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ABSTRACT: Mitochondrial dysfunction has been reported to occur in the mammary gland of dairy cows suffering from ketosis. Prohibitin 2 (PHB2) plays a crucial role in regulating mitophagy, which clears impaired mitochondria to maintain normal mitochondrial function. Therefore, the current study aimed to investigate how PHB2 mediates mitophagy, thereby influencing mitochondrial function in the immortalized bovine mammary epithelial cell line (MAC-T cells). First, mammary gland tissue and blood samples were collected from healthy cows (n = 15, BHB 3.0 mM). Compared with healthy cows, cows with clinical ketosis exhibited lower DMI, milk production, milk protein, milk lactose, and serum glucose. In contrast, milk fat, serum nonesterified fatty acids (NEFA) and BHB were greater in cows with clinical ketosis. The protein abundance of PHB2, peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α), mitofusin 2 (MFN2) in whole cell lysates (WCL), as well as PHB2, sequestosome-1 (SQSTM1, also called p62), microtubule-associated protein 1 light chain 3-II (MAP1LC3-II, also called LC3-II), and ubiquitinated proteins in mitochondrial fraction were significantly lower in cows with clinical ketosis. The ATP content of mammary gland tissue in cows with clinical ketosis was lower than that of healthy cows. Second, MAC-T were cultured and treated with NEFA (0, 0.3, 0.6, 1.2 mM). The MAC-T treated with 1.2 mM NEFA displayed decreased protein abundance of PHB2, PGC-1α, and MFN2 in WCL, as well as protein abundance of PHB2, p62, LC3-II, and ubiquitinated proteins in mitochondrial fraction. The content of ATP and JC-1 aggregates in 1.2 mM NEFA group were lower than in the 0 mM NEFA group. Additionally, 1.2 mM NEFA disrupted the fusion between mitochondria and lysosomes. The MAC-T were then pretreated with 100 nM rapamycin, followed by treatment with or without NEFA. Rapamycin alleviated impaired mitophagy and mitochondria dysfunction induced by 1.2 mM NEFA. Third, MAC-T were transfected with small interfering RNA to silence PHB2 or a plasmid for overexpression of PHB2, followed by treatment with or without NEFA. The silencing of PHB2 aggravated 1.2 mM NEFA-induced impaired mitophagy and mitochondrial dysfunction, whereas the overexpression of PHB2 alleviated these effects. Overall, this study provides evidence that PHB2, in regulation of mitophagy, is a mechanism for bovine mammary epithelial cells to counteract NEFA-induced mitochondrial dysfunction.

In order to improve the drying quality of rice, Indica and japonica hybrid rice were taken as the object and evaluated by waist burst rate, head rice rate, energy consumption and drying time in this experiment. Single factor and response surface analysis were combined to optimize the drying process. The effects of variable temperature-tempering drying on proteins structure and thermal properties of indica and japonica hybrid rice were investigated by differential scanning calorimetry. Fourier infrared spectroscopy and fluorescence spectroscopy. The results showed variable temperature-tempering drying (temperature range 30~60 ℃) that under the conditions of temperature rise 5 ℃, wind speed 1 m/s and tempering ratio 0.6, the rice could be kept in the glassy state, and the waistband burst rate and head rice rate after drying were 79.89% lower and 39.54% higher than those in the constant temperature group (60 ℃), respectively. Under these conditions, the polarity of rice proteins decreased and intermolecular aggregation occured, which improved the thermal stability of rice proteins, and the α-helix content increased from 16.21% to 17.64%. Scanning electron microscope results showed that the surface structure of protein was not significantly affected by variable temperature-tempering drying. The experiment explored and verified the drying mechanism of hybrid rice with variable temperature-tempering drying, which would provide a theoretical and practical reference for the research of high quality drying of hybrid rice.

ABSTRACT: During the perinatal period, dairy cows undergo negative energy balance, resulting in elevated circulating levels of nonesterified fatty acids (NEFA). Although increased blood NEFA concentrations are a physiological adaptation of early lactation, excessive NEFA in dairy cows is a major cause of fatty liver. Aberrant lipid metabolism leads to hepatic lipid accumulation and subsequently the development of fatty liver. Both inositol-requiring enzyme 1α (IRE1α) and c-Jun N-terminal kinase (JNK) have been validated for their association with hepatic lipid accumulation, including their regulatory functions in calf hepatocyte insulin resistance, oxidative stress, and apoptosis. Meanwhile, both IRE1α and JNK are involved in lipid metabolism in nonruminants. Therefore, the aim of this study was to investigate how IRE1α and JNK regulate lipid metabolism in bovine hepatocytes. An experiment was conducted on randomly selected 10 healthy cows (hepatic triglyceride [TG] content 5%). Liver tissue and blood samples were collected from experimental cows. Serum concentrations of NEFA and β-hydroxybutyrate (BHB) were greater, whereas serum concentrations of glucose and milk production were lower in cows with fatty liver. The western blot results revealed that dairy cows with fatty liver had higher phosphorylation levels of JNK, c-Jun, and IRE1α in the liver tissue. Three in vitro experiments were conducted using primary calf hepatocytes isolated from 5 healthy calves (body weight: 30–40 kg; 1 d old). First, hepatocytes were treated with NEFA (1.2 mM) for 0.5, 1, 2, 3, 5, 7, 9, or 12 h, which showed that the phosphorylated levels of JNK, c-Jun, and IRE1α increased in both linear and quadratic effects. In the second experiment, hepatocytes were treated with high concentrations of NEFA (1.2 mM) for 12 h with or without SP600125, a canonical inhibitor of JNK. Western blot results showed that SP600125 treatment could decrease the expression of lipogenesis-associated proteins (PPARγ and SREBP-1c) and increase the expression of fatty acid oxidation (FAO)-associated proteins (CPT1A and PPARα) in NEFA-treated hepatocytes. The perturbed expression of lipogenesis-associated genes (FASN, ACACA, and CD36) and FAO-associated gene ACOX1 were also recovered by JNK inhibition, indicating that JNK reduced excessive NEFA-induced lipogenesis and FAO dysregulation in calf hepatocytes. Third, short hairpin RNA targeting IRE1α (sh-IRE1α) was transfected into calf hepatocytes to silence IRE1α, and KIRA6 was used to inhibit the kinase activity of IRE1α. The blockage of IRE1α could at least partially suppressed NEFA-induced JNK activation. Moreover, the blockage of IRE1α downregulated the expression of lipogenesis genes and upregulated the expression of FAO genes in NEFA-treated hepatocytes. In conclusion, these findings indicate that targeting the IRE1α-JNK axis can reduce NEFA-induced lipid accumulation in bovine hepatocytes by modulating lipogenesis and FAO. This may offer a prospective therapeutic target for fatty liver in dairy cows.

