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Introduction: The health effects of ambient ozone have been investigated in many previous studies. However, the effects of long-term exposure to ambient ozone on the incidence of cardiovascular disease (CVD) remain inconclusive. Objectives: To estimate the associations of long-term exposure to maximum daily 8-hours average ozone (MDA8 O3) with the incidence of total CVD, heart disease, hypertension, and stroke. Methods: This was a prospective cohort study, and the data was obtained from the China Health and Retirement Longitudinal Survey (CHARLS) implemented during 2011–2018 and the China Family Panel Studies (CFPS) implemented during 2010–2018. We applied a Cox proportional hazards regression model to evaluate the associations of MDA8 O3 with total CVD, heart disease, hypertension, and stroke risks, and the corresponding population-attributable fractions (PAF) attributable to MDA8 O3 were also calculated. All analyses were conducted by R software. Results: The mean MDA8 O3 concertation of all included participants in the CHARLS and CFPS were 51.03 part per billion (ppb) and 51.15 ppb, respectively. In the CHARLS including 18,177 participants, each 10 ppb increment in MDA8 O3 concentration was associated with a 31% increase [hazard ratio (HR) = 1.31, 95% confidence interval (CI): 1.22–1.42] in the risk of incident heart disease, and the corresponding population-attributable fractions (PAF) was 13.79% [10.12%-17.32%]. In the CFPS including 30,226 participants, each 10 ppb increment in MDA8 O3 concentration was associated with an increase in the risk of incident total CVD (1.07 [1.02–1.13]), and hypertension (1.10 [1.03–1.18]). The PAFs of total CVD, and hypertension attributable to MDA8 O3 were 3.53% [0.82%-6.16%], and 5.11% [1.73%-8.38%], respectively. Stratified analyses showed greater associations in males, urban areas, and Southern China. Conclusions: Long-term exposure to MDA8 O3 may increase the incidence of CVD. Therefore, the policies that control O3 and related precursors are persistently needed.

Abstract With the advancement of science and technology, coal-washing plants are transitioning to intelligent, information-based, and professional sorting systems. This shift accelerates the construction a modern economic system characterized by green and low-carbon development, thereby promoting the high-quality advancement of the coal industry. Traditional manual gangue picking and multi-axis robotic arm gangue selection currently suffer from low recognition accuracy, slow sorting efficiency, and high worker labor intensity. This paper proposes a deep learning-based, non-contact gangue recognition and pneumatic intelligent sorting system. The system constructs a dynamic database containing key feature information such as the target gangue's contour, quality, and center of mass. The system elucidates the relationships between ejection speed, mass, volume, angle of incidence, and the impact energy matching mechanism. Demonstration experiments using the system prototype for coal gangue sorting reveal that, compared to existing robotic arm sorting methods in coal washing plants, this system achieves a gangue identification accuracy exceeding 97%, a sorting rate above 91%, and a separation time of less than 3 s from identification to separation, thereby effectively enhancing raw coal purity.

Sea buckthorn (Hippophae rhamnoides L.) contains a variety of biologically active compounds, including flavonoids, terpenoids, polysaccharides, organic acids, volatile oils, and vitamins. It has been demonstrated to be effective in the treatment of cardiovascular disorders. In this paper, we evaluated the pharmacological effects of sea buckthorn in cardiovascular diseases through preclinical studies, and revealed the mechanism of action of the active components in sea buckthorn in cardiovascular diseases, including anti-inflammatory, lipid oxidation regulation, antioxidant, vascular function modulation, anti-platelet aggregation, autophagy, intestinal microorganism regulation, and cell apoptosis reduction. In clinical trials, sea buckthorn was proven to be effective in managing lipid metabolism, blood pressure, and blood glucose levels in patients. We also extensively reviewed the safety of sea buckthorn medicine and its toxicity to numerous organs. To summarize, sea buckthorn has a beneficial effect on cardiovascular disease and may give a novel strategy for clinical intervention and therapy. This paper summarizes the phytochemistry, pharmacology, clinical applications, safety, and toxicity of sea buckthorn in order to better understand the mechanism of action of the various bioactive components in sea buckthorn, investigate its medicinal potential, and provide more options for the treatment of cardiovascular diseases.

The aging precipitated phases are of great significance for the strengthening and toughening of Al–Zn–Mg alloys. In this work, pre-precipitating was realized through equal channel angular pressing (ECAP) immediately followed by solid solution treatment at 475 °C for 6 h. Its corresponding strengthening and toughening effect on the room temperature (RT)-rolled Al–6Zn–1Mg alloy was systematically studied. The results indicate that pre-precipitating by ECAP can effectively improve the strength of the RT-rolled Al–6Zn–1Mg alloy and circumvent the strength-ductility trade-off. Microstructure characterization reveals that ECAP induces a large number of microshear bands, which can not only encourage recrystallization but also effectively promote the precipitation of the η′ phase. The synergistic effect of precipitation strengthening and dislocation strengthening contributes to the high strength of Al–6Zn–1Mg alloy, with UTS and YS increasing to ∼522 MPa and ∼400 MPa, respectively. Meanwhile, the ductility remains almost unchanged mainly due to the coordinated grain boundary sliding and the uniform and finely dispersed second phase particles. As a result, the strength-ductility trade-off is effectively avoided. The findings shed some light on optimizing the traditional aging treatment.

