Comprehensive assessment of cellular senescence in the tumor microenvironment.

Cellular senescence (CS), a state of permanent growth arrest, is intertwined with tumorigenesis. Due to the absence of specific markers, characterizing senescence levels and senescence-related phenotypes across cancer types remain unexplored. Here, we defined computational metrics of senescence levels as CS scores to delineate CS landscape across 33 cancer types and 29 normal tissues and explored CS-associated phenotypes by integrating multiplatform data from ~20 000 patients and ~212 000 single-cell profiles. CS scores showed cancer type-specific associations with genomic and immune characteristics and significantly predicted immunotherapy responses and patient prognosis in multiple cancers. Single-cell CS quantification revealed intra-tumor heterogeneity and activated immune microenvironment in senescent prostate cancer. Using machine learning algorithms, we identified three CS genes as potential prognostic predictors in prostate cancer and verified them by immunohistochemical assays in 72 patients. Our study provides a comprehensive framework for evaluating senescence levels and clinical relevance, gaining insights into CS roles in cancer- and senescence-related biomarker discovery.

HIV Disclosure Among Sexually Infected People Living with HIV and AIDS in China: Prevalence, Influencing Factors, and Negative Outcomes.

HIV disclosure is crucial for HIV prevention and control, but may also lead to discrimination, insult, and even violence against people living with HIV and AIDS (PLWHAs). In this study, we examined HIV disclosure, its influencing factors, and its association with intimate partner violence (IPV) among 1153 PLWHAs through the sexual route in Jinan, Shandong Province, China. Our results showed that 76.4% (881/1153) PLWHAs had disclosed someone about their HIV infection, the HIV disclosure rates among family members, friends, spouses, and current fixed partners of PLWHAs were 43.5% (501/1153), 47.9% (552/1153), 56.8% (129/227), and 43.2% (336/777), respectively. HIV disclosure was affected by socio-demographics, disease characteristics, and psycho-social factors and varied among family members, close friends, spouses, and current fixed sexual partners. Age ≤ 33 years (aOR 1.79, 95% CI 1.27-2.53), heterosexual infection route (aOR 1.52, 95% CI 1.06-2.17), HIV diagnosis time > 36 months (aOR 1.84, 95% CI 1.30-2.59), with other chronic diseases (aOR 1.87, 95% CI 1.34-2.61), lower self-stigma (aOR 4.03-4.36, 95% CI 1.98-8.74), higher social support (aOR 1.71-1.73, 95% CI 1.03-2.83), no depression (aOR 1.54, 95% CI 1.12-2.11), and no suicidal ideation (aOR 1.79, 95% CI 1.28-2.50) were all independently associated with increased likelihood of HIV disclosure. HIV disclosure was associated with an increased risk of IPV among current fixed sexual partners (aOR 1.87, 95% CI 1.38-2.54) and spouses (aOR 2.54, 95% CI 1.41-4.56). Our findings suggest that the HIV disclosure rate of PLWHAs is still low and is affected by multiple factors. There is an urgent need to design targeted and comprehensive interventions to improve HIV disclosure. IPV prevention should also be incorporated into the intervention system of HIV disclosure to ensure adequate and continuous support for PLWHAs.

Modified red light 5-aminolevulinic acid photodynamic therapy versus low-dose isotretinoin therapy for moderate to severe acne vulgaris: A prospective, randomized, multicenter study.

BACKGROUND: Modified 5-aminolevulinic acid photodynamic therapy (M-PDT) and isotretinoin (ISO) are effective treatments for moderate to severe acne vulgaris. OBJECTIVE: To evaluate the efficacy and adverse effects of M-PDT and ISO for moderate to severe acne vulgaris. METHODS: A multicenter, randomized clinical trial was conducted with participants randomly assigned to the M-PDT group (up to 5 weekly sessions following manual comedone extraction) or the ISO group (oral ISO, 0.5 mg/kg/d for 6 months) and followed up to 6-months after therapy. RESULTS: A total of 152 patients were allocated. The overall effective rates in the M-PDT group were significantly higher than the ISO group at 1 month (67.74% vs 10.26%), whereas the opposite was the case 1 month after treatment (75.81% vs 97.44%). Time to achieve 50% lesion improvement in the M-PDT group was significantly less than the ISO group (1 vs 8 weeks). Overall, 70.67% of the ISO group patients experienced systemic side effects such as hepatotoxicity, whereas side effects were skin-limited in the M-PDT group. LIMITATIONS: Limitations of this study included relatively low numbers of participants and high withdrawal rate. CONCLUSION: M-PDT offers a more rapid onset of improvement, comparable overall efficacy, good tolerability, and comparable durability of response compared with ISO.

