Polarization-engineered photon statistics and its tomography via optomagnonic interaction.

Cavity optomagnonics has received considerable research interest in recent years, due to the coherent magnetic Brillioun light scattering in the ferromagnetic material. Here, we theoretically propose and numerically verify a feasible scheme for the full polarization tomography on photon statistics in an optomagnonic whispering-gallery-mode microresonator system in the weak-coupling regime. By performing the polarization pre- and post-selections to manipulate the polarization states of the input and output photons, we find that the rich sub- and super-Poissonian photon statistics can be selectively generated, thanks to quantum interferences. In the parameter space of phase delay, the evolution from photon bunching to antibunching indicates the change from phase to amplitude squeezing. Our obtained result has potential applications in tunable quantum polarized light sources based on the cavity optomagnonic platform in micro-nano scale. It also offers a deeper understanding for full quantum cavity optomagnonics.

The role of age-associated alpha-synuclein aggregation in a conditional transgenic mouse model of Parkinson's disease: Implications for Lewy body formation.

Parkinson's disease (PD) is a common neurodegenerative disorder that is affecting an increasing number of older adults. Although PD is mostly sporadic, genetic mutations have been found in cohorts of families with a history of familial PD (FPD). The first such mutation linked to FPD causes a point mutation (A53T) in α-synuclein (α-syn), a major component of Lewy bodies, which are a classical pathological hallmark of PD. These findings suggest that α-syn is an important contributor to the development of PD. In our previous study, we developed an adenoviral mouse model of PD and showed that the expression of wild-type (WT) α-syn or a mutant form with an increased propensity to aggregate, designated as WT-CL1 α-syn, could be used to study how α-syn aggregation contributes to PD. In this study, we established a transgenic mouse model that conditionally expresses WT or WT-CL1 α-syn in dopaminergic (DA) neurons and found that the expression of either WT or WT-CL1 α-syn was associated with an age-dependent degeneration of DA neurons and movement dysfunction. Using this model, we were able to monitor the process of α-syn aggregate formation and found a correlation between age and the number and sizes of α-syn aggregates formed. These results provide a potential mechanism by which age-dependent α-syn aggregation may lead to the formation of Lewy bodies in PD pathogenesis.

Study on medicinal food plants in the Gaoligongshan Biosphere Reserve, the richest biocultural diversity center in China.

BACKGROUND: Traditional knowledge associated with medicinal food plants (MFPs) plays a vital role in fighting hidden hunger and safeguarding the health of local people. MFPs resources are abundant in the Gaoligongshan area, a biosphere reserve with the richest biocultural diversity in China. Local people of different linguistic groups also have rich traditional botanical knowledge. However, there are still few comprehensive and systematic studies on MFPs there. METHODS: Ethnobotanical investigation including market survey, semi-structured interviews, free listing and key informant interviews was conducted in the Gaoligongshan area, Western Yunnan, Southwest China. A total of 13 local farmers' markets were selected and information about medicinal food plants, including food categories, medicinal and edible parts, modes of consumption, medicinal effects, and distribution were collected. The relative occurrence frequency (RFO) and cultural food significance index (CFSI) were calculated to identify the culturally significant MFPs. RESULTS: A total of 184 species of MFPs, belonging to 83 families, were collected in the Gaoligongshan area, including vegetables (77), medicinal diets (26), fruits (25), spices (18), herbal tea (13), tea substitutes (11), substitutes for staple food (8), nuts (5), oils and fats (4), and dye material (1). The most frequently used families were Fabaceae, Asteraceae and Apiaceae, with 11, 10, and 9 species, respectively. The most frequently used plant parts were the stems, followed by fruits and leaves. Based on the evaluation results of the CFSI and RFO indices, 18 species of MFPs with magnificent local cultural importance have been screened out, such as Houttuynia cordata, Eryngium foetidum, Sechium edule, Centella asiatica and Pseudocydonia sinensis. CONCLUSION: These findings have guiding significance for conservation of traditional knowledge associated with MFPs and facilitation of scientific utilization of MFPs to meet local people's needs for a healthy life.

Bioactive self-healing umbilical cord blood exosomes hydrogel for promoting chronic diabetic wound healing.

