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Abstract Chimeric antigen receptor T (CAR-T) cell therapy has greatly improved the prognosis of relapsed and refractory patients with large B-cell lymphoma (LBCL). Early identification and intervention of patients who may respond poorly to CAR-T cell therapy will help to improve the efficacy. Ninety patients from a Chinese cohort who received CAR-T cell therapy and underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans at the screening stage (median time to infusion 53.5 days, range 27–176 days), 1 month and 3 months after CAR-T cell infusion were analyzed, with RNA-sequencing conducted on 47 patients at the screening stage. Patients with maximum diameter of the largest lesion (Dmax)

Abstract Poultry meat, an essential source of animal protein, requires stringent safety and quality measures to address public health concerns and growing international attention. This review examines both direct and indirect factors that compromise poultry meat quality in intensive farming systems. It highlights the integration of rapid and micro-testing with traditional methods to assess meat safety. The paper advocates for adopting probiotics, prebiotics, and plant extracts to improve poultry meat quality.

C24H18N6O7Na2, monoclinic, I2/a (no. 15), a = 9.9773(6) Å, b = 18.2319(14) Å, c = 14.2858(9) Å, β = 108.686(7)°, V = 2461.7(3) Å3, Z = 4, Rgt(F) = 0.0337, wRref(F2) = 0.0939, T = 200 K.

C12H14N4O4, triclinic, P1‾$P\overline{1}$ (no. 2), a = 6.79127(19) Å, b = 10.0328(3) Å, c = 10.0542(2) Å, α = 90.027(2)°, β = 97.124(2)°, γ = 101.983(3)°, V = 664.71(3) Å3, Z = 2, Rgt(F) = 0.0539, wRref(F2) = 0.1580, T = 292 K.

Introduction: Novel biomarkers reflecting liver fibrosis and the immune microenvironment may correlate with the risk of hepatocellular carcinoma (HCC) recurrence. This study aimed to evaluate the prognostic value of serum biomarkers in predicting HCC recurrence. Methods: Serum biomarkers, including M2BPGi, IL-6, IL-10, CCL5, VEGF-A, soluble PD-1, PD-L1, TIM-3, and LAG-3, were measured in 247 patients with HCC undergoing surgical resection. Factors associated with recurrence-free survival (RFS) and overall survival (OS) were evaluated. The ERASL-post model and IMbrave050 criteria were used to define HCC recurrence risk groups. Results: Serum M2BPGi levels significantly correlated with FIB-4 score, aspartate transaminase-to-platelet ratio index, ALBI score, alpha-fetoprotein (AFP), alanine transaminase, aspartate transaminase, IL-10, CCL5, VEGF-A, soluble PD-1, PD-L1, TIM-3, and LAG-3 levels. M2BPGi, VEGF-A, soluble PD-1, and TIM-3 levels significantly correlated with RFS. In multivariate analysis, M2BPGi >1.5 COI (hazard ratio [HR] = 2.100, p < 0.001), tumor size >5 cm (HR = 1.859, p = 0.002), multiple tumors (HR = 2.562, p < 0.001), AFP >20 ng/mL (HR = 2.141, p < 0.001), and microvascular invasion (HR = 1.954, p = 0.004) were independent predictors of RFS. M2BPGi levels significantly stratified the recurrence risk in ERASL-post and IMbrave050 risk groups. An M2BPGi-based model could significantly discriminate RFS in the overall cohort as well as in the IMbrave050 low- and high-risk groups. M2BPGi >1.5 COI was also an independent predictor of OS after resection (HR = 2.707, p < 0.001). Conclusion: Serum M2BPGi levels significantly correlated with surrogate markers of liver fibrosis, liver function, and immunology. M2BPGi is a significant predictor of HCC recurrence and survival after resection and could be incorporated into recurrence-prediction models.

