New aspects of a small GTPase RAB35 in brain development and function

In eukaryotic cells,organelles in the secretory,lysosomal,and endocytic pathways actively exchange biological materials with each other through intracellular membrane trafficking,which is the process of transporting the cargo of proteins,lipids,and other molecules to appropriate compartments via transport vesicles or intermediates.These processes are strictly regulated by various small GTPases such as the RAS-like in rat brain(RAB)protein family,which is the largest subfamily of the RAS superfamily.Dysfunction of membrane trafficking affects tissue homeostasis and leads to a wide range of diseases,including neurological disorders and neurodegenerative diseases.Therefore,it is important to understand the physiological and pathological roles of RAB proteins in brain function.RAB35,a member of the RAB family,is an evolutionarily conserved protein in metazoans.A wide range of studies using cultured mammalian cells and model organisms have revealed that RAB35 mediates various processes such as cytokinesis,endocytic recycling,actin bundling,and cell migration.RAB35 is also involved in neurite outgrowth and turnover of synaptic vesicles.We generated brain-specific Rab35 knockout mice to study the physiological roles of RAB35 in brain development and function.These mice exhibited defects in anxiety-related behaviors and spatial memory.Strikingly,RAB35 is required for the precise positioning of pyramidal neurons during hippocampal development,and thereby for normal hippocampal lamination.In contrast,layer formation in the cerebral cortex occurred superficially,even in the absence of RAB35,suggesting a predominant role for RAB35 in hippocampal development rather than in cerebral cortex development.Recent studies have suggested an association between RAB35 and neurodegenerative diseases,including Parkinson's disease and Alzheimer's disease.In this review,we provide an overview of the current understanding of subcellular functions of RAB35.We also provide insights into the physiological role of RAB35 in mammalian brain development and function,and discuss the involvement of RAB35 dysfunction in neurodegenerative diseases.

Nomogram for overall survival in ampullary adenocarcinoma using the surveillance,epidemiology,and end results database and external validation

BACKGROUND Ampullary adenocarcinoma is a rare malignant tumor of the gastrointestinal tract.Currently,only a few cases have been reported,resulting in limited information on survival.AIM To develop a dynamic nomogram using internal and external validation to predict survival in patients with ampullary adenocarcinoma.METHODS Data were sourced from the surveillance,epidemiology,and end results stat database.The patients in the database were randomized in a 7:3 ratio into training and validation groups.Using Cox regression univariate and multivariate analyses in the training group,we identified independent risk factors for overall survival and cancer-specific survival to develop the nomogram.The nomogram was validated with a cohort of patients from the First Affiliated Hospital of the Army Medical University.RESULTS For overall and cancer-specific survival,12(sex,age,race,lymph node ratio,tumor size,chemotherapy,surgical modality,T stage,tumor differentiation,brain metastasis,lung metastasis,and extension)and 6(age;surveillance,epidemiology,and end results stage;lymph node ratio;chemotherapy;surgical modality;and tumor differentiation)independent risk factors,respectively,were incorporated into the nomogram.The area under the curve values at 1,3,and 5 years,respectively,were 0.807,0.842,and 0.826 for overall survival and 0.816,0.835,and 0.841 for cancer-specific survival.The internal and external validation cohorts indicated good consistency of the nomogram.CONCLUSION The dynamic nomogram offers robust predictive efficacy for the overall and cancer-specific survival of ampullary adenocarcinoma.

Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins

Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.

Postnatal development of rat retina:a continuous observation and comparison between the organotypic retinal explant model and in vivo development

The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.

Database Management System Construction for the Evaluation Results of Intensive Land Use in the Development Areas of Hunan Province

Using spatial data integration and database technology,analyzing and integrating the assessment results in all the development zones at different time in Hunan Province,the paper is intended to construct the database and managerial system for the assessment results of land use intensity in development zones,thus formulating"one map"of Hunan Development zones and realizing the integrated management and application of the assessment results in all the development zones at any time of Hunan above the provincial level.It has been proved that the system has good application effect and promising development in land management for land management departments and development zones.

