Search

Laser power bed fusion (LPBF) as a widely used laser additive manufacturing, which has demonstrated a promising capability in the simultaneous formation of high-performance composites with unique microstructure. In order to further meet the urgent needs of aerospace sophisticated equipment, this work investigated the laser additive manufacturing of CrFeNb particles reinforced Ni-based superalloy composites with grain refinement and superior performance. A few CrFeNb particles were added to IN718 superalloy powder. The CrFeNb particles as a center of heterogeneous nucleation effectively facilitated to produce fine equiaxed grains and did not introduce significant residual stress in the as-deposited IN718 with CrFeNb composites. The stress concentration of the heat-treated IN718 with 4 wt% CrFeNb composites was significantly reduced. The grain orientation was not along the and tended towards random. The particle size of as-deposited IN718 with 4 wt% CrFeNb composites was refined and the average size was 13.46 μm. The unmelted CrFeNb particles were dissolved and diffused into the γ matrix during heat treatment. A hard brittle phase was rich in Nb and Mo elements along the grain boundary. Under the combined effect of three strengthening mechanisms, the mechanical properties of the IN718 with 4 wt% CrFeNb composites at room temperature were improved. The yield strength, tensile strength and microhardness of the heat-treated IN718 with 4 wt% CrFeNb composites reached to 1194 MPa, 1426 MPa and 521 HV, respectively. This study provides a new method and foundation for the preparation and application of IN718 composites with excellent performance.

Abstract Small cell lung cancer (SCLC) is an extremely aggressive cancer with a relatively low median survival rate after diagnosis. Treatment options such as chemotherapy or combination immunotherapy have shown clinical benefits, but resistance and relapse can occur. Antibody–drug conjugates (ADCs), as a novel class of biopharmaceutical compounds, have broad application prospects in the treatment of SCLC. ADCs consist of monoclonal antibodies that specifically target cancer cells and are attached to cytotoxic drugs, allowing for targeted killing of cancer cells while sparing healthy tissues. Current clinical studies focus on Delta-like protein 3 (DLL3), CD56, Trophoblast cell surface antigen 2 (Trop-2), B7-H3, and SEZ6. Although toxicities exceeding expectations have been observed with Rova-T, drugs targeting TROP-2 (Sacituzumab Govitecan), B7-H3 (DS-7300), and SEZ6 (ABBV-011) have shown exciting clinical benefits. In this review, we collect the latest clinical evidence to describe the therapeutic efficacy and safety of ADCs in SCLC and discuss prospects and challenges.

In high-rise buildings with large indoor and outdoor temperature difference, neglecting the effect of stack effect in smoke exhaust shafts may cause calculation error of the fluid network model. In this paper, the mathematical model of kitchen smoke exhaust system considering the influence of stack effect was put forward and it can be inserted different range hood sub-models. Compared with the results of six working conditions of the model without considering the stack effect, the error of the proposed model were reduced by 7.6%, 4.3%, 4.1%, 2.8%, 2.4%, and 2.1%. While the indoor and outdoor temperature difference varies from −5 °C to 49 °C, the effect of stack effect on the pressure in the flue and the flow rate for each user was studied for six operating rates s. The results show that under the combined effect of stack effect and flue resistance, the static pressure of the kitchen smoke exhaust system showed a low-high-low distribution, and the maximum static pressure in the flue moved toward the bottom with the increase of temperature difference. User flow rates exhibit a low-high-low-high distribution, with an increased flow rate in the bottom users and the largest flow rate in the top users.

Abstract Metastatic breast cancer (mBC) poses a significant threat to women's health and is a major cause of malignant neoplasms in women. Human epidermal growth factor receptor (HER)3, an integral member of the ErbB/HER receptor tyrosine kinase family, is a crucial activator of the phosphoinositide-3 kinase/protein kinase B signaling pathway. HER3 overexpression significantly contributes to the development of resistance to drugs targeting other HER receptors, such as HER2 and epidermal growth factor receptors, and plays a crucial role in the onset and progression of mBC. Recently, numerous HER3-targeted therapeutic agents, such as monoclonal antibodies (mAbs), bispecific antibodies (bAbs), and antibody–drug conjugates (ADCs), have emerged. However, the efficacy of HER3-targeted mAbs and bAbs is limited when used individually, and their combination may result in toxic adverse effects. On the other hand, ADCs are cytotoxic to cancer cells and can bind to target cells through antibodies, which highlights their use in targeted HER3 therapy for mBC. This review provides an overview of recent advancements in HER3 research, historical initiatives, and innovative approaches in targeted HER3 therapy for metastatic breast cancer. Evaluating the advantages and disadvantages of current methods may yield valuable insights and lessons.

