A screening strategy for identifying umami peptides with multiple bioactivities from Stropharia rugosoannulata using in silico approaches and SPR sensing.

Umami peptides from natural resources have garnered considerable attention for their potential bioactivities and flavor-enhancing characteristics. In this study, we constructed a database comprising 123 peptides from Stropharia rugosoannulata and screened for umami peptides with both angiotensin I-converting enzyme (ACE) and dipeptidyl peptidase-4 (DPP-IV) inhibitory activities using online prediction tools and molecular docking, and further confirmed by SPR sensing, intelligent sensory and activities test. Five peptides with varying chain lengths were synthesized and by evaluations analyses they exhibited strong umami, with thresholds ranging from 0.105 mmol/L to 0.547 mmol/L. According to the targeted SPR molecular interaction analysis, umami peptides and hT1R3 receptor exhibited a "fast-on/fast-off" binding mode with stronger intensity and persistence than MSG. Furthermore, in vitro experiments revealed that five peptides showed potent ACE and DPP-IV inhibitory activities. Notably, the EAF inhibitory activity was the most significant among the peptides. This comprehensive screening strategy provides a rapid approach for identifying high-sensitivity umami peptides with bioactivities.

Nano polystyrene microplastics could accumulate in Nile tilapia (Oreochromis niloticus): Negatively impacts on the intestinal and liver health through water exposure.

Microplastics (MPs) have become a significant concern for their potential toxicity. However, the correlation between the size of plastic particles and their toxicity remains inconclusive. Here, we investigate the toxic effects of different sizes (80 nm, 800 nm, 8 µm and 80 µm) polystyrene MPs (PS-MPs) on the model organism Nile tilapia (Oreochromis niloticus). The results of bioluminescent imaging indicate that the 80 nm PS-MPs are more likely to invade the body. H&E staining shows severe damage on the intestinal villi and distinct hepatic steatosis in the 80 nm group. EdU labeling shows that the proliferation activity of intestinal and liver cells reduces significantly in the 80 nm group. The gut microbiome analysis shows a severe imbalance of gut microbiota homeostasis in the 80 nm group. The analysis of liver transcriptomics and metabolomics shows that the liver lipid metabolism is disordered in the 80 nm group. In conclusion, this study confirms that the 80 nm PS-MPs are more likely to induce intestinal and liver toxicity. All the above lay the foundation for further study on the pathological damage of MPs to other organisms.

Calculation and analysis of agricultural carbon emission efficiency considering water-energy-food pressure: Modeling and application.

Agricultural carbon emission efficiency (ACEE) measurement, a tool for effectively achieving sustainable development goals, has garnered much attention. However, the impacts of resource pressures such as water, energy and food on ACEE have been overlooked, and the high dimensionality of the measurement model and insufficient sample data can easily distort the measurement results. Therefore, from a green development perspective, we established a new ACEE measurement framework considering the water-energy-food pressure index and a new integrated ACEE measurement model (CSMA-PPE-USSBM) that includes chaotic maps, the slime mould algorithm (SMA), projection pursuit evaluation (PPE) and the undesirable super slack-based measure (USSBM). The model was used to calculate ACEE in 13 prefecture-level municipalities in Heilongjiang Province, China, and analyze its spatiotemporal evolution and possible causes. The results showed that this model avoids the above problems. The reliability coefficient and stability coefficient reached 0.962 and 0.971, respectively; ACEE in Heilongjiang Province has much room for improvement, but there are obvious differences in carbon emission efficiency in different carbon emission type regions. The key driving forces of ACEE variation can generate significant scale effects. Provincial driving factors can affect ACEE variation in prefecture municipalities, where the influence range is limited or the influence of driving factors gradually emerges. The research results provide a theoretical reference for accurately measuring the regional ACEE and analyzing the driving mechanism of ACEE and green agricultural development.

Coiled-coil scallops (Chlamys farreri) peptide hydrogel with metal ionic and temperature tunable assembly.

Self-assembly of peptides is a powerful method of preparing nanostructured materials. Peptides frequently utilize charged groups as a convenient switch for controlling assembly state by pH, ionic strength or temperature. In this study, the molecular properties and gel-forming ability of Chlamys farreri protein hydrolysates were studied. According to self-assembled theory, the presence of isoleucine at position 'a' and leucine at 'd' causes a switch between coiled-coil structures. Compared to P-2-CG, the components of α-helix (23.60 ± 0.56%) were changed into ß-sheet (4.83 ± 2.86%) in the secondary structure of the hydrogel induced by ZnCl2. NMR siginals appeared at high field,which indicated hydrogen bonds were formed between P-2-CG and solvent environments at 20 °C. With temperature going up, the hydrogen bonds were broken and nanofibrils were changed into dense aggregates. We expected that P-2-CG could provide a new candidate for preparing metal-induced nanofibers or hydrogels with further applications in food industry.

