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Humans can listen to a target speaker even in challenging acoustic conditions that have noise, reverberation, and interfering speakers. This phenomenon is known as the cocktail-party effect. For decades, researchers have focused on approaching the listening ability of humans. One critical issue is handling interfering speakers because the target and non-target speech signals share similar characteristics, complicating their discrimination. Target speech/speaker extraction (TSE) isolates the speech signal of a target speaker from a mixture of several speakers with or without noises and reverberations using clues that identify the speaker in the mixture. Such clues might be a spatial clue indicating the direction of the target speaker, a video of the speaker's lips, or a pre-recorded enrollment utterance from which their voice characteristics can be derived. TSE is an emerging field of research that has received increased attention in recent years because it offers a practical approach to the cocktail-party problem and involves such aspects of signal processing as audio, visual, array processing, and deep learning. This paper focuses on recent neural-based approaches and presents an in-depth overview of TSE. We guide readers through the different major approaches, emphasizing the similarities among frameworks and discussing potential future directions., Comment: Submitted to IEEE Signal Processing Magazine on Apr. 25, 2022, and accepted on Jan. 12, 2023

Background: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. Summary: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. Key Messages: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Background: The kidney-brain crosstalk has been involved in Alzheimer’s disease (AD) with the mechanism remaining unclear. The anti-aging factor Klotho was reported to attenuate both kidney injury and AD pathologies. Objective: To investigate whether plasma Klotho participated in kidney-brain crosstalk in AD. Methods: We enrolled 33 PiB-PET-positive AD patients and 33 amyloid-β (Aβ)-negative age- and sex-matched cognitively normal (CN) controls from the Chongqing Ageing & Dementia Study (CADS). The levels of plasma Klotho, Aβ, and tau in the cerebrospinal fluid (CSF) were measured by enzyme-linked immunosorbent assay. Results: We found higher plasma Klotho and lower estimated glomerular filtration rate (eGFR) levels in AD patients compared with CN. The eGFR was positively associated with Aβ42, Aβ40 levels in CSF and negatively associated with CSF T-tau levels. Plasma Klotho levels were both negatively correlated with CSF Aβ42 and eGFR. Mediation analysis showed that plasma Klotho mediated 24.96% of the association between eGFR and CSF Aβ42. Conclusion: Renal function impacts brain Aβ metabolism via the kidney-brain crosstalk, in which the plasma Klotho may be involved as a mediator. Targeting Klotho to regulate the kidney-brain crosstalk provides potential therapeutic approaches for AD.

Y900 is one of the top hybrid rice (Oryza sativa) varieties, with its yield exceeding 15 t·hm−2. To dissect the mechanism of heterosis, we sequenced the male parent line R900 and female parent line Y58S using long-read and Hi-C technology. High-quality reference genomes of 396.41 Mb and 398.24 Mb were obtained for R900 and Y58S, respectively. Genome-wide variations between the parents were systematically identified, including 1,367,758 single-nucleotide polymorphisms, 299,149 insertions/deletions, and 4,757 structural variations. The level of variation between Y58S and R900 was the lowest among the comparisons of Y58S with other rice genomes. More than 75% of genes exhibited variation between the two parents. Compared with other two-line hybrids sharing the same female parent, the portion of Geng/japonica (GJ)-type genetic components from different male parents increased with yield increasing in their corresponding hybrids. Transcriptome analysis revealed that the partial dominance effect was the main genetic effect that constituted the heterosis of Y900. In the hybrid, both alleles from the two parents were expressed, and their expression patterns were dynamically regulated in different tissues. The cis-regulation was dominant for young panicle tissues, while trans-regulation was more common in leaf tissues. Overdominance was surprisingly prevalent in stems and more likely regulated by the trans-regulation mechanism. Additionally, R900 contained many excellent GJ haplotypes, such as NARROW LEAF1, Oryza sativa SQUAMOSA PROMOTER BINDING PROTEIN-LIKE13, and Grain number, plant height, and heading date8, making it a good complement to Y58S. The fine-tuned mechanism of heterosis involves genome-wide variation, GJ introgression, key functional genes, and dynamic gene/allele expression and regulation pattern changes in different tissues and growth stages.

