Two series of terpolymers with improved photostability were realized by the introduction of appropriate ratio of antioxidant butylated hydroxytoluene unit containing side chains.All-polymer solar cells and organic photodetectors (OPDs) with these terpolymers as both donors and acceptors have been prepared with simultaneously improved efficiency and stability.A feasible approach to develop terpolymers with antioxidant efficacy for improving the lifetime of organic solar cells and OPDs is proposed.The online version contains supplementary material available at 10.1007/s40820-023-01114-5. x = 0.05, 0.1, 0.2), are designed and synthesized. It was found that incorporating appropriate ratio of benzothiadiazole (BT) with BHT side chains on the conjugated backbone would induce negligible effect on the molecular weight, absorption spectra and energy levels of polymers, however, which would obviously enhance the photostability of these polymers. Consequently, all-polymer solar cells  and photodetectors were fabricated, and the all-PSC based on PTzBI-EHp-BTBHT0.05: N2200 realized an optimal power conversion efficiency (PCE) approaching ~ 10%, outperforming the device based on pristine PTzBI-EHp: N2200. Impressively, the all-PSCs based on BHT-featuring terpolymers displayed alleviated PCEs degradation under continuous irradiation for 300 h due to the improved morphological and photostability of active layers. The OPDs based on BHT-featuring terpolymers achieved a lower dark current at − 0.1 bias, which could be stabilized even after irradiation over 400 h. This study provides a feasible approach to develop terpolymers with antioxidant efficacy for improving the lifetime of OSCs and OPDs.It is of vital importance to improve the long-term and photostability of organic photovoltaics, including organic solar cells (OSCs) and organic photodetectors (OPDs), for their ultimate industrialization. Herein, two series of terpolymers featuring with an antioxidant butylated hydroxytoluene (BHT)-terminated side chain, PTzBI-EHp-BTBHTx and N2200-BTBHTx (The online version contains supplementary material available at 10.1007/s40820-023-01114-5. Organic photovoltaics based on organic semiconductors, including organic solar cells (OSCs) and organic photodetectors (OPDs), have attracted extensive attention owing to their merits of light-weight, flexibility, semi-transparency and large-scale processability. With printed electronics techniques such as spray-coating, stamping, screen-printing, inkjet printing, roll-to-roll processing, it is now possible to produce large-area OPDs at a very competitive cost and with promising performance compared to inorganic counterparts –5. Meanw2O, O2 and solar irradiation, the morphology instability under storage or operating has been recognized as another main reason for the degradation of devices [Generally, it has been recognized that the OSCs and OPDs are vulnerable to oxygen and moisture when they are exposed to ambient atmosphere, resulting in the degradation of device performance over time. Due to the inferior stability of organic semiconductors compared to inorganic ones, the devices degradation will also be accelerated during operation under light irradiation. It was found that the performance degradation was mainly originated from deterioration of conjugated materials caused by the radical reactions , 10–12.  devices . For non devices . The pla devices , however devices , 20. Add devices , 22.x = 0, 0.05, 0.1, 0.2), respectively. It was found that the introduction of BTBHT moiety on conjugated backbone would enhance the photostability without sacrificing the morphological stability of blend films. Consequently, the all-PSC based on PTzBI-EHp-BTBHT0.1: N2200 achieved an optimal PCE of 9.96%, and the devices based on polymers with BTBHT moiety exhibited higher PCEs retention after continuous light irradiation for 300 h under ambient atmosphere. Investigations revealed that the introduction of BTBHT moiety could significantly suppress the trap-assisted bimolecular recombination under irradiation, guaranteeing the efficient charge separation and transport within active layers and thus improving the device photostability. In addition, all-polymer OPDs have been fabricated, and lower dark current density (Jd) at − 0.1 V bias and higher specific detectivity (D*) were achieved for OPDs based on PTzBI-EHp-BTBHTx and N2200-BTBHTx . Noteworthy, OPDs based on PTzBI-EHp-BTBHTx: N2200  showed almost negligible Jd increase under continuous irradiation over 400 h, significantly outperforming the device based on PTzBI-EHp: N2200. As a result, photoplethysmography (PPG) sensors for real-time heart rate detection were carried out with our OPDs based on PTzBI-EHp-BTBHTx: N2200, and considerable detection resolution and sensitivity could be obtained. This study provides a feasible molecular design strategy to develop conjugated polymers for all-PSCs and OPDs with simultaneously improved morphological and photostability.All-polymer solar cells  or photodetectors with polymers as both donor and acceptor have been proved an effective approach to improve the morphological stability , 24. Herx = 0, 0.05, 0.1, 0.2) (Scheme S1). All terpolymers are synthesized straightforwardly, and the intermediates and resulting polymers were characterized with nuclear magnetic resonance (NMR) spectra . The copolymerized ratios of BT units in both polymers have been quantitatively confirmed by analyzing the 1H NMR spectra evolution of polymers with gradually increased ratio of BT units . More materials synthesis details were described in the Supporting Information. The resulting terpolymers are readily soluble in common organic solvents such as chloroform (CF), chlorobenzene (CB) and 1, 2-dichlorobenzene (o-DCB) at room temperature, enabling their solution processability for all-PSCs and OPDs.The design of our new polymer donors and acceptors is derived from the PTzBI-EHp and N2200, respectively. Varied molar percentages of BT units with antioxidant BHT group-terminated side chain were used as the third component monomer for terpolymerization to afford the target terpolymers, PTzBI-EHp-BTBHTx and N2200-BTBHTx  curves were acquired from DSC 2500 with filmed samples of 2–3 mg under nitrogen flow at heating and cooling rates of 10 °C min−1. Thermogravimetric analysis (TGA) measurements were measured on TG209F1 with powdered samples of 2–3 mg under nitrogen flow at heating and cooling rates of 10 °C min−1. UV–Vis–NIR absorption spectra were recorded on a SHIMADZU UV-3600 spectrophotometer from 300 to 1000 nm. Cyclic voltammetry (CV) was measured on a CHI 660A Electrochemical Workstation with Ferrocene/ferrocenium (Fc/Fc+) as the calibration standard, and the potential of saturated calomel electrodes (SCE) was internally calibrated as 0.39 V. The energy level was calculated according to the following equations: EHOMO = − (Eox + 4.41) eV and ELUMO = − (Ere + 4.41) eV, where Eox and Ere are the onset oxidation potential and onset reduction potential relative to Hg/Hg2Cl2, respectively.Molecular weights of polymers were measured on an Agilent Technologies PL-GPC 220 high-temperature chromatograph in 1,2,4-trichlorobenzene at 150 °C using a calibration curve of polystyrene standards. The 3/Ag. The patterned ITO glass substrates were cleaned sequentially by sonication with detergent once, deionized water three times, and then isopropanol twice, and then dried at 65 °C in a baking oven overnight. After UV-ozone treatment for 4 min, for the fabrication of OSC, the ITO substrates were coated with PEDOT:PSS (CLEVIOSTM P VP AI 4083 from Heraeus) at 3500 rpm for 30 s. For OPD device, the ITO substrates were coated with ZnO at 3000 rpm for 30 s. The ZnO solution was synthesized by mixing 0.4 g of zinc acetate dehydrate in 110 μL of ehtanolamine and 4 mL of methoxyethanol. After annealed in the air at 150 °C on a hot plate for 15 min, the substrates were transferred into a nitrogen-filled protected glove box. The solution of polymer donor: acceptor , with a total concentration of 9 mg mL−1) were spin-coated at 3000 rpm to afford an ~ 110 nm active layer for OSC devices and 1000 rpm to obtain ~ 230 nm active layer for OPD devices, respectively. Sequentially, the active layers were thermally annealed for 10 min. Then, a thin layer of PFNBr was coated from its methanol solution (1 mg mL−1) onto the active layer to form an electron transport layer for OSCs, and a 10 nm of MoO3 was deposited on the active layer to form a hole transport layer for OPDs. Lastly, 100 nm Ag was thermally deposited on top of all devices through a mask under a vacuum of ~ 1 × 10–7 mbar. The effective area of the devices was 0.0516 cm2. More characterization methods for the devices are described in the Supporting Information.The OSC devices were fabricated in a conventional device configuration of ITO/PEDOT:PSS/Active layer/PFNBr/Ag. The OPD devices were based on an inverted device structure of ITO/ZnO/Active layer/MoOMn) in the range of 31–45 kDa with the polydispersion index (PDI) of ~ 2.1, while polymers N2200-BTBHTx exhibited the Mn of 98–114 kDa with PDI of ~ 2.3. The corresponding parameters are summarized in Table The molecular structures of the polymer donors PTzBI-EHp-BTBHTx and acceptors N2200-BTBHTx are shown in Fig. x = 0.05, 0.1, 0.2) display the almost identical solution and film absorption compared to their pristine polymer PTzBI-EHp, and a red-shift of the absorption edge could be observed for the films. By contrast, N2200-BTBHTx  exhibited solution and film absorption with the similar absorption peaks compared to their pristine polymer N2200, and no red-shifted absorption could be observed for the films. Notably, the intensity enhancement of the charge-transfer absorption band (600–800 nm) could be observed for N2200-BTBHTx  compared to N2200, and an increase in 450–560 nm could be observed for N2200-BTBHT0.2 due to the superposition effect of the BTBHT moiety absorption. The optical bandgap  were similar to those of pristine PTzBI-EHp and N2200, respectively . As shown in Fig. 2. As shoTo gain more insights of the materials properties, the thermal properties of all polymers were evaluated by TGA and DSC measurements . The 5% weight loss temperatures over 400 °C of both PTzBI-EHp-BTBHTx and N2200-BTBHTx indicate that all polymers have good thermal stability. The DSC results of polymer donors PTzBI-EHp-BTBHTx show no obvious melting or crystallization peaks in the temperature range of 25–300 °C, indicating their amorphous characteristics. Differed from PTzBI-EHp-BTBHTx, all polymers N2200-BTBHTx exhibit