Particle size effect on surface/interfacial tension and Tolman length of nanomaterials: A simple experimental method combining with theoretical.

Surface tension and interfacial tension are crucial to the study of nanomaterials. Herein, we report a solubility method using magnesium oxide nanoparticles of different radii (1.8-105.0 nm, MgO NPs) dissolved in pure water as a targeted model; the surface tension and interfacial tension (and their temperature coefficients) were determined by measuring electrical conductivity and combined with the principle of the electrochemical equilibrium method, and the problem of particle size dependence is discussed. Encouragingly, this method can also be used to determine the ionic (atomic or molecular) radius and Tolman length of nanomaterials. This research results disclose that surface/interfacial tension and their temperature coefficients have a significant relationship with particle size. Surface/interfacial tension decreases rapidly with a radius <10 nm (while the temperature coefficients are opposite), while for a radius >10 nm, the effect is minimal. Especially, it is proven that the value of Tolman length is positive, the effect of particle size on Tolman length is consistent with the surface/interfacial tension, and the Tolman length of the bulk does not change much in the temperature range. This work initiates a new era for reliable determination of surface/interfacial tension, their temperature coefficients, ionic radius, and Tolman length of nanomaterials and provides an important theoretical basis for the development and application of various nanomaterials.

Association between amino acids and recent osteoporotic fracture: a matched incident case-control study.

Context: Osteoporotic fracture is a major public health issue globally. Human research on the association between amino acids (AAs) and fracture is still lacking. Objective: To examine the association between AAs and recent osteoporotic fractures. Methods: This age and sex matched incident case-control study identified 44 recent x-ray confirmed fracture cases in the Second Hospital of Jilin University and 88 community-based healthy controls aged 50+ years. Plasma AAs were measured by high performance liquid chromatography coupled with mass spectrometry. After adjusting for covariates (i.e., body mass index, milk intake >1 time/week, falls and physical activity), we conducted conditional logistical regression models to test the association between AAs and fracture. Results: Among cases there were 23 (52.3%) hip fractures and 21 (47.7%) non-hip fractures. Total, essential, and non-essential AAs were significantly lower in cases than in controls. In the multivariable conditional logistic regression models, after adjusting for covariates, each standard deviation increase in the total (odds ratio [OR]: 0.304; 95% confidence interval [CI]: 0.117-0.794), essential (OR: 0.408; 95% CI: 0.181-0.923) and non-essential AAs (OR: 0.290; 95%CI: 0.107-0.782) was negatively associated with recent fracture. These inverse associations were mainly found for hip fracture, rather than non-hip fractures. Among these AAs, lysine, alanine, arginine, glutamine, histidine and piperamide showed the significantly negative associations with fracture. Conclusion: There was a negative relationship between AAs and recent osteoporotic fracture; such relationship appeared to be more obvious for hip fracture.

Potential Benefits of Green Tea in Prostate Cancer Prevention and Treatment: A Comprehensive Review.

Prostate cancer is a prevalent and debilitating disease that necessitates effective prevention and treatment strategies. Green tea, a well-known beverage derived from the Camellia sinensis plant, contains bioactive compounds with potential health benefits, including catechins and polyphenols. This comprehensive review aims to explore the potential benefits of green tea in prostate cancer prevention and treatment by examining existing literature. Green tea possesses antioxidant, anti-inflammatory, and anti-carcinogenic properties attributed to its catechins, particularly epigallocatechin gallate. Epidemiological studies have reported an inverse association between green tea consumption and prostate cancer risk, with potential protection against aggressive forms of the disease. Laboratory studies demonstrate that green tea components inhibit tumor growth, induce apoptosis, and modulate signaling pathways critical to prostate cancer development and progression. Clinical trials and human studies further support the potential benefits of green tea. Green tea consumption has been found to be associated with a reduction in prostate-specific antigen levels, tumor markers, and played a potential role in slowing disease progression. However, challenges remain, including optimal dosage determination, formulation standardization, and conducting large-scale, long-term clinical trials. The review suggests future research should focus on combinatorial approaches with conventional therapies and personalized medicine strategies to identify patient subgroups most likely to benefit from green tea interventions.