In this study we design and fabricate an all-carbon OECT by using laser-induced graphene (LIG) as the electrode, and high output performances are achieved because of the porous structure on the LIG surface.

Generating sound effects that humans want is an important topic. However, there are few studies in this area for sound generation. In this study, we investigate generating sound conditioned on a text prompt and propose a novel text-to-sound generation framework that consists of a text encoder, a Vector Quantized Variational Autoencoder (VQ-VAE), a decoder, and a vocoder. The framework first uses the decoder to transfer the text features extracted from the text encoder to a mel-spectrogram with the help of VQ-VAE, and then the vocoder is used to transform the generated mel-spectrogram into a waveform. We found that the decoder significantly influences the generation performance. Thus, we focus on designing a good decoder in this study. We begin with the traditional autoregressive decoder, which has been proved as a state-of-the-art method in previous sound generation works. However, the AR decoder always predicts the mel-spectrogram tokens one by one in order, which introduces the unidirectional bias and accumulation of errors problems. Moreover, with the AR decoder, the sound generation time increases linearly with the sound duration. To overcome the shortcomings introduced by AR decoders, we propose a non-autoregressive decoder based on the discrete diffusion model, named Diffsound. Specifically, the Diffsound predicts all of the mel-spectrogram tokens in one step and then refines the predicted tokens in the next step, so the best-predicted results can be obtained after several steps. Our experiments show that our proposed Diffsound not only produces better text-to-sound generation results when compared with the AR decoder but also has a faster generation speed, e.g., MOS: 3.56 \textit{v.s} 2.786, and the generation speed is five times faster than the AR decoder., Accepted by TASLP2022

Biofilms are known to be a great challenge for their anti-bacterial activity as they obstruct drug action for deeper and more thorough bacteria-killing effects. Therefore, developing highly effective antibacterial agents to destroy biofilms and eradicate bacteria is of great significance. Herein, a new type of nanocomposites (denoted as poly(4-cyanostyrene)@silver@polylysine) is proposed, in which polylysine (PLL) could rapidly capture the biofilms and exhibit excellent antibacterial efficacy together with decorated silver (Ag) nanoparticles (NPs) through the charge effect and Ag

A pair of enantiomeric tetrahedral cages have been constructed using a hexapod ligand. By utilizing large aromatic triphenylene as the core, the crystal structure of the metallo-cages exhibited a hierarchical packing due to the π–π interaction.

Here we have achieved accurate ligand tailoring at specific sites on calixarene-protected Cu(ii)-based metallamacrocycles.

Permeable reactive barrier (PRB) remediation technology has been widely used in the remediation of groundwater contamination. In numerical simulations, neglecting the non-uniform distribution of heavy metal contamination along the depth may lead to deviations between simulation results and reality. The distribution of heavy metals in the soil layer around a non-ferrous mining area in Hezhou, Guangxi, southern China was investigated, and it was found that the standard Gaussian function could well describe the non-uniform distribution of heavy metals in the soil layer. A two-dimensional analytical model solved by the finite element method was used to simulate the migration process of heavy metal contamination in the aquifer and PRB. The results show that the uniform distribution of contaminants along the depth ignores the dilution effect, which may underestimate the service life of the PRB and lead to an overly conservative design of the PRB. The breakthrough time of the PRB decreases with the increase of the maximum initial concentration (Cin,max) and the high concentration range (σ), and increases almost linearly with the barrier thickness (Lw). An optimal design method for PRB location and thickness is proposed, which can provide a reference for the engineering application of PRB.

