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A significant amount of glycyrrhiza wastewater is generated in the cleaning process of glycyrrhiza. The wastewater contains polysaccharide, glycyrrhizic acid, liquiritin, and other polyphenols, which is expensive for cleanup and wastes medical resources. To reduce environmental pollution from glycyrrhiza wastewater and increase the resource usage efficiency of glycyrrhiza components. According to the physicochemical properties of the component in glycyrrhiza wastewater, the ultrasonic assisted membrane separation mode was adopted to regulate the micellar state of glycyrrhizic acid and enhance the differences in membrane separation of polysaccharides, saponins, and flavones, in order to achieve the classification and separation of polysaccharides, saponins, and flavones while removing organic matter in glycyrrhiza wastewater. However, the efficiency, application, and mechanism of ultrasonic-assisted membrane technology for the separation of polysaccharides, saponins, and flavonoids from glycyrrhiza wastewater remain unclear. This study presents a green and feasible technical strategy for glycyrrhiza wastewater treatment that was developed by adjusting the parameters of ultrasonic assisted membrane separation. In this study, the systematic separation mode of ultrasonic enhanced ultrafiltration combined with nanofiltration is provided. The SCQ-9200E ultrasonic system was provided for the study with adjustable ultrasonic power, and the ultrasonic frequency was 40 kHz. The glycyrrhizic acid micelle was changed using ultrasonic power, pH, and molecular weight cut off (MWCO), and the separation differences among polysaccharide, glycyrrhizic acid, and liquiritin were enhanced. The optimal polysaccharide separation parameters used in the first step: MWCO 30 kDa, ultrasonic power 500 W and pH 5.00, and the rejections of polysaccharide, glycyrrhizic acid, and liquiritin were 87.72 %, 8.01 %, and 6.57 %, respectively. The second step included the following parameters for the separation of liquiritin and glycyrrhizic acid: MWCO 10 kDa, ultrasonic power 100 W and pH 8.00, the rejections of liquiritin and glycyrrhizic acid were 9.22 % and 40.65 %, respectively. The third step is to remove the low molecular sugar in liquiritin by nanofiltration: MWCO 800 Da, pH 8.00, retention solution diluted and separated twice, the rejection of liquiritin and total sugar were 95.72 % and 3.70 %, respectively. Ultrasonic may regulate the microtopography of glycyrrhiza wastewater with the power intensity of 50 W/L, improving the mass transfer efficiency of glycyrrhizic acid and liquiritin in the ultrafiltration separation process. As the separation volume of wastewater increased from 2.00 L to 20.00 L, the concentrations of polysaccharide, glycyrrhizic acid, and liquiritin increased by 2.5–35.4 times, 0.6–15.2 times, and 2.4–32.8 times, respectively, significantly increasing the content of index components in wastewater and solving the problem of recycling and resource utilization in glycyrrhiza wastewater.

This study investigates the development and performance of a prefabricated permanent formwork using 3D textile-reinforced cementitious composites (3D-TRCC) and explores the experimental application of pneumatic air mat shoring (PAMS). Herein, we address challenges, such as high labor demands and construction waste, in traditional formwork. The 3D-TRCC exhibited high flexural strength and ductile behavior through multiple cracks during material tests and mock-up experiments, confirming its potential as a sustainable formwork material. The introduction of the PAMS significantly simplified the installation and dismantling of temporary structures, reducing construction time by 25.7 % compared with those of conventional methods. Numerical analysis supported the structural behavior observed in the mock-up tests and provided insights for optimizing design parameters. These findings shows that the combination of a 3D-TRCC permanent formwork with PAMS offers a promising solution for efficient and sustainable construction practices.

Endometrial cancer (ECs) stands as one of the three major malignancies impacting females globally, with its incidence steadily increasing. ECs can be categorized into two types based on their clinicopathological features. Type I ECs typically exhibit low stage, favorable histological types, and low histological grade, correlating with a more favorable prognosis. Conversely, Type II ECs present with advanced-stage disease, aggressive behavior, and poorer histological types, resulting in a worse prognosis.The expression level of progesterone receptors (PR) holds significant importance in determining the prognosis of patients with ECs. Elevated levels of PR are linked to a more favorable prognosis, primarily attributed to progesterone's inhibitory influence on cancer cell proliferation and invasion. Moreover, progesterone promotes cell cycle inhibition through its regulation of PR, further contributing to improved outcomes in ECs.Nicalin (NCLN) plays a crucial role in facilitating the translocation of multichannel membrane proteins to the endoplasmic reticulum membrane and is implicated in embryonic development. Structurally akin to NODAL Modulator (NOMO), NCLN antagonizes NOMO during embryogenesis, forming a complex that antagonizes the Nodal pathway, thereby influencing mesoderm development. However, the precise relationship between NCLN and ECs remains incompletely understood.Our research findings reveal that NCLN actively stimulates the proliferation of ECs cells and exhibits a positive correlation with PR, albeit without impacting ER. Moreover, the expression levels of NCLN in ECs demonstrate associations with distinct histological types. These observations suggest that NCLN could emerge as a promising marker in the histological classification of ECs.

Summary: Constipation and frailty are associated with intestinal dysbiosis. This study aims to identify intestinal microbial signatures that can differentiate between constipated elders accompanied by frailty and those without frailty. We collected stool samples from 61 participants and conducted 16S rRNA gene sequencing. Constipated patients with frailty (Constipation_F) exhibited reduced gut microbial diversities compared to constipated patients without frailty (Constipation_NF) and healthy individuals (C). From differential genera, random forest models identified 14, 8, and 5 biomarkers for distinguishing Constipation_F from Constipation_NF, Constipation_F from C, and Constipation_NF from C, respectively. Functional analysis revealed that pathways (P381-PWY and PWY-5507) related to vitamin B12 synthesis were reduced in Constipation_F, which aligns with the decreased abundances of vitamin-B12-producing Actinomyces and Akkermansia in this group. Our study unveils substantial differences in gut microbiota between constipated elders with frailty and those without, underscoring the diagnostic and therapeutic potential of genera involved in vitamin B12 synthesis.

The transformation of salvianolic acid B brought on by heat treatment recovery of ethanol eluent, which is a difficult problem in pharmaceutical technology, affects the purity of raw material when the medicinal raw material salvianolic acid B is purified by resin. Ultrasonic-assisted nanofiltration separation (UANS) was first employed to improve efficiency of resource utilization by regulating rejection and separating salvianolic acid B and rosmarinic acid from organic pharmaceutical wastewater. The rejection was related to three variables: ultrasonic power, pH, and ethanol concentration. But there were differences in the effects of variables on the rejections of salvianolic acid B and rosmarinic acid. The rejections of rosmarinic acid and salvianolic acid B showed a decreasing trend with an increase in ultrasonic power or a decrease in pH; however, when the concentration of ethanol was increased from 5 % to 35 %, the salvianolic acid B rejection increased from 84.96 % to 96.60 % and the rosmarinic acid rejection decreased from 35.09 % to 17.51 %. On the basis of response surface methodology (RSM), the optimal UANS parameters for solution conditions involving different ethanol concentrations are as follows: 10 % ethanol solution (ultrasonic power 500 W and pH 6.15), 20 % ethanol solution (ultrasonic power 500 W and pH 6.54), and 30 % ethanol solution (ultrasonic power 460 W and pH 6.34). The molecular proportions of salvianolic acid B were 10.75 %, 7.13 %, and 8.27 % in 10 %, 20 %, and 30 % ethanol wastewater, while the molecular proportions of rosmarinic acid were 40.52 %, 33.83 %, and 69.87 %, respectively. And the recoveries of salvianolic acid B in 10 %, 20 %, and 30 % ethanol wastewater were 93.56 %, 95.04 %, and 97.30 %, respectively, while the recoveries of rosmarinic acid were 3.19 %, 2.27 %, and 0.56 %. The molecular proportion and the rejection are correlated exponentially. In comparison with conventional nanofiltration separation (CNS), UANS is able to resolve the conflict between rosmarinic acid and salvianolic acid B in pharmaceutical wastewater, as well as enhance resource recycling and separation efficiency to prevent pollution of the environment from pharmaceutical wastewater. Experiments using UANS at different power intensities suggest that the ultrasonic at a power intensity of 46–50 W/L and the power density of 0.92–1.00 W/cm2 may resolve the separation conflict between rosmarinic acid and salvianolic acid B. This work suggests that UANS may be a significant advancement in the field of ultrasonic separation and has several potential uses in the water treatment industry.