The pivotal role of lithium (Li) in improving the comprehensive mechanical properties of third-generation Al–Li alloys remains significant even at a low content. However, the strengthening contribution of a low dosage lithium and its combination with different processing methods remain largely unknown. This study aimed to investigate the strengthening effects of room-temperature (RT) equal channel angular pressing (ECAP) and rolling on Al–0.6Li alloy. Microstructural evolution during processing was monitored by optical microscope (OM), scanning electron microscope (SEM), electron backscattered diffraction (EBSD), transmission electron microscope (TEM) and X-ray diffraction (XRD). The results revealed that simultaneous high ultimate tensile strength (UTS, 243 MPa) and yield strength (YS, 210 MPa) of the developed Al–0.6Li alloy were specifically achieved with a combination of RT ECAP and rolling, alongside an elongation (EL) of 9.5%. The gained strength improvement was primarily credited to the excellent fine-grain strengthening, as evidenced by a significant reduction in grain size from 101 μm to 1.47 μm, and dislocation strengthening, which, respectively, contributed to an increase of 91 MPa and 100 MPa in YS. Findings from this study demonstrate that with proper processing technology, the mechanical properties of Al–Li alloys with low Li content can be effectively improved, opening new avenues to develop high-performance Al–Li alloys.

BackgroundDuring the special period of the global spread of COVID-19, pregnant women are sensitive groups to the impacts of COVID-19 epidemic. However, the effects of lockdown measures implemented in response to the COVID-19 on fetal birthweight remain unclear.ObjectivesThis study investigated the associations of COVID-19 lockdown with birth weight in Chinese population.MethodsWe collected 730,153 data of participants from hospitals of five cities in the south of China, we defined the time period of level I response (1/23-2/24/2020) as level I lockdown, and women who were pregnant during level I lockdown as the exposure group. Women who were pregnant during the same calendar month from 2015 to 2019 were defined as the unexposed group. We quantitatively estimate the individual cumulative exposure dose by giving different weights to days with different emergency response levels. Generalized linear regression models were used to estimate the association between COVID-19 lockdown exposure with birth weight and risk of low birth weight (4,000 g).ResultsThe birth weight of the exposed group is heavier than the unexposed group (3,238.52 vs. 3,224.11 g: adjusted β = 24.39 g [95% CI: 21.88, 26.91 g]). The exposed group had a higher risk of macrosomia (2.8% vs. 2.6%; adjusted OR = 1.17 [95% CI: 1.12, 1.22]). More obvious associations were found between COVID-19 lockdown and macrosomia in women who experienced the lockdown in their early pregnancy. Women who experienced the lockdown at their 4–7 weeks of pregnancy showed statistically significant heavier birth weight than unexposed group (after adjustment): β = 1.28 (95% CI: 1.11, 1.46) g. We also observed a positive association between cumulative exposure dose of COVID-19 lockdown in all pregnant women and birth weight, after divided into four groups, Q1: β = 32.95 (95% CI: 28.16, 37.75) g; Q2: β = 18.88 (95% CI: 14.12, 23.64) g; Q3: β = 19.50 (95% CI: 14.73, 24.28) g; Q4: β = 21.82 (95% CI: 17.08, 26.56) g. However, there was no statistically significant difference in the risk of low birth weight between exposed and unexposed groups.ConclusionsThe COVID-19 lockdown measures were associated with a heavier birth weight and a higher risk of macrosomia. Early pregnancy periods may be a more susceptible exposure window for a heavier birth weight and a higher risk of macrosomia. We also observed a positive association between cumulative exposure dose of COVID-19 lockdown and birth weight. The government and health institutions should pay attention to the long-term health of the infants born during the COVID-19 lockdown period, and follow up these mothers and infants is necessary.

Microalgae are a group of microscopic eukaryotic organisms that can transform carbon dioxide into diverse bioactive compounds through photosynthesis using chlorophyll a. Over the past decade, biohybrid materials comprising live microalgae and other biocompatible components have exhibited tremendous potential in solving many medical challenges, such as oncotherapy, tissue reconstruction, and drug delivery. Microalgae immobilized within conventional biomaterials can maintain their photosynthetic activity for an extended period of time, thereby providing local oxygen and working as biocompatible interfacing materials for regulating cell activities. The motility of microalgae has also inspired the development of biohybrid microrobots, in which drug molecules can be bound to the surface of microalgae via noncovalent adsorption and delivered to the target area through precisely controlled locomotion. Moreover, the autofluorescence, phototaxis, and biomass production of microalgae can be integrated into the design of novel biohybrid materials with versatile functions. Furthermore, through appropriate genetic manipulation, engineered microalgae can endow biohybrid materials with novel properties, such as specific cell-targeting capability and the local release of recombinant proteins from algae cells—technologies that show promise for promoting and diversifying the clinical use of microalgae-based biohybrid materials (MBBMs) in several fields of biomedicine. Herein, we summarize the fabrication, physiology, and locomotion ability of MBBMs; we then review typical and recent reports on the use of MBBMs in the biomedical field; finally, we provide critical discussions on the challenges and future perspectives of MBBMs.