melting and crystallization peaks, and the melting temperature is gradually lowered with increasing the BTBHT moiety ratio from 0 to 0.2, indicating the introduction of BTBHT moiety may decrease the crystallinity of N2200.x = 0, 0.05, 0.1, 0.2), the absorption intensity decrease (500–700 nm) after 62 days of continuous light irradiation under ambient condition can be effectively suppressed when reasonable ratios of BTBHT moiety are incorporated. Particularly, 80% of the peak absorption can be remained for the PTzBI-EHp: N2200-BTBHT0.1 blend film, significantly higher than 58.7% for the PTzBI-EHp: N2200 film. Similarly, the absorption intensity decrease can be effectively decelerated for PTzBI-EHp-BTBHTx: N2200 -based blend films after light irradiation under ambient condition. . It should be noted that the absorption band in 500–650 nm of blend films can mainly ascribed to the PTzBI-EHp, while the absorption band in 680–800 nm is mainly ascribed to the N2200 and the weak absorption intensity in 680–800 nm is presumably due to the lower absorption coefficient of N2200 than PTzBI-EHp. As demonstrated in previous work, for PTzBI-EHp: N2200-BTBHTx blend films, the BHT groups could eliminate the radicals in both PTzBI-EHp and N2200 polymer chains, resulting in the suppressed deterioration of PTzBI-EHp even though the BHT group was attached into N2200 [A preliminary investigation on the stability of the polymers is to monitor their UV–Vis-NIR absorption spectra change during continuous aging under light and ambient condition. As shown in Fig. x = 0, 0.05, 0.1, 0.2) blend films are similar. In contrast, a fibrous structure can be observed in the PTzBI-EHp-BTBHT0.1: N2200 and PTzBI-EHp-BTBHT0.2: N2200 blend films  and transmission electron microscopy (TEM)  and short-circuit current densities (Jscs), which are in good accordance with the Jscs calculated by external quantum efficiency (EQE) spectral integral -based all-PSCs : N2200-BTBHTx  system were further fabricated, which showed no enhanced photovoltaic performance (as shown in Table S1). Therefore, we focus our discussion mainly on PTzBI-EHp-BTBHTx: N2200-BTBHTx system in this work.The photovoltaic performance of all-PSCs with synthesized polymers as active layers was evaluated. The statistical summary of photovoltaic parameters is shown in Table ral Fig. b. The hiSCs Fig. d, e. Con, encapsulated OSCs were firstly aged in the air at room temperature under continuous light irradiation with a solar simulator (an intensity of 100 mW cm−2 LED). The PCE values of devices were tracked during the aging experiment period until 300 h as shown in Fig. 2O and O2 ambient conditions was explored. As shown in Fig. S27, when exposed to light and ambient conditions, all unencapsulated devices exhibit faster degradation rates than those encapsulated devices. This further indicates that the entry of H2O and O2 in the atmosphere is the main cause of photooxidative degradation of OSCs. Notably, comparing with the device based on PTzBI-EHp: N2200, the devices based on both PTzBI-EHp-BTBHTx and N2200-BTBHTx  exhibited a slower PCE degradation after 6 h of exposure to light irradiation and ambient condition, further validating the efficacy of copolymerizing BTBHT moiety for preventing the free radical degradation pathway of conjugated polymers and eventually improving devices long-term stability. Moreover, the devices with antioxidant BHT groups also demonstrated superior long-term thermal stability. Device stability with different content of BHT groups was evaluated without encapsulation at 80 °C in N2-filled glovebox. As shown in Fig. S28, the trends of the PCE values are consistent with that of long-term stability of OSCs under light irradiation, indicating that the introduction of BHT groups also plays a positive role in the morphological stability.To verify the speculations that the polymers featured with antioxidant BHT groups can improve the stability of the OSCs in the air conditionGmax) are defined as /qL, where q represents elementary charge, L is the film thickness, and x = 0, 0.05, 0.1, 0.2): N2200, all devices show similar Gmax values of about 1.0 × 1028 m−3 s−1 and x = 0, 0.05, 0.1, 0.2): N2200 based all-PSCs. These results are consistent with the aforementioned similar FF values, which is recognized to be closely correlated to the exciton generation and charge recombination process [x = 0, 0.05, 0.1, 0.2), the Gmax value and Gmax values and x = 0.1, 0.2)-based devices indicate the inferior exciton generation and dissociation within active layers, which can well explain the lower FF and Jsc values in these two devices. The relevant Gmax values are summarized in Table S2.The exciton dissociation probability  current . The pho process . MeanwhiJsc was first determined. According to the power law a is an exponential factor and the exponent a represents the degree of bimolecular recombination. If no bimolecular recombination exists in the device, the exponent a value even after 300 h of aging. These results show that the introduction of BTBHT has little effect on the bimolecular recombination loss in these devices. As expected, we get similar results in OSCs based on PTzBI-EHp: N2200-BTBHTx systems. Furthermore, the relationship of Voc as a function of Voc and Non-geminate recombination dominates in OSCs and can be divided into two molecular recombination and trap-assisted recombination . In ordeose to 1 . The valinvolved . As showJd)-voltage (V) curves of OPDs based on the pristine and antioxidant BHT-modified polymers with the same processing conditions and device structure. It is obvious that a suppressed dark current density by almost one order of magnitude could be achieved for OPDs based on PTzBI-EHp-BTBHTx  and N2200-BTBHTx  compared to that based on PTzBI-EHp and N2200. Notably, the low Jd of the OPD devices is beneficial for achieving high-quality signals for broad utility in practical applications [Jd under reverse biases, indicating an improved ability to block the reverse injection current [To further check the photovoltaic performance of the synthesized polymers, organic photodetectors for light detecting were also fabricated. Figures ications –28. Furtications :1\docume current –32.Fig. D*) [2 in this work), Jd. Therefore, the EQE of the OPDs are relatively low compared to the OSC devices as a result of the low charge mobility of organic semiconductors and severe charge recombination in thick photoactive layers. The value of D* can be simply expressed by Jd)1/2 as the shot noise is dominant under reverse bias [D* values under − 0.1 V bias of devices based on BTBHT-featuring polymers are significantly higher than the control device, achieving the values over 1013 Jones (Jones = cm Hz1/2 W−1) at 350–750 nm. The maximum D* of 2.94 × 1013 and 5.35 × 1013 Jones at 600 nm could be obtained for OPDs based on PTzBI-EHp-BTBHT0.1: N2200 and PTzBI-EHp: N2200-BTBHT0.1, respectively.Another key figure-of-merit of OPD devises is the specific detectivity (D*) , 34, 35,rse bias , 37. MorJd under reverse bias of − 2 V for all the OPD devices. For devices based on PTzBI-EHp: N2200, the Jd value starts to remarkably increase after aging over 250 h. However, the Jd values of devices based on PTzBI-EHp-BTBHTx  show no obvious increase and can be stabilized at order lower than 10–8 mA cm−2, demonstrating the effectiveness of BTBHT units for preventing the degradation of OPDs. As for the stability of the dark current density based on polymer acceptors N2200-BTBHTx, to our surprise, the introduction of BTBHT moiety on N2200 has negligible influence on long-term Jd stability . We attribute this decreasing in OPD performance to the high noise signals of OPD devices after aging based on polymer acceptors N2200-BTBHTx .For the OPD based on BTBHT-featuring polymers PTzBI-EHp-BTBHTx and N2200-BTBHTx, we further evaluate the stability by monitoring the value of the dark current density during the aging procedure. The unencapsulated OPD devices were aged in the air condition at room temperature. Figures x: N2200  provided higher detectivity than the control device, facilitating increased resolution of PPG signal with clear systolic and diastolic peak.In addition, PPG sensors for real-time heart rate detection were carried out using our OPDs based on PTzBI-EHp-BTBHTx: N2200 because of its outstanding stability at air condition. PPG of a single red light source (light intensity of 0.72 mW) was recorded by detecting changes in the reflected light from the skin, which infers the arterial pulse wave. As displayed in Figs. x  and N2200-BTBHTx  were successfully synthesized. Appropriate ratio of BTBHT moiety in the conjugated backbone would not significantly affect the molecular weight, absorption and energy levels of polymers. Impressively, comparing with pristine polymer PTzBI-EHp and N2200, BHT-containing polymers exhibit enhanced photostability under continuous light irradiation over 60 days at ambient atmosphere. All-polymer solar cells and photodetectors based on obtained polymers were fabricated. The all-PSC based on PTzBI-EHp-BTBHT0.05: N2200 achieved an optimal PCE reaching ~ 10%, relatively higher than that of PTzBI-EHp: N2200 based cells. Noteworthy, all-PSCs based on polymers with BHT-featuring side chains achieved superior device stability under light irradiation of 300 h. The deep insight demonstrated that the suppressed trap-assisted charge recombination might be the main reason for the enhanced photostability of all-PSCs based on BTH-featuring polymers. In addition, all-polymer photodetectors have been fabricated with these polymers, and OPDs based on BHT-featuring polymers achieved lower Jd and higher D* than devices based on PTzBI-EHp: N2200. The D* over 1013 Jones could be obtained in the region of 350–750 nm for PTzBI-EHp-BTBHT0.05: N2200 based device. Moreover, OPDs based on PTzBI-EHp-BTBHTx: N2200  realized steady and low Jd under continuous irradiation over 300 h, whereas the Jd of PTzBI-EHp: N2200 based device was significantly increased after irradiation over 200 h. This study provides an effective molecular design approach to improve the stability of OSCs and OPDs, which may shed some light on the future material development for the ultimate industrialization of organic photovoltaics.In summary, a general strategy for enhancing the photostability of conjugated polymers was proposed with introducing the antioxidant BHT group on the side chains of terpolymers. Two series of polymer donors and acceptors, PTzBI-EHp-BTBHTSupplementary file1 (PDF 3778 kb)Below is the link to the electronic supplementary material.


