Key Development Research Articles

Bioinformatics deciphers the thebaine biosynthesis pathway in opium poppy: Hub genes, network analysis, and miRNA regulation

Thebaine, a vital precursor in the codeine and morphine pathway, shows promise in addiction treatment. We conducted a comprehensive study on the thebaine biosynthesis pathway in opium poppy, utilizing bioinformatics tools. The dataset comprising the thirteen genes associated with the thebaine biosynthesis pathway was compiled from an extensive review of published literature and validated using the NCBI BLAST tool. Utilizing STRING and Cytoscape, we analyzed gene interactions and visualized the molecular interaction network, respectively. To identify hub proteins, CytoHubba was administered. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) at STRING were used for the enrichment analysis of the hub genes. CytoCluster was used to analyze the network in clusters. Promoter regions of hub genes and potential miRNAs were explored using MEME and the psRNATarget database. Hub genes crucial to thebaine biosynthesis were identified, contributing to essential cellular functions like growth, development, stress response, and signal transduction. Metabolic processes emerged as pivotal for thebaine production, indicating a broader role for the thebaine pathway gene network beyond primary metabolite production. Cell component subnetwork genes demonstrated associations with anatomical units, indicating involvement in plant defense responses. Dominant molecular functions drove plant defense responses. KEGG pathway analysis highlighted the significance of metabolic pathways and biosynthesis of secondary metabolites. Cluster analysis emphasized the relevance of the biosynthesis of amino acids, confirming the link between primary and secondary metabolites. Promoter analysis suggested the potential involvement of signal transduction in thebaine production. Hub genes were targeted by 40 miRNAs, suggesting potential novel biomarkers or target genes within the thebaine biosynthesis pathway. Based on the role of miRNAs identified in connection with the hub genes of the thebaine production process, the secondary metabolite pathway of thebaine appears to be associated with several key plant pathways, e.g. growth, development and stress response. However, these findings, based on bioinformatics analysis, warrant further experimental validation and promise to advance our understanding of the biosynthesis of thebaine and its interactions with other genes and metabolic pathways that influence the production of metabolites.

Accurate identification of genes associated with brain disorders by integrating heterogeneous genomic data into a Bayesian framework

Genome-wide association studies (GWAS) have revealed many brain disorder-associated SNPs residing in the noncoding genome, rendering it a challenge to decipher the underlying pathogenic mechanisms. Here, we present an unsupervised Bayesian framework to identify disease-associated genes by integrating risk SNPs with long-range chromatin interactions (iGOAT), including SNP-SNP interactions extracted from ∼500,000 patients and controls from the UK Biobank, and enhancer-promoter interactions derived from multiple brain cell types at different developmental stages. The application of iGOAT to three psychiatric disorders and three neurodegenerative/neurological diseases predicted sets of high-risk (HRGs) and low-risk (LRGs) genes for each disorder. The HRGs were enriched in drug targets, and exhibited higher expression during prenatal brain developmental stages than postnatal stages, indicating their potential to affect brain development at an early stage. The HRGs associated with Alzheimer's disease were found to share genetic architecture with schizophrenia, bipolar disorder and major depressive disorder according to gene co-expression module analysis and rare variants analysis. Comparisons of this method to the eQTL-based method, the TWAS-based method, and the gene-level GWAS method indicated that the genes identified by our method are more enriched in known brain disorder-related genes, and exhibited higher precision. Finally, the method predicted 205 risk genes not previously reported to be associated with any brain disorder, of which one top-risk gene, MLH1, was experimentally validated as being schizophrenia-associated. iGOAT can successfully leverage epigenomic data, phenotype-genotype associations, and protein-protein interactions to advance our understanding of brain disorders, thereby facilitating the development of new therapeutic approaches. The work was funded by the National Key Research and Development Program of China (2024YFF1204902), the Natural Science Foundation of China (82371482), Guangzhou Science and Technology Research Plan (2023A03J0659) and Natural Science Foundation of Guangdong (2024A1515011363).

