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Abstract Understanding the mechanisms of invasion and metastasis in head and neck squamous cell carcinoma (HNSCC) is crucial for effective treatment, particularly in metastatic cases. In this study, we analyzed multicenter bulk sequencing and comprehensive single-cell data from 702,446 cells, leading to the identification of a novel subtype of cancer-associated fibroblasts (CAFs), termed Secreted Frizzled-Related Protein2 CAFs (SFRP2_CAFs). These cells, originating from smooth muscle cells, display unique characteristics resembling both myofibroblastic CAFs and inflammatory CAFs, and are linked to poorer survival outcomes in HNSCC patients. Our findings reveal significant interactions between SFRP2_CAFs and SPP1 tumor-associated macrophages, which facilitate tumor invasion and metastasis. Moreover, our research identifies Nuclear factor I/X (NFIX) as a key transcription factor regulating SFRP2_CAFs behavior, confirmed through gene regulatory network analysis and simulation perturbation.

Equitable access to sanitation for all is a goal of sustainable development, notably in rural areas. However, studies including economic, socio-cultural, and other factors that have been conducted to comprehensively assess rural sanitation at the community level in developing countries are limited. This study aimed to investigate the current state of rural environmental sanitation on the community level and to evaluate the characteristics of the diverse sub-clusters. A multidimensional environmental sanitation survey was conducted on 400 communities in Chongqing, China in 2020, and the priority options for improving sub-clusters’ sanitation were explored using cluster analysis. Among all communities, more than 60 % had positive village appearance, 50.50 % had domestic sewage treatment, and the coverage rate of household sanitary toilets was 72.28 %. The average content for lead, cadmium (Cd), and chromium in soil was 26.01, 0.53, and 54.47 mg/kg, respectively. The communities were clustered into 3 groups (I, II, III) based on similar characteristics including basic information, village appearance, water, sanitation, hygiene management, bio-vector control, and soil pollution. The proportion of cluster I, II, and III was 39.25 % (157/400), 31.75 % (127/400), and 29.00 % (116/400), respectively. Each cluster had its sanitation characteristics, and significant differences among the sub-clusters were observed in Cd of soil (p = 0.001), domestic sewage disposal ratio (p

Abstract Background Depression is a global health priority. Maintaining and delaying depressive symptoms in older adults is a key to healthy aging. This study aimed to identify depressive symptom trajectories, predictors and mortality, while also exploring the relationship between air quality and depressive symptoms in older adults in the Hong Kong community over 14 years. Methods This study is a longitudinal study in Hong Kong. The target population was community-dwelling older adults over age 65. Depressive symptoms were measured by the Geriatric Depression Scale (GDS-15). Group-based trajectory model was used to identify heterogeneity in longitudinal changes over 14 years and examine the associations between baseline variables and trajectories for different cohort members using multinomial logistic regression. The Kaplan–Meier method was employed to conduct survival analysis and explore the variations in survival probabilities over time among different trajectory group. Linear mixed model was used to explore the relationship between air quality and depressive symptoms. Results A total of 2828 older adults were included. Three different trajectories of depressive symptoms in older people were identified: relatively stable (15.4%), late increase (67.1%) and increase (17.5%). Female, more number of chronic diseases, poor cognitive function, and poor health-related quality of life (HRQOL) were significantly associated with other less favorable trajectories compared with participants with stable levels of depressive symptoms. The late increase group had a lower mortality rate than the relatively stable and increased groups. Lower baseline ambient air pollutant exposure to NO2 over 14 years was significantly associated with fewer depressive symptoms. Conclusions In this study, we found that a late increase in depressive symptoms was the predominant trend in older Chinese people in Hong Kong. Poorer HRQOL was predictive of less favorable trajectories of depressive symptoms. Ambient air pollution was associated with depressive symptoms. This novel observation strengthens the epidemiological evidence of longitudinal changes in depressive symptoms and associations with late-life exposure to air pollution.

