Human milk oligosaccharides (HMO) that promote the growth of beneficial gut microbes in infants are abundant in human milk. Streptococcus, one of the dominant genera in human milk microbiota, is also highly prevalent in the infant gut microbiota, possibly due to its adeptness at utilizing HMOs. While previous studies have mainly focused on HMO interactions with gut bacteria like Bifidobacterium and Bacteroides spp., the interaction with Streptococcus spp. has not been fully explored. In this study, Streptococcus spp. was isolated from human milk and identified to exhibit extensive capabilities in utilizing HMOs. Their consumption rates of 2′-fucosyllactose (2′-FL), 6′-sialyllactose (6′-SL), and lacto-N-tetraose (LNT) closely matched those of Bifidobacterium longum subsp. infantis ATCC 15697. Furthermore, we assessed the safety-related genes in the genomes of the Streptococcus species capable of utilizing HMOs, revealing potential virulence and resistance genes. In addition, no haemolytic activity was observed. These findings expand the knowledge of metabolic interactions and networks within the microbiota of human milk and the early life human gut. Full article

Aim: Transarterial chemoembolization (TACE) combined with lenvatinib, employing a 4-day lenvatinib administration followed by TACE without an interval (short-term LEN-TACE), was performed for hepatocellular carcinoma (HCC). The aim was to assess tumor hemodynamics following the 4-day lenvatinib and to evaluate the treatment outcomes after the short-term LEN-TACE. Methods: 25 unresectable HCC patients received this combined therapy. Lenvatinib (4–12 mg) was administrated for 4 days prior to TACE. Perfusion CT scans were obtained before and after the lenvatinib administration. Either cTACE (76%) or DEB-TACE (24%) were performed. Results: intra-tumor blood flow significantly decreased after the 4-day lenvatinib (p < 0.05). The TACE procedure was successful with no severe adverse events in all patients. The overall complete response (CR) rate was 75% (cTACE 84%, DEB-TACE 40%). The lipiodol-washout ratio between 1 week and 4 months after cTACE correlated with the arterial flow reduction ratio by lenvatinib prior to TACE (r = −0.55). The 12-month progression-free survival (PFS) rate was 75.0%. Conclusions: The short-term LEN-TACE is feasible and safe, demonstrating promising outcomes with a high CR ratio, contributing to lipiodol retention in the tumor after cTACE, and extended PFS. To confirm the advantages of this treatment protocol, a prospective clinical trial is mandatory. Full article

Tofts models have failed to produce reliable quantitative markers for prostate cancer. We examined the differences between prostate zones and lesion PI-RADS categories and grade group (GG) using regions of interest drawn in tumor and normal-appearing tissue for a two-compartment uptake (2CU) model (including plasma volume (v_p), plasma flow (F_p), permeability surface area product (PS), plasma mean transit time (MTT_p), capillary transit time (T_c), extraction fraction (E), and transfer constant (K_trans)) and exponential (amplitude (A), arrival time (t₀), and enhancement rate (α)), sigmoidal (amplitude (A₀), center time relative to arrival time (A₁ − T₀), and slope (A₂)), and empirical mathematical models, and time to peak (TTP) parameters fitted to high temporal resolution (1.695s) DCE-MRI data. In 25 patients with 35 PI-RADS category 3 or higher tumors, we found F_p and α differed between peripheral and transition zones. Parameters F_p, MTT_p, T_c, E, α, A₁ − T₀, and A₂ and TTP all showed associations with PI-RADS categories and with GG in the PZ when normal-appearing regions were included in the non-cancer GG. PS and K_trans were not associated with any PI-RADS category or GG. This pilot study suggests early enhancement parameters derived from ultrafast DCE-MRI may become markers of prostate cancer. Full article

