Photothermal Conversion of the Oleophilic PVDF/Ti3C2Tx Porous Foam Enables Non-Aqueous Liquid System Applicable Actuator.

Various physical and chemical reaction processes occur in non-aqueous liquid systems, particularly in oil phase systems. Therefore, achieving efficient, accurate, controllable, and cost-effective movement and transfer of substances in the oil phase is crucial. Liquid-phase photothermal actuators (LPAs) are commonly used for material transport in liquid-phase systems due to their remote operability and precise control. However, existing LPAs typically rely on materials like hydrogels and flexible polymers, commonly unsuitable for non-aqueous liquids. Herein, a 3D porous poly(vinylidene fluoride) (PVDF)/Ti3C2Tx actuator is developed using a solvent displacement method. It demonstrates directional movement and controlled material transport in non-aqueous liquid systems. When subject to infrared light irradiation (2.0 W cm-2), the actuator achieves motion velocities of 7.3 and 6 mm s-1 vertically and horizontally, respectively. The actuator's controllable motion capability is primarily attributed to the foam's oil-wettable properties, 3D porous oil transport network, and the excellent photothermal conversion performance of Ti3C2Tx, facilitating thermal diffusion and the Marangoni effect. Apart from multidimensional directions, the actuator enables material delivery and obstacle avoidance by transporting and releasing target objects to a predetermined position. Hence, the developed controllable actuator offers a viable solution for effective motion control and material handling in non-aqueous liquid environments.

Precisely Controlled Polymerization of Two-Dimensional Conducting Polymers in Quasi-Liquid Layer Enables Ultrahigh Sensing Performance.

Gas sensors based on conducting polymers offer great potential for high-performance room temperature applications due to their cost-effectiveness, high-sensitivity, and operational advantage. However, their current performance is limited by the deficiency of control in conventional polymerization methods, leading to poor crystallinity and inconsistent material properties. Here, the quasi-liquid layer (QLL) on the ice surface acts as a self-regulating nano-reactor for precise control of thermodynamics and kinetics in the polymerization, resulting in a 7.62 nm thick two-dimensional (2D) polyaniline (PANI) film matching the QLL thickness. The ultra-thin film optimizes the exposure of active sites, enhancing the detection of analyte gases at low concentrations. It is validated by fabricating a chemiresistive gas sensor with the 2D PANI film, demonstrating stable room-temperature detection of ammonia down to 10 ppt in ambient air with an impressive 10% response. This achievement represents the highest sensitivity among sensors of this kind while maintaining excellent selectivity and repeatability. Moreover, the QLL-controlled polymerization strategy offers an alternative route for precise control of the polymerization process for conducting polymers, enabling the creation of advanced materials with enhanced properties.

Efficacy and Safety of Tofacitinib in Patients with Polymyalgia Rheumatica (EAST PMR): An open-label randomized controlled trial.

BACKGROUND: Polymyalgia rheumatica (PMR) is a common inflammatory disease in elderly persons whose mechanism of pathogenesis has not been elucidated. Glucocorticoids are the main first-line treatments but result in numerous side effects. Therefore, there is a need to explore pathogenetic factors and identify possible glucocorticoid-sparing agents. We aimed to study the pathogenetic features of the disease and assess the efficacy and safety of Janus tyrosine kinase (JAK)-inhibitor tofacitinib in patients with PMR. METHODS AND FINDINGS: We recruited treatment-naïve PMR patients from the First Affiliated Hospital, Zhejiang University School of Medicine, between September 2020 and September 2022. In the first cohort, we found that the gene expression patterns of peripheral blood mononuclear cells (PBMCs) in 11 patients (10 female, 1 male, age 68.0 ± 8.3) with newly diagnosed PMR were significantly different from 20 healthy controls (17 female, 3 male, age 63.7 ± 9.8) by RNA sequencing. Inflammatory response and cytokine-cytokine receptor interaction were the most notable pathways affected. We observed marked increases in expression of IL6R, IL1B, IL1R1, JAK2, TLR2, TLR4, TLR8, CCR1, CR1, S100A8, S100A12, and IL17RA, which could trigger JAK signaling. Furthermore, tofacitinib suppressed the IL-6R and JAK2 expression of CD4+T cells from patients with PMR in vitro. In the second cohort, patients with PMR were randomized and treated with tofacitinib or glucocorticoids (1/1) for 24 weeks. All PMR patients underwent clinical and laboratory examinations at 0, 4, 8, 12, 16, 20, and 24 weeks, and PMR activity disease scores (PMR-AS) were calculated. The primary endpoint was the proportion of patients with PMR-AS ≤10 at weeks 12 and 24. Secondary endpoints: PMR-AS score, c-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) at weeks 12 and 24. Thirty-nine patients with newly diagnosed PMR received tofacitinib, and 37 patients received glucocorticoid. Thirty-five patients (29 female, 6 male, age 64.4 ± 8.4) and 32 patients (23 female, 9 male, age 65.3 ± 8.7) patients completed the 24-week intervention, respectively. There were no statistically significant differences in primary or secondary outcomes. At weeks 12 and 24, all patients in both groups had PMR-AS <10. PMR-AS, CRP, and ESR were all significantly decreased in both groups. No severe adverse events were observed in either group. Study limitations included the single-center study design with a short observation period. CONCLUSIONS: We found that JAK signaling was involved in the pathogenesis of PMR. Tofacitinib effectively treated patients with PMR as glucocorticoid does in this randomized, monocenter, open-label, controlled trial (ChiCTR2000038253). TRIAL REGISTRATION: This investigator-initiated clinical trial (IIT) had been registered on the website (http://www.chictr.org.cn/, ChiCTR2000038253).

