Polystyrene microplastics aggravate radiation-induced intestinal injury in mice.

Radiotherapy is a common treatment for abdominal and pelvic tumors, while the radiation-induced intestinal injury (RIII) is one of the major side-effects of radiotherapy, which reduces the life quality and impedes the treatment completion of cancer patients. Previous studies have demonstrated that environmental pollutant microplastics led to various kinds of injury in the gut, but its effects on RIII are still uncovered. In this study, we fed the C57BL/6J mice with distilled water or 50 µg/d polystyrene microplastics (PSMPs) for 17 days and exposed the mice to total abdominal irradiation (TAI) at day 14. Then the severity of RIII was examined by performing histopathological analysis and microbial community analysis. The results demonstrated that PSMPs significantly aggravated RIII in small intestine rather than colon of mice upon TAI. PSMPs increased levels of the histopathological damage and the microbial community disturbance in mice small intestine, shown by the overabundance of Akkermansiaceae and the decrease of microflora including Lactobacillaceae, Muribaculaceae and Bifidobacteriaceae. In conclusion, our results suggested that more microplastics exposure might led to more severe RIII, which should be considered in patients' daily diet adjustment and clinical radiotherapy plan evaluation. Furthermore, this study also called for the further researches to uncover the underlying mechanism and develop novel strategies to attenuate RIII in mice intestine.

Case Report and Literature Review: Orthostatic Hypotension Due to Multiple System Atrophy.

Objective: Multiple system atrophy (MSA) is a rare and fatal adult-onset neurodegenerative disease with multiple clinical and pathological variants. The etiology of MSA remains uncertain. Orthostatic hypotension (OH) is the main characteristic of MSA. An upright position can trigger a syncope attack, making it impossible for the patient to stand and walk briefly. Case Study: We report the case of a 67-year-old man with initial symptoms of recurrent syncope and this patient was hospitalized several times, despite multiple therapeutic interventions, his symptoms persisted. Eventually, this patient died at the age of 68 with a diagnosis of MSA. Conclusion: For those patients with neurogenic OH, an underlying neurodegenerative disease should always be considered. Prompt diagnosis, early aggressive treatment, and prediction of complications may have a huge impact on the prognosis of MSA. This article also reviews relevant reported cases to enrich the experience of treating MSA in the clinic.

Generalization of sequence effects from conflict to cueing tasks.

Cognitive control has been investigated in attentional conflict tasks for a long time. One representative phenomenon of adaptive cognitive control in these tasks is the congruency sequence effect (CSE), which means that a previous conflict will lead to reduced congruency effects at the current moment, reflecting increased control of attention toward the task at hand. One debating question is whether CSE can generalize between different conditions. Since a similar phenomenon (i.e., validity sequence effect, VSE) has been found in spatial cueing tasks, this study investigated whether the two sequential effects could generalize between each other. A cross-task sequence effect is found from previous flanker trials to current cueing trials when the task sets of the two tasks are either very similar or sufficiently dissimilar, and this C-VSE effect is influenced by the response mode of the experimental design. In addition, the VSE between trial n-2 and trial n is eliminated by the existence of an intermediate flanker trial, but the CSE between trial n-2 and trial n is still significant even with an intermediate cueing trial. Possible explanations of these findings are discussed. The findings suggest a close connection between orienting and executive control processes in attention networks and provide a new perspective and method for investigating the potential mechanisms of cognitive control.

Lead-free ferroelectrics with giant unipolar strain for high-precision actuators.

The trade-off between electrostrain and strain hysteresis for piezo/ferroelectric materials largely restrains the development of high precision actuators and remains unresolved over the past few decades. Here, a simple composition of (Bi0.5Na0.5)1-x/100Srx/100TiO3 in the ergodic relaxor state is collaboratively designed through the segregated domain structure with the ferroelectric core, local polarization heterogeneity, and defect engineering. The ferroelectric core can act as a seed to facilitate the field-induced nonpolar-to-polar transition. Together with the internal bias field caused by defect dipoles and adjusted through electric field cycling and heat treatment technology, a giant unipolar strain of 1.03% is achieved in the x = 30 ceramic with a low hysteresis of 27%, while the electric-field-independent large-signal piezoelectric strain coefficient of ~1000 pm/V and ultralow hysteresis of <10% can be obtained in the x = 35 ceramic. Intriguingly, the low-hysteresis high strain also exhibits near-zero remnant strain, excellent temperature and cycling stability.