Bioimpedance analysis (BIA)–body composition monitoring (BCM) has been used to evaluate the hydration and nutritional status of adults and children on dialysis. However, its clinical application still has challenges, so further exploration is valuable. We used BIA-BCM to evaluate the hydration and nutritional status of children undergoing chronic peritoneal dialysis from 1 July 2021 to 31 December 2022 in the Children’s Hospital of Fudan University to explore the clinical value of this method. A total of 84 children on chronic peritoneal dialysis (PD) were included. In the PD group, 16 (19.05%) and 31 (36.90%) had mild and severe overhydration (OH), respectively; 41.27% (26/63) had a low lean tissue index (LTI). In the PD group, patients with relative OH (Re-OH) > 5.6% had significantly higher systolic blood pressure (SBP) and SBP z score (SBPz). Patients with LTI > 12% had significantly higher body mass index (BMI) and BMI z score (BMIz). Canonical correlation analysis indicated a linear relationship (ρ = 0.708) between BIA-BCM hydration and the clinical hydration indicator and a linear relationship (ρ = 0.995) between the BIA-BCM nutritional indicator and the clinical nutritional indicator. A total of 56% of children on chronic peritoneal dialysis had OH, and 41% had a low LTI. In PD patients, SBP and SBPz were correlated with BIA-BCM Re-OH, and BMI and BMIz were correlated with BIA-BCM LTI. BIA-BCM indicators have good clinical value in evaluating hydration and nutrition.

Abstract Background Congenital anomalies of the kidney and urinary tract (CAKUT) are prevalent birth defects. Although pathogenic CAKUT genes are known, they are insufficient to reveal the causes for all patients. Our previous studies indicated GEN1 as a pathogenic gene of CAKUT in mice, and this study further investigated the correlation between GEN1 and human CAKUT. Methods In this study, DNA from 910 individuals with CAKUT was collected; 26 GEN1 rare variants were identified, and two GEN1 (missense) variants in a non-CAKUT group were found. Mainly due to the stability results of the predicted mutant on the website, in vitro, 10 variants (eight CAKUT, two non-CAKUT) were selected to verify mutant protein stability. In addition, mainly based on the division of the mutation site located in the functional region of the GEN1 protein, 8 variants (six CAKUT, two non-CAKUT) were selected to verify enzymatic hydrolysis, and the splice variant GEN1 (c.1071 + 3(IVS10) A > G) was selected to verify shear ability. Based on the results of in vitro experiments and higher frequency, three sites with the most significant functional change were selected to build mouse models. Results Protein stability changed in six variants in the CAKUT group. Based on electrophoretic mobility shift assay of eight variants (six CAKUT, two non-CAKUT), the enzymatic hydrolysis and DNA-binding abilities of mutant proteins were impaired in the CAKUT group. The most serious functional damage was observed in the Gen1 variant that produced a truncated protein. A mini-gene splicing assay showed that the variant GEN1 (c.1071 + 3(IVS10) A > G) in the CAKUT group significantly affected splicing function. An abnormal exon10 was detected in the mini-gene splicing assay. Point-mutant mouse strains were constructed (Gen1: c.1068 + 3 A > G, p.R400X, and p.T105R) based on the variant frequency in the CAKUT group and functional impairment in vitro study and CAKUT phenotypes were replicated in each. Conclusion Overall, our findings indicated GEN1 as a risk factor for human CAKUT.

