Memories are One-to-Many Mapping Alleviators in Talking Face Generation.

Talking face generation aims at generating photorealistic video portraits of a target person driven by input audio. According to the nature of audio to lip motions mapping, the same speech content may have different appearances even for the same person at different occasions. Such one-to-many mapping problem brings ambiguity during training and thus causes inferior visual results. Although this one-to-many mapping could be alleviated in part by a two-stage framework (i.e., an audioto- expression model followed by a neural-rendering model), it is still insufficient since the prediction is produced without enough information (e.g., emotions, wrinkles, etc.). In this paper, we propose MemFace to complement the missing information with an implicit memory and an explicit memory that follow the sense of the two stages respectively. More specifically, the implicit memory is employed in the audio-to-expression model to capture high-level semantics in the audio-expression shared space, while the explicit memory is employed in the neural-rendering model to help synthesize pixel-level details. Our experimental results show that our proposed MemFace surpasses all the state-of-theart results across multiple scenarios consistently and significantly.

Research on fine co-focus adjustment method for segmented solar telescope.

For segmented telescopes, achieving fine co-focus adjustment is essential for realizing co-phase adjustment and maintenance, which involves adjusting the millimeter-scale piston between segments to fall within the capture range of the co-phase detection system. CGST proposes using a SHWFS for piston detection during the co-focus adjustment stage. However, the residual piston after adjustment exceeds the capture range of the broadband PSF phasing algorithm( ± 30µm), and the multi-wavelength PSF algorithm requires even higher precision in co-focus adjustment. To improve the co-focus adjustment accuracy of CGST, a fine co-focus adjustment based on cross-calibration is proposed. This method utilizes a high-precision detector to calibrate and fit the measurements from the SHWFS, thereby reducing the impact of atmospheric turbulence and systematic errors on piston measurement accuracy during co-focus adjustment. Simulation results using CGST demonstrate that the proposed method significantly enhances adjustment accuracy compared to the SHWFS detection method. Additionally, the residual piston after fine co-focus adjustment using this method falls within the capture range of the multi-wavelength PSF algorithm. To verify the feasibility of this method, experiments were conducted on an 800mm ring segmented mirror system, successfully achieving fine co-focus adjustment where the remaining piston of all segments fell within ±15µm.

High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function.

Expression of the transcriptional regulator ZFP318 is induced in germinal center (GC)-exiting memory B cell precursors and memory B cells (MBCs). Using a conditional ZFP318 fluorescence reporter that also enables ablation of ZFP318-expressing cells, we found that ZFP318-expressing MBCs were highly enriched with GC-derived cells. Although ZFP318-expressing MBCs constituted only a minority of the antigen-specific MBC compartment, their ablation severely impaired recall responses. Deletion of Zfp318 did not alter the magnitude of primary responses but markedly reduced MBC participation in recall. CD40 ligation promoted Zfp318 expression, whereas B cell receptor (BCR) signaling was inhibitory. Enforced ZFP318 expression enhanced recall performance of MBCs that otherwise responded poorly. ZFP318-deficient MBCs expressed less mitochondrial genes, had structurally compromised mitochondria, and were susceptible to reactivation-induced cell death. The abundance of ZFP318-expressing MBCs, instead of the number of antigen-specific MBCs, correlated with the potency of prime-boost vaccination. Therefore, ZFP318 controls the MBC recallability and represents a quality checkpoint of humoral immune memory.

Application of Amorphous and Nanocrystalline Soft Magnetic Materials in Balanced-Force-Type Electromagnetic Relay.

The magnetic properties of soft magnetic materials, including their saturation magnetic induction strength and permeability, significantly affect the dynamic characteristics of electromagnetic relays. However, the soft materials most commonly used for relays in the magnetic conductive components of electromagnetic systems, such as electrical pure iron, limit further relay design improvement and optimization to a certain extent. Thus, this paper proposes the use of amorphous and nanocrystalline soft magnetic materials with good high-frequency magnetic properties in magnetic circuits. A wavelet analysis was conducted on the high-frequency components of the coil current while the relay operated, and the corresponding magnetic materials were selected. Considering the challenges in processing amorphous and nanocrystalline materials and collecting test data for the accuracy verification of simulation methods, we prepared a scaled-up prototype for use in dynamic characteristic tests. The simulation method was improved, yielding more accurate simulation results regarding the relay's dynamic characteristics. On this basis, six replacement schemes using amorphous and nanocrystalline materials were considered. The test results proved that this application could improve the relay's dynamic characteristics. Finally, a full-size sample with an iron core consisting of nanocrystalline alloy 1K107B was prepared, and the conclusions were verified in tests.

