Organ Systems Research Articles

Role of local angiotensin II signaling in bladder function.

Angiotensin II signaling plays a crucial role in many different diseases. Although it has been known for several decades that local angiotensin II signaling molecules are present in the bladder, the understanding of their functions there is still limited, especially compared with other organ systems such as cardiovascular and respiratory systems. This article reviews current literature regarding local angiotensin II signaling in the urinary bladder. By reviewing several decades of literature, the field has provided strong evidence to support the presence of local angiotensin II signaling in the bladder, including the expression of angiotensin type 1 receptor and angiotensin type 2 receptor in both human and animal tissues. In addition, evidence suggests a functional role of angiotensin type 1 receptor in mediating bladder contractions. In bladder disease models, angiotensin II signaling can be upregulated, and angiotensin type 1 receptor activity is associated with increases in inflammation, fibrosis, and oxidative stress. We also address the gaps in knowledge that remain in understanding local angiotensin II signaling in the bladder, including limitations on clinical translatability. Although there is a strong foundation regarding the local presence and role of angiotensin II signaling in the bladder, further research is needed to support translational applications.

Autothermal hydrogen release from liquid organic hydrogen carrier systems

A typical feature that the LOHC technology shares with other types of chemical hydrogen storage is that the release of hydrogen from the carrier requires an input of heat. In many use cases where waste heat from external sources is not available (e.g. in heavy-duty mobility), this is seen as a major drawback. In this paper, we show that autothermal LOHC dehydrogenation offers a very attractive way to overcome this drawback. In detail, we demonstrate autothermal hydrogen release from dicyclohexylmethane using diphenylmethane oxidation to benzophenone as source of heat. The full storage cycle involves benzophenone hydrodeoxygenation to dicyclohexylmethane, dicyclohexylmethane dehydrogenation to diphenylmethane, and diphenylmethane oxidation to benzophenone. We studied both the individual reaction steps using pure feedstocks and the integral cycle in which the intermediates and by-products of each reaction remain in the system for the subsequent reaction step. Although no efforts have yet been made to develop special catalyst materials for this purpose, the results with the applied commercial hydrodeoxygenation (Pd/C), dehydrogenation (Pt on alumina) and partial oxidation (VOx/TiO2) catalysts are already very promising. The storage cycle can be closed with high selectivity and with only minor total oxidation losses. The proposed concept of autothermal LOHC dehydrogenation offers the potential to increase the amount of useable hydrogen from a given amount of charged hydrogen carrier by up to 30%.

Dynamic performance analysis and optimization research on solar dual-stage evaporation multigeneration system

A novel solar dual-stage evaporation multigeneration system is proposed, with analysis on the impact of the parabolic trough collector area (APTC) and the volume of the heat storage tank (VHST) on performance under dynamic conditions. The particle swarm optimization- genetic algorithm and the minimum path method optimized the system’s overall performance. Results show that reducing APTC and increasing VHST can enhance energy performance within a certain range, but beyond specific thresholds, changes in APTC and VHST no longer affect it. As APTC and VHST increase, economic performance initially improves but then declines. The particle swarm optimization- genetic algorithm increased optimization efficiency and avoided local optima. When using the minimum path method, the dimensionless cumulative error was 0.63, balancing thermal and economic performance. Using toluene as the working fluid, the optimized system achieved thermal and exergy efficiencies of 56.06 % and 9.15 %, respectively, with a net present value of 58.12 M$, a payback period of 5.23 years, and an equivalent CO2 reduction of 24.8 kt, outperforming the solar organic Rankine cycle system in energy efficiency, economic performance, and carbon reduction potential. The solar dual-stage evaporation multigeneration system achieved the best performance with toluene as the working fluid, while heptane provided longer running time and greater carbon reduction potential. At low rated power generation, performance differences between toluene and heptane were minimal, while as the rated power generation increased, toluene showed significant advantages in thermal and economic performance.

