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This paper presents a decoupled modal reduction method for the steady-state vibration analysis of vibro-acoustic systems characterized by non-classical damping. The proposed approach initially reduces the order of the coupled governing equations of the vibro-acoustic system through the utilization of non-coupled modes, subsequently employing the complex mode superposition technique to address non-classical damping effects. By leveraging non-coupled modes, this method circumvents the need to solve for coupled modes as required in traditional modal reduction techniques, thereby diminishing both computational complexity and cost. Furthermore, the complex mode superposition method facilitates the decoupling of coupled governing equations with non-classical damping, enhancing computational efficiency. Numerical examples validate both the accuracy and effectiveness of this methodology. Given that modal decomposition is independent of frequency, an analysis of computational efficiency across various stages further substantiates that this method offers significant advantages in terms of efficiency for computational challenges encountered over a broad frequency range.

Background: AIDS-related NK/T-cell lymphoma is a rare subtype of AIDS-related lymphomas, characterized by a poor prognosis and lack of standardized treatment protocols. To date, there have been no reported cases of AIDS-associated NK/T-cell lymphoma in remission followed by treatment-related acute myeloid leukemia (t-AML), where both the lymphoma and AML achieved remission and long-term survival through chemotherapy alone. Case presentation: We report a case of a patient diagnosed with AIDS-related extra-nodal NK/T-cell lymphoma (ENKTCL). The patient achieved complete remission after receiving six cycles of chemotherapy, local radiotherapy, and combination antiretroviral therapy (cART). Throughout the follow-up period, the patient continued cART treatment, maintaining an HIV-RNA level below the lower limit of detection. However, 70 months later, the patient developed new symptoms and was subsequently diagnosed with acute myeloid leukemia (AML) M4 subtype. Following the completion of 10 cycles of chemotherapy and ongoing cART, the patient achieved complete remission of AML, with an overall survival time exceeding 103 months from the initial ENKTCL diagnosis. Conclusions: This case highlights the effectiveness of chemotherapy combined with cART in the treatment of AIDS-associated NK/T-cell lymphoma and secondary treatment-related leukemia. This approach may serve as a viable option for patients who are not candidates for bone marrow transplantation. Furthermore, this case underscores the importance of long-term follow-up in the management of AIDS-associated malignancies.

Abstract Background Biliary tract cancers have garnered significant attention due to their highly malignant nature. The relationship between abnormal lipid metabolism and tumor occurrence and development is a research hotspot. However, its correlation with biliary tract cancers is unclear. Methods We enrolled 78 patients with biliary tract cancers and obtained data on clinical characteristics, pathological findings, and preoperative blood lipid indices, including total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), triglycerides (TG), and lipoprotein (a) [Lp(a)]. Receiver operating characteristic (ROC) curves were used to determine the optimal predictive cutoff values of lipid indicators among the participants. Independent risk factors were determined using Cox regression, and survival was predicted using the Kaplan–Meier method. Statistical analyses were performed using SPSS software. Results Univariate Cox regression analysis revealed that the body mass index (BMI), tumor location, surgical margin, N stage, and abnormally increased LDL‐C, TG, and Lp(a) levels were significantly associated with poor prognosis of biliary tract cancers (p

Ecological compensation (EC) is essential to promote the coordinated and sustainable development of the watershed. Firstly, the synergetic development index system of the watershed EC was proposed, which includes the economic benefits, water conservation, pollution treatment, and environmental supervision. Then, the order degree of subsystems was calculated. Finally, the synergetic development level of the watershed EC was evaluated. Taking the upstream (Ma'anshan) and the downstream (Nanjing) of the Chu River as the case study area, the results showed that: (1) From 2011 to 2020, the synergetic development level between Ma'anshan and Nanjing has showed an upward trend; (2) The synergetic development level of the watershed EC in the Chu River has reached basic synergy in 2020; (3) Ma'anshan concentrates on protecting the water ecological environment while Nanjing concentrates on economic growth and water pollution control will improve the synergy degree. This study can provide references for the optimization of watershed EC mechanism, and to promote watershed coordinated development. HIGHLIGHTS The watershed ecological compensation (EC) synergetic development index system is proposed.; The synergy degree between upstream and downstream is analyzed.; The upstream focuses on ecological environment protection while the downstream focuses on water pollution control will improve the efficiency of EC.;