Background and purpose: Despite the superior dose conformity of proton therapy, the dose distribution is sensitive to daily anatomical changes, which can affect treatment accuracy. This study evaluated the dose recalculation accuracy of two synthetic computed tomography (sCT) generation algorithms in a commercial treatment planning system. Materials and methods: The evaluation was conducted for head-and-neck, thorax-and-abdomen, and pelvis sites treated with proton therapy. Thirty patients with two cone-beam computed tomography (CBCT) scans each were selected. The sCT images were generated from CBCT scans using two algorithms, Corrected CBCT (corrCBCT) and Virtual CT (vCT). Dose recalculations were performed based on these images for comparison with “ground truth” deformed CTs. Results: The choice of algorithm influenced dose recalculation accuracy, particularly in high dose regions. For head-and-neck cases, the corrCBCT method showed closer agreement with the “ground truth”, while for thorax-and-abdomen and pelvis cases, the vCT algorithm yielded better results (mean percentage dose discrepancy of 0.6 %, 1.3 % and 0.5 % for the three sites, respectively, in the high dose region). Head-and-neck and pelvis cases exhibited excellent agreement in high dose regions (2 %/2 mm gamma passing rate >98 %), while thorax-and-abdomen cases exhibited the largest differences, suggesting caution in sCT algorithm usage for this site. Significant systematic differences were observed in the clinical target volume and organ-at-risk doses in head-and-neck and pelvis cases, highlighting the importance of using the correct algorithm. Conclusions: This study provided treatment site-specific recommendations for sCT algorithm selection in proton therapy. The findings offered insights for proton beam centers implementing adaptive radiotherapy workflows.

Summary: Background: Contrast-enhanced CT scans provide a means to detect unsuspected colorectal cancer. However, colorectal cancers in contrast-enhanced CT without bowel preparation may elude detection by radiologists. We aimed to develop a deep learning (DL) model for accurate detection of colorectal cancer, and evaluate whether it could improve the detection performance of radiologists. Methods: We developed a DL model using a manually annotated dataset (1196 cancer vs 1034 normal). The DL model was tested using an internal test set (98 vs 115), two external test sets (202 vs 265 in 1, and 252 vs 481 in 2), and a real-world test set (53 vs 1524). We compared the detection performance of the DL model with radiologists, and evaluated its capacity to enhance radiologists’ detection performance. Findings: In the four test sets, the DL model had the area under the receiver operating characteristic curves (AUCs) ranging between 0.957 and 0.994. In both the internal test set and external test set 1, the DL model yielded higher accuracy than that of radiologists (97.2% vs 86.0%, p 0.99), and it detected 2 cases that had been missed by radiologists. Interpretation: The developed DL model can accurately detect colorectal cancer and improve radiologists’ detection performance, showing its potential as an effective computer-aided detection tool. Funding: This study was supported by National Science Fund for Distinguished Young Scholars of China (No. 81925023); Regional Innovation and Development Joint Fund of National Natural Science Foundation of China (No. U22A20345); National Natural Science Foundation of China (No. 82072090 and No. 82371954); Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application (No. 2022B1212010011); High-level Hospital Construction Project (No. DFJHBF202105).

Superconducting nanowire single-photon detectors (SNSPDs) have become a mainstream photon-counting technology that has been widely applied in various scenarios. So far, most multi-channel SNSPD systems, either reported in literature or commercially available, are polarization sensitive, that is, the system detection efficiency (SDE) of each channel is dependent on the state of polarization of the to-be-detected photons. Here, we reported an eight-channel system with fractal SNSPDs working in the wavelength range of 930 to 940 nm, which are all featured with low polarization sensitivity. In a close-cycled Gifford-McMahon cryocooler system with the base temperature of 2.2 K, we installed and compared the performance of two types of devices: (1) SNSPD, composed of a single, continuous nanowire and (2) superconducting nanowire avalanche photodetector (SNAP), composed of 16 cascaded units of two nanowires electrically connected in parallel. The highest SDE among the eight channels reaches 96−5+4%, with the polarization sensitivity of 1.02 and a dark-count rate of 13 counts per second. The average SDE for eight channels for all states of polarization is estimated to be 90 ± 5%. It is concluded that both the SNSPDs and the SNAPs can reach saturated, high SDE at the wavelength of interest, and the SNSPDs show lower dark-count (false-count) rates, whereas the SNAPs show better properties in the time domain. With the adoption of this system, we showcased the measurements of the second-order photon-correlation functions of light emission from a single-photon source based on a semiconductor quantum dot and from a pulsed laser. It is believed that this work will provide new choices of systems with single-photon detectors combining the merits of high SDE, low polarization sensitivity, and low noise that can be tailored for different applications.

Summary: Background: Sleep and circadian rhythm disruptions are common in patients with mood disorders. The intricate relationship between these disruptions and mood has been investigated, but their causal dynamics remain unknown. Methods: We analysed data from 139 patients (76 female, mean age = 23.5 ± 3.64 years) with mood disorders who participated in a prospective observational study in South Korea. The patients wore wearable devices to monitor sleep and engaged in smartphone-delivered ecological momentary assessment of mood symptoms. Using a mathematical model, we estimated their daily circadian phase based on sleep data. Subsequently, we obtained daily time series for sleep/circadian phase estimates and mood symptoms spanning >40,000 days. We analysed the causal relationship between the time series using transfer entropy, a non-linear causal inference method. Findings: The transfer entropy analysis suggested causality from circadian phase disturbance to mood symptoms in both patients with MDD (n = 45) and BD type I (n = 35), as 66.7% and 85.7% of the patients with a large dataset (>600 days) showed causality, but not in patients with BD type II (n = 59). Surprisingly, no causal relationship was suggested between sleep phase disturbances and mood symptoms. Interpretation: Our findings suggest that in patients with mood disorders, circadian phase disturbances directly precede mood symptoms. This underscores the potential of targeting circadian rhythms in digital medicine, such as sleep or light exposure interventions, to restore circadian phase and thereby manage mood disorders effectively. Funding: Institute for Basic Science, the Human Frontiers Science Program Organization, the National Research Foundation of Korea, and the Ministry of Health & Welfare of South Korea.

Objective: Shenshuai Yingyang Jiaonang (SSYYJN), a traditional Chinese medicine formula, can ameliorate muscle atrophy associated with chronic kidney disease (CKD). However, its mechanisms of action remain unclear. This study is to investigate the molecular mechanisms involved in the effects of SSYYJN in ameliorating muscle atrophy associated with CKD in rats. Methods: The chemical compounds of SSYYJN were identified by UPLC-Q-Orbitrap HRMS. Considering the dose-response relationship of the identified compounds, male SD rats were randomly divided into Sham, Model, SSYYJN, and α-Keto Acid (KA) groups. Subsequently, we assessed the therapeutic and anti-ferroptotic effects of SSYYJN. Network pharmacology studies were used to predict the molecular mechanism of SSYYJN on ferroptosis and were further verified for accuracy. Results: A total of 42 active compounds were identified from SSYYJN. SSYYJN alleviated muscle atrophy caused by CKD, as evidenced by changes in body weight, serum biochemical indices, mass and histopathology of the skeletal muscle, and the levels of MuRF1. SSYYJN reduced the levels of iron, MDA, and ROS, increased the levels of GSH, NAPDH, and Gpx4. Network pharmacology analysis indicated that SSYYJN exerted anti-ferroptotic effects that were closely related to the HIF-1α signaling pathway. Molecular protein and genetic test results showed that SSYYJN increased HIF-1α protein and increased SLC7A11. Conclusions: SSYYJN attenuates muscle atrophy in CKD by inhibiting ferroptosis through the activation of the HIF-1α/SLC7A11 pathway and might be a promising traditional Chinese medicine for muscle atrophy in CKD.