The deleterious effects of diabetes mellitus on wound healing have become a major public health concern worldwide. Given the complex microenvironment of diabetic wounds and the high prevalence of diabetes, the design and development of novel wound dressing materials with versatile capabilities is urgent. Extracellular vesicles (EVs) derived from human umbilical cord blood have demonstrated the potential to counter inflammation and accelerate wound healing. Herein, we explored the efficacy of incorporating human umbilical cord blood-derived exosomes (UCB-Exos) into an ABA-type amphiphilic hydrogel, which possesses the attributes of exosome (Exo) encapsulation, temperature-triggered reversible sol-gel conversion, and Exo-regulated release, for enhancing the stability and retention of Exos. We sought to examine the feasibility of this strategy in augmenting the therapeutic efficacy of UCB-Exos for the healing of diabetes-related wounds. The injectable hydrogel was conveniently applied directly onto the wound surface and the enclosed Exo significantly facilitated the healing process, resulting in faster wound closure, enhanced collagen deposition, accelerated re-epithelialization, and enhanced neo-vascularization within two weeks compared with the hydrogel-only treatment group. In summary, some hydrogels hold great promise for promoting wound healing in diabetics and represent a novel therapeutic option for diabetes-related ulcers.

Morphology, Histology, and Transcriptome Analysis of Gonadal Development in Octopus minor (Sasaki, 1920).

Octopus minor is an economically important species, but little is known about the histological pattern and regulatory mechanisms during gonadal development. In this study, we investigated the annual changes in total body weight (TW), gonad somatic index (GSI), gonadal histological features, and transcriptome of O. minor. The results indicated that both females and males showed a similar TW trend. The GSI peaked in June in females, while it remained constant at around 3% in males. Nine and four histological stages were observed in ovaries and testes, respectively. Our field sampling results implied that O. minor might have overwintering periods for both eggs and larvae. Transcriptome analysis revealed that a total of 1095 and 2468 genes were significantly expressed during ovarian and testicular development, separately. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis displayed that 126 GO terms and 5 KEGG pathways were significantly enriched in the ovarian group of advanced vitellogenic oocytes vs vitellogenic oocytes (AVO vs VO). The pathways "Ribosomal", "Cell cycle", and "Progesterone-mediated oocyte maturation" were predicted to promote yolk deposition. Additionally, the testicular comparison group of spent vs mature (Spent vs Mature) showed significant enrichment in 674 GO terms and 13 KEGG pathways, suggesting that energy metabolism and cell repair pathways may be involved in the spermatogenesis process. This work revealed the development process of the gonads and shed light on the potential regulatory pathways of O. minor, providing novel insights and laying a molecular basis for artificial breeding.

Recent advances of oxidative stress in thromboangiitis obliterans: biomolecular mechanisms, biomarkers, sources and clinical applications.

Oxidative stress (OS) has been identified as a key factor in the development of Thromboangiitis Obliterans (TAO). The detection of OS levels in clinical and scientific research practice is mainly based on the measurement of oxidative stress such as reactive oxygen species (ROS), reactive nitrogen species (RNS) and lipid peroxides. These markers are typically assessed through a combination of physical and chemical methods. Smoking is known to the state of OS in TAO, and OS levels are significantly increased in smokers due to inadequate antioxidant protection, which leads to the expression of apoptotic proteins and subsequent cell injury, thrombosis and limb ischemia. There, understanding the role of OS in the pathogenesis of TAO may provide insights into the etiology of TAO and a basis for its prevention and treatment.

Smartphone-based pH responsive 3-channel colorimetric biosensor for non-enzymatic multi-antibiotic residues.

Antibiotic residues in animal-derived food pose a risk to food safety and human health. Here, a smartphone-based pH-responsive 3-channel colorimetric biosensor is constructed for rapid detection of non-enzymatic multi-antibiotic residues in milk. In this system, a magnetic separation and enrichment approach is designed to specifically capture different antibiotic residues in complex environment. Indicators loaded on polydopamine-silver nanoparticles with excellently pH responsive visualization properties are utilized to ensure the high sensitivity of detection system. Moreover, smartphones are introduced to fulfill the demand for portable and on-site inspection of practical applications. It achieves simultaneous detection of oxytetracycline, kanamycin and streptomycin in the linear range of 1-105 pg/mL with detection limits of 0.085, 0.168, and 0.307 pg/mL, respectively. The practicality of the reported multi-antibiotic residues detection system is successfully demonstrated and evaluated challenging milk samples. Therefore, this system demonstrates the wide applications in multi-antibiotic residue analysis and food safety guarantee.

