Search

Abstract Allii Macrostemonis Bulbus (AMB) is a traditional Chinese medicine with medicinal and food homology. AMB has various biological activities, including anti-coagulation, lipid-lowering, anti-tumor, and antioxidant effects. Saponins from Allium macrostemonis Bulbus (SAMB), the predominant beneficial compounds, also exhibited lipid-lowering and anti-inflammatory properties. However, the effect of SAMB on atherosclerosis and the underlying mechanisms are still unclear. This study aimed to elucidate the pharmacological impact of SAMB on atherosclerosis. In apolipoprotein E deficiency (ApoE−/−) mice with high-fat diet feeding, oral SAMB administration significantly attenuated inflammation and atherosclerosis plaque formation. The in vitro experiments demonstrated that SAMB effectively suppressed oxidized-LDL-induced foam cell formation by down-regulating CD36 expression, thereby inhibiting lipid endocytosis in bone marrow-derived macrophages. Additionally, SAMB effectively blocked LPS-induced inflammatory response in bone marrow-derived macrophages potentially through modulating the NF-κB/NLRP3 pathway. In conclusion, SAMB exhibits a potential anti-atherosclerotic effect by inhibiting macrophage foam cell formation and inflammation. These findings provide novel insights into potential preventive and therapeutic strategies for the clinical management of atherosclerosis.

The warm flow characteristics and microstructural evolution features in a solution-treated 7075 aluminum alloy are revealed. An elastic-visco-plastic constitutive model is developed to capture the flow stress behavior of 7075 aluminum alloy under warm deformation. The variations of microstructure features, including grain and subgrain size, are also analyzed under warm deformation, and are further incorporated in the proposed unified constitutive model. The results indicate that the dynamic recovery (DRV), related to dislocation annihilation and formation/growth of sub-grains, is the domain softening mechanism. The DRV behavior is enhanced at higher temperatures or lower strain rates. Warm external temperature field assists the plastic deformation by means of activating and accelerating the dynamic softening, while the reduced strain rate also gives sufficient time for the softening. Through experimental validation, the proposed constitutive model successfully captures the grain/subgrain features and flow behavior of the studied 7075 aluminum alloy during warm deformation. The predicted result is in a great agreement with the experimental stress-strain data, demonstrating the excellent predictive performance of the model. Moreover, the proposed model also successfully predicts the average grain/subgrain size.

Abstract Hydrogen (H2) has emerged as a clean and versatile energy carrier to power a carbon‐neutral economy for the post‐fossil era. Hydrogen generation from low‐cost and renewable biomass by virtually inexhaustible solar energy presents an innovative strategy to process organic solid waste, combat the energy crisis, and achieve carbon neutrality. Herein, the progress and breakthroughs in solar‐powered H2 production from biomass are reviewed. The basic principles of solar‐driven H2 generation from biomass are first introduced for a better understanding of the reaction mechanism. Next, the merits and shortcomings of various semiconductors and cocatalysts are summarized, and the strategies for addressing the related issues are also elaborated. Then, various bio‐based feedstocks for solar‐driven H2 production are reviewed with an emphasis on the effect of photocatalysts and catalytic systems on performance. Of note, the concurrent generation of value‐added chemicals from biomass reforming is emphasized as well. Meanwhile, the emerging photo‐thermal coupling strategy that shows a grand prospect for maximally utilizing the entire solar energy spectrum is also discussed. Further, the direct utilization of hydrogen from biomass as a green reductant for producing value‐added chemicals via organic reactions is also highlighted. Finally, the challenges and perspectives of photoreforming biomass toward hydrogen are envisioned.

