Developing a nomogram for preoperative prediction of cervical cancer lymph node metastasis by multiplex immunofluorescence.

BACKGROUND: Most traditional procedures can destroy tissue natural structure, and the information on spatial distribution and temporal distribution of immune milieu in situ would be lost. We aimed to explore the potential mechanism of pelvic lymph node (pLN) metastasis of cervical cancer (CC) by multiplex immunofluorescence (mIF) and construct a nomogram for preoperative prediction of pLN metastasis in patients with CC. METHODS: Patients (180 IB1-IIA2 CC patients of 2009 FIGO (International Federation of Gynecology and Obstetrics)) were divided into two groups based on pLN status. Tissue microarray (TMA) was prepared and tumor-infiltrating immune markers were assessed by mIF. Multivariable logistic regression analysis and nomogram were used to develop the predicting model. RESULTS: Multivariable logistic regression analysis constructs a predictive model and the area under the curve (AUC) can reach 0.843. By internal validation with the remaining 40% of cases, a new ROC curve has emerged and the AUC reached 0.888. CONCLUSIONS: This study presents an immune nomogram, which can be conveniently used to facilitate the preoperative individualized prediction of LN metastasis in patients with CC.

A Systematic Review and Meta-analysis of Atherectomy Plus Balloon Angioplasty Versus Balloon Angioplasty Alone for Infrapopliteal Arterial Disease.

OBJECTIVE: The article aimed to compare the efficiency and safety of atherectomy plus balloon angioplasty (BA) with BA alone for the treatment of infrapopliteal arterial disease. METHODS: According to the inclusion and exclusion criteria, PubMed, Embase, and Cochrane Library database were searched for studies comparing atherectomy plus angioplasty and angioplasty alone in treating infrapopliteal artery lesions until November 2022. The endpoints included technical success, primary patency, clinically-driven target lesion revascularization (CD-TLR), periprocedural complications, distal embolization, target limb major amputation, and all-cause mortality. RESULTS: Ten studies met the requirements of our meta-analysis, including 7723 patients in the atherectomy plus BA group and 2299 patients in the BA alone group. The meta-analysis showed that atherectomy plus BA was associated with reduced CD-TLR (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.34, 0.78, p=0.002) and target limb major amputation (OR: 0.43, 95% CI: 0.19, 1.01, p=0.05) at 12-month follow-up. No statistically significant difference was found in technical success, primary patency, periprocedural complications, distal embolization, or all-cause mortality. Subgroup analysis found a higher rate of primary patency at 6 and 12 months (6 months: OR: 2.26, 95% CI: 1.11, 4.60, p=0.02; 12 months: OR: 2.38, 95% CI: 1.16, 4.86, p=0.02), and lower rates of CD-TLR (OR: 0.45, 95% CI: 0.25, 0.82, p=0.009) and target limb major amputation (OR: 0.43, 95% CI: 0.19, 1.01, p=0.05) at 12 months in patients treated with atherectomy plus drug-coated balloon (DCB) but not in patients treated with atherectomy plus plain old balloon angioplasty (POBA). CONCLUSIONS: This meta-analysis suggests that compared with BA alone, atherectomy plus BA may reduce the need for CD-TLR and the incidence of target limb major amputation at 12-month follow-up in the treatment of infrapopliteal artery occlusive lesions, even though there are no significant advantages in technical success, primary patency, periprocedural complications, distal embolization, or all-cause mortality. To go further, atherectomy plus DCB shows significant benefits in primary patency, CD-TLR, and target limb major amputation rate but atherectomy plus POBA does not'. However, due to the limitations of this article, more randomized controlled trials (RCTs) are needed to confirm these conclusions. CLINICAL IMPACT: According to our research, atherectomy combined with BA has the advantages of higher primary patency rate, lower CD-TLR and target limb significant amputation rate in treating infrapopliteal artery occlusive lesions, which may replace the current mainstream surgical method ---BA alone. For the clinician, although the surgery may take longer, it will significantly improve the prognosis and quality of life of patients and hold considerable significance for the management of patients with infrapopliteal arterial disease. Based on the characteristics of infrapopliteal artery disease, this study explored the feasibility of atherectomy combined with BA for infrapopliteal artery disease. Moreover, we found that atherectomy combined with DCB had better clinical efficacy, which should be the innovation of this study.