GAMYB transcription factor LoMYB65 from lily plays a vital role in pollen development

Lily(Lilium spp.)is an important horticultural crop,but its use is limited due to serious pollen contamination problems.There are many studies on pollen development in model plants,but few on flower crops such as lilies.Gibberellin(GA)is a large class of hormones and plays an important role in plant vegetative growth and reproductive development.GAMYB is a group of the R2R3-MYB family upregulated by gibberellin,and plays an important role in anther development.Here,we isolated a novel GAMYB,named LoMYB65,from lily,which was closely related to the AtMYB65 and AtMYB33 in Arabidopsis.Fluorescence quantitative PCR results showed that LoMYB65 was mainly expressed in lily anthers.LoMYB65 could be activated by 288μmol·L^(-1)GA3treatment and the LoMYB65 protein was located in the nucleus and cytoplasm,and had transactivation in yeast and tobacco leaf cells.The conserved motif within 226 amino acids of the C-terminal of LoMYB65 contributed to its transactivation.Overexpression of LoMYB65 caused dwarf phenotype,unnormal tapetum development,less seeds of siliques in transgenic Arabidopsis plants,the transgenic plants showed partly male sterile.Simultaneously,silencing of LoMYB65 with VIGS(Virus Induced Gene Silencing)in lily anthers caused unnormal pollen development and reduced the pollen amount.Overexpression of LoMYB65 in Arabidopsis and silencing of LoMYB65 in lily resulted in decreased pollen counts,so we speculate that LoMYB65 may be dose-dependent.Overall,these findings suggest that LoMYB65 may play an important role in anther development and pollen formation in lily.LoMYB65 may provide a useful candidate gene for pollenless breeding of lily.

A dynamic regulation of nitrogen on floret primordia development in wheat

Nitrogen(N)fertilization is critical for spike and floret development,which affects the number of fertile florets per spike(NFFs).However,the physiological regulation of the floret development process by N fertilization is largely unknown.A high temporal-resolution investigation of floret primordia number and morphology,dry matter,and N availability was conducted under three N fertilization levels:0(N0),120(N1)and 240(N2)kg ha^(−1).Interestingly,fertile florets at anthesis stage were determined by those floret primordia with meiotic ability at booting stage:meiotic ability was a threshold that predicted whether a floret primordium became fertile or abortive florets.Because the developmental rate of the 4th floret primordium in the central spikelet was accelerated and then they acquired meiotic ability,the NFFs increased gradually as N application increased,but the increase range decreased under N2.There were no differences in spike N concentration among treatments,but leaf N concentration was increased in the N1 and N2 treatments.Correspondingly,dry matter accumulation and N content of the leaf and spike in the N1 and N2 treatments was increased as compared to N0.Clearly,optimal N fertilization increased leaf N availability and transport of assimilates to spikes,and allowed more floret primordia to acquire meiotic ability and become fertile florets,finally increasing NFFs.There was no difference in leaf N concentration between N1 and N2 treatment,whereas soil N concentration at 0–60 cm soil layers was higher in N2 than in N1 treatment,implying that there was still some N fertilization that remained unused.Therefore,improving the leaf’s ability to further use N fertilizer is vital for greater NFFs.

Conventional Geothermal Systems and Unconventional Geothermal Developments: An Overview

This paper provides an overview of conventional geothermal systems and unconventional geothermal developments as a common reference is needed for discussions between energy professionals. Conventional geothermal systems have the heat, permeability and fluid, requiring only drilling down to °C, normal heat flow or decaying radiogenic granite as heat sources, and used in district heating. Medium-temperature (MT) 100°C - 190°C, and high-temperature (HT) 190°C - 374°C resources are mostly at plate boundaries, with volcanic intrusive heat source, used mostly for electricity generation. Single well capacities are °C - 500°C) and a range of depths (1 m to 20 Km), but lack permeability or fluid, thus requiring stimulations for heat extraction by conduction. HVAC is 1 - 2 m deep and shallow geothermal down to 500 m in wells, both capturing °C, with °C are either advanced by geothermal developers at <7 Km depth (Enhanced Geothermal Systems (EGS), drilling below brittle-ductile transition zones and under geothermal fields), or by the Oil & Gas industry (Advanced Geothermal Systems, heat recovery from hydrocarbon wells or reservoirs, Superhot Rock Geothermal, and millimeter-wave drilling down to 20 Km). Their primary aim is electricity generation, relying on closed-loops, but EGS uses fractures for heat exchange with earthquake risks during fracking. Unconventional approaches could be everywhere, with shallow geothermal already functional. The deeper and hotter unconventional alternatives are still experimental, overcoming costs and technological challenges to become fully commercial. Meanwhile, the conventional geothermal resources remain the most proven opportunities for investments and development.