Abstract Background Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating muscle weakness. Despite the availability of established therapies, the management of MG symptoms remains suboptimal, partially attributed to lack of efficacy or intolerable side-effects. Therefore, new effective drugs are warranted for treatment of MG. Methods By employing an analytical framework that combines Mendelian randomization (MR) and colocalization analysis, we estimate the causal effects of blood druggable expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) on the susceptibility of MG. We subsequently investigated whether potential genetic effects exhibit cell-type specificity by utilizing genetic colocalization analysis to assess the interplay between immune-cell-specific eQTLs and MG risk. Results We identified significant MR results for four genes (CDC42BPB, CD226, PRSS36, and TNFSF12) using cis-eQTL genetic instruments and three proteins (CTSH, PRSS8, and CPN2) using cis-pQTL genetic instruments. Six of these loci demonstrated evidence of colocalization with MG susceptibility (posterior probability > 0.80). We next undertook genetic colocalization to investigate cell-type-specific effects at these loci. Notably, we identified robust evidence of colocalization, with a posterior probability of 0.854, linking CTSH expression in TH2 cells and MG risk. Conclusions This study provides crucial insights into the genetic and molecular factors associated with MG susceptibility, singling out CTSH as a potential candidate for in-depth investigation and clinical consideration. It additionally sheds light on the immune-cell regulatory mechanisms related to the disease. However, further research is imperative to validate these targets and evaluate their feasibility for drug development.

Background and aims: Momordica charantia L. (M. charantia) has been traditionally utilized as a medicinal intervention for managing type 2 diabetes mellitus (T2DM). The current study was designed to offer a GRADE-assessed systematic review and meta-analysis of randomized controlled trials (RCTs) examining the impact of M. Charantia intake on glycemic indexes and the lipid profile of patients with T2DM. Methods: A comprehensive search was conducted across several databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, from the inception of each database until April 22, 2023. The Hartung-Knapp adjustment was applied to ensure conservative summary estimates with broad confidence intervals. Results: A total of eight trials involving 423 patients with T2DM were included in this study. Compared to the control group, the intake of M. charantia supplementation resulted in significant reductions in fasting blood glucose (FBG) (WMD: −0.85 mmol/L; 95%CI: −1.44, −0.26; p = 0.005; I2 = 73.4 %), postprandial glucose (PPG) (WMD: −2.28 mmol/L; 95%CI: −3.35, −1.21; p = 0.000; I2 = 66.9 %), glycosylated hemoglobin A1c (HbA1c) (WMD: −0.38 %; 95%CI: −0.53, −0.23; p = 0.000; I2 = 37.6 %), and total cholesterol (TC) (WMD: −0.38 mmol/L; 95%CI: −0.70, −0.07; p = 0.017; I2 = 63.6 %). These results remained statistically significant even after applying the Hartung-Knapp adjustment. However, no significant differences were observed in terms of triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Conclusions: The findings of this study suggest that M. charantia could serve as a potential alternative for individuals with T2DM, particularly those with elevated total cholesterol levels. However, further high-quality studies are necessary to validate these results.

The radio imaging method (RIM) is a non-destructive detection technique widely used in geophysical surveys and monitoring. However, it currently faces challenges in accurately detecting geological anomalies. To enhance detection accuracy, we propose a novel approach that integrates forward modeling and the deep learning UNet semantic segmentation architecture, termed the FM-UNet method. We first construct a forward model that reflects the geological characteristics of the target exploration area and validate it using field RIM survey data. Next, we use the RIM data generated from the forward model for inversion and construct the training dataset. Finally, we apply the deep learning UNet architecture to accurately predict the locations of geological anomalies within the exploration region. Our results demonstrate that the FM-UNet method effectively reduces the false geological anomaly (FGA) areas and significantly improves detection accuracy compared to traditional methods. Additionally, we compared the performance of four UNet architectures, with the Transformer UNet achieving the best results: the average ratio of FGA decreased by 37.37%, and the mean intersection over union (IoU) and average F1 score increased by 24.26% and 23.78%, respectively, confirming the feasibility of our approach.

