V-ToCs (Venom toxin clustering): A tool for the investigation of sequence and structure similarities in snake venom toxins.

Recently, there has been a major push toward the development of next-generation treatments against snakebite envenoming. However, unlike current antivenoms that rely on animal-derived polyclonal antibodies, most of these novel approaches are reliant on an in-depth understanding of the over 2,000 known snake venom toxins. Indeed, by identifying similarities (i.e., conserved epitopes) across these different toxins, it is possible to design cross-reactive treatments, such as broadly-neutralising antibodies, that target these similarities. Therefore, in this project, we built an automated pipeline that generates sequence and structural distance matrices and homology trees across all available snake venom toxin sequences and structures. To facilitate analysis, we also developed a user-friendly and high-throughput visualisation tool, coined "Venom TOxin CluStering" (V-ToCs). This tool allows researchers to easily investigate sequence and structure patterns in SVTs for a wide array of purposes, such as elucidating toxin evolution, and will also hopefully help guide the discovery and development of increasingly broadly-neutralising antivenoms in the near future.

Quasi-steady aerodynamic theory under-predicts glide performance in flying snakes.

Flying snakes (genus Chrysopelea) glide without the use of wings. Instead, they splay their ribs and undulate through the air. A snake's ability to glide depends on how well its morphing wing-body produces lift and drag forces. However, previous kinematics experiments under-resolved the body, making it impossible to estimate the aerodynamic load on the animal or to quantify the different wing configurations throughout the glide. Here, we present new kinematic analyses of a previous glide experiment, and use the results to test a theoretical model of flying snake aerodynamics using previously measured lift and drag coefficients to estimate the aerodynamic forces. This analysis is enabled by new measurements of the center of mass motion based on experimental data. We find that quasi-steady aerodynamic theory under-predicts lift by 35% and over-predicts drag by 40%. We also quantify the relative spacing of the body as the snake translates through the air. In steep glides, the body is generally not positioned to experience tandem effects from wake interaction during the glide. These results suggest that unsteady 3D effects, with appreciable force enhancement, are important for snake flight. Future work can use the kinematics data presented herein to form test conditions for physical modeling, as well as computational studies to understand unsteady fluid dynamic effects on snake flight.

Pilot-scale evaluation of a dynamic body-feed filtration system for primary clarification of snake antivenoms produced by the caprylic acid method.

The performance of dynamic body-feed filtration (DBF) in the removal of bulky solids produced during the manufacturing of snake antivenoms using the caprylic acid method was evaluated. For this purpose, diatomites with different filterability properties were compared in a bench-scale study to assess their effectiveness in removing the precipitated material formed after the addition of caprylic acid to equine hyperimmune plasma. C1000 diatomite at a concentration of 90 g/L of precipitated plasma showed the best performance. Then, the process was scaled up to three batches of 50 L of hyperimmune horse plasma. At this pilot scale, 108 ± 4% of the immunoglobulins present following plasma precipitation were recovered after DBF. The antivenoms generated using this procedure met quality specifications. When compared to open filtration systems commonly used at an industrial scale by many antivenom manufacturers, DBF has a similar yield and produces filtrates with comparable physicochemical characteristics. However, DBF ensures the microbiological quality of the primary clarification in a way that open systems cannot. This is because: 1) DBF is performed in a single-use closed device of depth filters which prevents microbial contamination, and 2) DBF removes bulky material in few minutes instead of the more than 24 h needed by open filtration systems, thus reducing the risk of contamination. It was concluded that DBF is a cost-effective, easily validated, and GMP-compliant alternative for primary clarification following caprylic acid precipitation of plasma in snake antivenom production.

Exploring Top-Down Mass Spectrometric Approaches To Probe Forest Cobra (Naja melanoleuca) Venom Proteoforms.

