Higher disease burden and lower utilization in mongolian with breast cancer: a 9-year retrospective cohort study of 18.19 million adults in China.

BACKGROUND: Whether health inequalities of disease burden and medical utilization exist by ethnicity in Asian breast cancer (BC) patients remains unclear. We aim to measure ethnic disparities in disease burden and utilization among Mongolian and Han female breast cancer patients in China. MATERIALS AND METHODS: Based on data extracted from Inner Mongolia Regional Health Information Platform, a retrospective cohort study was established during 2012-2021. Disease burden including incidence, 5-year prevalence, mortality, survival rate, and medical cost were analyzed and compared between Han and Mongolian patients. RESULTS: A total of 34,878 female patients (mean [SD] age, 52.34 [10.93] years) were included among 18.19 million Chinese, and 4,315 [12.03%] participants were Mongolian. Age-standardized rates of incidence are 32.68 (95% CI: 20.39-44.98) per 100,000. Higher age-specific incidence and 5-year prevalence were observed in Mongolian than in Han. The cost of breast cancer annually per capita was significantly lower for Mongolian than Han in FBC ($1,948.43 [590.11-4 776.42] vs. $2,227.35 [686.65-5,929.59], P<0.001). Mongolian females showed higher all-cause mortality (30.92, [95% CI: 28.15-33.89] vs. 27.78, [95% CI: 26.77-28.83] per 1,000, P=0.036) and breast cancer-specific mortality (18.78, [95% CI: 16.64-21.13] vs. 15.22, [95% CI: 14.47-16.00] per 1,000, P=0.002) than Han females. After adjusting covariates, Mongolian were associated with increased all-cause mortality (HR, 1.21, [95% CI, 1.09-1.34]; P<0.001) and breast cancer-specific mortality (HR, 1.31, [95% CI, 1.14-1.49]; P<0.001). CONCLUSION: The findings of this cohort study highlight a higher level of disease burden with unmet medical demand in Mongolian patients, suggesting that more practical efforts should be made for the minority. Further research is needed to explore the concrete mechanisms of the disparities as well as eliminate health disproportion.

Plant-LncPipe: a computational pipeline providing significant improvement in plant lncRNA identification.

Long non-coding RNAs (lncRNAs) play essential roles in various biological processes, such as chromatin remodeling, post-transcriptional regulation, and epigenetic modifications. Despite their critical functions in regulating plant growth, root development, and seed dormancy, the identification of plant lncRNAs remains a challenge due to the scarcity of specific and extensively tested identification methods. Most mainstream machine learning-based methods used for plant lncRNA identification were initially developed using human or other animal datasets, and their accuracy and effectiveness in predicting plant lncRNAs have not been fully evaluated or exploited. To overcome this limitation, we retrained several models, including CPAT, PLEK, and LncFinder, using plant datasets and compared their performance with mainstream lncRNA prediction tools such as CPC2, CNCI, RNAplonc, and LncADeep. Retraining these models significantly improved their performance, and two of the retrained models, LncFinder-plant and CPAT-plant, alongside their ensemble, emerged as the most suitable tools for plant lncRNA identification. This underscores the importance of model retraining in tackling the challenges associated with plant lncRNA identification. Finally, we developed a pipeline (Plant-LncPipe) that incorporates an ensemble of the two best-performing models and covers the entire data analysis process, including reads mapping, transcript assembly, lncRNA identification, classification, and origin, for the efficient identification of lncRNAs in plants. The pipeline, Plant-LncPipe, is available at: https://github.com/xuechantian/Plant-LncRNA-pipline.

Termination of convulsion seizures by destabilizing and perturbing seizure memory engrams.

Epileptogenesis, arising from alterations in synaptic strength, shares mechanistic and phenotypic parallels with memory formation. However, direct evidence supporting the existence of seizure memory remains scarce. Leveraging a conditioned seizure memory (CSM) paradigm, we found that CSM enabled the environmental cue to trigger seizure repetitively, and activating cue-responding engram cells could generate CSM artificially. Moreover, cue exposure initiated an analogous process of memory reconsolidation driven by mammalian target of rapamycin-brain-derived neurotrophic factor signaling. Pharmacological targeting of the mammalian target of rapamycin pathway within a limited time window reduced seizures in animals and interictal epileptiform discharges in patients with refractory seizures. Our findings reveal a causal link between seizure memory engrams and seizures, which leads us to a deeper understanding of epileptogenesis and points to a promising direction for epilepsy treatment.

