Causal effects of hypertensive disorders of pregnancy on structural changes in specific brain regions: a Mendelian randomization study.

This study utilized Mendelian randomization to explore the impact of hypertensive disorders of pregnancy and their subtypes on brain structures, using genome-wide association study data from the FinnGen consortium for hypertensive disorders of pregnancy exposure and brain structure data from the ENIGMA consortium as outcomes. The inverse-variance weighted method, along with Cochran's Q test, Mendelian randomization-Egger regression, Mendelian randomization-PRESSO global test, and the leave-one-out approach, were applied to infer causality and assess heterogeneity and pleiotropy. Findings indicate hypertensive disorders of pregnancy are associated with structural brain alterations, including reduced cortical thickness in areas like the insula, isthmus cingulate gyrus, superior temporal gyrus, temporal pole, and transverse temporal gyrus, and an increased surface area in the superior frontal gyrus. Specific associations were found for hypertensive disorders of pregnancy subtypes: chronic hypertension with superimposed preeclampsia increased cortical thickness in the supramarginal gyrus; preeclampsia/eclampsia led to thinner cortex in the lingual gyrus and larger hippocampal volume and superior parietal lobule surface area. Chronic hypertension was associated with reduced cortical thickness in the caudal and rostral anterior cingulate and increased surface area of the cuneus and thickness of the pars orbitalis cortex. Gestational hypertension showed no significant brain region changes. These insights clarify hypertensive disorders of pregnancies' neurological and cognitive effects by identifying affected brain regions.

Advancements in hand-drawn chemical structure recognition through an enhanced DECIMER architecture.

Accurate recognition of hand-drawn chemical structures is crucial for digitising hand-written chemical information in traditional laboratory notebooks or facilitating stylus-based structure entry on tablets or smartphones. However, the inherent variability in hand-drawn structures poses challenges for existing Optical Chemical Structure Recognition (OCSR) software. To address this, we present an enhanced Deep lEarning for Chemical ImagE Recognition (DECIMER) architecture that leverages a combination of Convolutional Neural Networks (CNNs) and Transformers to improve the recognition of hand-drawn chemical structures. The model incorporates an EfficientNetV2 CNN encoder that extracts features from hand-drawn images, followed by a Transformer decoder that converts the extracted features into Simplified Molecular Input Line Entry System (SMILES) strings. Our models were trained using synthetic hand-drawn images generated by RanDepict, a tool for depicting chemical structures with different style elements. A benchmark was performed using a real-world dataset of hand-drawn chemical structures to evaluate the model's performance. The results indicate that our improved DECIMER architecture exhibits a significantly enhanced recognition accuracy compared to other approaches. SCIENTIFIC CONTRIBUTION: The new DECIMER model presented here refines our previous research efforts and is currently the only open-source model tailored specifically for the recognition of hand-drawn chemical structures. The enhanced model performs better in handling variations in handwriting styles, line thicknesses, and background noise, making it suitable for real-world applications. The DECIMER hand-drawn structure recognition model and its source code have been made available as an open-source package under a permissive license.

Revealing the Limitation Induced by Hydroxyl in Regulating Solvation Structure of Zn2+ and Overcoming Challenges with Hybrid Additives towards Highly Stable Zinc Anodes.

In the field of electrolyte design for aqueous zinc-ion batteries (AZIBs), additives containing hydroxyl have been demonstrated to effectively modulate the solvation structure of Zn2+. However, reported studies typically focus solely on the effectiveness of hydroxyl while neglecting the issues that emerge during solvation structure regulation. The strong electron-attracting capability of Zn2+ attracts electrons from the oxygen in hydroxyl, thereby weakening the strength of hydroxyl, the hydrogen evolution reaction (HER) is also pronounced. This work innovatively reveals the limitation of hydroxyl-containing additives and proposes a synergistic regulation strategy based on hybrid additives. Arginine with a high isoelectric point is introduced into the electrolyte system containing hydroxyl additives. The protonation effect and electrostatic attraction of arginine enable it to absorb protons at the anode released by the weakened hydroxyl, thereby compensating for the limitation of hydroxyl additives. Under the synergistic action of hybrid additives, the Zn|Zn battery achieved stable deposition/stripping for over 1200 hours under 10 mA cm-2 and 10 mAh cm-2. Moreover, the Zn|Cu battery cycled for over 570 hours with a high Coulombic efficiency of 99.82%. This study presents a pioneering perspective for the further application of AZIBs.

