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Abstract Background Marfan syndrome (MFS) is a hereditary connective tissue disorder involving multiple systems, including ophthalmologic abnormalities. Most cases are due to heterozygous mutations in the fibrillin‐1 gene (FBN1). Other associated genes include LTBP2, MYH11, MYLK, and SLC2A10. There is significant clinical overlap between MFS and other Marfan‐like disorders. Purpose To expand the mutation spectrum of FBN1 gene and validate the pathogenicity of Marfan‐related genes in patients with MFS and ocular manifestations. Methods We recruited 318 participants (195 cases, 123 controls), including 59 sporadic cases and 88 families. All patients had comprehensive ophthalmic examinations showing ocular features of MFS and met Ghent criteria. Additionally, 754 cases with other eye diseases were recruited. Panel‐based next‐generation sequencing (NGS) screened mutations in 792 genes related to inherited eye diseases. Results We detected 181 mutations with an 84.7% detection rate in sporadic cases and 87.5% in familial cases. The overall detection rate was 86.4%, with FBN1 accounting for 74.8%. In cases without FBN1 mutations, 23 mutations from seven Marfan‐related genes were identified, including four pathogenic or likely pathogenic mutations in LTBP2. The 181 mutations included 165 missenses, 10 splicings, three frameshifts, and three nonsenses. FBN1 accounted for 53.0% of mutations. The most prevalent pathogenic mutation was FBN1 c.4096G>A. Additionally, 94 novel mutations were detected, with 13 de novo mutations in 14 families. Conclusion We expanded the mutation spectrum of the FBN1 gene and provided evidence for the pathogenicity of other Marfan‐related genes. Variants in LTBP2 may contribute to the ocular manifestations in MFS, underscoring its role in phenotypic diversity.

Abstract Background Familial exudative vitreoretinopathy (FEVR) is a severe clinically and genetically heterogeneous retinal disorder characterized with failure of vascular development of the peripheral retina. The symptoms of FEVR vary widely among patients in the same family, and even between the two eyes of a given patient. The purpose of this study was to investigate the molecular mechanisms by which the start codon mutation of the TSPAN12 causes difference in clinical manifestations between individuals in the same family. Methods Next‐generation sequencing (NGS)‐based target capture sequencing was performed in proband with a diagnosis of FEVR and their normal visual acuity family members. Cosegregation analysis of the candidate causative variant was performed in additional family members by using Sanger sequencing. Complete fundus examination, fundus fluorescein angiography (FFA), and family history collection were performed in all family members. Potential candidate causative variants were verified with reference to guidelines and standards from the American College of Medical Genetics and Genomics. Results We identified a novel heterozygous missense mutation (c.1A>G, p.M1V) localized in the start codon of the TSPAN12 and was detected as a potentially disease‐causing variant for the proband. Retrospective analysis of clinical data, fundus examination, and FFA showed that the mutant carrier presented peripheral retinal vascular anomalies in early stages, and visual acuity did not show significant effects. However, the proband who carried this mutation and his cousin showed typical high‐stage FEVR fundus changes coupled with a sharp decline in vision. Conclusions We report a novel start codon mutation (c.1A>G, p.M1V) in the TSPAN12 that causes clinically heterogeneous manifestations. Our results expand the mutation spectrums of TSPAN12, and will be valuable for disease diagnosis, prognosis, genetic counseling, and enriching our understanding of the role of the tetraspanin‐12 protein in the pathogenesis of FEVR.

Extensive studies of the crystal-rich inclusions (CIs) hosted in minerals in pegmatite have resulted in substantially different models for the formation mechanism of the pegmatite. In order to evaluate these previously proposed formation mechanisms, the total homogenization processes of CIs hosted in spodumene from the Jiajika pegmatite deposit in Sichuan, China, were observed in situ under external H2O pressures in a new type of hydrothermal diamond-anvil cell (HDAC). The CIs in a spodumene chip were loaded in the sample chamber of HDAC with water, such that the CIs were under preset external H2O pressures during heating to avoid possible decrepitation. Our in situ observations showed that the crystals within the CIs were dissolved in carbonic-rich aqueous fluid during heating and that cristobalite was usually the first mineral being dissolved, followed by zabuyelite and silicate minerals until their total dissolution at temperatures between 500 and 720°C. These observations indicated that the minerals within the CIs were daughter minerals crystallized from an entrapped carbonate- and silica-rich aqueous solution and therefore provided useful information for evaluating the formation models of granitic pegmatites.

