WeSinger 2: Fully Parallel Singing Voice Synthesis via Multi-Singer Conditional Adversarial Training

This paper aims to introduce a robust singing voice synthesis (SVS) system to produce very natural and realistic singing voices efficiently by leveraging the adversarial training strategy. On one hand, we designed simple but generic random area conditional discriminators to help supervise the acoustic model, which can effectively avoid the over-smoothed spectrogram prediction and improve the expressiveness of SVS. On the other hand, we subtly combined the spectrogram with the frame-level linearly-interpolated F0 sequence as the input for the neural vocoder, which is then optimized with the help of multiple adversarial conditional discriminators in the waveform domain and multi-scale distance functions in the frequency domain. The experimental results and ablation studies concluded that, compared with our previous auto-regressive work, our new system can produce high-quality singing voices efficiently by fine-tuning different singing datasets covering from several minutes to a few hours. A large number of synthesized songs with different timbres are available online https://zzw922cn.github.io/wesinger2 and we highly recommend readers to listen to them.Comment: accepted at ICASSP 202

Suppressing STAT3 activation impairs bone formation during maxillary expansion and relapse

Objectives: The mid-palatal expansion technique is commonly used to correct maxillary constriction in dental clinics. However, there is a tendency for it to relapse, and the key molecules responsible for modulating bone formation remain elusive. Thus, this study aimed to investigate whether signal transducer and activator of transcription 3 (STAT3) activation contributes to osteoblast-mediated bone formation during palatal expansion and relapse. Methodology: In total, 30 male Wistar rats were randomly allocated into Ctrl (control), E (expansion only), and E+Stattic (expansion plus STAT3-inhibitor, Stattic) groups. Micro-computed tomography, micromorphology staining, and immunohistochemistry of the mid-palatal suture were performed on days 7 and 14. In vitro cyclic tensile stress (10% magnitude, 0.5 Hz frequency, and 24 h duration) was applied to rat primary osteoblasts and Stattic was administered for STAT3 inhibition. The role of STAT3 in mechanical loading-induced osteoblasts was confirmed by alkaline phosphatase (ALP), alizarin red staining, and western blots. Results: The E group showed greater arch width than the E+Stattic group after expansion. The differences between the two groups remained significant after relapse. We found active bone formation in the E group with increased expression of ALP, COL-I, and Runx2, although the expression of osteogenesis-related factors was downregulated in the E+stattic group. After STAT3 inhibition, expansive force-induced bone resorption was attenuated, as TRAP staining demonstrated. Furthermore, the administration of Stattic in vitro partially suppressed tensile stress-enhanced osteogenic markers in osteoblasts. Conclusions: STAT3 inactivation reduced osteoblast-mediated bone formation during palatal expansion and post-expansion relapse, thus it may be a potential therapeutic target to treat force-induced bone formation

Comprehensive analysis of REST corepressors (RCORs) in pan-cancer

REST corepressors (RCORs) are the core component of the LSD1/CoREST/HDACs transcriptional repressor complex, which have been revealed differently expressed in various cancers, but the therapeutic and prognostic mechanisms in cancer are still poorly understood. In this study, we analyzed expression, prognostic value, molecular subtypes, genetic alteration, immunotherapy response and drug sensitivity of RCORs in pan-cancer. Clinical correlation, stemness index, immune infiltration and regulatory networks of RCORs in hepatocellular carcinoma (HCC) were detected through TCGA and GSCA database. In-vitro experiments were conducted to explore the role of RCOR1 in HCC cells. The expression of RCORs varied among different cancers, and have prognostic values in several cancers. Cancer subtypes were categorized according to the expression of RCORs with clinical information. RCORs were significantly correlated with immunotherapy response, MSI, drug sensitivity and genetic alteration in pan-cancer. In HCC, RCORs were considered as potential predictor of stemness and also had association with immune infiltration. The ceRNA-TF-kinase regulatory networks of RCORs were constructed. Besides, RCOR1 acts as an oncogene in HCC and promotes the proliferation of HCC cells by inhibiting cell cycle arrest and cell apoptosis. Taken together, our study revealed the potential molecular mechanisms of RCORs in pan-cancer, offering a benchmark for disease-related research