Finally, we organized an applicant-driven grant round to allocate funding to the ‘Neonatal Sepsis in Nigeria’ project to conduct a pilot study and awareness campaign. This work opens perspectives for the design of frugal educational programmes and the funding of context-specific, community-driven projects aimed at empowering local stakeholders in the global South.International development and aid are often conducted through the allocation of funding determined by decisions of non-locals, especially in the west for those in the global south. In addition, such funding is often disassociated from local expertise, therefore providing little long-term developmental impact and generating distrust. This is particularly true for conservation, as well as environmental and educational programmes. We hypothesize that by granting local people the educational tools and the necessary funding to develop their own projects through the use of an applicant-driven peer-review approach, it is possible to relocalize the decision-making process to the programme participants, with the potential to generate and select more relevant projects with developmental outcomes of higher quality. Here we created an online curriculum for antimicrobial resistance (AMR) education that was followed by 89 participants across Ghana, Tanzania, Nigeria and Uganda. We then created an open research programme that facilitated the creation of eight  Natural selection of antibiotic-resistant strains in these antibiotic-rich environments gives an advantage to new and emerging resistant strains in rural and urban settings globally, as well as clinical settings where antibiotics are more commonly used and required for medical treatment [Harmful bacteria cause more deaths per year worldwide than either AIDs or Malaria . For mosreatment . Soon thLow and middle-income countries (LMICs) bear the highest burdens of infectious diseases with potentially the least resources, and also have limited data on the epidemiology and burden of antimicrobial resistance . A 2017 The COVID-19 pandemic has underscored the importance of new paradigms for testing and researching infectious pathogens. The use of pathogen genomics has provided information to scientists in record time to help guide public health strategies. Hence recent efforts in Nigeria saw researchers use sequencing to study and characterize sequence types (STs) for AMR bacteria causing hospital-acquired infections . DatasetThere have been efforts in the past to improve the infrastructure of LMICs, especially in Africa, however the majority of these programmes have been initiated by projects coming from a western nation with control over project management at all levels . This haTherefore, similar to this emphasis on bottom-up – as opposed to top-down – change, a concept of ‘smart people before smart cities’ has become dominating sentiment, with the creation of opportunities for residents, in particular educational ones, being a priority that must go hand in hand with infrastructure improvements . This cade novo project creation.During the COVID-19 pandemic, international programmes of educational support were encouraged to make educational resources available online and disseminated locally where possible. This has shown to work well in some settings such as high schools  as well Just One Giant Lab (JOGL) is an NGO for collaborative science. In partnership with Hive Biolab, Kumasi, Ghana, University for Development Studies (UDS), Tamale, Ghana and Mbeya University of Science and Technology (MUST) Tanzania, and with the support from the Microbiology Society, JOGL hosted a grant round to catalyse project creation by participants in response to the need for increased capacity building and a focus on education organized a virtual training series on antimicrobial resistance (AMR). We also provided a training on the use of an AMR tracking app ‘microBIS.io’ for a pilot result. The goal of the workshop was to build the capacity of university students and laboratory technicians on the latest trends in AMR screening and testing, as well as increase AMR stewardship and empower them with the resources to become agents of change in reversing the spread and negative effects of AMR in Africa.All participants in the AMR workshop were invited to join the ‘Africa against AMR Community’ space on the JOGL collaborative network platform  as well The project team developed a curriculum to cover important aspects of microbiology, AMR, and innovative approaches to tackle the challenge Finally, at the end of the programme a grant round was conducted. In person practical sessions were held separately from the main programme, to coordinate with term times for participating academics, in Tanzania and Ghana, asynchronously ., and the names and identifiable aspects of members were removed before geotagging. Upon signup to the platform, consent is given for location tracking, in the user terms and conditions.Geotags of the coarse-grained information (town level) participant locations were pulled from the JOGL website and converted using Geo-Coder , and theParticipants were contacted through social media channels such as Twitter, Facebook and LinkedIn to advertise a free curriculum and grant round, in addition to on our constructed site. Existing media accounts with 4000+ followers allowed for sharing between individuals through connections.The course was composed of two parts – an online workshop series and onsite practical sessions. Each lecture was created 1 week ahead of schedule. The online workshop consisted of five modules delivered as weekly Zoom webinars from 21 September to 19 October. These sessions were recorded and the videos were uploaded on YouTube . PracticFor presenting the modules within the ‘Massive Open Online Course’ (MOOC), and the grant review round, we used a citizen science and project creation network called ‘Just One Giant Lab’ . This alCoordinators of the programme local to Ghana and Tanzania were found through the JPIAMR portal for collaborator finding, as well as through existing shared contacts. They were reached out through email and the collaboration was initiated at the grant writing stage, with further participants and partners invited after the grant award by our funders.Administration was conducted first through a google form (Data Summary) for the collection of emails. The resulting email spreadsheet, which included demographic information, was then used to liaise for the rest of the course.The grant round  leverageet al. [Similar to Masselot et al. , particiet al. , its modJOGL organized the ‘AMR in Africa Grant Round’ to support one research, innovation or education project tackling AMR in Africa. The call for proposals ran for 1 month, from 18 November to 18 December 2021. We used a proposal template as attached (Data Summary) with a focus on the antimicrobial resistance outcomes to encourage a formal application approach, then used the following format for administration . ApplicaThe virtual training attracted 89 participants (whom attended at least two online sessions) across the African continent from diverse backgrounds; such as laboratory technicians, students, researchers and innovators . More thde novo project creation and onboarding  may be due to the fact that the workshop was dominated by undergraduate students and early career lab technicians, who identified concepts they could apply in their day-to-day work. However, the modules on antimicrobial stewardship and digital mapping are equally relevant in developing additional leadership, coordination and digital literacy skills required for the next level of careers. Comments in particular on ministerial and governmental cooperation to improve outcomes and network are particularly significant changes that future programmes could integrate.In summary, the AMR workshop and curriculum as a means to build new projects were carried out to a satisfactory level with future iterations likely to alter the curriculum based on signup and topic interest, based on the team’s experience organizing and delivering the programme, and the feedback received from the participants  . There After the curricula, in total eight projects  applied In addition to the projects created, by creating a community internationally through the web, the collection of information for database-related programmes can be improved. A collaborator who took part in the education aspect of the programme, asked participants working in hospitals to gather data of location, and resistance of bacterial strains, which allowed the team to begin the creation of an antimicrobial resistance location database. Further success in reaching out to participants would allow an international map, and service not possible in on the ground programmes. We have supplied a sample of this data for illustrative purposes . In future programmes, such communities can be leveraged for similar community science outputs such as data gathering.Some of the participants met virtually for the first time because of the project. Throughout the development of the courses and practical sessions, there has been exchanges of good practices among participants who are from different countries and continents. The high level of collaboration shown throughout the project paved the way for future joint proposal writing for a bigger grant to curb the menace of AMR worldwide, and an active online science sharing community. Some participants have networked during the workshop and we hope this project provided the right platform for early career scientists in AMR to share their experiences with one another to tackle issues of AMR in Africa.de novo projects and organized a community review round that funded one project selected by applicants and participants of the online curriculum. As such, we performed a hybrid model of online curriculum and grant allocation. We worked with local partners and participants as community drivers, with democratic and local values upheld by decisions of applicants themselves, whilst encouraging a new collaborative project-based perspective in antimicrobrial resistance for medical staff, technicians, students and others.Through the use of a local network of contacts and the ‘Just One Giant Lab’ web platform, we were able to create an online curriculum for AMR and deliver this to a diverse audience-based predominantly around Uganda, Nigeria, Tanzania and Ghana. We hosted a programme fostering the creation of eight The techniques of applicant-driven grant decision-making, and online delivery of free educational resources as a pathway for science and awareness funding, provided some success across multiple sub-saharan African nations on a small scale. This method with further funding could help foster development in a cost-efficient manner and at an international scale. This programme and its scale would not have otherwise been possible in person due to travel costs, yet through an online medium, it allowed for capacity building with an educational programme as well as local project creation and curation. This technique opens perspectives to design frugal approaches, allowing a programme team to locally empower individuals in context-specific project catalysis and science education. The authors would encourage other similar initiatives, and also find it likely that if the initiative centred on antimicrobial resistance was possible in areas as culturally diverse as the regions presented it would be replicable in other consortiums nationally and internationally elsewhere, especially the global south.