Evaluation of Key Development Factors of a Buried Hill Reservoir in the Eastern South China Sea: Nonlinear Component Seepage Model Coupled with EDFM

The HZ 26-B buried hill reservoir is located in the eastern part of the South China Sea. This reservoir is characterized by the development of natural fractures, a high density, and a complex geological structure, featuring an upper condensate gas layer and a lower volatile oil layer. These characteristics present significant challenges for oilfield exploration. To address these challenges, this study employed advanced embedded discrete fracture methods to conduct comprehensive numerical simulations of the fractured buried hill reservoirs. By meticulously characterizing the flow mechanisms within these reservoirs, the study not only reveals their unique characteristics but also establishes an embedded discrete fracture numerical model at the oilfield scale. Furthermore, a combination of single-factor sensitivity analysis and the Pearson correlation coefficient method was used to identify the primary controlling factors affecting the development of complex condensate reservoirs in ancient buried hills. The results indicate that the main factors influencing the production capacity are the matrix permeability, geomechanical effects, and natural fracture length. In contrast, the impact of the threshold pressure gradient and bottomhole flow pressure is relatively weak. This study’s findings provide a scientific basis for the efficient development of the HZ 26-B oilfield and offer valuable references and insights for the exploration and development of similar fractured buried hill reservoirs.

Conditional generative adversarial network-assisted system for radiation-free evaluation of scoliosis using a single smartphone photograph: a model development and validation study

Adolescent idiopathic scoliosis (AIS) is the most common spinal disorder in children, characterized by insidious onset and rapid progression, which can lead to severe consequences if not detected in a timely manner. Currently, the diagnosis of AIS primarily relies on X-ray imaging. However, due to limitations in healthcare access and concerns over radiation exposure, this diagnostic method cannot be widely adopted. Therefore, we have developed and validated a screening system using deep learning technology, capable of generating virtual X-ray images (VXI) from two-dimensional Red Green Blue (2D-RGB) images captured by a smartphone or camera to assist spine surgeons in the rapid, accurate, and non-invasive assessment of AIS. We included 2397 patients with AIS and 48 potential patients with AIS who visited four medical institutions in mainland China from June 11th 2014 to November 28th 2023. Participants data included standing full-spine X-ray images captured by radiology technicians and 2D-RGB images taken by spine surgeons using a camera. We developed a deep learning model based on conditional generative adversarial networks (cGAN) called Swin-pix2pix to generate VXI on retrospective training (n=1842) and validation (n=100) dataset, then validated the performance of VXI in quantifying the curve type and severity of AIS on retrospective internal (n=100), external (n=135), and prospective test datasets (n=268). The prospective test dataset included 268 participants treated in Nanjing, China, from April 19th, 2023, to November 28th, 2023, comprising 220 patients with AIS and 48 potential patients with AIS. Their data underwent strict quality control to ensure optimal data quality and consistency. Our Swin-pix2pix model generated realistic VXI, with the mean absolute error (MAE) for predicting the main and secondary Cobb angles of AIS significantly lower than other baseline cGAN models, at 3.2° and 3.1° on prospective test dataset. The diagnostic accuracy for scoliosis severity grading exceeded that of two spine surgery experts, with accuracy of 0.93 (95% CI [0.91, 0.95]) in main curve and 0.89 (95% CI [0.87, 0.91]) in secondary curve. For main curve position and curve classification, the predictive accuracy of the Swin-pix2pix model also surpassed that of the baseline cGAN models, with accuracy of 0.93 (95% CI [0.90, 0.95]) for thoracic curve and 0.97 (95% CI [0.96, 0.98]), achieving satisfactory results on three external datasets as well. Our developed Swin-pix2pix model holds promise for using a single photo taken with a smartphone or camera to rapidly assess AIS curve type and severity without radiation, enabling large-scale screening. However, limited data quality and quantity, a homogeneous participant population, and rotational errors during imaging may affect the applicability and accuracy of the system, requiring further improvement in the future. National Key R&D Program of China, Natural Science Foundation of Jiangsu Province, China Postdoctoral Science Foundation, Nanjing Medical Science and Technology Development Foundation, Jiangsu Provincial Key Research and Development Program, and Jiangsu Provincial Medical Innovation Centre of Orthopedic Surgery.

