Safety and adherence of bictegravir/emtricitabine/tenofovir alafenamide for HIV post-exposure prophylaxis among adults in Guiyang China: a prospective cohort study.

BACKGROUND: The effectiveness of post-exposure prophylaxis (PEP) depends on participants adherence, making it crucial to assess and compare regimen options to enhance human immunodeficiency virus (HIV) prophylaxis strategies. However, no prospective study in China has shown that the completion rate and adherence of single-tablet regimens in HIV PEP are higher than those of multi-tablet preparations. Therefore, this study aimed to assess the completion rate and adherence of two HIV PEP regimens. METHODS: In this single-center, prospective, open-label cohort study, we included 179 participants from May 2022 to March 2023 and analyzed the differences in the 28-day medication completion rate, adherence, safety, tolerance, and effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and tenofovir disoproxil fumarate, emtricitabine, and dolutegravir (TDF/FTC + DTG). RESULTS: The PEP completion rate and adherence were higher in the BIC/FTC/TAF group than in the TDF/FTC + DTG group (completion rate: 97.8% vs. 82.6%, P = 0.009; adherence: 99.6 ± 2.82% vs. 90.2 ± 25.29%, P = 0.003). The incidence of adverse reactions in the BIC/FTC/TAF and TDF/FTC + DTG groups was 15.2% and 10.3% (P = 0.33), respectively. In the TDF/FTC + DTG group, one participant stopped PEP owing to adverse reactions (1.1%). No other participants stopped PEP due to adverse events. CONCLUSIONS: BIC/FTC/TAF and TDF/FTC + DTG have good safety and tolerance as PEP regimens. BIC/FTC/TAF has a higher completion rate and increased adherence, thus, is recommended as a PEP regimen. These findings emphasize the importance of regimen choice in optimizing PEP outcomes. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2200059994(2022-05-14), https://www.chictr.org.cn/bin/project/edit?pid=167391 ).

Identification of Keratoconus-Related Phenotypes in Three Ppip5k2 Mouse Models.

Purpose: It is necessary to establish a mouse model of keratoconus (KC) for research and therapy. We aimed to determine corneal phenotypes in 3 Ppip5k2 mouse models. Methods: Central corneal thickness (CCT) was determined using spectral domain optical coherence tomography (SD-OCT) in Ppip5k2+/K^ (n = 41 eyes), Ppip5k2K^/K^ (n = 17 eyes) and 2 knock-in mice, Ppip5k2S419A/+ (n = 54 eyes) and Ppip5k2S419A/S419A (n = 18 eyes), and Ppip5k2D843S/+ (n = 42 eyes) and Ppip5k2D843S/D843S (n = 44 eyes) at 3 and 6 months. Pachymetry maps were generated using the Mouse Corneal Analysis Program (MCAP) to process OCT images. Slit lamp biomicroscopy was used to determine any corneal abnormalities, and, last, hematoxylin and eosin (H&E) staining using corneal sections from these animals was used to examine morphological changes. Results: CCT significantly decreased from 3 to 6 months in the Ppip5k2+/K^ and Ppip5k2K^/K^ mice compared to their littermate controls. OCT-based pachymetry maps revealed abnormally localized thinning in all three models compared to their wild-type (WT) controls. Slit lamp examinations revealed corneal abnormalities in the form of bullous keratopathy, stromal edema, stromal scarring, deep corneal neovascularization, and opacities in the heterozygous/homozygous mice of the three models in comparison with their controls. Corneal histological abnormalities, such as epithelial thickening and stromal layer damage, were observed in the heterozygous/homozygous mice of the three models in comparison with the WT controls. Conclusions: We have identified phenotypic and histological changes in the corneas of three mouse lines that could be relevant in the development of animal models of KC.

Development of a Recombinase-Aided Amplification Assay for the Rapid Detection of Candida auris.

