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The high cell-density fermentation production of thermostable arabino-xylanase Xyn11A and its application in the whole wheat bread quality improvement were investigated. The high cell-density fermentation method was used to produce Xyn11A, and its effect in whole wheat bread quality improvement was evaluated by determining the pasting characteristics, rheological properties, specific volume, texture, differential scanning calorimeter (DSC) and scanning electron microscopy (SEM). The results showed that the supernatant xylanase enzyme activity was 1884 U/mL after fermentation of recombinant Pichia pastoris in a 5-L fermenter for 108 h. Pioneering the application of wheat arabinoxylanase Xyn11A in whole wheat dough, the gelatinization characteristics showed that with the addition of Xyn11A, the peak viscosity, trough viscosity, and final viscosity exhibited a trend of initially decreasing and then increasing. Rheological properties indicated that with varying amounts of Xyn11A added (0 to 6 mg/kg), the extensibility of the dough increased from 173 mm to 181.5 mm. The Mixolab measurements revealed that the dough's C1 (maximum dough consistency), C2 (gluten weakening trough), C3 (peak viscosity), C4 (retained viscosity), and C5-C4 (starch retrogradation rate) decreased from 1.119, 0.443, 1.568, 1.399, 0.963 Nm to 1.113, 0.437, 1.512, 1.252, 0.774 Nm, respectively. The wheat arabino-xylanase Xyn11A was further applied in whole wheat bread, and the specific volume of whole wheat bread showed a tendency to increase and then decrease, and the hardness showed a tendency to decrease and then increase, and the best effect was achieved when the addition amount was 6 mg/kg, which increased the specific volume of the whole wheat bread by 15.6%, and the hardness decreased by 26% compared with the control group without Xyn11A. Addition 6 mg/kg of Xyn11A in whole wheat bread, the hardness of bread decreased in a range of 19.4%~23.9% at 4 ℃ for different storage time (1~5 d), indicating the enzyme could delay the aging speed. DSC showed that the melting temperature as well as the differential scanning calorimetric integral enthalpy decreased with the addition of 6 mg/kg Xyn11A compared with the control group without Xyn11A, indicating that the addition of Xyn11A delayed the aging of whole wheat bread. SEM results showed that the addition of Xyn11A resulted in a more continuous dough microstructure and a denser and more homogeneous internal mesh of the bread. In summary, wheat arabinoxylanase Xyn11A would show excellent effects in improving the quality of whole wheat bread and delaying the staling process, demonstrating good potential in the modification of baked goods.

To investigate the effect of salt stress on the germination of sesame, a mixed salt solution of sodium chloride and calcium chloride was used as the culture medium to analyze the changes and correlations in growth characteristics, total phenolic content, total flavone content, antioxidant capacity, and antioxidant enzyme activity during the germination process of sesame. The results showed that salt stress could promote sesame germination and the accumulation of phenol and flavone, and improve the ABTS+ free radicals scavenging rate and the iron ion reduction ability of sesame. The effect of salt stress on antioxidant enzyme activity varied by enzyme species, and the treatment had a more obvious promoting effect on SOD and CAT activities compared with APX and POD activities. The correlation analysis results demonstrated that the total phenol of sesame cultured under salt stress was positively correlated with its total flavonoids, ABTS+ free radical scavenging rate, iron ion reducing ability, and POD enzyme activity. The correlation between total phenol and iron ion reducing ability, SOD activity and DPPH and hydroxyl radical scavenging ability, POD activity and iron ion reducing ability of sesame was enhanced by salt stress treatment. This study could lay a foundation for further deciphering the physiological mechanism of salt stress on sesame germination, and provide theoretical basis for the development of sesame functional foods.

Abstract Fusarium graminearum is a prominent pathogen responsible for causing head blight disease in small grain cereals, leading to substantial agricultural damage. A recent study revealed the infectivity of a hypovirus, Cryphonectria hypovirus 1 (CHV1), in F. graminearum. However, the effects of CHV1 on the pathogenicity and development of the fungus remain largely unexplored. In this study, we investigated the effects of CHV1 infection on F. graminearum and made several interesting discoveries. First, we observed that CHV1 infection attenuated the pathogenicity of F. graminearum and reduced its conidiation. CHV1 efficiently spread through various transmission modes, such as hyphal fusion and spores, including conidiospores and ascospores. However, the accumulation of the virus was reduced following transmission through spores. Interestingly, despite causing hypovirulence, CHV1 infection enhanced the production of deoxynivalenol (DON), a mycotoxin known to play a role in F. graminearum’s virulence and induction of DON production by a DON-inducing medium elevated CHV1 accumulation. The transcriptional expression of key regulatory genes involved in DON biosynthesis or toxisome formation was upregulated in response to CHV1 infection. Furthermore, our study revealed that CHV1 infection suppressed the formation of lipid droplets. Overall, our study provides insights of how the infection of a hypovirulence-inducing mycovirus affects the physiological and metabolic processes in F. graminearum.

The perfluorosulfonic acid (PFSA) ionomers are key materials for proton exchange membranes (PEMs) and catalyst layers (CLs). Their morphology is profoundly influenced by the chain assembly behavior of PFSA in dispersions. Hence, we combine the characterization techniques of dynamic light scattering (DLS), small-angle X-ray scattering (SAXS), and cryo-transmission electron microscopy (Cryo-TEM) to study the nanostructures of PFSA dispersions, and provide a structure model for diverse PFSA ionomers in water/ethanol solvent. It is seen that PFSA ionomers self-assembly into a rod-like particle in dilute dispersion. As the concentration increases, the primary rod aggregates gradually assemble into a swollen- or Gaussian-network structure. Beyond this feature, we see that different PFSA ionomers show different nanostructures in dispersion. For the long-side-chain (LSC) PFSA ionomers, the 800-LSC PFSA tends to form monodisperse rod-like aggregates that is in a highly ordered arrangement with a rod diameter of 3.16 nm and a length of 28.72 nm. As the equivalent weight (EW) increases to 960, the poor solubility of the main chains in water/ethanol solvents leads to the “end-to-end” assemblies of the primary rod particles and dendritic secondary aggregates. The short-side-chain (SSC) PFSA ionomer that shares the same backbone with 960-LSC PFSA exhibit remarkable mono-dispersity and ordered arrangement of rod-like aggregates in water/ethanol solvents due to the strong electrostatic repulsion.

Abstract The Internet of Things (IoT) devices spawn growing diverse social platforms and online data at the network edge, propelling the development of cross-platform applications. To integrate cross-platform data, user identity linkage is envisioned as a promising technique by detecting whether different accounts from multiple social networks belong to the same identity. The profile and social relationship information of IoT users may be inconsistent, which deteriorates the reliability of the effectiveness of identity linkage. To this end, we propose a topic and knowledge-enhanced model for edge-enabled IoT user identity linkage across social networks, named TKM, which conducts feature representation of user generated contents from both post-level and account-level for identity linkage. Specifically, a topic-enhanced method is designed to extract features at the post-level. Meanwhile, we develop an external knowledge-based Siamese neural network for user-generated content alignment at the account-level. Finally, we show the superiority of TKM over existing methods on two real-world datasets. The results demonstrate the improvement in prediction and retrieval performance achieved by utilizing both post-level and account-level representation for identity linkage across social networks.

