Dimension-Confined Growth of a Crack-Free PbS Microplate Array for Infrared Image Sensing.

Epitaxy of semiconductors is a necessary step toward the development of electronic devices such as lasers, detectors, transistors, and solar cells. However, the lattice ordering of semiconductor functional films is inevitably disrupted by excessive concentrated stress due to the mismatch of the thermal expansion coefficient. Herein, combined with the first-principles calculation, we find that a rigid film/substrate bilayer heterostructure with a large thermal expansion mismatch upon cooling to room temperature from growth is free of surface cracks when the rigid film exhibits a dimension smaller than the critical condition for the breaking energy. The principle has been verified in a PbS/SrTiO3 bilayer system that is crack free on PbS single-crystalline microplate arrays through the designing of a dimension-confined growth (DCG) method. Interestingly, this crack-free, large-scale PbS microplate array exhibits exceptional uniformity in morphology, dimensions, thickness, and photodetection properties, enabling a broad-band infrared image sensing. This work provides a new perspective to design materials and arrays that demand smooth and continuous surfaces, which are not limited only to semiconductor electronics but also include mechanical structures, optical materials, biomedical materials, and others.

High-performance and frost-resistance MXene co-ionic liquid conductive hydrogel printed by electrohydrodynamic for flexible strain sensor.

Conductive hydrogels with high performance and frost resistance are essential for flexible electronics, electronic skin, and soft robots. Nonetheless, the preparation of hydrogel-based flexible strain sensors with rapid response, wide strain detection range, and high sensitivity remains a considerable challenge. Furthermore, the inevitable freezing and evaporation of water in sub-zero temperatures and dry environments lead to the loss of flexibility and conductivity in hydrogels, which seriously limits their practical application. In this work, ionic liquids (ILs) and MXene are introduced into gelatin/polyacrylamide (PAM) precursor solution, and a PAM/gelatin/ILs/MXene/glycerol (PGIMG) hydrogel-based flexible strain sensor with MXene co-ILs ion-electron composite conductive network is prepared by combining the electrohydrodynamic (EHD) printing method and in-situ photopolymerization. The introduction of ILs provides an ionic conductive channel for the hydrogel. The introduction of MXene nanosheets forms an interpenetrating network with gelatin and PAM, which not only provides a conductive channel, but also improves the mechanical and sensing properties of the hydrogel-based flexible strain sensor. The prepared PGIMG hydrogel with the MXene co-ILs ion-electron composite conductive network demonstrates a tensile strength of 0.21 MPa at 602.82 % strain, the conductivity of 1.636 × 10-3 S/cm, high sensitivity (Gauge Factor, GF = 4.17), a wide strain detection range (1-600 %), and the response/recovery times (73 ms and 74 ms). In addition, glycerol endows the hydrogel with excellent freezing (-60 °C) and water retention properties. The application of the hydrogel-based flexible strain sensor in the field of human motion detection and information transmission shows the great potential of wearable devices, electronic skin, and information encryption transmission.

Skin pharmacokinetics of miltefosine in the treatment of post-kala-azar dermal leishmaniasis in South Asia.

