Low-Cost Photoelectric Flow Rate Sensors Based on a Flexible Planar Curved Beam Structure for Clinical Treatments.

In clinical treatments, reliable flow rate measurements ensure accurate drug delivery during infusions, precise gas delivery during artificial ventilations, etc., thereby reducing patient morbidity and mortality. However, precise flow rate sensors are costly, so medical devices with limited budgets choose cheaper but unsatisfactory flow rate measurement approaches, leading to increased medical risks. In this paper, we propose a photoelectric flow rate sensor based on a flexible planar curved beam structure (FPCBS). The FPCBS ensures low out-of-plane stiffness of the sensitive sheet and allows large deformation in the elastic range, enabling the flow rate sensor to measure the flow rate with high sensitivity over a wide range. Meanwhile, the flow rate sensor can be mass-produced using mature materials and manufacturing technology at less than $5 each. The flow rate sensors are integrated into a commercial infusion pump to measure drug infusion and a home ventilator to monitor respiration. The results are comparable to those measured by a commercial flow rate sensor, demonstrating the applicability of the sensor. Considering its proven outstanding performance at low cost, the flow rate sensor shows great potential in clinical treatment, medical diagnosis and other medical fields. This article is protected by copyright. All rights reserved.

A mitochondria-targeted far-red AIE fluorescent probe for distinguishing between mitophagy and ferroptosis in cancer cells.

A mitochondria-targeted far-red fluorescent probe LY-1 with AIE character was formulated to track cell viscosity alterations with excellent sensitivity and selectivity, which was used to discriminate between mitophagy and ferroptosis in cancer cells. Probe LY-1 is expected to be an effective vehicle for the diagnosis of mitochondrial viscosity relevant diseases.

Genotype-Phenotype Correlation Reanalysis in 83 Chinese Cases with OCRL Mutations.

Background: Both Lowe syndrome and Dent-2 disease are caused by variants in the OCRL gene. However, the reason why patients with similar OCRL gene mutations presented with different phenotypes remains uncertain. Methods: Children with hemizygous pathogenic or likely pathogenic variants in OCRL were compiled from published and unpublished consecutive cases from China. Furthermore, a Chi-square test was employed to analyze the correlation of the location and types of mutations on the phenotype of children with Lowe syndrome or Dent-2 disease. Results: Among the total 83 patients, 70.8% (34/48) cases of Lowe syndrome presented with truncating mutations, while only 31.4% (11/35) cases of Dent-2 disease presented with truncating mutation (Χ2 = 12.662; P < 0.001). Meanwhile, the majority of mutations in Dent-2 disease are located in Exon 2-12 (21/35, 60.0%), while the majority of mutations in Lowe syndrome are located in Exon 13-23 (39/48, 81.3%; Χ2 = 14.922; P < 0.001). Conclusions: Truncating mutations of the OCRL gene were more common in patients with Lowe syndrome than in Dent-2 disease, while mutation is more likely located at exon 2-12 in Dent-2 disease than that in Lowe syndrome. The type and location of mutation are important indicators for the phenotypes in patients with OCRL mutation. This is a large cohort study analyzing the genotype-phenotype correlation in patients with Lowe syndrome and Dent-2 disease in China. Our data may improve the interpretation of new OCRL variants and genetic counseling. Furthermore, a large international study would be necessary to illustrate the genotype-phenotype correlation in patients with OCRL mutations.

Expanding the Phenotypic and Genotypic Spectrum of ARFGEF1-Related Neurodevelopmental Disorder.

Mono-allelic loss-of-function variants in ARFGEF1 have recently caused a developmental delay, intellectual disability, and epilepsy, with varying clinical expressivity. However, given the clinical heterogeneity and low-penetrance mutations of ARFGEF1-related neurodevelopmental disorder, the robustness of the gene-disease association requires additional evidence. In this study, five novel heterozygous ARFGEF1 variants were identified in five unrelated pediatric patients with neurodevelopmental disorders, including one missense change (c.3539T>G), two canonical splice site variants (c.917-1G>T, c.2850+2T>A), and two frameshift (c.2923_c.2924delCT, c.4951delG) mutations resulting in truncation of ARFGEF1. The pathogenic/likely pathogenic variants presented here will be highly beneficial to patients undergoing genetic testing in the future by providing an expanded reference list of disease-causing variants.

