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• Arbuscular mycorrhizal (AM) fungi gain access to nutrient patches outside the rhizosphere by producing an extensive network of fine hyphae. Here, we focused on establishing the mechanism by which AM fungal hyphae reach discrete organic patches with a cohort of functional bacteria transported in a biofilm on their surface. • We investigated the mechanisms and impact of the translocation of phosphate solubilising bacteria (PSB) along AM fungal hyphae in bespoke microcosms. An in vitro culture experiment was also conducted to determine the direct impact of hyphal exudates of AM fungi upon the growth of PSB. • The extraradical hyphae of AM fungi can transport PSB to organic phosphorus (P) patches and enhance organic P mineralisation both under in vitro culture and soil conditions. Bacteria move in a thick water film formed around fungal hyphae. However, the bacteria cannot be transferred to the organic P patch without an energy source in the form of hyphal exudates. • Our results could be harnessed to better manage plant–microbe interactions and improve the ability of biological inocula involving AM fungi and bacteria to enhance the sustainability of agricultural crops in P limited conditions.

Although interstitial fluid (ISF) contains biomarkers of physiological significance and medical interest, sampling of ISF for clinical applications has made limited impact due to a lack of simple, clinically useful techniques that collect more than nanoliter volumes of ISF. This study describes experimental and theoretical analysis of ISF transport from skin using microneedle (MN) patches and demonstrates collection of >1 μL of ISF within 20 min in pig cadaver skin and living human subjects using an optimized system. MN patches containing arrays of submillimeter solid, porous, or hollow needles were used to penetrate superficial skin layers and access ISF through micropores (μpores) formed upon insertion. Experimental studies in pig skin found that ISF collection depended on transport mechanism according to the rank order diffusion < capillary action < osmosis < pressure-driven convection, under the conditions studied. These findings were in agreement with independent theoretical modeling that considered transport within skin, across the interface between skin and μpores, and within μpores to the skin surface. This analysis indicated that the rate-limiting step for ISF sampling is transport through the dermis. Based on these studies and other considerations like safety and convenience for future clinical use, we designed an MN patch prototype to sample ISF using suction as the driving force. Using this approach, we collected ISF from human volunteers and identified the presence of biomarkers in the collected ISF. In this way, sampling ISF from skin using an MN patch could enable collection of ISF for use in research and medicine.

The chemoattractant S1P is identified as an extrinsic factor that supports naive T cell survival, and acts via a signalling mechanism to maintain mitochondrial content and function. S1P signalling supports naive T cell survival Susan Schwab and colleagues identify sphingosine 1-phosphate (S1P) signalling through the S1P 1 receptor (S1P 1 R) as a novel survival factor for naive T cells. A diverse T cell repertoire is required to mount an effective immune response against foreign peptides. S1P is secreted by lymphatic endothelial cells and stimulates S1P 1 R on T cells, acting via a mechanism that serves to maintain mitochondrial content. This pathway may provide a therapeutic target for inhibiting self-reactive T cell trafficking. Effective adaptive immune responses require a large repertoire of naive T cells that migrate throughout the body, rapidly identifying almost any foreign peptide 1 . Because the production of T cells declines with age, naive T cells must be long-lived 2 . However, it remains unclear how naive T cells survive for years while constantly travelling. The chemoattractant sphingosine 1-phosphate (S1P) guides T cell circulation among secondary lymphoid organs, including spleen, lymph nodes and Peyer’s patches, where T cells search for antigens. The concentration of S1P is higher in circulatory fluids than in lymphoid organs, and the S1P 1 receptor (S1P 1 R) directs the exit of T cells from the spleen into blood, and from lymph nodes and Peyer’s patches into lymph 3 . Here we show that S1P is essential not only for the circulation of naive T cells, but also for their survival. Using transgenic mouse models, we demonstrate that lymphatic endothelial cells support the survival of T cells by secreting S1P via the transporter SPNS2, that this S1P signals through S1P 1 R on T cells, and that the requirement for S1P 1 R is independent of the established role of the receptor in guiding exit from lymph nodes. S1P signalling maintains the mitochondrial content of naive T cells, providing cells with the energy to continue their constant migration. The S1P signalling pathway is being targeted therapeutically to inhibit autoreactive T cell trafficking, and these findings suggest that it may be possible simultaneously to target autoreactive or malignant cell survival 4 .