Theranostic in nuclear medicine combines diagnostic imaging and internal irradiation therapy using different therapeutic nuclear probes for visual diagnosis and precise treatment. GLP-1R is a popular receptor target in endocrine diseases, non-alcoholic steatohepatitis, tumors, and other areas. Likewise, it has also made breakthroughs in the development of molecular imaging. It was recognized that GLP-1R imaging originated from the study of insulinoma and afterwards was expanded in application including islet transplantation, pancreatic β-cell mass measurement, and ATP-dependent potassium channel-related endocrine diseases. Fortunately, GLP-1R molecular imaging has been involved in ischemic cardiomyocytes and neurodegenerative diseases. These signs illustrate the power of GLP-1R molecular imaging in the development of medicine. However, it is still limited to imaging diagnosis research in the current molecular imaging environment. The lack of molecular-targeted therapeutics related report hinders its radiology theranostic. In this article, the current research status, challenges, and emerging opportunities for GLP-1R molecular imaging are discussed in order to open a new path for theranostics and to promote the evolution of molecular medicine. GLP-1R belongs to the subfamily of G protein-coupled receptors . It is win vivo. Based on this, the advent of GLP-1 analog opens a new direction for molecular imaging. Except the GLP1 analogue exendin-3 and its antagonist exendin-(9–39) are involved in GLP-1R molecular imaging studies as GLP-1 ligands. The most successful and widely used ligand for current GLP1R molecular imaging is still exendin-4. As the first generation GLP1 analog, it is a 39-amino acid peptide structure, which was discovered and extracted from Gila monster saliva and shared 53% identity with human GLP1  man GLP1 . Meanwhiman GLP1 . With thIn the initial exploration of molecular imaging of GLP-1R, Korner  first laEven before the discovery of exendin-4, its homolog exendin-3 was successfully synthesized by 125I labeling and utilized in two models of insulinoma (NEDH rats and RINm 5F cells) , which oInitially , Wild wa2Sar at pH 7.0, and the coupling products BaMalSar-exendin-4 and Mal2Sar-(exendin-4)2 were purified by HPLC with stirring at room temperature in yields greater than 90%  study , 18F-FBEAnd compared with FDG PET/CT, GLP1R molecular imaging is more friendly to patients with type 2 diabetes. It allows for a more visual assessment of GLP1R metabolic expression levels in the surviving myocardium at the molecular metabolic level. Therefore, in the future, it could complement the assessment of inflammation in the molecular metabolism of surviving post-infarction cardiomyocytes. And it can be used together with other routine tests to provide the evaluation value of surviving post-infarction cardiomyocytes from different perspectives including myocardial dynamics, perfusion and molecular metabolism. However, because only a few preclinical studies of GLP1R molecular imaging have been performed, there is a need for a larger future.GLP-1/GLP-1R in the endocrine field has been accompanied by the introduction of semaglutide, which has become a principal receptor target. The initial release of the SUSTAIN and PIONEER phase III clinical trials established its landmark importance in treating type 2 diabetes mellitus (T2DM) and obesity . More reIt is well known that a decrease in pancreatic islet beta cells causes diabetes . At firsThe GLP-1R antagonist exendin  is the m177-Lu, as an essential part of theranostics, does not perform satisfactorily in previous insulinoma imaging. Eriksson  initiallBefore the development of mesenchymal stem cells and pluripotent stem cells for the treatment of diabetes, the most effective treatment for type 1 diabetes (T1D) was portal vein islet transplantation. It primarily administered donor islets to the liver via the portal vein. In the hepatic sinusoids, the islet cells could proliferate and secrete insulin. Portal vein islet transplantation has achieved good results in protecting patients from severe hypoglycemia. Regarding pancreatic β-cells, it makes sense to monitor graft survival in patients with pancreatic β-cell transplantation with GLP-1R molecular imaging. Previous studies have clarified  that GLPInitially, 111In-Exendin-3 SPECT/CT imaging  detectedMoreover, a recent study  showed tBenign insulinoma is the most common cause of endogenous hyperinsulinemic hypoglycemia (EHH). GLP-1R molecular imaging will become the ideal choice for non-invasive localization and diagnosis of benign insulinoma patients in the future. The clinical presentation of CHI is similar to that of insulinoma, which can cause misdiagnosis. It must therefore be carefully excluded when diagnosing insulinoma with EHH symptoms. In the past, nesidioblastosis was synonymous with congenital hyperinsulinemia. Until 1995 , the genIn recent years, several studies  using diMEN-1 is an autosomal dominant genetic disease caused by mutations in its tumor suppressor gene. Most patients will gradually progress to multifocal functional or non-functional pancreatic neuroendocrine tumors. Therefore, seeking a non-invasive means of identification at an early stage is necessary. GLP-1R molecular imaging in patients with MEN-1 mutations is a subject of increasing research. It is a very positive sign for endocrinology. Molecular imaging can enhance the diagnosis of an ion channel or genetically inherited diseases such as CHI and MEN-1, which are rare in clinical practice.In 2019, That said, the results of an earlier study  are wortIn summary, from our summary of the current status of GLP-1R molecular imaging in endocrinology , we realThe expression of GLP-1R was initially detected in the nucleus tractus solitarius and hypothalamus. As the research progressed, so did other brain parts, such as the frontal cortex, hippocampus, amygdala, and substantia nigra. In addition to being primarily distributed in the pancreatic islet cell, it can appear selectively in the central nervous system . The theMolecular imaging has already become a crucial clinical tool in the diagnosis of AD and PD. For instance, the tracer 11C-PIB, as is now widely used for imaging AD age spots . HoweverFor the first time, The research on GLP-1R molecular imaging in neurodegenerative diseases and other central nervous system diseases has not achieved more extraordinary breakthroughs, limited to preclinical studies and related studies of blood-brain barrier penetration. There remains a significant gap in the comparative study of GLP-1R and neurodegenerative mechanisms and the improvement of symptoms in clinical patients. The experimental investigation of combining GLP-1R molecular imaging with other related nervous system diseases is an emerging opportunity in that uncharted territory. It could drive the neurology theranostic.As mentioned previously, ligand selection for GLP-1R molecular imaging is currently still centred on exendin-4. Although exendin-3 and exendin-(9–39) have also been involved as other ligands in studies of insulinoma and pancreatic β-cell mass determination. However, the structural form of the ligand for both exists only in the single form of Lys40-exendin-3, Lys27-exendin-(9–39) . DiverseA chelator is an organic molecule that can chelate with heavy metal ions. Both SPECT/CT and PET/CT present a more diverse selection of chelating agents to try in preclinical studies. Unfortunately the chelating agents that eventually translate to clinical use are mainly shown in In contrast to translational clinical chelators, preclinical studies have included the successful preparation of a variety of derivative chelators with 18F targeting markers. However, these chelators remain limited to preclinical studies, which may be related to the high cost of 18F radionuclides, high radiation burden, and cumbersome preparation of derivatives. A similar phenomenon is also seen in ligand selection. Both for Lys40-exendin-4 and Cys-exendin-4, their ligands are limited to exendin-4 itself. Therefore, there is an urgent need to find chelators with better affinity for the target peptide and to explore the preparation of more diverse and stable ligands in the future. This is also the key to successful diagnostic integration in GLP-1R molecular imaging.GLP-1R molecular imaging is currently the most promising non-invasive method for detecting benign insulinoma and other GLP-1R-positive diseases. The experimental expansion of various molecular probes has become a trend, and 68Ga-exendin has emerged in clinical transformation, becoming an efficient target probe choice for the localization of insulinoma. The diversity of nuclides in preclinical studies is awkward in the transition to clinical studies, as shown by our summary of the molecular imaging results of insulinoma. The main radiolabels that have been successfully translated into clinical practice are 111In, 99mTc and 68Ga. This is mainly due to their relatively low radiation load, the relative ease of preparation and their economic cost. The long half-life nuclides 89Zr, 64Cu and 177Lu, on the other hand, have greatly hindered the progress of their integration into clinical translational therapy due to the disadvantages of their high renal burden. This is the main issue that we need to urgently address in the future in the field of GLP-1R therapy.Meanwhile, the choice of ligand is also crucial in determining the labelling strategy and the prerequisite basis for peptide preparation. It has been mentioned many times that current research, both pre-clinical and clinical, is focused around exendin-4 ligands. The ligand, although based on exendin-4 taps into a more established type of more diverse forms including Lys40-exendin-4 and Cys40-exendin-4. However, the strategy of exendin-4-based peptide synthesis and preparation has not yet left the core of exendin-4. Is it possible to explore the future from the new generation of GLP-1R analogues such as semiglutide and use them as substrates to develop more ligands and peptides with better stability and lower renal radiation? Such a direction may become a new phase of exploration for GLP-1R molecular imaging afterwards. On the one hand, the high renal uptake of exendin-4 limits its clinical application and translation. Although the preparation of different derivatives to reduce renal uptake is still troublesome. It may lead to tumors in the distal tail of the pancreas that overlap with the kidneys. As a result, these lesions are missed during imaging, and the average uptake of duodenal Brunner’s glands may also be a source of confusion for tumor imaging with this tracer . On the In previous studies, adverse reactions such as nausea, vomiting, and hypoglycemia have been discovered in patients after imaging . TherefoThe performance of GLP-1R molecular imaging in diabetic BCM gives us insight and hope for theranostic. Recent studies have discovered novel targets in neuroendocrine tumors, such as the glucose-dependent insulin-biophilic polypeptide receptor (GIPR), the same hormone receptor as GLP-1R. Because it is expressed in gastrinoma and bronchial lung cancer, it holds great promise for molecular imaging of NENs when the GLP-1R is negative . The gal