Snake venoms are comprised of bioactive proteins and peptides that facilitate severe snakebite envenomation symptoms. A comprehensive understanding of venom compositions and the subtle heterogeneity therein is important. While bottom-up proteomics has been the well-established approach to catalogue venom compositions, top-down proteomics has emerged as a complementary strategy to characterize venom heterogeneity at the intact protein level. However, top-down proteomics has not been as widely implemented in the snake venom field as bottom-up proteomics, with various emerging top-down methods yet to be developed for venom systems. Here, we have explored three main top-down mass spectrometry methodologies in a proof-of-concept study to characterize selected three-finger toxin and phospholipase A2 proteoforms from the forest cobra (Naja melanoleuca) venom. We demonstrated the utility of a data-independent acquisition mode "MSE" for untargeted fragmentation on a chromatographic time scale and its improvement in protein sequence coverage compared to conventional targeted tandem mass spectrometry analysis. We also showed that protein identification can be further improved using a hybrid fragmentation approach, combining electron-capture dissociation and collision-induced dissociation. Lastly, we reported the promising application of multifunctional cyclic ion mobility separation and post-ion mobility fragmentation on snake venom proteins for the first time.

New perspective for pathomechanism and clinical applications of animal toxins: Programmed cell death.

Various animal toxins pose a significant threat to human safety, necessitating urgent attention to their treatment and research. The clinical potential of programmed cell death (PCD) is widely regarded as a target for envenomation, given its crucial role in regulating physiological and pathophysiological processes. Current research on animal toxins examines their specific components in pathomechanisms and injuries, as well as their clinical applications. This review explores the relationship between various toxins and several types of PCD, such as apoptosis, necroptosis, autophagy, ferroptosis, and pyroptosis, to provide a reference for future understanding of the pathophysiology of toxins and the development of their potential clinical value.

Behavior and Activity Patterns of the Critically Endangered Mangshan Pit Viper (Protobothrops mangshanensis) Determined Using Remote Monitoring.

This study focuses on understanding the behavior and activity patterns of the critically endangered Protobothrops mangshanensis in China in order to better provide scientific data for upcoming artificial breeding and propagation efforts. We conducted a long-term observation of 15 Mangshan pit vipers at different sites in Hunan Province during the summer and autumn of 2021. Our methods involved analyzing the influence of environmental factors such as temperature, relative humidity, and light condition on the snakes' day and night activity and behaviors. The results revealed that the wild behaviors of Protobothrops mangshanensis include resting, sunbathing, crawling, and exploring, with distinct rhythms in their diel behavior. The snakes' diel activity exhibits three peak periods which may be related to food activity and sunbathing. This study also highlights the complex interplay of environmental factors on the activity of Protobothrops mangshanensis. Relative humidity was identified as a critical factor accounting for the difference in activity between observation groups. There was little inter-individual variation among the 15 Protobothrops mangshanensis, even though these snakes used terrestrial and arboreal habitats under different environmental conditions. These findings enhance our understanding of Protobothrops mangshanensis behavior and provide a basis for effective conservation measures for this rare and critically endangered species.

A deep learning-based combination method of spatio-temporal prediction for regional mining surface subsidence.

In coal mining areas, surface subsidence poses significant risks to human life and property. Fortunately, surface subsidence caused by coal mining can be monitored and predicted by using various methods, e.g., probability integral method and deep learning (DL) methods. Although DL methods show promise in predicting subsidence, they often lack accuracy due to insufficient consideration of spatial correlation and temporal nonlinearity. Considering this issue, we propose a novel DL-based approach for predicting mining surface subsidence. Our method employs K-means clustering to partition spatial data, allowing the application of a gate recurrent unit (GRU) model to capture nonlinear relationships in subsidence time series within each partition. Optimization using snake optimization (SO) further enhances model accuracy globally. Validation shows our method outperforms traditional Long Short-Term Memory (LSTM) and GRU models, achieving 99.1% of sample pixels with less than 8 mm absolute error.

Evaluation of the International Society on Thrombosis and Haemostasis definition of major bleeding in Arizona rattlesnake bites.

