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Li Yang,1 Jing Yang,2 Guosen Bu,3 Rui Han,1 Jiamila Rezhake,1 Xiaolin La1 1Center of Reproductive Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, People’s Republic of China; 2Department of Gynaecology, The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, People’s Republic of ChinaCorrespondence: Xiaolin La, Center of Reproductive Medicine, The First Affiliated Hospital of Xinjiang Medical University, No. 137, Liyushannan Road, Urumqi, 830054, People’s Republic of China, Tel +86-991-4362889, Email 909232905@qq.comPurpose: Screening of pathological copy number variations (CNVs) is important for early-diagnosis of hereditary disease. This study was designed to investigate the efficiency of non-invasive prenatal testing (NIPT) in detecting fetal CNVs.Methods: This retrospective analysis included fetuses with CNVs between January 2018 and December 2020. Karyotype analysis and CNV sequencing (CNV-seq) were performed. We then analyzed the positive predictive values of the subchromosomal microdeletions and microduplications.Results: Fifty-eight subjects with aberrant CNVs were screened after NIPT, among which 44 finally underwent amniocentesis. CNV-seq confirmed the presence of CNVs in 24 cases. This indicated that false positivity rate of NIPT was 45.5%. Among 24 cases with CNVs after CNV-seq, only 4 showed consistent findings with karyotype analysis, which showed that karyotyping analysis yielded a missed diagnosis rate of 83.3% for the genome CNV. Positive predictive value (PPV) was 50.0% for CNVs with a length of < 5 Mb after NIPT screening. PPV for CNVs with a length of 5 Mb-10 Mb was 33.3%, while that for CNVs with a length of ≥ 10Mb was 60%. For CNVs duplication after NIPT, the PPV was 65.2%, while that for deletion was 36.4%.Conclusion: For CNVs detected after NIPT, it should be combined with ultrasonographic findings, karyotype analysis, CNV-seq or CMA to determine the pregnancy outcome. Expanding NIPT may increase the risk of unnecessary invasive surgery and unintended selective termination of pregnancy.Keywords: non-invasive prenatal screening, genome copy number variation, next-generation sequencing, prenatal diagnosis

Abstract Background Polyketide synthases (PKSs) are classified into three types based on their enzyme structures. Among them, type III PKSs, catalyzing the iterative condensation of malonyl-coenzyme A (CoA) with a CoA-linked starter molecule, are important synthases of valuable natural products. However, low efficiency and byproducts formation often limit their applications in recombinant overproduction. Results Herein, a rapid growth selection system is designed based on the accumulation and derepression of toxic acyl-CoA starter molecule intermediate products, which could be potentially applicable to most type III polyketides biosynthesis. This approach is validated by engineering both chalcone synthases (CHS) and host cell genome, to improve naringenin productions in Escherichia coli. From directed evolution of key enzyme CHS, beneficial mutant with ~ threefold improvement in capability of naringenin biosynthesis was selected and characterized. From directed genome evolution, effect of thioesterases on CHS catalysis is first discovered, expanding our understanding of byproduct formation mechanism in type III PKSs. Taken together, a whole-cell catalyst producing 1082 mg L−1 naringenin in flask with E value (evaluating product specificity) improved from 50.1% to 96.7% is obtained. Conclusions The growth selection system has greatly contributed to both enhanced activity and discovery of byproduct formation mechanism in CHS. This research provides new insights in the catalytic mechanisms of CHS and sheds light on engineering highly efficient heterologous bio-factories to produce naringenin, and potentially more high-value type III polyketides, with minimized byproducts formation.

Red abdominal shell disease is a major disease that has caused significant economic losses in Chinese soft-shelled turtle Pelodiscus sinensis aquaculture. Yet scarce information is available on Aeromonas dhakensis as a causal agent of red abdominal shell disease in P. sinensis. In the present study, a haemolytic and proteolytic A. dhakensis isolate (F04) was demonstrated as a causative agent of red abdominal shell disease in cultured P. sinensis. It carried virulent aerolysin, heat-labile cytotoxic enterotoxin, polar flagella, and lipase-encoding genes aer, alt, flaA, and lip, exhibited the mean lethal dose (LD50) value of 4.27×105 CFU/ml in P. sinensis, and developed multiple resistances against aminoglycosides, chloramphenicols, cephalosporins, lincosamides, macrolides, penicillins, peptides, sulfonamides, and tetracyclines antimicrobials. To our knowledge, this is the first study to identify a multiply resistant A. dhakensis strain as a pathogen of red abdominal shell disease in P. sinensis, and the findings of this study can also provide valuable insights into the virulence and antimicrobial resistance in Chinese soft-shelled turtle-pathogenic A. dhakensis.

Han Wu,&ast; Yang Zheng,&ast; Dan-Ni Liu, Xiao-Xia Liu, Qun-Di Yang, Qiu-Yun Su, Ying-Quan Wang, Yu-Zhuo Wang, Xue-Na La, Yan Shi,&ast; Chen Fu&ast; Division of Noncommunicable Diseases and Injury, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Shi; Chen Fu, Tel +86-21-62758710, Email shiyan@scdc.sh.cn; fuchen@scdc.sh.cnPurpose: This study aimed to investigate the relationship between sleep duration (SD) and stroke, and examine the effects of SD on stroke with or without metabolic syndrome (Mets) and its components among the adult residents in Shanghai, China.Participants and Methods: A total of 20,245 participants (51.72% male, mean age 44.66 years) were included from Shanghai Chronic Disease and Risk Factors Surveillance (SCDRFS) in 2017. The weighted logistic regressions were performed to examine the associations between SD and stroke in different status of Mets and its components.Results: The mean SD was 7.51± 0.03 h/d. After adjusting for all the potential factors, SD< 6 h/d (OR=1.73, 95% CI: 1.35– 2.20) or ≥ 10 h/d (OR=1.66, 95% CI: 1.08– 2.57) was significantly positively associated with stoke in the total participants; moreover, in the non-Mets group, only SD< 6 h/d (OR=1.77, 95% CI: 1.19, 2.64) significantly increased the risk of stroke; while, in the Mets group, SD< 6 h/d (OR=1.80, 95% CI:1.17– 2.76) and ≥ 10 h/d (OR=1.97, 95% CI: 1.00– 3.88) both had a positive significantly association with stoke. In addition, the effects of SD< 6 h/d on stroke were more pronounced among those with high WC (OR=2.24, 95% CI: 1.40– 3.58) and high TG (OR=2.60, 95% CI: 1.86– 3.62), and the effects of SD≥ 10 h/d on stroke were more evident among those with high TG (OR=2.28, 95% CI: 1.02– 5.08) and high FBG (OR=2.58, 95% CI: 1.30– 5.10).Conclusion: Both short and long SD were significantly positively associated with stroke in the total participants, and the associations were stronger in the Mets group; conversely, in the non-Mets group, only short SD was significantly positively associated with stroke, and no significant association was observed between long SD and stroke. Therefore, more precise sleep measures may be needed to prevent stroke according to the different status of Mets.Keywords: sleep duration, metabolic syndrome, stroke, Shanghai

The development of microbial communities is important for the growth of the fat greenling Hexagrammos otakii; however, the relationship between microbial communities and fish diet is poorly understood. Here, we used metagenomics sequencing to investigate the gut microbiota of H. otakii at three key time points during development. The gut microbial diversity and community composition of H. otakii presented stage-specific signatures and appeared to shift with different diets and environmental conditions such as NH4 + -NO2- etc. Metagenomics analysis indicated that the dominant phyla were Proteobacteria and Firmicutes. With dietary changes from rotifers and Artemia to formulated feed, the dominant genera shifted from Vibrio and Photobacterium to Lactococcus, and variations in the gut microbiota increased with age. Based on metagenomics functional annotation using the Kyoto Encyclopedia of Genes and Genomes database, growth and diet at different stages affected the metabolic function of the gut microbiome by activating carbohydrate and amino acid metabolism while weakening lipid and nucleotide metabolism. In addition, as predicted by the Carbohydrate-Active enZymes database, glycoside hydrolase and glycosyl transferases may be involved in food degradation. Our results suggest that the H. otakii gut microbiota assembly was coupled to animal development and host age-associated biotic features and changes. Diet had a considerable effect on these distinct communities at different times, indicating that the fish gut microbiota rapidly adapted to dietary shifts. The microbiota therefore likely plays an indispensable role in nutrient turnover and fermentation. These findings can provide guidance for the development of probiotics and the application of feed additives.

