Biochemical consequences of glucocerebrosidase 1 mutations in Parkinson’s disease

Parkinson’s disease(PD,OMIM#168600)is a common neurodegenerative disorder with a global prevalence of approximately 8.5 million.PD is characterized by four cardinal motor symptoms:bradykinesia,rigidity,resting tremor,and subsequently by postural instability.It usually involves non-motor symptoms such as rapid eye movement sleep disorder,dementia,anosmia,and autonomic dysfunction.The gene glucocerebrosidase 1(GBA1),which encodes the lysosomal enzyme glucocerebrosidase(GCase)(IUBMB:EC 3.2.1.45),shows strong linkage with PD;variants of GBA1 are the commonest genetic association with PD(Sidransky et al.,2009).Several mechanisms may underlie the relationship between GBA1 mutations/variants and the molecular pathology of PD(Figure 1A and B).

Neurological consequences of human calmodulin mutations

When calcium ions enter the cytosol,it is a stimulatory signal for cellular events.The calcium sensor calmodulin picks up the change in calcium concentration and relays this information to its more than 300 downstream interaction partners.In this way,calmodulin affects cellular processes such as fertilization,muscle contraction,neuronal firing,and apoptosis.That is,calmodulin is involved in(nearly)everything!The significance of calmodulin is emphasized by the fact that we all carry three different genes(CALM1,2,3)on different chromosomes that encode the exact same calmodulin protein,and these are all expressed in all cell types.Moreover,throughout vertebrate evolution,the protein sequence has remained completely unchanged.

Tau's function and dysfunction in the brain:when small changes have big consequences

With the increase of life expectancy and population growth,neurodegenerative diseases have risen too and are projected to be a major health public concern by 2050.Neurodegenerative diseases are characterized by the progressive decline of cognitive function leading to the subsequent loss of autonomy.Although the underlying causes of neurodegeneration are not well understood,aging is the main risk factor.

Lactate is a potentially harmful substitute for brain glucose fuel:consequences for metabolic restoration of neurotransmission

The metabolite lactate (L-lactate) can be generated and released by diverse brain cells,including neurons,astrocytes,and oligodendrocytes (Kann,2023;Rae et al.,2024).Lactate production usually requires the degradation of glucose (D-glucose)-and glycogen in astrocytes-to pyruvate by glycolysis and subsequent conversion of pyruvate to lactate by the enzyme lactate dehydrogenase(Figure 1A;Dienel,2019;Rae et al.,2024).

Associated Factors and Consequences of Uterine Fibroids in Hospitals in the Borgou Department of Benin in 2022

Introduction: Uterine fibroids are the most common gynecological tumors in women of childbearing age and have multiple clinical manifestations. Objective: To determine factors associated with uterine fibroids in the Borgou department of Benin in 2022. Method: Descriptive, analytical cross-sectional study from August 22 to September 22, 2022. The sample consisted of women consulting for gynecological problems in 6 hospitals in the Borgou department in the North of Benin. Results: Of the 744 women surveyed, 10.1% were diagnosed with uterine fibroids. Women with uterine fibroids were often married, paucigesture, and nulliparous. Their main reasons for consultation were the desire for motherhood (50.7%), pelvic pain (46.7%), and genital hemorrhage (14.7%). Age, history of miscarriage, high blood pressure, and diabetes were significantly associated with the presence of uterine fibroids (Conclusion: Uterine fibroids are common in hospitals in northern Benin. There were factors associated with them that should be taken into account in management strategies.