Analyzing land subsidence using Multi-temporal Interferometric Synthetic Aperture Radar (MT-InSAR) technology holds significant importance for the secure development of urban areas. Shenzhen, being a crucial component of the Pearl River Delta, faces the threat of land subsidence, similar to most deltaic cities. Numerous studies have already indicated the presence of severe land subsidence in certain localities of Shenzhen. However, due to limitations in data scope and research methodologies, the comprehensive spatial-temporal distribution of land subsidence across the entire city of Shenzhen remains unclear. This study initially employed MT-InSAR technology to process a total of 534 Sentinel-1A SAR images from three different frames (P11F71, P113F71, P11F65), covering the entire city of Shenzhen. This processing resulted in the generation of subsidence rate maps and subsidence time series. Subsequently, the temporal evolution patterns of the subsidence were analyzed while significant subsidence regions were identified. By integrating information from optical images reflecting human activities on the Earth’s surface, the study deduced the subsidence mechanisms in various significant subsidence areas. Research findings indicate that land subsidence in Shenzhen is primarily caused by construction activities, with a concentration in the western coastal areas of Shenzhen, reaching a maximum rate of 80 mm/yr, located at the estuary of Dongbao River (113.770385, 22.745305). The cumulative subsidence from March 2017 to June 2023 amounts to 500 mm. The expansion of the Qinglinjing Reservoir has led to an increased demand for water, resulting in a significant rise in formation pressure and subsequent land subsidence. InSAR land subsidence monitoring and analysis in urban areas can address the spatial and temporal resolution limitations of traditional subsidence monitoring methods, providing effective recommendations for widespread subsidence prevention and control. Full article

This paper presents laboratory devices on which measurements were carried out to prove the validity of the assumption about the reduction in vibrations transmitted to the conveyor belt structure generated by the impact forces of falling material grains in the places of transfer or on the hoppers of conveyor belts. In order to limit damage to the conveyor belts caused by the impact of the sharp edges of material grains, conveyor belts are supported by impact rollers or impact rubber rods. A special modification of the fixed conveyor idler is presented, which consists of inserting plastic brackets into the structurally modified roller axle holders of the fixed conveyor idler. Measurements showed that the specially modified fixed conveyor idler resulted in a higher damping of up to 15% of the impact forces of the falling weight on the rubberized hoop of the impact roller shell compared to the conventional fixed conveyor idler design. Measurements carried out show that the effective vibration velocity values detected at the points where the impact roller axis fits into the fixed roller table holder are higher than when using plastic brackets, up to 6% for a 108-mm-diameter roller, compared to steel impact roller brackets. Full article

Lavender essential oil (LEO) is applied topically for its soothing properties, serving not only as an antiseptic in wound care but also as an insect repellent. This study investigates the impact of carrier systems on LEO encapsulation, stability, and release kinetics for potential skincare applications. The LEO carrier impact on skin hydration and barrier function was also evaluated. Conventional emulsions (CEs) and nanoemulsions (NEs) with (CELs and NELs, respectively) and without LEO incorporation were analyzed for physicochemical properties, stability, and release mechanisms. The droplet size distribution and ζ-potential remained consistent in both CE and CEL, showing the minimal influence of LEO on those parameters. NE and NEL exhibited enhanced stability and higher LEO retention compared to CE and CEL (37.38 mg/mL ± 0.48 mg/mL and 50.96 mg/mL ± 2.00 mg/mL, respectively, p < 0.05), suggesting NE as a superior carrier system for LEO delivery. NEL retained LEO over 60 days at 4 °C without a significant reduction while CEL showed a notable reduction of 94.93% ± 0.08%. Release kinetics analysis showed zero-order release kinetics of LEO from both CEL and NEL (R²: 0.973 and 0.952, respectively), revealing a diffusion-based mechanism, particularly evident in NE formulations, supporting the controlled and sustained release of LEO constituents. NEL also promoted quicker skin barrier repair and enhanced skin hydration, sustaining effects for up to 120 min post application, surpassing CEL’s performance. These findings contribute to understanding the carrier system effects on LEO delivery and underscore NE as a promising vehicle for skincare applications. Further research should explore underlying mechanisms and conduct long-term safety and efficacy studies to fully exploit the therapeutic potential of NE in dermatological applications. Full article

