Global Strategy Research Articles

Research on integrating hydrogen energy storage with solar and wind power for Net-Zero energy buildings

Net Zero Energy Buildings (NZEBs) are evolving as a pillar concept as it fits in with the global Net Zero Energy Target strategy and the decarbonisation strategy of the building sector, which has been developed in response to climate change. The shift from existing building types to Net Zero Energy Buildings is a predominant trend. Net Zero Energy Buildings. This review paper explores the use of solar and wind energy as new sources of energy to generate electricity and hydrogen to store electricity as revolutionary solutions to achieve Net Zero Energy Buildings. It provides insights into the technological advances and challenges associated with hydrogen energy systems, including electrolyser efficiency, storage solution resolution, and fuel cell innovation. In addition, the paper highlights the key role of hydrogen in addressing the intermittency of renewable energy generation and enhancing the resilience and sustainability of Net Zero Energy Buildings systems. The potential for scaling up and commercialising hydrogen storage in the building sector is assessed through a detailed examination of current technologies, performance evaluations, and case studies. Despite facing a number of barriers from technical, economic, and policy perspectives, this paper argues that hydrogen storage can make a significant contribution to the decarbonisation of the built environment through continued technological innovation and framework improvement.

RETURNING TO SAID AND HIS «ORIENTALISM»

This article examines the impact of Edward Said’s concept of Orientalism on the contemporary geopolitical landscape. The authors argue that while the critique of Orientalism has significantly influenced academic discourse and domestic policies in Western countries, particularly the United States, it has not led to fundamental changes in global geopolitical strategy. The paper focuses on two key aspects: the natural connection between knowledge and power, which cannot be altered by anti-colonial declarations, and the shift of colonial discourse to new regions, specifically non-Western Europe. The authors posit that the strength of a modern state lies in its ability to dynamically bifurcate its image into internal and external faces, presenting different aspects to its society and foreign partners. Using the United States as a case study, the article demonstrates how internal anti-colonial discourse coexists with an unchanging foreign policy strategy of global dominance. The authors criticize the illusions about the possibility of changing the fundamental principles of US foreign policy, which has remained consistent since 1941. The paper emphasizes the continuation of a strategy aimed at fostering global dependence on the West, despite anti-colonial rhetoric. The article explores the complex interplay between domestic movements for social justice and decolonization, and the pragmatic realities of international relations. It argues that the deconstruction of Orientalism, while challenging the legitimacy of historical colonial practices, has not transformed the core geopolitical interests of Western states.The authors contend that the apparent dichotomy between internal anti-colonial discourse and external policy reflects both the complexity and strength of states like the US, where domestic and foreign policies can be shaped by different institutional and ideological forces. The paper also discusses the expansion of the concept of liberal democracy as an export product to regions deemed lacking in popular sovereignty.In conclusion, the article suggests that the critique of Orientalism, despite its academic and cultural impact, has been effectively neutralized in geopolitical practice. This is achieved through a shift in focus to regions not traditionally considered part of the «old» Western colonies, allowing for the implementation of economic partnership policies without the moral self-flagellation associated with charges of Orientalism. The paper ultimately argues that renaming reality does not change its underlying structure, and that the postmodern belief in the power of language to transform geopolitical realities is akin to magical thinking. It concludes that the critique of Orientalism has not fundamentally altered the eternal principles and interests guiding global geopolitical strategies.

Strategies to strengthen the resilience of primary health care in the COVID-19 pandemic: a scoping review