Pericentromeric satellite RNAs as flexible protein partners in the regulation of nuclear structure.

Pericentromeric heterochromatin is mainly composed of satellite DNA sequences. Although being historically associated with transcriptional repression, some pericentromeric satellite DNA sequences are transcribed. The transcription events of pericentromeric satellite sequences occur in highly flexible biological contexts. Hence, the apparent randomness of pericentromeric satellite transcription incites the discussion about the attribution of biological functions. However, pericentromeric satellite RNAs have clear roles in the organization of nuclear structure. Silencing pericentromeric heterochromatin depends on pericentromeric satellite RNAs, that, in a feedback mechanism, contribute to the repression of pericentromeric heterochromatin. Moreover, pericentromeric satellite RNAs can also act as scaffolding molecules in condensate subnuclear structures (e.g., nuclear stress bodies). Since the formation/dissociation of nuclear condensates provides cell adaptability, pericentromeric satellite RNAs can be an epigenetic platform for regulating (sub)nuclear structure. We review current knowledge about pericentromeric satellite RNAs that, irrespective of the meaning of biological function, should be functionally addressed in regular and disease settings. This article is categorized under: RNA Methods > RNA Analyses in Cells RNA in Disease and Development > RNA in Disease.

Polygraph-based deception detection and Machine Learning. Combining the Worst of Both Worlds?

At a time when developments in computational approaches, often associated with the now much-vaunted terms Machine Learning (ML) and Artificial Intelligence (AI), face increasing challenges in terms of fairness, transparency and accountability, the temptation for researchers to apply mainstream ML methods to virtually any type of data seems to remain irresistible. In this paper we critically examine a recent proposal to apply ML to polygraph screening results (where human interviewers have made a conclusion about deception), which raises several questions about the purpose and the design of the research, particularly given the vacuous scientific status of polygraph-based procedures themselves. We argue that in high-stake environments such as criminal justice and employment practice, where fundamental rights and principles of justice are at stake, the legal and ethical considerations for scientific research are heightened. Specifically, we argue that the combination of ambiguously labelled data and ad hoc ML models does not meet this requirement. Worse, such research can inappropriately legitimise otherwise scientifically invalid, indeed pseudo-scientific methods such as polygraph-based deception detection, especially when presented in a reputable scientific journal. We conclude that methodological concerns, such as those highlighted in this paper, should be addressed before research can be said to contribute to resolving any of the fundamental validity issues that underlie methods and techniques used in legal proceedings.

Prognostic and clinicopathological significance of tertiary lymphoid structure in non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the primary reason for cancer-related deaths globally. Tertiary lymphoid structure (TLS) is an organized collection of immune cells acquired in non-physiological, non-lymphoid tissues. High expression of TLS in tumor tissues is generally associated with better prognosis. This research aimed to investigate the prognostic and clinicopathological significance of TLS in patients with NSCLC. METHODS: A comprehensive literature search was conducted based on Pubmed, EMBASE, and Cochrane Library databases to identify eligible studies published up to December 8, 2023. The prognostic significance and clinicopathological value of TLS in NSCLC were evaluated by calculating the combined hazard ratios (HRs) and odds ratios (ORs) and their 95% confidence intervals (CIs). Following that, additional analyses, including subgroup analysis and sensitivity analysis, were conducted. RESULTS: This meta-analysis evaluated the prognostic and clinicopathological significance of TLS in 10 studies involving 1,451 patients with NSCLC. The results revealed that the high levels of TLS were strongly associated with better overall survival (OS) (HR = 0.48, 95% CI: 0.35-0.66, p < 0.001), disease-free survival (DFS)/recurrence-free survival (RFS) (HR = 0.37, 95% CI: 0.24-0.54, p < 0.001), and disease-specific survival (DSS) (HR = 0.45, 95% CI: 0.30-0.68, p < 0.001) in NSCLC patients. In addition, the increased expression of TLS was closely related to the Tumor Node Metastasis (TNM) stage of tumors (OR = 0.71, 95% CI: 0.51-1.00, p < 0.05) and neutrophil-lymphocyte ratio (NLR) (OR = 0.33, 95% CI: 0.17-0.62, p < 0.001). CONCLUSIONS: The results revealed that highly expressed TLS is closely associated with a better prognosis in NSCLC patients. TLS may serve as a novel biomarker to predict the prognosis of NSCLC patients and guide the clinical treatment decisions.

