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Abstract Objectives This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission. Methods We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks. Results Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse. Conclusion Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment.

Background: Pancreatic cancer is a serious, usually fatal disease and one of the most aggressive malignancies. Research into whether hormone replacement therapy (HRT) might protect against pancreatic cancer has yielded mixed results. This study aimed to investigate the potential association between HRT and the risk of pancreatic cancer in postmenopausal women. Methods: This population-based, retrospective study extracted data from the US National Inpatient Sample (NIS) 2008–2018. Hospitalized females aged ≥55 years were eligible for inclusion. Associations between HRT, other study variables, and pancreatic cancer diagnosis were determined using univariate and multivariable regression analyses. Results: After 1:4 matching by age, data of postmenopausal women with (n = 35,309) and without (n = 141,236) HRT were included in the analysis. The mean age was 73.4 years. Multivariable analyses showed that women with HRT had significantly decreased odds of pancreatic cancer (adjusted OR [aOR], 0.69, 95 % CI: 0.53–0.90). Compared to patients without HRT, patients with HRT in the 55-64-year-old group (aOR 0.48, 95 % CI: 0.32–0.74), 65-74-year-old group (aOR 0.49, 95 % CI: 0.34–0.71), non-hypertensive group (aOR 0.55, 95 % CI: 0.38–0.79), and non-hyperlipidemia group (aOR 0.59, 95 % CI: 0.42–0.82) had significantly decreased odds of pancreatic cancer. Conclusions: In US postmenopausal women, HRT is associated with a reduced risk of pancreatic cancer, especially those aged 55–74 year. Further study is needed to clarify the mechanisms underlying the associations.

Background: The Klebsiella oxytoca complex is an opportunistic pathogen that has been recently identified as an actual complex. However, the characteristics of each species remain largely unknown. We aimed to study the clinical prevalence, antimicrobial profiles, genetic differences, and interaction with the host of each species of this complex. Methods: One hundred and three clinical isolates of the K. oxytoca complex were collected from 33 hospitals belonging to 19 areas in China from 2020 to 2021. Species were identified using whole genome sequencing based on average nucleotide identity. Clinical infection characteristics of the species were analyzed. Comparative genomics and pan-genome analyses were performed on these isolates and an augmented dataset, including 622 assemblies from the National Center for Biotechnology Information. In vitro assays evaluating the adhesion ability of human respiratory epithelial cells and survivability against macrophages were performed on randomly selected isolates. Results: Klebsiella michiganensis (46.6%, 48/103) and K. oxytoca (35.92%, 37/103) were the major species of the complex causing human infections. K. michiganensis had a higher genomic diversity and larger pan-genome size than did K. oxytoca. K. michiganensis isolates with blaoxy-5 had a higher resistance rate to various antibiotics, antimicrobial gene carriage rate, adhesion ability to human respiratory epithelial cells, and survival rate against macrophages than isolates of other species. Conclusion: Our study revealed the genetic diversity of K. michiganensis and firstly identified the highly antimicrobial-resistant profile of K. michiganensis carrying blaoxy-5.

A kinetic-magnetohydrodynamic hybrid simulation is performed to investigate the Alfvén eigenmode (AE) and fishbone (FB)/FB-like (FBL) instabilities excited by neutral beam injection (NBI)-deposited energetic particles (EPs) in an HL-3 hybrid scenario. The hybrid scenario is characterized by a flat q -profile in the core due to off-axis electron cyclotron current drive (ECCD). A nonlinear simulation with multiple toroidal mode numbers indicates that the n = 2 β -induced AE (BAE) is excited initially in the linear stage and the n = 1 FB mode has the highest nonlinear saturation level. The EP distribution is modified only slightly in both real and velocity space from its initial state because of a narrow mode structure near the axis. Focusing on the n = 2 mode, sensitivity analysis indicates that mode activity and transition depend on the EP pressure, injected energy, and q -profile. The dominant unstable mode deviates from FBL mode to BAE by raising the EP pressure, and from BAE to toroidicity-induced AE by raising the. NBI injected energy. The mechanism is interpreted through a resonant condition and a corresponding transition threshold is observed. In addition, extending the flat shear region could increase the BAE width, resulting in stronger EP transport. Furthermore, a nonlinear simulation only considering n = 1 and n = 2 modes demonstrates that the low-energy EPs, as intermediates, gain energy from n = 2 mode, which subsequently transfers energy to the n = 1 mode through resonant interaction.