In order to improve the yield and quality of tiger nut oil, the strategy of ultrasonic-assisted n-hexane was studied by response surface methodology. In this study, the total phenolic content, total flavonoid content, free radical scavenging rate, fatty acid composition, and 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) clearance rate in oil samples were investigated at three temperatures including 25 ℃ (room temperature), 47 ℃ (optimal temperature for ultrasound assisted extraction), and 60 ℃ (high temperature). The results showed that a high tiger nut oil extraction yield of 25.01%±0.03% was obtained at a solid-liquid ratio of 1:15 (g/mL), ultrasonic time of 20 min, ultrasonic temperature of 47 ℃, and particle size of 70 mesh. The obtained oil sample was yellow-orange and slightly turbid with a unique aroma of beans. Besides, tiger nut oil had a certain scavenging effect on DPPH free radicals. Ultrasound could better dissolve the nutrients in tiger nut, but it had a large destruction effect on tiger nut flavonoids, while the content of phenolic acids significantly (P

Abstract. Background:. Patients who undergo coronary artery bypass grafting (CABG) are known to be at a significant risk of experiencing long-term adverse events, emphasizing the importance of regular assessments. Evaluating health-related quality of life (HRQoL) serves as a direct method to gauge prognosis. Our objective is to ascertain the prognostic significance of consecutive HRQoL assessments using the Physical Component Summary (PCS) and Mental Component Summary (MCS) derived from the Short-Form 36 (SF-36) health survey in CABG patients. Methods:. The study population consisted of 433 patients who underwent isolated elective CABG at Fuwai Hospital between 2012 and 2013. SF-36 assessments were conducted during both the hospitalization period and follow-up. The primary endpoint of the study was all-cause mortality, while the secondary outcome was a composite measure including death, myocardial infarction, stroke, and repeat revascularization. We assessed the relationships between the PCS and MCS at baseline, as well as their changes during the first 6 months after the surgery (referred to as ΔPCS and ΔMCS, respectively), and the observed outcomes. Results:. The patients were followed for an average of 6.28 years, during which 35 individuals (35/433, 8.1%) died. After adjusting for clinical variables, it was observed that baseline MCS scores (hazard ratio [HR] for a 1-standard deviation [SD] decrease, 1.57; 95% confidence interval [CI], 1.07–2.30) and ΔMCS (HR for a 1-SD decrease, 1.67; 95% CI, 1.09–2.56) were associated with all-cause mortality. However, baseline PCS scores and ΔPCS did not exhibit a significant relationship with all-cause mortality. Notably, there was a dose-response relationship observed between ΔMCS and the likelihood of all-cause mortality (HRs for the 2nd, 3rd and 4th quartiles compared to the 1st quartile, 0.33, 0.45 and 0.11, respectively). Conclusions:. Baseline MCS and changes in MCS were independent predictors for long-term mortality of CABG. Better mental health status and recovery indicated better prognosis.

Abstract Background and Aims Cardiac glycosides (CGs), traditionally used for heart failure, have shown potential as anti‐cancer agents. This study aims to explore their multifaceted mechanisms in cancer cell biology using proteome integral solubility alteration (PISA), focusing on the interaction with key proteins implicated in cellular metabolism and mitochondrial function. Methods We conducted lysate‐based and intact‐cell PISA assays on cancer cells treated with CGs (Digoxin, Digitoxin, Ouabain) to analyze protein solubility changes. This was followed by mass spectrometric analysis and bioinformatics to identify differentially soluble proteins (DSPs). Molecular docking simulations were performed to predict protein‐CG interactions. Public data including gene expression changes upon CG treatment were re‐analyzed for validation. Results The PISA assays revealed CGs’ broad‐spectrum interactions, particularly affecting proteins like PKM2, ANXA2, SLC16A1, GOT2 and GLUD1. Molecular docking confirmed stable interactions between CGs and these DSPs. Re‐analysis of public data supported the impact of CGs on cancer metabolism and cell signaling pathways. Conclusion Our findings suggest that CGs could be repurposed for cancer therapy by modulating cellular processes. The PISA data provide insights into the polypharmacological effects of CGs, warranting further exploration of their mechanisms and clinical potential.

The emergence of multidrug-resistant Pseudomonas aeruginosa isolates is a growing concern for public health, necessitating new therapeutic strategies. Gallium nitrate [Ga(NO3)3], a medication for cancer-related hypercalcemia, has attracted great attention due to its ability to inhibit P. aeruginosa growth and biofilm formation by disrupting iron metabolism. However, the antibacterial efficacy of Ga(NO3)3 is not always satisfactory. It is imperative to investigate the factors that affect the bactericidal effects of Ga(NO3)3 and to identify new ways to enhance its efficacy. This study focused on the impact of pH on P. aeruginosa resistance to Ga(NO3)3, along with the underlying mechanism. The results indicate that acidic conditions could increase the effectiveness of Ga(NO3)3 against P. aeruginosa by promoting the production of pyochelin and gallium uptake. Subsequently, using glutamic acid, a clinically compatible acidic amino acid, the pH was significantly lowered and enhanced the bactericidal and inhibitory efficacy of Ga(NO3)3 against biofilm formation by P. aeruginosa, including a reference strain PA14 and several multidrug-resistant clinical isolates. Furthermore, we used an abscess mouse model to evaluate this combination in vivo; the results show that the combination of glutamic acid and Ga(NO3)3 significantly improved P. aeruginosa clearance. Overall, the present study demonstrates that acidic conditions can increase the sensitivity of P. aeruginosa to Ga(NO3)3. Combining glutamic acid and Ga(NO3)3 is a potential strategy for the treatment of P. aeruginosa infections.

Modern food is evolving in the direction of green, healthy, and convenient products, and developing natural products with health benefits is an important direction for the food industry. Chlorella is rich in nutrients, such as carotene and fatty acids, which provide it with a variety of health benefits, and therefore widely used in the food industry as a health or functional food. This study reviews the research progress and specific applications of Chlorella in health, functional, and other foods, and expounds on the bottlenecks faced in the use of Chlorella in food industry. This review provides a theoretical basis for the research, utilisation, and production of new food materials involving Chlorella.

Abstract Semiconductor nanocrystals (NCs) are promising materials for various applications. Two of four recently identified CuαZnβSnγSeδ (CZTSe) domains demonstrate metallic character, while the other two exhibit semiconductor character. The presence of both metallic and semiconductor domains in one NC can hugely benefit future applications. In contrast to traditional band gap studies in the NC community, this study emphasizes that NC domain interfaces also affect the electronic properties. Specifically, the measured band gap of a tetrapod‐shaped CZTSe NC is demonstrated to originate from two specific domains (tetragonal I4¯ and monoclinic P1c1 Cu2ZnSnSe4). The heterojunction between these two semiconductor domains exhibits a staggered type‐II band alignment, facilitating the separation of photogenerated electron‐hole pairs. Interestingly, tetrapod NCs have the potential to be efficient absorber materials with higher capacitance in photovoltaic applications due to the presence of both semiconductor/semiconductor interfaces and metal/semiconductor “Schottky”‐junctions. For the two photo‐absorbing domains, the calculated absorption spectra yield maximum photon‐absorption coefficients of about 105 cm−1 in the visible and UV regions and a theoretical solar power conversion efficiency up to 20.8%. These insights into the structure‐property relationships in CZTSe NCs will guide the design of more efficient advanced optical CZTSe materials for various applications.

Drought is a serious natural disaster that causes huge losses to various regions of the world. To effectively cope with this disaster, we need to use drought indices to classify and compare the drought conditions of different regions. We can take appropriate measures according to the category of drought to mitigate the impact of drought. Recently, deep learning models have shown promising results in this domain. However, few of these models consider the relationships between different areas, which limits their ability to capture the complex spatio-temporal dynamics of droughts. In this study, we propose a novel multivariate spatio-temporal sensitive network (MSTSN) for drought prediction, which incorporates both geographical and temporal knowledge in the network and improves its predictive power. We obtained the standardized precipitation evapotranspiration index and meteorological data from the climatic research unit dataset, covering the period from 1961 to 2018. This is the first deep learning method that embeds geographical knowledge in drought prediction. We also provide a solid foundation for comparing our method with other deep learning baselines and evaluating their performance. Experiments show that our method consistently outperforms the existing state-of-the-art methods on various metrics, validating the effectiveness of geospatial and temporal information. HIGHLIGHTS A novel multivariate spatio-temporal sensitive network (MSTSN) is proposed for drought prediction.; The MSTSN model captures the relationships between different areas by graph neural network.; The MSTSN model extracts the long-term dependencies of data through a gated recurrent unit and enhances its effect by multi-head self-attention.; The MSTSN model predicts the spatial drought distribution closest to the actual distribution.;

It is inevitable for polyphenols and polysaccharides to interact during food preparation. Modifications in microstructure can lead to changes in the physical and chemical properties of food systems, which in turn may influence the nutritional characteristics and functional activities of the food. Recent studies have shown that, in addition to traditional Chinese medicine compounds, certain natural polysaccharides and polyphenols exhibit significant anti-inflammatory and antioxidant properties. These compounds are also associated with beneficial therapeutic effects for the prevention and treatment of acute lung injury. The objective of this study was to examine the synergistic antioxidant effects of chlorogenic acid (CA) and Lycium barbarum polysaccharide (LBP) in various ratios, along with their combined antioxidant and anti-inflammatory effects on LPS-induced inflammation in rat alveolar macrophages. Using the Combination Index (CI), which quantifies the synergistic or antagonistic effect of two substances, all four combinations showed synergistic antioxidant properties over a range of concentrations by in vitro antioxidant property experiments. However, based on comparing them, the four group ratios exhibited the highest antioxidant activity of the infusion at CA:LBP = 1:7, indicating synergistic interactions (CI < 1). In addition, the antioxidant and anti-inflammatory effects of the CA-LBP complex were observed to alleviate cellular inflammatory injury by reducing LPS-induced nitric oxide and reactive oxygen species production and inhibiting the release of inflammatory factors such as TNF-α and IL-6.

