This paper aims at showing the impact of novel imaging technologies and modern radiotherapy techniques on the management of cancer, with a particular focus on prostate adenocarcinoma. The manuscript explores the value of diagnostic imaging before treatment, the role of radiomics in predicting outcomes, the benefit of novel imaging in radiotherapy planning and the influence of advanced technologies in systemic treatment and in the management of other non-oncological conditions in order to tailor the best therapeutical strategies.Introduction: Targeted dose-escalation and reduction of dose to adjacent organs at risk have been the main goal of radiotherapy in the last decade. Prostate cancer benefited the most from this process. In recent years, the development of Intensity Modulated Radiation Therapy (IMRT) and Stereotactic Body Radiotherapy (SBRT) radically changed clinical practice, also thanks to the availability of modern imaging techniques. The aim of this paper is to explore the relationship between diagnostic imaging and prostate cancer radiotherapy techniques. Materials and Methods: Aiming to provide an overview of the integration between modern imaging and radiotherapy techniques, we performed a non-systematic search of papers exploring the predictive value of imaging before treatment, the role of radiomics in predicting treatment outcomes, implementation of novel imaging in RT planning and influence of imaging integration on use of RT in current clinical practice. Three independent authors  performed an independent review focusing on these issues. Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used, and grey literature was searched for further papers of interest. The final choice of papers included was discussed between all co-authors. Results: This paper contains a narrative report and a critical discussion of the role of new modern techniques in predicting outcomes before treatment, in radiotherapy planning and in the integration with systemic therapy in the management of prostate cancer. Also, the role of radiomics in a tailored treatment approach is explored. Conclusions: Integration between diagnostic imaging and radiotherapy is of great importance for the modern treatment of prostate cancer. Future clinical trials should be aimed at exploring the real clinical benefit of complex workflows in clinical practice. Improvement of clinical outcomes through targeted dose-escalation and reduction of dose to adjacent organs at risk has been the main goal of radiotherapy in the last decade. Due to its characteristic radiobiology, prostate cancer benefited the most from this process, with a significant improvement in the benefit-to-risk ratio. Implementation of three-dimensional conformal planning (3-d CRT) was the first step of this evolution, followed by the introduction of Cone-Beam Computed Tomography (CBCT) for set-up evaluation. In recent years, the development of Intensity Modulated Radiation Therapy (IMRT) and Stereotactic Body Radiotherapy (SBRT) techniques radically changed clinical practice and allowed us to re-consider the role of radiotherapy in different clinical scenarios. However, all these upgrades were made possible by the availability of modern imaging techniques, both for their diagnostic value and for the possibility of integrating their information with standard radiotherapy planning. In this paper, our purpose was to overview the close relationship between diagnostic imaging and prostate cancer radiotherapy techniques development.Similarly to other tumours ,2,3,4, mIntegration between modern imaging and radiomics may also be helpful for diagnosis ,18,19,20Novel metabolic imaging improved staging sensibility in prostate cancer and has been shown to have a significant impact on radiotherapy management ,46. HoweLocal ablative treatment has been shown to be a practice-changing approach in oligometastatic prostate cancer , and theDifferent types of diagnostic imaging are currently essential for prostate cancer diagnosis and treatment. Before radiotherapy delivery, mpMRI is widely used for diagnosis, and future development will allow the improvement of its diagnostic accuracy and to predict the biological aggressiveness of diseases even before a biopsy. This would allow an early and non-invasive assessment of disease in clinical practice. Moreover, early reports show that treatment toxicity after radiotherapy may be predicted by diagnostic imaging through radiomics features. During radiotherapy planning and delivery, three-dimensional imaging may allow the implementation of modern IGRT and refine the evaluation of dose distribution to healthy tissues. Moreover, information from diagnostic imaging may be integrated into radiotherapy planning to better tailor treatment  through co-registration with planning imaging. Finally, online MRI imaging allowed the development of MRI Linacs, able to safely deliver MRI-based IGRT with online adaptive protocols in order to shape radiotherapy planning on a daily basis, taking into account the inter- and intra-fraction variability of patients’ anatomy . LimitatAmong histologically confirmed tumours, new innovative technologies can provide better diagnostic refinement. As an example, Mungai and coll. showed how DCE MRI data can be helpful in recognizing the most frequent histopathological types of salivary neoplasms ; for whaAs a consequence, in the pre-treatment setting, this is of particular interest when diagnostic imaging could be integrated with clinical data to differentiate between benign or neoplastic findings, avoiding unnecessary histopathologic assessment through biopsy. Clinical trial design to address this issue is complicated and will probably require a large shared dataset of patients with a longitudinal follow-up. Moreover, as diagnostic imaging rapidly evolves, such databases could become obsolete if compared to current clinical standards. Currently, evidence from literature often does not allow to safely rely only on imaging for oncologic diagnosis. Larger series have been published for prostate cancer, but the number of patients included in these experiences is still too low  to draw firm conclusions. Second, radiomics may offer the possibility to predict adverse events before treatment, but the assessment of this opportunity needs analysis of large populations and datasets. In this setting, radiomic features may play a role in assessing survival and toxicity outcomes and in predicting treatment responses in different cancer populations. Among prostate cancer patients, many studies investigated the potential of radiomic signatures in predicting radiotherapy-induced gastrointestinal (GI) and genitourinary (GU) toxicities. Mostafei’s prospective work on 64 patients, whose pre-RT CT scans of the rectum and of the bladder were acquired and whose GI and GU toxicities were assessed, demonstrated that CT imaging features could predict radiation-induced toxicity and that integrating imaging and clinical/dosimetric features may enhance the predictive performance of radiotoxicity modelling . AbdollaFor what concerns the prediction of survival as well, many series underlined the potential of radiomic features in NSCLC surgically treated patients , in hepaInterestingly, in the setting of locally advanced rectal carcinomas treated with neoadjuvant chemo-radiation, texture analysis on T2-weighted MRI sequences was also investigated for the prediction of pathological response. If Crimì experience discouraged the use of radiomic features in the prediction of cPR in rectal cancer , on the The predictive function of radiomic features analysis for toxicity and treatment/survival outcomes is probably complicated by the fact that many radiomics features have been explored with different imaging methods, with significant heterogeneity in terms of aims and outcomes chosen for features of interest. Artificial intelligence will be needed to address this issue . For theThe use of Cone-Beam CT (CBCT) in locally advanced rectal carcinoma is effective for mesorectum organ motion assessment, and it is an appropriate method for treatment implementation . The rolParadoxically, the implementation of novel imaging in RT treatment planning is currently the most advanced field of research and, in our opinion, the most exploitable one. Indeed, RT technologies are often routinely available and are often already well implemented in clinical practice. Moreover, direct clinical outcomes and benefits are evaluable after treatment , and trial design is more traditional if compared to other research fields discussed above. However, much literature evidence is limited to retrospective case series, and prospective evidence should be advocated because the real clinical advantages of all techniques should be thoroughly evaluated to select patients who may benefit from a certain radiotherapy approach. Interestingly, the relationship between modern imaging methods and radiotherapy may constitute a paradigmatic example of a research field in which it would be complicated to wait for pre-treatment evidence, and assessing clinical oncological benefit from a certain approach could be more effective and less demanding in terms of the number of patients included in trials. Thus, a tight relationship between radiologists and radiotherapists should be advocated both in routine clinical practice and trial design in order to improve knowledge and maximize clinical benefit from technical innovation. Lastly, we must mention the fact that local treatment implemented by the integration of modern technologies may have an impact on systemic therapy in both oncological and non-oncological conditions. In prostate cancer, complete metastatic ablation of oligometastatic disease with SABR and integrated PSMA-PET may provide an alternative to early initiation of androgen deprivation therapy ; SBRT caIntegration between diagnostic imaging and radiotherapy is of cornerstone importance for the modern treatment of prostate cancer , and man


Since the dawn of nephrology, dietary intervention has been one of the cornerstones of therapeutic intervention, used by nephrologists in an attempt to reduce the symptoms and metabolic complications that characterize chronic kidney disease (CKD) and, possibly, to stop its evolution. Despite this, the available evidence that clearly demonstrates these effects is still relatively few, and this evidence is contradictory and often inconclusive. For these reasons, any opportunity to stimulate the collection of new data, experiences, and opinions on this sensitive issue for nephrological culture is welcome.Nutrients is to host scientific articles that can contribute to enriching the knowledge in this field.The aim of the present issue of This collection contains ten articles of great interest, each of which explores some of the most interesting and still poorly defined aspects concerning the topic in question.In this brief introduction, I will limit myself to providing you with a quick presentation of the topics addressed by each of the ten articles, referring to their in-depth look at the topics covered.Silvio Borrelli and colleagues  look at The handling of protein dietary intake in the different stages of CKD is another controversial issue, which was recently addressed by the Kidney Disease Outcomes Quality Initiative (K-DOQI) guidelines, which suggest restricting protein intake from the early stages of CKD. Elisa Longhitano and colleagues  dealt wiNutrients, I-Wen Wu and coworkers [The pivotal role of microbiota changes as pathogenic factors in a large series of diseases is a topic of growing interest. However, although in the CKD field, the interest in this problem grew exponentially in the last two decades, few and contradictory data are available to date. In a paper in the present issue of oworkers  report oWith the increasing number of end-stage renal disease (ESRD) patients, there was growing interest in the methods which could allow for delays in start of dialysis treatment, particularly for very elderly patients. One of the potential tools for this could be a marked reduction in protein intake; however, this could be associated with malnutrition and, hence, increased mortality rate. To counteract this potential negative outcome, many nephrologists started prescribing keto analogs (KA) as supplements. However, there is still scant evidence on whether these supplements are effective in improving the outcomes. The group of Yi-Chun Wang and colleagues  report dAlthough kidney transplantation (KT) represents the best therapeutic option for patients who achieved the ESRD, KT recipients are still burdened by a higher risk of mortality, particularly from cardio-vascular disease, infectious and neoplastic diseases, as compared with subjects from the general population matched for age and gender. The role of different components of the diet in this clinical setting is only partially clarified. Carolien P.J. Deen and co-workers  face a vThere is still great controversy regarding the potential benefit of a diet mainly based on foods of plant origin and/or fish-food as compared with a dietary behavior that privileges meat, dairy products and poultry in the field of CKD patients. In a very elegant study published in the present issue, Qingqing Cai and colleagues  evaluateAn increase in inflammatory markers is a quite common finding in CKD patients. Looking at the possible effects of different quality protein dietary composition on the inflammatory status in CKD, a systematic review and meta-analysis is carried out by Danielle Francesca Aycart and co-workers . From thRan Nakamichi et al.  address Nutrients. The authors particularly focused on the interaction between caloric intake and some relevant players in CKD-MBD, namely, phosphate, FGF23 and Vitamin D, discussing the results of studies carried out either in animals or humans. In addition to the classical mineral metabolism-related pathways by which caloric intake might affect bone health, the authors also dealt with some other non-mineral mediators . In this review, the authors conclude that dietary caloric prescriptions in CKD patients should also consider its possible effects on mineral and bone disorders.The derangements of mineral metabolism and the associated bone disease are hallmark of CKD patients (CKD-MBD). Many studies have addressed the role of protein intake in CKD-MBD progression. Much less attention has been paid to the possible role of caloric intake on this problem, which has been studied by Angela Vidal and colleagues  in this Kamyar Kalantar-Zadeh and coworkers  also deaI leave you now to read these very interesting articles, and wish you a good and profitable reading.


Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are essential to normal growth, metabolism, and body composition, but in acromegaly, excesses of these hormones strikingly alter them. In recent years, the use of modern methodologies to assess body composition in patients with acromegaly has revealed novel aspects of the acromegaly phenotype. In particular, acromegaly presents a unique pattern of body composition changes in the setting of insulin resistance that we propose herein to be considered an acromegaly-specific lipodystrophy. The lipodystrophy, initiated by a distinctive GH-driven adipose tissue dysregulation, features insulin resistance in the setting of reduced visceral adipose tissue (VAT) mass and intra-hepatic lipid (IHL) but with lipid redistribution, resulting in ectopic lipid deposition in muscle. With recovery of the lipodystrophy, adipose tissue mass, especially that of VAT and IHL, rises, but insulin resistance is lessened. Abnormalities of adipose tissue adipokines may play a role in the disordered adipose tissue metabolism and insulin resistance of the lipodystrophy. The orexigenic hormone ghrelin and peptide Agouti-related peptide may also be affected by active acromegaly as well as variably by acromegaly therapies, which may contribute to the lipodystrophy. Understanding the pathophysiology of the lipodystrophy and how acromegaly therapies differentially reverse its features may be important to optimizing the long-term outcome for patients with this disease. This perspective describes evidence in support of this acromegaly lipodystrophy model and its relevance to acromegaly pathophysiology and the treatment of patients with acromegaly. GH and IGF-1 are vital to normal growth, metabolism, and body composition , 3. In pThe acromegaly lipodystrophy originates in AT under the influence of GH excess. GH modulates AT metabolism and is lipolytic , 22–26. GH has important effects on protein metabolism that favor anabolism in muscle , 64, and1HMRS) imaging use has also enabled visualization of muscle lipid content in acromegaly. MRI revealed that inter-muscular AT (IMAT), AT located between muscle groups and beneath the fascia   . Becauses (ATMs) , 149 ands (ATMs) , acromegin vitro data suggest that GH may reduce adiponectin gene transcription (GH-induced changes in adipokines may also contribute to the development of IR in acromegaly. GH reduces leptin gene expression in VAT , and in cription . GH moducription , 181–183The effect of acromegaly on ghrelin is also relevant to the lipodystrophy. Ghrelin is an orexigenic hormone that is importantly linked to appetite and body composition –186 and GH has well-known direct effects on metabolism in peripheral tissues , but recThe acromegaly-specific lipodystrophy features IR in the setting of a unique body composition pattern of reduced VAT and IHL and of impaired lipid storage in SAT, resulting in ectopic lipid deposition in muscle . The lipThe original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by Institutional Review Board, Columbia University Irving Medical Center. The patients/participants provided their written informed consent to participate in this study.The author confirms being the sole contributor of this work and has approved it for publication.This work was funded by NIH grant DK110771.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Microneedles (MNs) are an emerging technology for user-friendly and minimally invasive injection, offering less pain and lower tissue damage in comparison to conventional needles. With their ability to extract body fluids, MNs are among the convenient candidates for developing biosensing setups, where target molecules/biomarkers are detected by the biosensor using the sample collected with the MNs. Herein, we discuss the 3D printing of microneedle arrays (MNAs) toward enabling point-of-care (POC) biosensing applications. The organization of needles in micro- and nano- scales on an array or patch, introduced the emerging term of microneedle arrays (MNAs), are prominent minimally invasive injection setups for medical and biomedical applications ranging from delivery of drugs and agents to body to extracting body fluids and bio signal acquisition, to name a few . MinimizOver the past decade, the fabrication method of MNAs has been advancing from molding, micro machining, and photolithography to the emerging method of 3D printing, where the structure is produced in a layer-by-layer manner using a computer-aided design (CAD) input . 3D prinAdvancements in nanotechnology and biosensing sciences have facilitated utilizing POC biosensing platforms in various fields, including medicine, industry, and defense ,9. A bioGenerally, MNA-based biosensing platforms utilize two main approaches for biomarker detection, i.e., direct and indirect detection. In brief, during the direct detection approach, whole procedures, including the sample obtaining and recognition of corresponding biomarkers and readout, occur in an all-in-one platform, while in the indirect approach, MNs are used for sampling and the detection procedure occurs in another instrument. It is worth mentioning that fabrication of the direct MNA-based biosensors needs various technologies such as microfluidics, nanotechnology and microfabrication which could be considered as a disadvantage regarding their application. However, their advantages exceed such limitations.in vivo monitoring of subcutaneous glucose in a normal mouse and in a diabetic mouse with a commercial glucometer demonstrated the accuracy of the device, facilitating future in vivo CGM studies , as an indicator of ketones. The developed biosensor demonstrated sensitive selectivity for the detection of target molecules in the artificial interstitial fluid (ISF). It also presented the ability for the detection of HB besides glucose and lactate, which could be considered as a simultaneous MNA-based biosensor with the capability of sensing multiple biomarkers of diabetic ketosis . AdditioDuring recent years, the development of MNA-based biosensors for the real-time detection/monitoring of various diseases such as cancer and diabetes has widely been investigated. Considering biofluids such as blood and ISF as rich sources of biomarkers, such MNA-based biosensors may be employed for both sample gathering and the read-out process . To obtaA highly porous gold MNA-based biosensor was fabricated using electrochemical self-templating approach . The MNASkin ISF is a biofluid containing information-rich biomarkers which can be utilized for several purposes such as diagnosis and prognosis of diseases, analysis of tumors, and drug inspection. Hence, 3D printing MNAs for ISF-collection and -analysis biosensors can enable a great opportunity for developing POC systems. An attempt in this regard took advantage of photopolymerization 3D printing technology for the fabrication of MNAs with open groove channels, which were aimed to be used for extraction of body liquids . The groin vivo detection of the target analyte (with an effective recovery). The developed platform was suggested as a potential approach for the further development of on-body measurement.Thanks to the MNAs, various studies have initiated to evaluate and investigate the ISF-originated biomarkers such as nucleic acids, proteins, and small molecules. Compared to the other biofluids such as blood, saliva, or urine, these biomarkers could be easily obtained. Organophosphorus nerve agents (OPNAs) are one of deadliest chemical ever produced for warfare application. Skin is one of the sites that could extensively be exposed to such chemicals. In this regard, an electrochemical MNA-based biosensor was designed for rapid, sensitive, and specific detection of OPNAs from ISF . Having For the purpose of sequence-specific sampling, isolation, and the detection of nucleic acid biomarkers from skin ISF, MNs coated with an alginate–peptide nucleic acid hybrid material were developed . The devSurface-enhanced Raman spectroscopy (SERS) is a robust method that has been applied for sensitive detection of various molecules based on Raman scattering of target analyte on a plasmonic surface. Considering the unique molecular specificity of Raman spectroscopy, so called biomolecule fingerprinting, SERS based biosensors could be employed for development of label-free POC MNA-based biosensors. In this regard, a biocompatible MNA-based sensor was fabricated for accurate detection of methylene blue (MB) as model analyte in mouse skin . The hisBiocompatibility is one of the main prerequisites for the devices that are in close contact with human body, which means that such devices should not cause any adverse effect or attract responsive behavior from the immune system. This highlights that MNA-based biosensors that are proposed for translation and commercialization purposes considering their benefits should satisfy biocompatibility requirements as well. While using biocompatible materials in the fabrication of MNA-based biosensors is an obvious solution to achieve this goal, immunomodulatory coatings can be used as an alternative approach when there is a limitation for choosing biocompatible materials. Aimed to decrease triggering of the immune system of the human body and promote integration with the surrounding organs, immunomodulatory coatings can be applied on the needles in the same way that a drug is coated. On the other hand, in the case that biodegradable materials are used in the fabrication procedure, residues of the degradation should be harmless to human body as well. In this regard, polycaprolactone (PCL) and polylactic acid (PLA) are among the examples that have been studied to be not only biocompatible but also not leaving behind any irritating degradation products . AnotherAnalysis of chemical data in biosensor systems usually requires several chemometrics methods dealing with mathematical and statistical models followed by optimization procedures, which can be time-consuming in systems that are aimed for smart rapid detection and/or sensing various parameters at once. One of the approaches to enable more advanced POC robust biosensor setups in the future can be enabled by the incorporation of various detection/sensing frameworks along with several analysis layouts. In this regard, the integration of artificial intelligence (AI) techniques, for instance, machine learning (ML) and deep learning (DL), can be a useful approach for big data analysis and automation of sensing. On the other hand, AI techniques can contribute to fabricating steps as well; for example, features of 3D-printed MNAs were reported to be optimized and predicted using ML and DL . On the Advances in the development of non-invasive MNA-based biosensing platforms for monitoring of various biomarkers is an interesting area in the field of biosensors. Considering the great potential of electrochemical and SERS techniques, the development and commercialization of MNA-based POC biosensors for the multianalyte detection of biomarkers would be an asset in the management and monitoring of different diseases. Interestingly, such biosensing devices would be proper candidates for developing wearable patches for the online monitoring of the desired biomarker with the minimum amount of invasiveness in the patients. For instance, the design and fabrication of MNA-based POC biosensing platforms (wearable patches) would be suggested for real-time monitoring of glucose in diabetic patients or sensing of lactic acid in athletes. Although many advances regarding the development and application of MNA-based biosensors for the detection of various biomarkers