Industrial water saving is an objective requirement for the high-quality development of the Yellow River Basin, as water resource is the largest rigid constraint. In this study, water resources input-output model, structural decomposition analysis (SDA) and structural path analysis (SPA) were constructed to decompose the driving factors of total water use in typical water-deficient provinces (Ningxia, Shanxi, and Henan) in China's Yellow River Basin, to calculate their water use at each production stage and identify their key water-saving pathways. The results were as follows: (i) Water intensity had the most obvious impact on total water saving, resulting in efficiency improvements of 81.39%, 9.21%, and 78.45% for each province, respectively. The next factor was the final demand structure, which suppressed total water-saving efforts by 24.23%, 11.52%, and 113.12% in the respective provinces. (ii) The key water-saving paths in the typical water-deficient provinces of the Yellow River Basin were primarily centered around Sector 1. (iii) Water intensity had a strong water-saving effect on the key paths in the three provinces, with contribution rates of 100.42%, 59.02%, and 42.34% for Ningxia, Henan, and Shanxi, respectively. Final demand also contributed to water-saving in the key paths of Shanxi and Henan, with contribution rates of 35.06% and 28.23%, respectively. However, it inhibited water-saving efforts in the key paths of Ningxia, reducing it by 8.64%. Policy measures should be tailored to local conditions.

Thrombocytopenia represents one of the most prevalent hematologic complications observed in patients infected with the human immunodeficiency virus (HIV). In this study, we sought to analyze the clinical characteristics and treatment outcomes of patients with coexisting HIV and thrombocytopenia. Specifically, we retrospectively examined the medical records of 45 patients diagnosed with HIV/AIDS and thrombocytopenia at the Yunnan Infectious Diseases Specialist Hospital between January 2010 and December 2020, all of whom received highly active antiretroviral therapy (HAART) with/without glucocorticoids. The median follow-up period was 79 days, ranging between 14 and 368 days, the total platelet count was higher after receiving treatment than before (Z = −5.662, P < .001). Among the cohort, 27 patients (60.0%) responded to treatment, with 12 patients (44.44%) experiencing relapse during the follow-up period. The response rate (80.00%) of newly diagnosed ITP were significantly higher than of persistent ITP (28.57%) and chronic ITP (38.46%) ($${\x}$$ 2 = 9.560, P = .008) and the relapse rate of the newly diagnosed ITP (30.00%) was significantly lower than the persistent ITP and chronic ITP (100.00%, 80.00%) ($${\x}$$2 = 6.750, P = .034). Notably, we found that the number of CD4+ T cells, duration of HIV infection, selection of HAART and type of glucocorticoids administered displayed no statistically significant effect on platelet count, treatment response, or relapse rate. However, we observed a significant decrease in platelet count in hepatitis C virus-positive individuals coinfected with HIV compared to those with HIV alone (Z = −2.855, P = .003). Our findings suggest that patients diagnosed with HIV and thrombocytopenia exhibit a low response rate to treatment and have an increased likelihood of relapse.

Diabetic Kidney Disease (DKD) is one of the significant microvascular consequences of type 2 diabetes mellitus with a complex etiology and protracted course. In the early stages of DKD, the majority of patients experience an insidious onset and few overt clinical symptoms and indicators, but they are prone to develop end-stage renal disease in the later stage, which is life-threatening. The abnormal amino acid metabolism is tightly associated with the development of DKD, which involves several pathological processes such as oxidative stress, inflammatory response, and immune response and is also closely related to autophagy, mitochondrial dysfunction, and iron death. With a focus on taurine, branched-chain amino acids (BCAAs) and glutamine, we explored the biological effects of various amino acid mechanisms linked to DKD, the impact of amino acid metabolism in the early diagnosis of DKD, and the role of amino acid metabolism in treating DKD, to offer fresh objectives and guidelines for later early detection and DKD therapy.