Abstract Background Lignocellulose is the most abundant renewable resource in the world and has attracted widespread attention. It can be hydrolyzed into sugars with the help of cellulases and hemicellulases that are secreted by filamentous fungi. Several studies have revealed that the Ras small GTPase superfamily regulates important cellular physiological processes, including synthesis of metabolites, sporulation, and cell growth and differentiation. However, it remains unknown how and to what extent Ras small GTPases participate in cellulase production. Results In this study, we found that the putative Ras small GTPase RSR1 negatively regulated the expression of cellulases and xylanases. Deletion of rsr1 (∆rsr1) significantly increased cellulase production and decreased the expression levels of ACY1-cAMP-protein kinase A (PKA) signaling pathway genes and the concentration of intracellular cyclic adenosine monophosphate (cAMP). Loss of acy1 based on ∆rsr1 (∆rsr1∆acy1) could further increase cellulase production and the expression levels of cellulase genes, while overexpression of acy1 based on ∆rsr1 (∆rsr1-OEacy1) significantly reduced cellulase production and transcriptional levels of cellulase genes. In addition, our results revealed that RSR1 negatively controlled cellulase production via the ACY1-cAMP-PKA pathway. Transcriptome analysis revealed significantly increased expression of three G-protein coupled receptors (GPCRs; tre62462, tre58767, and tre53238) and approximately two-fold higher expression of ACE3 and XYR1, which transcriptionally activated cellulases with the loss of rsr1. ∆rsr1∆ tre62462 exhibited a decrease in cellulase activity compared to ∆rsr1, while that of ∆rsr1∆tre58767 and ∆rsr1∆tre53238 showed a remarkable improvement compared to ∆rsr1. These findings revealed that GPCRs on the membrane may sense extracellular signals and transmit them to rsr1 and then to ACY1-cAMP-PKA, thereby negatively controlling the expression of the cellulase activators ACE3 and XYR1. These data indicate the crucial role of Ras small GTPases in regulating cellulase gene expression. Conclusions Here, we demonstrate that some GPCRs and Ras small GTPases play key roles in the regulation of cellulase genes in Trichoderma reesei. Understanding the roles of these components in the regulation of cellulase gene transcription and the signaling processes in T. reesei can lay the groundwork for understanding and transforming other filamentous fungi.

Abstract Background Trichoderma reesei Rut-C30 is a hypercellulolytic mutant strain that degrades abundant sources of lignocellulosic plant biomass, yielding renewable biofuels. Although Zn2+ is an activator of enzymes in almost all organisms, its effects on cellulase activity in T. reesei have yet to be reported. Results Although high concentrations of Zn2+ severely suppressed the extension of T. reesei mycelia, the application of 1–4 mM Zn2+ enhanced cellulase and xylanase production in the high-yielding cellulase-producing Rut-C30 strain of T. reesei. Expression of the major cellulase, xylanase, and two essential transcription activator genes (xyr1 and ace3) increased in response to Zn2+ stimulation. Transcriptome analysis revealed that the mRNA levels of plc-e encoding phospholipase C, which is involved in the calcium signaling pathway, were enhanced by Zn2+ application. The disruption of plc-e abolished the cellulase-positive influence of Zn2+ in the early phase of induction, indicating that plc-e is involved in Zn2+-induced cellulase production. Furthermore, treatment with LaCl3 (a plasma membrane Ca2+ channel blocker) and deletion of crz1 (calcineurin-responsive zinc finger transcription factor 1) indicated that calcium signaling is partially involved in this process. Moreover, we identified the zinc-responsive transcription factor zafA, the transcriptional levels of which declined in response to Zn2+ stress. Deletion of zafA indicates that this factor plays a prominent role in mediating the Zn2+-induced excessive production of cellulase. Conclusions For the first time, we have demonstrated that Zn2+ is toxic to T. reesei, although promotes a marked increase in cellulase production. This positive influence of Zn2+ is facilitated by the plc-e gene and zafA transcription factor. These findings provide insights into the role of Zn2+ in T. reesei and the mechanisms underlying signal transduction in cellulase synthesis.

Personalized recommender systems play a crucial role in assisting users in discovering items of interest from vast amounts of information across various domains. However, developing accurate personalized recommender systems remains challenging due to the need to balance model architectures, input feature combinations, and fusion of heterogeneous data sources. This study investigates the impacts of these factors on recommendation performance using the MovieLens and Book Recommendation datasets. Six models, including single-task neural networks, multi-task learning, and baselines, were evaluated with various input feature combinations using Root Mean Squared Error (RMSE) and Mean Absolute Error (MAE). The multi-task learning approach achieved significantly lower RMSE and MAE by effectively leveraging heterogeneous data sources for personalized recommendations through a shared neural network architecture. Furthermore, incorporating user data and content data progressively enhanced performance compared to using only item identifiers. The findings highlight the importance of advanced model architectures and fusing heterogeneous data sources for high-quality recommendations, providing valuable insights for designing effective recommender systems across diverse domains.

Birth weight is an indicator linking intrauterine environmental exposures to later-life diseases, and intrauterine metal exposure may affect birth weight in a sex-specific manner. We investigated sex-specific associations between prenatal exposure to metal mixtures and birth weight in a Chinese birth cohort. The birth weight of 1296 boys and 1098 girls were recorded, and 10 metals in maternal urine samples collected during pregnancy were measured using inductively coupled plasma mass spectrometry. Bayesian Kernel Machine Regression was used to estimate the association of individual metals or metal mixtures and birth weight for gestational age (BW for GA). The model showed a sex-specific relationship between prenatal exposure to metal mixtures and BW for GA with a significant negative association in girls and a non-significant positive association in boys. Cadmium (Cd) and nickel (Ni) were positively and negatively associated with BW for GA in girls, respectively. Moreover, increasing thallium (Tl) concentration lowered the positive association between Cd and BW for GA and enhanced the negative association between Ni and BW for GA in girls. When exposure to other metals increased, the positive association with Cd diminished, whereas the negative association with Ni or Tl increased. Our findings provide evidence supporting the complex effects of intrauterine exposure to metal mixtures on the birth weight of girls and further highlight the sex heterogeneity in fetal development influenced by intrauterine environmental factors.

