This study reports a congenital heart disease, characterized by ventricular wall thinning and septal defects, caused by a heterozygous missense mutation (R755 W) in the glycolytic gene PFKP (platelet isoform of phosphofructokinase-1). The pathogenic mechanism involves the PFKP mutation impairing enzyme activity, which inhibits cardiomyocyte proliferation and leads to the thinning of the compact myocardium. In the mouse model, we found that administering the downstream metabolite, fructose-1,6-bisphosphate, reversed the myocardial hypoplasia in fetal mice, providing proof-of-concept for in utero intervention. Clinically, we successfully prevented the transmission of the disease using preimplantation genetic testing, resulting in the birth of a healthy infant.

Thermostability is critical for the industrial applications of xylanase, including paper production, animal feed, and lignocellulosic biomass conversion. Here, we report that the rational introduction of surface-exposed glutamic acid (Glu) residues significantly enhances the thermostability of GH10 xylanases. Engineered variants of XT6, BhS7Xyl, and FXYN exhibited prolonged half-lives that were elevated by 2.5-, 1.5-, and 3-fold relative to their respective wild-type enzymes. The stabilization arises from strengthened conformational rigidity due to the formation of numerous new salt bridges. This strategy was further validated in two novel xylanases of Xyn466 and Xyn486 from Cellulomonas bogoriensis 69B4T. In contrast to disulfide bond engineering and ΔΔG-based engineering, surface Glu modification provides superior stabilization (Xyn466-9QE of 5.9-fold and Xyn486-11QE of 9.7-fold increased half-life at 60 °C) with lower mutational load. Our results provide a more efficient strategy with a higher success rate and lower activity trade-off for improving the thermostability of GH10 xylanases.

The β-xylosidase Cbxyl1 of GH43-1 subfamily from Cellulomonas bogoriensis 69B4T was expressed in Escherichia coli. It showed optimal activity at 30 °C and pH 7.0, retaining 40

Thermostability is critical for the industrial applications of xylanase, including paper production, animal feed, and lignocellulosic biomass conversion. Here, we report that the rational introduction of surface-exposed glutamic acid (Glu) residues significantly enhances the thermostability of GH10 xylanases. Engineered variants of XT6, BhS7Xyl, and FXYN exhibited prolonged half-lives that were elevated by 2.5-, 1.5-, and 3-fold relative to their respective wild-type enzymes. The stabilization arises from strengthened conformational rigidity due to the formation of numerous new salt bridges. This strategy was further validated in two novel xylanases of Xyn466 and Xyn486 from 69B4T. In contrast to disulfide bond engineering and Delta Delta G-based engineering, surface Glu modification provides superior stabilization (Xyn466-9QE of 5.9-fold and Xyn486-11QE of 9.7-fold increased half-life at 60 degrees C) with lower mutational load. Our results provide a more efficient strategy with a higher success rate and lower activity trade-off for improving the thermostability of GH10 xylanases.

BACKGROUND:Congenital heart disease (CHD) exhibits a marked male predominance in birth prevalence, yet the genetic mechanisms underlying this sex disparity remain poorly understood. This study investigates the contribution of rare damaging variants on autosomes and the X chromosome to sex differences in foetal CHD. METHODS:Parents of foetuses with CHD were recruited for the study. Rare damaging variants were identified by analysing whole-exome sequencing data from foetus-parental trios, and their contributions to sex differences were estimated through case-control studies. Functional enrichment analysis was conducted to assess functional differences in genetic variants between sexes. FINDINGS:820 foetal probands with CHD were recruited, including 487 males and 333 females. We identified a significant enrichment of X-linked rare damaging variants, primarily driven by maternally inherited hemizygous variants (MIHVs) in male probands (OR = 1·84, P < 0·05), which accounted for 7·2% of male cases in our cohort. These variants were not found to be enriched in female probands. Additionally, X-linked rare damaging de novo variants (DNVs) were not enriched in either male or female probands (female probands: 1·8% versus female controls: 0·7%, P = 0·6789; no DNVs observed in males). Gene-level variant burden analysis revealed three X-linked CHD candidate genes: DCX, CACNA1F, and MAP3K15. Autosomal rare variants did not show significant differences in variant burdens between sexes. Notably, male probands showed specific functional enrichments in cilia-related pathways for autosomal recessive variants, as well as in chromatin remodelling and nervous system development pathways for autosomal DNVs. INTERPRETATION:Male and female foetal CHD have significantly different genetic landscapes. The enrichment of X-linked rare damaging MIHVs in males provides a genetic explanation for the higher prevalence of CHD in males. This finding highlights the importance of incorporating sex-stratified approaches in clinical diagnostics and research. FUNDING:Natural Science Foundation of China and Key research and development project of Hebei Province.