Conditional Lead-Time Flexibility in an Assemble-to-Order System

Problem definition: We introduce and formalize a concept termed conditional lead-time flexibility (CLF), which refers to the industry practice where a manufacturer requests that its upstream suppliers dynamically adjust the pipeline orders’ remaining lead times. Over a finite horizon, an assemble-to-order manufacturer makes joint decisions on inventory replenishment and lead-time adjustment to minimize the total discounted expected cost. Methodology/results: The problem is formulated as a multiperiod dynamic programming with an enlarged state space to track the adjustable pipeline orders. The replenishment and lead-time adjustment decisions are made sequentially in each period. The analysis reveals that (i) the optimal cost-to-go function is both convex and additively separable, that (ii) both the optimal replenishment and lead-time adjustment decisions follow general base-stock policies, and that (iii) the convexity and additive separability allow us to perform a derivative analysis on the optimality equations and design an efficient algorithm. Managerial implications: Using real industry data, we numerically find that (i) CLF achieves notable cost savings over a wide range of parameters, that (ii) the value of CLF comes from both the order expediting and deferring, and that (iii) CLF outperforms dual sourcing when the unit adjustment cost is less than 40% of the unit ordering cost from the express source. Our findings underscore the importance of CLF. Funding: T. Deng acknowledges financial support from the National Key Research and Development Program of China [Grant 2022YFB3305602] and the National Natural Science Foundation of China (NSFC) [Grant 72188101]. Supplemental Material: The electronic companion is available at https://doi.org/10.1287/msom.2023.0520 .

Ambient particulate matter and chronic obstructive pulmonary disease mortality: a nationwide, individual-level, case-crossover study in China

Short-term exposure to particulate matter air pollution has been associated with the exacerbations of COPD, but its association with COPD mortality was not fully elucidated. We aimed to assess the association between short-term particulate matter exposure and the risk of COPD mortality in China using individual-level data. We derived 2.26 million COPD deaths from a national death registry database in Chinese mainland between 2013 and 2019. Exposures to fine particulate matter (PM2.5) and coarse particulate matter (PM2.5-10) were assessed by satellite-based models of a 1×1km resolution and assigned to each individual based on residential address. The associations of PM2.5 and PM2.5-10 with COPD mortality were examined using a time-stratified case-crossover design and conditional logistic regressions with distributed lag models. We further conducted stratified analyses by age, sex, education level, and season. Short-term exposures to both PM2.5 and PM2.5-10 were associated with increased risks of COPD mortality. These associations appeared and peaked on the concurrent day, attenuated and became nonsignificant after 5 or 7 days, respectively. The exposure-response curves were approximately linear without discernible thresholds. An interquartile range increase in PM2.5 and PM2.5-10 concentrations was associated with 4.23% (95% CI: 3.75%, 4.72%) and 2.67% (95% CI: 2.18%, 3.16%) higher risks of COPD mortality over lag 0-7d, respectively. The associations of PM2.5 andPM2.5-10 attenuated slightly but were still significant in the mutual-adjustment models. A larger association of PM2.5-10 was observed in the warm season. This individual-level, nationwide, case-crossover study suggests that short-term exposure to PM2.5 and PM2.5-10 might act as one of the environmental risk factors for COPD mortality. This study is supported by the National Key Research and Development Program of China (2023YFC3708304 and 2022YFC3702701), the National Natural Science Foundation of China (82304090 and 82030103), the 3-year Action Plan for Strengthening the Construction of the Public Health System in Shanghai (GWVI-11.2-YQ31), and the Science and Technology Commission of Shanghai Municipality (21TQ015).

Digital Financial Capability and Entrepreneurship in China: A Digital Economy Perspective

The digital economy is the fastest-growing sector in the world today, and will also be the key development direction of China in the future. The level of digital financial capability (DFC) determines whether households can fully embrace the inclusivity of digital finance and seize the business opportunities presented by the digital economy. Hence, we utilized panel data from the China Household Finance Survey (CHFS) and built a probit model with two-way fixed effects. The results revealed that DFC has a positive impact on household entrepreneurship through both supply- and demand-side mechanisms. The results also revealed that DFC has not only catalyzed the evolution of digital business models but has also enhanced the digital business performance of enterprises. The analysis of heterogeneity confirms that DFC can promote entrepreneurship in rural settings and in the retail and restaurant sectors. This research has important theoretical contributions and policy suggestions for governments to help them pay attention to the inclusive role of DFC in developing the digital economy.

