The correlation between TRIM28 expression and immune checkpoints in CRPC.

This study delves into the unexplored realm of castration-resistant prostate cancer (CRPC) by investigating the role of TRIM28 and its intricate molecular mechanisms using high-throughput single-cell transcriptome sequencing and advanced bioinformatics analysis. Our comprehensive examination unveiled dynamic TRIM28 expression changes, particularly in immune cells such as macrophages and CD8+ T cells within CRPC. Correlation analyses with TCGA data highlighted the connection between TRIM28 and immune checkpoint expression and emphasized its pivotal influence on the quantity and functionality of immune cells. Using TRIM28 knockout mouse models, we identified differentially expressed genes and enriched pathways, unraveling the potential regulatory involvement of TRIM28 in the cGAS-STING pathway. In vitro, experiments further illuminated that TRIM28 knockout in prostate cancer cells induced a notable anti-tumor immune effect by inhibiting M2 macrophage polarization and enhancing CD8+ T cell activity. This impactful discovery was validated in an in situ transplant tumor model, where TRIM28 knockout exhibited a deceleration in tumor growth, reduced proportions of M2 macrophages, and enhanced infiltration of CD8+ T cells. In summary, this study elucidates the hitherto unknown anti-tumor immune role of TRIM28 in CRPC and unravels its potential regulatory mechanism via the cGAS-STING signaling pathway. These findings provide novel insights into the immune landscape of CRPC, offering promising directions for developing innovative therapeutic strategies.

Experimental study on evaluation of density, P-wave velocity, thermal conductivity, and thermal diffusion coefficient of granite after thermal treatments by using PCA.

Temperature significantly influences the physical parameters of granite, resulting in variations in the rock's thermal conductivity. In order to examine the impact of changes in multiple physical parameters of granite at different temperatures on the thermal conductivity of rocks, Principal Component Analysis (PCA) was employed to determine the correlation between granite at different temperatures and various physical parameters, including density (ρ), P-wave velocity (P), thermal conductivity (KT), and thermal diffusion coefficient (KD). Utilizing the linear contribution rate, a single indicator 'y' was derived to comprehensively represent the thermal conductivity of rocks. Research findings indicate that within the temperature range of 150-450 °C, the 'y'-value is relatively high, signifying favorable thermal conductivity of the rock. Notably, longitudinal wave velocity demonstrates higher sensitivity to temperature changes compared to other physical parameters.

Global Prevalence and Hemagglutinin Evolution of H7N9 Avian Influenza Viruses from 2013 to 2022.

H7N9 avian influenza viruses have caused severe harm to the global aquaculture industry and human health. For further understanding of the characteristics of prevalence and hemagglutinin evolution of H7N9 avian influenza viruses, we generated the global epidemic map of H7N9 viruses from 2013 to 2022, constructed a phylogenetic tree, predicted the glycosylation sites and compared the selection pressure of the hemagglutinin. The results showed that although H7N9 avian influenza appeared sporadically in other regions worldwide, China had concentrated outbreaks from 2013 to 2017. The hemagglutinin genes were classified into six distinct lineages: A, B, C, D, E and F. After 2019, H7N9 viruses from the lineages B, E and F persisted, with the lineage B being the dominant. The hemagglutinin of highly pathogenic viruses in the B lineage has an additional predicted glycosylation site, which may account for their persistent pandemic, and is under more positive selection pressure. The most recent ancestor of the H7N9 avian influenza viruses originated in September 1991. The continuous evolution of hemagglutinin has led to an increase in virus pathogenicity in both poultry and humans, and sustained human-to-human transmission. This study provides a theoretical basis for better prediction and control of H7N9 avian influenza.

Macro/Microfracture evolution and instability behaviors of high-temperature granite under water-cooling subjected to Brazilian splitting test using the DIC technique.