Poly(ε-caprolactone) (PCL) is a widely used synthetic polymer with significant commercial applications, and its degradation and synthesis have become the focus of considerable research. In this study, we purified a PCL-degrading enzyme, PCLase0801, produced by Pseudomonas sp. DS0801. The enzyme was purified to homogeneity and had a molecular weight of 30.4 kDa. It exhibited optimal activity at 40°C and pH 8.0, hydrolyzing PCL into monomers, dimers, and trimers. The enzyme was identified as a lipase and showed good tolerance to organic solvents. Additionally, PCLase0801 catalyzed the ring-opening polymerization of ε-caprolactone, producing PCL with a molecular weight of 6050 g/mol and favorable structural properties. This work provides new insights into the potential applications of PCL-degrading enzymes in PCL treatment and biosynthesis.

The finite element simulation is a valid way for the rapid development of the root-cutting mechanism for hydroponic Chinese kale. The stem of the hydroponic Chinese kale was simplified as a transverse isotropic elastic body, and axial compression, three-point bending, and shear tests were performed. The ANSYS/LS-DYNA19.2 software was adopted for stem shear simulation, and the regression equation of the maximum simulated shear force was established. The optimized mechanical parameters were determined by minimizing the deviation between the maximum shear force obtained from the simulation and test. The three-dimensional scanning method was employed to establish the geometric model of the hydroponic Chinese kale stem. The cutting finite element simulation model and test platform were constructed. Displacement, deformation, and force measured from simulation and test were compared. Through measurement and simulation calibration, an axial elastic modulus of 6.22 MPa, axial Poisson's ratio of 0.46, radial elastic modulus of 3.56 MPa, radial Poisson's ratio of 0.44, radial shear modulus of 0.8 MPa, and a failure strain of 0.08 were determined. During the cutting simulation and test, the resulting maximum displacement deviations of the marking points on the end of the stem were 0.68 mm along the X-axis and 2.83 mm along the Y-axis, while the maximum deviations of the cutting and clamping force were 0.49 N and 0.77 N, respectively. The deformation and force variation laws of the kale stem in the cutting simulation and test process were basically consistent. It showed that the mechanical parameters calibrated by the simulation were accurate and effective, and the stem cutting simulation results with the finite element method were in good agreement with that of the cutting test. The study provided a reference for the rapid optimization design of the root-cutting mechanism for hydroponic Chinese kale harvest.

Medium additives have been shown to affect the synthesis of active products in fungi. This study investigated the effects of corn stalk, poplar sawdust, Tween-80, and oleic acid on mycelial biomass and physicochemical properties, as well as the bioactivity of polysaccharides, including exopolysaccharides (EPS) and intracellular polysaccharides (IPS), in the submerged culture of Bjerkandera fumosa. Results showed that the addition of corn stalk or poplar sawdust increased the production of EPS but decreased the production of IPS; Tween-80 had less effect on the production of EPS and IPS; and oleic acid stimulated polysaccharide production significantly. Polysaccharide property analysis showed that the addition of corn stalk or poplar sawdust promoted the production of high-molecular-weight components in polysaccharides and changed the monosaccharide composition of polysaccharides, as well as increased the mannose, glucuronic acid, and xylose contents of IPS. Tween-80 and oleic acid also changed the molecular weight distribution of polysaccharides but only slightly affected the composition of monosaccharides. The bioactivity assay indicated that the polysaccharides obtained by adding corn stalk possessed high hydroxyl radical scavenging and antitumor activities. The effect of poplar sawdust was slightly weaker than that of corn stalk. EPS and IPS obtained from a culture with Tween-80 and oleic acid possessed low antioxidant activity. Moreover, their antitumor activity was improved and lost, respectively. The results obtained in this work are useful for improving the understanding of the optimization and regulation of bioactive polysaccharide production in the submerged culture of B. fumosa.