Candida auris (C. auris) was first discovered in Japan in 2009 and has since spread worldwide. It exhibits strong transmission ability, high multidrug resistance, blood infectivity, and mortality rates. Traditional diagnostic techniques for C. auris have shortcomings, leading to difficulty in its timely diagnosis and identification. Therefore, timely and accurate diagnostic assays for clinical samples are crucial. We developed a novel, rapid recombinase-aided amplification (RAA) assay targeting the 18S rRNA, ITS1, 5.8S rRNA, ITS2, and 28S rRNA genes for C. auris identification. This assay can rapidly amplify DNA at 39 °C in 20 min. The analytical sensitivity and specificity were evaluated. From 241 clinical samples collected from pediatric inpatients, none were detected as C. auris-positive. We then prepared simulated clinical samples by adding 10-fold serial dilutions of C. auris into the samples to test the RAA assay's efficacy and compared it with that of real-time PCR. The assay demonstrated an analytical sensitivity of 10 copies/µL and an analytical specificity of 100%. The lower detection limit of the RAA assay for simulated clinical samples was 101 CFU/mL, which was better than that of real-time PCR (102-103 CFU/mL), demonstrating that the RAA assay may have a better detection efficacy for clinical samples. In summary, the RAA assay has high sensitivity, specificity, and detection efficacy. This assay is a potential new method for detecting C. auris, with simple reaction condition requirements, thus helping to manage C. auris epidemics.

Clathrin mediates membrane fission and budding by constricting membrane pores.

Membrane budding, which underlies fundamental processes like endocytosis, intracellular trafficking, and viral infection, is thought to involve membrane coat-forming proteins, including the most observed clathrin, to form Ω-shape profiles and helix-forming proteins like dynamin to constrict Ω-profiles' pores and thus mediate fission. Challenging this fundamental concept, we report that polymerized clathrin is required for Ω-profiles' pore closure and that clathrin around Ω-profiles' base/pore region mediates pore constriction/closure in neuroendocrine chromaffin cells. Mathematical modeling suggests that clathrin polymerization at Ω-profiles' base/pore region generates forces from its intrinsically curved shape to constrict/close the pore. This new fission function may exert broader impacts than clathrin's well-known coat-forming function during clathrin (coat)-dependent endocytosis, because it underlies not only clathrin (coat)-dependent endocytosis, but also diverse endocytic modes, including ultrafast, fast, slow, bulk, and overshoot endocytosis previously considered clathrin (coat)-independent in chromaffin cells. It mediates kiss-and-run fusion (fusion pore closure) previously considered bona fide clathrin-independent, and limits the vesicular content release rate. Furthermore, analogous to results in chromaffin cells, we found that clathrin is essential for fast and slow endocytosis at hippocampal synapses where clathrin was previously considered dispensable, suggesting clathrin in mediating synaptic vesicle endocytosis and fission. These results suggest that clathrin and likely other intrinsically curved coat proteins are a new class of fission proteins underlying vesicle budding and fusion. The half-a-century concept and studies that attribute vesicle-coat contents' function to Ω-profile formation and classify budding as coat-protein (e.g., clathrin)-dependent or -independent may need to be re-defined and re-examined by considering clathrin's pivotal role in pore constriction/closure.

Edaphic regulation of soil organic carbon fractions in the mattic layer across the Qinghai-Tibetan Plateau.