Purpose: The purpose of this study was to investigate the difference between the quantitative MRI values of Wiberg type III and stable patellar cartilage, and to improve the accuracy of MRI quantification in early patellar cartilage damage. Methods: The knee joints of 94 healthy volunteers were scanned by a GE Signa Pioneer 3.0-T synthetic MRI machine. According to the Wiberg classification, the patella was divided into types I-III. Types I-II made up the stable patella group, and type III made up the unstable patella group. Two radiologists independently measured patellar cartilage thickness and quantitative synthetic MRI values (T1, T2, PD) in both groups. Interobserver agreement for quantitative variables was assessed using the BlandAltman method. A third radiologist assessed differences in measurements. Results: The medial T2 and T1 value of Wiberg III patella did not show a normal distribution (all P > 0.05). Compared with the stable group, the Wiberg type III group had thinner cartilage of the medial surface of the patella (P 0.05). There was no significant difference in the cartilage thickness, T1, T2, or PD value of the lateral patella between the Wiberg type III and the stable group (P > 0.05). Conclusion: There were certain differences in the cartilage thickness of the medial surface of the patella and the quantitative value of synthetic MRI in Wiberg type III patellas. Quantitative studies of patellar cartilage MRI measurements need to consider the influence of patellar morphology.

To explore the effects of three pepper varieties on bacterial taxa and quality of Zhaguangjiao, Zhaguangjiao prepared using Capsicum frutescens Linn., Capsicum annuum L., and Capsicum annuum L. var. grossum (L.) Sendt. for the test group, while two control groups without the addition of any vegetables and with the addition of only Apium graveolens var. rapaceum were set up, and based on that, the quality of Zhaguangjiao was digitally evaluated and its bacterial taxa were resolved by high-throughput sequencing. Finally, the correlations between Zhaguangjiao quality and dominant bacterial genera were revealed. It was found that, compared with Zhaguangjiao prepared using Capsicum frutescens Linn., both the bacterial diversity and abundance of Zhaguangjiao prepared using Capsicum annuum L. and Capsicum annuum L. var. grossum (L.) Sendt. were higher. Zhaguangjiao prepared using Capsicum annuum L. and Capsicum annuum L. var. grossum (L.) Sendt. were dominated by Lactobacillus with average relative abundances of 77.53% and 94.41%, respectively, while Zhaguangjiao prepared using Capsicum frutescens Linn. was dominated by Pseudomonas with an average relative abundance of 67.35%. Compared with Zhaguangjiao prepared using Capsicum frutescens Linn., the sourness and content of aromatic compounds of Zhaguangjiao prepared using Capsicum frutescens Linn. was dominated by Pseudomonas were significantly higher, while the contents of organic sulfides, terpenes and nitrogen oxides among volatile substances were significantly lower. After Pearson correlation analysis, it was found that elevating the abundance of Lactobacillus in the fermentation system of Zhaguangjiao could obviously suppress the undesirable flavor and improve the content of aroma substances in Zhaguangjiao. Zhaguangjiao is popular for its sour and spicy taste, due to Capsicum annuum L. var. grossum (L.) Sendt. is less spicy, choosing Capsicum annuum L. as the main raw material to produce Zhaguangjiao has a positive effect enhancing the overall quality of the product.

Objectives To develop a core competency training curriculum system for emergency trauma nurses in China.Design A modified Delphi study design.Participants The selection criteria for participants identified in practitioner roles were to be currently engaged in trauma care for over 5 years, to serve as the manager of emergency or trauma surgery department, and to have a bachelor’s degree or higher. A total of 15 trauma experts from three grade A tertiary hospitals were invited to participate in this study by email or face to face in January 2022. The expert group comprised four trauma specialist doctors and 11 trauma specialist nurses. There were 11 women and 4 men. The age ranged from 32 to 50 (40.27±5.120) years. The number of years worked ranged from 6 to 32 (15.87±7.110).Results Two rounds of questionnaires were issued to 15 experts in each round, and the effective recovery rate was 100.00%. In this study, expert judgement=0.947, expert familiarity with the content=0.807 and authority coefficient=0.877, and the results are highly reliable. The Kendall’s W of the two rounds in this study ranged from 0.208 to 0.467, and the difference was statistically significant (p

C7H4Cl2N2O, monoclinic, P21/c (no. 14), a = 6.215(2) Å, b = 16.544(5) Å, c = 8.561(3) Å, β = 108.707(4)°, V = 833.8(5) Å3, Z = 4, R gt(F) = 0.0339, wRref (F 2) = 0.1265, T = 296 K.

Vibrio ponticus is a vital pathogen with potential danger for aquaculture animals. Yet V. ponticus pathogenic to the coral trout Plectropomus leopardus is still unknown. In this study, a virulent bacterial strain, temporarily named DX2, was isolated from diseased coral trout suffering liver necrosis with cell vacuolar degeneration, and was identified molecularly and phenotypically as V. ponticus. Besides, the DX2 isolate showed an LD50 value of 6.64×105 CFU mL-1, developed multiple resistances to cephalosporins, macrolides, penicillins, peptides, and sulfonamides antimicrobials, and was highly susceptible to doxycycline and florfenicol in aquaculture use. To the best of our knowledge, this is the first report of the pathogenicity of V. ponticus to the coral trout, and the findings provide a reference for the control of pathogenic V. ponticus in the coral trout.

C21H20N4O2, triclinic, P1‾$\overline{1}$ (no. 2), a = 5.874(3) Å, b = 16.526(7) Å, c = 20.147(8) Å, α = 67.140(5)°, β = 83.287(6)°, γ = 86.910(6)°, V = 1789.7(14) Å3, Z = 4, Rgt(F) = 0.0614, wRref(F2) = 0.1675, T = 296 K.

We propose a coupled-tolerant subwavelength photonic racetrack resonator (PRR) on the silicon-on-insulator (SOI) platform, in which a subwavelength grating (SWG) PRR is coupled to a symmetrical SWG bus waveguide. The material equivalent refractive index can be manipulated by the SWG characteristic and thus an additional fabrication degree of freedom can be achieved. The resonant characteristics can be improved significantly by controlling the pillar size and increasing the interaction length between SWG racetrack and bus waveguide (RBW). The simulation results show that the PRR has a high-quality factor and large extinction ratio around 1550nm. Two groups of SWG and strip waveguide (SW) PRRs are fabricated. The fabrication tolerance is tested when fabrication error is changed from 0 to 20 nm and the quality factor is more than 7000 in de-ionized water. The testing results show that the tolerance in SWG-PRR has a 2.0-fold improvement than that in the SW-PRR. Then a fabricated SWG-PRR is employed to monitor different concentration glycerol injected on the chip. An optimal quality factor of 9500 around 1550 nm and bulk sensitivity of 412± 0.5 nm/RIU are achieved. Therefore, the structure is a potential candidate for label-free sensing in medical diagnosis and environmental monitoring.

