Search

Abstract Objective This study aimed to identify features of white matter network attributes based on diffusion tensor imaging (DTI) that might lead to progression from mild cognitive impairment (MCI) and construct a comprehensive model based on these features for predicting the population at high risk of progression to Alzheimer’s disease (AD) in MCI patients. Methods This study enrolled 121 MCI patients from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Among them, 36 progressed to AD after four years of follow-up. A brain network was constructed for each patient based on white matter fiber tracts, and network attribute features were extracted. White matter network features were downscaled, and white matter markers were constructed using an integrated downscaling approach, followed by forming an integrated model with clinical features and performance evaluation. Results APOE4 and ADAS scores were used as independent predictors and combined with white matter network markers to construct a comprehensive model. The diagnostic efficacy of the comprehensive model was 0.924 and 0.919, sensitivity was 0.864 and 0.900, and specificity was 0.871 and 0.815 in the training and test groups, respectively. The Delong test showed significant differences (P 0.05) between the combined model and white matter network biomarkers. Conclusions A comprehensive model constructed based on white matter network markers can identify MCI patients at high risk of progression to AD and provide an adjunct biomarker helpful in early AD detection.

The rpl1001 gene encodes 60S ribosomal protein L10, which is involved in intracellular protein synthesis and cell growth. However, it is not yet known whether it is involved in the regulation of cell mitosis dynamics. This study focuses on the growth, spore production, cell morphology, the dynamics of microtubules, chromosomes, actin, myosin, and mitochondria of fission yeast (Schizosaccharomyces pombe) to investigate the impact of rpl1001 deletion on cell mitosis. RNA-Seq and bioinformatics analyses were also used to reveal key genes, such as hsp16, mfm1 and isp3, and proteasome pathways. The results showed that rpl1001 deletion resulted in slow cell growth, abnormal spore production, altered cell morphology, and abnormal microtubule number and length during interphase. The cell dynamics of the rpl1001Δ strain showed that the formation of a monopolar spindle leads to abnormal chromosome segregation with increased rate of spindle elongation in anaphase of mitosis, decreased total time of division, prolonged formation time of actin and myosin loops, and increased expression of mitochondrial proteins. Analysis of the RNA-Seq sequencing results showed that the proteasome pathway, up-regulation of isp3, and down-regulation of mfm1 and mfm2 in the rpl1001Δ strain were the main factors underpinning the increased number of spore production. Also, in the rpl1001Δ strain, down-regulation of dis1 caused the abnormal microtubule and chromosome dynamics, and down-regulation of hsp16 and pgk1 were the key genes affecting the delay of actin ring and myosin ring formation. This study reveals the effect and molecular mechanism of rpl1001 gene deletion on cell division, which provides the scientific basis for further clarifying the function of the Rpl1001 protein in cell division.

Abstract Background The kidney and eyes share common pathways and are thought to be closely connected. Chronic kidney disease and major eye diseases, such as cataract and glaucoma, are strongly associated with age. However, further investigation is needed to understand the joint impact of age and kidney diseases on eye diseases. In this study, we assessed the risk of eye diseases in relation to age and kidney failure in Taiwanese adults. Methods Our study included 127,561 cancer-free volunteers aged 30 to 70 years who participated in the Taiwan Biobank (TWB) project from 2008 to 2020. Information on the main exposures (kidney failure and age) and the outcome (eye diseases, including glaucoma, cataract, xerophthalmia, and retinal detachment) was collected through questionnaires. Results In general, kidney failure and older age were independently associated with a higher risk of eye, particularly cataract and retinal detachment: prevalence odds ratio (POR); 95% confidence interval (CI) = 2.480; 1.635–3.761 for cataract and 3.885; 1.968–7.666 for retinal detachment. A significant interaction between kidney failure and age on cataract was observed (p-value = 0.0002). Age-stratified analysis revealed a higher risk of cataract among patients with kidney failure aged below 50 (POR = 6.534; 95% CI = 2.493–17.124) and between 50 and 60 years (POR = 3.957; 95%CI = 1.986–7.881). Combining kidney failure and age (reference: no kidney failure and age 60 years. Combining cataract and age (reference: no cataract and age

PD control is a widely used model-free method; however, it often falls short of guaranteeing optimal performance. Optimal model-based control, such as the Linear Quadratic Regulator (LQR), can indeed achieve the desired control performance, but only for known linear systems. In this paper, we present a novel approach for designing optimal PD control for unknown mechanical systems. We utilize a conditional Generative Adversarial Network (GAN) and a Long Short-Term Memory (LSTM) neural network to approximate an optimal PD control. We employ Bayesian inference to generate PD control that can be applied at different operating points. This design mechanism ensures both stability and optimal performance. Finally, we apply this control methodology to lower limb prostheses, and the results demonstrate that the optimal PD control, using GAN and Bayesian inference, outperforms other classical controllers.

Abstract Adipose tissue-derived stem cells (ADSCs) have been shown to improve erectile function in animal models of erectile dysfunction. However, few studies have been carried out using a reliable in vivo imaging method to trace transplanted cells in real time, which is necessary for systematic investigation of cell therapy. The study aims to explore the feasibility of non-invasively monitoring intracavernous injection of ADSCs in rat and miniature pig corpus cavernosum using in vivo magnetic resonance (MR) imaging. Thirty-six male Sprague Dawley rats (10 weeks old) and six healthy, sexually mature male miniature pigs (20 kg weight) were obtained. ADSCs were isolated from paratesticular fat of donor rats and cultured. Then ADSCs were labeled with superparamagnetic iron oxide nanoparticles (SPIONs), a type of MR imaging contrast agent, before transplantation into rats and pigs. After intracavernous injection, all rats and pigs underwent and were analyzed by MR imaging at the day of ADSC transplantation and follow-up at 1, 2 and 4 weeks after transplantation. In addition, penile histological examination was performed on all rats and pigs before (n = 6) and at 1 day (n = 6), 1 week (n = 6), 2 weeks (n = 6) or 4 weeks (n = 12) after ADSC transplantation. SPION-labeled ADSCs demonstrated a strong decreased signal intensity compared with distilled water, unlabeled ADSCs or agarose gel. SPION-labeled ADSCs showed a hypointense signal at all concentrations, and the greatest hypointense signal was observed at the concentration of 1 × 106. MR images of the corpus cavernosum showed a hypointense signal located at the injection site. T2*-weighted signal intensity increased over the course of 1 week after ADSCs transplantation, and demonstrated a similar MR signal with that before ADSCs transplantation. After SPION-labeled ADSC injection, T2*-weighted MR imaging clearly demonstrated a marked hypointense signal in pig corpus cavernosum. The T2*-weighted signal faded over time, similar to the MR imaging results in rats. Obvious acute inflammatory exudation was induced by intracavernous injection, and the T2*-weighted signal intensity of these exudation was higher than that of the injection site. The presence of iron was detected by Prussian blue staining, which demonstrated ADSC retention in rat corpus cavernosum. Lack of cellular infiltrations were demonstrated by H&E staining before and 4 weeks after transplantation, which indicated no negative immune response by rats. Prussian blue staining was positive for iron oxide nanoparticles at 2 weeks after transplantation. SPION-labeled ADSCs showed a clear hypointense signal on T2-weight MRI in vitro and in vivo. The MR signal intensity in the corpus cavernosum of the rats and miniature pigs faded and disappeared over time after ADSC transplantation. These findings suggested that MR imaging could trace transplanted ADSCs in the short term in the corpus cavernosum of animals.