Abstract Trichoderma reesei RUT-C30 is a well-known high-yielding cellulase-producing fungal strain that converts lignocellulose into cellulosic sugar for resource regeneration. Calcium is a ubiquitous secondary messenger that regulates growth and cellulase production in T. reesei. We serendipitously found that adding Sr2+ to the medium significantly increased cellulase activity in the T. reesei RUT-C30 strain and upregulated the expression of cellulase-related genes. Further studies showed that Sr2+ supplementation increased the cytosolic calcium concentration and activated the calcium-responsive signal transduction pathway of Ca2+–calcineurin-responsive zinc finger transcription factor 1 (CRZ1). Using the plasma membrane Ca2+ channel blocker, LaCl3, we demonstrated that Sr2+ induces cellulase production via the calcium signaling pathway. Supplementation with the corresponding concentrations of Sr2+ also inhibited colony growth. Sr2+ supplementation led to an increase in intracellular reactive oxygen species (ROS) and upregulated the transcriptional levels of intracellular superoxide dismutase (sod1) and catalase (cat1). We further demonstrated that ROS content was detrimental to cellulase production, which was alleviated by the ROS scavenger N-acetyl cysteine (NAC). This study demonstrated for the first time that Sr2+ supplementation stimulates cellulase production and upregulates cellulase genes via the calcium signaling transduction pathway. Sr2+ leads to an increase in intracellular ROS, which is detrimental to cellulase production and can be alleviated by the ROS scavenger NAC. Our results provide insights into the mechanistic study of cellulase synthesis and the discovery of novel inducers of cellulase. Graphical Abstract

Background: It remains unclear whether type 2 diabetes and the complication of arthritis are causally related to the PM2.5 pollutant. Therefore, we aimed to investigate the associations of long-term PM2.5 exposure with type 2 diabetes and with arthritis in type 2 diabetes patients. Materials and methods: This study used data from the China Health and Retirement Longitudinal Survey (CHARLS) implemented during 2011–2018. The associations were analyzed by Cox proportional hazards regression models, and the population-attributable fraction (PAF) was calculated to assess the burden of type 2 diabetes and arthritis-attributable to PM2.5. Results: A total of 21,075 participants were finally included, with 19,121 analyzed for PM2.5 and type 2 diabetes risk and 12,427 analyzed for PM2.5 and arthritis risk, of which 1,382 with newly-diagnosed type 2 diabetes and 1,328 with arthritis during the follow-up. Overall, each 10 μg/m3 increment in PM2.5 concentration was significantly associated with an increase in the risk of type 2 diabetes (HR = 1.26, 95 %CI1.22 to 1.31), and the PAF of type 2 diabetes attributable to PM2.5 was 13.54 %. In type 2 diabetes patients, each 10 μg/m3 increment in PM2.5 exposure was associated with an increase in arthritis (HR = 1.42, 95 %CI: 1.28 to 1.57), and the association was significantly greater than that (H = 1.23, 95 %CI: 1.19 to 1.28) in adults without type 2 diabetes. The PAFs of arthritis-attributable to PM2.5 in participants with and without type 2 diabetes were 18.54 % and 10.69 %, respectively. Conclusion: Long-term exposure to PM2.5 may increase the risk of type 2 diabetes and make type 2 diabetes patients susceptible to arthritis.

Abstract Background The effects of COVID-19 lockdown measures on maternal and fetal health remain unclear. We examined the associations of COVID-19 lockdown with gestational length and preterm birth (PTB) in a Chinese population. Methods We obtained medical records of 595,396 singleton live infants born between 2015 and 2020 in 5 cities in Guangdong Province, South China. The exposed group (N = 101,900) included women who experienced the COVID-19 Level I lockdown (1/23–2/24/2020) during pregnancy, while the unexposed group (N = 493,496) included women who were pregnant during the same calendar months in 2015–2019. Cumulative exposure was calculated based on days exposed to different levels of emergency responses with different weighting. Generalized linear regression models were applied to estimate the associations of lockdown exposure with gestational length and risk of PTB (

Deep Learning (DL) has been broadly applied to solve big data problems in biomedical fields, which is most successful in image processing. Recently, many DL methods have been applied to analyze genomic studies. However, genomic data usually has too small a sample size to fit a complex network. They do not have common structural patterns like images to utilize pre-trained networks or take advantage of convolution layers. The concern of overusing DL methods motivates us to evaluate DL methods’ performance versus popular non-deep Machine Learning (ML) methods for analyzing genomic data with a wide range of sample sizes. In this paper, we conduct a benchmark study using the UK Biobank data and its many random subsets with different sample sizes. The original UK Biobank data has about 500k participants. Each patient has comprehensive patient characteristics, disease histories, and genomic information, i.e., the genotypes of millions of Single-Nucleotide Polymorphism (SNPs). We are interested in predicting the risk of three lung diseases: asthma, COPD, and lung cancer. There are 205,238 participants have recorded disease outcomes for these three diseases. Five prediction models are investigated in this benchmark study, including three non-deep machine learning methods (Elastic Net, XGBoost, and SVM) and two deep learning methods (DNN and LSTM). Besides the most popular performance metrics, such as the F1-score, we promote the hit curve, a visual tool to describe the performance of predicting rare events. We discovered that DL methods frequently fail to outperform non-deep ML in analyzing genomic data, even in large datasets with over 200k samples. The experiment results suggest not overusing DL methods in genomic studies, even with biobank-level sample sizes. The performance differences between DL and non-deep ML decrease as the sample size of data increases. This suggests when the sample size of data is significant, further increasing sample sizes leads to more performance gain in DL methods. Hence, DL methods could be better if we analyze genomic data bigger than this study.

