Effects of loading processes on contact forces when simulating static seating with a finite element human body model.

Seat interface forces, particularly shear forces, play an essential role in predicting the risk of pressure ulcers and seating discomfort. When a finite element human body model (HBM) is used for static seating simulation, the most common loading method is to put the model in a position close to the desired final posture and then 'drop' it from just above the seat by applying the gravity (DROP). This does not represent how people sit in a seat. In addition, high coefficients of friction (COF) are often used to prevent sliding, which may lead to unrealistically high tangential forces. This study aims to investigate the effects of the loading process and the COF on seating simulations with a HBM. We propose a new loading approach called 'drop and rotate' (D&R) to better mimic people sitting on a seat. With the trunk more flexed than the desired posture, the model is dropped to establish the contact between the buttocks and thighs, and the seat pan first, and then between the back and the backrest by rotating the hip. Simulations were performed using a recently developed and validated adult male model in two different seat configurations. Results show that the proposed D&R method was less sensitive to COF and gave a better prediction of contact forces, especially on the seat pan. However, its computational time is higher than the DROP method. The study highlights the importance of the loading process when simulating static seating.

Prediction of testicular histology in azoospermia patients through deep learning-enabled two-dimensional grayscale ultrasound.

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.

Defining precancer: a grand challenge for the cancer community.

The term 'precancer' typically refers to an early stage of neoplastic development that is distinguishable from normal tissue owing to molecular and phenotypic alterations, resulting in abnormal cells that are at least partially self-sustaining and function outside of normal cellular cues that constrain cell proliferation and survival. Although such cells are often histologically distinct from both the corresponding normal and invasive cancer cells of the same tissue origin, defining precancer remains a challenge for both the research and clinical communities. Once sufficient molecular and phenotypic changes have occurred in the precancer, the tissue is identified as a 'cancer' by a histopathologist. While even diagnosing cancer can at times be challenging, the determination of invasive cancer is generally less ambiguous and suggests a high likelihood of and potential for metastatic disease. The 'hallmarks of cancer' set out the fundamental organizing principles of malignant transformation but exactly how many of these hallmarks and in what configuration they define precancer has not been clearly and consistently determined. In this Expert Recommendation, we provide a starting point for a conceptual framework for defining precancer, which is based on molecular, pathological, clinical and epidemiological criteria, with the goal of advancing our understanding of the initial changes that occur and opportunities to intervene at the earliest possible time point.

Research on antibiotic resistance genes in wild and artificially bred green turtles (Chelonia mydas).

Sea turtles, vital to marine ecosystems, face population decline. Artificial breeding is a recovery strategy, yet it risks introducing antibiotic resistance genes (ARGs) to wild populations and ecosystems. This study employed metagenomic techniques to compare the distribution characteristics of ARGs in the guts of wild and artificially bred green turtles (Chelonia mydas). The findings revealed that the total abundance of ARGs in C. mydas that have been artificially bred was significantly higher than that in wild individuals. Additionally, the abundance of mobile genetic elements (MGEs) co-occurring with ARGs in artificially bred C. mydas was significantly higher than in wild C. mydas. In the analysis of bacteria carrying ARGs, wild C. mydas exhibited greater bacterial diversity. Furthermore, in artificially bred C. mydas, we discovered 23 potential human pathogenic bacteria (HPB) that contain antibiotic resistance genes. In contrast, in wild C. mydas, only one type of HPB carrying an antibiotic resistance gene was found. The findings of this study not only enhance our understanding of the distribution and dissemination of ARGs within the gut microbial communities of C. mydas, but also provide vital information for assessing the potential impact of releasing artificially bred C. mydas on the spread of antibiotic resistance.

Ecological adaptations of amphibians to environmental changes along an altitudinal gradient (Case Study: Bufo gargarizans) from phenotypic and genetic perspectives.