BackgroundPrimary Health Care (PHC) systems are pivotal in delivering essential health services during crises, as demonstrated during the COVID-19 pandemic. With varied global strategies to reinforce PHC systems, this scoping review consolidates these efforts, identifying and categorizing key resilience-building strategies.MethodsAdopting Arksey and O'Malley's scoping review framework, this study synthesized literature across five databases and Google Scholar, encompassing studies up to December 31st, 2022. We focused on English and Persian studies that addressed interventions to strengthen PHC amidst COVID-19. Data were analyzed through thematic framework analysis employing MAXQDA 10 software.ResultsOur review encapsulated 167 studies from 48 countries, revealing 194 interventions to strengthen PHC resilience, categorized into governance and leadership, financing, workforce, infrastructures, information systems, and service delivery. Notable strategies included telemedicine, workforce training, psychological support, and enhanced health information systems. The diversity of the interventions reflects a robust global response, emphasizing the adaptability of strategies across different health systems.ConclusionsThe study underscored the need for well-resourced, managed, and adaptable PHC systems, capable of maintaining continuity in health services during emergencies. The identified interventions suggested a roadmap for integrating resilience into PHC, essential for global health security. This collective knowledge offered a strategic framework to enhance PHC systems' readiness for future health challenges, contributing to the overall sustainability and effectiveness of global health systems.

RAG1/2 induces double-stranded DNA breaks at non-Ig loci in the proximity of single sequence repeats in developing B cells.

In developing B cells, V(D)J gene recombination is initiated by the RAG1/2 endonuclease complex, introducing double-stranded DNA breaks (DSBs) in V, D, and J genes and resulting in the formation of the hypervariable parts of immunoglobulins (Ig). Persistent or aberrant RAG1/2 targeting is a potential threat to genome integrity. While RAG1 and RAG2 have been shown to bind various regions genome-wide, the in vivo off-target DNA damage instigated by RAG1/2 endonuclease remains less well understood. In the current study, we identified regions containing RAG1/2-induced DNA breaks in mouse pre-B cells on a genome-wide scale using a global DNA DSB detection strategy. We detected 1489 putative RAG1/2-dependent DSBs, most of which were located outside the Ig loci. DNA sequence motif analysis showed a specific enrichment of RAG1/2-induced DNA DSBs at GA- and CA-repeats and GC-rich motifs. These findings provide further insights into RAG1/2 off-target activity. The ability of RAG1/2 to introduce DSBs on the non-Ig loci during the endogenous V(D)J recombination emphasizes its genotoxic potential in developing lymphocytes.

History of leprosy in Mexico: from the 15th century to the21st century

Leprosy is an infectious disease transmitted by the bacterium Mycobacterium leprae. While it’s not a new disease, its incidence over time has changed, and in some places, it has been eradicated. However, in other areas, it is still considered a public health problem, and Mexico is one of them. Throughout global history, diagnostic, therapeutic, prevention, control, and surveillance strategies have been implemented to reduce its incidence. Currently, our country is attached to various national and international programs for managing this disease, aiming to reduce its prevalence and eventually eradicate it. Nevertheless, many socioeconomic factors have hindered the complete achievement of these goals, which have been modified but not entirely eliminated. The purpose of this review was to conduct a retrospective analysis of leprosy management in Mexico, aiming to present the current situation to raise awareness of the potential seriousness of this disease becoming a public health priority again. This review also seeks to promote new research to identify the cause of the recent increase in cases over the past year. It includes a historical breakdown of the epidemiological trends of this disease in the country, as well as the various therapeutic and diagnostic measures and their impact in the current context.

Classification of international organizations and their role in the modern world

International organizations in the modern world play an important role in ensuring cooperation between states, developing global strategies and solving international problems. Classification of various international organizations into categories for the purpose of their systematic study is not based on a priori generally accepted criteria. Thus, none of the existing classifications of international organizations, even if they satisfy a significant part of differentiated research needs, can be considered as based on codified criteria. The relative typology of all international organizations entails their classification, sometimes based on criteria that serve the specific theoretical needs of a particular study. Although this is not the case here, it should be noted that the following distinctions of international organizations are mainly relevant to the study of the legal aspects of the phenomenon. International organizations can be classified according to various criteria, such as target orientation, structure, method of participation of states and others. One of the key criteria is functional orientation. Thus, there are political, economic, social, humanitarian and military organizations, each of which has its own specific tasks and functions. Some organizations are based on the principle of sovereignty, where each state has the right to make an independent decision on participation in the organization’s activities. In the light of globalization and the growing complexity ofinternationalrelations, understanding the classification of international organizations is becoming extremely important for solving global problems and ensuring peaceful coexistence in the international arena. Studying their functions, structures, and participation mechanisms helps countries and organizations to cooperate more effectively and solve important global issues. The role of international organizations in the modern world cannot be overestimated. They facilitate cooperation between states, resolve international conflicts, provide humanitarian aid, develop economies, and implement joint strategies for environmental protection. International organizations act as mediators and coordinators in solving major global problems, ensuring stability and progress in international relations.

