Polymer network comprised of steroidal rotors as promising storage material.

In this paper, we report a new generation of polymeric networks as potential functional material based on changes in molecular dynamics in the solid state. The material is obtained by free radical polymerization of a diacrylate derivative bearing a steroid (stator) and a 1,4-diethynyl-phenylene-d4 fragment (rotator). Polymer research using the PALS technique complements the knowledge about nanostructural changes occurring in the system in the temperature range -115 °C - +190 °C. It indicates the presence of two types of free nanovolumes in the system and the occurrence of phase transitions. The polymer is characterized using 1 H NMR, 2 H Solid Echo NMR, ATR-FTIR and Raman spectroscopies, thermal analysis, and porosimetry. It is proved that the applied procedure leads to the formation of a novel porous organic material containing multiple molecular rotors.

Polymer Network Comprised of Steroidal Rotors as a Promising Storage Material.

The front cover artwork is provided by Dr habil. Izabella Jastrzebska's group from the University of Bialystok, Poland. The image shows a polymeric network with molecular rotors (MR) as crosslinks. The MR rotation is slowed or inhibited when a molecule of stored gas is placed inside the polymer material. Read the full text of the Research Article at 10.1002/cphc.202300793.

Characterizing the Rise of Disseminated Gonococcal Infections in California, July 2020-July 2021.

BACKGROUND: California has experienced an increase in reported cases of disseminated gonococcal infection (DGI). Given significant morbidity associated with DGI and the ability of Neisseria gonorrhoeae to rapidly develop antibiotic resistance, characterization of these cases can inform diagnosis, management, and prevention of DGI. METHODS: As part of the public health response to increased reports of DGI, we used gonorrhea surveillance data reported to the California Department of Public Health to identify all DGI cases in a geographically-bound region. Standardized case report forms were used to collect epidemiologic risk factors and clinical information obtained from provider/laboratory reports, medical records, and patient interviews. RESULTS: From 1 July 2020 to 31 July 2021, we identified 149 DGI patients among 63 338 total gonorrhea infections, representing 0.24% of gonorrhea cases. Estimated incidence was 0.47 DGI cases per 100 000 person-years. Mean age of DGI patients was 40 years, and 75 (50%) were cisgender men, of whom only 13 were known to have male partners. Where reported, more than one-third (36%) used methamphetamine and nearly one-quarter (23%) experienced homelessness. Clinically, 61% lacked urogenital, pharyngeal, or rectal symptoms; 2 patients died in the hospital. Among 47 isolates from patients with antimicrobial susceptibility testing (AST) results available, all were susceptible to ceftriaxone and cefixime. CONCLUSIONS: Most DGI patients lacked urogenital symptoms and were not among populations for which routine gonorrhea screening is currently recommended. Expanding gonorrhea screening might prevent DGI. Cefixime is likely the best option if transitioning from parenteral to oral therapy when AST results are unavailable.

Dysfunction, oxidative stress markers, and cytokine expression in the placentae of mice experimentally infected with Neospora caninum.

Neosporosis is the major cause of abortion and reproductive failures in cattle, leading to significant economic losses. In this study, we evaluated the impact of Neospora caninum infection on oxidative stress (OS) markers and local cytokine mRNA expression at the placenta, as well as its effect on the progesterone (P4) serum levels and systemic cytokine profile in a pregnant mouse model. Infected pregnant mice (NC-1 group) showed increased percentages of fetal losses and IFN-γ serum levels, decreased serum progesterone, increased placental mRNA expression levels of both Th1-type (IFN-γ and TNF-α) and Th2-type (IL-4) cytokines, and inhibited expression of TGF-ß1 (Treg) compare to control dams (CONTROL group). In addition, lipid peroxidation and ROS were increased, whereas the antioxidant enzymes, superoxide dismutase (SOD), and catalase (CAT) activities were modified in the placentae of infected mice compared to control mice. These findings demonstrate that multiple factors, including placental OS, are involved in fetal losses associated with N. caninum infection in mice, thus OS contribution to the placental physiopathology of neosporosis in other hosts must not be ruled out.