Design of a Thermally Stable Heat-Resistant (Al2O3+Al3Ti)/Al Composite with Excellent High-Temperature Mechanical Properties: Multimechanism Synergistic Strengthening Strategy.

The effectiveness of the room-temperature strengthening strategy for aluminum (Al) is compromised at increased temperatures due to grain and precipitate phase coarsening. Overcoming the heightened activity of grain boundaries and dislocations poses a significant challenge in enhancing the high-temperature strength through traditional precipitation strengthening. This study presents novel strengthening strategies that integrate intergranular reinforcements, intragranular reinforcements, refined grain, and stacking faults within an (Al2O3+Al3Ti)/Al composite prepared using sol-gel and powder metallurgy technology. Excellent high-temperature tensile properties are achieved; also, a remarkable fatigue performance at increased temperatures that surpasses those of other existing Al alloys and composites is revealed. These superior characteristics can be attributed to its exceptionally stable microstructure and the synergistic strengthening mechanisms mentioned above. This work offers new insights into designing and fabricating thermally stable Al matrix composites for high-temperature applications.

The involvement of circulating miR-146a and miR-27a in patients with atherosclerotic cardiovascular disease after SARS-CoV-2 infection.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is a group of clinical diseases based on pathology of atherosclerosis that is the leading cause of mortality worldwide. There is a bidirectional interaction between ASCVD and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Alterations in circulating miRNAs levels are involved in the development of ASCVD in patients infected with SARS-CoV-2, however, the correlation between ASCVD co-infection with SARS-CoV-2 and alterations of cardiac-specific miRNAs is not well understood. HYPOTHESIS: The circulating miR-146a and miR-27a are involved in bidirectional interactions between ASCVD and SARS-CoV-2 infections. METHODS: Circulating miR-146a and miR-27a levels were measured in serum and PBMCs deriving from ASCVD patients and controls after SARS-CoV-2 infection by qRT-PCR analysis. The levels of neutralizing antibodies-resistant SARS-CoV-2 in human serum was determined by competitive magnetic particle chemiluminescence method. Interleukin (IL)-6 levels were detected by automatic biochemical analyzer using electrochemiluminescence. RESULTS: Significant downregulation of circulating miR-146a and upregulation of miR-27a in ASCVD patients after infection with SARS-CoV-2 compared with controls were observed, among which the alterations were more evident in ASCVD patients comorbid with hyperlipidemia and diabetes mellitus. Consistently, correlation analysis revealed that serum miR-146a and miR-27a levels were associated with the levels of lipids and glucose, inflammatory response, and immune function in ASCVD patients. Remarkably, SARS-CoV-2 S protein RBD stimulation of PBMCs derived from both ASCVD and controls significantly downregulated miR-146a, upregulated miR-27a expression levels, and promoted IL-6 release in vitro. CONCLUSIONS: The circulating miR-146a and miR-27a are involved in metabolism, inflammation, and immune levels in patients with ASCVD after SARS-CoV-2 infection, laying the foundation for the development of strategies to prevent the risk of SARS-CoV-2 infection in ASCVD patients.

Single-cell transcriptomics reveal the microenvironment landscape of perfluorooctane sulfonate-induced liver injury in female mice.

