The significance of lipid metabolism reprogramming of tumor-associated macrophages in hepatocellular carcinoma.

In the intricate landscape of the tumor microenvironment, tumor-associated macrophages (TAMs) emerge as a ubiquitous cellular component that profoundly affects the oncogenic process. The microenvironment of hepatocellular carcinoma (HCC) is characterized by a pronounced infiltration of TAMs, underscoring their pivotal role in modulating the trajectory of the disease. Amidst the evolving therapeutic paradigms for HCC, the strategic reprogramming of metabolic pathways presents a promising avenue for intervention, garnering escalating interest within the scientific community. Previous investigations have predominantly focused on elucidating the mechanisms of metabolic reprogramming in cancer cells without paying sufficient attention to understanding how TAM metabolic reprogramming, particularly lipid metabolism, affects the progression of HCC. In this review article, we intend to elucidate how TAMs exert their regulatory effects via diverse pathways such as E2F1-E2F2-CPT2, LKB1-AMPK, and mTORC1-SREBP, and discuss correlations of TAMs with these processes and the characteristics of relevant pathways in HCC progression by consolidating various studies on TAM lipid uptake, storage, synthesis, and catabolism. It is our hope that our summary could delineate the impact of specific mechanisms underlying TAM lipid metabolic reprogramming on HCC progression and provide useful information for future research on HCC and the development of new treatment strategies.

An Ortho-modification Strategy to Develop Brooker's Merocyanine Probe for Precise Monitoring of pH Changes in Urine.

As a non-invasive body fluid, urine pH is one of the important biomarkers for diseases such as the kidneys. Therefore, rapid and accurate detection of urine pH is of great clinical significance. A novel fluorescent probe (SPPH-Cl) was developed based on Brooker's merocyanine skeleton for pH detection. The pKa of SPPH-Cl was adjusted to 6.55 using a phenolic hydroxyl ortho substitution strategy, therefore, the fluorescence response range of SPPH-Cl to pH covers the urine physiological pH range (4.6-8.0). SPPH-Cl has excellent water solubility, stable recoverability, wide anti-interference capability, and sensitive reactions to pH fluctuations in pure aqueous solutions. SPPH-Cl has succeeded in applying to monitor the pH of volunteer urine samples based on a standard curve established in artificially simulated urine, and the detection results have accuracy comparable to pH meters. Therefore, this work provided a powerful molecule tool for detecting pH in urine samples.

Effect of transcutaneous electrical nerve stimulation (TENS) on the electromyographic activity of human masticatory muscles in young people with normal occlusion.

STATEMENT OF PROBLEM: Transcutaneous electrical nerve stimulation (TENS) has been used in several clinical areas. However, the effect of TENS on the masticatory muscles of young individuals with normal occlusion remains unclear. PURPOSE: The purpose of the study was to assess the effect of TENS on the surface electromyographic (sEMG) activity of masticatory muscles in a young population with normal occlusion. MATERIAL AND METHODS: Twenty residents (5 men and 15 women, mean 24.27 ±2.59 years) of Dalian Stomatological Hospital were enrolled as the study participants. A trained operator collected the required information from the participants. The experiment was divided into 3 stages: pre-TENS acquisition, TENS application, and post-TENS acquisition. The pre-TENS stage was performed using surface electromyography (sEMG) (Myotronics Inc) to acquire the potential values of masticatory muscles in the following 3 states 5 times each: resting, intercuspal occlusion (ICO), and maximum voluntary clench (clenching). The potential values of the anterior of temporalis (TA), the masseter (MM), the sternocleidomastoid (SCM), and the anterior digastric (DA) muscles were collected in the resting state, and TA and MM were collected in the ICO and clenching states. During the TENS application phase, a TENS Unit device (J5 Myomonitor) (J5) was used on each participant for 45 minutes. The post-TENS acquisition phase involved the same procedure as the pre-TENS phase. The experimental data were recorded, and the normality of each group was analyzed using the Shapiro-Wilk test in a statistical software program (IBM SPSS Statistics, v26.0). The paired-sample t test was used to compare the differences in the mean values of sEMG and the asymmetry index (As); the independent-sample t test was used to compare the activity index (Ac) and torque index (To) (α=.05). RESULTS: Significant differences were observed in the mean potential values of TA, MM, LSCM, and RDA before and after TENS in the resting state and RTA, LMM, and RMM before and after TENS in the clenching state (P<.05). Moreover, although AsDA values showed a significant difference (P=.027) before and after TENS in the resting state, the differences in As values for the other muscles in the resting state were statistically similar. Furthermore, in each state, the mean values of Ac and To after TENS showed no significant differences before and after TENS (P>.05). CONCLUSIONS: The resting EMG values of the TA and MM differed significantly before and after TENS. After TENS, the resting EMG activity decreased, whereas the functional EMG activity tended to increase.

