A lightweight speech enhancement network fusing bone- and air-conducted speech.

Air-conducted (AC) microphones capture the high-quality desired speech and ambient noise, whereas bone-conducted (BC) microphones are immune to ambient noise but only capture band limited speech. This paper proposes a speech enhancement model that leverages the merits of BC and AC speech. The proposed model takes the spectrogram of BC and AC speech as input and fuses them by an attention-based feature fusion module. The backbone network of the proposed model uses the fused signals to estimate mask of the target speech, which is then applied to the noisy AC speech to recover the target speech. The proposed model adopts a lightweight design of densely gated convolutional attention network (DenGCAN) as the backbone network, which contains encoder, bottleneck layers, and decoder. Furthermore, this paper improves an attention gate and integrates it into skip-connections of DenGCAN, which allows the decoder to focus on the key areas of the feature map extracted by the encoder. As the DenGCAN adopts self-attention mechanism, the proposed model has the potential to improve noise reduction performance at the expense of an increased input-output latency. Experimental results demonstrate that the enhanced speech of the proposed model achieves an average 1.870 wideband-PESQ improvement over the noisy AC speech.

Blocking FSH induces thermogenic adipose tissue and reduces body fat.

Menopause is associated with bone loss and enhanced visceral adiposity. A polyclonal antibody that targets the ß-subunit of the pituitary hormone follicle-stimulating hormone (Fsh) increases bone mass in mice. Here, we report that this antibody sharply reduces adipose tissue in wild-type mice, phenocopying genetic haploinsufficiency for the Fsh receptor gene Fshr. The antibody also causes profound beiging, increases cellular mitochondrial density, activates brown adipose tissue and enhances thermogenesis. These actions result from the specific binding of the antibody to the ß-subunit of Fsh to block its action. Our studies uncover opportunities for simultaneously treating obesity and osteoporosis.

Three-stage hybrid neural beamformer for multi-channel speech enhancement.

This paper proposes a hybrid neural beamformer for multi-channel speech enhancement, which comprises three stages, i.e., beamforming, post-filtering, and distortion compensation, called TriU-Net. The TriU-Net first estimates a set of masks to be used within a minimum variance distortionless response beamformer. A deep neural network (DNN)-based post-filter is then utilized to suppress the residual noise. Finally, a DNN-based distortion compensator is followed to further improve speech quality. To characterize the long-range temporal dependencies more efficiently, a network topology, gated convolutional attention network, is proposed and utilized in the TriU-Net. The advantage of the proposed model is that the speech distortion compensation is explicitly considered, yielding higher speech quality and intelligibility. The proposed model achieved an average 2.854 wb-PESQ score and 92.57% ESTOI on the CHiME-3 dataset. In addition, extensive experiments conducted on the synthetic data and real recordings confirm the effectiveness of the proposed method in noisy reverberant environments.

Mode matching-based beamforming with frequency-wise truncation order for concentric circular differential microphone arrays.

It is desired that a fixed beamformer should maintain the frequency-invariant beampattern and achieve the high white noise gain (WNG), i.e., high robustness against the mismatch in practice. However, existing methods for the design of concentric circular differential microphone arrays (CCDMAs) cannot achieve a compromise between the high robustness and the frequency-invariant beampattern. To address this problem, a new analytical expression for the synthesized beampattern of CCDMAs is derived without any truncation error. Then CCDMAs are designed by matching mode coefficients of the approximated synthesized beampattern to that of the target differential beampattern, where an adjustable truncation order is utilized to enable a trade-off between the robustness and the beampattern distortion. A simple and effective procedure is presented to determine the frequency-wise truncation order. The proposed method reduces to three existing methods, i.e., the Jacobi-Anger method, the improved Jacobi-Anger method, and the minimum mean square error-based method, for a fixed truncation order, which in turn establishes a close connection with these methods and provides a unified view on the design of the CCDMAs. The superiority of the proposed method in terms of robustness and beampattern distortion is demonstrated through computer simulations.

Time-domain sound field reproduction using the group Lasso.