Ox-LDL-Induced Vascular Smooth Muscle Cell Dysfunction Partly Depends on the Circ_0044073/miR-377-3p/AURKA Axis in Atherosclerosis.

Atherosclerosis (AS) is the main reason for most cardiovascular diseases. Circular RNA hsa_circ_0044073 (circ_0044073) has been found to promote AS progression. However, the specific regulatory mechanism of circ_0044073 in AS progression remains unclear.In this study, oxidized low-density lipoprotein (Ox-LDL) -stimulated human vascular smooth muscle cells (VSMCs) were used as AS cell models. The expression changes of circ_0044073 in serum samples and Ox-LDL-stimulated human VSMCs were assessed via real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability, proliferation, colony formation, migration, and invasion were assessed using 3- (4,5-Dimethylthiazol-2-yl) -2,5-Diphenyltetrazolium Bromide (MTT), 5-ethynyl-2'-deoxyuridine (EDU), colony formation, and transwell assays. Some protein levels were detected via Western blotting. The regulatory mechanism of circ_0044073 was predicted using bioinformatics analysis and validated by dual-luciferase reporter and RNA pull-down assays.We observed an overt increase in circ_0044073 expression in serum samples derived from AS patients and Ox-LDL-stimulated human VSMCs. Circ_0044073 was identified as a miR-377-3p sponge. Either circ_0044073 knockdown or miR-377-3p overexpression could impair Ox-LDL-induced human VSMC proliferation, migration, invasion, and inflammation. AURKA served as a miR-377-3p target, and circ_0044073 regulated AURKA expression by adsorbing miR-377-3p. Furthermore, AURKA overexpression partly reversed the effects of circ_0044073 inhibition on Ox-LDL-induced human VSMC proliferation, migration, invasion, and inflammation.Circ_0044073 promoted AS progression by elevating AURKA expression by functioning as a miR-377-3p sponge. Providing a proof-of-concept demonstration to support circ_0044073 might be a target for AS treatment.

Maternal Common Cold or Fever During Pregnancy and the Risk of Orofacial Clefts in the Offspring: A Systematic Review and Meta-analysis.

The common cold and/or an associated fever during pregnancy have/has been suspected to harm the developing fetus. We sought possible correlations between a maternal common cold or fever during pregnancy and the risk of orofacial clefts in the offspring.We systematically searched PubMed and Embase using appropriate keywords, and we checked the reference lists of retrieved articles. We used random-effects models to estimate overall relative risks.Incidence of orofacial clefts.We included 13 case-control studies. Modest but statistically significant associations were found between a maternal common cold and cleft lip with or without a cleft palate (CL/CP) (odds ratio [OR] 2.17; 95% confidence interval [CI] 1.66-2.83) and a cleft palate only (CPO) (OR 3.08; 95% CI 1.5-6.34). Furthermore, maternal fever was also associated with an increased risk of CL/CP (OR 1.91, 95% CI 1.3-2.8) and CPO (OR 1.48, 95% CI 0.83-2.63) in the offspring. Further analyses of maternal influenza (alone) yielded similar results.Although evidence of heterogeneity should be carefully evaluated, our findings suggest that maternal common cold or fever during pregnancy may be associated with a greater risk of CL/CP or CPO in the offspring. Future cohort studies using valid assessments of maternal common cold exposure during pregnancy that consider the severity of fever are needed to clarify the contribution of maternal common cold or fever status to the risk of orofacial clefts in children.