Marine-derived Penicillium fungi are productive sources of structurally unique and diverse bioactive secondary metabolites, representing a hot topic in natural product research. This review describes structural diversity, bioactivities and statistical research of 452 new natural products from marine-derived Penicillium fungi covering 2021 to 2023. Sediments are the main sources of marine-derived Penicillium fungi for producing nearly 56% new natural products. Polyketides, alkaloids, and terpenoids displayed diverse biological activities and are the major contributors to antibacterial activity, cytotoxicity, anti-inflammatory and enzyme inhibitory capacities. Polyketides had higher proportions of new bioactive compounds in new compounds than other chemical classes. The characteristics of studies in recent years are presented. Full article

The development of mucosal vaccines, which can generate antigen-specific immune responses in both the systemic and mucosal compartments, has been recognized as an effective strategy for combating infectious diseases caused by pathogenic microbes. Our recent research has focused on creating a nasal vaccine system in mice using enzymatically polymerized caffeic acid (pCA). However, we do not yet understand the molecular mechanisms by which pCA stimulates antigen-specific mucosal immune responses. In this study, we hypothesized that pCA might activate mucosal immunity at the site of administration based on our previous findings that pCA possesses immune-activating properties. However, contrary to our initial hypothesis, the intranasal administration of pCA did not enhance the expression of various genes involved in mucosal immune responses, including the enhancement of IgA responses. Therefore, we investigated whether pCA forms a complex with antigenic proteins and enhances antigen delivery to mucosal dendritic cells located in the lamina propria beneath the mucosal epithelial layer. Data from gel filtration chromatography indicated that pCA forms a complex with the antigenic protein ovalbumin (OVA). Furthermore, we examined the promotion of OVA delivery to nasal mucosal dendritic cells (mDCs) after the intranasal administration of pCA in combination with OVA and found that OVA uptake by mDCs was increased. Therefore, the data from gel filtration chromatography and flow cytometry imply that pCA enhances antigen-specific antibody production in both mucosal and systemic compartments by serving as an antigen-delivery vehicle. Full article

Whether to use face priors in the face super-resolution (FSR) methods is a symmetry problem.Various face priors are used to describe the overall and local face features, making the generation of super-resolution face images expensive and laborious. FSR methods that do not require any prior information tend to focus too much on the local features of the face, ignoring the modeling of global information. To solve this problem, we propose a dual-path facial image super-resolution network (SwinDPSR) fused with Swin Transformer. The network does not require additional face priors, and it learns global face shape and local face components through two independent branches. In addition, the channel attention ECA module is used to aggregate the global and local face information in the above dual-path sub-networks, which can generate corresponding high-quality face images. The results of face super-resolution reconstruction experiments on public face datasets and a real-scene face dataset show that SwinDPSR is superior to previous advanced methods both in terms of visual effects and objective indicators. The reconstruction results are evaluated with four evaluation metrics: peak signal-to-noise ratio (PSNR), structural similarity (SSIM), learned perceptual image patch similarity (LPIPS), and mean perceptual score (MPS). Full article

The gut microbiome significantly influences the health and productivity of silkworms (Bombyx mori), the cornerstone of sericulture. With the increasing use of cost-effective artificial diets in sericulture, it is crucial to understand how these diets impact the silkworm gut microbiomes. Here we employed 16S rRNA sequencing to delineate the impact of three distinct dietary regimens on the silkworm gut microbiomes: exclusive mulberry leaf diet (SY), exclusive artificial feed diet (SL), and a sequential transition from artificial feed to mulberry leaves (ZS). Our results unveiled stark differences in microbial diversity across the groups, with the ZS group displaying an intermediary complexity. LefSe and random forest analyses identified Methylobacteriaceae, Microbacterium, and Rhodococcus as significantly enriched in the ZS group, suggesting their potential to facilitate silkworms’ adaptation to dietary transitions. Functional profiling revealed differential pathway regulation, indicating a metabolic reconfiguration in response to dietary modulations. Notably, the enrichment of Lactobacillus and Weissella in both the SL and ZS groups highlights their potential as probiotics in artificial diets. Our findings provide insights into the diet adaptation mechanisms of silkworm gut microbiota, paving the way for harnessing the intestinal bacteria to enhance silkworm health and silk production through targeted microbial interventions in sericulture practices. Full article