The Importance of Setting Treatment Goals for Cardiovascular Diseases

Background: Guidelines are issued by most major organizations that focus on a specific disease entity. Guidelines should be a significant help to the practicing physician who may not be up-to-date with the recent medical literature. Unfortunately, when conflicting guidelines for a specific disease are published, confusion results. Purpose: This article provides a suggested guideline outcome measure that would benefit the physician and patient. Methods: A review of 19 different guidelines for cardiovascular disease treatment is one example of the lack of specific outcomes that currently exist. The basic problem with most guidelines is that they do not state the expected end result (i.e., the benefit to the patient) if that guideline is followed. When guidelines use cardiovascular disease risk factors to dictate therapy, the end benefit is never stated so that the patient can make an appropriate choice of which (if any) guideline to follow. Results: A good example is guidelines published by the American Heart Association for reducing cardiovascular disease. These guidelines are risk factor based and only indicate that cardiovascular disease would be reduced if followed. No specific percentage in the reduction of the incidence of disease is given. In contrast, when elimination of the disease is the stated goal of the guideline, the end result is clear. To date, this goal has been stated by only one organization devoted to eliminating cardiovascular disease. Conclusion: Guidelines need to be written to provide the physician and the patient with a specific end point that is expected when the guideline is followed. Patient acceptance and compliance will be much improved if the patient knows the risk/benefit of following the guideline’s recommendations.

Role of self-help groups on socioeconomic development and the achievement of Sustainable Development Goals(SDGs)among rural women in Cooch Behar District,India

This study examines the transformative role of self-help groups(SHGs)in the socioeconomic development of rural women in Cooch Behar District,India,and their contribution toward achieving Sustainable Development Goals(SDGs)of the United Nations.In this study,we explored the effect of SHGs on rural women by specifically addressing SDGs,such as no poverty(SDG 1),zero hunger(SDG 2),good health and well-being(SDG 3),quality education(SDG 4),and gender equality(SDG 5).Given this issue,a cross-sectional survey and comparison analyses are needed to assess the socioeconomic development of rural women and their awareness level before and after the participation of rural women in SHGs.The survey conducted as part of this study was divided into three sections,namely,demographic characteristics,socioeconomic development,and awareness level,with each focusing on different aspects.A group of 400 individuals who were part of SHGs completed the questionnaire survey form.The results showed that the participation of rural women in SHGs significantly improved their socioeconomic development and awareness level,as supported by both mean values and t test results.Memberships in SHGs and microcredit programs were the major elements that boosted the socioeconomic development of rural women,which also achieves SDGs 1,2,3,4,and 5.This study revealed that participation in SHGs and related financial services significantly aided rural women in economically disadvantaged communities in accumulating savings and initiating entrepreneurial ventures.Moreover,participation in SHGs was instrumental in enhancing the self-confidence,self-efficacy,and overall self-esteem of rural women.Finally,doing so enabled them to move more freely for work and other activities and to make family and common decisions.

Spatial differences of Sustainable Development Goals(SDGs)among counties(cities)on the northern slope of the Kunlun Mountains

The county(city)located on the northern slope of the Kunlun Mountains is the primary area to solidify and extend the success of Xinjiang Uygur Autonomous Region,China in poverty alleviation.Its Sustainable Development Goals(SDGs)are intertwined with the concerted economic and social development of Xinjiang and the objective of achieving shared prosperity within the region.This study established a sustainable development evaluation framework by selecting 15 SDGs and 20 secondary indicators from the United Nations’SDGs.The aim of this study is to quantitatively assess the progress of SDGs at the county(city)level on the northern slope of the Kunlun Mountains.The results indicate that there are substantial variations in the scores of SDGs among the nine counties and one city located on the northern slope of the Kunlun Mountains.Notable high scores of SDGs are observed in the central and eastern regions,whereas lower scores are prevalent in the western areas.The scores of SDGs,in descending order,are as follows:62.22 for Minfeng County,54.22 for Hotan City,50.21 for Qiemo County,42.54 for Moyu County,41.56 for Ruoqiang County,41.39 for Qira County,39.86 for Lop County,38.25 for Yutian County,38.10 for Pishan County,and 36.87 for Hotan County.The performances of SDGs reveal that Hotan City,Lop County,Minfeng County,and Ruoqiang County have significant sustainable development capacity because they have three or more SDGs ranked as green color.However,Hotan County,Moyu County,Qira County,and Yutian County show the poorest performance,as they lack SDGs with green color.It is important to establish and enhance mechanisms that can ensure sustained income growth among poverty alleviation beneficiaries,sustained improvement in the capacity of rural governance,and the gradual improvement of social security system.These measures will facilitate the effective implementation of SDGs.Finally,this study offers a valuable support for governmental authorities and relevant departments in their decision-making processes.In addition,these results hold significant reference value for assessing SDGs at the county(city)level,particularly in areas characterized by low levels of economic development.

