A comprehensive review on phosphatidylinositol-3-kinase (PI3K) and its inhibitors bearing pyrazole or indazole core for cancer therapy.

Cancer is a complex and multifaceted group of diseases with a high mortality rate characterized by uncontrolled proliferation of abnormal cells. Dysregulation of normal signalling pathways in cancer contributes to the different hallmarks of this disease. The signalling pathway of which phosphatidylinositol 3-kinase (PI3K) is a part is not an exception. In fact, dysregulated activation of PI3K signalling pathways can result in unbridled cellular proliferation and enhanced cell survival, thereby fostering the onset and advancement of cancer. Therefore, there is substantial interest in developing targeted therapies specifically aimed at inhibiting the PI3K enzyme and its associated pathways. Also, the therapeutic interest on pyrazoles and indazoles has been growing due to their various medicinal properties, namely, anticancer activity. Derivatives of these compounds have been studied as PI3K inhibitors, and they showed promising results. There are already some PI3K inhibitors approved by Food and Drug Administration (FDA), such as Idelalisib (Zydelig®) and Alpelisib (Piqray®). In this context, this review aims to address the importance of PI3K in cellular processes and its role in cancer. Additionally, it aims to report a comprehensive literature review of PI3K inhibitors, containing the pyrazole and indazole scaffolds, published in the last fifteen years, focusing on structure-activity relationship aspects, thus providing important insights for the design of novel and more effective PI3K inhibitors.

The polymicrobial nature of the oral cavity and claws of cats diagnosed by mass spectrometry and next-generation sequencing.

Close contact between cats and humans increases the risk of transmission of zoonotic pathogens, through bites and scratches due to the complexity of microorganisms in the oral and nail microbiotas of felines. This study investigated the presence of bacteria and fungi in the oral cavity and claws of 100 apparently healthy cats using conventional and selective microbiological culture media, and next-generation sequencing (NGS) and mass spectrometry (MALDI-TOF MS). Furthermore, antimicrobial susceptibility testing of bacteria isolates was performed by disc diffusion method. In total, 671 bacteria and 33 yeasts were identified by MALDI-TOF MS. Neisseria animaloris (10.8 %), Staphylococcus felis (8.5 %), and Pasteurella multocida (7 %) were the most prevalent bacteria in oral cavity samples (n = 343), while the most common yeast (n = 19) was Candida albicans (68.4 %). Staphylococcus pettenkoferi (13.4 %), Staphylococcus felis (6.4 %), and Staphylococcus simulans (5.8 %) were the prevalent bacteria identified in the claw samples (n = 328), while Rhodotorula mucilaginosa (57.2 %) was the most common yeast (n = 14). NGS predominantly identified the genera Moraxella, Neisseria, Pasteurella, and Fusobacterium in oral cavity samples, whereas enterobacteria and staphylococci were prevalent in nail bed samples. In addition, the genera Capnocytophaga and Bartonella were identified, which have been described in serious human infections secondary to feline aggressions. Levofloxacin, marbofloxacin, and amoxicillin/clavulanic acid were the most effective drugs against the main groups of bacteria identified. Multidrug resistance was observed in 17 % of the bacterial isolates. Furthermore, three staphylococci harboring the methicillin resistance gene mecA were identified. We highlight the complexity of microorganisms inhabiting the oral/claw microbiotas of cats, the high resistance rate of the isolates to conventional antimicrobial agents, and the zoonotic risk of aggressions caused by bites and scratches from domestic cats.

Nontypeable Haemophilus influenzae challenge during gammaherpesvirus infection enhances viral reactivation and latency.

Gammaherpesviruses are ubiquitous, lifelong pathogens associated with multiple cancers that infect over 95% of the adult population. Increases in viral reactivation, due to stress and other unknown factors impacting the immune response, frequently precedes lymphomagenesis. One potential stressor that could promote viral reactivation and increase viral latency would be the myriad of infections from bacterial and viral pathogens that we experience throughout our lives. Using murine gammaherpesvirus 68 (MHV68), a mouse model of gammaherpesvirus infection, we examined the impact of bacterial challenge on gammaherpesvirus infection. We challenged MHV68 infected mice during the establishment of latency with nontypeable Haemophilus influenzae (NTHi) to determine the impact of bacterial infection on viral reactivation and latency. Mice infected with MHV68 and then challenged with NTHi, saw increases in viral reactivation and viral latency. These data support the hypothesis that bacterial challenge can promote gammaherpesvirus reactivation and latency establishment, with possible consequences for viral lymphomagenesis.

