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Aplastic anemia (AA) is an autoimmune hematopoietic disease mediated by autoreactive T cells leading to bone marrow failure. However, the precise role of autoreactive T cells in the development of AA is not fully understood, hindering the advancement of therapeutic and diagnostic strategies. In this study, we conducted a single-cell transcriptome analysis of CD8+ T cells, conventional CD4+ T (CD4+ Tconv) cells, and Treg cells, to elucidate the potential disruption of T cell homeostasis in patients with AA. We identified changes in CD4+ Tconv cells, including loss of homeostasis in naïve and memory cells and increased differentiation potential in T helper type 1 (TH1), T helper type 2 (TH2), and T helper type 17 (TH17) cells. Additionally, we identified naïve and memory CD8+ T cells that were enforced into an effector state. CD127 is an ideal surface marker for assessing the immune state of CD8+ T cells，as identified by flow cytometry. Abnormal expression of TNFSF8 has been observed in AA and other autoimmune diseases. Flow cytometry analysis revealed that TNFRSF8 (CD30), a receptor for TNFSF8, was predominantly present in human Treg cells. Importantly, patients with AA have a decreased CD30+ Treg subset. RNA-sequencing analysis revealed, that the CD30+ Treg cells are characterized by high proliferation and a remarkable immunosuppressive phenotype. Taken, together, we propose that abnormal TNFSF8/TNFRSF8 signaling is involved in dysfunctional T cell immunity by increasing the destruction of CD30+ Treg cells.

Abstract Background Erythroid and myeloid differentiation disorders are commonly occurred in leukemia. Given that the relationship between erythroid and myeloid lineages is still unclear. To find the co-regulators in erythroid and myeloid differentiation might help to find new target for therapy of myeloid leukemia. In hematopoiesis, ALA (alpha lipoic acid) is reported to inhibit neutrophil lineage determination by targeting transcription factor ELK1 in granulocyte-monocyte progenitors via splicing factor SF3B1. However, further exploration is needed to determine whether ELK1 is a common regulatory factor for erythroid and myeloid differentiation. Methods In vitro culture of isolated CD34+, CMPs (common myeloid progenitors) and CD34+ CD371– HSPCs (hematopoietic stem progenitor cells) were performed to assay the differentiation potential of monocytes, neutrophils, and erythrocytes. Overexpression lentivirus of long isoform (L-ELK1) or the short isoform (S-ELK1) of ELK1 transduced CD34+ HSPCs were transplanted into NSG mice to assay the human lymphocyte and myeloid differentiation differences 3 months after transplantation. Knocking down of SRSF11, which was high expressed in CD371+GMPs (granulocyte-monocyte progenitors), upregulated by ALA and binding to ELK1-RNA splicing site, was performed to analyze the function in erythroid differentiation derived from CD34+ CD123mid CD38+ CD371– HPCs (hematopoietic progenitor cells). RNA sequencing of L-ELK1 and S-ELK1 overexpressed CD34+ CD123mid CD38+ CD371– HPCs were performed to assay the signals changed by ELK1. Results Here, we presented new evidence that ALA promoted erythroid differentiation by targeting the transcription factor ELK1 in CD34+ CD371– hematopoietic stem progenitor cells (HSPCs). Overexpression of either the long isoform (L-ELK1) or the short isoform (S-ELK1) of ELK1 inhibited erythroid-cell differentiation, but knockdown of ELK1 did not affect erythroid-cell differentiation. RNAseq analysis of CD34+ CD123mid CD38+ CD371– HPCs showed that L-ELK1 upregulated the expression of genes related to neutrophil activity, phosphorylation, and hypoxia signals, while S-ELK1 mainly regulated hypoxia-related signals. However, most of the genes that were upregulated by L-ELK1 were only moderately upregulated by S-ELK1, which might be due to a lack of serum response factor interaction and regulation domains in S-ELK1 compared to L-ELK1. In summary, the differentiation of neutrophils and erythrocytes might need to rely on the dose of L-ELK1 and S-ELK1 to achieve precise regulation via RNA splicing signals at early lineage commitment. Conclusions ALA and ELK1 are found to regulate both human granulopoiesis and erythropoiesis via RNA spliceosome, and ALA-ELK1 signal might be the target of human leukemia therapy.

Abstract Background Mesenchymal stem/stromal cells (MSCs) are of great therapeutic value due to their role in maintaining the function of hematopoietic stem/progenitor cells (HSPCs). MSCs derived from human pluripotent stem cells represent an ideal alternative because of their unlimited supply. However, the role of MSCs with neural crest origin derived from HPSCs on the maintenance of HSPCs has not been reported. Methods Flow cytometric analysis, RNA sequencing and differentiation ability were applied to detect the characteristics of stromal cells from 3D human brain organoids. Human umbilical cord blood CD34+ (UCB-CD34+) cells were cultured in different coculture conditions composed of stromal cells and umbilical cord MSCs (UC-MSCs) with or without a cytokine cocktail. The hematopoietic stroma capacity of stromal cells was tested in vitro with the LTC-IC assay and in vivo by cotransplantation of cord blood nucleated cells and stroma cells into immunodeficient mice. RNA and proteomic sequencing were used to detect the role of MSCs on HSPCs. Results The stromal cells, derived from both H1-hESCs and human induced pluripotent stem cells forebrain organoids, were capable of differentiating into the classical mesenchymal-derived cells (osteoblasts, chondrocytes, and adipocytes). These cells expressed MSC markers, thus named pluripotent stem cell-derived MSCs (pMSCs). The pMSCs showed neural crest origin with CD271 expression in the early stage. When human UCB-CD34+ HSPCs were cocultured on UC-MSCs or pMSCs, the latter resulted in robust expansion of UCB-CD34+ HSPCs in long-term culture and efficient maintenance of their transplantability. Comparison by RNA sequencing indicated that coculture of human UCB-CD34+ HSPCs with pMSCs provided an improved microenvironment for HSC maintenance. The pMSCs highly expressed the Wnt signaling inhibitors SFRP1 and SFRP2, indicating that they may help to modulate the cell cycle to promote the maintenance of UCB-CD34+ HSPCs by antagonizing Wnt activation. Conclusions A novel method for harvesting MSCs with neural crest origin from 3D human brain organoids under serum-free culture conditions was reported. We demonstrate that the pMSCs support human UCB-HSPC expansion in vitro in a long-term culture and the maintenance of their transplantable ability. RNA and proteomic sequencing indicated that pMSCs provided an improved microenvironment for HSC maintenance via mechanisms involving cell–cell contact and secreted factors and suppression of Wnt signaling. This represents a novel method for large-scale production of MSCs of neural crest origin and provides a potential approach for development of human hematopoietic stromal cell therapy for treatment of dyshematopoiesis.

