To conclude, there are three thematic policy conditions that are significant to AMR policy advocacy and implementation: committed personal championship, institutionalization of policies, and social norms facilitate AMR policy advocacy and implementation.Antimicrobial resistance (AMR) fundamentally weakens societal foundations economically and in health care. The development of well-considered policies against AMR is important. However, in many places, AMR policy implementation remains elusive. This study aims to identify enablers and deterrents as well as processes and conditions in AMR policy advocacy. It also aims to identify AMR implementation conditions where AMR national policies are adopted and, to a certain extent, formulated and implemented. This study adopts qualitative research methodology and applies the Grounded Theory Framework to identify thematic findings from interviews conducted in China, Japan, Norway, the United Kingdom (UK), and the United States of America (US). It was identified that AMR policy protagonists are critical to filtering AMR issues and identifying policies “fit to prioritize” and “fit to implement”. They have helped move policy prioritization needles in the UK and the US and engaged in diplomatic efforts in the UK. In these cases, no clientelism was considered. In the US, protagonists who talked to the right decision-makers in the right office at the right time both moved AMR issues from individuals to institutional agenda and from social norms to policy agenda.  COVID-19 has compellingly made the case that certain threats of infectious diseases can not only harm individuals directly but undermine the functioning of countries. Similar to severe pandemics, antimicrobial resistance (AMR) has the potential to fundamentally weaken societal foundations . Due to In past years, countries have strived to formulate AMR policies based on evidence, data, and scientific consensus on AMR transmission pathways, contributing practices, and conditions ,11,12. HTo address the question, we conducted a qualitative study to identify some of the enablers and deterrents and the processes and conditions. These variables affect AMR policy agenda-setting and advocacy among selected countries where AMR national policies are adopted and, to a certain extent, administrated. The narrative is identified so other countries might use some of the lessons and advance their own policies. Informants are purposefully recruited based on their roles centering on antimicrobial resistance and their policy representation in public services, public health, human health care, food–animal agriculture, pharmaceuticals, and the environmental sectors. A total of 34 open-ended, semi-structured, in-depth interviews were conducted. Interview coding and thematic development were conducted according to grounded theory ,20,21,22For clarity and comprehensiveness of the study, interviews were conducted based on a 30-item checklist that was established from the AMR-Intervene and AMR-PACT policy variables  23,24].,24.23,24A total of 34 interviews were conducted from 2019 to 2020 . OverallOf all informants, 12 interviewees are policy advisors to national action plans or personally champion the AMR agenda at ministerial or diplomatic levels. Fifteen interviewees are policy advisors to sub-national policy implementation. Sixteen interviewees are technocrats on AMR steering committees, policy representatives in agriculture, and human health care professional bodies. Six interviewees are bureaucrats in AMR leadership roles who formulate or adopt AMR policies. A summary of grounded theory theme-based and country-based key findings is listed in Individual champions were pivotal to advocate, initiate, and implement AMR policies. These AMR policy protagonists generated awareness, used bureaucratic ties, and lobbied decision-makers to raise the profile of AMR on the agenda based on personal, professional, public health, and social responsibilities. The success of these individual champions in shaping policy depended on access to key decision-makers in Norway, the US, and the UK. Policy advocacy on AMR was most successful when coupled with institutional and bureaucratic buy-in, bottom-up social norm support, and multistakeholder partnerships. By contrast, the lack of unified social norms on seeing antimicrobials as a common good gave a weaker voice to changing or prioritizing AMR on agendas in Japan and China. Some of these personal efforts had gone as far as directly changing national policy prioritization, overcoming diplomatic gridlock, and in some cases sustaining AMR policies in the long term. In Japan and China, AMR policy protagonists agreed that AMR policymaking would benefit from international support on technical and policy capacity building. In China, AMR policy personal champions were mostly technical advisors who have tried but were not able to directly influence key political decision making at national or sub-national levels. Alternatively, the absence might simply be due to the marked separation between the political and public health spheres All interviewees who were AMR policy protagonists found implementation of AMR policies challenging. Public health, medical, and policy experts who were able to influence policymakers indicated their frustration of failing to foresee or bridge the gap between prioritizing AMR policy at national levels and the implementation of policies at sub-national and sectoral levels. Interviewees from the UK, the US, Norway, China, and Japan recalled their actions during policy advocacy and that there was “little consideration” to see beyond the initial stage of the initiation of the policy process. Other UK policy experts emphasized anticipating conditions for policy implementation was just as important as policy initiation. The interviewees opined that the consequences of such gaps lead to failure to provide the needed infrastructure, resources, and governance for AMR policy implementation. Interview quotes are included as 2.1.1 to 2.1.4 in AMR policy protagonists who were allowed to advise policy at stages of policy initiation and formulation helped converge public, professional, and policy perspectives. They introduced or recombined relevant information, especially in the case of policy initiation impasse . DiffereComparatively, there were specific policymaking considerations within China and Japan. We found two distinct patterns in policy advocacy and implementation. First, interviewees from China and Japan—though some were considered by their countries as experts—described fewer links between technocrats and those that were politically powerful to influence policies. It was even less common for these individuals to have experience or access to political nexuses or to negotiate for diplomatic support. Overall, personal championship indicated a more important role in the UK and the US than in Japan or China. It appeared that it was uncommon culturally and socially in China or Japan to confer an important advisory role to an individual outside of established political structures. Most individuals interviewed in China and Japan had tried to reach or influence AMR policy decision making. Most interviewees from these countries also described a lack of political interest and political commitment as one of the major obstacles to the implementation of AMR policies. Interviewees from China and Japan opined that international peers were an important source of leadership to advocate and implement AMR policies.Personal championship was an essential enabler in AMR policy advocacy and also for maintaining long-term policy commitment. In some cases, reduced involvement from an individual champion was associated with a loss of AMR policy continuity. In cases when personal champions played a key role in the adoption of AMR policies by bureaucracies without institutionalization, lack of institutional memory was prominent in some countries. This lack of institutional memory continued to revert AMR policies to their earlier stages. For instance, during the discussion of AMR policy implementation in China, interviewees observed that individuals who led the AMR work often engage in endogenous effort and resources to influence guidelines and stewardship programs at the implementation phase and settings. However, the implementation and policy fidelity were individual-dependent and therefore more likely to be inconsistent. In the US, a change of political leadership led to AMR policy deprioritization. This emphasized the issue of long-term commitment to addressing AMR. Interview quotes are included as 2.2.1 to 2.2.3 in Interviewees suggested that prioritization and resource commitment on AMR need to transition from personal advocacy to institutionalization. Personal advocacy was much more prominent in the UK and the US than in Japan and China. Among these four countries, a commonality underpinned the ultimate implementation of policies—an individual or individuals from hospitals, farming, community pharmacies, public service systems, medical systems, and government offices stepped up endogenously, or in other cases followed through with their jobs. Interviewees opined AMR governance around organizational collaboration, orchestration, establishment, and enforcement of policies, guidelines, and regulations was built on personal investment and motivation rather than well-defined institutional processes. These findings stood in contrast with findings from Norway, which were indicated to be incorporated and institutionalized AMR policies based on their existing governance and administration capacity rather than by relying on individual champions.The example of Norway illustrated some of the factors that were important in supporting countries’ effective capacity to address AMR. Interviewees described sustained cross-sectoral collaboration to address AMR, which was based on a mutual understanding of its significance for local and global health and could use well-established infrastructure and political instruments. In Norway, AMR control, according to experts from both the public health sector and the veterinary sector, was seen as a core part of infectious disease control, food safety, and zoonotic disease prevention. Well-established cooperation among human, animal, and food sectors at government and non-government offices also helped AMR policy development. As a result, the governance, infrastructure, and cross-sectoral relationships provided the backbone for AMR policies. By comparison, interviews in the US, the UK, Japan, and China indicated a lower level of support for collaborative governance and policy prioritization to institutionalize which usually takes time and resources.Protagonists opined that economic and financial incentivization to increase antimicrobial innovation and reduce antimicrobial use was still very much in the hands of private industries. For antibiotic innovations, there were non-profit mechanisms such as Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) and Global Antibiotic Research & Development Partnership (GARDP) which brought new antibiotics to market . HoweverWithout social norms, interviewees opined that financial direction among antimicrobial users ultimately overrode the protagonists’ influences—be that antimicrobial stewardship, antimicrobial production quality control, or pharmaceutical innovation. Interviewees emphasized that local social norms such as patient antibiotics use compliance, food-producing animal farming industrial practices, and consumers’ willingness to pay for antibiotics-free food influenced antimicrobial