High-Mobility and Bias-Stable Field-Effect Transistors Based on Lead-Free Formamidinium Tin Iodide Perovskites

Electronic devices based on tin halide perovskites often exhibit a poor operational stability. Here, we report an additive engineering strategy to realize high-performance and stable field-effect transistors (FETs) based on 3D formamidinium tin iodide (FASnI3) films. By comparatively studying the modification effects of two additives, i.e., phenethylammonium iodide and 4-fluorophenylethylammonium iodide via combined experimental and theoretical investigations, we unambiguously point out the general effects of phenethylammonium (PEA) and its fluorinated derivative (FPEA) in enhancing crystallization of FASnI3 films and the unique role of fluorination in reducing structural defects, suppressing oxidation of Sn2+ and blocking oxygen and water involved defect reactions. The optimized FPEA-modified FASnI3 FETs reach a record high field-effect mobility of 15.1 cm2/(V·s) while showing negligible hysteresis. The devices exhibit less than 10% and 3% current variation during over 2 h continuous bias stressing and 4200-cycle switching test, respectively, representing the best stability achieved so far for all Sn-based FETs.</p

High-Mobility and Bias-Stable Field-Effect Transistors Based on Lead-Free Formamidinium Tin Iodide Perovskites

Electronic devices based on tin halide perovskites often exhibit a poor operational stability. Here, we report an additive engineering strategy to realize high-performance and stable field-effect transistors (FETs) based on 3D formamidinium tin iodide (FASnI3) films. By comparatively studying the modification effects of two additives, i.e., phenethylammonium iodide and 4-fluorophenylethylammonium iodide via combined experimental and theoretical investigations, we unambiguously point out the general effects of phenethylammonium (PEA) and its fluorinated derivative (FPEA) in enhancing crystallization of FASnI3 films and the unique role of fluorination in reducing structural defects, suppressing oxidation of Sn2+ and blocking oxygen and water involved defect reactions. The optimized FPEA-modified FASnI3 FETs reach a record high field-effect mobility of 15.1 cm2/(V·s) while showing negligible hysteresis. The devices exhibit less than 10% and 3% current variation during over 2 h continuous bias stressing and 4200-cycle switching test, respectively, representing the best stability achieved so far for all Sn-based FETs.</p

Strong enhancement of photoresponsivity with shrinking the electrodes spacing in few layer GaSe photodetectors

A critical challenge for the integration of the optoelectronics is that photodetectors have relatively poor sensitivities at the nanometer scale. It is generally believed that a large electrodes spacing in photodetectors is required to absorb sufficient light to maintain high photoresponsivity and reduce the dark current. However, this will limit the optoelectronic integration density. Through spatially resolved photocurrent investigation, we find that the photocurrent in metal-semiconductor-metal (MSM) photodetectors based on layered GaSe is mainly generated from the photoexcited carriers close to the metal-GaSe interface and the photocurrent active region is always close to the Schottky barrier with higher electrical potential. The photoresponsivity monotonically increases with shrinking the spacing distance before the direct tunneling happen, which was significantly enhanced up to 5,000 AW-1 for the bottom contacted device at bias voltage 8 V and wavelength of 410 nm. It is more than 1,700-fold improvement over the previously reported results. Besides the systematically experimental investigation of the dependence of the photoresponsivity on the spacing distance for both the bottom and top contacted MSM photodetectors, a theoretical model has also been developed to well explain the photoresponsivity for these two types of device configurations. Our findings realize shrinking the spacing distance and improving the performance of 2D semiconductor based MSM photodetectors simultaneously, which could pave the way for future high density integration of 2D semiconductor optoelectronics with high performances.Comment: 25 pages, 4 figure

Organic management increases beneficial microorganisms and promotes the stability of microecological networks in tea plantation soil