GOAL问卷和Epworth嗜睡量表联合筛查阻塞性睡眠呼吸暂停的效能

目的检验GOAL问卷和Epworth嗜睡量表(Epworth sleeping scale,ESS)在筛查阻塞性睡眠呼吸暂停(obstructive sleep apnea,OSA)中联合应用的效能。方法从睡眠医学中心招募2958例参与者,完成夜间多导睡眠图监测和筛查问卷,包括GOAL、ESS、STOP-Bang问卷(SBQ)和NoSAS评分。评估每个量表的敏感度、特异度、阳性预测值、阴性预测值、诊断优势比(diagnostic odds ratio,DOR)和受试者工作特征(ROC)曲线下面积(area under the curve,AUC)。结果GOAL问卷在筛选OSA方面具有更高的敏感度和DOR(敏感度为0.831,DOR为3.72),优于STOP-Bang问卷和NoSAS评分。当GOAL问卷和ESS量表相结合时,特异度和DOR分别显著上升至0.894和4.22。GOAL问卷得分为3且ESS量表≥11分的参与者极有可能患有OSA,概率为0.96。结论GOAL问卷和ESS量表相结合具有优秀的诊断能力,可有效筛查OSA。对疑似OSA患者进行GOAL问卷后的第二阶段进行ESS量表筛查,可以提高预测准确性和早期诊断。

Accident source term and radiological consequences of a small modular reactor

Considering the growing global demand for energy and the need for countries to achieve climate goals,there is an increasing global interest in small modular reactors(SMRs)and their applications.Accident source term and radiological consequence evaluations of SMRs are key components of nuclear and radiation safety reviews,which affect the site,exclusion area(EAB),and low population zone outer boundaries.Based on the design characteristics of the SMR and accident analysis results,a theoretical model of a whole-core fuel cladding damage accident was constructed to study the radioactivity released into the environment and its consequences.The accident source term and radiation dose calculation models were established to analyze the released amounts of radionuclides and the total effective dose affecting individuals at the site boundary.The results showed that the amount of radionuclides released into the environment after a whole-core fuel cladding damage accident reached 10^(14) Bq,among which the release amount of ^(133)Xe was the largest.The total effective dose at the site boundary 30 days after the accident was 8.65 mSv.The highest total effective dose affecting individuals occurred to the east-north-east.The results of the accident source term and radiological consequence provide technical support for site boundary dose assessments and reviews of SMRs.

Knowledge Gaps in Sustainable Development Goals (SDGs) Impacts on Biodiversity Conservation in Nairobi, Kenya

Sustainable Development Goals (SDGs) aim to ensure environmental sustainability is enhanced focusing on the future generation. Knowledge of the SDGs becomes pivotal in biodiversity conservation thus, a gap impacts such efforts on protecting and preserving biodiversity habits difficult. Nairobi City was chosen because of her unique ecosystem that habits wildlife and urban life with great prospects of being East Africa’s business hub. With an estimated double city population by 2030, knowledge of SDGs would be useful in enhancing biodiversity conservation in unique cities like Nairobi. Thus, a gap in the knowledge of SDGs threatens the future of biodiversity unless it is mitigated. The study employed a cross-sectional design that caters to qualitative and quantitative data. Data was collected using semi-structured questionnaires and key informant interviews. Data Envelopment Analysis (DEA) model was adopted to evaluate how determinants of human perceptions, decisions, and activities related to implementing sustainable development goals impact biodiversity conservation. Results indicate that respondents’ knowledge (30.5% ± 2.01%), attitudes (30.4% ± 1.56%), and practice (26.3% ± 0.08%) on implementation of SDGs was significantly low. Further, a majority believed that lack of awareness of SDGs 87% impacts biodiversity conservation, coupled with 12% and 1%, respectively, who opined that limited SDGs knowledge sharing and corruption were barriers to biodiversity conservation. The majority of respondents believed that increased awareness of SDGs (78.2% ± 2.61%), and strengthened institutional capacity (58.7% ± 3.01%) underscores SDGs’ importance in biodiversity conservation. Knowledge of SDGs is pivotal in the enhancement of biodiversity conservation.