Metal Halides for High-Capacity Energy Storage.

High-capacity electrochemical energy storage systems are more urgently needed than ever before with the rapid development of electric vehicles and the smart grid. The most efficient way to increase capacity is to develop electrode materials with low molecular weights. The low-cost metal halides are theoretically ideal cathode materials due to their advantages of high capacity and redox potential. However, their cubic structure and large energy barrier for deionization impede their rechargeability. Here, the reversibility of potassium halides, lithium halides, sodium halides, and zinc halides is achieved through decreasing their dimensionality by the strong π-cation interactions between metal cations and reduced graphene oxide (rGO). Especially, the energy densities of KI-, KBr-, and KCl-based materials are 722.2, 635.0, and 739.4 Wh kg-1 , respectively, which are higher than those of other cathode materials for potassium-ion batteries. In addition, the full-cell with 2D KI/rGO as cathode and graphite as anode demonstrates a lifespan of over 150 cycles with a considerable capacity retention of 57.5%. The metal halides-based electrode materials possess promising application prospects and are worthy of more in-depth researches.

Coaxial Graphene/MXene Microfibers with Interfacial Buffer-Based Lightweight Distance Sensors Assisting Lossless Grasping of Fragile and Deformable Objects.

Lossless and efficient robotic grasping is becoming increasingly important with the widespread application of intelligent robotics in warehouse transportation, human healthcare, and domestic services. However, current sensors for feedback of grasping behavior are greatly restricted by high manufacturing cost, large volume and mass, complex circuit, and signal crosstalk. To solve these problems, here, we prepare lightweight distance sensor-based reduced graphene oxide (rGO)/MXene-rGO coaxial microfibers with interface buffer to assist lossless grasping of a robotic manipulator. The as-fabricated distance microsensor exhibits a high sensitivity of 91.2 m-1 in the distance range of 50-300 µm, a fast response time of 116 ms, a high resolution of 5 µm, and good stability in 500 cycles. Furthermore, the high-performance and lightweight microsensor is installed on the robotic manipulator to reflect the grasp state by the displacement imposed on the sensor. By establishing the correlation between the microsensing signal and the grasp state, the safe, non-destructive, and effective grasp and release of the target can be achieved. The lightweight and high-powered distance sensor displays great application prospects in intelligent fetching, medical surgery, multi-spindle automatic machines, and cultural relics excavation.

From 1D to 2D: Controllable Preparation of 2D Ni-MOFs for Supercapacitors.

Controllable modulation strategies between one-dimensional (1D) and two-dimensional (2D) structures have been rarely reported for metal-organic frameworks (MOFs). Here, 1D, 1D/2D, and 2D Ni-MOFs can be facilely prepared by adjusting the ratio of Ni2+ and the pyromellitic acid linker. A low-dimensional structure can shorten the transmission distance, while MOFs with a high Ni2+ content can supply rich active sites for oxidation-reduction reactions. The 2D structure Ni-MOF with an optimized Ni2+/pyromellitic acid ratio presents a good performance of 1036 F g-1 at a current density of 1 A g-1 with a comparable rate performance of 62% at 20 A g-1. The study may offer a facile design to control the structure of MOFs for employing in electrochemical energy storage.