Abstract Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated promising efficacy in early trials for relapsed/refractory diffuse large B cell lymphoma (DLBCL). However, its efficacy in treating primary refractory DLBCL has not been comprehensively investigated, and the underlying resistance mechanisms remain unclear. Here, we report the outcomes of a phase I, open-label, single-arm clinical trial of relmacabtagene autoleucel (relma-cel), a CD19-targeted CAR-T cell product, with safety and efficacy as primary endpoints. Among the 12 enrolled patients, 8 experienced grade 4 hematologic toxicity of treatment-emergent adverse event. No grade ≥3 cytokine release syndrome or neurotoxicity occurred. Single-cell RNA sequencing revealed an increase proportion of C1QB-expressing macrophages in patients with progressive disease before CAR-T cell therapy. Cholesterol efflux from M2 macrophages was found to inhibit CAR-T cells cytotoxicity by inducing an immunosuppressive state in CD8+ T cells, leading to their exhaustion. Possible interactions between macrophages and CD8+ T cells, mediating lipid metabolism (AFR1-FAS), immune checkpoint activation, and T cell exhaustion (LGALS9-HAVCR2, CD86-CTLA4, and NECTIN2-TIGIT) were enhanced during disease progression. These findings suggest that cholesterol efflux from macrophages may trigger CD8+ T cell exhaustion, providing a rationale for metabolic reprogramming to counteract CAR-T treatment failure. Chinadrugtrials.org.cn identifier: CTR20200376.

Immune checkpoint blockade (ICB) treatment has demonstrated excellent medical effects in oncology, and it is one of the most sought after immunotherapies for tumors. However, there are several issues with ICB therapy, including low response rates and a lack of effective efficacy predictors. Gasdermin-mediated pyroptosis is a typical inflammatory death mode. We discovered that increased expression of gasdermin protein was linked to a favorable tumor immune microenvironment and prognosis in head and neck squamous cell carcinoma (HNSCC). We used the mouse HNSCC cell lines 4MOSC1 (responsive to CTLA-4 blockade) and 4MOSC2 (resistant to CTLA-4 blockade) orthotopic models and demonstrated that CTLA-4 blockade treatment induced gasdermin-mediated pyroptosis of tumor cells, and gasdermin expression positively correlated to the effectiveness of CTLA-4 blockade treatment. We found that CTLA-4 blockade activated CD8+ T cells and increased the levels of interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α) cytokines in the tumor microenvironment. These cytokines synergistically activated the STAT1/IRF1 axis to trigger tumor cell pyroptosis and the release of large amounts of inflammatory substances and chemokines. Collectively, our findings revealed that CTLA-4 blockade triggered tumor cells pyroptosis via the release of IFN-γ and TNF-α from activated CD8+ T cells, providing a new perspective of ICB.

Abstract Background Epstein–Barr virus (EBV) is a double‐stranded DNA herpesvirus and establishes life‐long infection in 95% of the world's populations. Main body EBV is critically involved in multiple diseases. Aberrant signaling pathways, immune escape, and metabolic reprogramming play essential roles in EBV‐mediated pathogenesis. However, the underlying mechanisms have not yet been fully elucidated. Here we reviewed recent advances on the epigenetic regulation of EBV pathogenesis, which may translate to potential therapeutic strategies in EBV‐associated diseases. Conclusion Growing evidence has suggested that viral infections reconstruct epigenome to modulate gene expression both in the host and the virus levels.