Dolostone, with its complex diagenetic history, has long been debate. The formation of patchy dolostone, which consists of various types of dolomites, is particularly controversial due to the superimposed diagenetic events. In this study, we conducted mineralogical and stable isotope geochemical analyses of the Ediacaran patchy dolostone from the Dengying Formation in South Qinling to elucidate the diagenetic processes involved. Microscopic examination reveals that the patchy dolostone can be classified into three types: Type I, composed of micritic to powdery crystalline dolomite (D1) and fine crystalline dolomite (D2); Type II, primarily consisting of medium-coarse crystalline dolomite (D3) along with D2; and Type III, characterized by the presence of saddle dolomite (SD) and D1. Cathodoluminescence and electron probe microanalysis indicate that D2 and D3 are enriched in Mn and Fe, whereas SD is depleted in Sr and Na compared to D1. Backscattered electron images reveal a prevalence of apatite, particularly in Type III dolostone. Calcite and quartz extensively replace the dolomites. Carbon and oxygen isotopes indicate that D1 has the highest δ13C and δ18O values, while D2 and D3 show negative shifts, and SD exhibits the lowest values. These observations suggest that the transition from D1 to D2 and D3 is due to recrystallization processes during burial. The formation of SD is likely the result of hydrothermal activity. Consequently, the patchy dolostone experienced three main stages of diagenesis, which included the recrystallization of D1 and the formation of SD. Considering the vertical distribution of the patchy dolostone and the occurrence of hyperkarst breccia dolostone, it is reasonable to infer that sea level variations are the primary cause of the formation of patchy dolostone.

Although thermosonication (TS) treatment has been widely used in food sterilization, the viable but non‐culturable (VBNC) of bacteria with TS treatment has still concerned potential food safety and public health. The molecular mechanism of VBNC status of bacteria with TS treatment is not clearly known. Therefore, in this study, we used Shewanella putrefaciens, which was a common putrefactive bacteria in aquatic products, to study the VBNC state of bacteria with TS treatment. Firstly, our results revealed that S. putrefaciens still could enter the VBNC state after TS treatments: 50 kHz, 300 W, 30 min ultrasonic treatment and 70 °C heating; Subsequently, we found the VBNC state of S. putrefaciens can resist the damage of TS treatment, such as cell wall break, DNA degradation, etc; Finally, four-dimensional data-independent acquisition-based proteomics showed that under VBNC state, S. putrefaciens upregulated functional proteins to resist TS treatment, such as: ribosomal proteins to accelerate the synthesis of stress proteins to counteract TS treatments, ornithine decarboxylase SpeF and MraY to repair TS treatment-induced damage, etc. Meanwhile, S. putrefaciens downregulates metabolic and transport functional proteins such as dehydrogenase to reduce the metabolism. Importantly, among those proteins, the ribosomal transcriptional regulatory protein family, such as rpsB, etc, may be the key proteins for S. putrefaciens entering VBNC state. This finding can provide some new strategies for preventing VBNC status of bacteria with TS treatment, such as: inhibition of key proteins, etc.

Diabetic cardiomyopathy (DCM) is a common severe complication of diabetes that occurs independently of hypertension, coronary artery disease, and valvular cardiomyopathy, eventually leading to heart failure. Previous studies have reported that Tectorigenin (TEC) possesses extensive anti-inflammatory and anti-oxidative stress properties. In this present study, the impact of TEC on diabetic cardiomyopathy was examined. The model of DCM in mice was established with the combination of a high-fat diet and STZ treatment. Remarkably, TEC treatment significantly attenuated cardiac fibrosis and improved cardiac dysfunction. Concurrently, TEC was also found to mitigate hyperglycemia and hyperlipidemia in the DCM mouse. At the molecular level, TEC is involved in the activation of AMPK, both in vitro and in vivo, by enhancing its phosphorylation. This is achieved through the regulation of endothelial-mesenchymal transition via the AMPK/TGFβ/Smad3 pathway. Furthermore, it was demonstrated that the level of ubiquitination of the adiponectin receptor 1 (AdipoR1) protein is associated with TEC-mediated improvement of cardiac dysfunction in DCM mice. Notably the substantial reduction of myocardial fibrosis. In conclusion, TEC improves cardiac fibrosis in DCM mice by modulating the AdipoR1/AMPK signaling pathway. These findings suggest that TEC could be an effective therapeutic agent for the treatment of diabetic cardiomyopathy.