BOPHY-Fullerene C60 Dyad as a Photosensitizer for Antimicrobial Photodynamic Therapy.

A novel BOPHY-fullerene C60 dyad (BP-C60 ) was designed as a heavy-atom-free photosensitizer (PS) with potential uses in photodynamic treatment and reactive oxygen species (ROS)-mediated applications. BP-C60 consists of a BOPHY fluorophore covalently attached to a C60 moiety through a pyrrolidine ring. The BOPHY core works as a visible-light-harvesting antenna, while the fullerene C60 subunit elicits the photodynamic action. This fluorophore-fullerene cycloadduct, obtained by a straightforward synthetic route, was fully characterized and compared with its individual counterparts. The restricted rotation around the single bond connecting the BOPHY and pyrrolidine moieties led to the formation of two atropisomers. Spectroscopic, electrochemical, and computational studies disclose an efficient photoinduced energy/electron transfer process from BOPHY to fullerene C60 . Photodynamic studies indicate that BP-C60 produces ROS by both photomechanisms (type I and type II). Moreover, the dyad exhibits higher ROS production efficiency than its individual constitutional components. Preliminary screening of photodynamic inactivation on bacteria models (Staphylococcus aureus and Escherichia coli) demonstrated the ability of this dyad to be used as a heavy-atom-free PS. To the best of our knowledge, this is the first time that not only a BOPHY-fullerene C60 dyad is reported, but also that a BOPHY derivative is applied to photoinactivate microorganisms. This study lays the foundations for the development of new BOPHY-based PSs with plausible applications in the medical field.

Effect of two preservation methods on the viability and enzyme production of a recombinant Komagataella phaffii (Pichia pastoris) strain.

The methylotrophic yeast Komagataella phaffii, previously known as Pichia pastoris, has been reported as a host for producing human recombinant lysosomal enzymes intended for enzyme replacement therapy. K. phaffii has advantages such as easy genetic handling, rapid growth, cost-effective mediums, and the ability to develop mammalian-like post-translational modifications. To maintain cell viability and enzyme activity over time, it is important to consider the bioprocess optimization and the proper selection and preservation of clones. In this study, we evaluated the effect of glycerol and skim milk in cryopreservation at -80 °C, as well as the use of skim milk or its combination with NaCl, disaccharides or sorbitol in freeze-drying on the cell viability and activity of a recombinant lysosomal enzyme (i.e., human ß-hexosaminidase-A) produced in K. phaffii GS115 strain. The results showed that cryopreservation with glycerol and skim milk, as well as freeze-drying using disaccharides and sorbitol with skim milk, maintained the viability above 80%. Although variations in enzyme activity among treatments were found, the use of disaccharides had a positive effect on the enzymatic activity levels. This is the first report of the evaluation of two suitable methods to preserve a recombinant K. phaffii strain, preventing the loss of viability and maintaining the activity of the recombinant protein.

The Potential of Selected Agri-Food Loss and Waste to Contribute to a Circular Economy: Applications in the Food, Cosmetic and Pharmaceutical Industries.

The food sector includes several large industries such as canned food, pasta, flour, frozen products, and beverages. Those industries transform agricultural raw materials into added-value products. The fruit and vegetable industry is the largest and fastest-growing segment of the world agricultural production market, which commercialize various products such as juices, jams, and dehydrated products, followed by the cereal industry products such as chocolate, beer, and vegetable oils are produced. Similarly, the root and tuber industry produces flours and starches essential for the daily diet due to their high carbohydrate content. However, the processing of these foods generates a large amount of waste several times improperly disposed of in landfills. Due to the increase in the world's population, the indiscriminate use of natural resources generates waste and food supply limitations due to the scarcity of resources, increasing hunger worldwide. The circular economy offers various tools for raising awareness for the recovery of waste, one of the best alternatives to mitigate the excessive consumption of raw materials and reduce waste. The loss and waste of food as a raw material offers bioactive compounds, enzymes, and nutrients that add value to the food cosmetic and pharmaceutical industries. This paper systematically reviewed literature with different food loss and waste by-products as animal feed, cosmetic, and pharmaceutical products that strongly contribute to the paradigm shift to a circular economy. Additionally, this review compiles studies related to the integral recovery of by-products from the processing of fruits, vegetables, tubers, cereals, and legumes from the food industry, with the potential in SARS-CoV-2 disease and bacterial diseases treatment.

