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Objective To explore the specific mutations in mitochondrial genes of woman with unexplained complete early embryo development arrest in order to provide new data support for further elucidating the underlying mechanisms. Methods A case-control study was conducted on 46 infertile woman admitted to the Sixth Medical Center of Chinese PLA General Hospital from May 2021 to November 2022. All of them underwent peripheral blood whole exome sequencing and mitochondrial gene mutation detection. Ten patients with complete embryo development arrest were finally subjected and assigned into the study group, and another 15 patients with 3 or more transplantable embryos were enrolled into the control group. No chromosomal abnormalities were observed in both male and female partners of all above cases. Baseline clinical data and embryo development data were collected and compared between the 2 groups of patients. Mitochondrial gene mutation sites and their associated genes were analyzed in the 2 groups, and functional annotation was performed for the specific mutation sites/genes. Results There were 5 specific mitochondrial mutation sites identified in the study group: MT-16172 (T>C), MT-12882 (C>T), MT-12406 (G>A), MT-10609 (T>C), and MT-16129 (G>A). All these mutation sites are located on the genes of the mitochondrial respiratory chain complex and mitochondrial regulatory genes. Conclusion Five specific mitochondrial mutation sites [MT-16172(T>C)、MT-12882(C>T)、MT-12406(G>A)、MT-10609(T>C)、MT-16129(G>A)] may be related to unexplained early embryo development arrest.

Muscles play an indispensable role in human life. Surface electromyography (sEMG), as a non-invasive method, is crucial for monitoring muscle status. It is characterized by its real-time, portable nature and is extensively utilized in sports and rehabilitation sciences. This study proposed a wireless acquisition system based on multi-channel sEMG for objective monitoring of grip force. The system consists of an sEMG acquisition module containing four-channel discrete terminals and a host computer receiver module, using Bluetooth wireless transmission. The system is portable, wearable, low-cost, and easy to operate. Leveraging the system, an experiment for grip force prediction was designed, employing the bald eagle search (BES) algorithm to enhance the Random Forest (RF) algorithm. This approach established a grip force prediction model based on dual-channel sEMG signals. As tested, the performance of acquisition terminal proceeded as follows: the gain was up to 1125 times, and the common mode rejection ratio (CMRR) remained high in the sEMG signal band range (96.94 dB (100 Hz), 84.12 dB (500 Hz)), while the performance of the grip force prediction algorithm had an R2 of 0.9215, an MAE of 1.0637, and an MSE of 1.7479. The proposed system demonstrates excellent performance in real-time signal acquisition and grip force prediction, proving to be an effective muscle status monitoring tool for rehabilitation, training, disease condition surveillance and scientific fitness applications. [ABSTRACT FROM AUTHOR]

Non-additive factors can significantly affect the crystallization pathways and hydrate phases of calcium oxalate. However, little is known about the mechanisms behind these phenomena. Our research investigated various factors affecting calcium oxalate crystallization in the absence of additives. We show that the formation of calcium oxalate hydrate phase in a supersaturated solution is inconsistent with thermodynamic stability. The metastable calcium oxalate trihydrate (COT) forms at lower concentrations (<1.25 mM), while the stable calcium oxalate monohydrate (COM) forms at intermediate concentrations, and the metastable calcium oxalate dihydrate (COD) forms at higher concentrations (>20 mM). The formation of the hydrate phase also depends on the method of mixing calcium and oxalate solutions. By utilizing an automatic titration apparatus, we show that the hydrate phase can be altered by adjusting either the titration rate of the calcium solution or the stirring speed. In addition, the calcium-to-oxalate ratio is important in determining the initial binding between calcium and oxalate ions. All these factors could be explained by the local concentration of calcium and oxalate upon mixing the solutions. The reduction of local concentration promotes the formation of COT. Thus, the hydrate phase is determined by a combination of thermodynamic and kinetic factors. These results significantly enhance our understanding of the crystallization pathway and hydrate phase selection of calcium oxalate. [ABSTRACT FROM AUTHOR]

The construction of ecological spur dikes and deep pool shoals can increase the diversity of water flow structures while also hastening the transport and transformation of pollutants. However, current research has paid little attention to the effects of the arrangement parameters on water purification capacity when the ecological spur dikes and deep pool shoals are combined. In this study, we investigated the purification capacity of ammonia nitrogen using the combination of spur dikes and deep pool shoals through laboratory flume experiments and numerical simulation. The laboratory flume experiments revealed that the combination of staggered spur dikes and the opposite side deep pool shoals provided the most effective purification. Secondly, in order to obtain the optimal arrangement parameters for the combination of ecological spur dikes and deep pool shoals more easily, the numerical model based on MIKE21 was validated using experimental results and applied to Section 2 of the Shiqiao River in Nanling County, Wuhu City, Anhui Province. The numerical simulation showed that the length of the spur dikes had the greatest impact on the purification effect, followed by the spacing of the spur dikes and the width of the deep pool shoals, the angle of the spur dikes, the spacing of the deep pool shoals, and the length of the deep pool shoals had the least effect. The optimal parameters for the combination of spur dikes and deep pool shoals are as follows: spur dike parameters: 60°(angle), 10 m(length), 17 m(spacing); deep pool shoal parameters: 60 m(length), 10 m(width), and 210 m(spacing). [ABSTRACT FROM AUTHOR]