Amid global rural decline, the main approach to rural revitalization (RR) is to transform rural ecological resources into development advantages by means of ecological product value realization (EPVR). The fragility of the karst ecological environment limits the development of the karst countryside, and agroforestry is an important way to achieve the ecological protection and economic development of the karst countryside. At present, research on EPVR and RR is rapidly developing. Although there is an increasing number of publications on EPVR and RR separately, the literature on their comprehensive analysis is lacking, and how the karst agroforestry ecosystem can be improved is unclear. The objective of this is to provide an overview of the current research status and challenges of EPVR and RR in order to optimize agroforestry ecosystems in karst desertification control (KDC). This paper systematically analyzed 263 relevant articles on EPVR and RR, and the results are as follows: (1) The number of studies increased exponentially after 2017. The research has primarily focused on the relationship between EPVR and RR, as well as the EPVR and the formation mechanisms of the eco-industry and value accounting of eco-products, which account for 95.53% of the total literature. China has published the most research in this area. At the intercontinental scale, this research is mainly concentrated in East Asia, Europe, and North America. (2) The main progress and landmark achievements in the research on EPVR and RR are summarized. Four key scientific questions that need to be addressed in the future are presented. (3) The above information highlights the three key areas for improving the agroforestry ecosystem in karst desertification control (KDC): the value accounting of eco-products, EPVR, and RR. This study found that EPVR and RR can improve the karst agroforestry ecosystem and further promote rural development, providing significant insights for the overall revitalization of rural areas worldwide and the scientific control of karst desertification.

The cultivation of cashew crops carries numerous economic advantages, and countries worldwide that produce this crop face a high demand. The effects of wind speed and wind direction on crop yield prediction using proficient deep learning algorithms are less emphasized or researched. We propose a combination of advanced deep learning techniques, specifically focusing on long short-term memory (LSTM) and random forest models. We intend to enhance this ensemble model using dynamic time warping (DTW) to assess the spatiotemporal data (wind speed and wind direction) similarities within Jaman North, Jaman South, and Wenchi with their respective production yield. In the Bono region of Ghana, these three areas are crucial for cashew production. The LSTM-DTW-RF model with wind speed and wind direction achieved an R2 score of 0.847 and the LSTM-RF model without these two key features R2 score of (0.74). Both models were evaluated using the augmented Dickey-Fuller (ADF) test, which is commonly used in time series analysis to assess stationarity, where the LSTM-DTW-RF achieved a 90% level of confidence, while LSTM-RF attained an 87.99% level. Among the three municipalities, Jaman South had the highest evaluation scores for the model, with an RMSE of 0.883, an R2 of 0.835, and an MBE of 0.212 when comparing actual and predicted values for Wenchi. In terms of the annual average wind direction, Jaman North recorded (270.5 SW°), Jaman South recorded (274.8 SW°), and Wenchi recorded (272.6 SW°). The DTW similarity distance for the annual average wind speed across these regions fell within specific ranges: Jaman North (±25.72), Jaman South (±25.89), and Wenchi (±26.04). Following the DTW similarity evaluation, Jaman North demonstrated superior performance in wind speed, while Wenchi excelled in wind direction. This underscores the potential efficiency of DTW when incorporated into the analysis of environmental factors affecting crop yields, given its invariant nature. The results obtained can guide further exploration of DTW variations in combination with other machine learning models to predict higher cashew yields. Additionally, these findings emphasize the significance of wind speed and direction in vertical farming, contributing to informed decisions for sustainable agricultural growth and development.

In recent years, the production of prepared and frozen foods has increased with economic development. However, during freezing, moisture migration forms ice crystals that damage food structure and reduce quality. This study investigates moisture migration changes in pre-fermented dough during frozen storage and effectiveness of Citrus fibre (CF) and Soya dietary fibre (SDF) on quality improvement. Pre-fermented frozen dough properties were evaluated at different freezing storage days with CF and SDF. Results showed frozen storage reduced water retention, converting deeply bound water to weakly bound and free water. Freezable water content increased significantly from 53% (fresh) to 56.95% (60d-control), forming disruptive ice crystals in gluten protein structure. SDF had superior water flow restriction compared to CF, preventing large ice crystal accumulation, enhancing water-holding capacity, and maintaining gluten protein structure. These findings lay a theoretical foundation for improving quality and industrial applications of pre-fermented frozen dough.

Abstract Targeted protein degradation via “hijacking” of the ubiquitin-proteasome system using proteolysis targeting chimeras (PROTACs) has evolved into a novel therapeutic modality. The design of PROTACs is challenging; multiple steps involved in PROTAC-induced degradation make it difficult to establish coherent structure-activity relationships. Herein, we characterize PROTAC-mediated ternary complex formation and degradation by employing von Hippel–Lindau protein (VHL) recruiting PROTACs for two different target proteins, SMARCA2 and BRD4. Ternary-complex attributes and degradation activity parameters are evaluated by varying components of the PROTAC’s architecture. Ternary complex binding affinity and cooperativity correlates well with degradation potency and initial rates of degradation. Additionally, we develop a ternary-complex structure modeling workflow to calculate the total buried surface area at the interface, which is in agreement with the measured ternary complex binding affinity. Our findings establish a predictive framework to guide the design of potent degraders.

Wheat allergy has become a serious health threat worldwide and its prevalence has increased alarmingly in the past few years. Factors such as food matrix and food processing may alter the structure of wheat proteins, and hence affect its allergenic properties. However, few reports have focused on the influence of Chinese traditional starter fermentation on wheat allergy. In this study, 5 starters from different regions of China were used for fermentation, and protein characteristics were monitored by sodium dodecyl sulfate polyacrylamide gel electropheresis, and immunoreactivity analyzed by immunoassay with allergenic serum was obtained from New Zealand white rabbits. The allergenicity of steamed and baked matrices was also evaluated. The results showed that the allergenicity of wheat dough was basically increased at the beginning and then decreased during fermentation, but specific trends depend on different starters. With the progress of fermentation, especially as pH value decreased to 3.0–4.0, the allergenicity decreased significantly. Baking and steaming can reduce the allergenicity of wheat matrix, but fermentation is not a key factor affecting the allergenic activity of proteins. Our results can provide a theoretical basis for controlling wheat allergenicity in food processing or producing hypoallergenic food.