Abstract The question of whether community nucleic acid testing contributes to an increase in infections within residential compounds has not been definitively answered. Shanghai, one of the largest cities in China, conducted city-wide community testing during its lockdown from late March to May 2022. This situation provided a unique opportunity to examine the effect of community testing on infection rates, as the lockdown largely eliminated confounding factors such as citizen mobility. In our study, based on a survey of 208 residential compounds in Shanghai and the daily infection data during the lockdown period, we found a significant correlation between community testing and infection risk in these compounds. However, after addressing potential issues of reverse causality and sampling bias, we found no significant causal link between community testing and infection risk. Furthermore, we discovered that increased awareness of mask-wearing correlated with a decrease in infections within the residential compounds during community testing. This suggests that the perceived correlation between community testing and infection risk may be confounded by residents’ adherence to mask-wearing practices. Our findings emphasize the need for public health decision-makers to reinforce the importance of mask-wearing during community testing, as a means to prevent infections among citizens.

Helminths produce calreticulin (CRT) to immunomodulate the host immune system as a survival strategy. However, the structure of helminth-derived CRT and the structural basis of the immune evasion process remains unclarified. Previous study found that the tissue-dwelling helminth Trichinella spiralis produces calreticulin (TsCRT), which binds C1q to inhibit activation of the complement classical pathway. Here, we used x-ray crystallography to resolve the structure of truncated TsCRT (TsCRTΔ), the first structure of helminth-derived CRT. TsCRTΔ was observed to share the same binding region on C1q with IgG based on the structure and molecular docking, which explains the inhibitory effect of TsCRT on C1q-IgG–initiated classical complement activation. Based on the key residues in TsCRTΔ involved in the binding activity to C1q, a 24 amino acid peptide called PTsCRT was constructed that displayed strong C1q-binding activity and inhibited C1q-IgG–initiated classical complement activation. This study is the first to elucidate the structural basis of the role of TsCRT in immune evasion, providing an approach to develop helminth-derived bifunctional peptides as vaccine target to prevent parasite infections or as a therapeutic agent to treat complement-related autoimmune diseases.

IntroductionPlant bacterial wilt is an important worldwide disease caused by Ralstonia solanacearum which is a complex of species.MethodsIn this study, we identified and sequenced the genome of R. solanacearum strain gd-2 isolated from tobacco.ResultsStrain gd-2 was identified as R. solanacearum species complex (RSSC) phylotype I sequevar 15 and exhibited strong pathogenicity to tobacco. The genome size of gd-2 was 5.93 Mb, including the chromosomes (3.83 Mb) and the megaplasmid (2.10 Mb). Gene prediction results showed that 3,434 and 1,640 genes were identified in the chromosomes and plasmids, respectively. Comparative genomic analysis showed that gd-2 exhibited high conservation with ten highly similar strain genomes and the differences between gd-2 and other genomes were mainly located at positions GI12-GI14. 72 type III effectors (T3Es) were identified and RipAZ2 was a T3E specific to gd-2 compared with other eight sequenced strain.DiscussionOur study provides a new basis and evidence for studying the pathogenic mechanism of R. solanacearum.

Exposure to environmental endocrine disruptors (EEDs) has become a global health concern, and EEDs are known to be potent inducers of constitutive androstane receptor (CAR). 1,4-bis [2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP, hereafter abbreviated as TC), a specific ligand for CAR, has been considered as a potential EED. Here, we analyzed the effect of TC exposure to female mice on the histological morphology of their alveoli in the basic unit of lactation. We quantified differences in the milk metabolome of the control and TC-exposed group while assessing the correlations between metabolites and neonatal growth. Mammary histological results showed that TC exposure inhibited alveolar development. Based on the milk metabolomic data, we identified a total of 1505 differential metabolites in both the positive and negative ion mode, which indicated that TC exposure affected milk composition. As expected, the differential metabolites were significantly enriched in the drug metabolism pathway. Further analyses revealed that differential metabolites were significantly enriched in multiple lipid metabolic pathways, such as fatty acid biosynthesis, suggesting that most differential metabolites were concentrated in lipids. Simultaneously, a quantitative analysis showed that TC exposure led to a decrease in the relative abundance of total milk lipids, affecting the proportion of some lipid subclasses. Notably, a portion of lipid metabolites were associated with neonatal growth. Taken together, these findings suggest that TC exposure may affect milk lipidomes, resulting in the inability of mothers to provide adequate nutrients, ultimately affecting the growth and health of their offspring.

With the increasing scarcity of Earth’s resources and the development of space science and technology, the exploration, development, and utilization of deep space-specific material resources (minerals, water ice, volatile compounds, etc.) are not only important to supplement the resources and reserves on Earth but also provide a material foundation for establishing extraterrestrial research bases. To achieve large depth in-situ condition-preserved coring (ICP-Coring) in the extreme lunar environment, first, lunar rock simulant was selected (SZU-1), which has a material composition, element distribution, and physical and mechanical properties that are approximately equivalent to those of lunar mare basalt. Second, the influence of the lunar-based in-situ environment on the phase, microstructure, and thermal physical properties (specific heat capacity, thermal conductivity, thermal diffusivity, and thermal expansion coefficient) of SZU-1 was explored and compared with the measured lunar rock data. It was found that in an air atmosphere, low temperature has a more pronounced effect on the relative content of olivine than other temperatures, while in a vacuum atmosphere, the relative contents of olivine and anorthite are significantly affected only at temperatures of approximately −20 and 200 °C. When the vacuum level is less than 100 Pa, the contribution of air conduction can be almost neglected, whereas it becomes dominant above this threshold. Additionally, as the testing temperature increases, the surface of SZU-1 exhibits increased microcracking, fracture opening, and unevenness, while the specific heat capacity, thermal conductivity, and thermal expansion coefficient show nonlinear increases. Conversely, the thermal diffusivity exhibits a nonlinear decreasing trend. The relationship between thermal conductivity, thermal diffusivity, and temperature can be effectively described by an exponential function (R2>0.98). The research results are consistent with previous studies on real lunar rocks. These research findings are expected to be applied in the development of the test and analysis systems of ICP-Coring in a lunar environment and the exploration of the mechanism of machine-rock interaction in the in-situ drilling and coring process.

Protection of podocytes is one of the important means to delay the progression of diabetic nephropathy (DN), and glucagon-like peptide-1 (GLP-1) has been shown to have a protective effect on the kidney in DN models, but whether it h as a protective effect on podocytes and the potential mechanisms of action remain largely unknown. In the present study, we established a type 2 diabetes mellitus (T2DM) mouse model by high-fat diet feeding combined with streptozotocin (STZ) induction and admini stered the intervention for 14 weeks. We found that liraglutide significantly ameliorate d podocyte injury in DN mice. Mechanistically, we detected glucagon-like peptide-1 receptor (GLP-1R) protein expression levels in kidney tissues by immunohistochemical stai ning, immunofluorescence staining, and western blotting and found that podocytes could express GLP-1R and liraglutide treatment could restore GLP-1R expression in the kidney tissues of DN mice. Furthermore, we found that NLRP3-induced inflammation and pyropt osis were positively correlated with podocyte injury in DN mice, and liraglutide inh ibited the expression of NLRP3-induced inflammation and pyroptosis-related proteins. Our results suggest that liraglutide protects DN mouse podocytes by regulating GLP-1R in renal tissues and by regulating NLRP3-induced inflammation and pyroptosis.