Due to the excellent electrothermal properties, outstanding resistance to electromigration and cost-effectiveness, Cu nanoparticles are considered as a promising bonding material for high-power device. However, few studies have analyzed the coalescence behavior mechanism of Cu nanoparticles during sintering under temperature dependent conditions. In this paper, a novel method combining atomic and macroscopic scales was adopted to investigate the coalescence behavior of Cu nanoparticles. The sintering microstructure and bonding quality of Cu nanoparticles at different temperatures were evaluated via in-situ Transmission electron microscopy (TEM) heating, and the evolution of dislocations and phase transitions was analyzed. Molecular dynamics (MD) simulation was employed to characterize the atomic scale evolution of solid-state liquid sintering process of Cu nanoparticles. The role of temperature and nanoparticle size in the sintering mechanism were investigated. The results indicate that high temperature during constant temperature sintering is beneficial for the formation of stable crystal structures in the sintering neck and reduces the generation of dislocations. Shockley dislocations can contribute to the constitution of HCP stacking fault within Cu nanoparticles, which deteriorates the sintering performance. The increase in sintering temperature prompts Cu atoms at the sintering neck to migrate horizontally rather than vertically. Compared to small-sized nanoparticles, significant driving energy was required in the sintering of large-sized nanoparticles during the continuous heating process. Shockley dislocations play a dominant role in phase transition stacking fault at high temperature. Additionally, the mechanical failure forms of Cu/Nano-Cu/Cu joints at different sintering temperatures were studied and verified through MD simulation.

Ultrasonic-assisted activated carbon separation (UACS) was first employed to improve product quality by regulating adsorption rate and removing bacterial endotoxin from salvia miltiorrhizae injection. The adsorption rate was related to three variables: activated carbon dosage, ultrasonic power, and pH. With the increase of activated carbon dosage from 0.05 % to 1.0 %, the adsorption rates of salvianolic acids and bacterial endotoxin increased simultaneously. The adsorption rates at which bacteria endotoxins increased from 52.52 % to 97.16 % were much higher than salvianolic acids. As the ultrasonic power increased from 0 to 700 W, the adsorption rates of salvianolic acids on activated carbon declined to less than 10 %, but bacterial endotoxin increased to more than 87 %. As the pH increased from 2.00 to 8.00, the adsorption rate of salvianolic acid dropped whereas bacterial endotoxin remained relatively stable. On the basis of response surface methodology (RSM), the optimal separation conditions were established to be activated carbon dose of 0.70 %, ultrasonic power of 600 W, and pH of 7.90. The experimental adsorption rates of bacterial endotoxin were 94.15 %, which satisfied the salvia miltiorrhizae injection quality criterion. Meanwhile, salvianolic acids' adsorption rates were 1.92 % for tanshinol, 4.05 % for protocatechualdehyde, 2.21 % for rosmarinic acid, and 3.77 % for salvianolic acid B, all of which were much lower than conventional activated carbon adsorption (CACA). Salvianolic acids' adsorption mechanism on activated carbon is dependent on the component's molecular state. Under ideal separation conditions, the molecular states of the four salvianolic acids fall between 1.13 % and 6.60 %. The quality of salvia miltiorrhizae injection can be improved while maintaining injection safety by reducing the adsorption rates of salvianolic acids to less than 5 % by the use of ultrasound to accelerate the desorption mass transfer rate on the activated carbon surface. When activated carbon adsorption was used in the process of producing salvia miltiorrhizae injection, the pH of the solution was around 5.00, and the proportion of each component's molecular state was tanshinol 7.05 %, protocatechualdehyde 48.93 %, rosmarinic acid 13.79 %, and salvianolic acid B 10.28 %, respectively. The loss of useful components was evident, and the corresponding activated carbon adsorption rate ranged from 20.74 % to 41.05 %. The average variation rate in plasma His and IgE was significant (P 0.05). The ultrasonic at a power intensity of 60 W/L and the power density of 1.20 W/cm2 may resolve the separation contradiction between salvianolic acids and bacterial endotoxin, according to experiments conducted with UACS at different power intensities. According to this study, UACS has a lot of potential applications in the pharmaceutical manufacturing industry and may represent a breakthrough in the field of ultrasonic separation.

Background and purpose: High-density dental fillings pose a non-negligible impact on head and neck cancer treatment. For proton therapy, stopping power ratio (SPR) prediction will be significantly impaired by the associated image artifacts. Dose perturbation is also inevitable, compromising the treatment plan quality. While plenty of work has been done on metal or amalgam fillings, none has touched on composite resin (CR) and glass ionomer cement (GIC) which have seen an increasing usage. Hence, this work aims to provide a detailed characterisation of SPR and dose perturbation in proton therapy caused by CR and GIC. Materials and methods: Four types of fillings were used: CR, Fuji Bulk (FB), Fuji II (FII) and Fuji IX (FIX). The latter three belong to GIC category. Measured SPR were compared with SPR predicted using single-energy computed tomography (SECT) and dual-energy computed tomography (DECT). Dose perturbation of proton beams with lower- and higher-energy levels was also quantified using Gafchromic films. Results: The measured SPR for CR, FB, FII and FIX were 1.68, 1.77, 1.77 and 1.76, respectively. Overall, DECT could predict SPR better than SECT. The lowest percentage error achieved by DECT was 19.7 %, demonstrating the challenge in estimating SPR, even for fillings with relatively lower densities. For both proton beam energies and all four fillings of about 4.5 mm thickness, the maximum dose perturbation was 3 %. Conclusion: This study showed that dose perturbation by CR and GIC was comparatively small. We have measured and recommended the SPR values for overriding the fillings in TPS.

Fermented foods have protective effects on body health. In our previously study, we found Lactiplantibacillus plantarum fermentation enhanced antioxidant activity of kiwifruit in vitro digestion. Then, in this work we explored the protective effect of fermented kiwi on intestinal injury induced by acute lipopolysaccharide (LPS) stress. Compared to non-fermented kiwi pulp (KP), Lactiplantibacillus plantarum fermented kiwi pulp (FKP-LP) contained more peptides, hormones and vitamins contents, lesser nucleic acid and carbohydrate contents. FKP-LP could relieve the intestinal injury by improving morphological of tight junction and upregulating tight junction proteins mRNA expression. Fermented kiwi maintained the mitochondrial morphology, mitochondrial respiratory function, and mitochondrial homeostasis, and relieved the LPS induced injury by regulating the contents of energy substances, and the respiratory chain complex enzyme activity through the pathway of AMPK and its downstream factors including PGC-1α, NRF1, NRF2, TFAM, and ULK2.

Ultrasonic-assisted supercritical fluid separation (USFS) was firstly applied to regulate solubility and remove plasticizers from ganoderma lucidum spores’ oil to improve product safety. Separation efficiency was related with four variables, including temperature, pressure and ultrasonic power. The QD-T6A ultrasonic generator probe, which provided for the study with adjustable ultrasonic power 0 W to 800 W and the ultrasonic frequency was 40 kHz, was fixed at the entrance of the primary separation kettle. The optimal separation conditions were determined to be temperature as 15.0 °C, pressure as 18.0 MPa, and ultrasonic power as 360 W of ultrasonic power on the basis of response surface methodology (RSM). Experimental Di-n-butylphthalate (DBP) and Diethyl phthalate (DEP) content were 0.09 mg and 0.04 mg, respectively, which were below the limits for plasticizers. Meanwhile, the total triterpene and ganoderic acid A contents were 6.89 g and 1.10 g, respectively, comparable to conventional supercritical fluid extraction. The experiments with USFS at different power intensities revealed that ultrasonic at a power intensity of 36 W/L and the power density of 0.20 W/cm2 could resolve the separation contradiction between ganoderma lucidum spores’ oil and plasticizers. This study revealed that USFS could be an innovation in the field of ultrasonic separation, with numerous potentials uses in pharmaceutical manufacturing.