INTRODUCTION: Post-kala-azar dermal leishmaniasis (PKDL) arises as a dermal complication following a visceral leishmaniasis (VL) infection. Current treatment options for PKDL are unsatisfactory, and there is a knowledge gap regarding the distribution of antileishmanial compounds within human skin. The present study investigated the skin distribution of miltefosine in PKDL patients, with the aim to improve the understanding of the pharmacokinetics at the skin target site in PKDL. METHODS: Fifty-two PKDL patients underwent treatment with liposomal amphotericin B (20 mg/kg) plus miltefosine (allometric dosing) for 21 days. Plasma concentrations of miltefosine were measured on study days 8, 15, 22 and 30, while a punch skin biopsy was taken on day 22. A physiologically based pharmacokinetic (PBPK) model was developed to evaluate the distribution of miltefosine into the skin. RESULTS: Following the allometric weight-based dosing regimen, median miltefosine concentrations on day 22 were 43.73 µg/g (IQR: 21.94-60.65 µg/g) in skin and 33.29 µg/mL (IQR: 25.9-42.58 µg/mL) in plasma. The median individual concentration ratio of skin to plasma was 1.19 (IQR: 0.79-1.9). In 87% (45/52) of patients, skin exposure was above the suggested EC90 PK target of 10.6 mg/L associated with in vitro susceptibility. Simulations indicated that the residence time of miltefosine in the skin would be more than 2-fold longer than in plasma, estimated by a mean residence time of 604 versus 266 hours, respectively. CONCLUSION: This study provides the first accurate measurements of miltefosine penetration into the skin, demonstrating substantial exposure and prolonged retention of miltefosine within the skin. These findings support the use of miltefosine in cutaneous manifestations of leishmaniasis. In combination with parasitological and clinical data, these results are critical for the future optimization of combination therapies with miltefosine in the treatment of PKDL.

Rapid expansion and international spread of M1UK in the post-pandemic UK upsurge of Streptococcus pyogenes.

The UK observed a marked increase in scarlet fever and invasive group A streptococcal infection in 2022 with severe outcomes in children and similar trends worldwide. Here we report lineage M1UK to be the dominant source of invasive infections in this upsurge. Compared with ancestral M1global strains, invasive M1UK strains exhibit reduced genomic diversity and fewer mutations in two-component regulator genes covRS. The emergence of M1UK is dated to 2008. Following a bottleneck coinciding with the COVID-19 pandemic, three emergent M1UK clades underwent rapid nationwide expansion, despite lack of detection in previous years. All M1UK isolates thus-far sequenced globally have a phylogenetic origin in the UK, with dispersal of the new clades in Europe. While waning immunity may promote streptococcal epidemics, the genetic features of M1UK point to a fitness advantage in pathogenicity, and a striking ability to persist through population bottlenecks.

Oral anticoagulants and cognitive impairment in patients with atrial fibrillation: A systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: This systematic review assesses the likelihood of developing dementia and cognitive impairment in patients with atrial fibrillation (AF) receiving non-vitamin K antagonist oral anticoagulants (NOACs) as opposed to vitamin K antagonists (VKAs). METHODS: We performed a systematic review with meta-analysis and trial sequential analysis (TSA), which encompassed both randomized controlled trials (RCTs) and observational studies. The objective was to assess the impact of NOACs and VKAs on the incidence of dementia in individuals diagnosed with AF. RESULTS: Out of 1914 studies that were screened, 31 studies were included in the final analysis, which consisted of nine RCTs or their subsequent post-hoc analyses, in addition to 22 observational studies. The meta-analysis shows that NOACs were associated with a decreased probability of developing dementia of any cause [Rate Ratio (RR): 0.88; 95 % confidence interval (95 % CI): 0.82-0.94], especially in patients below the age of 75 (RR: 0.78; 95 % CI: 0.73-0.84). Consistent patterns were observed across all forms of dementia and cognitive function decline. The overall evidence indicates notable variability in the outcome with a moderate-to-low degree of certainty. The TSA suggests that the total sample size of the included trials (155,647 patients) was significantly smaller than the required information size of 784,692 patients to discern the true effect of NOAC versus VKA in terms of reducing dementia risk. CONCLUSION: NOACs may reduce the likelihood of developing dementia in patients with AF, particularly in those under the age of 75. This review highlights the urgent necessity for thorough research to determine the efficacy of NOACs in safeguarding cognitive health.

3D porous conductive matrix based on phase-transited BSA and covalent coupling-stabilized transition ZnS-CNT for antifouling and on-site detection of nitrite in soil.