CO2 storage in organic nanopores with varying widths: Molecular simulation and simplified local density model.

Accurately characterizing CO2 adsorption behavior in organic nanopores is a prerequisite for estimating CO2 storage capacity in shale reservoirs with complex pore structures. This study employs grand canonical Monte Carlo (GCMC) molecular simulations to investigate the CO2 adsorption characteristics in organic nanopores with varying widths over a wide range of temperatures and pressures. Based on GCMC simulations, the pore width in the simplified Local-Density (SLD) adsorption model is related to key adsorption parameters, enabling the SLD model to evaluate CO2 storage density rapidly and accurately in organic nanopores under complex reservoir conditions. The research findings suggest that the features of CO2 excess adsorption curves are mainly influenced by temperature and the number of adsorption layers. Higher temperatures and increased adsorption layers result in higher pressure requirements to achieve the CO2 excess adsorption peak. Under high pressures, the number of adsorption layers plays a critical role in enhancing the adsorption capacity. Due to the constraints of pore size, there are fewer adsorption layers in micropores, leading to higher CO2 excess adsorption in mesopores than in micropores under high pressures. In the SLD model, the key parameter Λb decays exponentially with the increase of pore width. The average density of CO2 in the nanopores calculated by the modified SLD model is in good agreement with the simulation results. Finally, the research reveals that smaller organic nanopore widths result in higher CO2 densities, with limited sensitivity to temperature and pressure variations. Low pressure and high temperature reservoir conditions are unfavorable for CO2 storage, but adsorption significantly enhances CO2 storage density in nanopores, particularly in micropores.

A fluorescent dual-emitting platform for fluorescent "turn-on" ratiometric detection of ascorbic acid in beverages utilizing luminol-embedded iron-based metal-organic frameworks.

A fluorescent dual-emitting platform for fluorescent "turn-on" ratiometric detection of ascorbic acid in beverages was developed utilizing luminol-embedded iron-based metal-organic frameworks (luminol@Fe-DOBDC MOFs). Luminol@Fe-DOBDC MOFs with fluorescent emissions at 430 nm and 540 nm under excitation wavelength of 365 nm were applied to detect ascorbic acid on the basis of ascorbic acid triggering the reduction of Fe3+ into Fe2+. In the presence of ascorbic acid, fluorescent intensity at 540 nm was increased significantly while fluorescent intensity at 430 nm was changed slightly. Two emission peaks separated by 110 nm can eliminate environmental interferences by built-in self-calibration of ratiometric signal, enhancing the sensitivity and accuracy. The increasing ratiometric fluorescent intensity (I540 nm/I430 nm) has linear relationship with the concentration of ascorbic acid from 0.2 to 30 µM with limit of detection of 70 nM. It is an efficient, sensitive and accurate platform to detect ascorbic acid in commercial beverages using transition-metal-based MOFs.

A bifunctional core-shell gold@Prussian blue nanozyme enabling dual-readout microfluidic immunoassay of food allergic protein.

Food allergy has posed a great threat for public health due to its rising prevalence worldwide, and thus sensitive and reliable food allergen monitoring methods is of great significance. In this study, we prepared a bifunctional core-shell gold@Prussian blue nanoparticles (Au@PBNP) nanozyme, which not only could serve as an alternative to natural peroxidase for colorimetric immunoassay, but also act as a unique Raman label in Raman-silent region (1800-2800 cm-1) for SERS analysis. By combining microfluidic device, smartphone, and portable Raman spectrometer, a new smartphone/SERS dual-readout microfluidic immunoassay platform was established for portable detection of food allergic protein (i.e., alpha-lactalbumin (α-LA)). The established method for detection of α-LA showed a LOD of 0.011 ng/mL in a liner range of 0.2-600 ng/mL. Furthermore, this method was also challenged in spiked food samples with good average recoveries, showing a great potential in practical applications.

A performance degradation model of nitrile butadiene rubber (NBR) O-rings for hydrogen permeation effects under high-pressure.

