Hydrophilicity Dependent Distribution of Water at Ionic Liquids/Metal Interface Monitored by Electrochemical SERS.

The understanding of the interfacial processes is critically important for extending the practical application of ionic liquids, particularly for the role of interfacial water. In the electrochemical system based on ionic liquid electrolytes, small amounts of water at the interface generate a significant change in the electrochemical behaviors of ionic liquids. Therefore, the investigation on the interfacial behavior of water is highly desired in ionic liquids with different anions, water content, and hydrophilicity. Herein, based on the probe strategy, in situ surface enhanced Raman spectroscopy (SERS) combined with electrochemical control (EC-SERS) was developed to investigate the influence of hydrophilicity/hydrophobicity of ionic liquids on the interfacial water. The water-sensitive transformation reaction of 4,4'-dimercaptoazobenzene (DMAB) to para-aminothiophenol (PATP) was employed as a probe reaction for investigating the behavior of interfacial water. The changes of relative SERS intensities of DMAB to PATP served as an indication of the quantity variation of interfacial water. The results show that the transformation reaction efficiencies were critically dependent on the additional water contents, potential, and hydrophilicity of ionic liquids. With a very low molar fraction of additional water (Xw = 0.01), transformation efficiency of DMAB (the amount of interfacial water) followed the sequence of [BMIm]BF4 < [BMIm]PF6 < [BMIm]Tf2N. It was in agreement with the hydrophobicity order of the ionic liquids. With the increase in additional water content, the potential for the full transformation was positively moved, and the efficiency increased significantly. The stronger hydrophobicity allowed more water molecules to migrate to the interface, which was attributed to the difference in interactions between water and the anions of ionic liquids. It demonstrated that the small amount of water tended to gather at the interface in hydrophobic ionic liquids. Compared to traditional cyclic voltammetry, the EC-SERS technique combined with probe reactions is more sensitive to interfacial water. It is anticipated to develop as a promising tool for the investigating water-related issues at interfaces and to provide guidance to screen ionic liquids for practical application.

A Deep Mining Strategy for Peptide Rapid Identification in Lactobacillus reuteri Based on LC-MS/MS Integrated with FBMN and De Novo Sequencing.

Lactobacillus reuteri (L. reuteri) is widely recognized as a probiotic that produces prebiotics. However, studies on bioactive peptides or amino acid (AA) derivatives produced by L. reuteri are still lacking, whereas many bioactive peptides and AA derivatives have been found in other Lactobacillus species. In addition, rapid identification of peptides is challenged by the large amount of data and is limited by the coverage of protein databases. In this study, we performed a rapid and thorough profile of peptides in L. reuteri incorporating Global Natural Products Social Molecular Networking (GNPS) platform database searching, de novo sequencing, and deep mining, based on feature-based molecular networking (FBMN). According to FBMN, it was found that peptides containing identical or similar AA compositions were grouped into the same clusters, especially cyclic dipeptides (CDPs). Therefore, the grouping characteristics of clusters, differences in precursor ions, and characteristic fragment ions were utilized for the mining of deeply unknown compounds. Through this strategy, a total of 192 compounds, including 184 peptides, were rapidly identified. Among them, 53 CDPs, including four novel ones, were found for the first time in L. reuteri. Then, one of the novel CDPs, cyclo(5-OMe-Glu-4-OH-Pro), was isolated and characterized, which was consistent with the identification results. Moreover, some of the identified peptides exhibited considerable interactions with seven anti-inflammatory-related target proteins through molecular docking. According to the binding energies of peptides with different AA consistencies, it was considered that the existence of unnatural AAs in CDPs might contribute to their anti-inflammatory activity. These results provide a valuable strategy for the rapid identification of peptides, including CDPs. This study also reveals the substance basis for the potential anti-inflammatory effects exerted by L. reuteri.

Single-stage resection of uterine fibroids and intravascular leiomyomatosis: a case report.