Xinyang tablet alleviated cardiac dysfunction in a cardiac pressure overload model by regulating the receptor-interacting serum/three-protein kinase 3/FUN14 domain containing 1-mediated mitochondrial unfolded protein response and mitophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Xinyang tablet (XYT) has been used for heart failure (HF) for over twenty years in clinical practice, but the underlying molecular mechanism remains poorly understood. AIMS OF THE STUDY: In the present study, we aimed to explore the protective effects of XYT in HF in vivo and in vitro. MATERIALS AND METHODS: Transverse aortic constriction was performed in vivo to establish a mouse model of cardiac pressure overload. Echocardiography, tissue staining, and real-time quantitative PCR (qPCR) were examined to evaluate the protective effects of XYT on cardiac function and structure. Adenosine 5'-triphosphate production, reactive oxygen species staining, and measurement of malondialdehyde and superoxide dismutase was used to detect mitochondrial damage. Mitochondrial ultrastructure was observed by transmission electron microscope. Immunofluorescence staining, qPCR, and Western blotting were performed to evaluate the effect of XYT on the mitochondrial unfolded protein response and mitophagy, and to identify its potential pharmacological mechanism. In vitro, HL-1 cells and neonatal mouse cardiomyocytes were stimulated with Angiotensin II to establish the cell model. Western blotting, qPCR, immunofluorescence staining, and flow cytometry were utilized to determine the effects of XYT on cardiomyocytes. HL-1 cells overexpressing receptor-interacting serum/three-protein kinase 3 (RIPK3) were generated by transfection of RIPK3-overexpressing lentiviral vectors. Cells were then co-treated with XYT to determine the molecular mechanisms. RESULTS: In the present study, XYT was found to exerta protective effect on cardiac function and structure in the pressure overload mice. And it was also found XYT reduced mitochondrial damage by enhancing mitochondrial unfolded protein response and restoring mitophagy. Further studies showed that XYT achieved its cardioprotective role through regulating the RIPK3/FUN14 domain containing 1 (FUNDC1) signaling. Moreover, the overexpression of RIPK3 successfully reversed the XYT-induced protective effects and significantly attenuated the positive effects on the mitochondrial unfolded protein response and mitophagy. CONCLUSIONS: Our findings indicated that XYT prevented pressure overload-induced HF through regulating the RIPK3/FUNDC1-mediated mitochondrial unfolded protein response and mitophagy. The information gained from this study provides a potential strategy for attenuating mitochondrial damage in the context of pressure overload-induced heart failure using XYT.

Glutamate rescues heat stress-induced apoptosis of Sertoli cells by enhancing the activity of antioxidant enzymes and activating the Trx1-Akt pathway in vitro.

Heat stress reduces the number of Sertoli cells, which is closely related to an imbalanced redox status. Glutamate functions to maintain the equilibrium of redox homeostasis. However, the role of glutamate in heat treated Sertoli cells remains unclear. Herein, Sertoli cells from 3-week-old piglets were treated at 44 °C for 30 min (heat stress). Glutamate levels increased significantly following heat stress treatment, followed by a gradual decrease during recovery, while glutathione (GSH) showed a gradual increase. The addition of exogenous glutamate (700 µM) to Sertoli cells before heat stress significantly reduced the heat stress-induced apoptosis rate, mediated by enhanced levels of antioxidant substances (superoxide dismutase (SOD), total antioxidant capacity (TAC), and GSH) and reduced levels of oxidative substances (reactive oxygen species (ROS) and malondialdehyde (MDA)). Glutamate addition to Sertoli cells before heat stress upregulated the levels of glutamate-cysteine ligase, modifier subunit (Gclm), glutathione synthetase (Gss), thioredoxin (Trx1) and B-cell leukemia/lymphoma 2 (Bcl-2), and the ratio of phosphorylated Akt (protein kinase B)/total Akt. However, it decreased the levels of Bcl2-associated X protein (Bax) and cleaved-caspase 3. Addition of the inhibitor of glutaminase (Gls1), Bptes (Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide, 30 µM)to Sertoli cells before heat stress reversed these effects. These results inferred that glutamate rescued heat stress-induced apoptosis in Sertoli cells by enhancing activity of antioxidant enzymes and activating the Trx1-Akt pathway. Thus, glutamate supplementation might represent a novel strategy to alleviate the negative effect of heat stress.