The mattic layer is a main ecological function bearer of alpine meadow soils in the Qinghai-Tibet Plateau. It has high soil organic carbon (SOC) content with a variety of SOC fractions, which are thought to have different sensitivities to climate change. The effects of soil properties and climate on the SOC fractions in the mattic layer are not well understood. To address this, we analyzed the effects of environmental factors on two SOC fractions: particulate organic carbon (POC) and mineral-associated organic carbon (MAOC). A random forest model (RFM), partial correlation analysis, and structural equation model (SEM) were used to quantify the relative effects of soil and climatic factors on SOC fractions. We found that SOC and its fractions are primarily regulated by soil properties rather than climate. Partial correlation analysis and SEM revealed that climate indirectly affects SOC by influencing soil properties. Silt+Clay and exchangeable calcium (Caex) were found to be the strongest contributing factors of MAOC and POC, respectively. A distinct shift occurs in the mechanism underlying SOC stabilization with varying soil pH. In acidic and neutral environments, amorphous Al/Fe-(hydr) oxides contribute to the stability of MAOC, whereas free Al/Fe-(hydr) oxides promote SOC mineralization. Conversely, Caex positively influences the stabilization of both POC and MAOC throughout the pH range. These results can be extrapolated to predict SOC dynamics in future soil conditions affected by environmental change, especially for use in Earth system models.

Ultrafast evanescently coupled waveguide MUTC-PDs with high responsivity.

Novel evanescently coupled waveguide modified uni-traveling carrier photodiodes (MUTC-PDs) employing a thick multi-layer coupling waveguide are reported. To improve the optical-to-electrical (O/E) conversion efficiency, a thick multi-layer coupling waveguide with a gradually increased refractive index from the bottom layer to the absorption layer is utilized. The refractive index profile facilitates the upward transmission of incident light into the absorption region, thereby enhancing the evanescent coupling efficiency. Meanwhile, the coupling waveguide, with a total thickness of 1.75 µm, expands the mode field diameter, thereby reducing the input coupling loss. Additionally, the top layer of the coupling waveguide also serves as the drift layer. This configuration facilitates efficient light absorption within a short PD length, thus ensuring ultrawide bandwidth and high O/E conversion efficiency simultaneously. Without an additional spot size coupler or anti-reflection coating, the measured responsivity is as high as 0.38 A/W for the PD with an active area of 5 × 6 µm2. Meanwhile, an ultrawide 3-dB bandwidth of 153 GHz has been demonstrated.

Associated lifestyle factors of elevated plasma aldosterone concentration in community population, gender-stratified analysis of a cross-sectional survey.

BACKGROUND: Aldosterone plays important parts in development of cardio-metabolic diseases as end product of renin-angiotensin-aldosterone system. However, factors elevating circulating aldosterone are not clear, and lifestyle-related factors are suggested to be involved, whereas less studied. Therefore, we aimed to explore the association of lifestyle factors with plasma aldosterone concentration (PAC) in community population. METHODS: In this cross-sectional study, we recruited participants using multistage random sampling from Emin China in 2019, and collected data and fasting blood samples. The considered lifestyle factors included obesity parameters (neck circumference, abdominal circumference), alcohol consumption, blood pressure (BP), physical activity, sleep duration, sleep quality, mental state (depression and anxiety), fasting blood glucose (FBG), and lipid profiles (total cholesterol and triglyceride). PAC was measured using radioimmunoassay. We performed sex-stratified linear and logistic regressions to explore associated factors of PAC. Component analysis was further performed to identify the main factors affecting PAC. RESULTS: Twenty-seven thousand four hundred thirty-six participants with 47.1% men were included. Obesity parameters (neck circumference, abdominal circumference), glucose metabolism (FBG), psychological status (anxiety status in men and women, depression status in men), BP, liver function (in men), lipid metabolism (TC and TG in men), sleep parameters (sleep quality in women), and renal function (in women) are the main factors associated with elevated PAC. CONCLUSION: lower physical activity, alcohol consumption, higher BP, fat accumulation, dyslipidemia, higher fasting blood glucose, and presence of depression and anxiety were the main factors associated with eleveated PAC.

Anti-glioma effect of paclitaxel mediated by specific mode electroacupuncture stimulation and the related role of the Hedgehog pathway.