The multifactorial approach and the food allergen-specific substitutive diet as a tool to manage and ameliorate adverse reactions to foodstuffs in adulthood: study protocol for a randomized controlled trial—the ALASKA study

BackgroundAdverse reactions to foodstuffs (ARFS), specifically food allergy (FA) and food intolerance (FI), are increasing worldwide and represent a major public health concern. Thus, ARFS management, its identification, evaluation, and intervention, must provide a comprehensive solution.Objectives(a) To develop a multifactorial strategy for ARFS management in adults with FA and/or FI; (b) to describe the multiple influential variables in ARFS within the realm of ARFS management; and (c) to design a personalized food allergen-specific substitutive diet (FASSD), as a 6-month dietary treatment option for adults with ARFS and as a component of ARFS management.MethodsThe ALASKA study will consider the following main variables as part of the ARFS management: (1) demographics and clinical information; (2) symptomatology, food and beverages intake and physical activity; (3) hematobiochemical study; (4) immunology; (5) enzymatic activity; (6) anthropometry, body composition, and physical fitness; (7) QoL; (8) 6-month intervention; (9) end of the study; and (10) other assessments. The FASSD will be designed with special emphasis on the commonly lacking micronutrients in the ARFS population: niacin, Mg, K, P, Ca, Zn, B12, folate, Fe, and fiber.DiscussionThe ALASKA study protocol has been developed as a global strategy to manage and evaluate ARFS in Spanish adults older than 18 years of age. Approaching ARFS with multiple assessments, as influencing factors, will lead to a novel strategy for ARFS management. The FASSD has been designed as a personalized tool to avoid crucial micronutrient deficiencies that a current strict food allergen avoidance or elimination diet may provoke.Trial registrationThe protocol has been approved by the Ethics Committee of the UPM (REF.20200602) and registered on ClinicalTrials.gov (NCT05802017).

Computer-aided detection of tuberculosis from chest radiographs in a tuberculosis prevalence survey in South Africa: external validation and modelled impacts of commercially available artificial intelligence software

Computer-aided detection (CAD) can help identify people with active tuberculosis left undetected. However, few studies have compared the performance of commercially available CAD products for screening in high tuberculosis and high HIV settings, and there is poor understanding of threshold selection across products in different populations. We aimed to compare CAD products' performance, with further analyses on subgroup performance and threshold selection. We evaluated 12 CAD products on a case-control sample of participants from a South African tuberculosis prevalence survey. Only those with microbiological test results were eligible. The primary outcome was comparing products' accuracy using the area under the receiver operating characteristic curve (AUC) against microbiological evidence. Threshold analyses were performed based on pre-defined criteria and across all thresholds. We conducted subgroup analyses including age, gender, HIV status, previous tuberculosis history, symptoms presence, and current smoking status. Of the 774 people included, 516 were bacteriologically negative and 258 were bacteriologically positive. Diverse accuracy was noted: Lunit and Nexus had AUCs near 0·9, followed by qXR, JF CXR-2, InferRead, Xvision, and ChestEye (AUCs 0·8-0·9). XrayAME, RADIFY, and TiSepX-TB had AUC under 0·8. Thresholds varied notably across these products and different versions of the same products. Certain products (Lunit, Nexus, JF CXR-2, and qXR) maintained high sensitivity (>90%) across a wide threshold range while reducing the number of individuals requiring confirmatory diagnostic testing. All products generally performed worst in older individuals, people with previous tuberculosis, and people with HIV. Variations in thresholds, sensitivity, and specificity existed across groups and settings. Several previously unevaluated products performed similarly to those evaluated by WHO. Thresholds differed across products and demographic subgroups. The rapid emergence of products and versions necessitates a global strategy to validate new versions and software to support CAD product and threshold selections. Government of Canada.