(Invited) Achieving Robustness and Economic Viability in CO2 Electrolysis Scale-up: Key Results from RenewCO2

RenewCO2 is commercializing processes to convert carbon emissions from chemical manufacturing, which contributes 274 million metric tons of CO2eq annually in the U.S. alone. Our pioneering electrocatalytic Carbon Utilization Technology (eCUT) is adept at upcycling CO2 from hard-to-decarbonize industrial sources. By synthesizing commodity chemicals from CO2 emissions, eCUT promises high energy efficiency while producing carbon-negative materials. The critical innovation of RenewCO2’s eCUT process is deploying catalysts designed with readily available metals, optimizing the process to reduce CO2 into multi-carbon chemicals selectively with impressive energy efficiency.RenewCO2 has significantly advanced CO2 electrolyzer scale-up, focusing on demonstrating process robustness and economic feasibility. Targeting liquid products such as monomers (glycols), RenewCO2 has demonstrated cost-advantaged process economics compared to the incumbent petrochemical and bio-derived routes. We present detailed findings on the enhanced performance of our proprietary catalysts, which have shown remarkable endurance under prolonged operational conditions (1000 h of operation) in a scaled-up stack containing five 500 cm2 electrodes. The RenewCO2 team has demonstrated consistent electrolyzer performance with minimal degradation over extended periods. We also delve into improvements in energy efficiency, showcasing how these enhancements contribute to the overall process economics.The purification process is crucial in making carbon-negative materials from CO2 that do not require a green premium. In this regard, RenewCO2 has achieved remarkable progress in demonstrating a highly energy-efficient product purification. In collaboration with Argonne National Lab, we have developed an advanced electrochemical separation method that removes ionic species from the products to comply with strict industrial standards and increase their market value. A key development in this area is our innovative approach to electrodeionization, which combines ion-exchange membranes with electrically active media. This method exhibits low energy consumption, robustness, and simple operation. These advancements in the purification process are integral to our system’s overall efficiency and are pivotal in our pursuit of creating economically viable and sustainable electrochemical manufacturing solutions.On the economic front, we provide an in-depth analysis of the cost implications of scaling up. This includes a breakdown of the capital and operational costs, along with a comparative analysis with existing technologies. We discuss the main factors contributing to product cost and strategies to minimize them, such as the integration of low-cost materials and judicious choice of operating conditions.Our aim is to provide a transparent and comprehensive overview of the challenges and the state-of-the-art in scaling up CO2 electrolysis to liquid products, offering valuable insights for the scientific community and stakeholders in the field.

The Best of Both Worlds: Stacked Catalytic Layers for the Electrocatalytic Generation of CO in Zero-Gap Electrolyzers

Tailoring the properties of the catalytic layer (CL) alongside its architecture is a key development towards ensuring both improve efficiency and selectivity for CO2 electrolyzers. Traditionally, CLs for the CO2R consist of a single binder-material or a combination of them overtaking both the ion-conductance and maintenance of a hydrophobic environment.We herein decoupled these processes into two individual, stacked catalyst-containing layers. Specifically, a hydrophobic catalytic layer was herein placed on the GDL aiming to improve water management within the CL during CO2R in zero-gap electrolyzers, while A second catalytic layer bound by an ion-conducting binder allows for the conduction of OH- and HCO3-/CO3 2- during CO2R, improving both the ionic conductivity between the GDE and AEM as well as the mechanical adhesion between the different interfaces. Notably, we present the complete stepwise CL-optimization pathway, regarding both the single and segmented-CLs towards the CO2-CO conversion at current densities ≥ 300 mA cm2, highlighting the role of the operational parameters regarding scalability in different cell sizes and long-term stability > 100 h.

Hotspots and Trends in Key Competencies on SDG: A Visualized Analysis Based on Citespace

Objective: Key competencies, regarded as essential elements in the development of curricula, have attracted considerable attentions in educational theory. To enhance comprehension of recent advancements, trending subjects, and research frontiers in the field of key competencies, this study collected related research and to provide a more distinct overview of the developmental patterns in key competencies. Methods: This study reviewed key competencies research from 2000 to 2022 using Scopus and CiteSpace for visualization and analysis. Annual publishing volume and country (region) distributions were analyzed. Key competencies fields, basic contents, and research hotspots were analyzed using keyword co-occurrence. Research frontiers and development trends were analyzed using high-frequency keywords. Results: The number of articles has steadily increased since 2005. The USA published the most, collaborating with Indonesia, the Netherlands, Russia, and India. Key competencies development and focus areas include “student”, “21st century skill”, “education”, “curriculum”, “learning”. Developmental trends in key competencies include “education”, “article”, “professional competence”, “problem solving”. Conclusion: The definition of key competencies and the content of curriculum reforms are attributed to variations in environments, cultures, and values among different international organizations and countries. Key competencies such as “communication”, “information technology”, “collaboration”, and “mother tongue” are prioritized in educational environments.