To investigate the evolution and stability characteristics of granite thermal damage, a series of Brazilian splitting tests is conducted on high-temperature granite samples using digital image correlation (DIC) technology. The results show that the Brazilian tensile strength and P-wave velocity exhibit a clear decline beyond a temperature threshold of 450~600°C, with a linear relationship between them. The presence of micro-cracks alters the stress transfer path, disrupting the stress balance on the Brazilian disc and leading to complex fracture patterns. At temperatures below 450°C, high strain areas and the development of micro-cracks occur at both the upper and lower loading ends of the granite Brazilian disc. However, these phenomena are only observed at the upper loading end when the temperature exceeds 450°C. Thermal cracks also cause changes in the internal structure of rock samples, and temperature variations can affect both the P-wave velocity and tensile strength. In terms of the relationship between P-wave velocity and Brazilian tensile strength (BTS) of high-temperature granite under water cooling, the negative exponential function model proposed in this study fits the experimental data very well.

LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer.

Epigenetic alteration is a key feature that contributes to the progression of bladder cancer (BC) and long non-coding RNAs serve crucial role in the epigenetic modulation. This study was designed to explore the epigenetic regulation of LINC00592 in BC. LINC00592 expression in BC was examined. Then, LINC00592 was silenced in BC cell followed by cell behavior analyses using CCK-8, transwell, western blot, or flow cytometry. Potential downstream target of LINC00592 was explored using RNA pull-down assay and methylation of WIF1 was determined using methylated-specific PCR. In addition, WIF1 or/and LINC00592 were silenced in BC cells followed by cell behavior analyses to explore the regulation between them. Upregulation of LINC00592 was significantly detected in BC tissues and cells. In BC cells silencing LINC00592 suppressed the proliferation, migration, and epithelial-mesenchymal transitions (EMT), but enhanced apoptosis. Moreover, LINC00592 recruited DNMT1, DNMT3A, and DNMT3B to enhance WIF1 promoter methylation. In addition, WIF1 overexpression suppressed the proliferation, migration, as well as EMT, but enhanced apoptosis. Silencing WIF1 significantly attenuated the role of silencing LINC00592 in suppressing the proliferative, migratory, and EMT ability of BC cells, and increasing the apoptosis. LINC00592 promoted the growth and metastasis of BC via enhancing the promoter methylation of WIF1 and decreasing WIF1 transcription.

Prediction of in-hospital mortality in patients with exertional heatstroke: a 13-year retrospective study.

Hyperactivity of coagulation is common in exertional heatstroke (EHS). Disseminated intravascular coagulation (DIC) is the most severe form of coagulation dysfunction and associated with poor outcome. DIC, temperature and Glasgow coma scale score were identified as independent risk factors for in-hospital mortality by multivariate logistic regression analysis, and we developed a nomogram for predicting in-hospital mortality in a 13-year EHS patient cohort. The nomogram was assessed by calibration curves and bootstrap with 1,000 resamples. The receiver operating characteristic curve was constructed, and the area under the curve (AUC) was compared. Two hundred and ten patients were included. The in-hospital mortality was 9.0%, and the incidence of DIC was 17.6%. The AUC of the nomogram was 0.897 (95% CI 0.848-0.935, p < .0001) and was non-inferior to SOFA and APACHE II scores but superior to SIRS score, which were widely-used score systems of disease severity. The nomogram contributed to the adverse outcome prediction of EHS.

Na+/K+ enhanced the stability of the air/water interface of soy hull polysaccharide and intestinal mucus.

The stable energy barrier of mucin and soy hull polysaccharide (SHP) is established at the air/water interface in the intestinal fluid and is conducive to the absorption and transportation of nutrients. This study aimed to investigate the effect of different concentrations (0.5 % and 1.5 %) of Na+ and K+ on the energy barrier through the digestive system model in vitro. The interaction between ions and microwave-assisted ammonium oxalate-extracted SP (MASP)/mucus was characterized by particle size, zeta potential, interfacial tension, surface hydrophobicity, Fourier transform infrared spectroscopy, endogenous fluorescence spectroscopy, microstructure, and shear rheology. The results showed that the interactions between ions and MASP/mucus included electrostatic interaction, hydrophobic interaction, and hydrogen bond. The MASP/mucus miscible system was destabilized after 12 h, and the ions could improve the system stability to some extent. MASP aggregated continuously with the increase in the ion concentration, and large MASP aggregates were trapped above the mucus layer. Furthermore, the adsorption of MASP/mucus at the interface increased and then decreased. These findings provided a theoretical basis for an in-depth understanding of the mechanism of action of MASP in the intestine.