Toxicity mechanisms of plastic nanoparticles in three terrestrial species: antioxidant system imbalance and neurotoxicity.

The detrimental impacts of plastic nanoparticles (PNPs) are a worldwide concern, although knowledge is still limited, in particular for soil mesofauna. This study investigates the biochemical impact of 44 nm polystyrene PNPs on three soil models-Enchytraeus crypticus (Oligochaeta), Folsomia candida (Collembola) and Porcellionides pruinosus (Isopoda). Exposure durations of 3, 7 and 14 days (d) were implemented at two concentrations (1.5 and 300 mg kg-1 PNPs). Results revealed PNPs impact on the activities of the glutathione-dependent antioxidative enzyme, glutathione S-transferase (GST) and on the neurotransmitter acetylcholinesterase (AChE) for all three species. Catalase (CAT) played a minor role, primarily evident in F. candida at 300 mg kg-1 PNPs (CAT and GST response after 14 d), with no lipid peroxidation (LPO) increase. Even with the antioxidant defence, P. pruinosus was the most sensitive species for lipid oxidative damage (LPO levels increased after 7 d exposure to 300 mg kg-1 PNPs). Significant AChE inhibitions were measured already after 3 d to both PNP concentrations in F. candida and E. crypticus, respectively. Significant AChE inhibitions were also found in P. pruinosus but later (7 d). Overall, the toxicity mechanisms of PNPs involved antioxidant imbalance, being (mostly) the glutathione-associated metabolism part of that defence system. Neurotoxicity, linked to AChE activities, was evident across all species. Sensitivity to PNPs varied: P. pruinosus > F. candida ≅ E. crypticus. This pioneering study on PNPs toxicity in soil invertebrates underscores its environmental relevance, shedding light on altered biochemical responses, that may compromise ecological roles and soil ecosystem fitness.

Pyrazoles have a multifaceted anti-inflammatory effect targeting prostaglandin E2, cyclooxygenases and leukocytes' oxidative burst.

Elevated levels of prostaglandin E2 have been implicated in the pathophysiology of various diseases. Anti-inflammatory drugs that act through the inhibition of cyclooxygenase enzymatic activity, thereby leading to the suppression of prostaglandin E2, are often associated with several side effects due to their non-specific inhibition of cyclooxygenase enzymes. Consequently, the targeted suppression of prostaglandin E2 production with innovative molecules and/or mechanisms emerges as a compelling therapeutic strategy for the treatment of inflammatory-related diseases. Therefore, in this study, a systematic analysis of 28 pyrazole derivatives was conducted to explore their potential mechanisms for reducing prostaglandin E2 levels. In this context, the evaluation of these derivatives extended to examining their capacity to reduce prostaglandin E2in vitro in human whole blood, inhibit cyclooxygenase-1 and cyclooxygenase-2 enzymes, modulate cyclooxygenase-2 expression, and suppress oxidative burst in human leukocytes. The results enabled the establishment of significant structure-activity relationships, elucidating key determinants for their activities. In particular, the 4-styryl group on the pyrazole moiety and the presence of chloro substitutions were identified as key determinants. Pyrazole 8 demonstrated the capacity to reduce prostaglandin E2 levels by downregulating cyclooxygenase-2 expression, and pyrazole-1,2,3-triazole 18 emerged as a dual-acting agent, inhibiting human leukocytes' oxidative burst and cyclooxygenase-2 activity. Furthermore, pyrazole 26 demonstrated effective reduction of prostaglandin E2 levels through selective cyclooxygenase-1 inhibition. These results underscore the multifaceted anti-inflammatory potential of pyrazoles, providing new insights into the substitutions and structural frameworks that are beneficial for the studied activity.

Approaches for delivery of refractive and optical care services in community and primary care settings.