The majority of marine microbes remain uncultured, which hinders the identification and mining of CO2-fixing genes, pathways, and chassis from the oceans. Here, we investigated CO2-fixing microbes in seawater from the euphotic zone of the Yellow Sea of China by detecting and tracking their 13C-bicarbonate (13C-HCO3-) intake via single-cell Raman spectra (SCRS) analysis. The target cells were then isolated by Raman-activated Gravity-driven Encapsulation (RAGE), and their genomes were amplified and sequenced at one-cell resolution. The single-cell metabolism, phenotype and genome are consistent. We identified a not-yet-cultured Pelagibacter spp., which actively assimilates 13C-HCO3-, and also possesses most of the genes encoding enzymes of the Calvin-Benson cycle for CO2 fixation, a complete gene set for a rhodopsin-based light-harvesting system, and the full genes necessary for carotenoid synthesis. The four proteorhodopsin (PR) genes identified in the Pelagibacter spp. were confirmed by heterologous expression in E. coli. These results suggest that hitherto uncultured Pelagibacter spp. uses light-powered metabolism to contribute to global carbon cycling.

Abstract Background Xylanases have been successfully used in food, paper, and pulp industries and are considered to be a key player in the biodegradation of xylan to valuable end products. However, most of the natural xylanases present poor activity in high-temperature and high-alkali environment. Therefore, it is necessary to modify the enzymes to meet the increasing demands of industries. Results Directed evolution was used to improve the specific activity and pH stability of the xylanase (XynHBN188A) that originated from Bacillus pumilus HBP8. The xylanase XynHBN188A was mutated by error-prone PCR. The mutant, XynHBN188A217, was screened from the mutant library by functional screening. The specific activity of XynHBN188A217 was 3986.7 U/mg, which was 2.8-fold higher than that of wild type. The optimum temperature of XynHBN188A and XynHBN188A217 was 50 °C and 55 °C, respectively. The optimum pH of XynHBN188A and XynHBN188A217 was pH 8.0 and pH 7.5, respectively. The half-life at 60 °C of XynHBN188A217 was 20 min. Moreover, the pH stability of XynHBN188A217 was significantly better than that of XynHBN188A. Finally, homology models and molecular docking were used to identify the location of mutation sites and to explore the mechanism of the improved properties. Conclusion The xylanase XynHBN188A has been improved in the specific activity and pH stability by directed evolution. Also, the enlarged catalytic channel of mutant is beneficial for the substrates access and products release. It may contribute to the improved activity. The mutant XynHBN188A217 will be a potential candidate to be used for industrial application.

The genus Acinetobacter has recently emerged as bacterial pathogens associated with mass mortalities in aquaculture. Yet scarce information is available on Acinetobacter venetianus as a potential pathogen of whiteleg shrimp Penaeus vannamei. In the present study, an A. venetianus pathogen (SHF1) was confirmed as a causative agent of red leg disease in freshwater-cultured whiteleg shrimp. It showed a mean lethal dose (LD50) value of 3.8 × 105 CFU mL−1 and developed multiple resistances to phenicols, quinolones and tetracycline drugs used in aquaculture. In addition, the pathogenic A. venetianus could be effectively controlled by Bdellovibrio powder at 0.8 mg L−1, which exhibited significant antibacterial effect and displayed good protection against A. venetianus challenge in P. vannamei for six days. As far as we know, this is the first study to identify A. venetianus as a potential bacterial pathogen of red leg disease in freshwater-farmed whiteleg shrimp.

In a meta-transcriptome study of the giant freshwater prawn Macrobrachium rosenbergii sampled in 2018 from a hatchery, we identified a variant of Macrobrachium rosenbergii golda virus (MrGV) in postlarvae without clinical signs. The virus belongs to the family Roniviridae, and the genome of this MrGV variant, Mr-18, consisted of 28,957 nucleotides, including 4 open reading frames (ORFs): (1) ORF1a, encoding a 3C-like protein (3CLP) (4933 aa); (2) ORF1b, encoding a replicase polyprotein (2877 aa); (3) ORF2, encoding a hypothetical nucleocapsid protein (125 aa); and (4) ORF3, encoding a glycoprotein (1503 aa). ORF1a overlaps with ORF1b with 40 nucleotides, where a −1 ribosomal frameshift with slippage sequence 5′-G14925GGUUUU14931-3′ produces the pp1ab polyprotein. The genomic sequence of Mr-18 shared 97.80% identity with MrGV LH1-2018 discovered in Bangladesh. The amino acid sequence identities between them were 99.30% (ORF1a), 99.60% (ORF1b), 100.00% (ORF2), and 99.80% (ORF3), respectively. Phylogenetic analysis of the RNA-dependent RNA polymerase (RdRp) proteins revealed that they clustered together and formed a separate cluster from the genus Okavirus. The finding of MrGV in China warrants further studies to determine its pathogenicity and prevalence within the region.

Both spark ignition (SI) natural gas engines and compression ignition (CI) dual fuel (DF) engines suffer from knocking when the unburnt mixture ignites spontaneously prior to the flame front arrival. In this study, a parametric investigation is performed on the knocking performance of these two engine types by using the GT-Power software. An SI natural gas engine and a DF engine are modelled by employing a two-zone zero-dimensional combustion model, which uses Wiebe function to determine the combustion rate and provides adequate prediction of the unburnt zone temperature, which is crucial for the knocking prediction. The developed models are validated against experimentally measured parameters and are subsequently used for performing parametric investigations. The derived results are analysed to quantify the effect of the compression ratio, air-fuel equivalence ratio and ignition timing on both engines as well as the effect of pilot fuel energy proportion on the DF engine. The results demonstrate that the compression ratio of the investigated SI and DF engines must be limited to 11 and 16.5, respectively, for avoiding knocking occurrence. The ignition timing for the SI and the DF engines must be controlled after −38°CA and 3°CA, respectively. A higher pilot fuel energy proportion between 5% and 15% results in increasing the knocking tendency and intensity for the DF Engine at high loads. This study results in better insights on the impacts of the investigated engine design and operating settings for natural gas (NG)-fuelled engines, thus it can provide useful support for obtaining the optimal settings targeting a desired combustion behaviour and engine performance while attenuating the knocking tendency.

Nghiên cứu này đánh giá sức sinh sản của tôm sú mẹ gia hóa ở thế hệ G4, là sản phẩm của đề tài “Nghiên cứu ứng dụng công nghệ sinh học trong việc chọn tạo tôm sú (Penaeus monodon) bố mẹ tăng trưởng nhanh” trong điều kiện nuôi trong nhà. Tôm mẹ gia hóa thế hệ G4 có tỉ lệ thành thục là 100%. Ở lần đẻ thứ nhất, tôm mẹ có trọng lượng trung bình là 73,3±6,6 g, tỉ lệ đẻ là 50%, sức sinh sản thực tế là 283.556±75.801 trứng/tôm mẹ, tỉ lệ trứng thụ tinh là 84,9%±7,5% và tỉ lệ trứng nở là 96,3%±3,4%; ở lần đẻ thứ 2 có các số liệu lần lượt là: 78±2,5 g, 75,9%, 265.600±97.240 trứng/tôm mẹ, 91,8%±3,4% và 92,1%±4,4%; và đẻ lần 3: 75±7,5 g, 18,2%, 204.444±34.667 trứng/tôm mẹ, 72,4%±16,2% và 60,5%±45,4%. Kết quả nghiên cứu cho thấy sức sinh sản thực tế, tỉ lệ thụ tinh và tỉ lệ nở của trứng đã suy giảm khi tôm đẻ lần 3 (p