Background Mutations in the SETD5 gene lead to the autosomal dominant disorder termed Mental retardation type 23. Limited clinical reports have made it challenging to comprehensively delineate the clinical outcomes and mutation spectrum associated with this gene. Case presentation: In this study, a fetal case presenting an ostium primum atrial septal defect, a presumed upper ventricular septal defect was identified through fetal cardiac ultrasound. Following this discovery, an in-depth genetic assessment, encompassing whole exome sequencing, was executed on the fetus and both parents to pinpoint potential genetic origins. From the exome data, a previously undocumented variant (exon21: c.3601_3605del: p. W1201Efs*2) in the SETD5 gene (NM_001080517.3) surfaced. Lineage analysis validated this as a de novo variant. This mutation disrupts the gene's open reading frame, consequently affecting protein functionality. This is the first prenatal diagnosis of a fetus with a SETD5 mutation, advancing the time of diagnosis while broadening our understanding of the gene's mutation spectrum and clinical manifestations. Conclusions Our study confirms that congenital heart disease, including atrial and ventricular septal defects, is a prenatal clinical feature caused by mutations in this gene. Fetal cardiac ultrasound can be used as a means of early screening for such disorders, and the importance of prenatal whole-exome sequencing technology was emphasized.

Manually harvesting hydroponic leafy vegetables from a cultivation pipeline is labor-intensive and expensive. Rapidly grabbing hydroponic leafy vegetables grown in different positions and orientations in the planting hole is the primary issue for efficient mechanical harvesting. Thus, a novel grabbing mechanism with double-pivot rotation cross fingers is proposed. The fingers’ inner surfaces could envelop the grabbable area of the leafy vegetable in the grasping process and position each leafy vegetable stalk to the center of the planting hole before taking it out. A grabbing mechanism for harvesting hydroponic Chinese kale was designed and optimized with less than 1 mm of grasping error, enough enveloping range, and no collision with the extended leaves. Laboratory experiments were conducted to investigate centering and grabbing at different initial positions and inclination angles of the hydroponic Chinese kale and varied finger deflection speeds. It was indicated that for the grasping inclination angle and grabbing success rate, the initial inclination angle was a significant factor, as was the position, whereas the finger deflection speed was insignificant. As the initial inclination angle of matured hydroponic Chinese kale in different initial positions is mostly larger than 60°, the best results were achieved with a finger deflection speed in the range of 40° s−1 to 60° s−1 and grasping inclination angles of 85° to 95°, with a grabbing success rate of more than 95%. This showed the promising applicability of the studied grabbing mechanism for harvesting hydroponic Chinese kale or other varieties of leafy hydroponic vegetables with similar growth characteristics.

BackgroundMixed aortic valve disease (MAVD) is a frequent concomitant valve disease with unique cardiac pathological changes compared to predominant aortic stenosis (PAS). The previous studies about the MAVD are contradictory. Therefore, a new perspective is needed to assess the value of TAVR for this cohort of patients.MethodsFrom January 2018 to December 2021, 90 MAVD patients and 72 PAS patients who underwent TAVR in our hospital were collected. 1:1 propensity score matching analysis was used to control the bias in patient selection. The dynamic changes in left ventricular morphology and hemodynamics were compared by generalized estimating equations. Univariate or multivariate logistic regression analysis was used to screen for independent risk factors for the non-occurrence of left ventricular reverse remodeling (non-LVRR).ResultsAfter the matching procedure, 112 patients were included in the analysis (56 in each group). Baseline characteristics were similar between the two groups. LVRR occurred in both groups, but MAVD had greater left ventricular end-diastolic volume index and left ventricular mass index, a higher incidence of mitral regurgitation (MR), and a more pronounced transformation of ventricular geometry patterns. Post-operative MR (odd ratio [OR]: 10.05; 95% confidence interval [CI]: 2.08-48.57; p < .001) and coronary artery disease (OR: 2.82; 95% CI: 1.08-7.34; p = .034) were independent risk factors for non-LVRR.ConclusionLVRR also occurs in patients with MAVD, post-operative MR and coronary artery disease were independent risk factors for non-LVRR.