Physiological and structural traits contribute to thermotolerance in wild Australian cotton species.

BACKGROUND AND AIMS: Five species of cotton (Gossypium) were exposed to 38°C days during early vegetative development. Commercial cotton (Gossypium hirsutum) was contrasted with four wild cotton species (G. australe, G. bickii, G. robinsonii and G. sturtianum) that are endemic to central and northern Australia. METHODS: Plants were grown at daytime maxima of 30°C or 38°C for 25 d, commencing at the four-leaf stage. Leaf areas and shoot biomass were used to calculate relative rates of growth and specific leaf areas. Leaf gas exchange measurements revealed assimilation and transpiration rates, as well as electron transport rates (ETR) and carboxylation efficiency (CE) in steady-state conditions. Finally, leaf morphological traits (mean leaf area and leaf shape were quantified), along with leaf surface decorations, imaged using scanning electron microscopy. KEY RESULTS: Shoot morphology was differentially affected by heat, with three of the four wild species growing faster at 38°C than at 30°C, whereas early growth in G. hirsutum was severely inhibited by heat. Areas of individual leaves and leaf numbers both contributed to these contrasting growth responses, with fewer, smaller leaves at 38°C in G. hirsutum. CO2 assimilation and transpiration rates of G. hirsutum were also dramatically reduced by heat. Cultivated cotton failed to achieve evaporative cooling, contrasting with the transpiration-driven cooling in the wild species. Heat substantially reduced ETR and CE in G. hirsutum, with much smaller effects in the wild species. We speculate that leaf shape, as assessed by invaginations of leaf margins, and leaf size contributed to heat dispersal differentially among the five species. Similarly, reflectance of light radiation was also highly distinctive for each species. CONCLUSIONS: These four wild Australian relatives of cotton have adapted to hot days that are inhibitory to commercial cotton, deploying a range of physiological and structural adaptations to achieve accelerated growth at 38°C.

Oriented Structures for High Safety, Rate Capability, and Energy Density Lithium Metal Batteries.

Lithium metal batteries (LMBs) have emerged in recent years as highly promising candidates for high-density energy storage systems. Despite their immense potential, mutual constraints arise when optimizing energy density, rate capability, and operational safety, which greatly hinder the commercialization of LMBs. The utilization of oriented structures in LMBs appears as a promising strategy to address three key performance barriers: 1) low efficiency of active material utilization at high surface loading, 2) easy formation of Li dendrites and damage to interfaces under high-rate cycling, and 3) low ionic conductivity of solid-state electrolytes in high safety LMBs. This review aims to holistically introduce the concept of oriented structures, provide criteria for quantifying the degree of orientation, and elucidate their systematic effects on the properties of materials and devices. Furthermore, a detailed categorization of oriented structures is proposed to offer more precise guidance for the design of LMBs. This review also provides a comprehensive summary of preparation techniques for oriented structures and delves into the mechanisms by which these can enhance the energy density, rate capability, and safety of LMBs. Finally, potential applications of oriented structures in LMBs and the crucial challenges that need to be addressed in this field are explored.

Biosustainable Multiscale Transparent Nanocomposite Films for Sensitive Pressure and Humidity Sensors.