Mechanism of sensitivity to cisplatin, docetaxel, and 5-fluorouracil chemoagents and potential erbB2 alternatives in oral cancer with growth differentiation factor 15 overexpression.

The aim of this study was to: (a) explore the potential mechanism of cancer cell sensitivity to cisplatin, docetaxel, and 5-fluorouracil (TPF) in oral squamous cell carcinoma (OSCC) patients overexpressing growth differentiation factor 15 (GDF15); and (b) identify potential alternative agents for patients who might not benefit from inductive TPF chemotherapy. The results indicated that OSCC cells overexpressing GDF15 were sensitive to TPF through a caspase-9-dependent pathway both in vitro and in vivo. Immunoprecipitation combined with mass spectrometry revealed that the erbB2 protein was a potential GDF15-binding protein, which was verified by coimmunoprecipitation. Growth differentiation factor 15 overexpression promoted OSCC cell proliferation through erbB2 phosphorylation, as well as downstream AKT and Erk signaling pathways. When GDF15 expression was blocked, the phosphorylation of both the erbB2 and AKT/Erk pathways was downregulated. When OSCC cells with GDF15 overexpression were treated with the erbB2 phosphorylation inhibitor, CI-1033, cell proliferation and xenograft growth colony formation were significantly blocked (P < .05). Thus, GDF15-overexpressing OSCC tumors are sensitive to TPF chemoagents through caspase-9-dependent pathways. Growth differentiation factor 15 overexpression promotes OSCC proliferation through erbB2 phosphorylation. Thus, ErbB2 inhibitors could represent potential targeted drugs or an alternative therapy for OSCC patients with GDF15 overexpression.

Overcoming chemotherapy resistance using pH-sensitive hollow MnO2 nanoshells that target the hypoxic tumor microenvironment of metastasized oral squamous cell carcinoma.

BACKGROUND: Smart nanoscale drug delivery systems that target acidic tumor microenvironments (TME) could offer controlled release of drugs and modulate the hypoxic TME to enhance cancer therapy. The majority of previously reported MnO2 nanostructures are nanoparticles, nanosheets, or nanocomposites incorporated with other types of nanoparticles, which may not offer the most effective method for drug loading or for the controlled release of therapeutic payloads. Previous studies have designed MnO2 nanoshells that achieve tumor-specific and enhanced combination therapy for localized advanced cancer. However, the therapeutic effect of MnO2 nanoshells on metastatic cancer is still uncertain. RESULT: Here, intelligent "theranostic" platforms were synthesized based on hollow mesoporous MnO2 (H-MnO2) nanoshells that were loaded with chemotherapy agents docetaxel and cisplatin (TP) to form H-MnO2-PEG/TP nanoshells, which were designed to alleviate tumor hypoxia, attenuate angiogenesis, trigger the dissolution of Mn2+, and synergize the efficacy of first-class anticancer chemotherapy. The obtained H-MnO2-PEG/TP nanoshells decomposed in the acidic TME, releasing the loaded drugs (TP) and simultaneously attenuated tumor hypoxia and hypoxia-inducible factor-1α (HIF-1α) expression by inducing endogenous tumor hydrogen peroxide (H2O2) decomposition. In vitro experiments showed that compared with the control group, the proliferation, colony formation and migration ability of CAL27 and SCC7 cells were significantly reduced in H-MnO2-PEG/TP group, while cell apoptosis was enhanced, and the expression of hypoxia-inducible factor-1α(HIF-1α) was down-regulated. In vivo experiments showed that tumor to normal organ uptake ratio (T/N ratio) of mice in H-MnO2-PEG/TP group was significantly higher than that in TP group alone (without the nanoparticle), and tumor growth was partially delayed. In the H-MnO2-PEG/TP treatment group, HE staining showed that most of the tumor cells were severely damaged, and TUNEL assay showed cell apoptosis was up-regulated. He staining of renal and liver sections showed no obvious fibrosis, necrosis or hypertrophy, indicating good biosafety. Fluorescence staining showed that HIF-1α expression was decreased, suggesting that the accumulation of MnO2 in the tumor caused the decomposition of H2O2 into O2 and alleviated the hypoxia of the tumor. CONCLUSION: In conclusion, a remarkable in vivo and in vitro synergistic therapeutic effect is achieved through the combination of TP chemotherapy, which simultaneously triggered a series of antiangiogenic and oxidative antitumor reactions.