Background:The aortic bulge sign possibly indicates an arterial aneurysm, pseudoaneurysm, aortic dissection, or aortic diverticulum. The aortic diverticulum is a congenital abnormality of the aorta, mainly known as an aneurysmal remnant of the dorsal fourth aortic arch or ductus arteriosus. However, the diverticulum of another part of the aorta has rarely been reported.Case summary:We report a case of a 24-year-old male with a history of oral ulcer presented with recurrent hyperpyrexia and chest pain. Echocardiography and computed tomography showed the anomalous origin of the coronary arteries, aortic valve vegetations, and a bulge at the aortic root. The patient then received a Bentall procedure. The aorta and aortic valves were replaced by a valved conduit. The bulge with a normal arterial wall at the aortic root was considered to be a diverticulum. The infective endocarditis was verified as a secondary oral-derived streptococcal infection. The patient was discharged 15 days after surgery. Post-operative echocardiography had no positive findings.Conclusion:Our case report highlights the role of multimodal cardiovascular imaging for the diagnostic workup of rare disorders, such as the presence of a diverticulum in the aortic root in a patient with endocarditis and anomalous origin of the right coronary artery.

Maize starch was irradiated by a Co60 irradiator with different doses. The morphology and physicochemical properties of native and irradiated starches were investigated. Scanning electron microscopy showed that the shape and size of starch granules did not change after irradiation. However, the irradiated starch granules were easily destroyed by dissolution. Irradiation also caused the change of starch color, the decrease in the pH value, light transmittance, stability index, degree of polymerization, total sugar content, and the increase in the swelling index and the reducing sugar content. In this study, irradiated maize starch was also used as material for ethanol fermentation to investigate its potential as a pretreatment method. Results showed that the ethanol yield of cooked and raw starch fermentation using irradiated starch increased by 20.41 % and 5.18 %, respectively, and the ethanol concentration increased by 3 % and 2 %. This finding indicated that irradiation effectively improved the utilization rate of maize starch, making it an effective pretreatment method for ethanol fermentation.

Abstract Beaulieu-Boycott-Innes Syndrome (BBIS) is a rare autosomal recessive neurodevelopmental disorder genetic disorder caused by mutations in the THOC6 gene. The clinical characteristics caused by mutations in this gene and the range of variants have not yet been extensively described due to the dearth of pertinent clinical studies. Using prenatal cardiac ultrasonography, we discovered a fetus with a congenital double outlet right ventricle of the heart. The fetus as well as its parents were then subjected to a thorough genetic analysis, including whole exome sequencing, to ascertain the underlying genetic etiology. Two compound heterozygous variations for the THOC6 gene (NM_024339.5), neither of which has been reported, (exon12: c.826C>T:p.Q276* and exon3:c.178G>T:p.E60*), were identified by exome sequencing in the pre-documented individuals, and both of them received inheritances from their parents. Both of these factors affect the protein's function by changing the matching codon to a stop codon. We present a case of prenatal fetal THOC6 mutation, extending the mutation spectrum and clinical characteristics of the THOC6 gene, suggesting that the double outlet of the right ventricle of the heart may be a clinical feature caused by the mutation of the gene, and highlighting the importance of prenatal whole-exome sequencing technology in elucidating prenatal diagnosis and prognosis.