Guasha improves knee osteoarthritis by inhibiting chondrocyte apoptosis and regulating expression of autophagy-related genes and proteins in rats. / åˆ®ç—§å¯¹è†å ³èŠ‚éª¨å ³èŠ‚ç‚Žå¤§é¼ è½¯éª¨ç»†èƒžå‡‹äº¡åŠè‡ªå™¬çš„å½±å“.

OBJECTIVES: To observe the effect of Guasha on inflammation factors, apoptosis and autophagy in the cartilage tissue of knee joint in rats with knee osteoarthritis (KOA), so as to explore its mechanisms underlying improvement of KOA. METHODS: A total of 51 male SD rats were randomized into three groups：blank control, KOA model and Guasha (n= 17 in each group) . The rats in the blank control group received intra-articular injection of 0.9% NaCl solution in the right knee joint. The KOA model was established by intraarticular injection of glutamate sodium iodoacetic acid in the right knee joint. For rats of the Guasha group, Guasha (at a frequency of 1 time/s, and an applied pressure of 0.3-0.5 kgf) was applied to "Yanglingquan" (GB34) and "Xuehai"(SP10) areas of the right leg, once every other day, for 7 consecutive sessions. The circumference of the right knee was measured, The histopathological changes of right knee cartilage were observed after H.E. staining. The contents of inflammatory factors interleukin (IL)-1ß and tumor necrosis factor (TNF)-α in the right knee articular cartilage tissue were assayed using ELISA. The expression levels of autophagy-related key molecule Beclin-1 (homologous series of yeast Atg6), light chain protease complication 3 type II/I (LC3II/LC3 I), ubiquitin binding factor 62 (P62) and cysteine aspartate protease-3 (Caspase-3) mRNAs and proteins of the right knee articular cartilage tissue were measured using real-time fluorescent quantitative PCR and Western blot, separately. The apoptosis of chondrocytes was assayed using TUNEL staining, and the immunoactivity of LC3 determined using immunofluorescence staining. RESULTS: After modeling, the right knee circumfe-rence of the model and Guasha groups was significantly increased compared with the blank control group (P<0.01), and after the intervention, the knee circumference of the Guasha group was markedly decreased in comparison with that of the model group (P<0.05). Results of H.E. staining showed obvious degeneration and defects in the cartilage tissue, necrosis of a large number of chondrocytes, fibrous hyperplasia, accompanied by inflammatory cell infiltration, osteoclast increase, fibroplasia and bone trabecular destruction in the model group, which was relatively milder in the Guasha group. Compared with the blank control group, the expression of Beclin-1 and LC3 mRNAs and proteins, and LC immunofluorescence intensity in the right knee articular cartilage tissue were significantly down-regulated (P<0.01, P<0.001), whereas the expression of P62 and Caspase-3 mRNAs and proteins, the apoptosis rate, contents of IL-1ß and TNF-α in the right knee articular cartilage tissue considerably increased (P<0.01, P<0.001) in the model group. In contrast to the model group, the Guasha group had an apparent increase in the expression levels of Beclin-1 and LC3 mRNAs and proteins and LC immunofluorescence intensity in the right knee articular cartilage tissue (P<0.05), and a pronounced decrease in the expression of P62 and Caspase-3 mRNAs and proteins, the apoptosis rate, and contents of IL-1ß and TNF-α in the right knee articular cartilage tissue (P<0.05, P<0.01). CONCLUSIONS: Guasha stimulation of GB34 and SP10 can improve joint cartilage damage in KOA rats, which may be associated with its functions in inhibiting the excessive release of inflammatory factors and apoptosis, possibly by down-regulating the expression of P62 and Caspase-3 mRNAs and proteins and up-regulating the expression of Beclin-1 and LC3 mRNAs and proteins, and by promoting autophagy of chondrocytes.

Neuropeptides as Potential Biomarkers in Vascular Dementia.