Stathmin guides personalized therapy in oral squamous cell carcinoma.

The survival benefit from docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy in oral squamous cell carcinoma (OSCC) patients is not satisfactory. Previously, we identified that stathmin, a microtubule-destabilizing protein, is overexpressed in OSCC. Here, we further investigated its role as a biomarker that impacts on OSCC chemosensitivity. We analyzed the predictive value of stathmin on TPF induction chemotherapy and its impact on OSCC cell chemosensitivity. Then, we further investigated the therapeutic effects of the combination therapy of TPF chemotherapy and PI3K-AKT-mTOR inhibitors in vitro and in vivo. We found that OSCC patients with low stathmin expression benefited from TPF induction chemotherapy, while OSCC patients with high stathmin expression could not benefit from TPF induction chemotherapy. Stathmin overexpression promoted cellular proliferation and decreased OSCC cell sensitivity to TPF treatment. In addition, inhibition of the PI3K-AKT-mTOR signaling pathway decreased stathmin expression and phosphorylation. The combination therapy of TPF chemotherapy and PI3K-AKT-mTOR inhibitors exhibited a potent antitumor effect both in vitro and in vivo. Therefore, stathmin can be used as a predictive biomarker for TPF induction chemotherapy and a combination therapy regimen based on stathmin expression might improve the survival of OSCC patients.

High-risk lymph node ratio predicts worse prognosis in patients with locally advanced oral cancer.

BACKGROUND: To investigate the prognostic value of lymph node ratio (LNR), as well as the correlation with docetaxel, cisplatin, and 5-FU (TPF) induction chemotherapy, in patients with locally advanced oral squamous cell carcinoma (OSCC). METHODS: Two-hundred and forty-five patients from a phase 3 trial involving TPF induction chemotherapy in stage III/IVA OSCC patients (NCT01542931) were enrolled in this study between 2008 and 2010. The clinical and pathological data were collected and analyzed. The cutoff value for LNR was calculated on the receiver operating characteristic (ROC) curve. Univariate and multivariate Cox regression models, and Kaplan-Meier method were used for survival analysis. RESULTS: According to the ROC curve, the cutoff value for LNR was 7.6%. With a median follow-up period of 80 months, the OSCC patients with high-risk LNR (> 7.6%), or positive extranodal extension (ENE) had significantly worse clinical outcomes than patients with low-risk LNR (≤7.6%) or negative ENE. Multivariate analysis on pathological covariates showed that only high-risk LNR was an independent negative predictive factor for survival (P < .05). The cutoff value of LNR of 7.6% was also verified with the similar results using an open TCGA database, high-risk LNR indicating worse overall survival (P < .001) and disease-free survival (P < .001). CONCLUSION: Oral squamous cell carcinoma patients with high-risk LNR have a worse clinical outcome than patients with low-risk LNR. High-risk LNR is an independent negative predictive factor for clinical outcome in patients with locally advanced OSCC.

High-Efficiency Wavelet Compressive Fusion for Improving MEMS Array Performance.

