Preclinical models of atherosclerosis: An overview.

Atherosclerosis is a primary cause of illness and death globally and its mechanism is still unclear. Different animal models have been created to evaluate the progression of atherosclerosis, allowing researchers to carefully control the circumstances of the experiment as well as the nutrition and environmental risk factors. To investigate the negative effects of various interventions, pathophysiological alterations might be generated utilizing genetic or pharmacological methods. These models' molecular and pathophysiological mechanisms have been clarified through experiments, and they have served as platforms for the creation of new drugs. Different models can be employed to address various research problems, each with its own benefits and drawbacks. In the current review study, various species of atherosclerosis models are discussed, along with the viability of using them in experiments.

Discovery of SQSTM1/p62-dependent P-bodies that regulate the NLRP3 inflammasome.

Autophagy and ribonucleoprotein granules, such as P-bodies (PBs) and stress granules, represent vital stress responses to maintain cellular homeostasis. SQSTM1/p62 phase-separated droplets are known to play critical roles in selective autophagy; however, it is unknown whether p62 can exist as another form in addition to its autophagic droplets. Here, we found that, under stress conditions, including proteotoxicity, endotoxicity, and oxidation, autophagic p62 droplets are transformed to a type of enlarged PBs, termed p62-dependent P-bodies (pd-PBs). p62 phase separation is essential for the nucleation of pd-PBs. Mechanistically, pd-PBs are triggered by enhanced p62 droplet formation upon stress stimulation through the interactions between p62 and DDX6, a DEAD-box ATPase. Functionally, pd-PBs recruit the NLRP3 inflammasome adaptor ASC to assemble the NLRP3 inflammasome and induce inflammation-associated cytotoxicity. Our study shows that p62 droplet-to-PB transformation acts as a stress response to activate the NLRP3 inflammasome process, suggesting that persistent pd-PBs lead to NLRP3-dependent inflammation toxicity.

Nitrogen-fused Heterocycles: Empowering Anticancer Drug Discovery.

The worldwide impact of cancer is further compounded by the constraints of current anticancer medications, which frequently exhibit a lack of selectivity, raise safety apprehensions, result in significant adverse reactions, and encounter resistance mechanisms. The current situation highlights the pressing need to develop novel and more precise anticancer agents that prioritize safety and target specificity. Remarkably, more than 85% of drugs with physiological activity contain heterocyclic structures or at least one heteroatom. Nitrogen-containing heterocycles hold a significant position among these compounds, emerging as the most prevalent framework within the realm of heterocyclic chemistry. This article explores the medicinal chemistry behind these molecules, highlighting their potential as game-changing possibilities for anticancer medication development. The analysis highlights the inherent structural variety in nitrogen-containing heterocycles, revealing their potential to be customized for creating personalized anticancer medications. It also emphasizes the importance of computational techniques and studies on the relationships between structure and activity, providing a road map for rational medication design and optimization. Nitrogen-containing heterocycles are a promising new area of study in the fight against cancer, and this review summarises the state of the field so far. By utilizing their inherent characteristics and exploiting cooperative scientific investigations, these heterocyclic substances exhibit potential at the forefront of pioneering therapeutic approaches in combating the multifaceted obstacles posed by cancer.

Recent Advances in Nitrogen-Containing Heterocyclic Scaffolds as Antiviral Agents.

This study aims to provide a thorough analysis of nitrogen-containing heterocycles, focusing on their therapeutic implications for the development of targeted and effective antiviral drugs. To better understand how nitrogen-containing heterocycles can be used to create antiviral drugs, this review adopts a systematic literature review strategy to compile and analyze pertinent research studies. It combines information from various fields to understand better the compounds' mode of action and their therapeutic potential. This review paper summarizes data from multiple sources to highlight the promising potential of heterocycles containing nitrogen as promising possibilities for future antiviral treatments. The capacity to engage selectively and modulate critical pathways bodes well for their use in developing new viral therapies. In conclusion, nitrogen-containing heterocycles are shown to be of utmost importance in the field of medicinal chemistry, as emphasized by the review paper. It emphasizes the central importance of chemical insights and pharmacological potential in developing novel and effective antiviral medicines by bringing them together.

Hydrogel Breakthroughs in Biomedicine: Recent Advances and Implications.