In this work, a series of Fe-free AlCoaCrbNic (AlCo1.31Cr0.5Ni2.4, AlCo1.71Cr0.5Ni2.0, AlCo1.8Cr0.6Ni1.8, and AlCo1.16CrNi2.0 denoted as E1, E2, E3, and E4, respectively) medium-entropy alloys (MEAs) were designed though the mathematical model. Among the four MEAs, E2 and E3 exhibit uniform and typical eutectic structural characteristics, consisting of face-centered cubic (FCC) and ordered body-centered cubic (B2) phases, with ordered FCC (L12) nanoprecipitates uniformly distributed in the FCC matrix. The E4 alloy is composed of primary B2 phase and eutectic FCC + B2 phases, and the high-density Co- and Cr-rich BCC-structured spherical precipitates are distributed in the B2 phase. Importantly, the E1 alloy is characterized by a phase structure comprising both FCC and body-centered tetragonal (BCT) phases, a combination that is notably infrequent among high-entropy alloys. There are high-density twinning and stacking faults (SFs) in the BCT phase. All four alloys exhibit excellent compressive properties, with fracture strength surpassing 2000 MPa and compression ratio exceeding 30 %. The potentiodynamic polarization curves implied that the E4 MEA presented excellent corrosion resistance with the lowest corrosion current density of 4.05 × 10−7 A/cm2 and the lowest passive current density of 7.01 × 10−6 A/cm2 in 3.5 wt% NaCl solution. Moreover, the electrochemical impedance spectroscopy (EIS) test results also indicating that the E4 MEA has the best corrosion resistance among the four alloys because it has the highest electrode resistance (Rp = 171.76 × 103 Ω cm2). The ordered FCC/BCT phase structure in E1 alloy provides effective exploration for the development of new structured MEAs.

Hoxb5 exhibits preferential expression in hematopoietic stem cells (HSCs) and uniquely marks the long-term HSCs (LT-HSCs). Previous studies have demonstrated the remarkable capability of Hoxb5 to alter cell fates when enforced expression in blood progenitors, such as B cell progenitors and multipotent progenitors. Additionally, Hoxb5 deficiency does not hinder the generation of LT-HSCs. However, the specific impact of Hoxb5 deletion on LT-HSCs has remained unexplored. To address this, we developed a conditional Hoxb5 knockout-reporter mouse model, wherein Hoxb5 was knock out by the Vav-cre recombinase, and the endogenous Hoxb5 promoter drove the expression of the blue fluorescent protein (BFP). Our findings revealed that the primary recipients, who transplanted with HSCs indicating Hoxb5 deficiency by the presence of BFP (BFP-positive HSCs), exhibited comparable levels of donor chimerism and lineage chimerism to recipients transplanted with HSCs that spontaneously did not express Hoxb5 and thus lacked BFP expression (BFP-negative HSCs). However, during the secondary transplantation, recipients receiving total bone marrow (BM) from the primary recipients with BFP-positive HSCs showed significantly higher levels of donor chimerism and more robust multi-lineage chimerism compared to those receiving total BM from the primary recipients with BFP-negative HSCs. Our results indicate that deleting Hoxb5 in LT-HSCs transiently influences their lineage differentiation bias without compromising their long-term self-renewal capacity. These findings highlight the primary role of Hoxb5 in regulating lineage commitment decisions in LT-HSCs, while emphasizing that its presence is not indispensable for the maintenance of long-term self-renewal capacity.

Land surface temperature (LST) is a critical indicator of the earth’s surface environment, which has significant implications for research on the ecological environment and climate change. The influence of terrain on LST is complex due to its rugged and varied surface topography. The relationship between traditional terrain features and LST has been comprehensively discussed in the literature; however, terrain blockage has received less attention and could influence LST by hindering the redistribution of heat energy in mountain regions. Here, we investigate the influence of terrain blockage on the spatiotemporal variation in LST in mountain regions. We first propose a terrain feature framework to characterize the effect of terrain blockage from the perspective of heat energy redistribution and then adopt a random forest model to analyze the relationship between terrain blockage features and LST over a whole year. The results show that terrain blockage significantly influences the spatial heterogeneity of LST, which can be effectively simulated based on terrain blockage features, with a mean deviation of less than 0.15 K. Terrain blockage has a more pronounced influence on LST during the four months from June to September. This influence is also more evident during nighttime than daytime. Regarding LST in mountain regions, local terrain blockage features have a greater influence than global terrain blockage features. In spatial terms, the influence of terrain blockage on LST is uniform. Moreover, the diurnal variation in LST can also be effectively simulated based on terrain blockage. The contribution of this study lies in the finding that terrain blockage can influence the spatiotemporal variation in LST through the process of heat energy redistribution. The terrain blockage features proposed in this study may be useful for other studies of the ecological environment in mountain regions.

Negative Poisson's ratio (NPR) materials are a type of structural materials that show an atypical deformation response. In general, metal-based porous materials with NPR do not have good mechanical properties due to the substrate's limited yield strength and plasticity, as the NPR behavior is unlikely to play a continuous role in the deformation. AlCoCrFeNi2.1, a eutectic high-entropy alloy (EHEA) with high yield strength and high ductility was used to fabricate the NPR structures by laser powder bed fusion (LPBF) to enhance the structures mechanical properties and NPR behavior. Structures with four different sets of structural parameters were designed for this study. The microstructure and mechanical properties of AlCoCrFeNi2.1 EHEA, synthesized by LPBF were studied, and the strength and energy absorption effect of NPR porous structure materials were investigated by static and dynamic compression experiments. Research showed the large number of inter-phase interfaces provided by the nano-scale cellular eutectic microstructure effectively restrict dislocation movement, thereby enhancing the strength and toughness of this EHEA alloy, endowing it with superior impact resistance, fracture resistance, and mechanical energy absorption. The compressive performance and the mechanical energy absorption capacity of the 3D EHEA-based NPR porous structure strongly depend on the inclination angle Ф between the thick rod and the horizontal direction in the 2D single-body model design. The strength and energy absorption of the structure with a high inclination angle of 75° material are both higher than those of the structure with a low inclination angle of 45° by almost a factor of two.

Abstract Background Although most leptospirosis is mild, the severe form can cause multiple complications, with a fatality rate of over 50% even with ICU support. The clinical manifestations of leptospirosis vary depending on organs and tissues involved. Both cerebral artery and coronary artery can be damaged by leptospirosis. Although cerebral arteritis induced by leptospirosis has been reported, cerebral infarction caused by leptospirosis is rarely reported. Case presentation We report the case of a 79-year-old man admitted to intensive care unit (ICU) because of 3 days duration of fever, bloody sputum and dyspnea. Five days before he was admitted to hospital, he had harvested rice in flooded fields. After admission, leptospira interrogans DNA sequence was identified in bronchoalveolar lavage fluid (BALF) by next-generation sequencing (NGS). Microscopic agglutination test (MAT) showed the serum antibody of Mini serovars was 1,600 and Hebdomadis serovars was 800. On the eighth day of admission, the patient noted left hemiplegia. Cranial CT scan revealed low-density shadow in the right basal ganglia, so cerebral infarction was diagnosed. The patient’s condition rapidly deteriorated and he died on the eleventh day of admission despite penicillin treatment, invasive mechanical ventilation and continuous renal replacement support. Conclusion Neurologic leptospirosis manifested as cerebral occlusion, although rare, might be deadly and should not be ignored.