This paper considers a pair $(\mathbb{F},\tau )$, where $\mathbb{F}$ is a filtration representing the “public” flow of information that is available to all agents over time, and $\tau$ is a random time that might not be an $\mathbb{F}$-stopping time. This setting covers the case of a credit risk framework, where $\tau$ models the default time of a firm or client, and the setting of life insurance, where $\tau$ is the death time of an agent. It is clear that random times cannot be observed before their occurrence. Thus, the larger filtration, $\mathbb{G}$, which incorporates $\mathbb{F}$ and makes $\tau$ observable, results from the progressive enlargement of $\mathbb{F}$ with $\tau$. For this informational setting, governed by $\mathbb{G}$, we analyze the optimal stopping problem in three main directions. The first direction consists of characterizing the existence of the solution to this problem in terms of $\mathbb{F}$-observable processes. The second direction lies in deriving the mathematical structuresof the value process of this control problem, while the third direction singles out the associated optimal stopping problem under $\mathbb{F}$. These three aspects allow us to deeply quantify how $\tau$ impacts the optimal stopping problem and are also vital for studying reflected backward stochastic differential equations that arise naturally from pricing and hedging of vulnerable claims. Full article

Thermal energy storage is at the leading edge of various applications, including waste heat recovery, solar storage and zero-energy buildings. Phase change materials (PCMs) can be utilized to store heat through reversible solid–liquid phase transitions. PCMs provide high energy storage capacity at a constant temperature. The volume change during the phase transition, on the other hand, causes inconsistency in crystallization and leakage, increasing the system’s complexity and shortening the lifetime of these materials. These shortcomings can be diminished by impregnation in a porous matrix or encapsulation with an inert shell, resulting in shape-stabilized PCMs that maintain their macroscopic shape during phase change. The synthesis and properties of Bi/ZnO nanocomposites were investigated in order to obtain shape-stabilized phase change materials. All samples consisted of metallic Bi and oxide, doped with 1–3% at. zinc. Heat storage capacities between 31 and 49 Jg⁻¹ were obtained, depending on the mass fraction of the metal. All samples had good thermal reliability, retaining their heat storage properties after 50 consecutive heating–cooling cycles. An average oxide layer thickness of 75–100 nm is sufficient to prevent the molten metal leakage at temperatures above its melting point, resulting in shape-stabilized PCMs. Full article

Spectroscopy is a powerful tool to identify the specific fingerprints of analytes in a label-free way. However, conventional sensing methods face unavoidable barriers in analyzing trace-amount target molecules due to the difficulties of enhancing the broadband molecular absorption. Here, we propose a sensing scheme to achieve strong fingerprint absorption based on the angular-scanning strategy on an all-silicon metasurface. By integrating the mid-infrared and terahertz sensing units into a single metasurface, the sensor can efficiently identify 2,4-DNT with high sensitivity. The results reveal that the fingerprint peak in the enhanced fingerprint spectrum is formed by the linked envelope. It exhibits a significant enhancement factor exceeding 64-fold in the terahertz region and more than 55-fold in the mid-infrared region. Particularly, the corresponding identification limit of 2,4-DNT is 1.32 µg cm⁻², respectively. Our study will provide a novel research idea in identifying trace-amount explosives and advance practical applications of absorption spectroscopy enhancement identification in civil and military security industries. Full article