INTRODUCTION: Paclitaxel (PTX) cannot effectively treat glioma because it cannot cross the bloodbrain barrier (BBB). A specific mode electroacupuncture stimulation (SMES) can temporarily open the BBB, thereby improving drug delivery to the brain. This study aimed to observe SMES-mediated accumulation of PTX in the brain and its anti-glioma effect and explore the role of the Hedgehog pathway. METHODS: The acupoint selectivity of SMES in opening the BBB was examined in normal rats. The penetration and anti-glioma activity were determined in a C6-Luc glioma rat model. SMES was performed using 2/100 Hz, 3 mA, 6-6 s, and 40 min The survival curve was analysed by the KaplanMeier method, brain tumour pathology and size was observed by HE staining, and in vivo imaging system respectively. RESULTS: SMES-induced BBB opening had acupoint selectivity. SMES could improve PTX accumulation in brain and SMES-mediated PTX delivery showed enhanced anti-glioma activity due to better brain penetration. Hedgehog pathway was involved in SMES-mediated PTX delivery by regulating Occludin expression. CONCLUSION: SMES at the head acupoints to deliver PTX is a feasible and effective method for treating glioma. The Hedgehog pathway may play a key role in SMES-mediated PTX delivery across the BBB.

Site-Selective Growth of fcc-2H-fcc Copper on Unconventional Phase Metal Nanomaterials for Highly Efficient Tandem CO2 Electroreduction.

Copper (Cu) nanomaterials are a unique kind of electrocatalysts for high-value multi-carbon production in carbon dioxide reduction reaction (CO2RR), which holds enormous potential in attaining carbon neutrality. However, phase engineering of Cu nanomaterials remains challenging, especially for the construction of unconventional phase Cu-based asymmetric heteronanostructures. Here the site-selective growth of Cu on unusual phase gold (Au) nanorods, obtaining three kinds of heterophase fcc-2H-fcc Au-Cu heteronanostructures is reported. Significantly, the resultant fcc-2H-fcc Au-Cu Janus nanostructures (JNSs) break the symmetric growth mode of Cu on Au. In electrocatalytic CO2RR, the fcc-2H-fcc Au-Cu JNSs exhibit excellent performance in both H-type and flow cells, with Faradaic efficiencies of 55.5% and 84.3% for ethylene and multi-carbon products, respectively. In situ characterizations and theoretical calculations reveal the co-exposure of 2H-Au and 2H-Cu domains in Au-Cu JNSs diversifies the CO* adsorption configurations and promotes the CO* spillover and subsequent C-C coupling toward ethylene generation with reduced energy barriers.

To analyze the relationship between gut microbiota, metabolites and migraine: a two-sample Mendelian randomization study.

Background: It has been suggested in several observational studies that migraines are associated with the gut microbiota. It remains unclear, however, how the gut microbiota and migraines are causally related. Methods: We performed a bidirectional two-sample mendelian randomization study. Genome-wide association study (GWAS) summary statistics for the gut microbiota were obtained from the MiBioGen consortium (n = 18,340) and the Dutch Microbiota Project (n = 7,738). Pooled GWAS data for plasma metabolites were obtained from four different human metabolomics studies. GWAS summary data for migraine (cases = 48,975; controls = 450,381) were sourced from the International Headache Genetics Consortium. We used inverse-variance weighting as the primary analysis. Multiple sensitivity analyses were performed to ensure the robustness of the estimated results. We also conducted reverse mendelian randomization when a causal relationship between exposure and migraine was found. Results: LachnospiraceaeUCG001 (OR = 1.12, 95% CI: 1.05-1.20) was a risk factor for migraine. Blautia (OR = 0.93, 95% CI: 0.88-0.99), Eubacterium (nodatum group; OR = 0.94, 95% CI: 0.90-0.98), and Bacteroides fragilis (OR = 0.97, 95% CI: 0.94-1.00) may have a suggestive association with a lower migraine risk. Functional pathways of methionine synthesis (OR = 0.89, 95% CI: 0.83-0.95) associated with microbiota abundance and plasma hydrocinnamate (OR = 0.85, 95% CI: 0.73-1.00), which are downstream metabolites of Blautia and Bacteroides fragilis, respectively, may also be associated with lower migraine risk. No causal association between migraine and the gut microbiota or metabolites was found in reverse mendelian randomization analysis. Both significant horizontal pleiotropy and significant heterogeneity were not clearly identified. Conclusion: This Mendelian randomization analysis showed that LachnospiraceaeUCG001 was associated with an increased risk of migraine, while some bacteria in the gut microbiota may reduce migraine risk. These findings provide a reference for a deeper comprehension of the role of the gut-brain axis in migraine as well as possible targets for treatment interventions.