The objective of this review is to present a succinct summary of the latest advancements in the utilization of hydrogels for diverse biomedical applications, with a particular focus on their revolutionary impact in augmenting the delivery of drugs, tissue engineering, along with diagnostic methodologies. Using a meticulous examination of current literary works, this review systematically scrutinizes the nascent patterns in applying hydrogels for biomedical progress, condensing crucial discoveries to offer a comprehensive outlook on their ever-changing importance. The analysis presents compelling evidence regarding the growing importance of hydrogels in biomedicine. It highlights their potential to significantly enhance drug delivery accuracy, redefine tissue engineering strategies, and advance diagnostic techniques. This substantiates their position as a fundamental element in the progress of modern medicine. In summary, the constantly evolving advancement of hydrogel applications in biomedicine calls for ongoing investigation and resources, given their diverse contributions that can revolutionize therapeutic approaches and diagnostic methods, thereby paving the way for improved patient well-being.

Bioactive Exploration in Functional Foods: Unlocking Nature's Treasures.

BACKGROUND: Functional foods offer an appealing way to improve health and prevent chronic diseases, and this subject has received much attention lately. They are effective in preventing chronic diseases like cancer, diabetes, heart disease, and obesity, according to research. OBJECTIVE: This work presents an in-depth analysis of functional foods, covering key challenges from a scientific, legal, and commercial perspective. METHODS: Multiple databases were searched to find studies on functional foods included in the systematic literature review. Various aspects of functional foods, from their classification, impact on human wellness, effectiveness in inhibiting chronic diseases, the regulatory environment, global market trends, and industry challenges, are all clarified in this thorough review. RESULTS: This study aims to enhance understanding and establish a pathway for functional foods to be acknowledged as valid choices in the field of dietary supplements. It provides a thorough investigation of bioactive compounds present in functional foods, including but not limited to polyphenols, carotenoids, omega fatty acids, prebiotics, probiotics, and dietary fiber, along with an overview of their potential to mitigate chronic illnesses. We engage in an in-depth exploration of regulatory frameworks, shed light on groundbreaking research advancements, and meticulously examine strategies for commercialization and the variety of global challenges that accompany them. Establishing scientific consensus, navigating complex regulatory processes, dealing with skeptical consumers, and rising levels of competition are all problems that need to be solved in this field. CONCLUSION: The field of functional foods can advance further, promoting better public health outcomes, by deeply comprehending and addressing these complex dimensions.

Mitral Valve Echodensities in a Young-Adult Female with Relapsing Polychondritis, Transiently Positive Lupus Anticoagulant, and Systemic Embolism.

Background: Valvular strands seen on echocardiography carry a wide differential diagnosis and may not always have a clear etiology despite taking clinical context into account. The decision of whether to provide anticoagulation for these lesions can be challenging. Case Presentation. A young adult female with an extensive rheumatologic history involving relapsing polychondritis and positive lupus anticoagulant presents to the emergency department with a discolored and painful right toe, as well as right auricular pain and swelling. Initial work-up revealed a possible splenic infarct, vasculitis of the right lower extremity, and mitral valve echodensities on echocardiography, without evidence of infective endocarditis. Due to concern that nonbacterial thrombotic endocarditis may be the cause of the patient's thromboembolic event, her valvular lesions were treated with low molecular weight heparin while awaiting serial imaging. When follow-up echocardiography showed no change in the size of her mitral valve lesions, which would be most consistent with Lambl's excrescences, the care team still faced a decision about which long-term anticoagulation to prescribe. This patient of childbearing age wished to avoid the teratogenicity and long-term monitoring associated with warfarin therapy. Although warfarin was the preferred agent for the patient's rheumatologic comorbidities, she elected to receive enoxaparin therapy for long-term thromboembolism prophylaxis. Conclusions: Even when accounting for clinical context, valvular lesions seen on echocardiography often have uncertain etiology and may require time and serial imaging to determine which treatment to pursue. When long-term anticoagulation is provided for females of childbearing age, shared decision-making with consideration of the patient's personal priorities and comorbidities is essential.

An Exploration of Organoid Technology: Present Advancements, Applications, and Obstacles.