This paper reports the detection of ferric ions (Fe ^3+ ) based on nitrogen and sulfur co-doped carbon quantum dots. These nitrogen and sulfur co-doped carbon quantum dots were synthesized via a hydrothermal route using northern Shaanxi potatoes as carbon sources and ammonium sulfate as nitrogen and sulfur sources. The quantum yields of the carbon quantum dots were found to be 16.96% and 4.23% with and without doping, respectively. The structural details, morphology, and optical properties of carbon quantum dots were analyzed using Fourier transform infrared spectroscopy (FT-IR), x-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), ultraviolet-visible absorption spectroscopy (UV–vis), and fluorescence spectroscopy. The as-prepared co-doped carbon quantum dots were utilized as a fluorescent probe for detecting Fe ^3+ ions, where the fluorescence intensity of carbon quantum dots was remarkably quenched in the presence of Fe ^3+ ions. A good linear relationship for Fe ^3+ ion detection was obtained from 0 to 500 μ mol/L with a detection limit as low as 0.26 μ mol/L. Furthermore, the proposed method also provided satisfactory results in the tap water.

Background: Gastric intestinal metaplasia (IM) is the key link of gastric precancerous lesions. Ferroptosis is a novel form of programmed cell death. However, its impact on IM is unclear. The focus of this study is to identify and verify ferroptosis-related genes (FRGs) that may be involved in IM by bioinformatics analysis.Materials and methods: Differentially expressed genes (DEGs) were obtained from microarray dataset GSE60427 and GSE78523 downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed ferroptosis-related genes (DEFRGs) were obtained from overlapping genes of DEGs and FRGs got from FerrDb. DAVID database was used for functional enrichment analysis. Protein-protein interaction (PPI) analysis and Cytoscape software were used to screen hub gene. In addition, we built a receiver operating characteristic (ROC) curve and verified the relative mRNA expression by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Finally, the CIBERSORT algorithm was used to analyze the immune infiltration in IM.Results: First, a total of 17 DEFRGs were identified. Second, a gene module identified by Cytoscape software was considered as hub gene: PTGS2, HMOX1, IFNG, and NOS2. Third, ROC analysis showed that HMOX1 and NOS2 had good diagnostic characteristics. qRT-PCR experiments confirmed the differential expression of HMOX1 in IM and normal gastric tissues. Finally, immunoassay showed that the proportion of T cells regulatory (Tregs) and macrophages M0 in IM was relatively higher, while the proportion of T cells CD4 memory activated and dendritic cells activated was lower.Conclusion: We found significant associations between FRGs and IM, and HMOX1 may be diagnostic biomarkers and therapeutic targets for IM. These results may enhance our understanding of IM and may contribute to its treatment.

Background: Combination of Polygonum capitatum Buch.-Ham. ex D. Don extract (PCE) and ciprofloxacin (CIP) was commonly prescribed in the treatment of urinary tract infections. Their pharmacokinetic herb-drug interactions (HDIs) were focused in this study to assess potential impact on the safety and effectiveness.Methods: A randomized, three-period, crossover trial was designed to study the pharmacokinetic HDI between PCE and CIP in healthy humans. Their pharmacokinetic- and tissue distribution-based HDIs were also evaluated in rats. Gallic acid (GA) and protocatechuic acid (PCA) were chosen as PK-markers of PCE in humans and rats. Potential drug interaction mechanisms were revealed by assessing the effects of PCE on the activity and expression of multiple transporters, including OAT1/3, OCT2, MDR1, and BCRP.Results: Concurrent use of PCE substantially reduced circulating CIP (approximately 40%–50%) in humans and rats, while CIP hardly changed circulating GA and PCA. PCE significantly increased the tissue distribution of CIP in the prostate and testis of rats, but decreased in liver and lungs. Meanwhile, CIP significantly increased the tissue distribution of GA or PCA in the prostate and testis of rats, but decreased in kidney and heart. In the transporter-mediated in vitro HDI, GA and PCA presented inhibitory effects on OAT1/3 and inductive effects on MDR1 and BCRP.Conclusion: Multiple transporter-mediated HDI contributes to effects of PCE on the reduced systemic exposure and altered tissue distribution of CIP. More attention should be paid on the potential for PCE-perpetrated interactions.