Abstract Animal experiments suggest that selenium (Se) may alleviate cadmium (Cd) toxicity in animal liver and kidneys, but its effect on human liver and kidneys remains uncertain. In China, areas with black shale have shown elevated levels of Se and Cd. According to the USEPA (U.S. Environmental Protection Agency) evaluation method, the soil and rice in these areas pose significant risks. In black shale regions such as Enshi and Zhuxi County, residents who long‐term consume local rice may surpass safe Se and Cd intake levels. Significantly high median blood Se (B‐Se) and urine selenium (U‐Se) levels were detected in these areas, measuring 416.977 μg/L and 352.690 μg/L and 104.527 μg/L and 51.820 μg/L, respectively. Additionally, the median blood Cd (B‐Cd) and urine Cd (U‐Cd) levels were markedly elevated at 4.821 μg/L and 3.848 μg/L and at 7.750 μg/L and 7.050 μg/L, respectively, indicating substantial Cd exposure. Nevertheless, sensitive liver and kidney biomarkers in these groups fall within healthy reference ranges, suggesting a potential antagonistic effect of Se on Cd in the human body. Therefore, the USEPA method may not accurately assess Cd risk in exposed black shale areas. However, within the healthy ranges, residents in the Enshi study area had significantly greater median levels of serum creatinine and cystatin C, measuring 67.3 μmol/L and 0.92 mg/L, respectively, than those in Zhuxi did (53.6 μmol/L and 0.86 mg/L). In cases of excessive Se and Cd exposure, high Se and Cd levels impact the filtration function of the human kidney to some extent.

Abstract The response rate of cancer immune checkpoint inhibitors (ICI) varies among patients, making it challenging to pre-determine whether a particular patient will respond to immunotherapy. While gene mutation is critical to the treatment outcome, a framework capable of explicitly incorporating biology knowledge has yet to be established. Here we aim to propose and validate a mutation-based deep learning model for survival analysis on 1571 patients treated with ICI. Our model achieves an average concordance index of 0.59 ± 0.13 across nine types of cancer, compared to the gold standard Cox-PH model (0.52 ± 0.10). The “black box” nature of deep learning is a major concern in healthcare field. This model’s interpretability, which results from incorporating the gene pathways and protein interaction (i.e., biology-aware) rather than relying on a ‘black box’ approach, helps patient stratification and provides insight into novel gene biomarkers, advancing our understanding of ICI treatment.

The formation of prior particle boundaries (PPBs) in a new powder metallurgy superalloy during hot isostatic pressing (HIP) is investigated. Also, the impact of subsequent hot deformation on the elimination of PPBs is systematically studied. The PPBs involves large γ′ phases, carbides (MC and M6C) and oxides (Al2O3, SiO2 and ZrO2). The reactions among the superficial oxides, the adsorbed C and O elements on the particle surface and internally-migrated alloying elements are the dominant reasons for the formation of PPBs during HIP. Besides, the existence of surface tension and surface energy induces the carbon segregation, as well as the formation of PPBs. Thus, the density of PPBs decreases when the spacing between powders is shrunk by a rapid deformation. In hot forming process, the PPBs can be efficiently eliminated via raising deformation temperature/true strain or reducing strain rate. The interactions between dislocations and PPBs, as well as the occurrence of dynamic recrystallization (DRX) induced by the strain/orientation gradient, lead to the elimination of PPBs. The thermodynamic stability of carbides declines with the raised temperature. It indicates that the dissolution of carbides and the elimination of PPBs can be accelerated via raising the deformation temperature. The breakage or deformation behavior of PPBs during hot extrusion is investigated by numerical simulation. The deformation degree of PPBs increases with the raised extrusion ratio. The above important findings are useful for developing hot extrusion processing to effectively eliminate PPBs.

