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This study was designed to screen 6 lysosomal storage diseases (LSDs) in neonates using tandem mass spectrometry (MS/MS), and establish cutoff values for these LSDs with 3000 dried blood spots (DBS) samples. Cutoff values for α-L-iduronidase (IDUA), α-galactosidase (GLA), acid beta glucosidase (ABG), β-galactocerebrosidase (GALC), acid sphingomyelinase (ASM), and acid alpha glucosidase (GAA) were as follows: GLA, > 2.06 μmol/L·h; ABG, > 1.78 μmol/L·h; ASM, > 0.99 μmol/L·h; IDUA, > 1.33 μmol/L·h; GALC, > 0.84 μmol/L·h; and GAA, > 2.06 μmol/L·h. There were 30 positives in initial MS/MS screening test, and 15 samples were still positive with repeat testing. Their parents/guardians were recontacted and DBS samples were collected again for test. Only 1 child showed abnormal GAA enzyme activity after recontacting process, and was diagnosed with Pompe disease after genetic screening. Eventually, cutoff values of 6 specific enzyme activities were established and MS/MS is effective for early LSDs screening. [ABSTRACT FROM AUTHOR]

Summary: Drought, especially terminal drought, severely limits wheat growth and yield. Understanding the complex mechanisms behind the drought response in wheat is essential for developing drought‐resistant varieties. This study aimed to dissect the genetic architecture and high‐yielding wheat ideotypes under terminal drought.An automated high‐throughput phenotyping platform was used to examine 28 392 image‐based digital traits (i‐traits) under different drought conditions during the flowering stage of a natural wheat population. Of the i‐traits examined, 17 073 were identified as drought‐related. A genome‐wide association study (GWAS) identified 5320 drought‐related significant single‐nucleotide polymorphisms (SNPs) and 27 SNP clusters.A notable hotspot region controlling wheat drought tolerance was discovered, in which TaPP2C6 was shown to be an important negative regulator of the drought response. The tapp2c6 knockout lines exhibited enhanced drought resistance without a yield penalty. A haplotype analysis revealed a favored allele of TaPP2C6 that was significantly correlated with drought resistance, affirming its potential value in wheat breeding programs.We developed an advanced prediction model for wheat yield and drought resistance using 24 i‐traits analyzed by machine learning. In summary, this study provides comprehensive insights into the high‐yielding ideotype and an approach for the rapid breeding of drought‐resistant wheat. [ABSTRACT FROM AUTHOR]

Tissues are increasingly being analyzed at the single cell level in order to characterize cellular diversity and identify rare cell types. Single cell analysis efforts are greatly limited, however, by the need to first break down tissues into single cell suspensions. Current dissociation methods are inefficient, leaving a significant portion of the tissue as aggregates that are filtered away or left to confound results. Here, we present a simple and inexpensive microfluidic device that simultaneously filters large tissue fragments and dissociates smaller aggregates into single cells, thereby improving single cell yield and purity. The device incorporates two nylon mesh membranes with well-defined, micron-sized pores that operate on aggregates of different size scales. We also designed the device so that the first filtration could be performed under tangential flow to minimize clogging. Using cancer cell lines, we demonstrated that aggregates were effectively dissociated using high flow rates and pore sizes that were smaller than a single cell. However, pore sizes that were less than half the cell size caused significant damage. We then improved results by passing the sample through two filter devices in series, with single cell yield and purity predominantly determined by the pore size of the second membrane. Next, we optimized performance using minced and digested murine kidney tissue samples, and determined that the combination of 50 and 15 μm membranes was optimal. Finally, we integrated these two membranes into a single filter device and performed validation experiments using minced and digested murine kidney, liver, and mammary tumor tissue samples. The dual membrane microfluidic filter device increased single cell numbers by at least 3-fold for each tissue type, and in some cases by more than 10-fold. These results were obtained in minutes without affecting cell viability, and additional filtering would not be required prior to downstream applications. In future work, we will create complete tissue analysis platforms by integrating the dual membrane microfluidic filter device with additional upstream tissue processing technologies, as well as downstream operations such as cell sorting and detection.