The impact of long-term organic horticultural systems on energy outputs and carbon storages in relation to extreme rainfall events

Enhancing resilience of agroecosystems of Mediterranean area is a challenge that involves both researchers and different stakeholders and, in this context, increasing crop diversity by redesigning agricultural systems can be considered among the most important tools. Therefore, the response of agroecological practices to climate change effects was tested in a long-term experiment on organic horticultural crops (MITIORG), which is characterized by a soil hydraulic arrangement in ridges, strips and the use (with different management options) of cover crops within cash crops rotations. The main objective of this study was to show how powerful is the sustainability assessment of agroecological practices by converting crops yield and biomass into energy outputs and carbon storages, in diversified horticultural systems. The obtained outputs (expressed in energy and carbon equivalents) were evaluated and analyzed considering the site-specific meteorological data in more than 10 horticultural cropping cycles, from autumn-winter 2014-15 to autumn-winter 2020-21. The Ridge and Strips (RS) system 1 (RS1 - cover crops as living mulch on ridges and break crops in strips, both with no-till termination) showed an enhancement of about 18% of energy output and carbon (C) storages compared to RS2 (ridges and strips with green manured cover) when extreme precipitation events occurred. Moreover, RS3 (ridges and strips without cover crops) recorded a reduction of about 5 and 9% of energy output and C storage, respectively, compared to the mean of RS1 and RS2 in periods with extreme events. Our results highlighted that using more diversified agroecological systems improved their overall average outputs, ensuring greater resilience during extreme weather events, since at least part of crop productions was safeguarded. Therefore, it is important to combine techniques that allow long-term resilience, such as choosing and well managing cover crops (agroecological service crops), according to site and systems specific conditions.

Thiamine: An indispensable regulator of paediatric neuro-cardiovascular health and diseases.

Physicians are recommended to have a low threshold for suspecting thiamine deficiency especially in vulnerable populations. Laboratory diagnosis of thiamine deficiency needs to be implemented as a standard of care, especially in endemic regions. Further, public health policies on food fortification, mandatory supplementation, and surveillance are imperative to eliminate thiamine deficiency-induced health hazards. • South Asian countries report a higher incidence of neonatal and under-five mortalities, many of which are attributed to maternal and perinatal micronutrient deficiencies. • Preventable causes of neonatal/ infantile deaths include birth factors (low birth weight, birth asphyxia), infectious diseases (pneumonia, diarrhoea, tetanus, tuberculosis, measles, diphtheria, malaria, acute infections), deficiency diseases and genetic diseases (vitamin & mineral deficiencies, IEMs, congenital heart disease, unexplained PPHN, SIDS etc). • Acute thiamine deficiency presenting as multisystemic syndromes, has unfortunately been a long standing unresolved public health concern. However, accessible surveillance and diagnostic strategies remain elusive in most clinical settings. • Despite decades of reports and emerging guidelines, diagnosis of thiamine deficiency is often missed and policy mandates at national level are yet to be implemented even in endemic countries. • This review provides a comprehensive summary of the biochemical role of thiamine, its key functions and effects on major organ systems, the diagnostic gap, the enigmatic presentation of acute thiamine deficiency, the plausible role of thiamine in other pathologies and the preventive measures at individual and community level.

Ciphering of greenhouse gases from constructed wetlands in Lucknow (U. P. India)

This study evaluates how greenhouse gases (GHGs) contribute to global warming, drawing attention to the substantial effect of human activity on GHG concentrations in the atmosphere. The lower atmosphere warms as a consequence of the absorption as well as the emission of thermal infrared radiation by greenhouse gases, which are both naturally occurring and created by human beings. Since the 1950s, it has been determined that carbon dioxide (CO2) contributes a vital part in tweaking the environmental conditions, with other gases which include methane (CH4), nitrous oxide (N2O), and CFCs also playing a significant role. India is the third-biggest producer of greenhouse gases (GHGs) due to its enormous population and fast economic growth. This study looks into the GHG emissions from manmade wetlands (CWs) and seasonal assessments conducted in Lucknow and the neighboring wetlands. The emissions of nitrous oxide and methane from CWs are computed using particular formulas and parameters. Utilizing particular formulas and parameters, the emissions of methane and nitrous oxide from CWs are computed. The results emphasize the significance of efficient management techniques such as hydrological control, organic matter control, intermittent drying, shading, adding biochar, and hybrid systems in reducing greenhouse gas emissions from wetlands. The mitigation of the ecological consequences of chemical warfare and the fight against global warming necessitates these protocols.

