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Abstract Background Oral squamous cell carcinoma (OSCC) is a common head and neck cancer, and the incidence of OSCC is increasing. As the mortality of OSCC keeps increasing, it is crucial to clarify its pathogenesis and develop new therapeutic strategies. Methods Confocal laser scanning microscopy was used to evaluate the uptake of nanoparticles (NPs). The potential functions of USP30 were evaluated by cell counting kit (CCK)-8, flow cytometry, biochemical assay, coimmunoprecipitation, qRT–PCR, and immunoblotting. The antitumor effect of NP-loaded USP30 inhibitor MF-094 was evaluated in vitro and in vivo. Results In this study, increased USP30 expression was found in OSCC specimens and cell lines through qRT–PCR and immunoblotting. CCK-8, flow cytometry, and biochemical assay revealed that the deubiquitylated catalytic activity of USP30 contributed to cell viability and glutamine consumption of OSCC. Subsequently, USP30 inhibitor MF-094 was loaded in ZIF-8-PDA and PEGTK to fabricate ZIF-8-PDA-PEGTK nanoparticles, which exhibited excellent inhibition of cell viability and glutamine consumption of OSCC, both in vitro and in vivo. Conclusion The results indicated the clinical significance of USP30 and showed that nanocomposites provide a targeted drug delivery system for treating OSCC.

Few studies of monitoring rocky desertification based on Sentinel-2 MSI image with higher spatial and temporal resolutions have been reported. In this paper, nine typical surface parameters that derived from Sentinel-2 MSI image including three red edge indices have been introduced to establish two types of feature space monitoring index: point-to-line type and point-to-point type. The results show that: (1) The feature of space monitoring index based on Sentinel-2 MSI image has a higher applicability in obtaining rocky desertification information for karst zones; (2) The point-to-line BSI (bare soil index)-NDre1 (red edge index 1)feature space monitoring index of rocky desertification has the best applicability with R2=95.1% and root mean square error (RMSE)=0.872; (3) The feature space monitoring indexes that composed of red edge indices have a higher inversion accuracy, which indicates that the red edge indices are sensitive indicators of the rocky desertification condition and process;(4) The intensive and severe rocky desertification zones are mostly located in the southeast and central parts. The 3-dimensional or multidimensional feature space model will be constructed to improve the inversion accuracy of rocky desertification in further studies. The research results can provide methodological supports for revealing the rocky desertification evolution laws.

Context Ranunculus ternatus Thunb (Ranunculaceae), (RTT) is used clinically for the treatment of tuberculosis or as tumour adjuvant therapy, but its potential effect on diabetic nephropathy (DN) has not been studied. Objective To investigate the effect of RTT extract in renal fibrosis of DN. Materials and methods C57BL/6 mice were randomly divided into four groups (n = 12). Diabetes mellitus (DM) mice were induced by streptozotocin (STZ, 55 mg/kg/day) for five consecutive days and treated by RTT extract (2 g/kg). Afterward, blood glucose, HE and Masson staining were assayed. The expression levels of Vimentin, ɑ-SMA, TNF-ɑ, NF-κB p-p65, NF-κB p65, SMYD2, H3K36me3, H3K4me3 were determined by western blots. Firbronectin was respectively assayed by western blot and immunofluorescent staining. Results RTT extract significantly ameliorated renal injury and renal fibrosis in the renal tissue of STZ-induced diabetic mice as demonstrated by the decreased expression level of Fibronectin (65%), Vimentin and α-SMA (75% & 53%). In addition, the levels of TNF-α (57%), NF-κB p-p65 and NF-κB p65 (35% & 25%) were elevated in the DN mice. Importantly, these were alleviated after RTT extract treatment. Moreover, we observed that the protein levels of SMYD2 (30%), H3K36me3 and H3K4me3 (53% & 75%) were reduced in DN mice after treatment with RTT extract. Discussion and conclusions RTT extract mediates antifibrotic effects and anti-inflammatory responses in STZ-induced DN mainly through suppressing SMYD2 activation and H3K36me3 and H3K4me3 protein expression. RTT extract might have therapeutic potential against high glucose-induced nephropathy.

Due to the influence of reservoir water level, rainfall and geological conditions, the Three Gorges Reservoir area is a landslide hazard-prone area, and the landslide genesis mechanism and evolution process are also extremely complex.By taking the Xinpu Xia'ertai landslide as an example, this paper summarizes and analyses the resurgence law of large palaeo-landslides based on multiple sources of data, such as GPS displacement monitoring data, fracture data, rainfall and reservoir water level, and through a geotechnical creep compression model. The paper also verifies the mechanism of fracture formation on the trailing edge of the displaced landslide.The results show the following: ①Rainfall is the dominant factor of landslide deformation. Landslide deformation causes the landslide body to produce cracks and form rainfall infiltration channels, which intensifies rock fragmentation and weak layer mudification and reduces landslide stability; besides, concentrated and continuous rainfall can destabilize landslides. ②By comparing the predicted value of the model with the surface monitoring data, it is feasible to take annual rainfall as the controlling factor in the medium- and long-term landslide prediction model and help to improve the prediction accuracy of landslides. ③Pushing landslide trailing edge cracks consist of landslide pushing displacement and geotechnical body compression. In this paper, the compression creep model is introduced to calculate the crack width and compare it with the monitoring data. This shows that the compression creep model is suitable for this type of slope, and the average deformation modulus of the geotechnical body is obtained by applying the backpropagation of the geotechnical body creep compression model. Thus, we judge the degree of rock fragmentation, which provides a reference for landslide stability analysis and subsequent engineering management.

