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The inversion of substrate size specificity is an evolutionary roadblock for proteins. The Duf4243 dioxygenases GedK and BTG13 are known to catalyze the aromatic cleavage of bulky tricyclic hydroquinone. In this study, we discover a Duf4243 dioxygenase PaD that favors small monocyclic hydroquinones from the penicillic-acid biosynthetic pathway. Sequence alignments between PaD and GedK and BTG13 suggest PaD has three additional motifs, namely motifs 1-3, distributed at different positions in the protein sequence. X-ray crystal structures of PaD with the substrate at high resolution show motifs 1-3 determine three loops (loops 1-3). Most intriguing, loops 1-3 stack together at the top of the pocket, creating a lid-like tertiary structure with a narrow channel and a clearly constricted opening. This drastically changes the substrate specificity by determining the entry and binding of much smaller substrates. Further genome mining suggests Duf4243 dioxygenases with motifs 1-3 belong to an evolutionary branch that is extensively involved in the biosynthesis of natural products and has the ability to degrade diverse monocyclic hydroquinone pollutants. This study showcases how natural enzymes alter the substrate specificity fundamentally by incorporating new small motifs, with a fixed overall scaffold-architecture. It will also offer a theoretical foundation for the engineering of substrate specificity in enzymes and act as a guide for the identification of aromatic dioxygenases with distinct substrate specificities. The Duf4243 dioxygenases GedK and BTG13 are known to catalyze the aromatic cleavage of bulky tricyclic hydroquinone. Here, the authors discover a distinct Duf4243 dioxygenase PaD that favors small monocyclic hydroquinones from the penicillic-acid biosynthetic pathway and determine the structural basis for its changed substrate specificity. [ABSTRACT FROM AUTHOR]

The astrocyte-to-neuron lactate shuttle model entails that, upon glutamatergic neurotransmission, glycolytically derived pyruvate in astrocytes is mainly converted to lactate instead of being entirely catabolized in mitochondria. The mechanism of this metabolic rewiring and its occurrence in human brain are unclear. Here by using immunohistochemistry (4 brains) and imaging mass cytometry (8 brains) we show that astrocytes of the adult human neocortex and hippocampal formation express barely detectable amounts of mitochondrial proteins critical for performing oxidative phosphorylation (OXPHOS). These data are corroborated by queries of transcriptomes (107 brains) of neuronal versus non-neuronal cells fetched from the Allen Institute for Brain Science for genes coding for a much larger repertoire of entities contributing to OXPHOS, showing that human non-neuronal elements barely expressed mRNAs coding for such proteins. With less OXPHOS, human brain astrocytes are thus bound to produce more lactate to avoid interruption of glycolysis. Human brain astrocytes lack OXPHOS, ensuring lactate formation and shuttling to neurons. [ABSTRACT FROM AUTHOR]

Soft-matter-based photonic crystals like blue-phase liquid crystals (BPLC) have potential applications in wide-ranging photonic and bio-chemical systems. To date, however, there are limitations in the fabrication of large monocrystalline BPLCs. Traditional crystal-growth process involves the transition from a high-temperature disordered phase to an ordered (blue) phase and is generally slow (takes hours) with limited achievable lattice structures, and efforts to improve molecular alignment through post-crystallization field application typically prove ineffective. Here we report a systematic study on the molecular self-assembly dynamics of BPLC starting from a highly ordered phase in which all molecules are unidirectionally aligned by a strong electric field. We have discovered that, near the high-temperature end of the blue phase, if the applied field strength is then switched to an intermediate level or simply turned off, large-area monocrystalline BPLCs of various symmetries (tetragonal, orthorhombic, cubic) can be formed in minutes. Subsequent temperature tuning of the single crystal at a fixed applied field allows access to different lattice parameters and the formation of never-before-seen monoclinic structures. The formed crystals remain stable upon field removal. The diversity of stable monocrystalline BPLCs with widely tunable crystalline symmetries, band structures, and optical dispersions will significantly improve and expand their application potentials. Soft-matter-based photonic crystals like blue-phase liquid crystals (BPLC) have potential applications but face fabrication limitations for large monocrystalline structures. The authors report a method to rapidly form large-area monocrystalline BPLCs with various symmetries and tunable properties through an application of electric fields and temperature control. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is associated with cardiac conduction defects and is a strong risk factor for heart failure. Complete left bundle branch block (cLBBB), a cardiac conduction abnormality, may have an unfavorable effect on ventricular mechanical synchrony and lead to the progression of heart failure. Once heart failure develops, it seems to act together with underlying CKD in a vicious circle. Therefore, this study aimed to explore the influence of CKD in patients with cLBBB by assessing the estimated glomerular filtration rate (eGFR). We examined a hospital-based sample of 416 adult patients with cLBBB from 2010 to 2013. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cox proportional hazard models were used to estimate the hazard ratio for all-cause mortality and cardiovascular mortality. A total of 416 adult patients with a mean age of 71 ± 13 years were enrolled. The median follow-up period was 3.6 years. After adjusting for clinical, electrocardiographic parameters, and medication use, cox regression analysis showed that total mortality was significantly associated with older age (Hazard Ratio (HR) = 1.03, 95% CI = 1.01–1.05, p = 0.002), presence of congestive heart failure (HR = 2.39, 95% CI = 1.63–3.49, p < 0.001), advanced CKD (HR = 2.48, 95% CI = 1.71–3.59, p < 0.001), higher HR (HR = 1.02, 95% CI = 1.01–1.03, p < 0.001) and without use of ACEI/ARB (HR = 0.59, 95% CI = 0.41–0.85, p = 0.005) were independent predictors of the total mortality. Multivariate Cox hazard regression analysis demonstrated that, in comparison to patients lacking cLBBB, the coexistence of CKD (eGFR < 60 mL/min/1.73 m2) among those with LBBB significantly heightened the risks of both total mortality (HR ratio of 5.01 vs. 2.40) and CV death (HR ratio of 61.78 vs. 14.41) even following adjustment for clinical covariates and ECG parameters. In summary, within patients exhibiting cLBBB, the presence of CKD serves as a significant risk factor for all-cause mortality. [ABSTRACT FROM AUTHOR]

The recent rapid advancements in both sensing and machine learning technologies have given rise to the universal collection and utilization of people's biometrics, such as fingerprints, voices, retina/facial scans, or gait/motion/gestures data, enabling a wide range of applications including authentication, health monitoring, or much more sophisticated analytics. While providing better user experiences and deeper business insights, the use of biometrics has raised serious privacy concerns due to their intrinsic sensitive nature and the accompanying high risk of leaking sensitive information such as identity or medical conditions. In this paper, we propose a novel modality-agnostic data transformation framework that is capable of anonymizing biometric data by suppressing its sensitive attributes while retaining features relevant to downstream machine learning-based analyses that are of research and business values. We carried out a thorough experimental evaluation using publicly available facial, voice, motion, and EEG datasets. Results show that our proposed framework can achieve a high suppression level for sensitive information, while at the same time retain underlying data utility such that subsequent analyses on the anonymized biometric data could still be carried out to yield satisfactory accuracy. [ABSTRACT FROM AUTHOR]