have been achieved, still, some challenges in terms of real-time monitoring of biomarkers remain unsolved. In addition, in MNAs with nonconductive materials, effectively modifying the 3D-printed MNA-based biosensors with nanomaterials would be a concern. In this regard, MNs fabricated with metals can be considered as the initial solution for conductivity, however, fabrication of metals usually requires more time- and cost-consuming procedures. On the other hand, 3D printers are usually based on inks made with material family of polymers. Progress in the science of polymers is advancing to the development of novel conducting polymers such as polyaniline (PANI), polypyrrole (PPy), polythiophene (PTh), and polyacetylene . Hence, The other limitation that may affect the translation of MNA-based biosensing platforms from benches to beds would be their high cost of assembly processes, which need advanced laboratories. It is believed that further investigations should be performed to address the shortcomings associated with the application of 3D-printed MNA-based biosensing platforms. However, by the advancement of technology, particularly the development of innovative printing approaches and the application of affordable materials for microfabrication of MNAs, these biosensing platforms will smoothly find their place in the clinical trials and will be commercially available in the near future. Focusing on the number of clinical investigations of MNA-based biosensing platforms reveals that there is a demanding interest toward their development as new diagnostic techniques for detection of various biomarkers.The advances in technologies will revolutionize the field of POC biosensing platforms in terms of convenience, safety, non-invasiveness, biocompatibility, cost effectiveness, and ease of fabrication. In other words, by entering into the smart devices era, a new group of MNA-based biosensing platforms will emerge. Such health biosensors are expected to provide a real-time analysis reflecting the condition of the applied environment. It is believed that by integrating smartphone technologies into the MNA-based POC biosensors, a new generation of these devices will act as a game-changer in the field of detection. Initially, the monitoring and evaluation of glucose and its derivatives was the main purpose of developing MNA-based POC biosensors. Next, by understanding their advantages, their application in detection of other types of biomarkers has been initiated. An evaluation on the growing number of published papers about MNA-based POC biosensors demonstrates the increasing interest toward designing these devices, which are at the early stages of their road and will find their main role in the near future.


Agricultural productive services are important paths to realize the development of green agriculture, while the effect of agricultural productive services on the agricultural environment and its influencing mechanism are not yet clear. With the panel data of agricultural production in China from 2004 to 2019, by using multi-output stochastic frontier analysis with an output-oriented distance function, this study investigates agricultural environmental efficiency based on net carbon sinks. Then, this study explores the effect of agricultural productive services on agricultural environmental efficiency and its mechanisms by adopting ordinary least squares regression with fixed-effect panel model, causal steps approach, and spatial econometric method. The main findings are as follows: Firstly, agricultural productive services enhance agricultural productivity and agricultural environment by optimizing inputs and increasing outputs, and thus improve agricultural environmental efficiency. This result holds steadily after using instrumental variables to deal with endogeneity, changing the measurement of the dependent and independent variables, and subdividing the sample. Secondly, the pathways of agricultural productive services affecting agricultural environmental efficiency are mainly reflected in technology progress, planting structure adjustment, factor allocation optimization, and spatial spillover. Thirdly, due to the law of diminishing marginal returns, the impact of agricultural productive services on agricultural environmental efficiency is more significant when the level of agricultural productive services is relatively low. To improve agricultural environmental efficiency, we suggest implementing different productive service strategies in different regions, strengthening information integration, and improving infrastructure. Along with the increasing attention paid to environmental issues, the agricultural environment has gradually become one of the most attractive research topics in the agricultural field in China. Agricultural environment efficiency, which brings environmental factors into traditional agricultural technical efficiency, is an effective index to balance agricultural development and agricultural environment. Especially since China has set forth the aims of carbon peak in 2030 and carbon neutrality in 2060, agricultural environmental efficiency based on carbon emissions and its determinants have caused increasing concern. Existing fruitful studies on the determinants of agricultural environmental efficiency are developed from two aspects of the external agricultural environment and the internal productive factors. In terms of the external environment, agricultural development level ,2, urbanAt the same time, due to the ubiquity of small-scale and fragmented farming, agricultural productive services adapted to China’s national conditions have spread and popularized rapidly. Agricultural productive services are an essential driving force for improving agricultural productivity and promoting agricultural modernization , for itsAgricultural environmental efficiency is determined by agricultural inputs, outputs, and carbon emissions , which aIn summary, the literature on the impact of agricultural productive services on agricultural inputs and outputs are growing. However, the research on agricultural environmental impact is still scarce, which needs further theoretical analysis and empirical verification. In particular, carbon emissions are the inevitable product of modern agricultural production for null-jointness and weak disposability imposed on agricultural production. It means that the impact of agricultural productive services on agricultural environmental efficiency requires not only further theoretical analysis but also more micro-empirical results for verification. To fill this observed deficiency, this paper empirically examines the effects of productive agricultural services on agricultural environmental efficiency. Furthermore, comprehensive theoretical analyses and empirical tests are needed to explain the environmental effects of agricultural productive services, i.e., the mechanisms by which agricultural productive services contribute to agricultural environmental efficiency. To make up for this theoretical gap, this paper presents a comprehensive overview of the possible influencing pathways, and empirically validates some of them.In these contexts, based on the panel data of 30 provinces in mainland China from 2004 to 2019, this paper investigates the role of agricultural productive services in improving agricultural environmental efficiency. The findings indicate that agricultural productive services significantly improve agricultural environmental efficiency, which holds steady after endogeneity treatment and a series of robust analyses. Meanwhile, the impact of agricultural productive services on agricultural environmental efficiency shows a marginal decreasing trend. Further research conclusions suggest that the spread of agricultural productive services affects both agricultural inputs and outputs through promoting technology progress, changing cropping structure, and optimizing factor input structure. The above pathways have significant spatial spillover effects.This paper contributes to the existing research from the following three aspects. First, we examine the heterogeneity of agricultural productive services affecting agricultural environmental efficiency based on accurately measuring agricultural environmental efficiency, expanding not only the study of the effects of agricultural productive services, but also the analysis of the factors influencing agricultural environmental efficiency. Second, we develop an analytical framework for the impact of agricultural productive services on agricultural environmental efficiency, namely that agricultural productive services affect agricultural environmental efficiency through three aspects, i.e., inputs, outputs, and environmental factors. Third, we propose the main mechanisms through which agricultural productive services affect agricultural environmental efficiency at a theoretical level and test empirically through the causal steps approach for the mediating effect test.The remainder of this paper is structured as follows: the “Methodology and Data” section describes analysis framework, empirical methods, and the nature of data. Econometric results and discussion are presented in the “Results” and “Discussion” sections, and the “Conclusions” section sets out the main conclusions and some policy implications.In order to reveal the relationship between agricultural productive services and agricultural environmental efficiency in depth, we attempt to explore the influencing pathways of agricultural productive services on agricultural environmental efficiency from four aspects.Firstly, agricultural environmental efficiency is influenced by agricultural productive services through agricultural technology progress. Most farmers in China face high labor costs and credit constraints, making it challenging to purchase advanced and costly agricultural machinery and choose the reduction scheme for agricultural chemical materials. Agricultural productive services are the best solutions to these problems by reducing the cost of purchasing costly agricultural equipment and lowering the threshold for adopting advanced agricultural technology. On the one hand, the agricultural technology progress, which contains advanced farming technology and advanced energy technology, conduces to improve energy efficiency and directly reduces carbon emissions from energy consumption. On the other hand, agricultural technology progress can indirectly reduce carbon emissions by optimizing the structure of agricultural energy and fertilizer consumption. For example, the growing use of renewable energy can reduce the carbon emission intensity per unit of energy, and the increasing use of new biological fertilizers can increase the carbon sequestration capacity of soil.Secondly, agricultural environmental efficiency is influenced by agricultural productive services through agricultural planting structure adjustment. Agricultural productive services help to accelerate the large-scale development of agriculture, promote the proportion of grain sown area , and achThirdly, agricultural environmental efficiency is influenced by agricultural productive services through factor allocation optimization. Agricultural productive services are accompanied by the spatial flow of mechanical resources and the transmission of beneficial agricultural information, and thus realize the effective allocation of regional resources . The popFourthly, agricultural environmental efficiency is influenced by agricultural productive services through spatial spillover. From a regional perspective, the higher the level of agricultural productive