Neuropeptides are endogenous active substances within the central and peripheral nervous systems that play important roles in a wide range of brain functions, including metabolism, food intake, social behavior, reproduction, learning, sleep, and wakefulness. This article reviews recent advances in the involvement of neuropeptides in vascular dementia. Neuropeptides are present in the brain as chemical signals and last for nearly 50 years. Peptide hormones are chemical signals of the endocrine system. Thus, neuropeptides are the most diverse class of signaling molecules in the brain, involving the genomes of many mammals, encoding neuropeptide precursors and many bioactive neuropeptides. Here the aim is to describe the recent advances in classical neuropeptides, as well as putative neuropeptides from other families, in the control of or as diagnostic tools for vascular dementia. Additionally, its molecular mechanisms are described to explore new avenues of treatment and early diagnosis, as there is increasing evidence that dysregulation of vascular processes is associated with different pathological conditions.

Mechanistic insights into diversified photoluminescence behaviours of BF2 complexes of N-benzoyl 2-aminobenzothiazoles.

Many BF2 complexes of heteroaromatics are well known for their dual-state emission (DSE) properties. However, AIE and ACQ effects have also been observed in certain cases. To date, no rational explanations have been proposed for these uncommon photoluminescence (PL) behaviours. The current research prepared four BF2 complexes of N-benzoyl 2-aminobenzothiazoles with diversified photoluminescence (PL) properties as model compounds and utilized quantum chemical calculation tools to address this issue. Theoretical calculations revealed that the electron-donating groups (EDGs) at the para-position of the exocyclic phenyl ring exert significant influence on their ground-state electronic structures and vertical excitation features. Potential energy curve (PEC) analysis showed that the exocyclic phenyl ring and NMe2 could not function as effective rotors due to elevated energy barriers. Only the NPh2 of BFBB-3 could spontaneously rotate ∼60° to induce the formation of an emissive twisted intramolecular charge transfer (TICT) state. The two-channel model involving both vibronic relaxation and S0/S1 surface crossing revealed that the drastic narrowing of the S1/S0 energy gap in the region approaching minimun energy conical intersection (MECI) led to the generation of a dark state in BFBB-1. The small energy barrier to access the dark-state region makes the resulting fast internal conversion a competitive channel for excited-state deactivation. In contrast, the presence of EDGs in BFBB-2 and 4 inhibits this pathway, thereby resulting in intense fluorescence emissions in solution. In addition, crystallographic analysis illustrated that the F atoms perpendicular to the polyheterocycle promoted a slipped face-to-face packing mode and enhanced intermolecular interactions. The efficiencies of their solid-state emissions are mainly affected by the degree of π-π overlaps.

Community stability of free-living and particle-attached bacteria in a subtropical reservoir with salinity fluctuations over 3 years.

Changes in salinity have a profound influence on ecological services and functions of inland freshwater ecosystems, as well as on the shaping of microbial communities. Bacterioplankton, generally classified into free-living (FL) and particle-attached (PA) forms, are main components of freshwater ecosystems and play key functional roles for biogeochemical cycling and ecological stability. However, there is limited knowledge about the responses of community stability of both FL and PA bacteria to salinity fluctuations. Here, we systematically explored changes in community stability of both forms of bacteria based on high-frequency sampling in a shallow urban reservoir (Xinglinwan Reservoir) in subtropical China for 3 years. Our results indicated that (1) salinity was the strongest environmental factor determining FL and PA bacterial community compositions - rising salinity increased the compositional stability of both bacterial communities but decreased their α-diversity. (2) The community stability of PA bacteria was significantly higher than that of FL at high salinity level with low salinity variance scenarios, while the opposite was found for FL bacteria, i.e., their stability was higher than PA bacteria at low salinity level with high variance scenarios. (3) Both bacterial traits (e.g., bacterial genome size and interaction strength of rare taxa) and precipitation-induced factors (e.g., changes in salinity and particle) likely contributed collectively to differences in community stability of FL and PA bacteria under different salinity scenarios. Our study provides additional scientific basis for ecological management, protection and restoration of urban reservoirs under changing climatic and environmental conditions.

Genus Paeonia monoterpene glycosides: A systematic review on their pharmacological activities and molecular mechanisms.