Abstract Background Interpregnancy interval (IPI) is associated with a variety of adverse maternal and infant outcomes. However, reports of its associations with early infant neurodevelopment are limited and the mechanisms of this association have not been elucidated. Maternal–fetal glucose metabolism has been shown to be associated with infant neurodevelopmental. The objective of this study was to determine whether this metabolism plays a role in the relationship between IPI and neurodevelopment. Methods This prospective birth cohort study included 2599 mother-infant pairs. The IPI was calculated by subtracting the gestational age of the current pregnancy from the interval at the end of the previous pregnancy. Neurodevelopmental outcomes at 12 months in infants were assessed by the Ages and Stages Questionnaire Edition 3 (ASQ-3). Maternal fasting venous blood was collected at 24–28 weeks and cord blood was collected at delivery. The association between IPI and neurodevelopment was determined by logistic regression. Mediation and sensitivity analyses were also conducted. Results In our cohort, 14.0% had an IPI

Abstract Background Reactive oxygen species (ROS) overproduction and excessive hypoxia play pivotal roles in the initiation and progression of ulcerative colitis (UC). Synergistic ROS scavenging and generating O2 could be a promising strategy for UC treatment. Methods Ceria nanozymes (PEG-CNPs) are fabricated using a modified reverse micelle method. We investigate hypoxia attenuating and ROS scavenging of PEG-CNPs in intestinal epithelial cells and RAW 264.7 macrophages and their effects on pro-inflammatory macrophages activation. Subsequently, we investigate the biodistribution, pharmacokinetic properties and long-term toxicity of PEG-CNPs in mice. PEG-CNPs are administered intravenously to mice with 2,4,6-trinitrobenzenesulfonic acid-induced colitis to test their colonic tissue targeting and assess their anti-inflammatory activity and mucosal healing properties in UC. Results PEG-CNPs exhibit multi-enzymatic activity that can scavenge ROS and generate O2, promote intestinal epithelial cell healing and inhibit pro-inflammatory macrophage activation, and have good biocompatibility. After intravenous administration of PEG-CNPs to colitis mice, they can enrich at the site of colonic inflammation, and reduce hypoxia-induced factor-1α expression in intestinal epithelial cells by scavenging ROS to generate O2, thus further promoting disrupted intestinal mucosal barrier restoration. Meanwhile, PEG-CNPs can effectively scavenge ROS in impaired colon tissues and relieve colonic macrophage hypoxia to suppress the pro-inflammatory macrophages activation, thereby preventing UC occurrence and development. Conclusion This study has provided a paradigm to utilize metallic nanozymes, and suggests that further materials engineering investigations could yield a facile method based on the pathological characteristics of UC for clinically managing UC. Graphical Abstract