Abstract Background The filamentous fungus Trichoderma reesei is one of the best producers of cellulase and has been widely studied for the production of cellulosic ethanol and bio-based products. We previously reported that Mn2+ and N,N-dimethylformamide (DMF) can stimulate cellulase overexpression via Ca2+ bursts and calcium signalling in T. reesei under cellulase-inducing conditions. To further understand the regulatory networks involved in cellulase overexpression in T. reesei, we characterised the Mn2+/DMF-induced calcium signalling pathway involved in the stimulation of cellulase overexpression. Results We found that Mn2+/DMF stimulation significantly increased the intracellular levels of cAMP in an adenylate cyclase (ACY1)-dependent manner. Deletion of acy1 confirmed that cAMP is crucial for the Mn2+/DMF-stimulated cellulase overexpression in T. reesei. We further revealed that cAMP elevation induces a cytosolic Ca2+ burst, thereby initiating the Ca2+ signal transduction pathway in T. reesei, and that cAMP signalling causes the Ca2+ signalling pathway to regulate cellulase production in T. reesei. Furthermore, using a phospholipase C encoding gene plc-e deletion strain, we showed that the plc-e gene is vital for cellulase overexpression in response to stimulation by both Mn2+ and DMF, and that cAMP induces a Ca2+ burst through PLC-E. Conclusions The findings of this study reveal the presence of a signal transduction pathway in which Mn2+/DMF stimulation produces cAMP. Increase in the levels of cAMP activates the calcium signalling pathway via phospholipase C to regulate cellulase overexpression under cellulase-inducing conditions. These findings provide insights into the molecular mechanism of the cAMP–PLC–calcium signalling pathway underlying cellulase expression in T. reesei and highlight the potential applications of signal transduction in the regulation of gene expression in fungi.

Abstract Epithelial–mesenchymal transition (EMT) is involved in both physiological and pathological processes. EMT plays an essential role in the invasion, migration and metastasis of tumours. Autophagy has been shown to regulate EMT in a variety of cancers but not in head and neck squamous cell carcinoma (HNSCC). Herein, we investigated whether autophagy also regulates EMT in HNSCC. Analyses of clinical data from three public databases revealed that higher expression of fibronectin-1 (FN1) correlated with poorer prognosis and higher tumour pathological grade in HNSCC. Data from SCC-25 cells demonstrated that rapamycin and Earle’s balanced salt solution (EBSS) promoted autophagy, leading to increased FN1 degradation, while 3-methyladenine (3-MA), bafilomycin A1 (Baf A1) and chloroquine (CQ) inhibited autophagy, leading to decreased FN1 degradation. On the other hand, autophagic flux was blocked in BECN1 mutant HNSCC Cal-27 cells, and rapamycin did not promote autophagy in Cal-27 cells; also in addition, FN1 degradation was inhibited. Further, we identified FN1 degradation through the lysosome-dependent degradation pathway using the proteasome inhibitor MG132. Data from immunoprecipitation assays also showed that p62/SQSTM1 participated as an autophagy adapter in the autophagy–lysosome pathway of FN1 degradation. Finally, data from immunoprecipitation assays demonstrated that the interaction between p62 and FN1 was abolished in p62 mutant MCF-7 and A2780 cell lines. These results indicate that autophagy significantly promotes the degradation of FN1. Collectively, our findings clearly suggest that FN1, as a marker of EMT, has adverse effects on HNSCC and elucidate the autophagy–lysosome degradation mechanism of FN1.

ImportanceThe ongoing pandemic of COVID-19 is still affecting our life, but the effects of lockdown measures on gestational diabetes mellitus (GDM) in pregnant women remain unclear.AimTo investigate the association between COVID-19 lockdown and GDM.Subjects and MethodsMedical records of 140844 pregnant women during 2015-2020 were extracted from 5 hospitals in Guangdong Province, China. Pregnant women who underwent the COVID-19 Level I lockdown (1/23 - 2/24/2020) during pregnancy were defined as the exposed group (N=20472) and pregnant women who underwent the same calendar months during 2015-2019 (1/23 - 2/24) were defined as the unexposed group (N=120372). Subgroup analyses were used to explore the potential susceptible exposure window of COVID-19 lockdown on GDM. Cumulative exposure is quantitatively estimated by assigning different weights to response periods with different exposure intensities. A logistic regression model was used to estimate the association between COVID-19 lockdown exposure and GDM.ResultsThe rates of GDM in the exposed and unexposed groups were 15.2% and 12.4%, respectively. The overall analyses showed positive associations (odds ratio, OR=1.22, 95%CI: 1.17, 1.27) between lockdown exposure and GDM risk in all pregnant women. More pronounced associations were found in women who underwent the COVID-19 lockdown in their first four months of pregnancy, and the adjusted OR values ranged from 1.24 (95%CI: 1.10, 1.39) in women with 5-8 gestational weeks (GWs) to 1.35 (95%CI: 1.20, 1.52) with < 5 GWs. In addition, we found a positive exposure-response association of cumulative lockdown exposure with the risk of GDM.ConclusionsThe COVID-19 lockdown was associated with an increased risk of GDM, and the first four months of pregnancy may be the window for sensitive exposure.