BACKGROUND: Uncorrected refractive error is a leading cause of vision impairment which, in most cases, can be managed with the appropriate spectacle correction. In 2021, the World Health Assembly endorsed a global target of a 40-percentage-point increase in effective coverage of refractive error by 2030. To achieve this global target, equitable access to refractive and optical services within community and primary care settings needs to be strengthened. This review will inform the development of technical guidance to support improvements in the testing and correction of refractive error among World Health Organization (WHO) member states. OBJECTIVES: To determine the range of approaches for delivery of refractive and optical care services in community and primary care settings, and the methods employed for their evaluation. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and Global Health databases, grey literature, and annual reports and websites of relevant organizations involved in eye-care delivery from January 2002 to November 2022 to identify approaches for refractive and optical service delivery. SELECTION CRITERIA: We included observational and interventional studies, reviews, and reports from relevant organizations related to delivering refractive services and optical services for preschool and school-aged children and adults in community and primary care settings published between January 2002 and November 2022. We searched for studies and reports published within the last 20 years because vision impairment due to uncorrected refractive error has only recently become a public health and eye health priority, therefore we did not expect to find much relevant literature until after 2002. DATA COLLECTION AND ANALYSIS: Two review authors screened titles, abstracts and full texts, and extracted data. We resolved any discrepancies through discussion. We synthesized data, and presented results as tables, figures, and case studies. This project was led by the World Health Organization (WHO) Vision and Eye Care Programme. MAIN RESULTS: We identified 175 studies from searches of databases and grey literature, 146 records from company reports, and 81 records from website searches of relevant organizations that matched our inclusion criteria. Delivery approaches for refractive and optical services in community care included school-based, pharmacy, and outreach models, whereas primary care approaches comprised vision centre, health centre, and a combination of vision or health centre and door-to-door delivery. In community care, school-based and outreach approaches were predominant, while in primary care, a vision-centre approach was mainly used. In the WHO African region, the school-based and outreach approaches were mainly reported while, in the Americas, the outreach approach was mostly used. Very few approaches for service delivery were reported in the WHO Eastern Mediterranean region. Prominent gaps exist in the evaluation of the approaches, and few studies attempted to evaluate the approaches for delivery of refractive and optical care services. AUTHORS' CONCLUSIONS: We comprehensively describe a range of approaches for delivery of refractive and optical services in community and primary care. Further evaluation of their effectiveness will better inform the application of these service-delivery approaches. The study outcomes will help guide WHO member states in strengthening refractive and optical services at community and primary care levels. FUNDING: This scoping review was supported by the Vision and Eye care Programme, World Health Organization and ATscale Global Partnership. REGISTRATION: The protocol of this scoping review was published in the Open Source Framework.

Development and validation of the Ex-Care BR model: a multicentre initiative for identifying Brazilian surgical patients at risk of 30-day in-hospital mortality.

BACKGROUND: Surgical risk stratification is crucial for enhancing perioperative assistance and allocating resources efficiently. However, existing models may not capture the complexity of surgical care in Brazil. Using data from various healthcare settings nationwide, we developed a new risk model for 30-day in-hospital mortality (the Ex-Care BR model). METHODS: A retrospective cohort study was conducted in 10 hospitals from different geographic regions in Brazil. Data were analysed using multilevel logistic regression models. Model performance was assessed using the area under the receiver operating characteristic curve (AUROC), Brier score, and calibration plots. Derivation and validation cohorts were randomly assigned. RESULTS: A total of 107,372 patients were included, and 30-day in-hospital mortality was 2.1% (n=2261). The final risk model comprised four predictors related to the patient and surgery (age, ASA physical status classification, surgical urgency, and surgical size), and the random effect related to hospitals. The model showed excellent discrimination (AUROC=0.93, 95% confidence interval [CI], 0.93-0.94), calibration, and overall performance (Brier score=0.017) in the derivation cohort (n=75,094). Similar results were observed in the validation cohort (n=32,278) (AUROC=0.93, 95% CI, 0.92-0.93). CONCLUSIONS: The Ex-Care BR is the first model to consider regional and organisational peculiarities of the Brazilian surgical scene, in addition to patient and surgical factors. It is particularly useful for identifying high-risk surgical patients in situations demanding efficient allocation of limited resources. However, a thorough exploration of mortality variations among hospitals is essential for a comprehensive understanding of risk. CLINICAL TRIAL REGISTRATION: NCT05796024.

What are the short- and long-term abdominal consequences of an omentectomy? A systematic review.

This review provides an overview regarding the abdominal effects of an omentectomy, with or without extra-peritoneal reconstructions. In general, reported complication rates were low. Short-term complications involved ileus, bowel stenosis, abdominal abscess and sepsis (range 0.0%-23%). Donor-site hernia was mainly reported as long-term complication (up to 32%) and negligible gastrointestinal complications were observed. However, the level of evidence and methodological quality are quite low with a maximum of 8.5 years follow-up.

NR2E3 loss disrupts photoreceptor cell maturation and fate in human organoid models of retinal development.