Epidemic and animal studies have reported that perfluoroalkyl and polyfluoroalkyl substances (PFASs) are strongly associated with liver injury; however, to date, the effects of PFASs on the hepatic microenvironment remain largely unknown. In this study, we established perfluorooctane sulfonic acid (PFOS)-induced liver injury models by providing male and female C57BL/6 mice with water containing PFOS at varying doses for 4 weeks. Hematoxylin and eosin staining revealed that PFOS induced liver injury in both sexes. Elevated levels of serum aminotransferases including those of alanine aminotransferase and aspartate transaminase were detected in the serum of mice treated with PFOS. Female mice exhibited more severe liver injury than male mice. We collected the livers from female mice and performed single-cell RNA sequencing. In total, 36,529 cells were included and grouped into 10 major cell types: B cells, granulocytes, T cells, NK cells, monocytes, dendritic cells, macrophages, endothelial cells, fibroblasts, and hepatocytes. Osteoclast differentiation was upregulated and the T cell receptor signaling pathway was significantly downregulated in PFOS-treated livers. Further analyses revealed that among immune cell clusters in PFOS-treated livers, Tcf7+CD4+T cells were predominantly downregulated, whereas conventional dendritic cells and macrophages were upregulated. Among the fibroblast subpopulations, hepatic stellate cells were significantly enriched in PFOS-treated female mice. CellphoneDB analysis suggested that fibroblasts interact closely with endothelial cells. The major ligand-receptor pairs between fibroblasts and endothelial cells in PFOS-treated livers were Dpp4_Cxcl12, Ackr3_Cxcl12, and Flt1_complex_Vegfa. These genes are associated with directing cell migration and angiogenesis. Our study provides a general framework for understanding the microenvironment in the livers of female mice exposed to PFOS at the single-cell level.

Shearing brittle intermetallics enhances cryogenic strength and ductility of steels.

Precipitates are crucial for crafting mechanically strong metallic materials. In this work, we report the dislocation cutting of B2 (ordered body-centered cubic) nanoprecipitates, typically considered nonshearable intermetallics, in a lightweight compositionally complex steel during cryogenic tensile loading. Shearing is enabled by the high strength level for dislocation glide within the austenitic matrix, attributed to the substantial strengthening from subnanoscale local chemical ordering zones and the pronounced solid solution strengthening from the multiprincipal elements in the matrix. This mechanism not only harnesses the intense strengthening and strain hardening provided by otherwise impenetrable brittle nanoprecipitates but also introduces ductility through their sequential shearing with ongoing deformation. Our steel thus showcases ultrahigh cryogenic tensile strength up to 2 gigapascal at a remarkable tensile elongation of 34%. This study reveals a new strategy for designing high-performance structural materials.

The CsPbs2-interacting protein oxalate decarboxylase CsOxdC3 modulates morphosporogenesis, virulence, and fungicide resistance in Colletotrichum siamense.

The HOG MAPK pathway mediates diverse cellular and physiological processes, including osmoregulation and fungicide sensitivity, in phytopathogenic fungi. However, the molecular mechanisms underlying HOG MAPK pathway-associated stress homeostasis and pathophysiological developmental events are poorly understood. Here, we demonstrated that the oxalate decarboxylase CsOxdC3 in Colletotrichum siamense interacts with the protein kinase kinase CsPbs2, a component of the HOG MAPK pathway. The expression of the CsOxdC3 gene was significantly suppressed in response to phenylpyrrole and tebuconazole fungicide treatments, while that of CsPbs2 was upregulated by phenylpyrrole and not affected by tebuconazole. We showed that targeted gene deletion of CsOxdC3 suppressed mycelial growth, reduced conidial length, and triggered a marginal reduction in the sporulation characteristics of the ΔCsOxdC3 strains. Interestingly, the ΔCsOxdC3 strain was significantly sensitive to fungicides, including phenylpyrrole and tebuconazole, while the CsPbs2-defective strain was sensitive to tebuconazole but resistant to phenylpyrrole. Additionally, infection assessment revealed a significant reduction in the virulence of the ΔCsOxdC3 strains when inoculated on the leaves of rubber tree (Hevea brasiliensis). From these observations, we inferred that CsOxdC3 crucially modulates HOG MAPK pathway-dependent processes, including morphogenesis, stress homeostasis, fungicide resistance, and virulence, in C. siamense by facilitating direct physical interactions with CsPbs2. This study provides insights into the molecular regulators of the HOG MAPK pathway and underscores the potential of deploying OxdCs as potent targets for developing fungicides.

Aflatoxin B1-Induced Testosterone Biosynthesis Disorder via the ROS/AMPK Signaling Pathway in Male Mice.