Most commonly employed methods for analyzing InsPs have been geared towards resolving regioisomers, but they have not been capable of resolving enantiomers. In this study, we present a general approach for enantiomer assignment using NMR measurements. To achieve this goal, we used 31P-NMR in the presence of L-arginine amide as a chiral solvating agent, which enables the differentiation of enantiomers. Using chemically synthesized standard compounds allows for an unambiguous assignment of the enantiomers. This method was applied to highly phosphorylated inositol pyrophosphates, as well as to lowly phosphorylated inositol phosphates and bisphosphonate analogs. Our method will facilitate the assignment of biologically relevant isomers when isolating naturally occurring compounds from biological specimens.Inositol phosphates constitute a family of highly charged messenger molecules that play diverse roles in cellular processes. The various phosphorylation patterns they exhibit give rise to a vast array of different compounds. To fully comprehend the biological interconnections, the precise molecular identification of each compound is crucial. Since the  A generally applied assignment of the positions at the ring originates from another subclass of inositol phosphates, the phosphatidyl inositol phosphates, where the glycerol backbone is attached to the 1 position of the inositol , forming phosphoanhydride bonds, inositol pyrophosphates (PP-InsPs) are formed. One additional phosphate group generates PP-InsP5 . Six different PP-InsP5 isomers are possible, including two enantiomeric pairs (1/3-PP-InsP5 and 4/6-PP-InsP5), whereas the remaining two are achiral meso-compounds  are possible, including six pairs of enantiomers. Of note, both 1/3-PP-InsP5 and 4/6-PP-InsP5 have been identified in biological systems -inositol in combination with SAX-HPLC and subsequent scintillation counting. Gel electrophoresis (PAGE) is an alternative method that is inexpensive and readily available. Although it can separate higher InsPs, it has great difficulty distinguishing between PP-InsP regioisomers - and [13C2]-labeled myo-inositols in combination with 13C-, 31P-, and two-dimensional-NMR measurements . 5-. 5-1 (28myo-inositol (1) harbors a mirror plane through the 2/5 positions of the molecule. Depending on the substitution pattern, different sets of signals were obtained for the InsPs and PP-InsPs in the 31P{1H}-NMR spectrum. The monophosphate signals appear in the range from 2 to −2 ppm. Signals of the pyrophosphates are visible in the range of −8 to −12 ppm. The shifts are strongly dependent on the pH value and the counterions [As discussed above, nterions .5 enantiomers, we measured various InsP and PP-InsP compounds [2-InsP4 , we observed the typical signal set in the 31P-{1H}-NMR spectrum (31P-{1H}-NMR due to enantiotopicity. The addition of L-ArgNH2*HCl (8) creates a chiral environment that leads to diastereotopicity and a slight observable shift (Δppm up to 0.05 ppm) in some of the signals of each analyte (2*HCl (8), and no splitting of the signals was observed  showed identical resonances in the 31P-NMR spectrum when mixed together, and only one set of signals was observed (2*HCl (8), we observed the splitting of resonance signals to distinct subsets, both in the monophosphate region and for the signals of the pyrophosphate group (Δppm up to 0.1 ppm). By spiking with enantiopure compounds, we are able to make an absolute assignment (2*HCl (8), and—as expected—only one set of signals was observed. The experiment was also conducted with enantiopure 1- and 3-PP-InsP5 (3 and 7) and again could be applied successfully for an absolute assignment of enantiomer identity (6), they do not impede the assignment of the absolute configuration.As the method was successful in analyzing PPobserved a. Howevesignment c. In a cidentity . Althoug5. Therefore, a racemic mixture of 1,4,5,6-InsP4 (18) was synthesized (see 31P{1H}-NMR measurements were conducted. While the effectiveness of L-ArgNH2*HCl (8) was found to be largely independent of the pH value for InsP5, InsP7, and InsP8, a signal splitting into distinct subsets for InsP4 was only obtained within a narrow pH range. At a pH value between 7 and 8, we observed the expected splitting of the resonance signals (Δppm up to 0.06 ppm) in the presence of L-ArgNH2*HCl (8), whereas no splitting was observed in the absence of the chiral solvating agent (4 (18a), we were able to assign the signals to each respective enantiomer  under the same conditions mentioned above. The method was successful in resolving the enantiomer signals, but the pH adjustment was even more critical , which contains a non-hydrolyzable bisphosphonate (PCP) group substituting the diphosphate group. While these molecules do not occur in biology, we wanted to understand if the chiral solvating agent approach would also enable the determination of enantiomeric purity in such samples. Again, the addition of L-ArgNH2*HCl (8) resulted in the splitting of individual signals into subsets, independent of the pH value, allowing for the assignment of the respective enantiomers in principle (1 (28) with only three phosphate groups  in combination with 13C-, 31P-, and two-dimensional-NMR measurements [2*HCl (8) as a chiral solvating agent in combination with 31P-NMR measurements. The method previously published for analyzing InsP5 enantiomers [The accurate analysis and identification of regioisomers and enantiomers is a significant challenge but crucial for understanding the complex network of InsPs and PP-InsPs in biological systems ,23,37,38urements ,21,22,23ntiomers  has been2 method and purified by SAX column chromatography or PAGE [5, ca. 10 micrograms of material purified by PAGE was required for unambiguous enantiomer assignment. While this is a significant amount to isolate from biological samples, we and others have demonstrated that it is possible. Furthermore, the enantiomerically pure standard compounds need to be synthetically accessible, underscoring the importance of chemical synthesis in this interdisciplinary research area. An obvious advantage of the method described herein is that it relies on commercially available and cheap L-ArgNH2*HCl (8) that enables the resolution of enantiomeric pairs across a wide range of different inositol phosphorylation, pyrophosphorylation, and diphosphonate patterns. It is, therefore, a valuable addition to the current repertoire available to resolve the enantiomeric identity of InsPs and PP-InsPs.Our NMR-based method for enantiomer assignment can be used to assign the biologically relevant enantiomers of InsPs and PP-InsPs isolated from cells using, e.g., the TiO or PAGE . However


However, when GDP per capita and the governance index were included in the multivariable model, temperature change was no longer associated with AMR. Instead, the main predictors were antibiotic consumption , population density , and the governance index . Ensuring the appropriate use of antibiotics and improving governance efficiency are the most effective ways of counteracting AMR. It is necessary to conduct further experimental studies and obtain more detailed data to investigate whether climate change affects AMR.Although previous studies showed that warmer temperatures may be associated with increased antimicrobial resistance (AMR) rates, unmeasured factors may explain the observed relationship. We conducted a ten-year ecological analysis to evaluate whether temperature change was associated with AMR across 30 European countries, considering predictors that can determine a geographical gradient. Using four data sources, we created a dataset of: annual temperature change (FAOSTAT database); AMR proportions for ten pathogen–antibiotic combinations (ECDC atlas); consumption of antibiotics for systemic use in the community (ESAC-Net database); population density, gross domestic product (GDP) per capita, and governance indicators (World Bank DataBank). Data were obtained for each country and year (2010–2019) and analyzed through multivariable models. We found evidence of a positive linear association between temperature change and AMR proportion across all countries, years, pathogens, and antibiotics (β = 0.140; 95%CI = 0.039; 0.241;  Antimicrobial resistance (AMR) has become a significant threat to global health as a result of higher disease severity, prolonged illness, a substantial number of deaths and disability-adjusted life years (DALYs), and higher healthcare costs due to infections caused by antibiotic-resistant pathogens . This isFrom that point on, numerous national and international studies consistently estimated that the burden of infections with antibiotic-resistant bacteria exceeds that of other infectious diseases ,2,7,8,9.Escherichia coli and Klebsiella pneumoniae resistant to third-generation cephalosporin and to methicillin-resistant Staphylococcus aureus (MRSA) [In spite of a slight decline from 2019 to 2020, an increasing trend of infections, attributable deaths, and DALYs due to antibiotic-resistant pathogens has been observed during the last decade . These rs (MRSA) . Howevers (MRSA) . AMR proportions often correlate with levels of antibiotic consumption . In factIn the past decade, temperature changes in European countries have been observed and reported, resulting from human activities such as industrialization and deforestation, and from natural factors such as solar radiation and ocean currents . This waTo better investigate this topic, we tested the hypothesis that countries that experienced the greatest temperature change over the past decade have also reported a higher increase in AMR rates. With this purpose, we carried out a ten-year ecological analysis to evaluate whether temperature changes, and not simply local temperature, may have been associated with AMR proportions across European countries and over the years 2010–2019. The analysis also included important predictors and/or confounders that can determine the geographical gradient observed, helping to explain the hypothetical relationship reported by previous studies.K. pneumoniae than E. coli and S. aureus. While the proportion of E. coli resistant to carbapenem remained low overall, some countries exhibited an increasing trend of K. pneumoniae resistant to carbapenems. For all other combinations between Gram-negative pathogens and antibiotic classes, a moderate increase over time was observed for most countries, especially up until around 2014. For S. aureus, instead, there was a generally decreasing trend in the percentage of MRSA isolates. Except for carbapenem resistance, there were large variations between countries for all pathogens and antibiotic classes under consideration. Between 2010 and 2019, there was a significantly increasing trend in the weighted average of AMR in Europe A. HoweveIn the same years, there was also a significantly increasing trend in the annual temperature change B, even tp = 0.102; E. coli resistant to third-generation