AIM: To investigate the role of autophagy inhibitor 3-methyladenine (3-MA) on a diabetic mice model (DM) and the potential mechanism. METHODS: Male C57BL/6J mice were randomly divided into a normal control group (NC group) and an DM group. DM were induced by multiple low-dose intraperitoneal injection of streptozotocin (STZ) 60 mg/kg●d for 5 consecutive days. DM mice were randomly subdivided into untreated group (DM group), 3-MA (10 mg/kg●d by gavage) treated group (DM+3-MA group) and chloroquine (CQ; 50 mg/kg by intraperitoneal injection) treated group (DM+CQ group). The fasting blood glucose (FBG) levels were recorded every week. At the end of experiment, retinal samples were collected. The expression levels of pro-apoptotic proteins cleaved caspase-3, cleaved poly ADP-ribose polymerase 1 (PARP1) and Bax, anti-apoptotic protein Bcl-2, fibrosis-associated proteins Fibronectin and type 1 collagen α1 chain (COL1A1), vascular endothelial growth factor (VEGF), inflammatory factors interleukin (IL)-1β and tumor necrosis factor (TNF)-α, as well as autophagy related proteins LC3, Beclin-1 and P62 were determined by Western blotting. The oxidative stress indicators 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) were detected by commercial kits. RESULTS: Both 3-MA and CQ had short-term hypoglycemic effect on FBG and reduced the expression of VEGF and inflammatory factors IL-1β and TNF-α in DM mice. 3-MA also significantly alleviated oxidative stress indicators 8-OHdG and MDA, decreased the expression of fibrosis-related proteins Fibronectin and COL1A1, pro-apoptotic proteins cleaved caspase-3, cleaved PARP1, as well as the ratio of Bax/Bcl-2. CQ had no significant impact on the oxidative stress indicators, fibrosis, and apoptosis related proteins. The results of Western blotting for autophagy related proteins showed that the ratio of LC3 II/LC3 I and the expression of Beclin-1 in the retina of DM mice were decreased by 3-MA treatment, and the expression of P62 was further increased by CQ treatment. CONCLUSION: 3-MA has anti-apoptotic and anti-fibrotic effects on the retina of DM mice, and can attenuate retinal oxidative stress, VEGF expression and the production of inflammatory factors in the retina of DM mice. The underlying mechanism of the above effects of 3-MA may be related to its inhibition of early autophagy and hypoglycemic effect.

Background: We aimed to assess the value of stereotactic body radiotherapy (SBRT) delivered under the situation of controlled or progressed disease during ICI therapy in advanced or recurrent NSCLC. Methods: We retrospectively collected patients with advanced or recurrent NSCLC who received SBRT concurrently with ICI in our institution between January 2017 and December 2021. Patients were divided into two groups, including those for whom SBRT was delivered initially or to the residual tumors during the first- or later-line ICI treatment (Group 1), and those for whom SBRT was given to the progressed tumors irrespective of first- or later-line ICI treatment (Group 2). Results: A total of 144 patients were included. With median follow-up duration of 25.6 (range: 3.6 to 56.2) months, median progression-free survival (PFS) was 13.7 (95 % CI: 10.4 to 17.1) months and median overall survival (OS) was 52.8 [95 % CI: 30.6 to not available (NA)] months. In Group 1 (n = 78), median PFS was 17.9 (95 % CI: 14.5 to 29.8) months while median OS was not reached and 5-year OS rate was 61.2 %. In Group 2 (n = 66), median PFS was 8.0 (95 % CI: 6.0 to 13.1) months and median OS was 30.6 (95 % CI: 21.5 to NA) months. Conclusions: SBRT combined with ICI demonstrated favorable survival for advanced or recurrent NSCLC, delivered in a controlled-disease situation as well as to progressed diseases with salvage-intent. Future prospective studies are warranted to investigate the optimal SBRT dose regimen and appropriate combination strategy to synergize ICI.

Abstract The development of precious‐metal‐free catalysts with bifunctional activities for both oxygen reduction and evolution reactions (ORR/OER) is crucial for the advancement of regenerative fuel cells and rechargeable metal−air batteries. Manganese oxides (MnOx) have emerged as promising bifunctional catalysts. However, MnOx electrodes typically exhibit poor ORR/OER cycling stability owing to polarization‐induced MnOx redox reactions and phase transition. To address this issue, we developed metallic cation (i. e., Co2+, Ni2+, Cu2+, or Bi3+) doped MnOx/carbon electrodes using potentiodynamic, potentiostatic and galvanostatic methods. Among the explored dopant cations Ni2+ intercalated into MnOx under acidic conditions using a slow‐scan cyclic voltammetry method, significantly enhanced the ORR/OER activity and stability of MnOx. Alongside electrochemical doping, MnOx also underwent redox reactions leading to changes in Mn valence and phase transitions. The Ni‐incorporated MnOx gas diffusion electrode (GDE) demonstrated exceptional stability for over 120 accelerated OER and ORR cycles at ±10 mA cm−2 in 5 M KOH, surpassing the performance of the Pt/C−IrO2 benchmark. Furthermore, it achieved OER current densities of approximately 22 mA cm−2 at 1.65 VRHE, which was twice as high as that of Pt/C−IrO2.

In this paper, a two-dimensional (2D) thermo-hydro-mechanical dynamic (THMD) coupling analysis in the presence of a half-space medium is studied using Ezzat's fractional order generalized theory of thermoelasticity. Using normal mode analysis (NMA), the influence of the anisotropy of the thermal conduction coefficient, fractional derivatives, and frequency on the THMD response of anisotropy, fully saturated, and poroelastic subgrade is then analyzed with a time-harmonic load including mechanical load and thermal source subjected to the surface. The general relationships among the dimensionless physical variables such as the vertical displacement, excess pore water pressure, vertical stress, and temperature distribution are graphically illustrated. The NMA method does not require the integration and inverse transformation, increases the decoupling speed, and eliminates the limitation of numerical inverse transformation. The obtained results can guide the geotechnical engineering construction according to different values of load frequency, fractional order coefficient, and anisotropy of thermal conduction coefficient. This improves the subgrade stability and enriches the theoretical studies on thermo-hydro-mechanical coupling.