use. For instance, interviews from Norway confirmed strong social values and norms to protect public health as a key determinant behind AMR policy advocacy. Additionally, the younger generation was perceived to be the next social norm to facilitate prudent antimicrobial use in China. On the contrary, an interview in Japan provided insight that perceived hurt to national economics has driven social norm and policymakers to side with softer or different policies. Interview quotes are included as 2.3.1 to 2.3.7 in Variables that influence policy protagonists and AMR policy advocacy and implementation can be categorized as three levels of micro-, meso-, and macro-determinants . PersonaWe identified commonalities and variations in policymaking that are pertinent to the design and implementation of effective and sustainable AMR policies. First, AMR policy requires resources and planning, especially for implementation, which has proved to be a challenge in many countries. Though initiation and advocacy of policies were described, most countries either did not factor in or found out that they underestimated the amount of resources needed to successfully implement the policies in their action plans. Second, personal championship works well to advocate AMR policies in the respective cultures and societies of the US and the UK. However, individual champions from China and Japan do not appear to have equal success in advocating for policy change. Rather, Japan and China’s AMR policy advocacy benefits from strong international leadership and symbolic policy advocacy. Third, AMR policymaking is challenging in a public health network and social norm which are not ready to pull together politically and economically sustainable AMR efforts. Rather than relying solely on the private market for antibiotics innovation or stewardship, public–private partnerships and social norms are needed to overcome economic systems that are less developed in considering AMR as a public health entity.Policies for AMR are still at an early level of development in some countries for several reasons—in countries where individual championship is viewed with skepticism, policy development and implementation have often stalled and are not yet incorporated into bureaucratic structures and processes. For policy advocacy that relies on international and national peer influences, policies drafted and programmed were not given sufficient in situ consideration to tailor to sub-national and sector contexts. For policies that landed without infrastructure and governance, AMR advocacy was perceived to be a waste of political credit or time.Our article had several limitations. The first was the difficulty to recruit policy protagonists and decision-makers, especially in China and Japan. The narrative from decision makers in AMR policy development remained limited in these two countries. The second limitation was to recruit sufficient representation in face of the separation of technical protagonists and political decision-makers. The third limitation was interview variation that could occur with different interviewers’ office positions in different countries. Despite these limitations, three key points can be considered in some countries around AMR policy advocacy. First, public health offices should involve leaders in the field to ensure existing policies are being effectively implemented. Policymakers should engage these technical and policy protagonists to answer AMR policy questions because protagonists can help share the burden of policy decisions, fine-tune policy drafting, and help campaign for AMR policy implementation. Second, public offices can focus on policymaking at governance and infrastructure building, transitioning protagonists’ recommendations to sub-national levels, and focusing on institutionalizing AMR policymaking. Third, social norms are an important variable for policy advocacy and resource commitment in policy implementation. Countries were included for their diverse contexts, different policy advocacy processes, and policy processes around AMR national policies. Interviewers were key collaborators  who were invited to participate in this study because of their experiences and work in antimicrobial resistance policies. Training and interview guidance was provided to all interviewers. Interviews were piloted in Norway and China. Interviews were conducted in China  (September 2018 to November 2019), Norway , Japan , the United Kingdom , and the United States . Interviewees were individuals with track records of influencing AMR policies in China, Japan, Norway, the UK, and the US. Interviewees were primarily selected by knowledge of individuals’ expertise and their influences on AMR policies . FurtherFor interview planning and clarity, the core questions list and policy variables were developed from the AMR-IMPACT and AMR-Intervene frameworks . Face-toAll audio files were transcribed verbatim to Word documents. Familiarization with data was conducted by researchers listening to audio recordings (O.S.K.C. and P.L.) and reading interview transcripts (O.S.K.C. and P.L.). Transcribed interviews were imported into qualitative analysis software ATLAS-ti 8.4.25 (ATLAS ti Scientific Software Development GmbH. version 8) for analysis and codebook development. All identities of informants were delinked from the transcripts from the coding stage onwards.Researchers read recursively and iteratively among data, codes, and themes for constant comparison. All codes were sets of pre-designated English letters and Roman numerals simplified from variables designated in AMR-PACT and AMR-Intervene ,24. All Though individual championships, or “principal coalition actors” according to the Advocacy Coalition Framework ,38, are


Currently, cancer chemotherapeutic drugs still have the defects of high toxicity and low bioavailability, so it is critical to design novel drug release systems for cancer chemotherapy. Here, we report a method to fabricate electrospun drug-loaded organic/inorganic hybrid nanofibrous system for antitumor therapy applications. In this work, rod-like attapulgite (ATT) was utilized to load a model anticancer drug doxorubicin (DOX), and mixed with poly(lactic-co-glycolic acid) (PLGA) to form electrospun hybrid nanofibers. The ATT/DOX/PLGA composite nanofibers were characterized through various techniques. It is feasible to load DOX onto ATT surfaces, and the ATT/DOX/PLGA nanofibers show a smooth and uniform morphology with improved mechanical durability. Under neutral and acidic pH conditions, the loaded DOX was released from ATT/DOX/PLGA nanofibers in a sustained manner. In addition, the released DOX from the nanofibers could significantly inhibit the growth of tumor cells. Owing to the significantly reduced burst release profile and increased mechanical durability of the ATT/DOX/PLGA nanofibers, the designed organic–inorganic hybrid nanofibers may hold great promise as a nanoplatform to encapsulate different drugs for enhanced local tumor therapy applications. Electrospinning is a straightforward and universal nanomanufacturing technology for producing ultralong nanofibers with adjustable diameters ranging from several nanometers to microns ,2,3,4,5.Conventional ,37,38, cOur previous work has indicated that drug-loaded halloysite nanotubes (HNTs) ,49, lapoAttapulgite (ATT) is a type of naturally mined clay that is cost-effective and shows large specific surface, high porosity, and high surface activity as well as good biocompatibility ,53,54. Din vitro anticancer treatment applications.Here, DOX-loaded ATT was used to dope PLGA nanofibers to slow down the speed of drug release and enhance the mechanical durability of the nanofibers for enhanced local tumor therapy applications. Firstly, DOX was loaded on the ATT surface through physical adsorption, followed by mixing with PLGA solution for the preparation of electrospun nanofibers. Various analysis techniques were utilized to characterize the ATT/DOX/PLGA nanofibers. The DOX release manner of the ATT/DOX/PLGA nanofibers was evaluated by UV-vis spectroscopy under different pH conditions, and the antiproliferative activity was evaluated by resazurin reduction assay and phase contrast microscopic morphology observation. To our knowledge, this is the first report on the development of ATT-doped PLGA nanofibers with desirable drug release speed and mechanical durability for ATT water solution with different concentrations  and DOX water solution (2 mg/mL) were prepared at room temperature. Then equal amounts of ATT and DOX solutions were fully mixed and magnetically stirred in the dark at room temperature for 24 h. The mixture was centrifugated for 5 min at 5000 rpm and washed by water to produce the ATT/DOX complexes.The formed ATT/DOX complexes were then mixed with PLGA solution before electrospinning. For comparison, an equal amount of ATT (4 wt% to PLGA) or DOX (0.5 wt% to PLGA) was added to PLGA solution and magnetically stirred for 2 h before electrospinning. The procedure of formulation of electrospun nanofibers was similar to our previous reports ,52. The 2 incubator for 24 h at 37 °C. The release medium of each well was collected for evaluation of in vitro antiproliferative activity.A certain quantity of experimental and control samples was weighed, and all samples underwent UV sterilization overnight. All the samples were placed in a 6-well cell culture plate, and about 2 mL of 75% alcohol was added to soak and disinfect for 5 min, while UV irradiation was carried out for sterilization. Then, the alcohol was sucked out and each well was washed with PBS three times. We then added an appropriate volume of RPMI 1640 medium into each well , and placed the cell culture plates in a CO5 cells/mL was prepared, and 20 μL was added to a 96-well plate, so that the plating density of CAL 72 cells was 2 × 103 cells/well. Samples used for testing were: 100, 50, 20, or 10 μL fresh medium, free DOX solution ([DOX] = 200 μg/mL), ATT/DOX solution ([DOX] = 200 μg/mL), ATT particle solution with equivalent concentration of the ATT/DOX complexes, and immersion medium of the nanofibers of DOX/PLGA ([DOX] = 200 μg/mL according to theoretic DOX loading within the fibers), PLGA with equivalent DOX concentration of the release medium of DOX/PLGA, ATT/PLGA with equivalent DOX concentration of the release medium of DOX/PLGA, and ATT/DOX/PLGA ([DOX] = 200 μg/mL according to theoretic DOX loading within the fibers). The total volume was added to 200 μL/well using fresh medium. Each sample and concentration gradient were stored six parallel, and the samples were shaken well and then cultured in an incubator. The initial concentration of DOX is 200 μg/mL, so the concentration gradients after dilution were 100, 50, 20 and 10 μg/mL, respectively. After one day of culture at 37 °C and 5% CO2, the original medium was discarded, and 180 μL fresh medium and 20 μL resazurin solution added into each well (0.1 mg/mL dissolved in PBS and filtered for sterilization). Four hours after re-culture, cell viability was detected by a microplate reader . Meanwhile, the morphology of the treated cancer cells was observed by an inverted optical microscope .Cell suspension with a density of 1 × 10–1 were the O-H stretching vibration of water in ATT. The absorption band at 1654 cm–1 was the bending vibration of absorbed and zeolitic water in channels [–1 were the fingerprints of fibrous clay minerals  [−1 were assigned to the bending vibrations of the N-H of loaded DOX, and the peaks at 1414 cm−1 might be attributed to the in-plane stretching vibrations of the C–C single