The integration of molecular chain changes on a microscopic scale to achieve macroscopic performance is crucial in degradation processes concerning O-ring seals. Nonetheless, a comprehensive and compelling mathematical model that can describe molecular chains' material properties and macroscopic material properties simultaneously for O-rings under high-pressure conditions is yet to be established. In this paper, we propose a degradation model based on viscoelasticity and molecular chain statistics for hydrogen permeation. The proposed model aims to establish the relationship between the material molecular chains and macroscopic material properties, with a primary focus on accurately recognizing the performance degradation process of rubber sealing rings. We verify the model's reliability through uniaxial tensile strength experiments and high-pressure hydrogen immersion experiments, respectively. Predictions of the model exhibit favorable conformity with the experimental data concerning the above phenomena. Furthermore, we derive the number of molecular chains and maximum strain of the degradation process. Based on the similarity of the degradation process's descent, it is plausible to speculate that NBR properties' degradation can be characterized by the average number of molecular chains.

Investigating the relationship between inhibitory control and dietary adherence among patients with type 2 diabetes mellitus based on subjective and objective measures.

BACKGROUND: Dietary management has been recommended as the cornerstone of type 2 diabetes mellitus (T2DM) management. However, low adherence to dietary recommendations has been identified in both developed and developing countries. Previous research suggests that inhibitory control influences eating behavior, but few studies have been conducted in patients with T2DM. Thus, we aimed to explore the relationship between inhibitory control and dietary adherence among patients with T2DM. METHODS: A total of 393 patients with T2DM from the endocrinology departments of three tertiary hospitals in China were enrolled by the convenience sampling method. Dietary adherence was measured by the Dietary Behavior Adherence Scale for Patients with Type 2 Diabetes Mellitus. Additionally, inhibitory control was subjectively measured by the Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A) and objectively assessed by the stop signal task (SST) and the Stroop task. The relationship between inhibitory control and dietary adherence was analyzed using Pearson correlation analysis and hierarchical regression analysis. RESULTS: Subjectively measured inhibitory control had a significant predictive effect for dietary adherence after controlling for demographic and clinical variables. Adding the inhibitory control variable to the regression equation resulted in the following values: overall model F (19, 373) = 7.096, p < 0.001, increase in R2 value by 0.069, change in F (1, 373) = 35.219, p < 0.001. Similarly, the performance of the Stroop task had a significant predictive effect for dietary adherence to some foods, i.e., carbohydrate and fat. Adding the Stroop effect variable to the regression equation resulted in the following values: overall model F (19, 81) = 2.848, p = 0.005, increase in R2 value by 0.060, change in F (1, 81) = 8.137, p = 0.006. CONCLUSIONS: Inhibitory control was a predictor of dietary adherence in patients with T2DM. Future interventions should investigate whether inhibitory control training results in the improvement of dietary adherence in patients with T2DM.

ACS-20/FATP4 mediates the anti-ageing effect of dietary restriction in C. elegans.

Dietary restriction is an effective anti-ageing intervention across species. However, the molecular mechanisms from the metabolic aspects of view are still underexplored. Here we show ACS-20 as a key mediator of dietary restriction on healthy ageing from a genetic screen of the C. elegans acyl-CoA synthetase family. ACS-20 functions in the epidermis during development to regulate dietary restriction-induced longevity. Functional transcriptomics studies reveal that elevated expression of PTR-8/Patched is responsible for the proteostasis and lifespan defects of acs-20. Furthermore, the conserved NHR-23 nuclear receptor serves as a transcriptional repressor of ptr-8 and a key regulator of dietary restriction-induced longevity. Mechanistically, a specific region in the ptr-8 promoter plays a key role in mediating the transcription regulation and lifespan extension under dietary restriction. Altogether, these findings identify a highly conserved lipid metabolism enzyme as a key mediator of dietary restriction-induced lifespan and healthspan extension and reveal the downstream transcriptional regulation mechanisms.

Postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement in patients with childhood-onset craniopharyngioma.