Light weight, thinness, transparency, flexibility, and insulation are the key indicators for flexible electronic device substrates. The common flexible substrates are usually polymer materials, but their recycling is an overwhelming challenge. Meanwhile, paper substrates are limited in practical applications because of their poor mechanical and thermal stability. However, natural biomaterials have excellent mechanical properties and versatility thanks to their organic-inorganic multiscale structures, which inspired us to design an organic-inorganic nanocomposite film. For this purpose, a bio-inspired multiscale film was developed using cellulose nanofibers with abundant hydrophilic functional groups to assist in dispersing hydroxyapatite nanowires. The thickness of the biosustainable film is only 40 µm, and it incorporates distinctive mechanical properties (strength: 52.8 MPa; toughness: 0.88 MJ m-3) and excellent optical properties (transmittance: 80.0%; haze: 71.2%). Consequently, this film is optimal as a substrate employed for flexible sensors, which can transmit capacitance and resistance signals through wireless Bluetooth, showing an ultrasensitive response to pressure and humidity (for example, responding to finger pressing with 5000% signal change and exhaled water vapor with 4000% signal change). Therefore, the comprehensive performance of the biomimetic multiscale organic-inorganic composite film confers a prominent prospect in flexible electronics devices, food packaging, and plastic substitution.

White Roman Goose Feather-Inspired Unidirectionally Inclined Conical Structure Arrays for Switchable Anisotropic Self-Cleaning.

White Roman goose (Anser anser domesticus) feathers, comprised of oriented conical barbules, are coated with gland-secreted preening oils to maintain a long-term nonwetting performance for surface swimming. The geese are accustomed to combing their plumages with flat bills in case they are contaminated with oleophilic substances, during which the amphiphilic saliva spread over the barbules greatly impairs their surface hydrophobicities and allows the trapped contaminants to be anisotropically self-cleaned by water flows. Particularly, the superhydrophobic behaviors of the goose feathers are recovered as well. Bioinspired by the switchable anisotropic self-cleaning functionality of white Roman geese, superhydrophobic unidirectionally inclined conical structures are engineered through the integration of a scalable colloidal self-assembly technology and a colloidal lithographic approach. The dependence of directional sliding properties on the shape, inclination angle, and size of conical structures is systematically investigated in this research. Moreover, their switchable anisotropic self-cleaning functionalities are demonstrated by Sudan blue II/water (0.01%) separation performances. The white Roman goose feather-inspired coatings undoubtedly offer a new concept for developing innovative applications that require directional transportation and the collection of liquids.

Investigations on the EPR g factors and local structures for the orthorhombic and tetragonal Cu2+ centers in Pb[Zr0.54Ti0.46]O3.

The defect models of the orthorhombical and tetragonal Cu2+ centers in Pb[Zr0.54Ti0.46]O3 are attributed to Cu2+ ions occupying the sixfold coordinated octahedral Ti4+ site with and without charge compensation, respectively. The electron paramagnetic resonance (EPR) g factors gi (i = x, y, z) of the Cu2+ centers in Pb[Zr0.54Ti0.46]O3 are theoretically studied by using the perturbation formulas of a 3d9 ion under orthorhombically and tetragonally elongated octahedra. Based on the calculation, the impurity off-center displacements are about 0.253 and 0.162 Å for the orthorhombical and tetragonal Cu2+ centers, respectively. Meanwhile, the planar Cu2+-O2- bonds are found to experience the relative variation ΔR (≈0.102 Å) along the a- and b-axes for the orthorhombical Cu2+ center due to the Jahn-Teller (JT) effect. The theoretical EPR g factors based on the above local structures agree well with the observed values.

Carbon Structure Regulation Strategy for the Electrode of Vanadium Redox Flow Battery.

Vanadium redox flow battery (VRFB) is a type of energy storage device known for its large-scale capacity, long-term durability, and high-level safety. It serves as an effective solution to address the instability and intermittency of renewable energy sources. Carbon-based materials are widely used as VRFB electrodes due to cost-effectiveness and well-stability. However, pristine electrodes need proper modification to overcome original poor hydrophilicity and fewer reaction active sites. Adjusting the carbon structure is recognized as a viable method to boost the electrochemical activity of electrodes. This review delves into the advancements in research related to ordered and disordered carbon structure electrodes including the adjusting methods, structural characteristics, and catalytic properties. Ordered carbon structures are categorized into nanoscale and macroscale orderliness based on size, leading to improved conductivity and overall performance of the electrode. Disordered carbon structures encompass methods such as doping atoms, grafting functional groups, and creating engineered holes to enhance active sites and hydrophilicity. Based on the current research findings on carbon electrode structures, this work puts forth some promising prospects for future feasibility.