Many-body localization (MBL) of a disordered interacting boson system in one dimension is studied numerically at the filling faction one-half. The von Neumann entanglement entropy SvN is commonly used to detect the MBL phase transition but remains challenging to be directly measured. Based on the U(1) symmetry from the particle number conservation, SvN can be decomposed into the particle number entropy SN and the configuration entropy SC. In light of the tendency that the eigenstate’s SC nears zero in the localized phase, we introduce a quantity describing the deviation of SN from the ideal thermalization distribution; finite-size scaling analysis illustrates that it shares the same phase transition point with SvN but displays the better critical exponents. This observation hints that the phase transition to MBL might largely be determined by SN and its fluctuations. Notably, the recent experiments [A. Lukin, et al., Science 364, 256 (2019); J. Léonard, et al., Nat. Phys. 19, 481 (2023)] demonstrated that this deviation can potentially be measured through the SN measurement. Furthermore, our investigations reveal that the thermalized states primarily occupy the low-energy section of the spectrum, as indicated by measures of localization length, gap ratio, and energy density distribution. This low-energy spectrum of the Bose model closely resembles the entire spectrum of the Fermi (or spin XXZ) model, accommodating a transition from the thermalized to the localized states. While, owing to the bosonic statistics, the high-energy spectrum of the model allows the formation of distinct clusters of bosons in the random potential background. We analyze the resulting eigenstate properties and briefly summarize the associated dynamics. To distinguish between the phase regions at the low and high energies, a probing quantity based on the structure of SvN is also devised. Our work highlights the importance of symmetry combined with entanglement in the study of MBL. In this regard, for the disordered Heisenberg XXZ chain, the recent pure eigenvalue analyses in [J. Suntajs, et al., Phys. Rev. E 102, 062144 (2020)] would appear inadequate, while methods used in [A. Morningstar, et al., Phys. Rev. B 105, 174205 (2022)] that spoil the U(1) symmetry could be misleading. [ABSTRACT FROM AUTHOR]

Background: Patients with autoimmune diseases (AD) generally carry an increased risk of developing cancer. However, the effect of AD in hepatocellular carcinoma (HCC) patients receiving surgical treatment is uncertain. The present study aimed to investigate the potential influence of AD on the survival of HCC patients undergoing hepatectomies. Methods: Operated HCC patients were identified from the Chang Gung Research Database, and the survival outcomes of HCC patients with or without AD were analyzed ad compared. Cox regression model was performed to identify significant risk factors associated with disease recurrence and mortality. Results: From 2002 to 2018, a total of 5532 patients underwent hepatectomy for their HCC. Among them, 229 patients were identified to have AD and 5303 were not. After excluding cases who died within 30 days of surgery, the estimated median overall survival (OS) was 43.8 months in the AD (+) group and 47.4 months in the AD (–) group (P = 0.367). The median liver-specific survival and disease-free survival (DFS) were also comparable between the two groups. After Cox regression multivariate analysis, the presence of AD did not lead to a higher risk of all-cause mortality, liver-specific mortality, or disease recurrence. Conclusion: Our study demonstrated that autoimmune disease does not impair the OS and DFS of HCC patients undergoing liver resections. AD itself is not a risk factor for tumor recurrence after surgery. Patients eligible for liver resections, as a result, should be considered for surgery irrespective of the presence of AD. Further studies are mandatory to validate our findings. [ABSTRACT FROM AUTHOR]

Alkene hydrosilylation is one of the most concise and atom-economical methods to synthesize organosilicon molecules. Herein, we reported the precise immobilization of metal single atoms (M-SAs; M = Ru, Rh, Ir, Pd, Pt, and Au) into a porphyrinic metal-organic framework (MOF) of PCN-222 (PCN = porous coordination network), and then applied the resultant MOF composites of M-SAs@PCN-222 to alkene hydrosilylation. Under solvent-free conditions, Pt-SAs@PCN-222 displayed an especially high catalytic efficiency with the turnover frequency up to 119 s−1 and the maximum turnover number of 906,250 at room temperature. Experimental and theoretical studies revealed that there existed strong interactions between Pt-SAs@PCN-222 and the substrates, which helped to condense the substrates in the cavities of the porous catalysts. Further density functional theory calculations and molecular dynamics simulations disclosed that PCN-222 could transfer electrons to Pt-SAs to enhance the silane oxidative addition and drive the reaction to proceed smoothly via Chalk–Harrod pathway. [ABSTRACT FROM AUTHOR]

3-Bromofluoranthene (3-BrFlu) is the secondary metabolite of fluoranthene, which is classified as a polycyclic aromatic hydrocarbon, through bromination and exists in the fine particulate matter of air pollutants. Endothelial dysfunction plays a critical role in the pathogenesis of cardiovascular and vascular diseases. Little is known about the molecular mechanism of 3-BrFlu on endothelial dysfunction in vivo and in vitro assay. In the present study, 3-BrFlu included concentration-dependent changes in ectopic angiogenesis of the sub-intestinal vein and dilation of the dorsal aorta in zebrafish. Disruption of vascular endothelial integrity and up-regulation of vascular endothelial permeability were also induced by 3-BrFlu in a concentration-dependent manner through pro-inflammatory responses in vascular endothelial cells, namely, SVEC4-10 cells. Generation of pro-inflammatory mediator PGE2 was induced by 3-BrFlu through COX2 expression. Expression of COX2 and generation of pro-inflammatory cytokines, including TNFα and IL-6, were induced by 3-BrFlu through phosphorylation of NF-κB p65, which was mediated by phosphorylation of MAPK, including p38 MAPK, ERK and JNK. Furthermore, generation of intracellular ROS was induced by 3-BrFlu, which is associated with the down-regulated activities of the antioxidant enzyme (AOE), including SOD and catalase. We also found that 3-BrFlu up-regulated expression of the AOE and HO-1 induced by 3-BrFlu through Nrf-2 expression. However, the 3-BrFlu-induced upregulation of AOE and HO-1 expression could not be revised the responses of vascular endothelial dysfunction. In conclusion, 3-BrFlu is a hazardous substance that results in vascular endothelial dysfunction through the MAPK-mediated-NFκB pro-inflammatory pathway and intracellular ROS generation. [ABSTRACT FROM AUTHOR]

Holographic display offers the capability to generate high-quality images with a wide color gamut since it is laser-driven. However, many existing holographic display techniques fail to fully exploit this potential, primarily due to the system's imperfections. Such flaws often result in inaccurate color representation, and there is a lack of an efficient way to address this color accuracy issue. In this study, we develop a color-aware hologram optimization approach for color-accurate holographic displays. Our approach integrates both laser and camera into the hologram optimization loop, enabling dynamic optimization of the laser's output color and the acquisition of physically captured feedback. Moreover, we improve the efficiency of the color-aware optimization process for holographic video displays. We introduce a cascade optimization strategy, which leverages the redundant neighbor hologram information to accelerate the iterative process. We evaluate our method through both simulation and optical experiments, demonstrating the superiority in terms of image quality, color accuracy, and hologram optimization speed compared to previous algorithms. Our approach verifies a promising way to realize a high-fidelity image in the holographic display, which provides a new direction toward the practical holographic display. [ABSTRACT FROM AUTHOR]