Objective: Hypothalamic-pituitary axis dysfunction is a common complication in post-operative craniopharyngioma(CP) patients, and it greatly impacts the long-term quality of life of such patients. To better understand the effects of postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement therapy in patients with childhood CP, we assessed approximately 200 patients with childhood-onset CP postoperatively. Methods: Clinical details of patients with childhood-onset CP who underwent sellar tumor resection in Beijing Children's Hospital and Beijing Tiantan Hospital from 2018 to 2019 were retrieved retrospectively. The participants were followed up to assess the effects of post-operative long-term hormone replacement therapy and assess the tumor recurrence rate. Results: The median age of admission was 8.1 (1.8, 14.3) years. Headache (45.5%), visual impairment (39.5%), and nausea (33.0%) were the most common clinical manifestations. ACP accounted for 95% of all CP cases. The incidence of central adrenal insufficiency and central hypothyroidism within the first week after surgery was 56.2% and 70.3%, respectively. At the same time 85.5% of the patients required at least one dose of desmopressin to control urine output. Total survival and tumor recurrence rates were 98.6% and 26.1%, respectively, with a median follow-up time of 29.7 (19.0, 40.3) months. During the follow-up period, 28.1% patients met the diagnostic criteria for short stature, while 54.4% fit the criteria for obesity. In addition, 94.4% of the patients were taking at least one kind of hormone substitution, and 74.7% were taking three or more. The prevalence of levothyroxine, glucocorticoid, desmopressin, and growth hormone replacement therapy was 87.3%, 77.5%, 78.9% and 31.0%, respectively. The proportion of patients treated with the substitutive combination of levothyroxine, hydrocortisone, and desmopressin was 54.9%. Conclusion: This study is a large-sample systematic postoperative endocrine function evaluation of patients with childhood-onset CP. Due to the high prevalence of post-operative hypothalamic-pituitary dysfunction, patients with CP usually require long-term multiple hormone substitution therapy. Individualized management and accurate hormone replacement dosage for postoperative childhood-onset CP patients are of great importance.

Postoperative acute kidney injury after on-pump cardiac surgery in patients with connective tissue disease.

Objective: Patients with connective tissue disease have a poor prognosis after receiving cardiac surgery. This study described the clinical scenarios and investigated factors correlated with acute kidney injury (AKI) after on-pump cardiac surgery in patients with systemic lupus erythematosus (SLE) or vasculitis. Methods: Patients with SLE or vasculitis who underwent on-pump cardiac surgery from March 2002 to March 2022 were enrolled, while patients with preoperative renal dysfunction were excluded. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Uni- and multivariable analyses were performed to identify potential factors associated with postoperative AKI. Results: Among 123 patients enrolled, 39 (31.7%) developed AKI within seven days after receiving on-pump cardiac surgery. Four patients died in the hospital, resulting in an overall in-hospital mortality of 3.3%, and all deaths occurred in the AKI group. Patients in the AKI group also had longer ICU stays (median difference 3.0 day, 95% CI: 1.0-4.0, P < 0.001) and extubation time (median difference 1.0 days, 95% CI: 0-2.0, P < 0.001) than those in the non-AKI group. Multivariable logistic regression revealed that BMI over 24 kg/m2 (OR: 3.00, 95% CI: 1.24-7.28) and comorbid SLE (OR: 4.73, 95% CI: 1.73-12.93) were independently correlated with postoperative AKI. Conclusion: Factors potentially correlated with AKI following on-pump cardiac surgery in patients with connective tissue disease were explored. Clinicians should pay more attention to preoperative evaluation and intraoperative management in patients with risk factors.

Domain-Limited Sub-Nanometer Co Nanoclusters in Defective Nitrogen Doped Carbon Structures for Non-Invasive Drug Monitoring.

In this work, sub-nanometer Co clusters anchored on porous nitrogen-doped carbon (C─N─Co NCs) are successfully prepared by high-temperature annealing and pre-fabricated template strategies for non-invasive sensing of clozapine (CLZ) as an efficient substrate adsorption and electrocatalyst. The introduction of Co sub-nanoclusters (Co NCs) provides enhanced electrochemical performance and better substrate adsorption potential compared to porous and nitrogen-doped carbon structures. Combined with ab initio calculations, it is found that the favorable CLZ catalytic performance with C─N─Co NCs is mainly attributed to possessing a more stable CLZ adsorption structure and lower conversion barriers of CLZ to oxidized state CLZ. An electrochemical sensor for CLZ detection is conceptualized with a wide operating range and high sensitivity, with monitoring capabilities validated in a variety of body fluid environments. Based on the developed CLZ sensing system, the CLZ correlation between blood and saliva and the accuracy of the sensor are investigated by the gold standard method and the rat model of drug administration, paving the way for non-invasive drug monitoring. This work provides new insights into the development of efficient electrocatalysts to enable drug therapy and administration monitoring in personalized healthcare systems.