Salidroside ameliorates acetaminophen-induced acute liver injury through the inhibition of endoplasmic reticulum stress-mediated ferroptosis by activating the AMPK/SIRT1 pathway.

Acetaminophen (APAP) overdose has long been considered a major cause of drug-induced liver injury. Ferroptosis is a type of programmed cell death mediated by iron-dependent lipid peroxidation. Endoplasmic reticulum (ER) stress is a systemic response triggered by the accumulation of unfolded or misfolded proteins in the ER. Ferroptosis and ER stress have been proven to contribute to the progression of APAP-induced acute liver injury (ALI). It was reported that salidroside protects against APAP-induced ALI, but the potential mechanism remain unknown. In this study, male C57BL/6 J mice were intraperitoneally (i.p.) injected APAP (500 mg/kg) to induce an ALI model. Salidroside was i.p. injected at a dose of 100 mg/kg 2 h prior to APAP administration. Mice were sacrificed 12 h after APAP injection and the liver and serum of the mice were obtained for histological and biochemistry analysis. AML12 cells were used in in vitro assays. The results indicated that salidroside mitigated glutathione degradation via inhibiting cation transport regulator homolog 1 (CHAC1) to attenuate ferroptosis, and simultaneously suppressing PERK-eIF2α-ATF4 axis-mediated ER stress, thus alleviating APAP-induced ALI. However, PERK activator CCT020312 and overexpression of ATF4 inhibited the protective function of salidroside on CHAC1-mediated ferroptosis. Besides this, activation of the AMPK/SIRT1 signaling pathway by salidroside was demonstrated to have a protective effect against APAP-induced ALI. Interestingly, selective inhibition of SIRT1 ameliorated the protective effects of salidroside on ER stress and ferroptosis. Overall, salidroside plays a significant part in the mitigation of APAP-induced ALI by activating the AMPK/SIRT1 signaling to inhibit ER stress-mediated ferroptosis in the ATF4-CHAC1 axis.

Luminescence and Energy Transfer of Color-Tunable Y2Mg2Al2Si2O12:Eu2+,Ce3+ Phosphors.

Color-tunable phosphors can be obtained through codoping strategies and energy transfer regulation. Ce3+ and Eu2+ are the most common and effective activator ions used in phosphor materials. However, the energy transfer from Eu2+ to Ce3+ is rarely reported. In this work, Y2Mg2Al2Si2O12(YMAS):Eu2+,Ce3+ phosphors were successfully synthesized, which was confirmed by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Rietveld refinement, scanning electron microscopy (SEM) and element mapping images, and spectral information. The luminescent color of YMAS:Eu2+,Ce3+ phosphors could be tuned from blue to cyan to light green to yellow-green and finally to green-yellow, which was achieved by adjusting the energy transfer between different dopants. The energy transfer from Eu2+ to Ce3+ was confirmed by photoluminescence spectra and fluorescence decay curves. Within the experimental gradient, the energy transfer efficiency could reach up to 48%. At 373 K, the Y1.99Mg1.99Al2Si2O12:0.01Eu2+,0.01Ce3+ (YMAS:0.01Eu2+,0.01Ce3+) phosphor exhibited a total integral emission loss of only 8%, and the emission peak intensity decreased to 95%, indicating the excellent thermal stability. The white light-emitting diode (WLED) fabricated by the YMAS:0.01Eu2+,0.01Ce3+ phosphor has the same level correlated color temperature (CCT = 5841 K), greatly improved color rendering index (Ra = 87.8), and higher quality white light color (CIE = (0.3258, 0.3214)) than the WLED made by the YMAS:0.01Eu2+ phosphor, indicating that the performance of the phosphor was significantly improved by introducing Ce3+. This work provides an effective guide for the design and development of highly efficient color-tunable phosphors involving energy transfer from Eu2+ to Ce3+ in some specific materials, such as garnet structures.

