预热温度对激光选区熔化成形30%SiC_(p)/AlSi10Mg复合材料力学性能的影响

基板常温工况下激光选区熔化成形中等体积分数SiC_(p)/Al复合材料存在孔洞、裂纹等冶金缺陷,从而导致成形零件致密度低、力学性能差等问题。首先研究了固定优化成形工艺参数时,基板预热温度(200~400℃)对45μm的30%(质量分数,下同)SiC_(p)/AlSi10Mg成形零件表观致密度和力学性能的影响;进一步提高SiC_(p)质量分数至50%,再次评价了上述基板预热温度对成形性能的影响。结果表明,当SiC_(p)质量分数为30%时,升高基板预热温度可以减少成形零件的孔洞和裂纹,成形零件的表观致密度及力学性能显著提高;当基板预热至400℃时,成形零件表观致密度最高达到97.98%,与此同时极限抗压强度和极限抗拉强度分别为578 MPa和56 MPa;随着SiC_(p)质量分数进一步增加至50%,基板预热温度对成形零件致密化和力学性能的强化效果逐步减弱。本研究证明高温预热基板能够有效抑制激光选区熔化成形中等体积分数SiC_(p)/Al复合材料的冶金缺陷,为增材制造SiC_(p)/Al复合材料提供了工程应用解决方案。

水稻乙酰乳酸合酶Ala179Val突变赋予ALS抑制剂类除草剂广谱抗性

为了鉴定新型水稻突变体ALS179对乙酰乳酸合酶(ALS,acetolactate synthase)抑制剂类除草剂的抗性,本研究以野生型水稻华航31(HH31)、耐咪唑啉酮除草剂水稻ALS627突变体和甲基磺酸乙酯(EMS,ethyl methyl sulfone)诱变的新型水稻突变体ALS179为试验材料,通过不同浓度下的4类乙酰乳酸合酶抑制剂类除草剂包衣浸种和苗期喷施处理,进一步测定表型及相关酶活性指标来探究突变体ALS179的抗性。结果表明,经过除草剂包衣浸种以及苗期喷施处理后,突变体ALS179对苯磺隆、咪唑乙烟酸、双草醚及啶磺草胺具有不同程度的抗性,且乙酰乳酸合酶、过氧化物酶、过氧化氢酶和超氧化物歧化酶的活性随除草剂浓度的升高呈下降趋势。除了20×,30×的咪唑乙烟酸处理条件下过氧化氢酶和过氧化物酶的酶活性低于野生型HH31外,其他处理条件下ALS179的乙酰乳酸合酶、超氧化物歧化酶、过氧化氢酶和过氧化物酶的酶活性均高于野生型HH31。因此,本研究发现Ala179Val突变赋予了对ALS抑制剂类除草剂的广谱抗性,为后续ALS类除草剂广谱抗性水稻品系的培育提供遗传种质资源。

Gut flora in multiple sclerosis:implications for pathogenesis and treatment

Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.

Multifaceted superoxide dismutase 1 expression in amyotrophic lateral sclerosis patients:a rare occurrence?

Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.