IntroductionOrganic agriculture is highly regarded by people for its commitment to health, ecology, care, and fairness. The soil microbial community responds quickly to environmental changes and is a good indicator for evaluating soil microecology. Therefore, from the perspective of soil microbial communities, elucidating the impact of organic management on soil microecology in tea plantations has great significance for improving local tea plantation systems.MethodsThe study collected bulk soil from organic management (OM) and conventional management (CM) tea plantations in Pu'er City, a major tea-producing area in China, and analyzed their species diversity, structural composition, and co-occurrence networks using metagenomics technology.ResultsCompared with CM, the diversity index (Shannon) and evenness index (Heip) of soil fungi increased by 7.38% and 84.2% in OM tea plantations, respectively. The relative abundance of microorganisms related to the nitrogen cycle increased. Specifically, there was a significant increase in Rhodobiales, a 2-fold increase in Nitrospirae, and approximately 1.95 and 2.03 times increases in unclassified genera within Betaproteobacteria and Deltaproteobacteria, respectively. The relative abundance of plant residue degradation species, Gemmatimonadetes, Ascomycota, and Basidiomycota, increased by 2.8, 1, and 1.4 times, respectively. The OM was conducive to the establishment of collaborative relationships among bacterial species and increased the diversity and complexity of species relationships in fungal communities. The network stability of soil ecosystems was promoted. The organic tea plantations' keystone taxa contained mycorrhizal fungi (Pezoloma_ericae, Rhizophagus_irregularis, Rhizophagus_clarus), as well as species involved in soil nitrogen metabolism (Acidobacteria_bacterium, Acidobacteriia_bacterium_AA117, Sphingomonas_sp._URHD0007, Enhydrobacter_aerosaccus), pathogen (Erysiphe_pulchra), and parasites (Paramycosporidium saccamoeba). The partial least squares method (PLS-SEM) indicated that OM affected N-NH4+ negatively, increasing the abundance of fungi, and thereby positively affecting the Shannon index.ConclusionIn brief, reasonable organic management can improve the diversity of soil microorganisms, increase the relative abundance of beneficial bacteria in tea plantation soil, and promote the stability of the soil microbial ecological network

Precise and Rapid Validation of Candidate Gene by Allele Specific Knockout With CRISPR/Cas9 in Wild Mice

It is a tempting goal to identify causative genes underlying phenotypic differences among inbred strains of mice, which is a huge reservoir of genetic resources to understand mammalian pathophysiology. In particular, the wild-derived mouse strains harbor enormous genetic variations that have been acquired during evolutionary divergence over 100s of 1000s of years. However, validating the genetic variation in non-classical strains was extremely difficult, until the advent of CRISPR/Cas9 genome editing tools. In this study, we first describe a T cell phenotype in both wild-derived PWD/PhJ parental mice and F1 hybrids, from a cross to C57BL/6 (B6) mice, and we isolate a genetic locus on Chr2, using linkage mapping and chromosome substitution mice. Importantly, we validate the identification of the functional gene controlling this T cell phenotype, Cd44, by allele specific knockout of the PWD copy, leaving the B6 copy completely intact. Our experiments using F1 mice with a dominant phenotype, allowed rapid validation of candidate genes by designing sgRNA PAM sequences that only target the DNA of the PWD genome. We obtained 10 animals derived from B6 eggs fertilized with PWD sperm cells which were subjected to microinjection of CRISPR/Cas9 gene targeting machinery. In the newborns of F1 hybrids, 80% (n = 10) had allele specific knockout of the candidate gene Cd44 of PWD origin, and no mice showed mistargeting of the B6 copy. In the resultant allele-specific knockout F1 mice, we observe full recovery of T cell phenotype. Therefore, our study provided a precise and rapid approach to functionally validate genes that could facilitate gene discovery in classic mouse genetics. More importantly, as we succeeded in genetic manipulation of mice, allele specific knockout could provide the possibility to inactivate disease alleles while keeping the normal allele of the gene intact in human cells