The aim of this study was to investigate the effects of fermented Caragana korshinskii feed on meat quality in three muscle tissues (longissimus dorsi m., triceps brachii and biceps femoris) in Tan sheep. Sheep were randomly divided into two groups: the control group was fed a basic diet, and the experimental group was fed the basic diet supplemented with 10% fermented Caragana korshinskii. The results for the meat quality characteristics showed that the fermented Caragana korshinskii group had significantly greater more crude protein in all three muscles and more ash in the longissimus dorsi m. and triceps brachii than the control group. The fermented Caragana korshinskii group had a significantly higher ultimate pH in the biceps femoris and triceps brachii than the control group. The fermented Caragana korshinskii group had greater inosinic acid content in the longissimus dorsi m. and triceps brachii than the control group. The fermented Caragana korshinskii group had significantly higher levels of Asp, Thr, Glu and Ser in the triceps brachii than the control group. The fermented Caragana korshinskii group had significantly higher levels of C12:0 in the triceps brachii, of C15:0 and C16:0 in the biceps femoris, of C16:1 in the longissimus dorsi m. and triceps brachii, of C18:0 in the triceps brachii than the control group. Therefore, adding 10% fermented Caragana korshinskii to the diet of the sheep significantly improved the crude protein, ash, inosinic acid, partial amino acid and fatty acid contents as well as the ultimate pH and L* values in Tan sheep muscles.HIGHLIGHTS Fermentative caragana korshinskii was partially substituted for corn stalk to feed Tan sheep could significantly improve crude protein, ash, ultimate pH, L* value, inosinic acid, partial amino acid and fat acid species and content of Tan sheep. It was provided scientific basis for the rational utilization of caragana korshinskii resources by studying its effect on meat quality of Tan sheep. Fermented Caragana korshinskii solves the problem of lack of forage resources in China and the imbalance of forage supply in winter and spring in China.

Graphene has presented promising features for application in lithium ion batteries(LIBs) due to its superior electronic conductivity and high surface area. It has been successfully used for modifying cathode materials to meet the increasing demand for LIBs with longer cycle life. However, the improving effect of graphene on cycling stability is still unclear, which restricts its further application in LIBs. Herein, graphene coated hollow sphere-like structure LiNi0.5Mn1.5O4(LNMO) wasdesigned and the improvement mechanism of graphene coating on LNMO’s cycling stability was investigated. The results show that graphene coating not only contributes to suppress structural deformation from mechanistic reaction and extend solid-solution reaction, but also helps protect electrode from corrosion by the products from electrolyte decomposition and suppress the generation of surface defects, especially at high temperature. Owing to graphene coating, graphene coated LNMO can deliver a discharge capacity of 91 mAh g−1 with high capacity retention of 82.5% after 1000 cycles under 20C and 83.8 mAh g−1 with 94.5% capacity retention after 100 cycles under 2C at 55 °C. This work deeply explores the effect of graphene coating on cycling stability from crystal stability and surface stability, which will help a wider application of graphene in energy storage field.

The aim of this study was to investigate the effects of fermented Caragana korshinskii on the intramuscular fat content and varied expression of the intramuscular fat deposition-related genes FABP3, UBE3C, ADRB3, LIPE, and SCD among four muscle tissues (m. psoas, gluteus, quadriceps, and supraspinatus) of Tan sheep. Twenty-eight male animals of similar age (270 ± 10 days) and weight (24.6 ± 1.06 kg) were randomly divided into a control group (fed the basal diet) and an experimental group (fed the same diet except 10% of corn stalks were replaced with fermented C. korshinskii). Soxhlet petroleum-ether extraction and quantitative real-time PCR were applied to evaluate the fat content and gene expression in tissues, respectively. We observed a significant improvement (P < 0.05) in the intramuscular fat contents in the m. gluteus and supraspinatus of treated sheep compared to those of non treated sheep. The FABP3 mRNA level was markedly higher (P < 0.05) in the m. quadriceps and supraspinatus of treated sheep than in the control sheep. UBE3C mRNA levels were significantly decreased in the m. gluteus, quadriceps, and supraspinatus (P < 0.05) of treated sheep compared with those of the control sheep. ADRB3 mRNA levels were significantly lower (P < 0.05) in the m. psoas, gluteus, and supraspinatus of sheep fed fermented C. korshinskii than in the control group, whereas LIPE mRNA levels were significantly increased (P < 0.05) in the m. gluteus and quadriceps of sheep fed fermented C. korshinskii. The SCD mRNA levels in m. psoas, quadriceps, and supraspinatus of sheep fed fermented C. korshinskii were significantly higher than those of the control group (P < 0.05). Our results indicated that fermented C. korshinskii could partially replace the roughage used in Tan sheep feed, and its substitution affected the intramuscular fat content and altered the expression of intramuscular fat deposition-related genes. The present study lays a solid foundation for further exploring the utilization of C. korshinskii in ruminant husbandry.