Empowering women to combat osteoporosis:unveiling the causes,consequences,and control strategies

Osteoporosis is a common bone disease in women worldwide, leading to decreased bone density and an accelerated risk of fractures. The causes of osteoporosis in women include age (senile osteoporosis), menopause-associated hormonal changes, deficiencies in calcium and vitamin D, genetics, lifestyle factors, medical conditions, and some type of medications. The consequences of osteoporosis are colossal, consisting of fractures, decreased quality of life, psychological impacts, and economic burden. To effectively control the menace of osteoporosis in women, numerous strategies are advocated. Adequate calcium and vitamin D consumption through diet or supplements is vital. Regular weight-bearing activities and strength training that promote bone density. Maintaining a healthy life-style through avoiding smoking, limiting alcohol in-take and maintaining a wholesome body weight is essential. Hormone replacement therapy and some medications may be recommended in certain cases. Early detection through regular bone density and blood tests is crucial to lowering its impact. Creating a supportive network through educational programs and resources fosters awareness and empowerment. By engaging these strategies, women can be empowered to combat osteoporosis, reduce fracture risk, and build stronger bones for their overall well-being.

Research on the Spatiotemporal Evolution,and Optimized Paths of Carbon Pressure in Northwestern Sichuan under the Carbon Peaking and Carbon Neutrality Goals

Consolidating carbon sink capacity and reducing carbon pressure are important channels to achieve the carbon peaking and carbon neutrality goals actively yet prudently.In order to study the current situation of carbon pressure in the Northwestern Sichuan,we took the carbon pressure of the Aba Tibetan-Qiang autonomous prefecture(Aba prefecture)as an example and used the Intergovernmental Panel on Climate Change(IPCC)approach to measure the carbon emissions,carbon uptake,and the carbon balance index(CBI)of each county-level city in Aba prefecture from 2012 to 2020.The study found that:(a)There was a continuous trend of declining carbon emissions,increased carbon uptake,and decreased CBI in Aba prefecture during the sample period,but there is a large variability among county-level cities;(b)Aba prefecture differs in the spatiotemporal distribution of carbon emissions,carbon uptake,and CBI.Based on the research results,we propose several optimized paths for alleviating the current carbon pressure situation in the Northwestern Sichuan.

State of the HIV, Hepatitis B and C Virus Pandemic from 2003 to 2022 in Burkina Faso: Evolution of Prevalence Trends and Strategic Recommendations to Achieve the WHO’s Goal for Their Eradication by 2030

Background: The World Health Organization (WHO) has set a goal to eradicate or at least significantly reduce the prevalence the human immunodeficiency virus (HIV), hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) by 2030. The main objective was to provide an evolving overview of the prevalence of HIV, HBV and HCV infection between 2003 and 2022 in Burkina Faso. Methods: It was a retrospective cross-sectional study based on data from 2003 to 2022. The data were collected using information available in the databases of the HOSCO and CERBA laboratories and included all individuals who underwent HIV and/or HBV and/or HCV testing. Data analysis was performed using SPSS version 20.0, EpiInfo 7, and R version 4.1.0. Results were considered statistically significant if p Results: The study recorded 7432 samples and the mean age of the subjects was 27.98 ± 8.50 years. During this period, the respective prevalence of HIV, HBV, and HCV were 4.66% (346/7432), 8.77% (582/6636) and 5.54% (322/5816). However, from 2003 to 2022, there was a significant decrease (P y=−1.75x+12.59;y=−0.24x+10.01and y=−0.11x+6.02, with “y” corresponding to prevalence and “x” to the years. Conclusion: Burkina Faso needs to rigorously apply prevention and control strategies recommended by the WHO by 2030.