BACKGROUND: Genus Paeonia, which is the main source of Traditional Chinese Medicine (TCM) Paeoniae Radix Rubra (Chishao in Chinese), Paeoniae Radix Alba (Baishao in Chinese) and Moutan Cortex (Mudanpi in Chinese), is rich in active pharmaceutical ingredient such as monoterpenoid glycosides (MPGs). MPGs from Paeonia have extensive pharmacological effects, but the pharmacological effects and molecular mechanisms of MPGs has not been comprehensively reviewed. PURPOSE: MPGs compounds are one of the main chemical components of the genus Paeonia, with a wide variety of compounds and strong pharmacological activities, and the structure of the mother nucleus-pinane skeleton is similar to that of a cage. The purpose of this review is to summarize the pharmacological activity and mechanism of action of MPGs from 2012 to 2023, providing reference direction for the development and utilization of Paeonia resources and preclinical research. METHODS: Keywords and phrases are widely used in database searches, such as PubMed, Web of Science, Google Scholar and X-Mol to search for citations related to the new compounds, extensive pharmacological research and molecular mechanisms of MPGs compounds of genus Paeonia. RESULTS: Modern research confirms that MPGs are the main compounds in Paeonia that exert pharmacological effects. MPGs with extensive pharmacological characteristics are mainly concentrated in two categories: paeoniflorin derivatives and albiflflorin derivatives among MPGs, which contains 32 compounds. Among them, 5 components including paeoniflorin, albiflorin, oxypaeoniflorin, 6'-O-galloylpaeoniflorin and paeoniflorigenone have been extensively studied, while the other 28 components have only been confirmed to have a certain degree of anti-inflammatory and anticomplementary effects. Studies of pharmacological effects are widely involved in nervous system, endocrine system, digestive system, immune system, etc., and some studies have identified clear mechanisms. MPGs exert pharmacological activity through multilateral mechanisms, including anti-inflammatory, antioxidant, inhibition of cell apoptosis, regulation of brain gut axis, regulation of gut microbiota and downregulation of mitochondrial apoptosis, etc. CONCLUSION: This systematic review delved into the pharmacological effects and related molecular mechanisms of MPGs. However, there are still some compounds in MPGs whose pharmacological effects and pharmacological mechanisms have not been clarified. In addition, extensive clinical randomized trials are needed to verify the efficacy and dosage of MPGs.

A new phenolic compound from Persicaria capitata.

Persicaria capitata was a frequently used Hmong medicinal flora in China. In this study, one new phenolic compound, capitaone A (1) together with 20 known ones, were isolated from the whole herb of P. capitata. Among them, 7 components (4, 9-11, 15-16, 20-21) were discovered from P. capitata for the first time. Their chemical structures were elucidated on the basis of extensive NMR and MS spectrum. Furthermore, three compounds (15, 20, 21) displayed remarkable cytotoxic activities against two human cancer cell lines (A549 and HepG2).

Dynamics of nutrients, sensory quality and microbial communities and their interactions during co-fermentation of pineapple by-products and whey protein.

In this study, a new fermented food was developed using pineapple by-products and whey protein (2.6%) as raw materials through the co-fermentation of autochthonous lactic acid bacteria and yeast. To better understand the fermentation mechanism and the impact of microorganisms on the entire fermentation system, we tracked the changes in carbohydrate and amino acid profiles, organoleptic quality and microbial community during the fermentation process. Compared with unfermented samples, dietary fiber and free amino acids increased significantly as fermentation proceeded. The fermented samples were significantly lower in astringency and bitterness and significantly higher in sourness, umami and richness. The fermented products were richer in volatile compounds with floral, cheesy, fruity and other flavors. Relevant analyses showed that the core microbial community was highly correlated with the quality attributes of the fermented products. Microorganisms such as Lactococcus, Weissella, Hanseniaspora, Saccharomyces and Lachancea contributed significantly to the fermented products.

Role of estrogen in sex differences in memory, emotion and neuropsychiatric disorders.

Estrogen regulates a wide range of neuronal functions in the brain, such as dendritic spine formation, remodeling of synaptic plasticity, cognition, neurotransmission, and neurodevelopment. Estrogen interacts with intracellular estrogen receptors (ERs) and membrane-bound ERs to produce its effect via genomic and non-genomic pathways. Any alterations in these pathways affect the number, size, and shape of dendritic spines in neurons associated with psychiatric diseases. Increasing evidence suggests that estrogen fluctuation causes changes in dendritic spine density, morphology, and synapse numbers of excitatory and inhibitory neurons differently in males and females. In this review, we discuss the role of estrogen hormone in rodents and humans based on sex differences. First, we explain estrogen role in learning and memory and show that a high estrogen level alleviates the deficits in learning and memory. Secondly, we point out that estrogen produces a striking difference in emotional memories in men and women, which leads them to display sex-specific differences in underlying neuronal signaling. Lastly, we discuss that fluctuations in estrogen levels in men and women are related to neuropsychiatric disorders, including schizophrenia, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BPD), major depressive disorder (MDD), substance use disorder (SUD), and anxiety disorders.

