Population genomic analysis provides evidence of the past success and future potential of South China tiger captive conservation.

BACKGROUND: Among six extant tiger subspecies, the South China tiger (Panthera tigris amoyensis) once was widely distributed but is now the rarest one and extinct in the wild. All living South China tigers are descendants of only two male and four female wild-caught tigers and they survive solely in zoos after 60 years of effective conservation efforts. Inbreeding depression and hybridization with other tiger subspecies were believed to have occurred within the small, captive South China tiger population. It is therefore urgently needed to examine the genomic landscape of existing genetic variation among the South China tigers. RESULTS: In this study, we assembled a high-quality chromosome-level genome using long-read sequences and re-sequenced 29 high-depth genomes of the South China tigers. By combining and comparing our data with the other 40 genomes of six tiger subspecies, we identified two significantly differentiated genomic lineages among the South China tigers, which harbored some rare genetic variants introgressed from other tiger subspecies and thus maintained a moderate genetic diversity. We noticed that the South China tiger had higher FROH values for longer runs of homozygosity (ROH > 1 Mb), an indication of recent inbreeding/founder events. We also observed that the South China tiger had the least frequent homozygous genotypes of both high- and moderate-impact deleterious mutations, and lower mutation loads than both Amur and Sumatran tigers. Altogether, our analyses indicated an effective genetic purging of deleterious mutations in homozygous states from the South China tiger, following its population contraction with a controlled increase in inbreeding based on its pedigree records. CONCLUSIONS: The identification of two unique founder/genomic lineages coupled with active genetic purging of deleterious mutations in homozygous states and the genomic resources generated in our study pave the way for a genomics-informed conservation, following the real-time monitoring and rational exchange of reproductive South China tigers among zoos.

High-accuracy deep ANN-to-SNN conversion using quantization-aware training framework and calcium-gated bipolar leaky integrate and fire neuron.

Spiking neural networks (SNNs) have attracted intensive attention due to the efficient event-driven computing paradigm. Among SNN training methods, the ANN-to-SNN conversion is usually regarded to achieve state-of-the-art recognition accuracies. However, many existing ANN-to-SNN techniques impose lengthy post-conversion steps like threshold balancing and weight renormalization, to compensate for the inherent behavioral discrepancy between artificial and spiking neurons. In addition, they require a long temporal window to encode and process as many spikes as possible to better approximate the real-valued ANN neurons, leading to a high inference latency. To overcome these challenges, we propose a calcium-gated bipolar leaky integrate and fire (Ca-LIF) spiking neuron model to better approximate the functions of the ReLU neurons widely adopted in ANNs. We also propose a quantization-aware training (QAT)-based framework leveraging an off-the-shelf QAT toolkit for easy ANN-to-SNN conversion, which directly exports the learned ANN weights to SNNs requiring no post-conversion processing. We benchmarked our method on typical deep network structures with varying time-step lengths from 8 to 128. Compared to other research, our converted SNNs reported competitively high-accuracy performance, while enjoying relatively short inference time steps.

PD-1/PD-L1 affects Graves progression through lymphocytes on the proliferation, apoptosis and inflammatory cytokine secretion of thyroid follicular epithelial cells.

We aimed to investigate the role of programmed cell death protein 1 (PD-1) and T lymphocytes in the proliferation, apoptosis and secretion of cells from patients and mice with Graves' disease (GD). The levels of serum hormones, related antibodies and inflammatory cytokines in GD patients were determined by electrochemiluminescence immunoassay and ELISA. The percentages of CD4 and CD8 T-lymphocytes and PD-1 expression were examined by flow cytometry. A GD mouse model, a thyroid follicular epithelial cell, and a CD4+PD-1+, CD4+PD-1- and CD8+PD-1+, CD8+PD-1- T lymphocyte co-culture system were constructed. The viability, apoptosis-related markers, serum hormones, related antibodies and inflammatory cytokines in thyroid follicular epithelial cells were determined by CCK-8, Western blot, qTR-PCR, electrochemiluminescence immunoassay and ELISA. Elevated free thyroid hormones (FT3, FT4), thyroid hormone antibodies (TRAb, TPOAb and TGAb), inflammatory cytokines, and inhibited TSH were observed in GD patients. The percentage of CD4+ T cells was increased, while that of CD8+ T cells was reduced in GD patients. PD-1 expression level was lifted in both CD4+ and CD8+ cells from GD patients. In mouse thyroid follicular epithelial cells co-cultured with CD4+PD-1+ and CD8+PD-1+ T lymphocytes, the cell viability, TH and TRAb levels and inflammatory cytokines level were the highest, while the TSH level and apoptosis were the lowest. PD-1 positive T lymphocytes were able to promote viability and inhibit apoptosis of thyroid follicular epithelial cells, which further caused a more accelerated development of GD.