Megacity pathways in China under the dual carbon goal:The case of Shanghai

The pathways to achieving carbon neutrality at the city level are diverse due to varying energy supply and demand conditions.Shanghai faces obstacles such as limited land resources,high costs of renewable energy technologies,and instability of renewable energy.These challenges hinder the city’s efforts to achieve carbon peak and carbon neutrality(dual carbon).Therefore,Shanghai must identify and optimize its development path for renewable energy under the dual carbon goal.We employed the Low Emissions Analysis Platform Shanghai(LEAP-SH)model to simulate the impact of policies,such as industrial upgrading,energy efficiency improvement,energy structure optimization,increased technical innovation on energy,and ecological restoration,on the carbon emission pathways from 2022 to 2060 using five different scenarios.Our results indicate that Shanghai has the potential to achieve carbon neutrality in 2059 by promoting carbon reduction,pollution control,and green expansion.Moreover,we determined that the manufacturing industry;power generation industry;and transportation,storage,and mail services are the three major sectors for emission reduction under the dual carbon goal.Furthermore,the capacity and output of coal-fired power plants will be gradually replaced by offshore wind power in the dual carbon pathway.Finally,this study proposes countermeasures and suggestions for Shanghai to attain the dual carbon goal and high-quality development.

Strategies for Cultivating Public Funded Targeted Normal Students Based on Goal Management Theory : A Case Study of East, West and North Guangdong

Public funded targeted normal students are an important component of China's teacher team construction.Since its implementation in 2007,a large number of outstanding rural teachers who have been striving on the front line of education have been trained.Based on the theory of goal management,this paper explores the problems and countermeasures in the training of public funded targeted normal students.It strives to solve the problems of low willingness to teach and high default rates among public funded normal students,and hopes that the suggestions proposed in this paper can further promote the effective implementation of policies for public funded normal students.

LASG全球海洋-大气-陆面系统模式(GOALS/LASG)及其模拟研究

该文扼要介绍了ＬＡＳＧ第一版本全球海洋－大气－陆面系统模式（ＧＯＡＬＳ／ＬＡＳＧ）的发展和结构，及其对气候平均态、季节变化和年际变化的模拟，以及近期发展计划．

GOALS模式对热带太平洋ENSO年际变化特征的模拟评估

文中重点分析了中国科学院大气物理研究所LASG最新发展的全球大气环流谱模式 (R4 2L9)与一全球海洋环流模式 (T6 3L30 )耦合形成的全球海洋 大气 陆面气候系统模式 (GOALS/LASG)新版本已积分 30a的模拟结果 ,通过与多种观测资料的对比分析 ,讨论了赤道太平洋海表温度 (SST)的年际变化及其纬向传播、赤道东太平洋SST异常与其他洋面SST变化之间的遥相关关系、赤道太平洋浅表层海温的年际变化特征等研究内容。结果表明 ,GOALS模式模拟出了赤道太平洋SST异常出现不规则的年际变化特点 ;赤道东太平洋SST异常的向西传播过程 ;赤道太平洋混合层海温变化由西向东、由深层向浅层的传播过程 ;同时也模拟出了赤道东太平洋SST变化与赤道西太平洋以及与西南太平洋海温之间的反相关关系 ,与南印度洋和副热带大西洋SST之间的正遥相关关系等实际观测现象。但GOALS模式也存在明显的不足 ,如对赤道东、中太平洋SST异常的年际变化幅度明显偏小 ,没能模拟出赤道东太平洋的SST变化比赤道中太平洋强的特点 ;赤道太平洋SST从东向西的传播速度明显比实际观测慢得多 ,但混合层海温极值变化由西向东的传播速度明显比实际情况快得多 ;没能模拟出赤道东太平洋SST变化同西北太平洋SST的负相关和北印度洋海温变化的正相关现象 ,因此?