Nitrite plays a critical role in a variety of nitrification and denitrification processes in the nitrogen cycle. Due to the high surface energy, tendency to aggregate, and poor conductivity, current nitrite ZnS-based sensing platform could not meet the need of on-site nitrite detection in smart agriculture. In order to address these issues, the carboxylated carbon nanotube (CNT) was introduced to reduce the surface energy and prevented aggregation of ZnS, while ZnS-carboxylated CNT (ZnS-CNT) composite also provided excellent electrochemical conductivity. Furthermore, the introduction of phase transition BSA (PTB) created a three-dimensional porous conductive matrix without interfering with the mass transfer process of nitrite. The resulting sensing platform exhibited a linear detection range of 10 nM to 0.4 mM for nitrite, with a detection limit of 0.73 nM. And this sensing platform had the excellent antifouling ability to direct detection nitrite in real soil suspension. In addition, the sensing platform demonstrated remarkable resistance to interferences from pH variations, microbial presence, and organic pollutants that usually present in soil environment. Therefore, on-site detection of nitrite ions in soil environment was realized no needing complex pretreatments.

The Ending Effect in the Domain of Gambling: The Effect of Gain-Loss Status on Economic Decision-Making.

Previous studies have shown that people prefer risk-taking at the end of gambles, a phenomenon called the ending effect. By using the Guess Gambling Game, we investigated the impact of gain-loss status on the ending effect (Experiment 1) and whether and how this effect may be affected by time reference (Experiment 2) and gender (Experiment 1&2). In Experiment 1, we observed the ending effect only in the gain group. Furthermore, gender differences exist in the loss group behavior, females were more risk-averse than males, and males tend to investment more initially and then reduce their investment in a U-shaped pattern (Experiment 1&2). Next, in Experiment 2, the findings indicated that participants in the gain group made riskier decisions and were willing to allocate more money for additional decision opportunities, irrespective of the time conditions. Additionally, under time-limited condition, participants tended to make more decisions in the final round, aiming to maximize their choices times within the limited time. These results contribute to a better understanding of the boundary conditions surrounding the ending effect in risky decision-making and may offer a scientific basis for mitigating and intervening in irrational decision-making.

Pressure injury risk factors in patients undergoing general anesthesia surgeries.

BACKGROUND: Pressure injuries result from prolonged pressure and lead to tissue damage, infections, extended recovery times, and an economic burden. PURPOSE: To explore risk factors for pressure injuries in patients who underwent surgery under general anesthesia. METHODS: This retrospective study included patients who underwent surgery at a regional educational hospital in southern Taiwan from January 1, 2018, through December 31, 2018. RESULTS: A comprehensive multivariate analysis was used to identify the prominent risk factors for pressure injury among the 11 231 patients enrolled in this study. These risk factors were an age of ≥65 years; surgery duration of >120 minutes; diastolic blood pressure of <60 mm Hg for >30 minutes during surgery; intraoperative use of dopamine, norepinephrine, or epinephrine as vasopressors; American Society of Anesthesiologists physical classification of III or higher; minimum intraoperative body temperature of ≤35°C; blood loss of >500 mL; and a supine or prone surgical position. CONCLUSIONS: This study identified several pressure injury risk factors related to surgical conditions and patient characteristics. Surgical teams must monitor, control, and manage these factors, prioritize staff education, and adopt preventive protocols.

Restraining the shuttle effect of polyiodides and modulating the deposition of zinc ions to enhance the cycle lifespan of aqueous Zn-I2 batteries.

The boom of aqueous Zn-based energy storage devices, such as zinc-iodine (Zn-I2) batteries, is quite suitable for safe and sustainable energy storage technologies. However, in rechargeable aqueous Zn-I2 batteries, the shuttle phenomenon of polyiodide ions usually leads to irreversible capacity loss resulting from both the iodine cathode and the zinc anode, and thus impinges on the cycle lifespan of the battery. Herein, a nontoxic, biocompatible, and economical polymer of polyvinyl alcohol (PVA) is exploited as an electrolyte additive. Based on comprehensive analysis and computational results, it is evident that the PVA additive, owing to its specific interaction with polyiodide ions and lower binding energy, can effectively suppress the migration of polyiodide ions towards the zinc anode surface, thereby mitigating adverse reactions between polyiodide ions and zinc. Simultaneously, the hydrogen bond network of water molecules is disrupted due to the abundant hydroxyl groups within the PVA additive, leading to a decrease in water activity and mitigating zinc corrosion. Further, because of the preferential adsorption of PVA on the zinc anode surface, the deposition environment for zinc ions is adjusted and its nucleation overpotential increases, which is favorable for the dense and uniform deposition of zinc ions, thus ensuring the improvement of the performance of the Zn-I2 battery. This investigation has inspired the development of a user-friendly and high-performance Zn-I2 battery.