A time-domain sound field reproduction (SFR) method based on the group Lasso (GL) is presented. The proposed method optimizes the positions and the number of active loudspeakers in the time domain by iteratively solving a mixed-norm constrained optimization problem. Simulation results demonstrate that the proposed method achieves accurate broadband SFR using a small number of active loudspeakers and significantly outperforms the least-squares method when the desired sound field is under-sampled. Moreover, the GL algorithm can also be used to optimize the loudspeaker placement for sound field control systems.

Interpolation of the early part of the acoustic transfer functions using block sparse models.

Two types of block sparse models are presented to interpolate the early part of the acoustic transfer functions (eATFs) between the loudspeakers and the target spatial regions in reverberant rooms. The desired eATFs are modeled as a superposition of sound fields generated by a dense grid of equivalent point sources, which exhibit two kinds of block sparse structures under the far-field and small target region assumptions. Simulation results in the two-dimensional case demonstrate that the proposed models can provide accurate eATF interpolation over a broad frequency range using a small number of microphones.

Impact of corrupt admission on the mental health of Chinese adolescents.

Through preferential treatment by education officials or through bribery, some adolescents can obtain admission to a junior high school. However, it is unclear whether it affects the mental health of adolescents. This study used Propensity Score Matching to examine the effects of corruption on adolescent mental health. A total of 17,254 junior high school students sample (11-18 years old; 48.7% girls and 53.1% boys) were used from the China Education Panel Survey. 14.1% of adolescents attended a junior high school by corrupt means, corruption had a significantly negative effect on the mental health of these adolescents (ATT = -0.388, p < 0.01), the reasons grounded in the fact that they received more criticisms from teachers and wanted to leave their current school. In general, corruption in the admissions process can have detrimental effects on the mental health of adolescents. This study extends the previous articles on how to improve adolescent mental health and complements the application of cognitive dissonance theory. Findings from this study revealed that anti-corruption in the education sector is necessary, and the institutional design to ensure fair enrolment in basic education will contribute to the mental health of adolescents.

High internal phase emulsion stabilized by soy protein isolate-Rutin complex: Rheological properties, bioaccessibility and in vitro release kinetics.

High internal phase emulsions (HIPEs) are promising carrier materials for encapsulating and delivering hydrophobic bioactive compounds. By strategically adjusting the composition, particle size, or charge of HIPEs, it is possible to enhance both their stability and the bioaccessibility of hydrophobic polyphenols encapsulated within them. In this study, different soy protein isolate (SPI)-rutin (SPI-R) complexes (formed under various preheating temperatures) were used to stabilize HIPEs, while the particle size, and charge of HIPEs was further adjusted through different homogenization rates. The results demonstrated that an optimal preheating temperature of 70 °C for the complex and a homogenization rate of 15,000 rpm for HIPEs enhanced the stability of the entire emulsion system by producing more uniform and smaller droplet distribution with improved rheological properties. Furthermore, in vitro digestion experiments showed that HIPEs stabilized by the SPI-R complexes (HSR) at optimal homogenization rate had better loading efficiency (98.68 %) and bioaccessibility compared to other groups. Additionally, fitting results from release kinetics confirmed that rutin encapsulated by HSR could achieve sustained release effect. Overall, these findings suggest that HSR has great potential as an effective vehicle for delivering hydrophobic bioactive compounds like rutin within the food industry.

Chinese Herbal Compound Xiaoliu Pingyi Recipe Inhibits the Growth of Lung Adenocarcinoma by Regulating the Tumor Vascular Microenvironment.

