Genetic pathways in cerebral palsy:a review of the implications for precision diagnosis and understanding disease mechanisms

Ce rebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and posture.Patients with cerebral palsy are often only capable of limited activity,resulting from non-progressive disturbances in the fetal or neonatal brain.These disturbances severely impact the child’s daily life and impose a substantial economic burden on the family.Although cerebral palsy encompasses various brain injuries leading to similar clinical outcomes,the unde rstanding of its etiological pathways remains incomplete owing to its complexity and heterogeneity.This review aims to summarize the current knowledge on the genetic factors influencing cerebral palsy development.It is now widely acknowledged that genetic mutations and alterations play a pivotal role in cerebral palsy development,which can be further influenced by environmental fa ctors.Des pite continuous research endeavors,the underlying fa ctors contributing to cerebral palsy remain are still elusive.However,significant progress has been made in genetic research that has markedly enhanced our comprehension of the genetic factors underlying cerebral palsy development.Moreove r,these genetic factors have been categorized based on the identified gene mutations in patients through clinical genotyping,including thrombosis,angiogenesis,mitochondrial and oxidative phosphorylation function,neuronal migration,and cellular autophagy.Furthermore,exploring targeted genotypes holds potential for precision treatment.In conclusion,advancements in genetic research have substantially improved our understanding of the genetic causes underlying cerebral palsy.These breakthroughs have the potential to pave the way for new treatments and therapies,consequently shaping the future of cerebral palsy research and its clinical management.The investigation of cerebral palsy genetics holds the potential to significantly advance treatments and management strategies.By elucidating the underlying cellular mechanisms,we can develop to rgeted interventions to optimize outcomes.A continued collaboration between researchers and clinicians is imperative to comprehensively unravel the intricate genetic etiology of cerebral palsy.

Asymmetric expression of CA2 and CA13 linked to calcification in the bilateral mandibular condyles cause crossed beaks in chickens

Crossed beak is a complex mode of inheritance with prevalence ranging from 0.2 to 7.4% in at least 12 chicken strains worldwide.To reveal the intrinsic factors causing crossed beaks,genes expression patterns in bilateral mandibular condyle between affected and normal birds were characterized by RNA sequencing analysis in the present studies.Crossed beak was induced by short length of unilateral mandibular ramus,and a total of 110differentially expressed genes were up-or down-regulated in the affected(short)mandibular condyle side as compared to the normal side.Carbonic anhydrase 2(CA2)and Carbonic anhydrase 13(CA13)were enriched in the carbonate dehydratase activity,and high-expressed in mandibular condyle and osteoblasts(P<0.05).However,both were low-expressed in short mandibular condyle side of affected birds(P<0.05).The carbonate dehydratase inhibitor experiments confirmed that there is positive association between the calcification and carbonic anhydrase isoenzymes.Quantitative analysis with cetylpyridinium chloride showed a decrease in calcification when the cells were transfected with an anti-CA13 shRNA.Our research suggested that CA2 and CA13 are down-calcified in shortside mandibular condyle,and caused mandibular ramus to grow slowly.CA2 and CA13 have the critical role in crossed beaks by regulating calcification of mandibular condyle.

Reexamination of Sexual Dimorphism and Female Reproduction in the Many-Lined Sun Skink Eutropis multifasciata from China

We reexamined sexual dimorphism and female reproduction in the Many-Lined Sun Skink Eutropis multifasciata from Hainan,China. Our data confirm that adults are sexually dimorphic in body size and shape,with males being the larger sex and larger in head size but shorter in abdomen length than females of the same snoutvent length(SVL). The rate at which head width increased with SVL was greater in males as opposed to the previous conclusion that the rate does not differ between the sexes. Maternal size was the main determinant of reproductive investment,with larger females generally producing more,as well as larger,offspring. Females produced up to nine offspring per litter as opposed to the previously reported 2–7. Most females gave birth between March and August,a time period approximately four months longer than that(May–June) reported previously. Females with a higher fecundity tended to produce smaller offspring as opposed to the previous conclusion that females do not tradeoff offspring size against number. Litter size,neonate mass and litter mass remained remarkably constant among years,and litter mass was more tightly related to female body size than litter size or neonate mass. Smaller females could produce relatively heavier litters without a concomitant reduction in postpartum body condition.