Effect of the national integrated demonstration area for the prevention and control of noncommunicable diseases programme on behavioural risk factors in China: a synthetic difference-in-differences study

The government-led community-based Chinese National Integrated Demonstration Areas for the Prevention and Control of Noncommunicable Diseases programme was launched in 2011, but no rigorous impact evaluation has been conducted to date. We aimed to evaluate the causal effects of this programme on behavioural risk factors. We used data from the latest five waves of the China Chronic Disease and Risk Factor Surveillance. The primary outcome is a behavioural risk score combining current smoking, passive smoking, drinking in last month, regular exercise, body mass index, and waist circumference. We applied the synthetic difference-in-differences method and constructed synthetic controls from the non-demonstration areas with the outcome. The average treatment effects on the treated were estimated for overall effect and by short- (1-2), medium- (3-4), and long-term (6-7 years) effects. We identified 26 demonstration areas (N=72,193) and 100 non-demonstration areas (N=275,397). Participants in the demonstration areas had higher education and income levels and different pre-implementation trends than non-demonstration areas. Using synthetic controls instead of non-demonstration areas reduced these pre-implementation differences. Compared to the synthetic controls, declines were observed in current smoking (-1.78% [-4.51%, 0.96%]), passive smoking (-8.09% [-14.27%,-1.90%]), and drinking in last month (-4.04% [-8.75%, 0.67%]) but not in the other factors. Behavioural risk score declined by 1.05 short-term (95% CI:-1.84,-0.26), 1.15 medium-term (95% CI:-2.08,-0.22), 2.82 long-term (95% CI:-4.79,-0.85), and 1.54 overall (95% CI:-2.51,-0.56). The programme improved behavioural risk scores, primarily through reductions in the prevalence of smoking and drinking, and the effect was long-lasting. Our findings provided empirical evidence for utilizing an integrated prevention and control strategy to fight against NCD in China and other countries facing similar challenges. The China National Key Research and Development Program (2018YFC1315304 and 2017YFC1310902); National Natural Science Foundation of China (81872721).

Perceptions of Key Responsibilities and Professional Development Interests of Senior Educational Leaders: A Needs Assessment.

High-ranking educational leaders in academic medicine oversee multiple clinical programs. This requires them to prioritize dozens of emergent tasks and responsibilities daily, from educational policy and strategy to staff management, financial planning, onboarding of trainees, and facility planning and management. Identifying their key responsibilities and frequently used skills and competencies may clarify the educational needs of senior educational leaders and facilitate targeted professional development to promote effective and efficient performance. In August 2022 researchers interviewed 12 designated education officers (DEOs) from U.S. Department of Veterans Affairs (VA) Veterans Health Administration medical centers about their daily work and most challenging responsibilities. Content analysis of interview transcripts identified key responsibilities and activities identified by participants and prioritization of the perceived skills needed to complete them. Participants emphasized 4 key areas of responsibility: fiscal, administrative, affiliate partnership, and educational duties. They identified 12 skills as baseline requirements for effective performance for which additional professional development would be useful and suggested that both new and more established educational leaders receive targeted professional development and mentoring to foster these capacities. The key skills participants identified by area of perceived responsibility are relevant to VA DEOs, designated institutional officers, and senior academic leaders who develop health professions education programs, oversee clinical training, and manage educational change. Structured orientation programs and ongoing professional development for senior educational leaders could emphasize these areas of responsibility, potentially enriching DEOs' performance and reducing burnout.

Mapping Knowledge Landscapes and Emerging Trends in AI for Dementia Biomarkers: Bibliometric and Visualization Analysis.

With the rise of artificial intelligence (AI) in the field of dementia biomarker research, exploring its current developmental trends and research focuses has become increasingly important. This study, using literature data mining, analyzes and assesses the key contributions and development scale of AI in dementia biomarker research. The aim of this study was to comprehensively evaluate the current state, hot topics, and future trends of AI in dementia biomarker research globally. This study thoroughly analyzed the literature in the application of AI to dementia biomarkers across various dimensions, such as publication volume, authors, institutions, journals, and countries, based on the Web of Science Core Collection. In addition, scales, trends, and potential connections between AI and biomarkers were extracted and deeply analyzed through multiple expert panels. To date, the field includes 1070 publications across 362 journals, involving 74 countries and 1793 major research institutions, with a total of 6455 researchers. Notably, 69.41% (994/1432) of the researchers ceased their studies before 2019. The most prevalent algorithms used are support vector machines, random forests, and neural networks. Current research frequently focuses on biomarkers such as imaging biomarkers, cerebrospinal fluid biomarkers, genetic biomarkers, and blood biomarkers. Recent advances have highlighted significant discoveries in biomarkers related to imaging, genetics, and blood, with growth in studies on digital and ophthalmic biomarkers. The field is currently in a phase of stable development, receiving widespread attention from numerous countries, institutions, and researchers worldwide. Despite this, stable clusters of collaborative research have yet to be established, and there is a pressing need to enhance interdisciplinary collaboration. Algorithm development has shown prominence, especially the application of support vector machines and neural networks in imaging studies. Looking forward, newly discovered biomarkers are expected to undergo further validation, and new types, such as digital biomarkers, will garner increased research interest and attention.