EMS诱变的水稻不同位点突变体对ALS抑制剂类除草剂抗性差异

稻田杂草严重威胁水稻生长,培育抗除草剂水稻新品种,是高效解决稻田杂草危害的重要途径之一。本研究利用甲基磺酸乙酯(EMS)对华占水稻进行化学诱变,创建突变体,利用乙酰乳酸合成酶(ALS)抑制剂类除草剂甲咪唑烟酸(20 g/hm 2,有效成分)对突变体进行筛选,获得抗甲咪唑烟酸突变体材料,并对上述突变体的OsALS基因序列进行分析,明确其突变类型。最后对不同突变类型对甲氧咪草烟和甲基二磺隆的交互抗性进行分析。结果表明,华占水稻经EMS诱变和甲咪唑烟酸筛选后共获得11株抗甲咪唑烟酸突变体材料,其突变类型为Pro171Leu、Ser627Cys、Ser627Asn和Gly628Glu 4种。其中,Ser627Cys为首次发现的突变类型。4种突变类型对甲咪唑烟酸的抗性水平存在一定的差异,Ser627Asn、Ser627Cys、Pro171Leu、Gly628Glu突变类型的抗性指数分别为8.71、5.16、3.28和3.69。4种突变类型对甲氧咪草烟和甲基二磺隆的抗性亦存在显著差异。其中,Ser627Asn突变类型对甲氧咪草烟的抗性最高,抗性指数为20.57,Gly628Glu对甲基二磺隆抗性最高,抗性指数为5.11。综上,本研究通过EMS诱变获得了4种抗ALS抑制剂类除草剂的华占水稻突变类型,并鉴定了其对甲咪唑烟酸的抗性差异及对甲氧咪草烟和甲基二磺隆的交互抗性,为进一步的抗除草剂水稻品种培育和除草剂轮换使用提供依据。

ALS抑制剂类除草剂抗性水稻品系迁粳187选育及抗性鉴定

乙酰乳酸合酶[ALS,也称为乙酰羟酸合酶(AHAS),EC 4.1.3.18]抑制剂类除草剂是目前治理水稻田内杂草的高效化学防除方法,以金粳818、迁粳187这2个抗性水稻品种(系)为材料,徐稻3号为敏感型对照,分析经咪唑乙烟酸处理后靶标基因的相对表达量。研究发现,抗性材料的靶标基因相对表达量逐步下降,且最终下降至正常水平的60%左右。离体酶活检测结果表明,金粳818、迁粳187这类ALS发生Ser-653-Asn氨基酸替换的材料对咪唑乙烟酸的抗性是敏感型材料徐稻3号的千倍以上。

抗ALS抑制剂类除草剂分子标记的开发及应用

杂草严重制约水稻生产,培育具有乙酰乳酸合成酶(acetolactate synthase,ALS)抑制剂的广谱抗除草剂水稻新品种是应对稻田杂草危害的有效途径之一。本研究鉴定了抗ALS抑制剂类除草剂金粳818与感除草剂日本晴ALS基因的差异位点,开发特异分子标记。对以携带ALS抗性基因型的金粳818、津稻372为亲本的杂交后代进行除草剂喷施和分子标记辅助选择。开发了818ALSF/R、HDALSF/R两对分子标记,可以快速区分纯合显性、杂合、纯合隐性3种基因型,且与除草剂喷施结果一致;选育得到22S9和22S4两份抗除草剂优异水稻种质资源材料。通过对杂交后代分子标记辅助选择可快速筛选出具有ALS除草剂抗性基因的种质资源材料,提高了在抗ALS抑制剂类除草剂水稻种质中的筛选效率。

Circulating proteomic biomarkers for diagnosing sporadic amyotrophic lateral sclerosis:a cross-sectional study

Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke rs.In this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy controls.Su bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral sclerosis.Potential biomarke rs were selected based on functionality and expression specificity.To validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay.Eight substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle rosis.Subsequently,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively distinguished early-stage amyotrophic lateral sclerosis patients from controls(AUC=0.766,P<0.0001).Moreove r,the expression of three proteins(FK506 binding protein 1A,cathelicidin-related antimicrobial peptide,and hemoglobin beta-1)was found to increase with disease progression.The proteomic signatures developed in this study may help facilitate early diagnosis and monitor the progression of sporadic amyotrophic lateral sclerosis when used in co mbination with curre nt clinical-based parameters.

The pathogenic mechanism of TAR DNA-binding protein 43(TDP-43)in amyotrophic lateral sclerosis

The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory regions.However,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the disease.The disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized countries.The TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral sclerosis.This review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).

Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

Primary lateral sclerosis:more than just an upper motor neuron disease

Advances in clinical care and recent research achievements:Primary lateral sclerosis(PLS)has traditionally been regarded as a pure upper motor neuron condition,a view perpetuated by most medical textbooks.