BACKGROUND: Organisms have evolved a range of phenotypic and genetic adaptations to live in different environments along an altitudinal gradient. Herein, we studied the widely distributed Chinese toad, Bufo gargarizans, as a model and used an integrated phenotype-genotype approach to assess adaptations to different altitudinal environments. RESULTS: Comparison of populations from four altitudes (50 m, 1200 m, 2300 m, and 3400 m) showed more effective defenses among high-altitude toads. These included thickened epidermis, more epidermal capillaries and granular glands, greater gland size in skin, and higher antioxidant enzyme activities in plasma. High-altitude toads also showed increased erythrocytes and hematocrit and elevated hemoglobin concentration, potentially improving oxygen delivery. Elevated altitude led to a metabolic shift from aerobic to anaerobic metabolism, and high-altitude populations favored carbohydrates over fatty acids to fuel for energy metabolism. Differentially expressed genes were associated with adaptive phenotypic changes. For instance, expression of genes associated with fatty acid metabolism showed greater suppression at high altitude (3400 m), consistent with decreased flux of ß-hydroxybutyric acid and lower free fatty acids levels. Moreover, down-regulation of genes involved in carbon metabolism processes at high altitude (3400 m) were coincident with reduced TCA cycle flux. These results suggest that high-altitude toads adopt a metabolic suppression strategy for survival under harsh environmental conditions. Moreover, the hypoxia-inducible factor signaling cascade was activated at high altitude. CONCLUSIONS: Collectively, these results advance our comprehension of adaptation to high-altitude environments by revealing physiological and genetic mechanisms at work in Chinese toads living along altitudinal gradients.

Ultrasmall Enzyodynamic PANoptosis Nano-Inducers for Ultrasound-Amplified Hepatocellular Carcinoma Therapy and Lung Metastasis Inhibition.

Addressing the inefficiency of current therapeutic approaches for hepatocellular carcinoma is an urgent and pressing challenge. PANoptosis, a form of inflammatory programmed cell death, presents a dependable strategy for combating cancer by engaging multiple cell death pathways (apoptosis, pyroptosis, and necroptosis). In this study, an ultrasmall Bi2Sn2O7 nanozyme with ultrasound-magnified multienzyme-mimicking properties is designed and engineered as a PANoptosis inducer through destroying the mitochondrial function of tumor cells and enhancing the intracellular accumulation of toxic reactive oxygen species, finally triggering the activation of PANoptosis process. The role of PANoptosis inducer has been verified by the expression of related proteins, including cleaved Caspase 3, NLRP3, N-GSDMD, cleaved Caspase 1, p-MLKL, and RIPK3. The inclusion of external ultrasonic irradiation significantly augments the enzyodynamic therapeutic efficiency. In vitro and in vivo antineoplastic efficacy, along with inhibition of lung metastasis, validate the benefits of the Bi2Sn2O7-mediated PANoptosis pathway. This study not only elucidates the intricate mechanisms underlying Bi2Sn2O7 as a PANoptosis inducer, but also offers a novel perspective for the treatment of hepatocellular carcinoma.

Enrichment of antioxidant peptide from rice protein hydrolysates via rice husk derived biochar.

In this study, rice husk biochar was engineered with abundant iron ion sites to enhance the enrichment of antioxidant peptides from rice protein hydrolysates through metal-chelating interactions. The π-π interactions and metal ion chelation were identified as the primary mechanisms for the enrichment process. Through peptide sequencing, four peptides were identified: LKFL (P1: Leu-Lys-Phe-Leu), QLLF (P2: Gln-Leu-Leu-Phe), WLAYG (P3: Trp-Leu-Ala-Tyr-Gly), and HFCGG (P4: His-Phe-Cys-Gly-Gly). The vitro analysis and molecular docking revealed that peptides P1-P4 possessed remarkable scavenging ability against radicals and Fe2+ chelating ability. Notably, peptide P4 showed radical scavenging activity comparable to glutathione (GSH) against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethylbenzthiazoline-6-sulphonate (ABTS) radicals. Cellular experiments further confirmed that peptide P4 effectively protected HepG2 cells from oxidative stress-induced damage. The modified rice husk biochar proved to be an effective means for enriching rice antioxidant peptides from protein hydrolysates.

Role of UFMylation in tumorigenesis and cancer immunotherapy.