ObjectiveTo determine the comparative effects and safety of traditional Chinese medicine (TCM) interventions based on meridian theory for pain relief in patients with primary dysmenorrhea (PD).MethodsThis is a systematic review with network meta-analysis. Randomized controlled trials (RCTs) comparing meridian-based TCM interventions with waitlist, placebo, western medicine, and conventional therapies for PD pain. A SUCRA was used to estimate the probability ranking for the effects of interventions.Results57 RCTs involving 3,903 participants and 15interventions were included. Thirty-two RCTs were rated as low risk of bias. A network diagram was drawn with 105 pairs of comparisons. Compared with NSAIDs and waitlist, significantly better effects were found in acupressure [SMD = −1.51, 95%CI (−2.91, −0.12)/SMD = −2.31, 95%CI (−4.61, −0.02)], warm needling [SMD = −1.43, 95%CI (−2.68, −0.18)/SMD = −2.23, 95%CI (−4.43, −0.03)], moxibustion [SMD = −1.21, 95%CI (−1.85, −0.57)/SMD = −2.10, 95%CI (−3.95, −0.07)], and acupuncture [SMD = −1.09, 95%CI (−1.62, −0.55)/SMD = −1.89, 95%CI (−3.67, −0.11)]. No adverse events were detected.ConclusionFor PD pain, the effects of acupressure, acupuncture, warm needling, and moxibustion were superior to those of NSAIDs and waitlist. Oral contraceptive pill, electro-acupuncture, acupressure, and warm needling demonstrated higher probabilities of being better interventions. More high-quality clinical trials are needed to provide more robust evidence of this network.Systematic review registrationPROSPERO CRD42022373312.

Summary: Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous disease with dismal outcomes. We conducted an open-label, phase 2 nonrandomised, externally controlled study to evaluate the efficacy and safety of targeted agents plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) (CHOPX) for PTCL in the front-line setting. Methods: Eligible patients were ≥18 years of age and newly diagnosed PTCL. Patients in the CHOPX group received standard CHOP at Cycle 1. Specific targeted agents were added from Cycle 2, decitabine if TP53mut, azacytidine if TET2/KMT2Dmut, tucidinostat if CREBBP/EP300mut, and lenalidomide if without mutations above. Patients in the CHOP group received CHOP for 6 cycles. The primary endpoint was the complete response rate (CRR) at the end of treatment (EOT). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. The study was registered with ClinicalTrials.gov, NCT04480099. Findings: Between July 29, 2020, and Sep 22, 2022, 96 patients were enrolled and included for efficacy and safety analysis with 48 in each group. The study met its primary endpoint. CRR at EOT in the CHOPX group was superior to the CHOP group (64.6% vs. 33.3%, OR 0.27, 95%CI 0.12–0.64; p = 0.004). At a median follow-up of 24.3 months (IQR 12.0–26.7), improved median PFS was observed in the CHOPX group (25.5 vs. 9.0 months; HR 0.57, 95%CI 0.34–0.98; p = 0.041). The median OS was similar between two groups (not reached vs. 30.9 months; HR 0.55, 95%CI 0.28–1.10; p = 0.088). The most common grade 3–4 hematological and non-hematological adverse events in the CHOPX group were neutropenia (31, 65%) and infection (5, 10%). Interpretation: Targeted agents combined with CHOP demonstrated effective and safe as first-line treatment in PTCL. Biomarker-driven therapeutic strategy is feasible and may lead to promising efficacy specifically toward molecular features in PTCL. Funding: This study was supported by the National Key Research and Development Program (2022YFC2502600) and the General Program of the Shanghai Municipal Health Commission (202040400).

C36H42N4O10Mg, monoclinic, C2/c (no. 15), a = 16.4977(12) Å, b = 16.3866(10) Å, c = 12.5814(10) Å, β = 101.922(8)°, V = 3327.9(4) Å3, Z = 4, Rgt (F) = 0.0794, wRref (F 2) = 0.2021, T = 260 K.

Abstract Background Drawing on the extensive utilization of traditional Chinese medicine (TCM) to combat COVID-19 in Mainland China, experts designed a series of TCM anti-epidemic strategies. This study aims to understand Hong Kong CM practitioners’ application of and opinions on the “Chinese Medicine Anti-epidemic Plans.” Methods Online focus group interviews were conducted, and purposive sampling was employed to invite 22 CM practitioners to voluntarily participate in three interview sessions. The interviews were audio recorded, then transcribed verbatim. The transcripts were analyzed using template analysis. Results Three themes were derived: (1) facilitators of the “Chinese Medicine Anti-epidemic Plans,” (2) barriers of the “Chinese Medicine Anti-epidemic Plans,” and (3) expectations on improving the “Chinese Medicine Anti-epidemic Plans.” The participants could obtain relevant information from various sources, which highlights the value of the plans for TCM medicinal cuisine and non-pharmacologic therapies and guiding junior CM practitioners, supplementing Western medicine interventions, and managing Chinese herb reserves in clinics. However, the barriers included the lack of a specialized platform for timely information release, defective plan content, limited reference value to experienced CM practitioners, and lack of applicability to Hong Kong. The expectations of the CM practitioners for improving the plans were identified based on the barriers. Conclusions To enhance the implementation of the anti-epidemic plans, CM practitioners in Hong Kong expect to utilize a specific CM platform and refine the plans to ensure that they are realistic, focused, comprehensive, and tailored to the local context.