AbstractBackground The prognostic value of the Gustave Roussy immune (GRIm) score in cancer patients has been widely reported but remains inconsistent. The aim of this study is to systematically investigate the relationship between the GRIm score and survival outcomes in cancer patients.Methods Relevant literature was identified using electronic databases including Web of Science, PubMed, and Embase from the inception to March 2023. The primary endpoints were long-term oncological outcomes. Subgroup analysis and sensitivity analysis were conducted during the meta-analysis.Results Fifteen studies (20 cohorts) including 4997 cancer patients were enrolled. The combined results revealed that patients in the high GRIm group had a deteriorated overall survival (HR = 2.07 95%CI: 1.73–2.48; p

AbstractBackground Dietary fibre and cognitive function are associated with the risk of mortality, respectively. Inadequate dietary fibre intake and cognitive impairment frequently co-occur in older adults, but the combined effect of dietary fibre and cognitive function on mortality remains unknown. The study was to investigate the combined effect of dietary fibre and cognitive function on mortality over a 13-year follow-up in a representative of older adults from the U.S.Methods We analyzed data from two cycles of the National Health and Nutrition Examination Survey (NHANES) 1999–2000 and 2001–2002 with mortality follow-up data through 13 December 2015 obtained from Public-use Linked Mortality Files. Low dietary fibre intake was defined as the lowest quartile of dietary fibre intake. Cognitive impairment was defined as below the median of Digit Symbol Substitution Test. The separate and combined effects of low dietary fibre intake and cognitive impairment on all-cause and cause-specific mortality were assessed in older adults using weighted Cox proportional hazard models adjusting for potential confounders.Results A total of 2012 participants (weighted sample was 32,765,094) aged 60 years and older were enrolled in the study. After a median follow-up of 13.4 years, 1017 participants (50.4%) were identified as all-cause deaths, including 183 (9.1%) participants dying from cancer, 199 (9.9%) participants dying from cardiovascular disease, and 635 (31.5%) participants dying from non-cancer/non-cardiovascular disease. Participants with low dietary fibre intake and cognitive impairment had nearly twice the risk of all-cause (HR, 2.030; 95% CI, 1.406-2.931) and non-cancer/non-cardiovascular (HR, 2.057; 95% CI, 1.297–3.262) mortality, and over triple cancer (HR, 3.334; 95% CI, 1.685–6.599) mortality, compared to those without both.Conclusions The combination of low dietary fibre intake and cognitive impairment was associated with an increased risk of all-cause, cancer and non-cancer/non- cardiovascular mortality in older adults.

Abstract We examine the low‐frequency (LF) magnetic pulses recorded for the positive leader in two natural lightning flashes as recorded on the high‐speed video camera. The captured positive leader in both cases propagated in a stepwise manner at least over several milliseconds according to the concurrent sequence of LF magnetic pulses. By comparing with previous studies on positive leaders under different situations, the average inter‐pulse intervals (11.7 and 20.3 μs, respectively) obtained for our natural cases are shorter than that of upward positive leaders in rocket‐triggered (typically >25 μs) and tower‐initiated lightning (62 μs in one case). Hence, the stepwise propagation of positive leaders in natural lightning is likely more frequent than that in object‐induced lightning, reflecting a possible influence of ambient electric field and other meteorological factors on the stepwise feature of positive leader. The stepwise extension might be common for positive leaders developing in various scenarios.

IntroductionShort-term spinal cord stimulation (stSCS) is an effective treatment for postherpetic neuralgia (PHN). However, how exactly stSCS affects time-dynamic intrinsic brain activity in PHN patients is not clear. The purpose of this study was to examine the static and dynamic variability of neural activity in PHN patients after stSCS.MethodsIn this study, 10 patients with PHN underwent resting-state functional magnetic resonance imaging (rs-fMRI) at baseline and after SCS. The amplitude of low-frequency fluctuations (ALFF) and dynamic ALFF (dALFF) were used to investigate the static and dynamic variability of neural activity in PHN patients after stSCS. We additionally examined the associations between clinical parameters and functional changes in the brain.ResultsThere was a significant increase in dALFF in the left precuneus and right superior parietal gyrus, and a decrease in dALFF in the left inferior temporal gyrus, right gyrus rectus, left superior temporal gyrus, right orbitofrontal cortex, and left orbitofrontal cortex. There was significantly increased ALFF in the right inferior temporal gyrus, and decreased ALFF in the right lingual gyrus, left superior parietal gyrus, right superior parietal gyrus, and left precuneus. Furthermore, Pittsburgh sleep quality index scores were positively associated with dALFF changes in the left superior temporal gyrus and left orbitofrontal cortex. Hospital anxiety and depression scale scores and continuous pain scores exhibited significant negative correlation with dALFF changes in the right superior parietal gyrus.ConclusionThis study indicated that stSCS is able to cause dALFF changes in PHN patients, thus stSCS might alter brain functions to relieve pain, sleep, and mood symptoms. The findings provide new insights into the mechanisms of stSCS efficacy in the treatment of patients with PHN.

Background: Bone cancer pain (BCP) is one of the most ubiquitous and refractory symptoms of cancer patients that needs to be urgently addressed. Substantial studies have revealed the pivotal role of Cav3.2 T-type calcium channels in chronic pain, however, its involvement in BCP and the specific molecular mechanism have not been fully elucidated. Methods: The expression levels of Cav3.2, insulin-like growth factor 1(IGF-1), IGF-1 receptor (IGF-1R) and hypoxia-inducible factor-1α (HIF-1α) were detected by Western blot in tissues and cells. X-ray and Micro CT used to detect bone destruction in rats. Immunofluorescence was used to detect protein expression and spatial location in the spinal dorsal horn. Electrophoretic mobility shift assay used to verify the interaction between HIF-1α and Cav3.2. Results: The results showed that the expression of Cav3.2 channel was upregulated and blockade of this channel alleviated mechanical allodynia and thermal hyperalgesia in BCP rats. Additionally, inhibition of IGF-1/IGF-1R signaling not only reversed the BCP-induced upregulation of Cav3.2 and HIF-1α, but also decreased nociceptive hypersensitivity in BCP rats. Inhibition of IGF-1 increased Cav3.2 expression levels, which were abolished by pretreatment with HIF-1α siRNA in PC12 cells. Furthermore, nuclear HIF-1α bound to the promoter of Cav3.2 to regulate the Cav3.2 transcription level, and knockdown of HIF-1α suppresses the IGF-1-induced upregulation of Cav3.2 and pain behaviors in rats with BCP. Conclusion: These findings suggest that spinal Cav3.2 T-type calcium channels play a central role during the development of bone cancer pain in rats via regulation of the IGF-1/IGF-1R/HIF-1α pathway.

Abstract Tumor-associated macrophages (TAMs) are highly heterogeneous and play vital roles in tumor progression. Here we adopted a C57BL/6 mouse model imitating the late-stage colorectal liver metastasis (CRLM) by Mc38 colorectal cancer cell injection via the portal vein. With serial sections of CRLM biopsies, we defined 7–9 days post-injection as the critical period for tumor neovascularization, which was initiated from the innate liver vessels via vessel cooption and extended by vascular mimicry and thereof growth of CD34+cells. In samples with increasing-sized liver metastases, the infiltrated Ly6C+ CD11b+ F4/80− monocytes steadily gained the expression of F4/80, a Kupffer cell marker, before transformed into Ly6C− CD11bint F4/80+ cells, which, the same phenotype was also adapted by Ly6C− CD11b− F4/80+ Kupffer cells. F4/80+ TAMs showed proximity to neovascularization and tumor vessels, functionally angiogenic in vivo; and greatly promoted the activation of a few key angiogenic markers such as VEGFA, Ki67, etc. in endothelial cells in vitro. Depletion of macrophages or diversion of macrophage polarization during neovascularization impeded tumor growth and vascularization and resulted in greatly reduced F4/80+ TAMs, yet increased CD11b+ cells due to inhibition of TAM differentiation. In summary, our results showed dynamic and spatial–temporal F4/80+ TAM transformation within the tumor microenvironment and strengthened its role as perivascular and angiogenic TAMs in CRLM.

Most current deep learning-based news headline generation models only target domain-specific news data. When a new news domain appears, it is usually costly to obtain a large amount of data with reference truth on the new domain for model training, so text generation models trained by traditional supervised approaches often do not generalize well on the new domain—inspired by the idea of transfer learning, this paper designs a cross-domain transfer text generation method based on domain data distribution alignment, intermediate domain redistribution, and zero-shot learning semantic prototype transduction, focusing on the data problem with no reference truth in the target domain. Eventually, the model can be guided by the most relevant source domain data to generate headlines from the target domain news text through the semantic correlation between source and target domain data during the training process of generating headlines for the target domain news, even without any reference truth of the news headlines in the target domain, which improves the usability of the text generation model in real scenarios. The experimental results show that the proposed transfer text generation method has a good domain transfer effect and outperforms other existing transfer text generation methods in various text generation evaluation indexes, proving the proposed method's effectiveness in this paper.