Development and technology status of energy storage in depleted gas reservoirs

Utilizing energy storage in depleted oil and gas reservoirs can improve productivity while reducing power costs and is one of the best ways to achieve synergistic development of"Carbon Peak–Carbon Neutral"and"Underground Resource Utiliza-tion".Starting from the development of Compressed Air Energy Storage(CAES)technology,the site selection of CAES in depleted gas and oil reservoirs,the evolution mechanism of reservoir dynamic sealing,and the high-flow CAES and injection technology are summarized.It focuses on analyzing the characteristics,key equipment,reservoir construction,application scenarios and cost analysis of CAES projects,and sorting out the technical key points and existing difficulties.The devel-opment trend of CAES technology is proposed,and the future development path is scrutinized to provide reference for the research of CAES projects in depleted oil and gas reservoirs.

BMPRⅡ^(+)neural precursor cells isolated and characterized from organotypic neurospheres:an in vitro model of human fetal spinal cord development

Roof plate secretion of bone morphogenetic proteins(BMPs)directs the cellular fate of sensory neurons during spinal cord development,including the formation of the ascending sensory columns,though their biology is not well understood.Type-ⅡBMP receptor(BMPRⅡ),the cognate receptor,is expressed by neural precursor cells during embryogenesis;however,an in vitro method of enriching BMPRⅡ^(+)human neural precursor cells(hNPCs)from the fetal spinal cord is absent.Immunofluorescence was undertaken on intact second-trimester human fetal spinal cord using antibodies to BMPRⅡand leukemia inhibitory factor(LIF).Regions of highest BMPRⅡ^(+)immunofluorescence localized to sensory columns.Parenchymal and meningeal-associated BMPRⅡ^(+)vascular cells were identified in both intact fetal spinal cord and cortex by co-positivity with vascular lineage markers,CD34/CD39.LIF immunostaining identified a population of somas concentrated in dorsal and ventral horn interneurons,mirroring the expression of LIF receptor/CD118.A combination of LIF supplementation and high-density culture maintained culture growth beyond 10 passages,while synergistically increasing the proportion of neurospheres with a stratified,cytoarchitecture.These neurospheres were characterized by BMPRⅡ^(+)/MAP2ab^(+/–)/βⅢ-tubulin^(+)/nestin^(–)/vimentin^(–)/GFAP^(–)/NeuN^(–)surface hNPCs surrounding a heterogeneous core ofβⅢ-tubulin^(+)/nestin^(+)/vimentin^(+)/GFAP^(+)/MAP2ab^(–)/NeuN^(–)multipotent precursors.Dissociated cultures from tripotential neurospheres contained neuronal(βⅢ-tubulin^(+)),astrocytic(GFAP+),and oligodendrocytic(O4+)lineage cells.Fluorescence-activated cell sorting-sorted BMPRⅡ^(+)hNPCs were MAP2ab^(+/–)/βⅢ-tubulin^(+)/GFAP^(–)/O4^(–)in culture.This is the first isolation of BMPRⅡ^(+)hNPCs identified and characterized in human fetal spinal cords.Our data show that LIF combines synergistically with high-density reaggregate cultures to support the organotypic reorganization of neurospheres,characterized by surface BMPRⅡ^(+)hNPCs.Our study has provided a new methodology for an in vitro model capable of amplifying human fetal spinal cord cell numbers for>10 passages.Investigations of the role BMPRⅡplays in spinal cord development have primarily relied upon mouse and rat models,with interpolations to human development being derived through inference.Because of significant species differences between murine biology and human,including anatomical dissimilarities in central nervous system(CNS)structure,the findings made in murine models cannot be presumed to apply to human spinal cord development.For these reasons,our human in vitro model offers a novel tool to better understand neurodevelopmental pathways,including BMP signaling,as well as spinal cord injury research and testing drug therapies.

A Formulation of the Porous Medium Equation with Time-Dependent Porosity: A Priori Estimates and Regularity Results

We consider a generalized form of the porous medium equation where the porosity ϕis a function of time t: ϕ=ϕ(x,t): ∂(ϕS)∂t−∇⋅(k(S)∇S)=Q(S).In many works, the porosity ϕis either assumed to be independent of (or to depend very little of) the time variable t. In this work, we want to study the case where it does depend on t(and xas well). For this purpose, we make a change of unknown function V=ϕSin order to obtain a saturation-like (advection-diffusion) equation. A priori estimates and regularity results are established for the new equation based in part on what is known from the saturation equation, when ϕis independent of the time t. These results are then extended to the full saturation equation with time-dependent porosity ϕ=ϕ(x,t). In this analysis, we make explicitly the dependence of the various constants in the estimates on the porosity ϕby the introduced transport vector w, through the change of unknown function. Also we do not assume zero-flux boundary, but we carry the analysis for the case Q≡0.