Glasgow Coma Scale as an Indicator of Patient Prognosis: A Retrospective Study of 257 Patients with Heatstroke from 3 Medical Centers in Guangdong, China.

BACKGROUND Coma has been considered as a valuable symptom of heatstroke. This study aimed to evaluate the role of the Glasgow Coma Scale (GCS) as an indicator of prognosis of patients with heatstroke. MATERIAL AND METHODS From Jan 1st, 2013 to Dec 31st, 2020, the clinical courses of 257 heatstroke patients from 3 medical centers in Guangdong, China, were observed. Diagnosis of heatstroke was made according to Expert Consensus in China. GCSs were calculated on the 1st, 3rd, and 5th days after admission to intensive care units (ICUs). GCS £8, as a coma criterion, was employed to predict the outcomes. RESULTS Seventy-five patients (29.18%) were comatose at admission. Twenty-seven (10.50%) patients, including 24 (24/75, 32.00%) coma patients and 3 (3/182,1.65%) non-coma patients died during ICU stay (P<0.0001). Patients with GCS ≤8 had a 2-fold higher risk of death as compared with those with GCS >8. The area under curves (AUCs) of GCSs on the 1st, 3rd, and 5th days to predict mortality were 0.81 (0.70-0.91), 0.91 (0.84-0.98), and 0.91 (0.82-0.99), respectively. Each additional 1 year of age, 1/min of respiratory rate (RR), and 1% of hematocrit (HCT) increased the risk of death of coma patients by 3%, 6%, and 4%, respectively (all P≤0.05). Patients with improving GCSs had lower mortality rates than non-improving patients (5.71% vs 55.00%, P<0.0001) within 5 days after admission. CONCLUSIONS GCS ≤8 at admission predicted worse outcomes in heatstroke patients, which possibly enhanced the risks of death for other factors, including age, RR, and HCT.

Constructing Hypoxia-Tolerant and Host Tumor-Enriched Aggregation-Induced Emission Photosensitizer for Suppressing Malignant Tumors Relapse and Metastasis.

Photodynamic immunotherapy is a promising treatment strategy that destroys primary tumors and inhibits the metastasis and relapse of distant tumors. As reactive oxygen species are an intermediary for triggering immune responses, photosensitizers (PSs) that can actively target and efficiently trigger oxidative stress are urgently required. Herein, pyrrolo[3,2-b]pyrrole as an electronic donor is introduced in acceptor-donor-acceptor skeleton PSs (TP-IS1 and TP-IS2) with aggregation-induced emission properties and high absorptivity. Meanwhile, pyrrolo[3,2-b]pyrrole derivatives innovatively prove their ability of type I photoreaction, indicating their promising hypoxia-tolerant advantages. Moreover, M1 macrophages depicting an ultrafast delivery through the cell-to-cell tunneling nanotube pathway emerge to construct TP-IS1@M1 by coating the photosensitizer TP-IS1. Under low concentration of TP-IS1@M1, an effective immune response of TP-IS1@M1 is demonstrated by releasing damage-associated molecular patterns, maturating dendritic cells, and vanishing the distant tumor. These findings reveal insights into developing hypoxia-tolerant PSs and an efficient delivery method with unprecedented performance against tumor metastasis.

HMGB1-activatied NLRP3 inflammasome induces thrombocytopenia in heatstroke rat.