Photoluminescence and Color-Tunable Properties of Na4Ca4Mg21(PO4)18:Eu2+,Tb3+/Mn2+ Phosphors for Applications in White LEDs.

Here, the crystal structure, phase analysis, site occupancy, and luminescence properties of NCMP:Eu2+,Tb3+,Mn2+ have been studied for the first time. Under 335 nm ultraviolet excitation, the NCMP:Eu2+ phosphors show narrow-band blue emission. In addition, we discuss the reason for a continuous red shift for the emission spectra of NCMP:xEu2+ by raising the x value. The efficient ET processes of Eu2+ → Tb3+ and Eu2+ → Mn2+ were investigated by the luminescence spectra and decay curves. The ET efficiencies reach 92.58% at y = 0.15 for NCMP:0.01Eu2+,yTb3+ and 99.85% at z = 0.15 for NCMP:0.01Eu2+,zMn2+ phosphors, respectively. The efficient energy transfer processes greatly improve the quantum efficiency, luminous intensity, and thermal stability. Bright green and red emissions can be realized through changing the related ratio of Eu2+, Tb3+, and Mn2+. In addition, the excellent performance of the prepared white LED lamps utilizing a 385 nm chip combined with our prepared NCMP:Eu2+,Tb3+/Mn2+ phosphors indicates that NCMP:0.01Eu2+,yTb3+ and NCMP:0.01Eu2+,zMn2+ phosphors can be potential green and red phosphors for white LEDs.

Ca(Mg0.8Al0.2)(Si1.8Al0.2)O6:Ce3+,Tb3+ Phosphors: Structure Control, Density-Functional Theory Calculation, and Luminescence Property for pc-wLED Application.

A modified structure Ca(Mg0.8Al0.2)(Si1.8Al0.2)O6 (denoted as CMASO) from the evolution of CaMgSi2O6 (denoted as CMSO) codoped with Ce3+ and Tb3+ ions was designed successfully by solid reaction method for application in phosphor-converted white-light-emitting diode (pc-wLED). The Rietveld refinement of these two structures verified the changes derived from the replacement of some of the Mg2+ and Si4+ ions by Al3+ ions. The band gaps were calculated by density-functional theory (DFT) calculation method to verify the change of Al3+ ions replacing further, and the diffuse reflectance spectra (DRS) proved the veracity of the calculation result. The phosphors CMASO:Ce3+ showed blue emission excited by a wider excitation wavelength from 280 nm to 370 nm. The change of structure lead to the absorbable range broaden and the emission peak shifted to longer wavelength, compared with CMSO:Ce3+, although the amount of emitting center was the same. The reason for these phenomena was discussed in detail. The codoped phosphors CMASO:Ce3+,Tb3+ exhibited different emission colors from blue to green as the concentration of Tb3+ ions increased. Combined with commercial red phosphor CaAlSiN3:Eu2+ and ultraviolet LED (UV-LED) chips, the selected appropriate samples achieved white emission. The correlated color temperature (CCT) was 6137 K and the color rendering index (Ra) was 80.5, indicating that they could act as potential phosphors for possible applications in pc-wLED.

Study on the Local Structure and Luminescence Properties of a Y2Mg2Al2Si2O12:Eu3+ Red Phosphor for White-Light-Emitting Diodes.