Synergistic advantages of volcanic ash weathering in saline soils: CO2 sequestration and enhancement of plant growth.

Carbon dioxide (CO2) is a primary greenhouse gas that has experienced a surge in atmospheric concentration due to human activities and lifestyles. It is imperative to curtail atmospheric CO2 levels promptly to alleviate the multifaceted impacts of climate warming. The soil serves as a natural reservoir for CO2 sequestration. The scientific premise of this study is that CO2 sequestration in agriculturally relevant, organically-deficient saline soil can be achieved by incorporating alkaline earth silicates. Volcanic ash (VA) was used as a soil amendment for CO2 removal from saline soil by leveraging enhanced silicate rock weathering (ERW). The study pursued two primary objectives: first, we aimed to evaluate the impact of various doses of VA, employed as an amendment for organically-deficient soil, on the growth performance of key cultivated crops (sorghum and mung bean) in inland saline-alkaline agricultural regions of northeastern China. Second, we aimed to assess alterations in the physical properties of the amended soil through mineralogical examinations, utilizing X-ray diffraction (XRD) and scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDS) analyses, quantifying the increase in inorganic carbon content within the soil. In the potting tests, mung bean plant height exhibited a noteworthy increase of approximately 41 % with the addition of 10 % VA. Sorghum plant height and aboveground and belowground biomass dry weights increased with VA application across all tested doses. At the optimal VA application rate (20 %), the sorghum achieved a CO2 sequestration rate of 0.14 kg CO2·m-2·month-1. XRD and SEM-EDS analyses confirmed that the augmented inorganic carbon in the VA-amended soils stemmed primarily from calcite accumulation. These findings contribute to elucidating the mechanism underlying VA as an amendment for organically-deficient soils and provide an effective approach for enhancing the carbon sink capacity of saline soils.

Study on the strength deterioration characteristic and damage model of coal pillar dams with repeated water immersion in underground reservoirs.

The continuous operation of coal mine underground reservoirs exposes the coal pillar dams to mining disturbances and prolonged water immersion, resulting in the deterioration of coal pillars' mechanical properties and posing a serious threat to the dam stability. To this end, coal samples from the proposed pillar dam in the 5-2 coal seam of Daliuta Mine in Shendong Mining Area were selected for conducting water absorption tests and triaxial compression tests under conditions of repeated water immersion, in order to study the deterioration of the mechanical properties and acoustic emission damage characteristic of coal samples as well as the mechanism behind the deterioration of coal samples under the water-rock interaction. The results indicated that: (1) the saturated water content of coal samples exhibited a progressive increase as the water immersion times increased, but with a diminishing rate of growth. (2) As the water immersion times increased, the compressive strength, cohesive force, and internal friction angle of coal samples gradually decreased. Notably, the deterioration effect was more pronounced in compressive strength and cohesive force, while the decline in internal friction angle was relatively minor, and the total deterioration degree and the stage deterioration degree of the above three had evident cumulativity and non-uniformity. The progressive rise in water immersion times led to a gradual attenuation of the deterioration effect. Meanwhile, the confining pressure exhibited a certain inhibitory impact on the strength deterioration of coal samples. (3) Compared to the dry coal samples, the average AE count rate of coal samples subjected to a single water immersion exhibited a significant decrease, and subsequent water immersion for two, three, and four times resulted in a very minor decrease in the average AE count rate. (4) The AE cumulative ringing counts in coal samples exhibited varying degrees of reduction as water immersion times increased. Specifically, the most significant decrease in AE cumulative ringing counts occurred after the initial water immersion, followed by a gradual decrease thereafter. The energy-releasing capacity of coal samples decreased, while their plasticity exhibited a gradual increase. (5) A damage model was developed for coal samples based on the water immersion times. The model indicated that the damage to coal samples increased as the water immersion times increased, and the damage rate gradually decreased and eventually stabilized. (6) The deterioration mechanism of coals under the water-rock interaction was explained. Through repeated water immersion, the physical, chemical, and mechanical interactions between water and coal induced alterations in the internal microstructure of coal samples, resulting in the deterioration of mechanical properties such as compressive strength, cohesive force, and internal friction angle, which was a cumulative damage process from the microscopic to the macroscopic level.