Abstract Background Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse perinatal outcomes leading to high perinatal morbidity and mortality. However, few studies have examined twin pregnancies complicated by ICP. To assess the perinatal outcomes of twin pregnancies with ICP, a retrospective cohort study was conducted. Methods A total of 633 twin pregnancies and 1267 singleton pregnancies with ICP were included. In addition, a correlation study was performed on the matched total bile acid (TBA) levels from maternal serum, fetal umbilical venous blood, and amniotic fluid of 33 twin pregnancies from twin groups. Results When compared to singletons, twin pregnancies with ICP had a higher risk of cesarean section (CS) (96.4% vs. 76.1%), preterm birth (PTB) (82.6% vs. 19.7%), fetal distress (2.0% vs. 1.3%), and neonatal intensive care unit (NICU) admission (23.6% vs. 5.1%), which was significantly related to increasing TBA levels (P

Abstract Background Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent malignancies worldwide and is characterized by unfavorable prognosis, high lymph node metastasis and early recurrence. However, the molecular events regulating HNSCC tumorigenesis remain poorly understood. Therefore, uncovering the underlying mechanisms is urgently needed to identify novel and promising therapeutic targets for HNSCC. In this study, we aimed to explore the role of pleckstrin‐2 (PLEK2) in regulating HNSCC tumorigenesis. Methods The expression pattern of PLEK2 and its clinical significance in HNSCC were determined by analyzing publicly assessable datasets and our own independent HNSCC cohort. In vitro and in vivo experiments, including cell proliferation, colony formation, Matrigel invasion, tumor sphere formation, ALDEFLUOR, Western blotting assays and xenograft mouse models, were used to investigate the role of PLEK2 in regulating the malignant behaviors of HNSCC cells. The underlying molecular mechanisms for the tumor‐promoting role of PLEK2 were elucidated using co‐immunoprecipitation, cycloheximide chase analysis, ubiquitination assays, chromatin immunoprecipitation‐quantitative polymerase chain reaction, luciferase reporter assays and rescue experiments. Results The expression levels of PLEK2 mRNA and protein were significantly increased in HNSCC tissues, and PLEK2 overexpression was strongly associated with poor overall survival and therapeutic resistance. Additionally, PLEK2 was important for maintaining the proliferation, invasion, epithelial‐mesenchymal transition, cancer stemness and tumorigenesis of HNSCC cells and could alter the cellular metabolism of the cancer cells. Mechanistically, PLEK2 interacted with c‐Myc and reduced the association of F‐box and WD repeat domain containing 7 (FBXW7) with c‐Myc, thereby avoiding ubiquitination and subsequent proteasome‐mediated degradation of c‐Myc. Moreover, the c‐Myc signaling activated by PLEK2 was important for sustaining the aggressive malignant phenotypes and tumorigenesis of HNSCC cells. c‐Myc also directly bounded to the PLEK2 promoter and activated its transcription, forming a positive feedback loop. Conclusions Collectively, these findings uncover a previously unknown molecular basis of PLEK2‐enhanced c‐Myc signaling in HNSCC, suggesting that PLEK2 may represent a promising therapeutic target for treating HNSCC.

Objective To study the relationship between vascular endothelial cells (VEC) and autophagy, and its regulatory mechanism in steroid‐induced avascular necrosis of the femoral head (SANFH). Methods In cell experiment, VEC were isolated and cultured from the femoral head of Sprague–Dawley rats and divided into three groups: blank control group (Ctrl), methylprednisolone group (MP), and methylprednisolone+mTOR‐shRNA group (MP + shmTOR). The autophagy formation was observed by transmission electron microscope. The mRNA expression of PI3K, Akt, mTOR, Beclin1 and MAP1LC3 was detected by RT‐PCR and the protein expression was detected by Western blot and immunofluorescence. Expression of the damage marker 6‐keto‐PGF1α was detected by the ELISA method. In vivo experiment, after establishing the model, the grouping method was the same as cell experiment. Autophagosomes were observed by same method, and the expression of related factors was detected by the same method in cell experiment. Results In the cell experiment, autophagosomes in the MP group were significantly lower than in the Ctrl group, and the autophagosomes in the MP + shmTOR group were intermediate between two groups (P

Abstract Cisplatin resistance poses a substantial hurdle in effectively treating head and neck squamous cell carcinoma (HNSCC). Utilizing multiple tumor models and examining an internal HNSCC cohort, squalene epoxidase (SQLE) is pinpointed as a key driver of chemoresistance and tumorigenesis, operating through a cholesterol‐dependent pathway. Comprehensive transcriptomic analysis reveals that SQLE is essential for maintaining c‐Myc transcriptional activity by stabilizing the c‐Myc protein and averting its ubiquitin‐mediated degradation. Mechanistic investigation demonstrates that SQLE inhibition diminishes Akt's binding affinity to lipid rafts via a cholesterol‐dependent process, subsequently deactivating lipid raft‐localized Akt, reducing GSK‐3β phosphorylation at S9, and increasing c‐Myc phosphorylation at T58, ultimately leading to c‐Myc destabilization. Importantly, employing an Sqle conditional knockout mouse model, SQLE's critical role in HNSCC initiation and progression is established. The preclinical findings demonstrate the potent synergistic effects of combining terbinafine and cisplatin in arresting tumor growth. These discoveries not only provide novel insights into the underlying mechanisms of SQLE‐mediated cisplatin resistance and tumorigenesis in HNSCC but also propose a promising therapeutic avenue for HNSCC patients unresponsive to conventional cisplatin‐based chemotherapy.

