Research and Experience Reference on London’s Response to Climate Change in the Twenty-first Century

London’s approaches to tackling climate change after the 21st century are multifaceted and relatively systematic.The aim of this research paper is to analyse London’s actions in response to climate change and to draw out what valuable lessons London has for the world in terms of its response to climate change.This paper provides an in-depth analysis of London’s policies and actions on climate mitigation in the areas of“greenhouse gas emissions”and“energy infrastructure”,and climate adaptation actions in the areas of“city green belt and urban afforestation”,“UHI and thermal crisis management”and“water supply infrastructure and sustainable drainage”.It then examines the positive aspects of these actions to determine what London has to say about climate change to the rest of the world and other cities.This paper also discovers that to effectively mitigate and adapt to climate change,London has not only established carbon reduction targets,but also created a large academic research network,represented by the LCCP.At the same time,London has developed a scientific climate change adaptation planning framework(P2R2)that focuses on four key areas:Economic,environmental,health,and infrastructure sectors,and three types of risks:Flooding,heat,and water supply,and emphasizes the dynamics and flexibility of each adaptation strategy.

全科医学和初级保健横断面研究的基本设计和实施步骤

横断面研究是经典的研究设计方法之一,在临床各个专业中均有广泛的应用。在全科医学研究中大量科学问题的解答采用了横断面研究设计。这其中不仅包括了对人群健康特征,疾病特征或卫生服务现状的调查研究,还包括了面向社区人群的疾病筛查诊断方法构建等多种研究场景。在全科医学领域中,横断面研究可以做现况描述和比较分析,关联因素分析以及社区筛查诊断方法探索。开展横断面研究应包括研究设计和研究实施两个阶段,研究设计包括准确提炼研究目标,明确研究人群,研究因素及结局指标等临床要素以及确定样本获取方式,明确样本量的确定依据及合理的统计分析策略等方法学要素。研究实施,则需要通过完备的研究方案和病例报告表呈现研究设计思路,在伦理批准的前提下开展数据收集工作,同时注重数据管理工作质量并严格执行方案中的统计分析方法,求证医学问题。横断面研究的特点是相比于随访观察研究所需要的研究周期相对较短,不同基础的研究团队都能找到适合的研究方向,通过了解健康医疗现状,从探讨关联因素创建筛查方法等角度,服务社区医疗。

Simulation of the SMILE Soft X-ray Imager response to a southward interplanetary magnetic field turning

The Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)Soft X-ray Imager(SXI)will shine a spotlight on magnetopause dynamics during magnetic reconnection.We simulate an event with a southward interplanetary magnetic field turning and produce SXI count maps with a 5-minute integration time.By making assumptions about the magnetopause shape,we find the magnetopause standoff distance from the count maps and compare it with the one obtained directly from the magnetohydrodynamic(MHD)simulation.The root mean square deviations between the reconstructed and MHD standoff distances do not exceed 0.2 RE(Earth radius)and the maximal difference equals 0.24 RE during the 25-minute interval around the southward turning.

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).

The magnetosheath at high spectral resolution

While we eagerly anticipate SMILE’s(Solar wind Magnetosphere Ionosphere Link Explorer)unprecedented X-ray observations of the Earth’s magnetosheath and the initiation of a new era of magnetospheric research,it seems appropriate to look ahead to the abilities of the next generation of astrophysics missions.Of these,the Line Emission Mapper(LEM),a large aperture micro-calorimeter based mission,is currently planned to be able to observe the magnetosheath at high spectral resolution(~2 eV).With a field of view of~30′,LEM will allow higher spatial resolution and higher cadence measurement of the motion of a very small portion of the magnetopause over relatively short periods of time(multiple hours),complementing SMILE’s global mapping.LEM’s strength is its spectral resolution.It will be able to measure the abundance of a broad range of elements and ionization states,many of which are inaccessible to current in situ instruments,and will be able to separate the emission from the magnetosheath from the emission from the cosmic X-ray background using the difference in their relative velocities.