Abstract Background Previous Chinese studies focused on the prevalence and influential factors of hypertension; however, little is known about their self-care literacy and quality of life among the Bai older adults with hypertension. The purpose of this research was to explore the associations among health-promoting lifestyle, self-care agency, and health-related quality of life in Bai ethnic older patients with hypertension, as well as the related factors of hypertension self-care abilities. Methods A total of 472 Bai ethnic hypertension older adults aged 60 and above were enrolled in this study voluntarily from 5 rural communities of the Bai ethnic group. The Exercise of Self-Care Agency Scale (ESCAS) was employed to assess the Self-care ability of hypertension for the subjects, the Health-promoting lifestyle profile II(HPLP-II) was utilized to evaluate the health behavior, and MOS 36-Item Short Form Health Survey (SF-36) was chosen to assess the HRQOL for the studying population. All descriptive analyses, including demographic characteristics, socio-economic status, and clinical characteristics were stratified by Bai hypertensive elderly. Pearson correlation analysis model was used to examine the associations among health-promoting lifestyle, self-care agency, and health-related quality of life in Bai ethnic elderly with hypertension. Results The HPLP-II, ESCA, and of HRQOL levels of the subjects were low, and the mean HPLP and ESCA scores had no significant statistical variance among different age groups. Significant statistical differences were found in Bai elderly subjects in the domain of PF and PH as well as the overall score in SF-36(all P

In order to better identify the faults of gearbox under varying working conditions caused by noise and time-varying speed conditions， a fault identification method of gearbox under varying conditions is developed by combining DWAE and GRUNN， which could extract robust fault characteristics from noisy samples. The Adam and Dropout methods are used for training， and the softmax classifier is used to accurately identify the operating state of the gearbox under different working conditions. The results show that the six fault states of gears can be separated effectively when the model is used to identify gear faults， so as to meet the optimization function of gear state clustering. This model can extract the robust characteristic parameters of DWAE， and it can also use GRUNN to eliminate the gradient. When the number of training samples increased， the accuracy of waiting samples also improved significantly. When the number of samples is more than 200， stable accuracy could be obtained by testing the waiting samples， and the accuracy is the highest by dWAe-Grunn method. The model can maintain good accuracy under variable speed working conditions.

The microstructure and corrosion anisotropy of the Mg-5Li extruded sheet were investigated in this work. Three distinct samples cut from the normal plane (A), longitudinal plane (B), and cross-sectional plane (C) of the as-extruded sheet were prepared. The microstructure was analyzed using optical microscopy (OM), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The corrosion resistance and behaviors of the three samples in a 0.1 mol/L NaCl solution were evaluated by employing hydrogen evolution, mass loss testing, electrochemical assessments, and corrosion morphology analyses. The results revealed that sample A displayed a distinctive bimodal (0002) basal texture, along with clearly distinguishably larger grain sizes than the other samples. The effect of grain size and crystallographic orientation on the corrosion resistance was highlighted, indicating the pioneering corrosion resistance of sample A and the lowest corrosion resistance of sample C. Furthermore, all three samples exhibited the characteristic filiform corrosion during the initial stages of corrosion, progressing into the formation of corrosion pits, with sample C displaying pronounced susceptibility.

Huangjiu is rich in low-molecular-weight peptides and has an umami taste. In order for its umami peptides to be discovered, huangjiu was subjected to ultrafiltration, ethanol precipitation, and macroporous resin purification processes. The target fractions were gathered according to sensory evaluation. Subsequently, we used peptidomics to identify the sum of 4158 peptides in most umami fractions. Finally, six novel umami peptides (DTYNPR, TYNPR, SYNPR, RFRQGD, NFHHGD, and FHHGD) and five umami-enhancing peptides (TYNPR, SYNPR, NFHHGD, FHHGD, and TVDGPSH) were filtered via virtual screening, molecular docking, and sensory verification. Moreover, the structure–activity relationship was discussed using computational approaches. Docking analysis showed that all umami peptides tend to bind with T1R1 through hydrogen bonds and hydrophobic forces, which involve key residues HIS71, ASP147, ARG151, TYR220, SER276, and ALA302. The active site calculation revealed that the positions of the key umami residues D and R in the terminal may cause taste differences in identified peptides.

The challenge in using fully mechanized caving mining technology for thick coal seam mining is monitoring the mixing ratio of coal gangue during the top coal caving process. In this paper, we propose a passive wireless sensing system based on the second-order parity-time symmetric system operated around the exceptional point for the monitoring of coal gangue mixing, which has an LC resonance structure consisting of a spiral resonant coil and a parallel-plate capacitor at the wireless sensing end of the system. The parallel capacitor was designed as a sampling platform. When different proportions of the coal gangue mixture are placed on it, the capacitance value of the capacitor changes, changing the resonance frequency of the system. Our results indicated that the passive wireless sensing system could clearly distinguish the degree of mixing of the coal and gangue and has a higher sensitivity than the conventional system. The proposed system was compared with a mosquito resonant coil system of the same order, and the results indicated that the spiral resonant coil wireless sensing system has more significant advantages in the enhancement of sensitivity. This passive wireless sensing system provides an accurate method for the automatic identification of coal gangue in the top coal caving process; furthermore, it is inexpensive and highly operable.

Abstract Deficiency of P18 can significantly improve the self-renewal potential of hematopoietic stem cells (HSC) and the success of long-term engraftment. However, the effects of P18 overexpression, which is involved in the inhibitory effects of RUNX1b at the early stage of hematopoiesis, have not been examined in detail. In this study, we established inducible P18/hESC lines and monitored the effects of P18 overexpression on hematopoietic differentiation. Induction of P18 from day 0 (D0) dramatically decreased production of CD34highCD43− cells and derivative populations, but not that of CD34lowCD43− cells, changed the cell cycle status and apoptosis of KDR+ cells and downregulated the key hematopoietic genes at D4, which might cause the severe blockage of hematopoietic differentiation at the early stage. By contrast, induction of P18 from D10 dramatically increased production of classic hematopoietic populations and changed the cell cycle status and apoptosis of CD45+ cells at D14. These effects can be counteracted by inhibition of TGF-β or NF-κB signaling respectively. This is the first evidence that P18 promotes hematopoiesis, a rare property among cyclin-dependent kinase inhibitors (CKIs).

Abstract Improving resource utilization is an important goal of high-performance computing systems of supercomputing centers. To meet this goal, the job scheduler of high-performance computing systems often uses backfilling scheduling to fill short-time jobs into job gaps at the front of the queue. Backfilling scheduling needs to obtain the running time of the job. In the past, the job running time is usually given by users and often far exceeded the actual running time of the job, which leads to inaccurate backfilling and a waste of computing resources. In particular, when the predicted job running time is lower than the actual time, the damage caused to the utilization of the system’s computing resources becomes more serious. Therefore, the prediction accuracy of the job running time is crucial to the utilization of system resources. The use of machine learning methods can make more accurate predictions of the job running time. Aiming at the parallel application of aerodynamics, we propose a job running time prediction framework SU combining supervised and unsupervised learning and verify it on the real historical data of the high-performance computing systems of China Aerodynamics Research and Development Center (CARDC). The experimental results show that SU has a high prediction accuracy (80.46%) and a low underestimation rate (24.85%).

Effect of Zn on the corrosion behaviours of Mg-11Li-xZn (x = 0, 1, 3, 6; termed as L11, LZ111, LZ113, LZ116) alloys in 0.1 M NaCl solution has been investigated. The results reveal that corrosion resistance of four alloys increases following the order LZ116

The as-printed Al0.3CoCrFeNiCu high-entropy alloy (HEA) was fabricated from gas-atomized powders by selective laser melting (SLM) with the tailored printing parameters. The processing parameters, microstructural characteristics, mechanical properties and formed defects of the SLM-processed Al0.3CoCrFeNiCu HEA were examined in detail. The SLM-processed HEAs presented a simple disordered face centered cubic solid solution with columnar grains growing along the building direction and exhibiting a 〈001〉 preferred orientation. Dendritic-segregation, a common phenomenon occurring in as-cast counterparts was eliminated, thus providing a significant method to form a single-phase solid solution. The cellular structure in the columnar grains germinated perpendicular to the boundary of molten pools. In addition, dislocations induced by internal stress were observed. Accordingly, the SLM-processed Al0.3CoCrFeNiCu HEA exhibited superior microhardness and compressive strength. Finally, two types of defects were found in this SLM alloy, including irregular holes and hot cracks. The latter occurring on solid–liquid interface of molten pool were retarded by grain boundaries and then turned into muti-branches. Nevertheless, no crack-free sample could be prepared even though the printing parameters were optimized to achieve a high relative density of 99.08%, indicating this HEA was not suitable for SLM technology to prepare.