Medical Psychiatric Challenges in the Treatment of Obsessive-Compulsive Disorder and Eating Disorders

This paper examines the intricate relationship between Obsessive-Compulsive Disorder (OCD) and eating disorders (EDs), focusing on their diagnostic criteria, comorbidity, shared characteristics, and the profound medical and psychiatric complications that arise from these conditions. OCD is characterized by intrusive obsessions and compulsions that significantly impact daily functioning, while EDs, including Anorexia Nervosa, Bulimia Nervosa, and Binge-Eating Disorder, involve severe disturbances in eating behaviors and body image. These disorders often co-occur, with up to 41% of individuals with EDs also suffering from OCD. The shared symptoms, such as obsessions, compulsions, avoidance behaviors, and perfectionism, highlight the complex interplay between OCD and EDs, complicating diagnosis and treatment. The medical complications associated with this comorbidity are severe and varied, affecting multiple organ systems. Gastrointestinal issues, proctological problems, oral health deterioration, cardiological dysfunction, electrolyte imbalances, kidney disorders, and hormonal dysregulation are common. Additionally, sleep disorders are prevalent, further exacerbating both psychiatric and physical health outcomes. Effective treatment requires a holistic approach that addresses the unique needs of each individual, with integrated care involving specialists across medical and mental health fields. This comprehensive approach is crucial to mitigating the devastating impact of OCD and EDs, improving overall well-being and quality of life for affected individuals.

Alterations in Hurler-Scheie Syndrome Revealed by Mass Spectrometry-Based Proteomics and Phosphoproteomics Analysis.

Hurler-Scheie syndrome (MPS IH/S), also known as mucopolysaccharidosis type I-H/S (MPS IH/S), is a lysosomal storage disorder caused by deficiency of the enzyme alpha-L-iduronidase (IDUA) leading to the accumulation of glycosaminoglycans (GAGs) in various tissues, resulting in a wide range of symptoms affecting different organ systems. Postgenomic omics technologies offer the promise to understand the changes in proteome, phosphoproteome, and phosphorylation-based signaling in MPS IH/S. Accordingly, we report here a large dataset and the proteomic and phosphoproteomic analyses of fibroblasts derived from patients with MPS IH/S (n = 8) and healthy individuals (n = 8). We found that protein levels of key lysosomal enzymes such as cathepsin D, prosaposin, arylsulfatases (arylsulfatase A and arylsulfatase B), and IDUA were downregulated. We identified 16,693 unique phosphopeptides, corresponding to 4,605 proteins, in patients with MPS IH/S. We found that proteins related to the cell cycle, mitotic spindle assembly, apoptosis, and cytoskeletal organization were differentially phosphorylated in MPS IH/S. We identified 12 kinases that were differentially phosphorylated, including hyperphosphorylation of cyclin-dependent kinases 1 and 2, hypophosphorylation of myosin light chain kinase, and calcium/calmodulin-dependent protein kinases. Taken together, the findings of the present study indicate significant alterations in proteins involved in cytoskeletal changes, cellular dysfunction, and apoptosis. These new observations significantly contribute to the current understanding of the pathophysiology of MPS IH/S specifically, and the molecular mechanisms involved in the storage of GAGs in MPS more generally. Further translational clinical omics studies are called for to pave the way for diagnostics and therapeutics innovation for patients with MPS IH/S.

Protein phosphatase 1 suppresses PKR/EIF2α signaling during human cytomegalovirus infection.