Background Whether cardiac structure and function abnormalities associated with dysglycemia are sufficient to explain the increased risk of death or heart failure (HF) remains unclear. Methods and Results We analyzed 6059 participants (mean age, 75±5 years; 58% women; and 22% Black individuals) who attended the ARIC (Atherosclerosis Risk in Communities) study visit 5 examination (2011–2013). Participants were categorized as no diabetes, pre‐diabetes, and diabetes (on the basis of medical history and glycated hemoglobin values). We assessed whether diabetes modified the association between echocardiographic measures of cardiac structure and function and the composite of all‐cause death or HF hospitalization and then estimated the extent to which the increased risk of the composite outcome associated with diabetes was explained by cardiac structure and function. Diabetes was prevalent in 33.5% of the subjects. Death or HF occurred in 1111 (18%) at a rate of 3.6 per 100 person‐years. Both measures of cardiac structure and function and diabetes status were significantly associated with worse prognosis after accounting for clinical confounders. While diabetes was consistently associated with a higher risk of events, it did not significantly modify the association between cardiac abnormalities and the risk of death or HF, except for subjects with higher left atrial volume who showed higher relative risk of events (P for interaction

Abstract Alternate day fasting (ADF), the most popular form of caloric restriction, has shown to improve metabolic health in preclinical subjects, while intrinsic network underpinning the process remains unclear. Here, it is found that liver undergoes dramatic metabolic reprogramming during ADF, accompanied surprisingly with unique complex II dysfunction attributing to suspended complex II assembly via suppressing SDHAF4, a recently identified assembly factor. Despite moderate mitochondrial complex II dysfunction, hepatic Sdhaf4 knockout mice present intriguingly improved glucose tolerance and systemic insulin sensitivity, consistent with mice after ADF intervention. Mechanistically, it is found that hepatocytes activate arginine‐nitric oxide (NO) biosynthesis axle in response to complex II and citric acid cycle dysfunction, the release of NO from liver can target muscle and adipocytes in addition to its autocrine action for enhanced insulin sensitivity. These results highlight the pivotal role of liver in ADF‐associated systemic benefits, and suggest that targeting hepatic complex II assembly can be an intriguing strategy against metabolic disorders.

Alpine glaciers are vulnerable to climate changes, and their recession due to warming has already induced a large number of geohazards closely related to the glacial motion, such as debris flow. Strong coupling of the geology, geomorphology, climate, and glacial action controls the type, size, development, and frequency of debris flow along the Parlung Zangbo River, Southeastern (SE) Tibetan Plateau. Field investigation in recent years indicates that the north bank is prone to much more frequenter debris flows than the south bank. The sharp contrast between the two river banks is due to the different formation conditions of debris flows, especially glaciers and geomorphology. The present paper examines the differences in the glacier and geomorphology conditions for glacier-related debris flows to occur, through a combination of field investigation, interviews with local residents, and geomorphological parameter, and glacier distribution analysis in the ArcGIS platform. The result indicates that, compared to the south bank of the Parlung River, the north bank has more favorable conditions in the glacier and geomorphology south, which is more conducive to the occurrence of debris flow. In conclusion, three kinds of mechanisms due to different formation conditions, especially glacier and geomorphology, are analyzed. The glacier-related debris flows on the south and north banks occur through different mechanisms due to different formation conditions. The debris flows on the north bank primarily occur in modes I and III, while the south bank is dominated by modes II and III debris flows. Based on the result, effective measures are proposed for mitigating damage to roads and railways within this area.

An appropriate understanding of the hydraulic characteristics of the two-phase flow in the rock fracture network is important in many engineering applications. To investigate the two-phase flow in the fracture network, a study on the two-phase flow characteristics in the intersecting fractures is necessary. In order to describe the two-phase flow in the intersecting fractures quantitatively, in this study, a gas-water two-phase flow experiment was conducted in a smooth 3D model with intersecting fractures. The results in this specific 3D model show that the flow structures in the intersecting fractures were similar to those of the stratified wavy flow in pipes. The nonlinearity induced by inertial force and turbulence in the intersecting fractures cannot be neglected in the two-phase flow, and the Martinelli-Lockhart model is effective for the two-phase flow in intersecting fractures. Delhaye’s model can be adapted for the cases in this experiment. The turbulence of the flow can be indicated by the values of C in Delhaye’s model, but resetting the appropriate range of the values of C is necessary.