Due to anthropogenic emissions, the global CO₂ concentration increases at a rate of approximately 2 ppm per year. With over 130 countries and regions committing to carbon neutrality goals and continuously reducing anthropogenic CO₂ emissions, understanding how atmospheric CO₂ concentrations will change globally and in other regions has become an intriguing question. Examining different regions’ efforts to reduce anthropogenic CO₂ emissions through atmospheric CO₂ observations is also meaningful. We used prior and posterior fluxes to drive the TM5 model. The posterior fluxes were based on the China Carbon Monitoring, Verification and Support System for Global (CCMVS-G), which assimilated the atmospheric CO₂ concentration data from ground-based observation and satellite observation. We found that the CO₂ concentration obtained using the posterior fluxes was more in line with the actual situation. Then, we presented some experiments to estimate how global and regional CO₂ concentrations would change if certain key regions and the whole world achieved net zero emissions of anthropogenic CO₂. After removing carbon fluxes from China, North America, and Europe, global CO₂ concentrations decreased by around 0.58 ppm, 0.22 ppm, and 0.10 ppm, respectively. The most significant decrease occurred in the regions where fluxes were removed, followed by other areas at the same latitude affected by westerly winds. This indicates that fossil fuel flux is the main factor affecting CO₂ concentrations, and that meteorological-driven transportation also significantly impacts CO₂ concentrations. Most importantly, using this method, it is possible to quantitatively estimate the impact of achieving carbon neutrality in one region on CO₂ concentrations in local regions as well as globally. Full article

Background: The mortality rate of afebrile bacteremia has been reported to be as high as 45%. This investigation focused on the risk factors and predictive performance of scoring systems for the clinical outcomes of afebrile patients with monomicrobial gram-negative bacteria (GNB) in the emergency department (ED). Methods: We conducted a retrospective analysis of afebrile adult ED patients with monomicrobial GNB bacteremia from January 2012 to December 2021. We dissected the demographics, clinical pictures, and laboratory investigations. We applied five scoring systems and three revised systems to predict the clinical outcomes. Results: There were 600 patients included (358 males and 242 females), with a mean age of 69.6 ± 15.4 years. The overall mortality rate was 50.17%, reaching 68.52% (74/108) in cirrhotic patients. Escherichia coli was the leading pathogen (42.83%). The non-survivors had higher scores of the original MEDS (p < 0.001), NEWS (p < 0.001), MEWS (p < 0.001), qSOFA (p < 0.001), and REMS (p = 0.030). In univariate logistic regression analyses, several risk factors had a higher odds ratio (OR) for mortality, including liver cirrhosis (OR 2.541, p < 0.001), malignancy (OR 2.259, p < 0.001), septic shock (OR 2.077, p = 0.002), and male gender (OR 0.535, p < 0.001). The MEDS demonstrated that the best predictive power with the maximum area under the curve (AUC) was measured at 0.773 at the cut-off point of 11. The AUCs of the original NEWS, MEWS, qSOFA, and REMS were 0.663, 0.584, 0.572, and 0.553, respectively. We revised the original MEDS, NEWS, and qSOFA by adding red cell distribution width, albumin, and lactate scores and found a better predictive power of the AUC of 0.797, 0.719, and 0.694 on the revised MEDS ≥11, revised qSOFA ≥ 3, and revised NEWS ≥ 6, respectively. Conclusions: The original MEDS, revised MEDS, revised qSOFA, and revised NEWS were valuable tools for predicting the mortality risk in afebrile patients with monomicrobial GNB bacteremia. We suggested that clinicians should explore patients with the risk factors mentioned above for possible severe infection, even in the absence of fever and initiate hemodynamic support and early adequate antibiotic therapy in patients with higher scores of the original MEDS (≥11), revised MEDS (≥11), revised NEWS (≥6), and revised qSOFA (≥3). Full article