Recovery of Banana Waste-Loss from Production and Processing: A Contribution to a Circular Economy.

Banana is a fruit grown mainly in tropical countries of the world. After harvest, almost 60% of banana biomass is left as waste. Worldwide, about 114.08 million metric tons of banana waste-loss are produced, leading to environmental problems such as the excessive emission of greenhouse gases. These wastes contain a high content of paramount industrial importance, such as cellulose, hemicellulose and natural fibers that various processes can modify, such as bacterial fermentation and anaerobic degradation, to obtain bioplastics, organic fertilizers and biofuels such as ethanol, biogas, hydrogen and biodiesel. In addition, they can be used in wastewater treatment methods by producing low-cost biofilters and obtaining activated carbon from rachis and banana peel. Furthermore, nanometric fibers commonly used in nanotechnology applications and silver nanoparticles useful in therapeutic cancer treatments, can be produced from banana pseudostems. The review aims to demonstrate the contribution of the recovery of banana production waste-loss towards a circular economy that would boost the economy of Latin America and many other countries of emerging economies.

Synthesis of Chitosan Beads Incorporating Graphene Oxide/Titanium Dioxide Nanoparticles for In Vivo Studies.

Scaffold development for cell regeneration has increased in recent years due to the high demand for more efficient and biocompatible materials. Nanomaterials have become a critical alternative for mechanical, thermal, and antimicrobial property reinforcement in several biopolymers. In this work, four different chitosan (CS) bead formulations crosslinked with glutaraldehyde (GLA), including titanium dioxide nanoparticles (TiO2), and graphene oxide (GO) nanosheets, were prepared with potential biomedical applications in mind. The characterization of by FTIR spectroscopy, X-ray photoelectron spectroscopy (XRD), thermogravimetric analysis (TGA), energy-dispersive spectroscopy (EDS) and scanning electron microscopy (SEM), demonstrated an efficient preparation of nanocomposites, with nanoparticles well-dispersed in the polymer matrix. In vivo, subdermal implantation of the beads in Wistar rat's tissue for 90 days showed a proper and complete healing process without any allergenic response to any of the formulations. Masson's trichrome staining of the histological implanted tissues demonstrated the presence of a group of macrophage/histiocyte compatible cells, which indicates a high degree of biocompatibility of the beads. The materials were very stable under body conditions as the morphometry studies showed, but with low resorption percentages. These high stability beads could be used as biocompatible, resistant materials for long-term applications. The results presented in this study show the enormous potential of these chitosan nanocomposites in cell regeneration and biomedical applications.

Plant Serine Protease Inhibitors: Biotechnology Application in Agriculture and Molecular Farming.

The serine protease inhibitors (SPIs) are widely distributed in living organisms like bacteria, fungi, plants, and humans. The main function of SPIs as protease enzymes is to regulate the proteolytic activity. In plants, most of the studies of SPIs have been focused on their physiological role. The initial studies carried out in plants showed that SPIs participate in the regulation of endogenous proteolytic processes, as the regulation of proteases in seeds. Besides, it was observed that SPIs also participate in the regulation of cell death during plant development and senescence. On the other hand, plant SPIs have an important role in plant defense against pests and phytopathogenic microorganisms. In the last 20 years, several transgenic plants over-expressing SPIs have been produced and tested in order to achieve the increase of the resistance against pathogenic insects. Finally, in molecular farming, SPIs have been employed to minimize the proteolysis of recombinant proteins expressed in plants. The present review discusses the potential biotechnological applications of plant SPIs in the agriculture field.