Background: Exposure to particulate matter with aerodynamic diameters less than 2.5 µm (PM2.5) may increase the risk of 10-year atherosclerotic cardiovascular disease (ASCVD) risk. While PM2.5 is comprised of various components, the evidence on the correlation of its components with 10-year ASCVD risk and which component contributes most remains limited. Methods: Data were derived from the baseline assessments of China Multi-Ethnic Cohort (CMEC). In total, 69,722 individuals aged 35–74 years were included into this study. The annual average concentration of PM2.5 and its components (black carbon, ammonium, nitrate, sulfate, organic matter, soil particles, and sea salt) were estimated by satellite remote sensing and chemical transport models. The ASCVD risk of individuals was calculated by the equations from the China-PAR Project (prediction for ASCVD risk in China). The relationship between single exposure to PM2.5 and its components and predicted 10-year ASCVD risk was assessed using the logistic regression model. The effect of joint exposure was estimated, and the most significant contributor was identified using the weighted quantile sum approach. Results: Totally 69,722 participants were included, of which 95.8 % and 4.2 % had low and high 10-year ASCVD risk, respectively. Per standard deviation increases in the 3-year average concentration of PM2.5 mass (odds ratio [OR] 1.23, 95 % confidence interval [CI]: 1.12–1.35), black carbon (1.21, 1.11–1.33), ammonium (1.21, 1.10–1.32), nitrate (1.25, 1.14–1.38), organic matter (1.29, 1.18–1.42), sulfate (1.17, 1.07–1.28), and soil particles (1.15, 1.04–1.26) were related to high 10-year ASCVD risk. The overall effect (1.19, 1.11–1.28) of the PM2.5 components was positively associated with 10-year ASCVD risk, and organic matter had the most contribution to this relationship. Female participants were more significantly impacted by PM2.5, black carbon, ammonium, nitrate, organic matter, sulfate, and soil particles compared to others. Conclusion: Long-term exposure to PM2.5 mass, black carbon, ammonium, nitrate, organic matter, sulfate, and soil particles were positively associated with high 10-year ASCVD risk, while sea salt exhibited a protective effect. Moreover, the organic matter might take primary responsibility for the relationship between PM2.5 and 10-year ASCVD risk. Females were more susceptible to the adverse effect.

Background: Ambient particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) consists of various toxic constituents. However, the health effect of PM2.5 may differ depending on its constituents, but the joint effect of PM2.5 constituents remains incompletely understood. Objective: Our goal was to evaluate the joint effect of long-term PM2.5 constituent exposures on dyslipidemia and identify the most hazardous chemical constituent. Methods: This study included 67,015 participants from the China Multi-Ethnic Cohort study. The average yearly levels of PM2.5 constituents for all individuals at their residences were assessed through satellite remote sensing and chemical transport modeling. Dyslipidemia was defined as one or more following abnormal blood lipid concentrations: total cholesterol (TC) ≥ 6.22 mmol/L, triglycerides (TG) ≥ 2.26 mmol/L, high-density lipoprotein cholesterol (HDL-C)

Hot and humid conditions create challenges for tomato production under a controlled environment. Low tomato productivity is related to the lack of stress tolerance of existing cultivars and their ability to maximize fruit set and yield. The aim of this study was to evaluate the effectiveness of three management strategies, cultivar selection, grafting, and plant density, for the growth and production efficiency of organically grown hydroponic tomatoes under adverse environmental conditions in Qatar. The experiment used a split-split plot design with ‘Velocity F1’ and ‘Sigma F1’ as the main plot treatments and a factorial arrangement of grafting combinations and planting densities (3.5 and 5.5 plants/m2) as subplots. Tomato cultivar Velocity F1 grafted on Maxifort F1 resulted in greater vegetative growth and improved phenological attributes than nongrafted Velocity F1. Grafted ‘Velocity F1’ plants grown at 3.5 plants/m2 had an increase in leaf photosynthetic rates (18%), less transpiration loss (16%), and less electrolyte leakage (15%) while maintaining stomatal conductance and intercellular CO2 concentrations. At 9 weeks after transplanting, canopy growth was higher (24%) and flowering occurred earlier (3 days) with grafted ‘Velocity F1’ transplants than with nongrafted transplants. Higher fruit sets (20%), pollen viability (22%), and fewer flower drops (17%) were also observed for grafted ‘Velocity F1’ transplants than for nongrafted transplants. Marketable fruit yields were higher (26%) with grafted ‘Velocity F1’ grown at 3.5 plants/m2 than with nongrafted ‘Velocity F1’. Both grafted ‘Velocity F1’ and ‘Sigma F1’ fruits retained acceptable fruit color (L*, a*, b*, C*, °h), firmness, °Brix, titratable acidity, weight, and prolonged shelf life by 4 additional days than nongrafted ones. We conclude that grafted tomato ‘Velocity F1’ grown at a plant density of 3.5 plants/m2 was the best management strategy for enhancing seedlings quality, plant growth, and postharvest quality and alleviating abiotic stresses under this protected environment and hydroponic system.