We exploit bias polarity dependent low-frequency noise (LFN) spectroscopy to investigate charge transport dynamics in ultra-thin AlOx-based magnetic tunnel junctions (MTJs) with bipolar resistive switching (RS). By measuring the noise characteristics across the entire bias voltage range of bipolar RS, we find that the voltage noise level exhibits an bias polarity dependence. This distinct feature is intimately correlated with reconfiguring of the inherently existing oxygen vacancies ( V O.. ) in as-grown MTJ devices during the SET and RESET switching processes. In addition, we observe two-level random telegraph noise (RTN) with a longer and shorter tunneling length in the high resistance state (HRS) and low resistance state (LRS) at a low bias voltage. The intrinsic voltage fluctuations of RTN arise from the dynamics of electron trapping/de-trapping processes at the V O.. -related trap sites. Notably, the RTN magnitude is similar in LRS but nonidentical in that of HRS for different bias polarity. These findings strongly suggest that the inherent V O.. are distributed near the top CoFe/AlOx interface in the HRS; in contrast, they are expanded to the middle region of the AlOx in the LRS. More importantly, we demonstrate that the location and distribution of the inherent V O.. can be electrically tuned, which plays an essential role in the charge transport dynamics in the ultra-thin AlOx-based MTJs and have significant implications for developing emergent memory and logic devices. [ABSTRACT FROM AUTHOR]

Dengue fever is transmitted to humans through the bite of an infected mosquito and is prevalent in all tropical and subtropical climates worldwide. It is thus essential to model weekly dengue fever counts and other infectious diseases that exhibit spatial-temporal dynamics, overdispersion, spatial dependence, and a high number of zeros. To address these characteristics, this study introduces a spatial hurdle integer-valued GARCH (INGARCH) model and an improved version of the spatial zero-inflated generalized Poisson (ZIGP) INGARCH model with and without meteorological variables. Implementing two parameters in the distance function influences the spatial weight between two locations: one controls the decay rate, while the other shapes the decay curve. We employ these newly designed models to analyze time-series counts of infectious diseases - specifically, weekly cases of dengue hemorrhagic fever in four northeastern provinces of Thailand. Applying these models allow us to offer inferences, predictions, and model selections within a Bayesian framework through Markov chain Monte Carlo (MCMC) methods. We then compare models based on the Bayes factors and the mean squared error of fitting errors. The results for the spatial ZIGP INGARCH models are remarkably good, but the spatial INGARCH model incorporating meteorological variables outperforms the other two. [ABSTRACT FROM AUTHOR]

Plastic pollution is becoming a major health issue due to the recent discovery of microplastics and nanoplastics in living organisms and the environment, calling for advanced technologies to remove plastic waste. Here we review enzymes that degrade plastics with focus on plastic properties, protein engineering and polymers such as poly(ethylene terephthalate), poly(butylene adipate-co-terephthalate), poly(lactic acid), polyamide and polyurethane. The mechanism of action of natural and engineered enzymes has been probed by experimental and computation approaches. The performance of polyester-degrading enzymes has been improved via directed evolution, structure-guided rational design and machine learning-aided strategies. The improved enzymes display higher stability at elevated temperatures, and tailored substrate-binding sites. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) presents a formidable global health challenge, highlighted by its escalating prevalence, underscoring the critical need for precision health strategies and early detection initiatives. Leveraging artificial intelligence, particularly eXtreme Gradient Boosting (XGBoost), we devise robust risk assessment models for T2D. Drawing upon comprehensive genetic and medical imaging datasets from 68,911 individuals in the Taiwan Biobank, our models integrate Polygenic Risk Scores (PRS), Multi-image Risk Scores (MRS), and demographic variables, such as age, sex, and T2D family history. Here, we show that our model achieves an Area Under the Receiver Operating Curve (AUC) of 0.94, effectively identifying high-risk T2D subgroups. A streamlined model featuring eight key variables also maintains a high AUC of 0.939. This high accuracy for T2D risk assessment promises to catalyze early detection and preventive strategies. Moreover, we introduce an accessible online risk assessment tool for T2D, facilitating broader applicability and dissemination of our findings. Type 2 diabetes is a global health threat demanding precise healthcare methods. Here, the authors show that their AI-driven risk assessment models, integrating genetic, imaging, and demographic data, achieve high accuracy in identifying high-risk groups, promising advancements in prevention strategies. [ABSTRACT FROM AUTHOR]

Background: Polygonatum kingianum holds significant importance in Traditional Chinese Medicine due to its medicinal properties, characterized by its diverse chemical constituents including polysaccharides, terpenoids, flavonoids, phenols, and phenylpropanoids. The Auxin Response Factor (ARF) is a pivotal transcription factor known for its regulatory role in both primary and secondary metabolite synthesis. However, our understanding of the ARF gene family in P. kingianum remains limited. Methods and results: We employed RNA-Seq to sequence three distinct tissues (leaf, root, and stem) of P. kingianum. The analysis revealed a total of 31,558 differentially expressed genes (DEGs), with 43 species of transcription factors annotated among them. Analyses via gene ontology and the Kyoto Encyclopedia of Genes and Genomes demonstrated that these DEGs were predominantly enriched in metabolic pathways and secondary metabolite biosynthesis. The proposed temporal expression analysis categorized the DEGs into nine clusters, suggesting the same expression trends that may be coordinated in multiple biological processes across the three tissues. Additionally, we conducted screening and expression pattern analysis of the ARF gene family, identifying 12 significantly expressed PkARF genes in P. kingianum roots. This discovery lays the groundwork for investigations into the role of PkARF genes in root growth, development, and secondary metabolism regulation. Conclusion: The obtained data and insights serve as a focal point for further research studies, centred on genetic manipulation of growth and secondary metabolism in P. kingianum. Furthermore, these findings contribute to the understanding of functional genomics in P. kingianum, offering valuable genetic resources. [ABSTRACT FROM AUTHOR]

The frequently occurring browning of plant tissue cultures is a considerable problem in causing economic losses. However, the mechanism that causes browning of plant tissues is still controvesial and technologies to effectively prevent browning of plant tissues are still scarce. In the present work, two callus lines derived from grapevine shoot tips (ST-callus) and fruit flesh (F-callus) were used to investigate the relationship between callus-associated endophytes and callus browning. We observed the transfer of browning effects from grapevine brown calli to normal calli, in a contact cocultivation experiment, then detected the emergence of endophytic bacteria from brown calli when the calli were incubated in a microbial culture medium, and the isolates were identified as genus Bacilus. The inoculation of pure cultured B. sp. strain ST-B1 into normal calli at different concentrations caused gradient callus browning, validating the callus browning-causing (CBC) endophyte. In addition, the moderate inhibition of endophytic bacteria in grapevine calli by culturing the calli in ampicillin-containing media reduced the incidence and severity of callus oxidative browning. The experiments were performed separately on two types of grapevine calli, ST-callus (derived from the tip of grapevine shoots), and F-callus (derived from the pulp of grape berries), and gave similar results. The DNA sequence amplicon approach showed that the CBC endophytic bacteria were found in both the normal and brown calli, which differed greatly in their relative abundances. And compared to the normal calli, brown calli greatly reduced the diversity of bacterial endophytes, while the diversity of fungal endophytes between normal and browning calli showed no obvious difference. The work demonstrated that callus-associated endophytes are involved in causing oxidative browning of plant cells, and suggested technologies to minimize the occurrence of the oxidative browning during plant tissue culture practices.Key message: The study revealed a mechanism by which the callus-associated endophytes are causations in triggering oxidative browning of plant cells, and the maintanence of endophytic bacterial balance is fundamental to a healthy callus. The work also suggested technologies to minimise the occurrence of browning during plant tissue culture practices. [ABSTRACT FROM AUTHOR]