Breast cancer (BRCA) is the most diagnosed cancer worldwide and is responsible for the highest cancer-associated mortality among women. It is evident that anoikis resistance contributes to tumour cell metastasis, and this is the primary cause of treatment failure for BRCA. However, anoikis-related gene (ARG) expression profiles and their prognostic value in BRCA remain unclear. In this study, a prognostic model of ARGs based on The Cancer Genome Atlas (TCGA) database was established using a least absolute shrinkage and selection operator analysis to evaluate the prognostic value of ARGs in BRCA. The risk factor graph demonstrated that the low-risk group had longer survival than the high-risk group, implying that the prognostic model had a good performance. We identified 11 ARGs that exhibited differential expression between the two risk groups in TCGA and Gene Expression Omnibus databases. Through Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes enrichment analyses, we revealed that the screened ARGs were associated with tumour progression and metastasis. In addition, a protein–protein interaction network showed potential interactions among these ARGs. Furthermore, gene set enrichment analysis suggested that the Notch and Wnt signalling pathways were overexpressed in the high-risk group, and gene set variation analysis revealed that 38 hallmark genes differed between the two groups. Moreover, Kaplan–Meier survival curves and receiver operating characteristic curves were used to identify five ARGs (CD24, KRT15, MIA, NDRG1, TP63), and quantitative polymerase chain reaction was employed to assess the differential expression of these ARGs. Univariate and multivariate Cox regression analyses were then performed for the key ARGs, with the best prediction of 3 year survival. In conclusion, ARGs might play a crucial role in tumour progression and serve as indicators of prognosis in BRCA.

By employing both nonlinear gyrokinetic simulation and analytical theory, we have investigated the effects of zonal (electromagnetic) fields on the energetic particle’s (EPs) drive of reversed-shear Alfvén eigenmodes (AEs) in tokamak plasmas. Contrary to the conventional expectation, simulations with zonal fields that are turned on and off in the EP dynamics while keeping the full nonlinear dynamics of the thermal plasma indicate that zonal fields further enhance the instability drive and thus lead to a higher saturation level. These puzzling simulation results can be understood analytically in terms of the general fishbone-like dispersion relation with the correspondingly different EP phase-space structures induced by the zonal fields. Analytical expressions for the zonal fields that are beat driven by the reversed-shear AEs are also derived, and shown to be in good agreement with the simulation results.

With the advancement in membrane technology, membrane separation technology has been found increasingly widespread applications in the pharmaceutical industry. It is utilized in drug separation and purification, wastewater treatment, and the recycling of wastewater resources. This study summarizes the application history of membrane technology in the pharmaceutical industry, presents practical engineering examples of its applications, analyzes the various types of membrane technologies employed in the pharmaceutical sector, and finally, highlights the application cases of renowned international and Chinese membrane technology companies in the pharmaceutical field.

The effects of plasma nonuniformity on zero frequency zonal structure (ZFZS) excitation by drift Alfvén wave (DAW) instabilities in toroidal plasmas are investigated using nonlinear gyrokinetic theory. The governing equations describing nonlinear interactions among ZFZSs and DAWs are derived, with the contribution of DAW self-beating and radial modulation accounted for on the same footing, and the physics picture contributing to both channels clarified. The obtained equations are then used to derive the nonlinear dispersion relation, which is then applied to investigate ZFZS generation in several scenarios. In particular, it is found that the condition for zonal flow excitation by the kinetic ballooning mode (KBM) could be sensitive to plasma parameters and a more detailed investigation is needed to understand KBM nonlinear saturation, crucial for bulk plasma transport in future reactors.

Abstract Background The precancerous disease of breast cancer is an inevitable stage in the tumorigenesis and development of breast neoplasms. Quercetin (Que) has shown great potential in breast cancer treatment by inhibiting cell proliferation and regulating T cell function. γδ T cells are a class of nontraditional T cells that have long attracted attention due to their potential in immunotherapy. In this study, we revealed the immunomodulatory function of Que through regulation of the JAK/STAT1 signaling pathway, which was followed by the synergistic killing of breast cancer cells. Methods In the experimental design, we first screened target genes with or without Que treatment, and we intersected the Que target with the disease target by functional enrichment analysis. Second, MCF-10A, MCF-10AT, MCF-7 and MDA-MB-231 breast cancer cell lines were treated with Que for 0 h, 24 h and 48 h. Then, we observed the expression of its subsets by coculturing Que and γδ T cells and coculturing Que and γδ T cells with breast tumor cells to investigate their synergistic killing effect on tumor cells. Finally, Western blotting was used to reveal the changes in proteins related to the JAK/STAT1 signaling pathway after Que treatment in MCF-10AT and MCF-7 cells for 48 h. Results The pathway affected by Que treatment was the JAK/STAT1 signaling pathway and was associated with precancerous breast cancer, as shown by network pharmacology analysis. Que induced apoptosis of MCF-10AT, MCF-7 and MDA-MB-231 cells in a time- and concentration-dependent manner (P