services in a region , the greater the empowering effect on agricultural producers in the neighborhood. Relying on technological innovation, technology diffusion, specialized division of labor, collaboration, and the similarity of agricultural production resource endowment conditions in adjacent regions, agricultural machinery, which has apparent diffusion and spillover, forms the agricultural agglomeration effect and enhances the network connection effect in neighboring areas.Based on the above analysis, we establish an analysis framework shown in  as folloi at year t, To test the relationship between agricultural productive services and agricultural environmental efficiency, the ordinary least squares regression with fixed-effect panel model is employed:To explore the pathways of agricultural productive services affecting agricultural environmental efficiency, based on the test method of Baron and Kenny (1986) , the cauW represents the spatial weight matrix, and geographical distance matrix is adopted in the paper. We employ the Spatial Dubin Model with fixed effects to verify the spatial spillover effect of agricultural productive services on agricultural environmental efficiency:Biases might remain in empirical models because of two types of endogenous problems. The first is the omitted variable problem, i.e., some variables that affect both agricultural productive services and agricultural environmental efficiency are omitted from the regression model. The second is reverse causality, i.e., agricultural environmental efficiency might affect agricultural productive services. For example, provinces with high agricultural environmental efficiency level are usually regions with the high level of factor endowments. These regions, due to the high level of regional development and high price relative to labor, will adapt to local agricultural development requirements through large-scale adoption of agricultural productive services, which in turn contribute to the improvement of their agricultural productive services. This means that the core independent variable and the dependent variable suffer from reverse causality .To solve the problem of possible omitted variables, we employ a fixed-effect model with panel data to control the unobservable effects at provincial and time level, while adding as many control variables as possible in the regression analysis based on existing studies, such as rural human capital and production risk. To solve the problem of reverse causality, we introduce a suitable instrumental variable and employ two-stage least squares method to alleviate endogenous problems. The first stage is used to obtain prediction to replace endogenous variables, and the second stage is used to draw the final estimation result.2-equivalent) in the planting industry as the output variables because agriculture has the attribute of net carbon sinks. The calculation formula, coefficient of agricultural carbon sinks, and carbon emissions are based on the research of Zhu et al. (2022) [Following Zhu et al. , we adop. (2022) .The descriptive statistics on agricultural input and output variables on provincial level are shown in From the point of view of the demand side , the sown area and the number of farmers adopting productive services are the ideal indexes to measure the level of productive services; from the point of view of the supply side, the supplier  and the power of agricultural machinery for productive services are reasonable indicators. Limited by data availability, we employ the number of people engaged in agricultural productive services per unit area to measure the level of agricultural productive services.To solve the problem of endogeneity, the usual approach is to introduce a suitable instrumental variable . FollowiBased on the analysis in the “Literature Review” section, technology progress, planting structure, and input structure are selected to study the influencing mechanism of agricultural productive services affecting agricultural environmental efficiency. Agricultural machinery, which contains advanced planting and harvesting techniques, is accompanied by the transfer and diffusion of management techniques in its service process. Consequently, technology progress is characterized by the ratio of the total power of machinery to farmland area. There are significant differences between cash crops and grain crops in mechanical demand and agricultural chemical materials input , so the Agricultural operation scale, planting industry development level, rural human capital, production risk, regional economic development level, part-time employment of labor, and urban-rural income gap are controlled in our models. Agricultural operation scale (in hectare per household), which is an essential factor affecting the consumption of farm machinery and chemical materials , is reprChina Rural Statistical Yearbook and China Agricultural Machinery Industry Yearbook. In addition, price variables are deflated according to the price level in 2004.From the time perspective, agricultural mechanization and agricultural productive services have developed rapidly in China since 2004, and the data of agricultural productive services have been included in the national statistical yearbook since then. Therefore, the data employed in this study are the province-by-year panel of 30 provinces of mainland China from 2004 to 2019, and Tibet, Hong Kong, Macao, and Taiwan are excluded due to data unavailability. The annual data for each province associated with agricultural production are obtained from the annual The descriptive statistics on variables are shown in The regression results in columns (1) and (2) of Columns (3) and (4) of To further verify the robustness of the impact of productive agricultural services on agricultural environmental efficiency, we conduct the robustness analysis from three aspects: replacing the dependent variable, replacing the core independent variables, and subdividing the sample into main and non-main grain-producing areas.Firstly, we recalculate agricultural environmental efficiency using the translog production function and re-estimate the impact of agricultural productive services. The results in column (1) of Secondly, we adopt the number of productive service institutions per unit area to express the level of agricultural productive services. The results in column (2) of Thirdly, we divide the samples into main and non-main grain-producing areas. There are 13 provinces in main grain-producing areas, such as Heilongjiang and Henan, with a high level of agricultural productive services. The coefficients on agricultural productive services are positive and statistically significant at least at a 5% level in columns (3) and (4) of To examine the transmission mechanism of agricultural productive services to agricultural environmental efficiency, we employ Equations (2) and (3) for mediating effect tests from three perspectives of technology progress, planting structure, and input structure, and adopt the spatial econometric model for the spatial spillover effect test.Under the context of sustainable development, it is valuable to investigate agricultural productivity in combination with environmental factors and analyze its critical influencing factors. Our empirical results show that agricultural productive services have a positive impact on agricultural environmental efficiency. Although the existing literature does not directly explore the relationship between them, there are two related types of literature for comparison, both of which have the common basis—mechanization. One is about agricultural mechanization and agricultural environmental efficiency, but the conclusions of their relationship are not consistent. Jiang et al. believed that mechanization led to the decline of agricultural environmental performance based on the provincial data from 2000 to 2017 in China . In the Agricultural environmental efficiency is determined by agricultural productivity and agricultural carbon emissions . To be sThe path of agricultural productive services impacting agricultural environmental efficiency is determined by two aspects. The first aspect is to increase agricultural productivity. Studies have confirmed that agricultural productive services are applied to maximize total yield and benefit potential production. At the macro level, Sheng and Chancellor found that the hiring of capital services may lift the productivity of small farms in the Australian grains industry . At the From the perspective of carbon emissions, the adoption of agricultural productive services can reduce carbon emissions by lowering chemical inputs, but agricultural machinery and its fuel consumption, which support agricultural productive services, directly and indirectly cause carbon emissions. Moreover, in terms of outcome, the carbon emission effect of energy is greater than that of chemical input reduction. However, from the perspective of net carbon sinks, the planting industry showed a prominent positive net carbon sink characteristics and gradually increased.Technology progress is an essential driving force for productivity growth, and the production frontier will continue to expand outward with technology progress. Taking paddy smallholders in the Philippines, for example, the frontier output was significantly promoted by improved irrigation technology . If therAgricultural productive services help to achieve the concentration of crop varieties, especially the increase in the proportion of the sown area of grain crops. In general, compared to cash crops, grain crops have higher productivity, relatively fewer chemical inputs, and relatively lower environmental impact. In particular, it is worth mentioning that the carbon absorption rate of grain crops is relatively high, which can easily form more carbon sinks. For example, the carbon absorption rates of wheat and maize are 0.485 and 0.471, respectively, which are higher than that of cash crops (the carbon absorption rate is 0.45).As a product and cost of agricultural production are dual problems, the optimization of inputs structure means that the cost can be minimized with constant output. We should seek measures to improve agricultural productivity from a cost perspective in the case that the grain output per unit area cannot be significantly increased. Hence, the improvement of agricultural productivity lies in optimizing cost, which depends on the optimal allocation of different input factors. The spread of agricultural productive services has effectively solved the limitation of labor scarcity and realized the rational allocation of resources through the gains from specialization that arise from the division of labor.On a regional scale, the neighboring regions often have similar crop varieties, and the difference in the distribution along the latitude makes the crop maturity have time differences, which provides a broad market space for agricultural productive services. Agricultural productive services have obvious diffusion and spillover, for they not only serve the local agricultural production, but also provide support for neighboring regions. From the viewpoint of micro-entities, farmers can learn advanced knowledge, technology, and experience from other farmers, agricultural cooperatives, and agricultural production service organizations in adopting agricultural productive services, and thus promote productivity improvement through positive externalities of learning. Employing panel data of 13 prefecture-level cities in Jiangsu province of China from 2000 to 2016, Wu et al. revealed that the spatial spillover effect