Background: Smilax is a traditional medicine used for the clinical treatment of pelvic inflammatory disease (CPID), and its leaves have long been used as food by the Korean people in Asia. In previous studies, we found that flavonoids extract can improve CPID by inhibiting inflammation, which may be the main effective component of Smilax China, but its mechanism of action has not been fully elucidated. This study explores the mechanism by which Chinese rhizome flavonoids (FSCR) regulate the autophagy pathway of NLRP3 inflammasome and promote macrophage reprogramming. Methods: In the in vivo experiment, the sham surgery group and the CPID group were given physiological saline and FCSR for 7 days, respectively. We determined the expression of NLRP3 inflammasome autophagy pathway genes and proteins by observing the pathological damage of rat uteri through HE and Masson staining, immunofluorescence, RT-PCR, and WB experiments. Molecular docking simulation predicted the binding potential of flavonoids with the potential target VPS34, and knockdown experiments were conducted to validate the knockdown effect of lipopolysaccharide treatment on primary rat endometrial cells to simulate an in vitro CPID model. Results: FCSR significantly reduced serum IL-1β in CPID rats, TNF-α. The concentration of TAX2 reduced the infiltration of inflammatory cells and fibrosis of endometrial cells, promoted M2 polarization of macrophages, upregulated autophagy pathways, and inhibited the activation of NLRP3 inflammasomes. After knocking down the NLRP3 inflammasome autophagy target VPS34, the FSCR effect was eliminated. Conclusions: By targeting VPS34, FCSR potentially promotes autophagic cell reprogramming through the NLRP3 inflammasome related autophagy pathway.

Background and Aims: The clinical, prognostic, and therapeutic impact of adrenal insufficiency in acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) remains controversial and exact diagnostic criteria are lacking. We sought to determine the diagnostic and therapeutic value of cortisol measurement and glucocorticoid (GC) treatment in ALF and ACLF. Methods: 28-day transplant-free survival (TFS) was studied in relation to absolute cortisol concentrations and to GC treatment in ALF (n = 30) and ACLF (n = 34) patients. Cortisol concentrations and short synacthen test were assessed by chemiluminescence immunoassay and liquid chromatography-mass spectrometry. Clinicians decided independently on GC treatment. In relation, phenotypic and functional characteristics of circulating monocytes were assessed. Results: In ALF, baseline cortisol concentrations

Background and objectives: There are concerns about the serological responses to Coronavirus disease 2019 (COVID-19) vaccines in inflammatory bowel disease (IBD) patients, particularly those receiving anti-TNF therapy. This study aimed to systematically evaluate the efficacy of COVID-19 vaccines in IBD patients receiving anti-TNF therapy. Methods: Electronic databases were searched to identify relevant studies. We calculated pooled seroconversion rate after COVID-19 vaccination and subgroup analysis for vaccine types and different treatments were performed. Additionally, we estimated pooled rate of T cell response, neutralization response, and breakthrough infections in this population. Results: 32 studies were included in the meta-analysis. IBD patients receiving anti-TNF therapy had relatively high overall seroconversion rate after complete vaccination, with no statistical difference in antibody responses associated with different drug treatments. The pooled positivity rate of T cell response was 0.85 in IBD patients receiving anti-TNF therapy. Compared with healthy controls, the positivity of neutralization assays was significantly lower in IBD patients receiving anti-TNF therapy. The pooled rate of breakthrough infections in IBD patients receiving anti-TNF therapy was 0.04. Conclusions: COVID-19 vaccines have shown good efficacy in IBD patients receiving anti-TNF therapy. However, IBD patients receiving anti-TNF have a relatively high rate of breakthrough infections and a low level of neutralization response.

Background: Although it has been reported that miRNA carried by M2 microglial exosomes protects neurons from ischemia–reperfusion brain injury, the mechanism of action remains poorly understood. This study aimed to explore the miRNA signaling pathway by which M2-type microglia-derived exosomes (M2-exosomes) ameliorate oxygen–glucose deprivation/reoxygenation (OGD/R)-induced cytotoxicity in HT22 cells. Methods: BV2 microglia were induced by M2 polarization. Then, M2-exosomes were identified via transmission electron microscopy and special biomarker detection and co-cultured with HT22 cells. Cell proliferation was evaluated using the Cell Counting Kit-8 (CCK-8) assay. Intracellular concentrations of reactive oxygen species (ROS), Fe2+, glutathione (GSH), and malondialdehyde (MDA) were determined using dichlorofluorescein fluorescence and biochemical determination. miR-124-3p levels were determined using qRT-PCR, and protein expressions were examined via western blotting. Results: OGD/R suppressed the proliferation and induced the accumulation of Fe2+, ROS, and MDA and reduction of GSH in mouse HT22 cells, suggesting ferroptosis of HT22 cells. OGD/R-induced changes in the above mentioned indexes was ameliorated by M2-exosomes but restored by the exosome inhibitor GW4869. M2-exosomes with (mimic-exo) or without miR-124-3p (inhibitor-exo) promoted and suppressed proliferation and ferroptosis-associated indexes of HT22 cells, respectively. Moreover, mimic-exo and inhibitor-exo inhibited and enhanced NCOA4 expression in HT22 cells, respectively. NCOA4 overexpression reversed the protective effects of miR-124-3p mimic-exo in OGD/R-conditioned cells. NCOA4 was targeted and regulated by miR-124-3p. Conclusions: M2-exosome protects HT22 cells against OGD/R-induced ferroptosis injury by transferring miR-124-3p and NCOA4 into HT22 cells, with the latter being a target gene for miR-124-3p.

Despite the promising clinical benefits of therapies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) with antibodies in various cancers, resistance to these therapies will inevitably develop following treatment. Recent studies suggest that crosstalk between the EGFR and VEGF signaling pathways might be involved in the development of resistance. Therefore, simultaneous blockade of EGFR and VEGF signaling may be able to counteract this resistance and improve clinical outcomes. Here, we devised a fusion protein with two copies of VEGFR1 domain 2 connected to the C-terminus of cetuximab that can simultaneously bind to EGFR and VEGF and effectively inhibit target cell growth mediated by these two pathways. Furthermore, the fusion protein could bring soluble VEGF into target cells for degradation through internalization upon binding to EGFR. Tissue distribution in mice confirmed that the fusion protein effectively accumulated in tumors compared to its mAb counterpart cetuximab. These features resulted in stronger antitumor efficacies in vivo than the combination of bevacizumab and cetuximab. Thus, we provide a promising new strategy for the treatment of EGFR-overexpressing cancers.

Our previous studies showed that Salidroside (Sal), a glucoside of the phenylpropanoid tyrosol isolated from Rhodiola rosea L, alleviated severe acute pancreatitis (SAP) by inhibiting inflammation. However, the detailed mechanism remains unclear. Recent evidence has indicated a critical role of Sal in ameliorating inflammatory disorders by regulating pyroptosis. The present study aimed to explore the involvement of Sal and pyroptosis in the pathogenesis of SAP and investigate the potential mechanism. The effects of Sal on pyroptosis were first evaluated using SAP rat and cell model. Our results revealed that Sal treatment significantly decreased SAP-induced pancreatic cell damage and pyroptosis in vivo and in vitro, as well as reduced the release of lactate dehydrogenase (LDH), IL-1β and IL-18. Search Tool for Interacting Chemicals (STITCH) online tool identified 4 genes (CASP3, AKT1, HIF1A and IL10) as candidate targets of Sal in both rattus norvegicus and homo sapiens. Western blot and immunohistochemistry staining validated that Sal treatment decreased the phosphorylation levels of Akt and NF-κB p65, as well as cleaved caspase-3 and N-terminal fragments of GSDME (GSDME-N), suggesting that Sal might suppress pyroptosis through inactivating Akt/NF-κB and Caspase-3/GSDME pathways. Furthermore, overexpression of AKT1 or CASP3 could partially reverse the inhibitory effects of Sal on cell injury and pyroptosis, while downregulation of AKT1 or CASP3 promoted the inhibitory effects of Sal. Taken together, our data indicate that Sal suppresses SAP-induced pyroptosis through inactivating Akt/NF-κB and Caspase-3/GSDME pathways.

The transgenerational inheritance of phenotype induced by environmental factors is a new focus in epigenetic research. In this study, Drosophila melanogaster (F0) was cultured in the medium containing cadmium (Cd, 4.5 mg/kg) from eggs to adults, and offspring (F1-F4) were continuously kept in standard medium (without cadmium). The phenotype analysis showed that cadmium induced developmental defects on wings and apoptosis in the wing disc cells of Drosophila (F0). The wing defects were transmitted for at least four generations even without Cd afterwards. And the effect on the mRNA expression of wing development related genes (shg, omb, F-actin, Mekk1) can be maintained for at least two or three generations. More importantly, under cadmium stress, the post-translational modification (PTM) on the histones H3K4me3 in the third instar larvae and ovaries or testes of adult flies increased significantly, while the levels of H3K9me3 and H3K27me3 decreased significantly. The expression of histone methylation related genes (dSet-1, ash1, Lsd1) increased significantly and these changes can be transmitted to offspring from one or two generations in ovaries or testes. These results suggest that the phenotypic defects of wings caused by cadmium can be inherited to the offspring, and this transgenerational inheritance effect may be related to the epigenetic regulation of histone methylation. Therefore, the adaptability of offspring should be considered when evaluating the toxicity and environmental risk of cadmium.