Abstract Background The effect of different dual antiplatelet therapies on thrombotic events on the background of intravascular ultrasound (IVUS) guidance is unclear. We investigated whether ticagrelor can provide any additional benefit to clopidogrel in reducing thrombotic events in acute coronary syndrome (ACS) treated with drug- eluting stent (DES), when guided by IVUS or not. Methods A total of 5,666 ACS patients who underwent DES implantation and who were discharged on dual antiplatelet therapy were enrolled and grouped according to the use of IVUS or not. Each group was subdivided into two subgroups according to the type of P2Y12 inhibitor used after discharge. Propensity score matching (PSM) was used between the IVUS and no-IVUS groups. Covariate adjustment of Cox proportional hazards model was used between the ticagrelor and clopidogrel groups. Thrombotic event at 12 months was compared in groups separately. Results After PSM, 12-month follow-up data were available for 1,174 patients. Major adverse cardiac events (MACE) were less frequent in the IVUS-guided group (2.2% vs. 4.3%, P = 0.081) with a trend toward statistical significance. Comparison of antiplatelet regimens revealed significantly fewer major adverse cardiac and cerebrovascular events (MACCE) with ticagrelor in the entire PSM cohort and angiography-guided subgroup (2.9% vs. 5.7%, P = 0.035; 3.1% vs. 6.4%, P = 0.020, respectively). Among patients in the IVUS-guided group the outcome was comparable (2.5% vs. 4.4%, P = 0.312). Ticagrelor was associated with increasing bleeding incidence in the entire PSM cohort (1.3% vs. 3.3%, P = 0.030), mainly due to Bleeding Academic Research Consortium type 2 bleeding (0.7% vs. 2.6%, P = 0.010). The results were consistent after covariate adjustment of Cox proportional hazards model. Conclusion The comparison of ischemic benefit between ticagrelor and clopidogrel was similar in patients receiving IVUS guidance during stent implantation, probably due to the precise implantation of IVUS. Multicenter, randomized studies should be performed to validate this conclusion.

Abstract Background Hepatocellular carcinoma (HCC) remains a leading life-threatening health challenge worldwide, with pressing needs for novel therapeutic strategies. Sphingosine kinase 1 (SphK1), a well-established pro-cancer enzyme, is aberrantly overexpressed in a multitude of malignancies, including HCC. Our previous research has shown that genetic ablation of Sphk1 mitigates HCC progression in mice. Therefore, the development of PF-543, a highly selective SphK1 inhibitor, opens a new avenue for HCC treatment. However, the anti-cancer efficacy of PF-543 has not yet been investigated in primary cancer models in vivo, thereby limiting its further translation. Methods Building upon the identification of the active form of SphK1 as a viable therapeutic target in human HCC specimens, we assessed the capacity of PF-543 in suppressing tumor progression using a diethylnitrosamine-induced mouse model of primary HCC. We further delineated its underlying mechanisms in both HCC and endothelial cells. Key findings were validated in Sphk1 knockout mice and lentiviral-mediated SphK1 knockdown cells. Results SphK1 activity was found to be elevated in human HCC tissues. Administration of PF-543 effectively abrogated hepatic SphK1 activity and significantly suppressed HCC progression in diethylnitrosamine-treated mice. The primary mechanism of action was through the inhibition of tumor neovascularization, as PF-543 disrupted endothelial cell angiogenesis even in a pro-angiogenic milieu. Mechanistically, PF-543 induced proteasomal degradation of the critical glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3, thus restricting the energy supply essential for tumor angiogenesis. These effects of PF-543 could be reversed upon S1P supplementation in an S1P receptor-dependent manner. Conclusions This study provides the first in vivo evidence supporting the potential of PF-543 as an effective anti-HCC agent. It also uncovers previously undescribed links between the pro-cancer, pro-angiogenic and pro-glycolytic roles of the SphK1/S1P/S1P receptor axis. Importantly, unlike conventional anti-HCC drugs that target individual pro-angiogenic drivers, PF-543 impairs the PFKFB3-dictated glycolytic energy engine that fuels tumor angiogenesis, representing a novel and potentially safer therapeutic strategy for HCC.