Background: Thrombocytopenia, an early common complication in heatstroke (HS), has been widely considered as a mortality predictor of HS. The mechanism underlying thrombocytopenia in HS remains unknown. It is not known whether NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is activated in HS platelet, which, in turn, induces platelet activation and thrombocytopenia. This study tried to clarify the activation of the NOD-like receptor signaling pathway under HS conditions and investigate its roles in mediating HS-induced thrombocytopenia. Methods: Rat HS models were established in a certain ambient temperature and humidity. Platelets, isolated from blood, were counted and CD62P, an index of platelet activation, was measured by flow cytometry in all rats. The colocalization of NLRP3 inflammasome in platelet was detected by confocal fluorescence microscopy. Mitochondrial-derived reactive oxygen species (ROS) was detected using the molecular probes. Plasma HMGB1 and IL-1ß levels were measured by ELISA. Results: Platelet activation, showed by upregulated CD62P, and thrombocytopenia were observed in HS rats. HS activated the NLRP3 inflammasome, which was induced by elevated levels of ROS, while the upregulated CD62P and thrombocytopenia triggered by NLRP3 inflammasome were attributed to the high mobility group box protein 1 (HMGB1) inplasma. Moreover, inhibition of the NOD-like receptor signaling pathway in rats with HS suppressed platelet activation and the decline of platelet count. Similar results were obtained when the receptor toll-like receptor 4 (TLR4)/advanced glycation end product (RAGE) was blocked. Conclusions: The NOD-like receptor signaling pathway induces platelet activation and thrombocytopenia in HS rats. These findings suggested that the NLRP3 inflammasome might be the potential target for HS treatment.

Molecular Dynamics Simulation of Spreading of Mixture Droplets on Chemically Heterogeneous Surfaces.

The dynamic spreading process of mixed droplets on chemically heterogeneous surfaces has attracted significant attention owing to its extensive industrial applications. The spreading of mixture droplets on a chemically heterogeneous surface is more complex than that for pure fluid droplets and needs to be understood further. In this study, molecular dynamic simulations were performed to investigate the dynamic spreading process of R32/R1234yf mixture droplets and water/ethanol mixture droplets of radius 4.7-6.5 nm with different compositions, on chemically heterogeneous surfaces. The variation in the relative spreading radius with time was analyzed and compared with the molecular kinetic theory. It was observed that for the R32/R1234yf mixture, the actual component mole fraction did not deviate from the nominal one in the triple contact region, and the dynamic spreading behavior was identical to that for the pure fluids. Meanwhile, the converse was true for the ethanol/water mixture. The molecular kinetic theory could accurately predict the spreading of droplets for R32/R1234yf mixtures when the mixture properties were used. However, this was not feasible for ethanol/water mixtures. It was observed that the local physical properties in the triple contact line (including the mole fraction and the lyophilic and lyophobic area ratio) play key roles in the spreading of the ethanol/water mixture droplets. The prediction of the dynamic spreading of water/ethanol mixture droplets on chemically heterogeneous surfaces can be improved significantly by using local properties to modify the molecular kinetic theory.

The influence of laser-induced alignment on Z-scan properties of 2D carbon nanomaterials suspension dependent on polarization.

The Z-scan technique uses a single beam that can be used for observing the nonlinear or optical limiting properties of materials. For the first time, the Z-scan properties dependent on the polarization of 2D carbon nanomaterial suspension were experimentally investigated using optical Z-scan technology. The Z-scan curves of graphene and graphene oxide (GO) in N-methyl-2-pyrrolidinone suspensions exhibited strong polarization-dependent characteristics. In paper, a reverse saturated absorption (RSA) dip surrounded the lens focus when the horizontal polarized beam was focused in the suspension, and two saturated absorption (SA) peaks appeared adjacent to the dip. However, for the vertical polarized beam, only one RSA dip surrounded the lens focus, and the threshold was higher than the SA for a horizontally polarized beam. The transmission of RSA for the GO suspension was evidently lower than that of the graphene suspension. The polarization-dependent characteristic can be ascribed to the laser-induced alignment in case the suspension is moved in or out of the beam focal point. Furthermore, the polarization-dependent 2D carbon nanomaterial suspension can be applied in several practical purposes such as 2D material-based optical and opto-fludic devices.

Study on the Control of Membrane Fouling by Pulse Function Feed and CFD Simulation Verification.