A Review on Wine Flavour Profiles Altered by Bottle Aging.

The wine flavour profile directly determines the overall quality of wine and changes significantly during bottle aging. Understanding the mechanism of flavour evolution during wine bottle aging is important for controlling wine quality through cellar management. This literature review summarises the changes in volatile compounds and non-volatile compounds that occur during wine bottle aging, discusses chemical reaction mechanisms, and outlines the factors that may affect this evolution. This review aims to provide a deeper understanding of bottle aging management and to identify the current literature gaps for future research.

Expansion of the multifunctionality in off-stoichiometric manganites using post-annealing and high pressure: physical and electrochemical studies.

Prospects for the use of manganites in various areas of modern technologies require comprehensive studies of their physical and chemical properties. La0.9Mn1.1O3 (LMO) ceramics have been synthesized at an annealing temperature tann of 1150 °C with further post-annealing at 1250, 1350, and 1450 °C. As tann increases, the structure symmetry changes, and both the crystallite size and chemical defects increase. The post-annealing, on one hand, leads to a dramatic reduction of the magnetocaloric effect (MCE) |-ΔSmaxM| from 3.50 to 0.75 J (kg K)-1 at 2 T and a Curie temperature TC from 227 to 113 K with increasing tann. On the other hand, an external hydrostatic high-pressure P works oppositely enhancing ferromagnetic interactions. The saturation of -ΔSmaxM and TC is already achieved at a relatively low P of ≈ 0.4 GPa. LMO-1150 exhibits the best magnetocaloric characteristics compared with other studied samples. Moreover, the electrochemical characteristics of the LMO materials as electrocatalysts for overall water splitting (OER process) and features of their transformation in different 0.5 M K2SO4, 0.5 M K2HPO4, and 0.1 M K2B4O7 electrolytes have been studied thoroughly. After electrocatalysis of LMO, the magnetization M decreases and TC remains, which makes it possible to control the depletion of electrodes and predict their working time based on the magnetic measurements. All samples show the best OER activity in the 0.5 M K2HPO4 media. The obtained results demonstrate the ways for controlling the MCE of LMO under changing internal and external conditions, and an evaluation of the possibilities for their OER applications in electrocatalysts.

Sex hormones and acne: State of the art.

Acne is an androgen-dependent inflammatory disease of sebaceous follicles. Herein, we reviewed and discussed the underlying pathways of androgen biosynthesis and metabolism, non-genomic regulation of androgen receptor expression and function, posttranslational regulation of androgen excess in acne and acne-associated syndromes, such as polycystic ovary syndrome, and congenital adrenal hyperplasia. We provide insights into the involvement of sex hormones, particularly androgens, in skin homeostasis and acne pathogenesis, including comedogenesis, lipogenesis, microbiota, and inflammation. Advanced understanding of the action mechanisms of classical acne treatment and new development of antiandrogens, both topical and systemic, are also highlighted.

Multifunctionality of lanthanum-strontium manganite nanopowder.

Manganites are multifunctional materials which are widely used in both technology and devices. In this article, new prospects of their use as nanoparticles for various types of applications are demonstrated. For that, the ferromagnetic nanopowder of La0.6Sr0.4MnO3 has been synthesized by the sol-gel method with a subsequent annealing at 700-900 °C. The crystal structure, phase composition and morphology of nanoparticles as well as magnetic, magnetothermal and electrocatalytic properties have been studied comprehensively. The critical sizes of superparamagnetic, single-domain, and multi-domain states have been determined. It has been established that an anomalously wide temperature range of magnetocaloric properties is associated with an additional contribution to the magnetocaloric effect from superparamagnetic nanoparticles. The maximum values of the specific loss power are observed in the relaxation hysteresis region near the magnetic phase transition temperature. The electrochemical stability and features of the decomposition of nanoparticles in 1 M KOH and Na2SO4 electrolytes have been determined. A decrease in the particle size contributes to an increase in electrocatalytic activity for overall water splitting. Magnetocaloric and electrocatalytic results of the work indicate the prospects for obtaining the possibility of changing the temperature regime of electrocatalysis using contactless heating or cooling.

Semi-Supervised Learning With Heterogeneous Distribution Consistency for Visible Infrared Person Re-Identification.