Idiopathic mesenteric phlebosclerosis missed by a radiologist at initial diagnosis: A case report.

BACKGROUND: Idiopathic mesenteric phlebosclerosis (IMP) is a rare type of ischemic colitis characterized by thickening of the wall of the right hemicolon and calcification, sclerosis, and fibrosis of mesenteric veins. The diagnosis of IMP is based on typical clinical features and imaging findings. We report a case of IMP that was initially missed by the radiologist. CASE SUMMARY: A 77-year-old woman was admitted to the hospital due to chronic diarrhea for over 2 months. She had been consuming Chinese patent medicines (CPM) containing fructus gardeniae for more than 15 years. Colonoscopy revealed an edematous mucosa, bluish-purple discoloration, erosions, and ulcerations throughout the colorectal area. Abdominal computed tomography (CT) showed diffuse mural thickening of the entire colorectum, with tortuous thread-like calcifications in the right hemicolon, left hemicolon, and rectum. Most of the calcifications were located in the mesenteric vein. The diagnosis of IMP was established based on medical history, colonoscopy, CT findings, and histopathological examination. The patient was treated conservatively with papaverine and rifaximin, and CPM was stopped. Her diarrhea symptoms improved, indicating the effectiveness of the treatment. Over the next several years, she took opium alkaloids for an extended period and did not require hospitalization for the aforementioned gastrointestinal disorder. CONCLUSION: IMP is a rare gastrointestinal disease affecting Asian populations, possibly related to long-term herbal medicine intake. Accurate imaging analysis is crucial for diagnosis, but insufficient understanding of the disease can lead to misdiagnosis or missed diagnosis. Treatment strategies should be personalized.

Effectiveness of fecal DNA syndecan-2 methylation testing for detection of colorectal cancer in a high-risk Chinese population.

BACKGROUND: Colorectal cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. Syndecan-2 methylation (mSDC2) testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. Cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. mSDC2 testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. AIM: To validate the effectiveness of fecal DNA mSDC2 testing in the detection of CRC among a high-risk Chinese population to provide evidence-based data for the development of diagnostic and/or screening guidelines for CRC in China. METHODS: A high-risk Chinese cohort consisting of 1130 individuals aged 40-79 years was selected for evaluation via fecal mSDC2 testing. Sensitivity and specificity for CRC, advanced adenoma (AA) and advanced colorectal neoplasia (ACN) were determined. High-risk factors for the incidence of colorectal lesions were determined and a logistic regression model was constructed to reflect the efficacy of the test. RESULTS: A total of 1035 high-risk individuals were included in this study according to established criteria. Among them, 16 suffered from CRC (1.55%), 65 from AA (6.28%) and 189 from non-AAs (18.26%); 150 patients were diagnosed with polyps (14.49%). Diagnoses were established based upon colonoscopic and pathological examinations. Sensitivities of the mSDC2 test for CRC and AA were 87.50% and 40.00%, respectively; specificities were 95.61% for other groups. Positive predictive values of the mSDC2 test for CRC, AA and ACN were 16.09%, 29.89% and 45.98%, respectively; the negative predictive value for CRC was 99.79%. After adjusting for other high-risk covariates, mSDC2 test positivity was found to be a significant risk factor for the occurrence of ACN (P < 0.001). CONCLUSION: Our findings confirmed that offering fecal mSDC2 testing and colonoscopy in combination for CRC screening is effective for earlier detection of malignant colorectal lesions in a high-risk Chinese population.