The efficacy of concentrated growth factor and platelet-rich fibrin as scaffolds in regenerative endodontic treatment applied to immature permanent teeth: a retrospective study.

BACKGROUND: The aim of this retrospective study was to compare the efficacy of concentrated growth factor (CGF) and platelet-rich fibrin (PRF) as scaffolds in regenerative endodontic therapy (RET). METHODS: Necrotic immature permanent teeth treated with regenerative endodontic therapy during January 2018 to August 2022 were divided into the CGF and PRF groups according to the scaffold. The CGF and PRF groups included 7 and 6 teeth, respectively. The efficacy of regenerative endodontic therapy was analyzed based on the clinical and radiological outcomes at three different follow up periods: T1 (3-6 months), T2 (6-12 months) and T3 (12-24 months). Statistical analysis was performed using the independent T test, Mann-Whitney test and Fisher's exact test at a significance level of 0.05. RESULTS: The success rate of each stage in both groups was 100%. Through quantitative comparison of radiographic outcomes, there was no statistically significant difference between the two groups in terms of root development and periapical lesion healing at each stage, except that the increase rate of radiographic root area in PRF group in the T3 stage was above one in CGF group with statistically significance. CONCLUSIONS: Both CGF and PRF had a similar clinical performance regarding resolution of clinical signs and symptoms, periapical lesion healing, and continued root development as scaffolds in RET. Further prospective studies with large samples for longer follow-up periods are needed.

The phagocytic role of macrophage following myocardial infarction.

Myocardial infarction (MI) is one of the cardiovascular diseases with high morbidity and mortality. MI causes large amounts of apoptotic and necrotic cells that need to be efficiently and instantly engulfed by macrophage to avoid second necrosis. Phagocytic macrophages can dampen or resolve inflammation to protect infarcted heart. Phagocytosis of macrophages is modulated by various factors including proteins, receptors, lncRNA and cytokines. A better understanding of mechanisms in phagocytosis will be beneficial to regulate macrophage phagocytosis capability towards a desired direction in cardioprotection after MI. In this review, we describe the phagocytosis effect of macrophages and summarize the latest reported signals regulating phagocytosis after MI, which will provide a new thinking about phagocytosis-dependent cardiac protection after MI.

Treatment Outcome of Regenerative Endodontic Procedures for Necrotic Immature and Mature Permanent Teeth: A Systematic Review and Meta-Analysis Based on Randomised Controlled Trials.

PURPOSE: To analyse whether the stage of apical development affects the effectiveness of regenerative endodontic treatment by comparing the outcomes for necrotic mature and immature permanent teeth treated with regenerative endodontic procedures. MATERIALS AND METHODS: Multiple databases (PubMed, Cochrane Library, Web of Science, EMBASE and OpenGrey databases) were searched through February 17th, 2022. Inclusion criteria were randomised controlled trials that included treatment of necrotic immature or mature permanent teeth using any regenerative endodontic procedures (REPs) that aimed to achieve pulp revascularisation or regeneration. The Cochrane Risk of Bias 2.0 tool was used to assess risk of bias. The included indicators were asymptomatic sign, success, pulp sensitivity, and discolouration. The extracted data were expressed by percentage for statistical analysis. The random effect model was used to explain the results. Comprehensive Meta-Analysis Version 2 was used to perform the statistical analyses. RESULTS: Twenty-seven RCTs were eligible for inclusion in the meta-analysis. The success rates of necrotic immature and mature permanent teeth were 95.6% (95% CI, 92.4%-97.5%; I2=34.9%) and 95.5% (95%CI, 87.9%-98.4%; I2=0%), respectively. The asymptomatic rates of necrotic immature and mature permanent teeth were 96.2% (95%CI, 93.5%-97.9%; I2=30.1%) and 97.0% (95%CI, 92.6%-98.8%; I2=0%), respectively. The treatment of immature and mature necrotic permanent teeth with REPs yields high success rates and low symptomatic rates. The incidence of positive sensitivity response for electric pulp testing in necrotic immature permanent teeth (25.2% [95% CI, 18.2%-33.8%; I2=0%]) was lower than that in necrotic mature permanent teeth (45.4% [95% CI, 27.2%-64.8%; I2=75.2%]), and this difference was statistically significant. The restoration of pulp sensitivity seems to be more evident in necrotic mature permanent teeth than in necrotic immature permanent teeth. The crown discolouration rate of immature permanent teeth was 62.5% (95% CI, 49.7%-73.8%; I2=76.1%). Necrotic immature permanent teeth have a considerable crown discolouration rate. CONCLUSION: REPs for both immature and mature necrotic permanent teeth yield high success rates and promote root development. The vitality responses seem to be more evident in necrotic mature permanent teeth than in necrotic immature permanent teeth.