Background & Aim: Ammonia is central in the pathogenesis of brain edema in acute liver failure (ALF) with infection and systemic inflammation expediting development of intracranial hypertension (ICH). Patients with acetaminophen-induced ALF have increased neutrophil TLR9 expression which can be induced by ammonia. We determined whether ammonia-induced brain edema and immune dysfunction are mediated by TLR9 and if this could be prevented in a TLR9-deficient mouse model. Methods: Ammonium acetate (NH4-Ac; 4mmol/kg) was injected intraperitoneally in wild type (WT), Tlr9-/- and Lysm-Cre Tlr9fl/fl mice (TLR9 absent in neutrophils and macrophages including Kupffer cells) and compared to controls. Six hours after NH4-Ac injection, intracellular cytokine production was determined in splenic macrophages, CD4+ and CD8+ T cells. Brain water (BW) and total plasma DNA (tDNA) were also measured. The impact of the TLR9 antagonist ODN2088 (50μg/mouse) was evaluated. Results: Following NH4-Ac injection, BW, macrophage and T cell cytokine production increased (P < .0001) in WT but not Tlr9-/- mice (P < .001). ODN2088 inhibited macrophage and T cell cytokine production (P < .05) and prevented an increase in BW (P < .0001). Following NH4-Ac injection, macrophage cytokine production and BW were ameliorated in Lysm-Cre Tlr9fl/fl mice compared to WT mice (P < .05) but there was no difference compared to Tlr9-/- mice. Following NH4-Ac injection, plasma tDNA levels increased in WT and Tlr9-/- mice (P < .05) suggesting that TLR9 may be activated by DNA released from ammonia-stimulated cells. Conclusion: Ammonia-induced brain edema requires macrophage and T cell expression of TLR9. Amelioration of brain edema and lymphocyte cytokine production by ODN2088 supports exploration of TLR9 antagonism in early ALF to prevent progression to ICH. Keywords: Ammonia, Brain edema, Immune dysfunction, Toll-like receptor 9

We developed a strategy to combine conventional targeted therapy with immune checkpoint blockade using a tumor-targeting bispecific antibody (BsAb) to treat solid tumors. The BsAb was designed to simultaneously engage a tumor-associated antigen, epidermal growth factor receptor (EGFR), and programed cell death protein 1 (PD1). In addition to its direct anti-tumor activity via EGFR inhibition, the BsAb mediated efficient antibody-dependent cellular cytotoxicity (ADCC) and activated T cell antitumor im munity through blockade of PD1 from interacting with its counterpart, programed cell death ligand 1 (PDL1). Further, the BsAb exhibited a potent direct tumor cell killing activity in the presence of PBMC, most likely, via activating and, at the same time, physically engaging T cells with tumor cells. Taken together, we here illustrate a new strategy in the design and production of novel BsAbs with enhanced therapeutic efficacy through both direct tumor growth inhibition and T cell activation via tumor-targeted immune checkpoint blockade.

Summary: The increasing rising of multiple drug-resistant Staphylococcus aureus has become a major public health concern, underscoring a pressing need for developing therapies essentially based on the understanding of host defensive mechanism. In the present study, we showed that microRNA (miR)-127 played a key role in controlling bacterial infection and conferred a profound protection against staphylococcal pneumonia. The protective effect of miR-127 was largely dependent on its regulation of macrophage bactericidal activity and the generation of IL-22, IL-17, and anti-microbial peptides (AMPs), the pathway primarily driven by STAT3. Importantly, we revealed that the ubiquitin-editing enzyme A20, a genuine target of miR-127, specifically interacted with and repressed K63-ubiquitination of STAT3, thereby compromising its phosphorylation upon bacterial infection. Thus, our data not only identify miR-127 as a non-coding molecule with anti-bacterial activity but also delineate an unappreciated mechanism whereby A20 regulates STAT3-driven anti-microbial signaling via modulating its ubiquitination. : Molecular Mechanism of Behavior; Immunology; Microbiology; Bacteriology Subject Areas: Molecular Mechanism of Behavior, Immunology, Microbiology, Bacteriology

Poor flexibility and high contact resistance of conductive films are primary roadblock for the incorporation of Ag flake ink into practical applications. In this work, a novel and inexpensive Ag flake/ion composite ink was prepared to directly achieve the thick conductive films with excellent performances at 100 °C. The effect of Ag ion content on the resistivity and microstructures of the modified conductive film was investigated, and the flexibility and relative resistance change of the modified conductive film were measured by the cyclic bending test and compared with the traditional Ag flake ink. Consequently, the modified conductive film sintered from Ag flake/ion-0.5 in. exhibits low electrical resistivity of 4.83 × 10−5 Ω·cm, which is 42.9% lower than the Ag flake film sintered from the Ag flake ink, and the modified conductive film still displays smaller changes in resistivity and relative resistance after the cyclic bending tests. The enhanced conductivity and flexibility are attributed to the bridging effect of Ag nanoparticles (NPs) generated from the in–situ decomposition of Ag ion ink. These results demonstrate that the low-cost Ag flake/ion composite ink provides a tempting prospect for fabricating high-quality flexible printed electronics at low temperature. Keywords: Ag flake/ion composite ink, Conductive film, Flexibility, Resistivity

The sympathetic nervous system is a major efferent pathway through which the central nervous system controls the function of peripheral organs. Genetic and pharmacologic evidence in mice indicated that stimulation of the β2 adrenergic receptor (β2AR) in osteoblasts promotes bone loss, leading to the paradigm that high sympathetic nervous activity is deleterious to bone mass. However, considerably less data exist to understand the putative impact of endogenous norepinephrine (NE), released by sympathetic nerves, on bone homeostasis. In this study, we investigated the in vivo expression and activity of the norepinephrine transporter (NET), a membrane pump known to actively uptake NE from the extracellular space in presynaptic neurons. Consistent with previously published in vitro data showing NET uptake activity in differentiated osteoblasts, we were able to detect active NET-specific NE uptake in the mouse cortical bone compartment in vivo. This uptake was the highest in young mice and accordingly with an age-related reduction in NET uptake, NE bone content increased whereas Net RNA and protein expression decreased with age. Histologically, NET expression in adult mouse bones was detected in osteocytes via immunofluorescence. Lastly, taking advantage of tissue-specific fluorescent reporter mice, we used CLARITY imaging and light sheet microscopy to visualize the 3D distribution of sympathetic fibers in whole mount preparations of bone tissues. These analyses allowed us to detect tyrosine hydroxylase (TH)-positive sympathetic nerve fibers penetrating the cortical bone, where NET+ osteocytes reside. Together, these in vitro results support the existence of an age-dependent extraneuronal and osteocytic function of NET with potential to buffer the bone catabolic action of endogenous NE released by sympathetic nerves in vivo. Keywords: Sympathetic nerves, Bone remodeling, Norepinephrine, Transporter, Uptake, Osteocyte, Tracing, Imaging, Aging

Muscle development is regulated by a series of complicate processes, and non-coding RNAs (ncRNAs) such as lncRNA have been reported to play important roles in regulating skeletal myogenesis and diseases. Here we profile the expression of lncRNA in cattle skeletal muscle tissue from fetus and adult developmental stages and detect 13,580 lncRNA candidates. Many of these lncRNAs are differentially expressed between two developmental stages. We further characterize one abundant lncRNA with the highest expression level of all downregulated lncRNAs, which we named muscle differentiation-associated lncRNA (MDNCR). Via luciferase screening, RNA binding protein immunoprecipitation (RIP), and RNA pull-down assays, MDNCR was observed to directly bind to miR-133a with 32 potential binding sites. GosB was identified as a target of miR-133a by luciferase activity, quantitative real-time qPCR, and western blotting assays. Overexpression of MDNCR increased the expression of GosB, whereas this effect was abolished by miR-133a. We found that MDNCR promotes myoblast differentiation and inhibits cell proliferation by sponging miR-133a. These results demonstrate that MDNCR binding miR-133a promotes cell differentiation by targeting GosB in cattle primary myoblasts. Keywords: lncRNA, RNA-seq, cattle, myogenesis

Muscle development is regulated under a series of complicate processes, and non-coding RNAs, such as microRNAs (miRNAs) and circular RNAs (circRNAs), have been reported to play important roles in regulating myoblast proliferation and differentiation. We found that miR-107 expression was high in skeletal muscle of Qinchuan cattle. Overexpression of miR-107 inhibited bovine myoblasts differentiation and protected cells from apoptosis. Wnt3a was identified as a target of miR-107 by luciferase activity, real-time qPCR, and western blotting assays. Knockdown of Wnt3a inhibited bovine myoblasts differentiation and apoptosis, and this effect was similar to miR-107 overexpression. We also found circFGFR4 to promote myoblasts differentiation and to induce cell apoptosis. Via luciferase screening and RNA pull-down assays, circFGFR4 was observed to sponge miR-107. Overexpression of circFGFR4 increased the expression of Wnt3a, whereas this effect was abolished by miR-107. These results demonstrated that circFGFR4 binding miR-107 promotes cell differentiation via targeting Wnt3a in bovine primary myoblasts.