Advancing Neurological Health: Insights into Aging, Immunity, and Vascular Dynamics.

This editorial provides an overview of recent advancements in the understanding and treatment of neurological disorders, focusing on aging, immunity, and blood flow, as featured in this special issue. The first section explores the importance of identifying biomarkers of aging and aging-related diseases, such as Alzheimer's Disease, highlighting the emerging role of saliva-based biomarkers and the gut-brain axis in disease diagnosis and management. In the subsequent section, the dysregulated immune systems associated with aging are discussed, emphasizing the intricate landscape of the immune system during aging and its bidirectional relationship with neuroinflammation. Additionally, insights into the involvement of Myeloid-Derived Suppressor Cells (MDSCs) in Multiple Sclerosis (MS) pathogenesis are presented. The third section examines the role of microglia in neuroinflammation and various neurological diseases, including age-related macular degeneration (AMD) and Tuberculous Meningitis (TBM). Furthermore, the therapeutic potential of stem cell and extracellular vesicle-based therapies for stroke is explored, along with molecular mechanism of how inflammation regulates cerebral and myocardial ischemia. Finally, the importance of blood flow in maintaining vascular health and its impact on neurological disorders are discussed, highlighting the potential of novel assessment methods for optimizing patient care. Overall, this special issue offers valuable insights into the complex mechanisms underlying neurological disorders and identifies potential avenues for therapeutic intervention.

Size, distribution, and vulnerability of the global soil inorganic carbon.

Global estimates of the size, distribution, and vulnerability of soil inorganic carbon (SIC) remain largely unquantified. By compiling 223,593 field-based measurements and developing machine-learning models, we report that global soils store 2305 ± 636 (±1 SD) billion tonnes of carbon as SIC over the top 2-meter depth. Under future scenarios, soil acidification associated with nitrogen additions to terrestrial ecosystems will reduce global SIC (0.3 meters) up to 23 billion tonnes of carbon over the next 30 years, with India and China being the most affected. Our synthesis of present-day land-water carbon inventories and inland-water carbonate chemistry reveals that at least 1.13 ± 0.33 billion tonnes of inorganic carbon is lost to inland-waters through soils annually, resulting in large but overlooked impacts on atmospheric and hydrospheric carbon dynamics.

Boldness suppresses hoarding behavior in food hoarding season and reduces over-wintering survival in a social rodent.

The "pace-of-life" syndrome (POLS) framework can encompass multiple personality axes that drive important functional behaviors (e.g., foraging behavior) and that co-vary with multiple life history traits. Food hoarding is an adaptive behavior important for an animal's ability to adapt to seasonal fluctuations in food availability. However, the empirical evidence for the relationships between animal personality and hoarding behavior remains unclear, including its fitness consequences in the POLS framework. In this study, the Mongolian gerbil (Meriones unguiculatus), a social rodent, was used as a model system to investigate how boldness or shyness is associated with food hoarding strategies during the food hoarding season and their impact on over-winter survival and reproduction at both individual and group levels. The results of this study showed that, compared with shy gerbils, bold gerbils had a lower effort foraging strategy during the food hoarding season and exhibited lower over-winter survival rates. However, bold-shy personality differences had no effect on over-winter reproduction. These findings suggest that the personality is a crucial factor influencing the foraging strategy during the food hoarding season in Mongolian gerbils. Personality may be related to energy states or the reaction to environmental changes (e.g., predation risk and food availability) in bold or shy social animals. These results reflect animal life history trade-offs between current versus future reproduction and reproduction versus self-maintenance, thereby helping Mongolian gerbils in adapting to seasonal fluctuations in their habitat.