IntroductionConsiderable evidence indicates that some trees are more vulnerable than others during bamboo (Phyllostachys edulis) expansion, which can affect plant community structure and alter the environment, but there has been insufficient research on the growth status of surviving individuals in colonized forests.MethodsIn this study, we compared the annual growth increment, growth rate, and onset, cessation, and duration of radial growth of Alniphyllum fortunei, Machilus pauhoi, and Castanopsis eyrei in a bamboo-expended broadleaf forest (BEBF) and a bamboo-absent broadleaf forest (BABF) using high-resolution point dendrometers.ResultsWe found that the annual radial growth of A. fortunei, M. pauhoi, and C. eyrei was 22.5%, 172.2%, and 59.3% greater in BEBF than in BABF, respectively. The growth rates of M. pauhoi and C. eyrei in BEBF were significantly higher than in BABF by13.9 μm/d and 19.6 μm/d, whereas A. fortunei decreased significantly by 7.9 μm/d from BABF to BEBF. The onset and cessation of broad-leaf tree growth was later, and the growth duration was longer in BEBF compared to BABF. For example, A. fortunei and M. pauhoi in BEBF had more than one month longer growth duration than in BABF. Additionally, the nighttime growth rates of some surviving broad-leaf trees in BEBF was significantly higher than that in BABF.DiscussionThese results suggest that the surviving trees have plasticity and can adapt to atmospheric changes and competitive relationships after expansion of bamboo in one of two ways: by increasing their growth rates or by modifying onset and cessation of growth to extend the growth duration of trees or avoid the period of intense competition with bamboo, thereby growing better. Our research reveals for the first time how the growth of surviving broad-leaf trees adjusts to bamboo expansion. These results provide insights into how biological expansions impact primary production and have implications for forest management in the Anthropocene.

Summary: Hydrochlorothiazide (HCTZ) is reported to impair glucose tolerance and may induce new onset of diabetes, but the pharmacomicrobiomics of the adverse effect for HCTZ remains unknown. Mice-fed HCTZ exhibited insulin resistance and impaired glucose tolerance. By using FMT and antibiotic cocktail models, we found that HCTZ-induced metabolic disorder was mediated by commensal microbiota. HCTZ consumption disturbed the structure of the intestinal microbiota, causing abnormal elevation of Gram-negative Enterobacteriaceae and lipopolysaccharide (LPS) then leading to intestinal barrier dysfunction. Additionally, HCTZ activated TLR4 signaling and induced macrophage polarization and inflammation in the liver. Furthermore, HCTZ-induced macrophage polarization and metabolic disorder were abrogated by blocking TLR4 signaling. HCTZ consumption caused a significant increase in Gram-negative Enterobacteriaceae, which elevated the levels of LPS, thereby activating LPS/TLR4 pathway, promoting inflammation and macrophage polarization, and resulting in metabolic disorders. These findings revealed that the gut microbiome is the key medium underlying HCTZ-induced metabolic disorder.

Summary: Dual or multi-targets therapy targeting epidermal growth factor receptor variant III (EGFRvIII) and other molecular may relax the constraint for glioblastoma (GBM), putting forward the urgent requirement of finding candidate molecules. Here, the insulin-like growth factor binding protein-3 (IGFBP3) was considered a candidate, whereas the mechanisms of IGFBP3 production remain unclear. We treated GBM cells with exogenous transforming growth factor β (TGF-β) to simulate the microenvironment. We found that TGF-β and EGFRvIII transactivation induced the activation of transcription factor c-Jun, which specifically bound to the promoter region of IGFBP3 through Smad2/3 and ERK1/2 pathways and promoted the production and secretion of IGFBP3. IGFBP3 knockdown inhibited the activation of TGF-β and EGFRvIII signals and the malignant behaviors triggered by them in vitro and in vivo. Collectively, our results indicated a positive feedback loop of p-EGFRvIII/IGFBP3 under administration of TGF-β, blocking IGFBP3 may be an additional target in EGFRvIII-expressing GBM-selective therapeutic strategy.

Introduction Amphetamine-type stimulants (ATSs) are presenting a great challenge to global public health along with its worldwide abuse in recent years. Protracted amphetamine abstinence syndrome (PAAS) is one of the primary causes of relapse for ATS abusers during withdrawal. However, different conclusions are reached by previous trials. This study is designed to evaluate the efficacy and safety of acupuncture in treating PAAS.Methods and analysis Cochrane Central Register of Controlled Trials, PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, ProQuest Dissertation and Theses, Allied and Complementary Medicine Database (AMED), ClinicalTrials.gov and who.int/trialsearch will be searched from the inception to February 2023 and language will be restricted to English and Chinese. Eligible randomised controlled trials will be included. The primary outcome is the intensity of withdrawal syndrome. The secondary outcomes include: (1) intensity of pain, anxiety, depression and other associated symptoms; (2) number of participants with relapse; (3) retention of treatment and (4) nature and rate of adverse effects. Data synthesis will be performed by using RevMan (V.5.4). The quality of evidence will be evaluated by the Grading of Recommendations, Assessment, Development and Evaluation approach. This study will strictly adhere to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines.Ethics and dissemination Ethical approval is not required as this is a systematic review and meta-analysis based on previously published studies that do not involve patients’ privacy. The results of this study will be disseminated in a peer-reviewed journal.PROSPERO registration number CRD42022297761.

Slightly acidic electrolytic water (SAEW) treatment for seed germination is a promising technique for sustainable agriculture. This study investigated the antioxidant activity of germinated sesame seeds treated with SAEW for the first time. Specifically, the impact and correlation of SAEW on the activities of total phenols, total flavonoids, and antioxidant oxidase in sesame seeds were examined. The results showed that SAEW with low ACC inhibited sesame germination, SAEW with high ACC promoted sesame germination, and sesame buds treated with SAEW with 30 mg/L and 50 mg/L ACC showed lower antioxidant activity and total phenolic and flavone content compared to tap water. In contrast, SAEW with 30 mg/L ACC had no significant effect on sesame growth but positively influenced the antioxidant activity of sesame seed germination by promoting phenolic compound synthesis through increased phenylalanine ammonia-lyase (PAL) activity and enhancing antioxidant activity by boosting PAL, polyphenol oxidase (PPO), and peroxidase (POD) activities. Generally, antioxidant ability was the most prominent in SAEW with 30 mg/L ACC, and positive correlations between antioxidation and total phenols and flavonoids content were found in sesame. These findings provide valuable insights into the mechanisms underlying the enhanced antioxidant capacity observed in germinated sesame seeds under SAEW stress.

Abstract Background Protracted amphetamine abstinence syndrome is one of the primary causes of relapse for amphetamine-type drug abusers during withdrawal. However, the importance of the management of protracted amphetamine abstinence syndrome is underestimated. Electro-acupuncture may be a safe and effective alternative therapy for protracted amphetamine abstinence syndrome, but the evidence is limited. Methods The study is a prospective, two-center, randomized, waitlist controlled, open-label pragmatic trial. A total of 300 patients with protracted amphetamine abstinence syndrome will be recruited. All participants will be randomly assigned to an electro-acupuncture group or a waitlist group in a 1:1 ratio. Participants in the electro-acupuncture group will receive the electrical-acupuncture treatment. Waitlist group participants will not receive electro-acupuncture treatment but will be assessed at each visit. Treatments will be administered twice a week for a total of 4 consecutive weeks. The primary outcome in this study is the change in the ACSA between baseline (week 0) and the completion of treatment (week 4), and the secondary outcomes are changes in the Hamilton Depression Scale (HAMD), the visual analog scale (VAS), the Hamilton Anxiety Scale (HAMA), the Pittsburgh Sleep Quality Index (PSQI), the Montreal Cognitive Assessment (MoCA), and the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). Discussion This study will assess the effectiveness of acupuncture in PAAS in real-world settings to provide support for clinical decisions and a basis for subsequent trials comparing acupuncture with other positive regimens. Trial registration ClinicalTrials.gov ChiCTR2000040619 . Registered on 3 December 2020

With the rapid development of online social networks, text-communication has become an indispensable part of daily life. Mining the emotion hidden behind the conversation-text is of prime significance and application value when it comes to the government public-opinion supervision, enterprise decision-making, etc. Therefore, in this paper, we propose a text emotion prediction model in a multi-participant text-conversation scenario, which aims to effectively predict the emotion of the text to be posted by target speaker in the future. Specifically, first, an affective space mapping is constructed, which represents the original conversation-text as an n-dimensional affective vector so as to obtain the text representation on different emotion categories. Second, a similar scene search mechanism is adopted to seek several sub-sequences which contain similar tendency on emotion shift to that of the current conversation scene. Finally, the text emotion prediction model is constructed in a two-layer encoder-decoder structure with the emotion fusion and hybrid attention mechanism introduced at the encoder and decoder side respectively. According to the experimental results, our proposed model can achieve an overall best performance on emotion prediction due to the auxiliary features extracted from similar scenes and the adoption of emotion fusion as well as the hybrid attention mechanism. At the same time, the prediction efficiency can still be controlled at an acceptable level.