Summary: Proline accumulation is one of the most important adaptation mechanisms for plants to cope with environmental stresses, such as drought and freezing. However, the molecular mechanism of proline homeostasis under these stresses is largely unknown. Here, we identified a mitochondrial protein, DFR1, involved in the inhibition of proline degradation in Arabidopsis. DFR1 was strongly induced by drought and cold stresses. The dfr1 knockdown mutants showed hypersensitivity to drought and freezing stresses, whereas the DFR1 overexpression plants exhibited enhanced tolerance, which was positively correlated with proline levels. DFR1 interacts with proline degradation enzymes PDH1/2 and P5CDH and compromises their activities. Genetic analysis showed that DFR1 acts upstream of PDH1/2 and P5CDH to positively regulate proline accumulation. Our results demonstrate a regulatory mechanism by which, under drought and freezing stresses, DFR1 interacts with PDH1/2 and P5CDH to abrogate their activities to maintain proline homeostasis, thereby conferring drought and freezing tolerance. : Proline accumulation is very important for plants to cope with drought and freezing stresses. Ren et al. show that, in response to drought and freezing stresses, a mitochondrial protein DFR1 interacts with PDH1/2 and P5CDH to abrogate their activities to maintain proline homeostasis, thereby conferring drought and freezing tolerance. Keywords: Arabidopsis, DFR1, drought, freezing, proline degradation, PDH1, PDH2, P5CDH

In this data article, we developed a Au nanowire injector (Au NWI) for directly delivering plasmid into the 1-cell stage of the mouse embryos designed to successfully attach and detach the plasmid on the Au NWI, highly minimizing physical and chemical damage on the embryos. This data presents that a Au NWI system does not induce detrimental damages on development of embryos and efficiently express the green fluorescence protein in vitro. The data provided herein is in association with the research article related to reduce the occurrence of mosaicism by a Au NWI,” Suppressing Mosaicism by Au Nanowire Injector-driven Direct Delivery of Plasmids into Mouse Embryos” (Park et al., 2017 [1]).

Pelvic inflammatory disease (PID), an infection and inflammation disorder of the upper genital tract, results in infertility in approximately 20% of cases. No antibiotic that can alleviate the sequelae of PID has been identified. Smilax china L. rhizome (SCR), which are widely used in functional food and folk medicine, exhibit multiple pharmacological activities, such as anti-inflammatory, antioxidant and antitumour activities. In this study, the flavonoids of SCR (FSCR) were purified and analysed by UPLC-PDA-MS. The therapeutic effects of FSCR in a rat PID model were evaluated. FSCR-treated PID rats exhibited significantly decreased inflammation, ameliorated fibrosis, and enhanced production of matrix metalloproteinase (MMP)-2 and MMP-9 in uteri. Moreover, the phosphorylation of ERK1/2 and Smad2/3 was markedly inhibited by FSCR. These results indicate that FSCR exhibits robust anti-inflammatory and anti-fibrosis effects, possibly via inhibition of the ERK1/2 and TGF-β-Smad2/3 signalling pathways, and may be an effective candidate natural medicine for PID treatment.

Background: 18 F-sodium fluoride ( 18 F-NaF) positron emission tomography (PET)/computed tomography (CT) is a promising new approach for assessing microcalcification in vascular plaque., Objectives: This prospective study aimed to evaluate the associations between in vivo coronary 18 F-NaF PET/CT activity and ex vivo histological characteristics, to determine whether coronary 18 F-NaF activity is a novel biomarker of plaque pathological vulnerability, and to explore the underlying physiological environment of 18 F-NaF adsorption to vascular microcalcification., Methods: Patients with coronary artery disease (CAD) underwent coronary computed tomography angiography (CTA) and 18 F-NaF PET/CT. Histological vulnerability and immunohistochemical characteristics were evaluated in coronary endarterectomy (CE) specimens from patients who underwent coronary artery bypass grafting with adjunctive CE. Correlations between in-vivo coronary 18 F-NaF activity with coronary CTA adverse plaque features and with ex vivo CE specimen morphological features, CD68 expression, inflammatory cytokines expression (tumor necrosis factor-α, interleukin-1β), osteogenic differentiation cytokines expression (osteopontin, runt-related transcription factor 2, osteocalcin) were evaluated. High- and low- to medium-risk plaques were defined by standard pathological classification., Results: A total of 55 specimens were obtained from 42 CAD patients. Coronary 18 F-NaF activity of high-risk specimens was significantly higher than low- to medium-risk specimens (median [25th-75th percentile]: 1.88 [1.41-2.54] vs 1.12 [0.91-1.54]; P < 0.001). Coronary 18 F-NaF activity showed high discriminatory accuracy in identifying high-risk plaque (AUC: 0.80). Coronary CTA adverse plaque features (positive remodeling, low-attenuation plaque, remodeling index), histologically vulnerable features (large necrotic core, thin-fibro cap, microcalcification), CD68 expression, tumor necrosis factor-α expression, and interleukin-1β expression correlated with coronary 18 F-NaF activity (all P < 0.05). No significant association between coronary 18 F-NaF activity and osteogenic differentiation cytokines was found (all P > 0.05)., Conclusions: Coronary 18 F-NaF activity was associated with histological vulnerability, CD68 expression, inflammatory cytokines expression, but not with osteogenic differentiation cytokines expression. 18 F-NaF PET/CT imaging may provide a powerful tool for detecting high-risk coronary plaque and could improve the risk stratification of CAD patients., Competing Interests: Funding Support and Author Disclosures This study was funded by the Key Medical Specialty Program of Sailing Plans organized by Beijing Municipal Administration of Hospitals (grant numbers: ZYLX202110), the National Natural Science Foundation of China (grant numbers: 81871377, 81571717), and the Research on Clinical Characteristics of Capital (grant number: Z181100001718071). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