Prestress strategy is effective to inhibit crack advancement and toughen structural materials such as concrete and glass. However, it is difficult to be utilized in ceramic because of the solid‐state processing. In this work, nanocrystalline alumina ceramic with high compressive prestress and coherently aligned nanograins were successfully prepared by the ultra‐high pressure sintering technology. The as‐prepared ceramics exhibited remarkably enhanced mechanical properties, including hardness of 25.9 GPa and fracture toughness of 3.2 MPa·m1/2, which were respectively 36% and 51% higher than corresponding parameters of sapphire. Ultra‐high pressure generated compressive prestress as large as several hundred megapascal, and coherent nanograins in the dimensions of 10–15 nm, which markedly contributed to the simultaneously enhancement in toughness and hardness for ceramic materials. The prestressing strategy provides a new opportunity for fabricating advanced ceramics with high failure resistance. [ABSTRACT FROM AUTHOR]

HIV-1 protease (PR) plays a crucial role in the treatment of HIV as a key target. The global issue of emerging drug resistance is escalating, and PR mutations pose a substantial challenge to the effectiveness of inhibitors. HIV-1 PR is an ideal model for studying drug resistance to inhibitors. The inhibitor, darunavir (DRV), exhibits a high genetic barrier to viral resistance, but with mutations of residues in the PR, there is also some resistance to DRV. Inhibitors can impede PR in two ways: one involves binding to the active site of the dimerization protease, and the other involves binding to the PR monomer, thereby preventing dimerization. In this study, we aimed to investigate the inhibitory effect of DRV with a modified inhibitor on PR, comparing the differences between wild-type and mutated PR, using molecular dynamics simulations. The inhibitory effect of the inhibitors on PR monomers was subsequently investigated. And molecular mechanics Poisson–Boltzmann surface area evaluated the binding free energy. The energy contribution of individual residues in the complex was accurately calculated by the alanine scanning binding interaction entropy method. The results showed that these inhibitors had strong inhibitory effects against PR mutations, with GRL-142 exhibiting potent inhibition of both the PR monomer and dimer. Improved inhibitors could strengthen hydrogen bonds and interactions with PR, thereby boosting inhibition efficacy. The binding of the inhibitor and mutation of the PR affected the distance between D25 and I50, preventing their dimerization and the development of drug resistance. This study could accelerate research targeting HIV-1 PR inhibitors and help to further facilitate drug design targeting both mechanisms. [ABSTRACT FROM AUTHOR]

Bidirectional fermentation is a technology that utilizes fungi to ferment medicinal edible substrates, with synergistic and complementary advantages. In this work, a fermentation strategy was established to produce a high yield of γ-aminobutyric acid (GABA) and Monascus pigments (MPs) using Monascus and mulberry leaves (MLs). Firstly, the basic fermentation parameters were determined using single-factor experiments, followed by Plackett-Burman (PB) experimental design to identify MLs, glucose, peptone, and temperature as significant influencing factors. The fermentation parameters were optimized using an artificial neural network (ANN). Finally, the effects of bidirectional fermentation of MLs and Monascus were investigated by bioactivity analysis, microstructure observation, and RT-qPCR. The outcomes showed that the bidirectional fermentation significantly increased the bioactive content and promoted the secondary metabolism of Monascus. The established fermentation conditions were 44.2 g/L of MLs, 57 g/L of glucose, 15 g/L of peptone, 1 g/L of MgSO4, 2 g/L of KH2PO4, 8% (v/v) of inoculum, 180 rpm, initial pH 6, 32 °C and 8 days. The content of GABA reached 13.95 g/L and the color value of MPs reached 408.07 U/mL. This study demonstrated the feasibility of bidirectional fermentation of MLs and Monascus, providing a new idea for the application of MLs and Monascus. [ABSTRACT FROM AUTHOR]