INTRODUCTION: In 2023, a group of experts proposed that a definition of major bleeding in pharmaceutically anticoagulated patients be used in all snakebite trials. This includes bleeding that results in death, is life-threatening, causes chronic sequelae, or consumes major healthcare resources, including bleeding into a major area or hemoglobin concentration decrease ≥20 g/L. We hypothesized that a decline in hemoglobin concentration ≥20 g/L is common but rarely clinically significant in our population of Arizona rattlesnake bite patients. METHODS: Poison center records of rattlesnake bites in humans from 2018 through 2022 were retrospectively reviewed and assessed for major bleeding by the above criteria. RESULTS: Four hundred and eighty-one patients met the inclusion criteria, of whom 265 (55.1%) had a hemoglobin concentration decrease ≥20 g/L. No patients died, and there was no evidence of bleeding into a critical organ. Three patients (1.1%) received blood transfusions. A decrease in hemoglobin concentration ≥20 g/L was 100% sensitive for identifying the major bleeding-associated outcomes; however, specificity was only 45.2%. Measures of healthcare utilization and chronic sequelae were somewhat higher in patients with a decrease in hemoglobin concentration ≥20 g/L. DISCUSSION: Laboratory manifestations of hemotoxicity were common in this population, but hemorrhage was rare. While over half of patients met the major bleeding criterion of a decline in hemoglobin concentration ≥20 g/L, only 1.1% had bleeding that was potentially life-threatening as measured by receipt of a red blood cell transfusion. None died or had bleeding into a critical area. While nonspecific for major bleeding, a drop in hemoglobin concentration correlated with worse envenomation severity: these patients received more vials of antivenom, had a higher medical bill, a longer hospital stay, and were less likely to report full recovery at 90 days. CONCLUSIONS: A decrease in hemoglobin concentration ≥20 g/L should not be used as evidence of major bleeding for Arizona rattlesnake envenomation studies, but it may have a role as an indirect marker of envenomation severity.

Development and characterization of nanobody against envenomation by Naja naja oxiana.

Snakebites are considered a significant health issue. Current antivenoms contain polyclonal antibodies, which vary in their specificity against different venom components. Development and characterization of next generation antivenoms including nanobodies against Naja naja oxiana was the main aim of this study. Crude venom was injected into the Sephadex G50 filtration gel chromatography column and then toxic fractions were obtained. Then the corresponding fraction was injected into the HPLC column and the toxic peaks were identified. N. naja oxiana venom was injected into a camel and specific nanobodies screening was performed against the toxic peak using phage display technique. The obtained results showed that among the 12 clones obtained, N24 nanobody was capable of neutralizing P1, the most toxic peak obtained from HPLC chromatography. The molecular weight of P1 was measured with a mass spectrometer and was found to be about seven kDa. The results of the neutralization test of crude N. naja oxiana venom with N24 nanobody showed that 250 µg of recombinant nanobody could neutralize the toxic effects of 20 µg equivalent to LD50 × 10 of crude venom in mice. The findings indicate the potential of the developed nanobody to serve as a novel antivenom therapy.

Faith healing: the threat of "Surucucu" and the local cure of Amazon floodplain dwellers.

BACKGROUND: Snakebites are considered a neglected tropical disease responsible for many accidents, some fatal, and are related to poverty. The Brazilian Amazon has the highest incidence of snakebites per inhabitant, with the state of Pará having the most reported cases. For those who have difficult access to hospitals and pharmacies, this issue is even more urgent. METHODS: In this research, we worked together with the population of five riverine communities in Aritapera (Santarém-PA), a fluvial island located in the Lower Amazon floodplain (várzeas), in order to identify the species of venomous snakes and create a record of snakebites in the region and treatments carried out. RESULTS: Dwellers reported a high frequency of encounters throughout the year and mentioned five venomous ethnospecies, although we identified only Bothrops atrox. Approximately 28.7% of the participants had already been bitten, and in 15.8% of the interviews, they mentioned deaths from snakebites. The treatments varied between hospitalization (42.8%), home treatments (23.8%), both together (25.4%) and healers (7.9%). There were cases where no treatment, or just religious treatment, was performed. In general, no serious sequelae were reported. Although home treatments were more common in the past, many people maintained the practice of using them before going to the hospital. Among the most used are Pau X and the fat of the Amazon River Dolphin. The latter appears to be a recent discovery by locals and is considered very efficient both for humans and animals. CONCLUSION: Difficult access to health centers, a lack of energy to store antivenom and a high rate of encounters with snake place Aritapera dwellers in a vulnerable situation regarding snakebite accidents. In this context, they discovered treatments that improved their well-being until hospitalization. As the Amazon River dolphin is an endangered species, the use of its fat requires attention. In this sense, the dissemination of this knowledge is important to encourage studies that investigate which properties of this fat act as counterpoisons. By discovering substitutes that can be incorporated in other rural and remote communities, an economic and ecologically viable option for the health of residents can be promoted, in addition to valuing traditional knowledge.

First report of albinism for Achalinussheni (Serpentes, Xenodermidae), with extended diagnosis of the species.