Object detection: A novel AI technology for the diagnosis of hepatocyte ballooning.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has reached epidemic proportions worldwide and is the most frequent cause of chronic liver disease in developed countries. Within the spectrum of liver disease in MAFLD, steatohepatitis is a progressive form of liver disease and hepatocyte ballooning (HB) is a cardinal pathological feature of steatohepatitis. The accurate and reproducible diagnosis of HB is therefore critical for the early detection and treatment of steatohepatitis. Currently, a diagnosis of HB relies on pathological examination by expert pathologists, which may be a time-consuming and subjective process. Hence, there has been interest in developing automated methods for diagnosing HB. This narrative review briefly discusses the development of artificial intelligence (AI) technology for diagnosing fatty liver disease pathology over the last 30 years and provides an overview of the current research status of AI algorithms for the identification of HB, including published articles on traditional machine learning algorithms and deep learning algorithms. This narrative review also provides a summary of object detection algorithms, including the principles, historical developments, and applications in the medical image analysis. The potential benefits of object detection algorithms for HB diagnosis (specifically those combined with a transformer architecture) are discussed, along with the future directions of object detection algorithms in HB diagnosis and the potential applications of generative AI on transformer architecture in this field. In conclusion, object detection algorithms have huge potential for the identification of HB and could make the diagnosis of MAFLD more accurate and efficient in the near future.

General Self-Efficacy in Association With Insomnia Symptoms and Suicidal Ideation Among Chinese Community-Based Population.

Previous studies supported the association between insomnia symptoms and suicidal ideation in patients with mental or psychological diseases. This study aimed to examine the associations between insomnia symptoms, general self-efficacy, and suicidal ideation among community-based adult population. Standardized questionnaire was distributed to 2051 community-dwelling adults in Lishui district of Jiangsu Province in China, to assess their socio-demographics, insomnia symptoms, general self-efficacy, and suicidal ideation. Multiple binary logistic regression or linear regression and mediation analysis with bootstrap resampling method were performed. Results showed that the weighted prevalence of lifetime suicidal ideation was 6.38%. Insomnia symptom was associated with higher odds of suicidal ideation after adjusting for sociodemographics and mental health status (odds ratio [OR] = 2.85, 95% confidence interval [CI] [1.66, 4.89]), and the OR of insomnia symptom with suicidal ideation decreased but remained significant after additionally adjusting for general self-efficacy (OR = 2.62, 95% CI [1.52, 4.53]). Participants with insomnia symptom were also significantly associated with lower general self-efficacy (ß = -0.96; 95% CI [-1.70, -0.21]), whereas higher general self-efficacy was associated with a lower odds of suicidal ideation (OR = 0.92, 95% CI [0.87, 0.99]). In conclusion, general self-efficacy was associated with both insomnia symptom and suicidal ideation among the community-dwelling adult population.

A Novel Neurovascular Protection Method In Nasolabial Muscle Biomechanical Bionic Surgery For Secondary Unilateral Cleft Lip Repair: A Three-Dimensional Evaluation Of Short And Long-Term Results.

BACKGROUND: Neurovascular protection within the upper lip muscles is essential in muscle tension reconstruction and functional recovery during surgery. This study aimed to investigate a novel neurovascular protection method based on the intramuscular neurovascular partitions of the upper lip applied to nasolabial muscle biomechanical bionic surgery for secondary unilateral cleft lip repair and to evaluate postoperative outcomes. METHODS: From November 30, 2019 to October 31, 2020, 50 consecutive patients with secondary unilateral cleft lips who underwent the modified biomechanical bionic surgery were reviewed retrospectively. Three-dimensional (3D) photographs of patients were collected preoperatively, 7-day postoperatively, and during long-term follow-up (at least 6 months). The Global Aesthetic Improvement Scale was used to evaluate surgical subjective outcomes, and statistical analysis of nasolabial measurements on 3D photographs was used to evaluate objective outcomes before and after surgery. RESULTS: The Global Aesthetic Improvement Scale showed that 94% of patients had improved upper lip morphology and 92% had improved nasal morphology 7-day postoperatively. In all, 84% maintained favorable nasolabial morphology during long-term follow-up. Statistical results showed that the postoperative alar width, philtral depth, columellar angle, and nasal base inclination angle were significantly improved compared with preoperatively (P<0.01). The differences between the above 4 indexes were not statistically significant (P >0.05) between 7-day postoperatively and long-term follow-up, indicating that the postoperative lasting outcomes were satisfactory. CONCLUSIONS: The novel method of neurovascular protection in nasolabial muscle biomechanical bionic surgery can achieve a long-term improvement of labial-nasal morphology and function in patients with secondary unilateral cleft lip.

