Ultrasound deep learning radiomics and clinical machine learning models to predict low nuclear grade, ER, PR, and HER2 receptor status in pure ductal carcinoma in situ.

Background: Low nuclear grade ductal carcinoma in situ (DCIS) patients can adopt proactive management strategies to avoid unnecessary surgical resection. Different personalized treatment modalities may be selected based on the expression status of molecular markers, which is also predictive of different outcomes and risks of recurrence. DCIS ultrasound findings are mostly non mass lesions, making it difficult to determine boundaries. Currently, studies have shown that models based on deep learning radiomics (DLR) have advantages in automatic recognition of tumor contours. Machine learning models based on clinical imaging features can explain the importance of imaging features. Methods: The available ultrasound data of 349 patients with pure DCIS confirmed by surgical pathology [54 low nuclear grade, 175 positive estrogen receptor (ER+), 163 positive progesterone receptor (PR+), and 81 positive human epidermal growth factor receptor 2 (HER2+)] were collected. Radiologists extracted ultrasonographic features of DCIS lesions based on the 5th Edition of Breast Imaging Reporting and Data System (BI-RADS). Patient age and BI-RADS characteristics were used to construct clinical machine learning (CML) models. The RadImageNet pretrained network was used for extracting radiomics features and as an input for DLR modeling. For training and validation datasets, 80% and 20% of the data, respectively, were used. Logistic regression (LR), support vector machine (SVM), random forest (RF), and eXtreme Gradient Boosting (XGBoost) algorithms were performed and compared for the final classification modeling. Each task used the area under the receiver operating characteristic curve (AUC) to evaluate the effectiveness of DLR and CML models. Results: In the training dataset, low nuclear grade, ER+, PR+, and HER2+ DCIS lesions accounted for 19.20%, 65.12%, 61.21%, and 30.19%, respectively; the validation set, they consisted of 19.30%, 62.50%, 57.14%, and 30.91%, respectively. In the DLR models we developed, the best AUC values for identifying features were 0.633 for identifying low nuclear grade, completed by the XGBoost Classifier of ResNet50; 0.618 for identifying ER, completed by the RF Classifier of InceptionV3; 0.755 for identifying PR, completed by the XGBoost Classifier of InceptionV3; and 0.713 for identifying HER2, completed by the LR Classifier of ResNet50. The CML models had better performance than DLR in predicting low nuclear grade, ER+, PR+, and HER2+ DCIS lesions. The best AUC values by classification were as follows: for low nuclear grade by RF classification, AUC: 0.719; for ER+ by XGBoost classification, AUC: 0.761; for PR+ by XGBoost classification, AUC: 0.780; and for HER2+ by RF classification, AUC: 0.723. Conclusions: Based on small-scale datasets, our study showed that the DLR models developed using RadImageNet pretrained network and CML models may help predict low nuclear grade, ER+, PR+, and HER2+ DCIS lesions so that patients benefit from hierarchical and personalized treatment.

Intracranial aneurysm circulating exosome-derived LncRNA ATP1A1-AS1 promotes smooth muscle cells phenotype switching and apoptosis.

Exosomal long non-coding RNAs (LncRNAs) play a crucial role in the pathogenesis of cerebrovascular diseases. However, the expression profiles and functional significance of exosomal LncRNAs in intracranial aneurysms (IAs) remain poorly understood. Through high-throughput sequencing, we identified 1303 differentially expressed LncRNAs in the plasma exosomes of patients with IAs and healthy controls. Quantitative real-time polymerase chain reaction (qRT-PCR) verification confirmed the differential expression of LncRNAs, the majority of which aligned with the sequencing results. ATP1A1-AS1 showed the most significant upregulation in the disease group. Importantly, subsequent in vitro experiments validated that ATP1A1-AS1 overexpression induced a phenotype switching in vascular smooth muscle cells, along with promoting apoptosis and upregulating MMP-9 expression, potentially contributing to IAs formation. Furthermore, expanded-sample validation affirmed the high diagnostic value of ATP1A1-AS1. These findings suggest that ATP1A1-AS1 is a potential therapeutic target for inhibiting IAs progression and serves as a valuable clinical diagnostic marker.

Vegetation communities and soil properties along the restoration process of the Jinqianghe mine site in the Qilian Mountains, China.