Aeromonas hydrophila is a well-known bacterial pathogen associated with mass mortalities in aquaculture. Yet, few reports are available on whiteleg shrimp-pathogenic A. hydrophila. In the present study, a virulent isolate WS05 was confirmed as a causative agent of diseased freshwater-cultured whiteleg shrimp and showed a mean lethal dose (LD50) value of 4.8 × 104 CFU mL−1. It was identified phenotypically and molecularly as an A. hydrophila strain, and exhibited susceptibility to several veterinary antibiotics extensively used in aquaculture, including cotrimoxazole, doxycycline, florfenicol, neomycin, and tetracycline. In view of the strongest inhibition zone of florfenicol against isolate WS05, the synergistic effect of the combinations of florfenicol and herb extracts was further evaluated, and the result indicated that Punica granatum extract was a potential synergist of florfenicol against isolate WS05 and the fractional inhibitory concentration index (FICI) for the florfenicol-P. granatum extract was calculated as 0.31. When combined with 7.81 mg mL−1 P. granatum extract, the minimum inhibitory concentration (MIC) of florfenicol against isolate WS05 was reduced from 0.50 to 0.03 mg L−1, and its activity against isolate WS05 was also enhanced with a significant reduction of ≥3.61 log in cell density after 24 h of treatment compared with that in the single drug treatment. In addition, the protective effect was potentiated by the combination of florfenicol and P. granatum extract, with a cumulative mortality of 36.66% (p < 0.05) and 33.33% (p < 0.05) lower than that in the single treatment with florfenicol and P. granatum extract after the challenge with isolate WS05 for seven days. As far as we know, this is the first study to describe whiteleg shrimp-pathogenic A. hydrophila and suggest P. granatum extract as a potential synergist of florfenicol against the A. hydrophila pathogen.

The further thermal efficiency improvement of marine natural gas engine is constrained by a knocking phenomenon that commonly occurs in gas-fueled spark-ignited engines. It plays an important role to investigate how the knocking occurs and how to predict it based on the engine simulation model. In this paper, a two-zone model is developed to provide the prediction of knocking performance and NO emission, which is verified by engine test bed data from a transformed marine natural gas spark ignition (SI) engine. Cylindrical division theory is used to describe the shape of the two zones to decrease the computational cost, as well as a basic mechanism for NO concentration calculation. In order to solve the volume balance, three boundary parameters are introduced to determine the initial condition and mass flow between the two zones. Furthermore, boundary parameters’ variation and knocking factor (compression ratio and advanced ignition angle) will be discussed under different working conditions. Result shows that the two-zone model has sufficient accuracy in predicting engine performance, NO emission and knocking performance. Both the increasing compression ratio and advanced ignition angle have a promoting effect on knocking probability, knocking timing and knocking intensity. The knocking phenomenon can be avoided in the targeted natural gas SI engine by constraining the compression ratio smaller than 14 and advanced ignition angle later than 30° before top dead center (BTDC).

Non-alcoholic fatty liver disease (NAFLD) is a severe hepatic health threat with no effective treatment. Based on the results that Chenopodium quinoa Willd. flavonoids eluted with 30% ethanol (CQWF30) can effectively alleviate NAFLD, this study employed ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) to analyze the components of CQWF30., and screened for flavonoids with potential NAFLD-mitigating effects through network pharmacology. In vitro models using HepG2 and BEL-7402 cell lines induced with free fatty acid (FFA) showed that isorhamnetin administration reduced intracellular lipid deposition and reversed elevated triglyceride (TG) and total cholesterol (T-CHO) levels. In vivo experiments in high-fat diet (HFD) mice demonstrated that isorhamnetin significantly lowered serum and liver fat content, mitigated liver damage, and modulated bile acid metabolism by upregulating FXR and BSEP and downregulating SLCO1B3. Consequently, isorhamnetin shows promise as a treatment for NAFLD due to its lipid-lowering and hepatoprotective activities.

Background: Nonalcoholic fatty liver disease (NAFLD), a chronic metabolic disorder marked by excessive lipid deposition, represents a considerable health burden with no established efficacious treatment strategy. Quinoa (Chenopodium quinoa Willd.), valued for its health benefits, is replete with flavonoid bioactives. The aims of this work are to isolate and purify flavonoids from quinoa whole grain that can intervene in NAFLD and to elucidate some of the underlying mechanisms., Results: Chenopodium quinoa Willd. flavonoids (CQWF) were obtained successfully through an optimized ultrasonic extraction methodology, followed by isolation and purification utilizing macroporous resin D101. The study then explored the therapeutic potential of CQWF and its eluted fractions in models emulating NAFLD conditions: an in vitro fatty liver cell model induced by oleic acid (OA) and palmitic acid (PA) in the HepG2 and BEL-7402 cell lines, and an in vivo high-fat diet (HFD)-induced NAFLD model in C57BL/6N mice. The findings revealed a comprehensive mitigating effect of CQWF30 on NAFLD, manifesting in reduced intracellular lipid accumulation in steatotic hepatocytes and a concerted downregulation of key lipid metabolism genes, CD36 and FASN. Administration of CQWF30 reduced triglyceride (TG) levels in both the cellular model and the livers of HFD-fed mice. It also reduced serum concentrations of TG, total cholesterol (T-CHO), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), while increasing high-density lipoprotein cholesterol (HDL-C) in the mice., Conclusion: These results highlighted the promising therapeutic capacity of CQWF, particularly CQWF30. This research advances the exploration and utilization of flavonoids derived from quinoa whole grain, providing innovative dietary intervention strategies for NAFLD. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Chemoresistance is one of the difficulties in the treatment of colorectal cancer (CRC), and the enhanced stemness of tumor cells is the underlying contributing factor. Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a classical marker of CRC stem cells and can be an important potential target for CRC chemotherapy. Quinoa, a protein-rich plant, offers potential as a source of high-quality active peptides. Novelly, the study obtained quinoa protein hydrolysate (QPH) from whole quinoa grains by simulated digestion. In vivo experiments revealed that the tumor volume in the 5-FU+QPH group decreased from 145.90 ± 13.35 to 94.49 ± 13.05 mm 3 in the 5-FU group, suggesting that QPH enhances the chemosensitivity of CRC. Further, the most effective peptide QPH-FR from 631 peptides in QPH was screened by activity prediction, molecular docking, and experimental validation. Mechanistically, QPH-FR competitively suppressed the formation of the LGR5/RSPO1 complex by binding to LGR5, causing RNF43/ZNRF3 to ubiquitinate the FZD receptor, thereby suppressing the Wnt/β-catenin signaling pathway and exerting stemness inhibition. In summary, the study proposes that a novel peptide QPH-FR from quinoa elucidates the mechanism by which QPH-FR targets LGR5 to enhance chemosensitivity, providing theoretical support for the development of chemotherapeutic adjuvant drugs based on plant peptides.

Coherent polarization control of terahertz (THz) emission is crucial for applications in the THz field. Here, we demonstrate that the polarization of THz waves emitted from graphene through quantum interference can be coherently controlled by varying the relative phase between the co-circularly polarized laser fields. The polarization state of the THz wave emitted from graphene remains linearly polarized, while its direction can be arbitrarily changed by varying the relative phase. This work not only achieves the coherent polarization control of the THz waves emitted from graphene but also promotes the fundamental research of THz photonics in graphene.

