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Abstract In foundation pit engineering, the deformation prediction of adjacent pipelines is crucial for construction safety. Existing approaches depend on constitutive models, grey correlation prediction, or traditional feedforward neural networks. Due to the complex hydrological and geological conditions, as well as the nonstationary and nonlinear characteristics of monitoring data, this problem remains a challenge. By formulating the deformation of monitoring points as multivariate time series, a deep learning-based prediction model is proposed, which utilizes the convolutional neural network to extract the spatial dependencies among various monitoring points, and leverages the bi-directional long-short memory unit network to extract temporal features. Notably, an attention mechanism is introduced to adjust the trainable weights of spatial-temporal features extracted in the prediction. The evaluation of a real-world subway project demonstrates that the proposed model has advantages compared with current models, particularly in long-term prediction. It improves the Adjusted R2 index averagely by from 19.4 to 61.6 $$\%$$ % compared with existing models. The proposed model also exhibits a decrease in mean absolute error ranging from 51.5 to 70.3 $$\%$$ % compared to others. Experiments and analyses verify that the spatial-temporal dependencies in time series and the attention learning for spatial-temporal features can improve the prediction of such engineering problems.

Cerebral vascular bypass is a key method for the treatment of complex intracranial aneurysms. After nearly 60 years of exploration, its application range now covers the whole cerebral vascular region. With the advent of detachable coils and the mature application of related assistance techniques, endovascular intervention treatment is highly favored in the treatment of routine intracranial aneurysms due to its minimally invasive and rapid characteristics. The introduction of flow diverter (FD) has further ushered in a new era in the treatment of intracranial aneurysms. This article reviews the history and development of cerebral vascular bypass in the treatment of intracranial aneurysms, elaborates on the application and promotion of flow diverter, and discusses the limitations of endovascular intervention treatment in the flow diversion era. It also explores the application and prospects of a comprehensive cerebral vascular bypass system, reaffirming the application value of the whole - region cerebral vascular bypass technique.

Objective To explore the efficacy and safety of intracranial-intracranial bypass for the treatment of complex intracranial aneurysms. Methods and Results A total of 32 patients with complex intracranial aneurysms who were hospitalized for treatment at Huashan Hospital, Fudan University from January 2015 to December 2023 were included. Surgical methods included in-situ bypass, reimplantation, reanastomosis and bypass with interposition graft. For middle cerebral artery (MCA) aneurysms (n = 16), there were 5 cases of in-situ bypass, one case of reimplantation, 3 cases of reanastomosis, and 7 cases of bypass with interposition graft. For anterior cerebral artery (ACA) aneurysms (n = 8), there were 5 cases of in-situ bypass and 3 cases of reimplantation. For anterior communicating artery (ACoA) aneurysms (n = 2), both cases were in-situ bypass. For posterior circulation aneurysms (n = 6), there were 3 cases of in-situ bypass, 2 cases of reanastomosis, and one case of bypass with interposition graft. The intraoperative graft vessels patency rate was 100%. Among the 23 patients who participated in follow-up imaging for more than 6 months postoperatively, no obvious recurrence was indicated by imaging. Among the 28 patients who participated in modified Rankin Scale (mRS) follow-up, there was one case of 5, 5 cases of 3, 2 cases of 2, one case of 1, and 19 cases of 0. Postoperative hemorrhagic complications occurred in 3 cases (9.37%), and ischemic complications occurred in 10 cases (31.25%), with no patients requiring unplanned secondary surgery for complication treatment. Conclusions Intracranial-intracranial bypass has good efficacy and safety for the treatment of complex intracranial aneurysms and has unique advantages in the microsurgical treatment of complex intracranial aneurysms.