IR-780 Dye-based Targeting of Cancer-associated Fibroblasts Improves Cancer Immunotherapy by Increasing Intra-tumoral T Lymphocytes Infiltration.

BACKGROUND: Immune-checkpoint inhibitors (ICIs) against programmed death (PD)-1/PD-L1 pathway immunotherapy have been demonstrated to be effective in only a subset of patients with cancer, while the rest may exhibit low response or may develop drug resistance after initially responding. Previous studies have indicated that extensive collagen-rich stroma secreted by cancer-associated fibroblasts (CAFs) within the tumor microenvironment is one of the key obstructions of the immunotherapy for some tumors by decreasing the infiltrating cytotoxic T cells. However, there is still a lack of effective therapeutic strategies to control the extracellular matrix by targeting CAFs. METHODS: The enhanced uptake of IR-780 by CAFs was assessed by using in vivo or ex vivo nearinfrared fluorescence imaging, confocal NIR fluorescent imaging, and CAFs isolation testing. The fibrotic phenotype down-regulation effects and in vitro CAFs killing effect of IR-780 were tested by qPCR, western blot, and flow cytometry. The in vivo therapeutic enhancement of anti-PD-L1 by IR-780 was evaluated on EMT6 and MC38 subcutaneous xenograft mice models. RESULTS: IR-780 has been demonstrated to be preferentially taken up by CAFs and accumulate in the mitochondria. Further results identified low-dose IR-780 to downregulate the fibrotic phenotype, while high-dose IR-780 could directly kill both CAFs and EMT6 cells in vitro. Moreover, IR-780 significantly inhibited extracellular matrix (ECM) protein deposition in the peri-tumoral stroma on subcutaneous EMT6 and MC38 xenografts, which increased the proportion of tumor-infiltrating lymphocytes (TILs) in the deep tumor and further promoted anti-PD-L1 therapeutic efficacy. CONCLUSION: This work provides a unique strategy for the inhibition of ECM protein deposition in the tumor microenvironment by targeted regulating of CAFs, which destroys the T cell barrier and further promotes tumor response to PD-L1 monoclonal antibody. IR-780 has been proposed as a potential therapeutic small-molecule adjuvant to promote the effect of immunotherapy.

Total Synthesis of Carolacton and Demethylcarolactons with Potent Antiviral Activity.

Carolacton, a naturally occurring MTHFD1 inhibitor, exhibits potent inhibitory activity against various RNA viruses including SARS-CoV-2. Herein, we present a concise total synthesis of carolacton, featuring the Krische allylation, Marshall coupling, NHK coupling, and RCM reaction as key elements. Additionally, we have synthesized three simplified carolacton analogues, one of which, namely, 14-demethyl-carolacton, exhibited notable antiviral activity. The present work paves the way for further exploration of the therapeutic potential of carolacton and its analogues.

NaturalSpeech: End-to-End Text-to-Speech Synthesis With Human-Level Quality.

Text-to-speech (TTS) has made rapid progress in both academia and industry in recent years. Some questions naturally arise that whether a TTS system can achieve human-level quality, how to define/judge that quality, and how to achieve it. In this paper, we answer these questions by first defining the human-level quality based on the statistical significance of subjective measure and introducing appropriate guidelines to judge it, and then developing a TTS system called NaturalSpeech that achieves human-level quality on benchmark datasets. Specifically, we leverage a variational auto-encoder (VAE) for end-to-end text-to-waveform generation, with several key modules to enhance the capacity of the prior from text and reduce the complexity of the posterior from speech, including phoneme pre-training, differentiable duration modeling, bidirectional prior/posterior modeling, and a memory mechanism in VAE. Experimental evaluations on the popular LJSpeech dataset show that our proposed NaturalSpeech achieves -0.01 CMOS (comparative mean opinion score) to human recordings at the sentence level, with Wilcoxon signed rank test at p-level p >> 0.05, which demonstrates no statistically significant difference from human recordings for the first time.

The peripheral immune cell counts and mouth ulcers: A two-sample Mendelian randomization study.