cephalosporins  and K. pneumoniae resistant to fluoroquinolones . Marginally non-significant evidence was observed for a positive relationship with K. pneumoniae resistant to third-generation cephalosporins , and a negative relationship with MRSA  and E. coli resistant to aminopenicillins .Although we found no evidence of a linear association between annual temperature change and AMR across all countries, years, pathogens, and antibiotic classes . In the multivariable model, both antibiotic consumption  and population density  remained significantly and positively associated with AMR proportions.We also observed differences in antibiotic consumption and population density across countries and over the years . Unadjusp <0.001), population density , and the governance index . Note that the latter exhibited a negative relationship, indicating that AMR proportion decreased with the increasing governance index. A positive association with time was also evident , but not with the interaction term. However, European countries also differed in GDP per capita and governance index , two preE. coli and K. pneumoniae independent of the antibiotic tested. Except for K. pneumoniae resistant to carbapenems, the governance index was negatively associated with AMR proportion of all pathogen–antibiotic combinations. For most combinations of pathogens and antibiotics, positive relationships also remained significant, along with population density and antibiotic consumption. GDP per capita, instead, showed a relationship that was positive for K. pneumoniae resistant to aminoglycosides and negative for MRSA.The latter multivariable model was also applied for each combination between pathogen and antibiotic , and no Finally, we analyzed whether countries experiencing greater temperature changes also demonstrated greater differences in AMR over the past decade. Maps in When comparing these rankings, it became clear that countries experiencing greater temperature changes did not necessarily show a greater difference in AMR between 2010 and 2019. Accordingly, no correlation was evident between the 10-year average temperature change and the 10-year AMR difference across European countries .E. coli resistant to third-generation cephalosporins and K. pneumoniae resistant to fluoroquinolones or third-generation cephalosporins, and negative associations for E. coli resistant to aminopenicillins and MRSA. The findings of our study, using annual temperature change as the predictor, were partially consistent with those of previous studies which examined the association between AMR and annual minimum temperatures in the US and Europe [By analyzing data from 30 European countries over a ten-year period, we attempted to shed light on the relationship between temperature change and AMR. In general, our results showed that AMR proportions increased with increasing temperatures; however, the complexity and the multifaceted nature of the relationship highlights the need for understanding all the potentially involved factors. Using unadjusted models, we found significant or marginally significant relationships between temperature change and AMR, including positive associations for d Europe ,25. K. pneumoniae, multi-resistant E. coli, and MRSA [E. coli and K. pneumoniae [K. pneumoniae and Pseudomonas aeruginosa resistant to carbapenems increased with increasing average ambient temperature in 28 Chinese provinces over a 15-year period (2005–2019) [E. coli, K. pneumoniae, and S. aureus between 2013 and 2015 [Therefore, we replicated the model applied by McGough and colleagues  and adjuand MRSA . Similarand MRSA . The auteumoniae . There weumoniae ,25. Acco05–2019) . Across Our results from the multivariable analysis also revealed positive associations between AMR and both antibiotic consumption and population density, which align with prior findings in the US and China ,25. Howe2) emissions, where an increase in GDP per capita results in a corresponding rise in CO2 emissions [To gain a clearer understanding of whether the rise in AMR rates is a result of temperature change or just the convergence of different geographical gradients due to other factors, we further refined our analysis by considering GDP per capita and the governance index. The first is a summary measure of the country’s economic output per person, which was previously associated with climate change and AMR ,43,44,45missions . Insteadmissions ,48. In cmissions ,45. On tmissions ,45. To cmissions . Effectimissions ,30,50,51missions ,16,18,30missions ,16,18,30missions ,16,18,30When these factors were included in the fully-adjusted multivariable model, the relationship between temperature and AMR was no longer significant, both overall and stratified by pathogen and antibiotic class. These results were consistent with those reported by Collignon and colleagues, who evaluated anthropological and socioeconomic factors contributing to AMR globally . The autOur study and analysis shared some limitations with previous works on the same issue ,23,24,25Compared to previous studies, our analysis presents novelties that also represent some of its strengths. Firstly, we evaluated temperature as the mean temperature change with respect to a baseline climatology and not simply as the annual average temperature. Secondly, we used a larger amount of information on AMR, including data on ten combinations of pathogens and antibiotics. The period covered by our analysis was also consistent with previous studies. Finally, the introduction of additional predictors, such as the governance index, allowed us to disentangle the relationship between temperature and AMR.Drawing inspiration from previous research, our study was designed to provide a better understanding of the relationship between temperature change and AMR. Although warmer countries may report higher proportions of AMR, our study did not find a significant effect of temperature change. Rather, other factors—such as antibiotic use and a country’s governance—seem to determine a north-to-south geographical gradient for AMR. As a result of this evidence, ensuring the appropriate use of antibiotics and improving governance efficiency are the most effective ways to counteract AMR. It is necessary to conduct further experimental studies and obtain more detailed data to investigate whether and how climate change affects AMR.We conducted an ecological study of the evolution of AMR proportion of three common bacterial pathogens and different antibiotic classes over a 10-year period (2010–2019) across European countries and evaluated associations with temperature changes and other predictors. Data from 2020 onwards were not used to prevent the analysis from being affected by the COVID-19 pandemic. The study sample consisted of the following 30 countries from the European Union (EU) or the European Economic Area (EEA) and those participating in the EARS-net surveillance network : AustriaE. coli, K. pneumoniae, and S. aureus) that are the most common Gram-positive and Gram-negative pathogens causing infections globally. This choice was also motivated to align with previous published studies on the same issue [We used data on AMR proportions of three pathogens  was defined as the percentage of tested bacterial isolates that were non-susceptible to a given antibiotic for a given year, pathogen, and antibiotic class. To produce a summary measure of AMR, we first calculated the weighted average of AMR proportions for each country and year, normalized by pathogen and antibiotic class and weighted by the number of isolates tested [In this study, we analyzed data of 30 European countries for the following combinations between pathogens and antibiotics: s tested ,25. We nData on the mean annual temperature change were obtained from the FAOSTAT database, which provides information on surface air temperature changes (°C) for 192 countries over the period 1961–2020 . CountryAntibiotic consumption data were obtained from the European Surveillance of Antimicrobial Consumption Network (ESAC-Net) database . In gene2) and the gross domestic product per capita  for each country and year, using annual population estimates from the World Bank [In addition to temperature change and antibiotic consumption, we selected additional factors and/or confounders that may help predict AMR based on the previous literature ,23,24,25rld Bank . To inclrld Bank . These irld Bank . Each inrld Bank .To easily compare AMR proportions across different pathogen–antibiotic combinations, we first centered the data about the mean and normalized by the standard deviation for all pathogens and antibiotic classes. The weighted annual mean of these values was then used to depict the temporal trend of AMR from 2010 to 2019. Likewise, we plotted the temporal trend of the mean annual temperature change over the ten years. 2), antibiotic consumption (DDD per 1000 inhabitants per day), and the interaction between year and temperature change. These predictors were selected to align with the study by McGough and colleagues [We next plotted the relationship between mean annual temperature change and AMR for all pathogens and antibiotics, and used both simple and multivariable linear models to assess their association. In the unadjusted model, we evaluated the association between mean annual temperature change (°C) and normalized AMR values for each country, year, pathogen, and antibiotic class. In the multivariable model 1, we adjusted the relationship for country, year, population density . Compared to previous studies, we used a larger amount of information on AMR, including data on ten combinations between three pathogens and six antibiotic classes. To help unravel the relationship between temperature and AMR, our analysis also included additional predictors that had not been previously considered, such as the GDP per capita and a governance index. In line with previous findings, we initially demonstrated a positive linear association between temperature change and AMR proportion, adjusting for the effect of country, time, population density, antibiotic consumption, and the interaction between time and temperature change. However, when GDP per capita and the governance index were included in the multivariable model, temperature change was no longer associated with AMR. Accordingly, no correlation was evident when considering ten-year changes in temperature and AMR, with countries experiencing greater temperature changes that did not necessarily show a greater change in AMR. Antibiotic consumption, population density, and the governance index remained the main factors contributing to AMR. While AMR proportions increased with increasing antibiotic consumption and population density, the governance had an opposite effect. In fact, AMR proportions decreased with an increasing governance index. For this reason, ensuring the appropriate use of antibiotics and improving governance efficiency are still the most effective ways to counteract AMR. It is necessary to conduct further experimental studies and obtain more detailed data to investigate whether climate change affects AMR.