BACKGROUND: Uterine Fibroids (UFs) are common benign tumors in the female reproductive tract, but their progression to intravascular leiomyomatosis (IVL) is rare. Presently, there are few reports on single-stage resection of UFs and IVL. CASE PRESENTATION: A 47-year-old woman, G2P2, had been diagnosed multiple UFs four years ago and now developed heart failure. Imaging examinations revealed that UFs had invaded the right iliac vein and extended into the right atrium through the inferior vena cava. Through multidisciplinary collaboration and a single-stage resection, the patient has survived for over 24 months post-surgery, and her heart function has significantly improved compared to preoperative levels, with no recurrence of UFs observed. CONCLUSIONS: Single-stage resection of IVL and UF is feasible and advantageous for this case, and selecting the appropriate surgical approach is crucial.

Multi-omic Analyses Shed Light on The Genetic Control of High-altitude Adaptation in Sheep.

Sheep were domesticated in the Fertile Crescent and then spread globally, where they have been encountering various environmental conditions. The Tibetan sheep has adapted to high altitudes on the Qinghai-Tibet Plateau over the past 3000 years. To explore genomic variants associated with high-altitude adaptation in Tibetan sheep, we analyzed Illumina short-reads of 994 whole genomes representing ∼ 60 sheep breeds/populations at varied altitudes, PacBio High fidelity (HiFi) reads of 13 breeds, and 96 transcriptomes from 12 sheep organs. Association testing between the inhabited altitudes and 34,298,967 variants was conducted to investigate the genetic architecture of altitude adaptation. Highly accurate HiFi reads were used to complement the current ovine reference assembly at the most significantly associated ß-globin locus and to validate the presence of two haplotypes A and B among 13 sheep breeds. The haplotype A carried two homologous gene clusters: (1) HBE1, HBE2, HBB-like, and HBBC, and (2) HBE1-like, HBE2-like, HBB-like, and HBB; while the haplotype B lacked the first cluster. The high-altitude sheep showed highly frequent or nearly fixed haplotype A, while the low-altitude sheep dominated by haplotype B. We further demonstrated that sheep with haplotype A had an increased hemoglobin-O2 affinity compared with those carrying haplotype B. Another highly associated genomic region contained the EGLN1 gene which showed varied expression between high-altitude and low-altitude sheep. Our results provide evidence that the rapid adaptive evolution of advantageous alleles play an important role in facilitating the environmental adaptation of Tibetan sheep.

Global prevalence and disability-adjusted life years of hypertensive heart disease: A trend analysis from the Global Burden of Disease Study 2019.

Background: As hypertensive heart disease (HHD) presents a significant public health challenge globally, we analysed its global, regional, and national burdens and trends from 1990 to 2019. Methods: We used data from the Global Burden of Disease (GBD) 2019 study, focussing on the age-standardised prevalence rates (ASPRs) of HHD prevalence, age-standardised disability-adjusted life year (DALY) rates, average annual percentage change (AAPC), and risk factor attributions. We compared the HHD burden across sociodemographic index (SDI) strata, gender, age groups, and 204 countries and territories. Results: In 2019, the global prevalence of HHD was estimated at 18 598 thousand cases, with DALYs reaching 21 508 thousand. From 1990 to 2019, the ASPRs increased (AAPC = 0.21; 95% confidence interval (CI) = 0.17, 0.24), while the age-standardised DALY rates decreased (AAPC = -0.45; 95% CI = -1.23, -0.93). We observed the highest increase in ASPRs in high-middle SDI quantile countries, and an overall negative correlation between age-standardised DALY rates and SDI. Individuals above 70 years of age were the most affected, particularly elderly women. There has been a significant increase in HHD burden attributed to high body mass index (BMI) since 1990. The burden of HHD is concentrated in the middle SDI quintile, with population ageing and growth being major drivers for the increase in DALYs. We identified opportunities for reducing age-standardised DALY rates in the middle SDI quintile or lower. Conclusion: Despite a declining trend in the age-standardised DALY rates, the ASPRs of HHD continue to rise, especially in high-middle SDI regions. Meanwhile, countries in middle and lower SDI quintiles face a higher burden of age-standardised DALY rates. Targeted attention towards elderly women and controlling high BMI, alongside enhancing hypertension and HHD management awareness, is crucial for reducing the global burden of HHD.

Tandem Protocol for Diversified Deuteration of Secondary Aliphatic Amines under Mild Conditions.