Background: Anemia is linked to PM 2.5 (particulate matter with aerodynamic diameters of ⩽2.5 μm) exposure, which can increase the risk of various negative health outcomes. It remains unclear which PM 2.5 components are associated with anemia and the respective contribution of each component to this association. Objective: This study aimed at investigating the association between PM 2.5 and anemia in the general population and to identify the most critical PM 2.5 toxic components in this association. Design: Cross-sectional study. Methods: Our study involved a large cohort of 73,511 individuals aged 30–79 from China’s multi-ethnic population. We employed satellite observations and the chemical transport model (GEOS-Chem)to estimate the long-term exposure to PM 2.5 and its components. Anemia was defined, according to WHO guidelines, as Hb levels below 130 g/L for men and below 120 g/L for women. Through logistic regression, we investigated the association between PM 2.5 components and anemia. By utilizing weighted quantile sum (WQS) analysis, we identified key components and gained insights into their combined impact on anemia. Overall, our study sheds light on the relationship between PM 2.5 exposure, its constituents, and the risk of anemia in a large cohort. Results: PM 2.5 and three components, nitrate (NIT), organic matter (OM), and soil particles (SOIL), were associated with anemia. Per-standard deviation increase in the 3-year average concentrations of PM 2.5 [odds ratio (OR): 1.14, 95% confidence interval (CI): 1.01, 1.28], NIT (1.20, 1.06, 1.35), OM (1.17, 1.04, 1.32), and SOIL (1.22, 1.11, 1.33) were associated with higher odds of anemia. In WQS regression analysis, the WQS index was associated with anemia (OR: 1.29, 95% CI: 1.13, 1.47). SOIL has the highest weight among all PM 2.5 components. Conclusions: Long-term exposure to PM 2.5 and its constituents is associated with anemia. Moreover, SOIL might be the most critical component of the relationship between PM 2.5 and anemia. Our research increases the evidence of the association between PM 2.5 and anemia in the general population, and targeted emission control measures should be taken into consideration to mitigate the adverse effects of PM 2.5 -related anemia.

Investigating the enhancement of the interaction between laser and plasma is crucial for fundamental and applied physics research studies based on laser-induced acceleration and nuclear reactions. The improvement of energy conversion efficiency resulting in increasing reaction yields has been extensively studied by the interaction of femtosecond (fs) or picosecond (ps) lasers with nanowire targets. However, the effects of nanosecond (ns) lasers interacting with nanowire targets on energy absorption and production yield remain unknown. To address this issue, we conducted a deuterium–deuterium fusion experiment based on the collision of two plasmas induced by the interaction of the kilo-Joule-level nanosecond laser with nanowire targets. The experimental results of neutron detection indicate that the yields of nanowire targets remain at the same level as those of planar targets. We have used the counter-streaming collisionless plasma model to perform a numerical analysis of the output of nuclear reaction products at the center-of-mass energy (Ec.m.) values between 10 and 30 keV, and the calculation results are in good agreement with the experimental results. In addition, a magneto-hydrodynamic numerical simulation was also performed. It shows that the critical density of the target’s surface, which forms on the picosecond time scale, blocks the absorption of laser energy with nanosecond pulse length. Consequently, both our experimental and simulation results indicate that the enhancement factor is limited when a target with a spatial period less than µm is used in conjunction with a ns laser. Therefore, additional research is highly desirable to develop a target structure that can improve the efficiency of energy conversion between the laser and the target.

Nuclear fusion reactions which produce energies and most of the elements in the Universe are the keys to driving the process of the Big Bang nucleosynthesis, as well as the evolution of stars. For fusions in real astrophysical conditions, it is crucial to directly measure them in the plasma environments. However, it is challenging to obtain reaction cross sections quantitatively because of the high instabilities of plasma. Here, an innovative self-calibration method is proposed to eliminate the large uncertainties caused by the plasma instabilities. And for the first time, it is applied to investigating the deuteron-lithium nuclear-fusion reaction 7Li(D,n)8Be in the plasma, which is related to the Big Bang lithium abundance puzzle. Further, the reaction's astrophysical S-factor in the Gamow window around 173 keV in the plasma is measured to be S=(24±8) MeV⋅barn, which demonstrates from an experimental point of view that the coulomb screening effect does not play an essential role in this 7Li consuming reaction related to the Big Bang lithium abundance puzzle. This self-calibration method for nuclear reactions in the plasma can also be applied to exploring other nuclear-fusion reactions, such as 7Li(p,α)4He and 6Li(p,α)3He, as well as providing a new probe for detecting plasma dynamics.

Reliable photonuclear reaction rates in stellar conditions are essential for understanding the origin of the heavy stable neutron-deficient isotopes between ^74 Se and ^196 Hg, i.e., p -nuclei. However, many reaction rates of relevance still have to rely on the Hauser–Feshbach (HF) model due to the rarity of experimental progress. One such case is in the mass range of 160 for Dy, Er, Ho, and Tm isotopes. In this work we attempt to constrain the HF model in the TALYS package by reproducing the available experimental data on ^160 Dy( p , γ ) ^161 Ho and ^162 Er( p , γ ) ^163 Tm in the A ∼ 160 mass region, and examine the effects of level density, gamma strength function, and the optical model potential. The constrained model then allows us to calculate the reaction rates of ^157,159 Ho( γ , p ) and ^163,165 Tm( γ , p ) for the γ -process nucleosynthesis in a carbon-deflagration model for Type Ia supernovae. Our recommended rates differ from the JINA REACLIB by more than one order of magnitude in the temperature range 2–3 GK. This results in changes in the final abundance of p -nuclei in the A ∼ 160 mass range by −5.5% to 3% from those with JINA, which means that the uncertainty of ( γ , p ) reactions is not predominant for the synthesis of these nuclei.

