in A-dataset, whereas other types of injury were up to 1.00% lower. The average support for rules in the A-dataset rule base and the simplicity of the A-dataset decision tree were higher than those of B-dataset. The research demonstrates the value of open government data in prediction model development and knowledge elicitation to support policymaking in the traffic safety domain.

Metabolic Isolation, Stereochemical Determination, and Total Synthesis of Predominant Native Cholesteryl Phosphatidyl-α-glucoside from Carcinogenic Helicobacter pylori.

We report the isolation and stereochemical determination of the predominant native cholesteryl 6-O-phosphatidyl α-glucoside (CPG) from Helicobacter pylori via an integrated biological and chemical strategy. The strategy employed (i) the metabolic isolation of a CPG analogue and (ii) the enzymatic degradation of the analogue to obtain the native lactobacillic acid for the stereochemical determination. The absolute stereochemistry of the acid was found to be 11R and 12S. Using the new stereochemical data, we accomplished the total synthesis of predominant native CPG and other predominant αCG derivatives.

Are Electrocochleographic Changes an Early Sign of Cochlear Synaptopathy? A Prospective Study in Tinnitus Patients with Normal Hearing.

The mechanism of tinnitus accompanied by a normal audiogram remains elusive. This study aimed to investigate evidence of primary neural degeneration, also known as cochlear synaptopathy, in tinnitus patients with normal hearing thresholds. We analyzed the differences in electrocochleography (ECochG) measurements between normal-hearing subjects with and without tinnitus. Forty-five subjects were enrolled in this study: 21 were in the tinnitus group, defined by chronic tinnitus of over two months' duration with normal audiometric thresholds, and 24 were in the control group, defined by a lack of tinnitus complaints. Electrocochleograms were evoked by 1, 4, 6, and 8 kHz alternating-polarity tone bursts at sound pressure levels (SPLs) of 90−110 dB. The tinnitus group had smaller action potential (AP) amplitudes than the control group for 1, 4, 6, and 8 kHz tone bursts and showed significant amplitude reduction at 1 kHz 110 dB SPL (p < 0.01), 1 kHz 90 dB SPL (p < 0.05), and 4 kHz 110 dB SPL (p < 0.05). There were no significant differences in the summating potential/action potential (SP/AP) amplitude ratios across the four tested frequencies. A trend of reduced AP amplitudes was found in the tinnitus group, supporting the hypothesis that tinnitus might be associated with primary neural degeneration.

Comparing the Fracture Resistance and Modes of Failure in Different Types of CAD/CAM Zirconia Abutments with Internal Hexagonal Implants: An In Vitro Study.

Three groups of zirconia abutments (n = 5) consisting of different connection designs or manufacturers were investigated (All-Zr, ASC-Zr, and AM-Zr groups). All-electric dynamic test instruments were used to place static loading on a specimen with a crosshead speed set at 1 mm/min. A Kruskal-Wallis test and a post hoc Mann-Whitney U test were used for statistical evaluation. The mean fracture resistance was 252.37 ± 82.79 N for the All-Zr group, 384.62 ± 45.24 N for ASC-Zr group, and 361.83 ± 90.31 N for the AM-Zr group. The difference of fracture resistance between the three groups was marginally significant (Kruskal-Wallis test, p = 0.054), with the ASC zirconia abutment tending to have higher fracture resistance than the full zirconia abutment. The modes of failure among the three types of abutments are different. The All-Zr group showed an oblique fracture line starting from the buccal aspect at the region of the implant platform. While the ASC-Zr and AM-Zr groups showed a relatively horizontal fracture line with a greater distance from the implant platform. The titanium inserts cannot significantly improve the fracture resistance of the zirconia abutment. However, they may alter the modes of failure, allowing buccal fracture surfaces of the zirconia abutments to be placed away from the implant platform, thereby protecting the implant-abutment connection.

Effectiveness of innovative instructional module for professional competence in health literacy in medical students.

BACKGROUND: Physicians should be equipped with professional competence in health literacy to communicate more effectively with patients with limited health literacy. However, the health literacy curriculum has not yet been refined globally, and is scarce in Taiwan's medical education. We implemented an innovative instructional module to attain professional competence in health literacy among medical students and investigated its effects. METHODS: We adopted a quasi-experimental design and recruited 204 fifth-year Taiwanese medical students between December 2019 and May 2020. Participants who worked as clerks at the Department of Family Medicine of three medical schools in northern Taiwan were assigned to the experimental group through convenience sampling. A total of 98 students received a three-hour innovative instruction, including medical simulation videos, role-playing, and board games. Both the experimental and control groups completed the online pre-test and mail-in post-test. A generalized estimating equation was applied to measure the effects of the intervention. RESULTS: There was a significant difference between the experimental and control groups in terms of professional competence in health literacy in all three aspects. In terms of knowledge, the experimental group improved 12% more than the control group (𝛽=0.12, 95% CI: 0.05 ~ 0.19, p = 0.001). In terms of attitude, the experimental group improved by an average of 0.27 more points per question than the control group (𝛽=0.27, 95% CI: 0.08 ~ 0.46, p = 0.007). As for skill, the experimental group improved by an average of 0.35 more points per question than the control group (𝛽=0.35, 95% CI: 0.14 ~ 0.55, p = 0.001). CONCLUSION: The proposed innovative instructional module significantly improved fifth-year medical students' professional competence in health literacy, which is expected to benefit their future medical practices.

Studying wearable health technology in the workplace using the Behavior Change Wheel: a systematic literature review and content analysis.