AbstractMedical security support for rehabilitation therapy in China is different from that in other countries. We investigated whether the discharge plan to continue rehabilitation therapy in tertiary hospitals for patients after traumatic spinal cord injury (TSCI) was influenced by payment sources or other conditions. This was a cross-sectional, observational study. Information was collected on the general condition, caregiver, types of payment sources for continued rehabilitation, American Spinal Injury Association Impairment Scale (AIS) scores, and discharge plans. In total, 135 patients with TSCI (107 male, mean age 41.00 ± 13.73 years, mean spinal cord injury duration 238.43 ± 345.54 days) were enrolled. Medical insurance (43%) and out-of-pocket payments (27.4%) were the primary payment sources. Although most patients were beyond the acute phase, 40% continued rehabilitation therapy at other tertiary hospitals. The caregiver, payment sources, injury level, AIS level, and complete urinary tract infection (UTI) were different due to discharge plans (p > .05). Patients seemingly consider a higher AIS level and co-UTI as the requirement for tertiary hospital therapy. In non-medical insurance payment source patients, the discharge plan also differed due to the AIS level and co-UTI (p > .05). However, in medical insurance patients, the discharge plan differed only in terms of TSCI duration (p > .05). The restricted duration of medical coverage restricted the continuation of rehabilitation therapy and influenced the discharge plan of most patients with TSCI.

In order to investigate the effects of different storage temperatures on the storage quality and enzyme activities of Fritillaria thunbergii Miq from the soil, which were stored at 0, 5, 10 and 20 ℃ for 90 d. The changes in weight loss, sensory quality, color, hardness, total polysaccharides, alkaloids, malondialdehyde (MDA) contents, polyphenol oxidase (PPO), peroxidase (POD) and superoxide dismutase (SOD) activities of Fritillaria thunbergii Miq were explored at different storage temperatures. The results showed that the weight loss rate of Fritillaria thunbergii Miq at 0 ℃ for 90 d was only 7.17%, which was significantly lower than that at 5, 10 and 20 ℃ (9.92%, 19.77% and 30.28%) (P

Neuroinflammation and neurodegeneration are key processes that mediate the development and progression of neurological diseases. However, the mechanisms modulating these processes in different diseases remain incompletely understood. Advances in single cell based multi-omic analyses have helped to identify distinct molecular signatures such as Lgals3 that is associated with neuroinflammation and neurodegeneration in the central nervous system (CNS). Lgals3 encodes galectin-3 (Gal3), a β-galactoside and glycan binding glycoprotein that is frequently upregulated by reactive microglia/macrophages in the CNS during various neurological diseases. While Gal3 has previously been associated with non-CNS inflammatory and fibrotic diseases, recent studies highlight Gal3 as a prominent regulator of inflammation and neuroaxonal damage in the CNS during diseases such as multiple sclerosis, Alzheimer's disease, and Parkinson's disease. In this review, we summarize the pleiotropic functions of Gal3 and discuss evidence that demonstrates its detrimental role in neuroinflammation and neurodegeneration during different neurological diseases. We also consider the challenges of translating preclinical observations into targeting Gal3 in the human CNS.

Abstract This study aimed to evaluate the guiding role of left adrenal vein (LAV) for right adrenal venous sampling (AVS). A total of 347 patients who were diagnosed with primary aldosteronism (PA) and underwent successful AVS procedures from January 2020 to July 2021 were retrospectively analyzed. According to the different quadrant position of the orifice of right adrenal vein (RAV), the area where the orifice of RAV is located is divided into three areas: A, B, and C and the area A is further subdivided into A1, A2, and A3 areas. By counting the area where the orifice of RAV is located, the guiding role of the LAV on the RAV is determined. Most of the orifice of RAV are located in area A, and the proportions of areas A, B, and C was 96.8%, 1.4%, and 1.7%, respectively. In area A, areas A1, A2, and A3 account for 80.9%, 17.0%, and 2.1%, respectively. High body mass index, female and smaller the angle between the LAV and horizontal line was associated with the closer positional relationship between the LAV on the RAV. These findings suggest that most of the horizontal position of the RAV orifice is close to the horizontal position of the most distal end of the LAV, which indicate that the LAV location can play an important role on the guiding for right AVS. Additionally, body mass index, sex, and the angle of the LAV was largely related to location of the orifice of the RAV.