Advances in the Development of Pharmacological Chaperones for the Mucopolysaccharidoses.

The mucopolysaccharidoses (MPS) are a group of 11 lysosomal storage diseases (LSDs) produced by mutations in the enzymes involved in the lysosomal catabolism of glycosaminoglycans. Most of the mutations affecting these enzymes may lead to changes in processing, folding, glycosylation, pH stability, protein aggregation, and defective transport to the lysosomes. It this sense, it has been proposed that the use of small molecules, called pharmacological chaperones (PCs), can restore the folding, trafficking, and biological activity of mutated enzymes. PCs have the advantages of wide tissue distribution, potential oral administration, lower production cost, and fewer issues of immunogenicity than enzyme replacement therapy. In this paper, we will review the advances in the identification and characterization of PCs for the MPS. These molecules have been described for MPS II, IVA, and IVB, showing a mutation-dependent enhancement of the mutated enzymes. Although the results show the potential of this strategy, further studies should focus in the development of disease-specific cellular models that allow a proper screening and evaluation of PCs. In addition, in vivo evaluation, both pre-clinical and clinical, should be performed, before they can become a real therapeutic strategy for the treatment of MPS patients.

An ambipolar PEDOT-perfluorinated porphyrin electropolymer: application as an active material in energy storage systems.

The development of functional organic materials is crucial for the advancement of various fields, such as optoelectronics, energy storage, sensing, and biomedicine. In this context, we successfully prepared a stable ambipolar perfluoroporphyrin-based polymeric film by electrochemical synthesis. Our strategy involved the synthesis of a novel tetra-pentafluorophenyl porphyrin covalently linked to four 3,4-ethylenedioxythiophene (EDOT) moieties. The resulting monomer, EDOT-TPPF16, was obtained through a straightforward synthetic approach with a good overall yield. The unique molecular structure of EDOT-TPPF16 serves a dual function, with EDOT moieties allowing electropolymerization for polymeric film formation, while the electron-acceptor porphyrin core enables electrochemical reduction and electron transport. The electrochemical polymerization permits the polymer (PEDOT-TPPF16) synthesis and film formation in a reproducible and controllable manner in one step at room temperature. Spectroelectrochemical experiments confirmed that the porphyrin retained its optoelectronic properties within the polymeric matrix after the electrochemical polymerization. The obtained polymeric material exhibited stable redox capabilities. Current charge-discharge cycles and electrochemical impedance spectroscopy of the electrochemically generated organic film demonstrated that the polymer could be applied as a promising active material in the development of supercapacitor energy storage devices.

Sea cucumber (Holothuria glaberrima) intestinal microbiome dataset from Puerto Rico, generated by shotgun sequencing.

The sea cucumber (H. glaberrima) is a species found in the shallow waters near coral reefs and seagrass beds in Puerto Rico. To characterize the microbial taxonomic composition and functional profiles present in the sea cucumber, total DNA was obtained from their intestinal system, fosmid libraries constructed, and subsequent sequencing was performed. The diversity profile displayed that the most predominant domain was Bacteria (76.56 %), followed by Viruses (23.24 %) and Archaea (0.04 %). Within the 11 phyla identified, the most abundant was Proteobacteria (73.16 %), followed by Terrabacteria group (3.20 %) and Fibrobacterota, Chlorobiota, Bacteroidota (FCB) superphylum (1.02 %). The most abundant species were Porvidencia rettgeri (21.77 %), Pseudomonas stutzeri (14.78 %), and Alcaligenes faecalis (5.00 %). The functional profile revealed that the most abundant functions are related to transporters, MISC (miscellaneous information systems), organic nitrogen, energy, and carbon utilization. The data collected in this project on the diversity and functional profiles of the intestinal system of the H. glaberrima provided a detailed view of its microbial ecology. These findings may motivate comparative studies aimed at understanding the role of the microbiome in intestinal regeneration.

Immunogenicity, safety and dual DIVA-like character of a recombinant candidate vaccine against neosporosis in cattle.