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Background: Both European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD-IDSA) guidelines recommend simplified hepatitis C virus (HCV) treatment with pan-genotypic sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for eligible patients. This observational study used real-world data to assess these regimens' safety in eligible patients and develop an algorithm to identify patients suitable for simplified treatment by non-specialists. Methods: 7,677 HCV-infected patients from Taiwan Hepatitis C Registry (TACR) who received at least one dose of sofosbuvir/velpatasvir or glecaprevir/pibrentasvir, and fulfilled the EASL/AASLD-IDSA criteria for simplified treatment were analyzed. Multivariate analysis was conducted on patient characteristics and safety data. Results: Overall, 92.8% (7,128/7,677) of patients achieved sustained virological response and only 1.9% (146/7,677) experienced Grades 2–4 laboratory abnormalities in key liver function parameters (alanine aminotransferase, aspartate aminotransferase, and total bilirubin), with only 18 patients (0.23%) experiencing Grades 3–4 abnormalities. Age > 70 years old, presence of hepatocellular carcinoma, total bilirubin > 1.2 mg/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, and Fibrosis-4 > 3.25 were associated with higher risks of Grades 2–4 abnormalities. Patients with any of these had an odds of 4.53 times than that of those without in developing Grades 2–4 abnormalities (p < 0.01). Conclusions: Real-world data from Taiwan confirmed that simplified HCV treatment for eligible patients with pan-genotypic regimens is effective and well tolerated. The TACR algorithm, developed based on this study's results, can further identify patients who can be safely managed by non-specialist care. [ABSTRACT FROM AUTHOR]

Ultrasound imaging is a widely used technique for fatty liver diagnosis as it is practically affordable and can be quickly deployed by using suitable devices. When it is applied to a patient, multiple images of the targeted tissues are produced. We propose a machine learning model for fatty liver diagnosis from multiple ultrasound images. The machine learning model extracts features of the ultrasound images by using a pre-trained image encoder. It further produces a summary embedding on these features by using a graph neural network. The summary embedding is used as input for a classifier on fatty liver diagnosis. We train the machine learning model on a ultrasound image dataset collected by Taiwan Biobank. We also carry out risk control on the machine learning model using conformal prediction. Under the risk control procedure, the classifier can improve the results with high probabilistic guarantees. [ABSTRACT FROM AUTHOR]

This study investigates the sustainable logistics potential of countries along the Maritime Silk Road (MSR), an essential element of the Belt and Road Initiative (BRI), against a backdrop of increasing global emphasis on sustainability and efficient trade practices. Addressing the gap in existing literature, it explores how strategic positioning influences countries' logistics capabilities, integrating risk considerations and behavioral decision-making aspects into the assessment. Through a specialized Data Envelopment Analysis (DEA) model that incorporates Prospect Theory, this research provides a nuanced evaluation of economic performance, energy efficiency, infrastructure robustness, governance quality, and innovation capabilities. The analysis reveals significant findings, such as Vietnam's outstanding economic efficiency, Indonesia's notable achievements in sustainability and governance, and Malaysia's balanced efficiency, which collectively enhance the MSR's logistics framework. Additionally, India, Greece, Djibouti, and Kenya emerge as vital partners due to their diverse strengths. The introduction of a risk-aware DEA model, enriched with behavioral factors, marks a significant advancement in logistics assessment methodologies, offering a more comprehensive understanding of sustainable logistics practices along the MSR. The implications of this study are profound, providing valuable insights for policymakers, investors, and business leaders. It guides strategic decision-making, promoting sustainability in MSR trade activities while aligning with global eco-conscious practices and economic growth within the context of environmental stewardship and sustainable development. However, the research acknowledges limitations related to the indirect measurement of decision-makers' psychological behavioral coefficients and the focus on efficiency metrics without extensive exploration of cultural, political, or legal factors. This work sets a new precedent in sustainable logistics research, encouraging future studies to incorporate direct behavioral data and qualitative factors for a more enriched evaluation. Its innovative approach not only contributes to the academic discourse on sustainable logistics but also offers practical tools for enhancing the MSR's trade efficiency and sustainability. [ABSTRACT FROM AUTHOR]

Various treatment modalities have been applied to atrophic scars. Fractional CO2 laser treatment has attracted increasingly more attention because of its quicker recovery time and fewer side effects. However, its limitation of sculpting the edge is an urgent shortcoming. In order to achieve a more effective result with fewer complications, we have integrated ultrapulse CO2 and fractional CO2 lasers to for the treatment of facial atrophic scars. The study included 25 patients (10 males and 15 females) diagnosed with moderate to severe atrophic scars between August 2020 and July 2022. All subjects underwent the same surgical treatment. The effects were assessed at baseline, 1 week, 1 month, and 3 months using photographic evidence. Objective evaluation of the results was conducted using a quartile grading scale, while the subjects' satisfaction and any adverse events were also recorded. The patients in the study underwent more than two laser sessions (2–5), resulting in substantial improvement in their appearance. The time interval between each session was 3–6 months. The majority of the patients (19/25, 76%) had a significant or even excellent improvement. Any adverse events observed, such as erythema, superficial crusting, and PIH, were of a mild nature and temporary in duration. This treatment combined two CO2 lasers is an effective and safe choice for atrophic scars in Asians. [ABSTRACT FROM AUTHOR]

In this paper we propose a simple axiom which, along with the axioms of additivity (transfer) and dummy player, characterizes the Shapley value (the Shapley–Shubik power index) on the domain of TU (simple) games. The new axiom, cross invariance, demands payoff invariance on symmetric players across "quasi-symmetric games," that is, games where excluding null players, all players are symmetric. Additionally, we demonstrate that the axiom of additivity can be replaced by a new axiom called strong monotonicity, or it can be completely dropped if a stronger version of cross invariance is employed. We also show that the weighted Shapley values can be characterized using a weighted variant of cross invariance. Efficiency is derived rather than assumed in our characterizations. This fresh perspective contributes to a deeper understanding of the Shapley value and its applicability. [ABSTRACT FROM AUTHOR]

In many tornado climate studies, the number of tornado touchdowns is often the primary outcome of interest. These outcome measures are usually generated under a spatiotemporal correlation structure and contains many zeros due to the rarity of tornado occurrence at a specific location and time interval. To model the spatiotemporal count data with excess zeros, we propose a spatiotemporal zero-inflated Poisson (ZIP) model, which lends itself to ease of interpretation and computational simplicity. Technically, we embed a modified conditional autoregressive model in the ZIP model to describe the spatial and temporal correlations, where the probability of a pure zero in the ZIP is purposely designed to depend on locations but independent of time. Illustrated with the longitudinal tornado touchdown data in the state of Kansas from 1950 to 2015, our model suggests that the spatial correlation among the counties and the corresponding temperature are significant factors attributed to the tornado touchdowns. Through the model, we can also estimate the probabilities of no tornado touchdowns for each county over time. These estimated probabilities substantially help us understand the pattern of touchdowns and further identify the risk areas across Kansas. Moreover, these estimates can be iteratively updated when more current touchdown data are available. The final model for Kansas tornado touchdown data is evaluated using more recent data. [ABSTRACT FROM AUTHOR]