ObjectiveThe specific target area of repeated transcranial magnetic stimulation (rTMS) in treating neuropathic pain resulting from spinal cord injury (SCI-NP) remains uncertain.MethodsThirty-four participants with SCI-NP were allocated into three groups, namely, the motor cortex (M1, A) group, the left dorsolateral prefrontal cortex (LDLPFC, B) group, and the control (sham stimulation, C) group. The intervention was administered totally 10 times. Outcome measures assessed pre-(T0) and post-(T1)intervention, including Numerical Rating scale (NRS), anxiety (SAS), depression (SDS), sleep quality (PSQI), brief pain inventory (BPI), and impression of change.ResultsAll outcomes in groups A and B significantly changed after intervention (p

Under the same geological conditions, the thickness and length of the reinforced strip, the slope ratio of the reinforced embankment, the modulus of elasticity of the fill and the reinforced strip, and the friction angle at the interface between the reinforcement and the soil, are the main design parameters that have an important influence on the stress, deformation, and stability of the encompassing reinforced soil embankment. To quickly and accurately determine the optimal design parameters for reinforced soil embankments with wrapped faces, ensuring minimal cost, while maintaining structural safety, we propose a design parameter prediction model based on a GA–BP neural network. This model evaluates parameters within their specified ranges, using maximum lateral displacement, maximum vertical displacement, maximum stress in the XZ direction, the maximum shear strain increment, and the safety factor, as assessment criteria. The primary objective is to minimize the overall cost of the embankment. A comparison with five machine learning algorithms shows that the model has high prediction accuracy, and the optimal design parameter combinations obtained from the optimization search can significantly reduce the cost of the embankment, while controlling the displacement and stability of the embankment. Therefore, the GA–BP network is suitable for predicting the optimal design parameters of reinforced soil embankments with wrapped faces.

Two new polyketide derivatives, penirubenones A and B (1 and 2), and two naturally rare amino-bis-tetrahydrofuran derivatives, penirubenamides A and B (3 and 4), together with nine known compounds (5–13) were isolated from the marine-derived fungus Penicillium rubens BTBU20213035. The structures were identified by HRESIMS and 1D and 2D NMR analyses, and their absolute configurations were determined by a comparison of experimental and calculated electronic circular dichroism (ECD) spectroscopy and 13C NMR data. We found that 6 exhibited antibacterial activity against Staphylococcus aureus, with an MIC value of 3.125 μg/mL, and 1 and 2 showed synergistic antifungal activity against Candida albicans at 12.5 and 50 μg/mL with 0.0625 μg/mL rapamycin.

Biodiversity is the material basis for human survival. At present, the conservation of biodiversity is mainly carried out through nature reserves. As an essential supplement to the existing nature reserve systems in China, the mini reserve is an essential means to connect fragmented habitats for animals and plants and maintain the integrity of ecosystems. This study systematically collates and analyzes the organizational structure, system construction, daily work, and preliminary results of the community-based Qu'nan mini reserve through a literature review and field investigations. The results are as follows: (1) The construction of the Qu'nan mini reserve is based on the mindset of “self-construction, self-financing, self-management, and self-benefit”. It is managed mainly by “equal discussion and democratic consultation” which has been recognized and supported by local community residents, the local government, and the outside world. (2) The establishment, construction, and development of the mini reserve have not only enhance the protection awareness of community residents and increase the number and diversity of surrounding animal and plant populations. It also improves the living environment of the Qu'nan community and enriches the spiritual culture of residents. In addition, this paper also discusses the hidden dangers in the construction of conservation communities. Some feasible suggestions are proposed to provide a reference for developing biodiversity and traditional culture conservation, and other mini reserves in China.

Abstract Radiotherapy and chemotherapy remain the mainstay of treatment for colorectal cancer (CRC), although their efficacy is limited. A detailed understanding of the molecular mechanisms underlying CRC progression could lead to the development of new therapeutic strategies. Although it has been established that MYC signaling is dysregulated in various human cancers, direct targeting MYC remains challenging due to its "undruggable" protein structure. Post-translational modification of proteins can affect their stability, activation, and subcellular localization. Hence, targeting the post-translational modification of MYC represents a promising approach to disrupting MYC signaling. Herein, we revealed that NEK8 positively regulates CRC progression by phosphorylating c-MYC protein at serine 405, which exhibited enhanced stability via polyubiquitination. Our findings shed light on the role of NEK8/MYC signaling in CRC progression, offering a novel and helpful target for colorectal cancer treatment. Video Abstract

Clarifying the mechanical characteristics of gas hydrate-bearing sediments (GHBS) from a mechanical perspective is crucial for ensuring the long-term, safe, and efficient extraction of natural gas hydrates. In this study, seabed soft clay from the northern South China Sea was utilized to prepare clayey silt samples, aligning with gradation curves related to hydrate extraction projects in the Shenhu area of the South China Sea. Utilizing the high-pressure low-temperature hydrate triaxial testing system (ETAS), twelve sets of triaxial shear tests were conducted. The results highlight that increases in hydrate saturation and confining pressure significantly enhance GHBS’ strength and stiffness, with more pronounced volume expansion observed during shearing. These tests have elucidated the mechanical responses of GHBS. Subsequently, empirical formulas were developed to characterize their properties under varying conditions. Additionally, based on the experimental data, the micro-mechanisms of GHBS were analyzed, suggesting that hydrates notably contribute to the filling and cementing effects in GHBS, with these effects varying with changes in hydrate saturation and confining pressure. This study contributes to a deeper understanding of the fundamental mechanical properties of GHBS.