Clinical benefits of novel non-nucleoside reverse transcriptase inhibitors: A prospective cohort study.

INTRODUCTION: The efficacy and safety of ainuovirine+lamivudine+tenofovir (ANV+3TC+TDF) and efavirenz+lamivudine+tenofovir (EFV+3TC+TDF) have been confirmed in previous clinical trials; however, there are no related studies on patient-reported outcomes. This study aimed to evaluate the effectiveness and safety of these 2 antiretroviral therapy regimens and to understand the patient's symptom experience and subjective experience of sleep quality through patient-reported outcomes. METHODS: This is a single-center prospective cohort study with 243 patients evaluated from October 1, 2021 to June 30, 2022. Virological effectiveness and patient-reported outcomes results were analyzed. The primary endpoint was the proportion of HIV viral load <50 copies/mL (virological suppression rate) at 48 weeks and the changes in the HIV symptom index and Pittsburgh sleep quality index. RESULTS: The virological suppression rates in the ANV+3TC+TDF and EFV+3TC+TDF groups were 83.6% (102/122) and 87.6% (106/121), respectively, at 48 weeks. In the ANV+3TC+TDF group, the scores of HIV symptom index and pittsburgh sleep quality index in the 48th week were lower than the baseline level (p < 0.05). Logistic regression results showed that the baseline regimen EFV+3TC+TDF was a risk factor for dizziness/lightheadedness (odds ratio = 3.153, 95% confidence interval: 1.473-6.748, p = 0.003), sadness/depression odds ratio = 2.404, 95% confidence interval:1.188-4.871, p = 0.015), and difficulty sleeping (odds ratio = 2.802, 95% confidence interval: 1.437-5.463, p = 0.002) at 48 weeks. CONCLUSIONS: Both regimens showed good virological effectiveness; however, compared with ANV+3TC+TDF, the EFV+3TC+TDF regimen reduced the prevalence of HIV-related symptoms.

Dual role of GRHL3 in bladder carcinogenesis depending on histological subtypes.

The effect of grainyhead-like transcription factor 3 (GRHL3) on cancer development depends on the cancer subtypes as shown in tumor entities such as colorectal or oral squamous cell carcinomas. Here, we analyzed the subtype-specific role of GRHL3 in bladder carcinogenesis, comparing common urothelial carcinoma (UC) with squamous bladder cancer (sq-BLCA). We examined GRHL3 mRNA and protein expression in cohorts of patient samples, its prognostic role and its functional impact on tumorigeneses in different molecular and histopathological subtypes of bladder cancer. We showed for GRHL3 a reverse expression in squamous and urothelial bladder cancer subtypes. Stably GRHL3-overexpressing EJ28, J82, and SCaBER in vitro models revealed a tumor-suppressive function in squamous and an oncogenic role in the urothelial cancer cells affecting cell and colony growth, and migratory and invasive capacities. Transcriptomic profiling demonstrated highly subtype-specific GRHL3-regulated expression networks coined by the enrichment of genes involved in integrin-mediated pathways. In SCaBER, loss of ras homolog family member A (RHOA) GTPase activity was demonstrated to be associated with co-regulation of eukaryotic translation initiation factor 4E family member 3 (EIF4E3), a potential tumor suppressor gene. Thus, our data provide for the first time a detailed insight into the role of the transcription factor GRHL3 in different histopathological subtypes of bladder cancer.

Mapping specific groundwater nitrate concentrations from spatial data using machine learning: A case study of chongqing, China.