Background: Optimal lumbar puncture segment selection remains controversial. This study aims to analyze anatomical differences among L3-4, L4-5, and L5-S1 segments across age groups and provide quantitative evidence for optimized selection. Methods: 80 cases of CT images were collected with patients aged 10–80 years old. Threedimensional models containing L3-S1 vertebrae, dural sac, and nerve roots were reconstructed. Computer simulation determined the optimal puncture angles for the L3-4, L4-5, and L5-S1 segments. The effective dural sac area (ALDS), traversing nerve root area (ATNR), and area of the lumbar inter-laminar space (ALILS) were measured. Puncture efficacy ratio (ALDS/ALILS) and nerve injury risk ratio (ATNR/ALILS) were calculated. Cases were divided into four groups: A (10–20 years), B (21–40 years), C (41–60 years), and D (61–80 years). Statistical analysis was performed using SPSS. Results: 1) ALDS was similar among segments; 2) ATNR was greatest at L5-S1; 3) ALILS was greatest at L5-S1; 4) Puncture efficacy ratio was highest at L3-4 and lowest at L5-S1; 5) Nerve injury risk was highest at L5-S1. In group D, L5-S1 ALDS was larger than L3-4 and L4-5. ALDS decreased after age 40. Age variations were minimal across parameters. Conclusion: The comprehensive analysis demonstrated L3-4 as the optimal first-choice segment for ages 10–60 years, conferring maximal efficacy and safety. L5-S1 can serve as an alternative option for ages 61–80 years when upper interspaces narrow. This study provides quantitative imaging evidence supporting age-specific, optimized lumbar puncture segment selection. [ABSTRACT FROM AUTHOR]

Pasteurella multocida is an important bacterial pathogen that can cause diseases in both animals and humans. Its elevated morbidity and mortality rates in animals result in substantial economic repercussions within the livestock industry. The prevention of diseases caused by P. multocida through immunization is impeded by the absence of a safe and effective vaccine. Outer membrane vesicles (OMVs) secreted from the outer membrane of Gram-negative bacteria are spherical vesicular structures that encompass an array of periplasmic components in conjunction with a diverse assortment of lipids and proteins. These vesicles can induce antibacterial immune responses within the host. P. multocida has been shown to produce OMVs. Nonetheless, the precise characteristics and immunomodulatory functions of P. multocida OMVs have not been fully elucidated. In this study, OMVs were isolated from P. multocida using an ultrafiltration concentration technique, and their morphology, protein constitution, and immunomodulatory properties in RAW264.7 cells were studied. Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) revealed that the OMVs exhibited typical spherical and bilayered lipid vesicular architecture, exhibiting an average diameter of approximately 147.5 nm. The yield of OMVs was 2.6 × 1011 particles/mL. Proteomic analysis revealed a high abundance of membrane-associated proteins within P. multocida OMVs, with the capability to instigate the host's immune response. Furthermore, OMVs stimulated the proliferation and cellular uptake of macrophages and triggered the secretion of cytokines, such as TNF-ɑ, IL-1β, IL-6, IL-10, and TGF-β1. Consequently, our results indicated that OMVs from P. multocida could directly interact with macrophages and regulate their immune function in vitro. These results supported the prospective applicability of P. multocida OMVs as a platform in the context of vaccine development. Key points: • Preparation and characterization of P. multocida OMVs. • P. multocida OMVs possess a range of antigens and lipoproteins associated with the activation of the immune system. • P. multocida OMVs can activate the proliferation, internalization, and cytokine secretion of macrophages in vitro. [ABSTRACT FROM AUTHOR]

This study introduces an all-digital CMOS time-domain smart temperature sensor (STS) that offers a smaller circuit area and reduced complexity. In contrast to previous studies that utilized multiple delay lines or additional path selection circuits, the proposed new structure employs a single cyclic path and fewer delay lines. The functionality of high-resolution temperature sensing, pulse-shrinking time measurement, and built-in offset-error cancellation is achieved using only one cyclic delay line (CDL). The temperature-sensing delay line generates a thermal-dependent pulse width proportional to the absolute temperature (PTAT). Subsequently, a pulse-shrinking unit, implemented within the pulse-shrinking delay line, performs time-to-digital conversion by measuring the PTAT pulse width. Finally, a time-added delay line within the CDL incorporates a simple D-type Flip Flop to enable concise offset-error cancellation, thereby improving accuracy. This study further simplifies the cancellation circuitry to reduce the overall circuit area. The proposed sensor, fabricated using a TSMC 0.35 μ m CMOS process, occupies an area of 0.022 mm 2 , providing a cost-effective solution for pulse-shrinking STSs. The maximum inaccuracy after offset-error cancellation is 1. 3 ∘ C within a temperature range of 0 ∼ 80 ∘ C, with a high resolution of approximately 0. 035 ∘ C/LSB. This resolution enhancement significantly surpasses similar studies. By reducing circuit complexity, the proposed sensor successfully achieves improvements in both area and resolution. [ABSTRACT FROM AUTHOR]

Poly(aryl ether ketone) (PAEK) films with different crystallinities were obtained by controlling the cooling rate, which were subjected to the absorption and desorption of methylene chloride (CH2Cl2). We employed attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy analyses to investigate the diffusion behavior of CH2Cl2 in PAEK films with different crystallinities. According to the Fickian diffusion model, the calculated diffusion coefficients of CH2Cl2 in PAEK films were observed to decrease with increasing crystallinity. The effect of CH2Cl2 absorption and desorption on the mechanical properties of PAEK films with different crystallinity was further analyzed using tensile tests. The tensile tests exhibited that CH2Cl2 has two concurrent effects: plasticization and solvent-induced crystallization. Differential scanning calorimetry (DSC) and wide-angle X-ray diffraction (WXRD) techniques further confirmed solvent-induced crystallization behavior. The results would be beneficial to understand the solvent resistance of PAEK materials and consequently provide the practical application conditions of PAEK with a theoretical basis. [ABSTRACT FROM AUTHOR]

Precisely controlled spatial distributions of artificial light-harvesting systems in aqueous media are of significant importance for mimicking natural light-harvesting systems; however, they are often restrained by the solubility and the aggregation-caused quenching effect of the hydrophobic chromophores. Herein, we report one highly efficient artificial light-harvesting system based on peptoid nanotubes that mimic the hierarchical cylindrical structure of natural systems. The high crystallinity of these nanotubes enabled the organization of arrays of donor chromophores with precisely controlled spatial distributions, favoring an efficient Förster resonance energy transfer (FRET) process in aqueous media. This FRET system exhibits an extremely high efficiency of 98.6% with a fluorescence quantum yield of 40% and an antenna effect of 29.9. We further demonstrated the use of this artificial light-harvesting system for quantifying miR-210 within cancer cells. The fluorescence intensity ratio of donor to acceptor is linearly related to the concentration of intercellular miR-210 in the range of 3.3–156 copies/cell. Such high sensitivity in intracellular detection of miR-210 using this artificial light-harvesting system offers a great opportunity and pathways for biological imaging and detection, and for the further creation of microRNA (miRNA) toolbox for quantitative epigenetics and personalized medicine. [ABSTRACT FROM AUTHOR]