In the endoplasmic reticulum (ER) membrane, transmembrane (TM) domain insertion occurs through the Sec61 channel with its auxiliary components, including Sec62. Sec62 interacts with the Sec61 channel and is located on the front side of the Sec61 lateral gate, an entry site for TM domains to the lipid bilayer. Overexpression of Sec62 led to a growth defect in yeast, and we investigated its effects on protein translocation and membrane insertion by pulse labeling of Sec62 client proteins. Our data show that the insertion efficiency of marginally hydrophobic TM segments is reduced upon Sec62 overexpression. This result suggests a potential regulatory role of Sec62 as a gatekeeper of the lateral gate, thereby modulating the insertion threshold of TM segments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Lysine acetylation (Kac) on histone promotes relaxation of the chromatin conformation and favors gene transcription to regulate oncogenesis, whereas the total acetylation profiling of oral squamous cell carcinoma (OSCC) is unknown. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was utilised to investigate lysine acetylation features of tumor tissues and adjacent normal tissues from 9 patients with OCSS. 282 upregulated Kac sites in 234 proteins and 235 downregulated Kac sites in 162 proteins between OSCC tissues and paired adjacent normal tissues were identified. Different acetylation proteins (DAPs) were analyzed through KEGG-based and MCODE. These DAPs are enriched in the ribosome biogenesis pathway. Survival Analysis of hub genes with TCGA database was performed. In addition, IPA software was used to explore the connection between 9 core DAPs (RPS3, RPL24, RPL19, EIF4A2, RPL12, MYBPC1, RPS6, ARCN1, and TMEM9) and the different expression of KATs and KDACs identified in our proteomic. The study is the first comparative study of Kac modification on oral squamous cell carcinoma. We propose to put forward the hypothesis that the dysfunction of ribosome biogenesis caused by the change of Lysine acetylation, especially downregulated acetylation on RPS6 and RPS3 may associated with the pathogenesis of OSCC. SIGNIFICANCE: The study is the first comparative study of Kac modification on oral squamous cell carcinoma through LC-MS/MS-based modified proteomic. These DAPs are high enriched in the ribosome biogenesis pathway. Used MCODE and survival analysis, 9 core DAPs (RPS3, RPL24, RPL19, EIF4A2, RPL12, MYBPC1, RPS6, ARCN1, and TMEM9) were screened. IPA software was used to explore the connection between 9 core DAPs and the different expression of KATs and KDACs identified in our proteomic. In addition, we propose to put forward the hypothesis that the dysfunction of ribosome biogenesis caused by the change of Lysine acetylation, especially downregulated acetylation on RPS6 and RPS3 may associated with the pathogenesis of OSCC., (Copyright © 2022. Published by Elsevier B.V.)

Coccolithophore calcite production (CP) was investigated for the first time in the Bay of Bengal. Against expectation, calcite production was not fueled by the nutrient-enriched cold eddy because of the reduced light penetration. CP rate was observed to be higher at the anticyclonic eddy possibly benefited from rare species production. The adjoining river-induced shallow mixed-layer depth and eddy activity co-influenced CP rate. On average, the integrated CP rates were 0.04, 0.15, and 0.07 mmol C m -2  h -1 for the cyclonic eddy, anticyclonic eddy, and outer area, respectively. In the upper photic waters, CP rates showed a strong correlation with primary productivity (PP). However, a decoupling of CP and PP was observed in the lower photic zone due to differential light and nitrogen preferences in calcification and carbon fixation. Our findings could help to understand the biogenic response of eddy and inorganic-organic carbon association in the pelagic biogeochemical cycles., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Remote ischemic postconditioning (RIPostC) has recently emerged as a potential novel therapeutic strategy to achieve protection against acute myocardial infarction (AMI) injury. We aimed to evaluate the longitudinal cardioprotective effects of RIPostC on AMI using 99m Tc-MIBI SPECT myocardial perfusion imaging (MPI) and gated 18 F-FDG PET (GPET) in pigs., Methods: MI was induced in 12 Chinese pigs. RIPostC was conducted by four 5 min cycles of blood pressure cuff inflation applied to the lower limb immediately after AMI. MPI and GPET were performed longitudinally at baseline, 3rd, 14th, 28th, and 56th days after AMI. Total perfusion defect (TPD), hibernating myocardium (HM), scar, left ventricular (LV) remodeling (End diastolic volume, EDV), and bone marrow (BM) metabolic activity were analyzed, and inflammation biomarkers were measured., Results: In outcome evaluation, there was a significant attenuation in TPD (Δ value, at 14th, 28th and 56th days), HM (Δ value, at 14th, 56th days) and Scar (Δ value, at 14th, 28th days) in the RIPostC group compared with the control group (P < 0.05). Additionally, RIPostC attenuated LV enlargement (ΔEDV, at 14th day) (P < 0.05) in comparison to controls. BM 18 F-FDG uptake activity in the RIPostC group was lower than the control group (P < 0.05) at the 3rd day after AMI. There was a non-statistically significant trend of decreased MMP-2 levels in the RIPostC group post-AMI (P > 0.05)., Conclusions: RIPostC presented the longitudinal cardioprotective effects by preserving myocardial viability, reducing infarct size, attenuating LV remodeling at early stage post-AMI, and may also have an anti-inflammatory effect at the acute phase., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aims: To evaluate the diagnostic performance of computed tomography combined with ultrasound (CT/US) in metastatic central lymph nodes (CLNs) compared with US in patients with papillary thyroid cancer (PTC)., Material and Methods: Six-hundred patients with surgically proven PTC who underwent both US and CT examination before CLN dissection were evaluated retrospectively. All cases were divided into four subgroups according to the tumor size and number. Diagnostic performances of US, CT and CT/US were evaluated., Results: Among 600 patients with CLN dissection, CT/US showed higher sensitivity (89.10%) and accuracy (83.00%) than US alone (76.06%, 76.50%). In the subgroup of solitary non-microcarcinomas, the AUC of CT/US was significantly higher than that for US alone (0.827 vs. 0.722, P < 0.05). For the subgroup of solitary or multiple microcarcinomas, the performance efficiency of CT had no obvious advantage over that of US (0.698 vs. 0.740, 0.798 vs. 0.802, P > 0.05). For the subgroup of multiple non-microcarcinomas, CT, US and US/CT had high diagnostic efficacy (AUC > 0.8, Accuracy >80%. P > 0.05), and there was no significant difference between them., Conclusions: In the subgroup of solitary non-microcarcinoma, CT combined with US provided better diagnostic efficacy, and for those cases, complementary CT examination was recommended. In other subgroups, the diagnostic efficacy of US/CT was similar to that of US alone, and there was no significant benefit from additional CT examination., (Copyright © 2021. Published by Elsevier Inc.)

This study aimed to compare the patterns of β-amyloid deposition between patients with early-stage Alzheimer's disease (AD) with mild parkinsonism and those without parkinsonism. Sixty-one patients with early-stage AD (Clinical Dementia Rating [CDR], 0.5 or 1) who underwent 18 F-florbetaben ( 18 F-FBB) PET scans were enrolled. We performed comparative analyses of regional FBB uptake in the frontal, parietal, lateral temporal, medial temporal, occipital, anterior cingulate, and posterior cingulate cortices and in the precuneus, striatum, and thalamus between AD patients with mild parkinsonism (AD-p+; n = 23) and those without parkinsonism (AD-p-; n = 38). There was no significant difference in age, sex, years of education, Mini-Mental State Examination score, and white matter hyperintensity severity between groups. The AD-p+ group had lower composite scores in frontal/executive function domain than the AD-p- group. The AD-p+ group had a higher FBB uptake in the occipital cortex, but not in other cortical regions, than the AD-p- group. Our findings suggest that additional β-amyloid deposition in the occipital region is associated with mild parkinsonism in early-stage AD., Competing Interests: Conflicts of Interest No authors have no actual or potential conflicts of interest., (Copyright © 2021. Published by Elsevier Inc.)

Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the 2 most common causes of dementia. We compared the regional metabolism on 18 F-fluorodeoxyglucose positron emission tomography (PET) among 21 control subjects and cognitively impaired patients due to DLB (N = 63) and AD (N = 38). All participants underwent 18 F-Florbetaben (FBB) PET, and all DLB patients had abnormality on dopamine transporter PET. Both the FBB-positive DLB (N = 38) and FBB-negative DLB (N = 25) groups had increased metabolism in the bilateral central cerebellum, posterior putamen, and somatomotor cortices compared with the control and AD groups. Compared with the control group, the DLB and AD groups commonly exhibited hypometabolism in the bilateral lateral temporal, temporo-parietal junction, posterior cingulate, and precuneus cortices. Both DLB groups had additional hypometabolism in the bilateral thalami and dorsolateral prefrontal cortices, whereas the AD group did in the bilateral entorhinal cortices and hippocampi. Our results suggest that hypermetabolism in the somatomotor cortex, posterior putamen, or central cerebellum could be a useful imaging biomarker for detecting DLB patients, while entorhinal/hippocampal hypometabolism could be a specific biomarker for AD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The retinoic-acid inducible gene (RIG)-I is a cytoplasmic pattern recognition receptor that senses single-stranded (ss) or double-stranded (ds) RNA. RIG-I also senses AT-rich dsDNA, poly(dA:dT), through the action of an RNA polymerase III-transcribed RNA intermediate. Upon the binding of an RNA ligand, RIG-I binds to the mitochondrial antiviral-signaling protein (MAVS) and induces the formation of filamentous aggregates of MAVS, leading to the formation of a signaling complex that drives Type I interferon (IFN) responses. In the current study, we investigated the issue of whether the SUMOylation of MAVS induced by poly(dA:dT) affects the aggregation of MAVS in the RIG-I/MAVS pathway in human keratinocytes. Our results show that the poly(dA:dT)-induced secretion of IFN-β was dependent on RIG-I and MAVS. The inhibition of SUMOylation by Ginkgolic acid or Ubc9 siRNA was found to inhibit the poly(dA:dT)-induced secretion of IFN-β, suggesting that the SUMOylation is required for the poly(dA:dT)-activated RIG-I/MAVS pathway, which drives the secretion of IFN-β. In addition, treatment with poly(dA:dT) enhanced the formation of polymeric chains of small-ubiquitin like modifiers (SUMO)3, but not SUMO1 and SUMO2, on MAVS. Our results also show that the conjugation of SUMO3 to MAVS induced by poly (dA:dT) enhanced the aggregation of MAVS. These collective results show that the formation of SUMO3-conjugated chains of MAVS induced by poly (dA:dT), a ligand of RIG-I, enhances the aggregation of MAVS which, in turn, drives the secretion of IFN-β in human keratinocytes., Competing Interests: Declaration of competing interest The authors state no conflicts of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: This study aimed to assess the association between increased lesion peri-coronary adipose tissue (PCAT) density and coronary 18 F-sodium fluoride ( 18 F-NaF) uptake on positron emission tomography (PET) in stable patients with high-risk coronary plaques (HRPs) shown on coronary computed tomography angiography (CTA)., Background: Coronary 18 F-NaF uptake reflects the rate of calcification of coronary atherosclerotic plaque. Increased PCAT density is associated with vascular inflammation. Currently, the relationship between increased PCAT density and 18 F-NaF uptake in stable patients with HRPs on coronary CTA has not been characterized., Methods: Patients who underwent coronary CTA were screened for HRP, which was defined by 3 concurrent plaque features: positive remodeling; low attenuation plaque (LAP) (<30 Hounsfield units [HU]) and spotty calcification; and obstructive coronary stenosis ≥50% (plaque volume >100 mm 3 ). Patients with HRPs were recruited to undergo 18 F-NaF PET/CT. In lesions with stenosis ≥25%, quantitative plaque analysis, mean PCAT density, maximal coronary motion-corrected 18 F-NaF standard uptake values (SUVmax), and target-to-background ratios (TBR) were measured., Results: Forty-one patients (age 65 ± 6 years; 68% men) were recruited. Fifty-one lesions in 23 patients (56%) showed increased coronary 18 F-NaF activity. Lesions with 18 F-NaF uptake had higher surrounding PCAT density than those without 18 F-NaF uptake (-73 HU; interquartile range -79 to -68 HU vs. -86 HU; interquartile range -94 to -80 HU; p < 0.001). 18 F-NaF TBR and SUVmax were correlated with PCAT density (r = 0.63 and r = 0.68, respectively; all p < 0.001). On adjusted multiple regression analysis, increased lesion PCAT density and LAP volume were associated with 18 F-NaF TBR (β = 0.25; 95% confidence interval: 0.17 to 0.34; p < 0.001 for PCAT, and β = 0.07; 95% confidence interval: 0.03 to 0.11; p = 0.002 for LAP)., Conclusions: In patients with HRP features on coronary CTA, increased density of PCAT was associated with focal 18 F-NaF PET uptake. Simultaneous assessment of these imaging biomarkers by 18 F-NaF PET and CTA might refine cardiovascular risk prediction in stable patients with HRP features., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Coexisting Alzheimer's disease (AD) pathology is common in patients with dementia with Lewy bodies (DLB). To evaluate the cortical thinning in patients with DLB considering the effect of amyloid-β (Aβ), we compared the regional cortical thickness between control subjects and patients with DLB with abnormal dopamine transporter imaging. Seventeen (43.6%) of 39 patients with DLB and no control subjects had significant Aβ deposition on 18 F-florbetaben positron emission tomography. Compared to control (n = 15), Aβ-negative DLB group (n = 21) had cortical thinning in the bilateral insula, entorhinal, basal frontal, and occipito-parietal cortices. Compared to Aβ-negative DLB, Aβ-positive DLB group (n = 15) had a lower cortical thickness in the AD-prone brain regions in addition to the bilateral occipital, basal frontal, and somatomotor cortices. After controlling for the amount of Aβ deposition, DLB group had cortical thinning in the same regions affected in the Aβ-negative DLB group. In summary, patients with DLB had an Aβ-independent cortical thinning, while Aβ was associated with additional cortical thinning in the AD-prone brain regions and the aggravation of DLB-specific cortical thinning., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Quercetin, a polyphenol, belongs to a class of flavonoids that exerts anti-inflammatory effects. Interleukin (IL)-18 is a member of the IL-1 family cytokine that regulates immune responses and is implicated in various inflammatory skin diseases. Absent in melanoma 2 (AIM2) is a cytosolic double-stranded (ds) DNA sensor that recognizes the dsDNA of a microbial or host origin. Binding of dsDNA to AIM2 simulates caspase-1-dependent inflammasome activity, which leads to the production of IL-1β and IL-18. Increased levels of AIM2 have been observed in patients with inflammatory skin diseases. In the current study, we investigated the issue of whether or how Quercetin attenuates poly (dA:dT), a synthetic analog of microbial dsDNA, -induced IL-18 secretion in IFN-γ-primed human keratinocytes. Treatment with 5 and 10 μM of Quercetin inhibited the poly (dA:dT)-induced secretion of IL-18 after IFN-γ priming and before poly (dA:dT)-induced AIM2 activation. In addition, treatment with Quercetin at 10 μM, significantly inhibited the phosphorylation of JAK2 and STAT1, and the nuclear translocation of phosphorylated STAT1 in poly (dA:dT)-treated and IFN-γ-primed keratinocytes. These results suggest that treatment with Quercetin inhibits the poly (dA:dT)-induced secretion of IL-18 via down-regulation of the expressions of AIM2 and pro-caspase-1 by inhibiting the JAK2/STAT1 pathway in IFN-γ-primed keratinocytes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular risk. Among categories of NAFLD, hepatic fibrosis is most likely to affect mortality. Myocardial function and its energy metabolism are tightly linked, which might be altered by an insulin resistant condition such as NAFLD. We investigated whether hepatic steatosis and fibrosis were associated with myocardial dysfunction relative to myocardial glucose uptake., Methods: A total of 308 patients (190 without NAFLD, 118 with NAFLD) were studied in a tertiary care hospital. Myocardial glucose uptake was evaluated at fasted state using [ 18 F]-fluorodeoxyglucose-positron emission tomography ( 18 FDG-PET). Hepatic steatosis and fibrosis were assessed by transient liver elastography (Fibroscan®) with controlled attenuation parameter, which quantifies hepatic fat and by surrogate indices (fatty liver index and NAFLD fibrosis score). Cardiac structure and function were examined by echocardiogram., Results: Compared to those without NAFLD, patients with NAFLD had alterations in cardiac remodeling, manifested by increased left ventricular mass index, left ventricular end-diastolic diameter, and left atrial volume index (all p <0.05). Hepatic steatosis was significantly associated with left ventricular filling pressure (E/e' ratio), which reflects diastolic dysfunction (p for trend <0.05). Those without NAFLD were more likely to have higher myocardial glucose uptake compared to those with NAFLD. Significant hepatic fibrosis was also correlated with diastolic dysfunction and impaired myocardial glucose uptake. Using multivariable linear regression, E/e' ratio was independently associated with hepatic fibrosis (standardized β = 0.12 to 0.27; all p <0.05). Association between hepatic steatosis and E/e' ratio was also significant (standardized β = 0.10 to 0.15; all p <0.05 excluding the model adjusted for adiposity)., Conclusions: Hepatic steatosis and fibrosis are significantly associated with diastolic heart dysfunction. This association is linked with myocardial glucose uptake evaluated by 18 FDG-PET., Lay Summary: Non-alcoholic fatty liver disease is associated with an increased risk of cardiovascular disease. More severe forms of non-alcoholic fatty liver disease, where hepatic fibrosis occurs, are linked to increased mortality. In this study, we have shown that hepatic steatosis and fibrosis are associated with subclinical myocardial dysfunction. This association is linked to altered myocardial glucose uptake., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)