Inorganic-organic hybrid nanofibers were produced with precursor solutions of 1% wt. GO-filled Poly  fibers and scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) characterized the morphology and chemical composition of the spun fibers. Resin composite monomers were developed and a total of 5% nanofibers were incorporated into the experimental materials. Three groups were developed: G1 (control resin monomers), G2 (resin monomers/PLA nanofibers), and G3 (resin monomers/inorganic-organic hybrid nanofibers). Contact angle (n=3), flexural strength (n=22), elastic modulus (n=22), and Knoop hardness (n=6) were evaluated. The mean of the three indentations was obtained for each sample. The normality of data was assessed by QQ Plot with simulated envelopes and analyzed by Welch's method (p<0.05). Overall, SEM images showed the regular shape of nanofibers but were non-aligned. Compositional analysis from EDS (n=6) revealed the presence of carbon and oxygen (present in GO composition) and Si from the functionalization process. The results of contact angle (°) and hardness (Kg/mm2) for each group were as follow, respectively: G1 , G2  and G3 . The group G3 showed the highest Knoop hardness values (67.83 kg/mm2), and the flexural strength of all groups was adversely affected. The experimental resin composite composed of hybrid nanofibers with GO presented increased hardness values and hydrophilic behavior.This  Unlike conventional fillers, nanofibers are distributed and aligned uniformly ,In 2022, Velo et al. in vitro study synthesized inorganic-organic hybrid nanofibers filled with GO and, incorporated them into experimental resin composite monomers to evaluate their physical and mechanical properties.Thus, the present The hybrid nanofibers were fabricated with a modified air-blowing spinning technique, as described previously 2 for 40 seconds at a 1-mm distance. Wettability assessment with contact angle, three-point flexural strength, elastic modulus, and surface microhardness characterized the materials.A scanning electron microscope (SEM) coupled to energy-dispersive X-ray spectroscopy (EDS) assessed fiber morphology. The experimental resin monomers consisted of 49.5% BisGMA, 49.5% TEGDMA, 0.8% 2-dimethacrylate, and 0.2% camphorquinone. A rate of 5% of nanofibers composed of 1% GO was added slowly by manual mixing and homogenized for one minute Wettability was performed to evaluate material hydrophobicity after nanofiber functionalization. The samples (n=3) were separately mounted on glass microscope slides with a thin strip of Scotch-Magic™ Tape (3M). Droplets of distilled water (MILIQ) (3 µl) were inserted on each sample surface, and contact angles were obtained by averaging the results of three measurements per sample without repetition in the same sample area. Then, wettability capacity was recovered using KSV Instruments Ltd. equipment, model CAM101 2 (n=6) were prepared in stainless-steel split molds according to ISO 4049, changing the sample length to prevent overexposure or uncured regions considering the diameter of the LED curing device ,,Bar-shaped samples measuring 8×2×2 mm2) (n=6) were prepared by inserting the material into stainless-steel molds and covered with polyester tape. The sample surface was polished with decreasing abrasive papers  for two minutes each, followed by a felt disc with a diamond suspension  to obtain a flat and smooth surface suitable for evaluating hardness. Three indentations were made on the top surface of each specimen along a middle line spaced at 100 μm  with digital microhardness equipment . The mean of the three readings was recorded for each sample ,Disc-shaped samples . Normality was assessed with a QQ Plot with simulated envelopes. Paired comparison tests were performed between groups with sandwich variance estimators. For contact angle analysis, Welch’s ANOVA test was performed (p<0.05). The significance level was preset at 𝛼=0.05. Qualitative analyses were only described.SEM images assessed the morphology of GO nanofibers  and 2, sWhen evaluating microhardness, the values increased with nanofiber incorporation (G2 and G3). The group composed of GO hybrid nanofibers presented the highest hardness values (p < 0.0001). As for flexural strength, the values decreased with PLA nanofiber incorporation, and there was no difference between the control group (G1) and the group with GO hybrid nanofibers (G3) (p=0.88). The elastic modulus of G3 also did not differ from the control group (G1) (p=0.65).,Improvements in the physical and mechanical properties of restorative materials have been highlighted to ensure the long-term clinical success of restorations ,,In the current study, nanofibers composed of 1% GO were developed based on previous studies. It was demonstrated that adding 0.1-5% Despite the functionalization process of the nanofibers that occurred as demonstrated in the EDS by the presence of Si , some cl,,,,Our results are in contrast with some previous studies, which demonstrated that incorporating nanofibers into monomers usually increases flexural strength Conversely, microhardness increased for G2 and G3, which can be attributed to the resistance of nanofibers and GO structures, respectively. Overall, hardness is relevant to predicting the wear behavior and durability of the material and, can be influenced by the type of fillers, shape, and distribution within the matrix The contact angle results showed the hydrophilic behavior of the studied monomers, mainly attributed to silica, which improves GO dispersion and reduces material hydrophobicity, a significant property to facilitates ion exchange and the bioactive potential of the biopolymer ,The contact angle of a surface is also related to bacterial adhesion and, clinically, bacterial adhesion occurs mainly on hydrophobic surfaces In conclusion, the experimental resin composite with GO hybrid nanofibers presented increased hardness and hydrophilic behavior, representing a promising strategy for ion exchange in biomimetic conditions.


Antibody-mediated rejection (AMR) is a serious complication affecting the survival of patients receiving transplantation. Human cytomegalovirus (CMV) and Epstein–Barr virus (EBV) are common viral infections that occur after transplantation, frequently emerging as viral reactivation in donor grafts or transplant recipients. The present study aimed to investigate the association between CMV and EBV infections and early-onset AMR.This study was conducted at the Heart Transplantation Center of Padova General Hospital and included a cohort of 47 heart transplant recipients (HTxs), including 24 HTxs diagnosed with AMR and 23 control HTxs with no episodes of AMR. Only early cases of CMV and/or EBV infections (1–90 days after transplantation) were considered. Fisher’s exact test and logistic regression analysis were used to statistically analyze the correlation and association between AMR and CMV or EBV infection.We observed a positive statistical association between CMV and EBV infections  and between EBV infection and AMR . Logistic regression analysis revealed a direct statistical association between CMV and EBV infections and AMR risk . AMR occurrence was associated with increased viral loads of both CMV and EBV early after transplantation.These findings suggest the role of CMV and EBV infections as relevant risk factors for AMR in HTxs for the first time. Heart transplantation is a life-saving surgical procedure that is performed in the final stage of heart disease. Despite tremendous progress in transplant management, several post-transplant conditions, including acute and chronic graft rejection, still represent major complications that affect the functionality of durable and stable grafts , 2. In gActive cytomegalovirus (CMV) and/or Epstein–Barr virus (EBV) infections are major threats to heart transplant recipients (HTxs) –21. Bothde novo DSA. The participants in the control group were selected based on their CMV and EBV serostatus (R+) and similarities in the immunosuppressive regimen . Patients were enrolled after obtaining informed consent to participate in the study. The participating patients were provided with a written informed consent form along with a letter to their primary care physician indicating the purpose of the study and collection and handling of patient data. Patients with pre-existing or acquired immunodeficiency were not included in the study. All patients with AMR presented  regimen Table 1.AMR was diagnosed according to the International Society for Heart and Lung Transplantation guidelines , 25–31. Routine surveillance for viral reactivation or infection comprised weekly determination of CMV and EBV DNAemia during the first 100 days post-transplantation; this surveillance continued if there were clinical indications for infection. CMV and EBV DNAemia were evaluated by performing real-time polymerase chain reaction (PCR) on the Abi Prism 7900 HT system  using a system developed in-house , 33. The−1·day−1) for 4 days post-transplant. The immunosuppressive maintenance schemes are presented in All transplant recipients received transplant conditioning therapy via the administration of anti-thymocyte globulin . The variables considered for statistical analyses were CMV/EBV seropositivity before transplantation and early CMV and/or EBV DNAemia (occurring 1–90 days after transplantation). For Fisher’s exact test, all variables were coded as categorical or binary (yes/no). Logistic analysis was performed to investigate the association between viral infection (predictor variables) and AMR (dependent variables). Statistical significance was set at a p-value of <0.05.The association between CMV and EBV infections and AMR was investigated in 24 HTxs with AMR. The control group comprised 23 adult HTxs without AMR. The association between early CMV or EBV infection and AMR was also investigated using logistic regression analysis, with CMV or EBV as predictors of AMR (dependent variable) 4. EarlyActive CMV and EBV infections are considered major risk factors for acute T cell-mediated graft rejection, contributing to the accelerated progression of atherosclerosis and allograft loss –37. The This study has some limitations. It was a single-center study. Further, a small number of patients were enrolled in the study, and the primary focus was on patients with early post-transplant AMR. Nevertheless, AMR represents a rare event after heart transplantation. Moreover, other infectious agents may contribute to AMR onset; in the patients enrolled in this study, no clinical signs of herpes simplex virus 1/2 or varicella-zoster virus infection were observed. However, investigating the presence of other viral and non-viral infectious agents may provide critical insights into the microbial contribution to AMR initiation. Without a doubt, this finding needs to be further investigated in larger multicenter studies with more patients. We envision that if further studies confirm the association between early and overt EBV and CMV replication and AMR, strategies to prevent CMV and EBV infections using early post-transplant antiviral therapies may help reduce the incidence of AMR and improve the successful outcomes of heart transplantation.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by NRC AOP0401. The patients/participants provided their written informed consent to participate in this study.DA, AS, GF, and CM collected and analyzed the data and wrote the manuscript. DS, GG, AG, and LB supervised the study. CM performed statistical analyses. MF, GF, and AA analyzed the AMR data. All authors contributed to the article and approved the submitted version.