The effect of early versus delayed space closure on the rate of orthodontic tooth movement: a systematic review and meta-analysis.

BACKGROUND: Orthodontic space closure of extraction sites can be initiated early, within 1-week post-extraction, or it can be delayed for a month or more. OBJECTIVE: This systematic review aimed to evaluate the effect of early versus delayed initiation of space closure after tooth extraction on the rate of orthodontic tooth movement. SEARCH METHODS: Unrestricted search of 10 electronic databases was conducted until September 2022. SELECTION CRITERIA: Randomized controlled trials (RCTs) investigating the initiation time of space closure of extraction sites in patients undergoing orthodontic treatment were included. DATA COLLECTION AND ANALYSIS: Data items were extracted using a pre-piloted extraction form. The Cochrane's risk of bias tool (ROB 2.0) and the Grading of Recommendations, Assessment, Development, and Evaluation approach were used for quality assessment. Meta-analysis was undertaken if there are at least two trials reporting the same outcome. RESULTS: Eleven RCTs met the inclusion criteria. Meta-analysis revealed that early canine retraction resulted in a statistically significant higher rate of maxillary canine retraction when compared to delayed canine retraction [mean difference (MD); 0.17 mm/month, 95% CI: 0.06 to 0.28, P = 0.003, 4 RCTs, moderate quality]. Duration of space closure was shorter in the early space closure group, but not statistically significant (MD; 1.11 months, 95% CI: -0.27 to 2.49, P = 0.11, 2 RCTs, low quality). The incidence of gingival invaginations was not statistically different between early and delayed space closure groups (Odds ratio; 0.79, 95% CI: 0.27 to 2.29, 2 RCTs, P = 0.66, very low quality). Qualitative synthesis found no statistically significant differences between the two groups regarding anchorage loss, root resorption, tooth tipping, and alveolar bone height. CONCLUSIONS: Based on the available evidence, early traction within the first week after tooth extraction has a minimal clinically significant effect on the rate of tooth movement compared to delayed traction. Further high-quality RCTs with standardized time points and measurement methods are still needed. REGISTRATION: PROSPERO (CRD42022346026).

Monitoring Methodology Study of a Reservoir Built on the Karst Depression: A Large Scale Laboratory Simulation Test.

The karst depression with a natural negative landform is favorable for reservoir construction with less excavation work. The underground air-water pressure would be complicated after the construction of a reservoir that blocks the natural air-water channel (sinkhole, karst channel, etc.). To develop a monitoring system for the reservoir, a large-scale laboratory simulation test was carried out to study the air-pressure evolution and water migration process during water table fluctuation after the blockage of the sinkhole in a karst depression. The results are as follows. (1) The positive pressure jacking effect and the negative pressure sucking effect were observed in the karst channel and inside the model during groundwater table fluctuation. (2) A water imbibition test on the rock-like material was carried out with layered resistivity and layered NMR measurement. The relationship of resistivity and water saturation was developed based on Archie's equation. (3) The resistivity evolution during the test was monitored using the high-density electronic resistivity imaging method. The resistivity of the measured profile was sensitive to the variation of the water level, and the water migration process was quantified by the resistivity to water saturation conversion. (4) The suitability of many techniques for monitoring a reservoir built on the karst depression was discussed. The resistivity monitoring technique combined with the air-water pressure monitoring technique could provide useful information for safety and reliability assessment.

"From molecular to clinic": The pivotal role of CDC42 in pathophysiology of human papilloma virus related cancers and a correlated sensitivity of afatinib.