Abstract Background Phytophthora root rot (PRR) caused by Phytophthora sojae (P. sojae) is one of the most serious limitations to soybean production worldwide. The identification of resistance gene(s) and their incorporation into elite varieties is an effective approach for breeding to prevent soybean from being harmed by this disease. A valuable mapping population of 228 F8:11 recombinant inbred lines (RILs) derived from a cross of the resistant cultivar Guizao1 and the susceptible cultivar BRSMG68 and a high-density genetic linkage map with an average distance of 0.81 centimorgans (cM) between adjacent bin markers in this population were used to map and explore candidate gene(s). Results PRR resistance in Guizao1 was found to be controlled by a single Mendelian locus and was finely mapped to a 367.371-kb genomic region on chromosome 3 harbouring 19 genes, including 7 disease resistance (R)-like genes, in the reference Willliams 82 genome. Quantitative real-time PCR assays of possible candidate genes revealed that Glyma.03 g05300 was likely involved in PRR resistance. Conclusions These findings from the fine mapping of a novel Rps locus will serve as a basis for the cloning and transfer of resistance genes in soybean and the breeding of P. sojae-resistant soybean cultivars through marker-assisted selection.

When the drift kinetic effect of thermal ions is taken into account, a high-frequency fishbone-like mode (FLM) is found to be driven unstable by trapped thermal ions (TTIs) in tokamak plasmas, according to self-consistent magneto-hydrodynamic (MHD)-kinetic hybrid modeling utilizing the MARS-K code [Liu et al., Phys. Plasmas 15, 112503 (2008)] as well as an analytic theory. It is found that, similar to energetic particles, TTIs can also stabilize the internal kink mode, whereas the FLM is excited when the effective beta of TTIs exceeds a threshold value. The real frequency of the FLM is comparable to the bounce frequency of TTIs. The mode structure of the FLM can be significantly different from the conventional step-like function for the associated plasma radial displacement. This drift kinetic induced modification of the mode structure near the q = 1 surface is captured by non-perturbative MHD-kinetic hybrid computations with MARS-K. Furthermore, the FLM can only be triggered by TTIs at sufficiently high thermal temperatures. Both the FLM and the internal kink can be stabilized by sufficiently fast plasma toroidal rotation and parallel sound wave damping. These two conditions of high thermal temperature and (fast) flow stabilization, though making it challenging to observe the TTI-driven FLM in present day experiments, are favorable for the mode excitation in future reactor scale devices.

Adaptive changes in crops contribute to the diversity of agronomic traits, which directly or indirectly affect yield. The change of pubescence form from appressed to erect is a notable feature during soybean domestication. However, the biological significance and regulatory mechanism underlying this transformation remain largely unknown. Here, we identified a major-effect locus, PUBESCENCE FORM 1 (PF1), the upstream region of Mao1, that regulates pubescence form in soybean. The insertion of a Ty3/Gypsy retrotransposon in PF1 can recruit the transcription factor GAGA-binding protein to a GA-rich region, which up-regulates Mao1 expression, underpinning soybean pubescence evolution. Interestingly, the proportion of improved cultivars with erect pubescence increases gradually with increasing latitude, and erect-pubescence cultivars have a higher yield possibly through a higher photosynthetic rate and photosynthetic stability. These findings open an avenue for molecular breeding through either natural introgression or genome editing toward yield improvement and productivity. [ABSTRACT FROM AUTHOR]