of mechanization was significant on grain yield due to the cross-regional operation of mechanization .There are several reasons for this paper does not explore the pathway of scale operation, which is analyzed in some other articles . First, To the best of our knowledge, this is the first attempt to reveal the effect of agricultural productive services on agricultural environmental efficiency and its influencing mechanism at the provincial level in China.By comparing the effects of agricultural productive services on agricultural environmental efficiency in different regions in Based on the panel data of 30 provinces in China from 2004 to 2019, we adopt a multi-output stochastic frontier analysis method to measure agricultural environmental efficiency based on net carbon sink, then explore the effects and mechanisms of agricultural productive services on agricultural environmental efficiency using OLS with fixed-effect panel data, two-stage least squares with instrumental variable, causal steps approach, and a spatial econometric method. The main conclusions are as follows:Firstly, agricultural productive services have a significant contribution to agricultural environmental efficiency. Agricultural productive services enhance agricultural productivity as well as the agricultural environment through inputs and outputs, and then improve the efficiency of the agricultural environment. This result still holds after using instrumental variables to deal with endogeneity, changing the measurement of dependent and independent variables, and subdividing the sample. Secondly, the mechanism pathways of agricultural productive services affecting agricultural environmental efficiency are mainly reflected in technology progress, planting structure adjustment, factor allocation optimization, and spatial spillover. Advanced agricultural technology and management measures can improve agricultural productivity and energy efficiency, and optimize the energy consumption structure. A reasonable planting structure is conducive to reducing agricultural chemical inputs, improving factor utilization efficiency, and realizing economies of scale. The rational allocation of factors is the fundamental guarantee for the role of agricultural input resources such as labor, farmland, and chemical fertilizer. Agricultural agglomeration and different crop maturity periods make cross-regional services of agricultural productive services possible, thus generating spatial spillover effects. Thirdly, the impact of agricultural productive services on agricultural environmental efficiency is more significant in the regions with low agricultural productive services level because agricultural productive services, as a factor input in agricultural production, conform to the law of diminishing marginal returns.Given the above evidence and arguments, we draw some policy implications.Firstly, policy attention should be paid to improving the level of agricultural productive services continuously according to the actual situation in different regions. For regions with low level of agricultural producer services due to terrain factors or crop structure factors, the marginal contribution of agricultural producer services is more pronounced. It is valuable to promote appropriate agricultural productive services in these areas to promote the quality of agricultural development and environmental efficiency. For regions with a high agricultural producer services level, such as main grain-producing areas, the marginal contribution of agricultural producer services is relatively small. The critical measure is to update or replace the existing productive service equipment, and promote the use of agricultural productive services with more advanced technology and higher efficiency. Secondly, efforts should be made to strengthen information diffusion and regional cooperation to realize the positive spatial spillover effect of agricultural productive services. For regions with similar resource endowments and similar crop types, information cooperation is used to guide and promote the cross-regional operation of agricultural productive services, to achieve rational flow and scientific allocation of agricultural machinery. Thirdly, it is necessary to improve the operating conditions of agricultural productive services, such as appropriately increasing the investment in transportation infrastructure, guiding the centralized farmland transfer, and realizing regional agglomeration of crop planting. Improving transportation infrastructure can provide primary conditions and convenience for agricultural machinery operations. Farmland transfer and crop agglomeration are conducive to realizing economies of land scale and service scale in agricultural production. The scale of expansion is beneficial to cultivating the agricultural productive services market and introducing small farmers to modern agriculture.There are also some potential limitations in this paper. First, in terms of the research scope, this study was conducted at the provincial level. Future research can be conducted at the county level, which potentially has richer data and more accurate results. Second, in terms of the research depth, as agricultural productive services exist in all aspects of agricultural production, such as tillage, sowing, irrigation, fertilization, and harvesting, a possible research direction is to profoundly investigate the impact of different stages of productive services on agricultural environmental efficiency.


Antimicrobial nanoparticles have gained the status of a new generation of drugs that can kill bacterial pathogens by multiple means; however, nanoparticle resistance acquired by some bacterial pathogens has evoked a cause of concern. Several reports suggested that bacteria can develop nanoparticles, specifically metal nanoparticle resistance, by mechanisms: nanoparticle transformation-induced oxidative stress, membrane alterations, reversible adaptive resistance, irreversible modifications to cell division, and a change in bacterial motility and resistance. Surface properties, concentration and aggregation of nanoparticles, biofilm forming and metal exclusion capacity, and R plasmid and flagellin synthesis by bacteria are crucial factors in the development of nanoparticle resistance in bacteria. Studies reported the resistance reversal by modifying the surface corona of nanoparticles or inhibiting flagellin production by bacterial pathogens. Furthermore, strict regulation regarding the use and disposal of nano-waste across the globe, the firm knowledge of microbe–nanoparticle interaction, and the regulated disposal of nanoparticles in soil and water is required to prevent microbes from developing nanoparticle resistance. The authors reported that this nanoparticle-induced intracellular stress also caused an upregulation of the multidrug-resistant genes. These changes triggered decreased sensitivity to antibiotics such as penicillin, kanamycin, ciprofloxacin, and gentamycin. Thus, oxidative stress started a domino effect affecting the overexpression of membrane porin genes and MDR efflux genes such as marA and acrAB-tolC, thus promoting adaptive pathogenic evolution  and rfaC gene mutation to TiO2 nanoparticles and recorded the resistance or sensitivity. These bacteria with altered membranes could efficiently resist the toxicity of TiO2 nanoparticles its hypervesiculation capacity and regulation of osmotic stress. With an increasing concentration of TiO2 nanoparticles, the membrane integrity is compromised coupled with oxidative stress and lipid peroxidation. There is also an increase in the secreted membrane vesicles to cope with the toxicity. They could be mediating membrane stress relief through the shuttling of proteins, LPS, and other harmful peroxidation products that accumulate in the periplasmic space or cause modifications on the outer membrane . When the nanoparticles were removed from the growth medium for several days, the antibacterial sensitivity was restored. The development of this transient resistance is adaptive and not due to genetic changes but basically due to changes in the shape of bacteria. The resistant bacteria were oval shaped and switched to the typical rod-like shape when turned sensitive. The authors suggested this change in shape could be due to the lack of protein RodZ or envZ that provides binding sites on the cell membrane for cytoskeletal protein MreB. It is anticipated that the bacteria could have adapted to the low expression of RodZ and the high concentration of ZnO led to the oval phenotype. Another possible mechanism could be related to the porin proteins OmpC and OmpF. While OmpC is more restrictive than OmpF, it is the ratio of these porins that is influenced by the nanoparticles. ZnO nanoparticles could be binding to cAMP, thereby blocking the formation of the cAMP–CRP complex that would otherwise bind to the DNA for the production of OmpR. The resulting low expression of OmpR results in limited phosphorylation of OmpR which, in turn, will increase the expression of OmpF. This results in a more permeable outer membrane as OmpF is an open porin complex  ions through efflux pumps or reduction to its lesser toxic oxidation state Ag(0) is well established. The resistance is also attributed to E. coli deficiency in outer membrane proteins, resulting in the limited uptake of Ag. The sil operon in gram-negative bacteria is also well studied and encodes for efflux pumps: SilP (P-type ATPase) and SilCBA (antiporter) along with SilE and SilF  of the gram-negative bacteria  eliminated nanoparticle aggregation and bacterial resistance to Ag nanoparticles  in the purR gene that encodes PurR, a putative purine operon repressor. The mutation resulted in serine to tyrosine at position 169 in the binding motif of PurR. PurR binding to the operon generally downregulates the enzymes responsible for the synthesis of inosine monophosphate (a precursor of the adenosine and guanosine monophosphates)  effectively killed the silver nanoparticles-resistant bacteria by inducing strong interaction of GCN/Ag with the bacterial membrane , European Medicines Agency (Europe), and the Pharmaceuticals and Medical Devices Agency (Japan) have strict guidelines for manufacturing, uses, and nano-waste disposal which need to be followed in other countries as well.Similar to the case of antibiotics, long-term exposure to sub-lethal doses of nanoparticles to microbes may add to the development of resistant bacteria , antibiotic resistance genes, beta-lactams (blaCTX-M), quinolones (oqxAB), and aminoglycosides (aac-Ib-cr) resistance genes, were found in the plasmid of E. coli isolated from livestock animals , or coating the nanoparticles with PGRE, the resistance gain can be stopped (Panáček et al., In conclusion, it can be confirmed that microbes, particularly, bacteria are acquiring resistance against metal nanoparticles rapidly by employing multiple mechanisms. Several factors such as concentration, aggregation, and type of nanoparticles as well as flagellin production, biofilm-forming, and presence of R plasmid in microbes can affect the resistance development in microbes. Though it is a recent phenomenon, strict regulation, adherence to the rules regarding the use and disposal of nanoparticles, and a vigilant check on nanoparticles–environment interactions are required to prevent this problem from becoming as widespread as multidrug resistance.SK and MK: investigation, formal analysis, writing—original draft, editing, and visualization. MK: conceptualization. All authors contributed to the article and approved the submitted version.