High-quality genome assembly enables prediction of allele-specific gene expression in hybrid poplar.

Poplar (Populus) is a well-established model system for tree genomics and molecular breeding, and hybrid poplar is widely used in forest plantations. However, distinguishing its diploid homologous chromosomes is difficult, complicating advanced functional studies on specific alleles. In this study, we applied a trio-binning design and PacBio High-Fidelity long-read sequencing to obtain haplotype-phased telomere-to-telomere genome assemblies for the two parents of the well-studied F1 hybrid "84K" (Populus alba × P. tremula var. glandulosa). Almost all chromosomes, including the telomeres and centromeres, were completely assembled for each haplotype subgenome apart from two small gaps on one chromosome. By incorporating information from these haplotype assemblies and extensive RNA-seq data, we analyzed gene expression patterns between the two subgenomes and alleles. Transcription bias at the subgenome level was not uncovered, but extensive expression differences were detected between alleles. We developed machine-learning (ML) models to predict allele-specific expression (ASE) with high accuracy and identified underlying genome features most highly influencing ASE. One of our models with 15 predictor variables achieved 77% accuracy on the training set and 74% accuracy on the testing set. ML models identified gene body CHG methylation, sequence divergence, and transposon occupancy both upstream and downstream of alleles as important factors for ASE. Our haplotype-phased genome assemblies and ML strategy highlight an avenue for functional studies in Populus and provide additional tools for studying ASE and heterosis in hybrids.

Differential sedimentary evolution of typical aulacogens of Meso-Neoproterozoic in North China craton.

Many countries and regions in the world have obtained industrial oil flow in the Meso-Neoproterozoic sedimentary strata and formed commercial exploitation in recent years. The development horizon of high-quality source rocks in the Proterozoic in North China can be compared with the international, indicating that the Meso-Neoproterozoic in North China has great exploration potential. The sedimentary characteristics of typical aulacogen in multiple cratons in the Meso-Neoproterozoic North China Craton are compared and studied by using field outcrop data, drilling data and analysis and test data, aiming to provide sedimentary support for the prediction of oil and gas distribution and evaluation of exploration field in the Meso-Neoproterozoic in this area. The results show that there are four sedimentary systems in the study area, including Marine clastic rock sedimentary system, Marine carbonate sedimentary system, Marine-continental transitional facies sedimentary system and glacial sedimentary system. They are divided into seven sedimentary facies types: barrier coastal facies, non-barrier coast facies, shallow shelf facies, carbonate platform facies, reef facies, fan delta facies and glacial facies, and further divided into 15 subfacies and 21 microfacies. On this basis, the Meso-Neoproterozoic sedimentary filling sequences of two typical aulacogens, Yanliao and Xiong 'er, in the study area are clarified, showing that the formation time of each sedimentary filling sequence stage of different aulacogens is different, and the rock characteristics, lithology combination, lithologic structure, contact relationship, vertical sequence and sedimentary facies assemblage of the same sedimentary filling sequence stage are obviously different. The filling characteristics of the two aulacogens completely record the geological events related to the breakup of the Colombian supercontinent.

Glutathione S-transferase activity facilitates rice tolerance to the barnyard grass root exudate DIMBOA.