Influence of perceived social support on detection of social norm violation: evidence from N1 and N400.

Introduction: The perceived social support individuals receive from their others plays a crucial role in shaping conformity with social norms. However, the specific mechanism underlying perceived social support and the detection of social norms remains unclear. Methods: In this study, college students with high and low levels of perceived social support were asked to judge the appropriateness of stranger's behaviors (e.g., singing) in different situations (e.g., library). The participants' electroencephalography activities were analyzed aiming to uncover the neural mechanism underlying how perceived social support influences the detection of others' normative behavior. Results: The ERP results indicate that, for individuals with a lower level of perceived social support, larger amplitudes of the N1 component (related to primary processing) and the N400 component (related to cognitive conflict) were observed when detecting others' social norm violation compared to the conformity condition. However, for individuals with a higher level of perceived social support, no significant differences were found in detecting others' conformity or violation of social norms. Discussion: The results indicate that, when the perceived social support level of the individual is low, detecting others' social norm violation elicits deeper primary processing and stronger cognitive conflict compared to conformity condition.

Efficacy of cognitive functional therapy in patients with low back pain: A systematic review and meta-analysis.

BACKGROUND: Low back pain is a major public health problem worldwide, and there exists evidence that cognitive functional therapy may help improve patients' health condition. However, the utilization of cognitive functional therapy for low back pain is limited, and its clinical efficacy remains unclear. OBJECTIVES: To determine the efficacy of cognitive functional therapy in the management of disability, pain intensity, and fear-avoidance beliefs in low back pain patients. DESIGN: Systematic review and meta-analysis. METHOD: A comprehensive study search of Pubmed, Web of Science, Medline, CINAHL, Embase, PsycINFO, and the Cochrane Library databases was conducted from their inception to August 14th, 2023. Two researchers independently conducted the literature search and data extraction. All statistical analysis was performed using Stata Version 17.0. RESULTS: A total of eight randomized controlled trials were included. In the short-term, cognitive functional therapy significantly improved disability (7 studies, SMD = -1.05, 95 % CI = -1.74 to -0.35, I2 = 95.37 %, GRADE = very low), pain intensity (7 studies, SMD = -1.02, 95 % CI = -1.89 to -0.15, I2 = 97.21 %, GRADE = very low), and fear-avoidance beliefs (4 studies, SMD = -0.89, 95 % CI = -1.30 to -0.47, I2 = 82.49 %, GRADE = very low). In the medium-term, cognitive functional therapy also significantly improved disability (3 studies, SMD = -0.48, 95 % CI = -0.82 to -0.14, I2 = 77.97 %, GRADE = very low), pain intensity (3 studies, SMD = -0.34, 95 % CI = -0.58 to -0.10, I2 = 55.55 %, GRADE = very low), and fear-avoidance beliefs (2 studies, SMD = -0.62, 95 % CI = -1.19 to -0.04, I2 = 88.24 %, GRADE = very low). In the long-term, cognitive functional therapy significantly improved disability (4 studies, SMD = -0.54, 95 % CI = -0.95 to -0.13, I2 = 85.87 %, GRADE = very low) and fear-avoidance beliefs (3 studies, SMD = -0.76, 95 % CI = -1.17 to -0.34, I2 = 80.34 %, GRADE = very low). CONCLUSION: Cognitive functional therapy might be effective in reducing disability and fear-avoidance beliefs at any of short-, medium- and long-term follow-ups, and reducing pain at short- and medium-term follow-ups. No definitive conclusions can be drawn about the impact of cognitive functional therapy on low back pain patients due to the very low certainty evidence base. Additional rigorous randomized controlled trials are needed to further confirm these findings. REGISTRATION NUMBER: CRD42022287123 (PROSPERO).

Preparation and properties of phase-change materials with enhanced radial thermal conductivities based on anisotropic graphene aerogels.