Hyperbranched Polysiloxanes Based on Polyhedral Oligomeric Silsesquioxane Cages with Ultra-High Molecular Weight and Structural Tuneability.

Hyperbranched siloxane-based polymers with ultra-high molecular weight were synthesized by the Piers⁻Rubinsztajn reaction between octakis(dimethylsiloxy) octasilsesquioxane with different dialkoxysilanes, using tris(pentafluorophenyl) borane as the catalyst. The origin of the high molecular weight is explained by the high reactivity of the catalyst and strain energy of isolated small molecule in which all eight silane groups close into rings on the sides of a single cubic cage. The structural tuneability was further demonstrated by use of methyl(3-chloropropyl)diethoxysilane, which generates a polymer with similar ultra-high molecular weight. Introduction of phosphonate groups through the chloropropyl sites later leads to functionalized polymers which can encapsulate various transition metal nanoparticles.

Cyclic Polysiloxanes with Linked Cyclotetrasiloxane Subunits.

Cyclic polymers are an important class of macromolecules, but the structural diversity of the backbone is limited. Herein we report the use of the Piers-Rubinsztajn reaction for the one-step synthesis of cyclic polysiloxanes with novel structural features. Specifically, the B(C6 F5 )3 -catalyzed coupling of various organic tris(dimethylsiloxy)silane and trialkoxysilane compounds generated a series of cyclic polysiloxanes with cyclotetrasiloxane subunits. The thiolated cyclic polymers were also shown to be effective in directing the circular assembly gold nanoparticles. The presence of constrained rings in the backbone is unprecedented and may offer opportunities for novel applications of these cyclic polymers.

[Simultaneous modulated accelerated radiation therapy in the treatment of nasopharyngeal cancer].

OBJECTIVE: To evaluate the toxicity and clinical efficacy of simultaneous modulated accelerated radiation therapy (SMART) technique for nasopharyngeal carcinoma. METHODS: 110 patients with nasopharyngeal carcinoma underwent boost treatment with SMART at the dose of 2.5 Gy/time for 28 times for gross tumor volume (GTV) with the total dose of 70 Gy and the dose of 2.0 Gy/time once a day and 5 times a week, totally 28 times, with the total dose of 56 Gy for the clinical treatment volume (CTV). The GTV dose for 36 of these patients was boosted to 80 Gy. Follow-up was conducted for 24 months (7 - 44 months). RESULTS: Follow-up showed that the 1, 2, and 3-year survival rates were 97.02%, 88.72%, and 78.27%, respectively. The 1 - 3 year local relapse-free survival rate was 97.94% (95.10% - 100%). The 1, 2, and 3-yea local-regional relapse-free rates and distant metastasis-free rates were 95.21%, 89.83%, 76.10% and 95.38%, 85.71%, and 79.67%, respectively. According to the Fuzhou staging, the 3-year overall survival rate of the stage I - II patients was 100%, while the 3-year survival rate of the stage III patients was 74.33% and the 3-year survival rate of stage IV a patients was 62.96%. The acute toxicity was well tolerated except for the high incidence of severe mucositis. No grade 4 side effects occurred. Most of the patients showed Grade 0 to 1 late toxicity and xerostomia was a common side effect. No increase of toxicity was seen when the GTV dose was increased to 80 Gy. CONCLUSION: SMART yields superior dose distribution over the traditional radiotherapy in nasopharyngeal carcinoma at the early or advanced stages. The local-regional control was excellent and distant metastasis remains the main risk. Dose escalation to 80 Gy was safe and feasible. Toxicity of SMART is acceptable and tolerable.