Yes! We can end TB

In celebration of World Tuberculosis Day 2024, an e-poster titled "Yes! We Can End TB" was created by Sushant Kumar Yadav, a first-year medical student at B.P. Koirala Institute of Health Sciences, Nepal. This poster earned second place in a competition organized by the PSRN Student Chapter in association with the Department of Pulmonary, Critical Care, and Sleep Medicine at B.P. Koirala Institute of Health Sciences and Dharan Submetropolitan City, Nepal. The poster highlights the global efforts and strategies to eradicate tuberculosis, emphasizing public awareness, early diagnosis, and effective treatment.

A multinational firm’s global manufacturing location and outsourcing strategies

Due to rising labor costs in China and trade friction, many multinational firms (MNFs) consider moving manufacturing outside China to Southeast Asian Countries. Based on observations in real world, we build a three-tier supply chain model consisting of one component supplier, two contract manufacturers (CMs), an MNF, and a local original equipment manufacturer (OEM). The MNF monopolizes the market in country 1 (e.g., U.S.), but competes in country 2 (e.g., China) with the local OEM. The component supplier and one CM are located in country 2, and the other CM is located in country 3 (e.g., a country in Southeast Asia). We investigate the MNF’s global manufacturing location and procurement outsourcing strategies with considerations of tariffs and market environments. Currently, the MNF outsources its manufacturing to the CM in country 2, and decides whether to continue the cooperation with the current CM or develop a new CM in country 3. The MNF also considers whether to outsource its component procurement to the corresponding CM. Our study reveals that the MNF’s optimal strategy depends on the relative market sizes, the fixed cost of developing a new CM, as well as the manufacturing cost and tariff disadvantages in country 2. Interestingly, we find that the tariff disadvantage in country 2 does not always motivate the MNF to cooperate with the CM in country 3. Instead, an appropriate tariff may be beneficial to the MNF that manufactures in country 2. In addition, the MNF’s preferred procurement strategy is related to its manufacturing location. When cooperating with the CM in country 2, the MNF would switch from direct procurement to outsourced procurement as the market size of country 1 increases.

Statistical Analysis Plan for the AIRCARD Study: Individual Long-Term Air and Noise Pollution Exposure and Cardiovascular Disease Incidence and Mortality - A Prospective Cohort Study Utilizing DANCAVAS and VIVA Screening Trials.

The AIRCARD study is designed to investigate the relationship between long-term exposure to air and noise pollution and cardiovascular disease incidence and mortality. We aim to conduct a robust prospective cohort analysis assessing the cumulative and differential impacts of air and noise pollution exposure on cardiovascular disease and mortality. This study will adjust for relevant confounders, including traditional cardiovascular risk factors, socioeconomic indicators, and lipid-lowering agents. This prospective cohort study will include 27,022 male participants aged 65-74, recruited from the two large Danish DANCAVAS and VIVA trials, both population-based randomized, multicentered, clinically controlled studies. We will assess long-term exposure to air pollutants using the state-of-the-art DEHM/UBM/AirGIS modeling system and noise pollution through the Nord2000 and SoundPLAN models, covering data from 1979 to 2019. This statistical analysis plan is strictly formulated to predefine the analytical approach for all outcomes and key study variables before data access. The primary analysis will utilize Cox proportional hazards models, adjusted for confounders identified in our cohort (age, body mass index, hypertension, diabetes, smoking status, family history of heart disease, socioeconomic factors, and lipid-lowering agents). This statistical analysis plan further includes Spearman rank correlation to explore inter-pollutant associations. The AIRCARD study addresses global concerns about the impact of air and noise pollution on cardiovascular disease. This research is important for understanding how the pollutants contribute to cardiovascular disease. We aim to provide insights into this area, emphasizing the need for public health measures to mitigate pollution exposure. Our goal is to provide policymakers and healthcare professionals with information on the role of environmental factors in cardiovascular health that could influence global strategies to reduce the cardiovascular disease burden associated with pollution. The design of this SAP ensures transparency and verifiability, considering the complexities of evaluating environmental health impacts over an extended period.