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that infects the majority of the world's population. Lytic HCMV replication in immunocompromised individuals or neonates can lead to severe disease in multiple organ systems and even death. The establishment of lytic replication is driven by the first viral proteins expressed upon infection, the immediate early proteins, which play a key role in creating an intracellular environment conducive to virus replication. Two immediate early proteins, the functional orthologs pTRS1 and pIRS1, stimulate immediate early gene expression by suppressing antiviral PKR/eIF2α signaling and enhance the translation of viral mRNAs independent of PKR antagonism. To better understand the molecular functions of pTRS1, we used proximity labeling proteomics to identify proteins that interact with pTRS1 in infected cells. Multiple novel host and viral interactors were identified, including the catalytic subunits of the protein phosphatase 1 (PP1) holoenzyme. Mutations to a PP1 catalytic subunit known to disrupt binding to PP1 regulatory subunits decreased binding to pTRS1. pTRS1 immune complexes contained phosphatase activity, and inhibition of phosphatase activity in transfected or infected cells reversed the ability of pTRS1 to inhibit the antiviral kinase PKR. Depletion of individual PP1 catalytic subunits decreased virus replication and increased the phosphorylation of the PKR substrate eIF2α. Taken together, our data suggest potential novel functions for pTRS1 and define a novel role for PP1 as an antagonist of the antiviral PKR/eIF2α signaling axis during HCMV infection.IMPORTANCEThe human cytomegalovirus (HCMV) pTRS1 and pIRS1 proteins are critical regulators of HCMV replication, both during primary infection and during reactivation from viral latency. Thus, defining the molecular functions of pTRS1/pIRS1 is important for understanding the molecular events controlling HCMV replication and viral disease. These data provide new insights into potential pTRS1 functional roles, providing a starting point for others to understand new features of infected cell biology. Another important result of this study is the finding that specific protein phosphatase 1 (PP1) regulatory subunits are required to suppress PKR/eIF2α signaling, a critical cellular innate immune defense to viral infection. These data lay the groundwork for future efforts to discover therapeutics that disrupt pTRS1 interaction with PP1 allowing cellular defenses to limit HCMV replication and disease.

Historical Control Background Incidence of Spontaneous Nonneoplastic Lesions of Sprague Dawley Rats in 104-Week Carcinogenicity Studies.

Microscopic observation data collected from approximately 1800 male and female Sprague Dawley (SD) control rats used on 104-week carcinogenicity studies performed at North American Labcorp Early Development, Inc, Madison, WI, were retrospectively evaluated for spontaneous nonneoplastic findings. This study provides incidence of the most common spontaneous nonneoplastic microscopic findings in each organ system of SD rats encountered during 104-week carcinogenicity studies. Some of the most common spontaneous background findings were cardiomyopathy; chronic progressive nephropathy; uterine cystic endometrial hyperplasia; prostate inflammation; pulmonary alveolar macrophage infiltrates; hepatocyte vacuolation, bile duct hyperplasia, and basophilic foci in the liver; pancreatic fibrosis; splenic extramedullary hematopoiesis and pigment; decreased lymphocytes and epithelial hyperplasia in the thymus; ventral brain compression; cystic degeneration and hyperplasia of the adrenal cortex; and mammary gland hyperplasia. The most common nonneoplastic findings in male SD rats were chronic progressive nephropathy (80.9%) and rodent progressive cardiomyopathy (73.2%). The most common nonnenoplastic findings in female SD rats were cystic degeneration of the adrenal cortex (64.7%) and ventral compression of the brain due to pituitary neoplasms (62.7%).

Mapping Long COVID across the EU: definitions, guidelines and surveillance systems in EU Member States