Abstract Natural killer T cell lymphoma (NKTCL) is highly aggressive, with advanced stage patients poorly responding to intensive chemotherapy. To explore effective and safe treatment for newly diagnosed advanced stage NKTCL, we conducted a phase II study of anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab (NCT04096690). Twenty-two patients with a median age of 51 years (range, 24–74) were enrolled and treated with induction treatment of pegaspargase 2500 IU/m2 intramuscularly on day 1 and sintilimab 200 mg intravenously on day 2 for 6 cycles of 21 days, followed by maintenance treatment of sintilimab 200 mg for 28 cycles of 21 days. The complete response and overall response rate after induction treatment were 59% (95%CI, 43–79%) and 68% (95%CI, 47–84%), respectively. With a median follow-up of 30 months, the 2 year progression-free and overall survival rates were 68% (95%CI, 45–83%) and 86% (95%CI, 63–95%), respectively. The most frequently grade 3/4 adverse events were neutropenia (32%, n = 7) and hypofibrinogenemia (18%, n = 4), which were manageable and led to no discontinuation of treatment. Tumor proportion score of PD-L1, peripheral blood high-density lipoprotein cholesterol, and apolipoprotein A-I correlated with good response, while PD-1 on tumor infiltrating lymphocytes and peripheral Treg cells with poor response to pegaspargase plus sintilimab treatment. In conclusion, the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed, advanced stage NKTCL. Dysregulated lipid profile and immunosuppressive signature contributed to treatment resistance, providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.

Objective: To systematically evaluate and synthesize quantitative evidence regarding the effects of pediatric massage in infants and children under five years. Review methods: We conducted searches in databases including MEDLINE, Embase, Health Technology Assessment Database, the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Allied and Complementary Medicine, Embase, the China National Knowledge Infrastructure, Wanfang Data, SinoMed, and CQVIP up to February 2024. Two reviewers independently screened articles, extracted data, and conducted quality appraisals on the included studies. We focused on systematic reviews with meta-analyses comparing pediatric tuina with a waitlist control, placebo, medication, massage combined with other interventions, and usual care. Outcomes analyzed included physical, psychological, developmental, and safety-related measures for children and their caregivers. Methodological quality was assessed using AMSTAR 2, and evidence quality was evaluated using the GRADE approach. Pooled effect estimates and heterogeneity were extracted for each meta-analyzed outcome. Evidence evaluated as ‘high’ and ‘moderate’ quality by GRADEpro with low heterogeneity are presented in the result section. Results: Twenty-two systematic reviews with meta-analysis of 81 outcomes were included. Seven studies (31.8 %) were high quality, and the evidence of 6 (7.4 %) outcomes were evaluated as high quality. The meta-analysis results demonstrate significant benefits of pediatric massage for infants compared to routine care, with increased weight gain (MD 455.07 g; 95 % CI 86.33 to 823.8; I2 = 0 %) based on 2 studies with 157 cases, length growth (MD 1.58 cm; 95 % CI 1.42 to 1.74; I2 = 25 %) from 9 studies with 1294 cases, reduced fussing (MD -0.37 time; 95 % CI -0.53 to -0.21; I2 = 30 %) according to 3 studies with 271 cases, and lower post-intervention bilirubin levels (3 studies/345 cases; MD -31.75 mmol/L; 95 % CI -40.05 to -23.46; I2 = 0 %). Pediatric massage was associated with reduced diarrhea incidence compared to waitlist controls (2 RCTs/310 cases; RR 0.39; 95 % CI 0.2 to 0.76; I2 = 0 %) and improved psychomotor development indices (4 RCTs/466 cases; SMD -0.35; 95 % CI -0.54 to -0.15; I2 = 1.06 %). Additionally, pediatric massage significantly enhanced blood oxygen saturation variation post-procedure for pain management (5 RCTs/355 cases; MD 1.05; 95 % CI 0.51 to 1.58; I2 = 0 %). Conclusions: Pediatric massage significantly enhances mother-child attachment, promotes physical growth, reduces fussing, lowers bilirubin levels, improves motor and psychomotor development, as well as manages digestive conditions and pain in children under 5 years. Future research should improve study quality and comprehensively report adverse events.