Deuteration of amine compounds has been widely of concern because of its practical role in organic reaction mechanisms and drug research; however, only limited deuteration label methods are accessible with D2O as a deuterium source. Herein, we propose a convenient deuteration protocol, including preparing D2 by the AlGa activation method, using PtRu nanowires as catalysts, and utilizing the elementary step in the couple reaction involving an imine unit, to realize the rapid preparation of a secondary amine with a diversified deuteration label. The self-coupling between nitriles not only provides a symmetric secondary amine with four α-D atoms but also produces high-valued ND3 in an atomic-economic way.

Vascular access type and prognosis in elderly hemodialysis patients: a propensity-score-matched study.

BACKGROUND: To compare the impact of tunneled cuffed catheters (TCCs) and arteriovenous fistulas (AVFs) on outcomes in elderly hemodialysis (HD) patients. METHODS: A retrospective matched cohort study was performed. Propensity score matching (PSM) was applied to balance the baseline conditions, and we compared all-cause mortality, major adverse cardiovascular and cerebrovascular events (MACCEs), hospitalization, and infection rates between AVF and TCC patients ≥70 years old. Cox survival analysis was used to analyze the risk factors for death. RESULTS: There were 2119 patients from our center in the Chinese National Renal Data System (CNRDS) between 1 January 2010 and 10 October 2023. Among these patients, 77 TCC patients were matched with 77 AVF patients. There was no significant difference in all-cause mortality between the TCC and AVF groups (30.1/100 vs. 33.3/100 patient-years, p = 0.124). Among the propensity score-matched cohorts, no significant differences in Kaplan-Meier curves were observed between the two groups (log-rank p = 0.242). The TCC group had higher rates of MACCEs, hospitalization, and infection than the AVF group (33.7/100 vs. 29.5/100 patient-years, 101.2/100 vs. 79.5/100 patient-years, and 30.1/100 vs. 14.1/100 patient-years, respectively). Multivariate analysis showed that high Charlson comorbidity index (CCI) score was a risk factor for death. CONCLUSIONS: There was no significant difference in all-cause mortality between elderly HD patients receiving TCCs and AVFs. Compared with those with a TCC, elderly HD patients with an AVF have a lower risk of MACCEs, hospitalization, and infection.

[Multi-time Scale Variation of Atmospheric Ammonia Concentration and Dry Deposition in a Paddy Rice Region in Subtropical China].

Meteorological factors and anthropogenic activities significantly affect atmospheric ammonia （NH3） concentration and its dry deposition. Former studies have examined the spatial and temporal variability in atmospheric NH3 concentrations at monthly scales. However, the characteristics of atmospheric concentrations at finer time scales such as hourly and daily scales and the influencing factors remain unclear. In this study, atmospheric NH3 concentration and related meteorological factors were continuously monitored online for one year in a double cropping rice region in subtropical China, and atmospheric NH3 concentration and its meteorological influencing factors as well as dry deposition were analyzed at different time scales （hourly, daily, and monthly）. The main results were as follows： The annual average daily concentration of NH3 in the rice area varied from 0.01 to 58.0 µg·m-3 （in N, same below）, and the annual average concentration was 5.3 µg·m-3. On the hourly scale, the 24-hour dynamics of atmospheric NH3 concentration showed a unimodal pattern, and the time of the NH3 peak appearance in different seasons was different； the time of the peak that appeared in winter lagged behind that in the other seasons. From the perspective of daily scale, NH3 concentration was mainly affected by fertilization in the paddy fields, peaking at 1-3 days after fertilization and then gradually decreasing. On the monthly scale, NH3 concentration peaked at 12.8 µg·m-3 in July and was the lowest in October at 1.6 µg·m-3. On the hourly scale, NH3 concentration varied seasonally due to the influences of meteorological factors, mainly as follows： NH3 concentration showed significant positive correlations with air temperature and solar radiation in all four seasons and with wind speed in spring and summer, whereas it showed significant negative correlations with relative humidity except in winter. On the daily scale, NH3 concentration showed a significant positive correlation with air temperature, rainfall, and solar radiation, whereas it showed a significant negative correlation with relative humidity. On the monthly scale, no significant correlation existed between each meteorological factor and NH3 concentration. The annual dry deposition flux （in N） calculated from the hourly average NH3 concentration was 8.5 kg·ï¼ˆhm2·a）-1, which was 11.6% higher than the annual flux calculated from the daily average and 12.4% higher than the annual flux calculated from the monthly average. In summary, there were significant daily and seasonal variations in atmospheric NH3 concentration in the paddy rice region in subtropical China, and conducting hourly-scale observations of NH3 concentration can help to reveal the multi-time scale variations in NH3 concentration and to quantify NH3 dry deposition more accurately.