Abstract A mapping study had been conducted to provide insight into 1) Long COVID definitions, 2) guidelines and intelligence on diagnosis and treatment, and 3) surveillance systems, as used/implemented in EU Member States plus Iceland, Norway, the United States, Canada, New Zealand, and Australia. Findings show that most Long COVID definitions align with WHO or NICE criteria, although there are also notable differences between definitions. The study also found Long COVID guidelines for diagnosis and treatment in 21 out of 34 selected countries. Common elements include advocating a multidisciplinary approach, a central role for primary care, and the focus on rehabilitation. Some guidelines include recommendations for referral to specialised care and follow-up procedures. Guidelines also differ in their target audience and in terms of their focus specific symptoms or organ systems that are affected by Long COVID. When it comes to Long COVID surveillance systems only a limited number of (nine) registries were found. Five of the Long COVID registries are based on self-registration. As limited information is available for most registries, a detailed understanding of their structures and goals in comparison to others is hindered. In conclusion, the study underlines the interconnectedness of Long COVID definitions, the development of guidelines, and surveillance systems. Given the variability in definitions and the voluntary entry of patients into the existing registries, there are no good estimates yet of the total numbers of patients and the severity of their disease in EU Member States. Linking information from cohort studies and clinical trials may be necessary to provide the full picture of the burden of disease of Long COVID. Still, preliminary estimates indicate that a significant proportion of those infected with COVID-19 experience long lasting symptoms, leading to impaired quality of life, also placing a significant burden on national health systems in the future.

Substantial morbidity and mortality due to cardiovascular diseases in hospitalized vaccinated and un-vaccinated patients with COVID-19 from 16 countries: the WHF COVID-19 Long-term study

Abstract Background Long-term adverse consequences of the COVID-19 affect many organ systems, and this requires the identification and appropriate care of diverse symptoms. Purpose The World Heart Federation (WHF) international study describes the burden of clinical sequelae of COVID-19 up to 1 year after hospitalization, including patients from low- middle-and high-income countries. Methods We prospectively recruited patients hospitalized due to COVID-19 from 16 countries between January 2022 and June 2023. Patients were followed up at 1, 3, 6, and 9-12 months after hospital discharge. A standardized questionnaire administered by telephone collected data on long COVID symptoms, quality of life using the EuroQol 5 Dimension scale (EQ-5D), and disease outcomes including new onset diabetes and hypertension, major adverse cardiovascular events (MACE), and mortality. We report a descriptive analysis including demographic characteristics and outcomes up to one year after initial hospitalization. Results Of 2504 patients, the majority were Asian (78%), and male (56%). Mean age was 59.2 years (SD 19.9). Low- and lower-middle-income country participants constituted 65% of the cohort, with upper middle-income and high-income representing 20% and 15%, respectively. Follow-up rate was complete for 86%. 55% had received at least two doses of COVID-19 vaccination. At 1 month, 63% reported at least one persistent symptom, which decreased to 28% at 9-12 months. Fatigue was reported by 45% at 1-month and 17% at final follow-up. Anxiety occurred in 20% and 9% at these respective timepoints, and breathlessness in 12% and 6%. At 9-12 months, moderate to severe impairment of usual activities as measured by EQ-5D occurred in 19%, anxiety/depression in 10%, and mobility problems in 10%. The most frequent post-discharge new-onset illnesses were pulmonary embolism (7%), kidney problems (4%), and hypertension (3%). In-hospital mortality was 4% (n=102), and a further 12% (265 patients) died by one-year. The most common cause was sudden cardiac death (59%), respiratory disease including pulmonary embolism (13%), and stroke (6%). Conclusions We observed a significant burden of post-COVID-19 complications with one fifth of patients with persistent difficulties in usual activities at one year. This underscores the urgent need to understand the underlying mechanisms for organ damage and death, and for targeted preventive strategies and proactive management approaches to reduce them.