Albinism is an uncommon phenomenon and inherited condition in animals characterized by a partial or complete lack of melanin. The family Xenodermidae Gray, 1849, is a group of caenophidian snakes widely distributed in South, East, and Southeast Asia, including five recognized genera and 36 species. However, there are currently no reports of albinism in any species in Xenodermidae. Achalinussheni Ma, Xu, Qi, Wang, Tang, Huang & Jiang, 2023 was first described based on five male specimens from Loudi City and Nanyue District, Hunan Province, China. At the time, there were no descriptions on female individuals. In this study, we report in detail a collected albinistic specimen of A.sheni, which is the first discovery of wild albinism in the family Xenodermidae. We also provide photographs and descriptions of the first three female specimens of A.sheni and extend the diagnosis of this species.

The OROCHI (Observational Research of Clinical Course After mamusHI) Study: A Prospective, Observational, Multicenter Study on the Efficacy of Mamushi (Gloydius blomhoffii) Antivenom Serum.

BACKGROUND: Evidence on the efficacy of mamushi antivenom serum is limited. OBJECTIVE: To investigate the effectiveness of mamushi (Gloydius blomhoffii) antivenom serum. METHODS: The Observational Research Of the Clinical course after mamusHI bite (OROCHI) study was a prospective multicenter study conducted at 24 hospitals in Japan. Patients hospitalized due to mamushi bite were registered. The primary endpoint was the length of hospital stay. Secondary endpoints were adverse effects, pain (numerical rating scale), and grade of swelling. We performed a cohort analysis to compare outcomes between patients treated with mamushi antivenom serum (antivenom group) and those who were not treated with the serum (no-antivenom group). RESULTS: Overall, 106 patients were registered across 18 hospitals between April 22, 2020, and October 31, 2022. Of these, 92 were eligible for the analyses, with 53 and 39 in the antivenom and no-antivenom groups. The median (interquartile) length of hospital stay was not significantly different between the antivenom and no-antivenom groups (5 (3-6) days vs. 3 (1-8) days, P = 0.369). In multivariable analysis, the adjusted odds ratio for a hospital stay of >4 days was 1.331 in patients treated with mamushi antivenom serum (95% confidence interval (CI) = 0.744‒2.015, P = 0.574) and 6.154 in patients treated with cepharanthine (95% CI = 1.442-26.258, P = 0.014). Pain and the grade of swelling were worse in the antivenom group than in the no-antivenom group up to 24 h after arrival, but there were no differences in these outcomes after 48 h. CONCLUSION: Although the effectiveness of mamushi antivenom serum in reducing the length of hospitalization was not demonstrated, beneficial effects on pain and swelling were observed.

Cryptosporidium spp. in captive snakes from 26 provinces in China: Prevalence, molecular characterization, and symptoms.

Snakes are sometimes regarded as pets and are used in traditional Chinese medicine. Cryptosporidium spp. are frequently identified in snakes, representing an important pathogen and causing gastrointestinal diseases. Current data indicate that risk factors for infection and patterns of clinical symptom presentation may differ among Cryptosporidium spp. To better understand the infection status by Cryptosporidium spp., fecal samples were collected from 603 asymptomatic and 147 symptomatic snakes in 26 provinces of China. These samples came from Elaphe guttata, Elaphe obsoleta, Pituophis melanoleucus, Thamnophis sirtalis, Lampropeltis getulus, and Heterodon nasicus. The partial small subunit (SSU) rRNA gene was amplified using nested polymerase chain reaction (PCR) to investigate the infection rate of Cryptosporidium spp., and to assess evolutionary relationships and genetic characterization. A prevalence of 20% was recorded in asymptomatic snakes, with age identified as a significant risk factor. In contrast, 70% of symptomatic snakes were positive for Cryptosporidium spp., with Cryptosporidium serpentis and Cryptosporidium varanii (syn. C. saurophilum). Further analysis revealed a potential association between C. serpentis and regurgitation, and C. varanii and diarrhea, while neither species was linked to flatulence. To our knowledge, this is the first study to report Cryptosporidium spp. and associated clinical signs in symptomatic snakes in China. This study aims to enhance the understanding of Cryptosporidium infections, risk factors, and clinical manifestations in snakes, providing data crucial for the control and prevention of cryptosporidiosis.