As in other disciplines, there is a high demand for psychologists who have specialized training in aging, but the demand far outstrips the supply, with only 1% of clinical/counseling psychologists identifying aging as their area of focus. The field of geropsychology has held a series of training conferences, the last in 2006, to define a training model and aging-related competencies. Fifteen years later, the field gathered again for a conference focusing specifically on the pipeline, with the goals of 1) understanding the recent shortage of applicants for positions in academic settings, 2) addressing underrepresentation of individuals from diverse racial and ethnic backgrounds across clinical and academic geropsychology, and 3) implementing concrete solutions. In this symposium we describe our two-day, four-hour virtual national conference held in 2021, attended by more than 150 psychologists nationwide, including the structure and outcomes of the conference and the progress of several ongoing working groups. The first paper summarizes quantitative and qualitative findings of a pre-conference survey on perceptions of the geropsychology workforce. The second paper describes a career pathways webinar aimed at graduate students, interns, and fellows to attract students to diverse careers in aging. The third paper describes discussions about the impact of the pandemic on geropsychology training. The fourth paper presents a survey and efforts of a working group focused on post-licensure training. This presentation offers a possible model for others considering ways to galvanize interest and training in aging.


We compare and contrast the materials and mechanisms of continental crustal growth in the largest preserved regions of Phanerozoic and Archean juvenile additions to the crust, to test for similarities or differences in the formation of continents through time. We accomplish this through a comparison of map patterns, lithological contents, and structural and metamorphic evolution of the Phanerozoic Altaid orogenic system of Asia, with the Archean Superior Province of the North American Craton, using a method termed comparative orotomy. Both orogenic systems consist of collages of curvilinear belts of eroded arcs, some older continental slivers, and vast tracts of former subduction/accretionary complexes. These contain numerous shreds of portions of the ophiolite suite, slivers of island and continental arcs, and accreted oceanic plateau, all intruded by multiple magmatic suites during or between multiple deformation events, then sliced by large transcurrent fault systems and bent into large oroclinal structures. We make this comparison because the Superior Province is a typical Archean craton that was later, in the Paleoproterozoic, incorporated into the larger North American Craton, and has occupied a central position in several supercontinents  during its longevity. Since it is the largest single fragment of Archean continental cratonic lithosphere preserved on Earth, the Superior Province is widely regarded as a testing ground for how Earth's continental crust was formed. Likewise, the Altaids encompass the largest region of crustal growth for the Phanerozoic. Our comparison with the Altaids is needed, as in recent years many myths about how the planet may have responded to higher heat production and flow in the Archean have emerged, because of trends in the science where regional geology is ignored in favor of numerical models, isotopic proxies for assumed models of chemical behavior for crust-forming or tectonic processes, or comparisons with other-worldly bodies that bear little resemblance to our hydrous Earth. Thus, we return to the geological record, and here describe the map patterns, lithological associations, structural patterns and evolution of both the Altaids and Superior Province, showing how comparative tectonics, orotomy, is useful in the absence of meaningful paleomagnetic or biostratigraphic data. We pay particular attention to the style of preservation of disaggregated members of the ophiolite suite (ophirags) and their relationships with other tectonic units, and to the widespread but largely overlooked role of late-stage major transcurrent motions and structural slicing of both Archean and Phanerozoic orogenic systems in defining the present-day architecture of both orogenic systems. Comparative tectonic analysis of the Archean Superior and Phanerozoic Altaid orogens reveals remarkable similarities pointing to common processes involved in the formation of continental crust over four billion years of Earth history. In recent years, a debate has developed in the geoscience community about whether or not ‘modern-style’ plate tectonics operated in the Archean. This debate is based in part on claims that outcrop patterns of different cratons are unlike those produced in the Phanerozoic, and the fuliginous Archean geological record lacks ophiolites and remnants of oceanic crust and lithosphere, which are considered one of the diagnostic indicators of plate tectonics in Phanerozoic orogens, marking places where former oceans have closed. This is rooted in the fact that many geologists still apply the 1972 Penrose definition of ophiolites and insist that to be recognized as a slice of former oceanic lithosphere, the ophiolite must include the full suite grading down from pillow lavas to mixed pillow lavas and dikes, to a sheeted dike complex, into gabbros and layered gabbros, peridotites and dunites, and tectonized mantle harzburgites. Following Şengör and Natal’in's seminal paper in 2004, we here restrict the use of the term ophiolite to this full suite (which is rare even in Phanerozoic orogens), and we use the term ‘ophirag’ for any of the various components of the ophiolite suite that were shredded off from the oceanic crust during their history of formation, attempted subduction, obduction and incorporation into orogens and ultimately the continental crust. In this contribution, we describe and compare the geology and tectonic history of the dominantly Phanerozoic Altaid orogenic system  Both the Altaids and the Superior orogenic systems Fig.  contain sensu stricto .One of the most polarizing events in the history of ophiolite studies was the 1972 Geological Society of America (GSA) Penrose Field Conference on Ophiolites , where pThe basal unit of ‘Penrose-type’ ophiolites thus was defined as consisting of harzburgite , typically with a strong, high-temperature transposed tectonic fabric, forming a mantle harzburgite tectonite (e.g. ), and idA unit referred to as isotropic gabbro, up to 5 km thick, overlies the layered gabbro in ‘typical Penrose-type’ ophiolites Fig. . The isoThe next unit in a complete ‘Penrose-type’ ophiolite is the famous sheeted dike complex, typically 0.5–2 km thick  type ophiolites are overlain by deep-sea sediments. In Phanerozoic oceans these include partly dissolved pelagic limestones, cherts, red clay, carbonates, pyroclastic deposits, sulfides, Mn-rich deposits and biogenic oozes. As the oceanic crust and lithosphere moves across the ocean basin towards a trench, it is typically covered by progressively more continent- or arc-proximal clastic deposits , formingFollowing the Penrose definition of ophiolite , sho, sho31])Modern understanding of ophiolites thus incorporates the above knowledge that only the upper and dismembered portions of oceanic lithosphere may be preserved in accretionary orogens (e.g. ), and alIn cases where the rate of extension exceeds the ability of available magmatism to fill the gap created by the extension, oceanic spreading will produce a lithospheric structure where the crust is very thin or absent, and isolated volcanoes of pillow basalts fed by small gabbro intrusions rest directly over depleted mantle peridotite, or form oceanic extensional core complexes . The obWhile the above concepts evolved under the influence of the geosynclinal theory, Argand , who wasThe Altaids represent the world's best Phanerozoic analog for Archean greenstone/gneiss-tonalite complexes , accideIn the Altaids, ophiolitic crust is most commonly found as: (i) basement to oceanic arcs; (ii) remnants of former forearcs (forearc ophiolites) and in accretionary wedges (with MORB characteristics), both typically deformed in later transcurrent structures; and (iii) strongly attenuated and metamorphosed ophirags in collisional sutures, derived from the above types.et al. )ad hoc histories for old rocks, which, in many cases, result in models that have no Earthly analogs, and are unlikely to be correct.Thus, we suggest that comparative orotomy is a powerful method to understand some of the world's oldest rocks, by searching for similar orogens or other settings to compare with, instead of formulating nwac235_Supplemental_FileClick here for additional data file.