A newly identified IncY plasmid from multi-drug-resistant Escherichia coli isolated from dairy cattle feces in Poland.

This study reveals the identification of new strains of antibiotic-resistant Escherichia coli in cattle manure from a dairy farm in Poland, offering critical insights into the spread of drug resistance. Through whole-genome sequencing, researchers discovered novel plasmids within these bacteria, which carry genes resistant to multiple antibiotics. These findings are particularly alarming, as these plasmids can transfer between different bacterial species, potentially escalating the spread of antibiotic resistance. This research underscores the vital connection between the health of humans, animals, and the environment, emphasizing the concept of One Health. It points to the critical need for global vigilance and strategies to curb the proliferation of antibiotic resistance. By showcasing the presence of these strains and their advanced resistance mechanisms, the study calls for enhanced surveillance and preventive actions in both agricultural practices and healthcare settings to address the imminent challenge of antibiotic-resistant bacteria.

Identification of potential differences in salivary proteomic profiles between estrus and diestrus stage of estrous cycle in dairy cows

In the present study, a comparative global high-throughput proteomic analysis strategy was used to identify proteomic differences between estrus and diestrus stage of estrous cycle in dairy cows. Saliva was collected from cows during estrus and diestrus, and subjected to LC-MS/MS-based proteomic analysis. A total of 2842 proteins were detected in the saliva of cows, out of which, 2437 and 1428 non-redundant proteins were identified in estrous and diestrous saliva, respectively. Further, it was found that 1414 and 405 salivary proteins were specific to estrus and diestrus, respectively while 1023 proteins were common to both groups. Among the significantly dysregulated proteins, the expression of 56 proteins was down-regulated (abundance ratio <0.5) while 40 proteins were up-regulated (abundance ratio > 2) in estrous compared to diestrous saliva. The proteins, such as HSD17B12, INHBA, HSP70, ENO1, SRD5A1, MOS, AMH, ECE2, PDGFA, OPRK1, SYN1, CCNC, PLIN5, CETN1, AKR1C4, NMNAT1, CYP2E1, and CYP19A1 were detected only in the saliva samples derived from estrous cows. Considerable number of proteins detected in the saliva of estrous cows were found to be involved in metabolic pathway, PI3K-Akt signaling pathway, toll-like receptor signaling pathway, steroid biosynthesis pathway, insulin signaling pathway, calcium signaling pathway, estrogen signaling pathway, oxytocin signaling pathway, TGF-β signaling pathway and oocyte meiosis. On the other hand, proteins detected in saliva of diestrous cows were involved mainly in metabolic pathway. Collectively, these data provide preliminary evidence of a potential difference in salivary proteins at different stages of estrous cycle in dairy cows.

Multiview ensemble clustering of hypergraph p-Laplacian regularization with weighting and denoising

Multiview clustering has gained attention for its ability to incorporate complementary information from multiple sources of data, leading to better clustering results. However, these methods don't sufficiently mine high-dimensional information of non-linear subspace or ignore important high-level information between basic partitions (BPs), which are obtained via single-view clustering that could help to overcome differences between heterogeneous feature spaces and defined in Eq. (4). Additionally, existing multiview ensemble clustering methods neglect the noise arising from the generation phase. In light of this, we first propose a novel multiview subspace clustering method with hypergraph p-Laplacian regularization and denoising. Specifically, to utilize the high-dimensional information, a hypergraph p-Laplacian regularized term is added to the model along with low-rank subspace learning to capture the different hierarchical structures in the data. A denoising algorithm based on KMeans and K-nearest neighbor is used to minimize the noise of similarity matrix. Then utilizing this approach as a backbone, a multiview ensemble clustering of hypergraph p-Laplacian regularization with weighting and denoising method is proposed. A hybrid strategy and a novel global weighting ensemble strategy is further proposed to extract high-level information across all the BPs. By integrating hypergraph p-Laplacian operator, low-rank subspace learning, denoising, and weighting ensemble strategy in a unified framework, this ensemble approach adequately learns latent structures and complementary information. Experimental results on multiple datasets demonstrate the efficacy of this approach.