Heteroplasmic and homoplasmic m.616T>C in mitochondria tRNAPhe promote isolated chronic kidney disease and hyperuricemia.

Inherited kidney diseases are the fifth most common cause of end-stage renal disease (ESRD). Mitochondrial dysfunction plays a vital role in the progression of inherited kidney diseases, while mitochondrial-transfer RNA (mt-tRNA) variants and their pathogenic contributions to kidney disease remain largely unclear. In this study, we identified the pathogenic mt-tRNAPhe 616T>C mutation in 3 families and documented that m.616T>C showed a high pathogenic threshold, with both heteroplasmy and homoplasmy leading to isolated chronic kidney disease and hyperuricemia without hematuria, proteinuria, or renal cyst formation. Moreover, 1 proband with homoplamic m.616T>C presented ESRD as a child. No symptoms of nervous system evolvement were observed in these families. Lymphoblast cells bearing m.616T>C exhibited swollen mitochondria, underwent active mitophagy, and showed respiratory deficiency, leading to reduced mitochondrial ATP production, diminished membrane potential, and overproduction of mitochondrial ROS. Pathogenic m.616T>C abolished a highly conserved base pair (A31-U39) in the anticodon stem-loop which altered the structure of mt-tRNAPhe, as confirmed by a decreased melting temperature and slower electrophoretic mobility of the mutant tRNA. Furthermore, the unstable structure of mt-tRNAPhe contributed to a shortage of steady-state mt-tRNAPhe and enhanced aminoacylation efficiency, which resulted in impaired mitochondrial RNA translation and a significant decrease in mtDNA-encoded polypeptides. Collectively, these findings provide potentially new insights into the pathogenesis underlying inherited kidney disease caused by mitochondrial variants.

Clinical and Genetic Features in 31 Serial Chinese Children With Gitelman Syndrome.

Gitelman syndrome (GS, OMIM 263800) is a genetic congenital tubulopathy associated with salt loss, which is characterized by hypokalemic metabolic toxicity, hypocalciuria, and hypomagnesemia. GS, which is typically detected in adolescence or adulthood, has long been considered a benign tubular lesion; however, the disease is associated with a significant decrease in the quality of life. In this study, we assessed the genotype-phenotype correlations based on the medical histories, clinical symptoms, laboratory test results, and whole-exome sequencing profiles from pediatric patients with GS. Between January 2014 and December 2020, all 31 consecutively enrolled patients complained of fatigue, salt craving, and muscle weakness. Sixteen patients demonstrated growth retardation, and five patients presented with nocturia and constipation. All patients presented with hypokalemic metabolic alkalosis, normal blood pressure, hyperaldosteronism, and a preserved glomerular filtration rate, and 24 of the 31 (77.4%) patients had hypomagnesemia. Homozygous, compound heterozygous, and heterozygous mutations in SLC12A3 were detected in 4, 24, and 3 patients, respectively. GS patients often present with muscle weakness and fatigue caused by hypokalemia and hypomagnesemia. Therefore, early diagnosis of GS is important in young children to reduce the possibility of growth retardation, tetany, and seizures. Next-generation sequencing such as whole-exome or whole-genome sequencing provides a practical tool for the early diagnosis and improvement of GS prognosis. Further whole-genome sequencing is expected to reveal more variants in SLC123A among GS patients with single heterozygous mutations.

Numerical investigation of gaseous pollutant cross-transmission for single-sided natural ventilation driven by buoyancy and wind.

Single-sided natural ventilation was numerically investigated to determine the impact of buoyancy and wind on the cross-transmission of pollution by considering six window types commonly found in multistory buildings. The goal of this study was to predict the gaseous pollutant transmission using computational fluid dynamics based on the Reynolds-averaged Navier-Stokes equations and baseline k-ω turbulence equations. The results indicated that ventilation rates generally increased with increasing wind speeds if the effects of buoyancy and wind were not suppressed; however, the re-entry ratio representing the proportion of expelled air re-entering other floors and the corresponding risk of infection decreased. If the source of the virus was on a central floor, the risk of infection was the highest on the floors closest to the source. Different window types were also considered for determining their effectiveness in controlling cross-transmission and infection risk, depending on the source location and driving force (e.g., buoyancy and wind).