Background: Given the limitations of traditional pharmacology pedagogical method, diverse novel teaching methods have been widely explored. In this study, we performed a network meta-analysis (NMA) to evaluate the effects of different strategies in pharmacology education.Methods: Literature databases were searched from their inception to November 2022, and the studies were screened according to predefined inclusion and exclusion criteria to extract important information. Outcomes, including theoretical test scores, experimental test scores, subjective test scores, satisfaction scores, and the proportion of satisfaction, were analyzed using R software (version 3.6.1) and STATA (version 15). The NMA was conducted with a random-effects model under the Bayesian framework to calculate odds ratios (ORs) or mean differences (MDs) with associated 95% credible intervals (95% CIs). Surface under the cumulative ranking curve (SUCRA) probability values were calculated to rank the teaching methods examined.Results: A total of 150 studies involving 21,269 students were included. This NMA systematically evaluated 24 teaching strategies, such as problem-based learning (PBL), team-based learning (TBL), case-based learning (CBL) and flipped classrooms (FC), etc., The results of the NMA showed that, PBL combined with CBL was most likely to improve students’ theoretical and subjective test scores (SUCRA = 75.49 and 98.19%, respectively), TBL was most likely to improve the experimental test score (SUCRA = 92.38%) and the satisfaction score (SUCRA = 88.37%), while FC had the highest probability of being the best option for improving the proportion of satisfaction (SUCRA = 84.45%).Conclusion: The current evidence indicates that TBL, PBL combined with CBL, and FC might be optimal strategies for pharmacology education since they have a more beneficial effect on students.

ABSTRACT Infection by fungal pathogens is the main factor leading to postharvest rot and quality deterioration of fruit and vegetables. Rotting caused by Alternaria alternata is a concerning disease for numerous crops in both production and postharvest stages, especially tomato black spots. In this study, the double Petri dish assay showed that the VOCs of Ceratocystis fimbriata WJSK-1 and Mby inhibited the mycelial growth of fungal pathogen A. alternata, with a percentage inhibition of 52.2% and 42.9%. Then, HS-SPME-GC-MS technology was used to analyze the volatiles produced by two strains of C. fimbriata (WJSK-1, Mby), a total of 42 volatile single components were obtained, the main volatiles compounds identified include nine esters, 10 ketones, five alcohols, four aldehydes, three aromatic hydrocarbons, three heterocycles, four alkenes, three alkanes, and one acid. After that, the antifungal activity of a single volatile component was evaluated both in vitro and in vivo, four single components with antifungal effects were screened out, namely, benzaldehyde, nonanal, 2-Phenylethanol and isoamyl acetate, with IC50 values show the smallest values for benzaldehyde and nonanal at 0.11 μL mL−1, 0.04 μL mL−1. A. alternata exposed to VOCs had abnormal morphology for hyphae, delayed sporulation, and inhibited spore germination. In vivo experiment shows that the four volatile components can effectively suppress disease incidence on fungal-inoculated fruit; the two aldehydes (benzaldehyde and nonanal) have more prominent effect on delaying fruit onset of disease. The results showed that VOCs produced by C. fimbriata have potential as a fumigant for controlling black rot in cherry tomatoes. IMPORTANCE In this research, the volatile organic compounds (VOCs) produced based on C. fimbriata exhibited strong antifungal activity against the fungal pathogen A. alternata. Our aim is to explore their bacteriostatic components. HS-SPME-GC-MS technology was used to analyze the volatiles produced by the C. fimbriata strain (WJSK-1, Mby). Postharvest cherry tomato fruit black rot caused by A. alternata was treated both in vitro and in vivo, with pure individual components produced by C. fimbriata. The benzaldehyde, nonanal, 2-Phenylethanol, and isoamyl acetate from C. fimbriata can effectively inhibit growth of A. alternata, and delay disease. It has the potential to be developed as a new type of fumigant, a potential replacement for fungicides in the future.

Biomolecules, such as proteins and peptides, can be self-assembled. They are widely distributed, easy to obtain, and biocompatible. However, the self-assembly of proteins and peptides has disadvantages, such as difficulty in obtaining high quantities of materials, high cost, polydispersity, and purification limitations. The difficulties in using proteins and peptides as functional materials make it more complicate to arrange assembled nanostructures at both microscopic and macroscopic scales. Amino acids, as the smallest constituent of proteins and the smallest constituent in the bottom-up approach, are the smallest building blocks that can be self-assembled. The self-assembly of single amino acids has the advantages of low synthesis cost, simple modeling, excellent biocompatibility and biodegradability in vivo. In addition, amino acids can be assembled with other components to meet multiple scientific needs. However, using these simple building blocks to design attractive materials remains a challenge due to the simplicity of the amino acids. Most of the review articles about self-assembly focus on large molecules, such as peptides and proteins. The preparation of complicated materials by self-assembly of amino acids has not yet been evaluated. Therefore, it is of great significance to systematically summarize the literature of amino acid self-assembly. This article reviews the recent advances in amino acid self-assembly regarding amino acid self-assembly, functional amino acid self-assembly, amino acid coordination self-assembly, and amino acid regulatory functional molecule self-assembly.

Glioblastoma multiforme (GBM) is the most malignant intracranial tumor in adults, characterized by extensive infiltrative growth, high vascularization, and resistance to multiple therapeutic approaches. Among the many factors affecting the therapeutic effect, the immunosuppressive GBM microenvironment that is created by cells and associated molecules via complex mechanisms plays a particularly important role in facilitating evasion of the tumor from the immune response. Accumulating evidence is also revealing a close association of the gut microbiota with the challenges in the treatment of GBM. The gut microbiota establishes a connection with the central nervous system through bidirectional signals of the gut–brain axis, thus affecting the occurrence and development of GBM. In this review, we discuss the key immunosuppressive components in the tumor microenvironment, along with the regulatory mechanism of the gut microbiota involved in immunity and metabolism in the GBM microenvironment. Lastly, we concentrate on the immunotherapeutic strategies currently under investigation, which hold promise to overcome the hurdles of the immunosuppressive tumor microenvironment and improve the therapeutic outcome for patients with GBM.

Microorganism-produced volatile organic compounds (VOCs) are considered promising environmental-safety fumigants in food preservation. In this study, the VOCs from fungal Ceratocystis fimbriata strains (WSJK-1, Mby) were tested against postharvest fungi Monilinia laxa, Fusarium oxysporum, Monilinia fructicola, Botrytis cinerea, Alternaria solani, and Aspergillus flavus in vitro. The mycelial growth was significantly inhibited, in particular M. fructicola and B. cinerea (76.95, 76.00%), respectively. VOCs were identified by headspace solid-phase microextraction coupled with Gas Chromatography–Mass Spectrometry (HS-SPME-GC–MS); 40 compounds were identified. The antifungal activity of 21 compounds was tested by the minimum inhibitory concentrations (MIC) value. Benzaldehyde, 2-Phenylethanol, and 1-Octen-3-ol showed strong antifungal activity with the MIC in vitro ranging from 0.094 to 0.284 ml L−1 depending on the pathogen tested. The optical microscope showed serious morphological damage, including cell deformation, curling, collapse, and deficiency in mycelial or conidia cell structures treated with C. fimbriata VOCs and pure compounds. In vivo tests, C. fimbriata VOCs decreased brown rot severity in peaches, and compounds Benzaldehyde and 2-Phenylethanol could reduce peach brown rot in peaches at 60 μl L−1. The VOCs produced by C. fimbriata strain have good antifungal effects; low concentration fumigation could control peach brown rot. Its fragrance is fresh, safe, and harmless, and it is possible to replace chemical fumigants. It could be used as a potential biofumigant to control fruit postharvest transportation, storage, and food preservation. To the best of our knowledge, this is the first report on the antifungal activity and biocontrol mechanism of VOCs produced by C. fimbriata.