Title: Cryptosporidium spp. chez les serpents captifs de 26 provinces de Chine : prévalence, caractérisation moléculaire et symptômes. Abstract: Les serpents sont parfois considérés comme animaux de compagnie et sont utilisés en médecine traditionnelle chinoise. Des Cryptosporidium spp. sont fréquemment identifiés chez les serpents, ont un rôle d'agent pathogène important et provoquent des maladies gastro-intestinales. Les données actuelles indiquent que les facteurs de risque d'infection et les schémas de présentation des symptômes cliniques peuvent varier en fonction des espèces de Cryptosporidium. Pour mieux comprendre l'état d'infection par Cryptosporidium spp., des échantillons fécaux ont été collectés auprès de 603 serpents asymptomatiques et 147 serpents symptomatiques dans 26 provinces de Chine. Ces échantillons provenaient d'Elaphe guttata, Elaphe obsoleta, Pituophis melanoleucus, Thamnophis sirtalis, Lampropeltis getulus et Heterodon nasicus. Le gène de l'ARNr de la petite sous-unité partielle (SSU) a été amplifié à l'aide d'une réaction en chaîne par polymérase (PCR) imbriquée pour étudier le taux d'infection par Cryptosporidium spp. et évaluer les relations évolutives et la caractérisation génétique. Une prévalence de 20 % a été trouvée chez les serpents asymptomatiques, l'âge étant identifié comme un facteur de risque important. En revanche, 70 % des serpents symptomatiques étaient positifs à Cryptosporidium spp. avec Cryptosporidium serpentis et Cryptosporidium varanii (syn. C. saurophilum). Une analyse plus approfondie a révélé une association potentielle entre C. serpentis et la régurgitation, et C. varanii et la diarrhée, alors qu'aucune des deux espèces n'était liée aux flatulences. À notre connaissance, il s'agit ici de la première étude à signaler la présence de Cryptosporidium spp. et les signes cliniques associés chez des serpents symptomatiques en Chine. Cette étude vise à améliorer la compréhension des infections à Cryptosporidium, des facteurs de risque et des manifestations cliniques chez les serpents, en fournissant des données cruciales pour le contrôle et la prévention de la cryptosporidiose.

Compartment syndrome of arm secondary to snake bite on hand: a case report.

Introduction: Snake bites pose a significant common public health concern, with more prevalence in rural areas. Compartment syndrome (CS) is one of the rare and severe manifestations of snake bite wherein venom-induced swelling within a closed anatomical compartment leads to increased pressure, which may result in ischemic damage to nerves and muscle. Antisnake venom and prompt fasciotomy is recommended for management of CS secondary to snake bite. Case details: Here, the authors report a case of 47-year-old female with Green Pit Viper bite on the left hand. Upon arrival to hospital, initial resuscitation measures were initiated. Six hours following the bite, there was severe pain on passive stretch and paresthesia. Ten vials of antisnake venom administration along with fasciotomy of hand and arm resulted in notable alleviation of pain and swelling. Eighteen pints of blood was transfused for coagulopathy and low hemoglobin. After continued care of wound and intensive physiotherapy, functional limb could be achieved. Discussion: Snake bite envenomation is one of the biggest hidden health crises with case fatality rate of 7.8% in the southern plains of Nepal. As in our case, snake bites commonly affect upper extremities, accounting for around two third of all cases. CS must be differentiated from acute swelling, which sometimes may be difficult. Surgical decompression is indicated in presence of signs and symptoms of CS, in case of resource limited setting. Conclusion: Multidisciplinary and prompt management with initial resuscitation, ASV administration, fasciotomy, and rehabilitative measures can save both life and limb in such cases.

Exponential PID controller for effective load frequency regulation of electric power systems.

Load frequency regulation (LFR) is an indispensable scheme in planning electrical power production to provide consumers with stable, reliable and uninterrupted power. In the face of complicated power system (PS) structures with increasing and intricate power demand, new controllers that offer not only good performance, but also easy commissioning in practice are required. To this end, this research introduces an exponential PID (EXP-PID) controller as a new control scheme to ameliorate the LFR performance of PSs. This controller is simple to design and has a nonlinear feature inherited from two tunable exponential functions, which are placed in front of the PID controller and act on the error signal and its time derivative individually. To achieve the utmost performance, the EXP-PID controller's parameters are procured by a corrected variant of the snake optimizer (co-SO). To validate the proposed control scheme, various single-/multi-area single-/multi-source PSs favored in the area are considered as test benches. A thorough comparison with the state-of-the-art approaches is performed to disclose the true efficacy of our proposal. Among the rivals, co-SO tuned EXP-PID controller, despite its simplicity, is found to render credible and promising performance in mitigating frequency and tie-line power deviations effectively.