Poly(ionic liquid)s-Based Thermal-Responsive Microgel for Use as SERS Substrates with "ON-OFF" Switchable Effect.

A temperature-responsive surface-enhanced Raman scattering (SERS) substrate with "ON-OFF" switching based on poly(ionic liquid)s (PILs) block copolymer microgels have been designed and synthesized. The PIL units act as a joint component to anchor the gold nanoparticles (AuNPs) and analytes onto poly(N-isopropylacrylamide) (PNIPAm). This anchor allows the analytes to be fixed at the formed hot spots under temperature stimulus. Owing to the regulation of the PNIPAm segment, the SERS substrates exhibit excellent thermally responsive SERS activity with a reversible "ON-OFF" effect. Additionally, because of the anion exchange of PILs, microgels can introduce new analytes, which offers more flexibility for the system. The substrate shows excellent reversibility, controllability, and flexibility of SERS activity, which is expected to have a broad application in the field of practical SERS sensors.

Explainable geospatial-artificial intelligence models for the estimation of PM2.5 concentration variation during commuting rush hours in Taiwan.

PM2.5 concentrations are higher during rush hours at background stations compared to the average concentration across these stations. Few studies have investigated PM2.5 concentration and its spatial distribution during rush hours using machine learning models. This study employs a geospatial-artificial intelligence (Geo-AI) prediction model to estimate the spatial and temporal variations of PM2.5 concentrations during morning and dusk rush hours in Taiwan. Mean hourly PM2.5 measurements were collected from 2006 to 2020, and aggregated into morning (7 a.m.-9 a.m.) and dusk (4 p.m.-6 p.m.) rush-hour mean concentrations. The Geo-AI prediction model was generated by integrating kriging interpolation, land-use regression, machine learning, and a stacking ensemble approach. A forward stepwise variable selection method based on the SHapley Additive exPlanations (SHAP) index was used to identify the most influential variables. The performance of the Geo-AI models for morning and dusk rush hours had accuracy scores of 0.95 and 0.93, respectively and these results were validated, indicating robust model performance. Spatially, PM2.5 concentrations were higher in southwestern Taiwan for morning rush hours, and suburban areas for dusk rush hours. Key predictors included kriged PM2.5 values, SO2 concentrations, forest density, and the distance to incinerators for both morning and dusk rush hours. These PM2.5 estimates for morning and dusk rush hours can support the development of alternative commuting routes with lower concentrations.

Leishmania blood parasite dynamics during and after treatment of visceral leishmaniasis in Eastern Africa: A pharmacokinetic-pharmacodynamic model.

BACKGROUND: With the current treatment options for visceral leishmaniasis (VL), recrudescence of the parasite is seen in a proportion of patients. Understanding parasite dynamics is crucial to improving treatment efficacy and predicting patient relapse in cases of VL. This study aimed to characterize the kinetics of circulating Leishmania parasites in the blood, during and after different antileishmanial therapies, and to find predictors for clinical relapse of disease. METHODS: Data from three clinical trials, in which Eastern African VL patients received various antileishmanial regimens, were combined in this study. Leishmania kinetoplast DNA was quantified in whole blood with real-time quantitative PCR (qPCR) before, during, and up to six months after treatment. An integrated population pharmacokinetic-pharmacodynamic model was developed using non-linear mixed effects modelling. RESULTS: Parasite proliferation was best described by an exponential growth model, with an in vivo parasite doubling time of 7.8 days (RSE 12%). Parasite killing by fexinidazole, liposomal amphotericin B, sodium stibogluconate, and miltefosine was best described by linear models directly relating drug concentrations to the parasite elimination rate. After treatment, parasite growth was assumed to be suppressed by the host immune system, described by an Emax model driven by the time after treatment. No predictors for the high variability in onset and magnitude of the immune response could be identified. Model-based individual predictions of blood parasite load on Day 28 and Day 56 after start of treatment were predictive for clinical relapse of disease. CONCLUSION: This semi-mechanistic pharmacokinetic-pharmacodynamic model adequately captured the blood parasite dynamics during and after treatment, and revealed that high blood parasite loads on Day 28 and Day 56 after start of treatment are an early indication for VL relapse, which could be a useful biomarker to assess treatment efficacy of a treatment regimen in a clinical trial setting.