Despite the lack of high-level evidence, laparoscopic distal pancreatectomy (LDP) is frequently performed in patients with pancreatic ductal adenocarcinoma (PDAC) owing to advancements in surgical techniques. The aim of this study was to investigate the long-term oncologic outcomes of LDP in patients with PDAC via propensity score matching (PSM) analysis using data from a large-scale national database.A total of 1202 patients who were treated for PDAC via distal pancreatectomy across 16 hospitals were included in the Korean Tumor Registry System-Biliary Pancreas. The 5-year overall (5YOSR) and disease-free (5YDFSR) survival rates were compared between LDP and open DP (ODP).ODP and LDP were performed in 846 and 356 patients, respectively. The ODP group included more aggressive surgeries with higher pathologic stage, R0 resection rate, and number of retrieved lymph nodes. After PSM, the 5YOSRs for ODP and LDP were 37.3% and 41.4% (p = 0.150), while the 5YDFSRs were 23.4% and 27.2% (p = 0.332), respectively. Prognostic factors for 5YOSR included R status, T stage, N stage, differentiation, and lymphovascular invasion.LDP was performed in a selected group of patients with PDAC. Within this group, long-term oncologic outcomes were comparable to those observed following ODP.

This study aimed to develop a solid dispersion formulation of silymarin (Silymarin-SD) using freeze-drying method to enhance its oral bioavailability (BA) by inhibiting the intestinal first-pass effect and increasing its solubility and permeability. Silymarin-SD formulation (i.e., silymarin:tween 80:hydroxypropyl cellulose (HPC) = 1:1:3 (w/w/w) significantly increased silymarin permeability in the duodenum, jejunum, and ileum by decreasing the efflux ratio of silymarin and by inhibiting silymarin-glucuronidation activity, in which tween 80 played a crucial role. As a result, orally administered Silymarin-SD formulation increased plasma silymarin concentrations and decreased silymarin-glucuronide in rats compared with silymarin alone and silymmarin:D-α-tocopherol polyethylene glycol 1000 succinate (1:1, w/w) formulation. In addition to modulating intestinal first-pass effect, Silymarin-SD formulation showed a significantly higher cumulative dissolution for 120 min compared with that of silymarin from the physical mixture (PM) of the same composition as Silymarin-SD and silymarin alone; the relative BA of silymarin-SD increased to 215% and 589% compared with silymarin-PM and silymarin alone, respectively. This could be attributed to the amorphous status of the Silymarin-SD formulation without chemical interaction with excipients, such as tween 80 and HPC. Moreover, the hepatoprotective effect of Silymarin-SD in acetaminophen-induced acute hepatotoxicity, as estimated from the alanine aminotransferase and aspartate aminotransferase values, was superior to that of silymarin. In conclusion, the increase in the dissolution rate and intestinal permeability of silymarin, and the inhibition of silymarin-glucuronidation by the Silymarin-SD formulation, prepared using tween 80 and HPC, increased its plasma concentration and resulted in a superior hepatoprotective effect compared to silymarin.

Detailed syntheses are reported for the previously reported homoleptic 1-norbornyl complexes [M(norb)4] {M = Ti (1), Zr (3), Hf (4), and Mn (5)}. These compounds were characterized by combustion elemental analysis, NMR spectroscopy, single crystal X-ray diffraction (for 1 and 3), and SQUID magnetometry (for 5). The reaction by-product [{(norb)3Ti}2(μ-O)] (2) was also spectroscopically and structurally characterized. To assess the potential viability of 1 and 3–5 as precursors for thin film deposition by CVD or ALD, their volatility and thermal stability were evaluated by sublimation, thermogravimetric analysis, and in the case of 4, bulk thermolysis.