Abstract Background Periodontal ligament stem cells (PDLSCs) are the ideal seed cells for periodontal tissue regeneration. It is well established that persistent inflammation significantly impairs the osteogenic differentiation capability of PDLSCs. Therefore, maintaining PDLSC osteogenic potential under the inflammatory microenvironment is important for treating bone loss in periodontitis. The aim of our study was to explore the potential role of circular RNA BIRC6 (circBIRC6) in regulating osteogenic differentiation of PDLSCs in the inflammatory conditions. Methods Alkaline phosphatase staining, Alizarin Red staining, quantitative real-time polymerase chain reaction, western blotting and immunofluorescence staining were used to evaluated the effects of circBIRC6 on the osteogenic differentiation of PDLSCs. RNA pull-down and luciferase assays were performed to explore the interaction between circBIRC6 and miR-543. Then, the downstream signaling pathway affected by circBIRC6/miR-543 axis was further investigated. Results The expression level of circBIRC6 was higher in PDLSCs exposed to inflammatory stimulus and in periodontitis tissues compared to the respective controls. Downregulation of circBIRC6 enhanced the osteogenic potential of PDLSCs under the inflammatory conditions, and upregulation of circBIRC6 led to opposite findings. Mechanistically, we found that circBIRC6 modulated PDLSC osteogenic differentiation through sponging miR-543. More importantly, we have demonstrated that circBIRC6/miR-543 axis regulated the mineralization capacity of PDLSCs via PTEN/PI3K/AKT/mTOR signaling pathway in the inflammatory microenvironment. Conclusions In summary, the expression of miR-543 is significantly increased following circBIRC6 downregulation, leading to inhibition of PTEN and subsequently activation of PI3K/AKT/mTOR signaling pathway. Therefore, targeting circBIRC6 might represent a potential therapeutic strategy for improving bone loss in periodontitis.

In recent years, lithium-ion batteries using nickel-cobalt-manganese ternary materials as cathode materials have advantages of good electrical performance, high specific energy, green environmental protection, low cost, and high discharge stability. These have been widely used in new energy vehicles and portable electronics product areas. As a new generation of rechargeable batteries, lithium batteries have a certain service life, which is generally 3–5 years. Therefore, the rapid development of lithium-ion batteries has caused a blowout increase in the number of used lithium-ion batteries. Waste ternary lithium-ion batteries are very harmful to the environment and humans, but valuable metals such as lithium, nickel, cobalt, and manganese have a high recycling value. In terms of resource recycling and environmental protection, used lithium-ion batteries have a high recycling value. At present, the recycling of waste lithium-ion batteries is facing some problems. For example, the diversity of electrode materials makes their separation and purification difficult, and the high cost can also cause some problems such as secondary pollution. Therefore, it is necessary to find green and low-cost methods for the recycling of waste lithium-ion batteries. Microwave metallurgy has outstanding advantages in this respect. Therefore, this paper used the mechanically crushed ternary lithium battery as the raw material for studying the dielectric properties of the apparent density of the positive electrode material at room temperature and the microwave dielectric properties and absorption that change with temperature. Results show that at room temperature, the cathode material has the best dielectric performance at an apparent density of 1.484 g·cm–3. During the heating process, the cathode material has good microwave absorption performance at 25–700 ℃. At 400 ℃, the dielectric constant \begin{document}$ {\textit{ε}}_{\rm{r}}^{'} $\end{document} reaches the maximum value of 11.96 F·M–1. With the increase in the microwave power, the time for the positive electrode powder to rise to 700 °C is significantly shortened, and the maximum heating rate is in the range of 320–450 °C. The changing trend of the dielectric properties is consistent with the changing trend of the microwave heating characteristics.

Microbial community composition has increasingly emerged as a key determinant of antibiotic resistance gene (ARG) content. However, in activated sludge wastewater treatment plants (AS-WWTPs), a comprehensive understanding of the microbial community assembly process and its impact on the persistence of antimicrobial resistance (AMR) remains elusive. An important part of this process is the immigration dynamics (or community coalescence) between the influent and activated sludge. While the influent wastewater contains a plethora of ARGs, the persistence of a given ARG depends initially on the immigration success of the carrying population, and the possible horizontal transfer to indigenously resident populations of the WWTP. The current study utilized controlled manipulative experiments that decoupled the influent wastewater composition from the influent microbial populations to reveal the fundamental mechanisms involved in ARG immigration between sewers and AS-WWTP. A novel multiplexed amplicon sequencing approach was used to track different ARG sequence variants across the immigration interface, and droplet digital PCR was used to quantify the impact of immigration on the abundance of the targeted ARGs. Immigration caused an increase in the abundance of over 70 % of the quantified ARGs. However, monitoring of ARG amplicon sequence variants (ARG-ASVs) at the immigration interface revealed various immigration patterns such as (i) suppression of the indigenous mixed liquor ARG-ASV by the immigrant, or conversely (ii) complete immigration failure of the influent ARG-ASV. These immigration profiles are reported for the first time here and highlight the crucial information that can be gained using our novel multiplex amplicon sequencing techniques. Future studies aiming to reduce AMR in WWTPs should consider the impact of influent immigration in process optimisation and design.

Highlights Cas9 RNA functions as a miRNA sponge. Let-7 is the dominant regulated miRNA by Cas9 RNA. RNA sequence optimization of Cas9 by synonymous mutation improves its safety.