Protein post-translational modifications (PTMs) represent a crucial aspect of cellular regulation, occurring after protein synthesis from mRNA. These modifications, which include phosphorylation, ubiquitination, acetylation, methylation, glycosylation, Sumoylation, and palmitoylation, play pivotal roles in modulating protein function. PTMs influence protein localization, stability, and interactions, thereby orchestrating a variety of cellular processes in response to internal and external stimuli. Dysregulation of PTMs is linked to a spectrum of diseases, such as cancer, inflammatory diseases, and neurodegenerative disorders. UFMylation, a type of PTMs, has recently gained prominence for its regulatory role in numerous cellular processes, including protein stability, response to cellular stress, and key signaling pathways influencing cellular functions. This review highlights the crucial function of UFMylation in the development and progression of tumors, underscoring its potential as a therapeutic target. Moreover, we discuss the pivotal role of UFMylation in tumorigenesis and malignant progression, and explore its impact on cancer immunotherapy. The article aims to provide a comprehensive overview of biological functions of UFMylation and propose how targeting UFMylation could enhance the effectiveness of cancer immunotherapy strategies.

Effects of Dietary Fish Oil Supplementation on the Growth, Proximate Composition, and Liver Health of Chinese Stripe-Necked Turtle (Mauremys sinensis).

Dietary lipids provide energy for animals and can also be converted into other nutrients (such as non-essential amino acids), which play a role in saving protein. The Chinese stripe-necked turtle is a protected and endangered species that has been bred in captivity; however, basic data on lipid requirements remain unavailable. In this study, 360 Mauremys sinensis (body weight of 65.32 ± 0.15 g) were randomly divided into six groups with three replicates per group; the turtles were fed experimental diets supplemented with various levels of fish oil (i.e., 1% (control group, CG), 3.5% (HF-1), 6% (HF-2), 8.5% (HF-3), 11% (HF-4), and 13.5% (HF-5)) for 10 weeks. The results showed that compared with CG, increasing the fish oil level promoted the growth performance of turtles, and the HF-3 group achieved the best effect. The HF-4 group showed the highest increases in the hepatosomatic index and viscerosomatic index. In addition, increased lipid levels also increased the crude lipid content and reduced the crude protein content in muscle tissue. Oil red O staining showed that the liver lipid content increased with the level of supplemented fish oil, which is consistent with the results of the hepatosomatic index. Compared with CG, triglyceride, total cholesterol, and low-density lipoprotein cholesterol increased significantly in both the liver and serum when fish oil levels exceeded 8.5% (p < 0.05), while high-density lipoprotein cholesterol decreased significantly. Aspartate transaminase and cerealthirdtransaminase levels in serum increased significantly when fish oil levels exceeded 8.5% (p < 0.05). Moreover, the activities of antioxidant enzymes (GSH-Px, SOD, T-AOC, and CAT) and MDA showed similar results, indicating that high fish oil levels (8.5-13.5%) caused liver tissue damage in M. sinensis. Increased fish oil levels significantly upregulated the expression levels of cytokines (IFN-γ, TNF-α, TGF-ß1, IL-10, and IL-12) (p < 0.05), downregulated the expression levels of antioxidant enzyme-related genes (cat, mn-sod, and gsh-px), and increased apoptosis of liver cells. Supplementation of the diet with 3.5-6% fish oil improved the growth performance of M. sinensis, and the turtles maintained a beneficial immune status. The results provide a scientific basis for optimizing the commercial feed formula of M. sinensis.

Two-Dimensional Atomically Thin Piezoelectric Nanosheets for Efficient Pyroptosis-Dominated Sonopiezoelectric Cancer Therapy.

Sonopiezocatalytic therapy is an emerging therapeutic strategy that utilizes ultrasound irradiation to activate piezoelectric materials, inducing polarization and energy band bending to facilitate the generation of reactive oxygen species (ROS). However, the efficient generation of ROS is hindered by the long distance of charge migration from the bulk to the material surface. Herein, atomically thin Bi2O2(OH)(NO3) (AT-BON) nanosheets are rationally engineered through disrupting the weaker hydrogen bonds within the [OH] and [NO3] layer in the bulk material. The ultrathin structure of AT-BON piezocatalytic nanosheets shortens the migration distance of carriers, expands the specific surface area, and accelerates the charge transfer efficiency, showcasing a natural advantage in ROS generation. Importantly, the non-centrosymmetric polar crystal structure grants the nanosheets the ability to separate electron-hole pairs. Under ultrasonic mechanical stress, Bi2O2(OH)(NO3) nanosheets with the remarkable piezoelectric feature exhibit the desirable in vivo antineoplastic outcomes in both breast cancer model and liver cancer model. Especially, the AT-BON-induced ROS bursts lead to the activation of the Caspase-1-driven pyroptosis pathway. This study highlights the beneficial impact of bulk material thinning on enhancing ROS generation efficiency and anti-cancer effects.