BACKGROUND: Organoids are in vitro models that exhibit a three-dimensional structure and effectively replicate the structural and physiological features of human organs. OBJECTIVE: This work examines the potential applications of organoid technology, as well as the challenges and future directions associated with its implementation. METHODS: The manuscript was put together by conducting a comprehensive literature review, which involved an in-depth evaluation of globally renowned scientific research databases. RESULTS: The field of organoids has generated significant attention due to its potential applications in tissue development and disease modelling, as well as its implications for personalised medicine, drug screening, and cell-based therapies. The utilisation of organoids has proven to be effective in the examination of various conditions, encompassing genetic disorders, cancer, neurodevelopmental disorders and infectious diseases. CONCLUSION: The exploration of the wider uses of organoids is still in its early phases. Research shall be conducted to integrate 3D organoid systems as alternatives for current models, potentially improving both fundamental and clinical studies in the future.

Metabolic Alterations Caused by Simultaneous Loss of HK2 and PKM2 Leads to Photoreceptor Dysfunction and Degeneration.

HK2 and PKM2 are two main regulators of aerobic glycolysis. Photoreceptors (PRs) use aerobic glycolysis to produce the biomass necessary for the daily renewal of their outer segments. Previous work has shown that HK2 and PKM2 are important for the normal function and long-term survival of PRs but are dispensable for PR maturation, and their individual loss has opposing effects on PR survival during acute nutrient deprivation. We generated double conditional (dcKO) mice lacking HK2 and PKM2 expression in rod PRs. Western blotting, immunofluorescence, optical coherence tomography, and electroretinography were used to characterize the phenotype of dcKO animals. Targeted and stable isotope tracing metabolomics, qRT-PCR, and retinal oxygen consumption were performed. We show that dcKO animals displayed early shortening of PR inner/outer segments, followed by loss of PRs with aging, much more rapidly than either knockout alone without functional loss as measured by ERG. Significant alterations to central glucose metabolism were observed without any apparent changes to mitochondrial function, prior to PR degeneration. Finally, PR survival following experimental retinal detachment was unchanged in dcKO animals as compared to wild-type animals. These data suggest that HK2 and PKM2 have differing roles in promoting PR neuroprotection and identifying them has important implications for developing therapeutic options for combating PR loss during retinal disease.

Guidance document: risk assessment of patients with cirrhosis prior to elective non-hepatic surgery.

As a result of the increasing incidence of cirrhosis in the UK, more patients with chronic liver disease are being considered for elective non-hepatic surgery. A historical reluctance to offer surgery to such patients stems from general perceptions of poor postoperative outcomes. While this is true for those with decompensated cirrhosis, selected patients with compensated early-stage cirrhosis can have good outcomes after careful risk assessment. Well-recognised risks include those of general anaesthesia, bleeding, infections, impaired wound healing, acute kidney injury and cardiovascular compromise. Intra-abdominal or cardiothoracic surgery are particularly high-risk interventions. Clinical assessment supplemented by blood tests, imaging, liver stiffness measurement, endoscopy and assessment of portal pressure (derived from the hepatic venous pressure gradient) can facilitate risk stratification. Traditional prognostic scoring systems including the Child-Turcotte-Pugh and Model for End-stage Liver Disease are helpful but may overestimate surgical risk. Specific prognostic scores like Mayo Risk Score, VOCAL-Penn and ADOPT-LC can add precision to risk assessment. Measures to mitigate risk include careful management of varices, nutritional optimisation and where possible addressing any ongoing aetiological drivers such as alcohol consumption. The role of portal decompression such as transjugular intrahepatic portosystemic shunting can be considered in selected high-risk patients, but further prospective study of this approach is required. It is of paramount importance that patients are discussed in a multidisciplinary forum, and that patients are carefully counselled about potential risks and benefits.

Sex differences in permanent pacemaker implantation after transcatheter aortic valve replacement: a systematic review and meta-analysis.