Abstract Background Limb-girdle muscular dystrophies (LGMDs) are a group of heterogeneous inherited diseases predominantly characterized by limb-girdle muscle weakness and dystrophic changes on histological analysis. The frequency of LGMD subtypes varies among regions in China and ethnic populations worldwide. Here, we analyzed the prevalence of LGMD subtypes, their corresponding clinical manifestations, and molecular data in a cohort of LGMD patients in Southeast China. Methods A total of 81 consecutive patients with clinically suspected LGMDs from 62 unrelated families across Southeast China were recruited for targeted next-generation sequencing and whole-exome sequencing from July 2017 to February 2020. Results Among 50 patients (41 families) with LGMDs, the most common subtypes were LGMD-R2/LGMD2B (36.6%) and LGMD-R1/LGMD2A (29.3%). Dystroglycanopathies (including LGMD-R9/LGMD2I, LGMD-R11/LGMD2K, LGMD-R14/LGMD2N and LGMD-R20/LGMD2U) were the most common childhood-onset subtypes and were found in 12.2% of the families. A total of 14.6% of the families had the LGMD-R7/LGMD2G subtype, and the mutation c.26_33dupAGGTGTCG in TCAP was the most frequent (83.3%). The only patient with the rare subtype LGMD-R18/LGMD2S had TRAPPC11 mutations; had a later onset than those previously reported, and presented with proximal‒distal muscle weakness, walking aid dependency, fatty liver disease and diabetes at 33 years of age. A total of 22.0% of the patients had cardiac abnormalities, and one patient with LMNA-related muscular dystrophy/LGMD1B experienced sudden cardiac death at 37 years of age. A total of 15.4% of the patients had restrictive respiratory insufficiency. Muscle imaging in patients with LGMD-R1/LGMD2A and LGMD-R2/LGMD2B showed subtle differences, including more severe fatty infiltration of the posterior thigh muscles in those with LGMD-R1/LGMD2A and edema in the lower leg muscles in those with LGMD-R2/LGMD2B. Conclusion We determined the prevalence of different LGMD subtypes in Southeast China, described the detailed clinical manifestations and distinct muscle MRI patterns of these LGMD subtypes and reported the frequent mutations and the cardiorespiratory involvement frequency in our cohort, all of which might facilitate the differential diagnosis of LGMDs, allowing more timely treatment and guiding future clinical trials.

Perinereis species are essential benthonic animals in coastal ecosystems and have significant roles as live feed in aquaculture, owing to their high-protein and low-fat nutritional profile. Despite their ecological importance, the viral communities associated with these organisms need to be better understood. In this study, we generated 2.6 × 108 reads using meta-transcriptomic sequencing and de novo assembled 5.3 × 103 virus-associated contigs. We identified 12 novel RNA viruses from two species, Perinereis aibuhitensis and P. wilsoni, which were classified into four major viral groups: Picobirnaviridae, Marnaviridae, unclassified Picornavirales, and unclassified Bunyavirales. Our findings revealed the hidden diversity of viruses and genome structures in Perinereis, enriching the RNA virosphere and expanding the host range of Picobirnaviridae, Marnaviridae, and Bunyavirales. This study also highlighted the potential biosecurity risk of the novel viruses carried by Perinereis to aquaculture.

Live fish transport is an important aspect of aquaculture, especially at high densities, which might cause considerable stress and compromise product quality. This study investigated the effects of transport density and time on stress responses, innate immunity, and immune gene expression in juvenile yellow catfish. The fish were designated to five density groups: D11, D12, D13, D14, and D15 (500, 333, 250, 200, and 167 kg/m3). After 36 h of transport, only the D15 group had a 100% survival rate, followed by D14 with 83% survival, and 0% in the remaining three density groups. The damage to gill filaments and the liver worsened with increasing environmental stress severity. The results showed that with the prolonged transport time, plasma cortisol (COR), and catalase (CAT), malonaldehyde (MDA) and lysozyme (LZM) levels in the livers first increased and later gradually decreased after 16 h of transport, while the activity of superoxide dismutase (SOD) continued to rise. The activities of CAT and MDA content increased as the density increased. The expression of heat shock protein (HSP) 70 and 90, tumor necrosis factor α (TNF-α), and interleukin-1β (IL-1β) in juvenile livers in D11 group was significantly higher than the control group (p