Molecular evolution, diversification, and expression assessment of MADS gene family in Setaria italica, Setaria viridis, and Panicum virgatum.

KEY MESSAGE: This paper sheds light on the evolution and expression patterns of MADS genes in Setaria and Panicum virgatum. SiMADS51 and SiMADS64 maybe involved in the ABA-dependent pathway of drought response. The MADS gene family is a key regulatory factor family that controls growth, reproduction, and response to abiotic stress in plants. However, the molecular evolution of this family is rarely reported. Here, a total of 265 MADS genes were identified in Setaria italica (foxtail millet), Setaria viridis (green millet), and Panicum virgatum (switchgrass) and analyzed by bioinformatics, including physicochemical characteristics, subcellular localization, chromosomal position and duplicate, motif distribution, genetic structure, genetic evolvement, and expression patterns. Phylogenetic analysis was used to categorize these genes into M and MIKC types. The distribution of motifs and gene structure were similar for the corresponding types. According to a collinearity study, the MADS genes have been mostly conserved during evolution. The principal cause of their expansion is segmental duplication. However, the MADS gene family tends to shrink in foxtail millet, green millet, and switchgrass. The MADS genes were subjected to purifying selection, but several positive selection sites were also identified in three species. And most of the promoters of MADS genes contain cis-elements related to stress and hormonal response. RNA-seq and quantitative Real-time PCR (qRT-PCR) analysis also were examined. SiMADS genes expression levels are considerably changed in reaction to various treatments, following qRT-PCR analysis. This sheds fresh light on the evolution and expansion of the MADS family in foxtail millet, green millet, and switchgrass, and lays the foundation for further research on their functions.

Imaging performance of a mid-infrared metalens with a machining error.

Metalenses exhibit excellent performance as a new type of optical element; mid-infrared devices based on metalenses are advantageous to numerous applications in biomedical, military and industrial fields. The demand for large-area and high-efficiency mid-infrared metalenses has increased in recent years. However, the current processing methods for metalens production introduce different types of processing errors. Therefore, qualitative analyses of various errors that may exist in the processing of metalenses should be performed. In this study, we use the finite-difference time-domain calculation method and introduce various typical errors into a transmission phase-based mid-infrared metalens for simulation and analysis. The simulation results show that the defects caused by these processes affect focusing efficiency, and that some defects affect the quality of light. Subsequently, we prepare a metalens within the allowable error range and test its optical performances. The experiment confirms the excellent imaging performance of our metalens. Our study can help manufacturers identify defects to improve manufacturing processes, thereby enabling the incorporation of metalenses in industrial applications.

Observation on the clinical efficacy of external ventricular drain combined with intraventricular urokinase injection and intravenous piracetam in the treatment of intraventricular hemorrhage.

Objective: To observe the clinical efficacy of external ventricular drain combined with intraventricular urokinase injection and intravenous piracetam in the treatment of intraventricular hemorrhage. Methods: A randomized controlled trial was used in this study conducted at Baoding First Central Hospital, China from January 2017 to December 2019. Sixty patients with intraventricular hemorrhage were randomly divided into two groups. Patients in the control group were treated with external ventricular drain, while patients in the experimental group were given intraventricular urokinase injection and intravenous piracetam on the basis of the control group. The incidence of adverse drug reactions, hospitalization time, hematoma elimination time, and drainage tube removal time in two groups were compared and analyzed including the cerebrospinal fluid protein content, changes in GCS score, neurological function recovery (ADL score), and Glasgow outcome scale (GOS) of the two groups after treatment. Results: The hematoma elimination time, drainage tube removal time and hospitalization time of the experimental group were shorter than those of the control group, with a statistically significant difference (P<0.05). After treatment, compared with the control group, the protein content of cerebrospinal fluid in the experimental group decreased more significantly (P=0.00), the GCS score was higher (P=0.00), the overall good rate of neurological function was higher (P=0.04), while the rate of good prognosis was higher (P=0.03). Within one month of treatment, the incidence of surgical complications in experimental group was significantly lower than that in control group (P=0.04). Conclusions: External ventricular drain combined with intraventricular urokinase injection and intravenous piracetam is an effective method for the treatment of intraventricular hemorrhage, which is worthy of clinical promotion.