Structure determines properties, and properties determine applications, which is an important ideology of natural sciences. For optical materials, it is vital to lucubrate the corresponding relationship between the local crystal structure and luminescence properties for their design, synthesis, and application. This work reports a newly designed Y2Mg2Al2Si2O12(YMAS):Eu3+ red phosphor, in which difunctional Eu3+ ion is used as a red-light activator and spectroscopic probe. The qualitative and quantitative studies on the relationship between the local crystal structure and the luminescence properties of YMAS:Eu3+ are performed experimentally and computationally, using the Y3Al5O12 (YAG):Eu3+ as contrast. Moreover, compared with YAG:Eu3+, the newly designed YMAS:Eu3+ has stronger luminescence, superior Commission Internationale de L'Eclairage chromaticity coordinates, a lower optimal doping concentration, and equally excellent thermal stability. The satisfactory color-rendering index of packaged white-light-emitting diodes demonstrates its potential performance as a red phosphor. Briefly, this work provides not only a new case for the study of the local crystal structure and luminescence properties but also a new possibility for the application of a red phosphor in solid-state lighting.

Novel highly efficient single-component multi-peak emitting aluminosilicate phosphors co-activated with Ce3+, Tb3+ and Eu2+: luminescence properties, tunable color, and thermal properties.

A series of emission-tunable Ce3+/Tb3+/Eu2+ doped Ca2(Mg0.75Al0.25)(Si1.75Al0.25)O7 (denoted as CMAS) phosphors have been synthesized via a high temperature solid-state reaction method. The luminescence properties, color tuning, quantum yields (QYs), energy transfer of Ce3+ to Tb3+/Eu2+, thermal stability, performance of LED devices and ratiometric temperature sensing application have been systematically investigated, respectively. Importantly, through the study of thermal stability, we found that Ce3+ and Tb3+ co-doped samples were suitable for WLED applications, while Ce3+ and Eu2+ co-doped samples were suitable for temperature sensing applications. Due to the energy transfer, Ce3+/Tb3+ co-doped samples had high luminous efficiency and the quantum efficiency of more than 80% could be achieved. Their emission colors can modulate from blue to green. In addition, on the basis of the evaluation of the as-fabricated white LED lamps via selecting the corresponding phosphors, the CCT can reach 4275 K and the CRI can increase to 86.8, indicating that this series of phosphors can act as potential color-tunable phosphors for possible applications in ultraviolet light based white LEDs. Importantly, it is found that the fluorescence intensity ratio of CMAS : 5%Ce3+,0.5%Eu2+ displays linear correlation with temperature in a wide range of 253-373 K with a high sensitivity of 2.49% K-1, indicating that it could be a good candidate for ratiometric optical thermometry.

Combined OLA1 and CLEC3B Gene Is a Prognostic Signature for Hepatocellular Carcinoma and Impact Tumor Progression.

Hepatocellular carcinoma (HCC), partly because of its complexity and high heterogeneity, has a poor prognosis and an extremely high mortality rate. In this study, mRNA sequencing expression profiles and relevant clinical data of HCC patients were gathered from different public databases. Kaplan-Meier survival curves as well as ROC curves validated that OLA1|CLEC3B was an independent predictor with better predictive capability of HCC prognosis compared to OLA1 and CLEC3B separately. Further, the cell transfection experiment verified that knockdown of OLA1 inhibited cell proliferation, facilitated apoptosis, and improved sensitivity of HCC cells to gemcitabine. In this study, the prognostic model of HCC composed of OLA1/CLEC3B genes was constructed and verified, and the prediction ability was favorable. A higher level of OLA1 along with a lower level of CEC3B is a sign of poor prognosis in HCC. We revealed a novel gene pair OLA1|CLEC3B overexpressed in HCC patients, which may serve as a promising independent predictor of HCC survival and an approach for innovative diagnostic and therapeutic strategies.

Antimony(V) behavior during the Fe(II)-induced transformation of Sb(V)-bearing natural multicomponent secondary iron mineral under acidic conditions.