Objective: This study explored the causal association of peripheral immune cell counts with mouth ulcers (MUs) by two-sample Mendelian Randomization. Design: The counts of 12 circulating immune cell types (leukocytes, lymphocytes, monocytes, eosinophils, neutrophils, basophils, CD4+ cells, CD8+ cells, unswitched memory B cells, NK cells, B cells and a derived ratio (CD4+/CD8+)) were determined as the exposure. MUs were the outcome. The analysis was conducted mostly using the inverse-variance weighted (IVW) approach. MR Egger, weighted median, weighted mode and simple mode were used to detect the horizontal pleiotropy. Results: The IVW results for leukocytes and lymphocyte counts were OR = 0.93, 95 % CI = 0.88-0.98, p = 0.0115 and OR = 0.91, 95 % CI: 0.84-0.98, p = 0.0150, respectively. The Wald ratio result for CD4+ cell and CD8+ cell counts were OR = 0.70, 95 % CI: 0.65-0.75, p = 1.05 × 10-20 and OR = 1.25, 95 % CI: 1.19-1.31, p = 9.99 × 10-21, respectively. Conclusions: This study supports a causal effect of peripheral immune cell counts on MUs. Higher leukocyte, lymphocyte and CD4+ cell counts can protect against MUs, but higher CD8+ cell counts enhance the risk of MUs. This finding confirms host immune factors play a crucial role in the aetiology of MUs.

Pharmaceutical Manipulation of Mitochondrial F0F1-ATP Synthase Enables Imaging and Protection of Myocardial Ischemia/Reperfusion Injury Through Stress-induced Selective Enrichment.

To rescue ischemic myocardium from progressing to myocardial infarction, timely identification of the infarct size and reperfusion is crucial. However, fast and accurate identification, as well as the targeted protection of injured cardiomyocytes following ischemia/reperfusion (I/R) injury, remain significantly challenging. Here, a near infrared heptamethine dye IR-780 is shown that has the potential to quickly monitor the area at risk following I/R injury by selectively entering the cardiomyocytes of the at-risk heart tissues. Preconditioning with IR-780 or timely IR-780 administration before reperfusion significantly protects the heart from ischemia and oxidative stress-induced cell death, myocardial remodeling, and heart failure in both rat and pig models. Furthermore, IR-780 can directly bind to F0F1-ATP synthase of cardiomyocytes, rapidly decrease the mitochondrial membrane potential, and subsequently slow down the mitochondrial energy metabolism, which induces the mitochondria into a "quiescent state" and results in mitochondrial permeability transition pore inhibition by preventing mitochondrial calcium overload. Collectively, the findings show the feasibility of IR-780-based imaging and protection strategy for I/R injury in a preclinical context and indicate that moderate mitochondrial function depression is a mode of action that can be targeted in the development of cardioprotective reagents.

Collagen biomaterials promote the regenerative repair of abdominal wall defects in Bama miniature pigs.

Due to adhesion and rejection of recent traditional materials, it is still challenging to promote the regenerative repair of abdominal wall defects caused by different hernias or severe trauma. However, biomaterials with a high biocompatibility and low immunogenicity have exhibited great potential in the regeneration of abdominal muscle tissue. Previously, we have designed a biological collagen scaffold material combined with growth factor, which enables a fusion protein-collagen binding domain (CBD)-basic fibroblast growth factor (bFGF) to bind and release specifically. Though experiments in rodent animals have indicated the regeneration function of CBD-bFGF modified biological collagen scaffolds, its translational properties in large animals or humans are still in need of solid evidence. In this study, the abdominal wall defect model of Bama miniature pigs was established by artificial operations, and the defective abdominal wall was sealed with or without a polypropylene patch, and unmodified and CBD-bFGF modified biological collagen scaffolds. Results showed that a recurrent abdominal hernia was observed in the defect control group (without the use of mesh). Although the polypropylene patch can repair the abdominal wall defect, it also induced serious adhesion and inflammation. Meanwhile, both kinds of collagen biomaterials exhibited positive effects in repairing abdominal wall defects and reducing regional adhesion and inflammation. However, CBD-bFGF-modified collagen biomaterials failed to induce the regenerative repair reported in rat experiments. In addition, unmodified collagen biomaterials induced abdominal wall muscle regeneration rather than fibrotic repair. These results indicated that the unmodified collagen biomaterials are a better option among translational patches for the treatment of abdominal wall defects.

Energy saving and carbon reduction schemes for hospital with photovoltaic power generation and system upgrading technology.