Snakebites by venomous snakes in Brazilian serpentaria and zoos over a 10-year period (2012-2021).

Despite the wide range of institutions that maintain venomous snakes in captivity in Brazil there are no comprehensive data on the occurrence of snakebites and envenomations in these places. We examined the range of native and exotic species of venomous snakes kept by Brazilian zoos and serpentaria (scientific and commercial) and assessed the frequency of snakebites in workers handling these snakes during a 10-year period (2012-2021). Twenty-two (73.3%) of 30 institutions returned a standard questionnaire, including 15 serpentaria and 7 zoos that together kept 10,607 venomous snakes in 2022/2023. Commercial and scientific serpentaria had many more snakes (n = 10,550, consisting of 10,499 native specimens and 51 exotic specimens) than zoos (n = 57 native specimens), with two genera accounting for the majority of native species (Bothrops spp. = 84.5% and Crotalus durissus ssp. = 13.5%). Thirty-seven snakebites were reported and involved primarily the hands (33), seven of which occurred during venom extraction and 30 in other circumstances, most of them while handling/manipulating the cages or snake boxes (10) and restraining (9) or feeding (5) the snake. In addition, there were two cases of venom accidently sprayed on the face, including the eyes. Most bites were caused by Bothrops spp. (31), followed by C. durissus ssp. (4), Lachesis muta (1) and Micrurus corallinus (1). Thirty-three bites (89.2%) were treated with antivenom, with four bites to the fingers by Bothrops spp. resulting in local functional sequelae. There were 366,918 venom extractions with a ratio of 1.9 bites/100,000 extractions; no bites were recorded in the six institutions that sedated the snakes prior to venom extraction, which accounted for 22.7% of all extractions. These findings show that although snakebites are rare in Brazilian zoos and serpentaria, severe envenomation may occur. The occurrence of snakebites could be reduced by measures such as sedation of the snakes before venom extraction.

Sex-related differences in toxic manifestations induced by Bothrops atrox venom in mice.

Lancehead snakes of the genus Bothrops are responsible for 90% of the snakebites in Latin America. The objective of this study was to assess the LD50, physical, and hematological manifestations induced by B. atrox venom in male and female mice inoculated by different routes. B. atrox venom was inoculated in male and female mice by intramuscular (IM), subcutaneous (SC), intravenous (IV), and intraperitoneal (IP) routes. B. atrox venom LD50 was lower in male than female groups, regardless of the injection route. However, it was the lowest when the venom was inoculated by the IP route. Moreover, comparisons between male and female responses according to the injected venom dose showed higher edema-forming, local hemorrhagic, dermonecrotic, and myotoxic activities in male than in female mice. While the minimal hemorrhagic, and necrotic doses were not statistically different between the two groups, the difference between males and females was more pronounced at high venom doses. Hematological parameter changes were also more significant in male than in female mice. The venom decreased the levels of total leukocytes after 24 h of injection in male and female mice, with a more profound decrease in the male group. The micronucleus test, a tool for genotoxicity assessment, documented the mutagenic effects of B. atrox on leucocytes. We demonstrate the higher susceptibility of male mice to B. atrox venom than females. Sex differences must be considered when conducting experimental studies on snake venoms.

Importance of the Cysteine-Rich Domain of Snake Venom Prothrombin Activators: Insights Gained from Synthetic Neutralizing Antibodies.

Snake venoms are cocktails of biologically active molecules that have evolved to immobilize prey, but can also induce a severe pathology in humans that are bitten. While animal-derived polyclonal antivenoms are the primary treatment for snakebites, they often have limitations in efficacy and can cause severe adverse side effects. Building on recent efforts to develop improved antivenoms, notably through monoclonal antibodies, requires a comprehensive understanding of venom toxins. Among these toxins, snake venom metalloproteinases (SVMPs) play a pivotal role, particularly in viper envenomation, causing tissue damage, hemorrhage and coagulation disruption. One of the current challenges in the development of neutralizing monoclonal antibodies against SVMPs is the large size of the protein and the lack of existing knowledge of neutralizing epitopes. Here, we screened a synthetic human antibody library to isolate monoclonal antibodies against an SVMP from saw-scaled viper (genus Echis) venom. Upon characterization, several antibodies were identified that effectively blocked SVMP-mediated prothrombin activation. Cryo-electron microscopy revealed the structural basis of antibody-mediated neutralization, pinpointing the non-catalytic cysteine-rich domain of SVMPs as a crucial target. These findings emphasize the importance of understanding the molecular mechanisms of SVMPs to counter their toxic effects, thus advancing the development of more effective antivenoms.