With the rapid development of microelectromechanical systems (MEMS) technology, low-cost MEMS inertial devices have been widely used for inertial navigation. However, their application range is greatly limited in some fields with high precision requirements because of their low precision and high noise. In this paper, to improve the performance of MEMS inertial devices, we propose a highly efficient optimal estimation algorithm for MEMS arrays based on wavelet compressive fusion (WCF). First, the algorithm uses the compression property of the multiscale wavelet transform to compress the original signal, fusing the compressive data based on the support. Second, threshold processing is performed on the fused wavelet coefficients. The simulation result demonstrates that the proposed algorithm performs well on the output of the inertial sensor array. Then, a ten-gyro array system is designed for collecting practical data, and the frequency of the embedded processor in our verification environment is 800 MHz. The experimental results show that, under the normal working conditions of the MEMS array system, the 100 ms input array data require an approximately 75 ms processing delay when employing the WCF algorithm to support real-time processing. Additionally, the zero-bias instability, angle random walk, and rate slope of the gyroscope are improved by 8.0, 8.0, and 9.5 dB, respectively, as compared with the original device. The experimental results demonstrate that the WCF algorithm has outstanding real-time performance and can effectively improve the accuracy of low-cost MEMS inertial devices.

The impact of the health care workforce on under-five mortality in rural China.

BACKGROUND: Previous studies have focused on the relationship between increases in the health care workforce and child health outcomes, but little is known about how this relationship differs in contexts where economic growth differs by initial level and pace. This study evaluates the association between increased health professionals and the under-five mortality rate (U5MR) in rural Chinese counties from 2008 to 2014 and examines whether this relationship differs among counties with different patterns of economic growth over this period. METHODS: We estimated fixed effects models with rural counties as the unit of analysis to evaluate the association between health professional density and U5MR. Covariates included county-level gross domestic product (GDP) per capita, female illiteracy rate, value of medical equipment per bed, and province-level health expenditures (measured as a proportion of provincial GDP). To explore modification effects, we assessed interactions between health professionals and county types defined by county poverty status and county-level trajectories of growth in GDP per capita. U5MR data have been adjusted for county-level underreporting, and all other data were obtained from administrative and official sources. RESULTS: The U5MR dropped by 36.19% during the study period. One additional health professional per 1000 population was associated with a 2.6% reduction in U5MR, after controlling for other covariates. County poverty status and GDP trajectories moderated this relationship: the U5MR reductions attributed to a one-unit increase in health professionals were 6.8% among poor counties, but only 1.1% among non-poor ones. These reductions were, respectively, 6.7%, 0.7%, and 4.3% in counties with initially low GDP that slowly increased, medium-level GDP that rose at a moderate pace, and high GDP that rose rapidly. CONCLUSIONS: This study demonstrates that increased health professionals were associated with reductions in U5MR. The largest association was seen in poor counties and those with low and slowly increasing GDP per capita, which justifies further expansion of the health care workforce in these areas. This study could be instructive for other developing countries to achieve Sustainable Development Goal 3 by helping them identify where additional health professionals would make the greatest contribution.

Limb Salvage After Percutaneous Mechanical Thrombectomy in Patients with Acute Lower Limb Ischemia: A Retrospective Analysis from Two Institutions.

BACKGROUND: To evaluate the short-term outcomes of percutaneous mechanical thrombectomy (PMT) in patients with acute lower limb ischemia (ALI) and to analyze the effect of ALI of different etiologies on the limb salvage. MATERIALS AND METHODS: From January 2015 to December 2017, a retrospective analysis was performed on 112 patients (mean age: 66.5 years; 117 limbs in total; 66 limbs in 61 males) with ALI treated with PMT at 2 vascular institutions. Of the 117 limbs, 44 (41 patients) had acute arterial embolism, 36 (34 patients) had acute arterial thrombosis, and 37 (37 patients) had acute stent (31 limbs in 31 patients) or graft (6 limbs in 6 patients) thrombosis. The primary end point was limb salvage rate, and subgroups were analyzed by etiological factors. The secondary end points included patency rates, major bleeding complications, 30-day mortality, and reintervention rates. RESULTS: The 30-day mortality rate was 3.6%. The incidence of major bleeding complications was 2.7%. During the follow-up, the limb salvage rates at 1 year and 2 years were 83.8% and 74.7%, respectively. Subgroup analysis showed that the limb salvage rate in patients with acute arterial embolism was 92.9% at 2 years after PMT, which was higher than that in patients with acute arterial thrombosis (73.3%, P = 0.04, hazard ratio [HR]: 3.6, 95% confidence interval [CI]: 1.1-11.7) and acute stent/graft thrombosis (62.5%, P = 0.01, HR: 4.7, 95% CI: 1.5-13.6). CONCLUSIONS: PMT in patients with ALI is effective in preventing amputations over the 3-year study period with a reasonable safety profile, especially in patients with acute arterial embolism.