Integrating mechanical and cultural methods for weed control in organic chickpea

Abstract The Northern Great Plains of the United States is a major production region for organic pulse crops that are prone to yield losses due to weeds. Weed management in organic systems relies on the integration of several tactics to stack additive effects and for redundancy to deal with variable efficacy of individual weed management practices. To address the need for effective, integrated weed management, we conducted a 2-yr trial that evaluated the effects of planting date, seeding rate, and preemergent weed control practices (shallow tillage and flame weeding) on weed biomass, crop density, and yield in organically managed chickpea (Cicer arietinum L.) in Montana. Stacking weed management practices increased yields. Early planting had the largest effects on yields, increasing them by 1.8- to 3.6-fold compared with planting 10 to 14 d later. Increasing the seeding rate from the standard rate (43 viable seeds m−2) by 50% increased yields by 47% from 889 to 1,304 kg ha−1. Both preemergent weed control practices increased yields by 40% to 50 % relative to the non-weeded controls. By integrating all three practices, yields of organic chickpea increased greater than 6-fold from 318 kg ha−1 in the controls to 2,006 kg ha−1. The effects of weed control treatments on midseason weed biomass were complex and variable. Although efficacy of the cultural (seeding rate and planting date) and physical (preemergent) treatments on weed biomass varied between years and when combined with other treatments, their full integration, that is, early planted, at higher seeding rate, and preemergent weed control, produced consistently lower weed biomass (84% reduction on average) compared with the standard grower practice (later planting, standard seeding rate, no preemergent weed control). The results lend support to the concept of integrating multiple weed management practices to achieve weed control and high yields in organically managed crops.

Intra-specific variations in Schistosoma mansoni and their possible contribution to inconsistent virulence and diverse clinical outcomes.

Schistosoma mansoni was introduced from Africa to the Americas during the transatlantic slave trade and remains a major public health problem in parts of South America and the Caribbean. This study presents a comprehensive comparative analysis of three S. mansoni strains with different geographical origins-from Liberia, Belo Horizonte and Puerto Rico. We demonstrated significant variation in virulence and host-parasite interactions. We investigated the phenotypic characteristics of the parasite and its eggs, as well as the immunopathologic effects on laboratory mouse organ systems. Our results show significant differences in worm morphology, worm burden, egg size, and pathologic organ changes between these strains. The Puerto Rican strain showed the highest virulence, as evidenced by marked liver and spleen changes and advanced liver fibrosis indicated by increased collagen content. In contrast, the strains from Liberia and Belo Horizonte had a less pathogenic profile with less liver fibrosis. We found further variations in granuloma formation, cytokine expression and T-cell dynamics, indicating different immune responses. Our study emphasizes the importance of considering intra-specific variations of S. mansoni for the development of targeted therapies and public health strategies. The different virulence patterns, host immune responses and organ pathologies observed in these strains provide important insights for future research and could inform region-specific interventions for schistosomiasis control.

Long COVID in the UAE: symptomatology, gender gaps, and health implications among COVID-19 survivors

Abstract Background A growing number of COVID-19 survivors are experiencing symptoms post-SARS-CoV-2 infection, known as long COVID. It is a new multisystem condition and understanding its associated factors and its impact on individuals is crucial. This study aims to characterize long COVID in previously hospitalized patients in the UAE, identifying associated factors and assessing its impact on patients’ daily lives. Methods A multicenter retrospective cohort study was conducted in hospitals in Dubai and Sharjah from January 29, 2020 to October 14, 2021, involving RT-PCR confirmed cases. Clinical, epidemiologic, and long COVID data were collected via hospital records and phone interviews. Results Long COVID affected 48.7% of 533 patients, with 46.6% prevalence persisting over a year. A total of 43 symptoms across 11 organ systems were reported. Females had 1.83 times higher odds of long COVID (95% CI [1.22, 2.74], p = 0.003). Each additional initial symptom (AOR = 1.22, 95% CI [1.05, 1.40], p = 0.008), ICU admission (AOR = 1.77, 95% CI [1.06, 2.98], p = 0.030), and ≥ 2 comorbidities (AOR = 2.19, 95% CI [1.09, 4.40], p = 0.027) increased the odds of long COVID. Long COVID significantly impacted daily life, with poorer health ratings (AOR = 5.576, 95% CI [3.029, 10.265], p < .001), worse health status (AOR = 7.842, 95% CI [4.954, 12.415], p < .001), and work limitations due to physical (AOR = 4.808, 95% CI [3.229, 7.158], p < .001) and emotional issues (AOR = 3.149, 95% CI [2.01, 4.933], p < .001). This impact persisted beyond 12 months post-infection. Conclusions Long COVID presents prolonged multisystem involvement and substantial disability among survivors, necessitating further research to understand its lasting effects and intervention development to mitigate its impact Key messages • Long COVID poses a substantial challenge to public health in the UAE, affecting almost half of hospitalized survivors and extending its impact beyond 12 months post-infection. • Risk factors like gender initial symptoms, ICU stay, and comorbidities increase the risk of long COVID, warranting the need for tailored interventions and support strategies for vulnerable populations.