Each requires specific diagnostic and therapeutic approaches.▪Innovation: Developing broad-spectrum molecular techniques that can identify a range of pathogens simultaneously, thereby assisting in rapid diagnosis and treatment.Diversity of Pathogens:▪Challenge: The emergence of drug-resistant strains poses a significant threat to traditional treatments.▪Innovation: Understanding the molecular basis of drug resistance and developing targeted therapies to overcome or prevent resistance.Drug Resistance:▪Challenge: Early and accurate diagnosis is crucial for effective treatment, but traditional diagnostic methods may be slow or less sensitive.▪Innovation: Generating advancements in molecular diagnostics, including PCR-based techniques and next-generation sequencing, for faster and more precise identification of infectious agents.Diagnostic Challenges:▪Challenge: Designing vaccines that elicit a robust immune response against rapidly evolving pathogens.▪Innovation: Employing molecular techniques for vaccine development, including mRNA vaccines (with vaccines for COVID-19 serving as a successful example), which can be quickly adapted to new variants.Vaccine Development:▪Challenge: Tracking infectious disease outbreaks globally and implementing timely interventions.▪Innovation: Molecular epidemiological tools for the real-time tracking of pathogens, aiding surveillance and control measures.Global Surveillance:Hurdles:▪Innovation: CRISPR-based technologies for gene editing and diagnostics. CRISPR can be used to detect specific DNA or RNA sequences of pathogens, enabling precise and rapid diagnostics.CRISPR Technology:▪Innovation: Metagenomic approaches aid in the direct sequencing of genetic material from clinical samples, allowing for the detection of a wide range of pathogens without prior knowledge.Metagenomics:▪Innovation: Developing monoclonal antibodies and antibody cocktails as therapeutic options. This precise targeting can enhance treatment efficacy while minimizing side effects.Antibody Therapeutics:▪Innovation: Modulating the immune response using molecular techniques, such as enhancing the activity of T cells or using cytokines to enhance the immune system against infections.Immunotherapies:▪Innovation: Employing artificial intelligence, big data analytics, and molecular modeling techniques for predicting disease outbreaks, identifying potential drug candidates, and optimizing treatment regimens based on molecular data.Artificial Intelligence, Big Data, and Molecular Modeling Approaches:▪Innovation: Tailoring treatments based on individual genetic factors and the molecular characteristics of an infectious agent for more effective and targeted interventions.Personalized Medicine:New Innovations:The integration of molecular approaches in medicine allows for a more precise understanding of the mechanisms underlying infectious diseases, paving the way for targeted therapies, personalized medicine, and the development of new diagnostic tools. It also enables the identification of specific molecular targets for drug development, contributing to the fight against drug resistance ,2,3. DesIn conclusion, while molecular medicine has significantly advanced our understanding of and ability to manage infectious diseases, ongoing innovations are essential to address the evolving challenges, ensuring timely and effective responses to emerging threats. The integration of various technologies and a multidisciplinary approach will continue to shape the future of infectious disease control. Additionally, in tandem with these efforts, it is encouraging to see the scientific community actively working towards finding solutions despite the challenges posed by drug resistance. Recently, a crucial and timely Special Issue, “Molecular Medicine Applications in Infectious Diseases: Latest Innovations”, has been published, presenting interesting studies focusing on molecular medicine applications in the field of infectious diseases and the ongoing challenges and innovative solutions faced and developed therein. The Special Issue comprises three well-designed, original studies and three up-to-date literature review articles.Leishmania major, the LmjPES gene, which shares homology with the human oncogene PES1. The findings point to a potential role of LmjPES overexpression in the infectivity of Leishmania parasites, possibly via provoking increased cell infection rates in macrophages and enhanced inflammation in an animal model, indicating its potential as a target for developing treatments or interventions against leishmaniasis. The results contribute to our understanding of the molecular mechanisms involved in this parasite’s pathogenesis and could guide future efforts in drug development and disease control strategies.Understanding the functions of specific genes in parasites can provide insights into their biology and potentially open avenues for targeted treatments. Algarabel et al. (contribution 1) identified a potential player in Neuraminidase is a crucial enzyme for the influenza virus, and inhibiting its activity is a common strategy employed in antiviral drugs. The complexity of developing inhibitors that can effectively target multiple sites on the neuraminidase enzyme is no small feat. Molecular modeling is a powerful tool in drug discovery and design. In the case of antiviral drug development, understanding the structure of the target enzyme, such as neuraminidase, is essential for designing molecules that can effectively suppress its activity. Selecting the sulfonamide group in the linker for effective interaction with the unique arginine triad (Arg118-Arg292-Arg371) is a clever approach developed by Evteev and colleagues (contribution 2). In their work, molecular modeling revealed the sulfonamide group’s possible advantages in this context. This approach showcases a thoughtful strategy for designing inhibitors that could be more effective and resistant to viral mutations.® SQ HIV Genotyping Assay (Vela Diagnostics). The ability to detect drug resistance more quickly and adjust therapy promptly can make a significant difference in the lives of those living with HIV. Bonifacio et al. (contribution 3) provided a detailed evaluation related to the performance of the Vela Diagnostics NGS platform, particularly the Sentosa® SQ HIV Genotyping Assay that is designed for detecting drug resistance in HIV management. Their study suggests that the investigated assay shows promise in HIV resistance testing. The technology demonstrated good performance in terms of accuracy, reproducibility, and concordance with traditional sequencing methods. However, continual optimization efforts are needed to address technical challenges and achieve a more favorable balance between costs and processing speed.Next-generation sequencing (NGS) technologies seem to be a game-changer in HIV management, especially with regard to the SentosaHassan et al. (contribution 4), in their up-to-date review article, explore the therapeutic potential of plant-based non-flavonoid polyphenols in combating human herpesviruses. Their review highlights the diverse bioactivities of these natural compounds and their promise in addressing drug resistance challenges. It also discusses the molecular mechanisms supporting the therapeutic impact, suggesting that plant-based non-flavonoid polyphenols could offer a multifaceted approach to tackling herpesvirus infections.Flavonoids, with their natural origins, seem to hold a great deal of promise in the realm of controlling virus-associated cancers. Hassan and Šudomová (contribution 5) produced an up-to-date review article that emphasizes the potential of flavonoids in combating cancers associated with gamma-herpesviruses such as the Epstein–Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV). Their review delves into various categories of flavonoids and elucidates their mechanisms of action, shedding light on their promising roles as therapeutic agents against cancers linked to EBV and KSHV. The primary focus of their review revolves around the capacity of these flavonoids to hinder EBV and KSHV infections as well as their ability to impede the formation and growth of tumors associated with these viruses. The mechanisms through which flavonoids exert their effects are diverse, and this review explores the intricate details of how each type of flavonoid interacts with the viruses and influences tumor development. The collective insights provided in the review offer a comprehensive understanding of the potential therapeutic benefits of flavonoids in the context of these specific malignancies, offering avenues for further research and development of novel treatment strategies.Another review article, written by You and colleagues (contribution 6), provides a comprehensive overview of the relationship between impaired expression of the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR), an intracellular pathogen-recognition receptor, and the pathophysiology of otitis media (OM) in individuals with impaired innate immunity. This review suggests that NLRs are integral to the immune response in the context of OM and that their impairment can have significant implications for the development and course of this condition. Moreover, the interplay of NLR expression with bacterial infection, fluid characteristics, disease recurrence, tissue type, and surgical intervention adds another layer of complexity to our understanding of OM. This information may contribute to a better understanding of the immunological mechanisms underlying OM and potentially inform future therapeutic strategies.Since molecular medicine has taken the fight against infectious diseases to new heights, the Guest Editor would like to express his appreciation to all the authors who made significant contributions to this Special Issue and presented unique concepts, methods, and findings that can be used as a valuable platform for future research.


Artificial intelligence (AI) and robotics are having a soaring impact on our societies. They pervade our lives . There aGentili and Stano show that molecular and supramolecular chemistry can mimic some primary sensory, computing, communicating, and working actions of the human nervous system. In their second perspective, Gentili and Stano demonstrate that systems chemistry allows the design of more sophisticated modules to develop Chemical Robots. Chemical Robots should become capable of making rational decisions in environments dominated by uncertainty, partiality, and relativity of truth. These capabilities require the implementation of Fuzzy logic and Bayesian inference through molecules and their chemical reactions.Two contributions of this Research Topic outline the perspectives of CAI. They propose the first knowledge map for CAI, reporting its paradigms, which are the elements of the human nervous system; its domains, which are molecular, supramolecular, and systems chemistry; and finally, the problems CAI can face. In their first perspective, Gentili and Perez-Mercader. It is based on chemical micro-heterogeneity. Microheterogeneity refers to systems that are heterogeneous at the microscopic level. The heterogeneity can be at the level of single molecules  and/or inter-entities. It is intra-entities when it involves distinct conformers of a compound embedded in a homogeneous micro-environment. It is inter-entities when it is due to a complex mixture of different chemical compounds. Any micro-heterogeneous system can be exploited to encode a context-dependent Fuzzy set. This is the preliminary step for implementing Bayesian inference  engrafted into Synthetic Cells originates a minimal network to process Fuzzy logic. The fundamental ingredients are the Fuzzy proteins, i.e., proteins that exist as collections of conformers, capable of showing multi-responsive and context-dependent behavior.Networks constructed through nodes that are molecular Fuzzy sets allow to process Fuzzy logic. Sahoo and Baitalik present an alternative strategy for processing Fuzzy logic through molecules, which is hybrid because it is based on wetware and software. This hybrid strategy requires smooth analog input-output relationships of macroscopic variables, which can be modelled by building Fuzzy Logic Systems  that coordinate responses to stimuli in a specific manner. Hormones can communicate with certain body parts equipped with the necessary receptors to interpret and react to their signals. The dynamic, decentralized, and multifunctional properties of the hormonal system allow the design of innovative computing systems.Stano and Damiano advocate that trying to obtain intelligent chemical systems from scratch and in wetware can help understand intelligence and life. Life, conceived as a process, is a process of cognition. Therefore, a significant contribution to CAI will come from Synthetic Biology in general, and more specifically, from Synthetic Cells. Hence, Gentili and Stano propose how to quantitatively monitor the advancements in the technology of Synthetic Cells by determining their complexity degree through three approaches: 1) the reductionist, 2) the mesoscopic, and 3) the systemic one. A deeper understanding of intelligence and life will contribute to formulating more realistic models of Complex Systems and help humanity face the global challenges of this century (Finally, the last two contributions of this Research Topic face epistemological issues related to the development of CAI.  century .