The worldwide prevalence of Aflatoxin B1 (AFB1), which contaminates feedstock and food, is on the rise. AFB1 inhibits testosterone (T) biosynthesis, but the mechanism is not yet clear. By establishing in vivo and in vitro models, this study found the number of Leydig cells (LCs), T content, and the expression of T biosynthesis key enzymes were suppressed after AFB1 treatment. AFB1 exposure also increased reactive oxygen species (ROS) and promoted mitochondrial injury and mitochondrial pathway apoptosis. Moreover, the AMPK signaling pathway was activated, and using an AMPK inhibitor relieved apoptosis and the suppressed T biosynthesis key enzymes of LCs caused by AFB1 through regulating downstream p53 and Nur77. Additionally, adding ROS intervention could inhibit AMPK activation and alleviate the decreased T content caused by AFB1. In summary, AFB1 promotes the apoptosis of LCs and inhibits T biosynthesis key enzyme expression via activating the ROS/AMPK signaling pathway, which eventually leads to T synthesis disorder.

The hepatotoxicity of hexafluoropropylene oxide trimer acid caused by apoptosis via endoplasmic reticulum-mitochondrial crosstalk.

As a ubiquitous pollutant in the environment, hexafluoropropylene oxide trimer acid (HFPO-TA) has been proven to have strong hepatotoxicity. However, the underlying mechanism is still unclear. Consequently, in vivo and in vitro models of HFPO-TA exposure were established to investigate the detrimental effects of HFPO-TA on the liver. In vivo, we discovered that HFPO-TA enhanced endoplasmic reticulum (ER)-mitochondrial association, caused mitochondrial oxidative damage, activated ER stress, and induced apoptosis in mouse livers. In vitro experiments confirmed that IP3R overexpression on ER structure increased mitochondrial calcium levels, which led to mitochondrial damage and mitochondria-dependent apoptosis in HepG2 cells exposed to HFPO-TA. Subsequently, damaged mitochondria released a large amount of mitochondrial ROS, which activated ER stress and ER stress-dependent apoptosis. In conclusion, this study demonstrates that HFPO-TA can induce apoptosis by regulating the crosstalk between ER and mitochondria, ultimately leading to liver damage. These findings reveal the significant hepatotoxicity of HFPO-TA and its potential mechanisms.

Molten-Salt-Assisted Strategy Enables High-Rate Micron-Sized Single-Crystal Li-Rich, Mn-Based Layered Oxide Cathode Materials.

Li-rich Mn-based layered oxides (LMLOs) are expected to be the most promising high-capacity cathodes for the next generation of lithium-ion batteries (LIBs). However, the poor cycling stability and kinetics performance of polycrystalline LMLOs restrict their practical applications due to the anisotropic lattice stress and crack propagation during cycling. Herein, B-doped micron-sized single-crystal Co-free LMLOs were obtained by molten-salt (LiNO3 and H3BO3)-assisted sintering. The results reveal that the low-melting-point molten salt can serve as liquid-phase media to improve the efficiency of atomic mass transfer and crystal nucleation and growth. The modified single-crystal LMLO cathodes can resist the accumulation of anisotropic stress and strain during the cycling and reduce interface side reactions, thus achieving excellent high-voltage stability and kinetics performance. The reversible specific capacity of the single crystals is 210.8 mAh g-1 at 1C with a voltage decay rate of 1.95 mV/cycle and up to 161.1 mAh g-1 at 10C with a capacity retention of 81.06% after 200 cycles.

Comparative genomic analysis and multilocus sequence typing of Staphylococcus aureus reveals candidate genes for low-temperature tolerance.

Staphylococcus aureus is one of the most frequently detected foodborne pathogens in cold chain foods. Worryingly, small colony variants (SCVs) can survive in cold environments for a long time and can revert to rapidly growing cells in suitable environments, causing serious food safety issues. This study investigated the underlying mechanism of SCV formation at low temperature (4 °C) via comparative genomics. Multilocus sequence typing (MLST) of 105 strains of S. aureus was divided into 9 sequence types. The ST352 strains exhibited the greatest tolerance to low temperature, with a mean reduction in survival rate of 10.34 % (p < 0.05). Comparative genomics revealed a total of 1941 core genes in the three S. aureus strains, and BB-1 had 468 specific genes, which were enriched mainly in translation, DNA recombination, DNA repair, metabolic pathways, two-component systems, and quorum sensing. Molecular docking analysis revealed that the binding of the RsbW protein to the SigB protein of BB-1 decreased due to base mutations in rsbW, while the binding to the RsbV protein was enhanced. In addition, the results of real-time quantitative PCR showed that the RsbV-RsbW/SigB system of BB-1 may play a role in the low-temperature survival of S. aureus and the formation of SCVs. These results suggest that genes specific to BB-1 may contribute to the mechanism of adaptation to low temperature and the formation of SCVs. This study helps elucidate the causes of SCV formation by S. aureus at low temperature at the molecular level and provides a basis for exploring the safety control of cold chain food environments.