Boosting high initial coulombic efficiency of hard carbon by in-situ electrochemical presodiation

Hard carbon(HC)is a promising anode material for sodium ion batteries(SIBs),whereas inferior initial coulombic efficiency(ICE)severely limits its practical application.In the present work,we propose an in situ electrochemical presodiation approach to improve ICE by mixing sodium biphenyl(Na-Bp)dimethoxyethane(DME)solution with DME-based ether electrolyte.A solid electrolyte interface(SEI)could be formed beforehand on the HC electrode and Na^(+)was absorbed to nanopores and graphene stacks,compensating for the sodium loss and preventing electrolyte decomposition during the initial charge and discharge cycle.By this way,the ICE of half-cells was increased to nearly 100%and that of full-cells from 45%to 96%with energy density from 132.9 to 230.5 W h kg^(-1).Our work provides an efficient and facile method for improving ICE,which can potentially promote the practical application of HCbased materials.

Poultry genetic heritage cryopreservation and reconstruction:advancement and future challenges

Poultry genetics resources,including commercial selected lines,indigenous breeds,and experimental lines,are now being irreversibly lost at an alarming rate due to multiple reasons,which further threats the future livelihood and academic purpose.Collections of germplasm may reduce the risk of catastrophic loss of genetic diversity by guaranteeing that a pool of genetic variability is available to ensure the reintroduction and replenishment of the genetic stocks.The setting up of biobanks for poultry is challenging because the high sensitiveness of spermatozoa to freezing–thawing process,inability to cryopreserve the egg or embryo,coupled with the females being heterogametic sex.The progress in cryobiology and biotechnologies have made possible the extension of the range of germplasm for poultry species available in cryobanks,including semen,primordial germ cells,somatic cells and gonads.In this review,we introduce the state-of-the-art technologies for avian genetic resource conservation and breed reconstruction,and discuss the potential challenges for future study and further extending of these technologies to ongoing and future conservation efforts.

消毒剂对重组Ⅲ型人源化胶原蛋白促细胞黏附活性的影响

通过CCK8实验探究75%乙醇、碘伏、葡萄糖酸洗必泰、苯扎氯铵、苯扎溴铵对细胞的毒性以及对重组Ⅲ型人源化胶原蛋白(rhColⅢ)促细胞的黏附活性的影响,预测消毒剂的使用在面部填充时对胶原蛋白活性的影响,为临床应用提供指导。结果显示:各消毒剂对NIH/3T3小鼠胚胎成纤维细胞和HFB人皮肤成纤维细胞均表现出细胞毒性,比较结果为:葡萄糖酸洗必泰<苯扎氯铵、苯扎溴铵<75%乙醇、碘伏,该结果也间接提示75%乙醇、碘伏消毒效果较佳;将各消毒剂原液稀释100倍后,其对rhColⅢ促细胞黏附活性影响比较为:葡萄糖酸洗必泰、苯扎氯铵<75%乙醇<碘伏、苯扎溴铵。碘伏和苯扎溴铵工作液直接接触rhColⅢ均显著降低其促细胞黏附活性,碘伏、葡萄糖酸洗必泰、苯扎溴铵工作液直接接触rhColⅢ可导致其发生聚集。

Potential role of PANoptosis in neuronal cell death:commentary on"PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons"

See related article,pp 357-363Extensive neuronal cell death occurs during nervous system development to remove surplus,unwanted,and damaged cells.This is a highly regulated physiological process that plays a pivotal role in nervous system homeostasis and normal development.In some brain regions,more than half of the neurons are removed during normal development without interfering with the remaining cells.This gene-regulated neuronal cell deletion process is called programmed cell death(Fricker et al.,2018).