Multiple sclerosis (MS) was defined as a rare disease in China due to its low prevalence. For a long time, interferon β was the only approved disease-modifying therapy (DMT). Since the first oral DMT was approved in 2018, DMT approval accelerated, and seven DMTs were approved within 5 years. With an increasing number of DMTs being prescribed in clinical practice, it is necessary to discuss the standardized MS treatment algorithms depending on the disease activity and DMT availability. In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country.

BackgroundMiddle-aged and older adults frequently experience hearing loss and a decline in cognitive function. Although an association between hearing difficulty and cognitive function has been demonstrated, its temporal sequence remains unclear. Therefore, we investigated whether there are bidirectional relationships between hearing difficulty and cognitive function and explored the mediating role of depressive symptoms in this relationship.MethodWe used the cross-lagged panel model and the random-intercept cross-lagged panel model to look for any possible two-way link between self-reported hearing difficulty and cognitive function. To investigate depressive symptoms’ role in this association, a mediation analysis was conducted. The sample was made up of 4,363 adults aged 45 and above from the China Health and Retirement Longitudinal Study (CHARLS; 2011–2018; 44.83% were women; mean age was 56.16 years). One question was used to determine whether someone had a hearing impairment. The tests of cognitive function included episodic memory and intelligence. The Center for Epidemiologic Studies Depression Scale, which consists of 10 items, was used to measure depressive symptoms.ResultsA bidirectional association between hearing and cognition was observed, with cognition predominating (Wald χ2 (1) = 7.241, p

SKD11 has a wide range of applications in the tooling industry. However, due to its high mechanical strength and hardness, it is a difficult material to machine. To address the issues of low machining efficiency, severe tool electrode wear, and environmental pollution caused by traditional EDM, this paper proposes a more efficient and sustainable method of EDM production called short electric arc machining (SEAM). This paper discussed the mechanism of material removal by a short electric arc and then conducted experiments on SKD11 machining with various voltage parameters using a self-designed short electric arc milling machine, analysing the material removal rate (MRR), relative tool electrode wear ratio (REWR), and specific energy consumption (SEC) of the machined workpiece. The experimental results indicate that the maximum removal rate is 15,745 mm3/min, the REWR is significantly reduced to 1.4 %, and the energy consumption ratio is 76.84 KJ/cm3. Finally, the microscopic morphology and elemental composition of the workpiece and tool electrode were analyzed by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS), and the variation of cross-sectional grains was analyzed by electron backscatter diffraction (EBSD).It can be concluded that the short-arc milling method discussed in this paper can provide an efficient machining method for difficult-to-machine materials.

Identifying the types and vertical distribution of aerosols plays a significant role in evaluating the influence of aerosols on the climate system. Based on the aerosol optical properties obtained from Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO), this study analyzed the long-term aerosol characteristics of seven cities in East Asia (Ulaanbaatar, Beijing, Lanzhou, Shanghai, Lhasa, Hong Kong, and Bangkok) from 2007 to 2021, including the spatiotemporal variations of aerosol optical depth (AOD), the vertical stratification characteristics of aerosols, and the main aerosol subtype. The results showed that, except for Lhasa, the AOD values of all cities exhibited a trend of initially increasing and then decreasing over the years. Except for Shanghai, the high values of AOD in the other cities occurred in the spring and summer seasons, while the low values occurred in the autumn and winter seasons. In all four seasons, the AOD contribution within the 1–3 km range accounted for more than 50% of the total. In the autumn and winter seasons, this proportion reached over 80%. The main types of aerosols and their contributions varied at different altitudes. Overall, dust, polluted continental/smoke, polluted dust, and elevated smoke dominated in all aerosol layers across each city. On the other hand, clean marine, clean continental, and dusty marine had very small proportions, accounting for less than 5% of all the cities’ aerosol layers.