Highly Selective Wearable Smartsensors for Vapor/Liquid Amphibious Methanol Monitoring.

A wearable screen-printed electrochemical smartsensor with excellent selectivity for methanol quantification has been developed. This smartsensor consists of a printable sensing system modified with platinum (Pt) confined in a reduced graphene oxide (rGO) matrix, as well as a compact electronic interface for data collection. The real-time electrochemical signal from methanol could be remotely detected and transmitted to a smartphone by blue tooth. It performs good environmental adaptability of vapor/liquid amphibious behaviors. Owing to the uniform distribution of Pt loading on the rGO nanosheets, this sensor demonstrates high selectivity, sensitivity, stability, and recoverability both in vapor and liquid during temperature or humidity diversification, compared with other resistance-based sensors. It also achieves good bending and stretching performance, and it could be a possible candidate device for the quantification of methanol in different environments.

Size-tunable, highly sensitive microelectrode arrays enabled by polymer pen lithography.

By combining polymer pen lithography (PPL) patterning with in situ polymerization, we report a straightforward and bottom-up approach for bench-top fabrication of microelectrode arrays (MEAs) with well-controlled dimensions. The as-fabricated MEAs can be used to electrodeposit prussian blue in situ and work as a biosensor for H2O2 with a detection limit as low as 5 nM at a sensitivity of 0.7 A cm-2 M-1.

Unlocking the Electrocatalytic Activity of Antimony for CO2 Reduction by Two-Dimensional Engineering of the Bulk Material.

Two-dimensional (2D) materials are known to be useful in catalysis. Engineering 3D bulk materials into the 2D form can enhance the exposure of the active edge sites, which are believed to be the origin of the high catalytic activity. Reported herein is the production of 2D "few-layer" antimony (Sb) nanosheets by cathodic exfoliation. Application of this 2D engineering method turns Sb, an inactive material for CO2 reduction in its bulk form, into an active 2D electrocatalyst for reduction of CO2 to formate with high efficiency. The high activity is attributed to the exposure of a large number of catalytically active edge sites. Moreover, this cathodic exfoliation process can be coupled with the anodic exfoliation of graphite in a single-compartment cell for in situ production of a few-layer Sb nanosheets and graphene composite. The observed increased activity of this composite is attributed to the strong electronic interaction between graphene and Sb.

Tunable Fabrication of Molybdenum Disulfide Quantum Dots for Intracellular MicroRNA Detection and Multiphoton Bioimaging.

Molybdenum disulfide (MoS2 ) quantum dots (QDs) (size <10 nm) possess attractive new properties due to the quantum confinement and edge effects as graphene QDs. However, the synthesis and application of MoS2 QDs has not been investigated in great detail. Here, a facile and efficient approach for synthesis of controllable-size MoS2 QDs with excellent photoluminescence (PL) by using a sulfuric acid-assisted ultrasonic route is developed for this investigation. Various MoS2 structures including monolayer MoS2 flake, nanoporous MoS2 , and MoS2 QDs can be yielded by simply controlling the ultrasonic durations. Comprehensive microscopic and spectroscopic tools demonstrate that the MoS2 QDs have uniform lateral size and possess excellent excitation-independent blue PL. The as-generated MoS2 QDs show high quantum yield of 9.65%, long fluorescence lifetime of 4.66 ns, and good fluorescent stability over broad pH values from 4 to 10. Given the good intrinsic optical properties and large surface area combined with excellent physiological stability and biocompatibility, a MoS2 QDs-based intracellular microRNA imaging analysis system is successfully constructed. Importantly, the MoS2 QDs show good performance as multiphoton bioimaging labeling. The proposed synthesis strategy paves a new way for facile and efficient preparing MoS2 QDs with tunable-size for biomedical imaging and optoelectronic devices application.

Suppression of AcMNPV replication by adf and thymosin protein up-regulation in a new testis cell line, Ha-shl-t.