Measuring detachment of Aspergillus niger spores from colonies with an atomic force microscope.

Detachment of fungal spores from moldy surfaces and the subsequent aerosolization can lead to adverse health effects. Spore aerosolization occurs when the forces for aerosolization exceed the binding forces of spores with their colonies. The threshold force to detach a spore from a growing colony remains unknown. This investigation measured the detachment of spores of Aspergillus niger from a colony using an atomic force microscope (AFM). The spores were first affixed to the cantilever of the AFM with ultraviolet curing glue, and then, the colony was moved downward until the spores detached. The threshold detachment forces were inferred from the deflection of the cantilever. In addition, the spores were aerosolized in a wind tunnel by a gradual increase of the blowing air speed. The forces measured by the AFM were compared with the hydrodynamic forces for aerosolization. The AFM measurements revealed that a force of 3.27 ± 0.25 nN was required to detach a single spore from the 4-day-old colony, while 1.98 ± 0.13 nN was sufficient for the 10-day-old colony. Slightly smaller detachment forces were observed by the AFM than were determined by the aerosolization tests.

Experimental investigation on the coupled effect of effective stress and gas slippage on the permeability of shale.

Permeability is one of the most important parameters to evaluate gas production in shale reservoirs. Because shale permeability is extremely low, gas is often used in the laboratory to measure permeability. However, the measured apparent gas permeability is higher than the intrinsic permeability due to the gas slippage effect, which could be even more dominant for materials with nanopores. Increasing gas pressure during tests reduces gas slippage effect, but it also decreases the effective stress which in turn influences the permeability. The coupled effect of gas slippage and effective stress on shale permeability remains unclear. Here we perform laboratory experiments on Longmaxi shale specimens to explore the coupled effect. We use the pressure transient method to measure permeability under different stress and pressure conditions. Our results reveal that the apparent measured permeability is controlled by these two competing effects. With increasing gas pressure, there exists a pressure threshold at which the dominant effect on permeability switches from gas slippage to effective stress. Based on the Klinkenberg model, we propose a new conceptual model that incorporates both competing effects. Combining microstructure analysis, we further discuss the roles of stress, gas pressure and water contents on gas permeability of shale.

Gaseous pollutant transmission through windows between vertical floors in a multistory building with natural ventilation.

Natural ventilation is an effective strategy to control thermal comfort in buildings, and can be enhanced depending on the window style. The combination of natural ventilation and window can also facilitate the removal or dilution of gaseous pollutants from indoor sources in newly decorated buildings. However, the windows on the same facade may cause gaseous pollutant cross-transmission during single-sided natural ventilation between households on different floors close to the source. Although some research has focused on the pollutant cross-transmission in buildings, the simplification of windows into rectangular openings often affects accurate knowledge of pollutant transmission characteristics. Therefore, this investigation explored gaseous pollutant cross-transmission through real windows during single-sided, buoyancy-driven ventilation in a multistory building. Six types of windows were modeled for the indoor pollutant of gaseous formaldehyde (HCHO). Computational fluid dynamics (CFD) was utilized to solve characteristics of pollutant transmission inside and outside the multistory building. The results indicated that the ventilation rates, thermal profiles and pollutant transmission inside and outside the building varied for each window type, although the open window areas were identical. The re-entry ratio of exhausted air entering upper floors and the infection risk of epidemic viruses caused by airborne cross-transmission was sensitive to ventilation rates and window configurations, while the sensitivities for window configurations varied case by case. The comparisons also revealed that the specification of ambient temperature and pollutant release rate ultimately did not affect the evaluation of pollutant cross-transmission using CFD.

[Microbial diversity of Pyropia haitanensis phycosphere during cultivation].