Role of apoptosis-inducing factor in perinatal hypoxic-ischemic brain injury

Perinatal complications,such as asphyxia,can cause brain injuries that are often associated with subsequent neurological deficits,such as cerebral palsy or mental retardation.The mechanisms of perinatal brain injury are not fully understood,but mitochondria play a prominent role not only due to their central function in metabolism but also because many proteins with apoptosis-related functions are located in the mitochondrion.Among these proteins,apoptosis-inducing factor has already been shown to be an important factor involved in neuronal cell death upon hypoxia-ischemia,but a better understanding of the mechanisms behind these processes is required for the development of more effective treatments during the early stages of perinatal brain injury.In this review,we focus on the molecular mechanisms of hypoxic-ischemic encephalopathy,specifically on the importance of apoptosis-inducing factor.The relevance of apoptosis-inducing factor is based not only because it participates in the caspase-independent apoptotic pathway but also because it plays a crucial role in mitochondrial energetic functionality,especially with regard to the maintenance of electron transport during oxidative phosphorylation and in oxidative stress,acting as a free radical scavenger.We also discuss all the different apoptosis-inducing factor isoforms discovered,focusing especially on apoptosis-inducing factor 2,which is only expressed in the brain and the functions of which are starting now to be clarified.Finally,we summarized the interaction of apoptosis-inducing factor with several proteins that are crucial for both apoptosis-inducing factor functions(prosurvival and pro-apoptotic)and that are highly important in order to develop promising therapeutic targets for improving outcomes after perinatal brain injury.

Monochromatic green light stimulation during incubation shortened the hatching time via pineal function in White Leghorn eggs

Background:Effect of monochromatic green light illumination on embryo development has been reported in chickens.The avian pineal gland is an important photo-endocrine organ formed by a mediodorsal protrusion during embryonic development.However,the involvement of pineal gland in the light transduction process remains to be elucidated.In the present study,we investigated the influence of monochromatic green light on hatching time and explored the possible mechanism via pineal function.Results:A total of 600 eggs of White Leghorn(Shaver strain)were incubated under photoperiods of either 12 h of light and 12 h of darkness using monochromatic green light(12L:12D group)or 24 h of darkness(0L:24D group)for 18 d.Compared to 0L:24D group,the green light stimulation shortened the hatching time without extending the hatch window or impairing hatchability.The liver of embryos incubated in the 12L:12D light condition was heavier than those of the 0L:24D group on d 21 post incubation which may be linked to the observed increase in the serum concentration of insulin-like growth factor 1(IGF-1);primary secretion of the liver.Histological structure analysis of pineal gland demonstrated that the light stimulation increased follicle area,wall thickness and lumen area on d 10 and d 12 post incubation.Rhythmic function analysis demonstrated that three clock related genes(brain and muscle ARNT-like-1,BMAL1;circadian locomotor output cycles kaput,CLOCK;and cryptochrome-1,CRY1)and a melatonin rate-limiting enzyme related gene(arylalkylamine N-acetyltransferase,AANAT)were rhythmically expressed in the pineal gland of the 12L:12D group,but not in the 0L:24D group.Simultaneously,the light stimulation also increased the concentration of melatonin(MT),which was linked to hepatocyte proliferation and IGF-1 secretion in previous studies.Conclusions:The 12L:12D monochromatic green light stimulation during incubation shortened hatching time without impairing hatching performance.Pineal gland’s early histological development and maturation of its rhythmic function were accelerated by the light stimulation.It may be the key organ in the photo-endocrine axis that regulates embryo development,and the potential mechanism could be through enhanced secretion of MT in the 12L:12D group which promotes the secretion of IGF-1.