ObjectiveWe conducted a drug resistance and homology analysis of diarrheagenic Escherichia coli （DEC） in Fengxian District of Shanghai in order to provide a basis for clinical rational drug use， risk monitoring and early warning.MethodsDEC were isolated from diarrheal patients in Fengxian District， Shanghai from 2019 to 2022. The minimum inhibitory concentrations （MIC） of 21 drugs to the DEC were determined. Genotyping and homology analysis were conducted with pulsed-field gel electrophoresis （PFGE）.ResultsThe DEC detection rate of diarrhea cases was 18.99% （131/690）， including enteroaggregative E.coli （EAEC） 64.89% （85/131）， enterotoxigenic E.coli （ETEC） 22.14% （29/131）， enteropathogenic E.coli （EPEC） 12.21% （16/131）， and enterohemorrhagic E.coli （EHEC） 0.76%（1/131）. The DEC detection showed obvious seasonal characteristics with a high incidence in summer. The DEC multidrug resistance rate was 66.41% with a total of 65 drug resistance profiles. The five antimicrobial drugs with the highest resistance rate were ampicillin （60.31%）， nalidixic acid （51.91%）， cefazolin （50.38%）， tetracycline （44.27%）， and cotrimoxazole （35.11%）. The rate of DEC resistance to levofloxacin was significantly increased from 2019 to 2022. Cluster analysis showed that the similarity of 85 EAEC cluster was 58.4%‒100.0%， and 69 band patterns were obtained. The similarity of 29 ETEC cluster was 58.5%‒100.0%， and 13 band patterns were obtained， including 2 dominant band types. The similarity of 16 EAEC clusters was 53.9%‒100.0%， and 15 band patterns were obtained. Five groups of homologous strains were found， consistent with the resistance phenotypes.ConclusionAmong the diarrhea cases， the DEC epidemic intensity is high， the drug resistance situation is severe， and the risk of outbreak infection is high in Fengxian District， Shanghai. Therefore， health monitoring and prevention need to be strengthened.

BackgroundChronic respiratory disease is an important public health problem in the United States and globally. Diet, an important part of a healthy lifestyle, is also relevant to chronic respiratory health. We aimed to explore the relationship between overall dietary quality and the risk of chronic respiratory disease (CRD), include chronic bronchitis (CB), emphysema and asthma.MethodA total of 4,499 United States adults were extracted from the National Health and Nutrition Examination Survey (NHANES) in 2017–2018. Diet quality was assessed using 2 day, 24 h dietary recall data and quantified as the Healthy Diet Index (HEI)-2020 score. Binary logistic regression models, restricted cubic splines (RCS) and generalized additive modeling (GAM), the weighted quartile sum (WQS) and qgcom models were used to assess the relationship between HEI-2020 scores and risk of CB, emphysema and asthma.ResultsHigh HEI-2020 scores are associated with low risk of chronic respiratory disease (CB: 0.98, 0.97–0.99; emphysema: 0.98, 0.97–0.99; asthma: 0.98, 0.97–0.99) and consistent results across different dietary variable categorization (Tertile: CB: 0.58, 0.42–0.81; asthma: 0.51, 0.35–0.74; Quartile: CB: 0.57, 0.34–0.97; asthma: 0.56, 0.36–0.86) and different weighting models. Negative dose-response relationship between dietary quality and risk of chronic respiratory disease also shown in RCS and GAM models. The WQS and qgcom models also showed a healthy mixing effect of dietary components on respiratory disease, with high-quality proteins, vegetables, and fruits making the heaviest contributions.ConclusionHigher HEI-2020 scores were associated with lower risk of CB, emphysema, and asthma. Following Dietary Guidelines for Americans 2020–2025 could support enhanced respiratory health.