Visible infrared person re-identification (VI-ReID) exposes considerable challenges because of the modality gaps between the person images captured by daytime visible cameras and nighttime infrared cameras. Several fully-supervised VI-ReID methods have improved the performance with extensive labeled heterogeneous images. However, the identity of the person is difficult to obtain in real-world situations, especially at night. Limited known identities and large modality discrepancies impede the effectiveness of the model to a great extent. In this paper, we propose a novel Semi-Supervised Learning framework with Heterogeneous Distribution Consistency (HDC-SSL) for VI-ReID. Specifically, through investigating the confidence distribution of heterogeneous images, we introduce a Gaussian Mixture Model-based Pseudo Labeling (GMM-PL) method, which adaptively adjusts different thresholds for each modality to label the identity. Moreover, to facilitate the representation learning of unutilized data whose prediction is lower than the threshold, Modality Consistency Regularization (MCR) is proposed to ensure the prediction consistency of the cross-modality pedestrian images and handle the modality variance. Extensive experiments with different label settings on two VI-ReID datasets demonstrate the effectiveness of our method. Particularly, HDC-SSL achieves competitive performance with state-of-the-art fully-supervised VI-ReID methods on RegDB dataset with only 1 visible label and 1 infrared label per class.

Therapeutic potential of alternative splicing in cardiovascular diseases.

RNA splicing is an important RNA processing step required by multiexon protein-coding mRNAs and some noncoding RNAs. Precise RNA splicing is required for maintaining gene and cell function; however, mis-spliced RNA transcripts can lead to loss- or gain-of-function effects in human diseases. Mis-spliced RNAs induced by gene mutations or the dysregulation of splicing regulators may result in frameshifts, nonsense-mediated decay (NMD), or inclusion/exclusion of exons. Genetic animal models have characterised multiple splicing factors required for cardiac development or function. Moreover, sarcomeric and ion channel genes, which are closely associated with cardiovascular function and disease, are hotspots for AS. Here, we summarise splicing factors and their targets that are associated with cardiovascular diseases, introduce some therapies potentially related to pathological AS targets, and raise outstanding questions and future directions in this field.

Caloric restriction, Sirtuins, and cardiovascular diseases.

ABSTRACT: Caloric restriction (CR) is a well-established dietary intervention known to extend healthy lifespan and exert positive effects on aging-related diseases, including cardiovascular conditions. Sirtuins, a family of nicotinamide adenine dinucleotide (NAD + )-dependent histone deacetylases, have emerged as key regulators of cellular metabolism, stress responses, and the aging process, serving as energy status sensors in response to CR. However, the mechanism through which CR regulates Sirtuin function to ameliorate cardiovascular disease remains unclear. This review not only provided an overview of recent research investigating the interplay between Sirtuins and CR, specifically focusing on their potential implications for cardiovascular health, but also provided a comprehensive summary of the benefits of CR for the cardiovascular system mediated directly via Sirtuins. CR has also been shown to have considerable impact on specific metabolic organs, leading to the production of small molecules that enter systemic circulation and subsequently regulate Sirtuin activity within the cardiovascular system. The direct and indirect effects of CR offer a potential mechanism for Sirtuin modulation and subsequent cardiovascular protection. Understanding the interplay between CR and Sirtuins will provide new insights for the development of interventions to prevent and treat cardiovascular diseases.

Difference of ventricular synchrony between LBBP, LBFP and LVSP: A speckle tracking echocardiographic study.

PURPOSE: Left bundle branch area pacing (LBBAP) has emerged as a physiological and stable form of pacing. We aim to compare the mechanical ventricular synchrony of LBBP, LBFP, and LVSP. METHODS: Proximal Left bundle branch pacing (LBBP), left bundle fascicular pacing (LBFP) and left ventricular septal pacing (LVSP) were identified in patients with bradycardia who successfully underwent LBBAP. Patients with left ventricular ejection fraction (LVEF) < 50% or QRS duration (QRSd) ≥ 120 ms were excluded. By using electrocardiograms, the left ventricular activation time (LVAT) and QRS duration (QRSd) were measured to examine electrophysiological synchrony. As indications of mechanical synchrony, global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), and peak strain dispersion (PSD) were evaluated by using 2-dimensional speckle tracking echocardiography (2D-STE). RESULTS: In 56 patients, data were collected during LBBP (n = 18), LBFP (n = 16), and LVSP (n = 22). LVSP resulted in a longer LVAT (91.3 ± 14.9 ms) than LBBP (77.1 ± 10.8 ms, P < 0.05) and LBFP (72.1 ± 9.6 ms, P < 0.05), but all three groups had similar QRSd. There were no differences in GLS, GCS, GRS, or PSD between LBBP, LBFP, and LVSP. CONCLUSIONS: In patients with normal cardiac function and narrow QRS, though LBBAP with LBB capture resulted in better electrophysiological synchrony than without, the mechanical synchrony of the three groups was comparable.