Abstract Background The filamentous fungus Trichoderma reesei is a major workhorse employed to produce cellulase, which hydrolyzes lignocellulosic biomass for the production of cellulosic ethanol and bio-based products. However, the economic efficiency of biorefineries is still low. Results In this study, the truncation of cellulase activator ACE3 was identified and characterized in T. reesei classical mutant NG14 and its direct descendants for the first time. We demonstrated that the truncated ACE3 is the crucial cause of cellulase hyper-production in T. reesei NG14 branch. Replacing the native ACE3 with truncated ACE3 in other T. reesei strains remarkably improves cellulase production. By truncating ACE3, we engineered a T. reesei mutant, PC-3-7-A723, capable of producing more cellulase than other strains. In a 30-L fermenter, fed-batch fermentation with PC-3-7-A723 drastically increased the maximum cellulase titer (FPase) to 102.63 IU/mL at 240 h, which constitutes a 20–30% improvement to that of the parental strain PC-3-7. Conclusions This work characterized the function of truncated ACE3 and demonstrated that analysis of classical mutants allows rational engineering of mutant strains with improved cellulase production necessary to process lignocellulosic biomass. Our rational engineering strategy might be useful for enhancing the production of other bio-based products.

Many works are designed to improve efficiency or enhance security and privacy of publicly-auditable cloud storage. However, building timeliness for cloud storage has not been well studied. Few works presented time-sensitive cloud storage and only focused on specific issues, such as the earliest creation time of files or resistance against a procrastinating auditor. Therefore, there leaves an absence of building traceable timeliness for publicly-auditable cloud storage. In this paper, we propose a solution PPTPS to build Privacy-Preserving auditable service with Traceable timeliness for Public cloud Storage. First, we use the security properties of the blockchain to provide a time-stamp for each phase. It enables the timeliness of cloud storage. Second, we construct efficient publicly-verifiable cloud storage. Third, a customized random mask solution is proposed to prevent privacy leakage during the auditing phase. Moreover, we formally proved the security of PPTPS. At last, experimental results demonstrate that PPTPS is economically sound and technically viable.

TiNb2O7 (TNO) compound has been pursued tremendously due to its high theoretical capacity, high potential, and excellent cycle stability. Unfortunately, an intrinsic low electronic and ionic conductivity feature has restricted its broad applications in electrochemical energy storage fields. Two-dimensional (2D) nanostructures can effectively shorten Li-ion transport path and enhance charge transfer. Here, hierarchical structure TNO was constructed by using ethanol and acetic acid as particularly important organic chemicals of basic raw materials via a simple solvothermal reaction. Ethanol was found to play a critical role in the formation of 2D sheet structure. Meantime, reduced graphene oxide nanosheets can effectively improve electronic conductivity. As-obtained TiNb2O7 were wrapped further by graphene oxide nanosheets through a flocculation process. Their unique structure is beneficial to the final electrochemical performance. This study not only provides a general approach for the design of novel 2D nanomaterials wrapped by graphene because of the advantage of esterification reaction and flocculation reaction, but also improves the electronic and ionic conductivity simultaneously.

Captured by the low-cost and high theoretical specific capacity, Na-S systems have garnered much attention. However, their intermediate products (dissolved polysulfide) are always out of control. Considering the excellent space confinements and conductivity, they have been regarded as promising candidates. Herein, the hollow spheres with suitable thickness shell (~20 nm) are designed as hosting materials, accompanied by in-depth complexing. Benefitting from the abundant micro-pores (mainly about conical-type and slits-type pores < 1.0 nm), the active S4 molecules are successfully filled in the pores through vacuum tube sealing technology, effectively avoiding the process from solid S8 to liquid Na2S6. As cathode for Na-S systems, their capacity could remain at 920 mAh g−1 at 0.1 C after 100 cycles. Even at 10.0 C, the capacity still remained at about 310 mAh g−1 after 7000 cycles. Supported by the detailed kinetic behaviors, the improvement of ions diffusion behaviors is noted, bringing about the effective thorough redox reactions. Moreover, the enhanced surface-controlling behaviors further induces the evolution of rate properties. Therefore, their stable phase changing is further confirmed through in situ resistances. Thus, the work is anticipated to offer significant design for hosting carbon materials and complexing manners.

Abstract Background Cellulolytic enzymes produced by Trichoderma reesei are widely used for the industrial production of biofuels and chemicals from lignocellulose. We speculated that intracellular pH during the fermentation process can affect cellulase induction. Results In this study, two H+-ATPase genes, tre76238 and tre78757, were first identified in T. reesei. Deletion of tre76238 and tre78757 in T. reesei RUT-C30 confirmed that tre76238 has a major function in maintaining intracellular pH, whereas tre78757 has a minor function. The tre76238 deletion strain Δ76238 displayed a high level of cellulase production using cellulase-repressive glucose as a sole carbon source, along with intracellular acid accumulation and growth retardation. Our results indicated that intracellular acid accumulation in Δ76238 stimulated a significant increase in the cytosolic Ca2+ levels. Ca2+ channels were shown to be necessary for cellulase production using glucose as the carbon source in Δ76238. Delayed Δ76238 growth could be reversed by optimizing the medium’s nitrogen sources to produce ammonia for intracellular acid neutralization in the early phase. This may be useful for scale-up of cellulase production using glucose as the carbon source. Conclusions This study provides a new perspective for significant alterations in the cellulase expression pattern of T. reesei Δ76238, indicating a new mechanism for cellulase regulation under conditions of low intracellular pH.