In order to help China achieve the double carbon target of total carbon peak and high-quality sustainable economic development, and to enrich the work and content of energy conservation and emission reduction in the building sector, the most complex and energy-consuming hospitals are taken as the key projects for energy conservation and emission reduction to carry out feasibility studies. The reasons for the high energy consumption of the existing hospital buildings were analysed, and it was proposed to upgrade the existing systems (including air conditioning, hot water system and intelligent control system) and to generate photovoltaic power for the existing buildings, taking into account the characteristics of the local climate. The results of the study showed that the energy saving and emission reduction effect of the hospital was obvious after the programme was adopted.

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Ili Valley is an important ecological barrier in western China and an important economic zone of the Belt and Road Initiative. Exploring the driving factors of ecosystem service value (ESV) based on land use change is of great significance for optimizing regional ecological environment and coordinating human-land relationship. Based on three periods of land use data from 2000 to 2020 in Yili Valley, we used ArcGIS 10.8 and Origin to analyze the characteristics of land use change, temporal and spatial variations of ESV, and the synergy and trade-offs of ecosystem services, and explored the driving factors affecting the spatial differentiation of ESV and the interaction among factors by using Geo-Detector. The results showed that land use change in the study area was obvious from 2000 to 2020, with the area of grassland and water area being greatly reduced and the largest increase for the area of construction land. The ESV of grassland and water area and the service function of water resource supply decreased significantly. ESV high value areas were transformed to low value areas. Synergy was the dominant relationship among ecosystem services in the study area, which showed an increasing trend. Elevation was the main driving factor of ESV spatial differentiation in Yili Valley, and the low elevation plain area suitable for human activities on both sides of the basin was the low ESV value area. The interaction between all factors was manifested as enhanced relationship, while the explanatory power of natural factors was higher than that of social and economic factors.

PSGL-1 is an evolutionarily conserved antiviral restriction factor.

IMPORTANCE: Studying the co-evolution between viruses and humans is important for understanding why we are what we are now as well as for developing future antiviral drugs. Here we pinned down an evolutionary arms race between retroviruses and mammalian hosts at the molecular level by identifying the antagonism between a host antiviral restriction factor PSGL-1 and viral accessory proteins. We show that this antagonism is conserved from mouse to human and from mouse retrovirus to HIV. Further studying this antagonism might provide opportunities for developing new antiviral therapies.

Pseudomonas chlororaphis L5 and Enterobacter asburiae L95 biocontrol Dickeya soft rot diseases by quenching virulence factor modulating quorum sensing signal.

Virulence factor modulating (VFM) is a quorum sensing (QS) signal shared by and specific to Dickeya bacteria, regulating the production of plant cell wall degrading enzymes (PCWDEs) and virulence of Dickeya. High polarity and trace of VFM signal increase the difficulty of signal separation and structure identification, and thus limit the development of quorum quenching strategy to biocontrol bacterial soft rot diseases caused by Dickeya. In order to high-throughput screen VFM quenching bacteria, a vfmE-gfp biosensor VR2 (VFM Reporter) sensitive to VFM signal was first constructed. Subsequently, two bacterial strains with high quenching efficiency were screened out by fluorescence intensity measurement and identified as Pseudomonas chlororaphis L5 and Enterobacter asburiae L95 using multilocus sequence analysis (MLSA). L5 and L95 supernatants reduced the expression of vfm genes, and both strains also decreased the production of PCWDEs of D. zeae MS2 and significantly reduced the virulence of D. oryzae EC1 on rice seedlings, D. zeae MS2 on banana seedlings, D. dadantii 3937 on potato and D. fangzhongdai CL3 on taro. Findings in this study provide a method to high-throughput screen VFM quenching bacteria and characterize novel functions of P. chlororaphis and E. asburiae in biocontrolling plant diseases through quenching VFM QS signal.

Comparison and Evaluation of Two Combination Modes of Angiotensin for Establishing Murine Aortic Dissection Models.