Introduction: The formation of bars and pools, characterized by concave and convex bed morphology, is a typical feature of curved rivers. The channel bed morphology has a significant influence on the flow structures in curved channels.Methods: Based on data from physical model experiments, this study employs the RNG k-ε model and the VOF (Volume of Fluid) method to perform three-dimensional numerical simulations of flow in continuous curved channels.Results: By comparing the variations in flow structures between channels with a flat bed and channels with bars and pools, the results show that the presence of bars and pools leads to an increase in longitudinal flow velocity on the convex bank side near the entrance of the upstream bend, while in the downstream bend it is opposite. The high-velocity region shifts slower towards the concave bank along the bend. The presence of point bars weakens the circulation near the convex bank in the upstream bend, resulting in a smaller circulation intensity. The decrease in circulation intensity is the largest (−23.91%) at the apex of the bend. In the downstream bend, the remaining circulation from the upstream bend attenuates slower in the pool and has a greater impact distance, increasing the circulation intensity in the downstream bend. The section near the bend entrance shows the largest increase in circulation intensity, with a rate of 128.18%. The unevenness of the bed topography increases the unevenness of the bed shear stress in the downstream bend.Discussion: The findings of this study contribute to a deeper understanding of the complex flow structures and evolution trends in natural curved rivers, providing scientific basis for the management of curved river channels.

Objective: Exploring the clinical efficacy of camrelizumab in combination with first-line chemotherapy in patients with extensive-stage small-cell lung cancer (ES-SCLC). Methods: The clinical data of 35 patients with ES-SCLC who received camrelizumab combined with EC or EP regimen in First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from January 2020 to January 2023 were retrospectively analyzed. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were OS, ORR and DCR. SPSS 25.0 software was used for statistical analysis, Kaplan-Meier curve and Log-Rank test analysis, and survival curve was drawn. Results: The median PFS of 35 patients with SCLC was 7.4 months (95 % CI 6.75–9.81 months), .and the median OS was 12.5 months (95% CI,11.71-16.90 months). The ORR and DCR were 65.7 % and 74.3 %, respectively. Adverse events (AEs) were mainly concentrated in grade 1–2, and the probability of occurrence of grade 3 or above was low. Reactive Cutaneous Capillary Endothelial Proliferation (RCCEP) was the most common, followed by nausea &vomit and anemia. The other common AEs included abnormal thyroid function, decreased neutrophil count, skin rash and leucopenia. Conclusion: Camrelizumab in combination with first-line chemotherapy regimens prolonged OS and PFS in SCLC patients and showed efficacy and safety in real-world data.

Abstract Background As one of the most aggressive neuroendocrine tumors, small cell lung cancer (SCLC) has the most disappointing prognosis of all lung cancers. Although SCLC responds well to initial chemotherapy, the majority of patients experience disease recurrence within one year, and patient survival is poor. It is still necessary to explore the application of ICIs in SCLC since the beginning of the road to immunotherapy, which broke the 30‐year treatment deadlock of SCLC. Methods We searched PubMed, Web of Science, and Embase with search terms such as "SCLC", "ES‐SCLC", "ICIs", and "ICBs", and categorized and summarized the relevant literature obtained, and we compiled the latest progress about the application of ICIs in SCLC. Results We listed 14 clinical trials on ICIs, including 8 clinical trials on first‐line SCLC treatment, 2 clinical trials on second‐line SCLC treatment, 3 clinical trials on third‐line SCLC treatment, and 1 clinical trial on SCLC maintenance treatment. Conclusion ICIs in combination with chemotherapy can improve OS in SCLC patients, but the extent to which SCLC patients can benefit from ICIs is limited, and ICIs' combination treatment strategies still need to be continuously explored.