Abstract Oxidative stress promotes tissue injury in the central nervous system in neurological disorders such as multiple sclerosis (MS). To protect against this, antioxidant enzymes including superoxide dismutase-1 (SOD1), heme oxygenase-1 (HO-1), peroxiredoxin-5 (PRDX5) and glutathione peroxidase-4 (GPX4) may be upregulated. However, whether antioxidant enzyme elevation in mouse models of neurodegeneration corresponds to their expression in human diseases such as MS requires investigation. Here, we analyzed and compared the expression of SOD1, HO-1, PRDX5 and GPX4 in the murine spinal cord of three models of MS: focal lesions induced by (1) oxidized phosphatidylcholine or (2) lysophosphatidylcholine (lysolecithin), and (3) diffuse lesions of experimental autoimmune encephalomyelitis. Notably, CD68+ microglia/macrophages were the predominant cellular populations that expressed the highest levels of the detected antioxidant enzymes. Overall, the expression patterns of antioxidant enzymes across the models were similar. The increase of these antioxidant enzymes was corroborated in MS brain tissue using spatial RNA sequencing. Collectively, these results show that antioxidant capacity is relatively conserved between mouse models and MS lesions, and suggest a need to investigate whether the antioxidant elevation in microglia/macrophages is a protective response during oxidative injury, neurodegeneration, and MS.

Ghorbani and colleagues describe versican-V1 as an inhibitor of remyelination using transgenic mice that illuminate new GFP + oligodendrocytes. Mechanisms of versican-V1 include the direct inhibition of oligodendrocytes, and elevating Th17 cells.

Medical students in China and other non-English speaking countries are susceptible to English as a Foreign Language (EFL) writing anxiety. English writing is not only a vital component tested for admission to postgraduate and doctoral programs, but it is also critical for the publication of academic papers. Although there is mounting evidence indicating relationships between anxiety, self-esteem and mobile phone addiction, pathways between these three constructs within a structural equation model have not yet been examined. Furthermore, there has been a dearth of studies exploring EFL writing anxiety, from which medical students in China as well as other non-English speaking countries are prone to suffer. The study was to assess EFL writing anxiety among Chinese medical students and to examine the relationships between EFL writing anxiety, self-esteem, and mobile phone addiction, with an aim to offer empirical evidence for effective preventive or intervention measures to alleviate EFL writing anxiety. Cross-sectional data were obtained from 1,238 medical students in China, with the administration of a self-administered questionnaire comprising the Second Language Writing Anxiety Inventory (SLWAI), the Rosenberg Self Esteem Scale (RSES) and the Mobile Phone Addiction Tendency Scale (MPATS). The results indicated that both self-esteem and mobile phone addiction exerted significant direct effects on EFL writing anxiety. Self-esteem also had a significant indirect effect on EFL writing anxiety via the mediating role of mobile phone addiction. The path coefficients of self-esteem on EFL writing anxiety were significantly reduced when mobile phone addiction was modeled as a mediator. Efforts to alleviate EFL writing anxiety among medical students may benefit from enhancing self-esteem and establishing a healthy relationship with mobile phones.

Modern cold seeps are of fluctuant flux, which could result in variabilities of geochemical archives through intensively influencing the redox condition in pore fluids. However, the geochemical archives are not fully understood when the redox condition changes. Here, tubular carbonates from the Shenhu Sea Area were used to reconstruct the formation environment and redox conditions. The moderately negative δ13C values of the carbonates (−40.1‰ to −30.8‰, VPDB) indicate a mixed carbon source of thermogenic and biogenic methane. The low δ18O values (−2.7‰ to 1.0‰, VPDB) suggest a type of 18O-depleted pore fluid possibly influenced by gas hydrate formation. Co-variation of MoEF, WEF, CoEF, and CrEF suggests that high Fe contents in the rims of samples R1 and R2 are induced by Fe (oxyhydr)oxidation enrichment, while the positive correlation between MoEF and Mn/Al ratio indicates that high Mn contents in the rims of samples R3 and R4 are induced by Mn (oxyhydr)oxidation enrichment. The occurrence of Fe or Mn enrichment in the rims and the absence of Fe/Mn enrichment in the cores suggest Fe/Mn (oxyhydr)oxides forming in pore fluid rather than in bottom seawater. The carbonate phases of the rims enriched in Fe (oxyhydr)oxides are dominated by high magnesium calcite, while those of the rims enriched in Mn (oxyhydr)oxides are dominated by aragonite. The occurrence of Fe or Mn (oxyhydr)oxides corresponds to the previously proposed formation depth for the carbonate phase. The occurrence of dissolution textures in these rims indicates episodic oxic conditions, which would facilitate Fe2+/Mn2+ oxidation. We suppose that the Fe2+ and Mn2+ could be supplied through fluid seepage or diffusion from underlying sediments when the flux decreased. Similar archives may be applied to qualitatively reflect the changes of redox conditions in seep systems. Similar scenarios may help us understand the geochemical records in seeps of fluctuant flux.