Granulocyte-monocyte progenitors (GMPs) differentiate into both neutrophils and monocytes. Recently, uni-potential neutrophil progenitors have been identified both in mice and humans using an array of surface markers. However, how human GMPs commit to neutrophil progenitors and the regulatory mechanisms of fate determination remain incompletely understood. In the present study, we established a human neutrophil deficiency model using the small molecule alpha-lipoic acid. Using this neutrophil deficiency model, we determined that the neutrophil progenitor commitment process from CD371+ CD115– GMPs defined by CD34 and CD15 and discovered that critical signals generated by RNA splicing and rRNA biogenesis regulate the process of early commitment for human early neutrophil progenitors derived from CD371+ CD115– GMPs. These processes were elucidated by single-cell RNA sequencing both in vitro and in vivo derived cells. Sequentially, we identified that the transcription factor ELK1 is essential for human neutrophil lineage commitment using the alpha-lipoic acid (ALA)-inducing neutrophil deficiency model. Finally, we also revealed differential roles for long-ELK1 and short-ELK1, balanced by SF3B1, in the commitment process of neutrophil progenitors. Taken together, we discovered a novel function of ALA in regulating neutrophil lineage specification and identified that the SF3B1-ELK axis regulates the commitment of human neutrophil progenitors from CD371+ CD115– GMPs.

Strontium (Sr) belongs to the same group in the periodic table as calcium (Ca). Sr level can serve as an index of rumen Ca absorption capacity; however, the effects of Sr on Ca2+ metabolism are unclear. This study aims to investigate the effect of Sr on Ca2+ metabolism in bovine rumen epithelial cells. The bovine rumen epithelial cells were isolated from the rumen of newborn Holstein male calves (n = 3, 1 day old, 38.0 ± 2.8 kg, fasting). The half maximal inhibitory concentration (IC50) of Sr-treated bovine rumen epithelial cells and cell cycle were used to establish the Sr treatment model. Transcriptomics, proteomics, and network pharmacology were conducted to investigate the core targets of Sr-mediated regulation of Ca2+ metabolism in bovine rumen epithelial cells. The data of transcriptomics and proteomics were analyzed using bioinformatic analysis (Gene Ontology and Kyoto Encyclopedia of genes/protein). Quantitative data were analyzed using one-way ANOVA in GraphPad Prism 8.4.3 and the Shapiro–Wilk test was used for the normality test. Results presented that the IC50 of Sr treatment bovine rumen epithelial cells for 24 h was 43.21 mmol/L, and Sr increased intracellular Ca2+ levels. Multi-omics results demonstrated the differential expression of 770 mRNAs and 2436 proteins after Sr treatment; network pharmacology and reverse transcriptase polymerase chain reaction (RT-PCR) revealed Adenosylhomocysteine hydrolase-like protein 2 (AHCYL2), Semaphoring 3A (SEMA3A), Parathyroid hormone-related protein (PTHLH), Transforming growth factor β2 (TGF-β2), and Cholesterol side-chain cleavage enzyme (CYP11A1) as potential targets for Sr-mediated Ca2+ metabolism regulation. Together these results will improve the current comprehension of the regulatory effect of Sr on Ca2+ metabolism and pave a theoretical basis for Sr application in bovine hypocalcemia.

Abstract Background Precise quantification of microRNA is challenging since circulating mRNA and rRNA in the blood are usually degraded. Therefore, it is necessary to identify specific biomarkers for ovarian cancer. This study aimed to investigate candidate circular RNAs (circRNAs) involved in the pathogenic process of ovarian cancer after inhibition of chromodomain helicase DNA binding protein 1-like (CHD1L) and the corresponding mechanism. Methods CHD1L mRNA-targeted siRNA was designed and induced a decreased level of CHD1L function in SK-OV-3 and OVCAR-3 cells observed via transwell and wound healing assays and assessment of epithelial–mesenchymal transition (EMT)-related protein expression by immunofluorescence (IF) and western blotting (WB). After decreasing the level of CHD1L, RNA-seq was conducted, and the circRNA expression profiles were obtained. cirRNAs were then selected and validated by PCR together with Sanger sequencing, fluorescent in situ hybridization (FISH), and reverse transcriptase-quantitative PCR (RT-qPCR). Selected circRNA function in vitro was adjusted via interference and overexpression and assessed via transwell assay, tube formation, and EMT-related protein assay by IF and WB; tumor formation in vivo was followed via hematoxylin and eosin (HE) staining and immunohistochemistry of EMT-related proteins. Based on the competing endogenous RNA prediction of circRNA targets, candidate miRNAs were found, and their downstream mRNAs targeted by the selected miRNA were identified and validated by luciferase assay. The functions of these selected miRNA and mRNA were then further investigated through transwell and WB assay of EMT-related proteins. Results CHD1L was significantly upregulated in ovarian cancer tissues and patients with higher expression of CHD1L had a shorter relapse-free survival (P

The layered van der Waals CuInP2S6 (CIPS) features interesting functional behaviors, including reversible ferroelectric polarization, Cu ion migration, negative capacitance effect, etc. Here, the CIPS flakes were exfoliated from the CVT-grown high-quality single crystals, which were fabricated into metal/CIPS/metal heterostructures by conventional photolithography. It was found that the CIPS flakes persisted in the dominant out-of-plane polarization and the minor in-plane polarization. Clear hysteresis current–voltage (I–V) loops, as well as the rectifying character, were revealed in metal/CIPS/metal heterostructures, indicating the potential application as a memory device. Additionally, the different metal electrode could significantly modulate the Schottky-like barrier at metal/CIPS interfaces, resulting in symmetric or asymmetric I–V loops. The complicated I–V curves may have originated from the voltage-induced Cu ion migration, reversible ferroelectric polarization, and carrier (ion) trapping/detrapping. This work may facilitate the metal electrode selection for the ferroelectric CIPS-based device application.

As a technology for micro-deformed solid-phase connection, transient liquid phase (TLP) diffusion bonding plays a key role in the manufacture of heating components of aero engines. However, the harmful brittle phase and high hardness limit the application of TLP diffusion bonding in nickel-based superalloys. In this paper, a new strategy in which a low-boron and high-titanium interlayer can restrain the brittle phase and reduce the hardness of the TLP-diffusion-bonded joint is proposed. With this strategy, the Ni3Al joint can achieve a high strength of 860.84 ± 26.9 MPa under conditions of 1250 °C, 6 h and 5 MPa. The microhardness results show that the average microhardness of the joint area is 420.33 ± 3.15 HV and is only 4.3% higher than that of the Ni3Al base material, which proves that this strategy can effectively inhibit the formation of the harmful brittle phase in the joint area. The results of EBSD show that 7.7% of the twin boundaries exist in the isothermal solidification zone, and only small amounts of secondary precipitates are observed at the grain boundaries in the joint, which indicates that twin boundaries may play a dominant role in crack initiation. This study provides a feasible avenue to suppress the brittle phase in TLP-diffusion-bonded joints.