BackgroundCigarette smoking and particulate matter (PM) with aerodynamic diameter Q3, corresponding to PM2.5 ≤ 27.137, 27.137 38.205 μg/m3.ResultsThe prevalence of MS was significantly different according to PM2.5 exposure (p-value = 0.0280) and cigarette smoking (p-value 38.205 μg/m3, respectively. The risk of MS was significantly higher among former and current smokers with OR; 95% CI = 1.062; 1.008–1.118 and 1.531; 1.450–1.616, respectively, and a dose-dependent p-value 38.205 μg/m3, respectively. According to PM2.5 quartiles, current smokers had a higher risk of MS, regardless of PM2.5 levels (OR); 95% CI = 1.605; 1.444–1.785, 1.561; 1.409–1.728, 1.359; 1.211–1.524, and 1.585; 1.418–1.772 for PM2.5 ≤ 27.137, 27.137 38.205 μg/m3, respectively. After combining both exposures, the group, current smokers; PM2.5 > 38.205 μg/m3 had the highest odds (1.801; 95% CI =1.625–1.995).ConclusionPM2.5 and cigarette smoking were independently and jointly associated with a higher risk of MS. Stratified analyses revealed that cigarette smoking might have a much higher effect on MS than PM2.5. Nonetheless, exposure to both PM2.5 and cigarette smoking could compound the risk of MS.

ABSTRACT Antibiotic resistance screening is crucial in the construction of recombinant plasmids. The dfrB10 gene, a short-size trimethoprim (TMP)-resistance type B dihydrofolate reductase gene, is a promising antibiotic drug screening marker for plasmid construction in molecular genetic research. Currently, available plasmid backbones (without the resistance gene) were amplified using PCR, and then we ligated these products with dfrB10 gene fragments via homologous recombination to construct new plasmid vectors with TMP resistance. The cloning, expression, and gene editing functions of the new plasmids based on their different purposes were verified. By successfully replacing the original resistance genes of pUC19, pET28a, pcDNA3.1, and pX330 plasmids with dfrB10, we constructed a series of plasmids with TMP resistance. The change of the resistance selection marker to TMP did not affect the function of the plasmids compared to the original ones. Furthermore, a short (988 bp) TMP-resistant miniature tool plasmid, pTMi, was constructed based on the pUC19 plasmid. With the use of the dfrB10 gene as a resistance marker under TMP drug screening, various size-reduced tool plasmids can be routinely constructed. These plasmids have similar functions to the original ones and can be used for research applications in molecular genetics. IMPORTANCE Plasmid size is one of the factors affecting transfection efficacy in most of the molecular genetic research studies. One effective approach for reducing plasmid size is to replace relatively large, conventional antibiotic resistance genes with the short-size dfrB10 gene. The successful construct of a series of dfrB10-based tool plasmids and their functional validation, via comparison with original plasmids, suggest that dfrB10 is a potent drug resistance selection marker. The antibiotic trimethoprim offers convenient usage comparable to that of ampicillin or kanamycin. Additionally, fluorescence analysis has demonstrated the compatibility of TMP with protein expression in various host cells. Based on these findings, TMP-dfrB10 could be an alternative choice for future use in molecular genetic research studies that require miniature plasmids to achieve optimal results.

Abstract Bacterial infections pose a severe threat to human health due to the exacerbation of antibiotic resistance and intracellular bacterial infections. Research suggests that oligo(p-phenylene vinylene) (OPV), commonly employed in the manufacture of organic solar batteries, can help address this issue. This study demonstrates the ability of OPV to target and sterilize intracellular Porphyromonas gingivalis and methicillin-resistant Staphylococcus aureus (MRSA) photodynamically. Most notably, OPV specifically targets bacteria without affecting healthy cells under dark conditions. Its chemical composition includes a conjugated backbone and ionic imidazole side chains, which allow OPV to bind to cell membranes. Furthermore, dental blue light curing lamps may excite OPV. Compared with antibiotics and traditional photosensitizers, OPV proves to be a potentially superior solution to eradicate intracellular microbial infections, both in fundamental research and clinical applications.

Preeclampsia is a primary placental disorder, with impaired placental vascularization leading to uteroplacental hypoperfusion. We aimed to investigate differences in metal and metalloid content between the placentas of women with preeclampsia and healthy controls. This was a case–control study in 63 women with preeclampsia and 113 healthy women. Clinical data were obtained from medical records. Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the placental metals and metalloids content. Compared with healthy control subjects, preeclampsia was associated with a significantly lower concentration of essential elements (magnesium, calcium, iron, copper, zinc, and selenium) in the placental tissue. After multivariable adjustment, an interquartile range (IQR) increase in selenium concentration was associated with a reduced risk of preeclampsia with an OR of 0.50 (95% CI: 0.33–0.77). The joint effects of multiple selected metals and metalloids were associated with a reduced risk of preeclampsia. The lower placental magnesium, chromium, iron, zinc, and selenium concentrations of preeclampsia cases indicate a potential link to its pathogenesis. It also provides an intriguing avenue for future research in revealing the underlying mechanisms and potential intervention strategies for preeclampsia.

Abstract Background The brain is a highly mechanosensitive organ, and changes in the mechanical properties of brain tissue influence many physiological and pathological processes. Piezo type mechanosensitive ion channel component 1 (Piezo1), a protein found in metazoans, is highly expressed in the brain and involved in sensing changes of the mechanical microenvironment. Numerous studies have shown that Piezo1‐mediated mechanotransduction is closely related to glial cell activation and neuronal function. However, the precise role of Piezo1 in the brain requires further elucidation. Objective This review first discusses the roles of Piezo1‐mediated mechanotransduction in regulating the functions of a variety of brain cells, and then briefly assesses the impact of Piezo1‐mediated mechanotransduction on the progression of brain dysfunctional disorders. Conclusions Mechanical signaling contributes significantly to brain function. Piezo1‐mediated mechanotransduction regulates processes such as neuronal differentiation, cell migration, axon guidance, neural regeneration, and oligodendrocyte axon myelination. Additionally, Piezo1‐mediated mechanotransduction plays significant roles in normal aging and brain injury, as well as the development of various brain diseases, including demyelinating diseases, Alzheimer's disease, and brain tumors. Investigating the pathophysiological mechanisms through which Piezo1‐mediated mechanotransduction affects brain function will give us a novel entry point for the diagnosis and treatment of numerous brain diseases.

Abstract Postoperative delirium (POD) is a frequent and debilitating complication, especially amongst high risk procedures, such as orthopedic surgery. This kind of neurocognitive disorder negatively affects cognitive domains, such as memory, awareness, attention, and concentration after surgery; however, its pathophysiology remains unknown. Multiple lines of evidence supporting the occurrence of inflammatory events have come forward from studies in human patients’ brain and bio-fluids (CSF and serum), as well as in animal models for POD. β-arrestins are downstream molecules of guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs). As versatile proteins, they regulate numerous pathophysiological processes of inflammatory diseases by scaffolding with inflammation-linked partners. Here we report that β-arrestin1, one type of β-arrestins, decreases significantly in the reactive astrocytes of a mouse model for POD. Using β-arrestin1 knockout (KO) mice, we find aggravating effect of β-arrestin1 deficiency on the cognitive dysfunctions and inflammatory phenotype of astrocytes in POD model mice. We conduct the in vitro experiments to investigate the regulatory roles of β-arrestin1 and demonstrate that β-arrestin1 in astrocytes interacts with the dynamin-related protein 1 (Drp1) to regulate mitochondrial fusion/fission process. β-arrestin1 deletion cancels the combination of β-arrestin1 and cellular Drp1, thus promoting the translocation of Drp1 to mitochondrial membrane to provoke the mitochondrial fragments and the subsequent mitochondrial malfunctions. Using β-arrestin1-biased agonist, cognitive dysfunctions of POD mice and pathogenic activation of astrocytes in the POD-linked brain region are reduced. We, therefore, conclude that β-arrestin1 is a promising target for the understanding of POD pathology and development of POD therapeutics.