经3种ALK抑制剂及化疗治疗的1例非小细胞肺癌病例报道

棘皮动物微管相关蛋白4(echinoderm microlubule-associated protein-like 4, EML4)和间变淋巴瘤激酶基因(anaplastic lymphoma kinase, ALK)可发生断裂后融合为EML4-ALK基因。对于EML4-ALK阳性非小细胞肺癌(nonsmall cell lung cancer, NSCLC),一代至三代的ALK抑制剂的使用已显示出显著疗效,很多患者可以从药物治疗中实现长期获益,部分患者在优化的治疗模式下可取得超过7年的长期生存。本例患者为EML4-ALK融合基因阳性肺腺癌,治疗结局却明显不同于其他EML4-ALK融合基因阳性肺癌患者,经过一代至三代ALK抑制剂靶向治疗和化学治疗疾病进展快,耐药时间短,生存期短,获益有限。患者2019年7月15日开始先后口服克唑替尼、色瑞替尼、劳拉替尼靶向治疗,行贝伐珠单抗联合培美曲塞、卡铂化疗2个疗程,于2020年9月10日患者死亡,生存期15个月。同时治疗中表现出ALK抑制剂的常见不良反应。本文分析本例患者的治疗疗效及治疗困境,为EML4-ALK融合基因阳性肺癌患者治疗提供探索方向。

Effects of Nourishing “Yin”-Removing “Fire” Chinese Herb Mixture on the Differential Expression of GABA_AReceptor <i>α</i>Subunits in Hypothalamus of Precocious Puberty Female Rats

GABAergic input to Gonadotropin-releasing hormone (GnRH) neurons is necessary to initiate the onset of puberty and its action mainly depends on GABAA receptor of which the subunit composition, properties and consequently function varies during this period. Nourishing “Yin”-Removing “Fire” Chinese herb mixture, a Chinese herb-based formulation, has been proved that it may retard the initiation of pubertal development in female precocious puberty rats. Our objective is to investigate the effects of Nourishing “Yin”-Removing “Fire” Chinese herb mixture on the expression of GABAA receptor α subunits in hypothalamus. Female Sprague-Dawley rats were divided into normal (N), precocious puberty model (M) induced by danazol, model exposed to saline (MS) and model exposed to Chinese herb mixture (CHM) groups. All rats were administered by the Chinese herb mixture from P15 on. Coefficients of reproductive organs and serum gonadotropins and estradiol levels in M were significantly enhanced while they were significantly decreased in CHM. The hypothalamic GnRH mRNA was also significantly increased in M and in CHM, as well as ERα mRNA. At the mean time, the hypothalamic GABAA receptor α1 and α3 subunits mRNA were more significantly decreased in M than those of N, while they were more significantly enhanced in CHM than those in M (p 0.01), the protein expression of which in hypothalamus had the same trend as the mRNA expression. The evidence suggests that Nourishing “Yin”-Removing “Fire” Chinese herb mixture could significantly retard the sexual development of the precocious rats, and up-regulate the expressions of hypothalamic GABAA receptor α1 and α3 subunits. Our result indicated that GABAA receptor α1 and α3 subunits might involve in the effective treatment of herb mixture on idiopathic precocious puberty.

Clinical Value of rhBNP in the Treatment of Patients with Stanford Type B Aortic Dissection

Objective:To determine the clinical value of rhBNP in the treatment of patients with Stanford type B aortic dissection.Methods:From June 2018 to October 2021,162 patients with Stanford type B aortic dissection were selected from the Cardiology Department of Henan Provincial Chest Hospital and randomly divided into two groups:control group(81 patients)and observation group(81 patients).The patients in the control group were treated with conventional therapy.On the basis of the control group,the patients in the observation group were treated with rhBNP.The cardiac function,renal function,pulmonary function,and inflammatory indices before and after treatment for 72 hours,as well as the incidence of adverse reactions between the two groups were compared.Results:After treatment,the cardiac function(LVEF and NT-pro BNP),renal function(urine output for 24 hours,SCr,and Cys-C),pulmonary function(PaO_(2),SPO_(2),and PaO_(2)/FiO_(2)),and inflammatory(IL-6,hsCRP,and MCP-1)indices of the observation group improved significantly compared to those of the control group(p<0.05).Conclusion:rhBNP can improve cardiac function,renal function,and pulmonary function,as well as alleviate inflammation in patients with Stanford type B aortic dissection.Hence,in the treatment of patients with Stanford type B aortic dissection,rhBNP provides multi-organ protection.