Groundwater resources is not only important essential water resources but also imperative connectors within the intricate framework of the ecological environment. High nitrate concentrations in groundwater can exerting adverse impacts on human health. It is imperative to accurately delineate the distribution characteristics of groundwater nitrate concentrations. Four different machine learning models (Gradient Boosting Regression (GB), Random Forest Regression (RF), Extreme Gradient Boosting Regression (XG) and Adaptive Boosting Regression (AD)) which combine spatial environmental data and different radius contributing area was developed to predict the distribution of nitrate concentration in groundwater. The models use 595 groundwater samples and included topography, remote sensing, hydrogeological and hydrological, climate, nitrate input, and socio-economic predictor. Gradient Boosting Regression model outperforms the other models (R2 = 0.627, MAE = 0.529, RMSE = 0.705, PICP = 0.924 for test dataset) under 500 m radius contributing area. A high-resolution (1 km) groundwater nitrate concentration distribution map reveal in the majority of the study area, groundwater nitrate concentrations are below 1 mg/L and high nitrate concentration (>10 mg/L) proportion in southeast, northeast and central main urban area karst valley regions is 1.89%, 0.91%, and 0.38% respectively. In study area, hydrogeological conditions, soil parameters, nitrogen input factors, and percentage of arable land are among the most influential explanatory factors. This work, serving as the inaugural application of utilizing effective spatial methods for predicting groundwater nitrate concentrations in Chongqing city, furnish decision-making support for the prevention and control of groundwater pollution, particularly in areas primarily dependent on groundwater for water supply and holds profound significance as a milestone achievement.

Prognostic value and potential function of a novel heme-related LncRNAs signature in gastric cancer.

Heme is a coordination complex formed by the binding of iron ions and porphyrin rings. Its metabolic processes are associated with various cancers, including gastric cancer (GC). In recent years, long non-coding RNAs (LncRNAs) have been identified as key regulatory factors in GC. However, the role of LncRNAs associated with heme metabolism in GC and their relationship with prognosis have not been reported. In this study, we constructed a novel LncRNAs signature related to heme metabolism (HMlncSig) and validated its prognostic value for predicting the survival of GC patients through training, test, and entire cohorts. Kaplan-Meier analysis demonstrated that patients in the high-risk group had shorter survival times. Univariate and multivariate Cox regression analysis showed that HMlncSig was an independent prognostic indicator for GC patients, regardless of other clinical pathological features. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis and gene set variation analysis pathways showed that the activation of these markers may be involved in tumor progression, influencing the survival of GC patients. The nomogram, based on HMlncSig score and clinical features, demonstrated the strong predictive ability of this signature. Additionally, significant differences were observed between the high-risk and low-risk groups in terms of immune cell subtypes, expression of immune checkpoint genes, and response to chemotherapy and immunotherapy. Through clinical validation, we found that the risk score and heme levels of GC patients were both significantly elevated and correlated with the degree of malignancy. Furthermore, we found that AP000692.1, a key gene in this signature, promoted the proliferation, migration, and invasion of GC cells. In conclusion, our HMlncSig model has significant predictive value for the prognosis of GC patients and can provide clinical guidance for personalized immunotherapy.

Synergy of de-walled Ganoderma Lucidum spore powder (GLSP) on targeted therapy in advanced non-squamous non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutant: protocol for a randomized, double-blind, placebo-controlled study.

BACKGROUND: Osimertinib is regarded as a promising third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for advanced non-squamous non-small cell lung cancer (NSCLC) patients who developed T790M. However the adverse effects, primarily fatigue, remain an overwhelming deficiency of Osimertinib, hindering it from achieving adequate clinical efficacy for such NSCLC. Ganoderma lucidum has been used for thousands of years in China to combat fatigue, while Ganoderma Lucidum spores powder (GLSP) is the main active ingredient. The aim of this study is to investigate whether GLSP is sufficiently effective and safe in improving fatigue and synergizing with Osimertinib in non-squamous NSCLC patients with EGFR mutant. METHOD/DESIGN: A total of 140 participants will be randomly assigned to receive either de-walled GSLP or placebo for a duration of 56 days. The primary outcome measure is the fatigue score associated with EGFR-TKI adverse reactions at week 8, evaluated by the Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Patients (QLQ-C30). Secondary outcomes include evaluation of treatment effectiveness, assessment of quality of life (QoL), and exploration of immune indicators and gut microbiota relationships. Following enrollment, visits are scheduled biweekly until week 12. TRIAL REGISTRATION: China Clinical Trial Registry ChiCTR2300072786. Registrated on June 25, 2023.