Maximizing the speed and efficiency at which single cells can be liberated from tissues would dramatically advance cell-based diagnostics and therapies. Conventional methods involve numerous manual processing steps and long enzymatic digestion times, yet are still inefficient. In previous work, we developed a microfluidic device with a network of branching channels to improve the dissociation of cell aggregates into single cells. However, this device was not tested on tissue specimens, and further development was limited by high cost and low feature resolution. In this work, we utilized a single layer, laser micro-machined polyimide film as a rapid prototyping tool to optimize the design of our microfluidic channels to maximize dissociation efficiency. This resulted in a new design with smaller dimensions and a shark fin geometry, which increased recovery of single cells from cancer cell aggregates. We then tested device performance on mouse kidney tissue, and found that optimal results were obtained using two microfluidic devices in series, the larger original design followed by the new shark fin design as a final polishing step. We envision our microfluidic dissociation devices being used in research and clinical settings to generate single cells from various tissue specimens for diagnostic and therapeutic applications.

[Introduction] Through the analysis of the exsiting problems in conventional flexibility modification technology of thermal power units, a new type of flexibility modification technology is proposed, which is to embed a large-capacity high-temperature molten salt heat storage system in the traditional "boiler-turbine" thermal system. It weakens the original rigid connection of boiler-turbine coupling to achieve deep peak regulation and flexible operation of thermal power units. [Method] According to the different thermal characteristics of steam, water and molten salt, an integrated thermal system of "boiler-high temperature heat storage-steam engine" was established by thermal balance calculation. [Result] The results show that the deep peak regulation capability of thermal power unit is greatly improved after configuring high-temperature molten salt heat storage system, and the problems of conventional modification methods can be solved. At the same time, the ability of the units to provide high-parameter industrial steam will be greatly improved. This will effectively improve the economic efficiency of power plants and make up for the lack of peak regulation compensation mechanism. High-temperature molten salt heat storage technology can also be applied to the life extension of thermal power plants, not only increasing the grid's flexible peak regulation power supply, but also enabling old power plant enterprise assets continue to create benefits. [Conclusion] After a batch of thermal power units in the grid are modified by large-scale high-temperature molten salt heat storage technology, a large number of flexible peak regulation power sources are provided for the grid, without increasing the total coal consumption and effectively alleviating the problem of new energy power consumption. Meanwhile, steam turbines and generators are reserved, which can provide backup capacity and moment of inertia for the power system, to ensure the safety and stability of the power supply and the grid. The promotion of this technology will effectively promote the upgrading of thermal power plants and help achieve the goal of "carbon neutrality and carbon peak".

The ability to harvest single cells from tissues is currently a bottleneck for cell-based diagnostic technologies, and remains crucial in the fields of tissue engineering and regenerative medicine. Tissues are typically broken down using proteolytic digestion and various mechanical treatments, but success has been limited due to long processing times, low yield, and high manual labor burden. Here, we present a novel microfluidic device that utilizes precision fluid flows to improve the speed and efficiency of tissue digestion. The microfluidic channels were designed to apply hydrodynamic shear forces at discrete locations on tissue specimens up to 1 cm in length and 1 mm in diameter, thereby accelerating digestion through hydrodynamic shear forces and improved enzyme-tissue contact. We show using animal organs that our digestion device with hydro-mincing capabilities was superior to conventional scalpel mincing and digestion based on recovery of DNA and viable single cells. Thus, our microfluidic digestion device can eliminate or reduce the need to mince tissue samples with a scalpel, while reducing sample processing time and preserving cell viability. Another advantage is that downstream microfluidic operations could be integrated to enable advanced cell processing and analysis capabilities. We envision our novel device being used in research and clinical settings to promote single cell-based analysis technologies, as well as to isolate primary, progenitor, and stem cells for use in the fields of tissue engineering and regenerative medicine.