目的 应用超声心动图评价主动脉瓣二叶畸形经导管主动脉瓣置换术(TAVR)后发生瓣周漏(PVL)的危险因素.方法 回顾性分析TAVR手术患者共计363例,先天性主动脉瓣二叶畸形(BAV)60例,正常三叶式主动脉瓣(TAV)303例.瓣叶类型为分组变量,原始队列以1:1倾向性评分匹配法(PSM)筛选出PSM队列.采用多因素Logistic回归模型筛选术后中重度PVL的独立危险因素,使用受试者工作特征(ROC)曲线观察超声相关危险因素对术后中重度PVL的预测价值.结果 ①筛选出57对PSM队列组间基线数据无统计学意义(P＞0.05),两组间术后发生轻度PVL比例无统计学意义(P＞0.05),但BAV组术后发生中重度PVL的比例高于TAV组(P = 0.026).②57对PSM队列多因素Logistic回归分析显示,瓣叶类型(BAV)(OR = 6.103,95％CI:1.206～30.872,P= 0.029)、术前左室流出道(LVOT)形态指数(OR =0.896,95％CI:0.817～0.982,P = 0.019)与术后发生中重度PVL存在独立相关.③ROC曲线显示LVOT形态指数可预测BAV 组术后中重度 PVL 的发生[曲线下面积(AUC)= 0.744,95％CI:0.602～0.886,P=0.021].结论 TAVR术后BAV比TAV患者更易发生中重度PVL.LVOT形态指数是所有患者TAVR术后发生中重度PVL的独立危险因素,但仅对BAV具有一定预测价值.

BackgroundTranscatheter aortic valve replacement (TAVR) in the treatment of patients with pure native aortic valve regurgitation (NAVR) has been based on the “off-label” indications, while the absence of aortic valve calcification and difficulty in anchoring was found to significantly increase the risk of prosthesis malposition. The aim of this study was to explore the anatomical predictors of severe prosthesis malposition following TAVR with the self-expandable Venus-A Valve among patients with NAVR.MethodsA total of 62 patients with NAVR who underwent TAVR with Venus-A Valve at four Chinese clinical centers were retrospectively observed. The clinical features, aortic multidetector computed tomography (MDCT) data, and clinical outcomes were compared between non-/mild malposition and severe malposition groups. Univariate logistic regression analysis was used to identify the risk factors of severe prosthesis malposition, and the receiver operating characteristic (ROC) curve was used to explore the predictive value of the risk factors.ResultsValve migration to ascending aortic direction occurred in 1 patient, and the remaining 61 patients (including 19 severe malposition cases and 42 non-/mild malposition cases) were included in the analysis. The diameter and height of the sinotubular junction (STJ) and STJ cover index (STJCI, calculated as 100%*STJ diameter/nominal prosthesis crown diameter) were all greater in the severe malposition group (all p < 0.05). Logistic regression showed that STJ diameter (OR = 1.23, 95% CI 1.04–1.47, p = 0.017), STJ height (OR = 1.24, 95% CI 1.04–1.47, p = 0.017), and STJCI (OR = 1.08, 95% CI 1.01–1.16, p = 0.032) were potential predictors for severe prosthesis malposition. The area under the ROC curve was 0.72 (95% CI 0.58–0.85, p = 0.008) for STJ diameter, 0.70 (95% CI 0.55–0.86, p = 0.012) for STJ height, and 0.69 (95% CI 0.55–0.83, p = 0.017) for STJCI, respectively. The cutoff value was 33.2 mm for STJ diameter (sensitivity was 84.2% and specificity was 65.8%), 24.1 mm for STJ height (sensitivity was 57.9% and specificity was 87.8%), and 81.0% for STJCI (sensitivity was 68.4% and specificity was 68.3%), respectively.ConclusionLarger and higher STJ, as well as greater STJ to valve crown diameter ratio, may help identify patients at high risk for severe prosthesis malposition among patients with NAVR undergoing TAVR with Venus-A prosthesis valve.