Vulvectomy: Indications and Results in the General Surgery Department of the Ignace Deen Chu Hospital in Conakry

Introduction: The aim of this study was to report the indications and evaluate the results of vulvectomy in the general surgery department of Ignace Deen Hospital, CHU Conakry. Materials and Methods: This was a retrospective descriptive study, conducted over a period of five (05) years from January 1, 2018 to December 31, 2022, in the general surgery department of Ignace Deen Hospital, CHU Conakry. We included in our study all patient records in whom vulvectomy was performed. Results: We recorded 15 cases of vulvectomy out of 453 perineal surgeries, i.e. 3.31%, with a mean age of 43.56 years and extremes of 35 and 69 years. Vulvar cancer was the most common diagnosis (46.67%), followed by Buschke-Lowenstein (33.33%) and anal canal cancer extending to the vulva (20%). Six patients had undergone biopsy (40%). Vulvectomy with lymph node dissection was performed in only 9 patients (60%), and all surgical specimens were sent to anatomical pathology (100%). Conclusion: Vulvectomy is a surgical technique most often indicated for the treatment of vulvar cancer.

How to use the Surveillance,Epidemiology,and End Results(SEER)data:research design and methodology

In the United States(US),the Surveillance,Epidemiology,and End Results(SEER)program is the only comprehensive source of population-based information that includes stage of cancer at the time of diagnosis and patient survival data.This program aims to provide a database about cancer incidence and survival for studies of surveillance and the development of analytical and methodological tools in the cancer field.Currently,the SEER program covers approximately half of the total cancer patients in the US.A growing number of clinical studies have applied the SEER database in various aspects.However,the intrinsic features of the SEER database,such as the huge data volume and complexity of data types,have hindered its application.In this review,we provided a systematic overview of the commonly used methodologies and study designs for retrospective epidemiological research in order to illustrate the application of the SEER database.Therefore,the goal of this review is to assist researchers in the selection of appropriate methods and study designs for enhancing the robustness and reliability of clinical studies by mining the SEER database.

FE65:a hub for neurodevelopment

FE65,initially identified as a binding partner of amyloid precursor protein(APP),is an adaptor protein enriched in the brain and regulated during development.FE65 belongs to the FE65 protein family.This family is comprised of three members,FE65,FE65 like-1(FE65L1),and FE65 like-2(FE65L2).

Constructing a standard system of city sustainable development assessment technology based on the SDGs

Given the rapid development of China’s new urbanization,cities with different locations and varying functional positioning,resource endowments,and development stages have insufficient scientific and applicable technical tools for implementing the United Nations Sustainable Development Goals(SDGs).City managers and policymakers must urgently establish SDG benchmarks to diagnose city development.Moreover,successful experiences from similar cities regarding sustainable development and self-improvement must be learned from to promote diversified,sustainable development across the country.Furthermore,emerging technologies such as artificial intelligence,the Internet of Things,big data and 5G are widely used in smart cities.Therefore,there is a growing need for“knowledge-based,personalized and intelligent”technologies to support monitoring,evaluation,and decision-making processes facilitating sustainable development in cities.This paper uses standardization as the theoretical support and technical basis.This approach can help clarify the sustainable development processes in China and clarify the evaluation results of and provide data on horizontal city comparisons,which can be used to develop evaluation technology for sustainable development in cities and construct a standardized system.The results provide a standard framework for intelligent assessment and decision-making regarding cities’sustainable development capabilities in China.Evaluating major international standardization institutions reveals that the practices of Chinese national standards should be fully absorbed and integrated to guide the evaluation of smart,resilient,and low-carbon cities.To this end,an indicator library of city sustainable development is proposed to provide standard evaluation technology methods.Finally,analyzing the response relationship of the indicator library to SDGs reveals the need for a standardized knowledge map of sustainable development assessment techniques and methods from the perspective of integrated management for sustainable development in cities.