Aortic dissection (AD) is a potentially fatal cardiovascular emergency caused by separation of different layers of aortic wall. However, because of limited time window available for clinical research, there is an urgent need for an ideal animal research model. In recent years, the incidence of AD complicated by atherosclerosis has increased with improvements of living standards and changes of eating habits. Accordingly, considering multiple risk factors, we successfully and efficiently established a novel AD model through a high-fat diet combined with chronic angiotensin II (AngII) infusion. Compared with traditional chemical induction model using AngII and ß-aminopropionitrile, our model is more clinically relevant for atherosclerosis-related AD. Moreover, infiltration of neutrophils and apoptosis of vascular smooth muscle cells in AD tissues were more significant. In addition to enriching the existing models, the novel model may be a long-term useful tool for more in-depth investigation of AD mechanisms and preclinical therapeutic developments.

Activation of Kv7 channels normalizes hyperactivity of the VTA-NAcLat circuit and attenuates methamphetamine-induced conditioned place preference and sensitization in mice.

The brain circuit projecting from the ventral tegmental area (VTA) to the nucleus accumbens lateral shell (NAcLat) has a key role in methamphetamine (MA) addiction. As different dopamine (DA) neuron subpopulations in the VTA participate in different neuronal circuits, it is a challenge to isolate these DA neuron subtypes. Using retrograde tracing and Patch-seq, we isolated DA neurons in the VTA-NAcLat circuit in MA-treated mice and performed gene expression profiling. Among the differentially expressed genes, KCNQ genes were dramatically downregulated. KCNQ genes encode Kv7 channel proteins, which modulate neuronal excitability. Injection of both the Kv7.2/3 agonist ICA069673 and the Kv7.4 agonist fasudil into the VTA attenuated MA-induced conditioned place preference and locomotor sensitization and decreased neuronal excitability. Increasing Kv7.2/3 activity decreased neural oscillations, synaptic plasticity and DA release in the VTA-NacLat circuit in MA-treated mice. Furthermore, overexpression of only Kv7.3 channels in the VTA-NacLat circuit was sufficient to attenuate MA-induced reward behavior and decrease VTA neuron excitability. Activation of Kv7 channels in the VTA may become a novel treatment strategy for MA abuse.

Enhanced treatment of low C/N ratio rural sewage by a modified multi-stage tidal flow constructed wetland at low temperature: Quantitative contributions of key functional genera.

Rural sewage treatment was traditionally faced contradiction between low-treatment rates and the need for low-cost development. To address this challenge, we explored the coupling of effluent circulation and step-feeding strategies in a multi-stage tidal flow constructed wetland (TFCW) to achieve stable nitrogen (N) removal performance under conditions of low carbon-to-nitrogen (C/N) ratios and low temperatures. The modified multi-stage TFCW demonstrated the ability to significantly reduce the concentrations of effluent NH4+-N and NO3--N by 33.9 % and 54.8 % respectively, resulting in values of 7.47 mg/L and 3.93 mg/L. Additionally, it achieved an average TN removal efficiency of 69.2 %. The improved N removal performance of rural sewage by the modified multi-stage TFCW at low temperatures was primarily attributed to autotrophic nitrification, heterotrophic nitrification, and autotrophic denitrification. Among the identified functional genera, Nitrosomonas and Nitrosospira played key roles as autotrophic nitrification bacteria (ANB), contributing to 28.2 % of NH4+-N removal. The key heterotrophic nitrification bacteria (HNB) Acidovorax and Rudaea were mainly responsible for 71.3 % of NH4+-N removal via the two-step ammonia assimilation through the organic nitrogen pathway. Furthermore, Rhodanobacter and Acinetobacter emerged as key autotrophic denitrification bacteria (ADNB), accounting for 79.9 % of NO3--N conversion and removal. In summary, this study provides valuable theoretical insights and supports ongoing efforts in biological regulation to address the challenges associated with rural sewage treatment.

Bilateral insufficiency fracture of coracoid process: A rare case report.

A 69-year-old man was admitted to the hospital for a left femoral neck fracture. A preliminary chest computed tomography scan showed no coracoid process fracture. The patient had no history of trauma during his hospitalization. However, subsequent in-hospital computed tomography scan revealed bilateral coracoid process fracture. The patient underwent hip replacement surgery for femoral neck fracture, while conservative treatment was administered for the bilateral coracoid process fracture. After 1-year follow-up, the patient was diagnosed with bilateral insufficiency fracture of coracoid process after ruling out other types of fractures. The fractures did not heal while functions in both shoulders were adequate. Insufficiency fracture should be considered when fractures occur without trauma, especially in the presence of associated risk factors such as chronic renal failure and osteoporosis. For bilateral insufficiency fracture of coracoid process, conservative treatment is acceptable.