BackgroundThis study aims to explore the clinical value of low disease activity state (LDAS) in the treat-to-target strategy of pediatric systemic lupus erythematosus (pSLE) and find the risk factors for never reaching LDAS.MethodsA total of 272 children with SLE who were diagnosed and followed up in two tertiary hospitals in China during the period from January 2012 to December 2019 were involved in this study, and the clinical presentation, pathology, and treatment were retrospectively studied.ResultsThe male-to-female ratio was 1:5.2, the age at diagnosis was 11.1 years (IQR, 9.8–13.1 years), the disease duration was 1.0 month (IQR, 0.5–2.0 months), and follow-up was 36.5 months (IQR, 25.7–50.9 months). During follow-up, 230 children achieved LDAS, and 42 were never been in. Male (P = 0.018), mucosal ulcer (P = 0.048), liver function damage (P = 0.026), cardiac effusion (P = 0.034), anemia (P = 0.048), urine red blood cells (P = 0.017), urinary leukocytes (P = 0.032), and endothelial cell proliferation in renal biopsy (P = 0.004)—these indexes have statistical differences between the two groups in the baseline. At baseline, endothelial cell proliferation (P = 0.02) is an independent risk factor for never achieving LDAS by multivariate logistic analysis. During follow-up, non-compliance was a risk factor for never achieving LDAS by comparing between groups. Children with biologics achieved LDAS at a higher rate than children without biologics (P = 0.038). The proportion of organ damage in patients never been in LDAS was significantly higher than that in patients who achieved LDAS (P < 0.001).ConclusionEndothelial cell proliferation in renal biopsy and non-compliance during follow-up were independent risk factors for never achieving LDAS. At the end of the follow-up, the organ damage in the remission group was similar to that in the LDAS group, indicating that LDAS can be used as a target for pSLE treatment.

Objective To explore the effect of sodium butyrate on brain injury in mice with necrotizing enterocolitis (NEC). Methods A total of 137 3-day-old C57BL/6 mice were randomly divided into Control group (CON group, n=40, without maternal separation), NEC+PBS group (NP group, n=57) and NEC+butyrate group (NB group, n=40). The mice from the NP and NB groups were separated maternally and given either PBS or sodium butyrate by gavage from postnatal day 3 for 7 consecutive days, then a NEC model was established by formula feeding combined with hypoxia and hypothermia for 3 consecutive days. Survival rate, histopathological injury of the intestine, mRNA expression of TNF-α and IL-6 in the brain, and number of activated microglia and astrocytes were observed and detected. Morris water maze and transmission electron microscopy were employed to observe the long-term cognitive impairment and microstructure of myelin, respectively, for the adult mice (4 weeks old). Western blotting was used to measure the protein level of HMGB1 in the intestine and TLR4 as well as NF-κB in the brain. Results Compared with the CON group, the mice of the NP group showed increased mRNA expression of TNF-α(1.51± 0.20 vs 0.67±0.14) and IL-6 (2.03±0.39 vs 1.01±0.17) in the brain (both P < 0.05), raised number of activated microglia (751.00±82.35 vs 284.70±52.01, P < 0.05) and astrocytes (P < 0.05) in the hippocampus, and elevated protein levels of HMGB1 (1.76±0.19 vs 0.73±0.06) in the intestine as well as TLR4 (1.14±0.16 vs 0.81±0.01) and NF-κB (1.21±0.19 vs 0.60±0.15) in the brain (all P < 0.05). In addition, the adult mice in the NP group demonstrated the prolonged escape latency and decreased crossing-platform times, and increased G-ratio (all P < 0.05). After the administration of sodium butyrate, the mRNA expression levels of TNF-α(0.81±0.12 vs 1.51±0.20) and IL-6 (0.93±0.38 vs 2.03±0.39) in the brain were decreased, the activation of microglia was inhibited (468.00±99.59 vs 751.00±82.35), and the number of astrocytes was reduced (all P < 0.05). The decreased expression levels of HMGB1 (1.22±0.11 vs 1.76±0.19) in the intestine and TLR4 (0.88±0.06 vs 1.14±0.16) and NF-κB (0.70±0.19 vs 1.21±0.19) in the brain were also marked in the NB group (all P < 0.05). The adult mice of the NB group showed shortened escape latency, and increased crossing-platform times and myelin thickness (all P < 0.05). Conclusion Sodium butyrate alleviates the neuroinflammation by inhibiting the activation of TLR4-NF-κB signal pathway in the NEC brain, and thus exerts protective effect against NEC-associated brain injury.