Abstract Exercise affords broad benefits for people with multiple sclerosis (PwMS) including less fatigue, depression, and improved cognition. In animal models of multiple sclerosis (MS), exercise has been shown to improve remyelination, decrease blood–brain barrier permeability and reduce leukocyte infiltration. Despite these benefits many PwMS refrain from engaging in physical activity. This barrier to participation in exercise may be overcome by uncovering and describing the mechanisms by which exercise promotes beneficial changes in the central nervous system (CNS). Here, we show that acute bouts of exercise in mice profoundly alters the proteome in demyelinating lesions. Following lysolecithin induced demyelination of the ventral spinal cord, mice were given immediate access to a running wheel for 4 days. Lesioned spinal cords and peripheral blood serum were then subjected to tandem mass tag labeling shotgun proteomics workflow to identify alteration in protein levels. We identified 86 significantly upregulated and 85 downregulated proteins in the lesioned spinal cord as well as 14 significantly upregulated and 11 downregulated proteins in the serum following acute exercise. Altered pathways following exercise in demyelinated mice include oxidative stress response, metabolism and transmission across chemical synapses. Similar acute bout of exercise in naïve mice also changed several proteins in the serum and spinal cord, including those for metabolism and anti-oxidant responses. Improving our understanding of the mechanisms and duration of activity required to influence the injured CNS should motivate PwMS and other conditions to embrace exercise as part of their therapy to manage CNS disability.

Abstract Background Chondroitin sulfate proteoglycans (CSPGs) are potent inhibitors of axonal regrowth and remyelination. More recently, they have also been highlighted as a modulator of macrophage infiltration into the central nervous system in experimental autoimmune encephalomyelitis, an inflammatory model of multiple sclerosis. Methods We interrogated results from single nucleotide polymorphisms (SNPs) lying in or close to genes regulating CSPG metabolism in the summary results from two publicly available systematic studies of multiple sclerosis (MS) genetics. A demyelinating injury model in the spinal cord of exostosin-like 2 deficient (EXTL2-/-) mice was used to investigate the effects of dysregulation of EXTL2 on remyelination. Cell cultures of bone marrow-derived macrophages and primary oligodendrocyte precursor cells and neurons were supplemented with purified CSPGs or conditioned media to assess potential mechanisms of action. Results The strongest evidence for genetic association was seen for SNPs mapping to the region containing the glycosyltransferase exostosin-like 2 (EXTL2), an enzyme that normally suppresses CSPG biosynthesis. Six of these SNPs showed genome-wide significant evidence for association in one of the studies with concordant and nominally significant effects in the second study. We then went on to show that a demyelinating injury to the spinal cord of EXTL2−/− mice resulted in excessive deposition of CSPGs in the lesion area. EXTL2−/− mice had exacerbated axonal damage and myelin disruption relative to wild-type mice, and increased representation of microglia/macrophages within lesions. In tissue culture, activated bone marrow-derived macrophages from EXTL2−/− mice overproduce tumor necrosis factor α (TNFα) and matrix metalloproteinases (MMPs). Conclusions These results emphasize CSPGs as a prominent modulator of neuroinflammation and they highlight CSPGs accumulating in lesions in promoting axonal injury.

Superpixel is an essential tool for computer vision. In practice, classic superpixel algorithms do not exhibit good boundary adherence with fewer superpixels, which will greatly hamper further analysis. To remedy the defect, a superpixel boundary optimization framework is proposed in this paper. There are three steps in the framework. Firstly, based on the proposed information measure function, the under-segmented superpixels generated by classic superpixel algorithms are screened out. Secondly, with the two invariant centroids method, these under-segmented superpixels are re-segmented to improve the accuracy in boundary adherence. Finally, smaller superpixels are merged to maintain the same number with initial superpixels. Quantitative evaluations on the BSDS500 exhibit that the performance of the classic superpixel algorithms is improved by employing the framework, especially on the condition of fewer superpixels.

Waveguide–plasmon polaritons sustained in metallic photonic crystal slabs show fascinating properties, such as narrow bandwidth and ultrafast dynamics crucial for biosensing, light emitting, and ultrafast switching. However, the patterning of metallic photonic crystals using electron beam lithography is challenging in terms of high efficiency, large area coverage, and cost control. This paper describes a controllable patterning technique for the fabrication of an Ag grating structure on an indium–tin oxide (ITO) slab that enables strong photon–plasmon interaction to obtain waveguide–plasmon polaritons. The Ag grating consisting of self-assembled silver nanoparticles (NPs) exhibits polarization-independent properties for the excitation of the hybrid waveguide–plasmon mode. The Ag NP grating can also be annealed at high temperature to form a continuous nanoline grating that supports the hybrid waveguide–plasmon mode only under transverse magnetic (TM) polarization. We tuned the morphology and the periodicity of the Ag grating through the concentration of silver salt and the photoresist template, respectively, to manipulate the strong coupling between the plasmon and the waveguide modes of different orders.

Summary: Oxidized phosphatidylcholine (OxPC) found in multiple sclerosis brain lesions mediates neurodegeneration. Microglia are prominent responders to the OxPC insult, and thus, studying their protective or noxious functions is important to help halt neurodegeneration. Here, we present protocols including cell isolation and culture, animal surgeries, as well as tissue processing and isolation to study the microglia response to OxPC-mediated neurodegeneration in vitro and in vivo.For complete details on the use and execution of this protocol, please refer to Dong et al. (2021).