Abstract Background Cellulolytic enzymes produced by the filamentous fungus Trichoderma reesei are commonly used in biomass conversion. The high cost of cellulase is still a significant challenge to commercial biofuel production. Improving cellulase production in T. reesei for application in the cellulosic biorefinery setting is an urgent priority. Results Trichoderma reesei hyper-cellulolytic mutant SS-II derived from the T. reesei NG14 strain exhibited faster growth rate and more efficient lignocellulosic biomass degradation than those of RUT-C30, another hyper-cellulolytic strain derived from NG14. To identify any genetic changes that occurred in SS-II, we sequenced its genome using Illumina MiSeq. In total, 184 single nucleotide polymorphisms and 40 insertions and deletions were identified. SS-II sequencing revealed 107 novel mutations and a full-length wild-type carbon catabolite repressor 1 gene (cre1). To combine the mutations of RUT-C30 and SS-II, the sequence of one confirmed beneficial mutation in RUT-C30, cre1 96, was introduced in SS-II to replace full-length cre1, forming the mutant SS-II-cre1 96. The total cellulase production of SS-II-cre1 96 was decreased owing to the limited growth of SS-II-cre1 96. In contrast, 57 genes mutated only in SS-II were selected and knocked out in RUT-C30. Of these, 31 were involved in T. reesei growth or cellulase production. Cellulase activity was significantly increased in five deletion strains compared with that in two starter strains, RUT-C30 and SS-II. Cellulase production of T. reesei Δ108642 and Δ56839 was significantly increased by 83.7% and 70.1%, respectively, compared with that of RUT-C30. The amount of glucose released from pretreated corn stover hydrolyzed by the crude enzyme from Δ108642 increased by 11.9%. Conclusions The positive attribute confirmed in one cellulase hyper-producing strain does not always work efficiently in another cellulase hyper-producing strain, owing to the differences in genetic background. Genome re-sequencing revealed novel mutations that might affect cellulase production and other pathways indirectly related to cellulase formation. Our strategy of combining the mutations of two strains successfully identified a number of interesting phenotypes associated with cellulase production. These findings will contribute to the creation of a gene library that can be used to investigate the involvement of various genes in the regulation of cellulase production.

Abstract Background The filamentous fungus Trichoderma reesei produces cellulase enzymes that are widely studied for lignocellulose bioconversion to biofuel. N,N-dimethylformamide (DMF) is a versatile organic solvent used in large quantities in industries. Results In this study, we serendipitously found that biologically relevant concentrations of extracellular DMF-induced cellulase production in the T. reesei hyper-cellulolytic mutant Rut-C30 and wild-type strain QM6a. Next, by transcriptome analysis, we determined that plc-e encoding phospholipase C was activated by DMF and revealed that cytosolic Ca2+ plays a vital role in the response of T. reesei to DMF. Using EGTA (a putative extracellular Ca2+ chelator) and LaCl3 (a plasma membrane Ca2+ channel blocker), we demonstrated that DMF induced a cytosolic Ca2+ burst via extracellular Ca2+ and Ca2+ channels in T. reesei, and that the cytosolic Ca2+ burst induced by DMF-mediated overexpression of cellulase through calcium signaling. Deletion of crz1 confirmed that calcium signaling plays a dominant role in DMF-induced cellulase production. Additionally, 0.5–2% DMF increases the permeability of T. reesei mycelia for cellulase release. Simultaneous supplementation with 1% DMF and 10 mM Mn2+ to T. reesei Rut-C30 increased cellulase activity approximately fourfold compared to that without treatment and was also more than that observed in response to either treatment alone. Conclusions Our results reveal that DMF-induced cellulase production via calcium signaling and permeabilization. Our results also provide insight into the role of calcium signaling in enzyme production for enhanced cellulase production and the development of novel inducers of cellulase.

In recent years, a typical representation of the next-generation Internet architecture, named data networking (NDN), and a critical form of the underwater Internet of Things (IoT), underwater acoustic sensor networks (UASNs), have attracted widespread attention in academia. Meanwhile, since the battery energy of the sensor node is limited and the battery is difficult to replace or recharge in underwater environments, extending the networks' lifetime has become a key issue in UASNs. In this paper, we try to deploy a UASN on NDN architecture and explore the energy consumption of the NDN-based UASN under shallow water and deep water conditions based on the relay network topology. A simulation is carried out to compare the delay performance of NDN-based and IP-based UASNs and validate the result. It is believed that the study could provide a theoretical criterion for the selection of the direct or relay path to optimize energy consumption in the future deployment of NDN-based UASNs.

Objectives: The World Health Organization (WHO) proposed the Integrated Care for Older People (ICOPE) screening tool to identify older people with priority conditions associated with declines in intrinsic capacity (IC). We aimed to determine the clinical utility of the WHO ICOPE screening tool in a Chinese population.Method: A total of 376 adults aged 68.65 ± 11.41 years participated in the study. IC was assessed with the WHO ICOPE screening tool, covering five domains: cognitive, locomotor, sensory, vision, and psychological capacity. We assessed the activities of daily living (ADL); instrumental activities of daily living (IADL); the Fried frailty phenotype; FRAIL scale; Strength, Assistance With Walking, Rising From chair, Climbing Stairs, and Falls (SARC-F) scale; Mini-mental State Examination (MMSE); Geriatric Depression Scale (GDS); social frailty; and quality of life.Results: There were 260 (69.1%) participants who showed declines in one or more IC dimensions. The percentages of decline in mobility, cognition, vitality, hearing, vision, and psychological capacity were 25.3, 46.8, 16.2, 15.4, 11.7, and 12.0%, respectively. IC decreased with increasing age. After adjusting for age, sex, and multimorbidity, participants with declines in IC were more likely to be older, frail, and disabled. They also had worse physical, mental, and overall health. There was a higher prevalence of declines in IC in participants with frailty. After adjusting for age, IC was positively correlated with walking speed, resilience score, and MMSE score and negatively correlated with frailty, SARC-F score, IADL score, GDS score, and physical and mental fatigue. The IC score was not associated with body composition variables such as fat-free mass, body fat percentage, or visceral fat area. Higher IC was associated with better quality of life. The area under the curve of the receiver operating characteristic (AUC-ROC) for the ICOPE screening tool vs. Fried phenotype, FRAIL, ADL disability, IADL disability, and SARC-F were 0.817, 0.843, 0.954, 0.912, and 0.909, respectively.Conclusion: Our research affirms that the ICOPE screening tool is useful to identify adults with poor physical and mental function in a Chinese sample. This tool may assist in identifying declines in IC in an integrative care model and help slow down function decline and onset of care dependence.