ABSTRACT Genetic competence for natural transformation, considered one of the three main mechanisms leading to horizontal gene transfer in bacteria, is able to promote evolution, through genomic plasticity, and foster antibiotic resistance and virulence factors spreading. Conserved machinery and actors required to perform natural transformation have been shown to accumulate at different cellular localizations depending on the model organism considered. In this study, we investigate the transformation apparatus composition, localization, and dynamics in the human pathogen Staphylococcus aureus. We particularly show that most of the natural transformation actors co-localize in clusters. We also reveal that the localization of natural transformation proteins is dynamic, following the cell cycle. Ultimately, the natural transformation apparatus is preferentially established in the vicinity of the division septum. All these results demonstrate that DNA binding, uptake, and recombination are spatially and temporally coordinated to ensure S. aureus natural transformation. Finally, we hypothesize that S. aureus competent cells would initiate and then block cell division to ensure the success of natural transformation before the final constriction of the cytokinetic ring. IMPORTANCE Natural transformation, considered one of the three main mechanisms leading to horizontal gene transfer in bacteria, is able to promote genomic plasticity and foster antibiotic resistance spreading. Conserved machinery and actors required to perform natural transformation have been shown to accumulate at different cellular localizations depending on the model organism considered. Here, we show in the human pathogen Staphylococcus aureus that DNA binding, uptake, and recombination are spatially and temporally coordinated to ensure S. aureus natural transformation. We also reveal that localization of natural transformation proteins occurs in the vicinity of the division septum allowing S. aureus competent cells to block cell division to ensure the success of natural transformation before the final constriction of the cytokinetic ring.

Abstract To perform natural transformation, one of the three main Horizontal Gene Transfer mechanisms, bacteria need to enter a physiological differentiated state called genetic competence. Interestingly, new bacteria displaying such aptitude are often discovered, and one of the latest is the human pathogen Staphylococcus aureus. Here, we show an optimized protocol, based on planktonic cells cultures, leading to a large percentage of the population activating the development of competence and a significant improvement of S. aureus natural transformation efficiencies. Taking advantage of these conditions, we perform transcriptomics analyses to characterize the regulon of each central competence regulator. SigH and ComK1 are both found essential for activating natural transformation genes but also important for activation or repression of peripheral functions. Even though ComK2 is not found important for the control of transformation genes, its regulon shows an important overlap with that of SigH and ComK1. Finally, we propose that microaerobic conditions, sensed by the SrrAB two-component system, are key to activate competence in S. aureus.

【Background and objective】 Gold pear is a main fruit in northern China and its production relies on irrigation and fertilization. The purpose of this paper is to study the effects of different combinations of irrigation and nitrogen-fertilization on nitrogen uptake by roots and its translocation in the trees. 【Method】 The experiment was conducted in an orchard; it consisted of three irrigation treatments by keeping the lowest soil water content controlled for irrigation at 75 (HW), 65 (MW) and 55% (LW) of the field capacity, respectively, and three nitrogen treatments by applying 486 kg/hm2 (HF), 324 kg/hm2 (MF) and 162 kg/hm2 (LF), respectively. Standard irrigation and fertilization used by local farmers was taken as the control (CK). In each treatment, we measured nitrogen content in different parts of the tree at different growth stages. 【Result】 At fruit-expansion stage, the total nitrogen content in spring shoots and leaves were the highest in MW+MF, increasing by 26.20% and 8.66% respectively, compared to CK; the total nitrogen content differed significantly in spring shoots but not in leaves between the treatments. At maturity stage, the total nitrogen content in spring shoots was the highest in MW+MF, reaching 0.74 g/kg, and least in HW +MF, dropping to 0.54 g/kg. The total nitrogen content in the leaves in HW+MF was the highest, reaching 1.83 g/kg, and least in HW+LF being 1.70 g/kg. The nitrogen content in fruits in LW+HF was the highest, reaching 0.82 g/kg, a 52.70% increase compared to CK. The treatments did not result in considerable changes in total nitrogen contents in spring shoots and leaves, but significantly changed the total nitrogen contents in shoots and fruits. Correlation analysis did not find correlation between total nitrogen contents in spring shoots, leaves and fruits. The total nitrogen content in spring shoots and fruit were positively but insignificantly correlated, while total nitrogen content in leaves was negatively but insufficiently correlated with the total nitrogen content in spring shoots and fruits. 【Conclusion】 For all treatments we compared, keeping the lowest soil water controlled for irrigation at 65% of the field capacity combined with 300~350 kg/hm2 of nitrogen fertilization is optimal for yield and fruit quality of the golden pear in the studied area.