Ni单原子负载氮掺杂多孔碳促进锂硫电池中的多硫化物转化

由分散在氮掺杂碳载体上的原子级金属位点组成的单原子催化剂(M SAC@NC)因其具有最大的原子利用率、独特的物理化学性质和优异的催化活性,已成为Li-S电池中的高性能电催化材料.本文采用物理吸附和热解相结合的方法,成功制备了一系列具有相似结构和理化性质的M SAC@NC(M=Ni,Co,Fe).双球差校正高角环形暗场扫描透射电子显微镜和X射线吸收光谱表明成功形成了单原子金属位点.此外,对硫氧化还原反应的催化活性趋势为Ni SAC@NC>Co SAC@NC>Fe SAC@NC,其中Ni SAC@NC在0.5C下表现出1280.6mAh g^(-1)的最高容量,循环800次后,平均每圈容量衰减率仅为0.07%,具有优异的电池性能.

Synergistic Effect of Nitrogen/Phosphorus Co-Doping and Molybdenum Carbide Induced Electron Redistribution of Carbon Layer to Boost Hydrogen Evolution Reaction

The development of highly efficient non-precious-metal-based electrocatalysts for the hydrogen evolution reaction is imperative for promoting the large-scale application of electrochemical water splitting.Herein,nitrogen/phosphorus co-doped carbon nanorods encapsulated Mo_(2)C nanoparticles(Mo_(2)C@PNc)have been prepared by pre-phosphating treatment in combination of the coordination with polydopamine and the subsequent pyrolysis.The phosphating temperature has a significant effect on the content of phosphorus within the resultant Mo_(2)C@PNC,and the optimal catalyst delivers superior HER activity with the low overpotential of 104 mV at a current density of 10 mAcm^(-2) and good stability for 8 h,which has been theoretically demonstrated to originate from the synergistic effect between P doping and Mo_(2)C induced electron redistribution of nitrogen-doped carbon layer.

Targeting Peripheral μ-opioid Receptors or μ-opioid Receptor-Expressing Neurons Does not Prevent Morphine-induced Mechanical Allodynia and Anti-allodynic Tolerance

The chronic use of morphine and other opioids is associated with opioid-induced hypersensitivity(OIH)and analgesic tolerance.Among the different forms of OIH and tolerance,the opioid receptors and cell types mediating opioid-induced mechanical allodynia and anti-allodynic tolerance remain unresolved.Here we demonstrated that the loss of peripheralμ-opioid receptors(MORs)or MOR-expressing neurons attenuated thermal tolerance,but did not affect the expression and maintenance of morphine-induced mechanical allodynia and anti-allodynic tolerance.To confirm this result,we made dorsal root ganglia-dorsal roots-sagittal spinal cord slice preparations and recorded low-threshold Aβ-fiber stimulation-evoked inputs and outputs in superficial dorsal horn neurons.Consistent with the behavioral results,peripheral MOR loss did not prevent the opening of Aβmechanical allodynia pathways in the spinal dorsal horn.Therefore,the peripheral MOR signaling pathway may not be an optimal target for preventing mechanical OIH and analgesic tolerance.Future studies should focus more on central mechanisms.

支气管扩张合并强直性脊柱炎单肺移植一例

肺移植可有效治疗多种终末期肺病,如慢性阻塞性肺疾病、肺纤维化、矽肺和支气管扩张等[1]。强直性脊柱炎(ankylosing spondylitis,AS)是一种慢性进行性炎症性疾病,主要侵犯以骶髂关节为代表的中轴关节及少数下肢为主的外周关节,严重者晚期出现脊柱畸形和关节强直[2],严重脊柱侧弯的患者可因胸壁扭曲而导致严重的肺功能受限和胸腔容积减小。严重脊柱和胸壁畸形曾被认为是肺移植的绝对禁忌证。目前,国外已有数例脊柱侧弯患者行肺移植报道,预后良好[3,4,5]。浙江大学医学院附属第一医院为1例支气管扩张合并AS患者行左肺移植,现报道如下。

A quantification model of Traditional Chinese Medicine syndromes in children with idiopathic precocious puberty and early puberty