BACKGROUND: The traditional Chinese medicine (TCM) Xiaoliu Pingyi recipe (XLPYR) has been clinically used for several decades, demonstrating favorable therapeutic effects. However, the underlying regulatory mechanisms remain unclear. The aim of this study was to explore the anti-tumor effects of XLPYR and its regulatory role in the vascular microenvironment through in vivo and in vitro experiment. MATERIALS AND METHODS: In the in vivo study, a C57BL/6J mouse model of lung adenocarcinoma (LUAD) allografts was established, and various interventions were administered for 14 days (Model group: administered normal saline via oral gavage; Pemetrexed (PEM) group: intraperitoneally injected with a solution of pemetrexed, once every 3d; XLPYR group: administered XLPYR via oral gavage; Combination (COMBI) group: received XLPYR via oral gavage simultaneously with intraperitoneal injection of pemetrexed solution). Tumor volume and weight were then compared among the groups. The impact of XLPYR on the tumor vascular microenvironment was assessed using immunohistochemistry staining. In the in vitro study, XLPYR-containing serum was prepared by oral administration to SD rats. The CCK-8 assay evaluated the effect of the serum on the proliferation of normal lung epithelial BEAS-2B cells and LUAD A549 cells, determining the optimal intervention concentrations. The cell migration and invasion abilities were evaluated using the wound-healing assay and Transwell assay, respectively. Finally, ELISA assay measured VEGF secretion levels in the LUAD cell supernatant, and RT-qPCR and Western Blot were employed to detect differences in HIF-1α, VEGFA, Ang-2, and PI3K/Akt mRNA and protein expression levels in both in vivo and in vitro experiments. RESULTS: In the in vivo study, XLPYR significantly inhibited the growth of mice LUAD allografts, with enhanced anti-tumor effects observed with prolonged drug intervention. Immunohistochemistry staining revealed reduced MVD and increased pericyte coverage in all intervention groups. Regarding vascular function, FITC-Dextran extravasation in the tumor tissues of the Model group was significantly higher than in the intervention groups, particularly with lower extravasation in the COMBI group compared to the PEM group. In the in vitro study, XLPYR demonstrated a time- and concentration-dependent inhibitory effect on LUAD cells, and with greater sensitivity in inhibiting LUAD cells compared to BEAS-2B cells. The wound-healing assay and Transwell assay confirmed that XLPYR significantly suppressed the migration and invasion abilities of LUAD cells. ELISA experiments further revealed a significant decrease in VEGF expression in the supernatant of each intervention group. RT-qPCR and Western Blot results showed consistent findings between the in vivo and in vitro experiments. HIF-1α, VEGFA, and Ang-2 mRNA and protein expression levels were significantly downregulated in the PEM group, XLPYR group, and COMBI group. There were no significant differences in the expression of PI3K and Akt mRNA and total protein, but the expression levels of phosphorylated p-PI3K and p-Akt were notably downregulated. CONCLUSION: XLPYR significantly inhibited C57BL/6J mouse LUAD allograft growth and improved the vascular microenvironment, thereby intervening in tumor angiogenesis and inducing vascular normalization. It suppressed LUAD cell proliferation, migration, and invasion, while reducing VEGF concentration in the cell supernatant. The regulatory mechanism may involve inhibiting PI3K/Akt protein phosphorylation and downregulating angiogenesis-related factors, such as HIF-1α, VEGF, and Ang-2.

Xiaoliu Pingyi Pecipe Inhibits Lung Pre-Metastatic Niche Formation and Prevents Myeloid-Derived Suppressor Cells Recruitment.

BACKGROUND: Metastasis, a leading cause of cancer-related deaths, involves complex mechanisms. The premetastatic niche (PMN) is a crucial contributor to this process. Myeloid-derived suppressor cells (MDSCs) play an important role in PMN formation and promote tumor progression and metastasis. The Xiaoliu Pingyi recipe (XLPYR), a traditional Chinese medicine, is effective in preventing postoperative recurrence and metastasis in cancer patients. OBJECTIVE: This study investigated the effects of XLPYR on MDSCs recruitment and on the expression of PMN markers and elucidated the mechanisms involved in the prevention of tumor metastasis. METHODS: C57BL/6 mice were subcutaneously injected with Lewis cells and treated with cisplatin and XLPYR. Tumors were resected after 14 days after the establishment of a model of lung metastasis, and tumor volume and weight were measured. Lung metastases were observed 21 days after resection. MDSCs in the lung, spleen, and peripheral blood were detected by flow cytometry. Western blotting, qRT-PCR and ELISA were used to detect the expression of S100A8, S100A9, MMP9, LOX, and IL-6/STAT3 in premetastatic lung tissue. RESULTS: XLPYR treatment inhibited tumor growth and prevented lung metastasis. Compared to mice without subcutaneous tumor cell transplantation, the model group had an increased proportion of MDSCs, higher expression of S100A8, S100A9, MMP9, and LOX in the premetastatic lung. XLPYR treatment reduced the proportion of MDSCs, S100A8, S100A9, MMP9, and LOX expression, and downregulated the IL-6/STAT3 pathway. CONCLUSIONS: XLPYR may prevent MDSCs recruitment and reduce the expression of S100A8, MMP9, LOX, and IL6/STAT3 in premetastatic lung tissue, thus reducing lung metastases.