Pioneering Colorectal cancer screening: blood-based DNA tests as a global strategy for early detection - Editorial.

Pioneering Colorectal cancer screening: blood-based DNA tests as a global strategy for early detection - Editorial.

“The Sea Has Waves, The Fula Has Cows”: Moving Waters, Labour and Capital in Anthropocene Senegal

In times of climate crisis, water has become a crucial resource of environmental justice and geopolitics, but its scarcity is socially constructed. It depends on socio-economic structures, cultural politics, and the sciences that are mobilized to manage its fluid processes. This essay argues for the necessity of a hydrosociological approach that integrates the current Anthropocene debates on the technological transformation of planet Earth with more reflection on waterscapes, especially in the Global South. Drawing on a recent publication by Maura Benegiamo, Capitalist developments in the Senegal Delta are here considered as exemplary of global investment strategies that produce brutal forms of extractivism, while displacing money, water, land, and people. Waterscapes reengineering of the Senegal flows, for the monocrop production of agrofuel, is alienating the Fula people of the Sahel the grazing land for their cattle. Such case calls for a political reassessment of the hydrosocial question of the Anthropocene along complementary lines of inquiry: socio-economic, cultural-political, ideological, and epistemological.

Hepatitis B infection and immunity in migrant children and pregnant persons in Europe: a systematic review and meta-analysis.

The WHO's global hepatitis strategy aims to achieve viral hepatitis elimination by 2030. Migrant children and pregnant persons represent an important target group for prevention strategies. However, evidence on the burden of chronic hepatitis B (CHB) infection and the factors affecting its incidence is lacking. EMBASE, Global Health, Global Index Medicus, Web of Science and Medline were searched for articles in any language from 1 January 2012 to 8 June 2022. Studies reporting CHB prevalence, disease severity, complications and/or prevention strategies, including vaccination, prevention of vertical transmission and access to care/treatment for migrant children and pregnant migrants, were included. Pooled estimates of CHB prevalence and hepatitis B vaccination (HBV) coverage among migrant children were calculated using random effects meta-analysis. 42 studies were included, 27 relating to migrant children and 15 to pregnant migrants across 12 European countries, involving data from 64 773 migrants. Migrants had a higher incidence of CHB than host populations. Among children, the pooled prevalence of CHB was higher for unaccompanied minors (UAM) (5%, [95% CI: 3-7%]) compared to other child migrants, including internationally adopted children (IAC) and refugees (1%, [95% CI: 1-2%]). Region of origin was identified as a risk factor for CHB, with children from Africa and pregnant migrants from Africa, Eastern Europe and China at the highest risk. Pooled estimates of HBV vaccine coverage were lower among UAM (12%, [95% CI: 3-21%]) compared to other child migrants (50%, [95% CI: 37-63%]). A range of modifiable determinants of HBV prevalence in migrant children and pregnant persons were identified, including sub-optimal screening, prevention and continuum of care. There is a need to develop evidence-based approaches in hepatitis care for these groups, thereby contributing towards global viral hepatitis elimination goals.

Projects and Realities of Forming a Great Eurasian Space

Aim. Analyze three options for the development and construction of the Eurasian space (Russian, Chinese and Turkic) and identify the advantages and risks associated with both the expansion of integration processes and external influence on states that are members of coalitions of the nonWestern world.Tasks. To trace the evolution of supranational structural formations in the Eurasian space after the collapse of the Soviet Union and their appearance in declarations, agreements and other legal documents, starting with statements about “the formation and development of a common economic space, pan-European and Eurasian markets”.To identify the characteristic features of globalization of all spheres of human existence, which has given rise to the need to understand the “landscape of global risks”, “global existential catastrophe” as an event leading “to the end of the existence of our descendants”, which together determined the transition to the formation of nation states, geopolitical and geo-economic coalitions in the Greater Eurasia space (“Central Asian Five”, EEAS, SCO, CSTO, UTC).Results. The concept of three main projects for the construction of Greater Eurasia is substantiated: Russian, based on the revival of the Eurasian ideology of N. S. Trubetskoy, P. N. Savitsky and G. V. Vernadsky; the Chinese “Belt and Road”, aimed at transforming the idea of the Great Silk Road into a Community of a Common Destiny for Humanity; Turkic, claiming to recreate the Turkic civilization with the goal of “bringing world civilizations closer together” on the Eurasian continent.The author’s position is argued regarding the need to ensure coplanarity and unidirectionality of the three vectors of implementation of Eurasian projects with the consistency of political decisions and actions of the three poles of power in the Greater Eurasian space — Russia, China and Turkey.Conclusions. Currently, the coordination of political decisions and actions of the three poles of power in the Greater Eurasian space, taking into account the principles of convergence of national interests in interstate unions, global geopolitical processes of multi-agent interaction and global security strategy in a polycentric world, is becoming relevant.