BACKGROUND: There is limited evidence on the effect of sex on permanent pacemaker implantation (PPMI) after transcatheter aortic valve replacement (TAVR). The primary objective of this meta-analysis was to determine the role of sex among patients requiring PPMI post-TAVR. METHODS: A literature search was conducted using the SCOPUS, MEDLINE, and CINAHL databases for studies published until October 2022. Eligible studies included published randomized controlled trials (RCTs) and Observational Cohort Studies (OCS) articles that reported PPMI as an outcome of pacemaker status following TAVR. This study was performed per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. Publication bias was estimated using a Funnel plot and Egger's test. Data were pooled using a random-effects model. The primary endpoint was the sex difference in PPMI after TAVR, with odds ratios and 95% confidence intervals (CIs) extracted. RESULTS: Data was obtained from 63 studies, and a total of 79,655 patients were included. The cumulative PPMI rate was 15.5% (95% CI, 13.6%-17.7%). The pooled analysis revealed that while there were more females than males undergoing TAVR (51.6%, 95% CI 50.4%-52.8%), males have a 14.5% higher risk for post-TAVR PPMI than females (OR 1.145, 95% CI 1.047-1.253, P < 0.01). CONCLUSIONS: Males are more likely to experience PPMI after TAVR than females. Further research needs to be done to better explain these observed differences in outcomes.

Defining Peri-Operative Myocardial Injury during Cardiac Surgery Using High-Sensitivity Troponin T.

OBJECTIVE: Cut-offs for high-sensitivity troponin (hs-Tn) elevations to define prognostically significant peri-operative myocardial injury (PMI) in cardiac surgery is not well-established. We evaluated the associations between peri-operative high-sensitivity troponin T (hs-TnT) elevations and 1-year all-cause mortality in patients undergoing cardiac surgery. METHODS: The prognostic significance of baseline hs-TnT and various thresholds for post-operative hs-TnT elevation at different time-points on 1-year all-cause mortality following cardiac surgery were assessed after adjusting for baseline hs-TnT and EuroSCORE in a post-hoc analysis of the ERICCA trial. RESULTS: 1206 patients met the inclusion criteria. Baseline elevation in hs-TnT >x1 99th percentile upper reference limit (URL) was significantly associated with 1-year all-cause mortality (adjusted hazard ratio 1.90, 95% confidence interval 1.15-3.13). In the subgroup with normal baseline hs-TnT (n = 517), elevation in hs-TnT at all post-operative time points was associated with higher 1-year mortality, reaching statistical significance for elevations above: ≥100 × URL at 6 h; ≥50 × URL at 12 and 24 h; ≥35 × URL at 48 h; and ≥30 × URL at 72 h post-surgery. Elevation in hs-TnT at 24 h ≥ 50 × URL had the optimal sensitivity and specificity (73% and 75% respectively). When the whole cohort of patients was analysed, including those with abnormal baseline hs-TnT (up to 10 × URL), the same threshold had optimal sensitivity and specificity (66% and 70%). CONCLUSIONS: Both baseline and post-operative hs-TnT elevations are independently associated with 1-year all-cause mortality in patients undergoing cardiac surgery. The optimal threshold to define a prognostically significant PMI in our study was ≥50 × URL elevation in hs-TnT at 24 h.

SARS-CoV-2 infection causes periodontal fibrotic pathogenesis through deregulating mitochondrial beta-oxidation.

The global high prevalence of COVID-19 is a major challenge for health professionals and patients. SARS-CoV-2 virus has four structural protein components: the spike protein, envelope protein, membrane protein, and nucleocapsid protein. The SARS-CoV-2 virus mutates predominantly in the spike proteins, whilst the other key viral components usually remain stable. Essentially the pathological functions of the SARS-CoV-2 virus on different cell types are still largely unknown. Previous studies have shown that the human oral cavity can potentially act as reservoir of the SARS-CoV-2 virus. However, the consequence of SARS-CoV-2 viral infection on human oral health has not been systematically examined. COVID-19 can cause severe oral mucosa lesions and is likely to be connected with poor periodontal conditions. Fibroblasts are the major cell type inside periodontal ligament (PDL) and express the SARS-CoV-2 receptor: Angiotensin-converting enzyme 2 (ACE2), whose expression level can increase upon bacterial infection hence potentially provide a direct route of SARS-CoV-2 infection to PDL fibroblasts. In this research, we aimed to study the pathogenicity of SARS-CoV-2 viral components on human fibroblasts. We found that by exposing to SARS-CoV-2, especially to the viral envelope and membrane proteins, the human periodontal fibroblasts could develop fibrotic pathogenic phenotypes, including hyperproliferation that was simultaneously induced with increased apoptosis and senescence. The fibrotic degeneration was mediated by a down-regulation of mitochondrial ß-oxidation in the fibroblasts. Fatty acid ß-oxidation inhibitor, etomoxir treatment could mirror the same pathological consequence on the cells, similar to SARS-CoV-2 infection. Our results therefore provide novel mechanistic insights into how SARS-CoV-2 infection can affect human periodontal health at the cell and molecular level with potential new therapeutic targets for COVID-19 induced fibrosis.