The Soft X-ray Imager(SXI)on the SMILE Mission

The Soft X-ray Imager(SXI)is part of the scientific payload of the Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)mission.SMILE is a joint science mission between the European Space Agency(ESA)and the Chinese Academy of Sciences(CAS)and is due for launch in 2025.SXI is a compact X-ray telescope with a wide field-of-view(FOV)capable of encompassing large portions of Earth’s magnetosphere from the vantage point of the SMILE orbit.SXI is sensitive to the soft X-rays produced by the Solar Wind Charge eXchange(SWCX)process produced when heavy ions of solar wind origin interact with neutral particles in Earth’s exosphere.SWCX provides a mechanism for boundary detection within the magnetosphere,such as the position of Earth’s magnetopause,because the solar wind heavy ions have a very low density in regions of closed magnetic field lines.The sensitivity of the SXI is such that it can potentially track movements of the magnetopause on timescales of a few minutes and the orbit of SMILE will enable such movements to be tracked for segments lasting many hours.SXI is led by the University of Leicester in the United Kingdom(UK)with collaborating organisations on hardware,software and science support within the UK,Europe,China and the United States.

Layered Potassium Titanium Niobate/Reduced Graphene Oxide Nanocomposite as a Potassium‑Ion Battery Anode

With graphite currently leading as the most viable anode for potassium-ion batteries(KIBs),other materials have been left relatively underexamined.Transition metal oxides are among these,with many positive attributes such as synthetic maturity,longterm cycling stability and fast redox kinetics.Therefore,to address this research deficiency we report herein a layered potassium titanium niobate KTiNbO5(KTNO)and its rGO nanocomposite(KTNO/rGO)synthesised via solvothermal methods as a high-performance anode for KIBs.Through effective distribution across the electrically conductive rGO,the electrochemical performance of the KTNO nanoparticles was enhanced.The potassium storage performance of the KTNO/rGO was demonstrated by its first charge capacity of 128.1 mAh g^(−1) and reversible capacity of 97.5 mAh g^(−1) after 500 cycles at 20 mA g^(−1),retaining 76.1%of the initial capacity,with an exceptional rate performance of 54.2 mAh g^(−1)at 1 A g^(−1).Furthermore,to investigate the attributes of KTNO in-situ XRD was performed,indicating a low-strain material.Ex-situ X-ray photoelectron spectra further investigated the mechanism of charge storage,with the titanium showing greater redox reversibility than the niobium.This work suggests this lowstrain nature is a highly advantageous property and well worth regarding KTNO as a promising anode for future high-performance KIBs.

Adenosine A_(2A)receptor blockade attenuates excitotoxicity in rat striatal medium spiny neurons during an ischemic-like insult

During brain ischemia,excitotoxicity and peri-infarct depolarization injuries occur and cause cerebral tissue damage.Indeed,anoxic depolarization,consisting of massive neuronal depolarization due to the loss of membrane ion gradients,occurs in vivo or in vitro during an energy failure.The neuromodulator adenosine is released in huge amounts during cerebral ischemia and exerts its effects by activating specific metabotropic receptors,namely:A_(1),A_(2A),A_(2B),and A_(3).The A_(2A)receptor subtype is highly expressed in striatal medium spiny neurons,which are particularly susceptible to ischemic damage.Evidence indicates that the A2Areceptors are upregulated in the rat striatum after stroke and the selective antagonist SCH58261 protects from exaggerated glutamate release within the first 4 hours from the insult and alleviates neurological impairment and histological injury in the following 24 hours.We recently added new knowledge to the mechanisms by which the adenosine A2Areceptor subtype participates in ischemia-induced neuronal death by performing patch-clamp recordings from medium spiny neurons in rat striatal brain slices exposed to oxygen and glucose deprivation.We demonstrated that the selective block of A2Areceptors by SCH58261 significantly reduced ionic imbalance and delayed the anoxic depolarization in medium spiny neurons during oxygen and glucose deprivation and that the mechanism involves voltage-gated K+channel modulation and a presynaptic inhibition of glutamate release by the A2Areceptor antagonist.The present review summarizes the latest findings in the literature about the possibility of developing selective ligands of A2Areceptors as advantageous therapeutic tools that may contribute to counteracting neurodegeneration after brain ischemia.

Targeting muscle to treat Charcot-Marie-Tooth disease

Charcot-Marie-Tooth disease(CMT)is a hereditary peripheral neuropathy causing muscle weakness/wasting and sensory dysfunction predominantly in limb extremities.CMT patients display gait abnormalities,foot deformities,loss of sensation and decreased/absent deep tendon reflexes,with motor symptoms usually being more prominent than sensory.