Abstract Glioblastoma (GBM) as the most common primary malignant brain tumor exhibits a high incidence and degree of malignancy as well as poor prognosis. Due to the existence of formidable blood–brain barrier (BBB) and the aggressive growth and infiltrating nature of GBM, timely diagnosis and treatment of GBM is still very challenging. Among different imaging modalities, magnetic resonance imaging (MRI) with merits including high soft tissue resolution, non-invasiveness and non-limited penetration depth has become the preferred tool for GBM diagnosis. Furthermore, multimodal imaging with combination of MRI and other imaging modalities would not only synergistically integrate the pros, but also overcome the certain limitation in each imaging modality, offering more accurate morphological and pathophysiological information of brain tumors. Since contrast agents contribute to amplify imaging signal output for unambiguous pin-pointing of tumors, tremendous efforts have been devoted to advances of contrast agents for MRI and multimodal imaging. Herein, we put special focus on summary of the most recent advances of not only MRI contrast agents including iron oxide-, manganese (Mn)-, gadolinium (Gd)-, 19F- and copper (Cu)-incorporated nanoplatforms for GBM imaging, but also dual-modal or triple-modal nanoprobes. Furthermore, potential obstacles and perspectives for future research and clinical translation of these contrast agents are discussed. We hope this review provides insights for scientists and students with interest in this area. Graphical abstract

Abstract Background Therapy with genetically modified mesenchymal stem cells (MSCs) has clinical translation promise. Optimizing the targeting migratory ability of MSCs relies on accurate imaging of the distribution and extravasation kinetics of MSCs, and the corresponding imaging results could be used to predict therapeutic outcomes and guide the optimization of the treatment program. Among the different imaging modalities, second near-infrared (NIR-II) optical-resolution photoacoustic microscopy (OR-PAM) has merits, including a fine resolution, a deep penetration, a high sensitivity, and a large signal-to-background ratio. It would be an ideal candidate for precise monitoring of MSCs, although it has not been tested for this purpose so far. Results Penetrating peptide-decorated conjugated polymer nanoparticles (TAT-CPNPs) with strong NIR-II absorbance were used to label chemokine-receptor genetically modified MSCs, which were subsequently evaluated under intravital NIR-II OR-PAM regarding their targeting migratory ability. Based on the upregulation of chemokine (C-X-C motif) ligand 10 in the inflamed ears of contact hypersensitivity mice, MSCs with overexpression of corresponding receptor, chemokine (C-X-C motif) receptor 3 (Cxcr3) were successfully generated (MSCCxcr3). TAT-CPNPs labeling enabled NIR-II photoacoustic imaging to discern MSCCxcr3 covered by 1.2 cm of chicken breast tissue. Longitudinal OR-PAM imaging revealed enhanced inflammation-targeting migration of MSCCxcr3 over time attributed to Cxcr3 gene modification, which was further validated by histological analysis. Conclusions TAT-CPNPs-assisted NIR-II PA imaging is promising for monitoring distribution and extravasation kinetics of MSCs, which would greatly facilitate optimizing MSC-based therapy. Graphical Abstract

Metabolic product accumulation exhibited variations among mulberry (Morus alba L.) leaves (MLs) at distinct growth stages, and this assessment was conducted using a combination of analytical techniques including high-performance liquid chromatography (HPLC), gas chromatography–mass spectrometry (GC-MS), and liquid chromatography–mass spectrometry (LC-MS). Multivariate analysis was applied to the data, and the findings were correlated with antioxidant activity and α-glucosidase inhibitory effects in vitro. Statistical analyses divided the 27 batches of MLs at different growth stages into three distinct groups. In vitro assays for antioxidant activity and α-glucosidase inhibition revealed that IC50 values were highest at the Y23 stage, which corresponds to the ‘Frost Descends’ solar term. In summary, the results of this study indicate that MLs at different growth stages throughout the year can be categorized into three primary growth stages using traditional Chinese solar terms as reference points, based on the observed variations in metabolite content.

The Qinghai–Tibet Plateau region has significant altitude fluctuations and complex climate changes. However, the current global weighted average temperature (Tm) model does not fully consider the impact of meteorological and elevation factors on it, resulting in existing models being unable to accurately predict the Tm in the region. Therefore, this study constructed a weighted average temperature refinement model (XTm) related to surface temperature, water vapor pressure, geopotential height, annual variation, and semi-annual variation based on measured data from 13 radiosonde stations in the Qinghai–Tibet Plateau region from 2008 to 2017. Using the Tm calculated via the numerical integration method of radiosonde observations in the Qinghai–Tibet Plateau region from 2018 to 2019 as a reference value, the quality of the XTm model was tested and compared with the Bevis model and GPT2w (global pressure and temperature 2 wet) model. The results show that for 13 modeling stations, the bias and root-mean-square (RMS) values of the XTm model were −0.02 K and 2.83 K, respectively; compared with the Bevis, GPT2-1, and GPT2w-5 models, the quality of XTm was increased by 47%, 38%, and 47%, respectively. For the four non-modeling stations, the average bias and RMS values of the XTm model were 0.58 K and 2.78 K, respectively; compared with the other three Tm models, the RMS values and the mean bias were both minimal. In addition, the XTm model was also used to calculate the global navigation satellite system (GNSS) precipitable water vapor (PWV), and its average values for the theoretical RMSPWV and RMSPWV/PWV generated by water vapor calculation were 0.11 mm and 1.03%, respectively. Therefore, in the Qinghai–Tibet Plateau region, the XTm model could predict more accurate Tm values, which, in turn, is important for water vapor monitoring.