Impact of concomitant medications on the efficacy of immune checkpoint inhibitors: an umbrella review.

Introduction: Cancer is a major global health concern, and immune checkpoint inhibitors (ICIs) offer a promising treatment option for cancer patients. However, the efficacy of ICIs can be influenced by various factors, including the use of concomitant medications. Methods: We searched databases (PubMed, Embase, Cochrane Library, Web of Science) for systematic reviews and meta-analyses for systematic reviews and meta-analyses on the impact of concomitant medications on ICIs efficacy, published from inception to January 1, 2023. We evaluated the methodological quality of the included meta-analyses, and re-synthesized data using a random-effects model and evidence stratification. Results: We included 23 publications, comprising 11 concomitant medications and 112 associations. Class II-IV evidence suggested that antibiotics have a negative impact on ICIs efficacy. However, ICIs efficacy against melanoma, hepatocellular carcinoma, and esophageal squamous cell carcinoma was not affected, this effect was related to the exposure window (class IV). Class III evidence suggested that proton pump inhibitors have a negative impact on ICIs efficacy; nevertheless, the efficacy against melanoma and renal cell carcinoma was not affected, and the effect was related to exposure before the initiation of ICIs therapy (class II). Although class II/III evidence suggested that steroids have a negative impact, this effect was not observed when used for non-cancer indications and immune-related adverse events (class IV). Class IV evidence suggested that opioids reduce ICIs efficacy, whereas statins and probiotics may improve ICIs efficacy. ICIs efficacy was not affected by histamine 2 receptor antagonists, aspirin, metformin, ß-blockers, and nonsteroidal anti-inflammatory agents. Conclusion: Current evidence suggests that the use of antibiotics, PPIs, steroids, and opioids has a negative impact on the efficacy of ICIs. However, this effect may vary depending on the type of tumor, the timing of exposure, and the intended application. Weak evidence suggests that statins and probiotics may enhance the efficacy of ICIs. Aspirin, metformin, ß-blockers, and NSAIDs do not appear to affect the efficacy of ICIs. However, caution is advised in interpreting these results due to methodological limitations. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO,identifier, CRD42022328681.

Lipid-lowering drugs affect lung cancer risk via sphingolipid metabolism: a drug-target Mendelian randomization study.

Background: The causal relationship between lipid-lowering drug (LLD) use and lung cancer risk is controversial, and the role of sphingolipid metabolism in this effect remains unclear. Methods: Genome-wide association study data on low-density lipoprotein (LDL), apolipoprotein B (ApoB), and triglycerides (TG) were used to develop genetic instrumental variables (IVs) for LLDs. Two-step Mendelian randomization analyses were performed to examine the causal relationship between LLDs and lung cancer risk. The effects of ceramide, sphingosine-1-phosphate (S1P), and ceramidases on lung cancer risk were explored, and the proportions of the effects of LLDs on lung cancer risk mediated by sphingolipid metabolism were calculated. Results: APOB inhibition decreased the lung cancer risk in ever-smokers via ApoB (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.70-0.92, p = 0.010), LDL (OR 0.82, 95% CI 0.71-0.96, p = 0.040), and TG (OR 0.63, 95% CI 0.46-0.83, p = 0.015) reduction by 1 standard deviation (SD), decreased small-cell lung cancer (SCLC) risk via LDL reduction by 1 SD (OR 0.71, 95% CI 0.56-0.90, p = 0.016), and decreased the plasma ceramide level and increased the neutral ceramidase level. APOC3 inhibition decreased the lung adenocarcinoma (LUAD) risk (OR 0.60, 95% CI 0.43-0.84, p = 0.039) but increased SCLC risk (OR 2.18, 95% CI 1.17-4.09, p = 0.029) via ApoB reduction by 1 SD. HMGCR inhibition increased SCLC risk via ApoB reduction by 1 SD (OR 3.04, 95% CI 1.38-6.70, p = 0.014). The LPL agonist decreased SCLC risk via ApoB (OR 0.20, 95% CI 0.07-0.58, p = 0.012) and TG reduction (OR 0.58, 95% CI 0.43-0.77, p = 0.003) while increased the plasma S1P level. PCSK9 inhibition decreased the ceramide level. Neutral ceramidase mediated 8.1% and 9.5% of the reduced lung cancer risk in ever-smokers via ApoB and TG reduction by APOB inhibition, respectively, and mediated 8.7% of the reduced LUAD risk via ApoB reduction by APOC3 inhibition. Conclusion: We elucidated the intricate interplay between LLDs, sphingolipid metabolites, and lung cancer risk. Associations of APOB, APOC3, and HMGCR inhibition and LPL agonist with distinct lung cancer risks underscore the multifaceted nature of these relationships. The observed mediation effects highlight the considerable influence of neutral ceramidase on the lung cancer risk reduction achieved by APOB and APOC3 inhibition.