In this study, anisotropic graphene aerogels are prepared using the heat-flow method. Then, graphene aerogels with nanosilver particles are prepared via a silver mirror reaction. The aerogels are soaked in paraffin wax and the effects on the properties of the wax are investigated. The thermal conductivity of pure paraffin wax is 0.2553 W m-1 K-1. For the prepared PCM, the aerogel content was 0.92 vol%; this increases to 1.2234 W m-1 K-1, which corresponds to a thermal conductivity enhancement efficiency of 582%. The axial thermal conductivity is 1.4953 W m-1 K-1, which corresponds to a thermal conductivity enhancement efficiency of 746%. The graphene aerogels with the nanosilver particles show high phase-change efficiency. Owing to the significant improvements in the axial and thermal conductivities, the radial and axial heat transfer properties show good consistency suitable for practical applications.

CO2 hydrogenation over Fe-Co bimetallic catalysts with tunable selectivity through a graphene fencing approach.

Tuning CO2 hydrogenation product distribution to obtain high-selectivity target products is of great significance. However, due to the imprecise regulation of chain propagation and hydrogenation reactions, the oriented synthesis of a single product is challenging. Herein, we report an approach to controlling multiple sites with graphene fence engineering that enables direct conversion of CO2/H2 mixtures into different types of hydrocarbons. Fe-Co active sites on the graphene fence surface present 50.1% light olefin selectivity, while the spatial Fe-Co nanoparticles separated by graphene fences achieve liquefied petroleum gas of 43.6%. With the assistance of graphene fences, iron carbides and metallic cobalt can efficiently regulate C-C coupling and olefin secondary hydrogenation reactions to achieve product-selective switching between light olefins and liquefied petroleum gas. Furthermore, it also creates a precedent for CO2 direct hydrogenation to liquefied petroleum gas via a Fischer-Tropsch pathway with the highest space-time yields compared to other reported composite catalysts.

Single-Component Dual-Functional Autoboost Strategy by Dual Photodynamic and Cyclooxygenase-2 Inhibition for Lung Cancer and Spinal Metastasis.

Coloading adjuvant drugs or biomacromolecules with photosensitizers into nanoparticles to enhance the efficiency of photodynamic therapy (PDT) is a common strategy. However, it is difficult to load positively charged photosensitizers and negatively charged adjuvants into the same nanomaterial and further regulate drug release simultaneously. Herein, a single-component dual-functional prodrug strategy is reported for tumor treatment specifically activated by tumor microenvironment (TME)-generated HOCl. A representative prodrug (DHU-CBA2) is constructed using indomethacin grafted with methylene blue (MB). DHU-CBA2 exhibited high sensitivity toward HOCl and achieved simultaneous release of dual drugs in vitro and in vivo. DHU-CBA2 shows effective antitumor activity against lung cancer and spinal metastases via PDT and cyclooxygenase-2 (COX-2) inhibition. Mechanistically, PDT induces immunogenic cell death but stimulates the gene encoding COX-2. Downstream prostaglandins E2 and Indoleamine 2,3 dioxygenase 1 (IDO1) mediate immune escape in the TME, which is rescued by the simultaneous release of indomethacin. DHU-CBA2 promotes infiltration and function of CD8+ T cells, thus inducing a robust antitumor immune response. This work provides an autoboost strategy for a single-component dual-functional prodrug activated by TME-specific HOCl, thereby achieving favorable tumor treatment via the synergistic therapy of PDT and a COX-2 inhibitor.

Clinical advances in TNC delivery vectors and their conjugate agents.