Top-down exfoliation is one of the most promising approaches for the scalable production of 2D materials, but the current techniques are limited by low yield of monolayers. Here, the authors report the exfoliation of graphene and other layered materials via viscous-polymer-assisted ball-milling, leading to a production of graphene products with monolayer percentage up to 97.9% at a yield of 78.3%.

The effects of hypereutectic Al-17Si-4Cu-0.5Mg alloy were prepared by semisolid extrusion. The effect of solution time on microstructure and properties of hypereutectic Al-17Si-4Cu-0.5Mg alloy was studied. Results show that spheroidization occurs in the Si phase with the increase of solution time. When the solution time reaches 10 h, the circularity of eutectic Si is 0.72. High concentration of Cu element is enriched around Si phase in as cast state. After solution for 1 h, Cu element is rapidly dissolved into the matrix. As solution time is increased from 1 h to 16 h, the diffraction peak intensity of θ(Al2Cu) and Q(Al5Si6Cu2Mg8) phases on the XRD curve is decreased, and the dislocation density in the alloy matrix is greatly reduced. After aging treatment at 180℃ is performed on the solution treated samples, the θ' and Q' phases precipitate. As the solution time increases, the alloy strength value shows a "double peak" phenomenon. After solution treatment for 1 h, the tensile strength of the alloy reaches 269 MPa and the yield strength is 233 MPa. Compared with the unheated alloy, they are increased by 43.3% and 42.7%, respectively. This is mainly because there is still larger dislocation density in the matrix at the initial stage of solution, and the precipitation has stronger pinning hindrance to the dislocation after aging treatment. When the solution time is 10 h, the tensile strength and yield strength of the alloy reach 311 MPa and 263 MPa, respectively. The roundness of Si phase and the strengthening effect of fine precipitates are the main reasons for the formation of the second strength peak.

Objective: This study aimed to identify the predictors and threshold of failure in neonatal acute respiratory distress syndrome. Methods: Newborns with severe acute respiratory distress syndrome aged 0–28 days and gestational age ≥36 weeks were included in the study if their cases were managed with non-extra corporal membrane oxygenation treatments. Patients were divided into two groups according to whether they died before discharge. Predictors of non-extra corporal membrane oxygenation treatment failure were sought, and the threshold of predictors was calculated. Results: A total of 103 patients were included in the study. A total of 77 (74.8%) survived hospitalization and were discharged, whereas 26 (25.2%) died. Receiver operating characteristic analysis of oxygen index, pH, base excess, and combinations of these indicators demonstrated the advantage of the combination of oxygen index and base excess over the others variables regarding their predictive ability. The area under the curve for the combination of oxygen index and base excess was 0.865. When the cut-off values of oxygen index and base excess were 30.0 and −7.4, respectively, the sensitivity and specificity for predicting death were 77.0% and 84.0%, respectively. The model with base excess added a net reclassification improvement of 0.090 to the model without base excess. Conclusion: The combination of oxygen index and base excess can be used as a predictor of outcomes in neonates receiving non-extra corporal membrane oxygenation treatment for acute respiratory distress syndrome. In neonates with acute respiratory distress syndrome, if oxygen index >30 and base excess