Fe(II)-induced phase transformations of secondary iron minerals have attracted considerable attention due to their influence on antimony (Sb) mobility. However, Fe(II)-induced natural multicomponent secondary iron mineral (nmSIM) transformations and the corresponding repartitioning of Sb on nmSIM under acidic conditions upon Fe(II) exposure have not been systematically examined. Herein, we investigated the effect of Fe(II) on nmSIM mineralogy and Sb mobility in Sb(V)-bearing nmSIM at pH 3.8 and 5.6 at various Fe(II) concentrations over 15 d. The Sb(V)-bearing nmSIM phase transformation occurred under both strongly and weakly acidic conditions without Fe(II) exposure, while the presence of Fe(II) significantly intensified the transformation, and substantial amounts of intermediary minerals, including jarosite, ferrihydrite, lepidocrocite and fougerite, formed during the initial reaction stage, especially at pH 5.6. X-ray diffraction (XRD) analyses confirmed that goethite and hematite were the primary final-stage transformation products of Sb(V)-bearing nmSIM, regardless of Fe(II) exposure. Throughout the Sb(V)-bearing nmSIM transformation at pH 3.8, Sb release was inversely related to the Fe(II) concentration in the initial stage, and after maximum release was achieved, Sb was gradually repartitioned onto the nmSIM. No Sb repartitioning occurred in the absence of Fe(II) at pH 5.6, but the introduction of Fe(II) suppressed Sb release and improved Sb repartitioning on nmSIM. This transformation was conducive to Sb reimmobilization on Sb(V)-bearing nmSIM due to the structural incorporation of Sb into the highly crystalline goethite and hematite generated by the Sb(V)-bearing nmSIM transformation, and no reduction of Sb(V) occurred. These results imply that Fe(II) can trigger mineralogical changes in Sb(V)-bearing nmSIM and have important impacts on Sb partitioning under acidic conditions. These new insights are essential for assessing the mobility and availability of Sb in acid mine drainage areas.

The trajectories and associations of sleep disturbance symptoms with suicidal ideation in adolescents: A three-wave longitudinal study.

BACKGROUND: This study aimed to investigate the developmental trajectories of sleep disturbance symptoms and examine whether specific trajectory memberships of sleep disturbance symptoms could prospectively predict suicidal ideation (SI) among a large sample of Chinese adolescents over one year. METHODS: A three-wave longitudinal study was conducted from April 2021 to June 2022, with a sample of 19,095 adolescents from Shenzhen in Guangdong Province, China (51.2 % males; mean age = 12.4 ± 1.6 years at baseline). Socio-demographics (at baseline), SI, sleep disturbance symptoms (at each assessment), depressive symptoms (at the last follow-up), and negative life events (at two follow-ups) were assessed. Data were analyzed employing Growth Mixture Modeling and binary logistic regressions. RESULTS: The Growth Mixture Modeling identified four trajectories of sleep disturbance symptoms over one year: resistant group (76.2 %), delayed-dysfunction group (8.8 %), recovery group (7.4 %), and chronic-dysfunction group (7.6 %). Binary logistic regression analysis revealed that adolescents in the group of delayed-dysfunction (OR = 2.86, 95 % CI = 2.51-3.27) and chronic-dysfunction (OR = 2.14, 95 % CI = 1.84-2.47) exhibited higher risks of developing SI compared to those in the resistant group, even after controlling for socio-demographics, negative life events, depressive symptoms, and baseline SI. CONCLUSIONS: These findings underscore the importance of identifying individuals at higher risks of sleep disturbance and providing personalized and effective mental health services to reduce the incidence of SI.

Changes and relevant factors in depressive and anxiety symptoms among Chinese adolescents after the "Double Reduction" policy: A repeated cross-sectional survey with a nested longitudinal subsample.

BACKGROUND: The Chinese government has enacted the "Double Reduction" Policy, which aims to reduce students' academic burden and promote their mental health, but there is limited research examining the policy's impact on students' well-being. This study aims to evaluate changes in students' mental health problems before and after the "Double Reduction" Policy and explore relevant influential factors. METHODS: A total of 101,976 elementary and junior high school students were recruited before the "Double Reduction" Policy, and 91,832 students were recruited one year later. Through data integration, a total of 36,637 students participated in both web-based surveys and provided complete data on all measures. RESULTS: As a whole, we found that the prevalence of students' depression (12.1 % to 9.2 %) and anxiety (8.9 % to 6.2 %) tended to decline after the "Double Reduction" Policy. Attending private school, reduced homework, more extracurricular activities, more time with parents, reduced academic stress, and sleep duration ≥8 h/n were associated with the decrease in the likelihood of mental health problems in students. Female gender, negative life events, and negative impact of COVID-19 as risk factors for mental health. CONCLUSIONS: These findings indicated that the "Double Reduction" Policy has improved the well-being of Chinese students. Reducing students' homework burden and alleviating their academic pressure are beneficial for their mental health. Increasing time for extracurricular activities and interaction with parents, as well as ensuring sufficient sleep for students, are also effective ways to prevent the onset and exacerbation of mental health symptoms in adolescents.