Spatial Differentiation and Convergence Trend of High-quality Development Level of China’s Tourism Economy

This paper aims to interpret the connotation of high-quality development of tourism economy(HQTE)from the perspective of the new development concepts of innovation,coordination,green,openness and sharing,and then to evaluate the spatial differenti-ation of China’s HQTE based on provincial panel data from 2009 to 2018.Specifically,we employ the spatial convergence model to ex-plore the absolute and conditionalβconvergence trends of HQTE in the whole country and the eastern,central and western regions of China.Our empirical results reveal that:1)within the decade,from 2009 to 2018,regions of China with the highest HQTE index is its eastern region followed by the central region and then the western region,but the fastest growing one is the western region of China fol-lowed by the central region and then the eastern region.2)Whether or not the spatial effect is included,there are absolute and condition-alβconvergence in HQTE in the whole country and aforementioned three regions.3)The degree of government attention as well as the level of economic development and location accessibility are the positive driving factors for the convergence of HQTE in the whole country and the three regions.The degree of marketization and human capital have not passed the significance test either in the whole country or in the three regions.The above conclusions could deepen the understanding of the regional imbalance and spatial conver-gence characteristics of HQTE,clarify the primary development objects,and accomplish the goal of China’s HQTE.

Development and Validation of a UPLC Method for the Determination of Docetaxel and Its Related Substances in Pharmaceutical Dosage Forms, an Antineoplastic Agent

A novel, simple, and sensitive Ultra Performance Liquid Chromatography (UPLC) method was developed and validated for the quantification of process-related impurities and degradants, as well as the assay of Docetaxel. The stability-indicating capability of the method was demonstrated through forced degradation studies and a comprehensive mass balance evaluation. Chromatographic separation was achieved using an ACQUITY UPLC BEH C18 column (100 × 2.1 mm, 1.7 µm), with gradient elution. The mobile phase A comprised a mixture of water, methanol, and acetonitrile (500:300:200, v/v/v), while mobile phase B was acetonitrile and water (800:200, v/v). The flow rate was set at 0.4 mL/min, with detection at 232 nm using a photodiode array detector. The method exhibited excellent performance, with a tailing factor of 1.10 for Docetaxel. The method was rigorously validated for precision, accuracy, linearity, LOD, LOQ, ruggedness, specificity, and robustness. Forced degradation studies confirmed the method’s suitability for stability analysis. Stability testing on the drug substance was conducted following ICH guidelines.

The HD-Zip transcription factor LcATHB15 is involved in litchi seed development by promoting the expression of the splicing regulator LcSR45

Litchi (Litchi chinensis Sonn.) is a well-known tropical and subtropical woody fruit that originated from southern China (Wei et al.,2017;Hu et al.,2022).Based on the development of the embryo,litchi varieties can be divided into three distinct groups:large-seeded cultivars,small (abortive)-seeded cultivars and partial abortive-seeded cultivars.Seedless or the reduction in seed size due to embryo abortion is a desirable trait in fruit trees as it directly influences the texture and economic value of fleshy fruits,making small (abortive)-seeded litchi cultivars the most preferred.However,in current production practices,there is no efficient method available to induce or promote high seed abortion in litchi fruit.Therefore,understanding the stenospermy mechanisms of litchi seed development is of great significance for improving agricultural practices and managing genetic resources.

Construction of an indicator library for cities’sustainable development

Cities are key to countries’strategies for achieving the UN’s sustainable development goals(SDGs).In China,evaluating cities’sustainable development(CSD)processes and abilities requires establishing an indicator library for cities’sustainable development(ILCSD).Based on the SDG framework,and referring to typical evaluation systems and international standards,this study proposes an ILCSD,aiming to promote new urbanization and high-quality development in China.Using a step-by-step“eliminate-replace-augment”indicator selection method that takes mature indicators from existing standards for city evaluation,we form an ILCSD that responds to the SDGs while meeting China’s specific needs.Using the ILCSD,cities can select a set of indicators to assess and monitor their strengths and weaknesses.Through empirical analysis,we verify the feasibility of using ILCSD to construct a CSD evaluation system for Beijing,China.For the first time,ILCSD has established a mapping relationship between the core indicators from domestic and foreign standards of city development and the SDGs.It provides a tool for cities in different regions,at different stages of development and with different endowment types to select high-quality indicators according to local conditions,effectively solving the“last mile”problem of SDGs implementation at the city level.In the process of implementing indicators,we further suggest that important indicators with incomplete statistical data should nevertheless be included in the scope of cities’statistical monitoring.This study’s findings can facilitate China’s contribution to global sustainable development indicators and to future revisions of international standards.