Identifying the Antitumor Effects of Curcumin on Lung Adenocarcinoma Using Comprehensive Bioinformatics Analysis.

Background: As the main component of turmeric (Curcuma longa L.), curcumin is widely used in the treatment of various diseases. Previous studies have demonstrated that curcumin has great potential as a therapeutic agent, but the lack of understanding of the functional mechanism of the drug has hindered the widespread use of the natural product. In the present study, we used comprehensive bioinformatics analysis and in vitro experiments to explore the anti-tumor mechanism of curcumin. Materials and Methods: LUAD mRNA expression data were obtained from TCGA database and differentially expressed genes (DEGs) were identified using R software. Functional enrichment analysis was conducted to further clarify its biological properties and hub genes were identified by a protein-protein interaction (PPI) network analysis. Survival analysis and molecular docking were used to analyze the effectiveness of the hub genes. By an in vitro study, we evaluated whether curcumin could influence the proliferation, migration, and invasion activities of LUAD cells. Results: In this study, 1783 DEGs from LUAD tissue samples compared to normal samples were evaluated. Functional enrichment analysis and the PPI network revealed the characteristics of the DEGs. We performed a topological analysis and identified 10 hub genes. Of these, six genes (INS, GCG, SST, F2, AHSG, and NPY) were identified as potentially effective biomarkers of LUAD. The molecular docking results indicated that curcumin targets in regulating lung cancer may be INS and GCG. We found that curcumin significantly inhibited the proliferation, migration, and invasion of LUAD cells and significantly decreased the expression of the INS and GCG genes. Conclusion: The results of this study suggest that the therapeutic effects of curcumin on LUAD may be achieved through the intervention of INS and GCG, which may act as potential biomarkers for LUAD prevention and treatment.

PD-1/L1 inhibitors may increase the risk of pericardial disease in non-small-cell lung cancer patients: a meta-analysis and systematic review.

Background: The advent of PD-1/L1 inhibitors has changed the landscape for patients with non-small-cell lung cancer (NSCLC). Meanwhile, the adverse events of PD-1/L1 inhibitors have been focused. Methods: The Cochrane Central Register of Controlled Trials, PubMed and Embase databases and ClinicalTrials.gov were searched from inception to February 2021. Results: 18 studies involving 11,394 patients with NSCLC were included. PD-1/L1 inhibitor monotherapy was associated (relative risk, 95% confidence interval) with an increased risk of pericardial effusion (2.72 [1.45-5.12]; p = 0.002) and cardiac tamponade (2.76 [1.15-6.62]; p = 0.023), whereas PD-1/L1 inhibitors combined with chemotherapy did not increase the risk of pericardial effusion and cardiac tamponade (3.08 [0.93-10.21]; p = 0.066 and 3.27 [0.37-28.94]; p = 0.288, respectively). Conclusion: For patients with NSCLC, treatment with PD-1/L1 inhibitor monotherapy increases the risk of pericardial effusion and cardiac tamponade, but PD-1/L1 inhibitors combined with chemotherapy do not.