Metabolic syndrome and cardiovascular disease among adult cancer patients: results from NHANES 2007-2018.

BACKGROUND: Metabolic syndrome (MetS) is a risk factor for cardiovascular disease (CVD), and CVD is a major challenge for cancer patients. This study aimed to investigate the prevalence and association of MetS and CVD among adult cancer patients. METHODS: This cross-sectional study included cancer patients aged > 18 years from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. The prevalence of MetS and CVD was calculated using weighted analysis. Multivariable logistic regression was used to assess the association between MetS and CVD. RESULTS: The study included 2658 adult cancer patients, of whom 1260 exhibited MetS and 636 had CVD. The weighted prevalence of MetS and CVD in cancer patients was 45.44%, and 19.23%, respectively. Multivariable logistic regression showed a 79% increased risk in higher CVD prevalence in cancer patients with MetS, with the OR (95% CI) of 1.79 (1.31, 2.44). Notably, obesity, elevated blood pressure (BP), high glucose, and low high density lipoprotein cholesterol (HDL-C) in the MetS components were significantly associated with higher CVD prevalence after adjusting for covariates. Moreover, the risk of CVD prevalence in cancer patients increased with more MetS components. Notably, MetS was more strongly linked to CVD in patients aged < 65 and women. CONCLUSIONS: Among adult cancer patients, over two-fifths (45.44%) were estimated to have MetS, while about one-fifth (19.23%) were considered to have CVD. Notably, obesity, elevated BP, high glucose, low HDL-C, and higher number of MetS components were found to be significantly associated with higher CVD prevalence among cancer adults. Cancer patients under 65 and women with MetS may be at increased risk of CVD.

Mesoporous Graphene Oxide Nanocomposite Effective for Combined Chemo/Photo Therapy Against Non-Small Cell Lung Cancer.

Introduction: Lung cancer is the most common cancer worldwide, among which non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancers. Chemotherapy, a mainstay modality for NSCLC, has demonstrated restricted effectiveness due to the emergence of chemo-resistance and systemic side effects. Studies have indicated that combining chemotherapy with phototherapy, such as photodynamic therapy (PDT) and photothermal therapy (PTT), can enhance efficacy of therapy. In this work, an aminated mesoporous graphene oxide (rPGO)-protoporphyrin IX (PPIX)-hyaluronic acid (HA)@Osimertinib (AZD) nanodrug delivery system (rPPH@AZD) was successfully developed for combined chemotherapy/phototherapy for NSCLC. Methods: A pH/hyaluronidase-responsive nanodrug delivery system (rPPH@AZD) was prepared using mesoporous graphene oxide. Its morphology, elemental composition, surface functional groups, optical properties, in vitro drug release ability, photothermal properties, reactive oxygen species production, cellular uptake and cell viability were evaluated. In addition, the in vivo therapeutic effect, biocompatibility, and imaging capabilities of rPPH@AZD were verified by a tumor-bearing mouse model. Results: Aminated mesoporous graphene oxide (rPGO) plays a role as a drug delivery vehicle owing to its large specific surface area and ease of surface functionalization. rPGO exhibits excellent photothermal conversion properties under laser irradiation, while PPIX acts as a photosensitizer to generate singlet oxygen. AZD acts as a small molecule targeted drug in chemotherapy. In essence, rPPH@AZD shows excellent photothermal and fluorescence imaging effects in tumor-bearing mice. More importantly, in vitro and in vivo results indicate that rPPH@AZD can achieve hyaluronidase/pH dual response as well as combined chemotherapy/PTT/PDT anti-NSCLC treatment. Conclusion: The newly prepared rPPH@AZD can serve as a promising pH/hyaluronidase-responsive nanodrug delivery system that integrates photothermal/fluorescence imaging and chemo/photo combined therapy for efficient therapy against NSCLC.