Tumor Neurobiology in the Pathogenesis and Therapy of Head and Neck Cancer.

The neurobiology of tumors has attracted considerable interest from clinicians and scientists and has become a multidisciplinary area of research. Neural components not only interact with tumor cells but also influence other elements within the TME, such as immune cells and vascular components, forming a polygonal relationship to synergistically facilitate tumor growth and progression. This review comprehensively summarizes the current state of the knowledge on nerve-tumor crosstalk in head and neck cancer and discusses the potential underlying mechanisms. Several mechanisms facilitating nerve-tumor crosstalk are covered, such as perineural invasion, axonogenesis, neurogenesis, neural reprogramming, and transdifferentiation, and the reciprocal interactions between the nervous and immune systems in the TME are also discussed in this review. Further understanding of the nerve-tumor crosstalk in the TME of head and neck cancer may provide new nerve-targeted treatment options and help improve clinical outcomes for patients.

Hybrid Filtering Compensation Algorithm for Suppressing Random Errors in MEMS Arrays.

To solve the high error phenomenon of microelectromechanical systems (MEMS) due to their poor signal-to-noise ratio, this paper proposes an online compensation algorithm wavelet threshold back-propagation neural network (WT-BPNN), based on a neural network and designed to effectively suppress the random error of MEMS arrays. The algorithm denoises MEMS and compensates for the error using a back propagation neural network (BPNN). To verify the feasibility of the proposed algorithm, we deployed it in a ZYNQ-based MEMS array hardware. The experimental results showed that the zero-bias instability, angular random wander, and angular velocity random wander of the gyroscope were improved by about 12 dB, 10 dB, and 7 dB, respectively, compared with the original device in static scenarios, and the dispersion of the output data was reduced by about 8 dB in various dynamic environments, which effectively verified the robustness and feasibility of the algorithm.

Aspirin versus low-molecular-weight heparin for thromboprophylaxis after orthopaedic surgery: a systematic review and meta-analysis.

The article aimed to compare the efficiency and safety of aspirin with low-molecular-weight heparin (LMWH) for thromboprophylaxis in orthopaedic surgery patients. According to the inclusion and exclusion criteria, PubMed, Embase and Cochrane Library database were searched for studies comparing aspirin and LMWH in venous thromboembolism (VTE) prophylaxis until 25 April 2023. The outcome measures included deep venous thrombosis(DVT)/Pulmonary embolism(PE) events, major bleeding events, wound complications, wound infection and death. Six studies met the requirements of our meta-analysis, including 12 470 patients in the aspirin group and 10 857 patients in the LMWH group. The meta-analysis showed that results showed that LMWH was superior to aspirin in preventing VTE events (odds ratio (OR) 1.44, 95% CI 1.24-1.68, P  < 0.00001), whereas there was no significant difference between them in bleeding events (OR 0.95, 95% CI 0.86-1.05, P  = 0.33), wound complication (OR 0.58, 95% CI 0.28-1.17, P  = 0.13), wound infection (OR 1.12, 95% CI 0.86-1.47, P  = 0.39) and mortality (OR 1.04, 95% CI 0.70-1.55, P  = 0.83). In addition, subgroup analysis showed that compared with aspirin, LMWH was more likely to reduce the incidence of DVT events in orthopaedic surgery patients (OR 1.59, 95% CI 1.33-1.91, P  < 0.00001), whereas there was no advantage in reducing the incidence of PE events (OR 1.22, 95% CI 0.62-2.40, P  = 0.56). Despite the similar safety profiles, this meta-analysis showed that LMWH was significantly superior to aspirin in thromboprophylaxis after orthopaedic surgery. LMWH was still the first-line drug for thrombosis prevention in patients who underwent major orthopaedic surgeries.