The shuttle effect is understood to be the most significant issue that needs to be solved to improve the performance of lithium–sulfur batteries. In this study, ultrathin two-dimensional Fe–Co bimetallic oxide nanosheets were prepared using graphene as a template, which could rapidly catalyze the conversion of polysulfides and inhibit the shuttle effect. Additionally, such ultrathin nanostructures based on graphene provided sufficient active sites and fast diffusion pathways for lithium ions. Taking into account the aforementioned benefits, the ultrathin two-dimensional Fe–Co bimetallic oxide nanosheets modified separator assembled lithium–sulfur batteries delivered an incredible capacity of 1044.2 mAh g−1 at 1 C and retained an excellent reversible capacity of 859.4 mAh g−1 after 100 cycles. Even under high loading, it still achieved high area capacity and good cycle stability (92.6% capacity retention).

Previous studies have shown that some of the histone deacetylases (HDACs) play diverse roles in the regulation of ovarian somatic cell development, oocyte maturation and early embryonic development in different species including sheep. This study aimed to clarify whether HDAC1 also played pivotal roles in regulating oocyte maturation in Tan sheep. The results showed that HDAC1 was expressed in the nuclei of both the granulosa cells and oocytes of the growing follicles in the Tan sheep’s ovaries. However, the level of HDAC1 was unaffected by luteinizing hormone (LH) induction in cultured granulosa cells. Meanwhile, the specific inhibition of HDAC1 using pyroxamide did not induce significant changes in the expression levels of EGF-like growth factors in vitro, whereas both the cumulus expansion and oocyte maturation of the cultured cumulus oocyte complexes (COCs) were significantly inhibited by pyroxamide. Additionally, the numbers of histone acetylation sites (H4K5, H4K12, H3K14 and H3K9) in ovarian granulosa cells were significantly increased. In conclusion, a constant expression of HDAC1 in the growing follicles of Tan sheep may be pivotal for supporting oocyte growth and maturation, although its action may not be closely correlated with LH induction, nor does it directly affect the expression of the EGF-like factors. Our study implies that there may exist diverse functions of the respective HDACs in modulating female reproduction in sheep.

Predominant odorants in modern and traditional types of Chinese xiaoqu liquor (Baijiu) were identified and compared by the combined use of gas chromatography−olfactometry, odor activity values (OAVs), and multivariate analyses. A total of 79 aroma compounds were identified in a typical modern type xiaoqu Baijiu (M) and a typical traditional type xiaoqu Baijiu (T), 42 of them had OAV > 1 in both M and T samples. The main differences between the two samples were obtained for the concentration of 23 aroma-active compounds. A total of 22 samples made by different brewing processes were analyzed to confirm the differences. Partial least squares discriminant analysis confirmed that 20 compounds could be used as potential markers for discrimination between modern type xiaoqu Baijiu and traditional type xiaoqu Baijiu. Their difference in content is between 1.5 and 17.9 times for modern type xiaoqu Baijiu and traditional type xiaoqu Baijiu. The results showed the aroma characteristics of modern and traditional type xiaoqu Baijiu clearly and comprehensively, which will provide guidance for modern Baijiu quality control and evaluation.