World War II and Industrialization Policies in Latin America: The Cases of Argentina and Brazil

Abstract Raúl Prebisch and Celso Furtado were two important contributors to development economics and to the theories and policies defended by the United Nations Economic Commission for Latin America (ECLAC). In this article, we argue that understanding their ideas, and how industrialization became a key concern, requires paying closer attention to the geopolitical changes brought by World War II. We discuss how Argentina and Brazil, their home countries, navigated the troubled waters brought by the war and the international trade disruptions and turned state-led industrialization into a key development strategy. After the war, the United States became the new hegemonic power and adopted a universalist foreign policy, based on the newly created international agencies. At home, the internationalist businessmen promoted the partnership capitalism that became central to the foreign policy during the Truman administration and onwards, making industrialization a key interest. Internationalism was also the way that Latin American countries used to counteract the US hegemony even before the war, which culminated in the creation of ECLAC after the war. The intellectual paths of Prebisch and Furtado toward industrialization policies were shaped by the changing international order and by local developments in their countries including the building of a more scientific statistical system that would better help the state to design development policies.

Exploring Low-Grade Iron Ore Beneficiation Techniques: A Comprehensive Review

The beneficiation of low-grade iron ores is a key research and development topic in the mineral processing industry. The gradual exhaustion of high-grade iron ore reserves, and rising consumer iron and steel demand globally necessitate efficient low-quality iron ore beneficiation to meet steelmaking quality requirements. This comprehensive review explores various beneficiation techniques for low-quality iron ore, focusing on conventional methods including comminution, froth flotation and gravity separation. This article discusses the principles, processes, and equipment used in these techniques and highlights recent advancements and research efforts in the field. This review also emphasizes the importance of effective beneficiation processes in enhancing economic viability, sustainable resource management, and environmental conservation. Furthermore, it presents a case study of iron ore deposits in Botswana, highlighting the potential economic growth and sustainable development that can be achieved by maximizing resource utilization through reductive roasting, followed by magnetic separation of iron ore using semi-bituminous coal as a reductant. Overall, this review provides valuable insights into low-grade iron ore beneficiation techniques and their significance in meeting the growing demand for high-quality iron and steel products.

Homoharringtonine synergizes with venetoclax in early Tcell progenitor acute lymphoblastic leukemia: Bench and bed.

Early Tcell precursor acute lymphoblastic leukemia (ETP-ALL) is a distinct subtype of T-ALL with a poor prognosis. To find a cure, we examined the synergistic effect of homoharringtonine (HHT) in combination with the BCL-2 inhibitor venetoclax (VEN) in ETP-ALL. Using invitro cellular assays and ETP-ALL xenograft models, we first investigated the synergistic activity of HHT and VEN in ETP-ALL. Next, to explore the underlying mechanism, we employed single-cell RNA sequencing of primary ETP-ALL cells treated with HHT or VEN alone or in combination and validated the results with western blot assays. Based on the promising preclinical results and given that both drugs have been approved for clinical use, we then assessed this combination in clinical practice. Our results showed that HHT synergizes strongly with VEN both invitro and invivo in ETP-ALL. Mechanistic studies demonstrated that the HHT/VEN combination concurrently downregulated key anti-apoptotic proteins, i.e., MCL1, leading to enhanced apoptosis. Importantly, the clinical results were very promising. Six patients with ETP-ALL with either refractory/relapsed (R/R) or newly diagnosed disease were treated with an HHT/VEN-based regimen. All patients achieved complete remission (CR) after only one cycle of treatment. Our findings demonstrate that a combination of HHT/VEN is effective on ETP-ALL and represents the "backbone" of a promising and safe regimen for newly diagnosed and R/R patients with ETP-ALL. This work was funded by the National Cancer Institute, Gehr Family Foundation, George Hoag Family Foundation, National Natural Science Foundation of China, and Key Research and Development Program of Zhejiang Province of China.