Accessible silicate reservoirs on Earth (i.e., the depleted mantle and continental crust) are depleted in Nb relative to chondrites, as expressed by their subchondritic Nb/Ta ratios. Mixtures of continental crust and depleted mantle cannot produce chondritic Nb/Ta ratios; therefore, another geochemical reservoir with a superchondritic Nb/Ta ratio is necessary to balance the low Nb contents of the continental crust. We investigated alkaline igneous rocks with superchondritic Nb/Ta ratios (20.4–24.8). Their high Nb/Ta ratios were inherited from their lithospheric mantle source rather than being produced by magmatic differentiation. Geochemical data show that an enriched mantle domain with superchondritic Nb/Ta ratios can be produced by the interaction of subducted carbonate-rich sediment-derived melts with the lithospheric mantle, and the enriched lithospheric mantle is a potential superchondritic reservoir.

BackgroundResistance training is often a part of the routine training regimen for competitive swimmers. However, due to the variety of resistance training methodology, the results can be inconsistent and sometimes unsatisfactory. Clear recommendations are still lacking at present.Aims1) Quantify the impact of resistance training on swimmers’ upper limb maximum strength, front crawl performance and key technical parameters; 2) Find out the key technical parameters for improving front crawl performance—stroke rate or length; 3) Through subgroup analysis determine the best methodology of resistance training to enhance the front crawl.MethodsSystematic search in the PubMed, Embase, and Web of Science databases. Meta-analyses using the inverse-variance are performed to compare swimmers’ upper limb maximum strength, front crawl performance and key technical parameters in resistance training and habitual aquatic training. A subgroup analysis was performed to examine whether the results were affected by the methodology of resistance training.ResultsThirteen studies (267 competitive swimmers) met the inclusion criteria. The results of meta-analysis showed that resistance training significantly improved upper limbs maximum muscle strength, and 25, 50, 100, and 200 m front crawl performance in competitive swimmers. And improvements in swimming performance may simply resulted from resistance training increasing stroke rate rather than stroke length. In addition, the results of subgroup analysis showed that only concurrent resistance training (CRT) and power training (PT) ultimately improved swimming performance by increasing the maximum muscle strength of the upper limbs.ConclusionResistance training significantly enhances competitive swimmers’ upper limb strength and front crawl performance across various distances. The improvement in performance is likely attributed to an increased stroke rate rather than stroke length. In addition, CRT and PT are particularly effective, indicating the importance of selecting the appropriate methodology of resistance training for optimal swimming performance enhancement.Systematic review registrationhttps://doi.org/10.17605/OSF.IO/3JEGW.