Surface-enhanced Raman scattering (SERS) provides an alternative rapid detection method for pesticide residues in food, but fenvalerate possesses poor affinity to the novel metal substrate, thus restricting its analysis. To break this bottleneck, a SERS-active platform with an Ag/rGO composite structure was engineered using a facile method for fenvalerate detection. Ag nanoparticles with a 60 nm diameter can grow evenly on the top and bottom of rGO layers under intense ultrasonic oscillation, and rGO in hybrid material acts as an ideal hotspot holder between the gaps of Ag nanoparticles, not only allowing the interaction area to be enhanced both electromagnetically and chemically but also enabling the capture and enrichment of fenvalerate pesticide molecules into the “hotspot” area to improve detection sensitivity. Ag/rGO composite substrate possesses superior SERS performance with an ultralow detectable concentration of 4-aminothiophenol (10−10 M) and good reproducibility, endowing the material with a better enhancement effect than pure Ag nanoparticles. When used as the SERS substrate for fenvalerate detection, Ag/rGO composite material showed excellent performance in both experiments and theoretical calculation, with the limit of detection (LOD) of fenvalerate being as low as 1.69 × 10−5 mg/kg and a detection model with an R2 of 99.2%, demonstrating its exciting potential as a SERS substrate for pesticides detection.

Congenital anomalies of the kidney and urinary tract (CAKUT) is a general term for a class of diseases that are mostly caused by intrauterine genetic development limitation. Without timely intervention, certain children with CAKUT may experience progressive decompensation and a rapid decline in renal function, which will ultimately result in end-stage renal disease. At present, a comprehensive understanding of the pathogenic signaling events of CAKUT is lacking. The role of long noncoding RNAs (lncRNAs) in renal development and disease have recently received much interest. In previous research, we discovered that mice overexpressing the lncRNA 4933425B07Rik (Rik) showed a range of CAKUT phenotypes, primarily renal hypoplasia. The current study investigated the molecular basis of renal hypoplasia caused by Rik overexpression. We first used Rapid Amplification of cDNA ends (RACE) to obtain the full-length sequence of Rik in Rik+/+;Hoxb7 mice. Mouse proximal renal tubule epithelial cells (MPTCs) line with Rik overexpression was constructed using lentiviral methods, and mouse metanephric mesenchyme cell line (MK3) with Rik knockout was then constructed by the CRISPR‒Cas9 method. We performed RNA-seq on the Rik-overexpressing cell line to explore possible differentially expressed molecules and pathways. mRNA expression was confirmed by qRT‒PCR. Reduced levels of Wnt10b, Fzd8, and β-catenin were observed when Rik was expressed robustly. On the other hand, these genes were more highly expressed when Rik was knocked out. These results imply that overabundance of Rik might inhibit the Wnt/β-catenin signaling pathway, which may result in renal hypoplasia. In general, such research might help shed light on CAKUT causes and processes and offer guidance for creating new prophylactic and therapeutic strategies.

In this article, a method of railway catenary insulator defects detection is proposed, named RCID-YOLOv5s. In order to improve the network’s ability to detect defects in railway catenary insulators, a small object detection layer is introduced into the network model. Moreover, the Triplet Attention (TA) module is introduced into the network model, which pays more attention to the information on the defective parts of the railway catenary insulator. Furthermore, the pruning operations are performed on the network model to reduce the computational complexity. Finally, by comparing with the original YOLOv5s model, experiment results show that the average precision (AP) of the proposed RCID-YOLOv5s is highest at 98.0%, which can be used to detect defects in railway catenary insulators accurately.

ObjectivesAiming at the operation support scheduling of carrier-based aircraft, this paper proposes a scheduling optimization algorithm based on apprenticeship learning which can quickly generate a operation support schedule for a carrier-based aircraft fleet. MethodsUsing the apprenticeship learning method, the executed and unexecuted tasks in expert demonstrations are compared in pairs to construct a sample set, and the support task scheduling classifier is trained based on the deck features of aircraft carrier. On this basis, a support task apprenticeship learning algorithm for a carrier-based aircraft fleet is designed and compared with the traditional genetic algorithm （GA） in terms of solving solution, solving time and resource allocation. ResultsThe results show that the operation support schedule obtained by the apprenticeship scheduling algorithm is equivalent to that by the traditional GA, but the rate of convergence is increased nearly fourfold, and the support resources are more evenly distributed. ConclusionsThe apprenticeship scheduling algorithm proposed in this paper can adequately learn from expert experiences and solve the problem of static single-objective carrier-based aircraft support scheduling. As such, this study provides references for further research in the field of dynamic multi-objective carrier-based aircraft support scheduling.