Abstract Background The HOX genes are master regulators of embryogenesis that are also involved in hematopoiesis. HOXA9 belongs to a cluster of HOX genes that play extensively studied roles in hematopoiesis and leukemogenesis. Methods We established HOXA9-inducible human embryonic stem cells (HOXA9/hESCs) with normal pluripotency and potential for hematopoiesis, which could be used to analyze gene function with high accuracy. HOXA9/hESCs co-cultured with aorta–gonad–mesonephros-derived stromal cells (AGM-S3) were induced to overexpress HOXA9 with doxycycline (DOX) at various times after hematopoiesis started and then subjected to flow cytometry. Results Induction of HOXA9 from Day 4 (D4) or later notably promoted hematopoiesis and also increased the production of CD34+ cells and derived populations. The potential for myelogenesis was significantly elevated while the potential for erythrogenesis was significantly reduced. At D14, a significant promotion of S phase was observed in green fluorescent protein positive (GFP+) cells overexpressing HOXA9. NF-κB signaling was also up-regulated at D14 following induction of HOXA9 on D4. All of these effects could be counteracted by addition of an NF-κB inhibitor or siRNA against NFKB1 along with DOX. Conclusions Overexpression of HOXA9 starting at D4 or later during hematopoiesis significantly promoted hematopoiesis and the production of myeloid progenitors while reduced the production of erythroid progenitors, indicating that HOXA9 plays a key role in hematopoiesis and differentiation of hematopoietic lineages.

p15INK4b (cyclin-dependent kinase inhibitor 2B, CDKN2B, p15), a cyclin-dependent kinase inhibitor (CKI) belonging to the INK4 family, plays an important role in hematopoiesis. Its expression level was positively related to the blockage effects of RUNX1b at the early stage. Experiments using human embryonic stem cell (hESC) lines with inducible p15 expression suggested that p15 overexpression can significantly decrease the proportion of KDR+ cells in S and G2-M stages 4 days after induction from day 0. Moreover, p15 overexpression from the early stage can decrease production of CD34highCD43− cells and their derivative populations, but not CD34lowCD43− cells. These effects were weakened if induction was delayed and disappeared if induction started after day 6. All these effects were counteracted by inhibition of TGF-β signaling. TGF-β1 stimulation elicited similar effects as p15 overexpression. RUNX1 overexpression and activation of the TGF-β signaling pathway upregulate the expression of p15, which is partially responsible for blockade of hematopoiesis and relevant to a change in the cell cycle status. However, it is possible that other mechanisms are involved in the regulation of hematopoiesis.

The rarity and complexity of histology lead to the low diagnosis rate and high misdiagnosis rate of combined small cell lung cancer (C-SCLC). Nowadays, C-SCLC has no commonly recommended therapeutic regimen, mainly conforming to SCLC treatment. Here, we report a patient initially diagnosed as IIIA “lung squamous cell carcinoma” by a small specimen. Radical resection was achieved after neoadjuvant immunochemotherapy, and the final surgical pathology was C-SCLC containing three different histological components. Moreover, in the literature review, we explored the therapeutic effect of neoadjuvant immunotherapy in C-SCLC, expounded the therapeutic conflicts among heterogeneous components, and analyzed the pathology complexity at the tissue, cell, and molecule levels in-depth, including possible genetic characteristics, origin, and evolution by next-generation sequencing (NGS).

BackgroundLong-term excessive use of morphine leads to addictive diseases and affects cognitive function. Cognitive performance is associated with genetic characteristics.MiR-124 plays a critical regulatory role in neurogenesis, synaptic development, brain plasticity, and the use of addictive substances. As a scaffold protein, IQGAP1 affects learning and memory dose-dependent. However, the role of miR-124 and its target protein as potential addiction biomarkers and the impact on cognitive function have not been fully explored.MethodA total of 40 patients with morphine dependence and 40 cases of healthy people were recruited. We collected basic and clinical information about the two groups. The Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire-9(PHQ-9), Montreal Cognition Assessment Scale (MoCA), Pittsburgh Sleep Quality Index (PSQI) were used to assess the severity of depression, anxiety, depressive symptoms, cognitive dysfunction, and sleep quality.ResultsCompared to the control group, the morphine-dependent group had higher GAD-7, PHQ-9, PSQI scores, and more elevated miR-124 levels but lower MOCA scores and IQGAP1 levels. MiR-124, IQGAP1, the average intake last year were related to OASI scores.MiR-124, IQGAP1, PHQ-9 were associated with MOCA scores. In the multiple regression model, the levels of miR-124 and IQGAP1 were independent factors influencing the severity of morphine dependence. The level of miR-124 was an independent factor influencing the severity of cognitive impairment in patients with morphine dependence. In addition, the luciferase report confirmed that IQGAP1 mRNA is the direct target of miR-124.ConclusionMiR-124 and its target protein IQGAP1 are involved in the regulation of addiction and cognitive function in patients with morphine dependence.

In this study, we establish a mathematical rule for accelerating the prediction of low-cost Co-free AlCraFebNic FCC/B2-structured eutectic medium entropy alloys (EMEAs). The mathematical formulas are c ≥ 1.0, 4.38a + 4.28b + 3.97c ≈ 20.55, and c − a ˃ 1.0. With this rule, we successfully predict the AlCr1.18FeNi2.8 and AlCrFe1.46Ni2.5 eutectic alloys and verify their eutectic morphology by experiments. Both the AlCr1.18FeNi2.8 and AlCrFe1.46Ni2.5 EHEAs exhibit excellent compressive mechanical properties, with yield stress higher than 500 MPa, compressive fracture strength higher than 2450 MPa, and fracture strain > 40%, which can be attributed to their unique lamellar microstructure. Moreover, both alloys exhibit good corrosion resistance in 3.5 wt.% NaCl solution. Among them, the AlCr1.18FeNi2.8 EHEA exhibits better corrosion resistance due to the higher content of the FCC phase.

The corrosion behavior of α-Mg and β-Li phases in a duplex Mg–8Li (wt. %) alloy is investigated in this work. The results reveal that the Mg–8Li alloy has a eutectic structure and is composed of equivalent α-Mg and β-Li phases. Corrosion preferentially propagates toward the α-Mg phase following initial corrosion at the α-Mg/β-Li interface. The surface of the β-Li phase is eventually destroyed after a longer immersion time. Meanwhile, the β-Li phase shows intergranular corrosion, while transgranular corrosion filaments can be seen in the α-Mg phase. Unlike the α-Mg phase, the local potential distribution on the polarization plot of the β-Li phase indicates that the surface film provides excellent protection, which is also confirmed by the results of Raman spectroscopy.

Background: The composition of the gut microbiota is associated with the response to immunotherapy for different cancers. However, the majority of previous studies have focused on a single cancer and a single immune checkpoint inhibitor. Here, we investigated the relationship between the gut microbiota and the clinical response to anti-programmed cell death protein 1 (PD-1) immunotherapy in patients with advanced cancers. Method: In this comprehensive study, 16S rRNA sequencing was performed on the gut microbiota of pre-immunotherapy and post-immunotherapy, of 72 advanced cancer patients in China. Results: At the phylum level, Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria were the main components of the microbiota in the 72 advanced cancer patients. At the genus level, Bacteroides and Prevotella were the dominant microbiota among these 72 patients. The PD_whole_tree, Chao1, Observed_species and Shannon indices of R.0 and R.T were higher than those of NR.0 and NR.T. The results of LEfSe showed that Archaea, Lentisphaerae, Victivallaceae, Victivallales, Lentisphaeria, Methanobacteriaceae, Methanobacteria, Euryarchaeota, Methanobrevibacter, and Methanobacteriales were significantly enriched in the response group before immunotherapy (R.0), and the Clostridiaceae was significantly enriched in the non-response group before immunotherapy (NR.0) (p < 0.05). Lachnospiraceae and Thermus were significantly enriched in the response group after immunotherapy (R.T), and Leuconostoc was significantly enriched in R.0 (p < 0.05). ROC analysis showed that the microbiota of R.T (AUC = 0.70) had obvious diagnostic value in differentiating Chinese cancer patients based on their response to immunotherapy. Conclusions: We demonstrated that the gut microbiota was associated with the clinical response to anti-PD-1 immunotherapy in cancer patients. Taxonomic signatures enriched in responders were effective biomarkers to predict the clinical response. Our findings provide a new strategy to improve the efficiency of responses to immunotherapy among cancer patients.