Current remarks and future directions on the interactions between metabolic dysfunction-associated fatty liver disease and COVID-19

During the outbreak of the coronavirus disease 2019(COVID-19)pandemic,particular interest rose regarding the interaction between metabolic dysfunctionassociated fatty liver disease(MAFLD)and the COVID-19 infection.Several studies highlighted the fact that individuals with MAFLD had higher probability of severe acute respiratory syndrome coronavirus 2 infection and more severe adverse clinical outcomes.One of the proposed mechanisms is the inflammatory response pathway,especially the one involving cytokines,such as interleukin 6,which appeared particularly elevated in those patients and was deemed responsible for additional insult to the already damaged liver.This should increase our vigilance in terms of early detection,close follow up and early treatment for individuals with MAFLD and COVID-19 infection.In the direction of early diagnosis,biomarkers such as cytokeratin-18 and scoring systems such as Fibrosis-4 index score are proposed.COVID-19 is a newly described entity,expected to be of concern for the years to come,and MAFLD is a condition with an ever-increasing impact.Delineating the interaction between these two entities should be brought into the focus of research.Reducing morbidity and mortality of patients with COVID-19 and MAFLD should be the ultimate objective,and the optimal way to achieve this is by designing evidence-based prevention and treatment policies.

Does photobiomodulation require glucose to work effectively?

A main requirement for cells to function normally is the availability of glucose.Glucose,available either direct from circulation or storage,is converted to the essential energy that cells need to drive critical intrinsic functions.If cells are deprived of glucose,they become dysfunctional and suffer distress.Photobiomodulation,the use of specific wavelengths of light on body tissues,has been shown to promote,through small organelles called mitochondria,the metabolism of glucose to make energy for cells;this energy can be used to improve cell function and survival.In this perspective,we hypothesize that the availability of glucose is central to the core mechanism of photobiomodulation;that photobiomodulation is at its most efficient in stimulating mitochondrial activity and improving cell function when there is glucose readily available.

Preface to the Special Issue on Modeling and Data Analysis Methods for the SMILE mission

The SMILE(Solar wind Magnetosphere Ionosphere Link Explorer)project(http://www.nssc.cas.cn/smile/,https://www.cosmos.esa.int/web/smile/mission)is a joint spacecraft mission of the European Space Agency(ESA)and the Chinese Academy of Sciences(CAS)with an expected launch in 2025.SMILE aims to study the global interactions of solar wind–magnetosphere–ionosphere innovatively by imaging the Earth’s magnetosheath and cusps in soft X-rays and the northern auroral region in ultraviolet(UV)while simultaneously measuring plasma and magnetic field parameters in the solar wind and magnetosheath along a highly-elliptical and highly-inclined orbit.This special issue is composed of 22 articles,presenting recent progress in modeling and data analysis techniques developed for the SMILE mission.In this preface,we categorize the articles into the following seven topics and provide brief summaries:(1)instrument descriptions of the Soft X-ray Imager(SXI),(2)numerical modeling of the X-ray signals,(3)data processing of the X-ray images,(4)boundary tracing methods from the simulated images,(5)physical phenomena and a mission concept related to the scientific goals of SMILE-SXI,(6)studies of the aurora,and(7)ground-based support for SMILE.

Data,digital worlds,and the avatarization of health care

Significant technological trends are impacting health care,from consumerisation,datafication,circular economy,and platformization of services.Web 3.0,or the Internet of Value,enables direct peer-to-peer value exchange,opening up new business models that will impact health care.Among the many technologies that will also be part of the healthcare transformation is artificial intelligence,which shocked the world with the debut of ChatGPT in 2022.This opinion piece will explore how AI underpins the health transformation and,far from being an enemy of health,is the critical friend health care has been waiting for.

Deep Reinforcement Learning-Based Task Offloading and Service Migrating Policies in Service Caching-Assisted Mobile Edge Computing

Emerging mobile edge computing(MEC)is considered a feasible solution for offloading the computation-intensive request tasks generated from mobile wireless equipment(MWE)with limited computational resources and energy.Due to the homogeneity of request tasks from one MWE during a longterm time period,it is vital to predeploy the particular service cachings required by the request tasks at the MEC server.In this paper,we model a service caching-assisted MEC framework that takes into account the constraint on the number of service cachings hosted by each edge server and the migration of request tasks from the current edge server to another edge server with service caching required by tasks.Furthermore,we propose a multiagent deep reinforcement learning-based computation offloading and task migrating decision-making scheme(MBOMS)to minimize the long-term average weighted cost.The proposed MBOMS can learn the near-optimal offloading and migrating decision-making policy by centralized training and decentralized execution.Systematic and comprehensive simulation results reveal that our proposed MBOMS can converge well after training and outperforms the other five baseline algorithms.