Energy transfer for Ce3+ → Tb3+ → Sm3+ induced bright white emission in single-phase CaLa4(SiO4)3O:Ce3+, Tb3+, Sm3+ phosphors and their application in white-light-emitting diodes.

The emergence of phosphor-converted white-light-emitting diodes has crucial significance in the sustainable development of energy; hence, the evolution of phosphors with eminent luminescence and high stability is imperative. In this study, a tri-doped system composed of rare earth ions Ce3+, Tb3+, and Sm3+ incorporated into a CaLa4(SiO4)3O host is reported, and the energy transfer, tunable single-phase white emission, and favorable thermostability of the Ce3+-Tb3+-Sm3+ system were explored. Rietveld refinement results coincided with the original model of the crystal structure, and a band gap energy of 4.612 eV calculated using density functional theory (DFT) demonstrated the system as an appropriate luminescent host with a wide energy gap. Furthermore, ET processes for Ce3+ → Tb3+, Tb3+ → Sm3+, and Ce3+ → Tb3+ → Sm3+ were investigated via steady-state photoluminescence and decay measurements. Besides, the activation energies of CLSO:3%Ce3+, 9%Tb3+, y%Sm3+ (y = 7, 9) were 0.205 eV and 0.223 eV, respectively, showing outstanding thermal quenching resistance. Devices made with LED beads containing CLSO:3%Ce3+, 9%Tb3+, y%Sm3+ (y = 7, 9) phosphors exhibited bright white light with CCT ≈ 3586 and 3307 K and Ra ≈ 81.0 and 78.5, respectively. This study demonstrates that energy transfer for Ce3+-Tb3+-Sm3+ in a tri-doped system offers an interesting design prospect for promoting single-phase white emission phosphors.

Delivery of Yersinia pestis antigens via Escherichia coli outer membrane vesicles offered improved protection against plague.

Outer membrane vesicles (OMVs) from Gram-negative bacteria can be used as a vaccine platform to deliver heterologous antigens. Here, the major protective antigens of Yersinia pestis, F1 and LcrV, were fused either with the leader sequence or the transmembrane domain of the outer membrane protein A (OmpA), resulting in chimeric proteins OmpA-ls-F1V and OmpA46-159-F1V, respectively. We show that OmpA-ls-F1V and OmpA46-159-F1V can be successfully delivered into the lumen and membrane of the OMVs of Escherichia coli, respectively. Mutation of ompA but not tolR in E. coli enhanced the delivery efficiency of OmpA-ls-F1V into OMVs. The OmpA-ls-F1V protein comprises up to 20% of the total protein in OMVs derived from the ompA mutant (OMVdA-ALS-F1V), a proportion significantly higher than the 1% observed for OmpA46-159-F1V in OMVs produced by an ompA mutant that expresses OmpA46-159-F1V, referred to as OMVdA-LATM5-F1V. Intramuscular (i.m.) immunization of mice with OMVdA-ALS-F1V induced significantly higher levels of serum anti-LcrV and anti-F1 IgG, and provided higher efficacy in protection against subcutaneous (s.c.) Y. pestis infection compared to OMVdA-LATM5-F1V and the purified recombinant F1V (rF1V) protein adsorbed to aluminum hydroxide. The three-dose i.m. immunization with OMVdA-ALS-F1V, administered at 14-day intervals, provides complete protection to mice against s.c. infection with 130 LD50 of Y. pestis 201 and conferred 80% against intranasal (i.n.) challenge with 11.4 LD50 of Y. pestis 201. Taken together, our findings indicate that the engineered OMVs containing F1V fused with the leader sequence of OmpA provide significantly higher protection than rF1V against both s.c. and i.n. infection of Y. pestis and more balanced Th1/Th2 responses.IMPORTANCEThe two major protective antigens of Y. pestis, LcrV and F1, have demonstrated the ability to elicit systemic and local mucosal immune responses as subunit vaccines. However, these vaccines have failed to provide adequate protection against pneumonic plague in African green monkeys. Here, Y. pestis F1 and LcrV antigens were successfully incorporated into the lumen and the surface of the outer membrane vesicles (OMVs) of E. coli by fusion either with the leader sequence or the transmembrane domain of OmpA. We compared the humoral immune response elicited by these OMV formulations and their protective efficacy in mice against Y. pestis. Our results demonstrate that the plague OMV vaccine candidates can induce robust protective immunity against both s.c. and i.n. Y. pestis infections, surpassing the effectiveness of rF1V. In addition, immunization with OMVs generated a relatively balanced Th1/Th2 immune response compared to rF1V immunization. These findings underscore the potential of OMVs-based plague vaccines for further development.