Encroachment of woody plants has negative effects on grass species and seriously challenging livestock production and pastoral livelihood in semi-arid savanna. The effect of thinning and season on grass species composition and biomass was investigated in lowland grazing area for three seasons. The study consisted of 15 plots (each 50 m × 50 m), thinned to differing intensities. The plots were located next to each other on a homogeneous area of 3.8 ha. Five thinning intensities (0, 25, 50, 75, and 100%) were allocated randomly to the plots and replicated three times. The 0% plot was left unthinned referred to as the control plot. The remaining plots were thinned to the equivalents of 25, 50, 75, and 100% of the tree density of that of the control plot. A two-way analysis of variance and Tukey Honest Significant Differences tests were used to compare responses of grass species. Ordination of variables was carried out by multivariate technique using correspondence analysis to explore the similarity relationship of plots, seasons and species. The differences in species composition and biomass in the control and the thinned plots were significant (p < 0.05). Higher grass species composition and biomass were documented in thinned plots than in the control plot. Species abundance in thinned plots ranged from 11 to 12, while that of the 0% plot was six species. Grass biomass (Kg ha-1) varied from 2,688.4 ± 736.8 to 5,035.8 ± 743.9 across thinned plots, whereas in the control plot the yield was 885.8 ± 369.1. The result showed that grass species composition and biomass increased with the increasing intensity of thinning. Grass values appeared to be optimum at the heavy intensity of thinning woody plants. Seasons were also significant with the highest values recorded in the rainy season. Rainfall played an important role by interacting with thinning and influenced total grass values. Overall, thinning that combined improved soil moisture negatively influenced woody cover and enhanced grass species composition and biomass production. Thinning of bushes to the 75% of tree density would sustain the original savanna and maximize forage production for grazers.

Summary: GATA2 is essential for the endothelial-to-hematopoietic transition (EHT) and generation of hematopoietic stem cells (HSCs). It is poorly understood how GATA2 controls the development of human pluripotent stem cell (hPSC)-derived HS-like cells. Here, using human embryonic stem cells (hESCs) in which GATA2 overexpression was induced by doxycycline (Dox), we elucidated the dual functions of GATA2 in definitive hematopoiesis before and after the emergence of CD34+CD45+CD90+CD38– HS-like cells. Specifically, GATA2 promoted expansion of hemogenic precursors via the EHT and then helped to maintain HS-like cells in a quiescent state by regulating cell cycle. RNA sequencing showed that hPSC-derived HS-like cells were very similar to human fetal liver-derived HSCs. Our findings will help to elucidate the mechanism that controls the early stages of human definitive hematopoiesis and may help to develop a strategy to generate hPSC-derived HSCs. : In this article, Professor Ma and his colleagues at IBT of CAMS & PUMC show that overexpression of GATA2 promoted expansion of hemogenic precursors through EHT, and thereafter enhanced the maintenance of HS-like cells in dormancy by cell-cycle arrest. hESC-derived HS-like cells were highly similar to human fetal liver (FL) HSCs. Keywords: GATA2, hESCs, hematopoietic stem cells, definitive hematopoiesis, cell cycle

Myosin heavy chain 9 (MYH9) gene encodes a protein named non-muscle heavy chain IIA (NMHC IIA), interacting with actin and participating in various biological processes. Mutations in MYH9 cause an array of autosomal dominant disorders, known as MYH9-related diseases (MYH9-RD). However, the role of MYH9 in normal hematopoiesis remains largely unexplored. By using Mx1-cre Myh9 conditional knockout mice, we established an inducible system to precisely inactivate Myh9 function in hematopoietic cells in vivo. The results showed that deletion of Myh9 led to severe defects in hematopoiesis, characterized by pancytopenia, drastic decreases of hematopoietic stem/progenitor cells (HSPC), and bone marrow failure, causing early lethality in mice. The defect in hematopoiesis caused by Myh9 ablation is cell autonomous. In addition, Myh9 deletion impairs HSPC repopulation capacity and increases apoptosis. RNA sequencing results revealed significant alterations in the expression of genes related to HSC self-renewal and maintenance, while multiple signal pathways were also involved, including genes for HSC and myeloid cell development, intrinsic apoptosis, targets of mTOR signaling, and maturity of hematopoietic cells. Our present study suggests an essential role for Myh9 in the survival and maintenance of HSPC in normal hematopoiesis.

To meet the demand for the separation of specific substances, the construction of porous composite aerogels with a high specific surface area and a strong adsorption capacity is still a challenge. Herein, a sodium alginate/bentonite composite aerogel was efficiently prepared through supercritical fluid drying. The aerogel’s volume shrank less during supercritical drying, maintaining its original three-dimensional mesh structure. The resulting aerogel had a large specific surface area (445 m2/g), a low density (0.059 g/cm3), and a large pore volume (3.617 cm3/g). Due to the fixation and intercalation effects, bentonite was uniformly dispersed in the sodium alginate matrixes. The adsorption of lysozyme by the composite aerogel was evaluated, and the results showed that the optimal adsorption pH was 8 when the pH of the phosphoric acid buffer solution was between pH = 5 and 8.5. The time for adsorption to reach equilibrium was 8 h. The adsorption capacity increased with the increase in bentonite content, and when the initial concentration of lysozyme was from 0.2 to 1.2 g/L, the adsorption capacity first increased and then stabilized, and the maximum adsorption amount was 697 mg/g. The adsorption behavior was simulated in the isothermal region, and the linear correlation coefficient of Langmuir isothermal adsorption fitting was found to be 0.997. Thus, this composite aerogel with strong adsorption capacity can be used as a good alternative to enzymatic adsorbents or immobilized materials.