Although many carriers for the delivery of chemotherapeutic drugs have been investigated, the disadvantages of passive targeting and uncontrolled drug release limit their utility. Herein, hyaluronic acid (HA) was hydrophobically modified to serve as a carrier for binding to cluster determinant 44 (CD44) overexpressed on tumor cell surfaces. Specifically, after deacetylation, HA was grafted to dodecylamine or tetradecylamine to afford amphiphilic zwitterionic polymer micelles, designated dHAD and dHAT, respectively, for the delivery of paclitaxel (PTX). The micelles were negatively charged at pH 7.4 and positively charged at pH 5.6, and this pH sensitivity facilitated PTX release under acidic conditions. The cell uptake efficiencies of the dHAD-PTX and dHAT-PTX micelles by MCF-7 cells after 4 h of incubation were 96.9% and 95.4%, respectively, and their affinities for CD44 were twice that of HA. Furthermore, the micelles markedly inhibited tumor growth both in vitro and in vivo, with IC50 values of 1.943 μg/mL for dHAD-PTX and 1.874 μg/mL for dHAT-PTX for MCF-7 cells; the tumor inhibition rate of dHAD-PTX (92.96%) was higher than that of dHAT-PTX (78.65%). Importantly, dHAD and dHAT micelles showed negligible systemic toxicity. Our findings suggest that these micelles are promising delivery vehicles for antitumor drugs.

Natural products are one of the essential sources of innovative drugs. Trigothysoid N, a natural daphnane diterpenoid obtained from Trigonostemon thyrsoideus, possessed the strong ability to inhibit the proliferation of A549 cells. Besides interrupting the cell cycle, the mechanism examination revealed that trigothysoid N can inhibit tumor proliferation and migration by targeting mitochondria, regulating the STAT3/FAK signal pathway, and suppressing angiogenesis. In addition to the possible mechanism, in vivo antitumor experiments were performed to explore the potential of trigothysoid N for treating non-small cell lung cancer (NSCLC). Collectively, these findings supported the great potential of trigothysoid N as a hopeful therapeutic agent against NSCLC.

Abstract Background Urinary incontinence is an increasingly common problem, especially among older people in nursing homes. Nursing assistants are the leading workforce in nursing homes, and their knowledge and attitudes regarding urinary incontinence have garnered considerable attention in the context of aging in China. However, most previous studies on this issue have focused on registered nurses. This study aimed to explore nursing assistants’ knowledge, attitudes and training needs with regard to urinary incontinence. Methods We conducted a two-part mixed-methods study. After institutional manager approval, we surveyed the knowledge and attitudes of 509 nursing assistants regarding urinary incontinence. We carried out semi-structured interviews with 40 nursing assistants to elicit detailed information on training needs. Results In general, knowledge about urinary incontinence was poor (14.00 ± 4.18), although attitudes were primarily positive (35.51 ± 3.19). Most nursing assistants were very willing to learn more about urinary incontinence (93.9%, 478/509), but time constraints and low educational background may be barriers to learning motivation. The three preferred training styles among nursing assistants were face-to-face guidance from a mentor, training combining theory with practice, and online video training. Conclusions Chinese nursing assistants had poor knowledge but positive attitudes toward urinary incontinence. Facility managers should focus on developing training and learning mechanisms regarding urinary incontinence. It is important to adopt diverse training styles according to the actual situation of nursing homes.

Abstract Raman spectra of two series of InAs/AlAs short-period superlattices were measured at room temperature to investigate the impact of strain on the phonon modes taking into consideration the confinement effect and interface mode. The evolution of strain in the InAs layer and the AlAs layer was studied in (InAs)2/(AlAs)2 superlattices grown at various temperatures (400–550 °C). While the strain existed in the AlAs layer remained almost constant, the strain in the InAs layer varied significantly as the growth temperature increased from 500 to 550 °C. The confinement effect on the optical phonons was analyzed based on results from (InAs)n/(AlAs)n grown at 450 °C (n = 2, 3, 4, and 5). Additionally, the confinement effect was found to be stronger in shorter periods with higher interface quality. The interface phonon modes were resolved between the longitudinal optical and transverse optical phonon modes, which assist in the rough estimation of the thickness of the layers. The disorder-activated acoustic phonon modes at the low-frequency side were also addressed.