bond skeleton of DOX  ,60. For n of DOX a. Compar001 cm−1 b and ATTcm−1 (−1 a. These X-ray diffraction (XRD) was used to observe the crystalline structure of ATT before and after DOX loading . The chaThe loading of DOX onto the ATT surfaces was also studied by UV−vis spectroscopy. As shown in The DOX-loaded ATT was incorporated within PLGA nanofibers by electrospinning to form the ATT/DOX/PLGA composite nanofibers. The ATT/DOX/PLGA nanofibers were characterized by TEM and fluorescence microscopic imaging. TEM images of the ATT/DOX complexes showed that the DOX loading onto the surface of the ATT had no obvious impact on the morphology of the ATT, as compared to free ATT  Figure . The shaSimilar to our previous studies ,52, the The surface hydrophilicity of nanofibers is critical for their interaction with cells. We studied the effects of ATT and ATT/DOX incorporation on the surface hydrophilicity of PLGA nanofibers . The conNotably, the mechanical properties of PLGA nanofibers were improved after doping ATT or ATT/ DOX complexes. It was obvious that the breaking strength and Young’s modulus of the ATT/PLGA and ATT/DOX/PLGA nanofibers were much higher than those of PLGA nanofibers , which wFor antitumor therapeutic applications, it is important to understand the release kinetics of a drug delivery system. We then explored the release kinetics of DOX from the ATT/DOX/PLGA nanofibers in different pH conditions. For comparison, DOX release from the ATT/DOX complexes and DOX/PLGA nanofibers was also investigated. As shown in in vitro antitumor efficacy of the nanofibers. As shown in In order to develop an efficient drug delivery system, it is necessary to retain the antitumor activity of drug molecules encapsulated in the ATT/PLGA nanofibers. Therefore, we used DOX release medium of the ATT/DOX/PLGA nanofibers to evaluate in vitro antiproliferative activity of the drug-loaded nanofibers, the morphologies of cells treated with free DOX, or the release medium of ATT/DOX complexes, ATT/DOX/PLGA nanofibers, or DOX/PLGA nanofibers were observed by phase-contrast microscopy for 24 h (To further confirm for 24 h . They alin vitro cancer therapy applications. The anticancer drug DOX can be successfully loaded onto the ATT particle surface, and the ATT/DOX/PLGA composite nanofibers have a smooth and uniform morphology with improved mechanical durability. Under neutral and acidic pH conditions, the loaded DOX can be released from ATT/DOX/PLGA nanofibers in a sustained manner. Furthermore, the released DOX from the nanofibers could significantly inhibit the growth of cancer cells in vitro. The ATT/DOX-doped PLGA nanofibers can significantly improve the mechanical properties of electrospun PLGA nanofibers, which could be used as a functional material for tissue engineering scaffold for enhanced local tumor therapy applications. In addition, ATT particles and PLGA nanofibers have dual sustained-release effects on drug molecules. In future work, the dispersion of ATT and DOX/ATT in electrospinning solution may be further improved through the surface modification of ATT, so that ATT can maximize the mechanical properties of the fibers. Further in vivo experiments should also be performed to prove the antitumor efficacy of these composite nanofibers.In summary, we have prepared ATT/DOX/PLGA composite nanofibers through electrospinning for


Although antipsychotics were discovered over fifty years ago, it took another decade until dopamine antagonism was demonstrated as central to their clinical effectiveness. Since accumulated evidence implicates the dopamine system in the pathophysiology of schizophrenia, all licensed first-line treatments operate primarily via antagonism of the dopamine D2 receptor. However, dopamine D2 receptor blockade does not effectively treat negative, cognitive and affective symptoms and, in a significant proportion of patients, it does not improve positive symptoms either. Therefore, additional neurochemical targets were considered. The “revised dopamine hypothesis” proposes that positive symptoms emerge due to hyperactive dopamine transmission in mesolimbic areas, while hypoactive dopamine transmission via the mesocortical pathway in the prefrontal cortex is linked to negative, cognitive, and partly affective symptoms. In this context, the role of D3 receptors were recognised. However, there is also evidence for the involvement of other neurotransmitter systems, suggesting that dopamine signalling relies on a suite of receptors that are thought to either facilitate or inhibit neurotransmitter activity through several interconnected neural circuits. Furthermore, there seem to be clusters of symptoms that cross the boundaries of disorders. Symptoms having similar pathophysiology at neurotransmitter level can be treated with the same drug or class of drugs. Thus, one particular drug might be effective in more than one indication. This lecture aims to illustrate the process of a new drug development by explaining how the underlying pathophysiology on receptor level impacts clinical studies and vice versa.Employee of Gedeon Richter Plc.


Within the era of battery technology, the urgent demand for improved and safer electrolytes is immanent. In this work, novel electrolytes, based on pyrrolidinium-bistrifluoromethanesulfonyl-imide polymeric ionic liquids (POILs), equipped with quadrupolar hydrogen-bonding moieties of ureido-pyrimidinone (UPy) to mediate self-healing properties were synthesized. Reversible addition–fragmentation chain-transfer (RAFT) polymerization was employed using S,S-dibenzyl trithiocarbonate as the chain transfer agent to produce precise POILs with a defined amount of UPy and POIL-moieties. Kinetic studies revealed an excellent control over molecular weight and polydispersity in all polymerizations, with a preferable incorporation of UPy monomers in the copolymerizations together with the ionic monomers. Thermogravimetric analysis proved an excellent thermal stability of the polymeric ionic liquids up to 360 °C. By combining the results from differential scanning calorimetry (DSC), broadband dielectric spectroscopy (BDS), and rheology, a decoupled conductivity of the POILs from glass transition was revealed. While the molecular weight was found to exert the main influence on ionic conductivity, the ultimate strength and the self-healing efficiency (of up to 88%) were also affected, as quantified by tensile tests for both pristine and self-healed samples, evidencing a rational design of self-healing electrolytes bearing both hydrogen bonding moieties and low-molecular-weight polymeric ionic liquids. Kasssn. ≥ 106 M−1 in CDCl3) /[DBTTC] = 20:1 at 70 °C (red square) showed first-order kinetics within the investigated time (7 h), while increasing the reaction temperature to 80 °C (blue circle) with the same monomer to CTA ratio drastically boosted the reaction rate, and the polymerization reached its maximum conversion within 3 h. As represented by the orange triangles in ILA]/[DBTTC] ratio was increased to 100:1, the polymerization at 80 °C showed pseudo-first-order reaction kinetics, and after a 7-hour reaction, it reached a final conversion of 67%. As shown in ILA]/[DBTTC] ratio increased from 20: to 100:1, and subsequently to 200:1, the conversion also rose from 62% to 67%, and finally to 79%. Control over the molecular weight was also improved as the ratio increased, as evidenced by the decreasing deviation between the theoretical and experimental molecular weights calculated via 1H NMR .In this work, S,S-dibenzyl trithiocarbonate (DBTTC) was used as a chain transfer agent (CTA) for the RAFT polymerization owing to its excellent control over acrylate monomers  and ioni liquids . To obta1H NMR, proving the preciseness of this strategy. Therefore we also prepared our acrylate-based polypyrrolidinium following this strategy  showed similar kinetics as the homopolymerization entry 2 , this indicated a higher reactivity catalyzed by the HBs in monomer UPyA, presumably due to the attractive association of UPyA in compared to the repulsive ionic nature of ILA. Despite the difficulties of copolymerizing non-ionic and ionic monomers, the control over molecular weight by DBTTC remained moderate in all cases, while control over polydispersity was less pronounced compared to the homopolerizations, which again was anticipated again due to the strong association among UPy moieties and ionic clusters of pyrrolidinium and TFSI ions.As shown in CPILU-y with different UPy contents were prepared. As shown in CPILU-y altered from a gel (5%) to a glassy solid (25%) and finally to a powdery material (>25%), indicating increased interchain forces due to the quadrupolar HBs of UPy moieties.In order to find the proper fraction of UPy on the polymer chain for application as self-healing electrolytes, ILA demonstrated excellent thermal stability up to 348 °C as shown in the UPyA showed lower stability until 198 °C. For the homopolymers POIL-2 and POIL-3 the thermal stabilities were slightly higher than that of the monomer, manifesting a minor influence by molecular weight on the thermal stability. The thermal stabilities of the POIL-x are comparable with those of similar polypyrrolidinium-polymers as previously reported [UPyA was incorporated into the polymer backbone the thermal stability showed a decreasing trend as the UPyA fraction increased. The degradation of the copolymer CPILU-y was found to be a two-step process, where the UPy moieties were decomposed first at around 200 °C, followed by the ionic moieties decomposing at around 360 °C (see TOnset /°C), indicating a resonable thermal stability compared to the homopolymers.To understand the thermal stability of the POILs thermogravimetric analysis (TGA) was employed. The 5%-weight-loss temperature and the degradation onset temperature are listed in reported . HoweverTgs are listed in POIL-x and the UPy content of the CPILU-y indeed influenced the glass transition temperature. When the molecular weight increased from 11 kDa to 40 kDa, Tg also increased from −13 °C (POIL-2) to 7 °C (POIL-3), which is potentially indicative of more restricted chain motions. When only 4% of the UPy moieties were introduced into the polymers, Tg drastically increased from −13 °C to 9 °C, revealing that the dimerizable UPy moieties act as a strong “chain-hardener” in comparison to the increase of molecular weight. If the UPy content increased from 4% to 14% and then to 24%, Tg increased further from 9 °C to 13 °C and to 30 °C, respectively, this evidenced stiffer chain segments in CPILU-6 and CPILU-7 as a result of a denser UPy dimerization.For the electrolytes used in batteries, it is often observed that the batteries can provide different local temperatures which could introduce a temperature-controlled structural transition of the electrolytes, causing changes in the physical and chemical properties of the electrolytes and further affecting the performance of the batteries, but also reaching temperatures sufficient to activate dynamic self-healing processes. Therefore, the thermal behavior of the polymers in this work was studied by differential scanning calorimetry (DSC). As shown in POIL-2 showed a higher conductivity compared to the high-molecular-weight POIL-3, matching the conclusions that—in line with expectations—low-molecular-weight POILs generally offer higher conductivity [CPILU-5), the conductivity was barely influenced by the non-conductive UPy moieties as compared to the homopolymer POIL-2 . As shown in uctivity ,26,27,28reported ,46,47 thTg/T), as shown in Tg, segmental motion was enabled, and the