Abstract Background The value of postoperative radiotherapy in tubular breast carcinoma patients under 65 years is uncertain. Methods Data on patients with estrogen receptor positive T1N0M0 tubular breast carcinoma who were younger than 65 years and who received breast-conserving surgery between 2000 and 2013 were retrieved from the Surveillance, Epidemiology and End Results database. Demographic, clinicopathologic features, and receipt of postoperative radiotherapy were analyzed to investigate effects on survival. Results Data from 2442 patients were analyzed, of whom 2020 (82.7%) received postoperative radiotherapy and 422 (17.3%) did not. The number of patients treated with or without postoperative radiotherapy showed no differences during the study period (p = 0.184). Radiotherapy was more likely to be administered in patients with well differentiated tumors. Multivariate Cox analysis showed that postoperative radiotherapy delivery was significantly correlated with better breast cancer-specific survival (BCSS) (hazard ratio [HR] 0.297, 95% confidence interval [CI] 0.105–0.836, p = 0.022) and overall survival (OS) (HR 0.656, 95% CI 0.441–0.978, p = 0.038). Ten 10-year BCSS was 99.3% in patients who received postoperative radiotherapy and 98.1% in those who did not (p = 0.020), and 10-year OS was 93.4 and 91.0%, respectively (p = 0.029). Postoperative radiotherapy increased BCSS and OS in the subgroups of age

BackgroundAs an emerging therapy with a promising efficacy, immunotherapy has been widely used in the treatment of solid tumors and hematologic malignancies. This clinical study compares the efficacy of tislelizumab, a domestic immune checkpoint inhibitor (ICI), to that of sorafenib when used as a first-line therapeutic option in hepatocellular carcinoma (HCC), and the concurrence of HCC and non-Hodgkin’s lymphoma (NHL) is rare, especially in the treatment of ICIs.Case presentationA 61-year-old patient presenting with primary HCC and indolent B-cell lymphoma had a partial clinical response to tislelizumab for his primary HCC. Besides, we described a phenomenon of pseudo-progression and delayed diagnosis of his lymphoma during a long course of treatment.ConclusionTislelizumab, an immunotherapeutic option with a favorable efficacy and toxicity, can be used to manage double primary tumors. However, studies should aim to elucidate the probable mechanisms of this therapy. Pseudo-progression and separation remission make the treatment of double primary tumors even more challenging, which calls for additional caution in patients undergoing immunotherapy to avoid misdiagnosis and, therefore, begin early appropriate interventions.

Objectives To identify root causes of preventable adverse drug events (pADEs) contributing to hospital admission; to develop key messages which identify actions patients/families and healthcare providers can take to prevent common pADEs found; to develop a surveillance learning system for the community.Methods Cross-sectional observational study; 120 patients and families, 61 associated healthcare providers were interviewed then root cause analysis was performed to develop key learning messages and an electronic reporting tool was designed. Most common pADE-related medical conditions and their root causes and most common pADE root causes of entire cohort are reported.Results Most common pADE-related medical conditions: chronic obstructive pulmonary disease/asthma (13.3%), bleeding (12.5%), hypotension (12%), heart failure (10%), acute kidney injury (5%) and pneumonia (5%). Most common root causes were: providers not confirming that the patient/family understands information given (29.2%), can identify how a medication helps them/have their concerns addressed (16.7%), can identify if a medication is working (14.1%) or causing a side effect (23.3%); can enact medication changes (7.5%); absence of a sick day management plan (12.5%), and other action plans to help patients respond to changes in their clinical status (10.8%); providers not assessing medication use and monitoring competency (19.2%). Ten key learning messages were developed and a pADE surveillance learning system was implemented.Conclusions To prevent pADEs, providers need to confirm that patients/families understand information given, how a medication helps them, how to recognise and respond to side effects, how to enact medication changes and follow action plans; providers should assess patient’s/families’ medication use and monitoring competency.

Abstract Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) plays a critical role in Alzheimer’s disease (AD) pathogenesis. This study aimed to investigate the relationship between microRNA-149 (miR-149) and BACE1, and evaluate the clinical significance and biological function of miR-149 in AD progression. Bioinformatics analysis and a luciferase reporter assay were used to confirm the interaction between miR-149 and BACE1. Expression of miR-149 and BACE1 was estimated using quantitative real-time PCR. The clinical significance of miR-149 in AD diagnosis and severity determination was evaluated using ROC analysis. The effect of miR-149 on Aβ accumulation and neuronal viability was analyzed in Aβ-treated SH-SY5Y cells. miR-149 was found directly binding the 3’-UTR of BACE1 and was negatively correlated with BACE1 in AD patients and cell model. Serum miR-149 expression was downregulated in AD patients and served as a potential diagnostic biomarker. The overexpression of miR-149 in Aβ-treated SH-SY5Y cells resulted in inhibited Aβ accumulation and enhanced neuronal viability. This study demonstrated that serum miR-149 is decreased in AD patients and serves as a candidate diagnostic biomarker, and that the overexpression of miR-149 may suppress Aβ accumulation and promote neuronal viability by targeting BACE1 in AD model cells.

Hematopoietic stem cells (HSC) are dominantly quiescent under homeostasis, which is a key mechanism of maintaining the HSC pool for life-long hematopoiesis. Dormant HSC are poised to be immediately activated in certain conditions and can return to quiescence after homeostasis has been regained. At present, the molecular networks of regulating the threshold of HSC dormancy, if existing, remain largely unknown. Here, we show that deletion of Nupr1, a gene preferentially expressed in HSC, activated quiescent HSC under homeostasis, which conferred a competitive engraftment advantage for these HSC without compromising their stemness or multi-lineage differentiation capacity in serial transplantation settings. Following an expansion protocol, the Nupr1-/- HSC proliferated more robustly than their wild-type counterparts in vitro. Nupr1 inhibits the expression of p53 and rescue of this inhibition offsets the engraftment advantage. Our data reveal a new role for Nupr1 as a regulator of HSC quiescence, which provides insights for accelerating the engraftment efficacy of HSC transplantation by targeting the HSC quiescence-controlling network.

Obtaining T cells by reprogramming is one of the major goals in regenerative medicine. Here, we describe a protocol for generating functional T cells from Hoxb5-expressing pro/pre-B cells in vivo. This protocol includes the construction of Hoxb5 recombinant plasmids, retroviral packaging, isolation and viral transduction of pro/pre-B cells, cell transplantation, and phenotypic analysis of induced T cells. The procedure is reproducible and straightforward, providing an approach for generating induced T cells for translational research. Keywords: Hoxb5, Retrovirus, Pro/pre-B cells, T cells

DC collection network offers an attractive alternative to AC network for photovoltaic, as it avoids the charging current issues and reduces the size and weight. Variable voltage gain DC/DC converters play an important role in DC collection network. Two topologies suitable for photovoltaic DC collection are studied. Boost and LLC converter and active clamp isolated full-bridge boost converter are two converters with high and variable voltage conversion ratio suitable for the photovoltaic system. This work investigates the two converters comprehensively. The topologies are analysed so as to summarise and compare the characteristic of the converters. Soft switching condition is compared to help extend the zero voltage switching range. Voltage and current stress of the two converters are calculated. Loss comparison is made with the theoretical analysis. Advantages and disadvantages are summarised to get a deep insight into their application field.

Introduction: It is still controversial whether post-mastectomy radiotherapy (PMRT) is necessary for women with T1-2 N1mic ER-positive HER2-negative breast cancer. The 21-gene recurrence score (RS) assay has been validated in T1-2 N1 breast cancer to be prognostic of locoregional recurrence (LRR) and overall survival (OS). This study aims to evaluate the predict value of 21-gene recurrence score assay for the benefit of PMRT in T1-2 N1mic ER-positive HER2-negative breast cancer.Methods: A population-based cohort study was performed on women with T1-2 N1mic ER-positive HER2-negative breast cancer who underwent mastectomy and were evaluated using the 21-gene RS in the Surveillance, Epidemiology, and End Results (SEER) registry between 2004 and 2015. Clinical characteristics as well as OS and breast cancer-specific survival (BCSS) were compared between patients with and without PMRT in patients with a Low-, Intermediate-, and High-RS. Multivariate COX regression analysis was performed to investigate if the 21-gene RS assay could predict benefit of PMRT in this group of breast cancer patients.Results: A total of 1571 patients met the criteria of our study and were enrolled, including 970 patients in the Low-Risk group (score 30). In the High-Risk group, there were more patients with age ≥50 (87.0 vs. 64.3%, P = 0.040) and received chemotherapy with a borderline significance (91.3 vs. 72.9%, P = 0.066) in the PMRT subgroup than in the no PMRT subgroup. In all three groups, OS was comparable between the PMRT subgroup and the no PMRT subgroup. Furthermore, multivariate analysis did not show any OS benefit for PMRT based on the 21-gene recurrence score.Conclusion: This study showed that the 21-gene RS assay was not able to predict the benefit of PMRT for OS in women with T1-2 N1mic ER-positive HER2-negative breast cancer. However, further prospective larger sample-size trials are warranted to determine if a benefit exists.