The excessive input of nutrients into rivers can lead to contamination and eutrophication, which poses a threat to the health of aquatic ecosystems. It is crucial to identify the sources of contaminants to develop effective management plans for eutrophication. However, traditional methods for identifying pollution sources have been insufficient, making it difficult to manage river health effectively. High-throughput sequencing offers a novel method for microbial community source tracking, which can help identify dominant pollution sources in rivers. The Wanggang River was selected for study, as it has suffered accelerated eutrophication due to considerable nutrient input from riparian pollutants. The present study identified the dominant microbial communities in the Wanggang River basin, including Proteobacteria, Actinobacteria, Bacteroidetes, Cyanobacteria, Verrucomicrobia, and Firmicutes. The Source Tracker machine-learning classification system was used to create source-specific microbial community fingerprints to determine the primary sources of contaminants in the basin, with agricultural fertilizer being identified as the main pollutant source. By identifying the microbial communities of potential pollution sources, the study determined the contributing pollutant sources in several major sections of the Wanggang River, including industry, urban land, pond culture, and livestock land. These findings can be used to improve the identification of pollution sources in specific environments and develop effective pollution management plans for polluted river water.

Gastric cancer (GC) is a highly fatal malignant tumor in the world. Most of the patients are in an unresectable state when they have symptoms. Systemic treatment is the primary treatment for advanced patients. Among them, the Human epidermal growth factor receptor 2 (HER2) is an important therapeutic target. With the continuous optimization of chemotherapeutic drugs and chemotherapy regimens, the prognosis of some HER2-positive GC patients has been greatly improved. However, the needs of GC patients with a low level of HER2 expression still need to be met. Several targeted drugs against human epidermal growth factor receptor 2 emerged in recent years, including Antibody-drug Conjugates (ADC), novel humanized anti-HER2 monoclonal antibodies, and Tyrosine kinase inhibitors (TKI). As an important breakthrough in treating HER2-positive GC, ADC became one of the fastest-growing anti-tumor drugs. Some drugs also showed an anti-tumor effect on GC with low expression of HER2. It may also be the key to the treatment of low expression of HER2 GC in the future. This article mainly reviews several promising ADC drugs for the treatment of HER2 low-expression GC and related trials.

Objectives Flight-deck support operations are the most critical link in the process of launch and recovery of carrier-based aircraft.The reasonable allocation of support personnel can enable to improve the capability of supporting the aircraft fleet operation and the sortie generation rate, thereby enhancing the overall combat effectiveness of the carrier.Method Aiming at the personnel configuration problem of the carrier-based aircraft flight-deck operation support, considering the complex realistic environment and based on the makespan of the aircraft fleet operation support, load balance and cumulative transfer time of support personnel on flight deck, a multi-objective mathematical programming model is established to obtain the required numbers of support personnel and skill allocation scheme. An integer encoding method and decoding method based on the event-based scheduling policy are designed, and an improved NSGA2-based personnel optimization algorithm is proposed to solve the problem.Results The simulation results show that this algorithm can effectively solve the established mathematical model, and the simulation results meet the actual combat requirements. Conclusion The improved NSGA2 algorithm can combine the carrier-based aircraft support process, numbers of personnel and skill allocation to provide the carrier-based aircraft support operation with a multi-objective optimized scheduling plan.