OBJECTIVE:To establish a quantification model of Traditional Chinese Medicine(TCM)syndromes by sampling patients undergoing idiopathic precocious puberty(IPP)and early puberty.METHODS:A questionnaire for classifying and quantifying TCM syndromes was designed and administered.All the results were analyzed;the relationship between 3 types of syndrome and 47symptoms were summated.Meanwhile,the frequency distribution of each symptom or sign was aggregated.Fuzzy mathematics was used to develop a quantification model ofTCM syndromes.RESULTS:We found that precocious puberty had 3types of syndrome,including hyperactivity of fire due to Yin deficiency(Syndrome I),depressed liver Qi transforming into fire(Syndrome II),and end retention of damp heat(Syndrome III).In the IPP group,Syndrome I was the most common principal syndrome(100%).Forty-six patients(43.81%)werediagnosed with Syndrome I accompanied by Syndrome II and 11(10.48%)were diagnosed with Syndrome I accompanied by Syndrome III.In the early puberty group,Syndrome I was also the main syndrome(98.39%).The degrees of most symptoms were mild to moderate.Reddened tongue was the most common tongue manifestation(62.86%prevalence)in the IPP group.The most common pulse manifestations were slippery pulse,thread pulse,and taut pulse.The Asymptotic Normalization Coefficient(ANC)method was used to quantify the TCM syndromes in 167 cases.Diagnostic accuracy rate reached 91%,comparable to expert diagnosis.CONCLUSION:We find that there are 3 types of syndrome in the IPP group and in the early puberty group.Syndrome I(hyperactivity of fire due to Yin deficiency)is the main syndrome in the two groups.ANC may be an appropriate for quantification model ofTCM syndromes.

Regulating nitrogen vacancies within graphitic carbon nitride to boost photocatalytic hydrogen peroxide production

Introducing nitrogen vacancies is an effective method to improve the catalytic performance of g-C_(3)N_(4)-based photocatalysts,whereas understanding how nitrogen vacancies types affect the catalytic performance remains unclear.Herein,two different types of nitrogen vacancies were successfully introduced into g-C_(3)N_(4)by pyrolysis of melamine under argon and ammonia atmosphere with subsequent HNO3 oxidation.The pyrolysis atmosphere is found to have a significant influence on the introduced nitrogen vacancies type,where tertiary nitrogen groups(N_(3)C)and sp2-hybridized nitrogen atoms(N_(2)C)were the preferred sites for the formation of nitrogen vacancies under ammonia and argon pyrolysis,respectively.Moreover,nitrogen vacancies from N3C are experimentally and theoretically demonstrated to facilitate the narrowed band gap and the improved oxygen absorption capability.As expected,the optimal catalyst exhibits high H_(2)O_(2)yield of 451.8µM,which is 3.8 times higher than the pristine g-C_(3)N_(4)(119.0µM)after 4 h and good stability after10 photocatalytic runs.

Creating Healthy Enterprises:the Workplace Health Action Plan in China

Summary On October 21,2019,the“Notice on promoting the healthy enterprises”and“Specification of Healthy Enterprise Construction(trial)”were issued jointly by the National Patriotic Health Campaign Committee Office and six other government partners.As one of the objectives and tasks of the occupational health protection action(2019–2030),this multisectoral“Healthy Enterprise”Action Plan(HEAP)serves as the first“healthy cell”project carried out at the national level as an indispensable part of the Healthy China Initiative and the Healthy City Movement.

Molecular engineering and biomedical applications of ultra-sensitive fluorescent probe for Ag^(+)

A series of probes KJ-x(x=1-3)with carbon chains of different lengths based on the matrix of rhodamine B were engineered to detect Ag^(+)in aqueous solution in this work.Among them,KJ-1 is selected as the best option after in vitro investigation in view of its most sensitive and rapid response to Ag^(+),whose possible sensing mechanism is studied by experimental investigation and theoretical calculation.To identify the practical application of the probe,the detection of Ag^(+)in nonantibiotic fungicide Silver&Health and differentiation between normal hepatocytes and hepatoma cells using confocal imaging was conducted.