OBJECTIVE: Pyropia haitanensis is of great commercial importance and wildly cultivated in Zhejiang and Fujian provinces. To observe the characteristics and changes of phycosphere microbial communities during cultivation can help us monitor the potential pathogens and microbial factors affecting the health of cultivated seaweeds. METHODS: The morphological characteristics and the diversity of phycosphere and surrounding seawater microbes were studied by pure culture method and polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE). Similarity analysis was carried out online with the 16S rDNA (bacteria) and 18S rDNA (fungi) sequences in GenBank. The phycosphere microbial diversity during different growth stages, cultivated areas and periods was studied. RESULTS: Totally 467 bacteria and 55 fungi were isolated during P. haitanensis cultivation. The diversity of fungi was smaller than that of bacteria. The bacteria were classified into 41 genera, belonging to Alphaproteobacteria, Gammaproteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. The dominant bacterial communities were Alphaproteobacteria and Gammaproteobacteria. Most of the fungi were classified into Ascomycota, only one strain belonging to the Basidiomycota, Agaricomycetes. Bacteria of 19 specific genera were isolated from P. haitanensis while 13 specific genera were isolated from the surrounding seawater. Most actinomycetes and fungi were isolated from the conchocelis cultured indoors, which was different from the microbial communities of the thalli in intertidal zone. Within the isolated microbes, we found that some strains had very high similarity with those pathogens such as Cobetia marina (C. marina, P. haitanensis red-rotting disease), Phoma porphyrae (P. yezoensis disease) and saprotrophic fungi Fusarium sp. and Aspergillus sp.. CONCLUSION: The diversity of Pyropia phycoshpere microbes during cultivation was affected by the seaweed morphology, culture time and environmental factors. The strains that shared high similarity with Pyropia pathogens were found in this study, which would cause our great attention to these potential pathogens for Pyropia diseases.

MicroRNA-98 and microRNA-214 post-transcriptionally regulate enhancer of zeste homolog 2 and inhibit migration and invasion in human esophageal squamous cell carcinoma.

BACKGROUND: The enhancer of zeste homolog 2 (EZH2) was found to be overexpressed and associated with tumor metastasis in esophageal squamous cell carcinoma (ESCC). On the other hand, it was reported that miR-26a, miR-98, miR-101, miR-124, miR-138 and miR-214 could inhibit the expression of EZH2 in some tumors. However, the role of miRNAs in the regulation of EZH2 expression in human ESCC has not been documented. The aim of this study was to determine the role of these miRNAs in the regulation of tumor metastasis via EZH2 overexpression in human ESCC. METHODS AND RESULTS: The expression of these miRNAs and EZH2 mRNA were examined by qPCR and the expression of EZH2 protein was detected by western blot. The role of these miRNAs in migration and invasion was studied in ESCC cell line (Eca109) transfected with miRNA mimics or cotransfected with miRNA mimics and pcDNA-EZH2 plasmid (without the 3'-UTR of EZH2). Through clinical investigation, we found that miR-98 and miR-214 expression was significantly lower in ESCC tissues than in matched normal tissues, and the expression level of miR-98 and miR-214 was inversely correlated to EZH2 protein expression and the clinical features such as pathological grade, tumor stage and lymph node metastasis in ESCC. In Eca109 cells, overexpression of miR-98 and miR-214 significantly inhibited the migration and invasion of ESCC cells, which was reversed by transfection of EZH2. CONCLUSIONS: These findings suggest that decreased expression of miR-98 and miR-214 might promote metastasis of human ESCC by inducing accumulation of EZH2 protein.

Evaluation of ghost cell survival in the area of radiofrequency ablation.

BACKGROUND AND AIM: Researchers have demonstrated dead cells in radiofrequency ablation (RFA) lesions that have morphological similarities to viable tumor cells and are thus referred to as ghost cells. However, studies on how long ghost cells persist have not been systematically performed. METHODS: A tumor model was established by implanting VX2 tumor tissue into the livers of 48 New Zealand rabbits. Two weeks later, these tumors were eliminated with RFA. The lesions were resected at 0 weeks, 1 week, 2 weeks, 4 weeks, 8 weeks, or 12 weeks after treatment, and samples were stained either with hematoxylin and eosin (HE) or nicotinamide adenine dinucleotide (NADH). The presence of the cells and the morphological changes that they underwent were examined by light microscopy. RESULTS: Four weeks after RFA, there were no obvious morphological changes observed in HE-stained ghost cells, and NADH staining revealed no viable cells. Eight weeks after RFA, the cell structure became indistinct. Twelve weeks after RFA, ghost cells were no longer present. CONCLUSIONS: The morphological characteristics of ghost cells are maintained for at least 4 weeks, during which time HE staining cannot be used to differentiate ghost cells from residual tumor cells. NADH staining for cell viability is necessary to differentiate residual tumor cells from ghost cells. This evidence adds to our understanding of the mechanisms of RFA when used on solid tumors.