A complex-function fluid controller placed in front of a membrane module was used to control the velocity change with feed fluid and reduce membrane fouling. Using humic acid as the simulated pollutant, the effects of the square wave function, sine function, reciprocal function, and power function feeding on the membrane flux were investigated. For sine function feeding, the membrane-specific flux was the largest and was maintained above 0.85 under the intermittent frequency of 9 s. Compared with the final membrane-specific flux with steady-flow feeding of 0.55, functional feeding could significantly reduce membrane fouling. SEM results showed that sine feeding led to slight contamination on the membrane surface. Furthermore, the Computational Fluid Dynamics (CFD) simulation results showed that the shear force of sine function feeding was about three times that of the steady flow (6 × 105 N). Compared with steady feeding, functional feeding could significantly improve the shear force on the membrane surface and reduce membrane fouling.

Halogen Bonding: A New Platform for Achieving Multi-Stimuli-Responsive Persistent Phosphorescence.

Monotonous luminescence has always been a major factor limiting the application of organic room-temperature phosphorescence (RTP) materials. Enhancing and regulating the intermolecular interactions between the host and guest is an effective strategy to achieve excellent phosphorescence performance. In this study, intermolecular halogen bonding (CN⋅⋅⋅Br) was introduced into the host-guest RTP system. The interaction promoted intersystem crossing and stabilized the triplet excitons, thus helping to achieve strong phosphorescence emission. In addition, the weak intermolecular interaction of halogen bonding is sensitive to external stimuli such as heat, mechanical force, and X-rays. Therefore, the triplet excitons were easily quenched and colorimetric multi-stimuli responsive behaviors were realized, which greatly enriched the luminescence functionality of the RTP materials. This method provides a new platform for the future design of responsive RTP materials based on weak intermolecular interactions between the host and guest molecules.

Na+/Ca2+ induced the migration of soy hull polysaccharides in the mucus layer in vitro.

This study aimed to investigate the mechanism of Na+/Ca2+-induced soy hull polysaccharide (SHP) migration in the mucus layer. The viscosity, potential, microstructure, SHP migration, and metabolite migration were analyzed. The results showed that Na+ had little effect on the viscosity of polysaccharides, while Ca2+ increased the viscosity of polysaccharides. Na+ and Ca2+ promoted the migration of SHP particles by reducing the zeta potential, while they decreased the migration of SHP chyle particles by increasing the aggregation. SHP was fermented by gut microbiota to produce a large number of short-chain fatty acids (SCFAs). Compared with Ca2+, Na+ increased the migration of total SCFAs in the mucus layer. The high-Na+/Ca2+ mucus internal environment had a specific effect on the transport of nutrients in the intestine.

Rational design of pyrrole derivatives with aggregation-induced phosphorescence characteristics for time-resolved and two-photon luminescence imaging.

Pure organic room-temperature phosphorescent (RTP) materials have been suggested to be promising bioimaging materials due to their good biocompatibility and long emission lifetime. Herein, we report a class of RTP materials. These materials are developed through the simple introduction of an aromatic carbonyl to a tetraphenylpyrrole molecule and also exhibit aggregation-induced emission (AIE) properties. These molecules show non-emission in solution and purely phosphorescent emission in the aggregated state, which are desirable properties for biological imaging. Highly crystalline nanoparticles can be easily fabricated with a long emission lifetime (20 µs), which eliminate background fluorescence interference from cells and tissues. The prepared nanoparticles demonstrate two-photon absorption characteristics and can be excited by near infrared (NIR) light, making them promising materials for deep-tissue optical imaging. This integrated aggregation-induced phosphorescence (AIP) strategy diversifies the existing pool of bioimaging agents to inspire the development of bioprobes in the future.

The Effect of Natural Soluble Polysaccharides on the Type 2 Diabetes through Modulating Gut Microbiota: A Review.