Safety and efficacy of allogenic human amniotic epithelial cells transplantation via ovarian artery in patients with premature ovarian failure: a single-arm, phase 1 clinical trial

Premature ovarian failure (POF) is a prevalent and severe condition that impairs female health but there is currently no effective treatment available to restore ovarian function. Human amniotic epithelial cells (hAECs) exhibit ovarian protection in pre-clinical models. Thus, we conducted a single-arm, phase 1 clinical trial to assess the safety and efficacy of allogenic hAECs in treating POF. A total of 35 patients received 6×107 hAECs via ovarian artery and completed a five-month follow-up from December 30, 2020 to January 31, 2022. The follow-up assessments were conducted at various intervals after hAECs treatment, including one month (Visit-1, V-1), three months (Visit-2, V-2), and five months (Visit-3, V-3) post-treatment. The primary endpoints were incidence of adverse events (AEs), and clinically significant laboratory abnormalities. Secondary endpoints included evaluation of transvaginal ultrasound results, sex hormone levels, Menopausal Quality of Life (MENQOL) questionnaire, as well as reproductive indicators. This trial was registered at www.clinicaltrials.gov as NCT02912104. No serious AEs were observed throughout the five-month follow-up period. The most common AE was hematoma (7/35, 20.00%), and other AEs include pelvic pain (4/35, 11.43%), fever (2/35, 5.71%), anaphylaxis (2/35, 5.71%), and hepatotoxicity (1/35, 2.86%). After hAECs transplantation (hAECT), significant improvements were observed in the levels of endometrial thickness, left ovarian volume, sex hormones (follicle-stimulating hormone (FSH) and estradiol (E2)), and MENQOL scores in all patients during the five-month follow-up period. Among them, 13 participants (37.14%) experienced spontaneous menstrual bleeding, and 20.00% (7/35) reported more than one regular menstrual bleeding post-hAECT. In this response group, significant improvements were observed in endometrial thickness, left ovarian volume, levels of FSH, E2, anti-Müllerian hormone (AMH), and MENQOL scores one month after hAECT in comparison to pre-hAECT. hAECT via ovarian artery is safe, well-tolerated and temporarily ameliorates endometrial thickness, ovarian size, hormone levels, and menopausal symptoms in POF patients. Further randomized controlled trial of hAECs with longer follow-up period and a larger sample size is warranted. National Natural Science Foundation of China (No. 82271664), the Interdisciplinary Program of Shanghai Jiao Tong University (YG2022ZD028), the Shanghai Municipal Health Committee (202240345), Shanghai Key Laboratory of Embryo Original Diseases (No. Shelab2022ZD01), Shanghai Municipal Education Commission (No.20152236), and National Key Research and Development Program of China (No. 2018YFC1004802), Shanghai Clinical Research Center for Cell Therapy, China (No. 23J41900100).

International Development Trends in the Field of Agricultural Resources and the Environment

The development trends and research layout of agricultural resources and the environment (ARE) are the focus of global attention. In this study, we compiled a data set of SCI papers published in the ARE field since the 13th Five-Year Plan. Thereafter, the topic extraction model of Latent Dirichlet Allocation (LDA) was used to mine the text content so as to explore the research layout of global ARE. The results show that, between 2016 and the time of this study, 31,559 articles were published in the ARE field, exhibiting an overall upward trend. During this time, China and the United States were the main forces in paper publishing. The Chinese Academy of Sciences (CAS), Northwest Agriculture and Forestry University, and the US Department of Agriculture were the top three publishing institutions. Research institutes in China, the United States, Russia, Sweden, the Netherlands, Brazil, and Australia cooperated closely, and the CAS was at the center of the cooperation network. The clustering results of text topics based on the LDA model show that three topics—namely, the interaction mechanisms of plants, the rhizosphere, and microorganisms; the mechanisms and predictive evaluation of soil landslides or erosion; and the decomposition and interaction response of organic matter in agroforestry ecosystems—have been the hot research areas in this field since 2016. The management and efficient utilization of farmland nutrients, and the technology and mechanisms of agricultural waste resource utilization have become key research directions since 2019. The research layouts of China and the United States in this field were analyzed, and the similarities and differences were compared. In addition, suggestions for the future development of ARE are proposed. This study is of great significance for the overall development trend of ARE, the timely tracking of scientific research hotspots, outlining key research and development directions, and promoting scientific and technological innovation.