Background: Human papilloma virus (HPV)-related cancers are global health challenge. Insufficient comprehension of these cancers has impeded the development of novel therapeutic interventions. Bioinformatics empowered us to investigate these cancers from new entry points. Methods: DNA methylation data of cervical squamous cell carcinoma (CESC) and anal squamous cell carcinoma (ASCC) were analyzed to identify the significantly altered pathways. Through analyses integrated with RNA sequencing data of genes in these pathways, genes with strongest correlation to the TNM staging of CESC was identified and their correlations with overall survival in patients were assessed. To find a potential promising drug, correlation analysis of gene expression levels and compound sensitivity was performed. In vitro experiments were conducted to validate these findings. We further performed molecular docking experiments to explain our findings. Results: Significantly altered pathways included immune, HPV infection, oxidative stress, ferroptosis and necroptosis. 10 hub genes in these pathways (PSMD11, RB1, SAE1, TAF15, TFDP1, CORO1C, JOSD1, CDC42, KPNA2 and NUP62) were identified, in which only CDC42 high expression was statistically significantly correlated with overall survival (Hazard Ratio: 1.6, P = 0.045). Afatinib was then screened out to be tested. In vitro experiments exhibited that the expression level of CDC42 was upregulated in HaCaT/A431 cells transfected with HPV E6 and E7, and the inhibitory effect of afatinib on proliferation was enhanced after transfection. CDC42-GTPase-effector interface-EGFR-afatinib was found to be a stable complex with a highest ZDOCK score of 1264.017. Conclusion: We identified CDC42 as a pivotal gene in the pathophysiology of HPV-related cancers. The upregulation of CDC42 could be a signal for afatinib treatment and the mechanism in which may be an increased affinity of EGFR to afatinib, inferred from a high stability in the quaternary complex of CDC42-GTPase-effector interface-EGFR-afatinib.

Selective inhibition of HDAC6 promotes bladder cancer radiosensitization and mitigates the radiation-induced CXCL1 signalling.

BACKGROUND: Although trimodality therapy resecting tumours followed by chemoradiotherapy is emerged for muscle-invasive bladder cancer (MIBC), chemotherapy produces toxicities. Histone deacetylase inhibitors have been identified as an effective strategy to enhance cancer radiotherapy (RT). METHODS: We examined the role of HDAC6 and specific inhibition of HDAC6 on BC radiosensitivity by performing transcriptomic analysis and mechanism study. RESULTS: HDAC6 knockdown or HDAC6 inhibitor (HDAC6i) tubacin exerted a radiosensitizing effect, including decreased clonogenic survival, increased H3K9ac and α-tubulin acetylation, and accumulated γH2AX, which are similar to the effect of panobinostat, a pan-HDACi, on irradiated BC cells. Transcriptomics of shHDAC6-transduced T24 under irradiation showed that shHDAC6 counteracted RT-induced mRNA expression of CXCL1, SERPINE1, SDC1 and SDC2, which are linked to cell migration, angiogenesis and metastasis. Moreover, tubacin significantly suppressed RT-induced CXCL1 and radiation-enhanced invasion/migration, whereas panobinostat elevated RT-induced CXCL1 expression and invasion/migration abilities. This phenotype was significantly abrogated by anti-CXCL1 antibody, indicating the key regulator of CXCL1 contributing to BC malignancy. Immunohistochemical evaluation of tumours from urothelial carcinoma patients supported the correlation between high CXCL1 expression and reduced survival. CONCLUSION: Unlike pan-HDACi, the selective HDAC6i can enhance BC radiosensitization and effectively inhibit RT-induced oncogenic CXCL1-Snail-signalling, thus further advancing its therapeutic potential with RT.

Precisely Controllable Artificial Muscle with Continuous Morphing based on "Breathing" of Supramolecular Columns.

Skeletal muscles are natural motors executing sophisticated work through precise control of linear contraction. Although various liquid crystal polymers based artificial muscles have been designed, the mechanism based on mainly the order-disorder transition usually leads to discrete shape morphing, leaving arbitrary and precise deformation a huge challenge. Here, one novel photoresponsive hemiphasmidic side-chain liquid crystal polymer with a unique "breathing" columnar phase that enables continuous morphing is presented. Due to confinement inside the supramolecular columnar assembly, the cooperative movements of side-chains and backbones generate a significant negative thermal expansion and lead to temperature-controllable muscle-like elongation/contraction in the oriented polymer strip. The irreversible isomerization of the photoresponsive mesogens results in the synergistic phototunable bending and high-contrast fluorescence change. Based on the orthogonal responses to heat and light, controllable arm-like bending motions of this material, which is applicable in constructing advanced artificial muscles or intelligent soft robotics, are further demonstrated.