Necroptosis enhances 'don't eat me' signal and induces macrophage extracellular traps to promote pancreatic cancer liver metastasis.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 'don't eat me' signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial-mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery.

Whole-genome resequencing reveals genomic variation and dynamics in Ethiopian indigenous goats.

Ethiopia has about 52 million indigenous goats with marked phenotypic variability, which is the outcome of natural and artificial selection. Here, we obtained whole-genome sequence data of three Ethiopian indigenous goat populations (Arab, Fellata, and Oromo) from northwestern Ethiopia and analyzed their genome-wide genetic diversity, population structure, and signatures of selection. We included genotype data from four other Ethiopian goat populations (Abergelle, Keffa, Gumuz, and Woyto-Guji) and goats from Asia; Europe; and eastern, southern, western, and northern Africa to investigate the genetic predisposition of the three Ethiopian populations and performed comparative genomic analysis. Genetic diversity analysis showed that Fellata goats exhibited the lowest heterozygosity values (Ho = 0.288 ± 0.005 and He = 0.334 ± 0.0001). The highest values were observed in Arab goats (Ho = 0.310 ± 0.010 and He = 0.347 ± 4.35e-05). A higher inbreeding coefficient (FROH = 0.137 ± 0.016) was recorded for Fellata goats than the 0.105 ± 0.030 recorded for Arab and the 0.112 ± 0.034 recorded for Oromo goats. This indicates that the Fellata goat population should be prioritized in future conservation activities. The three goat populations showed the majority (∼63%) of runs of homozygosity in the shorter (100-150 Kb) length category, illustrating ancient inbreeding and/or small founder effects. Population relationship and structure analysis separated the Ethiopian indigenous goats into two distinct genetic clusters lacking phylogeographic structure. Arab, Fellata, Oromo, Abergelle, and Keffa represented one genetic cluster. Gumuz and Woyto-Guji formed a separate cluster and shared a common genetic background with the Kenyan Boran goat. Genome-wide selection signature analysis identified nine strongest regions spanning 163 genes influencing adaptation to arid and semi-arid environments (HOXC12, HOXC13, HOXC4, HOXC6, and HOXC9, MAPK8IP2), immune response (IL18, TYK2, ICAM3, ADGRG1, and ADGRG3), and production and reproduction (RARG and DNMT1). Our results provide insights into a thorough understanding of genetic architecture underlying selection signatures in Ethiopian indigenous goats in a semi-arid tropical environment and deliver valuable information for goat genetic improvement, conservation strategy, genome-wide association study, and marker-assisted breeding.

Incidence of Carotid Blowout Syndrome in Patients with Head and Neck Cancer after Radiation Therapy: A Cohort Study.

Carotid blowout syndrome (CBS) is a rare yet life-threatening complication that occurs after radiation therapy (RT). This study aimed to determine the incidence of CBS in patients with head and neck cancer (HNC) undergoing contemporary RT and to explore potential discrepancies in the risk of CBS between nasopharyngeal cancer (NPC) and non-NPC patients. A total of 1084 patients with HNC who underwent RT between 2013 and 2023 were included in the study. All patients were under regular follow-ups at the radio-oncology department, and underwent annual contrast-enhanced computed tomography and/or magnetic resonance imaging for cancer recurrence surveillance. Experienced neuroradiologists and vascular neurologists reviewed the recruited patients' images. Patients were further referred to the neurology department for radiation vasculopathy evaluation. The primary outcome of this study was CBS. Patients were categorized into NPC and non-NPC groups and survival analysis was employed to compare the CBS risk between the two groups. A review of the literature on CBS incidence was also conducted. Among the enrolled patients, the incidence of CBS in the HNC, NPC, and non-NPC groups was 0.8%, 0.9%, and 0.7%, respectively. Kaplan-Meier analysis revealed no significant difference between the NPC and non-NPC groups (p = 0.34). Combining the findings for our cohort with those of previous studies revealed that the cumulative incidence of CBS in patients with HNC is 5% (95% CI = 3-7%) after both surgery and RT, 4% (95% CI = 2-6%) after surgery alone, and 5% (95% CI = 3-7%) after RT alone. Our findings indicate a low incidence of CBS in patients with HNC undergoing contemporary RT. Patients with NPC may have a CBS risk close to that of non-NPC patients. However, the low incidence of CBS could be a potentially cause of selection bias and underestimation bias.