An adaptive snake optimization algorithm incorporating Subtraction-Average-Based Optimizer for photovoltaic cell parameter identification.

Accurate parameter identification of photovoltaic (PV) models is essential for the optimal operation and control of PV systems. However, PV cell modeling exhibits nonlinearity and involves numerous challenging-to-solve unknown parameters, thereby reducing the utilization efficiency of solar energy in PV systems. Therefore, this paper proposes an enhanced Snake algorithm (ISASO) that integrates Subtraction Average-Based Optimization (SABO) to address the shortcomings of traditional PV model parameter identification methods, such as low accuracy, slow convergence, and susceptibility to local optima. The SABO algorithm, which updates the positions of search agents using a consistent arithmetic mean position throughout the optimization process, demonstrates high convergence. By integrating SABO's global search strategy into the exploration phase of SO, the global search capability of SO is further enhanced, mitigating the risk of early local optima in the original SO. Additionally, the Tent chaotic map initialization method is incorporated into standard SO to improve the quality of the initial population and enhance population diversity. A dynamic learning factor and adaptive inertia weight strategy are also employed to accelerate the convergence speed of the SO algorithm, balancing its exploration and exploitation capabilities. To validate the performance of ISASO, it is applied to the CEC2005 benchmark functions and employed to identify the optimal parameters of various PV models. Statistical and analytical results reveal that ISASO markedly outperforms existing methods in parameter identification accuracy and reliability, achieving the lowest Root Mean Square Error (RMSE) values between standard and simulated data. Additionally, the superior performance of ISASO is further verified by comparative analysis with existing meta-heuristic algorithms and the Friedman mean ranking statistical method. Therefore, ISASO can be considered as a reliable and effective method to accurately estimate solar PV model parameters.

Novel GPIb-independent platelet aggregation induced by botrocetin: Implications for diagnosis and antithrombotic therapy.

BACKGROUND: Snake venom botrocetin facilitates von Willebrand factor (VWF) binding to platelet GPIbα and has been widely used for the diagnosis of von Willebrand diseases and GPIb-related disorders. Botrocetin is also commonly employed for the development/characterization of antithrombotics targeting the GPIb-VWF axis. OBJECTIVE: To explore the alternative receptor(s)/mechanisms participate in botrocetin-induced platelet aggregation. METHODS: The effects of botrocetin on platelet aggregation were examined using platelets from wild-type, VWF and fibrinogen-deficient, GPIbα-deficient, IL4Rα/GPIbα-transgenic and αIIbß3-deficient mice, Bernard-Soulier syndrome (BSS) and healthy human samples. Platelet-fibrinogen and platelet-VWF interaction were measured using flow cytometry. GPIbα-VWF binding was evaluated utilizing ELISA. Botrocetin-αIIbß3 and botrocetin-GPIbα interactions were measured using ELISA and fluorescence anisotropy assays. Heparinized whole blood from healthy donors was examined for thrombus formation and growth in a perfusion chamber. RESULTS: Botrocetin could induce aggregation of platelets from a BSS patient and GPIbα-deficient mice as well as platelets lacking the N-terminal extracellular domain of GPIbα. Botrocetin could interact with αIIbß3 and facilitated αIIbß3-VWF interaction independent of GPIb. Botrocetin competitively bound to the ligand-binding domain of activated rather than resting αIIbß3. Although botrocetin-induced platelet aggregation requires VWF, strikingly, in the absence of VWF, botrocetin blocked fibrinogen and other ligand binding to αIIbß3, and inhibited platelet aggregation and thrombus formation. Consistently, recombinant botrocetin defective in VWF binding inhibited αIIbß3 and GPIb-mediated platelet aggregation, spreading and thrombus formation. CONCLUSION: Our study provides insights into avoiding the misdiagnosis of GPIb-related disorders and developing botrocetin mutants as potential new antithrombotics that may simultaneously target both αIIbß3 and GPIbα.