Introduction: We conducted a non-inferiority analysis using real-world data to compare the survival outcomes of stage T1-2N2-3 (tumor size ≤5 cm and four or more node metastases) breast cancer after breast-conserving surgery (BCS) and mastectomy (MAST).Methods: The study included patients with stage T1-2N2-3 invasive breast carcinoma from the Surveillance, Epidemiology, and End Results program, who underwent BCS or MAST between 2004 and 2012, along with both radiotherapy and chemotherapy. The statistical analyses used included the chi-squared test, multivariate Cox proportional hazards models, and propensity score matching (PSM).Results: The study population comprised 13,263 patients, including 4,787 (36.1%) and 8,476 (63.9%) patients who were treated with BCS and MAST, respectively. Patients with younger age and advanced stage were more likely to have received MAST. The probability of receiving MAST increased over the years, while the probability of BCS decreased (p < 0.001). The 5-year breast cancer-specific survival (BCSS) was 86.1% in the BCS cohort compared to 83.1% in the MAST cohort (p < 0.001). Surgical procedure was an independent prognostic factor for BCSS. Patients who received MAST had worse BCSS than those treated with BCS (hazard ratio = 1.179, 95% confidence interval = 1.087–1.278, p < 0.001). These results remained significant after stratification by age, tumor grade, T stage, N stage as well as marital status. Similar results were obtained after PSM.Conclusions: BCS resulted in noninferior outcome than MAST in patients with T1-2/N2-3 invasive breast carcinoma. BCS may therefore be an optimal treatment option when both treatment options are feasible and appropriate.

Introduction: To assess the role of the 21-gene recurrence score (RS) assay on decision-making of postoperative radiotherapy (RT) following breast-conserving surgery (BCS) in elderly women with early-stage breast cancer.Methods: The 21-gene RS for elderly (≥65 years) women with stage T1–2N0M0 estrogen receptor-positive breast cancer who underwent BCS from 2004 to 2015 was obtained from the Surveillance, Epidemiology, and End Results program. We estimated the association of 21-gene RS and adjuvant RT related to breast cancer-specific survival (BCSS) using propensity score matching (PSM).Results: We identified 18,456 patients, of which 15,326 (83.0%) received postoperative RT. Of identified patients, 58.9, 34.0, and 7.1% of patients had a low-, intermediate-, and high-risk RS, respectively. Receipt of postoperative RT was not related to the year of diagnosis according to the 21-gene RS groups. Multivariate analysis suggested that receipt of postoperative RT was an independent predictor of better BCSS before (hazard ratio [HR] 0.587, 95% confidence interval [CI] 0.426–0.809, P = 0.001) and after (HR 0.613, 95%CI 0.390–0.963, P = 0.034) PSM. However, subgroups analyses indicated that receipt of postoperative RT was related to better BCSS in women with intermediate-risk RS before (HR 0.467, 95%CI 0.283–0.772, P = 0.003) and after (HR 0.389, 95%CI 0.179–0.846, P = 0.017) PSM, but not in women with low- and high-risk RS groups before and after PSM.Conclusions: Although causation cannot be implied, adjuvant RT in elderly women was associated with a greater effect size in patients with an intermediate-risk RS.

Background: The clinical value of 21-gene recurrence score (RS) in various breast cancer histologic subtypes is not well established.Aims: To assess the distribution and outcomes of the 21-gene RS among various T1-T2N0 estrogen receptor-positive breast cancer histologic subtypes.Methods: Using the Surveillance, Epidemiology and End Results database, we investigated the distribution and outcomes of the 21-gene RS among various breast cancer histologic subtypes between 2004 and 2015. The histologic subtypes with 200 or more cases were further analyzed.Results: We identified 83,665 patients including eight histologic subtypes. The most common subtype was invasive ductal carcinoma not otherwise specified (IDC NOS) (77.9%), followed by lobular carcinoma NOS, mixed infiltrating duct and lobular carcinoma (IDC-L), mucinous adenocarcinoma, tubular adenocarcinoma, micropapillary ductal carcinoma, cribriform carcinoma NOS, and intraductal papillary adenocarcinoma with invasion with 10.8, 7.7, 2.1, 0.6, 0.3, 0.2, and 0.2%, respectively. The 5-years breast cancer specific survival (BCSS) was 98.8, 98.8, 98.9, 99.6, 100, 100, 100, and 100%, respectively (P = 0.011). Patients with IDC NOS (8.9%), micropapillary ductal carcinoma (8.8%), and intraductal papillary adenocarcinoma with invasion (8.2%) had significantly higher percentage of high-risk RS compared to other histologic subtypes (1.0–3.8%) (P < 0.001). The mean RS was higher in IDC NOS, lobular carcinoma NOS, and IDC-L compared to other subtypes. In multivariate analysis, 21-gene RS was the independent prognostic factor in patients with IDC NOS (P < 0.001), lobular carcinoma NOS (P < 0.001), and IDC-L (P < 0.001), patients with a higher RS was associated with poor BCSS.Conclusion: Our results demonstrate that there is a significant difference in distribution of 21-gene RS in T1-T2N0 estrogen receptor-positive breast cancer with different histologic subtypes. Long-term studies with larger series are needed to confirm the role of the 21-gene RS array in prognosis assessment and chemotherapy decision-making in special histologic subtypes with favorable prognosis.

Most of the existing chaotic particle swarm optimization algorithms use logistic chaotic mapping. However, the chaotic sequence which is generated by the logistic chaotic mapping is not uniform enough. As a solution to this defect, this paper introduces the Anderson chaotic mapping to the chaotic particle swarm optimization, using it to initialize the position and velocity of the particle swarm. It self-adaptively controls the portion of particles to undergo chaos update through a change of the fitness variance. The numerical simulation results show that the convergence and global searching capability of the modified algorithm have been improved with the introduction of this mapping and it can efficiently avoid premature convergence.

To overcome the under injection in water-flooding treatment of low permeability reservoir, this paper introduces the grey correlation degree method to the dynamic connectivity between injection and production wells. First, it is proved that Deng’s model, focusing on the proximity between sequences, does not apply to the dynamic connectivity between injection and production wells. Then, the author built a new correlation degree model which reflects the similarity between sequences, and analysed the properties of the model. The new model can reflect the negative correlation between sequences, and outperforms Deng’s model in the simulation. Then, the results of Deng’s model and the new model were compared based on the parameter sequences of the real injection and production wells. The results show that the results of the new model are consistent with the actual production situation. Compared with Deng’s model, the new model reflect the exact difference and connectivity variation between wells.

The stability of topological close-packed (TCP) phases were found to be well related to the average value of the d-orbital energy level \( \overline{Md} \) for most reported high entropy alloys (HEAs). Excluding some HEAs that contain high levels of the elements aluminum and vanadium, the results of this study indicated that the TCP phases form at \( \overline{Md} \) > 1.09. This criterion, as a semi-empirical method, can play a key role in designing and preparing HEAs with high amounts of transitional elements.