Microneedle patches provide an alternative to conventional needle-and-syringe immunisation, and potentially offer improved immunogenicity, simplicity, cost-effectiveness, acceptability, and safety. We describe safety, immunogenicity, and acceptability of the first-in-man study on single, dissolvable microneedle patch vaccination against influenza. The TIV-MNP 2015 study was a randomised, partly blinded, placebo-controlled, phase 1, clinical trial at Emory University that enrolled non-pregnant, immunocompetent adults from Atlanta, GA, USA, who were aged 18–49 years, naive to the 2014–15 influenza vaccine, and did not have any significant dermatological disorders. Participants were randomly assigned (1:1:1:1) to four groups and received a single dose of inactivated influenza vaccine (fluvirin: 18 μg of haemagglutinin per H1N1 vaccine strain, 17 μg of haemagglutinin per H3N2 vaccine strain, and 15 μg of haemagglutinin per B vaccine strain) (1) by microneedle patch or (2) by intramuscular injection, or received (3) placebo by microneedle patch, all administered by an unmasked health-care worker; or received a single dose of (4) inactivated influenza vaccine by microneedle patch self-administered by study participants. A research pharmacist prepared the randomisation code using a computer-generated randomisation schedule with a block size of 4. Because of the nature of the study, participants were not masked to the type of vaccination method (ie, microneedle patch vs intramuscular injection). Primary safety outcome measures are the incidence of study product-related serious adverse events within 180 days, grade 3 solicited or unsolicited adverse events within 28 days, and solicited injection site and systemic reactogenicity on the day of study product administration through 7 days after administration, and secondary safety outcomes are new-onset chronic illnesses within 180 days and unsolicited adverse events within 28 days, all analysed by intention to treat. Secondary immunogenicity outcomes are antibody titres at day 28 and percentages of seroconversion and seroprotection, all determined by haemagglutination inhibition antibody assay. The trial is completed and registered with ClinicalTrials.gov, number NCT02438423. Between June 23, 2015, and Sept 25, 2015, 100 participants were enrolled and randomly assigned to a group. There were no treatment-related serious adverse events, no treatment-related unsolicited grade 3 or higher adverse events, and no new-onset chronic illnesses. Among vaccinated groups (vaccine via health-care worker administered microneedle patch or intramuscular injection, or self-administered microneedle patch), overall incidence of solicited adverse events (n=89 vs n=73 vs n=73) and unsolicited adverse events (n=18 vs n=12 vs n=14) were similar. Reactogenicity was mild, transient, and most commonly reported as tenderness (15 [60%] of 25 participants [95% CI 39–79]) and pain (11 [44%] of 25 [24–65]) after intramuscular injection; and as tenderness (33 [66%] of 50 [51–79]), erythema (20 [40%] of 50 [26–55]), and pruritus (41 [82%] of 50 [69–91]) after vaccination by microneedle patch application. The geometric mean titres were similar at day 28 between the microneedle patch administered by a health-care worker versus the intramuscular route for the H1N1 strain (1197 [95% CI 855–1675] vs 997 [703–1415]; p=0·5), the H3N2 strain (287 [192–430] vs 223 [160–312]; p=0·4), and the B strain (126 [86–184] vs 94 [73–122]; p=0·06). Similar geometric mean titres were reported in participants who self-administered the microneedle patch (all p>0·05). The seroconversion percentages were significantly higher at day 28 after microneedle patch vaccination compared with placebo (all p<0·0001) and were similar to intramuscular injection (all p>0·01). Use of dissolvable microneedle patches for influenza vaccination was well tolerated and generated robust antibody responses. National Institutes of Health.