Excessive alcohol consumption has led to the prevalence of gastrointestinal ailments. Alleviating gastric disorders attributed to alcohol-induced thinning of the mucus layer has centered on enhancing mucin secretion as a pivotal approach. In this study, foxtail millet bran polyphenol BPIS was divided into two components with MW < 200 D and MW > 200 D by molecular interception technology. Combined with MTT, cell morphology observation, and trypan blue staining, isoferulic acid (IFA) within the MW < 200 D fraction was determined as the effective constituent to mitigate ethanol-induced damage of gastric epithelial cells. Furthermore, a Wistar rat model with similar clinical features to alcohol-induced gastric mucosal injury was established. Then, gastric morphological observation, H&E staining, and assessments of changes in gastric hexosamine content and gastric wall binding mucus levels were carried out, and the results revealed that IFA (10 mg/Kg) significantly ameliorated alcohol-induced gastric mucosal damage. Finally, we applied techniques including Co-IP, molecular docking, and fluorescence spectroscopy and found that IFA inhibited the alcohol-induced downregulation of N-acetylgalactosamintransferase 2 (GALNT2) activity related to mucus synthesis through direct interaction with GALNT2 in gastric epithelial cells, thus promoting mucin synthesis. Our study lays a foundation for whole grain dietary intervention tailored to individuals suffering from alcoholic gastric mucosal injury.

Introduction: This study was designed to compare three-dimensional (3D) laparoscopy and conventional two-dimensional (2D) laparoscopy in surgical performance and clinical assessment during laparoscopic radical hysterectomy with pelvic lymphadenectomy (LRHND) for treating early-stage cervical cancer., Material and Methods: In this study, we included 67 consecutive patients underwent LRHND for treating early-stage cervical cancer by the experienced laparoscopic surgeons between August 2018 and December 2020. amongst these patients, 32 patients underwent 3D laparoscopy (2D group) and 35 patients underwent 2D laparoscopy (2D group). Demographic data, clinical and surgical parameters were obtained from each patient. An end-of-operation questionnaire was administered regarding subjective perception of 3D laparoscopy system., Results: Patient characteristics, including age, BMI, FIGO stage, and histology, were comparable between the two groups. Compared with 2D imaging system, 3D system significantly shortened the operation time, especially bilateral lymph node dissection time. Blood loss was lower in 3D group compared with 2D group. There were no significant differences regarding pelvic nodes retrieved, incidence of complications, hospital stay, the recovery time of bowel, abdominal drainage fluid, hospitalization costs and visual symptoms. In addition, 3D system significantly improved depth perception and precision, and reduced surgical strain and eye strain for surgeon. No statistical difference was observed in visual symptoms and adverse events between the two groups. The surgeon was more willing to accept 3D laparoscopy., Conclusion: The 3D laparoscopy is safe, feasible and comfortable, with obvious advantage in depth perception, precision and surgical strain. It triggered no increase in the complications and adverse events., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: The inability of patients with recurrent implantation failure (RIF) to achieve pregnancy and a live birth after multiple high-quality embryo transfer treatments has been recognized as a major obstacle to successful application of artificial reproductive technologies. The objective of this study was to establish and validate a nomogram for prediction of subsequent first-cycle live births to guide clinical practice in patients diagnosed with RIF., Methods: A total of 538 patients who underwent in vitro fertilization/intracytoplasmic sperm injection treatment and were first diagnosed with RIF at the Reproductive Center of the First Affiliated Hospital of Xinjiang Medical University between January 2017 and December 2020 were enrolled. The patients were randomly divided into a training cohort (n=408) and a validation set (n=175) in a ratio of 7:3. A nomogram model was constructed using the training set based on the results of univariate and multivariate logistic regression analyses and validated in the validation set., Results: Age, body mass index, duration of RIF, endometrial thickness, type of embryo transferred, and number of previous biochemical pregnancies were included in the nomogram for prediction of subsequent first-cycle live births in patients diagnosed with RIF. Analysis of the area under the receiver-operating characteristic curve, calibration plots, and decision curve analysis showed that our predictive model for live births had excellent performance., Conclusion: We have developed and validated a novel predictive model that estimates a woman's chances of having a live birth after a diagnosis of RIF and provides clinicians with a personalized clinical decision-making tool., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Gong, Zhang, Zhu, Wang, Wang, Liu, La and Ding.)

Background: This study focuses on the risk of early miscarriage in patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). These patients commonly experience heightened stress levels and may discontinue treatment due to emotional burdens associated with repeated failures. Despite the identification of numerous potential factors contributing to early miscarriage, there exists a research gap in integrating these factors into predictive models specifically for IVF/ICSI patients. The objective of this study is to develop a user-friendly nomogram that incorporates relevant risk factors to predict early miscarriage in IVF/ICSI patients. Through internal and external validation, the nomogram facilitates early identification of high-risk patients, supporting clinicians in making informed decisions., Methods: A retrospective analysis was conducted on 20,322 first cycles out of 31,307 for IVF/ICSI treatment at Sun Yat-sen Memorial Hospital between January 2011 and December 2020. After excluding ineligible cycles, 6,724 first fresh cycles were included and randomly divided into a training dataset (n = 4,516) and an internal validation dataset (n = 2,208). An external dataset (n = 1,179) from another hospital was used for validation. Logistic and LASSO regression models identified risk factors, and a multivariable logistic regression constructed the nomogram. Model performance was evaluated using AUC, calibration curves, and decision curve analysis (DCA)., Results: Significant risk factors for early miscarriage were identified, including female age, BMI, number of spontaneous abortions, number of induced abortions and medical abortions, basal FSH levels, endometrial thickness on hCG day, and number of good quality embryos. The predictive nomogram demonstrated good fit and discriminatory power, with AUC values of 0.660, 0.640, and 0.615 for the training, internal validation, and external validation datasets, respectively. Calibration curves showed good consistency with actual outcomes, and DCA confirmed the clinical usefulness. Subgroup analysis revealed variations; for the elder subgroup (age ≥35 years), female age, basal FSH levels, and number of available embryos were significant risk factors, while for the younger subgroup (age <35 years), female age, BMI, number of spontaneous abortions, and number of good quality embryos were significant., Conclusions: Our study provides valuable insights into the impact factors of early miscarriage in both the general study population and specific age subgroups, offering practical recommendations for clinical practitioners. We have taken into account the significance of population differences and regional variations, ensuring the adaptability and relevance of our model across diverse populations. The user-friendly visualization of results and subgroup analysis further enhance the applicability and value of our research. These findings have significant implications for informed decision-making, allowing for individualized treatment strategies and the optimization of outcomes in IVF/ICSI patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer XY declared a shared parent affiliation with the author(s) MZ, XJ, XH, YZ, and QZ to the handling editor at the time of review., (Copyright © 2024 Zhang, Ji, Hu, Zhu, Ma, Xu, La and Zhang.)

Objective: Intestinal flora homeostasis in rats with type 2 diabetes mellitus (T2DM) was evaluated to explore the effects of total Astragalus saponins (TAS) on hepatic insulin resistance (IR)., Methods: Six-week-old male Sprague-Dawley rats were fed high-fat and high-sugar diet for 4 weeks and intraperitoneally injected with streptozotocin to induce T2DM, and they were then randomly divided into control, model, metformin, and TAS groups. Stool, serum, colon, and liver samples were collected after 8 weeks of drug administration for relevant analyses., Results: TAS reduced fasting blood glucose, 2-hour postprandial blood glucose, area under the curve of oral glucose tolerance test, glycated serum protein, homeostasis model assessment of insulin resistance, total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels in T2DM rats but increased insulin, C-peptide, and high-density lipoprotein cholesterol levels. Moreover, TAS improved the morphology and structure of liver and colon tissues and improved the composition of the intestinal microbiome and bacterial community structure at different taxonomic levels. In addition, TAS increased the protein expression of hepatic IRS-1, PI3K, PDK1, and p-AKT and decreased the protein expression of p-GSK-3β. Meanwhile, TAS increased the mRNA expression of liver PDK1, PI3K, and GS and decreased the mRNA expression of GSK-3β., Conclusion: TAS can ameliorate T2DM-related abnormal glucose and blood lipid metabolism, intestinal dysbiosis, and IR., Competing Interests: ZC was employed by Oriental Herbs Kft. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ma, La, Zhang, Xu, Tian, Fu, Wang, Wu, Chen, Chang and Li.)