To assess the efficacy and safety of the combination of immune checkpoint inhibitors (ICIs) and target therapy (anti-angiogenesis or EGFR inhibitors) as a second-line or subsequent treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M NPC), we conducted a retrospective study. In this study, previously treated R/M NPC patients were administered one of the following treatment: ICIs combined with target therapy and chemotherapy (ITC), ICIs combined with target therapy alone (IT), ICIs combined with chemotherapy (IC), or chemotherapy alone (C). The primary endpoint under consideration was progression-free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety measures. A total of 226 patients participated in this study, with 70 receiving the ITC regimen, 48 receiving IT, 48 treated with IC, and 60 undergoing C alone. The median PFS for the four cohorts was 20.67, 13.63, 12.47, and 7.93 months respectively. Notably, ITC regimen yielded the most favorable PFS among these cohorts. The ITC cohort exhibited a comparable tumor response and safety profile to the IT and IC cohorts (p > 0.05), but superior tumor response compared to the C cohort (p < 0.05). The ITC regimen also conferred a significant improvement in OS when comparing to C alone (HR 0.336, 95%CI 0.123–0.915, p = 0.033). The IT and IC regimens achieved a nearly identical PFS (HR 0.955, 95%CI 0.515–1.77, p = 0.884), although the IT regimen was associated with a lower occurrence of SAEs in contrast to the IC regimen (p < 0.05). In addition, the IT regimen demonstrated superior PFS (HR 0.583, 95%CI 0.345–0.985, p = 0.044) and fewer SAEs when compared to C alone (p < 0.05). These findings collectively support the notion that the combination of ICIs, target and chemotherapy exhibits robust antitumor activity in previously treated R/M NPC patients, without a significant increase in adverse events. [ABSTRACT FROM AUTHOR]

Near infrared energy remains untapped toward the maneuvering of entire solar spectrum harvesting for fulfilling the nuts and bolts of solar hydrogen production. We report the use of Au@Cu7S4 yolk@shell nanocrystals as dual-plasmonic photocatalysts to achieve remarkable hydrogen production under visible and near infrared illumination. Ultrafast spectroscopic data reveal the prevalence of long-lived charge separation states for Au@Cu7S4 under both visible and near infrared excitation. Combined with the advantageous features of yolk@shell nanostructures, Au@Cu7S4 achieves a peak quantum yield of 9.4% at 500 nm and a record-breaking quantum yield of 7.3% at 2200 nm for hydrogen production in the absence of additional co-catalysts. The design of a sustainable visible- and near infrared-responsive photocatalytic system is expected to inspire further widespread applications in solar fuel generation. In this work, the feasibility of exploiting the localized surface plasmon resonance property of self-doped, nonstoichiometric semiconductor nanocrystals for the realization of wide-spectrum-driven photocatalysis is highlighted. Near infrared energy remains untapped toward the maneuvering of entire solar spectrum harvesting for fulfilling nuts and bolts of solar hydrogen production. Here, the authors report the use of Au@Cu7S4 yolk@shell nanocrystals for hydrogen production from untapped near infrared energy. [ABSTRACT FROM AUTHOR]

Dengue is one of the world's most rapidly spreading mosquito-borne viral diseases. As it is found mostly in urban and semi-urban areas, urbanization and associated human activities that affect the environment and larval habitats could become risk factors (e.g., lane width, conditions of street ditches) for the spread of dengue. However, there are currently no systematic studies of micro-scale urbanization-based risk factors for the spread of dengue epidemics. We describe the study area, two micro-scale environmental risk factors associated with urbanization, and meteorological data. Since the observations involve spatial and temporal correlations, we also use some statistical methods for the analysis of spatial and spatial-temporal data for the relationship between urbanization and dengue. In this study, we analyzed data from Kaohsiung, a densely populated city in southern Taiwan, and found a positive correlation between environmental risk factors associated with urbanization (ditches positive for mosquito larvae and closely packed streets termed "dengue lanes") and clustering effects in dengue cases. The statistical analysis also revealed that the occurrence of positive ditches was significantly associated with that of dengue lanes in the study area. The relationship between climate variables and positive ditches was also analyzed in this paper, indicating a relationship between dengue and both rainfall and temperature, with temperature having a greater effect. Overall, this work is immediately relevant and applicable for policymakers in government, who will need to reduce these favorable habitats for vector-born disease spreaders and implement regulations for new urban constructions to thus reduce dengue spread in future outbreaks. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to review current delivery room (DR) resuscitation intensity in Chinese tertiary neonatal intensive care units and to investigate the association between DR resuscitation intensity and short-term outcomes in preterm infants born at 24+0–31+6 weeks' gestation age (GA). Methods: This was a retrospective cross-sectional study. The source population was infants born at 24+0–31+6 weeks' GA who were enrolled in the Chinese Neonatal Network 2019 cohort. Eligible infants were categorized into five groups: (1) regular care; (2) oxygen supplementation and/or continuous positive airway pressure (O2/CPAP); (3) mask ventilation; (4) endotracheal intubation; and (5) cardiopulmonary resuscitation (CPR). The association between DR resuscitation and short-term outcomes was evaluated by inverse propensity score-weighted logistic regression. Results: Of 7939 infants included in this cohort, 2419 (30.5%) received regular care, 1994 (25.1%) received O2/CPAP, 1436 (18.1%) received mask ventilation, 1769 (22.3%) received endotracheal intubation, and 321 (4.0%) received CPR in the DR. Advanced maternal age and maternal hypertension correlated with a higher need for resuscitation, and antenatal steroid use tended to be associated with a lower need for resuscitation (P < 0.001). Severe brain impairment increased significantly with increasing amounts of resuscitation in DR after adjusting for perinatal factors. Resuscitation strategies vary widely between centers, with over 50% of preterm infants in eight centers requiring higher intensity resuscitation. Conclusions: Increased intensity of DR interventions was associated with increased mortality and morbidities in very preterm infants in China. There is wide variation in resuscitative approaches across delivery centers, and ongoing quality improvement to standardize resuscitation practices is needed. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent gastrointestinal malignancies with high mortality worldwide. Emerging evidence indicates that long noncoding RNAs (lncRNAs) are involved in human cancers, including ESCC. However, the detailed mechanisms of lncRNAs in the regulation of ESCC progression remain incompletely understood. LUESCC was upregulated in ESCC tissues compared with adjacent normal tissues, which was associated with gender, deep invasion, lymph node metastasis, and poor prognosis of ESCC patients. LUESCC was mainly localized in the cytoplasm of ESCC cells. Knockdown of LUESCC inhibited cell proliferation, colony formation, migration, and invasion in vitro and suppressed tumor growth in vivo. Mechanistic investigation indicated that LUESCC functions as a ceRNA by sponging miR-6785-5p to enhance NRSN2 expression, which is critical for the malignant behaviors of ESCC. Furthermore, ASO targeting LUESCC substantially suppressed ESCC both in vitro and in vivo. Collectively, these data demonstrate that LUESCC may exerts its oncogenic role by sponging miR-6785-5p to promote NRSN2 expression in ESCC, providing a potential diagnostic marker and therapeutic target for ESCC patients. [ABSTRACT FROM AUTHOR]

Endothelial cells (ECs) and bone marrow stromal cells (BMSCs) play crucial roles in supporting hematopoiesis and hematopoietic regeneration. However, whether ECs are a source of BMSCs remains unclear. Here, we evaluate the contribution of endothelial-to-mesenchymal transition to BMSC generation in postnatal mice. Single-cell RNA sequencing identifies ECs expressing BMSC markers Prrx1 and Lepr; however, this could not be validated using Prrx1-Cre and Lepr-Cre transgenic mice. Additionally, only a minority of BMSCs are marked by EC lineage tracing models using Cdh5-rtTA-tetO-Cre or Tek-CreERT2. Moreover, Cdh5+ BMSCs and Tek+ BMSCs show distinct spatial distributions and characteristic mesenchymal markers, suggestive of their origination from different progenitors rather than CDH5+ TEK+ ECs. Furthermore, myeloablation induced by 5-fluorouracil treatment does not increase Cdh5+ BMSCs. Our findings indicate that ECs hardly convert to BMSCs during homeostasis and myeloablation-induced hematopoietic regeneration, highlighting the importance of using appropriate genetic models and conducting careful data interpretation in studies concerning endothelial-to-mesenchymal transition. Endothelial cells (ECs) and bone marrow stromal cells (BMSCs) support hematopoiesis and hematopoietic regeneration. Whether ECs are a source of BMSCs remains unclear. Here, using lineage tracing models the authors show that ECs are not a source of BMSCs during homeostasis and regeneration. [ABSTRACT FROM AUTHOR]