In drylands, the underlying vegetation structure is associated with ecosystem functioning and ecosystem resilience. Although scale‐dependent patterns are also predicted, empirical evidence often demonstrates that patch sizes are distributed according to a power‐law probability distribution function or truncated power‐law probability distribution function for a varied range of environmental conditions. Using satellite images and field measures, we assessed the spatial pattern of vegetation patches for a wide range of vegetation cover values in a large set of Mediterranean dryland (MDL) plots, focusing on the statistical distribution function that better fits the patch sizes. We found that power‐law or truncated power‐law probability distribution function does not always fit the observed patch size frequencies, while lognormal probability density function always fit well to them, implying that the vegetation structure is scale dependent for a large range of conditions. We show how the sampling approach, fit methods, and system dimensionality can affect the patch size distribution, which can explain some conflicting evidence obtained from the empirical data. Our findings question the robustness of criticality as the underlying mechanism driving vegetation patterns in MDLs. The better fit to patch size distribution provided by lognormal as compared with power‐law indicates that multiplicative effects of multivariate local influences underlie pattern formation, and suggests that the role of plant–plant facilitation can be overestimated for a large range of conditions.

HighlightsFactors affecting microneedle insertion into skin are reviewed.The use of artificial and computational skin models for the simulation of needle insertion is summarized.Skin structures and models, as well as mechanical analyses, used to determine transdermal microneedle ability to insert into skin are highlighted in the review.Transdermal microneedle (MN) patches are a promising tool used to transport a wide variety of active compounds into the skin. To serve as a substitute for common hypodermic needles, MNs must pierce the human stratum corneum (~ 10 to 20 µm), without rupturing or bending during penetration. This ensures that the cargo is released at the predetermined place and time. Therefore, the ability of MN patches to sufficiently pierce the skin is a crucial requirement. In the current review, the pain signal and its management during application of MNs and typical hypodermic needles are presented and compared. This is followed by a discussion on mechanical analysis and skin models used for insertion tests before application to clinical practice. Factors that affect insertion (e.g., geometry, material composition and cross-linking of MNs), along with recent advancements in developed strategies (e.g., insertion responsive patches and 3D printed biomimetic MNs using two-photon lithography) to improve the skin penetration are highlighted to provide a backdrop for future research.

The body naturally and continuously secretes sweat for thermoregulation during sedentary and routine activities at rates that can reflect underlying health conditions, including nerve damage, autonomic and metabolic disorders, and chronic stress. However, low secretion rates and evaporation pose challenges for collecting resting thermoregulatory sweat for non-invasive analysis of body physiology. Here we present wearable patches for continuous sweat monitoring at rest, using microfluidics to combat evaporation and enable selective monitoring of secretion rate. We integrate hydrophilic fillers for rapid sweat uptake into the sensing channel, reducing required sweat accumulation time towards real-time measurement. Along with sweat rate sensors, we integrate electrochemical sensors for pH, Cl − , and levodopa monitoring. We demonstrate patch functionality for dynamic sweat analysis related to routine activities, stress events, hypoglycemia-induced sweating, and Parkinson’s disease. By enabling sweat analysis compatible with sedentary, routine, and daily activities, these patches enable continuous, autonomous monitoring of body physiology at rest. Low secretion rates and evaporation pose challenges for collecting resting thermoregulatory sweat for non-invasive analysis of body physiology. Here the authors present wearable microfluidics-based patches for continuous sweat monitoring at rest that enable detection of pH, Cl − , and levodopa for dynamic sweat analysis related to routine activities, stress events, hypoglycemia-induced sweating, and Parkinson’s disease.