Unraveling the cross-talk between N6-methyladenosine modification and non-coding RNAs in breast cancer: Mechanisms and clinical implications.

In recent years, breast cancer (BC) has surpassed lung cancer as the most common malignant tumor worldwide and remains the leading cause of cancer death in women. The etiology of BC usually involves dysregulation of epigenetic mechanisms and aberrant expression of certain non-coding RNAs (ncRNAs). N6-methyladenosine (m6A), the most prevalent RNA modification in eukaryotes, widely exists in ncRNAs to affect its biosynthesis and function, and is an important regulator of tumor-related signaling pathways. Interestingly, ncRNAs can also regulate or target m6A modification, playing a key role in cancer progression. However, the m6A-ncRNAs regulatory network in BC has not been fully elucidated, especially the regulation of m6A modification by ncRNAs. Therefore, in this review, we comprehensively summarize the interaction mechanisms and biological significance of m6A modifications and ncRNAs in BC. Meanwhile, we also focused on the clinical application value of m6A modification in BC diagnosis and prognosis, intending to explore new biomarkers and potential therapeutic targets.

Plasma microRNA-320c as a Potential Biomarker for the Severity of Knee Osteoarthritis and Regulates cAMP Responsive Element Binding Protein 5 (CREB5) in Chondrocytes.

Objective: Osteoarthritis (OA) is a commonly known prevalent joint disease, with limited therapeutic methods. This study aimed to investigate the expression of plasma microRNA-320c (miR-320c) in patients with knee OA and to explore the clinical value and potential mechanism of miR-320c in knee OA. Methods: Forty knee OA patients and 20 healthy controls were enrolled. The levels of plasma miR-320c and plasma inflammatory cytokines were measured by real-time PCR or ELISA. Correlations of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and cytokine levels with the miR-320c expression level were evaluated by Pearson correlation analysis. Then, a receiver operating characteristic (ROC) curve was drawn to analyse the diagnostic value of miR-320c in OA. Finally, the interaction of miR-320c and cAMP responsive element binding protein 5 (CREB5) was determined using a luciferase reporter assay, and the effect of CREB5 on the cAMP pathway was assessed. Results: The expression level of plasma miR-320c was significantly higher in OA patients than in healthy controls (p < 0.05). The increased plasma miR-320c level was positively correlated with the WOMAC score (r = 0.796, p < 0.001) and the plasma interleukin (IL)-1ß (r = 0.814, p < 0.001) and IL-6 (r = 0.695, p < 0.001) levels in patients with OA. ROC curve analysis demonstrated the relatively high diagnostic accuracy of plasma miR-320c for OA. Furthermore, the luciferase reporter assay results showed that miR-320c regulates CREB5 expression by binding to the CREB5 3'-untranslated region. Moreover, suppression of CREB5 significantly reduced the expression levels of c-fos and c-jun. Conclusion: Our results indicate that plasma miR-320c may serve as a potential novel predictor of the severity of knee OA and that miR-320c may play an important role in the pathogenesis of OA through inhibiting the cAMP pathway by targeting CREB5.

Polysulfide Anions [Sx]2- (x = 2, 3, 4, 5): Promising Functional Building Units for Infrared Nonlinear Optical Materials.