conductivity was coupled with the segmental motion, thus following the Vogel−Fulcher−Tammann (VFT) equation. At temperatures below Tg, segments were frozen, and the conductivity plot displayed Arrhenius behavior, which is comparable to the conductive behavior of inorganic glasses [Tg is roughly equal to 10–15 S·cm−1 in an ionic system, the charge transport is then fully governed by the structural relaxation of the system, which is segmental motion in case of polymer electrolytes. For our polymers, the conductivities at Tg, as listed in –15 S·cm−1) for the fully relaxation-coupled systems. As a consequence, the polymers in this work exhibited a certain degree of decoupled ion transport from the segmental dynamics. To clearly visualize this behavior, the decoupling index defined as Rσ, Tg = 15 + log σTg [CPILU-5 with 4% UPy moieties, with a decoupling index of 8.4. The least-decoupled homopolymer can be observed in the case of the homopolymer POIL-2  and CPILU-10   and a poor ductility at 32% tensile strain. This could be attributed to the more entangled segments in the high-molecular-weight CPILU-10 which hindered self-healing by UPy dimerization.For the pristine specimen, increasing the molecular weight from 10 kDa to 67 kDa indeed drastically enhanced the mechanical strength from 0.34 MPa (POIL-x and copolymers CPILU-y bearing quadrupolar hydrogen bonds were synthesized via RAFT polymerization using DBTTC as chain transfer agent. Kinetic studies revealed that the HBs monomer UPyA showed preferable incorporation in a copolymerization of ILA, anticipated as the attractive association of UPyA. While the synthesized homopolymers were thermally stable up to 360 °C, the introduction of UPy moieties into the polymer chains decreased the thermal stability and altered the decomposition into a two-step process. Examining a combination of data from DSC, BDS, and rheology, a decoupling of conductivity from the glass transition was observed in all polymers, while the trend of the zero shear viscosity values of all the polymers matched that of their conductivity values. A copolymer with 4% UPy content displayed the highest decoupling index of 8.4, proving that both, self-healing and excellent conductivities can be embedded into the same type of a POIL using complex hydrogen-bonding. While copolymers with low molecular weights demonstrated both better conductivity and self-healing efficiency, the high-molecular-weight samples showed higher ultimate strength but lower healing efficiency and conductivity. This work proves that HBs are a useful tool for designing electrolytes with unique properties like decoupled conductivity and self-healing ability, which can contribute to battery science and electronic devices such as supercapacitors in the future.Novel polymeric ionic liquids


Polyisoprene, with a high degree of polymerization, is the main component of natural rubber. In the industrial production process, it is necessary to adjust the length of the macromolecule of polyisoprene to improve its plasticity. It is thus of vital importance to explore the effect of the degree of polymerization of polyisoprene on its properties, e.g., mechanical property and thermal property. Molecular dynamics simulations link microstructure to macroscopic properties. In this paper, Moltemplate was used to establish polyisoprene models with different degrees of polymerization, and the mechanical properties of polyisoprene under uniaxial tension were analyzed under an OPLS all-atom force field. The results showed that the strength and elastic modulus of the material increased with the increase in the degree of polymerization of the molecular chain. In the process of tensile loading, the non-bonded potential energy played a dominant role in the change of the total system potential energy. Then, the thermal conductivity of polyisoprene with different degrees of polymerization was calculated by the non-equilibrium molecular dynamics method (NEMD). The thermal conductivity of PI was predicted to converge to 0.179 W/(m·K). The mechanism of thermal conductivity of the polymer containing branched chains was also discussed and analyzed. The research content of this paper aims to provide theoretical support for improving the mechanical and thermal properties of natural rubber base materials. The mai06 g/mol ,3,4. Rel06 g/mol ,8.Molecular dynamics simulation (MD) combines classical mechanics with statistical mechanics to calculate and analyze the mechanical properties of materials and establishes the relationship between microstructure and macroscopic properties ,10. ThisIn order to study the mechanical properties of polymers by the MD method, the correlation was established between the molecular model and the continuum model ,14. FurtOn the other hand, there are also many studies that calculate the thermal conductivity of polymers by MD simulation ,18,19. XThe description of thermal conductivity is more complicated for polymers containing branched chains. Because of the disordered arrangement of the molecular chain segments, the crystallization ability of the branched polymer chain is generally weak. Thus, there are more amorphous components and an incomplete crystal structure appears in its molecular structure . For exap = 50, 100, 150, and 200, Mw = 3304, 6604, 9904, and 13,204 g/mol, respectively) was calculated by the non-equilibrium molecular dynamics method (NEMD) and compared with that of polybutadiene. Then, the mechanism of thermal conductivity of the polymer containing branched chains was discussed and analyzed. The research content of this paper aims to provide theoretical support for improving the mechanical and thermal properties of natural rubber base materials.In this paper, Moltemplate software  was usedThe main component of natural rubber is cis-1, 4-polyisoprene. In this article, a polyisoprene (PI) molecular model was established by Moltemplate. As depicted in p = 100, for example) is vividly illustrated in 5 time steps using Langevin dynamics at 900 K followed by relaxation for 3 × 105 time steps using NVT dynamics at 900 K under a Nose–Hoover’s thermostat. Thirdly, the simulation ran for 5 × 105 time step to cool the system from 900 K to 298 K, and successively ran for 1 × 105 time steps to decrease the pressure to one bar. In the third step, the simulation ran under NPT conditions to allow the simulation box to contract to natural size at ambient temperature. After finishing the above process, a much more realistic molecular model of polyisoprene was fabricated, which was the initial model for tension simulation and thermal conductivity calculation simulation.The molecular model established above was absolutely unrealistic; not only the size of the simulation box but also the spacing between the molecules were unrealistically large. Therefore, a three-step equilibration process was required before tension simulation and thermal conductivity calculation. The process , elasticity modulus (E), elongation at σmax (e), and elongation at break (he) were annotated on each figure. Detailed data is exhibited in From max, and elongation at break as a function of p, respectively. It can be concluded from max, E, and he increased as p increased. As p escalated, σmax increased from 0.164 GPa to 0.271 GPa, the value of E steadily raised from 0.085 GPa to 0.180 GPa, and he increased from 256.5% to 466.3%. However, the value of e was not sensitive to p. In the above four cases, the value of e was always approximately 160%. In other words, under uniaxial tensile action, the maximum stress of PI usually appeared at 160% strain.To visualize the change trend of the above parameters, As the degree of polymerization decreased, the plasticization of PI increased, while the maximum strength, modulus, and elongation at break all decreased. Thus, polyisoprene should be processed according to its target product to equilibrate its properties and plasticization.As depicted in In addition, the peak of non-bonding energy was positively correlated with the degree of polymerization, which suggested stronger inter-chain interactions. This explained that the strength and modulus increased as the degree of polymerization increased in terms of molecular energy. These results validated that the MD method was reliable to study the mechanical properties of PI.p, and the increase in amplitude gradually slowed down. It was reported that the thermal conductivity of polymers had a significant relationship with the length of the molecular model . In our p < 150, the increase rate of thermal conductivity is relatively large, and the thermal conductivity increases approximately linearly. According to Liu et al. [p was small. In this mode, the phonon was more susceptible to the interference of scattering in the cold and hot areas at the boundary and transfers less heat. Therefore, the thermal conductivity was lower. When p increased with the system size increasing, the system of heat transfer changed from the ballistic phonon heat transfer to diffuse phonon heat transfer, also called the ballistic diffusion phonon heat transfer. In the process of heat transfer, the system receives less scattering interference from the boundary, and the heat transfer increases, so the thermal conductivity increases. However, the diffusion phonon heat transfer was realized by the collision of phonons and phonons. The increase of the phonon collision probably decreased the phonon mean free path. Therefore, the increasing trend of thermal conductivity gradually slows down. Based on the above variation of thermal conductivity, the exponential function was selected to fit the data, and a good fitting result was obtained, as shown in When the degree of polymerization u et al. , the heaC, sound velocity v, and phonon mean free path L:β represents the dimension characteristics of materials. β = 1/3 for isotropic three-dimensional crystal materials, β = 1/2 for isotropic two-dimensional crystal materials, and β = 1 for one-dimensional materials. Compared with polybutadiene, the branched chains in polyisoprene destroy the symmetry of the polymer chain, resulting in the lattice inhomogeneity of the system. Therefore, phonons are prone to collision, which restricts the mean free path L of phonons. Therefore, the thermal conductivity of polyisoprene was lower than that of straight chain polymers, such as polyethylene and polybutadiene [According to quantum mechanics , one of utadiene .In this study, all-atom molecular models of polyisoprene with different degrees of polymerization were established. Based on the OPLS all-atom force field and NEMD method, the mechanical and thermal properties of the material were tested by molecular dynamics simulation. During uniaxial tensile deformation, the strength and elastic modulus of polyisoprene increased with the increase in the molecular chain polymerization degree. Through the analysis of the system energy in the deformation process, it could be found that the non-bonded potential energy played a dominant role in the change of the total potential energy of the system. As the degree of polymerization increased, the increase of PI thermal conductivity became inapparent, which could be well fitted by exponential function. As a result, the thermal conductivity of PI was predicted to converge to 0.179 W/(m·K). Compared with polyethylene and polybutadiene, polyisoprene had low thermal conductivity and a more obvious size effect due to the branch in the main chain. The results of this paper could provide theoretical support for improving the mechanical and thermal properties of natural rubber base materials.