Respiratory motion-induced vertebral movements can adversely impact intraoperative spine surgery, resulting in inaccurate positional information of the target region and unexpected damage during the operation. In this paper, we propose a novel deep learning architecture for respiratory motion prediction, which can adapt to different patients. The proposed method utilizes an LSTM-AE with attention mechanism network that can be trained using few-shot datasets during operation. To ensure real-time performance, a dimension reduction method based on the respiration-induced physical movement of spine vertebral bodies is introduced. The experiment collected data from prone-positioned patients under general anaesthesia to validate the prediction accuracy and time efficiency of the LSTM-AE-based motion prediction method. The experimental results demonstrate that the presented method (RMSE: 4.39%) outperforms other methods in terms of accuracy within a learning time of 2 min. The maximum predictive errors under the latency of 333 ms with respect to the x, y, and z axes of the optical camera system were 0.13, 0.07, and 0.10 mm, respectively, within a motion range of 2 mm.

This paper focuses on analyzing and studying digital capitalism using a textual analysis model in the context of Marxist political economy. The magnitude of the angle between text vectors can be used to measure the similarity between digital capitalism and political economy. An iterative computational approach is employed to address the issue of overfitting in text. Constructing a BERT model involves formulating a self-attentive mechanism and setting up an embedding layer. The direction of digital capitalism’s ideology in the political economy context is examined about its characteristics. The results show that digital labor is more secretive regarding office location than traditional labor, with a secrecy rate of 60%. Unpaidness, large quantity, and potential value dominate data characteristics, with 90% unpaid data.

ATG1/ATG13, a core kinase complex regulator in the macroautophagy/autophagy machinery during autophagosome formation, is modulated in a sophisticated manner by posttranslational ubiquitination to determine proper autophagy levels in eukaryotic cells. However, the mechanisms that regulate the stability and activity of this complex remain elusive. We recently identified two negative regulators of autophagy, 14-3-3λ and 14-3-3k, that help redundantly regulate autophagy by directly associating with SINAT and ATG13s. The specific interaction between the molecular adaptors 14-3-3λ and 14-3-3κ and phosphorylated ATG13a is crucial for SINAT-mediated ubiquitination and degradation of ATG13a, and for maintenance of the ATG1-ATG13 complex. Consistent with the function of 14-3-3s in autophagy, the 14-3-3λ 14-3-3κ double mutant exhibits enhanced tolerance to nutrient deprivation with constitutive induction of autophagy. These findings demonstrate that 14-3-3λ and 14-3-3k coordinate with SINATs to regulate both the homeostasis of ATG13 phosphorylation and the induction of autophagy in plants.

The Permian to Triassic period represents a pivotal phase in the evolution of the Paleo-Asian Ocean, marked by significant tectonic transitions from subduction, collision, and post-orogenic extension. The timing of closure of the Paleo-Asian Ocean in northeastern China has always been controversial. In this contribution, the petrology, zircon U-Pb geochronology and geochemistry are conducted on granite found in well HFD1, Songliao Basin, eastern part of Central Asian orogenic belt. Zircon U-Pb dating indicates that granite crystallized at 258.9 ± 2.2 Ma, as the product of magmatism occurred in the early Late Permian. The rocks have high SiO2, Al2O3, Na2O content, negative Eu anomaly, light enrichment of rare-earth elements, depletion of heavy rare-earth elements, high Sr (448.29–533.11 ppm, average 499.68 ppm), low Yb (0.49–0.59 ppm, average 0.54 ppm), Y (4.23–5.19 ppm, average 4.49 ppm), and high Sr/Y ratios (98–125, average 112) and can be classified as O-type adakite. This is the first discovery of late Paleozoic adakite in the Songliao Basin and the neighboring areas. The geochemistry of adakite indicates derivation by partial melting of MORB-type subducted oceanic crust, indicating that the subduction of the Paleo-Asian Oceanic lithosphere lasted until at least 258.9 Ma.