FIDO (Fast Identity Online) is a set of network identity standards established by the FIDO Alliance. It employs a framework based on public key cryptography to facilitate multi-factor authentication (MFA) and biometric login, ensuring the robust protection of personal data associated with cloud accounts and ensuring the security of server-to-terminal device protocols during the login process. The FIDO Alliance has established three standards: FIDO Universal Second Factor (FIDO U2F), FIDO Universal Authentication Framework (FIDO UAF), and the Client to Authenticator Protocols (CTAP). The newer CTAP, also known as FIDO2, integrates passwordless login and two-factor authentication. Importantly, FIDO2’s support for major browsers enables users to authenticate their identities via FIDO2 across a broader range of platforms and devices, ushering in the era of passwordless authentication. In the FIDO2 framework, if a user’s device is stolen or compromised, then the private key may be compromised, and the public key stored on the FIDO2 server may be tampered with by attackers attempting to impersonate the user for identity authentication, posing a high risk to information security. Recognizing this, this study aims to propose a solution based on the FIDO2 framework, combined with blockchain technology and access control, called the FIDO2 blockchain architecture, to address existing security vulnerabilities in FIDO2. By leveraging the decentralized nature of the blockchain, the study addresses potential single points of failure in FIDO2 server centralized identity management systems, thereby enhancing system security and availability. Furthermore, the immutability of the blockchain ensures the integrity of public keys once securely stored on the chain, effectively reducing the risk of attackers impersonating user identities. Additionally, the study implements an access control mechanism to manage user permissions effectively, ensuring that only authorized users can access corresponding permissions and preventing unauthorized modifications and abuse. In addition to proposing practical solutions and steps, the study explains and addresses security concerns and conducts performance evaluations. Overall, this study brings higher levels of security and trustworthiness to FIDO2, providing a robust identity authentication solution. Full article

This contribution focuses on the detection of tracer particles within non-homogeneous bulk media, aiming to enhance insights into particulate systems. Polarimetric radar measurements are employed, utilizing cross-polarizing channels in order to mitigate interference from bulk media reflections. To distinguish the tracer particle in the measurements, a resonant cross-polarizing structure is constructed, facilitating the isolation of frequency signatures from the surrounding bulk clutter. In addition to characterizing the bulk and tracer components, this study provides a detailed presentation and discussion of the measurement setup, along with the employed signal processing methods. The effectiveness of the proposed methods is demonstrated through comprehensive measurements, where a tracer particle is systematically positioned at various locations. The results affirm the feasibility and efficacy of the approach, highlighting its applicability for enhanced dynamic monitoring in particulate systems within industrial processes. Full article

Although Herpes simplex virus type 1 (HSV-1) has been deeply studied, significant gaps remain in the fundamental understanding of HSV-host interactions: our work focused on studying the Infected Cell Protein 27 (ICP27) as an inhibitor of the Absent-in-melanoma-2 (AIM 2) inflammasome pathway, leading to reduced pro-inflammatory cytokines that influence the activation of a protective innate immune response to infection. To assess the inhibition of the inflammasome by the ICP27, hTert-immortalized Retinal Pigment Epithelial cells (hTert-RPE 1) infected with HSV-1 wild type were compared to HSV-1 lacking functional ICP27 (HSV-1∆ICP27) infected cells. The activation of the inflammasome by HSV-1∆ICP27 was demonstrated by quantifying the gene and protein expression of the inflammasome constituents using real-time PCR and Western blot. The detection of the cleavage of the pro-caspase-1 into the active form was performed by using a bioluminescent assay, while the quantification of interleukins 1β (IL-1β) and 18 (IL-18)released in the supernatant was quantified using an ELISA assay. The data showed that the presence of the ICP27 expressed by HSV-1 induces, in contrast to HSV-1∆ICP27 vector, a significant downregulation of AIM 2 inflammasome constituent proteins and, consequently, the release of pro-inflammatory interleukins into the extracellular environment reducing an effective response in counteracting infection. Full article