CYCLOPEp Builder: Facilitating cyclic peptide and nanotube research through a user-friendly web platform.

The study of cyclic peptides (CPs) and self-assembling cyclic peptide nanotubes (SCPNs) is pivotal in advancing applications in diverse fields such as biomedicine, nanoelectronics, and catalysis. Recognizing the limitations in the experimental study of these molecules, this article introduces CYCLOPEp Builder, a comprehensive web-based application designed to facilitate the design, simulation, and visualization of CPs and SCPNs. The tool is engineered to generate molecular topologies, essential for conducting Molecular Dynamics simulations that span All-Atom to Coarse-Grain resolutions. CYCLOPEp Builder's user-friendly interface simplifies the complex process of molecular modeling, providing researchers with the ability to readily construct CPs and SCPNs. The platform is versatile, equipped with various force fields, and capable of producing structures ranging from individual CPs to complex SCPNs with different sequences, offering parallel and antiparallel orientations among them. By enhancing the capacity for detailed visualization of molecular assemblies, CYCLOPEp Builder improves the understanding of CP and SCPN molecular interactions. This tool is a step forward in democratizing access to sophisticated simulations, offering an invaluable resource to the scientific community engaged in the exploration of supramolecular structures. CYCLOPEp is accessible at http://cyclopep.com/.

Alfin-like (AL) transcription factor family in Oryza sativa L.: Genome-wide analysis and expression profiling under different stresses.

Oryza sativa L. is the world's most essential and economically important food crop. Climate change and ecological imbalances make rice plants vulnerable to abiotic and biotic stresses, threatening global food security. The Alfin-like (AL) transcription factor family plays a crucial role in plant development and stress responses. This study comprehensively analyzed this gene family and their expression profiles in rice, revealing nine AL genes, classifying them into three distinct groups based on phylogenetic analysis and identifying four segmental duplication events. RNA-seq data analysis revealed high expression levels of OsALs in different tissues, growth stages, and their responsiveness to stresses. RT-qPCR data showed significant expression of OsALs in different abiotic stresses. Identification of potential cis-regulatory elements in promoter regions has also unveiled their involvement. Tertiary structures of the proteins were predicted. These findings would lay the groundwork for future research to reveal their molecular mechanism in stress tolerance and plant development.

Efficacy of auxetic lattice structured shoe sole in advancing footwear comfort-From the perspective of plantar pressure and contact area.

Introduction: Designing footwear for comfort is vital for preventing foot injuries and promoting foot health. This study explores the impact of auxetic structured shoe soles on plantar biomechanics and comfort, motivated by the integration of 3D printing in footwear production and the superior mechanical properties of auxetic designs. The shoe sole designs proposed in this study are based on a three-dimensional re-entrant auxetic lattice structure, orthogonally composed of re-entrant hexagonal honeycombs with internal angles less than 90 degrees. Materials fabricated using this lattice structure exhibit the characteristic of a negative Poisson's ratio, displaying lateral expansion under tension and densification under compression. Methods: The study conducted a comparative experiment among three different lattice structured (auxetic 60°, auxetic 75° and non-auxetic 90°) thermoplastic polyurethane (TPU) shoe soles and conventional polyurethane (PU) shoe sole through pedobarographic measurements and comfort rating under walking and running conditions. The study obtained peak plantar pressures (PPPs) and contact area across seven plantar regions of each shoe sole and analyzed the correlation between these biomechanical parameters and subjective comfort. Results: Compared to non-auxetic shoe soles, auxetic structured shoe soles reduced PPPs across various foot regions and increased contact area. The Auxetic 60°, which had the highest comfort ratings, significantly lowered peak pressures and increased contact area compared to PU shoe sole. Correlation analysis showed that peak pressures in specific foot regions (hallux, second metatarsal head, and hindfoot when walking; second metatarsal head, third to fifth metatarsal head, midfoot, and hindfoot when running) were related to comfort. Furthermore, the contact area in all foot regions was significantly associated with comfort, regardless of the motion states. Conclusion: The pressure-relief performance and conformability of the auxetic lattice structure in the shoe sole contribute to enhancing footwear comfort. The insights provided guide designers in developing footwear focused on foot health and comfort using auxetic structures.