Tenascin C (TNC), a glycoprotein that is abundant in the tumor extracellular matrix (ECM), is strongly overexpressed in tumor tissues but virtually undetectable in most normal tissues. Many TNC antibodies, peptides, aptamers, and nanobodies have been investigated as delivery vectors, including 20A1, α-A2, α-A3, α-IIIB, α-D, BC-2, BC-4 BC-8, 81C6, ch81C6, F16, FHK, Ft, Ft-NP, G11, G11-iRGD, GBI-10, 19H12, J1/TN1, J1/TN2, J1/TN3, J1/TN4, J1/TN5, NJT3, NJT4, NJT6, P12, PL1, PL3, R6N, SMART, ST2146, ST2485, TN11, TN12, TNFnA1A2-Fc, TNfnA1D-Fc, TNfnBD-Fc, TNFnCD-Fc, TNfnD6-Fc, TNfn78-Fc, TTA1, TTA1.1, and TTA1.2. In particular, BC-2, BC-4, 81C6, ch81C6, F16, FHK, G11, PL1, PL3, R6N, ST2146, TN11, and TN12 have been tested in human tissues. G11-iRGD and simultaneous multiple aptamers and arginine-glycine-aspartic acid (RGD) targeting (SMART) may be assessed in clinical trials because G11, iRGD and AS1411 (SMART components) are already in clinical trials. Many TNC-conjugate agents, including antibody-drug conjugates (ADCs), antibody fragment-drug conjugates (FDCs), immune-stimulating antibody conjugates (ISACs), and radionuclide-drug conjugates (RDCs), have been investigated in preclinical and clinical trials. RDCs investigated in clinical trials include 111In-DTPA-BC-2, 131I-BC-2, 131I-BC-4, 90Y-BC4, 131I81C6, 131I-ch81C6, 211At-ch81C6, F16124I, 131I-tenatumomab, ST2146biot, FDC 131I-F16S1PF(ab')2, and ISAC F16IL2. ADCs (including FHK-SSL-Nav, FHK-NB-DOX, Ft-NP-PTX, and F16*-MMAE) and ISACs (IL12-R6N and 125I-G11-IL2) may enter clinical trials because they contain components of marketed treatments or agents that were investigated in previous clinical studies. This comprehensive review presents historical perspectives on clinical advances in TNC-conjugate agents to provide timely information to facilitate tumor-targeting drug development using TNC.

Nuclear-Targeted Nanostrategy Regulates Spatiotemporal Communication for Dual Antitumor Immunity.

Intercellular communication between tumor cells and immune cells regulates tumor progression including positive communication with immune activation and negative communication with immune escape. An increasing number of methods are employed to suppress the dominant negative communication in tumors such as PD-L1/PD-1. However, how to effectively improve positive communication is still a challenge. In this study, a nuclear-targeted photodynamic nanostrategy is developed to establish positive spatiotemporal communication, further activating dual antitumor immunity, namely innate and adaptative immunity. The mSiO2 -Ion@Ce6-NLS nanoparticles (NPs) are designed, whose surface is modified by ionic liquid silicon (Ion) and nuclear localization signal peptide (NLS: PKKKRKV), and their pores are loaded with the photosensitizer hydrogen chloride e6 (Ce6). Ion-modified NPs enhance intratumoral enrichment, and NLS-modified NPs exhibit nuclear-targeted characteristics to achieve nuclear-targeted photodynamic therapy (nPDT). mSiO2 -Ion@Ce6-NLS with nPDT facilitate the release of damaged double-stranded DNA from tumor cells to activate macrophages via stimulator of interferon gene signaling and induce the immunogenic cell death of tumor cells to activate dendritic cells via "eat me" signals, ultimately leading to the recruitment of CD8+ T-cells. This therapy effectively strengthens positive communication to reshape the dual antitumor immune microenvironment, further inducing long-term immune memory, and eventually inhibiting tumor growth and recurrence.

Improved photosynthetic performance under unilateral weak light conditions in a wide-narrow-row intercropping system is associated with altered sugar transport.