Non-canonical secretion pathways, collectively known as unconventional protein secretion (UPS), are alternative secretory mechanisms usually associated with stress-inducing conditions. UPS allows proteins that lack a signal peptide to be secreted, avoiding the conventional endoplasmic reticulum-Golgi complex secretory pathway. Molecules that generally rely on the canonical pathway to be secreted may also use the Golgi bypass, one of the unconventional routes, to reach the extracellular space. UPS studies have been increasingly growing in the literature, including its implication in the biology of several diseases. Intercellular communication between brain tumor cells and the tumor microenvironment is orchestrated by various molecules, including canonical and non-canonical secreted proteins that modulate tumor growth, proliferation, and invasion. Adult brain tumors such as gliomas, which are aggressive and fatal cancers with a dismal prognosis, could exploit UPS mechanisms to communicate with their microenvironment. Herein, we provide functional insights into the UPS machinery in the context of tumor biology, with a particular focus on the secreted proteins by alternative routes as key regulators in the maintenance of brain tumors.

Background: A tertiary-hospital-based retrospective study (2011-2019) was conducted to determine the mediating role of hypertensive disorders of pregnancy and abnormal placentations between advanced maternal age and adverse neonatal outcomes. Methods: Data from a tertiary-hospital-based retrospective study (n= 23051) was used and conducted regression-based mediation analysis to assess the mediating role of hypertensive disorders of pregnancy and abnormal placentation between the advanced maternal age and adverse neonatal outcomes. Results: After adjusting for confounding factors, the indirect effect of advanced maternal age on preterm births, perinatal mortality, and low birth weight mediated by hypertensive disorders of pregnancy was [aOR 4.95 (95% CI: 4.05, 5.85)], [aOR 2.82 (95% CI: 1.78, 3.86)], and [aOR 5.90 (95% CI: 4.93, 6.87)], respectively. The indirect effect of advanced maternal age on preterm births and low birth weight mediated by abnormal placentation was [aOR 6.83 (95% CI: 5.70, 7.97)] and [aOR 4.18 (95% CI: 3.26, 5.11)]. About, 23%, 37%, and 17% of the effect of advanced maternal age on preterm births, perinatal mortality, and low birth weight was mediated by hypertensive disorders of pregnancy, respectively. Furthermore, abnormal placentation mediates the association between advanced maternal age and preterm births by 18% and low birth weight by 23%. Conclusion: Hypertensive disorders of pregnancy and abnormal placentation partially mediate the association between advanced maternal age and adverse neonatal outcomes.

Abstract Desalination technology provides one promising solution to the global water shortage problem yet brings about a new challenge of managing massive waste brines. Recently, interfacial solar steam generation technology has gained increasing attention for brine treatment due to its high energy‐conversion efficiency and applicability to hypersaline brines. However, it is challenging to maintain high performance because of salt fouling problem. Herein, this study presents a novel salt excretion approach to maintaining the evaporation efficiency of interfacial solar steam systems for improved long‐term stability in brine desalination. By creating a directional flow, accumulated salts are excreted via discharging the concentrated brine. This approach is effective and applicable for brines with a broad range of concentration owing to its tuneable concentrating performance. With the capability of continuously producing clean water and near‐saturation brine, this work advances solar steam technologies toward practical applications, such as brine concentration and resource recovery.

Sustainability is critical in addressing global challenges posed by prolonged pandemics that impact health, economies, and the environment. Here, we introduce a molecular engineering approach for thermoregulated antimicrobial management inspired by firewalking rituals. The study uses in situ spectroscopy and multi-scale modeling to validate a hierarchical design. Efficient light-to-thermal energy conversion is achieved by engineering the molecular band structure. Rapid nanoscale hyperthermia is facilitated through thermal engineering. This approach significantly reduces the half-life of pathogens such as Escherichia coli, influenza A, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to 1.4 min while maintaining a low perceived temperature on human skin. Standard disease infection and epidemic models show this technologys potential to flatten outbreak curves and delay peak infection rates, which is crucial during the early stages of pandemics when developing vaccines and antiviral drugs takes time. The scalable manufacturing and broad antimicrobial applicability hold great promise for controlling emerging infectious diseases and diverse bioprotective applications.