Background: Gen1 mutation can cause various phenotypes of congenital anomaly of the kidney and urinary tract (CAKUT). An intrauterine low-protein isocaloric diet can also cause CAKUT phenotypes in offspring. However, single factors such as gene mutation or abnormal environmental factor during pregnancy can only explain part of the pathogenesis of CAKUT. Objectives: A low-protein isocaloric diet was fed to Gen1-mutant mice throughout pregnancy to establish a Gen1-mutant mouse model exposed to a low-protein isocaloric intrauterine environment. The mice were divided into 4 groups: normal (22%) protein diet (ND) + wild-type mice (CON group), ND + Gen1PB/+ mice (Gen1PB/+ group), low (6%)-protein isocaloric diet (LD) + wild-type mice (LD group), and the LD + Gen1PB/+ groups. Methods: The experimental design included observing proportion and distribution of CAKUT phenotypes of neonatal mice; evaluating the number of ureteric buds (UBs) on embryonic day (E) 11.5, the location of UBs on E11.5, and length of the common nephric duct (CND); isolating embryonic kidneys on E11.5 from the Gen1PB/+ group and culturing embryonic kidneys in medium containing 10% serum or serum-free medium to observe the branching of UBs; and detecting the p-PLCγ, p-Akt, and p-ERK1/2 in UBs and CND on E11.5, as well as the apoptosis and proliferation of tissues by immunofluorescence staining. Results: We found that the incidence of CAKUT in offspring of Gen1PB/+ mice under an intrauterine low-protein isocaloric diet environment was significantly increased, and a duplicated collecting system was the dominant phenotype of CAKUT. During the early stage of metanephric development, ectopic protrusion of UBs may appear and lower locations of UBs in Gen1PB/+ mice under an intrauterine low-protein isocaloric diet environment and the number of UB branches in the serum-free culture condition significantly decreased. Further examination revealed that p-PLCγ signaling and tissue apoptosis were abnormal in UBs and the CND at the early stage of kidney development. Conclusions: The aforementioned findings suggest that an intrauterine low-protein isocaloric diet can aggravate the occurrence of CAKUT in Gen1-mutant mice, which might affect key steps in the metanephric development, such as the protrusion of UBs, which might be related to mediate UBs and CND apoptosis through p-PLCγ signaling.

ObjectivesThis paper proposes an algorithm for optimizing the layout of carrier aircraft in a hangar. MethodsTo solve the problem of the mixed layout of aircraft in a hangar, based on the basic spatial combination relationship, this paper sets up a combinatorial relationship library, optimizes the solution space and converts the constrained two-dimensional layout problem into a combinatorial optimization problem. A hangar layout model is established with the maximum number of carrier aircraft and maximum number of emergency dispatch aircraft, and a heuristic algorithm is used to solve the model.ResultsUsing the case study of a USS Nimitz-class aircraft carrier, the resulting layout scheme can maximize the total number of carrier aircraft while ensuring the number of emergency dispatch aircraft, and the results satisfy actual business constraints and requirements. Compared with the layout scheme of USS aircraft carrier, the area utilization rate of hangar deck is increased by 16.92%.Conclusions The proposed algorithm can be used to effectively solve the layout problem of carrier aircraft in a hangar.

Congenital anomalies of the kidney and urinary tract (CAKUT) are some of the most common developmental defects and have a complicated etiology, indicating an interaction of (epi-) genetic and environmental factors. Single gene mutations and copy number variations (CNVs) do not explain most cases of CAKUT, and simultaneous contributions of more than one gene (di-, oligo-, or polygenic effects; i.e., complex genetics) may lead to the pathogenesis of CAKUT. Robo2 plays a key role in regulating ureteric bud (UB) formation in the embryo, with mutations leading to supernumerary kidneys. Gen1 is a candidate gene associated with CAKUT because of its important role in early metanephric development in mice. We established a mouse model with double disruption of Robo2 and Gen1 using a piggyBac transposon and found that double gene mutation led to significantly increased CAKUT phenotypes in Robo2PB/+Gen1PB/+ mouse offspring, especially a duplicated collecting system. Increased ectopic UB formation was observed in the Robo2PB/+Gen1PB/+ mice during the embryonic period. Robo2 and Gen1 exert synergistic effects on mouse kidney development, promoting cell proliferation by activating the GDNF/RET pathway and downstream MAPK/ERK signaling. Our findings provide a disease model for CAKUT as an oligogenic disorder.