Over the past decade, genetic testing in prostate cancer (PCa) has become increasingly important, both in research and clinical application. Studies on potential clinical indications have expanded across the entire disease spectrum, from risk prediction in mutation carriers and patients with localized disease, to treatment planning and selection in those with advanced disease stages. This Research Topic is aimed at facilitating the exchange of scientific knowledge in PCa genomics and the implementation of individualized management of PCa patients across different disease stages, with the ultimate goal of optimizing patient care. This series includes four articles, which cover the relationship between the PCa microenvironment and oncological outcomes, and the broader role of genetic testing in PCa management.Quan et al. used bioinformatics and clinical tumor tissues to demonstrate that three HLM regulators  were consistently upregulated in advanced PCa . They also found that several HLM phenotype-related genes were predictive of tumor aggressiveness, recurrence-free survival, and responses to novel therapies with immune checkpoint inhibitors, which may provide a new therapeutic opportunity for patients with advanced PCa. Another study  investigated the association between genomic landscapes and responsiveness to poly (ADP-ribose) polymerase (PARP) inhibitors, a recently approved therapy for BRCA-mutated metastatic castration-resistant PCa. Their analysis of co-segregating genes among men with advanced PCa who harbored BRCA1 and/or BRCA2 alterations demonstrated that, in contrast to BRCA1, BRCA2 had no significant associations with any gene, which implies its status of main driver mutation and thus higher sensitivity to PARP inhibition. These studies may enhance the understanding of prognostic factors, optimize treatment selection, and encourage further evaluation of the tumor genomic microenvironment in patients with advanced PCa.To facilitate risk prediction and treatment selection, understanding the molecular mechanisms associated with PCa progression is crucial. Epigenetic reprogramming through dysregulated histone lysine methylation (HLM) is considered to accelerate the development of PCa. In a comprehensive analysis of 91 HLM regulators acknowledged to influence PCa, Chiu et al) to address the indications, methods, and therapeutic implications of genetic testing in patients with PCa across different disease stages, with the aim of providing guidance to clinicians in Hong Kong, and possibly across the Asia-Pacific region, regarding who and what to test for in selected populations. While the methods and techniques of genetic testing are ever-changing, analysis of circulating tumor DNA (ctDNA) from blood plasma remains an emerging and convenient approach, particularly when tumor tissue is not readily available. Kwan et al. reviewed the current and potential applications for ctDNA analysis in metastatic PCa, which include prognosis prediction, treatment planning, and characterization of treatment resistance. They also discussed the possible limitations in interpreting ctDNA findings, particularly false-negative results that occur with low tumor content, and the approaches to optimize assay design, including correction for clonal hematopoiesis of indeterminate potential and germline variants. With the advancement of assay technology and accessibility, the role of genetic testing in the management of PCa continues to evolve, potentially informing the implementation of precision medicine initiatives and treatment individualization.With the development of research on prognostic and therapeutic biomarkers, the clinical value of genetic testing in the management of PCa is increasingly recognized. Representatives of the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology established a set of consensus statements (Further research on PCa genomics is expected and warranted. Molecular mechanisms of mutations and actionable biomarkers in specific patient populations are among the fields of clinical significance. Randomized trials and real-world studies alike are eagerly awaited to provide insights on how novel diagnostic, therapeutic, and management approaches based on genetic informatics could improve clinical outcomes in patients with both localized and advanced PCa.This manuscript was drafted and critically reviewed by DP, AA, EC, RK, and OS. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Massive open online courses (MOOCs) have emerged as an innovative educational technology relevant to and affecting higher education, professional development, and lifelong learning. This paper introduces the principles of MOOCs and reviews the development of these platforms over time. We reflect upon the considerable investment by institutions to develop, deliver and promote such courses, particularly in public health. While open to interpretation, the inherent power, influence, and effectiveness of MOOCs is unquestionable. The potential contribution of MOOCs to public health education is immense, with almost universal reach and access. However, apart from research into participant engagement and knowledge, MOOC-related research and evaluation continue to lag with the rapid proliferation of these courses in response to emerging challenges, as seen with the Coronavirus Disease 19 (COVID-19) pandemic. This makes analyzing the contribution of MOOCs to public health education, health promotion and community programs challenging. This perspective article provides a robust rationale for the necessity of MOOCs and their utility in upskilling health professionals and the general public. It builds on current knowledge to comprehensively explore the factors influencing the development, and application of MOOCs. Public health is an interdisciplinary field concerned with understanding and influencing the population's health and wellbeing. While public health professionals assume various roles and responsibilities, the workforce must profoundly understand population health, including the social and ecological determinants of health. Public health education seeks to advance knowledge of public health evidence and interventions and aims to develop skills to address public health issues and influence change at a population level. Most public health schools offer interdisciplinary and multidisciplinary programs to support career preparation therefore drawing on and developing partnerships with non-traditional public health disciplines is necessary to tackle complex problems, with recent examples from engineering in humanitarian action  and urbaThe Coronavirus Disease 19 (COVID-19) pandemic has stretched many health services across the globe. Given the rising costs of health and social care systems in many countries , 8, therThe original aim of the MOOC was to offer a self-organized learning experience in a field of study facilitated by experts in the area . It was Since their inception, MOOCs have evolved into two types of courses: the Connectivist MOOC (cMOOC) and the Extended MOOC (xMOOC) . The maiMany universities and colleges worldwide use MOOCs to provide a “flipped classroom” model for improved learning , 28. ThiThe numerous Australian, US and UK universities that supported the emergence of MOOCs continue to provide central coordination and multiple MOOC offerings . The OrgA review of MOOCs in health education during the COVID-19 lockdown in 2021 by Dolores et al.  reportedThe earliest MOOC developments in public health education were recorded by the Johns Hopkins Bloomberg School of Public Health (JHSPH) during its 2012–2013 academic year. The school's decision to offer MOOCs was based on its already extensive experience with online and open education . This inMOOCs have materialized as effective tools for scaling-up education . McAuleyThe personalization of MOOCs is a growing trend aimed at improving learners' individual experiences . ResearcTargeted training outside traditional degree programs facilitates higher efficiency for higher education systems, including continuing professional development programs . This ofHealth professionals increasingly access MOOCs to support their professional development . MOOCs oThe interdisciplinary field of public health does not have a single preferred training modality , therefoThe COVID-19 pandemic challenged health systems globally, requiring them to respond with an integrated, multidisciplinary approach to preparedness, prevention, and management. Despite a whole of government response, Australia's federal division of power allowed policy formulation and innovation to occur at the state level, reflecting the impact of the pandemic for local communities. Tasmania's COVID-19 response aimed to contain the virus, minimize transmission, and protect vulnerable people and groups. This necessitated a range of evolving measures, including lockdowns and restricted travel, which had significant consequences on individuals and communities, including economic, social and psychological impacts.The island state of Tasmania is isolated from the rest of Australia, with a limited public health workforce. It soon became evident that building a robust, skilled workforce was essential to an effective response. To advance existing expertise, close skill gaps and build surge capacity, creative solutions were explored to target and engage a large audience and deliver online training. As a result of agile leadership, a public health MOOC was developed in collaboration with the University of Tasmania and Public Health Services, Department of Health Tasmania . This MOOne of the most successful MOOCs during the COVID-19 pandemic was delivered by the World Health Organization (WHO) through their interactive platform, OpenWHO . OpenWHOvia mobile or desktop devices. In addition, OpenWHO courses are offered in multilingual formats and local languages of communities affected by particular outbreaks, including one in sign language  and United Nations Information Centers(UNRIC)  agencies and programs responded to the COVID-19 pandemic with innovative learning solutions for individuals, organizations and institutions s(UNRIC) , 85. Thes(UNRIC) , 85.Open online learning courses have grown substantially in recent years, with millions of new users enrolled . Class CThe original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.SB and KM contributed to the conception and design of the article. SB wrote the first draft of the manuscript. KM and RP wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.


A comprehensive understanding of the effects of NEFA on oocytes in vitro would improve our understanding of the impacts of natural exposure in vivo.Fatty acids (FA) are one of the substrates that can be oxidized for energy production. The blood concentration of all types of FA varies according to different nutrition conditions, and follicular fluid levels are generally in line with serum levels. Elevated levels of FA, especially non-esterified fatty acids (NEFA), are commonly found in females with metabolic issues, which are often related to subfertility in many species including humans, pigs, cattle, and mice. Long-time exposure to an excessive quantity of fatty acids impairs the cell structure and functions causing injuries in tissues and organs, resulting in lipotoxicity and eventually hampering health and fertility. High levels of saturated NEFA can have detrimental effects on granulosa cells, oocyte quality, and embryo development. Although the harmful effects of FA are established in reproductive tissues, how granulosa cells and cumulus cells respond and cooperate with oocytes when exposed to NEFA requires further understanding. This review provides a summary of the adverse impacts of exposure to NEFA during Exposure to excess FAs affects the health of eggs, early embryos, and children born from these. The way different cell types react to excess FAs has not been studied very extensively, especially in pigs which provide a good model to investigate the impact of nutrition on the ovaries in humans. This review also looks at the way cells surrounding the egg react to FAs to help our understanding of the impact of excess fatty acids on female fertility. In the follicle, the developing oocyte is surrounded by cumulus cells attached to the mural granulosa cells, and the roles of these two types of granulosa cells in maintaining the quality of the oocyte are determinant. Cumulus cells are regarded as nutritive cells because they provide the oocyte with paracrine factors and metabolic substrates including pyruvate. Mural granulosa cells communicate with cumulus cells via cell junctions to exchange metabolites, growth factors, and signaling messengers. Besides, the follicular fluid (FF) serves as another substrate supplier and the amounts of nutrients in FF are dependent on those in the bloodstream. Therefore, the composition of the FF and the oocyte reflects the mother’s nutrition. The facts that mitochondria are the units responsible for energy production and that most mitochondria in an individual originate from the oocyte, and are therefore derived from the mother, highlight the influence of maternal nutrition on the oocyte and potentially on the energy metabolism of the offspring.Female fertility relies heavily on ovarian function and the resulting oocyte quality. The oocyte, which oversees subsequent development, is a relatively dependent entity. Although it can be matured and fertilized Fatty acid (FA) concentrations are affected by the diet and the lipolysis of stored lipids. The FA concentrations, especially non-esterified fatty acids (NEFA), which are also known as free fatty acids (FFA), are increased during both over- and under-nutrition conditions, and the elevated levels are associated with low embryo development in humans, cattle, and pigs , mature COCs consume higher amounts of substrates and store more energy for fertilization and subsequent early embryo development. Moreover, during all the stages of development from immature oocyte to expanded blastocyst, most of the ATP (about 95%) is generated by oxidative metabolism , and tricarboxylic acid (TCA) in oocytes. Metabolism of pyruvate, glutamine, and glycine by the Krebs cycle increases during tabolism . DiffereIn addition to playing important roles in many biological functions including biological membrane construction, cell–cell interactions, steroid synthesis, and signaling, lipids also act as a source of nutrients. Decreased triglyceride, phospholipids, cholesterol, and total lipids during oocyte maturation suggest the important role of lipid metabolism in oocyte maturation . FAs arein vitro compared to cumulus cells and oocytes matured in vivo in pig  and lipids (free fatty acids) to generate energy to maintain and support their biological development; however, these metabolic processes produce side products such as reactive oxygen species (ROS). Basal ROS production is an unavoidable natural mechanism in cells, but prolonged and high ROS production can cause oxidative stress which induces apoptosis. The ‘quiet embryo hypothesis’ described by The lipid content of oocytes varies from species to species. Before maturation, pig oocytes contain 74 ng of triglycerides out of a total lipid content of 161 ng, and bovine oocytes contain 23 ng of triglycerides out of the total lipid content of 63 ng . More stThe analysis of FA profiles in pigs showed that the proportions of free saturated FA are 46, 40, and 37% in oocytes, FF, and serum, respectively; and the proportions of free mono-unsaturated FA are 27, 36, and 46% in oocytes, FF, and serum, respectively; and the proportions of free polyunsaturated FA are 27, 24, and 15% in oocytes, FF, and serum, respectively . The NEFA content decreased during follicular development, and the large follicles had the lowest level of NEFA which was similar to the serum level. In porcine oocytes, the amount of triglycerides, which is the major constituent of total lipid, decreased during maturation but remained stable until blastocyst development  is a metabolic status achieved in the period after calving when the food intake does not satisfy the high energy demand of milk production in cattle. During this period, cows suffer from metabolic and endocrine issues, resulting in ovarian problems, poor oocyte quality, and reduced reproductive performance. Another obvious change is the two- to three-fold increase in the serum and follicular fluid NEFA levels in postpartum cows compared to the levels of prepartum cows , can desaturate saturated FA into mono-unsaturated FA. The inhibition of SCD decreased lipid storage in bovine cumulus cells and impaired blastocyst formation, suggesting a protective role of cumulus cells that decrease the negative effects of NEFA on oocytes  can rescue cardiac mitochondria from lipotoxicity . Fonds de recherche du Québec – Nature et technologies (FRQNT) provided a fellowship to Meihong Shi.Meihong Shi designed and wrote the paper, and Marc-André Sirard designed and revised the paper.