Abstract Background The filamentous fungus Trichoderma reesei Rut-C30 is one of the most vital fungi for the production of cellulases, which can be used for biofuel production from lignocellulose. Nevertheless, the mechanism of transmission of external stimuli and signals in modulating cellulase production in T. reesei Rut-C30 remains unclear. Calcium is a known second messenger regulating cellulase gene expression in T. reesei. Results In this study, we found that a biologically relevant extracellular Mn2+ concentration markedly stimulates cellulase production, total protein secretion, and the intracellular Mn2+ concentration of Rut-C30, a cellulase hyper-producing strain of T. reesei. Furthermore, we identified two Mn2+ transport proteins, designated as TPHO84-1 and TPHO84-2, indicating that they are upstream in the signaling pathway that leads to cellulase upregulation. We also found that Mn2+ induced a significant increase in cytosolic Ca2+ concentration, and that this increased cytosolic Ca2+ might be a key step in the Mn2+-mediated regulation of cellulase gene transcription and production. The utilization of LaCl3 to block plasma membrane Ca2+ channels, and deletion of crz1 (calcineurin-responsive zinc finger transcription factor 1) to interrupt calcium signaling, showed that Mn2+ exerts the induction of cellulase genes via calcium channels and calcium signaling. To substantiate this, we identified a Ca2+/Mn2+ P-type ATPase, TPMR1, which could play a pivotal role in Ca2+/Mn2+ homeostasis and Mn2+ induction of cellulase genes in T. reesei Rut-C30. Conclusions Taken together, our results revealed for the first time that Mn2+ stimulates cellulase production, and demonstrates that Mn2+ upregulates cellulase genes via calcium channels and calcium signaling. Our research also provides a direction to facilitate enhanced cellulase production by T. reesei.

This data article contains data related to the research article entitled “Copper-mediated on-off control of gene expression in filamentous fungus Trichoderma reesei” (Wang et al., 2017) [1]. Four kinds of copper responsive promoters were designed. Quantitative PCR (qPCR) was performed to determine relative mRNA levels of red fluorescent protein gene (rfp) extracted from cells grown under different concentrations of CuSO4. Three deletion vectors were constructed by using a copper-mediated self-excision cassette instead of a xylose-mediated self-excision cassette (Zhang et al., 2016) [2] to knock out xyn1, one of the two major specific endo-β-1,4-xylanases (Rauscher et al., 2006) [3], xyr1, the key transcriptional activator of cellulolytic and xylanolytic genes (Lichius et al., 2015) [4], and ace3, a factor essential for cellulase production (Häkkinen et al., 2014) [5]. This data article reports the primers, vector construction, and qPCR assay. Keywords: Trichoderma reesei, Filamentous fungus, Copper responsive promoter, Quantitative real-time PCR, Plasmid construction, Gene expression

With the global expansion of International Baccalaureate (IB), tensions have emerged between IB and the national education systems. This poses challenges to international education governance in many countries. In mainland China, IB programmes have rapidly become more prevalent since their introduction in 1991. However, new policies have imposed censorship and restrictions on international programmes regarding international education as a potential threat to China's educational sovereignty, cultural identity, and educational equity. Shanghai has the highest number of IB schools and the strictest policies in mainland China. To understand China's international education policy governance, this study traces the policy evolution of Shanghai's IB education through document analysis and interviews. Furthermore, this study examines the responses, perceptions, and demands of non-governmental stakeholders regarding current restrictive policies. Results show that the development of IB education in Shanghai has undergone three stages of policy transformation: support, regulation, and restriction. Against this policy transformation, non-governmental stakeholders believe that IB education is a "necessity". Therefore, this study suggests that IB education governance in China should incorporate the elements of network governance.

Most hydrophobic clay minerals, such as clinochlore, are known to cause problems in the recovery of cassiterite. In this study, a new reagent scheme, i.e., sodium oleate (NaOL) as a collector and Al (III) ions as a depressant, for reverse flotation separation of cassiterite and clinochlore was investigated. The flotation performance and interaction mechanism were studied by microflotation tests, adsorption tests, contact angle measurements, and X-ray photoelectron spectroscopy (XPS) analysis. Results of single mineral flotation experiments showed that NaOL had a different flotation performance on cassiterite and clinochlore, and the addition of Al (III) ions could selectively inhibit the floatability of cassiterite. Reverse flotation tests performed on mixed minerals indicated that the separation of cassiterite and clinochlore could be achieved in the presence of NaOL and Al (III) ions. Adsorption experiments demonstrated that Al (III) ions hindered the adsorption of NaOL on cassiterite surfaces but exerted little influence on the adsorption of NaOL on clinochlore surfaces. Results of contact angle measurements indicated that Al (III) ions could impede the hydrophobization process of cassiterite in NaOL solution. XPS results showed that aluminum species were adsorbed onto the cassiterite surfaces through the interaction with O sites.