BACKGROUND: In paddy fields, the noxious weed barnyard grass secretes 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (DIMBOA) to interfere with rice growth. Rice is unable to synthesize DIMBOA. Rice cultivars with high or low levels of allelopathy may respond differently to DIMBOA. RESULTS: In this study, we found that low concentrations of DIMBOA (≤ 0.06 mM) promoted seedling growth in allelopathic rice PI312777, while DIMBOA (≤ 0.08 mM) had no significant influence on the nonallelopathic rice Lemont. DIMBOA treatment caused changes in the expression of a large number of glutathione S-transferase (GST) proteins, which resulting in enrichment of the glutathione metabolic pathway. This pathway facilitates plant detoxification of heterologous substances. The basal levels of GST activity in Lemont were significantly higher than those in PI312777, while GST activity in PI312777 was slightly induced by increasing DIMBOA concentrations. Overexpression of GST genes (Os09g0367700 and Os01g0949800) in these two cultivars enhanced rice resistance to DIMBOA. CONCLUSIONS: Taken together, our results indicated that different rice accessions with different levels of allelopathy have variable tolerance to DIMBOA. Lemont had higher GST activity, which helped it tolerate DIMBOA, while PI312777 had lower GST activity that was more inducible. The enhancement of GST expression facilitates rice tolerance to DIMBOA toxins from barnyard grass root exudates.

Waste to Wealth: Dynamics and metabolic profiles of the conversion of jackfruit flake into value-added products by different fermentation methods.

Thus far, little is known about whether jackfruit flake, a byproduct of jackfruit, can be used as a fermentation substrate to obtain value-added products through microbial fermentation. Here, jackfruit flake puree was fermented by three different ways: spontaneous fermentation (JF), inoculated with LAB (JFL), inoculated co-fermentation with LAB and yeast (JFC). In contrast to JF, the total polyphenol and flavonoid content and syndrome-associated enzyme inhibition are significantly increased in JFC at the end of fermentation. Electronic tongue analysis revealed that the JFC was significantly lower in astringency and higher in bitterness. 41 volatile compounds were identified during fermentation by HS-SPME-GC-MS, and JFC was richer in honey, rose, and fruity flavors. A total of 290 compounds were screened for discriminative pre- and post-fermentation differential metabolites by non-target metabolomics analysis. These results provide a potential reference for the conversion of jackfruit waste into functional products using fermentation.

A novel integrated Urban flood risk assessment approach coupling GeoDetector-Dematel and clustering method.

Urban flood risk assessment plays a crucial role in disaster prevention and mitigation. A scientifically accurate assessment and risk stratification method are of paramount importance for effective flood risk management. This study aims to propose a comprehensive urban flood risk assessment approach by coupling GeoDetector-Dematel and Clustering Method to enhance the accuracy of urban flood risk evaluation. Based on simulation results from hydraulic models and existing literature, the research established a set of urban flood risk assessment indicators comprising 10 metrics across two dimensions: hazard factors and vulnerability factors, among which vulnerability factors include exposure factors, sensitivity factors, and adaptability factors. Subsequently, the research introduced the GeoDetector-Dematel method to determine indicator weights, significantly enhancing the scientific rigor and precision of weight calculation. Finally, the research employed the K-means clustering method to risk zonation, providing a more scientifically rational depiction of the spatial distribution of urban flood risks. This novel comprehensive urban flood risk assessment method was applied in the Fangzhuang area of Beijing. The results demonstrated that this integrated approach effectively enhances the accuracy of urban flood risk assessment. In conclusion, this research offers a new methodology for urban flood risk assessment and contributes to decision-making in disaster prevention and control measures.

Molecular characterization, antibacterial and immunoregulatory activities of liver-expressed antimicrobial peptide 2 in black rockfish, Sebastes schlegelii.