The return of straw and manure to agricultural fields can impact soil organic carbon (SOC) and biological properties. However, there is a lack of research on how using swine manure, maize straw, and various conditioners together affects soil bacterial and fungal populations. This study aimed to investigate six treatments, namely, only maize straw (S00), maize straw combined with swine manure (S0Z), maize straw combined with biochar and swine manure (SCZ), maize straw combined with boron slag and swine manure (SBZ), maize straw combined with biological agent and swine manure (SJZ), and maize straw combined with bio-organic fertilizer and swine manure (SFZ). The results showed that after the two-year return, all treatments increased the SOC content in 2023, which was 12.55–26.89% higher than S00, and the SCZ treatment significantly increased the soil organic carbon (SOC), dissolved organic carbon (DOC), easily oxidizable carbon (EOC), particulate organic carbon (POC), and microbial biomass carbon (MBC) content by 26.89%, 25.44%, 56.88%, 16.08%, and 43.54%, compared to S00. A redundancy analysis (RDA) showed that the continuous application of manure, maize straw, and conditioners has a positive impact on the diversity and abundance of soil microbial communities, enhancing the accumulation of soil carbon. Furthermore, our research revealed that soil fungi exhibited higher sensitivity in soil carbon composition following the addition of manure, straw, and conditioners to agricultural fields than bacteria. In conclusion, the addition of different conditioners to the fields is beneficial to biodiversity conservation from the perspective of achieving soil carbon storage and soil protection. Our findings suggested that the combination of maize straw, biochar, and swine manure has been proven to be the most effective treatment for increasing labile organic carbon fractions and enhancing the microbial community. Full article

Studies of Phytophthora impact in forests generally focus on individual species without recognition that Phytophthora occur in multispecies communities. This study investigated community structure of Phytophthora species in the rhizosphere of Agathis australis (kauri) in Te Wao Nui o Tiriwa/Waitākere Ranges, New Zealand, in the context of kauri dieback disease expression. Soil sampling and tree monitoring were conducted on 767 randomly selected mature kauri trees. Phytophthora species were detected using both soil baiting and DNA metabarcoding of environmental DNA (eDNA). Four species were detected with soil baiting (P. agathidicida, P. cinnamomi, P. multivora, and P. pseudocryptogea/P. cryptogea) and an additional three species with metabarcoding (P. kernoviae, P. cactorum/P. aleatoria and an unknown clade 7 species). Phytophthora cinnamomi was the most abundant species and was distributed throughout the forest. Both P. multivora and P. agathidicida were limited to forest edges, suggesting more recent introductions. P. agathidicida presence was strongly correlated with declining canopy health, confirming its role as the main driver of kauri dieback. The limited distribution of P. agathidicida and infrequent detections (11.0% samples) suggests that that this species is spreading as an introduced invasive pathogen and provide hope that with strategic management (including track upgrades and closures, restricting access to uninfected areas, and continual monitoring) uninfected areas of the forest can be protected. The frequent detections of P. cinnamomi and P. multivora from symptomatic trees in the absence of P. agathidicida suggest more research is needed to understand their roles in kauri forest health. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with high mortality due to early metastatic dissemination and high chemoresistance. All these factors are favored by its extracellular matrix (ECM)-rich microenvironment, which is also highly hypoxic and acidic. Gemcitabine (GEM) is still the first-line therapy in PDAC. However, it is quickly deaminated to its inactive metabolite. Several GEM prodrugs have emerged to improve its cytotoxicity. Here, we analyzed how the acidic/hypoxic tumor microenvironment (TME) affects the response of PDAC cell death and invadopodia-mediated ECM proteolysis to both GEM and its C18 prodrug. Methods: For this, two PDAC cell lines, PANC-1 and Mia PaCa-2 were adapted to pH_e 6.6 or not for 1 month, grown as 3D organotypic cultures and exposed to either GEM or C18 in the presence and absence of acidosis and the hypoxia inducer, deferoxamine. Results: We found that C18 has higher cytotoxic and anti-invadopodia activity than GEM in all culture conditions and especially in acid and hypoxic environments. Conclusions: We propose C18 as a more effective approach to conventional GEM in developing new therapeutic strategies overcoming PDAC chemoresistance. Full article