While dysfunction and death of light-detecting photoreceptor cells underlie most inherited retinal dystrophies, knowledge of the species-specific details of human rod and cone photoreceptor cell development remains limited. Here, we generated retinal organoids carrying retinal disease-causing variants in NR2E3, as well as isogenic and unrelated controls. Organoids were sampled using single-cell RNA sequencing (scRNA-Seq) across the developmental window encompassing photoreceptor specification, emergence, and maturation. Using scRNA-Seq data, we reconstruct the rod photoreceptor developmental lineage and identify a branch point unique to the disease state. We show that the rod-specific transcription factor NR2E3 is required for the proper expression of genes involved in phototransduction, including rhodopsin, which is absent in divergent rods. NR2E3-null rods additionally misexpress several cone-specific phototransduction genes. Using joint multimodal single-cell sequencing, we further identify putative regulatory sites where rod-specific factors act to steer photoreceptor cell development. Finally, we show that rod-committed photoreceptor cells form and persist throughout life in a patient with NR2E3-associated disease. Importantly, these findings are strikingly different from those observed in Nr2e3 rodent models. Together, these data provide a road map of human photoreceptor development and leverage patient induced pluripotent stem cells to define the specific roles of rod transcription factors in photoreceptor cell emergence and maturation in health and disease.

Bioelectrical impedance phase angle and nutritional status in children with intestinal failure on prolonged parenteral nutrition.

OBJECTIVE: To compare the phase angle (PhA) through bioelectrical impedance (BIA) of children with intestinal failure (IF) using prolonged parenteral nutrition (PN) followed by an Intestinal Rehabilitation Program, with a control group. METHODS: Children under 10 years of age with IF using prolonged PN for >60 days (study group) were included. The control group consisted of healthy children without chronic pathologies, matched by sex and age. Anthropometric parameters evaluated were: weight, height, weight/age z-score (W/A), height/age z-score (H/A), BMI, BMI/A z-score, arm circumference, triceps skinfold, subscapular skinfold, mid-arm muscle circumference. BIA parameters were resistance (R), reactance (Xc), and phase angle (PhA). RESULTS: Twenty-eight children were included in the study group, median (IQR) age was 11 (8-27) months, 53.6 % were male. In the control group, 28 children were included, median (IQR) age was 12.5 (8-24.7) months, 50 % were male. Children from the study group had W/A z-scores and H/A z-scores significantly lower than controls. There was no significant difference between PhA in the study group and controls, [median (IQR) 4.3° (3.8;4.6) vs 4.0° (3.8;5.4) respectively, p = 0.980]. Prematurity was significantly higher in the study group than in the controls, but there was no significant correlation between gestational age at birth and PhA of the children from the study group. CONCLUSION: Children with IF using prolonged PN showed lower W/A and H/A compared to the control group, but without significant difference between the PhA of children with IF compared to controls.

Horizontal transfer and the widespread presence of Galileo transposons in Drosophilidae (Insecta: Diptera).

Galileo is a transposon notoriously involved with inversions in Drosophila buzzatii by ectopic recombination. Although widespread in Drosophila, little is known about this transposon in other lineages of Drosophilidae. Here, the abundance of the canonical Galileo and its evolutionary history in Drosophilidae genomes was estimated and reconstructed across genera within its two subfamilies. Sequences of this transposon were masked in these genomes and their transposase sequences were recovered using BLASTn. Phylogenetic analyses were employed to reconstruct their evolutionary history and compare it to that of host genomes. Galileo was found in nearly all 163 species, however, only 37 harbored nearly complete transposase sequences. In the remaining, Galileo was found highly fragmented. Copies from related species were clustered, however horizontal transfer events were detected between the melanogaster and montium groups of Drosophila, and between the latter and the Lordiphosa genus. The similarity of sequences found in the virilis and willistoni groups of Drosophila was found to be a consequence of lineage sorting. Therefore, the evolution of Galileo is primarily marked by vertical transmission and long-term inactivation, mainly through the deletion of open reading frames. The latter has the potential to lead copies of this transposon to become miniature inverted-repeat transposable elements.

Reducing citrus effluent toxicity: Biological-electrochemical treatment with diamond anode.