Diabetes strongly influences the patient's quality of life. The incidence of type 2 diabetes (T2D) accounts for approximately 90% of diabetic patients. Natural polysaccharides have been widely used for diabetes management. Changes in gut microbiota can also be used for the prevention and treatment of diabetes. In this review, the effects of different natural polysaccharides on gut microbiota, as well as the relationship between diabetes and the gut microbiome are summarized. The intestine is the primary location in which natural polysaccharides exert their biological activities and plays an important role in maintaining healthy bodily functions. Polysaccharides change the composition of the gut microbiota, which inhibits pathogen invasion and promotes beneficial bacterial growth. In addition, the gut microbiota degrade polysaccharides and produce metabolites to further modify the intestinal environment. Interestingly, the metabolites (short chain fatty acids and other bioactive components) have been shown to improve gut health, control glycemia, lower lipids, reduce insulin resistance, and alleviate inflammation. Therefore, understanding the underlying mechanisms by which soluble polysaccharides improve T2D through regulating the gut microbiota and provide a future reference for the management of T2D and its associated complications.

Response of photosynthetic characteristics and non-structural carbohydrate accumulation of Betula ermanii seedlings to drought stress.

We explored the effects of drought stress on photosynthetic characteristics and non-structural carbohydrate (NSC) accumulation of the timberline tree species Betula ermanii in Changbai Mountain with a drought control experiment. The results showed that drought significantly reduced the net photosynthetic rate and stomatal conductance, but increased water use efficiency (WUE) of B. ermanii seedlings. Drought dramatically improved the contents of soluble sugar and total NSC in leaves, barks, stems, and roots of B. ermanii seedlings, but significantly reduced their starch content. The stomatal conductance, photosynthetic rate and WUE decreased rapidly as the drought continued, whereas the contents of soluble sugar, starch and NSC increased and then declined. At the end of the experiment, 90% of the leaves turned yellow, and the ratios of soluble sugar to starch in the stems, barks and roots under the drought treatment were significantly higher than those in the control. These results demonstrated that B. ermanii might be a drought-avoidance species that could reduce water loss by rapidly reducing stomatal conductance and improving WUE under drought stress. B. ermanii might have evolved priority storage strategy to cope with water deficit through improving the content of soluble sugar in organs and increasing the transformation rate between starch and sugar. With the extension of drought stress, seedlings tended to die, since water stress might exceed the threshold of the plant self-regulation capacity. However, the content of NSC in organs did not decrease, suggesting that the death of B. ermanii under drought stress might not be caused by carbon starvation.

Excitation-Dependent Triplet-Singlet Intensity from Organic Host-Guest Materials: Tunable Color, White-Light Emission, and Room-Temperature Phosphorescence.

A series of organic host-guest materials with multifunctional luminescence were constructed. Four isoquinoline derivatives were used as the guests, and benzophenone was used as the host. The doped system exhibited excellent dual emission with cyan fluorescence and orange-yellow room-temperature phosphorescence, and the dual emission could be combined into almost pure white-light emission. Importantly, the relative intensity of the fluorescence-phosphorescence could be adjusted by changing the excitation wavelength, with the phosphorescence intensity being significantly higher than the fluorescence intensity under shorter excitation wavelengths and vice versa under longer excitation wavelengths. Therefore, three-color emission switching among cyan, white, and orange could be achieved by simply adjusting the excitation wavelength. The results of experimental and theoretical calculations indicated that the excitation-dependent emission colors were caused by different transfer paths for excitons under different excitation wavelengths. These materials with multifunctional luminescence could be used as writable inks for advanced anticounterfeiting.

Research Advances in the Subtype of Sepsis-Associated Thrombocytopenia.

The incidence and mortality of sepsis in the intensive care unit (ICU) are extremely high. Thrombocytopenia, one of the most common laboratory abnormalities, is correlated with prognosis in sepsis. The pathophysiology of sepsis-associated thrombocytopenia (SAT) remains unclear and may be associated with several factors such as platelet activation due to vascular injury and pathogen, suppression of bone marrow, platelet-targeted antibodies and desialylation. This review summarized all these possible mechanisms in the 3 subtypes of SAT: increased platelet consumption, reduced platelet production and increased platelet destruction. Based on the clinically available platelet parameters, the evidence for identifying SAT subtypes and the recent progress in treatments according to these subtypes are proposed to provide new prospects for the management of SAT.