New dammarane-type triterpenoids from hydrolyzate of total Gynostemma pentaphyllum saponins with protein tyrosine phosphatase 1B inhibitory activity.

Protein tyrosine phosphatase 1B (PTP1B) is a key factor and regulator of glucose, lipid metabolism throughout the body, and a promising target for treatment of type 2 diabetes mellitus (T2DM). Gynostemma pentaphyllum is a famous oriental traditional medicinal herbal plant and functional food, which has shown many beneficial effects on glucose and lipid metabolism. The aim of the present study is to assess the inhibitory activity of five new and four known dammarane triterpenoids isolated from the hydrolysate product of total G. pentaphyllum saponins. The bioassay data showed that all the compounds exhibited significant inhibitory activity against PTP1B. The structure-activity relationship showed that the strength of PTP1B inhibitory activity was mainly related to the electron-donating group on its side chain. Molecular docking analysis suggested that its mechanism may be due to the formation of competitive hydrogen bonding between the electron-donating moiety and the Asp48 amino acid residues on the PTP1B protein.

Digestate induces significantly higher N2O emission compared to urea under different soil properties and moisture.

Digestate is considered as an option for recycling resources and a part of the substitution for chemical fertilizers to reduce environmental impacts. However, its application may lead to significant nitrous oxide (N2O) emissions because of its high concentration of ammonium and degradable carbon. The research objectives are to evaluate how N2O emissions respond to digestate as compared to urea application and whether this depends on soil properties and moisture. Either digestate or urea (100 mg N kg-1) was applied with and without a nitrification inhibitor of 3,4-dimethylpyrazole phosphate (DMPP) to three soil types (fluvo-aquic soil, black soil, and latosol) under three different soil moisture conditions (45, 65, and 85% water-filled pore space (WFPS)) through microcosm incubations. Results showed that digestate- and urea-induced N2O emissions increased exponentially with soil moisture in the three studied soils, and the magnitude of the increase was much greater in the alkaline fluvo-aquic soil, coinciding with high net nitrification rate and transient nitrite accumulation. Compared with urea-amended soils, digestate led to significantly higher peaks in N2O and carbon dioxide (CO2) emissions, which might be due to stimulated rapid oxygen consumption and mineralized N supply. Digestate-induced N2O emissions were all more than one time higher than those induced by urea at the three moisture levels in the three studied soils, except at 85% WFPS in the fluvo-aquic soil. DMPP was more effective at mitigating N2O emissions (inhibitory efficacy: 73%-99%) in wetter digestate-fertilized soils. Overall, our study shows the contrasting effect of digestate to urea on N2O emissions under different soil properties and moisture levels. This is of particular value for determining the optimum of applying digestate under varying soil moisture conditions to minimize stimulated N2O emissions in specific soil properties.

Haplotype-based noninvasive prenatal diagnosis of methylmalonic acidemia and the discovery of a recurrent pathogenic haplotype associated with c.609G>A.

BACKGROUND: Early diagnosis and intervention are crucial for the prognosis of methylmalonic acidemia (MMA). However, research focused on early prenatal diagnosis of MMA is limited. METHODS: A 161.89kb capture panel was designed for selectively enriching highly heterozygous SNPs. Fetal genotypes were inferred using relative haplotype dosage (RHDO) and Bayes factor, followed by invasive prenatal diagnosis (IPD) for validation. A core pathogenic haplotype associated with c.609G>A was identified based on the frequency differences between pathogenic and normal haplotypes. RESULTS: We recruited 41 pregnancies at risk of MMA with a median gestational age of 8+2  weeks. The assay success rate of NIPD-MMA for maternal variants was 92.7% (38/41), and after incorporating the paternal result, the overall assay success rate reached 100% (41/41). All NIPD results were concordant with IPD. Notably, a core haplotype (hap_2), comprising 28 SNPs, demonstrates significant enrichment within pathogenic haplotypes bearing the c.609G>A variation. On average, c.609G>A carriers had 22.38 heterozygous loci within these 28 SNPs. CONCLUSION: NIPD-MMA presents a viable choice for early, accurate, and safe prenatal diagnosis. Furthermore, the discovery of the recurrent core pathogenic haplotype provides a novel approach for haplotype phasing and has the potential for realizing proband-independent NIPD in the future.