Objective To investigate the relationship between pretreatment plasma D-dimer levels and survival in Chinese patients with small cell lung cancer (SCLC). Methods This retrospective study enrolled 82 patients with SCLC treated at Beijing Chaoyang Hospital, Capital Medical University, from January 2012 to January 2015. All patients were followed up. Associations between pretreatment plasma D-dimer levels measured by immunoturbidimetric assay and clinical outcomes were analyzed by Kaplan–Meier and multivariate analyses, using a cut-off level of 0.55 mg/L fibrinogen equivalent units (FEU). Results Median progression-free survival (PFS) and overall survival (OS) were significantly higher in patients with low D-dimer levels (≤0.55 mg/L FEU; 8.0 and 17.0 months, respectively) compared with patients with high levels (>0.55 mg/L FEU; 5.0 and 9.0 months, respectively). Plasma D-dimer levels, Karnofsky performance status, N stage, TNM stage, treatment, and neuron-specific enolase (NSE) levels were significantly associated with PFS, while D-dimer levels, N stage, TNM stage, and treatment were significantly associated with OS. Multivariate analysis revealed that TNM stage, treatment, and NSE levels were independently associated with PFS, while D-dimer levels and treatment were independently associated with OS. Conclusions Pretreatment plasma D-dimer levels were independently associated with OS in patients with SCLC.

Using FeCl3 and FeSO4 as precursors, Fe3O4 were prepared by co-precipitation method via FeCl3 and FeSO4 aqueous solutions successively added to NaOH solution. The sample was proved by X-ray powder diffraction, transmission electron microscope, ultraviolet–visible spectrophotometry and magnetic measurement. The results showed that the prepared Fe3O4 material was composed of an average diameter of about 15 nm particles and nano rods with well-crystallized magnetite and stronger superparamagnetic, getting a saturation magnetization of 49.5 emu g−1. This Fe3O4 material was found to be an effective catalyst for photodegradation of naphthalene with or without H2O2 under visible light irradiation, getting 81.1% and 74.3% degradation rate in these two cases, respectively. The degradation pathway in the absence and presence of H2O2 was analysed via measurement of the distribution of degradation products by GC-MS and adsorption of reactants on the surface of the catalyst by in situ DRIFTS spectra.

What are laws of nature? This issue has always been one of the core issues of philosophy of science. Info-computationalism uses algorithms and information to explain laws of nature, and analyses its nature from the perspective and invariance, which opens up a new path for laws of nature. Therefore, this paper, based on the theory of info-computationalism, compares them to Cartwright’s concept of laws of nature. It is found that we can follow the laws in computers to understand the laws of nature, and regard the laws of nature as human, metaphorical, prescriptive and creative products.

The electronic band structure and valley splitting of the WSe _2 /NiCl _2 heterostructure have been investigated by density functional theory and Berry curvature calculations. We demonstrate that the valley polarization of monolayer WSe _2 is induced due to the magnetic proximity effect caused by the single layer of ferromagnetic NiCl _2 . The magnitude of valley splitting depends on the stacking configurations of WSe _2 /NiCl _2 , and the maximum value of valley splitting reaches −11.87 meV. Large valley splitting can be achieved by adjusting the layer spacing and constructing a NiCl _2 /WSe _2 /NiCl _2 heterojunction with Ni spins arranged in parallel between two NiCl _2 sheets. The valley-contrasting Berry curvature between the K and K ′ valleys suggests that the WSe _2 /NiCl _2 -based heterostructure could potentially be used as a valleytronic device to realize the valley-polarized anomalous Hall effect as both spin and valley filter.