Neosporosis is the major infectious cause of abortion and reproductive losses in cattle worldwide; however, there are no available vaccines or drugs to control this disease. Recently, a dual (positive and negative) DIVA-like (Differentiation of Infected from Vaccinated Animals) vaccine was evaluated in a pregnant mouse model of neosporosis, showing promising immunogenic and protective results. The current report aimed to study the safety, the dose-dependent immunogenicity and the dual DIVA-like character of a recombinant subunit vaccine composed of the major surface antigen from Neospora caninum (rNcSAG1) and the carrier/adjuvant Heat shock protein 81.2 from Arabidopsis thaliana (rAtHsp81.2) in cattle. Healthy heifers were separated and assigned to experimental groups A-F and subcutaneously immunized with 2 doses of vaccine formulations 30 days apart as follows: A (n = 4): 50 µg rNcSAG1 + 150 µg rAtHsp81.2; B (n = 4): 200 µg rNcSAG1 + 600 µg rAtHsp81.2; C (n = 4): 500 µg rNcSAG1 + 1,500 µg rAtHsp81.2; D (n = 3): 150 µg rAtHsp81.2; E (n = 3):1,500 µg rAtHsp81.2, and F (n = 3) 2 ml of sterile PBS. The immunization of heifers with the different vaccine or adjuvant doses (groups A-E) was demonstrated to be safe and did not modify the mean value of the evaluated serum biomarkers of metabolic function (GOT/ASP, GPT/ALT, UREA, Glucose and total proteins). The kinetics and magnitude of the immune responses were dose-dependent. The higher dose of the vaccine formulation (group C) stimulated a broad and potent humoral and cellular immune response, characterized by an IgG1/IgG2 isotype profile and IFN-γ secretion. In addition, this was the first time that dual DIVA-like character of a vaccine against neosporosis was demonstrated, allowing us to differentiate vaccinated from infected heifers by two different DIVA compliant test approaches. These results encourage us to evaluate its protective efficacy in infected pregnant cattle in the future.

Photoinactivation of Planktonic Cells, Pseudohyphae, and Biofilms of Candida albicans Sensitized by a Free-Base Chlorin and Its Metal Complexes with Zn(II) and Pd(II).

Invasive candidiasis is an important cause of morbidity and mortality, and its occurrence is increasing due to the growing complexity of patients. In particular, Candida albicans exhibits several virulence factors that facilitate yeast colonization in humans. In this sense, the photodynamic inactivation of yeasts is a promising new alternative to eliminate fungal infections. Herein, the photodynamic activity sensitized by a free-base chlorin (TPCF16) and its complexes with Zn(II) (ZnTPCF16) and Pd(II) (PdTPCF16) was investigated in order to eliminate C. albicans under different forms of cell cultures. A decrease in cell survival of more than 5 log was found in planktonic cells incubated with 5 µM TPCF16 or ZnTPCF16 upon 15 min of white-light irradiation. The mechanism of action mainly involved a type II pathway in the inactivation of C. albicans cells. In addition, the photodynamic action induced by these chlorins was able to suppress the growth of C. albicans in a culture medium. These photosensitizers were also effective to photoinactivate C. albicans pseudohyphae suspended in PBS. Furthermore, the biofilms of C. albicans that incorporated the chlorins during the proliferation stage were completely eradicated using 5 µM TPCF16 or ZnTPCF16 after 60 min of light irradiation. The studies indicated that these chlorins are effective photosensitizing agents to eliminate C. albicans as planktonic cells, pseudohyphae, and biofilms.

Tuning the Molecular Structure of Corroles to Enhance the Antibacterial Photosensitizing Activity.