Epigenetic regulation of mRNA mediates the phenotypic plasticity of cancer cells during metastasis and therapeutic resistance (Review).

Plasticity, the ability of cancer cells to transition between differentiation states without genomic alterations, has been recognized as a major source of intratumoral heterogeneity. It has a crucial role in cancer metastasis and treatment resistance. Thus, targeting plasticity holds tremendous promise. However, the molecular mechanisms of plasticity in cancer cells remain poorly understood. Several studies found that mRNA, which acts as a bridge linking the genetic information of DNA and protein, has an important role in translating genotypes into phenotypes. The present review provided an overview of the regulation of cancer cell plasticity occurring via changes in the transcription and editing of mRNAs. The role of the transcriptional regulation of mRNA in cancer cell plasticity was discussed, including DNA­binding transcriptional factors, DNA methylation, histone modifications and enhancers. Furthermore, the role of mRNA editing in cancer cell plasticity was debated, including mRNA splicing and mRNA modification. In addition, the role of non­coding (nc)RNAs in cancer plasticity was expounded, including microRNAs, long intergenic ncRNAs and circular RNAs. Finally, different strategies for targeting cancer cell plasticity to overcome metastasis and therapeutic resistance in cancer were discussed.

Context-Dependent Regulation of Peripheral Nerve Abundance by the PI3K Pathway in the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma.

Recent studies have highlighted neurons and their associated Schwann cells (SCs) as key regulators of cancer development. However, the mode of their interaction with tumor cells or other components of the tumor microenvironment (TME) remains elusive. We established an SC-related 43-gene set as a surrogate for peripheral nerves in the TME. Head and neck squamous cell carcinoma (HNSCC) from The Cancer Genome Atlas (TCGA) were classified into low, intermediate and high SC score groups based on the expression of this gene set. Perineural invasion (PNI) and TGF-ß signaling were hallmarks of SChigh tumors, whereas SClow tumors were enriched for HPV16-positive OPSCC and higher PI3K-MTOR activity. The latter activity was partially explained by a higher frequency of PTEN mutation and PIK3CA copy number gain. The inverse association between PI3K-MTOR activity and peripheral nerve abundance was context-dependent and influenced by the TP53 mutation status. An in silico drug screening approach highlighted the potential vulnerabilities of HNSCC with variable SC scores and predicted a higher sensitivity of SClow tumors to DNA topoisomerase inhibitors. In conclusion, we have established a tool for assessing peripheral nerve abundance in the TME and provided new clinical and biological insights into their regulation. This knowledge may pave the way for new therapeutic strategies and impart proof of concept in appropriate preclinical models.

Non-releasing poly (ionic liquid) based hydrogel accelerates diabetic wound healing.

Persistent bacterial colonization, abnormal inflammatory responses, and impaired angiogenesis pose significant challenges to effective wound repair, particularly in diabetic wounds. Employing exogenous bioactive substances in wound dressings is a recognized approach to dynamically respond to the wound microenvironment and accelerate the repair process. However, this strategy can lead to the development of drug resistance and induce further tissue damage. To address these challenges, we are synthesizing a novel hydrogel for diabetic wound treatment using functional poly (ionic liquid) and modified dextran. The hydrogel is characterized by its excellent tissue adhesion, exceptional self-healing capacity, and substantial compressive deformation. It exhibits broad antibacterial activity, reduces the expression of pro-inflammatory cytokines and enhances the healing in diabetic wounds. Its efficacy is superior to that of the positive control group. This innovative non-releasing hydrogel presents as a promising alternative to conventional antibiotics, offering significant potential for the treatment and healing of diabetic chronic wounds.