3D printed hemodialysis access and subcutaneous volume model as a guide for cannulation: A proof of concept training tool.

A 54-year-old underwent brachiocephalic arteriovenous fistula placement. Following maturation of the access, consistent cannulation for routine hemodialysis was challenging for clinical specialists. A three-dimensional intraluminal access model was generated, but clinical specialists adept at cannulation had difficulty orienting the model to the patient's anatomy without repeat supervision. When provided the model prima facie, 50% (4/8) clinical specialists were not able to spatially orient the model appropriately in the x-axis with respect to the coronal plane (2/8) or in the z-axis with respect to the transverse plane (2/8). Spatial renderings of the subcutaneous volume available for cannulation were then printed and physically applied to the vascular access model resulting in appropriate spatial orientation among all clinical specialists (n = 12) that were presented the models for the first time. Mean Kt/V increased during the 3-month period directly following model introduction. This case demonstrates the potential utility of 3D-modeling to readily visualize the subcutaneous volume of a hemodialysis vascular access and reduce cannulation error.

MALAT1 promotes platelet activity and thrombus formation through PI3k/Akt/GSK-3ß signalling pathway.

BACKGROUND: Ischaemic stroke and other cardiovascular illnesses are characterised by abnormalities in the processes of thrombosis and haemostasis, which rely on platelet activity. In platelets, a wide variety of microRNAs (long non-coding RNA, lncRNAs) is found. Due to the absence of nuclear DNA in platelets, lncRNAs may serve as critical post-transcriptional regulators of platelet activities. However, research into the roles of lncRNAs in platelets is limited. OBJECTIVE: The purpose of this study is to learn more about the molecular mechanism by which MALAT1 affects platelet activity and thrombus formation. METHODS/RESULTS: The CD34+ megakaryocytes used in this research as an in vitro model for human megakaryocytes and platelets. Cell adhesion and spreading are enhanced in the absence and presence of agonists in CD34+ megakaryocytes subjected to MALAT1 knockdown (KD). The adhesion and activity of platelet-like particles produced by MALAT1 KD cells are significantly enhanced at rest and after thrombin activation. Thrombus development on a collagen matrix is also greatly enhanced in the microfluidic whole-blood perfusion model: platelets lacking MALAT1 exhibit elevated accumulation, distributing area and activity. In addition, MALAT1-deficient mice bleed less and form a stable occlusive thrombus more quickly than wild-type mice. PTEN and PDK1 regulated the activity of MALAT1 in platelets to carry out its PI3k/Akt/GSK-3ß signalling pathway-related function. CONCLUSION: The suppression of MALAT1 expression significantly increases platelet adhesion, spreading, platelet activity, and thrombus formation. lncRNAs may constitute a unique class of platelet function modulators.

Weakly supervised semantic segmentation of histological tissue via attention accumulation and pixel-level contrast learning.

Objective. Histopathology image segmentation can assist medical professionals in identifying and diagnosing diseased tissue more efficiently. Although fully supervised segmentation models have excellent performance, the annotation cost is extremely expensive. Weakly supervised models are widely used in medical image segmentation due to their low annotation cost. Nevertheless, these weakly supervised models have difficulty in accurately locating the boundaries between different classes of regions in pathological images, resulting in a high rate of false alarms Our objective is to design a weakly supervised segmentation model to resolve the above problems.Approach. The segmentation model is divided into two main stages, the generation of pseudo labels based on class residual attention accumulation network (CRAANet) and the semantic segmentation based on pixel feature space construction network (PFSCNet). CRAANet provides attention scores for each class through the class residual attention module, while the Attention Accumulation (AA) module overlays the attention feature maps generated in each training epoch. PFSCNet employs a network model containing an inflated convolutional residual neural network and a multi-scale feature-aware module as the segmentation backbone, and proposes dense energy loss and pixel clustering modules are based on contrast learning to solve the pseudo-labeling-inaccuracy problem.Main results. We validate our method using the lung adenocarcinoma (LUAD-HistoSeg) dataset and the breast cancer (BCSS) dataset. The results of the experiments show that our proposed method outperforms other state-of-the-art methods on both datasets in several metrics. This suggests that it is capable of performing well in a wide variety of histopathological image segmentation tasks.Significance. We propose a weakly supervised semantic segmentation network that achieves approximate fully supervised segmentation performance even in the case of incomplete labels. The proposed AA and pixel-level contrast learning also make the edges more accurate and can well assist pathologists in their research.