The increase in the antibiotic resistance of bacteria is a serious threat to public health. Photodynamic inactivation (PDI) of micro-organisms is a reliable antimicrobial therapy to treat a broad spectrum of complex infections. The development of new photosensitizers with suitable properties is a key factor to consider in the optimization of this therapy. In this sense, four corroles were designed to study how the number of cationic centers can influence the efficacy of antibacterial photodynamic treatments. First, 5,10,15-Tris(pentafluorophenyl)corrole (Co) and 5,15-bis(pentafluorophenyl)-10-(4-(trifluoromethyl)phenyl)corrole (Co-CF3) were synthesized, and then derivatized by nucleophilic aromatic substitution with 2-dimethylaminoethanol and 2-(dimethylamino)ethylamine, obtaining corroles Co-3NMe2 and Co-CF3-2NMe2, respectively. The straightforward synthetic strategy gave rise to macrocycles with different numbers of tertiary amines that can acquire positive charges in an aqueous medium by protonation at physiological pH. Spectroscopic and photodynamic studies demonstrated that their properties as chromophores and photosensitizers were unaffected, regardless of the substituent groups on the periphery. All tetrapyrrolic macrocycles were able to produce reactive oxygen species (ROS) by both photodynamic mechanisms. Uptake experiments, the level of ROS produced in vitro, and PDI treatments mediated by these compounds were assessed against clinical strains: methicillin-resistant Staphylococcus aureus and Klebsiella pneumoniae. In vitro experiments indicated that the peripheral substitution significantly affected the uptake of the photosensitizers by microbes and, consequently, the photoinactivation performance. Co-3NMe2 was the most effective in killing both Gram-positive and Gram-negative bacteria (inactivation > 99.99%). This work lays the foundations for the development of new corrole derivatives having pH-activable cationic groups and with plausible applications as effective broad-spectrum antimicrobial photosensitizers.

Chitosan-Polyvinyl Alcohol Nanocomposites for Regenerative Therapy.

Tissue accidents provide numerous pathways for pathogens to invade and flourish, causing additional harm to the host tissue while impeding its natural healing and regeneration. Essential oils (EOs) exhibit rapid and effective antimicrobial properties without promoting bacterial resistance. Clove oils (CEO) demonstrate robust antimicrobial activity against different pathogens. Chitosan (CS) is a natural, partially deacetylated polyamine widely recognized for its vast antimicrobial capacity. In this study, we present the synthesis of four membrane formulations utilizing CS, polyvinyl alcohol (PVA), and glycerol (Gly) incorporated with CEO and nanobioglass (n-BGs) for applications in subdermal tissue regeneration. Our analysis of the membranes' thermal stability and chemical composition provided strong evidence for successfully blending polymers with the entrapment of the essential oil. The incorporation of the CEO in the composite was evidenced by the increase in the intensity of the band of C-O-C in the FTIR; furthermore, the increase in diffraction peaks, as well as the broadening, provide evidence that the introduction of CEO perturbed the crystal structure. The morphological examination conducted using scanning electron microscopy (SEM) revealed that the incorporation of CEO resulted in smooth surfaces, in contrast to the porous morphologies observed with the n-BGs. A histological examination of the implanted membranes demonstrated their biocompatibility and biodegradability, particularly after a 60-day implantation period. The degradation process of more extensive membranes involved connective tissue composed of type III collagen fibers, blood vessels, and inflammatory cells, which supported the reabsorption of the composite membranes, evidencing the material's biocompatibility.

AMG 837: a potent, orally bioavailable GPR40 agonist.

The discovery that certain long chain fatty acids potentiate glucose stimulated insulin secretion through the previously orphan receptor GPR40 sparked interest in GPR40 agonists as potential antidiabetic agents. Optimization of a series of ß-substituted phenylpropanoic acids led to the identification of (S)-3-(4-((4'-(trifluoromethyl)biphenyl-3-yl)methoxy)phenyl)hex-4-ynoic acid (AMG 837) as a potent GPR40 agonist with a superior pharmacokinetic profile and robust glucose-dependent stimulation of insulin secretion in rodents.

Effect of surfactant content on rheological, thermal, morphological and surface properties of thermoplastic starch (TPS) and polylactic acid (PLA) blends.