TRPV3 promotes sebocyte inflammation via transcriptional modulating TLR2 in acne.

Acne is a common chronic inflammatory disease of the pilosebaceous unit. Transient receptor potential vanilloid 3 (TRPV3) is an ion channel that is involved in inflammatory dermatosis development. However, the involvement of TRPV3 in acne-related inflammation remains unclear. Here, we used acne-like mice and human sebocytes to examine the role of TRPV3 in the development of acne. We found that TRPV3 expression increased in the skin lesions of Propionibacterium acnes (P. acnes)-injected acne-like mice and the facial sebaceous glands (SGs) of acne patients. TRPV3 promoted inflammatory cytokines and chemokines secretion in human sebocytes and led to neutrophil infiltration surrounding the SGs in acne lesions, further exacerbating sebaceous inflammation and participating in acne development. Mechanistically, TRPV3 enhanced TLR2 level by promoting transcriptional factor phosphorylated-FOS-like antigen-1 (p-FOSL1) expression and its binding to the TLR2 promoter, leading to TLR2 upregulation and downstream NF-κB signaling activation. Genetic or pharmacological inhibition of TRPV3 both alleviated acne-like skin inflammation in mice via the TLR2-NF-κB axis. Thus, our study revealed the critical role of TRPV3 in sebaceous inflammation and indicated its potential as an acne therapeutic target.

Translation directionality and translator anxiety: Evidence from eye movements in L1-L2 translation.

While considerable research on the impact of anxiety on second language learning has been carried out in international contexts, the impact of anxiety on the translator's undertaking L2 translation, a sort of anxiety arising from the translation directionality, as well as the structure of cognitive mechanism for translational anxiety, remain under-explored. Adopting the eye-tracking and key-logging approach to data collection, this study implemented an eye-tracking experiment with EFL learners at a Chinese university to probe into how the participants responded to L1 and L2 translation-tasks and the mechanism involved in these processes. It is found that translation directionality does have a great impact on the processing of translation, which causes the change of cognitive load and then leads to the change of levels in translator anxiety. The finding further confirms the key premises of the Processing Proficiency Model and the Revised Hierarchical Model with attendant implications for translation processes.

Effect of 3.5 % NaCl solution with different Na2S concentrations on ultrasonic cavitation erosion behaviors of HVOF sprayed WC-Ni coatings.

In this article, the WC-10Ni coatings were fabricated by HVOF spray, then the ultrasonic cavitation erosion performances of the coatings in distilled water and 3.5 wt% NaCl solution with various Na2S concentrations (0, 20 and 200 ppm) were investigated. The results of the cumulative volume loss of the coating in different mediums showed that the coating exhibited enhanced cavitation erosion resistance with the increase of Na2S concentrations in medium. The reason for the improvement on the cavitation erosion performance was the growth of corrosion product films containing sulphide. In comparison with the coating after cavitation erosion in medium without Na2S, no large craters and deep grooves were observed on the eroded coating surface in medium with Na2S. The ultrasonic cavitation damage of the coating manifests as the spall of the metal binder phase (Ni) and exposure of the hard phase (WC).

[Prokaryotic expression and polyclonal antibodies preparation and identification of human focal adhesion kinase (FAK)].

Objective To Clone, express, and purify the focal adhesion kinase (FAK) gene C-terminal focal adhesion location sequence (aa798-aa1041), and to prepare and identify the rabbit anti-FAK polyclonal antibodies. Methods The C-terminal (2671 bp-3402 bp) gene of the FAK gene was amplified by PCR in vitro and cloned into pCZN1 vector to construct a pCZN1-FAK recombinant expression vector. The recombinant expression vector was transformed into E. coli expression strain BL21 (DE3) competent cells, and then induced by isopropy-ß-D-thiogalactoside (IPTG). The protein was purified by affinity chromatography resin Ni-NTA and immunized with New Zealand white Rabbit to prepare polyclonal antibodies. The antibody titer was detected by indirect ELISA and the specificity was identified by Western blot analysis. Results The pCZN1-FAK recombinant expression vector was successfully constructed. The FAK protein was mainly expressed in the form of inclusion bodies. After purification of the target protein, the prepared rabbit anti-FAK polyclonal antibody showed a titer of 1:512 000, and could specifically react with exogenous and endogenous FAK proteins. Conclusion The FAK protein is successfully cloned, expressed and purified, and a rabbit anti-FAK polyclonal antibody is prepared, which can be used for the specific detection of endogenous FAK protein.