Background and Aims: Aspirin leads to substantial benefits for the secondary prevention of cardiovascular disease (CVD). We aimed to cast more light on aspirin’s role for the primary prevention of CVD.Methods: Databases were searched for clinical trials comparing aspirin vs. no aspirin use in this meta-analysis. Efficacy and safety profiles were rigorously investigated. Trial sequential analysis (TSA) was used to determine the robustness of the results.Results: Fourteen studies with 163,840 participants were eligible (mean follow-up 6.2 y). Aspirin intake was found to be associated with 9, 13, and 12% reductions in the risk of cardiovascular events (CV events) (relative risk [RR]: 0.91, 95% confidence intervals [CI]: 0.87–0.96; risk difference (RD): 0.29%; absolute risk percentage (AR%): 7.61%; number needed to treat (NNT): 345), myocardial infarction (RR: 0.87, 95% CI: 0.77–0.97; RD: 0.21%; AR%: 11.11%; NNT: 488) and ischemic stroke (RR: 0.88, 95% CI: 0.80–0.96; RD: 0.21%; AR%: 16.14%; NNT: 476), respectively; aspirin intake was also associated with 40%, 30%, and 57% increases in the risk of major bleeding (RR: 1.40, 95% CI: 1.29–1.53; RD: 0.47%; AR%: 27.85; NNT: 214), intracranial bleeding (RR: 1.30, 95% CI: 1.11–1.52; RD: 0.10%; AR%: 22.99%; NNT: 1,000) and major gastrointestinal bleeding (RR: 1.57, 95% CI: 1.38–1.78; RD: 0.32%; AR%: 36.70%; NNT: 315), respectively. Further, populations with low doses of aspirin intake (≤100 mg), populations

The active contour model is widely used to segment images. For the classical magnetostatic active contour (MAC) model, the magnetic field is computed based on the detected points by using an edge detector. However, noise and nontarget points are always detected. Thus, MAC is nonrobust to noise and the extracted objects may be deviant from the real objects. In this paper, a magnetostatic active contour model with a classification method of sparse representation is proposed. First, rough edge information is obtained with some edge detectors. Second, the extracted edge contours are divided into two parts by sparse classification, that is, the target object part and the redundant part. Based on the classified target points, a new magnetic field is generated, and contours evolve with MAC to extract the target objects. Experimental results show that the proposed model could decrease the influence of noise and robust segmentation results could be obtained.

Alveolar macrophages (AMs) are CD44 expressing cells that reside in the alveolar space where they maintain lung homeostasis by serving critical roles in immunosurveillance and lipid surfactant catabolism. AMs lacking CD44 are unable to bind the glycosaminoglycan, hyaluronan, which compromises their survival and leads to reduced numbers of AMs in the lung. Using RNA sequencing, lipidomics and multiparameter flow cytometry, we demonstrate that CD44−/− mice have impaired AM lipid homeostasis and increased surfactant lipids in the lung. CD44−/− AMs had increased expression of CD36, a lipid scavenger receptor, as well as increased intracellular lipid droplets, giving them a foamy appearance. RNA sequencing revealed the differential expression of genes associated with lipid efflux and metabolism in CD44−/− AMs. Lipidomic analysis showed increased lipids in both the supernatant and cell pellet extracted from the bronchoalveolar lavage of CD44−/− mice. Phosphatidylcholine species, cholesterol, oxidized phospholipids and levels of reactive oxygen species (ROS) were increased in CD44−/− AMs. Oxidized phospholipids were more cytotoxic to CD44−/− AMs and induced greater lung inflammation in CD44−/− mice. Reconstitution of CD44+/+ mice with CD44−/− bone marrow as well as adoptive transfer of CD44−/− AMs into CD44+/+ mice showed that lipid accumulation in CD44−/− AMs occurred irrespective of the lung environment, suggesting a cell intrinsic defect. Administration of colony stimulating factor 2 (CSF-2), a critical factor in AM development and maintenance, increased AM numbers in CD44−/− mice and decreased phosphatidylcholine levels in the bronchoalveolar lavage, but was unable to decrease intracellular lipid accumulation in CD44−/− AMs. Peroxisome proliferator-activated receptor gamma (PPARγ), downstream of CSF-2 signaling and a regulator of lipid metabolism, was reduced in the nucleus of CD44−/− AMs, and PPARγ inhibition in normal AMs increased their lipid droplets. Thus, CD44 deficiency causes defects in AMs that lead to abnormal lipid accumulation and oxidation, which exacerbates oxidized lipid-induced lung inflammation. Collectively, these findings implicate CD44 as a regulator of lung homeostasis and inflammation.

New polyketide-derived oligophenalenone dimers, bacillisporins K and L (1 and 2) and xanthoradone dimer rugulosin D (3), together with four known compounds, bacillisporin B (4), macrosporusone D (5), rugulosin A and penicillide (6 and 7), were isolated from the marine-derived fungus Talaromyces sp. BTBU20213036. Their structures were determined by detailed analysis of HRESIMS, 1D and 2D NMR data, and the absolute configurations were determined on the basis of calculated and experimental electronic circular dichroism (ECD). The antibacterial and antifungal activities of these compounds were tested against Gram-positive—Staphylococcus aureus, Gram-negative—Escherichia coli, and fungal strain—Candida albicans. These compounds showed potential inhibitory effects against S. aureus with minimum inhibitory concentrations ranging from 0.195 to 100 µg/mL.