Abstract Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancer, the third leading cause of cancer-associated death worldwide. With the increasing prevalence of metabolic conditions, non-alcoholic fatty liver disease (NAFLD) is emerging as the fastest-growing HCC risk factor, and it imposes an additional layer of difficulty in HCC management. Dysregulated hepatic lipids are generally believed to constitute a deleterious environment cultivating the development of NAFLD-associated HCC. However, exactly which lipids or lipid regulators drive this process remains elusive. We report herein that sphingosine kinase 2 (SphK2), a key sphingolipid metabolic enzyme, plays a critical role in NAFLD-associated HCC. Ablation of Sphk2 suppressed HCC development in NAFLD livers via inhibition of hepatocyte proliferation both in vivo and in vitro. Mechanistically, SphK2 deficiency led to downregulation of ceramide transfer protein (CERT) that, in turn, decreased the ratio of pro-cancer sphingomyelin (SM) to anti-cancer ceramide. Overexpression of CERT restored hepatocyte proliferation, colony growth and cell cycle progression. In conclusion, the current study demonstrates that SphK2 is an essential lipid regulator in NAFLD-associated HCC, providing experimental evidence to support clinical trials of SphK2 inhibitors as systemic therapies against HCC.

To solve error propagation and exorbitant computational complexity of signal detection in wireless multiple-input multiple-output-orthogonal frequency division multiplexing (MIMO-OFDM) systems, a low-complex and efficient signal detection with iterative feedback is proposed via a constellation point feedback optimization of minimum mean square error-ordered successive interference cancellation (MMSE-OSIC) to approach the optimal detection. The candidate vectors are formed by selecting the candidate constellation points. Additionally, the vector most approaching received signals is chosen by the maximum likelihood (ML) criterion in formed candidate vectors to reduce the error propagation by previous erroneous decision, thus improving the detection performance. Under a large number of matrix inversion operations in the above iterative MMSE process, effective and fast signal detection is hard to be achieved. Then, a symmetric successive relaxation iterative algorithm is proposed to avoid the complex matrix inversion calculation process. The relaxation factor and initial iteration value are reasonably configured with low computational complexity to achieve good detection close to that of the MMSE with fewer iterations. Simultaneously, the error diffusion and complexity accumulation caused by the successive detection of the subsequent OSIC scheme are also improved. In addition, a method via a parallel coarse and fine detection deals with several layers to both reduce iterations and improve performance. Therefore, the proposed scheme significantly promotes the MIMO-OFDM performance and thus plays an irreplaceable role in the future sixth generation (6G) mobile communications and wireless sensor networks, and so on.

Abstract Background Screening is often recommended as a first step in frailty management. Many guidelines call to implicate frailty screening into practice in the primary care setting. However, few countries or organizations implement it. Understanding and clarifying the stakeholders’ views and issues faced by the implementation is essential to the successful implementation of frailty screening. However, the systematic review on stakeholders’ views of frailty screening in primary care is decidedly limited. Our objective was to explore the perspective of older adults, caregivers, and healthcare providers on frailty screening and determine the enablers and barriers to implementing frailty screening in primary care. Methods A systematic search of six databases and other resources was conducted following JBI’s three-step search strategy. The search resulted in 7362 articles, of which 97 were identified for further assessment according to the inclusion criteria. After the full-text screening, quality assessment and data extraction were carried out using the tools from Joanna Briggs Institute (JBI). Moreover, reviewers used the approach of meta-aggregative of JBI to analyze data and synthesis the findings. Results Six studies were included. A total of 63 findings were aggregated into 12 categories and then further grouped into three synthesized findings:1) capacity of healthcare providers and older adults; 2) opportunity in the implementation of frailty screening; 3) motivation in the implementation of frailty screening. These themes can help identify what influences the implementation of screening from the perspective of stakeholders. Conclusions This meta-synthesis provides evidence on the barriers and enablers of frailty screening in primary care, from the aspects of psychological, physical, social, material, etc. However, stakeholder perspectives of frailty screening have not been adequately studied. More research and efforts are needed to explore the influencing factors and address the existing barriers.