Rational design of vitamin C/defective carbon van der Waals heterostructure for enhanced activity,durability and storage stability toward oxygen reduction reaction

Metal-free defective carbon materials with abundant active sites have been widely studied as low-cost and efficient oxygen reduction reaction(ORR)electrocatalysts in metal-air batteries.However,the active sites in defective carbon are easily subjected to serious oxidation or hydroxylation during ORR or storage,leading to rapid degradation of activity.Herein,we design a van der Waals heterostructure comprised of vitamin C(VC)and defective carbon(DC)to not only boost the activity but also enhance the durability and storage stability of the DC-VC electrocatalyst.The formation of VC van der Waals between DC and VC is demonstrated to be an effective strategy to protect the defect active sites from oxidation and hydroxylation degradation,thus significantly enhancing the electrochemical durability and storage anti-aging performance.Moreover,the DC-VC van der Waals can reduce the reaction energy barrier to facilitate the ORR.These findings are also confirmed by operando Fourier transform infrared spectroscopy and density functional theory calculations.It is necessary to mention that the preparation of this DC-VC electrocatalyst can be scaled up,and the ORR performance of the largely produced electrocatalyst is demonstrated to be very consistent.Furthermore,the DC-VC-based aluminum-air batteries display very competitive power density with good performance maintenance.

Portal hypertension in patients with nonalcoholic fatty liver disease:Current knowledge and challenges

Portal hypertension(PH)has traditionally been observed as a consequence of significant fibrosis and cirrhosis in advanced non-alcoholic fatty liver disease(NAFLD).However,recent studies have provided evidence that PH may develop in earlier stages of NAFLD,suggesting that there are additional pathogenetic mechanisms at work in addition to liver fibrosis.The early development of PH in NAFLD is associated with hepatocellular lipid accumulation and ballooning,leading to the compression of liver sinusoids.External compression and intraluminal obstacles cause mechanical forces such as strain,shear stress and elevated hydrostatic pressure that in turn activate mechanotransduction pathways,resulting in endothelial dysfunction and the development of fibrosis.The spatial distribution of histological and functional changes in the periportal and perisinusoidal areas of the liver lobule are considered responsible for the pre-sinusoidal component of PH in patients with NAFLD.Thus,current diagnostic methods such as hepatic venous pressure gradient(HVPG)measurement tend to underestimate portal pressure(PP)in NAFLD patients,who might decompensate below the HVPG threshold of 10 mmHg,which is traditionally considered the most relevant indicator of clinically significant portal hypertension(CSPH).This creates further challenges in finding a reliable diagnostic method to stratify the prognostic risk in this population of patients.In theory,the measurement of the portal pressure gradient guided by endoscopic ultrasound might overcome the limitations of HVPG measurement by avoiding the influence of the pre-sinusoidal component,but more investigations are needed to test its clinical utility for this indication.Liver and spleen stiffness measurement in combination with platelet count is currently the best-validated non-invasive approach for diagnosing CSPH and varices needing treatment.Lifestyle change remains the cornerstone of the treatment of PH in NAFLD,together with correcting the components of metabolic syndrome,using nonselective beta blockers,whereas emerging candidate drugs require more robust confirmation from clinical trials.

Biomaterials-based anti-inflammatory treatment strategies for Alzheimer's disease

The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alzheimer's disease are not clear,but neuroinflammation can link various hypotheses of Alzheimer's disease;hence,targeting neuroinflammation may be a new hope for Alzheimer's disease treatment.Inhibiting inflammation can restore neuronal function,promote neuro regeneration,reduce the pathological burden of Alzheimer's disease,and improve or even reverse symptoms of Alzheimer's disease.This review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease;reports the mechanisms and characteristics of small-molecule drugs(e.g.,nonsteroidal anti-inflammatory drugs,neurosteroids,and plant extracts);macromolecule drugs(e.g.,peptides,proteins,and gene therapeutics);and nanocarriers(e.g.,lipid-based nanoparticles,polymeric nanoparticles,nanoemulsions,and inorganic nanoparticles)in the treatment of Alzheimer's disease.The review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.