Neutral tone (T0) is a special tone form in Mandarin that contains tonal and stress information. Compared with canonical tones, T0 has a much shorter duration and reduced pitch contour. Its tonal contour is determined by the preceding canonical tone. However, not much is known about the perception of tonal and stress information in T0. In the current study, we investigate (1) whether T0 can be perceived as lexically unstressed by stress-language listeners; and (2) how Mandarin (tone language)- and Dutch (stress language)-learning infants perceive T0. Three experiments were conducted. In Experiment 1, Dutch adults identified T0 as unstressed when presented with disyllabic sequences ending in T0. In Experiment 2, we used the visual fixation paradigm to test 4- to 6-month-old and 10- to 12-month-old Dutch and Mandarin infants on pseudoword discrimination (/pan1san4/ [high-level + high-falling] and /pan1san0/ [high-level + mid-falling]). T4 and T0 each exhibit a similar falling contour. The results show that (1) after being habituated to neutral tone sequences (/pan1san0/), Dutch infants discriminated the T1T0–T1T4 contrast; and (2) neither age groups of Mandarin infants discriminated the tone contrast. Assuming Mandarin infants’ lack of discrimination might be due to the similar F0 contours, we tested Mandarin infants in Experiment 3 using a more salient contrast, /pan1san2/ (high-level + mid-rising) and /pan1san0/. While no overall discrimination was observed, those who were habituated to /pan1san0/ demonstrated discrimination. The continuous discrimination of Dutch infants suggests that they might process neutral–canonical tone contrast as lexical stress rather than as tonal information. Overall, Mandarin infants’ failure implies that the representation of T0 is not complete during their 1st year of life; the acquisition of tonal categories may therefore take longer than we expected.

Stress granules (SGs) contain stalled messenger ribonucleoprotein complexes and are related to the regulation of mRNA translation. Picornavirus infection can interfere with the formation of SGs. However, the detailed molecular mechanisms and functions of picornavirus-mediated regulation of SG formation are not clear. Here, we found that the 2A protease of a picornavirus, EV71, induced atypical stress granule (aSG), but not typical stress granule (tSG), formation via cleavage of eIF4GI. Furthermore, 2A was required and sufficient to inhibit tSGs induced by EV71 infection, sodium arsenite, or heat shock. Infection of 2A protease activity-inactivated recombinant EV71 (EV71-2AC110S) failed to induce aSG formation and only induced tSG formation, which is PKR and eIF2α phosphorylation-dependent. By using a Renilla luciferase mRNA reporter system and RNA fluorescence in situ hybridization assay, we found that EV71-induced aSGs were beneficial to viral translation through sequestering only cellular mRNAs, but not viral mRNAs. In addition, we found that the 2A protease of other picornaviruses such as poliovirus and coxsackievirus also induced aSG formation and blocked tSG formation. Taken together, our results demonstrate that, on one hand, EV71 infection induces tSG formation via the PKR-eIF2α pathway, and on the other hand, 2A, but not 3C, blocks tSG formation. Instead, 2A induces aSG formation by cleaving eIF4GI to sequester cellular mRNA but release viral mRNA, thereby facilitating viral translation.

Cutaneous eruption is a common drug-adverse reaction, characterised by keratinocytes inflammation and apoptosis. Shuanghuanglian injeciton (SHLI) is a typical Chinese medicine injection, which is used to treat influenza. It has been reported that SHLI has the potential to induce cutaneous adverse eruptions. However, the mechanisms remain unclear. Since desmoglein 1 (DSG1) shows a crucial role in maintaining skin barrier function and cell susceptibility, we assume that DSG1 plays a critical role in the cutaneous eruptions induced by SHLI. In our study, retinoic acid (RA) was selected to downregulate the DSG1 expression, and lipopolysaccharide (LPS) was first used to identify the susceptibility of the DSG1-deficiency Hacat cells. Then, SHLI was administrated to normal or DSG1-deficient Hacat cells and mice. The inflammatory factors and apoptosis rate were evaluated by RT-PCR and flow cytometry. The skin pathological morphology was observed by hematoxylin and eosin (HE) staining. Our results show that treated only with SHLI could not cause IL-4 and TNF-α mRNA increases in normal Hacat cells. However, in the DSG1-deficient Hacat cells or mice, SHLI induced an extreme increase of IL-4 and TNF-α mRNA levels, as well as in the apoptosis rate. The skin tissue showed a local inflammatory cell infiltration when treated with SHIL in the DSG1-deficient mice. Thus, we concluded that DSG1 deficiency was a potential causation of SHLI induced eruptions. These results indicated that keratinocytes with DSG1 deficiency were likely to induce the cutaneous eruptions when stimulated with other medicines.