The body fluid status in acute stroke is a crucial determinant in early stroke recovery but a real-time method to monitor body fluid status is not available. This study aims to evaluate the relationship between salivary conductivity and body fluid status during the period of intravenous fluid hydration. Between June 2020 to August 2022, patients presenting with clinical signs of stroke at the emergency department were enrolled. Salivary conductivities were measured before and 3 h after intravenous hydration. Patients were considered responsive if their salivary conductivities at 3 h decreased by more than 20% compared to their baseline values. Stroke severity was assessed using the National Institutes of Health Stroke Scale, and early neurological improvement was defined as a decrease of ≥ 2 points within 72 h of admission. Among 108 recruited patients, there were 35 of stroke mimics, 6 of transient ischemic attack and 67 of acute ischemic stroke. Salivary conductivity was significantly decreased after hydration in all patients (9008 versus 8118 µs/cm, p = 0.030). Among patients with acute ischemic stroke, the responsive group, showed a higher rate of early neurological improvement within 3 days compared to the non-responsive group (37% versus 10%, p = 0.009). In a multivariate logistic regression model, a decrease in salivary conductivity of 20% or more was found to be an independent factor associated with early neurological improvement (odds ratio 5.42, 95% confidence interval 1.31–22.5, p = 0.020). Real-time salivary conductivity might be a potential indicator of hydration status of the patient with acute ischemic stroke. [ABSTRACT FROM AUTHOR]

Current study proposes an effective way to modify the properties of super-sulfated cement (SSC) paste and mortar with preheated flue gas desulfurization (FDG) gypsum at different temperatures and durations, and different sulfate compositions. Preheated FGDs with temperatures between 25 and 150 °C and durations between 0 and 24 h were used to replace 5, 10 and 15 mass/% of slag in SSC. Besides the ordinary Portland cement, the sodium hydroxide (NaOH) was also used as the alkali activator. Both anhydrite and sodium sulfate with five different contents were used to provide the ions of SO3 to react with the ions of Ca and Al released from slag during hydration to form ettringite. Experimental results showed that partial replacement of untreated FDG with either the specifically preheated FDG or the commercial sulfates noticeably enhanced the early hydration of modified SSC pastes with setting time being significantly shortened and increased the compressive strength, while the NaOH solution delayed the setting time and reduced the compressive strength. Microstructural examinations revealed that using partial preheated FDG or commercial anhydrite did not alter the hydrated components, but significantly enhanced the fractions and stabilized the crystallization of those hydrates with hydration time. [ABSTRACT FROM AUTHOR]

Biomolecules modulate inorganic crystallization to generate hierarchically structured biominerals, but the atomic structure of the organic-inorganic interfaces that regulate mineralization remain largely unknown. We hypothesized that heterogeneous nucleation of calcium carbonate could be achieved by a structured flat molecular template that pre-organizes calcium ions on its surface. To test this hypothesis, we design helical repeat proteins (DHRs) displaying regularly spaced carboxylate arrays on their surfaces and find that both protein monomers and protein-Ca2+ supramolecular assemblies directly nucleate nano-calcite with non-natural {110} or {202} faces while vaterite, which forms first in the absence of the proteins, is bypassed. These protein-stabilized nanocrystals then assemble by oriented attachment into calcite mesocrystals. We find further that nanocrystal size and polymorph can be tuned by varying the length and surface chemistry of the designed protein templates. Thus, bio-mineralization can be programmed using de novo protein design, providing a route to next-generation hybrid materials. Most proteins mediating biomineralization in nature are not well structured, and the structures of the relevant protein-mineral interfaces regulating mineralization are elusive. Here, the authors computationally design proteins that modulate calcium carbonate mineralization to generate hybrid materials and elucidate the roles of designed proteins in controlling mineralization. [ABSTRACT FROM AUTHOR]

This study investigates the effect of the consumption of caffeinated chewing gum on the performance of Romanian deadlift on the flywheel training device. A total of 19 participants completed a randomized, cross-over, single-blind experiment with food-grade caffeinated chewing gum trial (CAF) or placebo trail (PL). Gum were chewed for 10 min and rest for 15 min prior to the Romanian deadlift test using the inertial resistance training machine. 5 sets of 6 Romanian deadlifts were performed, with a 3-min rest between sets, followed by a 7-day washout period before the next set of trials. The average power, average force, total peak power, peak concentric power, peak eccentric power, heart rate, and rating of perceived exertion (RPE) for each trials were analyzed using paired-T test. Compared to placebo, caffeinated chewing gum trial enhanced peak concentric power (P = 0.016, Cohen's d = 0.44), peak eccentric power (P = 0.005, Cohen's d = 0.55), average power (P = 0.013, Cohen's d = 0.43), and total work (P = 0.026, Cohen's d = 0.28). However, in average force (P = 0.063, Cohen's d = 0.50), RPE (P = 0.266), and heart rate (P = 0.143), were no significant differences between trials. Caffeinated chewing gum with a dose of caffeine of 200 mg for 10 min may acutely enhance Romanian deadlift performance on the flywheel machine. [ABSTRACT FROM AUTHOR]

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Bullous pemphigoid is one of the most common autoimmune bullous diseases occurring primarily in the elderly. Pathogenic autoantibodies against BP180 and BP230 at the dermal–epidermal junction cause subepidermal blisters, erosions, and intense pruritus, all of which adversely affect the patients' quality of life and may increase their morbidity and mortality. Current systemic treatment options for bullous pemphigoid are limited to corticosteroids and immunosuppressants, which can have substantial side effects on these vulnerable patients that even exceed their therapeutic benefits. Therefore, more precisely, targeting therapies to the pathogenic cells and molecules in bullous pemphigoid is an urgent issue. In this review, we describe the pathophysiology of bullous pemphigoid, focusing on autoantibodies, complements, eosinophils, neutrophils, proteases, and the T helper 2 and 17 axes since they are crucial in promoting proinflammatory environments. We also highlight the emerging therapeutic targets for bullous pemphigoid and their latest discoveries in clinical trials or experimental studies. Further well-designed studies are required to establish the efficacy and safety of these prospective therapeutic options. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare the clinical features, treatment, and clinical outcome of patients with tandem occlusion and isolated intracranial occlusion through endovascular treatment (EVT). Methods: Patients with acute cerebral infarction who received EVT in two stroke centers were retrospectively included. According to MRI or CTA results, the patients were divided into tandem occlusion group or isolated intracranial occlusion group. The baseline data, etiological classification, treatment, post-stroke complications, image features, and clinical outcome were compared. Multivariate logistic regression analysis was used to evaluate the related factors affecting the prognosis of patients with EVT. Results: Among 161 patients with acute cerebral infarction, there were 33 cases (20.5%) in the tandem occlusion group and 128 cases (79.5%) in the isolated intracranial occlusion group. Compared with isolated intracranial occlusion, the patients with tandem occlusion had higher rates of large artery atherosclerosis (P = 0.028), symptomatic intracerebral hemorrhage (sICH) (P = 0.023), bilateral infarction (P = 0.042), and longer time for endovascular procedure (P = 0.026). There was no significant statistical difference in 90-day mRS score between the two groups (P = 0.060). Multivariate logistic regression identified the following independent predictors of poor functional outcome: older age, high fasting blood glucose, infarction area > 1/3, and hemorrhagic transformation. Conclusions: Compared with isolated intracranial occlusion, there was not a worse prognosis among patients with tandem occlusion who received EVT. [ABSTRACT FROM AUTHOR]