Miscibility in biopolymeric blends is a critical process that requires evaluation of the effect of surfactants or coupling agents under conditions similar to processing. Different mixtures in the molten state of plasticized starch and polylactic acid in the presence of a surfactant (Tween 20) at different concentrations were studied. This allowed knowing the rheological, thermal and surface behavior of the mixtures. The results of the dynamic rheological analysis showed increases in viscosity in the presence of the surfactant, in which strong interactions were produced at high shear rates that reflect possible crosslinking between the polymer chains, in addition to intermolecular interactions that were evidenced in the infrared spectrum. Likewise, the storage and loss modulus showed transitions mainly from viscous to elastic typical for thermoplastics. The thermogravimetric analysis did not show significant changes between the mixtures. However, the calorimetric analysis showed changes in the crystallinity of the mixtures, the tensoactive promotes greater freedom of movement and rearrangements in the microstructure with decrease of interface between polymers, and less compaction of the material induced by the emulsion. Analysis derived from biopolymeric films against contact with water shows significant changes. Interaction with water in short times (in the order of minutes) according to the sessile drop technique, favors hydrophilicity by increasing the concentration of Tween 20. However, interaction with water for prolonged times (in the order of hours), shows that the absorption reaches saturation in samples a stabilization in the absorption is observed. The results demonstrate that the miscibility of PLA in AS was achieved in the presence of the tween, under conventional processing conditions. The stability of the different formulations allows the production of films for packaging and biomedical applications.

Neosporosis in sheep: A systematic review and meta-analysis of global seroprevalence and related risk factors.

Neosporosis is recognized as the main cause of abortions in cattle worldwide and there is an increasing concern about its role in ovine reproductive losses; however, epidemiological studies regarding neosporosis in sheep are still limited. This meta-analysis aimed to estimate the global pooled seroprevalence and associated risk factors of ovine neosporosis. In the current report, a comprehensive strategy of search and data collection from 7 worldwide databases was performed. A final set of 73 studies (80 datasets) published from 2000 to 2021 were selected based on inclusion criteria, comprising data on 35,740 sheep (corresponding to 37,565 evaluated samples) from 30 countries worldwide. The global pooled seroprevalence of Neospora caninum infection in sheep estimated by the random-effects model was 13% (95% CI, 10-15) and showed high heterogeneity (Q = 5147.15, I2 = 98%, p< 0.001). Furthermore, by meta-analyses of subgroups it was demonstrated for the first time that seroprevalence significantly varied between continents (highest in Africa; 20%, 95% CI, 4-44), WHO regions (highest in African Region; 42%, 95% CI, 36-48), countries (highest in Colombia; 79%, 95% CI, 61-92%) and diagnostic methods (highest by IFAT; 17%, 95% CI, 12-23). Meta-regression indicated significant increasing trends in the prevalence of ovine neosporosis with decrease in geographical latitude (coefficient = -0.013; p<0.001), whereas longitude did not influence it (coefficient = -0.001; p=0.365). Regarding associated risk factors, older sheep were more likely to be infected with N. caninum than younger ones (OR 1.42; 95% CI 1.08-1.87), and sheep bred under intensive or semi-intensive systems resulted less susceptible to be seropositive than those bred under extensive system (OR 0.65; 95% CI 0.42-0.99 and OR 0.74; 95% CI 0.62-0.89, respectively). Conversely, no apparent association was found between seroprevalence and other variables, such as sex (OR 1.06; 95% CI 0.9-1.24), the presence of dogs on the farm (OR 1.15; 95% CI 0.63-2.12) or the presence of abortion (OR 1.80; 95% CI 0.87-3.74). In conclusion, the seroprevalence of ovine neosporosis is widely and heterogeneously distributed throughout the world, and it is negatively associated with increasing geographical latitude. In addition, age and extensive production system represent risk factors, which suggest that the horizontal transmission route is relevant for this host species. It is recommended to pay more attention to this disease and emphasize the global need for more indexed studies concerning the seroprevalence and risk factors of ovine neosporosis to better understand the epidemiology of this coccidian infection.