Leucaena leucocephala biomass (organic manure) with mineral fertiliser on rainwater use efficiency, agronomic efficiency, grain and stover yields for two sorghum varieties (Macia and SV1) under rainwater harvesting techniques. The experiment was laid in split-split plot arrangement with rainwater harvesting method as main plot factor, with Leucaena biomass + NPK fertiliser as subplot factor and sorghum variety as sub-sub plot factor over three cropping seasons. Data collected include rainwater use efficiency, agronomic efficiency, grain and stover yields. Results show that tied contours have significantly (p ≤ 0.05) higher grain and stover yields from all varieties and seasons. Irregardless of sorghum variety, tied contours had significant (p ≤ 0.05) sorghum grain and stover yield followed by infiltration pits and lastly standard contours. Grain and stover yields improved with increasing levels of Leucaena biomass + NPK fertiliser combination. Highest grain yields observed were 1.146 t ha−1 (Macia) and 1.1 t ha−1 (SV1) from tied contour +15 t ha−1 biomass +150 kg ha−1 NPK fertiliser treatments. Rainwater use efficiency was significantly (p ≤ 0.05) higher from tied contours compared to infiltration pits and standard contour. Rainwater use efficiency was statistically (p ≤ 0.05) influenced by increasing application levels of Leucaena biomass + NPK fertiliser in all seasons. Agronomic efficiencies were considerably (p ≤ 0.05) affected by rainwater harvesting, Leucaena biomass + NPK fertiliser and interaction of all factors. It can therefore be concluded that Leucaena biomass + NPK fertiliser, tied contours and infiltration pits improve sorghum yields. Augmenting 2.5 t ha−1 biomass with 25 kg ha−1 NPK fertiliser under tied contours and Macia have better agronomic efficiency.Food security in semi-arid regions is threatened by declining soil fertility, soil moisture stress and long frequent droughts as a result of erratic rainfall. Therefore we assessed the effects of augmenting  L. leucocephala; NPK fertiliser; Sorghum; Semi-arid regions; Sandy soils.Rainwater harvesting;  Small hLeucaena leucocephala biomass has the capacity to increase soil organic matter, microbial population and improve soil structure  under rainwater harvesting techniques.Climate change is another factor which negatively affected crop production in SSA . Rainfalrainfall . Performrainfall . Sorghum kg ha−1 . There i kg ha−1  particul kg ha−1 . Integra kg ha−1 . Several kg ha−1  reported22.1Zea mays), sorghum (Sorghum bicolor) and groundnuts (Arachis hypogea).The study was carried out as on-farm experiment in ward 11  of Chivi District, which is located at 78 km west of Masvingo in southeastern part of Zimbabwe. The area is located in agroecological region V which is characterised by monomodal rainfall with a 30 year average of 335 mm per season . The exp2.22) method was used to determine soil pH. Soil organic carbon (SOC) and available phosphorous were determined using wet digestion and Oslen method respectively  was produced by mixing all samples thoroughly. The sample dried on shade, grounded and sieved using 2 mm sieve. The Bouyoucos hydrometer method was used to determine soil texture  and totaectively .2.3Leucaena biomass + NPK fertiliser used as sub-plot factor at five application rates  + NPK fertiliser (kg ha−1)) and two sorghum varieties (Macia and SV1) were tested. Treatments were replicated three times and repeated from 2017/18 to 2019/20 cropping seasons. Tied contours used were constructed using cross ties after every 5 m producing structures which were 5 m in length × 0.5 m breath × 1 m deep. Cross tie were constructed by leaving soil between each contour. Infiltration pits (IP) were constructed along the contour and measured 3 m in length × 0.5 m breath × 1 m deep with spacing of 0.5 m in each contour. Standard contour of 35 m long was a control treatment. Rainwater harvesting techniques were spaced at 1.5 m. Every sub plot factor measured 20 m long and 5 m wide, replicated three times. Two rows at edge of every plot were used as buffer lines. Sub-sub plot factor were measuring 2 m long × 4.5 m wide and replicated three times. The plots were on an average slope of 3%.A completely randomised block design was used with treatments arranged in split-split plot. Rainwater harvesting methods were used as main treatment factor at three levels  with Leucaena biomass was incorporated at a rate of 0, 2.5, 5, 10 and 15 t ha−1 and NPK fertiliser at a rate of 0, 25, 50, 100 and 150 kg ha−1 mixed together. Leucaena biomass used was obtained from 5 year old trees which contained 3.5% nitrogen, 0.2% P2O5, 0.42% magnesium, 1.35% calcium and 1.8% K2O. NPK fertiliser used contains 7% N, 14% P2O5 and 7% K2O. The recommended application rates of NPK fertiliser is 350 kg ha−1. Planting was done on 20 December 2017, 12 December 2018 and 30 December 2019 for 2017/2018, 2018/2019 and 2019/2020 seasons respectively. Sorghum seeds were sown using spacing of 0.75 m between rows and 0.2 m within rows achieving plant population of 66666 plants ha−1. Weeding was done twice using hand hoe. Top dressing of sorghum plants was done using using ammonium nitrate fertiliser (34.5% N) at a rate of 150 kg ha−1. Split application was done at a rate of 26 kg N ha−1 per split, 3 and 7 weeks after emergence. Fall armyworm was controlled using Demise 65EC during vegetative and prior flowering stage.Land preparation was followed by ploughing using animal drawn mouldboard plough to a depth between 15 cm and20cm. Ploughing was done between the block and did not interfere with rainwater harvesting methods. 2.4−1 under favourable conditions (−1 under optimum condition. The variety has not been widely grown in Chivi and was used to compare its performance with Macia.The experiment used two sorghum varieties (Macia and SV1) as test crop. Macia is an open pollinated variety which is widely grown in Chivi due to its drought tolerance and it thrive well under harsh conditions. Macia variety attains its physiological maturity with an average of 115–120 days. The variety has a yield potential of 3–6 t handitions . SV1 is nditions . Yield p2.52.5.1Rainfall was measured using a standard rain gauge installed in the experimental site throughout the growing seasons. Rainfall data was collected every morning at 5 am and recorded in the book. Monthly rainfall was calculated by summing up all daily values. Days dry per month were determined.2.5.22 per treatment plot. Panicles were hand cut using sharp knife and stover was cut closer to the ground. Heads were sun dried, threshed and grain moisture tested using moisture meter. Grains with moisture content of 13.5% were winnowed, weighed and weight extrapolated to tonnes per hectare. Grain yield obtained was adjusted to 13.5% grain moisture content using the following formula:Grain and stover yields were harvested from 9 m Adjusted yield = Actual yield × )(100−U) Where A i2.5.3This is the efficiency in which rainfall is converted to grain, calculated after harvesting of grain using formula by −1 rainfall) =  RWUE  .2.5.4The agronomic efficiency was calculated as crop yield increase from control treatment divided by amount of amendment applied as given below:Agronomic efficiency (AE) = lied(kg) .2.62).Data was subjected to two way analysis of variance (ANOVA) for split-plot analysis using Genstat 14th edition. The least significance differences (LSD) was used to identify and separate significant means at 5% levels. Regression analysis was done use Microsoft Excel to estimate correlation coefficient  received during 2017/18 and 2019/20 seasons . The lea3.2c kg−1 sodium, 0.15 cmolc kg−1 potassium, 0.68 cmolc kg−1 magnesium and 1.25 cmolc kg−1 calcium during the 2017/18 cropping season before planting  with 0.02% total nitrogen and 0.27% SOC. Exchangeable cations were 0.11 cmolplanting . An incrrtiliser . The res3.3−1 and a lowest (0.743 t ha−1) were observed over a period of three years. Stover yields ranged from 2.482 t ha−1 and the lowest was 2.305 t ha−1 observed from the standard contour. Mean stover yield was highest (2.447 t ha−1) and a lowest (2.326 t ha−1) from tied contours and standard contours over three years respectively (Rainwater harvesting techniques significantly (p ≤ 0.05) affected sorghum grain yields for both varieties, with the trend tied contours having the greatest yield (p ≤ 0.05) followed by infiltration pits and lastly the standard contour . The samectively .Table 3E3.4Leucaena biomass + NPK fertiliser show significant effects (p ≤ 0.05) on grain yields of both Macia and SV1 sorghum varieties. Increasing application rate of Leucaena biomass + NPK fertiliser show increased grain yield for both varieties although Macia outperformed SV1 variety. Increasing Leucaena biomass + NPK fertiliser levels show increase in three