A three-dimensional FEM(finite element model)is established, including penstocks with initial defect (ovality), backfill concrete, drainage cushion and surrounding rock. The nonlinear static calculation of the model is carried out. The stability of penstocks with backfill concrete, drainage cushion and surrounding rock under external pressure is studied. The sensibility of the embedded penstocks to initial defect, initial gap and elastic modulus of drainage cushion is analyzed. The results of finite element method, Jacobsen method and strength formula in SL281 are compared and analyzed. The results indicate that the FEM of penstocks, backfill concrete and surrounding rock with initial defects is easy to converge by nonlinear calculation; the ovality and gap have little influence on the critical external pressure of the embedded penstocks with stiffener ring, while the drainage cushion has a certain influence on the critical external pressure; the critical external pressure calculated by SL281 is low and safe; compared with Jacobsen method, the critical external pressure of the finite element method is increased by about 14%; for the embedded penstocks with drainage cushion, the finite element method can be used to calculate the influence of the drainage cushion on the critical external pressure, and the appropriate reduction factor can be obtained, and then the Jacobsen result can be modified by the reduction factor.

STUDY QUESTION Is the chromosome copy number of the trophectoderm (TE) of a human reconstituted embryos after spindle transfer (ST) representative of the inner cell mass (ICM)? SUMMARY ANSWER Single-cell multi-omics sequencing revealed that ST blastocysts have a higher proportion of cell lineages exhibiting intermediate mosaicism than conventional ICSI blastocysts, and that the TE of ST blastocysts does not represent the chromosome copy number of ICM. WHAT IS KNOWN ALREADY Preimplantation genetic testing for aneuploidy (PGT-A) assumes that TE biopsies are representative of the ICM, but the TE and ICM originate from different cell lineages, and concordance between TE and ICM is not well-studied, especially in ST embryos. STUDY DESIGN, SIZE, DURATION We recruited 30 infertile women who received treatment at our clinic and obtained 45 usable blastocysts (22 from conventional ICSI and 23 reconstituted embryos after ST). We performed single-cell multi-omics sequencing on all blastocysts to predict and verify copy number variations (CNVs) in each cell. We determined the chromosome copy number of each embryo by analysing the proportion of abnormal cells in each blastocyst. We used the Bland–Altman concordance and the Kappa test to evaluate the concordance between TE and ICM in the both groups. PARTICIPANTS/MATERIALS, SETTING, METHODS The study was conducted at a public tertiary hospital in China, where all the embryo operations, including oocytes retrieval, ST, and ICSI, were performed in the embryo laboratory. We utilized single-cell multi-omics sequencing technology at the Biomedical Pioneering Innovation Center, School of Life Sciences, Peking University, to analyse the blastocysts. Transcriptome sequencing was used to predict the CNV of each cell through bioinformatics analysis, and the results were validated using the DNA methylation library of each cell to confirm chromosomal normalcy. We conducted statistical analysis and graphical plotting using R 4.2.1, SPSS 27, and GraphPad Prism 9.3. MAIN RESULTS AND THE ROLE OF CHANCE Mean age of the volunteers, the blastocyst morphology, and the developmental ratewere similar in ST and ICSI groups. The blastocysts in the ST group had some additional chromosomal types that were prone to variations beyond those enriched in the blastocysts of the ICSI group. Finally, both Bland–Altman concordance test and kappa concordancetest showed good chromosomal concordance between TE and ICM in the ICSI blastocysts (kappa = 0.659, P  < 0.05), but not in ST blastocysts (P  = 1.000), suggesting that the TE in reconstituted embryos is not representative of ICM. Gene functional annotation (GO and KEGG analyses) suggests that there may be new or additional pathways for CNV generation in ST embryos compared to ICSI embryos. LIMITATIONS, REASONS FOR CAUTION This study was mainly limited by the small sample size and the limitations of single-cell multi-omics sequencing technology. To select eligible single cells, some cells of the embryos were eliminated or not labelled, resulting in a loss of information about them. The findings of this study are innovative and exploratory. A larger sample size of human embryos (especially ST embryos) and more accurate molecular genetics techniques for detecting CNV in single cells are needed to validate our results. WIDER IMPLICATIONS OF THE FINDINGS Our study justifies the routine clinical use of PGT-A in ICSI blastocysts, as we found that the TE is a good substitute for ICM in predicting chromosomal abnormalities. While PGT-A is not entirely accurate, our data demonstrate good clinical feasibility. This trial was able to provide correct genetic counselling to patients regarding the reliability of PGT-A. Regarding ST blastocysts, the increased mosaicism rate and the inability of the TE to represent the chromosomal copy number of the ICM are both biological characteristics that differentiate them from ICSI blastocysts. Currently, ST is not used clinically on a large scale to produce blastocysts. However, if ST becomes more widely used in the future, our study will be the first to demonstrate that the use of PGT-A in ST blastocysts may not be as accurate as PGT-A for ICSI blastocysts. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by grants from the National Key R&D Program of China (2018YFA0107601) and the National Key R&D Program of China (2018YFC1003003). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]