Understanding the Underlying Mechanism of an Abnormal P Wave.

This case report describes a patient in their 70s presenting to the hospital with dyspnea and fatigue.

SLC27A2 is a potential immune biomarker for hematological tumors and significantly regulates the cell cycle progression of diffuse large B-cell lymphoma.

BACKGROUND: Research on the fatty acid metabolism related gene SLC27A2 is currently mainly focused on solid tumors, and its mechanism of action in hematological tumors has not been reported. METHOD: This study aims to explore the pathological and immune mechanisms of the fatty acid metabolism related gene SLC27A2 in hematological tumors and verify its functional role in hematological tumors through cell experiments to improve treatment decisions and clinical outcomes of hematological tumors. RESULT: This study identified the fatty acid metabolism related gene SLC27A2 as a common differentially expressed gene between DLBCL and AML. Immune microenvironment analysis showed that SLC27A2 was significantly positively correlated with T cell CD4 + , T cell CD8 + , endothelial cells, macrophages, and NK cells in DLBCL. In AML, there is a significant negative correlation between SLC27A2 and B cells, T cell CD8 + , and macrophages. SLC27A2 participates in the immune process of hematological tumors through T cell CD8 + and macrophages. The GESA results indicate that high expression of SLC27A2 is mainly involved in the fatty acid pathway, immune pathway, and cell cycle pathway of DLBCL. The low expression of SLC27A2 is mainly involved in the immune pathway of AML. Therefore, SLC27A2 is mainly involved in the pathological mechanisms of hematological tumors through immune pathways, and cell experiments have also confirmed that SLC27A2 is involved in the regulation of DLBCL cells. CONCLUSION: In summary, our research results comprehensively report for the first time the mechanism of action of SLC27A2 in the immune microenvironment of DLBCL and AML, and for the first time verify the cycle and apoptotic effects of the fatty acid related gene SLC27A2 in DLBCL cells through cell experiments. Research can help improve the treatment of AML and DLBCL patients.

The Enhanced Performance of Oxide Thin-Film Transistors Fabricated by a Two-Step Deposition Pressure Process.

It is usually difficult to realize high mobility together with a low threshold voltage and good stability for amorphous oxide thin-film transistors (TFTs). In addition, a low fabrication temperature is preferred in terms of enhancing compatibility with the back end of line of the device. In this study, α-IGZO TFTs were prepared by high-power impulse magnetron sputtering (HiPIMS) at room temperature. The channel was prepared under a two-step deposition pressure process to modulate its electrical properties. X-ray photoelectron spectra revealed that the front-channel has a lower Ga content and a higher oxygen vacancy concentration than the back-channel. This process has the advantage of balancing high mobility and a low threshold voltage of the TFT when compared with a conventional homogeneous channel. It also has a simpler fabrication process than that of a dual active layer comprising heterogeneous materials. The HiPIMS process has the advantage of being a low temperature process for oxide TFTs.

Frailty and psychiatric disorders: A bidirectional Mendelian randomization study.