Immune-checkpoint (IC) modulators like the poliovirus receptor (PVR) and programmed death ligand 1 (PD-L1) attenuate innate and adaptive immune responses and are potential therapeutic targets for diverse malignancies, including triple-negative breast cancer (TNBC). The retinoblastoma tumor suppressor, pRB, controls cell growth through E2F1-3 transcription factors, and its inactivation drives metastatic cancer, yet its effect on IC modulators is contentious. Here, we show that RB-loss and high E2F1/E2F2 signatures correlate with expression of PVR, CD274 (PD-L1 gene) and other IC modulators and that pRB represses whereas RB depletion and E2F1 induce PVR and CD274 in TNBC cells. Accordingly, the CDK4/6 inhibitor, palbociclib, suppresses both PVR and PD-L1 expression. Palbociclib also counteracts the effect of CDK4 on SPOP, leading to its depletion, but the overall effect of palbociclib is a net reduction in PD-L1 level. Hydrochloric acid, commonly used to solubilize palbociclib, counteracts its effect and induces PD-L1 expression. Remarkably, lactic acid, a by-product of glycolysis, also induces PD-L1 as well as PVR. Our results suggest a model in which CDK4/6 regulates PD-L1 turnover by promoting its transcription via pRB-E2F1 and degradation via SPOP and that the CDK4/6-pRB-E2F pathway couples cell proliferation with the induction of multiple innate and adaptive immunomodulators, with direct implications for cancer progression, anti-CDK4/6- and IC-therapies.

Fifteen new diterpenoids, namely xishaklyanes A-O (1-15), along with three known related ones (16-18), were isolated from the soft coral Klyxum molle collected from Xisha Islands, South China Sea. The stereochemistry of the new compounds were elucidated by a combination of detailed spectroscopic analyses, chemical syntheses, quantum chemical calculations and comparison with the reported data. The absolute configuration of compound 18 was established by the modified Mosher's method for the first time. In bioassay, some of these compounds exhibited considerable antibacterial activities on fish pathogenic bacteria, and compound 4 showed the most effective activity with MIC of 0.225 g/mL against Lactococcus garvieae.

Background Ventilator-induced lung injury (VILI) is caused by overdistension of the alveoli by the repetitive recruitment and derecruitment of alveolar units. This study aims to investigate the potential role and mechanism of fibroblast growth factor 21 (FGF21), a metabolic regulator secreted by the liver, in VILI development. Methods Serum FGF21 concentrations were determined in patients undergoing mechanical ventilation during general anesthesia and in a mouse VILI model. Lung injury was compared between FGF21-knockout (KO) mice and wild-type (WT) mice. Recombinant FGF21 was administrated in vivo and in vitro to determine its therapeutic effect. Results Serum FGF21 levels in patients and mice with VILI were significantly higher than in those without VILI. Additionally, the increment of serum FGF21 in anesthesia patients was positively correlated with the duration of ventilation. VILI was aggravated in FGF21-KO mice compared with WT mice. Conversely, the administration of FGF21 alleviated VILI in both mouse and cell models. FGF21 reduced Caspase-1 activity, suppressed the mRNA levels of Nlrp3, Asc, Il-1β, Il-18, Hmgb1 and Nf-κb, and decreased the protein levels of NLRP3, ASC, IL-1β, IL-18, HMGB1 and the cleaved form of GSDMD. Conclusions Our findings reveal that endogenous FGF21 signaling is triggered in response to VILI, which protects against VILI by inhibiting the NLRP3/Caspase-1/GSDMD pyroptosis pathway. These results suggest that boosting endogenous FGF21 or the administration of recombinant FGF21 could be promising therapeutic strategies for the treatment of VILI during anesthesia or critical care.

Background The Mg–Al-lactate layered double hydroxide nanosheet (LDH-NS) has shown great potential as an optimal nanocarrier for extensive use in plants. However, previous studies in plant sciences have not provided a clear description of the application for the LDH-NSs-based double-stranded RNA (dsRNA) delivery (LDH-dsRNA) system in different tissues of both model and non-model species. Results LDH-NSs were synthesized by using the co-precipitation method, while the dsRNAs targeting genes of interest were prepared in vitro using T7 RNA polymerase. The LDH-dsRNA bioconjugates with a neutral charge were produced by incubating with the mass ratio of LDH-NSs to dsRNA at 3:1, which were then introduced into intact plant cells using three different approaches, including injection, spray, and soak. The LDH-dsRNA delivery method was optimized by inhibiting the expression of the Arabidopsis thaliana ACTIN2 gene. As a result, soaking A. thaliana seedlings in a medium containing LDH-dsRNA for 30 min led to the silencing of 80% of the target genes. The stability and effectiveness of the LDH-dsRNA system were further confirmed by the high-efficiency knockdown of plant tissue-specific genes, including that encoding phytoene desaturase (PDS), WUSCHEL (WUS), WUSCHEL-related homeobox 5 (WOX5), and ROOT HAIR DEFECTIVE 6 (RHD6). In addition, the LDH-dsRNA system was employed in cassava, where it was found that the expression of the gene encoding nucleotide-binding site and leucine-rich repeat (NBS-LRR) was significantly reduced. As a result, the resistance of cassava leaves to pathogens was weakened. Noteworthy, the injection of LDH-dsRNA into leaves resulted in a significant downregulation of target genes in both stems and flowers, indicating the successful transport of LDH-dsRNA from leaves to other parts of plants. Conclusions LDH-NSs have proven to be a highly effective molecular tool for delivering dsRNA into intact plant cells, enabling accurate control of target gene expression.