Background: A hallmark signature of the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC) is abundantly infiltration of cancer-associated fibroblasts (CAFs), which facilitate HNSCC progression. However, some clinical trials showed targeted CAFs ended in failure, even accelerated cancer progression. Therefore, comprehensive exploration of CAFs should solve the shortcoming and facilitate the CAFs targeted therapies for HNSCC.Methods: In this study, we identified two CAFs gene expression patterns and performed the single‐sample gene set enrichment analysis (ssGSEA) to quantify the expression and construct score system. We used multi-methods to reveal the potential mechanisms of CAFs carcinogenesis progression. Finally, we integrated 10 machine learning algorithms and 107 algorithm combinations to construct most accurate and stable risk model. The machine learning algorithms contained random survival forest (RSF), elastic network (Enet), Lasso, Ridge, stepwise Cox, CoxBoost, partial least squares regression for Cox (plsRcox), supervised principal components (SuperPC), generalised boosted regression modelling (GBM), and survival support vector machine (survival-SVM).Results: There are two clusters present with distinct CAFs genes pattern. Compared to the low CafS group, the high CafS group was associated with significant immunosuppression, poor prognosis, and increased prospect of HPV negative. Patients with high CafS also underwent the abundant enrichment of carcinogenic signaling pathways such as angiogenesis, epithelial mesenchymal transition, and coagulation. The MDK and NAMPT ligand–receptor cellular crosstalk between the cancer associated fibroblasts and other cell clusters may mechanistically cause immune escape. Moreover, the random survival forest prognostic model that was developed from 107 machine learning algorithm combinations could most accurately classify HNSCC patients.Conclusion: We revealed that CAFs would cause the activation of some carcinogenesis pathways such as angiogenesis, epithelial mesenchymal transition, and coagulation and revealed unique possibilities to target glycolysis pathways to enhance CAFs targeted therapy. We developed an unprecedentedly stable and powerful risk score for assessing the prognosis. Our study contributes to the understanding of the CAFs microenvironment complexity in patients with head and neck squamous cell carcinoma and serves as a basis for future in-depth CAFs gene clinical exploration.

BackgroundWe developed a novel system for quantifying DNA damage response (DDR) to help diagnose and predict the risk of Alzheimer’s disease (AD).MethodsWe thoroughly estimated the DDR patterns in AD patients Using 179 DDR regulators. Single-cell techniques were conducted to validate the DDR levels and intercellular communications in cognitively impaired patients. The consensus clustering algorithm was utilized to group 167 AD patients into diverse subgroups after a WGCNA approach was employed to discover DDR-related lncRNAs. The distinctions between the categories in terms of clinical characteristics, DDR levels, biological behaviors, and immunological characteristics were evaluated. For the purpose of choosing distinctive lncRNAs associated with DDR, four machine learning algorithms, including LASSO, SVM-RFE, RF, and XGBoost, were utilized. A risk model was established based on the characteristic lncRNAs.ResultsThe progression of AD was highly correlated with DDR levels. Single-cell studies confirmed that DDR activity was lower in cognitively impaired patients and was mainly enriched in T cells and B cells. DDR-related lncRNAs were discovered based on gene expression, and two different heterogeneous subtypes (C1 and C2) were identified. DDR C1 belonged to the non-immune phenotype, while DDR C2 was regarded as the immune phenotype. Based on various machine learning techniques, four distinctive lncRNAs associated with DDR, including FBXO30-DT, TBX2-AS1, ADAMTS9-AS2, and MEG3 were discovered. The 4-lncRNA based riskScore demonstrated acceptable efficacy in the diagnosis of AD and offered significant clinical advantages to AD patients. The riskScore ultimately divided AD patients into low- and high-risk categories. In comparison to the low-risk group, high-risk patients showed lower DDR activity, accompanied by higher levels of immune infiltration and immunological score. The prospective medications for the treatment of AD patients with low and high risk also included arachidonyltrifluoromethane and TTNPB, respectively,ConclusionsIn conclusion, immunological microenvironment and disease progression in AD patients were significantly predicted by DDR-associated genes and lncRNAs. A theoretical underpinning for the individualized treatment of AD patients was provided by the suggested genetic subtypes and risk model based on DDR.