Optimal design of dual air-gap closed-loop TMR current sensor based on minimum magnetic field uniformity coefficient.

Advanced sensor technology provides accurate information for transparent monitoring and real-time control of the power grid. Tunnel magnetoresistance (TMR) elements with high sensitivity and linearity provide a new technical means for current measurement in medium-voltage DC power distribution systems. This paper proposes a dual air-gap closed-loop TMR current sensor and its optimal design method based on the magnetic field's minimum uniformity coefficient. The dual air-gap structure reduces the measurement error caused by the eccentricity of the wire, and the theory and modelling of the minimum magnetic field uniformity coefficient optimise the key parameters, such as the inner radius of the magnetic core, the distance of the air-gap and the area size of the section side. Finally, a sensor prototype with a rated measurement current of ± 50 A was developed. The experiment results show that the relative error of the proposed TMR current sensor is less than 0.2% under the rated current. The conclusion can be drawn that the proposed sensor with the optimised design effectively improves the measurement accuracy.

Characteristics, sources of volatile organic compounds, and their contributions to secondary air pollution during different periods in Beijing, China.

Continuous measurements of volatile organic compounds (VOCs), ozone (O3), fine particulate matter (PM2.5), and related parameters were conducted between April 2020 and March 2021 in Beijing, China, to characterize potential sources of VOCs and their impacts on secondary organic aerosols (SOAs) and O3 levels. The annual average mixing ratio of VOCs was 17.4 ± 10.1 ppbv, with monthly averages ranging from 11.6 to 25.2 ppbv. According to the empirical kinetic modeling approach (EKMA), O3 formation during O3 season was "VOCs-limited", while it was in a "transition" regime during O3 pollution episodes. In the O3 season, higher ozone formation potential (OFP) of m/p-xylene, o-xylene, toluene, isopentane, and n-butane were evident during O3 pollution episodes, in line with the increasing contributions of solvent usage and coating, as well as gasoline evaporation to OFP obtained through a matrix factorization model (PMF). Aromatics contributed the most to the secondary organic aerosol formation potential (SOAFP). In the non-O3 season, the contribution of vehicle exhaust to SOAFP elevated on hazy days, thereby revealing the importance of traffic-derived VOCs for PM2.5 pollution. Our results indicate that the prior control of different VOC sources should vary by season, thereby facilitating the synergistic control of O3 and PM2.5 in Beijing.

Peripheral-Free Calibration Method for Redundant IMUs Based on Array-Based Consumer-Grade MEMS Information Fusion.

The MEMS array-based inertial navigation module (M-IMU) reduces the measurement singularities of MEMS sensors by fusing multiple data processing to improve its navigation performance. However, there are still existing random and fixed errors in M-IMU navigation. The calibration method calibrates the fixed error parameters of M-IMU to further improve navigation accuracy. In this paper, we propose a low-cost and efficient calibration method to effectively estimate the fixed error parameters of M-IMU. Firstly, we manually rotate the M-IMU in multiple sets of different attitudes (stationary), then use the LM-calibration algorithm to optimize the cost function of the corresponding sensors in different intervals of the stationary-dynamic filter separation to obtain the fixed error parameters of MEMS, and finally, the global fixed error parameters of the M-IMU are calibrated by adaptive support fusion of the individual MEMS fixed error parameters based on the benchmark conversion. A comparison of the MEMS calibrated separately by the fusion-calibration algorithm and the LM-calibration algorithm verified that the calibrated MEMS array improved the measurement accuracy by about 10 db and reduced the dispersion of the output data by about 8 db compared to the individual MEMS in a multi-dimensional test environment, indicating the robustness and feasibility of the fusion calibration algorithm.