Enhanced Propylene/Propane Separation via Aniline-Decorated ZIF-8 Membrane: Lattice Rigidity Adjustment and Adsorption Site Introduction.

Metal-organic framework (MOF)-based membranes excel in molecular separation, attracting significant research interest. The crystallographic microstructure and selective adsorption capacity of MOFs closely correlate with their gas separation performance. Here, aniline was added to the ZIF-8 synthesis in varying concentrations. Aniline, encapsulated within ZIF-8 cavities, interacts strongly with the 2-methylimidazole linker, resulting in both a shift in crystallographic phase from I_43m to Cm in Rietveld refinement of X-ray diffraction (XRD) patterns and the selective adsorption behavior between propylene and propane. Consequently, an aniline decorative ZIF-8 (Anix-ZIF-8) membrane was prepared using a fast current-driven synthesis method, which exhibits good propylene/propane separation selectivity of up to 85. Calculation of the interaction energy between aniline and the various crystallographic phases of ZIF-8 using density functional theory (DFT) further verifies that aniline not only promotes the formation of crystallographic Cm phase, but also enhances the adsorption selectivity of propylene over propane. Aniline modification effectively tunes the crystallographic microstructure of ZIF-8, thereby, improving molecular sieving capabilities.

Lysosomal TFEB-TRPML1 Axis in Astrocytes Modulates Depressive-like Behaviors.

Lysosomes are important cellular structures for human health as centers for recycling, signaling, metabolism and stress adaptation. However, the potential role of lysosomes in stress-related emotions has long been overlooked. Here, it is found that lysosomal morphology in astrocytes is altered in the medial prefrontal cortex (mPFC) of susceptible mice after chronic social defeat stress. A screen of lysosome-related genes revealed that the expression of the mucolipin 1 gene (Mcoln1; protein: mucolipin TRP channel 1) is decreased in susceptible mice and depressed patients. Astrocyte-specific knockout of mucolipin TRP channel 1 (TRPML1) induced depressive-like behaviors by inhibiting lysosomal exocytosis-mediated adenosine 5'-triphosphate (ATP) release. Furthermore, this stress response of astrocytic lysosomes is mediated by the transcription factor EB (TFEB), and overexpression of TRPML1 rescued depressive-like behaviors induced by astrocyte-specific knockout of TFEB. Collectively, these findings reveal a lysosomal stress-sensing signaling pathway contributing to the development of depression and identify the lysosome as a potential target organelle for antidepressants.

Extraction of antimicrobial peptides from pea protein hydrolysates by sulfonic acid functionalized biochar.

The extraction methods for antimicrobial peptides (AMPs) from plants are varied, but the absence of a standardized and rapid technique remains a challenge. In this study, a functionalized biochar was developed and characterized for the extraction of AMPs from pea protein hydrolysates. The results indicated that the biochar mainly enriched AMPs through electrostatic interaction, hydrogen bonding and pore filling. Then three novel cationic antimicrobial peptides were identified, among which the RDLFK (Arg-Asp-Leu-Phe-Lys) had the greatest inhibitory effect against Staphylococcus aureus and Bacillus subtilis, showcasing IC50 value of 2.372 and 1.000 mg/mL, respectively. Additionally, it was found that RDLFK could damage bacterial cell membranes and penetrate the cells to inhibit DNA synthesis. These results provided that the biochar-based extraction method presents an efficient and promising avenue for isolating AMPs, addressing a critical gap in the current methodologies for their extraction from plant sources.

Procedural volume is linearly associated with mortality, major complications, and readmissions in patients undergoing malignant brain tumor resection.