Anthropogenic events and responses to environmental stress are shaping the genomes of Ethiopian indigenous goats.

Anthropological and biophysical processes have shaped livestock genomes over Millenia and can explain their current geographic distribution and genetic divergence. We analyzed 57 Ethiopian indigenous domestic goat genomes alongside 67 equivalents of east, west, and north-west African, European, South Asian, Middle East, and wild Bezoar goats. Cluster, ADMIXTURE (K = 4) and phylogenetic analysis revealed four genetic groups comprising African, European, South Asian, and wild Bezoar goats. The Middle Eastern goats had an admixed genome of these four genetic groups. At K = 5, the West African Dwarf and Moroccan goats were separated from East African goats demonstrating a likely historical legacy of goat arrival and dispersal into Africa via the coastal Mediterranean Sea and the Horn of Africa. FST, XP-EHH, and Hp analysis revealed signatures of selection in Ethiopian goats overlaying genes for thermo-sensitivity, oxidative stress response, high-altitude hypoxic adaptation, reproductive fitness, pathogen defence, immunity, pigmentation, DNA repair, modulation of renal function and integrated fluid and electrolyte homeostasis. Notable examples include TRPV1 (a nociception gene); PTPMT1 (a critical hypoxia survival gene); RETREG (a regulator of reticulophagy during starvation), and WNK4 (a molecular switch for osmoregulation). These results suggest that human-mediated translocations and adaptation to contrasting environments are shaping indigenous African goat genomes.

A Prelimbic Cortex-Thalamus Circuit Bidirectionally Regulates Innate and Stress-Induced Anxiety-Like Behavior.

Anxiety-related disorders respond to cognitive behavioral therapies, which involved the medial prefrontal cortex (mPFC). Previous studies have suggested that subregions of the mPFC have different and even opposite roles in regulating innate anxiety. However, the specific causal targets of their descending projections in modulating innate anxiety and stress-induced anxiety have yet to be fully elucidated. Here, we found that among the various downstream pathways of the prelimbic cortex (PL), a subregion of the mPFC, PL-mediodorsal thalamic nucleus (MD) projection, and PL-ventral tegmental area (VTA) projection exhibited antagonistic effects on anxiety-like behavior, while the PL-MD projection but not PL-VTA projection was necessary for the animal to guide anxiety-related behavior. In addition, MD-projecting PL neurons bidirectionally regulated remote but not recent fear memory retrieval. Notably, restraint stress induced high-anxiety state accompanied by strengthening the excitatory inputs onto MD-projecting PL neurons, and inhibiting PL-MD pathway rescued the stress-induced anxiety. Our findings reveal that the activity of PL-MD pathway may be an essential factor to maintain certain level of anxiety, and stress increased the excitability of this pathway, leading to inappropriate emotional expression, and suggests that targeting specific PL circuits may aid the development of therapies for the treatment of stress-related disorders.

Waiting for self-healing as a primary management strategy for lower lip mucoceles.

OBJECTIVES: Oral mucoceles are most frequently encountered on the lower lip. A variety of treatment options are currently employed, including surgical excision, pharmacological injections, and laser therapy. However, each of these approaches may introduce risks and potential complications. Clinical practice has demonstrated a potential for self-healing in lower lip mucoceles, making a conservative observational approach more appealing. This research is a prospective study aimed at evaluating the self-healing capacity of lower lip mucoceles. METHODS: In this prospective study, patients with mucoceles were encouraged to intentionally delay medical intervention and to wait for self-healing. Disappearance of the mucocele for at least 3 months was defined as self-healing. RESULTS: Thirty patients with lower lip mucoceles were included. With no intervention, 24 patients (80%) reported self-healing of lower lip mucoceles. The mean natural duration of the mucoceles was 3.63 (± 4.7; 1-24) months. After self-healing of the mucocele, the patients were followed up for 17.21 (± 9.45; 2-30) months and there were no reported recurrences. CONCLUSIONS: Lower lip mucoceles have a high potential for self-healing and patients may be routinely encouraged to wait for self-healing. CLINICAL RELEVANCE: The high self-healing rate observed in this study suggests that a conservative, non-interventional approach might be considered as the first-line management for lower lip mucoceles.