Wearable Health Technology (WHT) is considered to be fast, feasible, and effective in workplace health promotion programs. This study aims to analyze behavior change strategies applied to WHT products used by employees in health promotion programs. A systematic literature review of WHT in workplace health promotion between 2006 and 2020 was conducted. The Behavior Change Wheel (BCW) was used to undertake the content analysis. We identified 14 articles of WHT in the workplace. First, physical activity and weight management were the most common health issue. Second, using the BCW, we found guidelines, regulation and communication were the most frequently applied policy categories. Third, education, enablement and training were the most common intervention functions. For example, the promoter could provide health education information by WHT. Moreover, encouraging online would motivate employees to improve health behavior. There has been a growing interest in WHT with increasing complexity in research designs and specifications. While using WHT can be an appropriate strategy to adopt as employee health projects, other interventions should be considered, for incentivization and modeling, etc. The results of this study suggest using WHT should take related health behavior theories or variables into consideration to form a comprehensive health promotion programs.

Taiwanese Vegetarians Are Associated with Lower Dementia Risk: A Prospective Cohort Study.

The number of people living with dementia globally is increasing rapidly, and there is no effective therapy. Dietary pattern is one important risk factor for the development and progression of dementia. We undertake this study to determine whether Taiwanese vegetarian diet in midlife affects dementia incidence in later years in a prospective cohort. We followed 5710 participants (average age less than 60) in the Tzu Chi Vegetarian Study (TCVS). We started recruiting in 2005 and followed until the end of 2014 when the database changed from ICD-9-CM to ICD-10-CM codes. The incidence of dementia was obtained through linkage to the National Health Insurance Research Database. We used Cox proportional hazards regression to estimate the hazard ratio of dementia between vegetarians and nonvegetarians. There were 121 cases of dementia (37 vegetarians and 84 nonvegetarians) diagnosed. Vegetarians were associated with reduced risk of clinically overt dementia compared with nonvegetarians (hazard ratio = 0.671, confidence interval: 0.452−0.996, p < 0.05) after adjusting for gender, age, smoking, drinking, education level, marriage, regular exercise, and comorbidities with stepwise regression.

Rapid Detection of Virus Nucleic Acid via Isothermal Amplification on Plasmonic Enhanced Digitizing Biosensor.

Rapid detection for infectious diseases is highly demanded in diagnosis and infection prevention. In this work, we introduced a plasmonic enhanced digitizing biosensor for the rapid detection of nucleic acids. The sensor successfully achieved the detection of loop-mediated isothermal amplification for the hepatitis virus in this work. The sensor comprised a nanodisc array and Bst polymerases conjugated on the rough surface of a nanodisc. The rough surface of the nanodisc provided plasmonic hot spots to enhance the fluorescence signal. The virus DNA was detected by conducting a modified loop-mediated isothermal amplification with fluorescence resonance energy transfer reporter conjugated primers on the sensor. The modified isothermal amplification improved the signal contrast and detection time compared to the original assay. By integrating the modified amplification assay and plasmonic enhancement sensor, we achieved rapid detection of the hepatitis virus. Nucleic acid with a concentration of 10-3 to 10-4 mg/mL was detected within a few minutes by our design. Our digitizing plasmonic nanoarray biosensor also showed 20-30 min earlier detection compared to conventional loop-mediated isothermal amplification sensors.

People's desire to be in nature and how they experience it are partially heritable.

Nature experiences have been linked to mental and physical health. Despite the importance of understanding what determines individual variation in nature experience, the role of genes has been overlooked. Here, using a twin design (TwinsUK, number of individuals = 2,306), we investigate the genetic and environmental contributions to a person's nature orientation, opportunity (living in less urbanized areas), and different dimensions of nature experience (frequency and duration of public nature space visits and frequency and duration of garden visits). We estimate moderate heritability of nature orientation (46%) and nature experiences (48% for frequency of public nature space visits, 34% for frequency of garden visits, and 38% for duration of garden visits) and show their genetic components partially overlap. We also find that the environmental influences on nature experiences are moderated by the level of urbanization of the home district. Our study demonstrates genetic contributions to individuals' nature experiences, opening a new dimension for the study of human-nature interactions.

Distinct Survival Outcomes in Subgroups of Stage III Pancreatic Cancer Patients: Taiwan Cancer Registry and Surveillance, Epidemiology and End Results registry.

PURPOSE: Pancreatic cancer is one of the most malignant cancers with poor survival. The latest edition of the American Joint Committee on Cancer (AJCC) staging system classifies the majority of operable pancreatic cancer patients as stage-III, while dramatic heterogeneity is observed among these patients. Therefore, subgrouping is required to accurately predict their prognosis and define a treatment plan. This study conducts a cohort study to provide a more precise classification system for stage-III pancreatic cancer patients by utilizing clinical variables. METHODS: We analyzed survival using log-rank tests, univariate Cox-regression models, and Kaplan-Meier survival curves for stage-III pancreatic ductal adenocarcinoma (PDAC) patients from the Taiwan Cancer Registry (TCR). Patients were further divided into subgroups using classification and regression tree (CART) algorithm. All results were validated using the SEER database. RESULTS: Among stage-III PDAC patients, lymph node and tumor grade showed significant association with survival. Patients with N2 stage had higher mortality risks (hazard ratio [HR] = 2.30, 95% confidence interval [CI] 1.71-3.08, p < 0.0001) than N0 patients. Patients with grade 3 also had higher risk of mortality (HR = 3.80, 95% CI 2.25-6.39, p < 0.0001) than grade 1 patients. The CART algorithm stratified stage-III patients into four subgroups with significantly different survival rates. The median survival of the four subgroups was 23.5, 18.4, 14.5, and 9.0 months, respectively (p < 0.0001). Similar results were observed with SEER data. CONCLUSIONS: Lymph node involvement and tumor grade are predictive factors for survival in stage-III PDAC patients. This new precise classification system can be used to guide treatment planning in advanced-stage pancreatic cancer.