Long-term monitoring of a fetus with heart failure is an undeniable challenge for prenatal cardiology. Echocardiography is constrained by many fetal and maternal factors, and it is difficult to maintain the reproducibility of the measured and analyzed parameters. In our study, we presented the possibilities of using modern speckle tracking technology in combination with standard echocardiography parameters that may be insufficient or less sensitive in the context of monitoring life-threatening fetal conditions. Our analysis shows the superiority of the parameters used to assess fetal cardiac architecture, such as the GSI Global sphericity Index, and fetal cardiac function, such as the FAC fractional area change and the EF ejection fraction, which temporal change may indicate a worsening condition of the fetus with heart failure. The significant increase in the parameters of fetal heart size in speckle tracking allows for an improved echocardiographic diagnosis and monitoring of the fetus with heart failure and the prognostic conclusions about the clinical condition after birth. Significant decreases in FAC for the left and right ventricles and EF for the left ventricle may indicate an unfavourable prognosis for the monitored fetus due to heart failure. For longitudinal echocardiographic monitoring during fetal life, there is no consensus on the best approach to evaluate fetal cardiovascular function. Compared to postnatal echocardiographic evaluation, fetal evaluations may be complicated by various fetal positions and orientations, making serial assessment with a single measurement more challenging. Therefore, we compared conventional echocardiographic measurements with speckle-tracking derived assessments  Figure  to deterDuring the first pregnancy of a 26-year-old woman, the first trimester evaluation demonstrated active herpes labialis and shingles, which were treated with Aciclovir. New onset of ascites, hydrops testis, and ductus venosus reversal flow was seen at 30 weeks of gestation. With the subsequent development of fetal cardiomegaly, cardiac hypertrophy, pericardial effusion, mitral, tricuspid, and pulmonary valve regurgitation, and fetal heart failure, transplacental digoxin treatment was initiated, along with dexamethasone and cefuroxime. The standard echo-sonographic findings are presented in Our analysis and interpretation of the standard and advanced echocardiographic parameters using speckle tracking technology allowed us to evaluate the efficacy of prenatal treatment with digoxin. Digoxin was administered from week 30 to week 32. Standard size of the HA/CA (heart area/chest area) was constant, and a detailed speckle tracking analysis revealed a significant prolongation of the TL transverse length dimension and a shortening of the BAL-basal–apical length dimension, thereby reducing the GSI-global Sphericity Index GSI = BAL/TL) , which sFetal circulatory failure may have various causes and, therefore, it is very difficult to assess the effectiveness of any treatment . So far,FAC should generally take values ≥35% . In our The speckle tracking analysis performed in our case allows a detailed monitoring of a fetus with heart failure.


Biofilm formation is a fundamental part of life cycles of bacteria which affects various aspects of bacterial-host interactions including the development of drug resistance and chronic infections. In clinical settings, biofilm-related infections are becoming increasingly difficult to treat due to tolerance to antibiotics. Bacterial biofilm formation is regulated by different external and internal factors, among which quorum sensing (QS) signals and nucleotide-based second messengers play important roles. In recent years, different kinds of anti-biofilm agents have been discovered, among which are the Chinese herbal medicines (CHMs). CHMs or traditional Chinese medicines have long been utilized to combat various diseases around the world and many of them have the ability to inhibit, impair or decrease bacterial biofilm formation either through regulation of bacterial QS system or nucleotide-based second messengers. In this review, we describe the research progresses of different chemical classes of CHMs on the regulation of bacterial biofilm formation. Though the molecular mechanisms on the regulation of bacterial biofilm formation by CHMs have not been fully understood and there are still a lot of work that need to be performed, these studies contribute to the development of effective biofilm inhibitors and will provide a novel treatment strategy to control biofilm-related infections. Biofilm is a self-protective state formed by bacteria to adapt to the poor living environment. It is a microbial community attached to biotic or abiotic surfaces and wrapped by self-produced extracellular polymeric matrix (EPS) that contains extracellular polysaccharides, nucleic acids (extracellular DNA and extracellular RNA), amyloid proteins, lipids, and many other biomolecules . All bacStrategies for combating bacterial biofilms have been classified into three main categories: (i) changing the properties of susceptible surfaces to prevent biofilm formation; (ii) regulating signaling pathways to inhibit biofilm formation; (iii) applying external forces to eradicate the biofilm . BesidesTraditional Chinese medicine (TCM) is one of the oldest healing systems which includes herbal medicine, acupuncture, moxibustion, massage, food therapy, and physical exercise, and have been used for a long history in China against various diseases . Many TCQuorum sensing (QS) is a bacterial communication system that plays a pivotal role in regulating bacterial biofilm formation . QS is dvia QS in the literatures, as well as their targets.The regulatory mechanism of the bacterial QS system has been extensively studied. It has been found that the system can be targeted for the development of antibacterial inhibitors, and such inhibitors are called Quorum Sensing Inhibitors QSIs; . In addiCitri Reticulatae  to impair QS signaling and biofilm formation. In vivo, naringin and hesperidin protects mice from endotoxin shock through inhibition of bacterial numbers and inflammatory cytokine release -producing bacteria of gut microbiota to alleviate lung injury  n. According to the number of isoprene or isopentane (C5H8), terpenoids and their derivatives are divided into several subclasses including monoterpenes, sesquiterpenes, diterpenes, triterpenes, tetriterpenes, and polyterpenes  or regulatory proteins (ExpR) and performing molecular docking simulation tests, carvacrol and eugenol have the ability to bind ExpI/ExpR, which in turn leads to decreased accumulation of the intracellular QS signaling molecule AHL and inhibit biofilm formation . They can inhibit MRSA biofilm formation and virulence factor expression by prevention of the activation of AgrA upon binding or phosphorylation of the helper gene regulator AgrA to DNA  and ursolic acid , upon which the expressions of genes related to the QS system  are downregulated , reduces the ability of P. aeruginosa to form biofilms and inhibits virulence factors expression by competing with signaling molecules for receptor proteins , thereby blocked the QS signaling  and raspberry. Some natural organic acids have certain biological activities including antibacterial , schisandra  as a major component together with other anti-biofilm compounds such as EGCG, propyl gallate, and octyl gallate (Libidibia ferrea (Mart. ex Tul.) inhibits Streptococcus pyogenes biofilms by downregulation of the expression of gtfB, gtfC and gtfD genes , broad bean roots and Sophora flavescens. It has anti-inflammatory, antibacterial, antioxidant, immunomodulatory and anticancer effects (E. coli (a strain that showed resistant to different antibiotics) biofilms by downregulation of QS-related genes luxS, pfS, sdiA, hflX, motA and fliA  inhibit P. aeruginosa biofilm formation by reduction of AHL and EPS  by binding to cell surface receptors, regulating the enzymatic activity of intracellular metabolic systems, amplifying the original signal and thus inducing intracellular expression of a series of specific genes, and ultimately affecting a variety of physiological and biochemical processes in bacteria . Second . mutans , Bacillusubtilis , S. aure. aureus , P. aeruruginosa , K. pneueumoniae , and E.  inhibition or activation of second messenger synthases; (ii) inhibition or activation of second messenger degradation enzymes; and (iii) competition for signaling pathway receptor proteins , an active ingredient in plants, inhibits S. aureus biofilm formation by interfering with initial attachment and the synthesis of polysaccharide intercellular adhesin , the Natural Science Foundation of Jilin Province , the Fundamental Research Funds for the Central Universities, Shandong Provincial Modern Agricultural Industry Technology System (SDAIT-27), and Key Technology Research and Development Program of Shandong (2021TZXD012).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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