One challenge of the citrus industry is the treatment and disposal of its effluents due to their high toxicity, substantial organic load, and consequent resistance to conventional biotechnological processes. This study introduces a novel approach, using electrochemical oxidation with a boron-doped diamond anode to efficiently remove organic compounds from biodegraded pulp wash (treated using the fungus Pleurotus sajor-caju.) The findings reveal that employing a current density of 20 mA cm-2 achieves notable results, including a 44.1% reduction in color, a 70.0% decrease in chemical oxygen demand, an 88.0% reduction in turbidity, and an impressive 99.7% removal of total organic carbon (TOC) after 6 h of electrolysis. The energy consumption was estimated at 2.93 kWh g-1 of removed TOC. This sequential biological-electrochemical procedure not only significantly reduced the mortality rate (85%) of Danio rerio embryos but also reduced the incidence of morphologically altered parameters. Regarding acute toxicity (LC50) of the residue, the process demonstrated a mortality reduction of 6.97% for D. rerio and a 40.88% lethality decrease for Lactuca sativa seeds. The substantial reduction in toxicity and organic load observed in this study highlights the potential applicability of combined biological and electrochemical treatments for real agroindustrial residues or their effluents.

Use of Medicinal Plants in the Process of Wound Healing: A Literature Review.

The literature on the use of medicinal plants in wound healing was comprehensively searched to obtain and assess the data. The data were procured via clinical studies that utilized medicinal plants and their compounds in vitro and in vivo for wound healing. This review collected data from electronic databases, including Google Scholar, PubMed, Science Direct, Web of Science, SciFinder, Thesis, and Scopus, using the search terms "natural products", "wound healing", and "natural compounds", along with the keywords "plants", "extracts", and "phytochemicals". Results from the last decade reveal a total of 62 families and 109 genera of medicinal plants, and their compounds have been studied experimentally both in vivo and in vitro and clinically found to effectively promote healing. This activity is related to the presence of secondary metabolites such as flavonoids, alkaloids, saponins, tannins, terpenoids, and phenolic compounds, which act at different stages through different mechanisms to exert anti-inflammatory, antimicrobial, and antioxidant effects, confirming that the use of medicinal plants could be an adequate alternative to current conventional practices for treating wounds.

Evaluation of the immunomodulatory effect of Bougainvillea xbuttiana (Var. Orange) on the cytokine production induced by Botrhops jararaca venom in macrophages / Evaluación del efecto inmunomodulador de Bougainvillea xbuttiana (var. naranja) sobre la producción de citoquinas de macrófagos inducida pelo veneno de Bothrops jararaca

To study the effect of 50% ethanol extract of Bougainvillea xbuttiana on the enzymatic activity, cell via bility and cytokine production provoked by the venom of Bothrops jararaca in macro - phages. Three assays were used to study the effects of B. xbuttiana extract on the damage pro - duced by B. jararaca : Enzymatic activity was detected by measuring the proteoly tic and phos - pholipase A2; macrophages cytotoxicity was determined by the MTT method; levels of cytokine were evaluated using ELISA and a biological assay. After treatment with 300 µg/mL B. xbuttiana extract for 30 min, the proteolytic and phospholipase A2 activities of the venom were reduced to 95 and 61%, respectively. In macrophages cultures treated with B. xbuttiana extract combined with venom, the production of TNF - α, IL - 6 and IFN - γ was reduced, whereas IL - 10 was potenti - ated. Our results support the potential effect of the B. xbuttiana extract as a complementary therapy against the toxicity caused by the venom of B . jararaca snakes

Estudiar el efecto del extracto etanólico al 50% de Bougainvillea xbuttiana sobre la actividad enzimática viabilidad celular y producci ón de citoquinas provocada por el veneno de Bothrops jararaca en macrófagos Se utilizaron tres ensayos para estudiar los efectos del extracto de B. xbuttiana sobre el daño producido por B. jararaca : Se detectó actividad enzimática mediante la medición del proteolítico y fosfolipasa A2; la citotoxicidad de los macrófagos se determinó por el método MTT; Los niveles de citoquinas se evaluaron utilizando ELISA y un ensayo biológico. Después del tratamiento con 300 µg/mL de extracto de B. xbuttiana durante 30 mi n, las actividades proteolíticas y de fosfolipasa A2 del veneno se redujeron a 95 y 61%, respectivamente. En cultivos de macrófagos tratados con extracto de B. xbuttiana combinado con veneno, la producción de TNF - α, IL - 6 e IFN - γ se redujeron, mientras que IL - 10 se potenció. Nuestros resultados apoyan el efecto potencial del extracto de B. xbuttiana como terapia complementaria frente a la toxicidad provocada por el veneno de B. jararaca .

A review of poly(ADP-ribose)polymerase-1 (PARP1) role and its inhibitors bearing pyrazole or indazole core for cancer therapy.