Background: Triglycerides (TG) levels were associated with microalbuminuria in diabetes. However, this association was barely investigated in non-diabetic hypertensive patients. We aimed to investigate such an association in non-diabetic hypertensive patients and the factors would affect it. Methods: We enrolled 445 eligible non-diabetic hypertensive patients and analyzed the association between TG and microalbuminuria. Results: Urinary microalbumin levels were significantly increased in patients with high TG levels (≥ 1.7 mmol/L). Multivariate logistic regression analysis identified that ln (TG) [odds ratio (OR): 2.273, 95% confidence interval (CI): 1.140 to 4.532, P = 0.020] were independently associated with microalbuminuria in all patients. Multinomial logistic regression analysis further revealed that highest tertile of TG level (≥ 1.76 mmol/L) significantly correlated with microalbuminuria (OR: 2.164, 95% CI: 1.336 to 3.507, P = 0.002) and the association remained significant after adjustments of sex, body mass index, ln(age), ln(systolic blood pressure), ln[diastolic blood pressure (DBP) (OR: 1.990, 95% CI: 1.197 to 3.308, P = 0.008). Association between TG and microalbuminuria was no longer significant when patients were limited to those with low-density lipoprotein cholesterol (LDL-C) treatment target achieved. However, in a forced model of multivariate regression analysis by eliminating ln (DBP), ln (TG) resumed the association with microalbuminuria (OR: 2.722, 95% CI: 1.122 to 6.605, P = 0.027). Conclusions: TG levels were associated with microalbuminuria in non-diabetic hypertensive patients, and the independence of association was supposed to be affected by baseline LDL-C and blood pressure levels.

Hyperspectral unmixing (HU) is a research hotspot of hyperspectral remote sensing technology. As a classical HU method, the nonnegative matrix factorization (NMF) unmixing method can decompose an observed hyperspectral data matrix into the product of two nonnegative matrices, i.e., endmember and abundance matrices. Because the objective function of NMF is the traditional least-squares function, NMF is sensitive to noise. In order to improve the robustness of NMF, this paper proposes a maximum likelihood estimation (MLE) based NMF model (MLENMF) for unmixing of hyperspectral images (HSIs), which substitutes the least-squares objective function in traditional NMF by a robust MLE-based loss function. Experimental results on a simulated and two widely used real hyperspectral data sets demonstrate the superiority of our MLENMF over existing NMF methods.

Abstract Guppy (Poecilia reticulata) is an ideal model for studying environmental estrogens, and its large caudal fin has a high capacity to regenerate. This study analyzed the feasibility of caudal fin for detecting vitellogenin (Vtg), the most commonly used biomarker of environmental estrogens. Firstly, a sandwich ELISA for guppy Vtg was developed using purified lipovitellin and its antibody and it had a working range of 7.8–1000 ng/mL and detection limit of 3.1 ng/mL. The ELISA was used to detect tissue distribution of Vtg. In male guppy exposed to 50 and 100 ng/L 17β-estradiol (E2), Vtg concentration in caudal fin was higher than that in whole fish, brain, eyes, gonad, and skin, and was close to that in the liver. Furthermore, male guppies were exposed to environmental concentrations of 17a-ethinylestradiol (EE2) and bisphenol S (BPS) to validate the utility of caudal fin Vtg for detecting estrogenic activities. The lowest observed effect concentration of EE2 and BPS were lower than 2 ng/L and 1 μg/L, which were below or equal to the values reported for other species, demonstrating that caudal fin Vtg was highly sensitive to estrogenic chemicals. Therefore, caudal fins of guppies are suggested as alternative samples for Vtg biomarker detection.

Background: The effect of magnesium on stroke has been consistently discussed less, and the results of previous studies have been contradictory. We reviewed the latest literature and quantified robust evidence of the association between magnesium intake and stroke risk.Methods: PubMed, EMBASE, the Cochrane Library, the Web of Science and ClinicalTrials.gov were searched through inception to January 15, 2019 for prospective cohort studies on magnesium intake and the incidence of stroke.Results: Fifteen studies with low bias involving 18 cohorts were entered into this study. The summary relative risk (RR) was significantly reduced by 11% for total stroke (RR: 0.89 [95% CI, 0.83–0.94]; P < 0.001) and by 12% for ischemic stroke (RR: 0.88 [95% CI, 0.81–0.95]; P = 0.001), comparing the highest magnesium intake category to the lowest. After adjusting for calcium intake, the inverse association still existed for total stroke (RR: 0.89 ([95% CI, 0.80–0.99]; P = 0.040). There was an inverse but non-significant association for hemorrhagic stroke, subarachnoid hemorrhage and intracerebral hemorrhage. The quantitative associations for total and ischemic stroke were robust. Importantly, high-risk females who had a body mass index (BMI) ≥25 kg/m2 and who were subjected to a ≥12 y follow-up exhibited a greater decrease in RRs as a result of magnesium intake. For each 100 mg/day increase in magnesium, the risk for total stroke was reduced by 2% and the risk for ischemic stroke was reduced by 2%.Conclusions: Increasing magnesium intake may be a crucial component of stroke prevention that acts in a dose-dependent manner. However, the conclusion is limited by the observational nature of the studies examined, and further randomized controlled trials are still needed.

Hyaluronan is a hygroscopic glycosaminoglycan that contributes to both extracellular and pericellular matrices. While the production of hyaluronan is essential for mammalian development, less is known about its interaction and function with immune cells. Here we review what is known about hyaluronan in the lung and how it impacts immune cells, both at homeostasis and during lung inflammation and fibrosis. In the healthy lung, alveolar macrophages provide the first line of defense and play important roles in immunosurveillance and lipid surfactant homeostasis. Alveolar macrophages are surrounded by a coat of hyaluronan that is bound by CD44, a major hyaluronan receptor on immune cells, and this interaction contributes to their survival and the maintenance of normal alveolar macrophage numbers. Alveolar macrophages are conditioned by the alveolar environment to be immunosuppressive, and can phagocytose particulates without alerting an immune response. However, during acute lung infection or injury, an inflammatory immune response is triggered. Hyaluronan levels in the lung are rapidly increased and peak with maximum leukocyte infiltration, suggesting a role for hyaluronan in facilitating leukocyte access to the injury site. Hyaluronan can also be bound by hyaladherins (hyaluronan binding proteins), which create a provisional matrix to facilitate tissue repair. During the subsequent remodeling process hyaluronan concentrations decline and levels return to baseline as homeostasis is restored. In chronic lung diseases, the inflammatory and/or repair phases persist, leading to sustained high levels of hyaluronan, accumulation of associated immune cells and an inability to resolve the inflammatory response.