Abstract To provide a basis for further optimization of the polio sequential immunization schedule, this study evaluated the effectiveness of booster immunization with one dose of bivalent oral poliovirus vaccine (bOPV) at 48 months of age after different primary polio immunization schedules. At 48 months of age, one dose of bOPV was administered, and their poliovirus types 1–3 (PV1, PV2, and PV3, respectively)-specific neutralizing antibody levels were determined. Participants found to be negative for any type of PV-specific neutralizing antibody at 24, 36, or 48 months of age were re-vaccinated with inactivated polio vaccine (IPV). The 439 subjects who received a bOPV booster immunization at the age of 48 months had lower PV2-specific antibody levels compared with those who received IPV. One dose of IPV during basic polio immunization induced the lowest PV2-specific antibody levels. On the basis of our findings, to ensure that no less than 70% of the vaccinated have protection efficiency, we recommend the following: if basic immunization was conducted with 1IPV + 2bOPV (especially Sabin strain-based IPV), a booster immunization with IPV is recommended at 36 months of age, whereas if basic immunization was conducted with 2IPV + 1bOPV, a booster immunization with IPV is recommended at 48 months of age. A sequential immunization schedule of 2IPV + 1bOPV + 1IPV can not only maintain high levels of antibody against PV1 and PV3 but also increases immunity to PV2 and induces early intestinal mucosal immunity, with relatively good safety. Thus, this may be the best sequential immunization schedule for polio in countries or regions at high risk for polio.

Selective dorsal neurotomy (SDN) is a surgical treatment for primary premature ejaculation (PE), but there is still no standard surgical procedure for selecting the branches of the dorsal penile nerves to be removed. We performed this study to explore the value of intraoperative neurophysiological monitoring (IONM) of the penile sensory-evoked potential (PSEP) for standard surgical procedures in SDN. One hundred and twenty primary PE patients undergoing SDN were selected as the PE group and 120 non-PE patients were selected as the normal group. The PSEP was monitored and compared between the two groups under both natural and general anesthesia (GA) states. In addition, patients in the PE group were randomly divided into the IONM group and the non-IONM group. During SDN surgery, PSEP parameters of the IONM group were recorded and analyzed. The differences in PE-related outcome measurements between the perioperative period and 3 months' postoperation were compared for the PE patients, and the differences in effectiveness and complications between the IONM group and the non-IONM group were compared. The results showed that the average latency of the PSEP in the PE group was shorter than that in the normal group under both natural and GA states (P < 0.001). Three months after surgery, the significant effective rates in the IONM and non-IONM groups were 63.6% and 34.0%, respectively (P < 0.01), and the difference in complications between the two groups was significant (P < 0.05). IONM might be useful in improving the short-term therapeutic effectiveness and reducing the complications of SDN.

Abstract Background Cumulative preclinical and clinical evidences showed radiotherapy might augment systemic antitumoral responses to immunotherapy for metastatic non-small cell lung cancer, but the optimal timing of combination is still unclear. The overall infiltration and exhausted subpopulations of tumor-infiltrating CD8+ T cells might be a potential biomarker indicating the response to immune checkpoint inhibitors (ICI), the alteration of which is previously uncharacterized during peri-irradiation period, while dynamic monitoring is unavailable via repeated biopsies in clinical practice. Methods Basing on tumor-bearing mice model, we investigated the dynamics of overall infiltration and exhausted subpopulations of CD8+ T cells after ablative irradiation. With the understanding of distinct metabolic characteristics accompanied with T cell exhaustion, we developed a PET radiomics approach to identify and visualize T cell exhaustion status. Results CD8+ T cell infiltration increased from 3 to 14 days after ablative irradiation while terminally exhausted populations significantly predominated CD8+ T cells during late course of this infiltrating period, indicating that 3–7 days post-irradiation might be a potential appropriate window for delivering ICI treatment. A PET radiomics approach was established to differentiate T cell exhaustion status, which fitted well in both ICI and irradiation settings. We also visualized the underlying association of more heterogeneous texture on PET images with progressed T cell exhaustion. Conclusions We proposed a non-invasive imaging predictor which accurately assessed heterogeneous T cell exhaustion status relevant to ICI treatment and irradiation, and might serve as a promising solution to timely estimate immune-responsiveness of tumor microenvironment and the optimal timing of combined therapy.

Obesity has been associated with the development of 13 different types of cancers, including breast cancer. Evidence has indicated that cancer-associated adipocytes promote the proliferation, invasion, and metastasis of cancer. However, the mechanisms that link CAAs to the progression of obesity-related cancer are still unknown. Here, we found the mature adipocytes in the visceral fat of HFD-fed mice have a CAAs phenotype but the stromal vascular fraction of the visceral fat has not. Importantly, we found the derivate of the potent PPARγ antagonist GW9662, BZ26 inhibited the reprogramming of mature adipocytes in the visceral fat of HFD-fed mice into CAA-like cells and inhibited the proliferation and invasion of obesity-related breast cancer. Further study found that it mediated the browning of visceral, subcutaneous and perirenal fat and attenuated inflammation of adipose tissue and metabolic disorders. For the mechanism, we found that BZ26 bound and inhibited PPARγ by acting as a new modulator. Therefore, BZ26 serves as a novel modulator of PPARγ activity, that is, capable of inhibiting obesity-related breast cancer progression by inhibiting of CAA-like cell formation, suggesting that inhibiting the reprogramming of mature adipocytes into CAAs or CAA-like cells may be a potential therapeutic strategy for obesity-related cancer treatment.

The metaverse, where the virtual and real world are fused, is currently under rapid development. Immersive and vivid experience in the metaverse requires human–machine interaction devices that, unlike those currently available, are simultaneously imperceptible, convenient to use, inexpensive, and safe. Herein, an optical‐nanofiber‐based gesture‐recognition wristband that can accurately recognize gestures and be used to interact with a robotic hand is proposed and realized. Requiring only three optical‐nanofiber‐based pressure sensors, the wristband is simple in structure, convenient to use, and remarkably imperceptible to the user. With the assistance of a machine‐learning algorithm, a maximum recognition accuracy of 94% is achieved for testers with different physiques. A robotic hand can be remotely controlled by the wristband through gestures. The wristband has broad application prospects and is a promising solution for advanced human–machine‐interaction devices. An interactive preprint version of the article can be found here: https://doi.org/10.22541/au.167022827.77928491/v1.