Ligand-Receptor Interaction-Induced Intracellular Phase Separation: A Global Disruption Strategy for Resistance-Free Lethality of Pathogenic Bacteria.

Addressing the global challenge of bacterial resistance demands innovative approaches, among which multitargeting is a widely used strategy. Current strategies of multitargeting, typically achieved through drug combinations or single agents inherently aiming at multiple targets, face challenges such as stringent pharmacokinetic and pharmacodynamic requirements and cytotoxicity concerns. In this report, we propose a bacterial-specific global disruption approach as a vastly expanded multitargeting strategy that effectively disrupts bacterial subcellular organization. This effect is achieved through a pioneering chemical design of ligand-receptor interaction-induced aggregation of small molecules, i.e., DNA-induced aggregation of a diarginine peptidomimetic within bacterial cells. These intracellular aggregates display affinity toward various proteins and thus substantially interfere with essential bacterial functions and rupture bacterial cell membranes in an "inside-out" manner, leading to robust antibacterial activities and suppression of drug resistance. Additionally, biochemical analysis of macromolecule binding affinity, cytoplasmic localization patterns, and bacterial stress responses suggests that this bacterial-specific intracellular aggregation mechanism is fundamentally different from nonselective classic DNA or membrane binding mechanisms. These mechanistic distinctions, along with the peptidomimetic's selective permeation of bacterial membranes, contribute to its favorable biocompatibility and pharmacokinetic properties, enabling its in vivo antimicrobial efficacy in several animal models, including mice-based superficial wound models, subcutaneous abscess models, and septicemia infection models. These results highlight the great promise of ligand-receptor interaction-induced intracellular aggregation in achieving a globally disruptive multitargeting effect, thereby offering potential applications in the treatment of malignant cells, including pathogens, tumor cells, and infected tissues.

A global springback compensation method for manufacturing metallic seal ring with complex cross-section and submillimeter precision

The fabrication of complex thin-walled components with irregular cross-sectional geometries often necessitates multi-pass forming processes. The springback phenomena at the microscale level contribute significantly difficulty to the precise control of geometrical accuracy for such components. To achieve submillimeter precision control of micro features in metal seal rings, this research proposed a global springback compensation method to facilitate the attainment of the optimized surfaces of dies. Through the analysis of changes in cross-sectional shape, stress distribution and bending moment in the multiple stages, several partition points were set up to divide the cross-section into four zones. For a partitional control of the manufactured surface, the compensation magnitudes for each segment are determined by iteratively refining the compensation factors using the secant method. The iteration of compensation factors is based on the deviation of dimensions measured by finite element simulation, which greatly saves experimental costs. The experimental results indicate that the predictive dimensional alterations by the global compensation agree with the experimental ones exhibiting a maximum error of less than 3 %. Furthermore, the springback behavior during the unloading and trimming stages coupling caused a dimensional error of 14.9 % for the wave width and 8.3 % for the peak width. Following the application of coupled compensation through two iterations, a distinct decrease in the relative average errors of springback values for both part width and peak width, achieving reductions to 2.4 % and 0.6 %, respectively. Compared to the traditional single springback compensation technique, the global compensation strategy effectively mitigates the out-of-tolerance issues induced by the trimming process.