Abstract BackgroundExercise offers substantial health benefits but can induce oxidative stress and inflammation, especially in high-intensity formats such as high-intensity interval exercise (HIIE). Exergaming has become an effective, enjoyable fitness tool for all ages, particularly older adults. Enzyme supplements may enhance exercise performance by improving lactate metabolism and reducing oxidative stress. ObjectiveThis study investigates the efficacy of fruit and vegetable enzyme supplementation in modulating fatigue and enhancing aerobic capacity in older adults following HIIE through exergaming. MethodsThe study recruited 16 older adult female participants and allocated them into 2 distinct groups (enzyme and placebo) based on their pretest lactate levels. This division used pairwise grouping to guarantee comparability between the groups, ensuring the integrity of the results. They engaged in HIIE using Nintendo Switch Ring Fit Adventure, performing 8 sets of 20 seconds of maximum effort exercise interspersed with 30 seconds of rest, totaling 370 seconds of exercise. Key metrics assessed included blood lactate levels, heart rate, rating of perceived exertion, and training impulse. Participants in the enzyme group were administered a fruit and vegetable enzyme supplement at a dosage of 30 mL twice daily over a period of 14 days. ResultsThe enzyme group showed significantly lower blood lactate levels compared to the placebo group, notably after the fourth (mean 4.29, SD 0.67 vs mean 6.34, SD 1.17 mmol/L; PPPP ConclusionsThe study indicates that fruit and vegetable enzyme supplementation can significantly reduce blood lactate levels in older adults following HIIE through exergaming. This suggests a potential role for these enzymes in modulating lactate production or clearance during and after high-intensity exercise. These findings have implications for developing targeted interventions to enhance exercise tolerance and recovery in older adults.

ABSTRACT Plant‐based proteins continue to gain popularity as a sustainable alternative to animal proteins due to their nutritional, functional and health benefits. Dry and wet fractionation methods are increasingly being used for the production of value‐added pulse protein ingredients. The objective of this study was to compare the nutritional properties, protein quality, physicochemical properties and secondary structure of Australian faba bean and yellow pea protein concentrates and protein isolates obtained by dry and wet fractionation. Amino acid scores highlighted that faba bean and yellow pea protein isolates and concentrates were deficient in the sulphur‐containing amino acids, methionine and cysteine and tryptophan. Faba bean (63.7%) and yellow pea protein (63.0%) isolates had higher in vitro protein digestibility‐corrected amino acid scores compared to the protein concentrates, being 50.7% and 54.4%, respectively. Fourier‐transform infrared spectroscopy revealed different secondary structures between protein concentrates and isolates, especially for the amide I region. Faba bean and yellow pea protein concentrates had higher protein solubility (46.2% and 50.1%, respectively) and higher foaming capacity (65% and 59%, respectively) compared to the protein isolates. Water‐holding capacity was higher for faba bean and yellow pea protein isolates, being 4.3% and 4.0 g/g, respectively. These findings demonstrate that faba bean and yellow pea protein concentrates and isolates have unique functional properties that can be exploited for use in a diverse range of new and existing food applications.

ObjectiveTo examine the dose–response relationship between specific types of exercise for alleviating Timed up and Go (TUG) in Parkinson’s disease PD.DesignSystematic review and Bayesian network meta-analysis.Data sourcesPubMed, Medline, Embase, PsycINFO, Cochrane Library, and Web of Science were searched from inception until February 5th, 2024.Study analysisData analysis was conducted using R software with the MBNMA package. Effect sizes of outcome indicators were expressed as mean deviation (MD) and 95% confidence intervals (95% CrI). The risk of bias in the network was evaluated independently by two reviewers using ROB2.ResultsA total of 73 studies involving 3,354 PD patients. The text discusses dose–response relationships in improving TUG performance among PD patients across various exercise types. Notably, Aquatic (AQE), Mix Exercise (Mul_C), Sensory Exercise (SE), and Resistance Training (RT) demonstrate effective dose ranges, with AQE optimal at 1500 METs-min/week (MD: −8.359, 95% CI: −1.398 to −2.648), Mul_C at 1000 METs-min/week (MD: −4.551, 95% CI: −8.083 to −0.946), SE at 1200 METs-min/week (MD: −5.145, 95% CI: −9.643 to −0.472), and RT at 610 METs-min/week (MD: −2.187, 95% CI: −3.161 to −1.278), respectively. However, no effective doses are found for Aerobic Exercise (AE), Balance Gait Training (BGT), Dance, and Treadmill Training (TT). Mind–body exercise (MBE) shows promise with an effective range of 130 to 750 METs-min/week and an optimal dose of 750 METs-min/week (MD: −2.822, 95% CI: −4.604 to −0.996). According to the GRADE system, the included studies’ overall quality of the evidence was identified moderate level.ConclusionThis study identifies specific exercise modalities and dosages that significantly enhance TUG performance in PD patients. AQE emerges as the most effective modality, with an optimal dosage of 1,500 METs-min/week. MBE shows significant benefits at lower dosages, catering to patients with varying exercise capacities. RT exhibits a nuanced “U-shaped” dose–response relationship, suggesting an optimal range balancing efficacy and the risk of overtraining. These findings advocate for tailored exercise programs in PD management, emphasizing personalized prescriptions to maximize outcomes.Systematic Review Registration: International Prospective Register of Systematic Reviews (PROSPERO) (CRD42024506968).