Background: Antiphospholipid syndrome (APS) is a group of clinical syndromes of thrombosis or adverse pregnancy outcomes caused by antiphospholipid antibodies, which increase the incidence of in vitro fertilization failure in patients with infertility. However, the common mechanism of repeated implantation failure (RIF) with APS is unclear. This study aimed to search for potential diagnostic genes and potential therapeutic targets for RIF with APS., Methods: To obtain differentially expressed genes (DEGs), we downloaded the APS and RIF datasets separately from the public Gene Expression Omnibus database and performed differential expression analysis. We then identified the common DEGs of APS and RIF. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed, and we then generated protein-protein interaction. Furthermore, immune infiltration was investigated by using the CIBERSORT algorithm on the APS and RIF datasets. LASSO regression analysis was used to screen for candidate diagnostic genes. To evaluate the diagnostic value, we developed a nomogram and validated it with receiver operating characteristic curves, then analyzed these genes in the Comparative Toxicogenomics Database. Finally, the Drug Gene Interaction Database was searched for potential therapeutic drugs, and the interactions between drugs, genes, and immune cells were depicted with a Sankey diagram., Results: There were 11 common DEGs identified: four downregulated and seven upregulated. The common DEG analysis suggested that an imbalance of immune system-related cells and molecules may be a common feature in the pathophysiology of APS and RIF. Following validation, MARK2, CCDC71, GATA2, and KLRC3 were identified as candidate diagnostic genes. Finally, Acetaminophen and Fasudil were predicted as two candidate drugs., Conclusion: Four immune-associated candidate diagnostic genes (MARK2, CCDC71, GATA2, and KLRC3) were identified, and a nomogram for RIF with APS diagnosis was developed. Our findings may aid in the investigation of potential biological mechanisms linking APS and RIF, as well as potential targets for diagnosis and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Ge, Zhang and La.)

Chemotherapy represents a major type of clinical treatment against colorectal cancer (CRC). Aberrant drug efflux mediated by transporters acts as a key approach for tumor cells to acquire chemotherapy resistance. Increasing evidence implies that tumor-associated macrophages (TAMs) play a pivotal role in both tumorigenesis and drug resistance. Nevertheless, the specific mechanism through which TAMs regulate drug efflux remains elusive. Here, we discovered that TAMs endow CRC cells with resistance to 5-fluorouracil (5-FU) treatment via a cell-cell interaction-mediated MRP1-dependent drug efflux process. Mechanistically, TAM-secreted C-C motif chemokine ligand 17 (CCL17) and CCL22, via membrane receptor CCR4, activated the PI3K/AKT pathway in CRC tumor cells. Specifically, phosphorylation of AKT inactivated IP3R and induced calcium aggregation in the ER, resulting in the activation of ATF6 and upregulation of GRP78. Accordingly, excessive GRP78 can interact with MRP1 and promote its translocation to the cell membrane, causing TAM-induced 5-FU efflux. Taken together, our results demonstrated that TAMs promote CRC chemotherapy resistance via elevating the expression of GRP78 to promote the membrane translocation of MRP1 and drug efflux, providing direct proof for TAM-induced drug resistance., (© 2023. The Author(s).)

Macrophages in hypoxic regions of advanced colorectal tumors often exhibit M2-type features, but prefer oxygen-consuming lipid catabolism, which is contradictory in oxygen demand and supply. In this study, the results from bioinformatics analysis and intestinal lesions immunohistochemistry of 40 colorectal cancer patients illustrated that glucose-regulatory protein 78 (GRP78) was positively correlated with M2 macrophages. Furthermore, tumor-secreted GRP78 could enter macrophages and polarize them to M2-type. Mechanistically, entered GRP78 located in lipid droplets of macrophages, and elevated protein stabilization of adipose triglyceride lipase ATGL by interacting with it to inhibit its ubiquitination. Increased ATGL promoted the hydrolysis of triglycerides and the production of arachidonic acid (ARA) and docosahexaenoic acid (DHA). Excessive ARA and DHA interacted with PPARγ to encourage its activation, which mediated the M2 polarization of macrophages. In summary, our study showed that secreted GRP78 in the tumor hypoxic microenvironment mediated the domestication of tumor cells to macrophages and maintained tumor immunosuppressive microenvironment by promoting lipolysis, and the lipid catabolism not only provides energy for macrophages but also plays an important role in maintenance of immunosuppressive properties., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Salvianolic acid A (SAA) is the main active component of the classic anti-atherosclerotic drug Salvia miltiorrhiza Bunge. Inflammation-induced infiltration of monocyte/macrophages into the vascular wall is the initiating step in atherogenesis, and targeted blocking of this step may provide a promising avenue for the precise treatment of atherosclerosis. However, the effect of salvianolic acid A on macrophages is still unknown., Aim of the Study: To evaluate the effect of SAA on macrophage infiltration and the underlying mechanism of SAA against atherosclerosis., Materials and Methods: Vascular endothelial cells were stimulated with lipopolysaccharide (LPS) to simulate the inflammatory environment, and its effect on monocyte/macrophages was evaluated. Mass spectrometry was used to identify the proteins that play a key role and further validated them. LncRNA sequencing, western blot analysis, RNA immunoprecipitation, and RNA pulldown were used to elucidate the mechanism of SAA against atherosclerosis. Finally, ApoE -/- mice were fed a high-fat diet to creat an in vivo atherosclerosis model. Secretory GRP78 content, lipid levels, plaque area, macrophage infiltration, and degree of inflammation were assessed by standard assays after 16 weeks of intragastric administration of SAA or biweekly tail vein injections of GRP78 antibody., Results: After LPS stimulation, the increased secretion of GRP78 recruits circulating monocyte/macrophages and drives monocyte/macrophage adhesion and invasion into the vascular intima to promote atherosclerosis progression. Interestingly, SAA exerts anti-atherosclerosis effects by inhibiting the secretion of GRP78. Further mechanistic studies indicated that SAA upregulates the expression of lncRNA NR2F2-AS1, which reverses the abnormal localization of the KDEL receptor (KDELR) caused by inflammation. It promotes the homing of GRP78 from the Golgi apparatus to the endoplasmic reticulum rather than secreting outside the cell., Conclusion: SAA alleviates atherosclerosis by inhibiting GRP78 secretion via the lncRNA NR2F2-AS1-KDELR axis. The findings not only provide a new direction for the precise therapy of atherosclerosis based on secretory GRP78 but also elucidate the pharmacological mechanism of SAA against atherosclerosis, putting the foundation for further development and clinical application of SAA drugs., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Supercritical fluid chromatography is proving to be a good separation and sample preparation tool for various analytical applications and, as such, has gained the attention of the anti-doping community. Here, the applicability of supercritical fluid chromatography hyphenated to tandem mass spectrometry for routine doping control analysis was tested. A multi-analyte method was developed to cover 197 drugs and metabolites that are prohibited in sport. More than 1000 samples were analyzed by applying a "dilute and inject" approach after hydrolysis of glucuronide metabolites. Additionally, a comparison with routinely used liquid chromatography-mass spectrometry was performed with 250 of the 1000 samples and a number of past positive anti-doping samples. It revealed some features where supercritical fluid chromatography-tandem mass spectrometry was found to be complementary or advantageous to liquid chromatography-mass spectrometry for anti-doping purposes, such as better retention of analytes that are poorly retained in reversed-phase liquid chromatography. Our results suggest that supercritical fluid chromatography-tandem mass spectrometry is sensitive (limit of detection <50% relevant minimum required performance level required by the World Anti-Doping Agency for anti-doping analysis), reproducible, robust, precise (analytes of interest area coefficient of variation <5%; retention time difference coefficient of variation <1%) and complementary to existing techniques currently used for routine analysis in the World Anti-Doping Agency accredited laboratories., (© 2023 Wiley-VCH GmbH.)