The utilisation of recycled aggregate concrete (RAC) is commonly recognised as one of the most effective means to achieve cleaner and sustainable development in civil engineering. To promote the application of RAC, prestressing technique can be employed to overcome the inherent disadvantages of RAC beams associated with poor cracking resistance and large deflections. However, the research on the prestressed RAC beam is quite limited, and no research has been performed on their long-term behaviour. This paper presents a finite element (FE) analysis for investigating the long-term behaviour of RAC beams prestressed with carbon fibre-reinforced polymer (CFRP) tendons considering the effects of concrete creep, concrete shrinkage, tendon relaxation as well as the cracking and tension stiffening of concrete. Based on the principle of superposition, the variations of the stress and strain with time are considered in the numerical analysis using step-by-step method. The FE model is calibrated with the experimental results obtained from the literature. Based on the validated model, a comprehensive parametric study is performed to investigate the effects of the replacement ratio of recycled coarse aggregate (RCA), concrete strength, reinforcement ratio, prestress level, and sustained load level on the long-term behaviour of prestressed RAC beams. The obtained results demonstrate that increasing the prestress load is an effective way to reduce the long-term deflection of RAC beams, and the use of RAC with low RCA replacement ratio is suggested. Besides, the main causes of the long-term deflection and axial shorting of the CFRP prestressed RAC beams are also studied. This research provides a pioneering and insightful study of the long-term behaviour of CFRP prestressed RAC beams. The obtained results demonstrate that the time-dependent effects should be well considered in the design before the prestressed RAC beam is used in practice.

The Ti47Al2Cr2Nb alloy fatigue specimens were prepared by investment casting, and three kinds of surface processes were applied to fatigue specimens. These three processes were sand-blasting (SB), sand-blasting and shot-peening (SBSP) and sand-blasting and mechanical grinding (SBMG). The surface characteristics before and after thermal exposure at 700 °C for 24 h were investigated. The high cycle fatigue behaviors of specimens after thermal exposure were evaluated. The results showed that the surface roughness (Ra) values after SB, SBSP and SBMG processes were 1.71, 0.99 and 0.06 μm, respectively. After thermal exposure, they increased slightly for all three processes. The SB process caused work hardening in the near-surface region and the work hardening reached saturation after the SB process. Due to the mechanical grinding process removing an uncertain thick hardening layer, the maximum hardness after SBMG process was noticeably lower than those after SB and SBSP processes. After thermal exposure, the maximum hardness after all three processes significantly recovered. Deformed layers were formed beneath SB and SBSP surfaces. After thermal exposure, a depth-dependent gradient microstructure was formed in the surface layer. The SBMG specimens had the highest fatigue limit of 350 MPa. This was attributed to the SBMG specimens having very smooth surfaces and keeping some work hardening in the surface layers. The fatigue fractures were typical brittle cleavage fractures. The fracture modes included interlamellar and trans-lamellar fractures. The dislocation slip and mechanical twins were the main deformation mechanisms.

This study systematically investigated the high cycle fatigue behaviors and deformation mechanisms in Ti47Al2Cr2Nb alloy at room temperature and 700 °C through scanning electron microscope and transmission electron microscope. The results showed that high temperature deteriorated the fatigue performances, especially under the higher stress levels. Large scatter in fatigue lifetimes under the lower stress levels was observed at high temperature. After 107 cycles, the high cycle fatigue limit at 700 °C was about 20 MPa lower than that at room temperature. Fracture morphologies showed that brittle fracture presented at both temperatures and fatigue cracks initiated from the surfaces. Fracture modes at room temperature included trans-lamellar and trans-γ grain fractures, while those at 700 °C included trans-lamellar, interlamellar and inter-γ gain fractures. Fatigue deformation at both temperatures mainly occurred in the γ phase, dislocation multiplication and slip bands were found in the deformation microstructures. Dislocation slip was the main deformation mechanism at both temperatures. A few mechanical twins were observed in the deformation microstructures of room temperature. Slip bands and mechanical twins transferred through γ/γ true-twin interfaces with a deflection while they transferred through γ/γ rotational boundaries straightly. Mechanical twins had a blocking effect on slip bands, resulting in the dislocation arrays in slip bands piling up at the intersections.

Abstract Tobacco bacterial wilt has seriously affected tobacco production. Ethyl methanesulfonate (EMS) induced tobacco bacterial wilt resistant mutants are important for the control of tobacco bacterial wilt. High-throughput sequencing technology was used to study the rhizosphere bacterial community assemblages of bacterial wilt resistant mutant tobacco rhizosphere soil (namely KS), bacterial wilt susceptible tobacco rhizosphere soil (namely GS) and bulk soil (namely BS) in Xuancheng, Huanxi, Yibin and Luzhou. Alpha analysis showed that the bacterial community diversity and richness of KS and GS in the four regions were not significantly different. However, analysis of intergroup variation in the top 15 bacterial communities in terms of abundance showed that the bacterial communities of KS and GS were significantly different from BS, respectively. In addition, pH, alkali-hydrolysable nitrogen (AN) and soil organic carbon (SOC) were positively correlated with the bacterial community of KS and negatively correlated with GS in the other three regions except Huanxi. Network analysis showed that the three soils in the four regions did not show a consistent pattern of network complexity. PICRUSt functional prediction analysis showed that the COG functions were similar in all samples. All colonies were involved in RNA processing and modification, chromatin structure and dynamics, etc. In conclusion, our experiments showed that rhizosphere bacterial communities of tobacco in different regions have different compositional patterns, which are strongly related to soil factors.

Flexible strain sensors play an important role in electronic skins, wearable medical devices, and advanced robots. Herein, a highly sensitive and fast response optical strain sensor with two evanescently coupled optical micro/nanofibers (MNFs) embedded in a polydimethylsiloxane (PDMS) film is proposed. The strain sensor exhibits a gauge factor as high as 64.5 for strain ≤ 0.5% and a strain resolution of 0.0012% which corresponds to elongation of 120 nm on a 1 cm long device. As a proof-of-concept, highly sensitive fingertip pulse measurement is realized. The properties of fast temporal frequency response up to 30 kHz and a pressure sensitivity of 102 kPa−1 enable the sensor for sound detection. Such versatile sensor could be of great use in physiological signal monitoring, voice recognition and micro-displacement detection.

We realised a provably-secure symmetric private information retrieval supported by a quantum-secure key-exchange network. Our demonstration achieves secure retrieval of 582-byte fingerprint files from a database with 800 entries.

Lunar soils returned by China’s Chang’E−5 (CE5) mission record the unique information of solar wind essential to understanding the preservation and distribution of lunar surficial water. Here the authors report abundant water formed by solar wind implantation in minerals of CE5 lunar soils; the water content in CE5 lunar soils is estimated to be ~ 170 ppm.

To develop accurate and accessible prediction methods for assessing pathologic response following NICT prior to surgery, we conducted a retrospective study including 137 patients with esophageal squamous cell carcinoma (ESCC) who underwent surgery after two cycles of NICT between January 2019 and March 2022 at our center. We collected clinical parameters to evaluate the dynamic changes in the primary tumor. Univariate and multivariate analyses were performed to determine the correlations between these parameters and the pathologic response of the primary tumor. Subsequently, we constructed prediction models for pCR and MPR using multivariate logistic regression. The MPR prediction Model 2 was internally validated using bootstrapping and externally validated using an independent cohort from our center. The univariate logistic analysis revealed significant differences in clinical parameters reflecting tumor regression among patients with varying pathologic responses. The clinical models based on these assessments demonstrated excellent predictive performance, with the training cohort achieving a C-index of 0.879 for pCR and 0.912 for MPR, while the testing cohort also achieved a C-index of 0.912 for MPR. Notably, the MPR prediction Model 2, with a threshold cut-off of 0.74, exhibited 92.7% specificity and greater than 70% sensitivity, indicating a low rate of underestimating residual tumors. In conclusion, our study demonstrated the high accuracy of clinical assessment-based models in pathologic response prediction, aiding in decision-making regarding organ preservation and radiotherapy adjustments after induction immunochemotherapy.