Intercropping improves resource utilization. Under wide-narrow-row maize (Zea mays) intercropping, maize plants are subjected to weak unilateral illumination and exhibit high photosynthetic performance. However, the mechanism regulating photosynthesis under unilateral weak light remains unknown. We investigated the relationship between photosynthesis and sugar metabolism in maize under unilateral weak light. Our results showed that the net photosynthetic rate (Pn) of unshaded leaves increased as the level of shade on the other side increased. On the contrary, the concentration of sucrose and starch and the number of starch granules in the unshaded leaves decreased with increased shading due to the transfer of abundant C into the grains. However, sink loss with ear removal reduced the Pn of unshaded leaves. Intense unilateral shade (40% to 20% normal light), but not mild unilateral shade (60% normal light), reduced grain yield (37.6% to 54.4%, respectively). We further found that in unshaded leaves, Agpsl, Bmy, and Mexl-like expression significantly influenced sucrose and starch metabolism, while Sweet13a and Sut1 expression was crucial for sugar export. In shaded leaves, expression of Sps1, Agpsl, and Sweet13c was crucial for sugar metabolism and export. This study confirmed that unshaded leaves transported photosynthates to the ear, leading to a decrease in sugar concentration. The improvement of photosynthetic performance was associated with altered sugar transport. We propose a narrow-row spacing of 40 cm, which provides appropriate unilateral shade and limits yield reduction.

Liuwei Dihuang pills attenuate ovariectomy-induced bone loss by alleviating bone marrow mesenchymal stem cell (BMSC) senescence via the Yes-associated protein (YAP)-autophagy axis.

CONTEXT: Liuwei Dihuang pill (LWDH) has been used to treat postmenopausal osteoporosis (PMOP). OBJECTIVE: To explore the effects and mechanisms of action of LWDH in PMOP. MATERIALS AND METHODS: Forty-eight female Sprague-Dawley rats were divided into four groups: sham-operated (SHAM), ovariectomized (OVX), LWDH high dose (LWDH-H, 1.6 g/kg/d) and LWDH low dose (LWDH-L, 0.8 g/kg/d); the doses were administered after ovariectomy via gavage for eight weeks. After eight weeks, the bone microarchitecture was evaluated. The effect of LWDH on the differentiation of bone marrow mesenchymal stem cells (BMSCs) was assessed via osteogenesis- and lipogenesis-induced BMSC differentiation. The senescence-related biological indices were also detected using senescence staining, cell cycle analysis, quantitative real-time polymerase chain reaction and western blotting. Finally, the expression levels of autophagy-related proteins and Yes-associated protein (YAP) were evaluated. RESULTS: LWDH-L and LWDH-H significantly modified OVX-induced bone loss. LWDH promoted osteogenesis and inhibited adipogenesis in OVX-BMSCs. Additionally, LWDH decreased the positive ratio of senescence OVX-BMSCs and improved cell viability, cell cycle, and the mRNA and protein levels of p53 and p21. LWDH upregulated the expression of autophagy-related proteins, LC3, Beclin1 and YAP, in OVX-BMSCs and downregulated the expression of p62. DISCUSSION AND CONCLUSIONS: LWDH improves osteoporosis by delaying the BMSC senescence through the YAP-autophagy axis.

Eyeless cave-dwelling Leptonetela spiders still rely on light.

Subterranean animals living in perpetual darkness may maintain photoresponse. However, the evolutionary processes behind the conflict between eye loss and maintenance of the photoresponse remain largely unknown. We used Leptonetela spiders to investigate the driving forces behind the maintenance of the photoresponse in cave-dwelling spiders. Our behavioral experiments showed that all eyeless/reduced-eyed cave-dwelling species retained photophobic response and that they had substantially decreased survival at cave entrances due to weak drought resistance. The transcriptomic analysis demonstrated that nearly all phototransduction pathway genes were present and that all tested phototransduction pathway genes were subjected to strong functional constraints in cave-dwelling species. Our results suggest that cave-dwelling eyeless spiders still use light and that light detection likely plays a role in avoiding the cave entrance habitat. This study confirms that some eyeless subterranean animals have retained their photosensitivity due to natural selection and provides a case of mismatch between phenotype and genotype or physiological function in a long-term evolutionary process.

Global, regional, and national prevalence of hearing loss from 1990 to 2019: A trend and health inequality analyses based on the Global Burden of Disease Study 2019.