ObjectivesTo explore the correlation between mitochondrial quantity and the blastocyst development timeline as well as their respective contributions to early pregnancy.MethodsA retrospective study was conducted using a dataset comprising 2,633 embryos that underwent preimplantation genetic testing for aneuploidy (PGT-A) between January 2016 and December 2023. The study was divided into three subsets to address distinct aspects: the representativeness of a single trophectoderm (TE) biopsy for mitochondrial quantity (n=43), the correlation between morphokinetic features and mitochondrial quantity (n=307), and the association analysis among mitochondrial quantity, blastocyst timeline factor, and reproductive outcomes (n=2,283). Distribution assessment of mitochondrial quantity across an individual blastocyst involved the identification within multiple biopsies and spent culture media. Timeline evaluation included correlating mitochondrial quantity with time-lapse datasets. Finally, multivariate logistic regression models, incorporating potential effectors alongside mitochondrial quantity, were employed to analyze their respective contributions to early pregnancy endpoints.ResultsOf distribution assessment, mitochondrial quantity exhibited an even distribution across the entire trophectoderm (Spearman’s ρ=0.82), while no detectable mtDNAs in the corresponding spent culture media. Then the timeline correlation study revealed significant association between mitochondrial quantity and blastocyst features of both the day of expanded blastocyst formation (95% Confidence intervals, CIs: 0.27~4.89, p=0.03) and the timing of expanded blastocyst formation (tEB) (95% CIs: -0.24~-0.01, p=0.04) in the regression model, indicating a strong dependency between mitochondrial quantity and the blastocyst development timeline. For the contribution to early pregnancy, multivariate logistic regression models showed that the day of expanded blastocyst formation contributed to four endpoints persistently: positive for HCG (odd ratio, OR: 0.71, p=0.006), gestational sac (OR: 0.78, p=0.04), fetal heartbeat (OR: 0.71, p=0.004), and progression to 14 weeks (OR: 0.69, p=0.002). Contrastingly, no notable correlation was observed between the mitochondrial quantity and these endpoints.ConclusionsStrong interaction was observed between mitochondrial quantity and the blastocyst timeline, particularly the timing of expanded blastocyst formation. It suggests that the primary determinant influencing pregnancy outcomes lies in the time-dependent parameter of blastocyst rather than in the specific mitochondrial quantity.

The parameter mismatch caused by the parameter uncertainties and unknown disturbances degrades the performance of finite-control-set model predictive control (FCS-MPC). This paper presents a model-free fault-tolerant predictive control (MFFTPC) method based on an extended sliding mode observer (ESMO) for the surface-mounted permanent magnet synchronous motor (SPMSM) drive system. First, considering parameter uncertainties and unknown disturbances, a novel ultra-local model (ULM) is established for the PMSM drive system. Next, a finite-control-set model-free fault-tolerant predictive current controller (FCS-MFFTPCC) is designed in the current loop, and the model-free deadbeat fault-tolerant predictive speed controller (MFDFTPSC) is designed in the speed loop. Then, unknown parts of the novel ULM are estimated by the designed ESMO and compensated for the errors caused by the parameter mismatches. Thus, the presented method reduces the dependence on the precise model and eliminates the effect caused by parameter mismatches on the MPC control performance of the SPMSM drive system.