Background: A number of live birth predictive model during assisted reproductive technology treatment have been available in recent years, but few targeted evaluating the chances of live birth in poor ovarian response(POR) patients. The aim of this study was to develop a nomogram based on POSEIDON criteria to predict live birth in patients with expected POR., Methods: This retrospective cohort study using clinical data from 657 patients in POSEIDON Groups 3 and 4 (antral follicle count [AFC] ≤5 and AMH <1.2 ng/ml) in the Center for Reproductive Medicine, First Affiliated Hospital of Xinjiang Medical University, and Construction a nomogram model t., Results: Among 657 expected POR patients, 111 (16.89%) had live births, and 546 (83.11%) did not have live births. These were divided into a training set(n=438) and a validation set (n=219). Multivariate logistic regression analysis showed that the age (OR = 0.91, 95% CI: 0.86-0.97), BMI (OR = 1.98, 95% CI: 1.09-3.67), AMH (OR = 3.48, 95% CI: 1.45-8.51), normal fertilized oocytes (OR = 1.40, 95% CI: 1.21-1.63), and the basal FSH (OR = 0.89, 95% CI: 0.80-0.98) of the female were independent factors predicting live birth in patients with expected POR. Then, an individualized nomogram prediction model was built from these five factors. The area under the ROC curve of the live birth prediction model was 0.820 in the training set and 0.879 in the validation set., Conclusion: We have developed a nomogram combining clinical and laboratory factors to predict the probability of live birth in patients with an expected POR during IVF/ICSI, which can helpful for clinician in decision-making. However, the data comes from the same center, needs a prospective multicenter study for further in-depth evaluation and validation of this prediction model., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gong, Zhang, Zhu, Wang, Wang, Liu, Zhang and La.)

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and has become a growing public health concern worldwide. Polyphenols may improve high-fat diet (HFD)-related NAFLD. Our previous study found that ferulic acid (FA) and p-coumaric acid (p-CA) were the polyphenols with the highest content in foxtail millet. In this study, we investigated the mechanism underlying the impact of ferulic acid and p-coumaric acid (FA/p-CA) on non-alcoholic fatty liver (NAFLD). The association of FA and p-CA with fatty liver was first analyzed by network pharmacology. Synergistic ameliorating of NAFLD by FA and p-CA was verified in oleic acid (OA) and palmitic acid (PA) (FFA)-treated hepatocytes. Meanwhile, FA/p-CA suppressed final body weight and TG content and improved liver dysfunction in HFD-induced NAFLD mice. Mechanistically, our data indicated that FA and p-CA bind to histone deacetylase 1 (HDAC1) to inhibit its expression. The results showed that peroxisome proliferator activated receptor gamma (PPARG), which is positively related to HDAC1, was inhibited by FA/p-CA, and further suppressed fatty acid binding protein (FABP) and fatty acid translocase (CD36). It suggests that FA/p-CA ameliorate NAFLD by inhibiting free fatty acid uptake via the HDAC1/PPARG axis, which may provide potential dietary supplements and drugs for prevention of NAFLD.

Background: This retrospective study assessed the precision of noninvasive prenatal testing (NIPT) in detecting microdeletion/microduplication syndromes (MMSs) and nonsyndromic copy number variations (CNVs). Methods: The study included 19,086 singleton pregnancies screened on NIPT using high-throughput sequencing. Pregnancies with CNVs on NIPT underwent amniocentesis for karyotyping and CNV sequencing (CNV-seq). We analyzed pathogenic MMSs and nonsyndromic CNVs separately, dividing the CNVs into subgroups based on fragment size and fetal ultrasound findings. Results: A total of 170 abnormalities were detected by NIPT, of which 113 (66.5%) underwent invasive testing. The positive predictive value (PPV) of CNV-seq for all types of CNV detected by NIPT was 35.4%, with PPVs of 61.5 and 27.6% for pathogenic MMSs and nonsyndromic CNVs, respectively. PPVs for NIPT showed different values depending on gestational characteristics, with the highest PPV for NIPT in the group with increased nuchal thickness (66.7%) and for the abnormal ultrasound group (57.1%). CNVs ≤5 Mb with normal ultrasound findings were generally associated with a healthy fetus. Conclusion: NIPT can detect chromosomal aberrations in the first trimester, with high performance for MMSs. However, due to the low PPV for nonsyndromic CNVs, and the good pregnancy outcome in most cases, the introduction of expanded NIPT would cause an increase in unnecessary invasive procedures and inappropriate terminations of pregnancy.

To verify whether the placenta harbors bacteria, and to explore the composition of placental microbiota (if yes) and its association with adverse pregnancy outcomes. The placental microbiota was detected by 16S rRNA gene sequencing technology. In the process of detecting placental samples, exogenous marine bacterial DNA that does not exist in the human body was artificially added to obtain a visible 16S band. At the same time, the sterile samples, such as scissors, sheets, and cotton swabs, in delivery and operating rooms were collected as the environmental control samples. As a result, a total of 2,621,009 sequences were obtained from 71 samples, 88.9% of which came from artificially added exogenous bacterial DNA, suggesting that the placenta contained fewer bacteria. After removing the operational taxonomic units (OTUs) that coexisted in environmental controls, the placenta was annotated with 11 phyla, 22 classes, 43 orders, 79 families, and 157 genera. The β diversity analysis showed that there were significant differences in the placental microbiota between 10 women with gestational diabetes mellitus (GDM) ( p AMOVA = 0.01) or 19 women with premature rupture of membranes (PROM) ( p AMOVA = 0.004), and 21 women without adverse pregnancy outcomes, respectively. There were higher abundances of genera Bifidobacterium, Duncaniella , and Ruminococcus in the placenta samples of women with GDM. The genera of Bacteroides, Paraprevotella , and Ruminococcus were more enriched in the placental samples of women with PROM. The authors concluded that the placenta may harbor small amounts of microbiota, and significant differences in the dominant microbiota of the placenta were observed between those pregnant women with and without adverse pregnancy outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 La, Wang, Xiong, Shen, Chen, Zhang, Yang, Cai, Zheng and Jiang.)

Insulin resistance (IR) is a pivotal pathological characteristic that affects the occurrence and development of type 2 diabetes mellitus (T2DM). Thus, the effective control of IR is of great significance for diabetes prevention and treatment. Traditional Chinese medicine (TCM) represents a valuable tool handed down to the world by the Chinese nation and has a long history of use for diabetes clinical therapy. In this study, we focused on a self-drafted TCM-patented formula, Sanghuang Tongxie Formula (SHTXF), which exhibits clinical efficacy in the treatment of diabetes. To explore the effect and molecular mechanism of SHTXF on IR in vivo , Drosophila melanogaster was used and a ( Collagen ) Cg > InR K1409A diabetic IR fly model was established. SHTXF water extract was found to contribute toward carbohydrate clearance from the circulating system by converting it into triglycerides (TAG), not glycogen, for nutrient storage. In addition, SHTXF activated phosphatidylinositol-3-kinase (PI3K) activity and improved protein kinase B (PKB, also termed Akt) phosphorylation. Finally, SHTXF promoted Drosophila Forkhead Box O (dFoxO) cytoplasmic localization and inhibited its transcriptional activity. Taken together, these findings not only highlight the positive role of SHTXF in ameliorating IR via the PI3K/Akt pathway but also provide potential drug targets and key insights for use in T2DM clinical treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cao, La, Zhang, Wang, Li, Bo, Chang, Gao, Tian, Wu and Li.)