心脏血管瘤是一种罕见的心脏原发性良性肿瘤,最早由Uskoff于1893年发现并报道[1],文献资料以个案报道多见.心脏血管瘤可发生在心脏的任何位置,包括心外膜、心肌、心内膜,常见于右心室、左室壁、室间隔,罕见于心外膜、房间隔及瓣膜上,以累及右心系统较为多见,单纯累及房间隔罕见.本文分析1例房间隔海绵状血管瘤的临床资料并复习相关文献,希望加强对心脏血管瘤的认识.

Poly(ε-caprolactone) (PCL) is an artificial polyester with commercially promising application. In this study, two novel PCL-degrading enzymes named PCLase I and PCLase II were purified to homogeneity from the culture supernatant of an effective polyester-degrading bacterium, Pseudomonas hydrolytica sp. DSWY01T. The molecular masses of PCLase I and PCLase II were determined to be 27.5 and 30.0 kDa, respectively. The optimum temperatures for the enzyme activities were 50 and 40°C, and the optimum pH values were 9.0 and 10.0, respectively. The two enzymes exhibited different physical and chemical properties, but both enzymes could degrade PCL substrates into monomers and oligomers. Weight loss detection and scanning electron microscopy revealed that PCLase I had more effective degradation ability than PCLase II. The genes of the two enzymes were cloned on the basis of the peptide fingerprint analysis results. The sequence analysis and substrate specificity analysis results showed that PCLase I and PCLase II were cutinase and lipase, respectively. Interface activation experiment also confirmed this conclusion. Structural analysis and modeling were further performed to obtain possible insights on the mechanism.

心脏原发性肿瘤较为罕见,尸检证实发病率为0.002％～0.3％o[1],其中恶性肿瘤占25％,左心系统恶性肿瘤发病率比右心系统恶性肿瘤发病率更低,并且左心房恶性肿瘤极易被误诊为黏液瘤[2].原发于心脏的恶性肿瘤多为肉瘤[3],其中以血管肉瘤较为常见,纤维肉瘤罕见.本文选取陆军军医大学第二附属医院收治的1 例左心房纤维肉瘤患者,对其临床表现、超声心动图特征、组织病理学检查结果进行总结,报道如下.

目的 本研究旨在基于贝叶斯网络的大数据分析探讨胎儿心脏病(FHD)的相关因素,并定量分析从单因素到多因素累积暴露的对FHD的相对风险比.方法 连续入组从2010年6月至2018年7月于首都医科大学附属北京安贞医院母胎医学会诊中心接受胎儿超声心动图检查的孕妇(n=16086,包括孕有异常胎儿的孕妇3312例),获得26个孕妇和胎儿因素,包括年龄,合并症,药物暴露,引产史和先天性心脏病病史,近亲结婚,孕妇和配偶的不良习惯,以及是否是双胎及是否伴有心律失常,基于所有变量构建贝叶斯网络,并通过联合树推理算法,预测两组的胎儿CHD患病率,从而得到不同暴露因素组合条件下的胎儿CHD的风险比(RR).考虑到孕周对模型预测准确度的提升作用,将孕周分组进行了敏感性分析.结果 单因素分析显示,双胎妊娠、自发流产、配偶吸烟的RR分别为1.50、1.38、1.11;当多个因素结合在一起时风险逐渐升高.当是否为双胎与流产史或吸烟配偶相结合时,我们发现FHD的RR更高(RR=1.96或1.63).以此类推,当同时存在五个因素时,包括是否为双胎、孕早期上呼吸道感染、孕妇精神压力、贫血以及自发流产史或配偶吸烟时FHD风险高于小于5个的因素组合(RR=2.62或2.28).除上述因素外,其他因素不会继续增加FHD风险.我们进一步根据孕周分组(A组:≥16周,<28周;B组≥28周,<40周)进行敏感性分析,结果发现趋势同上.结论 基于贝叶斯网络学习结果,我们发现与FHD直接相关因素包括自发流产,妊娠早期上呼吸道感染,贫血和孕妇精神压力,以及双胎和吸烟配偶.上述组合因素越多,FHD的风险就越高.这些发现提示对存在这些危险因素的孕妇加强管理及产前咨询是非常重要的.