Despite our knowledge of the protective role of antibodies passed to infants through breast milk, our understanding of immunity transfer via maternal leukocytes is still limited. To emulate the immunological interface between the mother and her infant while breast-feeding, we used murine pups fostered after birth onto MHC-matched and MHC-mismatched dams. Overall, data revealed that: 1) Survival of breast milk leukocytes in suckling infants is possible, but not significant after the foster-nursing ceases; 2) Most breast milk lymphocytes establish themselves in specific areas of the intestine termed Peyer's patches (PPs); 3) While most leukocytes in the milk bolus were myeloid cells, the majority of breast milk leukocytes localized to PPs were T lymphocytes, and cytotoxic T cells (CTLs) in particular; 4) These CTLs exhibit high levels of the gut-homing molecules α4β7 and CCR9, but a reduced expression of the systemic homing marker CD62L; 5) Under the same activation conditions, transferred CD8 T cells through breast milk have a superior capacity to produce potent cytolytic and inflammatory mediators when compared to those generated by the breastfed infant. It is therefore possible that maternal CTLs found in breast milk are directed to the PPs to compensate for the immature adaptive immune system of the infant in order to protect it against constant oral infectious risks during the postnatal phase.

Single band-edge states can trap light and function as high-quality optical feedback for microscale lasers and nanolasers. However, access to more than a single band-edge mode for nanolasing has not been possible because of limited cavity designs. Here, we describe how plasmonic superlattices—finite-arrays of nanoparticles (patches) grouped into microscale arrays—can support multiple band-edge modes capable of multi-modal nanolasing at programmed emission wavelengths and with large mode spacings. Different lasing modes show distinct input–output light behaviour and decay dynamics that can be tailored by nanoparticle size. By modelling the superlattice nanolasers with a four-level gain system and a time-domain approach, we reveal that the accumulation of population inversion at plasmonic hot spots can be spatially modulated by the diffractive coupling order of the patches. Moreover, we show that symmetry-broken superlattices can sustain switchable nanolasing between a single mode and multiple modes. Arrays of nanoparticles grouped into microscale arrays support multiple nanolasing modes that can be tailored by changing the geometry of the superlattice.

By exploiting geometric constraints and interfacial forces instead of chemistry, colloidal clusters can be controllably coalesced into particles with uniformly distributed surface patches. Particle patching turned inside-out 'Patchy' particles are colloidal particles with patches, usually in predetermined geometries, on their surfaces. These patches can be used to directionally bond particles together or for other applications where different surface chemistries are valuable. Introducing patches in geometrically ordered locations on a spherical surface can involve multistep processes, potentially limiting the scale on which such particles can be made. Now Stefano Sacanna and colleagues have developed a method—'colloidal fusion'—that involves the controlled coalescence of colloidal clusters into a single particle. At the core of the original cluster is a plasticizable particle, which is extruded outwards to eventually form the patches on the final particle. The location of the patches is therefore defined and controlled by the packing geometry of the original cluster. Patches on the surfaces of colloidal particles 1 , 2 , 3 , 4 , 5 provide directional information that enables the self-assembly of the particles into higher-order structures. Although computational tools can make quantitative predictions and can generate design rules that link the patch motif of a particle to its internal microstructure and to the emergent properties of the self-assembled materials 6 , 7 , 8 , the experimental realization of model systems of particles with surface patches (or ‘patchy’ particles) remains a challenge. Synthetic patchy colloidal particles are often poor geometric approximations of the digital building blocks used in simulations 9 , 10 and can only rarely be manufactured in sufficiently high yields to be routinely used as experimental model systems 11 , 12 , 13 , 14 . Here we introduce a method, which we refer to as colloidal fusion, for fabricating functional patchy particles in a tunable and scalable manner. Using coordination dynamics and wetting forces, we engineer hybrid liquid–solid clusters that evolve into particles with a range of patchy surface morphologies on addition of a plasticizer. We are able to predict and control the evolutionary pathway by considering surface-energy minimization, leading to two main branches of product: first, spherical particles with liquid surface patches, capable of forming curable bonds with neighbouring particles to assemble robust supracolloidal structures; and second, particles with a faceted liquid compartment, which can be cured and purified to yield colloidal polyhedra. These findings outline a scalable strategy for the synthesis of patchy particles, first by designing their surface patterns by computer simulation, and then by recreating them in the laboratory with high fidelity.