In daily life, there are a variety of complex sound sources. It is important to effectively detect certain sounds in some situations. With the outbreak of COVID-19, it is necessary to distinguish the sound of coughing, to estimate suspected patients in the population. In this paper, we propose a method for cough recognition based on a Mel-spectrogram and a Convolutional Neural Network called the Cough Recognition Network (CRN), which can effectively distinguish cough sounds.

The striped flea beetle, Phyllotreta striolata (Fabricius), damages crops in the Brassicaceae. The genetic data for this pest are insufficient to reveal its insecticide resistance mechanisms or to develop molecular markers for resistance monitoring. We used PacBio Iso-Seq technology to sequence the full-length transcriptome of P. striolata. After isoform sequence clustering and removal of redundant transcripts, a total of 41,293 transcripts were obtained, and 35,640 of these were annotated in the database of gene products. Structure analysis uncovered 4,307 alternative splicing events, and 3,836 sequences were recognized as lncRNAs. Transcripts with the complete coding region of important detoxification enzymes were further classified. There were 57 transcripts of P450s distributed in CYP2, CYP3, CYP4, and Mito CYP clades, 29 transcripts of ESTs from 4 functional groups, 17 transcripts of GSTs classified into 5 families, 51 transcripts of ABCs distributed in 6 families, and 19 transcripts of UGTs. Twenty-five lncRNAs were predicted to be regulators of these detoxification genes. Full-length transcriptome sequencing is an efficient method for molecular study of P. striolata and it is also useful for gene function analysis.

Vaccines represent one of the most significant inventions in human history and have revolutionized global health. Generally, a vaccine functions by triggering the innate immune response and stimulating antigen-presenting cells, leading to a defensive adaptive immune response against a specific pathogens antigen. As a key element, adjuvants are chemical materials often employed as additives to increase a vaccines efficacy and immunogenicity. For over 90 years, adjuvants have been essential components in many human vaccines, improving their efficacy by enhancing, modulating, and prolonging the immune response. Here, we provide a timely and comprehensive review of the historical development and the current status of adjuvants, covering their classification, mechanisms of action, and roles in different vaccines. Additionally, we perform systematic analysis of the current licensing processes and highlights notable examples from clinical trials involving vaccine adjuvants. Looking ahead, we anticipate future trends in the field, including the development of new adjuvant formulations, the creation of innovative adjuvants, and their integration into the broader scope of systems vaccinology and vaccine delivery. The article posits that a deeper understanding of biochemistry, materials science, and vaccine immunology is crucial for advancing vaccine technology. Such advancements are expected to lead to the future development of more effective vaccines, capable of combating emerging infectious diseases and enhancing public health.

Abstract: Research Summary: We use a novel longitudinal dataset, constructed from 16 downloads of VentureXpert records collected over 20 years, to characterize the international migration of venture‐capital‐backed startups. We find that: (i) 1078 firms in our sample (1.4%) migrate; (ii) countries with high levels of in‐migration also have high levels of out‐migration; (iii) migrating firms move to places with more investors; (iv) pre‐move investors and their connections most strongly predict migration patterns; and (v) movers raise more money than non‐movers, primarily from investors at their destinations. Overall, these patterns appear inconsistent with those expected if startups move primarily in search of talent or customers. Instead, the flows across countries look more like international trade, with startups seeking capital, and social connections between investors defining the shipping lanes. Managerial Summary: Although many high‐profile startups have relocated their headquarters from one country to another, systematic information on this phenomenon has been scarce. How frequently do these moves happen? Why do startups move? Over 20 years, we have built a database that can begin to answer these questions. International moves appear rare. When startups do move, they tend to move to places with more venture capital, particularly when their existing investors have connections in those places. Movers, moreover, raise more money than non‐movers, mostly from investors in their destination countries. Capital availability, rather than access to talent or proximity to customers, appears to be the strongest predictor of startup migration.