Towards smart sustainable development through value stream mapping - a systematic literature review.

Value Stream Mapping (VSM) is a standard Lean tool for identifying and reducing waste. It is used to create value and improve the performance of any industry. The value of the VSM has greatly expanded from conventional to smart over time; hence, researchers and practitioners in this sector are paying more emphasis. Comprehensive review research is needed to understand VSM-based smart, sustainable development from a triple-bottom-line perspective. The primary goal of this research is to look at various insights from the historical literature that can help with the adoption of smart, sustainable development through VSM. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) with a fifteen-year time range (2008-2022) is being considered to study various insights and gaps in value stream mapping. Analysis of the significant outcomes presents an eight-point study agenda: year, national context, research method, sector, wastes, VSM type, applied tools, and analysis indicators. The critical finding implies that empirical qualitative research dominates the research sector. Effective VSM implementation requires balancing the three sustainable dimensions of economic, environmental, and social through digitalization. The circular economy should also bolster research on the intersection of sustainability applications and new digital paradigms such as industry revolution 4.0.

Hidden attributes of zymosan in the pathogenesis of inflammatory diseases: A tale of the fungal agent.

Inflammation triggers immune system-mediated actions that contribute to the development of multiple diseases. Zymosan, a polysaccharide derived from the Saccharomyces cerevisiae cell wall, is mainly made up of glucan and mannan residues and is used as an inflammatory agent. Zymosan is a fungal product that activates the immune system through the activation of inflammatory signaling pathways, and releases a variety of harmful chemicals including pattern recognition receptors, reactive oxygen species (ROS), and the excitatory amino acid glutamate, cytokines, adhesion molecules, etc. Furthermore, we will dive into the molecular mechanistic insights through which this fungal agent induces and influences various inflammatory diseases such as cardiovascular, neuroinflammation, diabetes, arthritis, and sepsis. Based on the evidence, zymosan appears to be a promising inflammatory-inducing agent. Nonetheless, more animal data is the need of the hour to catch a glimpse and unravel the capacity of zymosan.

Outcomes of Liver Transplantation in Patients With Preexisting Coronary Artery Disease.

BACKGROUND: Advances in surgical and medical technology over the years has made liver transplantation possible for older and higher risk patients. Despite rigorous preoperative cardiac testing, cardiovascular events remain a major cause of death after orthotopic liver transplantation (OLT). However, there are little data on the outcomes of OLT in patients with preexisting coronary artery disease (CAD). This study aimed to compare all-cause and cardiovascular mortality of patients with and without history of CAD undergoing OLT. METHODS: Six hundred ninety-three adult patients with cirrhosis underwent liver transplantation between July 2013 and December 2018 (female n = 243, male n = 450; median age 59). RESULTS: During the study period of 5 y (median follow-up, 24.1 mo), 92 of 693 patients (13.3%) died. All-cause mortality in the CAD group was significantly higher than in the non-CAD group (26.7% versus 9.6%; P <0.01). Cardiovascular events accounted for 52.5% of deaths (n = 21) in patients with CAD compared with 36.5% (n = 19) in non-CAD patients. At 6 mo, patients with combined nonalcoholic steatohepatitis (NASH)/CAD had significantly worse survival than those with CAD or NASH alone ( P <0.01). After 6 mo, patients with CAD alone had similar survival to those with combined NASH/CAD. CONCLUSIONS: Patients with preexisting CAD before liver transplantation are at higher risk of death from any cause, specifically cardiovascular-related death. This risk increases with coexisting NASH. The presence of NASH and CAD at the time of liver transplant should prompt the initiation of aggressive risk factor modification for patients with CAD.

Hypothermia as an Adjunctive Therapy to Percutaneous Intervention in ST-Elevation Myocardial Infarction: A Systematic Review and Meta-Analysis of Randomized Control Trials.