year mean yield (0.61–1.01 t ha−1 and 0.62–0.95 t ha−1) for Macia and SV1 varieties respectively. Highest grain yield (1.08 t ha−1) was obtained from Leucaena biomass + NPK fertiliser treatment with 15 t ha−1Leucaena biomass +150 kg ha−1 NPK fertiliser in 2017/18 season under Macia variety. The relationship between grain yield and Leucaena biomass + NPK fertiliser were significantly (p ≤ 0.05) correlated with R2 ranging from 0.88-0.96 for Macia and 0.96–0.97 for SV2 (Leucaena biomass + NPK fertiliser at different level throughout the three seasons compared to Macia variety. SV1 had a higher (R2 = 0.97) correlation in 2019/20 season compared to all other seasons and Macia variety  was observed. Increasing Leucaena biomass + NPK fertiliser levels show significant effect on stover yields with highest yield of 2.56 t ha−1 observed in 2017/18 season from 15 t ha−1Leucaena biomass +150 kg ha−1 NPK fertiliser + Macia variety. Regardless of Leucaena biomass + NPK fertiliser and season, Macia showed higher stover yields than SV1. The results also show significant correlation  between different levels of Leucaena biomass + NPK fertiliser and stover yield (2 = 0.86–0.91) to Leucaena biomass + NPK fertiliser levels. The highest correlation (R2 = 0.91) was observed in 2019/20 season (2 = 0.83–0.89) between SV1 stover yields and Leucaena biomass + NPK fertiliser levels. The highest correlation (R2 = 0.89) was observed in 2018/19 season  by different er yield . Macia s0 season . Further9 season .Figure 23.5Leucaena biomass + NPK fertiliser × variety show significant interaction effects (p ≤ 0.05) on sorghum grain yields across all treatments (Leucaena biomass + NPK fertiliser × Macia variety had yield advantage compared to SV1 variety. The highest grain yield (1.146 t ha−1) was obtained from tied contour +15 t ha−1Leucaena biomass +150 kg ha−1 NPK fertiliser + Macia variety during 2017/18 cropping season. Tied contour × Leucaena biomass + NPK fertiliser × Macia variety had the highest grain yields (0.612–1.146 t ha−1) followed by infiltration pits (0.604–1.104 t ha−1) throughout the three cropping seasons. Sorghum variety SV1 had yields ranging from 0.609–1.1 t ha−1 (tied contour × Leucaena biomass + NPK fertiliser) and 0.595–1.021 t ha−1 (infiltration pits × Leucaena biomass + NPK fertiliser). However, standard contour × Leucaena biomass + NPK fertiliser had the lowest grain yields ranging from 0.571–0.989 t ha−1 (Macia) and 0.581–917 t ha−1 (SV1) compared to other RWH practices × Leucaena biomass + NPK fertiliser levels (Rainwater harvesting practices × eatments . Effectsr levels .Table 4I3.6Leucaena biomass + NPK fertiliser × sorghum variety had significant interaction effect (p ≤ 0.05) on stover yield throughout three cropping seasons. Regardless of RWH and season, stover yields from Macia were greater than those obtained from SV1 at each application rate of Leucaena biomass + NPK fertiliser  over three years (−1 mm−1) from Macia variety in 2018/19 season and a lowest of 2.31 kg ha−1 mm−1 from standard contour + SV1 in 2019/20 season. Results also show significant differences (p ≤ 0.05) among varieties. Standard contour treatments had the lowest RWUE regardless of variety and season, with RWUE ranging from 2.31–2.75 kg ha−1 mm−1  affected RWUE in all seasons. Effects of RWH techniques were significant on RWUE for both varieties except in 2017/18 season where no significant effect was observed (p > 0.05). Macia variety had higher RWUE which ranged from 2.58–2.91 kg haee years . Tied coa−1 mm−1 .Figure 3Leucaena biomass + NPK fertiliser levels regardless of sorghum variety and season. Increasing Leucaena biomass + NPK fertiliser levels over control show significant increase in RWUE with highest (3.53 kg ha−1 mm−1) and lowest of 2.02 kg ha−1 mm−1 observed from Macia variety. Macia variety responds well from different levels of Leucaena biomass + NPK fertiliser, with three year mean ranging from 2.02–3.33 kg ha−1 mm−1 compared to 2.16–3.16 kg ha−1 mm−1 from SV1 variety. RWUE from Macia was positively correlated to Leucaena/NPK fertiliser levels but less than that of SV1 (2 = 0.96–0.97) to Leucaena biomass + NPK fertiliser application rates. The highest correlation (R2 = 0.97) was observed in 2019/20 cropping season from SV1 variety (Leucaena biomass + NPK fertiliser levels in 2017/18 cropping season.RWUE was considerably affected (p ≤ 0.05) by t of SV1 . SV1 var variety . Macia vLeucaena biomass + NPK fertiliser and sorghum variety (−1 mm−1) was obtained in 2018/19 from tied contour +15 t ha−1Leucaena biomass +150 kg ha−1 NPK fertiliser treatment + Macia variety. Furthermore, lowest RWUE (1.88 kg ha−1 mm−1) was observed from SC with no amendment under Macia variety  by interaction of RWH,  variety . Highest variety . Tied co3.8−1 was obtained in 2017/18 season from Macia grown under tied contours. Sorghum agronomic efficiency was considerably affected (p ≤ 0.05) by RWH methods (Higher sorghum agronomic efficiency (AE) of 0.054 kg kg methods . On averSorghum agronomic efficiency was statistically influenced (p ≤ 0.05) by different application rates of Leucaena biomass + NPK fertiliser. Higher AE of 0.074 kg kg−1 was observed from Macia variety +2.5 t ha−1Leucaena biomass +25 kg ha−1 NPK fertiliser in 2019/20 cropping season  by integration of RWH and Leucaena biomass + NPK fertiliser except in 2017/18 season where no significant effect (p > 0.05) on AE was observed  during the experimental period. Tied contours and IP recorded higher yields compared to SC which had the lowest grain yields at all seasons and varieties. This may have been associated to increased soil moisture content by tied contour and infiltration pits which increased water availability leading to higher grain yield. This was in agreement with results from related studies by several authors e.g.  who repoLeucaena biomass with NPK fertiliser increased sorghum grain yields and can be a better option as integrated soil fertility management. Grain yields were significantly increased with increase in application rates of nutrient sources. Organic nutrient sources such as Leucaena biomass have the capacity to increase SOC, microbial population and soil total porosity  with results from this study. Results from this study were in agreement with results by −1) after using infiltration pits (IP) and cattle manure + NPK fertiliser in Tanzania. This was linked to reduced soil erosion, surface runoff and increased soil moisture in plant root zone . Findings obtained corroborates with results by Sorghum agronomic efficiency declined with increasing application levels of Leucaena biomass + NPK fertiliser. This was in agreement with results by −1. This was also affirmed by −1. Macia variety proved to have better agronomic efficiency than SV1 and it is a promising variety to improve food security in semi-arid regions especially in SSA. Integration of RWH and Leucaena biomass + NPK fertiliser show significant effect on AE. These results were contrary to findings by Tied contours had better sorghum AE compared to infiltration pits and standard contour. Higher AE was observed from Macia variety than SV1. Highest AE from tied contours was in agreement with findings by 5Leucaena biomass with NPK fertiliser has the potential to improve soil fertility, nutrient availability to crops and sorghum yields. Tied contours and infiltration pits had higher sorghum yields than SC in all cropping seasons. Tied contours and Macia variety had better agronomic efficiency when combined with 2.5 t ha−1Leucaena biomass +25 kg ha−1 NPK fertiliser. Augmenting Leucaena biomass with NPK fertiliser under tied contours and Macia variety proved to increase sorghum yields, rainwater water use efficiency and have better agronomic efficiencies in semi-arid regions. Although 15 tha-1Leucaena biomass +150 kg ha−1 NPK fertiliser gave higher yields, they have low agronomic efficiency compared to 2.5 t ha−1Leucaena biomass +25 kg ha−1 NPK fertiliser. We can conclude that tied contours combined with 5 t ha−1Leucaena biomass +50 kg ha−1 NPK + Macia can be adopted by farmers to reduce food insecurity in semi-arid regions due to higher yield increment compared to other treatments. Therefore smaller quantities of Leucaena biomass can be used and the rest turned in to fodder for livestock.Results from this study clearly demonstrated that augmenting Andrew Tapiwa Kugedera: Conceived and designed the experiments; Performed the experiments; Analyzed and interpreted the data; Wrote the paper.Ronald Mandumbu, George Nyamadzawo: Conceived and designed the experiments; Contributed reagents, materials, analysis tools or data.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Data included in article/referenced in the article.The authors declare no conflict of interest.No additional information is available for this paper.