Abstract Mitochondrial epigenetics is rising as intriguing notion for its potential involvement in aging and diseases, while the details remain largely unexplored. Here it is shown that among the 13 mitochondrial DNA (mtDNA) encoded genes, NADH‐dehydrogenase 6 (ND6) transcript is primarily decreased in obese and type 2 diabetes populations, which negatively correlates with its distinctive hypermethylation. Hepatic mtDNA sequencing in mice unveils that ND6 presents the highest methylation level, which dramatically increases under diabetic condition due to enhanced mitochondrial translocation of DNA methyltransferase 1 (DNMT1) promoted by free fatty acid through adenosine 5’‐monophosphate (AMP)‐activated protein kinase (AMPK) activation. Hepatic knockdown of ND6 or overexpression of Dnmt1 similarly impairs mitochondrial function and induces systemic insulin resistance both in vivo and in vitro. Genetic or chemical targeting hepatic DNMT1 shows significant benefits against insulin resistance associated metabolic disorders. These findings highlight the pivotal role of ND6 epigenetic network in regulating mitochondrial function and onset of insulin resistance, shedding light on potential preventive and therapeutic strategies of insulin resistance and related metabolic disorders from a perspective of mitochondrial epigenetics.

Abstract Grazing is one of the major anthropogenic driving factors influencing community structure and ecological function of grasslands. Fencing has been proved to be one of the main measures for rehabilitating degraded grasslands in northwestern China. However, data from combined empirical studies on the effects of different management regimes in desert grasslands are lacking. So we selected long‐term fencing (fenced since 1991), mid‐term fencing and seasonal fencing (fenced since 2002), and adjacent free‐grazing grasslands to investigate vegetation and soil properties on southwest Mu Us desert. Our results showed that fencing increased plant cover, height, aboveground biomass (AGB) of different plant life‐form groups, Shannon–Wiener diversity index, Evenness index, Simpson index, total soil nitrogen, total soil phosphorus, and soil organic matter, but decreased plant density, species richness, Richness index, soil bulk density, water content, and pH. However, 22–24 years of long‐term complete fencing might cause redegradation of vegetation and soil nutrients, characterized by the reduction of some vegetation properties, biodiversity, total AGB, and some soil properties. Seasonal fencing with 11–13 year was more beneficial to vegetation restoration than that with completely fencing measures. Our study suggests that appropriate artificial disturbances, such as seasonal fencing (winter grazing and summer fencing), should be used after long‐term fencing in order to maintain grassland productivity and biodiversity. These findings will help to provide theoretical support for vegetation restoration and sustainable management in grassland under grazing prohibition at Mu Us desert.

Borehole pressure relief technology is an effective way to reduce the elastic energy in the surrounding rock of deep roadways, thereby reducing the risk of regional rock bursts. To avoid large deformation of the roadway caused by pressure relief holes with large diameters and insufficient pressure relief with small pore diameters, this study proposes precise pressure relief holes with nonequal diameters in order to achieve strong pressure relief with minimal disturbance based on the abutment pressure distribution pattern. To verify the pressure relief effect of the nonequal diameter holes, numerical simulations were performed in FLAC3D. This study investigated stress field, deformation laws, and plastic failure zone of roadway surrounding rock with 100 mm pressure relief holes, nonequal diameter precision pressure relief hole (100 mm + 300 mm), and 300 mm pressure relief holes. The simulation results show that, as the diameter of the pressure relief hole increases, the coupling effect of evenly spaced adjacent pressure relief holes is strengthened, thus improving the pressure relief efficiency. When pressure relief holes of nonequal diameter are adopted, the stress environment of the surrounding rock is clearly improved compared to100 mm pressure relief holes, and the plastic failure range increased by 2-3 times. The roof-to-floor convergence with nonequal diameter is 30.8% that of 300 mm pressure relief holes and 41% that of 100 mm pressure relief holes. Furthermore, the rib displacement is 30.4% and 46.9% that of 300 mm and 100 mm pressure relief holes, respectively. Thus, precise pressure relief holes with nonequal diameter provide both strong pressure relief associated with large diameter holes and small disturbance of small diameter of small holes. This study provides a reference for precise pressure relief application with pressure relief holes.