INTRODUCTION: In the setting of acute ST-elevation myocardial infarction (STEMI), several randomized control trials (RCTs) suggested a potential benefit with the use of therapeutic hypothermia (TH). However, results from previous studies are contradictory. METHOD: We performed a comprehensive literature search for studies that evaluated the efficacy and safety of adjunctive TH compared to the standard percutaneous coronary intervention (PCI) in awake patients with STEMI. The primary outcomes were the infarct size (IS) and microvascular obstruction (MVO) assessed by cardiac imaging at the end of follow-up. The secondary outcomes were major adverse cardiovascular events (MACE), procedure-related complications, and door-to-balloon time. Relative risk (RR) or the mean difference (MD) and corresponding 95 % confidence intervals (CIs) were calculated using the random-effects model. RESULTS: A total of 10 RCTs, including 706 patients were included. As compared to standard PCI, TH was not associated with a statistically significant improvement in the IS (MD: -0.87 %, 95%CI: -2.97, 1.23; P = 0.42) or in the MVO (MD: 0.11 %, 95%CI: -0.06, 0.27; P = 0.21). MACE and its components were comparable between the two groups. However, the TH approach was associated with an increased risk of infection and prolonged door-to-balloon time. Furthermore, there was a trend in the TH group toward an increased incidence of stent thrombosis and paroxysmal atrial fibrillation. CONCLUSIONS: According to our meta-analysis of published RCTs, TH is not beneficial in awake patients with STEMI and has a marginal safety profile with potential for care delays. Larger-scale RCTs are needed to further clarify our results.

Acute Left Atrial Appendage Thrombus Formation During Transcatheter Mitral Valve Edge-to-Edge Repair.

We present a case of a 75-year-old man who developed an acute left atrial appendage thrombus immediately following mitral valve transcatheter edge to edge repair despite adequate intraprocedural anticoagulation. The patient was managed with enoxaparin to warfarin bridging with no obvious thromboembolic events on follow-up. Attention to anticoagulation is important to reduce thromboembolic risk during mitral valve transcatheter edge to edge repair. (Level of Difficulty: Intermediate.).

Outcomes of balloon vs basket catheter for clearance of choledocholithiasis: a systematic review and meta-analysis.

Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) is the mainstay for treatment of choledocholithiasis. It is unclear whether balloon or basket catheters are better for extraction of stones ≤ 10 mm in size. We performed a meta-analysis of studies comparing rates of complete stone extraction and adverse events after ERCP using balloon vs basket catheters for bile duct stones ≤ 10 mm in size. Methods Cochrane database, PubMed, Web of Science, and Embase were searched from inception to October 2021. Randomized control trials comparing outcomes of balloon vs basket catheter were included. Data extraction of articles was carried out by two authors using predefined inclusion criteria. Metanalysis was carried out using the Revman 5.4.1. software using a random-effects model. Results Three studies with a total of 508 patients were included in the final analysis. For common bile duct stones ≤ 10 mm, balloon catheters had higher complete stone clearance rates than basket catheters (relative risk 1.1, confidence interval 1.03, 1.18, P  = 0.006). Heterogeneity among studies was low (Tau 2  = 0.0; P  = 0.47, I 2  = 0 %). There was no difference in the rate of complications. Conclusions Meta-analysis of three studies indicates that balloon catheters have a higher success rate compared to basket catheters for complete stone extraction for choledocholithiasis ≤ 10 mm with no significant difference in the rate of complications.

How, where and when is SPINK3 bound and removed from mouse sperm?

Sperm capacitation in mammals is a fundamental requirement to acquire their fertilizing capacity. Little is known about the action mechanism of the molecules that prevent capacitation from occurring prematurely. These molecules are known as decapacitation factors (DFs) and they must be removed from the sperm surface for capacitation to occur successfully. Serine protease inhibitor Kazal type 3 (SPINK3) has been proposed as one of these DFs. Here, we evaluate how this protein binds to mouse sperm and its removal kinetics. We describe that SPINK3 is capable of binding to the membrane of mature epididymal sperm through protein-lipid interactions, specifically to lipid rafts subcellular fraction. Moreover, cholera toxin subunit b (CTB) avoids SPINK3 binding. We observe that SPINK3 is removed from the sperm under in vitro capacitating conditions and by the uterine fluid from estrus females. Our ex vivo studies show the removal kinetics of this protein within the female tract, losing SPINK3 formerly from the apical region of the sperm in the uterus and later from the flagellar region within the oviduct. The presence of acrosome-reacted sperm in the female duct concurs with the absence of SPINK3 over its surface.