The partition coefficients of drug and drug-like molecules between an aqueous and organic phase are an important property for developing new therapeutics. The predictive power of computational methods is used extensively to predict partition coefficients of molecules. The application of quantum chemical calculations is used to develop methods to develop structure–activity relationship models for such prediction, either based on molecular fragment methods, or via direct calculation of solvation free energy in solvent continuum. The applicability, merits, and shortcomings of these developments are revisited here. Organic-Water or simply logP) [The importance of the accurate prediction of physicochemical properties is quintessential, not only in drug development efforts but also toward applications in material science for molecules with desirable properties. The importance of quantitative structure activity/property relationships (QSAR/QSPR) is undoubtedly essential in chemistry and biology ,2,3,4. Tly logP) . A studyly logP) .From a physical chemistry perspective, for non-ionic and neutral forms of compounds, logP is expressed as in Equation (1), where R is the molar gas constant and T is the temperature in K.Whereas, for ionic compounds, whose overall ionization in solution is pH dependent, often logD is used instead of logP. The logD determines the ratio of the sum of the concentrations of all ionized and unionized forms of the compound in each of the two phases of interest (Equation (2)).For molecules whose aqueous ionization constants are known, logD is related to logP via Equation (3). The significance of logD values becomes clear if one looks into the vast range of physiological pH values in the human body, e.g., stomach: ~2; plasma: 7.4; small intestine: ~5–6.8. .(3)logDor bases .OW) was traditionally used as a measure of the lipophilicity and/or hydrophobicity of compounds, strictly speaking the hydrophobicity can be defined as the aggregation propensity of substances in aqueous medium, and n-octanol very poorly represents lipid bilayers. For passive diffusion of drug molecules, which is considered as one of the major pathways of drug absorption, the partition coefficient between aqueous phase and organic phase is directly related to membrane permeability . While the distribution of a compound between n-octanol and water mixture  based methods, and the whole molecule approach. The fragment-based approach is guided by the principle of averaged contributions of simple fragments corrected against large experimental datasets ,24. An eferences ,28. Withferences . The earferences ,31,32,33The solvation properties are a direct outcome of the electronic structure of a molecule, and therefore, electronic structure calculations seem to be an excellent starting point for calculation of logP. The use of quantum chemical methods is applied for two very specific regimes of methods: first, for the development of descriptors to assist in computation of logP using the whole molecule-based approaches; and second, direct calculation of solvation free energy using different continuum solvation models. The following discussion is divided into two sections, viz. applications of quantum mechanics based molecular descriptors for logP prediction, and direct prediction of logP via free energy of solvation calculations.π = logPX − logPH where the parameter π is obtained by regression analysis against standard databases. This simple looking equation leads to a plethora of models involving molecular properties, and more significantly intrinsic electronic properties, which can be partitioned over atoms present in a molecule. The application of empirical and quantum chemical (QC) methods to derive such descriptors have become very popular. The QC methods were more accurate and well suited for calculating atomic partial-charges, molecular orbital (MO) energies, dipole moments, and many other properties. In earlier days, the demand for heavy computational resources to generate molecular wave function had restricted the use of the QM descriptors; however, semi-empirical calculations became quite popular, which were developed within the mathematical framework of molecular orbital theory, but with more generalizations and approximations (SCF-MO). There are several semi-empirical methods available which have been benchmarked against experimental atomic and molecular data to be used for generation of molecular descriptors [2 = 0.985, s = 0.15.Since the first demonstration by Hanch and Fujita, that logP can be calculated using a linear correlation method, several similar methods were reported for various purposes, mostly for QSAR/QSPR analysis  and hydrophilicity (HM) indices were calculated using quantum chemical calculation . For an overview of the lipophilicity predictions, based on QSAR models in drug design, please see reference [The parameters used in this relation are nolecules ,37. For olecules . For a lolecules . The vanolecules . A theorolecules . The reseference . There aThe accuracy of implicit solvation methods for solvation free energy calculations, and the role of molecular conformations are two major limitations that handicap applications of direct logP estimations using electronic structure calculations. The positive sides of implicit solvation models are (i) reduced computation time in comparison to an explicit all atom calculation, (ii) inherent parameterization to reproduce experimental macroscopic properties of small molecules and ions, and (iii) for an arbitrary geometry of solute “…continuum models automatically give configurationally sampled solvent effect” . One shoOW of 20 neutral drug molecules, the best performers were SMD and COSMO-RS methods, whereas molecular mechanics (MM) based methods performed poorly [solvation is often the limiting step for correct prediction of the partition coefficients. The COSMO-RS method can use a priori prediction of solubilities of a large class of compounds. The first report of training COSMO-RS on a 150 drug-like compound database and testing on a pesticides database containing 107 entries provided rms deviation of 0.66–0.61 log units [3, p-F3C-C6H4-). Very recently, Patel and Roy reported a systematic analysis of the effect of atomic radii on logP calculations of 56 fluorinated drug molecules using DFT functionals [The accurate prediction of hydration free energy by Minnesota solvation model  was an encouraging step towards using an implicit solvation model for logP prediction, as well as using hydration free energy as a descriptor in drug design ,44. In ad poorly . The autd poorly . Indeed,og units . One of og units . Ouimet og units . These actionals . The stactionals .OW calculation for a large set of compounds using semi-empirical quantum chemical methods with dielectric continuum models found significant deviations between computed and experimental data [A direct logPtal data . An imprtal data . Fizer etal data . For thioctanol-water were reported by Kovalenko and co-workers [Amongst physics-based methods, the three-dimensional reference interaction site model (3D-RISM) theory has also been applied successfully toward prediction of partition coefficients. The theory uses first principle statistical mechanics to describe properties of molecular solvents using modest computational resources. The theory has been extended significantly to apply in quantum-chemical calculation using the RISM-SCF method ,56. The -workers ,63. It ilogP calculation/prediction based on a case specific manner. For similar molecular structures to be used for high throughput virtual screening, the empirical logP predictions based on atom/fragment addition approaches may often suffice. Thus, QSAR/QSPR approaches are adequate here. However, this is clearly not the case for systems with novel and/or exotic fragments, which is often the case for development of new pharmaceuticals. The descriptor-based methods should be developed with special care so as to have a minimum of five times more compounds in the training database, than the number of molecular descriptors used. The whole molecule-based methods may work very well for such a scenario. It is worth, for such cases, to treat the molecular descriptor in the most accurate way possible. For instance, an error in calculating atomic charges and resultant multiple moments would result in significant deviation of molecular dipole moment from the actual value, and would interfere with all subsequent calculations based on these descriptors. The semi empirical AM1 method-based charges are often a good choice to start with. Further desired improvements should be guided by necessity and available computational resources. The quantum chemical calculations are an excellent choice for specific solvation property calculations and should be used judiciously. For small molecular sizes, electronic structure calculations with explicit solvation methods are the best; moreover, for a relatively larger system size, a hybrid approach is recommended. Deploying a hybrid approach is non-trivial and requires understanding of the amount of explicit solvent molecules to be added per molecule of substrate to represent the solvation shell, before immersing the entire supramolecular structure in a dielectric continuum model. The molecular solvation theory-based methods, such as 3D-RISM, should be properly standardized for their use in different solvents before setting off to use them for large molecular databases [It is important to address the suitability of a choice of atabases . Of cour


The social defeat hypothesis of psychosis posits that an outsider status or subordinate position is a common denominator of several psychosis risk factors, leads to elevated striatal dopamine function and thereby to an increased risk for the disorder. The purpose of this paper is to examine whether this hypothesis offers a good explanation for the increased psychosis risk for migrants from developing countries. Method: Review of literature. Results: The outsider status and subordinate position of many migrants from developing countries in Europe, and of Africans in particular, is evident. It is also clear that racism contributes to this situation. An interpretation of racism as psychotogenic is supported by findings of increased risks for other discriminated groups, such as homosexuals, individuals with a low IQ or a hearing impairment. The single study that examined dopamine function in migrants reported indeed elevated stress-induced dopamine release and dopamine synthesis capacity . Recently, we examined the time course of the RR of treatment for psychosis for all migrants to the Netherlands . Contrary to our expectations, the RR for migrants from sub-Saharan Africa was already increased in the year of arrival , particularly for those aged 10-20 years . Conclusion: The social defeat hypothesis accords well with a psychotogenic effect of racism, but replications of the dopamine study are needed. The finding of an increased risk for Africans in the year of arrival suggests that racism is not the single cause of their increased risk.No significant relationships.