Host cytoskeletons facilitate the entry, replication, and egress of viruses because cytoskeletons are essential for viral survival. One mechanism of resisting viral infections involves regulating cytoskeletal polymerization/depolymerization. However, the molecular mechanisms of regulating these changes in cytoskeleton to suppress viral replication remain unclear. We established a cell line (named Ha-shl-t) from the pupal testis of Helicoverpa armigera (Lepidoptera: Noctuidae). The new testis cell line suppresses Autographa californica multiple nucleocapsid nucleopolyhedrovirus (AcMNPV) replication via disassembly of cytoskeleton. Up-regulation of thymosin (actin disassembling factor) and adf (actin depolymerizing factor) reduces F-actin. Silencing thymosin or adf or treating cells with the F-actin stabilizer phalloidin led to increased AcMNPV replication, while treating cells with an F-actin assembly inhibitor cytochalasin B decreased viral replication. We infer that Ha-shl-t cells utilize F-actin depolymerization to suppress AcMNPV replication by up-regulating thymosin and adf. We propose Ha-shl-t as a model system for investigating cytoskeletal regulation in antiviral action and testicular biology generally.

Lighting the way to sustainable development: Physiological response and light control strategy in microalgae-based wastewater treatment under illumination.

The Sustainable Development Goals link pollutant control with carbon dioxide reduction. Toward the goal of pollutant and carbon reduction, microalgae-based wastewater treatment (MBWT), which can simultaneously remove pollutants and convert carbon dioxide into biomass with value-added metabolites, has attracted considerable attention. The photosynthetic organism microalgae and the photobioreactor are the functional body and the operational carrier of the MBWT system, respectively; thus, light conditions profoundly influence its performance. Therefore, this review takes the general rules of how light influences the performance of MBWT systems as a starting point to elaborate the light-influenced mechanisms in microalgae and the light control strategies for photobioreactors from the inside out. Wavelength, light intensity and photoperiod solely or interactively affect biomass accumulation, pollutant removal, and value-added metabolite production in MBWT. Physiological processes, including photosynthesis, photooxidative damage, light-regulated gene expression, and nutrient uptake, essentially explain the performance influence of MBWT and are instructive for specific microalgal strain improvement strategies. In addition, light causes unique reactions in MBWT systems as it interacts with components such as photooxidative damage enhancers present in types of wastewater. In order to provide guidance for photobioreactor design and light control in a large-scale MBWT system, wavelength transformation, light transmission, light source distribution, and light-dark cycle should be considered in addition to adjusting the light source characteristics. Finally, based on current research vacancies and challenges, future research orientation should focus on the improvement of microalgae and photobioreactor, as well as the integration of both.

Adaptive decision support model for sustainable transport system using fuzzy AHP and dynamical Dijkstra simulations.

Concerning decisions for modern public transportation project, the lack of consensus between stakeholders and foreseeability of future transportation requirements might cause poor sustainability of the project. Unfortunately, many decision models give decision opinions without the test of the sustainability. Therefore, a dynamical Dijkstra simulation model is proposed to simulate the real traffic flows. In the model, the cost of the road connections is dynamically updated according to the change of the passenger flows. Then a combined decision support model using fuzzy AHP and dynamical Dijkstra simulation tests is designed. The combined model is capable of analyzing and creating consensus among different stakeholder participants in a transport development problem. The application of FAHP and dynamical Dijkstra ensures that the consensus creation is not only based on the FAHP decision making process but also on the response of the simulated execution of the decisions by dynamical Dijkstra. Thus, the decision makers by FAHP can firstly make their initial preferences in transportation planning, given the pairwise comparison matrices and generate the related weight for the traffic control parameters. And the dynamical Dijkstra simulations test the plan's setting and gives a response to iteratively adjust the FAHP matrices and parameters. The combined model is tested in different scenarios. And the results show that by the application of the proposed model, decision-makers can be more aware of the conflicts of interests among the involved groups, and they can pay more attention to possible violations causing by the change of traffic environment, including the citizen numbers, the construction cost, the roll cost, and etc., to get a more sustainable plan.

Elderly-onset rheumatoid arthritis vs. polymyalgia rheumatica: Differences in pathogenesis.