Unraveling the potential of acute intermittent hypoxia as a strategy for inducing robust repair in multiple sclerosis

Multiple sclerosis(MS)is a debilitating inflammatory disease of the central nervous system characterized by immune-mediated segmental demyelination and variable degrees of axonal and neuronal degeneration that contribute to disability.Inducing efficient and effective repair programs following demyelination is a major goal and challenge in MS.Conventional MS therapies focus largely on modulating the immune aspects of the disease contributing to lesions.While this alleviates some symptoms and mitigates damage,it does not tackle the fundamental challenge of effective remyelination,which few MS patients experience,especially in the progressive phase of the disease.

Multiple sclerosis is at a checkpoint: advancing the program

Multiple sclerosis(MS) is a chronic inflammatory and demyelinating disease of the central nervous system(CNS). Patients with MS experience sensory and motor function loss due to myelin and/or axon damage perpetuated by infiltrating immune cells(Hauser and Cree, 2020).

Carboplatin restores neuronal toxicity in FUS-linked amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis(ALS),also known as Lou Geh rig's disease,is a progressive neurodegenerative disorder that affects motor neurons in the brain and spinal cord.This leads to muscle weakness,paralysis,and ultimately,respiratory failure(Cha and Kim,2022).

Status of biomarker development for frontotemporal dementia and amyotrophic lateral sclerosis

Frontotemporal dementia(FTD) and amyotrophic lateral sclerosis(ALS) are neurodegenerative diseases that belong to the same disease spectrum,with overlapping of genetic and pathological features.Genetic mutations in TARDBP,C9ORF72,MAPT,and GRN have been identified in these diseases.

Metabolites and micronutrition in modulating amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disease.The majority of ALS cases are sporadic with only about 20%of familial forms.Even in families with genetic predisposition,there is significant phenotypic variability,suggesting that ALS onset may be triggered by a combination of genetic factors.

MAP4K inhibition as a potential therapy for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis(ALS)is a rare neurological disease,featuring gradual loss of muscle controls due to degeneration of motor neurons.Unfortunately,there is currently no cure for ALS.The available therapies only offer a limited extension of survival by several months,begging for more options of therapeutics.

Assistive techniques and their added value for tremor classification in multiple sclerosis

Tremor occurs in about half of multiple sclerosis(MS)patients.MS tremor has a broad frequency range of 2.5-7 Hz,with a higher prevalence of postural tremor(44%)compared to intentional tremor(6%)(Alusi et al.,2001).Tremor may affect the upper and lower extremities,head,and trunk,and may even affect the vocal cords in isolated cases of palatal tremor.MS tremor is classically attributed to lesions of the brain stem,cerebellum,or cerebellar peduncles,and tremor intensity has been shown to correlate with the number of lesions or their functional connections.However,recent work has demonstrated that inflammatory damage to the cerebello-thalamic and cortico-thalamic pathways might also play an important role in causing tremor,as it co-occurs with other signs and symptoms of MS such as dysarthria,dysmetria,dysdiadochokinesia,and dystonia(Alusi et al.,2001).

Insight into endoplasmic reticulum-mitochondria contacts in human amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis(ALS) is a fastprogressing fatal neurodegenerative disease and the most common form of motor neuron disease.There is currently no cure and approximately 90% of cases are sporadic.ALS shares genetic causes,clinical and neuropathological features with frontotemporal dementia,the second most common form of presenile dementia.ALS and frontotemporal dementia are therefore considered a disease spectrum(Abramzon et al.,2020).

Disruption of neuronal actin barrier promotes the entry of disease-implicated proteins to exacerbate amyotrophic lateral sclerosis pathology

Amyotrophic lateral sclerosis(ALS)is a devastating neurological disease characterized by the accumulation of aberrant proteins in motor neurons of the brain and spinal cord.Patients with ALS develop skeletal muscle weakness,resulting in death from respiratory paralysis,which usually occurs 2-4 years after clinical onset(Goutman et al.,2022).