This paper proposes an improved frequency domain turbo equalization (IFDTE) with iterative channel estimation and feedback to achieve both a good performance and low complexity in underwater acoustic communications (UWACs). A selective zero-attracting (SZA) improved proportionate normal least mean square (SZA-IPNLMS) algorithm is adopted by utilizing the sparsity of the UWAC channel to estimate it using a training sequence. Simultaneously, a set-membership (SM) SZA differential IPNLMS (SM SZA-DIPNLMS) with variable step size is adopted to estimate the channel status information (CSI) in the iterative channel estimation with soft feedback. In this way, the computational complexity for iterative channel estimation is reduced effectively with minimal performance loss. Different from traditional schemes in UWACs, an IFDTE with expectation propagation (EP) interference cancellation is adopted to estimate the a posteriori probability of transmitted symbols iteratively. A bidirectional IFDTE with the EP interference cancellation is proposed to further accelerate the convergence. THe simulation results show that the proposed channel estimation obtains 1.9 and 0.5 dB performance gains, when compared with those of the IPNLMS and the l0-IPNLMS at a bit error rate (BER) of 10−3. The proposed channel estimation also effectively reduces the unnecessary updating of the coefficients of the UWAC channel. Compared with traditional time-domain turbo equalization and FDTE in UWACs, the IFDTE obtains 0.5 and 1 dB gains in the environment of SPACE’08 and it obtains 0.5 and 0.4 dB gains in the environment of MACE’04 at a BER of 10−3. Therefore, the proposed scheme obtains a good BER performance and low complexity and it is suitable for efficient use in UWACs.

Background: Immune-checkpoint blockade (ICB) has been routinely implemented to treat head and neck squamous cell carcinoma (HNSCC) patients. However, only a few patients benefit from immune checkpoint inhibitor (ICI) therapies.Methods: In this study, we used a combined cohort (including the GSE41613, GSE65858, TCGA, and CELL cohorts) to identify hub genes significantly associated with ICB and activated CD8+ T-cell gene signatures. We performed single‐sample gene set enrichment analysis (ssGSEA) to quantify the expression of hub genes; we then constructed a novel immune signature named “the IMS” that can predict immunotherapy responsiveness, prognosis, immune infiltration, and clinical characteristics. Data from the GSE102349 external cohort and the pembrolizumab cohort obtained from a clinical trial were used to validate the efficiency of the IMS. In addition, we revealed potential mechanisms of the antitumor response by analyzing the HNSCC single-cell database. Finally, we used the LASSO algorithm to build an IMS-related risk model.Results: The high IMS group was associated with significant immune activation, better prognosis, and increased immunotherapy responsiveness; thus, the IMS potentially represents a candidate biomarker for ICB. Moreover, a tumor microenvironment with a higher IMS underwent remarkable metabolic reprogramming characterized by enrichment in the glycolysis/gluconeogenesis, oxidative phosphorylation, and citrate cycle (TCA cycle) pathways. We also revealed key information on cellular crosstalk between the IMS and other immune lineages, which may mechanistically explain immune escape. In addition, we constructed and validated a risk prediction model (CD2, TBC1D10C, and CD3E) that could stratify HNSCC patients based on survival and response to ICB treatment.Conclusion: IMS is a signature closely correlated with the tumor immune microenvironment. The findings of this study contribute to the understanding of the immune landscape in HNSCC patients. IMS may aid in the clinical management of HNSCC patients through the identification of effective immunotherapies for specific patients.