BackgroundOptimization of fat grafting continues to gain increasing attention in the field of regenerative medicine. "Nanofat grafting" implements mechanical emulsification and injection of standard lipoaspirate for the correction of superficial rhytides and skin discoloration; however, little is known about the cellular constituents of the graft. Based on recent evidence that various stressors can induce progenitor activity, the authors hypothesized that the shear forces used in common fat grafting techniques may impact their regenerative capacities.MethodsLipoaspirates were obtained from 10 patients undergoing elective procedures. Half of each sample was subjected to nanofat processing; the other half was left unchallenged. The viscosity of each sample was measured for computational analysis. The stromal vascular fraction of each sample was isolated, quantified, and analyzed by means of flow cytometry with two multicolor fluorescence antibody panels.ResultsStandard lipoaspirate is ideally suited for mechanical stress induction. The mechanical emulsification involved in nanofat processing did not affect cell number; however, viability was greatly reduced when compared with the stromal vascular fraction of standard lipoaspirate. Interestingly, nanofat processing resulted in stress-induced stromal vascular fraction with a higher proportion of endothelial progenitor cells, mesenchymal stem cells, and multilineage differentiating stress-enduring cells. Single-parameter analysis also revealed significant increases in CD34, CD13, CD73, and CD146 of the stress-induced stromal vascular fraction, markers associated with mesenchymal stem cell activity.ConclusionsMechanical processing used in techniques such as nanofat grafting induces the up-regulation of progenitor phenotypes consistent with multipotency and pluripotency. These data provide a first step in characterizing the potential regenerative benefits realized through stress induction in fat grafting.Clincal question/level of evidenceTherapeutic, V.

Health care integration is an important way to achieve healthy ageing and meet the personalized health care needs of the elderly. Based on 16 policies on health care integration introduced at the national level in China from 2013 to 2022, the open coding process of grounded theory was used to set up variable indicators and construct a PMC index model for quantitative evaluation of the policies. The results of the study show that the mean value of the PMC index of 16 policies is 7.42, including 12 excellent policies and 4 good policies. Through the PMC curve and depression index, it is found that the overall quality of the combined medical care and support policy in China is good, but it still needs further optimization and improvement in terms of policy timeliness, policy tools, policy operability and policy innovation.

Tumors tissues house a diverse array of cell types, requiring powerful cell-based analysis methods to characterize cellular heterogeneity and identify rare cells. Tumor tissue is dissociated into single cells by treatment with proteolytic enzymes, followed by mechanical disruption using vortexing or pipetting. These procedures can be incomplete and require significant time, and the latter mechanical treatments are poorly defined and controlled. Here, we present a novel microfluidic device to improve mechanical dissociation of digested tissue and cell aggregates into single cells. The device design includes a network of branching channels that range in size from millimeters down to hundreds of microns. The channels also contain flow constrictions that generate well-defined regions of high shear force, which we refer to as "hydrodynamic micro-scalpels", to progressively disaggregate tissue fragments and clusters into single cells. We show using in vitro cancer cell models that the microfluidic device significantly enhances cell recovery in comparison to mechanical disruption by pipetting and vortexing after digestion with trypsin or incubation with EDTA. Notably, the device enabled superior results to be obtained after shorter proteolytic digestion times, resulting in fully viable cells in less than ten minutes. The device could also be operated under enzyme-free conditions that could better maintain expression of certain surface markers. The microfluidic format is advantageous because it enables application of well-defined mechanical forces and rapid processing times. Furthermore, it may be possible to directly integrate downstream processing and detection operations to create integrated cell-based analysis platforms. The enhanced capabilities enabled by our novel device may help promote applications of single cell detection and purification techniques to tumor tissue specimens, advancing the current understanding of cancer biology and enabling molecular diagnostics in clinical settings.

The adsorption thermodynamics and kinetics of CO2 and six combustion products (H2O, SO2, N2, O2, NO and NO2) of two most commonly used commercial zeolites (13X and 5A) were studied based on validated molecular simulations. Adsorption isotherms at wide range of temperatures (253–333 K) were fitted by a Langmuir model, obtaining equilibrium parameters including the adsorption capacity, strength, heterogeneity and CO2 selectivity from the mixture. The diffusion coefficients, isosteric adsorption heats and distributions of potential energy were simulated for further explanation. The comprehensive evaluation results suggest that, in actual combustion product mixtures, the presence of H2O in combustion products has a significant impact on CO2 capture efficiency. Under the influence of water, the adsorption capacity of CO2 was reduced by over 80%. [ABSTRACT FROM AUTHOR]