Cancer is a disease with a high mortality rate characterized by uncontrolled proliferation of abnormal cells. The hallmarks of cancer evidence the acquired cells characteristics that promote the growth of malignant tumours, including genomic instability and mutations, the ability to evade cellular death and the capacity of sustaining proliferative signalization. Poly(ADP-ribose) polymerase-1 (PARP1) is a protein that plays key roles in cellular regulation, namely in DNA damage repair and cell survival. The inhibition of PARP1 promotes cellular death in cells with homologous recombination deficiency, and therefore, the interest in PARP protein has been rising as a target for anticancer therapies. There are already some PARP1 inhibitors approved by Food and Drug Administration (FDA), such as Olaparib and Niraparib. The last compound presents in its structure an indazole core. In fact, pyrazoles and indazoles have been raising interest due to their various medicinal properties, namely, anticancer activity. Derivatives of these compounds have been studied as inhibitors of PARP1 and presented promising results. Therefore, this review aims to address the importance of PARP1 in cell regulation and its role in cancer. Moreover, it intends to report a comprehensive literature review of PARP1 inhibitors, containing the pyrazole and indazole scaffolds, published in the last fifteen years, focusing on structure-activity relationship aspects, thus providing important insights for the design of novel and more effective PARP1 inhibitors.

Ecotoxicity Assessment of Nanomaterials: Latest Advances and Prospects.

In the fast-evolving landscape of nanotechnology, the widespread applications of engineered nanomaterials (ENMs) have undoubtedly revolutionized various industries, ranging from healthcare and electronics to agriculture and environmental remediation [...].

Barriers to research in family medicine-interviews with Portuguese family physician researchers.

BACKGROUND: There is a need for a deeper understanding of the barriers to research in family medicine (FM) and to consider the perceptions and perspectives of professionals. Our study aims to provide a strategic view for research capacity building in FM. We included the perspective of family physician researchers (FPR) on the existing barriers to investigation in this context. OBJECTIVES: To understand and characterize the barriers to research in FM (personal and structural), from the perspective of Portuguese family physicians who are researchers. METHODS: A qualitative study, of phenomenological nature, was performed, through the conduction of semi-structured interviews with FPR, from 2019 to 2022. Data analysis and thematic coding were done on MAxQDA®, with inductive and deductive approaches, until data saturation was reached. RESULTS: A total of 12 family physicians/researchers were interviewed. Seven main themes were identified as barriers to research: time, professional valorization, funding, ethics committees, infrastructure, management/institutions, and participants. Each theme is divided into subthemes that make it possible to assess how a barrier can affect researchers in performing research activities. CONCLUSION: Our study highlights the identification of 7 main barriers. Structuring them into sub-themes not only improved the organization of our results but also provided robust support for the next phase, namely the application of a survey with the aim of gaining a deeper insight into the repercussions that these barriers to FPR have at a national level. This research is crucial to laying the foundations for a policy document that offers well-defined and tailored recommendations to address the barriers we have uncovered.

Using process-oriented model output to enhance machine learning-based soil organic carbon prediction in space and time.

Monitoring and modelling soil organic carbon (SOC) in space and time can help us to better understand soil carbon dynamics and is of key importance to support climate change research and policy. Although machine learning (ML) has attracted a lot of attention in the digital soil mapping (DSM) community for its powerful ability to learn from data and predict soil properties, such as SOC, it is better at capturing soil spatial variation than soil temporal dynamics. By contrast, process-oriented (PO) models benefit from mechanistic knowledge to express physiochemical and biological processes that govern SOC temporal changes. Therefore, integrating PO and ML models seems a promising means to represent physically plausible SOC dynamics while retaining the spatial prediction accuracy of ML models. In this study, a hybrid modelling framework was developed and tested for predicting topsoil SOC stock in space and time for a regional cropland area located in eastern China. In essence, the hybrid model uses predictions of the PO model in unsampled years as additional training data of the ML model, with a weighting parameter assigned to balance the importance of SOC values from the PO model and real measurements. The results indicated that temporal trends of SOC stock modelled by PO and ML models were largely different, while they were notably similar between the PO and hybrid models. Cross-validation showed that the hybrid model had the best performance (RMSE = 0.29 kg m-2), with a 19 % improvement compared with the ML model. We conclude that the proposed hybrid framework not only enhances space-time soil carbon mapping in terms of prediction accuracy and physical plausibility, it also provides insights for soil management and policy decisions in the face of future climate change and intensified human activities.