New Benthic Fossils from the Late Ediacaran Strata of Southwestern China

The Jiangchuan Biota from the Jiucheng Member(Mb.)of the Dengying Formation(Fm.),discovered in Jiangchuan,eastern Yunnan,China,is marked by copious macrofossils at the apex of the Ediacaran strata.This fauna features benthic algae with varied holdfasts and other fossils of indeterminate taxonomic affinity and is compositionally unique compared to the Shibantan and Gaojiashan biotas of the Dengying Fm.and the Miaohe and Wenghui biotas of the Doushantuo Fm.,elsewhere in China.One novel benthic saccular macroalgal fossil,named here Houjiashania yuxiensis gen.and sp.nov.,from the Jiangchuan Biota is based on fossils that are sausage-shaped,elongate,tubular,ranging from 0.3 to 4 cm in length,and up to 0.8 cm in diameter.One terminus is blunt and rounded to an obtuse angle,the other is bent with a spread-out surface resembling a holdfast,suggesting a three-dimensional thallus.Thin,stipe-shaped outgrowths,likely vestiges of sessile saccular life forms,are prevalent in macroalgal fossils of analogous size and shape,as well as present brown algae Scytosiphonaceae,such as Colpomenia and Dactylosiphon.The new findings augment the diversity of benthic algae,such as those known from the Early Neoproterozoic Longfengshan Biota in North China.The benthic algal macrofossils in the Jiucheng Mb.add to knowledge of Late Ediacaran metaphyte diversification and offer more clues about the evolutionary positioning of primitive macroalgae.The co-occurrence of numerous planktonic and benthic multicellular algae and planktonic microbes might have facilitated ecologically the more extensive later Cambrian explosion evidenced by the Chengjiang Biota in Yunnan.

Hepatolithiasis:Epidemiology,presentation,classification and management of a complex disease

The term hepatolithiasis describes the presence of biliary stones within the intrahepatic bile ducts,above the hilar confluence of the hepatic ducts.The disease is more prevalent in Asia,mainly owing to socioeconomic and dietary factors,as well as the prevalence of biliary parasites.In the last century,owing to migration,its global incidence has increased.The main pathophysiological mechanisms involve cholangitis,bile infection and biliary strictures,creating a self-sustaining cycle that perpetuates the disease,frequently characterised by recurrent episodes of bacterial infection referred to as syndrome of“recurrent pyogenic cholangitis”.Furthermore,long-standing hepatolithiasis is a known risk factor for development of intrahepatic cholangiocarcinoma.Various classifications have aimed at providing useful insight of clinically relevant aspects and guidance for treatment.The management of symptomatic patients and those with complications can be complex,and relies upon a multidisciplinary team of hepatologists,endoscopists,interventional radiologists and hepatobiliary surgeons,with the main goal being to offer relief from the clinical presentations and prevent the development of more serious complications.This comprehensive review provides insight on various aspects of hepatolithiasis,with a focus on epidemiology,new evidence on pathophysiology,most important clinical aspects,different classification systems and contemporary management.

Seroprevalence of SARS-COV-2 Exposure among “High-Risk” Populations (Healthcare Workers, People Who Attend Markets, and School Children) in Zanzibar

In Zanzibar, from the start of the pandemic in March 2020 to the time of sampling in December 2020, SARS-CoV-2 seroprevalence data was limited. We conducted a seroprevalence study to evaluate the magnitude of SARS-CoV-2 exposure among healthcare workers, school children, and people who attended general markets in Zanzibar. The objectives of the study were to analyse the total antibodies from selected higher-risk population groups in order to determine magnitude in SARS CoV-2 exposure. Blood samples were collected from eligible and consented participants (adults and children), and their serum was analyzed for total antibodies against SARS-CoV-2 using ELISA. A questionnaire was used to collect participants’ demographic and clinical data. The overall SARS-CoV-2 seroprevalence across all age groups was 33%, and a higher seroprevalence was observed in the 40 - 49 years’ age group relative to other ages as well as in those who attended markets. A runny nose (18.8% of participants) was the most frequently reported SARS-CoV-2 infection-related symptom. Multivariable analysis showed significantly higher odds of infection in people living in urban districts. The findings provide insight into SARS-CoV-2 infection among school children, health workers, and people who attended markets in Zanzibar in the early stages of the pandemic. Exposure in these groups might have been influenced by infection and prevention strategies taken by the government, as well as shopping behavior, school overcrowding, and population density in urban settings. The study had methodological limitations, including cross-sectional design. Further, well-designed, longitudinal studies are recommended to understand exposure and transmission at a population level.