Automated immunoassay of serum NY-ESO-1 and XAGE1 antibodies for predicting clinical benefit with immune checkpoint inhibitor (ICI) in advanced non-small cell lung cancer.

BACKGROUND: NY-ESO-1 and XAGE1 cancer/testis antigens elicit humoral and cellular immune responses in NSCLC patients. We aimed to predict clinical benefit with ICI monotherapy, using an automated immunoassay of NY-ESO-1/XAGE1 antibodies (Abs). METHODS: This study enrolled 99 NSCLC patients who received nivolumab after chemotherapy, including 21 patients harboring EGFR, ALK, or KRAS alterations. The cutoff value (10 units/mL) of NY-ESO-1 and XAGE1 Ab was determined based on Ab levels in non-malignant controls, and NY-ESO-1/XAGE1 Abs in NSCLC were measured before nivolumab. Differences in PFS and OS between the Ab-positive and Ab-negative groups were retrospectively analyzed using Cox regression analysis after applying inverse probability of treatment weighting (IPTW). RESULTS: NY-ESO-1/XAGE1 Abs were positive in 28 NSCLC, who responded more highly to nivolumab than the Ab-negatives (response rate 50.0% vs. 15.5 %, p < 0.0007). The IPTW-adjusted positives and negatives for NY-ESO-1/XAGE1 Abs were 24.5 and 70.2, respectively. The Ab-positives showed longer IPTW-adjusted PFS (HR = 0.59, 95 % CI: 0.39-0.90, p = 0.014) and IPTW-adjusted OS (HR = 0.51, 95 % CI: 0.32-0.81, p = 0.004) than the Ab-negatives. Among NSCLC harboring driver genes, the Ab-positives (n = 10) showed longer PFS (HR = 0.34, 95 % CI: 0.13-0.89, p = 0.029) and OS (HR = 0.27, 95 % CI: 0.098-0.75, p = 0.012) than the Ab-negatives (n = 11). CONCLUSION: Our immunoassay of NY-ESO-1/XAGE1 Abs is probably useful for predicting the clinical benefit with nivolumab in NSCLC, including those harboring driver genes. These results suggest that our immunoassay may be useful in ICI monotherapy for NSCLC.

In-Sensor Tactile Fusion and Logic for Accurate Intention Recognition.

Touch control intention recognition is an important direction for the future development of human-machine interactions (HMIs). However, the implementation of parallel-sensing functional modules generally requires a combination of different logical blocks and control circuits, which results in regional redundancy, redundant data, and low efficiency. Here, a location-and-pressure intelligent tactile sensor (LPI tactile sensor) unprecedentedly combined with sensing, computing, and logic is proposed, enabling efficient and ultrahigh-resolution action-intention interaction. The LPI tactile sensor eliminates the need for data transfer among the functional units through the core integration design of the layered structure. It actuates in-sensor perception through feature transmission, fusion, and differentiation, thereby revolutionizing the traditional von Neumann architecture. While greatly simplifying the data dimensionality, the LPI tactile sensor achieves outstanding resolution sensing in both location (<400 µm) and pressure (75 Pa). Synchronous feature fusion and decoding support the high-fidelity recognition of action and combinatorial logic intentions. Benefiting from location and pressure synergy, the LPI tactile sensor demonstrates robust privacy as an encrypted password device and interaction intelligence through pressure enhancement. It can recognize continuous touch actions in real time, map real intentions to target events, and promote accurate and efficient intention-driven HMIs.

Exploring snake venoms beyond the primary sequence: From proteoforms to protein-protein interactions.