Extreme Thermal Insulation and Tradeoff of Thermal Transport Mechanisms between Graphene and WS2 Monolayers.

Controlling and understanding the heat flow at a nanometer scale are challenging, but important for fundamental science and applications. Two-dimensional (2D) layered materials provide perhaps the ultimate solution for meeting these challenges. While there have been reports of low thermal conductivities (several mW m-1 K-1) across the 2D heterostructures, phonon-dominant thermal transport remains strong due to the nearly-ideal contact between the layers. Here, this work experimentally explores the heat transport mechanisms by increasing the interlayer distance from perfect contact to a few nanometers and demonstrates that the phonon-dominated thermal conductivity across the WS2/graphene interface decreases further with the increasing interlayer distance until the air-dominated thermal conductivity increases again. This work finds that the resulting tradeoff of the two heat conduction mechanisms leads to the existence of a minimum thermal conductivity at 2.11 nm of 1.41 × 10-5 W m-1 K-1, which is two thousandths of the smallest value reported previously. This work provides an effective methodology for engineering thermal insulation structures and understanding heat transport at the ultimate small scales.

Curcumin suppresses metastasis of triple-negative breast cancer cells by modulating EMT signaling pathways: An integrated study of bioinformatics analysis.

This study aimed to use bioinformatics approaches for predicting the anticancer mechanisms of curcumin on triple-negative breast cancer (TNBC) and to verify these predictions through in vitro experiments. Initially, the Cell Counting Kit-8 (CCK8) assay was employed to rigorously investigate the influence of curcumin on the proliferative capacity of TNBC cells. Subsequently, flow cytometry was employed to meticulously assess the impact of curcumin on cellular apoptosis and the cell cycle regulation. Transwell assays were employed to meticulously evaluate the effect of curcumin on the motility of TNBC cells. RNA sequencing was conducted, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of differentially expressed genes, aiming to elucidate the potential anticancer mechanisms underlying curcumin's effects. To thoroughly elucidate the interactions among multiple proteins, we constructed a protein-protein interaction (PPI) network. Finally, the expression levels of several key proteins, including fibronectin, mTOR, ß-Catenin, p-Akt, Akt, N-Cadherin, p-S6, and S6, were assessed using the western blot. The CCK8 assay results showed that curcumin significantly inhibited the proliferation of Hs578T and MDA-MB-231 cells. Flow cytometry results showed that curcumin induced apoptosis in these cells and arrested the cell cycle at the G2/M phase. Additionally, Transwell assay results showed that curcumin effectively reduced the motility of Hs578T and MDA-MB-231 cells. Enrichment analysis of RNA sequencing data showed that the mechanism of action of curcumin was significantly associated with signaling pathways such as pathways in cancer, focal adhesion, and PI3K-Akt signaling pathways. Subsequently, we constructed a protein-protein interaction network to elucidate the interactions among multiple proteins. Finally, Western blotting analysis showed that curcumin significantly decreased the expression levels of key proteins including Fibronectin, mTOR, ß-Catenin, p-Akt, Akt, N-Cadherin, p-S6, and S6. Curcumin exhibits its therapeutic potential in TNBC by modulating multiple signaling pathways. It may inhibit the epithelial-mesenchymal transition process by downregulating the expression of proteins involved in the mTOR and PI3K-Akt signaling pathways, thereby suppressing the motility of TNBC cells. These findings provide experimental evidence for considering curcumin as a potential therapeutic strategy in the treatment of TNBC.