Biodiversity is under threat due to human-induced changes in land use. While various aspects of biodiversity are increasingly studied in response to these changes, there is limited understanding of their effects on the structure and composition of bird communities in dryland regions. We examined the impacts of land use change on birds in the semi-arid area of the Longxi Loess Plateau by considering taxonomic diversity, functional diversity, and phylogenetic diversity. We analyzed both the α- and β-diversity of avian communities across different dimensions of diversity and calculated functional and phylogenetic structures using the net relatedness index. Our findings revealed that species richness was highest in farmland and abandoned farmland, while artificial mixed forests exhibited the highest number of unique species. Functional and phylogenetic α-diversity was greater in farmland and abandoned farmland when compared to the other four land use types. Moreover, the taxonomic diversity in artificial mixed forests, artificial Caragana korshinskii forests, and artificial Platycladus orientalis forests surpassed that in typical grasslands, but no differences were observed in functional and phylogenetic diversity. Regarding β-diversity, turnover patterns dominated multidimensional dissimilarity, with taxonomic turnover and total dissimilarity lower than their functional counterparts but higher than phylogenetic counterparts. Based on the present findings, we emphasize the long-term cessation of ongoing silvicultural initiatives to safeguard bird diversity in the semi-arid region of the Longxi Loess Plateau. This is crucial for narrowly distributed species such as Alectoris magna, as they face heightened vulnerability to losses.

The dispersion relation for high toroidal mode number n beta-induced Alfvén eigenmodes (BAEs) excited by magnetically trapped energetic ions generated with ion-cyclotron resonance heating via precessional resonance in low magnetic shear (s) tokamak plasma is investigated analytically and numerically. The dynamics of the energetic particles (EPs) is treated non-perturbatively and finite drift orbit width (FOW) effects are taken into account. It is found that, depending on the plasma parameters, the most unstable mode can be either the BAE mode or the energetic particle mode (EPM). Both modes can resonate with the trapped-particles' magnetic precessional drifts and become unstable. The mode frequencies and growth rates depend strongly on the EP parameters. FOW can stabilize high-n BAE modes by reducing the wave-particle interaction. Magnetic shear has an important effect on the growth rate of the modes. For BAE, the growth rate presents the trend of first increase and following decrease with the increase of s. The peak positions of the mode growth rate move towards small s with increasing EPs' density. Besides, the BAE growth rate increases with n for small kϑρLE, and decreases for kϑρLE > 0.34. On the other hand, the EPM becomes stable for sufficiently large s and enters into the second stability regime. [ABSTRACT FROM AUTHOR]

The two-dimensional global stability and mode structures of high-n beta-induced Alfvén eigenmodes excited by energetic ions in tokamaks are examined both analytically and numerically, employing the WKB-ballooning mode representation along with the generalized fishbone like dispersion relation. Here, n >> 1 is the toroidal mode number. Our results indicate that (i) the lowest radial bound state corresponds to the most unstable eigenmode, and (ii) the anti-Hermitian contributions due to wave-energetic particle resonance give rise to the twisting radial mode structures. [ABSTRACT FROM AUTHOR]

Studying the spatio-temporal niche partitioning among closely related sympatric species is essential for understanding their stable coexistence in animal communities. However, consideration of niche partitioning across multiple ecological dimensions is still poor for many sympatric pheasant species. Here, we studied temporal activity patterns and spatial distributions of the Blue Eared Pheasant (EP, Crossoptilon auritum) and Blood Pheasant (BP, Ithaginis cruentus) in the Qilian Mountains National Nature Reserve (QMNNR), Northwestern China, using 137 camera traps from August 2017 to August 2020. Kernel density estimation was applied to analyze diel activity patterns, and the Maxent model was applied to evaluate their suitable distributions and underlying habitat preferences. Eight Galliformes species were captured in 678 detection records with 485 records of EP and 106 records of BP over a total of 39,206 camera days. Their monthly activity frequencies demonstrate temporal partitioning but their diel activity patterns do not. Furthermore, 90.78% of BP distribution (2867.99 km2) overlaps with the distribution of EP (4355.86 km2) in the QMNNR. However, BP manifests a high dependence on forest habitats and shows larger Normalized Difference Vegetation Index (NDVI) values, while EP showed obvious avoidance of forest with NDVI greater than 0.75. Hence, differentiation in monthly activity patterns and partitioning in habitat preference might facilitate their coexistence in spatiotemporal dimensions. Conservation actions should give priority to highly overlapping areas in the center and east of the QMNNR and should strengthen forest landscape connectivity, as they provide irreplaceable habitats for these threatened and endemic Galliformes.