Macrophages, as central components of innate immunity, feature significant heterogeneity. Numerus studies have revealed the pivotal roles of macrophages in the pathogenesis of liver fibrosis induced by various factors. Hepatic macrophages function to trigger inflammation in response to injury. They induce liver fibrosis by activating hepatic stellate cells (HSCs), and then inflammation and fibrosis are alleviated by the degradation of the extracellular matrix and release of anti-inflammatory cytokines. MicroRNAs (miRNAs), a class of small non-coding endogenous RNA molecules that regulate gene expression through translation repression or mRNA degradation, have distinct roles in modulating macrophage activation, polarization, tissue infiltration, and inflammation regression. Considering the complex etiology and pathogenesis of liver diseases, the role and mechanism of miRNAs and macrophages in liver fibrosis need to be further clarified. We first summarized the origin, phenotypes and functions of hepatic macrophages, then clarified the role of miRNAs in the polarization of macrophages. Finally, we comprehensively discussed the role of miRNAs and macrophages in the pathogenesis of liver fibrotic disease. Understanding the mechanism of hepatic macrophage heterogeneity in various types of liver fibrosis and the role of miRNAs on macrophage polarization provides a useful reference for further research on miRNA-mediated macrophage polarization in liver fibrosis, and also contributes to the development of new therapies targeting miRNA and macrophage subsets for liver fibrosis.

Abstract Mass spectrometry-based targeted proteomics allows objective protein quantitation of clinical biomarkers from a single section of formalin-fixed, paraffin-embedded (FFPE) tumor tissue biopsies. We combined high-field asymmetric waveform ion mobility spectrometry (FAIMS) and parallel reaction monitoring (PRM) to increase assay sensitivity. The modular nature of the FAIMS source allowed direct comparison of the performance of FAIMS-PRM to PRM. Limits of quantitation were determined by spiking synthetic peptides into a human spleen matrix. In addition, 20 clinical samples were analyzed using FAIMS-PRM and the quantitation of HER2 was compared with that obtained with the Ventana immunohistochemistry assay. FAIMS-PRM improved the overall signal-to-noise ratio over that from PRM and increased assay sensitivity in FFPE tissue analysis for four (HER2, EGFR, cMET, and KRAS) of five proteins of clinical interest. FAIMS-PRM enabled sensitive quantitation of basal HER2 expression in breast cancer samples classified as HER2 negative by immunohistochemistry. Furthermore, we determined the degree of FAIMS-dependent background reduction and showed that this correlated with an improved lower limit of quantitation with FAIMS. FAIMS-PRM is anticipated to benefit clinical trials in which multiple biomarker questions must be addressed and the availability of tumor biopsy samples is limited.

There are many unmeasurable branches along with distribution lines. The sensitivity and speed of traditional three-stage overcurrent protection lacks when applied to these lines. Even the phasor differential protection cannot identify internal faults sensitively to maintain sufficient safety under external faults. With 5G communication is penetrating the field of power grid automation, a comprehensive protection scheme for branched distribution lines is proposed. Firstly, analyze negative sequence currents phase characteristics under internal or external faults, and negative-sequence current phase-comparison protection is proposed. Secondly, in some harsh working conditions, 5G communication's synchronization cannot be guaranteed, or even out of step. A positive sequence amplitude differential protection is introduced. Finally, the three-stage overcurrent protection is combined to form a complete set of protection coordination schemes when communication interruption or some extreme situations. A 10 kV active distribution network model is built in PSCAD/EMTDC to verify the proposed protection criteria and scheme. The simulation results demonstrate the effectiveness of the proposed protection criteria and scheme.

Abstract The importance of neuroglia in maintaining normal brain function under physiological and pathological conditions has been supported by growing evidence in recent years. The most important issues regarding glial metabolism and function include the cooperation between glial populations and neurons, morphological and functional changes in pathological states, and the role in the onset and progression of neurodegenerative diseases. Although lipid accumulation and further lipid droplet production in neurodegenerative disease brain models have been observed for a long time, the dynamic development of brain lipid droplet research in recent years suggests its role in the development and progression of neurodegenerative diseases was previously underestimated. First recognized as organelles of lipid storage, lipid droplets (LDs) have emerged as an important organelle in metabolic diseases, inflammation, and host defense. Dynamic changes in lipid metabolism within neurons and glial cells resulting in lipid accumulation and lipid droplet formation are present in brain models of various neurodegenerative diseases, yet their role in the brain remains largely unexplored. This paper first reviews the metabolism and accumulation of several major lipids in the brain and discusses the regulation of lipid accumulation in different types of brain cells. We explore the potential role of intracellular lipid accumulation in the pathogenesis of neurodegeneration, starting from lipid metabolism and LDs biogenesis in glial cells, and discuss several pathological factors that promote lipid droplet formation, mainly focusing on oxidative stress, energy metabolism and glial cell-neuron coupling, which are closely related to the etiology and progression of neurodegenerative diseases. Finally, the directions and challenges of intracellular lipid metabolism in glial cells in neurodegeneration are discussed.

Mechanical stability of lamellar microstructure in γ-TiAl has been studied, for the first time, from the perspective of three different γ/γ lamellar interfaces evolution at atomic scale via molecular dynamics simulations. Results indicate that small lamellar spacing promotes the formation of longitudinal twinning, thus influences the mechanical stability of TiAl lamellar structure. Pseudo-twin (PT) and rotational boundary (RB) lamellar interfaces transfer to each other while the true-twin (TT) lamellar interface migrates directly and annihilates resulting from interaction with longitudinal twinning during deformation. Therefore, compared with the TiAl lamellar structure with TT interface, structure with PT and RB interfaces exhibit higher mechanical stability.

IntroductionHow does environmental education affect environmental quality? There is no consensus among theorists. This paper is devoted to exploring the influence mechanism of environmental education and environmental quality under the background of a low-carbon economy from a theoretical model and empirical analysis.MethodsThe research method of this paper includes two aspects. First, from the consideration of the central planner, this paper draws on and improves the Ramsey Model to explore the interaction mechanism among environmental education, environmental quality and green growth. Second, this paper uses provincial panel data from China from 2011 to 2017 for empirical analysis, which mainly verifies the impact mechanism of environmental education on environmental quality.Results and discussionThe theoretical model shows that environmental education enhances green consumption intention through residents' environmental awareness and enhances enterprises' cleaner production motivation through environmental pressure. Correspondingly, the pressure to improve environmental quality will also promote the economy's endogenous growth through the digital economy's transformation and the accumulation of human capital. The empirical analysis confirms that environmental education can improve environmental quality through green consumption and pollution control. Still, the effect of improving environmental quality only through pollution control is not apparent, and pollution control needs to be combined with environmental education, especially in high-pollution areas. Finally, this paper puts forward some suggestions for optimizing environmental education.