In this paper, a fully discretized finite difference scheme is derived for two-dimensional wave equation with damped Neumann boundary condition. By discrete energy method, the proposed difference scheme is proven to be of second-order convergence and of unconditional stability with respect to both initial conditions and right-hand term in a proper discretized L2 norm. The theoretical result is verified by a numerical experiment.

“Pit-in-pit” foundations, where the overall pit is divided into inner and outer pits, present a wide range of engineering problems and yet have received little detailed study. Among the many factors that affect the stability of a deep foundation pit, loading and rainfall are the two most important. Therefore, in this study, physical model experiments are carried out in the laboratory based on a pit-in-pit foundation that is typical of engineering applications in China, simulating the deformation of the system under different loading and rainfall flow conditions. Optical fibers along with constant resistance and large deformation (CRLD) bolts are adopted to collectively monitor the stress and strain inside the pit-in-pit foundation, assisted by fiber Bragg grating (FBG) displacement meters. The results of the monitoring show that the position of the inner pit relative to the outer pit has a strong influence on the stability of the outer pit. The side on which the inner pit is closest to the outer pit wall is the most prone to instability and should thus be reinforced. Comparison and analysis of monitoring results obtained with optical fibers and CRLD bolts allow a potentially dangerous slip surface to be identified, indicating the value of using this type of collective monitoring in deep foundation pits.

337 Lake Donghu is a 32-km 2 shallow, subtropical lake near the Yangtze River (P.R. China) that has experienced dramatic changes in the past five decades. These changes include: (1) a trophic state change from mesotrophy to hypertrophy; (2) dense blooms of cyanobacteria during every summer from the 1970s to 1984; (3) a cessation of blooms starting in 1985, with no recurrence; and (4) an increase, coincident with bloom declines, in the production of silver and bighead carp (filter-feeders) by more than tenfold. There are several possible explanations for the disappearance of blooms, including changes in nutrient concentrations, increased zooplankton grazing, and increased grazing on algae by fish. The long-term data suggest that changes in nutrients or in zooplankton were not important, but that the remarkably increased fish densities might have played the key role. To test this hypothesis, in situ enclosure experiments were conducted in three years. The main conclusions are as follows: (1) an increased stocking of the lake with carp played a decisive role in the elimination of cyanobacteria blooms; (2) both silver and bighead carp can eliminate cyanobacteria blooms directly by grazing; (3) zooplankton cannot suppress the blooms; and (4) the lake still is vulnerable to the outbreak of blooms, should fish grazing decline. The critical biomass of carp is approximately 50 g m 3 . The results suggest the applicability of a new food-web manipulation (increased stocking with filter-feeding fish) for controlling cyanobacteria blooms in hypereutrophic lakes. The approach differs from traditional biomanipulation in Europe and North America, where piscivores are added to control planktivores, and this in turn increases zooplankton and decreases algae. The new biomanipulation method is being used or being tested to counteract cyanobacteria blooms in many Chinese lakes such as Lake Dianchi?Xie and Liu: Biomanipulation to Control Cyanobacteria TheScientificWorld (2001) 1, 337-356 in Yunnan Province, Lake Chaohu in Anhui Province, and Lake Taihu in Jiangsu Province. The method has great potential as an important component of an integrated approach to counteract cyanobacteria blooms, especially in lakes where nutrient inputs cannot be reduced sufficiently, and where zooplankton cannot effectively control phytoplankton production.

An explicit finite difference scheme for one-dimensional Burgers equation is derived from the lattice Boltzmann method. The system of the lattice Boltzmann equations for the distribution of the fictitious particles is rewritten as a three-level finite difference equation. The scheme is monotonic and satisfies maximum value principle; therefore, the stability is proved. Numerical solutions have been compared with the exact solutions reported in previous studies. The L2, L∞ and Root-Mean-Square (RMS) errors in the solutions show that the scheme is accurate and effective.

A new numerical method based on Bernstein polynomials expansion is proposed for solving one-dimensional elliptic interface problems. Both Galerkin formulation and collocation formulation are constructed to determine the expansion coefficients. In Galerkin formulation, the flux jump condition can be imposed by the weak formulation naturally. In collocation formulation, the results obtained by B-polynomials expansion are compared with that obtained by Lagrange basis expansion. Numerical experiments show that B-polynomials expansion is superior to Lagrange expansion in both condition number and accuracy. Both methods can yield high accuracy even with small value of N.