Using the theoretical framework of the generalized fishbone-like dispersion relation, the linear properties of beta-induced Alfven eigenmodes (BAEs) and energetic particle continuum modes (EPMs) excited by anisotropic slowing-down energetic ions are investigated analytically and numerically. The resonant contribution of energetic ions to the potential energy perturbation as well as fluid-like term describing the background plasma and adiabatic contribution of energetic ions are derived. For high-mode numbers, numerical results show smooth transition between the EP continuous spectrum and BAEs in the gap. EPMs and/or BAEs are destabilized by energetic ions, with real frequencies and growth rates strongly dependent on the energetic particle density and resonant frequency. [ABSTRACT FROM AUTHOR]

The stability of high torodial mode number (n) beta-induced Alfvén eigenmodes excited by precessional resonance of magnetically trapped energetic electrons in low magnetic-shear tokamak plasma is investigated. The dispersion relation of the energetic-electron beta-induced Alfvén eigenmodes (e-BAE) is derived and solved analytically and numerically. It is found that the contribution of the trapped energetic electrons to the e-BAE dispersion relation is limited to the ideal MHD structure of the BAE. Numerical results show that, for typical equilibrium parameters, the e-BAE can be destabilized by the energetic electrons, and the mode frequency is consistent with the experimental observation. Varying the background plasma parameters can lead to transitions between e-BAEs and energetic particle modes. Moreover, the dependence of the e-BAE frequencies and growth rates on energetic electron parameters shows that the growth rates monotonically increase(decrease) with the energetic electron density(the normalized energetic electron density scale length), and the frequencies are not much affected. The frequency and growth rate are sensitive to the energetic electron temperature, and there exists a maximum growth rate. [ABSTRACT FROM AUTHOR]

The toroidicity-induced Alfven eigenmode (TAE) excited by energetic (fast) ions was first simulated using the GTC code for HL-2A experiments. The simulation results indicate that the fraction of energetic ions is about 3% in the experiments. The critical density of energetic ions to excite the TAE mode is around 0.023, which is in good agreement with the theoretical expectation of 0.026. The real frequency of TAE with toroidal mode number n  =  3 is around 211 kHz and is inversely proportional to the square root of electron density, which is quantitatively in agreement with the experimental observation (Ding et al 2013 Nucl. Fusion53 043015). The frequency is in resonance with the summations of toroidal precession frequency and transit frequency of passing energetic ions, indicating that resonance with passing energetic ions is dominant for the excitation of the modes in the experiment. It is also checked by the phase space structures of (strength of energetic particle distribution function) that the TAE modes are mainly induced by passing energetic ions in HL-2A. The growth rates of TAE modes increase with fast ion density and its gradient. In addition, lower n TAE modes, such as n  =  1 can also be driven by energetic ions when off-axis heating with higher beam energy is employed in the experiment. The width of radial mode structures for lower n modes is usually wider than those for higher n modes. The perpendicular wave vector of the modes and Larmor radius of ions satisfy the relation . Finally, the polarization of the mode shows that the perturbed parallel electric field is much smaller than the electrostatic parallel electric field. [ABSTRACT FROM AUTHOR]