In this work, we present an extension of the spectral conjugate gradient (SCG) methods for solving unconstrained vector optimization problems, with respect to the partial order induced by a pointed, closed and convex cone with a nonempty interior. We first study the direct extension version of the SCG methods and its global convergence without imposing an explicit restriction on parameters. It shows that the methods may lose their good scalar properties, like yielding descent directions, in the vector setting. By using a truncation technique, we then propose a modified self-adjusting SCG algorithm which is more suitable for various parameters. Global convergence of the new scheme covers the vector extensions of three different spectral parameters and the corresponding Perry, Andrei, and Dai–Kou conjugate parameters (SP, N, and JC schemes, respectively) without regular restarts and any convex assumption. Under inexact line searches, we prove that the sequences generated by the proposed methods find points that satisfy the first-order necessary condition for Pareto-optimality. Finally, numerical experiments illustrating the practical behavior of the methods are presented. [ABSTRACT FROM AUTHOR]

Objective: Nanoparticles (NPs) hold a great promise in combating rheumatoid arthritis, but are often compromised by their toxicities because the currently used NPs are usually synthesized by chemical methods. Our group has previously fabricated Ångstrom-scale silver particles (AgÅPs) and demonstrated the anti-tumor and anti-sepsis efficacy of fructose-coated AgÅPs (F-AgÅPs). This study aimed to uncover the efficacy and mechanisms of F-AgÅPs for arthritis therapy. Methods: We evaluated the efficacy of F-AgÅPs in collagen-induced arthritis (CIA) mice. We also compared the capacities of F-AgÅPs, the commercial AgNPs, and the clinical drug methotrexate (MTX) in protecting against K/BxN serum-transfer arthritis (STA) mice. Moreover, we evaluated the effects of F-AgÅPs and AgNPs on inflammation, osteoclast formation, synoviocytes migration, and matrix metalloproteinases (MMPs) production in vitro and in vivo. Meanwhile, the toxicities of F-AgÅPs and AgNPs in vitro and in vivo were also tested. Results: F-AgÅPs significantly prevented bone erosion, synovitis, and cartilage damage, attenuated rheumatic pain, and improved the impaired motor function in mouse models of CIA or STA, the anti-rheumatic effects of which were comparable or stronger than AgNPs and MTX. Further studies revealed that F-AgÅPs exhibited similar or greater inhibitory abilities than AgNPs to suppress inflammation, osteoclast formation, synoviocytes migration, and MMPs production. No obvious toxicities were observed in vitro and in vivo after F-AgÅPs treatment. Conclusions: F-AgÅPs can effectively alleviate arthritis without notable toxicities and their anti-arthritic effects are associated with the inhibition of inflammation, osteoclastogenesis, synoviocytes migration, and MMPs production. Our study suggests the prospect of F-AgÅPs as an efficient and low-toxicity agent for arthritis therapy. [ABSTRACT FROM AUTHOR]

Insects and pathogens release effectors into plant cells to weaken the host defense or immune response. While the imports of some bacterial and fungal effectors into plants have been previously characterized, the mechanisms of how caterpillar effectors enter plant cells remain a mystery. Using live cell imaging and real-time protein tracking, we show that HARP1, an effector from the oral secretions of cotton bollworm (Helicoverpa armigera), enters plant cells via protein-mediated endocytosis. The entry of HARP1 into a plant cell depends on its interaction with vesicle trafficking components including CTL1, PATL2, and TET8. The plant defense hormone jasmonate (JA) restricts HARP1 import by inhibiting endocytosis and HARP1 loading into endosomes. Combined with the previous report that HARP1 inhibits JA signaling output in host plants, it unveils that the effector and JA establish a defense and counter-defense loop reflecting the robust arms race between plants and insects. The authors find that cotton bollworms secrete effectors into plant to weaken JA signaling via host endocytosis system while JA inhibits endocytosis to restrict effector imports. The defense and counter-defense loop between effector and JA reflects a robust arms race between plant and insect. [ABSTRACT FROM AUTHOR]

Religious diversity education has become increasingly prominent in the last few years. As the region with the second-highest religious diversity globally, Chinese Taiwan provides its students religious education early on, thus minimising misunderstandings and discrimination on the basis of religion. To diversify teaching methods, educators have adopted interactive technology as one of the primary teaching aids. This study aims to develop and evaluate the impact of an interactive technology, augmented reality (AR) in the provision of religious education. A series of experiments were conducted during the 2020 Taipei Lantern Festival of Religious Education Exhibition to explore whether using the interactive technology system significantly improved learning outcomes in comparison to traditional learning methods. To this end, a total of 50 elementary students across two experimental (n = 24) and control (n = 26) groups were recruited to participate in the study. A mixed-methods approach was used to analyse students' subjective and objective learning outcomes. The results of the study showed that the experimental group performed significantly better in both subjective and objective learning outcomes. The findings obtained from the open-ended questions showed interactive AR technology system use positively affected the learning process. In conclusion, this study proposes that combining religious diversity education with interactive AR technology has the potential to improve students' motivation, engage their interest, improve learning outcomes, and contribute to an increased awareness of religious diversity. It may also be helpful in limiting students' cognitive overload during the learning process. [ABSTRACT FROM AUTHOR]

Abnormal polyglutamine (polyQ) expansion and fibrillization occur in Huntington's disease (HD). Amyloid modifier SERF enhances amyloid formation, but the underlying mechanism is not revealed. Here, the fibrillization and toxicity effect of SERF1a on Htt-exon1 are examined. SERF1a enhances the fibrillization of and interacts with mutant thioredoxin (Trx)-fused Httex1. NMR studies with Htt peptides show that TrxHttex1-39Q interacts with the helical regions in SERF1a and SERF1a preferentially interacts with the N-terminal 17 residues of Htt. Time-course analysis shows that SERF1a induces mutant TrxHttex1 to a single conformation enriched of β-sheet. Co-expression of SERF1a and Httex1-polyQ in neuroblastoma and lentiviral infection of SERF1a in HD-induced polypotent stem cell (iPSC)-derived neurons demonstrates the detrimental effect of SERF1a in HD. Higher level of SERF1a transcript or protein is detected in HD iPSC, transgenic mice, and HD plasma. Overall, this study provides molecular mechanism for SERF1a and mutant Httex1 to facilitate therapeutic development for HD. Small amyloid modifier protein SERF1a induces aggregation of polyglutamine expanded huntingtin protein (htt-polyQ) through α-helical regions and exacerbates polyQ-induced toxicity, and the interaction is intensified by enhancing α-helical content. [ABSTRACT FROM AUTHOR]