Identifying extracerebellar characteristics in a large cohort of 319 Chinese patients with spinocerebellar ataxia type 3

To the Editor:Spinocerebellar ataxia type 3(SCA3)is the predominant subtype,representing 48-73%of all SCAs in the Chinese population.[1]It primarily manifests as progressive ataxia,characterized by unsteady gait,dysarthria,and limb clumsiness,due to cerebellar and interconnected gray matter damage.Notably,extracerebellar features such as extrapyramidal and oculomotor abnormalities,and spasticity,often remain underrecognized.This complexity can lead to misdiagnosis,underscoring the necessity for a more comprehensive understanding of both cerebellar and extracerebellar symptoms.

Genetic spectrum and clinical features in a cohort of Chinese patients with autosomal recessive cerebellar ataxias

Background:Although many causative genes have been uncovered in recent years,genetic diagnosis is still missing for approximately 50%of autosomal recessive cerebellar ataxia(ARCA)patients.Few studies have been performed to determine the genetic spectrum and clinical profile of ARCA patients in the Chinese population.Methods:Fifty-four Chinese index patients with unexplained autosomal recessive or sporadic ataxia were investigated by whole-exome sequencing(WES)and copy number variation(CNV)calling with ExomeDepth.Likely causal CNV predictions were validated by CNVseq.Results:Thirty-eight mutations including 29 novel ones were identified in 25 out of the 54 patients,providing a 46.3%positive molecular diagnostic rate.Ten different genes were involved,of which four most common genes were SACS,SYNE1,ADCK3 and SETX,which accounted for 76.0%(19/25)of the positive cases.The de novo microdeletion in SACS was reported for the first time in China and the uniparental disomy of ADCK3 was reported for the first time worldwide.Clinical features of the patients carrying SACS,SYNE1 and ADCK3 mutations were summarized.Conclusions:Our results expand the genetic spectrum and clinical profiles of ARCA patients,demonstrate the high efficiency and reliability of WES combined with CNV analysis in the diagnosis of suspected ARCA,and emphasize the importance of complete bioinformatics analysis of WES data for accurate diagnosis.

Optical experimental solution for the multiway number partitioning problem and its application to computing power scheduling

Quantum computing is an emerging technology that is expected to realize an exponential increase in computing power. Recently,its theoretical foundation and application scenarios have been extensively researched and explored. In this work, we propose efficient quantum algorithms suitable for solving computing power scheduling problems in the cloud-rendering domain, which can be viewed mathematically as a generalized form of a typical NP-complete problem, i.e., a multiway number partitioning problem.In our algorithm, the matching pattern between tasks and computing resources with the shortest completion time or optimal load balancing is encoded into the ground state of the Hamiltonian;it is then solved using the optical coherent Ising machine, a practical quantum computing device with at least 100 qubits. The experimental results show that the proposed quantum scheme can achieve significant acceleration and save 97% of the time required to solve combinatorial optimization problems compared with classical algorithms. This demonstrates the computational advantages of optical quantum devices in solving combinatorial optimization problems. Our algorithmic and experimental work will advance the utilization of quantum computers to solve specific NP problems and will broaden the range of possible applications.

Engineering W/O/W pickering emulsion for the enhanced antigen delivery and immune responses

Tumor immunotherapy,particularly cancer vaccines,holds promise for combating cancer by harnessing tailored immune responses against malignant cells.However,conventional approaches face challenges in efficiently delivering antigens for optimal immune activation.Emulsion adjuvants,like MF59,enhance cellular uptake but struggle to induce robust CD8^(+)T cell responses.Here,we introduce a novel strategy employing a water-in-oil-in-water(W/O/W)multiple Pickering emulsion(mPE)for antigen delivery.The mPE,utilizing biocompatible,pH-sensitive particles,encapsulates antigens within the inner water phase,ensuring enhanced intracellular processing and dictating the intracellular fate of antigens for improved cross-presentation.In vitro and in vivo studies demonstrated that mPEs induced robust dendritic cells activation and antigen cross-presentation,leading to a significantly enhanced immune response.Notably,calcium phosphate-stabilized mPE(CaP-mPE)illustrated the more robust IFN-γ^(+)T cell responses.In comparison with traditional surfactant-stabilized multiple emulsions,CaP-mPE significantly inhibit tumor growth and effectively prolong the survival of tumor-bearing mice.This innovative approach offers a promising avenue for the development of effective cancer vaccines with potent cellular immune responses.