In this study, the authors found that the incidence of pericardial effusion and cardiac tamponade in non-small-cell lung cancer patients treated with PD-1/L1 inhibitors was 0.63% and 0.35%, respectively, and in chemotherapy was 0.07% and less than 0.01%, respectively. The authors found that PD-1/L1 inhibitors combined with chemotherapy did not increase the risk of cardiac adverse events (AEs); however, the risk of cardiac AEs with PD-1/L1 inhibitor monotherapy should be considered, and the damage of pembrolizumab to the pericardium needs further attention. The mechanism of pericardial effusion and cardiac tamponade is not well understood, and pseudoprogression cannot be ruled out. Although the incidence of cardiac AEs is low, the prevention and management of immunotherapy should be paid attention to.

Nano-realgar suppresses lung cancer stem cell growth by repressing metabolic reprogramming.

BACKGROUND: Recent studies in cancer biology suggest that metabolic glucose reprogramming is a potential target for cancer treatment. However, little is known about drug intervention in the glucose metabolism of cancer stem cells (CSCs) and its related underlying mechanisms. METHODS: The crude realgar powder was Nano-grinded to meets the requirements of Nano-pharmaceutical preparations, and Nano-realgar solution (NRS) was prepared for subsequent experiments. Isolation and characterization of lung cancer stem cells (LCSCs) was performed by magnetic cell sorting (MACS) and immunocytochemistry, respectively. Cell viability and intracellular glucose concentration were detected by MTT assay and glucose oxidase (GOD) kit. Protein expressions related to metabolic reprogramming was detected by ELISA assay. Determination of the expression of HIF-1α and PI3K/Akt/mTOR pathways was carried out by RT-PCR and western blotting analysis. A subcutaneous tumor model in BALB/c-nu mice was successfully established to evaluate the effects of Nano-realgar on tumor growth and histological structure, and the expression of HIF-1α in tumor tissues was measured by immunofluorescence. RESULTS: Nano-realgar inhibits cell viability and induces glucose metabolism in LCSCs, and inhibits protein expression related to metabolic reprogramming in a time- and dose-dependent manner. Nano-realgar downregulated the expression of HIF-1α and PI3K/Akt/mTOR pathways in vitro and in vivo. Nano-realgar inhibits tumor growth and changes the histological structure of tumors through in vivo experiments and consequently inhibits the constitutive activation of HIF-1α signaling. CONCLUSIONS: These results reveal that Nano-realgar inhibits tumor growth in vitro and in vivo by repressing metabolic reprogramming. This inhibitory effect potentially related to the downregulation HIF-1α expression via PI3K/Akt/mTOR pathway.

Prognostic Value of MicroRNA-15a in Human Cancers: A Meta-Analysis and Bioinformatics.

BACKGROUND: Although several studies have proved the relationship between the prognostic value of miRNA-15a and different types of cancer, the result remains controversial. Thus, a meta-analysis was conducted to clarify the prognostic value of miRNA-15a expression level in human cancers. METHODS: We enrolled appropriate literature by searching the databases of PubMed, Embase, and Web of Science. Subsequently, we extracted HRs and their 95% CIs and calculated pooled results of miRNA-15a for overall survival (OS) and disease-free survival (DFS). Besides, subgroup analysis, sensitivity analysis, and publication bias were also revealed in this study. We also further validated this meta-analysis using the Kaplan-Meier plotter database. RESULT: 10 studies, including 1616 patients, were embraced in our meta-analysis. The result showed the lower expression of miRNA-15a significantly predicted adverse OS (HR=2.17, 95% CI: 1.41-3.34), but there is no significant association between the expressing level and DFS in cancer patient (HR=2.04, 95% CI: 0.60-6.88). Based on Kaplan-Meier plotter database, we found the same results in bladder Carcinoma, head-neck squamous cell carcinoma, liver hepatocellular carcinoma, lung squamous cell carcinoma, pancreatic ductal adenocarcinoma, rectum adenocarcinoma, stomach adenocarcinoma, and uterine corpus endometrial carcinoma, but opposite results were found in cervical squamous cell carcinoma and esophageal carcinoma. CONCLUSION: Low expressing levels of miRNA-15a indicated poor OS, while miRNA-15a can be used as a prediction biomarker in different cancer types.