Organic cropping systems balance environmental impacts and agricultural production

Agriculture provides food to a still growing population but is a major driver of the acceleration of global nutrient flows, climate change, and biodiversity loss. Policies such as the European Farm2Fork strategy aim to mitigate the environmental impact of land-use by fostering organic farming. To assess long-term environmental impact of organic food production we synthesized more than four decades of research on agronomic and environmental performance of the oldest system comparison experiment on organic and conventional cropping systems (DOK experiment). Two organic systems (bioorganic and biodynamic) are compared with two conventional (manure-based integrated and mineral-based) systems all with the same arable crop rotation including grass-clover, and manure from livestock integrated in all except the mineral-based system. Organic systems used 92% less pesticides and 76% less mineral nitrogen than conventional systems. Nitrogen use efficiency, that also considers biological nitrogen fixation, was above 85% for all systems. Organic fertilization with farmyard manure maintained or increased soil carbon and nitrogen stocks in the long term, especially in the biodynamic system with manure compost. Conventional mineral-based cropping reduced soil organic carbon and nitrogen stocks. Higher soil organic carbon stocks in organic cropping did not translate to increased N2O emissions, which were the main driver for 56% lower soil-based, area-scaled climate impact compared to the integrated conventional system with manure. Organic cropping systems, especially compost-based biodynamic, showed enhanced soil health, richness of micro- and macrofauna and weed species. Highest yields were achieved in integrated conventional system, with highest total nitrogen inputs and enhanced soil health compared to pure mineral fertilization. Yet, these benefits come at the cost of lower nitrogen use efficiency and higher N2O emissions. Despite a rigorous reduction of inputs yields of the organic systems achieved 85% of the conventional systems. We demonstrate at field level that organic cropping systems with reduced external nutrient inputs have less climate impact and a larger in-situ biodiversity, while providing a fertile ground for the future development of sustainable agricultural production systems.

The Management of Fungal Diseases in Organic Production Systems Through a Mixture of Durum Wheat Varieties

Fungal diseases are a yield-limiting factor for wheat. Their management in organic production systems is one of the prevailing challenges because it must be based mainly on indirect measures through agricultural practices. Variety mixtures are one of these practices, a concept that has been demonstrated to improve several factors affecting yield. Recently, it has become a practice that enables sustainability in agriculture. Our research aim is to evaluate the capacity of this practice to control three fungal diseases (foliar and ear) on durum wheat. This study was conducted over two consecutive years (2019 and 2020) at two locations: a certified organic farm in the Benslimane region (2019) and the National School of Agriculture farm in Meknes (2020). Four durum wheat varieties (Isly, Tarek, Karim, and Nassira) were used to create the mixture. The parameters that were monitored were the disease severity, the grain yield, and its components. The analysis of variance for the three fungal diseases’ severity was significant. The variety that showed resistance to all diseases was the Isly variety, and the most susceptible variety was the Nassira variety. The resistance of the other varieties to the diseases was variable from one year to the other. The mixture showed average severity values. It allowed a reduction in the severity of leaf rust of 47% during the first year and 30% during the second year compared to the most susceptible variety (Nassira). In the case of HLB (helminthosporiosis leaf blight), it reduced the disease by 47% during the first year and 34% during the 2020 season. For ear disease, Fusarium head blight (FHB), the reduction was 68% during the year 2019 and 49% during 2020. The mixture also ensured yield stability between the two trial years (1.66 t ha−1 and 1.54 t ha−1).