[Freeze resistance analysis of different wheat cultivars based on the relationships between physiological indices and grain yield].

A pot experiment with twenty wheat cultivars was conducted to investigate the superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities and the MDA, soluble protein and soluble sugar contents of functional leaves as well as the grain yield, 1000-grain weight, and grain morphological characters under low temperature stress. Low temperature (-4 degrees C) stress at stem elongation stage resulted in the changes of grain morphology and yield characters. For most of test cultivars, their grain length-width ratio, grain roundness, and sterile spikelets increased, and their grain equivalent diameter, grain area, 1000-grain weight, and grain yield decreased. Path analysis indicated that after treated with low temperature at stem elongation stage, the SOD activity and soluble sugar content of functional leaves, especially the SOD activity (direct path coefficient -0. 578) , were the dominant factors affecting grain yield. Taking the percentage of decreased grain yield due to low temperature stress as the assessment criterion, the test twenty winter wheat cultivars were divided into three groups. Cultivars Jimai 19, Jimai 20, Liangxing 99, Shannong 1135, Shannong 8355, Taishan 23, Taishan 9818, Wennong 6, and Yannong 21 belonged to high freeze resistance group, cultivars Linmai 2, Weimai 8, Yannong 19, and Zimai 12 were of low freeze resistance group, and the other seven cultivars belonged to medium freeze resistance group. The seedling stage comprehensive assessment index (D value) had a significant negative correlation with the percentage of decreased grain yield (r = -0. 512*), suggesting that the stronger freeze resistance of wheat at seedling stage was beneficial to the higher wheat grain yield, and seedling stage was the critical period to be selected to identify the freeze resistance of wheat.

Quantify impacted scope of human expired air under different head postures and varying exhalation rates.

Many researches indicate human respiration flow and background ventilation are two important aspects leading to possible respiratory disease spread. However, current studies on respiration flow and the resulted exhaled pollutant dispersion are limited, because different head postures, respiration mode, breath rate, room ventilation and so on, can exert profound impacts that are not understood very clearly. To evaluate the role of head postures on transmission of human exhaled pollutants, this study uses a computational fluid dynamics (CFD) program to study the exhalation flow of a sitting adult in a calm indoor office. Four different head postures are considered: sitting upright viewing front, sitting upright but head tilted viewing upward, sitting upright but head turned viewing the lateral, and sitting but pillowing head on a table. Based on the decay percentage of a gas concentration, the impacted scope of expired air is identified. The common posture by sitting upright viewing front is selected to investigate the change of impacted scope with increasing exhalation rates. The experimental test is also carried out using a breathing thermal manikin. This study finds out that the impacted scope of expired air under different head postures is different. The horizontal impacted distance is highly dependent on the specified threshold concentration. If a person sits around at a table and makes a deep exhalation, other people shall be apart from him/her with a larger distance to be free from the exhaled pollutant exposure, once his/her thermal plume is blocked by the table.

An under-aisle air distribution system facilitating humidification of commercial aircraft cabins.

Air environment in aircraft cabins has long been criticized especially for the dryness of the air within. Low moisture content in cabins is known to be responsible for headache, tiredness and many other non-specific symptoms. In addition, current widely used air distribution systems on airplanes dilute internally generated pollutants by promoting air mixing and thus impose risks of infectious airborne disease transmission. To boost air humidity level while simultaneously restricting air mixing, this investigation uses a validated computational fluid dynamics (CFD) program to design a new under-aisle air distribution system for wide-body aircraft cabins. The new system supplies fully outside, dry air at low momentum through a narrow channel passage along both side cabin walls to middle height of the cabin just beneath the stowage bins, while simultaneously humidified air is supplied through both perforated under aisles. By comparing with the current mixing air distribution system in terms of distribution of relative humidity, CO2 concentration, velocity, temperature and draught risk, the new system is found being able to improve the relative humidity from the existent 10% to the new level of 20% and lessen the inhaled CO2 concentration by 30%, without causing moisture condensation on cabin interior and inducing draught risks for passengers. The water consumption rate in air humidification is only around 0.05 kg/h per person, which should be affordable by airliners.