Congenital anomalies of the kidney and urinary tract (CAKUT) is a common birth defect and is the leading cause of end-stage renal disease in children. The etiology of CAKUT is complex and includes mainly genetic and environmental factors. However, these factors cannot fully explain the etiological mechanism of CAKUT. Recently, participation of long non-coding RNAs (lncRNAs) in the development of the circulatory and nervous systems was demonstrated; however, the role of lncRNAs in the development of the kidney and urinary tract system is unclear. In this study, we used the piggyBac (PB) transposon-based mutagenesis to construct a mouse with lncRNA 4933425B07Rik (Rik) PB insertion (RikPB/PB) and detected overexpression of Rik and a variety of developmental abnormalities in the urinary system after PB insertion, mainly including renal hypo/dysplasia. The number of ureteric bud (UB) branches in the RikPB/PB embryonic kidney was significantly decreased in embryonic kidney culture. Only bone morphogenetic protein 4 (Bmp4), a key molecule regulating UB branching, is significantly downregulated in RikPB/PB embryonic kidney, while the expression levels of other molecules involved in the regulation of UB branching were not significantly different according to the RNA-sequencing (RNA-seq) data, and the results were verified by quantitative real-time polymerase chain reaction (RT-PCR) and immunofluorescence assays. Besides, the expression of pSmad1/5/8, a downstream molecule of BMP4 signaling, decreased by immunofluorescence. These findings suggest that abnormal expression of Rik may cause a reduction in the UB branches by reducing the expression levels of the UB branching-related molecule Bmp4, thus leading to the development of CAKUT.

Over the past few decades, the topography and river-tide-salt dynamic characteristics of the Pearl River Delta (PRD) have undergone a myriad of changes due to the unnatural evolution process induced by diverse human activities, such as dam construction, land reclamation, sand excavation, and dredging for navigation. To investigate the impact of human activities on hydrodynamic structures in the PRD of the Modaomen Estuary (ME) during the dry season, a three-dimensional river-tide-salt dynamic model was used to simulate the hydrodynamic characteristics of the ME for different historical periods. The model results indicate that large-scale land reclamation weakened the tidal dynamics and mixing effects in the ME, promoting gravity circulation with opposite velocity directions at the surface and bottom within 15 km downstream of the estuary. Additionally, riverbed downcutting enhanced the tidal dynamics, which intensified saltwater intrusion, leading to the spatial scale-of-gravity circulation expanding 1–2 times. The enhancement of riverbed downcutting on the tidal dynamics in the ME was significantly greater than the weakening effect of land reclamation. Hence, due to the comprehensive influence of human activities between the 1970s and 2010, the hydrodynamic structures in the ME changed from a state of atypical gravity circulation, with nonobvious stratification, to a state of highly stratified and large-scale gravity circulation. The pollutant diffusion in the ME under different scenarios is also discussed in this paper. The results show that reclamation results in weakening of tidal dynamics, which is not conducive to the mixing and diffusion of pollutants in the estuary. However, the narrowed estuary due to land reclamation is conducive to the rapid entry of pollutants into the open sea.

The relationship between CDOM (Chromophoric dissolved organic matter) and the bacterial community was investigated in ice-covered Baiyangdian Lake. The results showed that environmental parameters significantly differed in Baiyangdian Lake, whereas a-diversity was not significantly different. Moreover, the microbial and functional communities exhibited significant differences, and T (Temperature), pH, ORP (Oxidation-reduction potential), DO (Dissolved oxygen), NO3−-N, NH4+-N, and Mn (Manganese) were the main environmental factors of these differences, based on redundancy analysis and the Mantel test. Biomarkers of the microbial and functional communities were investigated through linear discriminant analysis effect size and STAMP analysis. The number of biomarkers in the natural area was highest among the typical zones, and most top functions were related to carbohydrate metabolism. Two protein-like components (C1 and C2) and one humic-like component (C3) were identified by parallel factor analysis, and C1 was positively related to C2 (R = 0.99, p < 0.001), indicating the same sources. Moreover, CDOM significantly differed among the typical zones (p < 0.001). The high biological index, fluorescence index, β:α, and low humification index indicated a strong autochthonous component and aquatic bacterial origin, which was consistent with the results of UV-vis absorption spectroscopy. Network analysis revealed non-random co-occurrence patterns. The bacterial and functional communities interacted closely with CDOM. The dominant genera were CL500-29_marine_group, Flavobacterium, Limnohabitans, and Candidatus_Aquirestis. Random forest analysis showed that C1, C2, and C3 are important predictors of α- and β-diversity in the water bacterial community and its functional composition. This study provides insight into the interaction between bacterial communities and DOM (Dissolved organic matter) in ice-covered Baiyangdian Lake.