Abstract Tubulointerstitial fibrosis (TIF) is involved in the development of diabetic kidney disease (DKD). Transforming growth factor β1 (TGF-β1) is involved in the extensive fibrosis of renal tissue by facilitating the partial epithelial-mesenchymal transition (EMT), increasing the synthesis of extracellular matrix (ECM), inhibiting degradation, inducing apoptosis of renal parenchyma cells, and activating renal interstitial fibroblasts and inflammatory cells. Recent studies indicated that bone morphogenetic protein-7 (BMP-7) upregulated the expression of endogenous SnoN against renal TIF induced by TGF-β1 or hyperglycemia. Nevertheless, the mechanisms underlying the BMP-7-mediated restoration of SnoN protein level remains elusive. The present study demonstrated the increased expression of BMP-7 in diabetic mellitus (DM) mice by hydrodynamic tail vein injection of overexpressed BMP-7 plasmid, which attenuated the effects of DM on kidney in mice. Partial tubular EMT and the accumulation of Collagen-III were resisted in DM mice that received overexpressed BMP-7 plasmid. Similar in vivo results showed that BMP-7 was competent to alleviate NRK-52E cells undergoing partial EMT in a high-glucose milieu. Furthermore, exogenous BMP-7 activated the Smad1/5 pathway to promote gene transcription of SnoN and intervened ubiquitination of SnoN; both effects repaired the SnoN protein level in renal tubular cells and kidney tissues of DM mice. Therefore, these findings suggested that BMP-7 could upregulate SnoN mRNA and protein levels by activating the classical Smad1/5 pathway to refrain from the partial EMT of renal tubular epithelial cells and the deposition of ECM in DKD-induced renal fibrosis.

Abstract Process mining, which aims to mine a high-quality process model from event log, provides a powerful tool to support the design, enactment, management, and analysis of operational business processes. However, the task is not easy because the algorithm needs to discover various complex process structures, handle noisy and incomplete event logs and balance multiple performance indicators. In this paper, a novel algorithm (called PSOMiner) for process mining is proposed, which consists of a discrete particle swarm optimization algorithm and guided local mutation. The former is in charge of searching the solution space of causal matrix and the latter is used to help the algorithm skip out the local optimum when it suffers from premature. A fine-grained scoring strategy which used to assign a score to each position of a particle (i.e. causal matrix) is presented to direct the mutation. The experiments were performed on 28 synthetic event logs with/without noise and 4 real-life event logs, and three classical algorithms of process mining (ETM, Hybrid ILP Miner, HM) were chosen for comparison. The results show that (1) PSOMiner achieved the best f-score on 25 synthetic event logs; (2) The average f-score of PSOMiner is 0.825 on 4 real-life event logs, which is superior to ETM whose average f-score is 0.703.

Execution time, reliability, and energy consumption are the three main performance parameters of processor scheduling for real-time embedded systems. It is very meaningful to optimize the energy optimization of processor scheduling to satisfy the requirements on time limit and reliability. This paper tries to optimize the energy consumption of the processor under three constraints: the partial ordering relations between task modules, the time limit, and the reliability. Based on directed acrylic graph (DAG) and quantum particle swarm optimization (QPSO), two scheduling algorithms were developed for the problem, namely, DAG_QPSO_I and DAG_QPSO_II. The two algorithms were compared with each other, and with other intelligent algorithms. The results show that the proposed algorithms are superior in optimization effect and efficiency, DAG_QPSO_I makes energy consumption more efficient than DAG_QPSO_II, and DAG_QPSO_II meets stricter requirements on time limit and reliability than DAG_QPSO_I.

Abstract Background Little is known about the associations between healthy dietary patterns and metabolic dysfunction-associated fatty liver disease (MAFLD) in less-developed ethnic minority regions (LEMRs), where the prevalence of MAFLD is increasing rapidly and dietary habits are quite different from those in developed countries. Moreover, a significant subset of MAFLD individuals in LEMRs are nonobese, but the efficacy of dietary patterns on MAFLD individuals with different obese statuses is also unclear. We aimed to test the associations of two wildly recommended a priori dietary patterns—Alternate Mediterranean diet (AMED) and Dietary Approaches to Stop Hypertension (DASH)—with the risk of MAFLD in the total population, and further in nonobese and obese individuals. Methods We recruited 99,556 participants in the China Multi-Ethnic Cohort Study, an ongoing cohort study in less-developed southwest China. Using validated food frequency questionnaire, each participant was assigned an AMED score and a DASH score. MAFLD was ascertained as hepatic steatosis on ultrasound together with diabetes, overweight/obesity, or two other metabolic risk factors. We performed logistic regression with inverse probability of exposure weighting (IPEW) to examine associations between two dietary patterns and MAFLD, adjusting for potential confounders under the guidance of directed acyclic graphs. Further, analyses were stratified by body mass index. Results We included 66,526 participants (age 49.5±11.0; 62.6% women), and the prevalence of MAFLD was 16.1%. Participants in the highest quintile of DASH score showed strong inverse associations with risks of MAFLD (OR = 0.85; 95% CI, 0.80-0.91; P trend

Abstract Operational factors and microbial interactions affect the ecology in anaerobic digestion systems. From 12 lab-scale reactors operated under distinct engineering conditions, bacterial communities were found driven by temperature, while archaeal communities by both temperature and substrate properties. Combining the bacterial and archaeal community clustering patterns led to five sample groups (ambient, mesophilic low-solid-substrate, mesophilic, mesophilic co-digestion and thermophilic) for co-occurrence network analysis. Network topological properties were associated with substrate characteristics and hydrolysis-methanogenesis balance. The hydrolysis efficiency correlated (p