Short-term effect of coil handle orientations on fMRI-guided rTMS on insomnia: A case report.

Introduction: The coil handle orientation plays a pivotal role in the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS). However, there is currently no consensus on the optimal individualized coil handle orientation, especially for non-motor areas. Case presentation: The present case reported a short-term effect of functional connectivity (FC)-guided rTMS with coil handle posterior-anterior 45° (PA45°) and posterior-anterior 135° (PA135°) on a patient with insomnia. Notably, in this case, the PA45° orientation was nearly perpendicular to the adjacent sulcus, while the PA135° orientation was almost parallel to it. Local brain activity and functional connectivity were assessed using resting-state functional magnetic resonance imaging (RS-fMRI). Additionally, motor evoked potentials (MEPs) were captured both pre and post-rTMS sessions. Findings: The coil handle orientation PA45° outperformed the PA135° in both RS-fMRI and MEP outcomes. Moreover, a 9-day rTMS treatment led to discernible improvements in symptoms of depression and anxiety, complemented by a modest enhancement in sleep quality.

[Detection of IgG protein in human urine based on vertical flow paper microfluidic chip].

The kidney is the body's most important organ and the protein components in urine could be detected for diagnosing certain diseases. The amount of IgG protein in urine could be used to determine the degree of kidney function damage. IgG protein in human urine was detected by vertical flow paper-based microfluidic chip, double-antibody sandwich immunoreaction, and cell phone image processing. The results showed that using an IgG antibody concentration of 500 µg/mL and a gold standard antibody concentration of 100 µg/mL, the image signal showed a good linear relationship in the range of IgG concentration of 0.2-3.2 µg/mL, with R2=0.973 3 achieved. A complete set of detection devices were designed and the detection method showed good non-specificity.

Localized Surface Plasmon-Enhanced Infrared-to-Visible Upconversion Devices Induced by Ag Nanoparticles.

Upconversion devices (UCDs) have motivated tremendous research interest with their excellent potential and promising application in photovoltaic sensors, semiconductor wafer detection, biomedicine, and light conversion devices, especially near-infrared-(NIR)-to-visible upconversion devices. In this research, a UCD that directly turned NIR light located at 1050 nm into visible light located at 530 nm was fabricated to investigate the underlying working mechanism of UCDs. The simulation and experimental results of this research proved the existence of the quantum tunneling phenomenon in UCDs and found that the quantum tunneling effect can be enhanced by a localized surface plasmon.

SIRT6 is an epigenetic repressor of thoracic aortic aneurysms via inhibiting inflammation and senescence.

Thoracic aortic aneurysms (TAAs) develop asymptomatically and are characterized by dilatation of the aorta. This is considered a life-threating vascular disease due to the risk of aortic rupture and without effective treatments. The current understanding of the pathogenesis of TAA is still limited, especially for sporadic TAAs without known genetic mutation. Sirtuin 6 (SIRT6) expression was significantly decreased in the tunica media of sporadic human TAA tissues. Genetic knockout of Sirt6 in mouse vascular smooth muscle cells accelerated TAA formation and rupture, reduced survival, and increased vascular inflammation and senescence after angiotensin II infusion. Transcriptome analysis identified interleukin (IL)-1ß as a pivotal target of SIRT6, and increased IL-1ß levels correlated with vascular inflammation and senescence in human and mouse TAA samples. Chromatin immunoprecipitation revealed that SIRT6 bound to the Il1b promoter to repress expression partly by reducing the H3K9 and H3K56 acetylation. Genetic knockout of Il1b or pharmacological inhibition of IL-1ß signaling with the receptor antagonist anakinra rescued Sirt6 deficiency mediated aggravation of vascular inflammation, senescence, TAA formation and survival in mice. The findings reveal that SIRT6 protects against TAA by epigenetically inhibiting vascular inflammation and senescence, providing insight into potential epigenetic strategies for TAA treatment.