Endothelial dysfunction plays a key role in the pathogenesis of cardiovascular disease. However, the gender-related differences in risk factors for endothelial dysfunction are controversial. We investigated the gender differences in the risk factor profiles for endothelial dysfunction in Chinese hypertensive patients.Vascular endothelial functions in 213 hypertensive patients were measured by digital reactive hyperemia peripheral arterial tonometry (RH-PAT). Peripheral blood samples were collected, and the self-reported smoking and alcohol consumption status, age, body mass index, heart rate, blood pressure and drug administrations were recorded.RH-PAT indexes were attenuated in both male and female hypertensive patients [1.60 (1.38-2.02) vs. 1.63 (1.44-1.98)]. Multivariate logistic regression analysis identified plasma creatinine (p < 0.001), total cholesterol (p = 0.001), homocysteine (p = 0.002) and smoking (p < 0.001) as the independent factors correlated with gender (male). Multivariate linear regression analysis further identified homocysteine as the factor that is significantly and independently correlated with the decrease in the RH-PAT indexes in female patients (odds ratio: -0.166, 95% confidence interval: -0.292 to -0.040, p = 0.01). However, none of these four factors were correlated with the RH-PAT indexes in male patients.There are gender-related differences in the risk factors for endothelial dysfunction in Chinese hypertensive patients. Homocysteine is an independent factor for endothelial dysfunction in female hypertensive patients.

Polychlorinated biphenyls (PCBs) are a group of persistent organochlorine compounds that have the potential to disrupt the homeostasis of thyroid hormones (THs) in fish, particularly juveniles. In this study, thyroid histology, plasma TH levels, and iodothyronine deiodinase (IDs, including ID1, ID2, and ID3) gene expression patterns were examined in juvenile Japanese flounder (Paralichthys olivaceus) following 25- and 50-day waterborne exposure to environmentally relevant concentrations of a commercial PCB mixture, Aroclor 1254 (10, 100, and 1000 ng/L) with two-thirds of the test solutions renewed daily. The results showed that exposure to Aroclor 1254 for 50 d increased follicular cell height, colloid depletion, and hyperplasia. In particular, hypothyroidism, which was induced by the administration of 1000 ng/L Aroclor 1254, significantly decreased plasma TT4, TT3, and FT3 levels. Profiles of the changes in mRNA expression levels of IDs were observed in the liver and kidney after 25 and 50 d PCB exposure, which might be associated with a reduction in plasma THs levels. The expression level of ID2 mRNA in the liver exhibited a dose-dependent increase, indicating that this ID isotype might serve as sensitive and stable indicator for thyroid-disrupting chemical (TDC) exposure. Overall, our study confirmed that environmentally relevant concentrations of Aroclor 1254 cause significant thyroid disruption, with juvenile Japanese flounder being suitable candidates for use in TDC studies.

Background Inflammation-exacerbated secondary brain injury and limited tissue regeneration are barriers to favourable prognosis after intracerebral haemorrhage (ICH). As a regulator of inflammation and lipid metabolism, Liver X receptor (LXR) has the potential to alter microglia/macrophage (M/M) phenotype, and assist tissue repair by promoting cholesterol efflux and recycling from phagocytes. To support potential clinical translation, the benefits of enhanced LXR signalling are examined in experimental ICH.Methods Collagenase-induced ICH mice were treated with the LXR agonist GW3965 or vehicle. Behavioural tests were conducted at multiple time points. Lesion and haematoma volume, and other brain parameters were assessed using multimodal MRI with T2-weighted, diffusion tensor imaging and dynamic contrast-enhanced MRI sequences. The fixed brain cryosections were stained and confocal microscopy was applied to detect LXR downstream genes, M/M phenotype, lipid/cholesterol-laden phagocytes, oligodendrocyte lineage cells and neural stem cells. Western blot and real-time qPCR were also used. CX3CR1CreER: Rosa26iDTR mice were employed for M/M-depletion experiments.Results GW3965 treatment reduced lesion volume and white matter injury, and promoted haematoma clearance. Treated mice upregulated LXR downstream genes including ABCA1 and Apolipoprotein E, and had reduced density of M/M that apparently shifted from proinflammatory interleukin-1β+ to Arginase1+CD206+ regulatory phenotype. Fewer cholesterol crystal or myelin debris-laden phagocytes were observed in GW3965 mice. LXR activation increased the number of Olig2+PDGFRα+ precursors and Olig2+CC1+ mature oligodendrocytes in perihaematomal regions, and elevated SOX2+ or nestin+ neural stem cells in lesion and subventricular zone. MRI results supported better lesion recovery by GW3965, and this was corroborated by return to pre-ICH values of functional rotarod activity. The therapeutic effects of GW3965 were abrogated by M/M depletion in CX3CR1CreER: Rosa26iDTR mice.Conclusions LXR agonism using GW3965 reduced brain injury, promoted beneficial properties of M/M and facilitated tissue repair correspondent with enhanced cholesterol recycling.