The observations of transient luminous events from space-borne platform extend our exploration on the mysteries of sprite phenomenology from continental thunderstorms to oceanic thunderstorms. By combining with ground-based measurements of causative strokes for hundreds of red sprites observed by the Imager of Sprites and Upper Atmospheric Lightnings (ISUAL) during 2004–2016, there is a consensus that negative cloud-to-ground (CG) strokes spawned by oceanic thunderstorms are more readily to produce sprites. The existing ground-based observations in both Caribbean Sea and near the coast of South China, mainly due to the contributions from numerous amateurs, are generally consistent with the implications of ISUAL observations. However, the physical mechanisms that might cause the enhancement of negative CG strength in the ocean remain not completely understood. There have been analyses on several cases of oceanic thunderstorms abundant in producing negative sprites. It seems that the production of negative sprites heavily depends on the size of parent thunderstorms, and they are often generated by thunderstorm conditions that are also favorable for gigantic jets.

BackgroundPorphyromonas gingivalis (Pg), the keystone pathogen in chronic periodontitis, is reported to initiate Alzheimer’s disease pathologies in preclinical studies. However, the specific mechanisms and signaling pathways acting on the brain still need to be further explored. Outer membrane vesicles are derived from Gram-negative bacteria and contain many virulence factors of bacteria. We hypothesized that outer membrane vesicles are an important weapon of Porphyromonas gingivalis to initiate Alzheimer’s disease pathologies.MethodsThe outer membrane vesicles of Porphyromonas gingivalis (Pg OMVs, 4 mg/kg) or saline were delivered to 14-month-old mice by oral gavage every other day for eight weeks. Behavioral alterations were assessed by the open field test, Morris water maze, and Y-maze test. Blood–brain barrier permeability, neuroinflammation, tau phosphorylation, and NLRP3 inflammasome-related protein were analyzed.ResultsPg OMVs impaired memory and learning ability of mice and decreased tight junction–related gene expression ZO-1, occludin, claudin-5, and occludin protein expression in the hippocampus. Pg OMVs could be detected in the hippocampus and cortex three days after oral gavage. Furthermore, Pg OMVs activated both astrocytes and microglia and elevated IL-1β, tau phosphorylation on the Thr231 site, and NLRP3 inflammasome–related protein expression in the hippocampus. In in vitro studies, Pg OMV (5 µg/ml) stimulation increased the mRNA and immunofluorescence of NLRP3 in BV2 microglia, which were significantly inhibited by the NLRP3 inhibitor MCC950. In contrast, the tau phosphorylation in N2a neurons was enhanced after treatment with conditioned media from Pg OMV-stimulated microglia, which was attenuated after pretreatment with MCC950.ConclusionsThese results indicate that Pg OMVs prompt memory dysfunction, neuroinflammation, and tau phosphorylation and trigger NLRP3 inflammasome in the brain of middle-aged mice. We propose that Pg OMVs play an important role in activating neuroinflammation in the AD-like pathology triggered by Porphyromonas gingivalis, and NLRP3 inflammasome activation is a possible mechanism.

IntroductionThe efficacy of short-term spinal cord stimulation (stSCS) as a treatment for neuropathic pain in patients with postherpetic neuralgia (PHN) has already been validated. However, the potential alterations in brain functionality that are induced by such treatment have yet to be completely elucidated.MethodsThis study use resting-state functional magnetic resonance imaging (rs-fMRI) to detect the changes in regional homogeneity (ReHo) and degree centrality (DC) related to stimulator-induced pain relief in patients with PHN. A total of 10 patients with PHN underwent an MRI protocol at baseline and after stSCS. Alterations in ReHo and DC were then compared between baseline and after stSCS. We investigated the relationship between clinical parameters and functional changes in the brain.ResultsClinical parameters on pain, emotion, and sleep quality were correlated with ReHo and DC. ReHo and DC were significantly altered in the middle temporal gyrus, precuneus, superior frontal gyrus, supramarginal gyrus, inferior parietal lobule, rolandic operculum, middle occipital gyrus, superior parietal gyrus, and the precentral gyrus after stSCS. A significant correlation was detected between ReHo changes in the middle occipital gyrus, precuneus, inferior parietal gyrus, and changes in pain, emotion, and sleep quality. A significant negative correlation was detected between DC changes in the middle temporal gyrus, rolandic operculum, supramarginal gyrus, precuneus, inferior parietal gyrus, and changes in pain, emotion, and sleep quality.ConclusionThis study found that stSCS is able to induce ReHo and DC changes in patients with PHN, thus suggesting that stSCS can change brain function to alleviate pain, sleep, and emotional disorder.

A wide-field high resolution microscopy with sub-micron resolution and high contrast image was demonstrated by using the isotropy frequency-domain extension imaging (IFEI), which was successfully applied to submicron-scale structure detection of fused silica wafer for the first time. Employing the frequency-domain extension and the isotropic period matching, the IFEI extended the bandwidth of coherent transfer function of the conventional wide-field microscopy, thereby improving the resolution to break the diffraction limit. In this method, a quantitative measurement of 200 nm was achieved using fused silica wafer with prefabricated etched structure on the surface. By imaging 81 nm gold nanoparticles, the system resolution calibration was achieved. And corresponding system’s lateral resolution of approximately 179.5 nm was obtained, which was 1.72 times higher than the conventional wide-field microscopy image. Moreover, the reconstructed IFEI images of ultra-precision processed fused silica optics were demonstrated to present the finer structures of sub-micron digs and scratches formed in the optics manufacturing process.

Surface-enhanced Raman spectroscopy (SERS) has attracted much attention because of its high sensitivity, high speed, and simple sample processing, and has great potential for application in the field of pesticide residue detection. However, SERS is susceptible to the influence of a complex detection environment in the detection of pesticide residues on the surface of fruits, facing problems such as interference from the spectral peaks of detected impurities, unclear dimension of effective correlation data, and poor linearity of sensing signals. In this work, the enhanced raw data of the pesticide thiram residues on the fruit surface using gold nanoparticle (Au-NPs) solution are formed into the raw data set of Raman signal in the IoT environment of Raman spectroscopy principal component detection. Considering the non-linear characteristics of sensing data, this work adopts kernel principal component analysis (KPCA) including radial basis function (RBF) to extract the main features for the spectra in the ranges of 653∼683 cm−1, 705∼728 cm−1, and 847∼872 cm−1, and discusses the effects of different kernel function widths (σ) to construct a qualitative analysis of pesticide residues based on SERS spectral data model, so that the SERS spectral data produce more useful dimensionality reduction with minimal loss, higher mean squared error for cross-validation in non-linear scenarios, and effectively weaken the interference features of detecting impurity spectral peaks, unclear dimensionality of effective correlation data, and poor linearity of sensing signals, reflecting better extraction effects than conventional principal component analysis (PCA) models.