BACKGROUND: The association between frailty and psychiatric disorders has been reported in observational studies. However, it is unclear whether frailty facilitates the appearance of psychiatric disorders or vice versa. Therefore, we conducted a bidirectional Mendelian randomization (MR) study to evaluate the causality. METHODS: Independent genetic variants associated with frailty index (FI) and psychiatric disorders were obtained from large genome-wide association studies (GWAS). The inverse variance weighted method was utilized as the primary method to estimate causal effects, followed by various sensitivity analyses. Multivariable analyses were performed to further adjust for potential confounders. RESULTS: The present MR study revealed that genetically predicted FI was significantly and positively associated with the risk of major depressive disorder (MDD) (odds ratio [OR] 1.79, 95 % confidence interval [CI] 1.48-2.15, P = 1.06 × 10-9), anxiety disorder (OR 1.61, 95 % CI 1.19-2.18, P = 0.002) and neuroticism (OR 1.38, 95 % CI 1.18-1.61, P = 3.73 × 10-5). In the reverse MR test, genetic liability to MDD (beta 0.232, 95 % CI 0.189-0.274, P = 1.00 × 10-26) and neuroticism (beta 0.128, 95 % CI 0.081-0.175, P = 8.61 × 10-8) were significantly associated with higher FI. Multivariable analyses results supported the causal association between FI and MDD and neuroticism. LIMITATIONS: Restriction to European populations, and sample selection bias. CONCLUSIONS: Our study suggested a bidirectional causal association between frailty and MDD neuroticism, and a positive correlation of genetically predicted frailty on the risk of anxiety disorder. Developing a deeper understanding of these associations is essential to effectively manage frailty and optimize mental health in older adults.

Gene-Environment Interactions and Gene-Gene Interactions on Two Biological Age Measures: Evidence from Taiwan Biobank Participants.

PhenoAge and BioAge are two commonly used biological age (BA) measures. The author here searched for gene-environment interactions (GxE) and gene-gene interactions (GxG) on PhenoAgeAccel (age-adjusted PhenoAge) and BioAgeAccel (age-adjusted BioAge) of 111,996 Taiwan Biobank (TWB) participants, including a discovery set of 86,536 TWB2 individuals and a replication set of 25,460 TWB1 individuals. Searching for variance quantitative trait loci (vQTLs) provides a convenient way to evaluate GxE and GxG. A total of 4 nearly independent (linkage disequilibrium measure r2 < 0.01) PhenoAgeAccel-vQTLs are identified from 5,303,039 autosomal TWB2 SNPs (p < 5E-8), whereas no vQTLs are found from BioAgeAccel. These 4 PhenoAgeAccel-vQTLs (rs35276921, rs141927875, rs10903013, and rs76038336) are further replicated by TWB1 (p < 5E-8). They are located in the OR51B5, FAM234A, and AXIN1 genes. All 4 PhenoAgeAccel-vQTLs are significantly associated with PhenoAgeAccel (p < 5E-8). A phylogenetic heat map of the GxE analyses showed that smoking exacerbated the PhenoAgeAccel-vQTLs' aging effects, while higher educational attainment attenuated the PhenoAgeAccel-vQTLs' aging effects. Body mass index, chronological age, alcohol consumption, and sex do not prominently modulate PhenoAgeAccel-vQTLs' aging effects. Based on these vQTL results, rs141927875-rs35276921 interaction (p = 4.7E-61) and rs76038336-rs10903013 interaction (p = 3.3E-116) on PhenoAgeAccel are detected.

[Research Progress in the Correlation Between Dopamine and Clinical Characterization of Narcolepsy].

Dopamine,a neurotransmitter ubiquitous in the body fluids,blood,and urine of mammals and humans,is responsible for regulating their functions and metabolism.The dopamine system is involved in the neurobiological mechanisms of narcolepsy in animals and humans.However,researchers have drawn different or even opposite conclusions when measuring the dopamine level in the cerebrospinal fluid of narcolepsy patients.Studies have confirmed that the occurrence of narcolepsy is related to the irreversible loss of orexins.The autoimmune reaction caused by the interactions of environmental factors with genetic factors destroys the hypothalamic orexin neurons and reduces orexin secretion,thereby lowering the level of arousal.We introduce the research progress and current status of dopamine and clinical characterization of narcolepsy by reviewing more than 40 articles published from 1982 to 2023,aiming to provide a reference for studying the relationship between the dopamine level and clinical characterization of narcolepsy and searching for the biomarkers of type 2 narcolepsy.