A new way to conceptualize intolerance of uncertainty among adolescents: Embracing the network perspective.

Intolerance of uncertainty (IU), a pivotal transdiagnostic risk factor in psychopathology, is defined as a dispositional incapacity to withstand uncertainty distress, driving maladaptive cognitive, emotional and behavioural reactions to uncertainty. However, the intricate interplay among these components, particularly in adolescents, remains underexplored; yet understanding this interplay is crucial for supporting mental health. To address this gap, we employed a network approach to conceptualize IU in 5672 non-clinical Chinese adolescents (Mage = 14.13 years, SDage = 1.96 years, range = 10-19 years, 46.6% boys), combining graphical Gaussian models (GGM) and directed acyclic graphs (DAG). Our analyses revealed a tripartite network comprising cognitive, behavioural and emotional components. Notably, 'frustration' and 'work with hindrance' emerged as key drivers, while 'catastrophizing belief' served as a critical bridge linking different components. These findings underscore the importance of alleviating uncertainty-induced frustration and enhancing coping skills for behavioural impediments to mitigate adolescent IU. Additionally, therapeutic interventions should prioritize modifying and re-evaluating catastrophizing beliefs related to uncertainty.

LncRNA SNHG11 reprograms glutaminolysis in hepatic stellate cells via Wnt/ß-catenin/GLS axis.

Long non-coding RNAs (lncRNAs) have been identified as decisive regulators of liver fibrosis. Hepatic stellate cells (HSCs), major hepatic cells contributing to liver fibrosis, undergo metabolic reprogramming for transdifferentiation and activation maintenance. As a crucial part of metabolic reprogramming, glutaminolysis fuels the tricyclic acid (TCA) cycle that renders HSCs addicted to glutamine. However, how lncRNAs reprogram glutamine metabolism in HSCs is unknown. For this research, we characterized the pro-fibrogenic function of small nucleolar host gene 11 (SNHG11). Our data showed that in carbon tetrachloride (CCl4, 7 µL/g, intraperitoneally) treated C57BL/6J mice, SNHG11 expression was highly up-regulated in fibrotic livers and activated primary HSCs. SNHG11 knockdown attenuated the accumulation of fibrotic markers α-SMA and Col1A1 in liver fibrosis tissues and activated HSCs. Western blot and qRT-PCR assays demonstrated that glutaminase (GLS), the rate-limiting enzyme for glutaminolysis, was a downstream target of SNHG11. Furthermore, SNHG11 upregulated glutaminolysis in HSCs through the activation of the Wnt/ß-catenin signaling pathway. The results highlighted that SNHG11 is a glutaminolysis-regulated lncRNA that promotes liver fibrosis. A novel insight into the metabolic mechanism that reprograms glutaminolysis in HSCs could be exploited as anti-fibrotic targets.

Cynarin alleviates acetaminophen-induced acute liver injury through the activation of Keap1/Nrf2-mediated lipid peroxidation defense via the AMPK/SIRT3 signaling pathway.