Snakebite envenomation has been a long-standing global issue that is difficult to treat, largely owing to the flawed nature of current immunoglobulin-based antivenom therapy and the complexity of snake venoms as sophisticated mixtures of bioactive proteins and peptides. Comprehensive characterisation of venom compositions is essential to better understanding snake venom toxicity and inform effective and rationally designed antivenoms. Additionally, a greater understanding of snake venom composition will likely unearth novel biologically active proteins and peptides that have promising therapeutic or biotechnological applications. While a bottom-up proteomic workflow has been the main approach for cataloguing snake venom compositions at the toxin family level, it is unable to capture snake venom heterogeneity in the form of protein isoforms and higher-order protein interactions that are important in driving venom toxicity but remain underexplored. This review aims to highlight the importance of understanding snake venom heterogeneity beyond the primary sequence, in the form of post-translational modifications that give rise to different proteoforms and the myriad of higher-order protein complexes in snake venoms. We focus on current top-down proteomic workflows to identify snake venom proteoforms and further discuss alternative or novel separation, instrumentation, and data processing strategies that may improve proteoform identification. The current higher-order structural characterisation techniques implemented for snake venom proteins are also discussed; we emphasise the need for complementary and higher resolution structural bioanalytical techniques such as mass spectrometry-based approaches, X-ray crystallography and cryogenic electron microscopy, to elucidate poorly characterised tertiary and quaternary protein structures. We envisage that the expansion of the snake venom characterisation "toolbox" with top-down proteomics and high-resolution protein structure determination techniques will be pivotal in advancing structural understanding of snake venoms towards the development of improved therapeutic and biotechnology applications.

Sustained innate interferon is an essential inducer of tertiary lymphoid structures.

Tertiary lymphoid structures (TLS) resemble follicles of secondary lymphoid organs and develop in nonlymphoid tissues during inflammation and cancer. Which cell types and signals drive the development of TLS is largely unknown. To investigate early events of TLS development in the lungs, we repeatedly instilled p(I:C) plus ovalbumin (Ova) intranasally. This induced TLS ranging from lymphocytic aggregates to organized and functional structures containing germinal centers. We found that TLS development is independent of FAP+ fibroblasts, alveolar macrophages, or CCL19 but crucially depends on type I interferon (IFN-I). Mechanistically, IFN-I initiates two synergistic pathways that culminate in the development of TLS. On the one hand, IFN-I induces lymphotoxin (LT)α in lymphoid cells, which stimulate stromal cells to produce the B-cell-attracting chemokine CXCL13 through LTßR-signaling. On the other hand, IFN-I is sensed by stromal cells that produce the T-cell-attracting chemokines CXCL9, CXCL10 as well as CCL19 and CCL21 independently of LTßR. Consequently, B-cell aggregates develop within a week, whereas follicular dendritic cells and germinal centers appear after 3 weeks. Thus, sustained production of IFN-I together with an antigen is essential for the induction of functional TLS in the lungs.

Microbial ice-binding structures: A review of their applications.

Microorganisms' ice-binding structures (IBS) are macromolecules with potential commercial value in agriculture, food technology, material technology, cryobiology, and medicine. Microbial ice-structuring or microbial ice-binding particles, with their multi-applications, are simple to use, effective in low amounts, non-toxic, and environmentally friendly. Due to their source and composition diversities, microbial ice-binding structures are gaining attention because they are useable in various conditions. Some microorganisms also produce structures with dual ice-nucleating and anti-freezing properties. Structures that promote ice formation (ice nucleating particles- INPs) act as ice nuclei, lowering the energy barrier between supercooled liquid and ice, causing ice crystals to form. In contrast, anti-freeze particles (AFPs) prevent ice formation and recrystallization through several mechanisms, including disturbing the formation of string hydrogen bonds amongst water molecules, melting already formed ice crystals, and preventing crystal formation by binding to specific sites. Knowledge of the type and function of microbial ice-binding structures lends fundamental insight for possible scaling the production of cheap, functional, and advanced microbial structure-inspired mimics and by-products. This review focuses on microbial ice-binding structures and their potential uses in the food, medicinal, environmental, and agricultural sectors.