Infrared nonlinear optical (IR NLO) materials play significant roles in laser technology. The novel functional building units (FBUs) are of great importance in constructing NLO materials with strong second harmonic generation (SHG). Herein, polysulfide anion [Sx]2- (x = 2, 3, 4, 5) units are investigated on NLO-related properties and structure-performance relationships. Theoretical calculations uncover that the [Sx]2- (x = 2, 3, 4, 5) units are potential IR NLO FBUs with large polarizability anisotropy (δ), hyperpolarizability (ß) and wide HOMO-LUMO gap. Fourteen crystals including [Sx]2- (x = 2, 3, 4, 5) units are calculated and analyzed. The results show that these units can result in a wide IR transmittance range, significant SHG effects, wide band gap Eg (Na2S4: Eg = 3.09 eV), and large birefringence Δn [BaS3 (P21212): Δn = 0.70]. More importantly, it is highlighted that the crystal materials including with [Sx]2- (x = 2, 3, 4, 5) groups are good candidates for the exploration of the outstanding IR NLO materials.

Uneven Strain Distribution Induces Consecutive Dislocation Slipping, Plane Gliding, and Subsequent Detwinning of Penta-Twinned Nanoparticles.

Twin structures possess distinct physical and chemical properties by virtue of their specific twin configuration. However, twinning and detwinning processes are not fully understood on the atomic scale. Integrating in situ high resolution transmission electron microscopy and molecular dynamic simulations, we find tensile strain in the asymmetrical 5-fold twins of Au nanoparticles leads to twin boundary migration through dislocation sliding (slipping of an atomic layer) along twin boundaries and dislocation reactions at the 5-fold axis under an electron beam. Migration of one or two layers of twin planes is governed by energy barriers, but overall, the total energy, including surface, lattice strain, and twin boundary energy, is relaxed after consecutive twin boundary migration, leading to a detwinning process. In addition, surface rearrangement of 5-fold twinned nanoparticles can aid in the detwinning process.

The fatty acid 2-hydroxylase CsSCS7 is a key hyphal growth factor and potential control target in Colletotrichum siamense.

SCS7 is a fatty acid 2-hydroxylase required for the synthesis of inositol phosphorylceramide but is not essential for normal growth in Saccharomyces cerevisiae. Here, we demonstrate that the Colletotrichum siamense SCS7 homolog CsSCS7 plays a key role in hyphal growth. The CsSCS7 deletion mutant showed strong hyphal growth inhibition, small conidia, and marginally reduced sporulation and also resulted in a sharp reduction in the full virulence and increasing the fungicide sensitivity. The three protein domains (a cytochrome b5 domain, a transmembrane domain, and a hydroxylase domain) are important to CsSCS7 protein function in hyphal growth. The fatty acid assay results revealed that the CsSCS7 gene is important for balancing the contents of multiple mid-long- and short-chain fatty acids. Additionally, the retarded growth and virulence of C. siamense ΔCsSCS7 can be recovered partly by the reintroduction of homologous sequences from Magnaporthe oryzae and Fusarium graminearum but not SCS7 of S. cerevisiae. In addition, the spraying of C. siamense with naked CsSCS7-double-stranded RNA (dsRNAs), which leads to RNAi, increases the inhibition of hyphal growth and slightly decreases disease lesions. Then, we used nano material Mg-Al-layered double hydroxide as carriers to deliver dsRNA, which significantly enhanced the control effect of dsRNA, and the lesion area was obviously reduced. These data indicated that CsSCS7 is an important factor for hyphal growth and affects virulence and may be a potential control target in C. siamense and even in filamentous plant pathogenic fungi.IMPORTANCECsSCS7, which is homologous to yeast fatty acid 2-hydroxylase SCS7, was confirmed to play a key role in the hyphal growth of Colletotrichum siamense and affect its virulence. The CsSCS7 gene is involved in the synthesis and metabolism of fatty acids. Homologs from the filamentous fungi Magnaporthe oryzae and Fusarium graminearum can recover the retarded growth and virulence of C. siamense ΔCsSCS7. The spraying of double-stranded RNAs targeting CsSCS7 can inhibit hyphal growth and reduce the disease lesion area to some extent. After using nano material Mg-Al layered double hydroxide as carrier, the inhibition rates were significantly increased. We demonstrated that CsSCS7 is an important factor for hyphal growth and affects virulence and may be a potential control target in C. siamense and even in filamentous plant pathogenic fungi.