CHIP drives proteasomal degradation of NUR77 to alleviate oxidative stress and intrinsic apoptosis in cisplatin-induced nephropathy

Carboxy-terminus of Hsc70-interacting protein (CHIP), an E3 ligase, modulates the stability of its targeted proteins to alleviate various pathological perturbations in various organ systems. Cisplatin is a widely used chemotherapeutic agent, but it is also known for its alarming renal toxicity. The role of CHIP in the pathogenesis of cisplatin-induced acute kidney injury (AKI) has not been adequately investigated. Herein, we demonstrated that CHIP was abundantly expressed in the renal proximal tubular epithelia, and its expression was downregulated in cisplatin-induced AKI. Further investigation revealed that CHIP overexpression or activation alleviated, while its gene disruption promoted, oxidative stress and apoptosis in renal proximal tubular epithelia induced by cisplatin. In terms of mechanism, CHIP interacted with and ubiquitinated NUR77 to promote its degradation, which consequently shielded BCL2 to maintain mitochondrial permeability of renal proximal tubular cells in the presence of cisplatin. Also, we demonstrated that CHIP interacted with NUR77 via its central coiled-coil (CC) domain, a non-canonical interactive pattern. In conclusion, these findings indicated that CHIP ubiquitinated and degraded its substrate NUR77 to attenuate intrinsic apoptosis in cisplatin-treated renal proximal tubular epithelia, thus providing a novel insight for the pathogenesis of cisplatin-induced AKI.

Flame retardancy, thermal, and mechanical properties of flame retardant PA6/SGF and PPS/PA6/SGF composites

AbstractFlame retardant polyamide 6/short glass fiber (FR PA6/SGF) and polyphenylene sulfide/PA6/SGF (FR PPS/PA6/SGF) composites were prepared by melt extrusion blending using aluminum diethylphosphinate (ADPP) as flame retardant. The thermogravimetric analysis (TGA) indicated that the flame retardant composites showed good thermal degradation with increasing ADPP loading. Flame retardancy mechanisms were studied by analyzing the residue chars. ADPP provided better flame inhibition, promoted formation of carbonaceous char, and improved thermal stability of PA6/SGF. Meanwhile, due to the self‐extinguishing performance of PPS, the flame retardancy of PPS/PA6/SGF was greatly affected by only 3.0 wt% of ADPP. With increasing ADPP content, both storage and loss moduli of FR PA6/SGF and FR PPS/PA6/SGF were increased accompanied with a slight increase of tan δ peak as compared to PA6/SGF and PPS/PA6/SGF, respectively. Besides, notched impact strengths of FR PA6/SGF‐10.0 and FR PPS/PA6/SGF‐10.0 increased by 69% and 5%, while tensile strengths decreased by approximately 5% and 32%, as compared to PA6/SGF and PPS/PA6/SGF, respectively. It demonstrates that ADPP and PPS components are efficient inorganic–organic hybrid flame retardant system. This provides a novel and innovative method for preparing halogen‐free flame retardant reinforced polyamide composites.

A real-world pharmacovigilance study of FDA Adverse Event Reporting System (FAERS) for gemcitabine

ABSTRACT Background Gemcitabine is widely used in the treatment of various cancers. This study aims to evaluate gemcitabine-associated adverse events (AEs) using the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Research design and methods We analyzed data spanning from January 2004 to June 2023. Employing reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) algorithms, we identified AEs with positive signals in patients administered gemcitabine. Results Out of 16,623,939 reports, 23,645 involved gemcitabine as the ‘primary suspected (PS)’ resulting in 74,306 AEs. Consistent with the reports in the specification and clinical trials, thrombocytopenia, pyrexia, neutropenia, and anemia were the most common AEs. Notably, our study identified some unexpected AEs such as abdominal pain, pleural effusion, ascites, and gastrointestinal hemorrhage, among others. The most significant SOC was ‘Blood and lymphatic system disorders’. The median onset time for gemcitabine-related AEs was 24 days (interquartile range [IQR] 6–82 days), with most cases occurring within the initial 30 days following gemcitabine administration. Conclusion Gemcitabine is associated with a broad spectrum of AEs affecting multiple organ systems, with a notable incidence of hospitalization. The study highlights both expected and unexpected AEs, which could enhance future clinical applications and safety of gemcitabine.