PURPOSE: Improved outcomes have been noted in patients undergoing malignant brain tumor resection at high-volume centers. Studies have arbitrarily chosen high-volume dichotomous cutoffs and have not evaluated volume-outcome associations at specific institutional procedural volumes. We sought to establish the continuous association of volume with patient outcomes and identify cutoffs significantly associated with mortality, major complications, and readmissions. We hypothesized that a linear volume-outcome relationship can estimate likelihood of adverse outcomes when comparing any two volumes. METHODS: The patient cohort was identified with ICD-10 coding in the Nationwide Readmissions Database(NRD). The association of volume and mortality, major complications, and 30-/90-day readmissions were evaluated in multivariate analyses. Volume was used as a continuous variable with two/three-piece splines, with various knot positions to reflect the best model performance, based on the Quasi Information Criterion(QIC). RESULTS: From 2016 to 2018, 34,486 patients with malignant brain tumors underwent resection. When volume was analyzed as a continuous variable, mortality risk decreased at a steady rate of OR 0.988 per each additional procedure increase for hospitals with 1-65 cases/year(95% CI 0.982-0.993, p < 0.0001). Risk of major complications decreased from 1 to 41 cases/year(OR 0.983, 95% CI 0.979-0.988, p < 0.0001), 30-day readmissions from 1 to 24 cases/year(OR 0.987, 95% CI 0.979-0.995, p = 0.001) and 90-day readmissions from 1 to 23 cases/year(OR 0.989, 95% CI 0.983-0.995, p = 0.0003) and 24-349 cases/year(OR 0.9994, 95% CI 0.999-1, p = 0.01). CONCLUSION: In multivariate analyses, institutional procedural volume remains linearly associated with mortality, major complications, and 30-/90-day readmission up to specific cutoffs. The resulting linear association can be used to calculate relative likelihood of adverse outcomes between any two volumes.

Limb circumference measurements contributing to the diagnosis of snake venom-induced compartment syndrome.

Background: The present study aimed to investigate the relationship between swollen limb circumference and compartment pressure after a snakebite and to evaluate the diagnostic value of the circumference difference between the healthy and affected sides and the circumference growth rate for snake venom-induced compartment syndrome (CS). Method: The study was based on a prospective cohort study of snakebite patients at the emergency department of West China Hospital from May 2021 to October 2022. The snakebite patients were divided into the CS and non-compartment syndrome (NCS) groups. The diagnostic value of the circumference of the swollen limb for the CS after snakebite was evaluated using a receiver-operating characteristic curve analysis, and the cut-off value of the circumference of the swollen limb for CS after snakebite was calculated with sensitivity and specificity. Result: The present study enrolled 115 patients with severely swollen limbs after snakebite. The mean age was 59.1 ± 13.6 years, with 58 (50.4 %) female cases and 57 (49.6 %) male cases. There were 33 (28.7 %) cases where the upper limbs were injured and 82 (71.3 %) cases where the lower limbs were injured. These patients were divided into CS (n = 19) and NCS (n = 96) groups. The area under the curve (AUC) for the 15 cm circumference difference and circumferential growth rate of the upper edge of the patella was 0.683 (95 % CI 0.508 to 0.858, P = 0.037), and 0.685 (95 % CI 0.512 to 0.858, P = 0.035). The optimal cut-off values for the 15 cm circumference difference and circumferential growth rate of the upper edge of the patella to distinguish CS and NCS were 2.8 cm (sensitivity = 76.9 %, specificity = 66.7 %) and 7 % (sensitivity = 76.9 %, specificity = 66.7 %), respectively. Conclusion: Limb circumference measurement is a non-invasive, convenient, effective, and repeatable bedside test that can assist clinicians in the early detection of suspected snake venom-induced CS in patients exhibiting limb swelling after snake bites.

A GDSL motif-containing lipase modulates Sclerotinia sclerotiorum resistance in Brassica napus.