An Investigation of Public Participation on Policy Formulation in Devolved Government in Keiyo South Sub County, Elgeyo Marakwet County, Kenya

Citizens in many county governments are not empowered to understand their role in development issues and feel that policy makers do not put into consideration their contribution in major decision making particularly affecting key development programs. Citizens in many counties feel more often than not that their predicaments have not been addressed effectively by their governments, bring in a lot of conflicts which at times has resulted in public unrest. This study therefore focused on establishing an investigation of public participation on policy formulation in devolved governments in Keiyo South Sub County, Elgeyo Marakwet County, Kenya. The objectives of this study were to: establish the contribution of public participation in policy formulation in devolved government of Keiyo South Sub County, Elgeyo Marakwet County, Kenya and to determine the level of public participation on policy formulation in devolved government of Keiyo South Sub County, Elgeyo Marakwet County, Kenya. The study was based on Participatory Communication Theory and Ladder of Citizen Participation Theory. The study used a mixed-method approach, integrating both qualitative and quantitative research. The study adopted a descriptive survey design. The target population was 115 and the researcher obtained a sample size of 89 respondents using Yamane formulae. The study used stratified random sampling to select the respondents. The study used questionnaires and an interview schedule to collect dataThe statistical package for social sciences (SPSS) version 24 was used to analyze quantitative data from the closed-ended questions. Data was analyzed using descriptive and inferential statistics. Descriptive statistics involved frequencies, percentages, standard deviation, and arithmetic mean. Inferential statistics involved correlation and multiple regression. The analyzed data was presented in the form of charts and tables. Privacy was maintained during the entire research period, and participation was entirely voluntary, free from coercion or inducement. The findings demonstrated that respondents agreed with the statement that member’s ideas and contributions in the public participation are given priorities (Mean=3.70, standard deviation=1.40), further, the findings indicated that that the respondents agreed with the statement that there is a moderate level of public participation on policy formulation (Mean=3.73, standard deviation=1.39). The study concluded that significant number of respondents believed in a high level of grassroots participation and others held contrary views, indicating that there may be disparities in how stakeholders perceive the depth of involvement. The study recommended that policy makers and county authorities should take steps to ensure that public participation processes are equitable and inclusive.

Targeted agents plus CHOP compared with CHOP as the first-line treatment for newly diagnosed patients with peripheral T-cell lymphoma (GUIDANCE-03): an open-label, multicentre phase 2 clinical trial

Peripheral T-cell lymphoma (PTCL) is a heterogeneous disease with dismal outcomes. We conducted an open-label, phase 2 nonrandomised, externally controlled study to evaluate the efficacy and safety of targeted agents plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) (CHOPX) for PTCL in the front-line setting. Eligible patients were ≥18 years of age and newly diagnosed PTCL. Patients in the CHOPX group received standard CHOP at Cycle 1. Specific targeted agents were added from Cycle 2, decitabine if TP53 mut, azacytidine if TET2/KMT2D mut, tucidinostat if CREBBP/EP300 mut, and lenalidomide if without mutations above. Patients in the CHOP group received CHOP for 6 cycles. The primary endpoint was the complete response rate (CRR) at the end of treatment (EOT). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. The study was registered with ClinicalTrials.gov, NCT04480099. Between July 29, 2020, and Sep 22, 2022, 96 patients were enrolled and included for efficacy and safety analysis with 48 in each group. The study met its primary endpoint. CRR at EOT in the CHOPX group was superior to the CHOP group (64.6% vs. 33.3%, OR 0.27, 95%CI 0.12-0.64; p=0.004). At a median follow-up of 24.3 months (IQR 12.0-26.7), improved median PFS was observed in the CHOPX group (25.5 vs. 9.0 months; HR 0.57, 95%CI 0.34-0.98; p=0.041). The median OS was similar between two groups (not reached vs. 30.9 months; HR 0.55, 95%CI 0.28-1.10; p=0.088). The most common grade 3-4 hematological and non-hematological adverse events in the CHOPX group were neutropenia (31, 65%) and infection (5, 10%). Targeted agents combined with CHOP demonstrated effective and safe as first-line treatment in PTCL. Biomarker-driven therapeutic strategy is feasible and may lead to promising efficacy specifically toward molecular features in PTCL. This study was supported by the National Key Research and Development Program (2022YFC2502600) and the General Program of the Shanghai Municipal Health Commission (202040400).