Risk factors and long-term health consequences of macrosomia:a prospective study in Jiangsu Province,China

We sought to determine risk factors associated with fetal macrosomia and to explore the long-term consequence of infant macrosomia at the age of 7 years.A prospective population based cohort study was designed to examine the associations between maternal and perinatal characteristics and the risk of macrosomia.A nested case-control study was conducted to explore the long-term health consequence of infant macrosomia.The mean maternal age of the macrosomia group was 24.74±3.32 years,which is slightly older than that in the control group（24.35±3.14 years,P = 0.000）.The mean maternal body mass index（BMI） at early pregnancy was 22.75±2.81 kg/m 2,which was also higher than that in the control group（21.76±2.59 kg/m 2,P = 0.000）.About 64.6% of macrosomic neonates were males,compared with 51.0% in the control group（P = 0.000）.Compared with women with normal weight（BMI：18.5-23.9 kg/m 2）,women who were overweight（BMI：24-27.9 kg/m 2） or obese（BMI ≥ 28 kg/m 2）,respectively,had a 1.69-fold（P = 0.000） and a 1.49-fold（P = 0.000） increased risks of having a neonate with macrosomia,while light weight（BMI〈18.5 kg/m 2） women had an approximately 50% reduction of the risk.Furthermore,macrosomia infant had a 1.52-fold and 1.50-fold risk,respectively,of developing overweight or obesity at the age of 7 years（P = 0.001 and P = 0.000）.Older maternal age,higher maternal BMI at early pregnancy and male gender were independent risk factors of macrosomia.Macrosomic infant was associated with an increased predisposition to develop overweight or obesity at the beginning of their childhood.

The North Atlantic Oscillation Simulated by Versions 2 and 4 of IAP/ LASG GOALS Model

The capabilities of two versions of the Global–Ocean–Atmosphere–Land–System model (i.e. GOALS–2 and GOALS–4) developed at State Key Laboratory of Atmospheric Sciences and Geophysical Fluid Dynamics (LASG), are validated in terms of the simulations of the winter North Atlantic Oscillation (NAO), which is currently the subject of considerable scientific interest. The results show that both GOALS–2 and GOALS–4 exhibit a realistic NAO signal associated with relatively reasonable spatial patterns of sea level pressure, surface air temperature, and precipitation. Generally speaking, the associated patterns of precipitation in GOALSs match better with the observation in comparison with the case of surface temperature. For the imprint of NAO on the ocean, or perhaps a coupling between the two fluids, the associated tripole patterns of the North Atlantic SST anomaly are presented distinctly in GOALS–2, for GOALS-4 however, this is not the case. Spatially, the models’ main deficiencies appear to be that the simulated Icelandic lows shift northward apparently, which in turn result in the blemish of GOALSs in reproducing the accompanied surface wind anomalies. For the interannual and even longer time scale variations of DJF sea level pressure (SLP) over the North Atlantic region, GOALSs reproduce the center with the strongest variability rationally, but the intensities are far weaker than the observation. Key words North Atlantic Oscillation (NAO) - Model evaluation - GOALS model This study was jointly supported by the National key Project (Grant No. 96-908-02-03), the Excel-lent National Key Laboratory Research Project (Grant NO. 49823002), Chinese Academy of Sciences (CAS) under grant “ Bai Ren Ji Hua” for “ Validation of Coupled Climate Models”, and IAP innova-tion fund (No.8-1204).The authors gratefully acknowledge Dv. Jin Xuingze, Mr. Liu Xiying in IAP /LASG, and Dr. Gong Daoyi in Geophysical Department of Peking University for providing ardent help.