Sclerotinia stem rot (SSR) caused by Sclerotinia sclerotiorum (Lib.) De Bary is a devastating disease infecting hundreds of plant species. It also restricts the yield, quality, and safe production of rapeseed (Brassica napus) worldwide. However, the lack of resistance sources and genes to S. sclerotiorum has greatly restricted rapeseed SSR-resistance breeding. In this study, a previously identified GDSL motif-containing lipase gene, Brassica napus GDSL LIPASE-LIKE 1 (BnaC07.GLIP1), encoding a protein localized to the intercellular space, was characterized as functioning in plant immunity to S. sclerotiorum. The BnaC07.GLIP1 promoter is S. sclerotiorum-inducible and the expression of BnaC07.GLIP1 is substantially enhanced after S. sclerotiorum infection. Arabidopsis (Arabidopsis thaliana) heterologously expressing and rapeseed lines overexpressing BnaC07.GLIP1 showed enhanced resistance to S. sclerotiorum, whereas RNAi suppression and CRISPR/Cas9 knockout B. napus lines were hyper-susceptible to S. sclerotiorum. Moreover, BnaC07.GLIP1 affected the lipid composition and induced the production of phospholipid molecules, such as phosphatidylethanolamine, phosphatidylcholine and phosphatidic acid, which were correlated with decreased levels of reactive oxygen species (ROS) and enhanced expression of defense-related genes. A B. napus bZIP44 transcription factor specifically binds the CGTCA motif of the BnaC07.GLIP1 promoter to positively regulate its expression. BnbZIP44 responded to S. sclerotiorum infection, and its heterologous expression inhibited ROS accumulation, thereby enhancing S. sclerotiorum resistance in Arabidopsis. Thus, BnaC07.GLIP1 functions downstream of BnbZIP44 and is involved in S. sclerotiorum resistance by modulating the production of phospholipid molecules and ROS homeostasis in B. napus, providing insights into the potential roles and functional mechanisms of BnaC07.GLIP1 in plant immunity and for improving rapeseed SSR disease-resistance breeding.

M3NetFlow: A novel multi-scale multi-hop graph AI model for integrative multi-omic data analysis.

Multi-omic data-driven studies, characterizing complex disease signaling system from multiple levels, are at the forefront of precision medicine and healthcare. The integration and interpretation of multi-omic data are essential for identifying molecular targets and deciphering core signaling pathways of complex diseases. However, it remains an open problem due the large number of biomarkers and complex interactions among them. In this study, we propose a novel Multi-scale Multi-hop Multi-omic graph model, M3NetFlow, to facilitate generic multi-omic data analysis to rank targets and infer core signaling flows/pathways. To evaluate M3NetFlow, we applied it in two independent multi-omic case studies: 1) uncovering mechanisms of synergistic drug combination response (defined as anchor-target guided learning), and 2) identifying biomarkers and pathways of Alzheimer 's disease (AD). The evaluation and comparison results showed M3NetFlow achieves the best prediction accuracy (accurate), and identifies a set of essential targets and core signaling pathways (interpretable). The model can be directly applied to other multi-omic data-driven studies. The code is publicly accessible at: https://github.com/FuhaiLiAiLab/M3NetFlow.

Prehospital Intervention Among Black Patients With Traumatic Injury in Los Angeles County.

This cohort study examined the differences in prehospital treatment received by patients with traumatic injury belonging to different racial and ethnic groups between 2013 and 2020 in Los Angeles County.

Application of Eight Machine Learning Algorithms in the Establishment of Infertility and Pregnancy Diagnostic Models: A Comprehensive Analysis of Amino Acid and Carnitine Metabolism.

To explore the effects of altered amino acids (AAs) and the carnitine metabolism in non-pregnant women with infertility (NPWI), pregnant women without infertility (PWI) and infertility-treated pregnant women (ITPW) compared with non-pregnant women (NPW, control), and develop more efficient models for the diagnosis of infertility and pregnancy, 496 samples were evaluated for levels of 21 AAs and 55 carnitines using targeted high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Three methods were used to screen the biomarkers for modeling, with eight algorithms used to build and validate the model. The ROC, sensitivity, specificity, and accuracy of the infertility diagnosis training model were higher than 0.956, 82.89, 66.64, and 82.57%, respectively, whereas those of the validated model were higher than 0.896, 77.67, 69.72, and 83.38%, respectively. The ROC, sensitivity, specificity, and accuracy of the pregnancy diagnosis training model were >0.994, 96.23, 97.79, and 97.69%, respectively, whereas those of the validated model were >0.572, 96.39, 93.03, and 94.71%, respectively. Our findings indicate that pregnancy may alter the AA and carnitine metabolism in women with infertility to match the internal environment of PWI. The developed model demonstrated good performance and high sensitivity for facilitating infertility and pregnancy diagnosis.