Background: In frozen-thawed embryo transfer (FET) cycles, endometrial thickness (EMT) has been used routinely as the main clinical monitoring index. However, the current findings are conflicting., Method: This was a single-center retrospective study of 2,054 couples (2,562 cycles) who underwent FET (including cleavage stage embryos and blastocysts) between January 2017 and August 2020 in the reproductive centers of First Affiliated Hospital of Xinjiang Medical University. The primary outcome measure was the ongoing pregnancy rate (OPR); the secondary outcome was the clinical pregnancy rate., Results: After stratified analysis and adjusting for confounders such as maternal age, duration of infertility, number of high-quality embryos transferred, endometrial preparation protocol, number of transfer cycles, and stages of embryo transferred, we found a curvilinear relationship between EMT and the OPR in women < 35 years of age. For women with EMT ≤ 8 mm, the OPR increased by 150% for cleavage stage embryo transfer for every 1 mm increase in the EMT; similarly, it increased by 97% for blastocyst stage FET. However, there was a linear relationship between EMT and OPR in women aged ≥ 35 years. When blastocysts were transferred, for every 1 mm increase in the EMT the OPR increased significantly by 12%. But OPR after frozen-thawed cleavage stage embryos transfer did not increase significantly with increased EMT., Conclusions: Our study showed that the OPR increased significantly with increased EMT between young women aged < 35 years with EMT ≤ 8 mm and older women who underwent transfer of blastocysts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tian, Zhang, Qiu, Yang, La and Cui.)

Aim: We aim to establish a predictive model for the evaluation of fecundity based on infertility-related factors., Methods: A total of 410 expectant couples who visited the First Affiliated Hospital of Xinjiang Medical University on January 1, 2017 and June 10, 2019 were included in this study. The 1-year follow-up was carried out to investigate the pregnancy of the female. They were divided into model group and test group, respectively. The basic information, life behavior and clinical indices were screened using the Logistics regression analysis and LASSO regression analysis. In addition, the multivariate logistic regression was used to establish the model for the prediction of fecundity risk., Results: The risk factors for the predictive model included female age and occupational pressure, gynecological disease, anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), fasting plasma glucose (FPG), depression, as well as male smoking. The area under the curve (AUC) for the model A and model B was 0.954 (0.931 ~ 0.978) and 0.955 (0.931 ~ 0.979), respectively. The AUC in the test group was 0.917 (0.869 ~ 0.965) and 0.921 (0.873 ~ 0.968). There were no statistical differences in the fitting value and measured values in the model group., Conclusions: We established a predictive model for the evaluation of fecundity, which showed a satisfactory accuracy and discriminatory power., (© 2022 Japan Society of Obstetrics and Gynecology.)

Background: The oral microbiota plays vital roles in both oral and systemic health, but limited studies have explored the transition of the female oral microbiota from preconception to pregnancy along with pronounced hormonal fluctuations., Aim: To characterize the oral microbiota among women in preconception and pregnancy through a prospective study and to explore the associations between the oral microbiota and oral hygiene practices., Methods: A total of 202 unstimulated saliva samples were collected from 101 women in both preconception and late pregnancy. The oral microbiota was analyzed using 16S rRNA gene sequencing., Results: The Ace and phylogenetic diversity (PD) index were significantly lower in the third trimester than preconception. The pathogenic taxa Prevotella and Atopobium parvulum were significantly higher during late pregnancy than preconception. Women with overall better oral hygiene practice showed lower richness     and diversity     in preconception compared to women with poorer oral hygiene practice. The abundance of pathogens such as Dialister during both preconception and pregnancy decreased among women with better oral hygiene practice., Conclusions: The composition of the oral microbiota changed slightly from preconception to late pregnancy, with more pathogens in saliva samples during pregnancy. Improving oral hygiene practices has the potential to maintain oral micro-ecological balance., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Gliomas are the most common and aggressive malignancies of the central nervous system. Histone deacetylases (HDACs) are important targets in cancer treatment. They regulate complex cellular mechanisms that influence tumor biology and immunogenicity. However, little is known about the function of HDACs in glioma. The Oncomine, Human Protein Atlas, Gene Expression Profiling Interactive Analysis, Broad Institute Cancer Cell Line Encyclopedia, Chinese Glioma Genome Atlas, OmicShare, cBioPortal, GeneMANIA, STRING, and TIMER databases were utilized to analyze the differential expression, prognostic value, and genetic alteration of HDAC and immune cell infiltration in patients with glioma. HDAC1/2 were considerable upregulated whereas HDAC11 was significantly downregulated in cancer tissues. HDAC1/2/3/4/5/7/8/11 were significantly correlated with the clinical glioma stage. HDAC1/2/3/10 were strongly upregulated in 11 glioma cell lines. High HDCA1/3/7 and low HDAC4/5/11 mRNA levels were significantly associated with overall survival and disease-free survival in glioma. HDAC1/2/3/4/5/7/9/10/11 are potential useful biomarkers for predicting the survival of patients with glioma. The functions of HDACs and 50 neighboring genes were primarily related to transcriptional dysregulation in cancers and the Notch, cGMP-PKG, and thyroid hormone signaling pathways. HDAC expression was significantly correlated with the infiltration of B cells, CD4 + T cells, CD8 + T cells, macrophages, neutrophils, and dendritic cells in glioma. Our study indicated that HDACs are putative precision therapy targets and prognostic biomarkers of survival in glioma patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Yan, Liang, Chen, Liu, Wu, Zheng, Dang, La and Liu.)

The heterogeneity and plasticity of muscle fibers are essential for the athletic performance of horses, mainly at the adaption of exercises and the effect on muscle diseases. Skeletal muscle fibers can be generally distinguished by their characteristics of contraction as slow and fast type myofibers. The diversity of contractile properties and metabolism enable skeletal muscles to respond to the variable functional requirements. We investigated the muscle fiber composition and metabolic enzyme activities of splenius muscle and gluteus medius muscle from Mongolian horses. The deep RNA-seq analysis of detecting differentially expressed mRNAs, lncRNAs, circRNAs and their correlation analysis from two muscles were performed. Splenius muscle and gluteus medius muscle from Mongolian horses showed a high divergence of myofiber compositions and metabolic enzyme activities. Corresponding to their phenotypic characteristics, 57 differentially expressed long noncoding RNAs and 12 differentially expressed circle RNAs were found between two muscles. The analysis results indicate multiple binding sites were detected in lncRNAs and circRNAs with myofiber-specific expressed miRNAs. Among which we found significant correlations between the above noncoding RNAs, miRNAs, their target genes, myofiber-specific developmental transcript factors, and sarcomere genes. We suggest that the ceRNA mechanism of differentially expressed noncoding RNAs by acting as miRNA sponges could be fine tuners in regulating skeletal muscle fiber composition and transition in horses, which will operate new protective measures of muscle disease and locomotor adaption for racehorses., (Copyright © 2021 Elsevier Inc. All rights reserved.)