Endothelial inflammation is a multifaceted physiological process that plays a pivotal role in the pathogenesis and progression of diverse diseases, encompassing but not limited to acute lung infections like COVID-19, coronary artery disease, stroke, sepsis, metabolic syndrome, certain malignancies, and even psychiatric disorders such as depression. This inflammatory response is characterized by augmented expression of adhesion molecules and secretion of pro-inflammatory cytokines. In this study, we discovered that saponins from Allium macrostemon bulbs (SAMB) effectively inhibited inflammation in human umbilical vein endothelial cells induced by the exogenous inflammatory mediator lipopolysaccharide or the endogenous inflammatory mediator tumor necrosis factor-α, as evidenced by a significant reduction in the expression of pro-inflammatory factors and vascular cell adhesion molecule-1 (VCAM-1) with decreased monocyte adhesion. By employing the NF-κB inhibitor BAY-117082, we demonstrated that the inhibitory effect of SAMB on VCAM-1 expression may be attributed to the NF-κB pathway’s inactivation, as characterized by the suppressed IκBα degradation and NF-κB p65 phosphorylation. Subsequently, we employed a murine model of lipopolysaccharide-induced septic acute lung injury to substantiate the potential of SAMB in ameliorating endothelial inflammation and acute lung injury in vivo. These findings provide novel insight into potential preventive and therapeutic strategies for the clinical management of diseases associated with endothelial inflammation.

Understanding the interplay between superconductivity and magnetism has been a longstanding challenge in condensed matter physics. Here, the authors uncover a sensitive coupling between the two within the pressure-tuned phase diagram of EuTe 2 and find that certain magnetic orders can stabilize conventional superconductivity far exceeding the Pauli limit.

Abstract Discoveries of tetraquarks not only enrich the hadronic spectrum but also provide more platforms to understand quantum chromodynamics. We study the production processes of hidden-charm and open-charm tetraquarks in B decays by analyzing their topological amplitudes. Relations between different channels are found, which confront tests by experiments to probe the nature of the tetraquarks. Furthermore, promising channels to find more tetraquarks are proposed.

Immune checkpoint inhibitors (ICIs) therapy has emerged as a promising treatment strategy for breast cancer (BC). However, current reliance on immunohistochemical (IHC) detection of PD-L1 expression alone has limited predictive capability, resulting in suboptimal efficacy of ICIs for some BC patients. Hence, developing novel predictive biomarkers is indispensable to enhance patient selection for immunotherapy. In this context, utilizing liquid biopsy (LB) can provide supplementary or alternative value to PD-L1 IHC testing for identifying patients most likely to benefit from immunotherapy and exhibit favorable responses. This review discusses the predictive and prognostic value of LB in breast cancer immunotherapy, as well as its limitations and future directions. We aim to promote the individualization and precision of immunotherapy in BC by elucidating the role of LB in clinical practice.

Theabrownins (TB), a signature phenolic-derivative via complex microbial fermentation, has multiple health-promoting effects, including antioxidant, anti-obesity and hypoglycemic effects. However, the effect of TB on colitis remains unclear. In this study, we investigated the effect of TB on DSS-induced colitis in mice. TB treatment significantly relieved weight loss (p