Overdose of Acetaminophen (APAP) is a major contributor to acute liver injury (ALI), a complex pathological process with limited effective treatments. Emerging evidence links lipid peroxidation to APAP-induced ALI. Cynarin (Cyn), a hydroxycinnamic acid derivative, exhibits liver protective effects, but whether it mitigates APAP-induced ALI is unclear. Our aim was to verify the protective impact of Cyn on APAP-induced ALI and elucidate the molecular mechanisms governing this process. Herein, the regulation of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) interaction was determined to be a novel mechanism underlying this protective impact of Cyn against APAP-induced ALI. Nrf2 deficiency increased the severity of APAP-induced ALI and lipid peroxidation and counteracted the protective effect of Cyn against this pathology. Additionally, Cyn promoted the dissociation of Nrf2 from Keap1, enhancing the nuclear translocation of Nrf2 and the transcription of downstream antioxidant proteins, thereby inhibiting lipid peroxidation. Molecular docking demonstrated that Cyn bound competitively to Keap1, and overexpression of Keap1 reversed Nrf2-activated anti-lipid peroxidation. Additionally, Cyn activated the adenosine monophosphate-activated protein kinase (AMPK)/sirtuin (SIRT)3 signaling pathway, which exhibits a protective effect on APAP-induced ALI. These findings propose that Cyn alleviates APAP-induced ALI by enhancing the Keap1/Nrf2-mediated lipid peroxidation defense via activation of the AMPK/SIRT3 signaling pathway.

Cross-Lagged Panel Networks of Sleep Inertia Across Its Distinct Change Patterns Among Intern Nurses with Shift Work in China.

Purpose: Although experimental psychopathology using PET, EEG, and fMRI is at the forefront of understanding the underlying mechanisms of sleep inertia, many questions concerning causality remain unanswerable due to ethical constraints and the use of small and heterogeneous samples in experimental methods. There is a pressing need for a novel perspective in a large and relatively homogeneous population to fully capture and elucidate longitudinal processes and dynamic causality that culminate in episodes of sleep inertia over time. Therefore, this study aimed to reveal the causal relationships between symptoms of sleep inertia across its distinct patterns. Patients and Methods: A total of 1636 intern nurses participated in the first survey (94.1% validity rate), then 1277 intern nurses were followed up (82.9% tracing rate). Symptoms of sleep inertia were self-reported using the Sleep Inertia Questionnaire. The cross-lagged panel network models were used to examine unique longitudinal relationships between symptoms of sleep inertia across distinct trajectories. Results: Four distinct trajectories of sleep inertia were established. Additionally, we found differences in those symptoms with the highest influence on other symptoms at the subsequent point across the networks of four trajectories, particularly, "Difficulty in concentrating" in the persistent-high group and "Feeling tense" in the deteriorating groups. Conclusion: The current study highlights changes in sleep inertia based on the long-term course over time. Notably, symptoms of "Difficulty in concentrating" and "Feeling tense" are imperative to address these specific symptoms within subpopulations.

Targeting Hepatic Stellate Cell Death to Reverse Hepatic Fibrosis.

To date, the incidence and mortality of chronic liver diseases such as cirrhosis and hepatocellular carcinoma due to the continued progression of hepatic fibrosis are increasing annually. Unfortunately, although a large number of studies have exhibited that some drugs have great potential for anti-fibrosis in animal and clinical trials, no specific anti-fibrosis drugs have been developed, and there is no better treatment for advanced cirrhosis than liver transplantation. It is a prevailing viewpoint that hepatic stellate cells (HSCs), as the mainstay of extracellular matrix secretion, are of great concern in the development of hepatic fibrosis. Therefore, targeting HSCs becomes extremely important to confront hepatic fibrosis. As previous studies described, inhibition of HSC activation and proliferation, induction of HSC death, and restoration of HSC quiescence are effective in reversing hepatic fibrosis. This review focuses on the current status of research on the treatment of hepatic fibrosis by inducing HSC death and elucidates the HSC death modes in detail and the crosstalk between them.