Introduction: Limited studies have focused on how the COVID-19 outbreak and thereby lockdown had affected the youth’s food ordering patterns, which was associated with their dietary behaviors and could have longer term impacts on their later-life health status if the trend persists. This study aimed to evaluate changes in food ordering patterns among youths in China after the COVID-19 outbreak. Methods: The data were obtained from a national retrospective survey (COINLICS) conducted in early May 2020 via social media platforms in China among more than 10,000 youth participants at 3 educational levels. Participants reported their basic sociodemographic characteristics, weight status, and lifestyles including food ordering patterns. We described and compared their weight status and food ordering patterns before COVID-19 (January) and under lockdown (February). Results: We observed significant changes in youths’ weight status and food ordering patterns under lockdown. A significant increase was observed in the prevalence of overweight/obesity (13.5%–17.0%) and obesity (8.7–10.8%), which varied by sex and educational level. Overall, the average weekly frequency of food ordering among the Chinese students had declined, with the largest decrease seen among graduate students, followed by undergraduate and high/vocational school students. Regardless of types of food, the percentage of participating youths who started ordering under lockdown was all lower than that of youths who stopped ordering. Among those who had still ordered foods under lockdown, a larger percentage of female than male high/vocational school students ordered barbecue/grill and cakes/pastries; no significant differences were found across the educational levels. Conclusion: The participating youths’ food ordering patterns had significantly changed during the COVID-19 lockdown, with heterogeneities observed to different extents between sexes and across educational levels. Our findings would inform policy makers and health professionals of these changes in time, for better policy making and public health practice.

IntroductionDiabetic kidney disease (DKD) is one of the complications of diabetes; however, the pathogenesis is not yet clear. A recent study has shown that senescence is associated with the course of DKD. In the present study, we explored whether senescent renal tubular cells promote renal tubulointerstitial fibrosis by secreting Sonic hedgehog (Shh) which mediates fibroblast activation and proliferation in DKD.MethodsA 36-week-old db/db mice model and the renal tubular epithelial cells were cultured in high glucose (HG, 60 mmol/L) medium for in vivo and in vitro experiments.ResultsCompared to db/m mice, blood glucose, microalbuminuria, serum creatinine, urea nitrogen, and UACR (microalbuminuria/urine creatinine) were markedly increased in db/db mice. Collagen III, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF-α) were also increased in db/db mice kidneys, suggesting fibrosis and inflammation in the organ. Moreover, the detection of SA-β-galactosidase (SA-β-Gal) showed that the activity of SA-β-Gal in the cytoplasm of renal tubular epithelial cells increased, and the cell cycle inhibition of the expression of senescence-related gene cell cycle inhibitor p16INK4A protein and p21 protein increased, indicating that renal fibrosis in db/db mice was accompanied by cell senescence. Furthermore, Shh is highly expressed in the injured renal tubules and in the kidney tissue of db/db mice, as detected by enzyme-linked immunosorbent assay (ELISA). The results of immunofluorescence staining showed increased positive staining for Shh in renal tubular epithelial cells of db/db mice and decreased positive staining for Lamin B1, but increased positive staining for γH2A.X in cells with high Shh expression; similar results were obtained in vitro. In addition, HG stimulated renal tubular epithelial cells to secrete Shh in the supernatant of the medium. D-gal treatment of renal tubular epithelial cells increased the protein levels of Shh and p21. We also found enhanced activation and proliferation of fibroblasts cultured with the supernatant of renal tubular epithelial cells stimulated by HG medium but the proliferative effect was significantly diminished when co-cultured with cyclopamine (CPN), an inhibitor of the Shh pathway.DiscussionIn conclusion, HG induces renal tubular epithelial cell senescence, and the secretion of senescence-associated proteins and Shh mediates inflammatory responses and fibroblast activation and proliferation, ultimately leading to renal fibrosis.

Background: Numerous studies have shown that residential greenness positively correlates with enhanced health. Metabolic dysfunction-associated fatty liver disease (MAFLD) affects about a quarter of the population while lacking specific treatments. Given that the association between green space and MAFLD is still unknown, we explored the association between residential greenness and MAFLD as well as the potential mechanisms based on the baseline survey of the China Multi-Ethnic Cohort (CMEC). Methods: Residential greenness was expressed as normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI). MAFLD was assessed through hepatic steatosis, the presence of overweight/obesity, type 2 diabetes mellitus, and evidence of metabolic dysregulation. We used logistic regression to examine the association between NDVI/EVI and the prevalence of MAFLD. Moreover, we utilized causal mediation analyses to explore the role of physical activity and ambient particulate matters (PM1, PM2.5, and PM10) on the association between residential greenness and MAFLD. Results: We included 72,368 participants from the CMEC and found that residential greenness was negatively associated with the prevalence of MAFLD. For an interquartile range (IQR) increase in NDVI500 m and EVI500 m, the odds ratio (OR) of MAFLD were 0.78 (95 %CI: 0.75, 0.81) and 0.81 (95 %CI: 0.78, 0.84), respectively. Greater association between residential greenness and MAFLD was observed among males. Air pollutants and physical activity could mediate a partial effect (8.5–22.9 %) of residential greenness on MAFLD. Conclusion: Higher residential greenness was associated with decreased risk of MAFLD. Moreover, the association was greater among males. The protective effects of residential greenness may be achieved by mitigating the hazardous effects of air pollutants and encouraging physical activity.