As a severe public health issue, hearing loss has caused an increasingly disease burden, especially in the elderly population. Hearing loss may inevitably induce asymmetric hearing, which makes it difficult for elderly individuals to locate sound sources, therefore resulting in increased postural instability and falling risk. To emphasize the public health emergence of hearing loss, we investigated the temporal trend of prevalence of hearing loss over the last 30 years and further predicted its changes in the next 20 years, decomposed the trend according to demographic factors and epidemiological changes, and quantified the cross-country healthy inequalities, using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. In 2019, there were more than 140 million cases of hearing loss worldwide, a 93.89% increase from 70 million cases in 1990. The age-standardized rate (ASR) also increased with an estimated annual percentage change of 0.08% per year. Population growth and aging are the major drivers contributing to the changes, accounting for 60.83% and 35.35%. Of note, the contribution of aging varies showing a gradual increasing trend with sociodemographic index (SDI) elevating. Also notable, there were significant health inequalities across 204 countries and territories, with slope index of inequality rising over time. Projection of the global burden of hearing loss from 2020 to 2040 indicated progressive increases in both case number and ASR. These reflect the heavy disease burden of hearing loss that needed more targeted and efficient strategies in its prevention and management.

Golgi Apparatus-Targeted Photodynamic Therapy for Enhancing Tumor Immunogenicity by Eliciting NLRP3 Protein-Dependent Pyroptosis.

Innate and adaptive immunity is important for initiating and maintaining immune function. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome serves as a checkpoint in innate and adaptive immunity, promoting the secretion of pro-inflammatory cytokines and gasdermin D-mediated pyroptosis. As a highly inflammatory form of cell death distinct from apoptosis, pyroptosis can trigger immunogenic cell death and promote systemic immune responses in solid tumors. Previous studies proposed that NLRP3 was activated by translocation to the mitochondria. However, a recent authoritative study has challenged this model and proved that the Golgi apparatus might be a prerequisite for the activation of NLRP3. In this study, we first developed a Golgi apparatus-targeted photodynamic strategy to induce the activation of NLRP3 by precisely locating organelles. We found that Golgi apparatus-targeted photodynamic therapy could significantly upregulate NLRP3 expression to promote the subsequent release of intracellular proinflammatory contents such as IL-1ß or IL-18, creating an inflammatory storm to enhance innate immunity. Moreover, this acute NLRP3 upregulation also activated its downstream classical caspase-1-dependent pyroptosis to enhance tumor immunogenicity, triggering adaptive immunity. Pyroptosis eventually led to immunogenic cell death, promoted the maturation of dendritic cells, and effectively activated antitumor immunity and long-lived immune memory. Overall, this Golgi apparatus-targeted strategy provided molecular insights into the occurrence of immunogenic pyroptosis and offered a platform to remodel the tumor microenvironment.

Simulation test study on filling flow law of gangue slurry in goaf.

The disposal and utilization of solid waste of coal gangue is one of the main problems in coal mining in China. Injecting coal gangue into goaf in the form of slurry can effectively solve the problems of ground stacking and environmental pollution prevention. In order to obtain the flow law of gangue slurry in the void of the accumulated rock in the goaf, a visualization simulation test device for gangue slurry permeation grouting in the goaf was independently designed. The flow and diffusion characteristics, flow and diffusion velocity changes, void pressure changes, and viscosity changes of three mass concentrations (76%, 78%, 80%) of gangue slurry in the void between caved rock blocks in goaf were studied by visual grouting simulation test. The results show that: (1) The seepage process of gangue slurry in the goaf simulation test is divided into three diffusion forms, namely radial diffusion, axial diffusion, and bidirectional diffusion. The three diffusion forms are interrelated and inseparable. (2) The initial flow velocity of the slurry with different concentrations is different under the same permeation grouting pressure, and the higher the slurry concentration, the smaller the initial flow velocity of the slurry. The velocity of the slurry has a nonlinear relationship with the diffusion distance of the slurry. (3) With the permeation and diffusion of slurry, pressure sensors at different positions are subjected to pressure from bottom to top and enter the pressure boost stage, gradually forming stress peaks. When the slurry exceeds the position of the pressure sensor, the pressure on the pressure sensor is weakened and begins to enter the pressure relief stage, and the stress decline trend gradually becomes gentle with time. (4) The water loss effect occurs during slurry flow interaction with rock mass, resulting in slurry viscosity increasing. The viscosity of the slurry affects the difference in the amount of viscosity change. The research results can provide a certain theoretical basis for the goaf gangue slurry filling project.