Rheumatoid arthritis is a chronic autoimmune disease that mainly affects the facet joints. Elderly-onset rheumatoid arthritis appears to exhibit symptoms similar to those of polymyalgia rheumatica, characterized by morning stiffness and pain in the shoulder and hip joints. Both diseases develop in the elderly, and it is sometimes challenging to distinguish them. Here, we identify the differences in pathogenesis between elderly-onset rheumatoid arthritis and polymyalgia rheumatica to assist with a clear differential diagnosis and effective early intervention.

Controllable Degradation of Polyurethane Thermosets with Silaketal Linkages in Response to Weak Acid.

Polyurethane (PU) thermosets offer great favors to our daily life on account of their excellent mechanical, physical, and chemical properties as well as appreciable biocompatibility. Nevertheless, PU waste is increasingly causing environmental and health-related problems as it is mostly resistant to chemical degradation under mild conditions. Herein, we report a kind of PU thermoset with silaketal leakages in its main chains to enable polymer degradation in response to weak acids, even in edible vinegar. The degradation rate is significantly influenced by the alkyl substituents on the silicon atoms, with entire degradation in hours, days, weeks, or months. Besides controllable degradation, investigations are also provided into the recycling of PU thermosets by means of thermal reprocessing based on carbamate bond exchange or repolymerization of degradation residuals. Because of the controllable degradation and easy recycling, this particular kind of PU thermoset exhibits great potential in manufacturing green polymer products that can be decomposed by nature or reutilized after disposal.

Facile patterning of reduced graphene oxide film into microelectrode array for highly sensitive sensing.

In this study, we develop a new technique to fabricate a reduced graphene oxide (rGO)-based microelectrode array (MEA) with low-cost soft lithography. To prepare patterned rGO, a polydimethylsiloxane (PDMS) mold with an array of microwells on its surface is fabricated using soft lithography, and GO is assembled on an indium tin oxide (ITO) electrode with a layer-by-layer method. The rGO pattern is formed by closely contacting the assembled GO film onto the ITO electrode with the PDMS mold filled with hydrazine solution in the microwells to selectively reduce the localized GO into the rGO. The MEA with patterned rGO as the microelectrode is characterized with Kelvin probe force microscopy (KFM), atomic force microscopy (AFM), and cyclic voltammetry (CV) with ferricyanide in aqueous solution as the redox probe. The KFM and AFM results demonstrate that each rGO pattern prepared under the present conditions is 3 µm in diameter, which is close to that of the PDMS mold we use. The CV results show that the rGO patterned onto the ITO exhibits a sigmoid-shaped voltammogram up to 200 mVs(-1) with a microampere level current response, suggesting that the rGO-based electrode fabricated with soft lithography behalves like a MEA. To demonstrate the potential electroanalytical application of the rGO-based MEA, prussian blue (PB) is electrodeposited onto the rGO-based MEA to form the PB/rGO-based MEA. Electrochemical studies on the formed PB/rGO-based MEA reveal that MEA shows a lower detection limit and a larger current density for the detection of H(2)O(2), as compared with the macroscopic rGO electrode. The method demonstrated here provides a simple and low-cost strategy for the fabrication of graphene-based MEA that are useful for electroanalytical applications.

Reduced Graphene Oxide-Polypyrrole Aerogel-Based Coaxial Heterogeneous Microfiber Enables Ultrasensitive Pressure Monitoring of Living Organisms.

Pressure sensors for living organisms can monitor both the movement behavior of the organism and pressure changes of the organ, and they have vast perspectives for the health management information platform and disease diagnostics/treatment through the micropressure changes of organs. Although pressure sensors have been widely integrated with e-skin or other wearable systems for health monitoring, they have not been approved for comprehensive surveillance and monitoring of living organisms due to their unsatisfied sensing performance. To solve the problem, here, we introduce a novel structural design strategy to manufacture reduced graphene oxide-polypyrrole aerogel-based microfibers with a typical coaxial heterogeneous structure, which significantly enhances the sensitivity, resolution, and stability of the derived pressure microsensors. The as-fabricated pressure microsensors exhibit ultrahigh sensitivities of 12.84, 18.27, and 4.46 kPa-1 in the pressure ranges of 0-20, 20-40, and 40-65 Pa, respectively, high resolution (0.2 Pa), and good stability in 450 cycles. Furthermore, the microsensor is applied to detect the movement behavior and organic micropressure changes for mice and serves as a platform for monitoring micropressure for the integrative diagnosis both in vivo and in vitro of organisms.