Comparison of Different Anti-Demodex Strategies: A Systematic Review and Meta-Analysis.

BACKGROUND: Demodex mites are related to some inflammatory diseases such as rosacea and blepharitis and could be harmful in patients with immunodeficiency or immunosuppression, especially notable in patients using biologic like dupilumab. In order to have an objective observation of different anti-Demodex strategies, we conducted this study, based on interventional clinical evidence with quantified Demodex mite data. METHODS: We used the PubMed, Embase, ClinicalTrials.gov, Medline, and International Clinical Trials Registry Platform (ICTRP) as databases. To assess the risk of bias, the RoB2 and ROBINS-I tools were used. The certainty of evidence was assessed following the GRADE guideline. Furthermore, the effect sizes (ESs) of different strategies were compared in different time periods (0-1, 1-2, 2-3, >3 months), as well as Demodex decrease rates. RESULTS: 1,618 studies were identified in the databases, with 21 of which included in the final quantitative synthesis. Interventions in these studies included ivermectin, tea tree oil (TTO), permethrin, crotamiton, metronidazole, light therapies, combined therapies, and other therapies. During 0-1 month, the ES varied from 0.07 (cleanser) to 1.95 (systemic ivermectin-metronidazole). During 1-2 months, the ES varied from 0.88 (topical permethrin) to 4.40 (topical ivermectin). During 2-3 months, the ES varied from 0.79 (topical permethrin) to 8.37 (topical ivermectin). During the time of 3 months, the ES varied from 0.59 (topical permethrin) to 2.25 (intense pulsed light [IPL]). In terms of Demodex decrease rates, topical ivermectin, TTO, permethrin, IPL, and baby shampoo had achieved a nearly 100% decrease. The reported adverse events were mostly mild, without severe adverse events reported in any of the studies. CONCLUSIONS: We found ivermectin (topical and systemic), ivermectin-metronidazole (topical), and TTO (topical) are promising anti-Demodex interventions. In addition to traditional pharmacotherapy, light therapies, especially IPL and skin cleansing, could also be considered as effective methods to control Demodex mite infestation.

Silencing of Long Noncoding RNA TUG1 Ameliorates Atherosclerosis-Induced Myocardial Injury by Upregulating microRNA-30b-3p and Downregulating Brd4.

ABSTRACT: Long noncoding RNAs and microRNAs (miRNAs) are emerging biomarkers involved in human diseases, and we focused on the roles of long noncoding RNA taurine upregulated gene 1 (TUG1) and miR-30b-3p in the related mechanisms of atherosclerosis-induced myocardial injury. ApoE-deficient mice were fed with high-fat diet to establish atherosclerotic models and then were subjected to either TUG1 downregulation or miR-30b-3p upregulation treatment. The serum myocardial enzymes, inflammatory biomarkers, pathological changes, intramyocardial macrophage infiltration, and apoptosis of cardiomyocytes in atherosclerotic mice were determined. The expression of TUG1, miR-30b-3p, and bromodomain protein 4 (Brd4) in atherosclerotic models was evaluated. Moreover, the correlations of TUG1, miR-30b-3p, and Brd4 were verified. TUG1 and Brd4 were increased while miR-30b-3p was decreased in atherosclerotic mice. The silenced TUG1 or elevated miR-30b-3p attenuated atherosclerosis-induced myocardial injury mainly by reducing serum myocardial enzyme content and inflammatory response, improving pathological changes, and preventing macrophage infiltration and cardiomyocyte apoptosis in atherosclerotic mice. Mechanistically, TUG1 could competitively bind with miR-30b-3p to prevent the degradation of its target gene Brd4. This study reveals that the silencing of TUG1 ameliorates atherosclerosis-induced myocardial injury by upregulating miR-30b-3p and downregulating Brd4, which may provide novel targets for atherosclerosis treatment.