Ganoderma lucidum Polysaccharide Supplementation Significantly Activates T-Cell-Mediated Antitumor Immunity and Enhances Anti-PD-1 Immunotherapy Efficacy in Colorectal Cancer.

Ganoderma lucidum polysaccharide (GLP) is a prebiotic with immunomodulatory effects. However, the therapeutic potential of GLP in tumor immunotherapy has not been fully explored, especially in T cell-mediated antitumor immunity. In this study, we found that GLP significantly inhibited tumor growth and activated antitumor immunity in colorectal cancer (CRC). In the spleens and tumor tissues, the proportion of cytotoxic CD8+T cells and Th1 helper cells increased, while immunosuppressive Tregs decreased. Additionally, microbiota dysbiosis was alleviated by GLP, and short-chain fatty acid production was increased. Meanwhile, GLP decreased the ratio of kynurenine and tryptophan (Kyn/Trp) in the serum, which contributed to antitumor immunity of T cells. More importantly, the combination of GLP and the immune checkpoint inhibitor anti-PD-1 monoclonal antibody further enhanced the efficacy of anti-PD-1 immunotherapy. Thus, GLP as a prebiotic has the potential to be used in tumor immunotherapy.

Meta-analysis of the GALAD model for diagnosing primary hepatocellular carcinoma.

BACKGROUND: Ever since the GALAD (gender-age-Lens culinaris agglutinin-reactive alpha-fetoprotein-alpha-fetoprotein-des-gamma-carboxy prothrombin) logistic regression model was established to diagnose hepatocellular carcinoma (HCC), there has been no high-level evidence that evaluates and summarizes it. OBJECTIVE: This meta-analysis was performed to assess the diagnostic ability of the GALAD model. METHODS: The following databases were systematically searched for original diagnostic studies on HCC: PubMed, Embase, Medline, the Web of Science, Cochrane Library, China National Knowledge Infrastructure Wanfang (China), Wiper and the Chinese BioMedical Literature Database. After screening the search results according to our criteria, the Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to evaluate the methodologic qualities, and statistical software were used to output the statistics. RESULTS: Ultimately, 10 studies were included and analyzed. The results revealed the pooled sensitivity and specificity of the GALAD model to be 0.86 (95% confidence interval [CI]: 0.82, 0.90) and 0.90 (95% CI: 0.87, 0.92), respectively, for all-stage HCC. The area under the curve (AUC) was 0.94. For early-stage HCC, the pooled sensitivity and specificity of the GALAD model were 0.83 (95% CI: 0.78, 0.87) and 0.81 (95% CI: 0.78, 0.83), respectively. The AUC was 0.90. CONCLUSION: This meta-analysis confirmed that the GALAD model has excellent diagnostic performance for early-stage and all-stage HCC and can maintain high sensitivity and specificity in early-stage HCC. Therefore, the GALAD model is qualified for screening early-stage canceration from chronic liver disease.

Advances in Microfluidic Paper-Based Analytical Devices (µPADs): Design, Fabrication, and Applications.

Microfluidic Paper-based Analytical Devices (µPADs) have emerged as a new class of microfluidic systems, offering numerous advantages over traditional microfluidic chips. These advantages include simplicity, cost-effectiveness, stability, storability, disposability, and portability. As a result, various designs for different types of assays are developed and investigated. In recent years, µPADs are combined with conventional detection methods to enable rapid on-site detection, providing results comparable to expensive and sophisticated large-scale testing methods that require more time and skilled personnel. The application of µPAD techniques is extensive in environmental quality control/analysis, clinical diagnosis, and food safety testing, paving the way for on-site real-time diagnosis as a promising future development. This review focuses on the recent research advancements in the design, fabrication, material selection, and detection methods of µPADs. It provides a comprehensive understanding of their principles of operation, applications, and future development prospects.