BackgroundThe 5-year event-free survival rate for childhood acute lymphoblastic leukemia (ALL) has increased to more than 85%. However, the 5-year overall survival rate in children with relapsed/refractory ALL did not exceed 50%. In the past decade, immunotherapies (such as blinatumomab and chimeric antigen receptor T-cell therapy) were approved for relapsed/refractory B-ALL, transforming the treatment environment for children with relapsed/refractory ALL.ObjectiveThis study aimed to explore how immunotherapy can be incorporated into salvage regimens for pediatric patients with relapsed/refractory ALL by retrospectively analyzing the diagnosis and treatment process of seven children with relapsed/refractory leukemia and observing the side effects of the two strategies and long-term survival.MethodsThe clinical features and treatment responses of patients aged

Humans are exposed to different kinds of environmental contaminants or drugs throughout their lifetimes. The widespread presence of these compounds has raised concerns about the consequent adverse effects on lactating women. The constitutive androstane receptor (CAR, Nr1i3) is known as a xenobiotic sensor for environmental pollution or drugs. In this study, the model environmental chemical 1, 4-bis [2-(3, 5-dichloropyridyloxy)] benzene, TCPOBOP (TC), which is a highly specific agonist of CAR, was used to investigate the effects of exogenous exposure on lactation function and offspring health in mice. The results revealed that TC exposure decreased the proliferation of mammary epithelial cells during pregnancy. This deficiency further compromised lobular-alveolar structures, resulting in alveolar cell apoptosis, as well as premature stoppage of the lactation cycle and aberrant lactation. Furthermore, TC exposure significantly altered the size and number of milk lipid droplets, suggesting that TC exposure inhibits milk lipid synthesis. Additionally, TC exposure interfered with the milk lipid metabolism network, resulting in the inability of TC-exposed mice to efficiently secrete nutrients and feed their offspring. These findings demonstrated that restricted synthesis and secretion of milk lipids would indirectly block mammary gland form and function, which explained the possible reasons for lactation failure and retarded offspring growth.

We report a facile and effective inorganic polycondensation combined with aerosol-spray strategy towards high-performance photocatalyst by fabricating mesoporous Ti1-xSnxO2 (0 < x < 1) solid solution. Such Ti1-xSnxO2 nanocrystals with high Sn-doped contents are self-assembled into mesoporous spheres can effectively promote visible-light harvest and high quantum yield, leading a longer lifetime of the photoelectron-hole pairs and less recombination. Such the photocatalysts enhanced photocatalytic activity for the degradation of Rhodamine B (RhB). The representative Ti0.9Sn0.1O2 and Ti0.8Sn0.2O2 compounds reach an optimum degradation of ≈50% and 70%, respectively, after 120 min irradiation under visible irradiation. The mesoporous Ti1-xSnxO2 solid solution could inhibit the recombination of electron-hole pairs, which promote reaction thermodynamics and kinetics for RhB degradation.

In many cases robots are directly in touch with humans, this interaction is necessary to design control systems that take into account a human-machine relation. Particularly important is the case when humans share the control with a robot. So, in order to validate control schemes, it is necessary to test them in an environment where the human-machine interaction exists, what could be even dangerous for humans. We present a model of human useful to test controllers, and propose a scheme for human-in-the-loop under shared control. We test the model and the scheme in a lower limb prosthesis that implies naturally a human-machine interaction. Apart from this research, we propose an efficient and low-cost controller for the prosthesis, based on a sensory exoextension and a neuro-decoder consisting of a multilayer perceptrons. The results show the effectiveness of human model to emulate the human interaction.

This study proposes a performance optimization scheme of liquid asphalt mixtures (LAMs) based on epoxy resin-based material modification and investigates its various performances. First, thermogravimetric analysis and headspace gas chromatography–mass spectrometry were used to analyze the differences between liquid asphalt before and after curing to clarify the formation mechanism of its adhesive force. Second, a molecular model was established. The best epoxy resin and curing agent types were evaluated using an improved Flory–Huggins model and the quantum computing method. Finally, two performance optimization schemes were established to reinforce the performance defects of the mixture caused by residual diluents. Results show that liquid asphalt solidification is a physical process of volatilization of diluents. Bisphenol A epoxy resin and a polyether amine curing agent are compatible with liquid asphalt and prone to curing reactions; thus, they are most suitable as epoxy resin-based modifiers. A solution obtained by adding 2% waterborne epoxy resin and 30% mineral powder replaced with cement can significantly improve the initial strength, strength generation rate, and low-temperature crack resistance of the LAM while optimizing high-temperature performance. This LAM modification can ensure that roads repaired using the modified LAM in a low-temperature environment can be quickly opened to use and improve the durability of the road surface.

With high incidence rate, cancer is the main cause of death in humans. Non-coding RNAs, as novel master regulators, especially long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play important roles in the regulation of tumorigenesis. lncRNA NEAT1 has recently gained much attention, as it is dysregulated in a broad spectrum of cancers, where it acts as either an oncogene or a tumor suppressor gene. Accumulating evidence shows that NEAT1 is correlated with the process of carcinogenesis, including proliferation, invasion, survival, drug resistance, and metastasis. NEAT1 is considered to be a biomarker and a novel therapeutic target for the diagnosis and prognosis of different cancer types. The mechanisms by which NEAT1 plays a critical role in cancers are mainly via interactions with miRNAs. NEAT1-miRNA regulatory networks play significant roles in tumorigenesis, which has attracted much attention from researchers around the world. In this review, we summarize the interaction of NEAT1 with miRNAs in the regulation of protein-coding genes in cancer. A better understanding of the NEAT1-miRNA interactions in cancer will help develop new diagnostic biomarkers and therapeutic approaches.

Abstract Omics-based tools were coupled with bioinformatics for a systeomics analysis of two biopharma cell types: Chinese hamster ovary (M-CHO and CHO-K1) and SP2/0. Exponential and stationary phase samples revealed more than 10,000 transcripts and 6000 proteins across these two manufacturing cell lines. A statistical comparison of transcriptomics and proteomics data identified downregulated genes involved in protein folding, protein synthesis and protein metabolism, including PPIA-cyclophilin A, HSPD1, and EIF3K, in M-CHO compared to SP2/0 while cell cycle and actin cytoskeleton genes were reduced in SP2/0. KEGG pathway comparisons revealed glycerolipids, glycosphingolipids, ABC transporters, calcium signaling, cell adhesion, and secretion pathways depleted in M-CHO while retinol metabolism was upregulated. KEGG and IPA also indicated apoptosis, RNA degradation, and proteosomes enriched in CHO stationary phase. Alternatively, gene ontology analysis revealed an underrepresentation in ion and potassium channel activities, membrane proteins, and secretory granules including Stxbpt2, Syt1, Syt9, and Cma1 proteins in M-CHO. Additional enrichment strategies involving ultracentrifugation, biotinylation, and hydrazide chemistry identified over 4000 potential CHO membrane and secretory proteins, yet many secretory and membrane proteins were still depleted. This systeomics pipeline has revealed bottlenecks and potential opportunities for cell line engineering in CHO and SP2/0 to improve their production capabilities.