Dalian je drugo najpomembnejše mesto na jugu province Liaoning na severovzhodu Kitajske. Nekoč je tam stalo naselje Qingniwa, ki so ga med letoma 1858 in 1950 drug za drugim zasedli Britanci, Japonci in Rusi. Vsak osvajalec je v mestu uvedel svoj arhitekturni slog. Rusi so mesto med drugo svetovno vojno odvzeli Japoncem, leta 1950 pa so ga končno vrnili Kitajski. Po letu 1950 je bila večina stavb in območij iz časa ruskega imperija porušena zaradi prenove, ki je potekala v mestu. Največje spremembe so se zgodile po letu 1984, ko so mesto razglasili za posebno gospodarsko območje, zlasti pa v 90. letih 20. stoletja, ko je postal župan Bo Xilai, ki je v mestu uredil parke, avtoceste in krožišča. Tradicionalno grajeno okolje je skoraj izginilo; danes je to sodobno mesto, v katerem se gradijo obsežna stanovanjska naselja. V njem prevladujejo stanovanjske stolpnice, v katerih živi 5,72 milijona prebivalcev. Leta 2011 je bila med 400 prebivalci opravljena anketa, v kateri so morali ti izraziti svoje mnenje o življenju v Dalianu in na njegovem ureditvenem območju ter oceniti svoje življenjske pogoje in stopnjo zadovoljstva s stanovanji. Rezultati ankete so jasno razkrili negotovost večine anketirancev glede spremenljivk, povezanih s kakovostjo stanovanj ter z naravo, s kakovostjo in z dostopnostjo razpoložljivih storitev. Kljub temu je največ anketirancev navedlo, da imajo javni promet, odprte prostore, parke in rekreativne površine na voljo blizu doma.

Dalian is the second–most important city in the southern part of Liaoning Province in northeast China. The city can trace its history back to the Qingniwa settlement. This settlement was occupied from 1858 until 1950 in succession by the British, Japanese and Russian Empires, with each imposing its own building styles on the city. However, from 1950, when the city was finally returned to China by the Russians, who had captured it from the Japanese during the Second World War, most of the imperial buildings and sites were lost to redevelopment within the city. The most dramatic changes have taken place since 1984, when the city was declared a Special Economic Zone, and particularly during the 1990s, when Bo Xilai became the mayor and introduced parks, extensive motorways and many traffic circles. At present, having lost most of its traditional built environment, Dalian is a modern city marked by dramatic housing developments and dominated by multi-family high-rise buildings to accommodate its population of 5.72 million. In 2011, a survey was conducted among 400 inhabitants of the city to ascertain their perceptions concerning life in Dalian and the Dalian Development Zone, their living conditions and their level of satisfaction with their housing. From the survey, it was clear that the majority of the interviewees were uncertain about the variables concerning the structural quality of their housing units and the nature, quality and accessibility of the services provided. However, most of them indicated that public transport, open spaces, parks and recreational facilities were within easy reach of their housing units.

To improve nutrient content of goat milk, we describe the construction of a vector (pBLAC) containing a hybrid goat β-lactoglobulin (BLG) promoter/cytomegalovirus (CMV) enhancer. We also describe the generation of transgenic goats expressing rhLA by somatic cell nuclear transfer (SCNT). Of 334 one-cell stage embryos derived from three transgenic cell lines and 99 embryos derived from non-transgenic (NT) cells surgically transferred to the oviducts of 37 recipients, two recipients delivered two kids (2%) from the non-transfected line and five recipients delivered six kids (1.8%) from transgenic cell lines, three of which died within 2 days. Compared to the NT donor cells, transfection of donor cells does not negatively affect the development of nuclear transfer embryos into viable transgenic offspring. However, the clone efficiency in cell line number 1 was lower than that in numbers 2 and 3, and in the NT lines (0.9% versus 1.9% 2.4% and 2%; P