Pancreatic cystic lesions (PCLs) are occasionally found in solid organ transplant (SOT) recipients. In such recipients, the risk of cancer is increased due to immunosuppressive therapy. This study investigated the prevalence of PCLs and described their clinical course in immunosuppressed patients following SOT.The presence of PCLs in a retrospective cohort of 805 consecutive SOT recipients from 2009 to 2019 was examined. The characteristics of PCLs were compared using initial and follow-up imaging, where available. These results were compared to an age- and sex-matched immunocompetent control group monitored for at least 12 months.PCLs were present in 15 of 805 SOT patients (seven liver and eight kidney transplantations). The median diameter of the largest lesion was 20 mm (range, 0.2-60 mm) and 60% of lesions were benign. During follow-up imaging, the cyst size remained stable in 46.7%, increased in 13.3%, and decreased in 40.0% of the SOT group. Significantly more of the SOT patients showed PCL size reductions (P=0.007). Among SOT patients diagnosed with intraductal papillary mucinous neoplasms (6/15), worrisome features were noted in one patient at the time of cyst diagnosis. Differences in the development of worrisome features between the study and control groups were not statistically significant.The malignant transformation of PCLs in SOT recipients is rare and most such PCLs can be managed conservatively. The presence of a PCL should therefore not affect transplant eligibility.

This study aimed to compare the diagnostic accuracy of shear wave elastography (SWE) with that of shear wave dispersion (SWD) in evaluation of hepatic parenchyma in patients with liver tumors before resection.A total of 174 patients with liver tumors were prospectively enrolled. SWE and SWD examinations were performed. Fibrosis stage and necroinflammatory activity were determined histopathologically according to the Scheuer standard. We compared the diagnostic accuracy of SWE and SWD.Both SWE and SWD values of the liver were highly correlated with liver fibrosis stage (P .05, respectively). Both SWE and SWD values of the liver were moderately correlated with necroinflammatory activity (P .05, respectively). Both SWE and SWD values of the liver were not correlated with steatosis (P .05, respectively). Both SWE and SWD values were significantly different among the patients with different stages of liver fibrosis (P .001, respectively). The area under the receiver operating characteristic (ROC) curve of SWE value was 0.982, 0.977, 0.969, and 0.984 for predicting S ≥ 1, S ≥ 2, S ≥ 3, and S = 4, respectively. The optimal cutoff SWE values were 6.9, 7.9, 8.7, and 10.6 kPa for S ≥ 1, S ≥ 2, S ≥ 3, and S = 4, respectively. The area under the ROC curve of SWD value was 0.967, 0.960, 0.925, and 0.954 for predicting S ≥ 1, S ≥ 2, S ≥ 3, and S = 4, respectively. The optimal cutoff SWD values were 11.2, 12.0, 13.2, and 16.0 m/s/kHz for S ≥ 1, S ≥ 2, S ≥ 3, and S = 4, respectively.SWE and SWD could be noninvasive and accurate for predicting the stage of liver fibrosis in patients with liver tumors before surgery. SWE was more accurate than SWD in predicting severe fibrosis (S ≥ 3) and cirrhosis (S = 4).