The tectonic evolution of the Paleo-Asian Ocean (PAO) has been well studied, including its gradual narrowing and closure by subduction. However, aspects of the tectonic evolution of the oceanic domain remain unclear, including the exact timing and nature of the closure. The Central Asian Orogenic Belt (CAOB) was formed by the closure of the PAO and, therefore, contains information about the tectonic evolution of the oceanic domain. Here, we report a study of the petrology, geochronology, and geochemistry of the Taohaiyingzi section of the Permian Linxi Formation in Alukhorqin Banner (Northeast China) in the central part of the CAOB. A newly discovered andesitic tuff from the lower part of the Linxi Formation yields a weighted mean 206Pb/238U age of 262.2 ± 1.1 Ma (n = 87), indicating that the lower part of the Linxi Formation of the Taohaiyingzi section was deposited during the late Guadalupian. Provenance weathering indicators show that the sedimentary rocks of the Linxi Formation are of low maturity. Element geochemical characteristics indicate that the Linxi Formation clastic rocks were derived from eroded magmatic rocks that formed in a continental arc setting and were deposited close to the arc in a continental arc basin environment. The active margin setting was generated by the subduction of the paleo-Asian oceanic plate beneath the Xilinhot–Songliao block. The inferred palaeosalinity of the sedimentary environment changed gradually from brackish to fresh water, suggesting the end of oceanic plate subduction during the late Guadalupian, and the closure of the PAO during or after the Lopingian.

Endothelial pro-inflammatory activation is pivotal in cardiac ischemia–reperfusion (I/R) injury pathophysiology. The dried flower bud of Edgeworthia gardneri (Wall.) Meisn. (EG) is a commonly utilized traditional Tibetan medicine. However, its role in regulating endothelium activation and cardiac I/R injury has not been investigated. Herein, we showed that the administration of EG ethanolic extract exhibited a potent therapeutic efficacy in ameliorating cardiac endothelial inflammation (p < 0.05) and thereby protecting against myocardial I/R injury in rats (p < 0.001). In line with the in vivo findings, the EG extract suppressed endothelial pro-inflammatory activation in vitro by downregulating the expression of pro-inflammatory mediators (p < 0.05) and diminishing monocytes’ firm adhesion to endothelial cells (ECs) (p < 0.01). Mechanistically, we showed that EG extract inhibited the nuclear factor kappa-B (NF-κB), c-Jun N-terminal kinase (JNK), extracellular regulated protein kinase (ERK), and p38 mitogen-activated protein kinase (MAPK) signaling pathways to attenuate EC-mediated inflammation (p < 0.05). Collectively, for the first time, this study demonstrated the therapeutic potential of EG ethanolic extract in alleviating I/R-induced inflammation and the resulting cardiac injury through its inhibitory role in regulating endothelium activation.

In the present work, the effects of aging treatment on the microstructures of a TC18 alloy are studied. The influence of aging treatment on the tensile properties and failure mechanisms is systematically analyzed. It is found that the size and morphology of the primary α (αp) phases are insensitive to aging temperature and time. Furthermore, the aging temperature and time dramatically influence the precipitation of the secondary α (αs) phases. Massive αs phases precipitate and gradually coarsen, and finally weave together by increasing the aging temperature or extending the aging time. The variations in αp and αs phases induced by aging parameters also affect the mechanical properties. Both yield strength (YS) and ultimate tensile strength (UTS) first increase and then decrease by increasing the aging temperature and time, while ductility first decreases and then increases. There is an excellent balance between the strengths and ductility. When the aging temperature is changed from 450 to 550 °C, YS varies from 1238.6 to 1381.6 MPa, UTS varies from 1363.2 to 1516.8 MPa, and the moderate elongation ranges from 9.0% to 10.3%. These results reveal that the thickness of αs phases is responsible for material strengths, while the content of α phases can enhance material ductility. The ductile characteristics of the alloy with coarser αs phases are more obvious than those with thinner αs phases. Therefore, the aging treatment is helpful for the precipitation and homogeneous distribution of αs phases, which are essential for balancing the strengths and ductility of the studied Ti alloy.