Inherently conductive polymers (CPs) can generally be switched between two or more stable oxidation states, giving rise to changes in properties including conductivity, color, and volume. The ability to prepare CP nanofibers could lead to applications including water purification, sensors, separations, nerve regeneration, wound healing, wearable electronic devices, and flexible energy storage. Electrospinning is a relatively inexpensive, simple process that is used to produce polymer nanofibers from solution. The nanofibers have many desirable qualities including high surface area per unit mass, high porosity, and low weight. Unfortunately, the low molecular weight and rigid rod nature of most CPs cannot yield enough chain entanglement for electrospinning, instead yielding polymer nanoparticles via an electrospraying process. Common workarounds include co-extruding with an insulating carrier polymer, coaxial electrospinning, and coating insulating electrospun polymer nanofibers with CPs. This review explores the benefits and drawbacks of these methods, as well as the use of these materials in sensing, biomedical, electronic, separation, purification, and energy conversion and storage applications. Inherently conductive polymers (CPs) possess conjugated backbones that can be reversibly oxidized and reduced via chemical or electrochemical means. Changes in oxidation state are accompanied by changes in properties including conductivity, color, reactivity, and volume. In the year 2000, the Nobel Prize in Chemistry was awarded to Alan Heeger, Alan MacDiarmid, and Hideki Shirakawa, for their critical work in the field of CPs. CPs have superior electrical and optical properties that are comparable with those of metals and inorganic semiconductors . They diElectrospinning is a versatile and straightforward way of producing nanofibers from a variety of materials, including polymers, composites, semiconductors, and ceramics . AlthougWhile many researchers still prefer this route, for both economic feasibility and ease of customization, the demand for production-scale electrospinning equipment is also growing. Several companies worldwide now specialize in manufacturing, selling, and servicing electrospinning equipment ,60. ThesNanofibers produced via electrospinning can be manipulated in a variety of different ways, and their final diameter, alignment, and structure all depend on the parameters used during the electrospinning process. For example, different electrospinning setups can produce nanofibers ranging in diameter from 1.6 nm to 2000 nm ,64,65. TA wide variety of inexpensive, commercially available (“commodity”) polymers have been electrospun, but there are inherent difficulties associated with electrospinning CPs. This review focuses on the production of CP nanofibers via electrospinning, as well as the applications of CP nanofibers . A brief2 hybridized backbone is responsible for the unique electronic and optical properties of CPs. Resonance delocalization of electrons and cations (holes) formed during the oxidation (doping) process   is the intrinsic viscosity, c is the polymer concentration, and kH is the Huggins coefficient. Because [η] is related to the viscosity average molecular weight (Mv) of a linear polymer by the Mark–Houwink–Sakurada equation  is Polymer solution viscosity is related to the extent of polymer chain molecular entanglement within that solution. Polymer chain entanglement and, therefore, solution viscosity can be increased by increasing either the concentration or the strength of intermolecular interactions . Viscous solutions are necessary to overcome the electrostatic and coulombic repulsion forces that stretch the electrospinning jet. At lower viscosities, the jet partially breaks up, and the free solvent molecules in the solution instead form spheres, resulting in the formation of beads . co-glycolic acid) (PLGA), polystyrene (PS), and poly(methyl methacrylate) (PMMA) , polypropylene (PP), poly(vinyl chloride) (PVC), poly(acrylonitrile) (PAN), poly(ethylene oxide) (PEO), polycaprolactone (PCL), polycaprolactam , poly(lactic-) (PMMA) . NaturalSimple linear polymers like PE, PP, and PS are ruled by weak van der Waals forces ,152 and Process parameters, such as needle tip diameter, shape, and location, flow rate of polymer solution, electric potential, solution temperature, and relative humidity also impact fiber formation. The distance between the needle tip and collector determines the extent of solvent evaporation from the nanofibers and deposition on the collector; collector rotation can result in nanofiber alignment during deposition . StudiesGenerally, nanofibers have high aspect ratios and large specific surface areas; depending on the chemical structure of the polymer, nanofibers may also have a high degree of flexibility and high mechanical strength . Other mIt is possible to increase electrospinning temperature by heating the polymer solution, using a controlled temperature chamber ,163 or aHumidity can also have profound effects on nanofibers ,168. HowCP electrospinning has not received as much attention as electrospinning of other polymers that are easier to work with. CPs tend to have rigid backbones, low molecular weights, and low degrees of chain entanglement, which make them inadequate for electrospinning purposes ,171,172.Neat electrospinning of CPs is challenging to achieve. In addition to their rigid backbones and low molecular weights, many CPs are insoluble in organic solvents ,173. ThiGonzález et al.  demonstrA novel method using binary solvents for electrospinning neat poly  (MEH-PPV) was studied by Zhong et al.  They expCoaxial electrospinning has emerged as a successful technique to obtain CP-containing nanofibers. Coaxial electrospinning produces core–sheath-structured nanofibers by forming a fiber that consists of complementary materials in the core and sheath . Coaxialw = 65,000 Da) dissolved in chloroform for the inner core and poly(methyl methacrylate)  dissolved in N,N-dimethylformamide (DMF) as the outer shell. Smooth and continuous PANI/PMMA nanofibers were obtained with diameters ca. 1440 nm. The PMMA outer shell could be removed via immersion in an isopropanol solution for 1 h to yield neat PANI nanofibers with decreased diameters of ca. 620 nm  for the fibers prepared from chloroform and chlorobenzene relative to those prepared from TCB. P3HT nanofibers prepared from chloroform offered the additional benefit of enhanced ductility relative to the fibers prepared from chlorobenzene or TCB.Chen and coworkers used coaxial electrospinning to prepare nanofibers with P3HT cores and PMMA shells . The PMMw = 87,000 Da) in CHCl3 at a concentration of 11–13%; at lower concentrations, beaded fibers formed. The researchers observed that, during electrospinning of neat P3HT, the needle tip became blocked after about 10 s, due to the P3HT crystallizing as the solvent evaporated. To combat this, they utilized a coaxial electrospinning setup in which additional CHCl3 was delivered via the outer, nonconductive nozzle, while P3HT solution in CHCl3 was delivered via the inner, conductive nozzle. Smooth, uniform P3HT nanofibers with an average thickness of ~500 nm were obtained. The coaxial setup allowed for neat P3HT nanofibers to be generated without the aid of a carrier polymer and with no adverse impacts to the electrical properties of the CP used.Coaxial needles can be used in the preparation of electrospun CP nanofibers in ways other than the typical ones described above. In a slightly different approach to electrospinning using coaxial needles, Lee and coworkers  conducteco-glycolic acid) caprolactone) (PLGA), as shown in Typically, neat CP solutions for electrospinning must be at a low concentration to facilitate the dissolution of the CP chains. These low-concentration CP solutions are often not viscous enough for electrospinning due to lack of chain entanglement. A carrier or host polymer is a high-molecular-weight polymer that is used in electrospinning to help an electrospinning solution reach an adequate viscosity for electrospun nanofiber formation. High-molecular-weight carrier polymers reach chain entanglement at low concentrations; hence, the addition of small amounts of high-molecular-weight carrier polymer can enable electrospinning of CPs with minimal impact on CP properties . Thus, COne disadvantage of electrospinning using these carrier polymers is that, while the carrier polymers impart beneficial properties, at higher carrier polymer concentrations, the resultant nanofiber blends may not possess the desired CP properties, such as conductivity or electrochromism. In addition to increasing insulating content, electrospinning CPs with carrier polymers may also introduce surfactants or byproduct impurities .The research group of Nobel Prize winner Alan MacDiarmid conducted some of the early investigations into electrospun CPs utilizing carrier polymers or coating nonconductive nanofibers. They electrospun blends of doped PANI with PEO (50–89%)  or PS  and poly(ethylene glycol) dimethacrylate (PEGDMA) for bioelectronic sensor applications as demonstrated by Fallahi et al.  An incre−1, while a second dip coating increased conductivity to 0.9 S·mm−1, and a third dip coating increased conductivity to 2 S·cm−1. Conversely, tensile strength saw a decrease in elongation to break as more dip coatings were applied, uncoated e-PU and one PEDOT:PSS dip coating exhibited ca. 400% elongation at break, while two dip coatings decreased elongation at break to ca. 230%, and three dip coatings reduced elongation at break to ca. 40%. This dip coating method produced PEDOT:PSS/PU fabrics exhibiting highly stable conductivities as stretchable conductors for flexible electronics comparable to those in recent literature . T. T2+ to The ability of CPs to be modified with a wide range of bioactive species has led to extensive development of CP biosensors , SensorsSensors that can be worn on the human body have also been developed, for applications including the detection of harmful substances in an area , analysiAn ammonia detector was constructed out of in situ polymerized PPy on sintered electrospun PVP/vanadyl acetylacetonate/gold(III) chloride trihydrate . Sweat p2 . C. C277]. 4 and PMMA, coated onto the PANI/PVA nanofibers. The same behavior was observed in a device constructed from electrospun PANI/silk fibroin nanofibers, with the addition of good processability and conductivity sufficient to light up LEDs (3 synthesized in ionic liquids . A. A4 and  liquids . Fluores liquids . Electrospinning polymers leads to high surface area and potential for alignment, giving rise to applications in textiles and filtration. The additional benefits of tunable optoelectronic properties of CPs lead to even more nanofiber applications, including sensors, tissue engineering, drug delivery, electrochromics, energy storage, and photovoltaics. Thus, even though electrospinning CPs is very challenging, researchers continue to develop approaches to overcome the barriers. Rigidity and low molecular weight are the two main challenges for neat electrospinning of CPs; instead of regular nanofiber formation, bead-on-a-string geometries are formed ,191, or Overcoming the barriers of CP electrospinning has led to investigation of CP nanofibers for use in a wide variety of applications. The biocompatibility of several CPs has been demonstrated ,254,255,The high surface areas are also useful for sensors, where surface area may directly relate to sensing ability . ChangesCP nanofibers have also been explored for use in separations and purification, because the high-surface-area, porous structures can be used to absorb species or immobilize reactants. Removal/extraction occurs via ion exchange , chemicaCPs, commodity polymers, and, in some cases, nanoparticles, can be combined in seemingly innumerable ways to form electrospun nanofibers with a wide range of properties. The ability to control the properties by changing the formulation is one of the reasons these materials are of such interest. Efforts will continue to directly electrospin neat CPs by increasing molecular weight and improved solubility, with the possible end goal of enhanced conductivity in aligned CP nanofibers. As the utility of these materials continues to become more widely known, additional unexpected applications will arise. When applications of CP nanofibers are further developed, an increased focus on production-scale electrospinning equipment is sure to follow.