LEAP2 (liver expression antimicrobial peptide 2), is an antimicrobial peptide widely found in vertebrates and mainly expressed in liver. LEAP2 plays a vital role in host innate immunity. In teleosts, a number of LEAP2 homologs have been reported, but their in vivo effects on host defense are still limited. In this study, a LEAP2 homolog (SsLEAP2) was identified from black rockfish, Sebastes schlegelii, and its structure, expression as well as biological functions were analyzed. The results showed that the open reading frame of SsLEAP2 is 300 bp, with a 5'- untranslated region (UTR) of 375 bp and a 3' - UTR of 238 bp. The deduced amino acid sequence of SsLEAP2 shares the highest overall identity (96.97%) with LEAP2 of Sebastes umbrosus. SsLEAP2 possesses conserved LEAP2 features, including a signal peptide sequence, a prodomain and a mature peptide, in which four well-conserved cysteines formed two intrachain disulphide domain. The expression of SsLEAP2 was highest in liver and could be induced by experimental infection with Listonella anguillarum, Edwardsiealla piscicida and Rock bream iridovirus C1 (RBIV-C1). Recombinant SsLEAP2 (rSsLEAP2) purified from Escherichia coli was able to bind with various Gram-positive and Gram-negative bacteria. Further analysis showed that rSsLEAP2 could enhance the respiratory burst activity, and induce the expression of immune genes including interleukin 1-ß (IL-1ß) and serum amyloid A (SAA) in macrophages; additionally, rSsLEAP2 could also promote the proliferation and chemotactic of peripheral blood lymphocytes (PBLs). In vivo experiments indicated that overexpression of SsLEAP2 could inhibit bacterial infection, and increase the expression level of immune genes including IL-1ß, tumor necrosis factor ligand superfamily member 13B (TNF13B) and haptoglobin (HP); conversely, knock down of SsLEAP2 promoted bacterial infection and decreased the expression level of above genes. Taken together, these results suggest that SsLEAP2 is a novel LEAP2 homolog that possesses apparent antibacterial activity and immunoregulatory property, thus plays a critical role in host defense against pathogens invasion.

Out-of-plane pressure and electron doping inducing phase and magnetic transitions in GeC/CrS2/GeC van der Waals heterostructure.

Out-of-plane pressure and electron doping can affect interlayer interactions in van der Waals materials, modifying their crystal structure and physical and chemical properties. In this study, we used magnetic monolayer 1T/1T'-CrS2 and high symmetry 2D-honeycomb material GeC to construct a GeC/CrS2/GeC triple layered van der Waals heterostructure (vdWH). Based on density functional theory calculations, we found that applying out-of-plane strain and doping with electrons could induce a 1T'-to-1T phase transition and consequently the ferromagnetic (FM)-to-antiferromagnetic (AFM) transition in the CrS2 layer. Such a phase and magnetic transition arises from the pressure and electron-induced interlayer interaction enhancement. The electron doping can effectively decrease the critical compressive stress from ∼4.3 GPa (charge neutrality) to ∼664 MPa (Q = 9 × 10-3 e- per atom) for the FM-to-AFM transition. These properties could be used to fabricate and program the 2D lateral FM/AFM heterostructures for artificial controlled spin texture and miniaturized spintronic devices.

Sequential gene expression analysis of myelodysplastic syndrome transformation identifies HOXB3 and HOXB7 as the novel targets for mesenchymal cells in disease.

BACKGROUND: Myelodysplastic syndrome (MDS) is known to arise through the pathogenic bone marrow mesenchymal stem cells (MSC) by interacting with hematopoietic stem cells (HSC). However, due to the strong heterogeneity of MDS patients, it is difficult to find common targets in studies with limited sample sizes. This study aimed to describe sequential molecular changes and identify biomarkers in MSC of MDS transformation. METHODS: Multidimensional data from three publicly available microarray and TCGA datasets were analyzed. MDS-MSC was further isolated and cultured in vitro to determine the potential diagnostic and prognostic value of the identified biomarkers. RESULTS: We demonstrated that normal MSCs presented greater molecular homogeneity than MDS-MSC. Biological process (embryonic skeletal system morphogenesis and angiogenesis) and pathways (p53 and MAPK) were enriched according to the differential gene expression. Furthermore, we identified HOXB3 and HOXB7 as potential causative genes gradually upregulated during the normal-MDS-AML transition. Blocking the HOXB3 and HOXB7 in MSCs could enhance the cell proliferation and differentiation, inhibit cell apoptosis and restore the function that supports hematopoietic differentiation in HSCs. CONCLUSION: Our comprehensive study of gene expression profiling has identified dysregulated genes and biological processes in MSCs during MDS. HOXB3 and HOXB7 are proposed as novel surrogate targets for therapeutic and diagnostic applications in MDS.

Present situation and prospect of immunotherapy for unresectable locally advanced esophageal cancer during peri-radiotherapy.

Four major studies (Checkmate577, Keynote-590, Checkmate649 and Attraction-4) of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy, represented by anti-programmed death protein (PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer, from the aspects of proof of concept, long-term survival, overall survival rate and progression-free survival. For unresectable or inoperable nonmetastatic esophageal cancer, concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines. Because its curative effect is still not ideal, it is necessary to explore radical radiotherapy and chemotherapy in the future, and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1. This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.