Lactiplantibacillus plantarum, a typical ecological species against pathogens, used due to its bacteriocin yield in fermented foods, was proven to have the capacity to lower cholesterol. In this study, using L. plantarum ATCC8014 as the control, L. plantarum WLPL21 and ZDY04 were probed with whole-genome sequencing to ascertain their potential ability to lower cholesterol and yield bacteriocins, as well as to further evaluate their survival capacity in vitro. Our results showed 386 transport-system genes in both L. plantarum WLPL21 and ZDY04. Correspondingly, the in vitro results showed that L. plantarum WLPL21 and ZDY04 could remove cholesterol at 49.23% and 41.97%, respectively, which is 1.89 and 1.61 times that of L. plantarum ATCC8014. The survival rates of L. plantarum WLPL21 and ZDY04 in 1% H2O2, pH 3.0, and 0.3% bile salt were higher than those of L. plantarum ATCC8014. Our results exhibited a complete gene cluster for bacteriocin production encoded by L. plantarum WLPL21 and ZDY04, including plnJKR, plnPQAB, plnEFI, plnSUVWY, and plnJK; and plnMN, plnPQA and plnEFI, respectively, compared with only plnEF in L. plantarum ATCC8014. The present study suggests that the combination of genomic analysis with in vitro evaluations might be useful for exploring the potential functions of probiotics.

BackgroundChronic pressure overload triggers pathological cardiac hypertrophy that eventually leads to heart failure. Effective biomarkers and therapeutic targets for heart failure remain to be defined. The aim of this study is to identify key genes associated with pathological cardiac hypertrophy by combining bioinformatics analyses with molecular biology experiments.MethodsComprehensive bioinformatics tools were used to screen genes related to pressure overload-induced cardiac hypertrophy. We identified differentially expressed genes (DEGs) by overlapping three Gene Expression Omnibus (GEO) datasets (GSE5500, GSE1621, and GSE36074). Correlation analysis and BioGPS online tool were used to detect the genes of interest. A mouse model of cardiac remodeling induced by transverse aortic constriction (TAC) was established to verify the expression of the interest gene during cardiac remodeling by RT-PCR and western blot. By using RNA interference technology, the effect of transcription elongation factor A3 (Tcea3) silencing on PE-induced hypertrophy of neonatal rat ventricular myocytes (NRVMs) was detected. Next, gene set enrichment analysis (GSEA) and the online tool ARCHS4 were used to predict the possible signaling pathways, and the fatty acid oxidation relevant pathways were enriched and then verified in NRVMs. Furthermore, the changes of long-chain fatty acid respiration in NRVMs were detected using the Seahorse XFe24 Analyzer. Finally, MitoSOX staining was used to detect the effect of Tcea3 on mitochondrial oxidative stress, and the contents of NADP(H) and GSH/GSSG were detected by relevant kits.ResultsA total of 95 DEGs were identified and Tcea3 was negatively correlated with Nppa, Nppb and Myh7. The expression level of Tcea3 was downregulated during cardiac remodeling both in vivo and in vitro. Knockdown of Tcea3 aggravated cardiomyocyte hypertrophy induced by PE in NRVMs. GSEA and online tool ARCHS4 predict Tcea3 involved in fatty acid oxidation (FAO). Subsequently, RT-PCR results showed that knockdown of Tcea3 up-regulated Ces1d and Pla2g5 mRNA expression levels. In PE induced cardiomyocyte hypertrophy, Tcea3 silencing results in decreased fatty acid utilization, decreased ATP synthesis and increased mitochondrial oxidative stress.ConclusionOur study identifies Tcea3 as a novel anti-cardiac remodeling target by regulating FAO and governing mitochondrial oxidative stress.

Protein phosphatase 6 (PP6) is a member of the PP2A-like subfamily, which plays a critical role in many fundamental cellular processes. We recently reported that PP6 is essential for female fertility. Here, we report that PP6 is involved in meiotic recombination and that germ cell-specific deletion of PP6 by Stra8-Cre causes defective spermatogenesis. The PP6-deficient spermatocytes were arrested at the pachytene stage and defects in DSB repair and crossover formation were observed, indicating that PP6 facilitated meiotic double-stranded breaks (DSB) repair. Further investigations revealed that depletion of PP6 in the germ cells affected chromatin relaxation, which was dependent on MAPK pathway activity, consequently preventing programmed DSB repair factors from being recruited to proper positions on the chromatin. Taken together, our results demonstrate that PP6 has an important role in meiotic recombination and male fertility.