Iron loading has been reported to be a common stress in the development of cells, and this might be related to bone loss and osteoporosis. Astragaloside IV (ASI‐IV), a pure compound derived from Radix Astragali, has been reported to exhibit cardioprotective, anti‐inflammatory, antioxidant, antiasthmatic and anticancer effects. The aim of this study was to investigate whether ASI‐IV could reverse iron loading‐induced inhibition of cell viability, proliferation, pluripotency and osteogenesis and promote adipogenesis of bone marrow mesenchymal stem cells (BMSCs). Ferric ammonium citrate (FAC) was used to stimulate iron loading conditions. ASI‐IV was observed to ameliorate the FAC‐induced reduction of cell viability, proliferation, pluripotency and osteogenesis of BMSCs. In addition, ASI‐IV could block the increased adipogenesis of BMSCs after FAC treatment. We intraperitoneally injected mice with 250 mg·kg−1 iron dextran, with or without ASI‐IV (40 mg·kg−1), for 4 weeks. ASI‐IV inhibited the iron loading‐induced bone loss of these mice. Furthermore, ASI‐IV played a protective role in iron loading‐induced abnormal differentiation of BMSCs by regulating iron homeostasis and metabolism. In summary, our study suggesteds that ASI‐IV might have potentials for development into a novel therapeutic strategy for the treatment of iron loading‐induced abnormal differentiation of BMSCs and osteoporosis.

Abstract Plants have evolved genetic and physiological mechanisms to mitigate the adverse effects of high temperature. CARBOXYL TERMINUS OF THE HSC70-INTERACTING PROTEINS (CHIP) is a conserved chaperone-dependent ubiquitin E3 ligase that targets misfolded proteins. Here, we report functional analysis of the SlCHIP gene from tomato (Solanum lycopersicum) in heat tolerance. SlCHIP encodes a CHIP protein with three tandem tetracopeptide repeat (TPR) motifs and a C-terminal U box domain. Phylogenetic analysis of CHIP homologs from animals, spore-bearing and seed plants revealed a tree topology similar to the evolutionary tree of the organisms. Expression of SlCHIP was induced under high temperature and was also responsive to plant stress hormones. Silencing of SlCHIP in tomato reduced heat tolerance based on increased heat stress symptoms, reduced photosynthetic activity, elevated electrolyte leakage and accumulation of insoluble protein aggregates. The accumulated protein aggregates in SlCHIP-silenced plants were still highly ubiquitinated, suggesting involvement of other E3 ligases in ubiquitination. SlCHIP restored the heat tolerance of Arabidopsis chip mutant to the wild type levels. These results indicate that tomato SlCHIP plays a critical role in heat stress responses most likely by targeting degradation of misfolded proteins that are generated during heat stress.

Li, Cebrian et al. show that a combination of peptide D-11 and vancomycin exhibits a potent antimicrobial activity against a panel of Gram-negative pathogens without apparent toxicity. They find that this combination is also effective in clearing Pseudomonas aeruginosa in mice, providing a potential antimicrobial therapy for humans.

With the development of bionic computer vision for images processing, researchers have easily obtained high-resolution zoom sensing images. The development of drones equipped with high-definition cameras has greatly increased the sample size and image segmentation and target detection are important links during the process of image information. As biomimetic remote sensing images are usually prone to blur distortion and distortion in the imaging, transmission and processing stages, this paper improves the vertical grid number of the YOLO algorithm. Firstly, the light and shade of a high-resolution zoom sensing image were abstracted, and the grey-level cooccurrence matrix extracted feature parameters to quantitatively describe the texture characteristics of the zoom sensing image. The Simple Linear Iterative Clustering (SLIC) superpixel segmentation method was used to achieve the segmentation of light/dark scenes, and the saliency area was obtained. Secondly, a high-resolution zoom sensing image model for segmenting light and dark scenes was established to made the dataset meet the recognition standard. Due to the refraction of the light passing through the lens and other factors, the difference of the contour boundary light and dark value between the target pixel and the background pixel would make it difficult to detect the target, and the pixels of the main part of the separated image would be sharper for edge detection. Thirdly, a YOLO algorithm with an improved vertical grid number was proposed to detect the target in real time on the processed superpixel image array. The adjusted aspect ratio of the target in the remote sensing image modified the number of vertical grids in the YOLO network structure by using 20 convolutional layers and five maximum aggregation layers, which was more accurately adapted to “short and coarse” of the identified object in the information density. Finally, through comparison with the improved algorithm and other mainstream algorithms in different environments, the test results on the aid dataset showed that in the target detection of high spatial resolution zoom sensing images, the algorithm in this paper showed higher accuracy than the YOLO algorithm and had real-time performance and detection accuracy.

A transverse excitation magnetic flux leakage (MFL) inline detector, with a diameter of 711 mm, was developed in response to the difficulty in detecting axial metal loss defects of long-distance oil and gas pipelines. Linked by the driver and the recorder, the transverse excitation MFL inline detector is mainly composed of a support system, a drive system, a magnetization system, a sensor system, and an acquisition system, etc. With excitation design of auxiliary magnetic poles, the magnetization system of the transverse excitation MFL inline detector can, in addition to meeting the magnetization saturation requirement of the pipeline wall thickness, improve the magnetization effect, reduce the MFL field gradient at the sensor position, and enhance the quantification accuracy for defects. Traction test and industrial application verification were conducted on a new pipeline transverse excitation MFL inline detector, and the results indicate that, the data signals of axial grooves and axial cracklike defects, which are acquired by the transverse excitation MFL inline detector, are clearer compared with the axial excitation MFL detector. This may inevitably contribute to the improved detection accuracy and detection rate of axial defects, as well as the great engineering significance for detecting and identifying axial pipeline defects.

ABSTRACT WCK 5222 (cefepime/zidebactam) is a β-lactam/β-lactamase inhibitor combination that is effective against a broad range of highly drug-resistant bacterial pathogens, including those producing metallo-β-lactamase. In this study, we isolated a multidrug-resistant Pseudomonas aeruginosa clinical strain that is resistant to a variety of β-lactam antibiotics and the ceftazidime-avibactam combination. A metallo-β-lactamase gene blaDIM-2 was identified on a self-transmissible megaplasmid in the strain, which confers the resistance to β-lactam antibiotics, leaving WCK 5222 potentially one of the last treatment resorts. In vitro passaging assay combined with whole-genome sequencing revealed mutations in the pbpA gene (encoding the zidebactam target protein PBP2) in the evolved resistant mutants. Among the mutations, a V516M mutation increased the bacterial virulence in a murine acute pneumonia model. Reconstitution of the mutations in the reference strain PAO1 verified their roles in the resistance to zidebactam and revealed their influences on cell morphology in the absence and presence of zidebactam. Microscale thermophoresis (MST) assays demonstrated that the mutations reduced the affinity between PBP2 and zidebactam to various extents. Overall, our results revealed that mutations in the pbpA gene might be a major cause of evolved resistance to WCK 5222 in clinical settings. IMPORTANCE Antibiotic resistance imposes a severe threat on human health. WCK 5222 is a β-lactam/β-lactamase inhibitor combination that is composed of cefepime and zidebactam. It is one of the few antibiotics in clinical trials that are effective against multidrug-resistant Pseudomonas aeruginosa, including those producing metallo-β-lactamases. Understanding the mechanisms and development of bacterial resistance to WCK 5222 may provide clues for the development of strategies to suppress resistant evolvement. In this study, we performed an in vitro passaging assay by using a multidrug-resistant P. aeruginosa clinical isolate. Our results revealed that mutations in the zidebactam target protein PBP2 play a major role in the bacterial resistance to WCK 5222. We further demonstrated that the mutations reduced the affinities between PBP2 and zidebactam and resulted in functional resistance of PBP2 to zidebactam.

Methamphetamine (METH), an amphetamine-type psychostimulant, is highly abused worldwide. Chronic abuse of METH causes neurodegenerative changes in central dopaminergic neurons with numerous neuropsychiatric consequences. Neuronal apoptosis plays a critical role in METH-induced neurotoxicity and may provide promising pharmacological targets for preventing and treating METH addiction. In recent years, accumulating evidence has revealed that natural products may possess significant potentials to inhibit METH-evoked neuronal apoptosis. In this review, we summarized and analyzed the improvement effect of natural products on METH-induced neuronal apoptosis and their potential molecular mechanisms on modulating dopamine release, oxidative stress, mitochondrial-dependent apoptotic pathway, endoplasmic reticulum stress-mediated apoptotic pathway, and neuroinflammation. Hopefully, this review may highlight the potential value of natural products in modulating METH-caused neuronal apoptosis and provide useful information for future research and developments of novel and efficacious pharmacotherapies in this field.