The study explores the impact of mine grassland restoration on plant communities and soil properties in alpine grasslands, a subject of significant interest due to the observed relationship between grassland changes, plant communities, and soil properties. While prior research has mainly focused on the consequences of grassland degradation on plant diversity and soil characteristics, the specific effects of varying restoration degrees in alpine mining grasslands at the regional scale remain poorly understood. To address this knowledge gap, we established 15 sampling plots (0.5m×0.5m) across five different restoration degrees within alpine mining grasslands in the Qilian Mountains, China. Our objective was to assess the variations in plant diversity and soil properties along these restoration gradients. We conducted comprehensive analyses, encompassing soil properties [soil water content (SWC), available nitrogen (AN), total phosphorus (TP), nitrate nitrogen (NO3-N), ammonium nitrogen (NH4-N), total nitrogen (TN), available phosphorus (AP), soil organic carbon (SOC), nitrate nitrogen, soil pH, and electrical conductivity (EC)], plant characteristics (height, density, frequency, coverage, and aboveground biomass), and plant diversity indices (Simpson, Shannon-Wiener, Margalef, Dominance, and Evenness indexes). Our findings included the identification and collection of 18 plant species from 11 families and 16 genera across the five restoration degrees: Very Low Restoration Degree (VLRD), Low Restoration Degree (LRD), Moderate Restoration Degree (MRD), High Restoration Degree (HRD), and Natural Grassland (NGL). Notably, species like Carex duriuscula, Cyperus rotundus, and Polygonum viviparum showed signs of recovery. Principal component analysis and Pearson correlation analysis revealed that soil pH, SWC, SOC, NO3-N, and AN were the primary environmental factors influencing plant communities. Specifically, soil pH and EC decreased as restoration levels increased, while SWC, AN, TP, NH4-N, TN, AP, SOC, and NO3-N exhibited a gradual increase with greater restoration efforts. Furthermore, the HRD plant community demonstrated similarities to the NGL, indicating the most effective natural recovery. In conclusion, our study provides valuable insights into the responses of plant community characteristics, plant diversity, and soil properties across varying restoration degrees to environmental factors. It also elucidates the characteristics of plant communities along recovery gradients in alpine grasslands.

Identification of clinically relevant subsets CD39+PD-1+CD8+ T cells and CD39+ regulatory T cells in intrahepatic cholangiocarcinoma using single-cell CyTOF.

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive liver malignancy with limited treatment options and a dismal prognosis. The tumor immune microenvironment (TIME) is crucial for iCCA progression, yet its comprehensive characterization remains incomplete. This study utilized mass cytometry by time of flight (CyTOF) to comprehensively analyze immune cell populations in fresh iCCA tumor samples and adjacent peritumor liver tissues. Notably, NK cell percentages significantly decreased in iCCA lesions compared to peritumor liver tissues. Conversely, an enrichment of immunosuppressive CD39+Foxp3+CD4+ regulatory T cells (CD39+T-regs) and exhausted-like CD8+T cells (with pronounced CD39 and PD-1 expression) within TIME was identified and confirmed by multiplex immunofluorescence staining in an independent patient cohort (n = 140). Crucially, tumor-infiltrating CD39+T-regs and CD39+PD-1+CD8+T cells emerged as independent prognostic indicators associated with an unfavorable prognosis in iCCA. These findings unveil the intricate immune landscape within iCCA, offering valuable insights for disease management and novel cancer immunotherapies.

Class I HDAC inhibitors enhance antitumor efficacy and persistence of CAR-T cells by activation of the Wnt pathway.

Epigenetic modification shapes differentiation trajectory and regulates the exhaustion state of chimeric antigen receptor T (CAR-T) cells. Limited efficacy induced by terminal exhaustion closely ties with intrinsic transcriptional regulation. However, the comprehensive regulatory mechanisms remain largely elusive. Here, we identify class I histone deacetylase inhibitors (HDACi) as boosters of CAR-T cell function by high-throughput screening of chromatin-modifying drugs, in which M344 and chidamide enhance memory maintenance and resistance to exhaustion of CAR-T cells that induce sustained antitumor efficacy both in vitro and in vivo. Mechanistically, HDACi decrease HDAC1 expression and enhance H3K27ac activity. Multi-omics analyses from RNA-seq, ATAC-seq, and H3K27ac CUT&Tag-seq show that HDACi upregulate expression of TCF4, LEF1, and CTNNB1, which subsequently activate the canonical Wnt/ß-catenin pathway. Collectively, our findings elucidate the functional roles of class I HDACi in enhancing CAR-T cell function, which provides the basis and therapeutic targets for synergic combination of CAR-T cell therapy and HDACi treatment.

SDMI-Net: Spatially Dependent Mutual Information Network for semi-supervised medical image segmentation.

Semi-supervised medical image segmentation strives to polish deep models with a small amount of labeled data and a large amount of unlabeled data. The efficiency of most semi-supervised medical image segmentation methods based on voxel-level consistency learning is affected by low-confidence voxels. In addition, voxel-level consistency learning fails to consider the spatial correlation between neighboring voxels. To encourage reliable voxel-level consistent learning, we propose a dual-teacher affine consistent uncertainty estimation method to filter out some voxels with high uncertainty. Moreover, we design the spatially dependent mutual information module, which enhances the spatial dependence between neighboring voxels by maximizing the mutual information between the local voxel blocks predicted from the dual-teacher models and the student model, enabling consistent learning at the block level. On two benchmark medical image segmentation datasets, including the Left Atrial Segmentation Challenge dataset and the BraTS-2019 dataset, our method achieves state-of-the-art performance in both quantitative and qualitative aspects.

Associations of combined phenotypic aging and genetic risk with incident cancer: A prospective cohort study.

Background: Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of site-specific and overall cancer. Methods: Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) with cancer incidence by genetic risk group among 374,463 participants from the UK Biobank. We generated PhenoAge using chronological age and nine biomarkers, PhenoAgeAccel after subtracting the effect of chronological age by regression residual, and an incidence-weighted overall cancer polygenic risk score (CPRS) based on 20 cancer site-specific polygenic risk scores (PRSs). Results: Compared with biologically younger participants, those older had a significantly higher risk of overall cancer, with hazard ratios (HRs) of 1.22 (95% confidence interval, 1.18-1.27) in men, and 1.26 (1.22-1.31) in women, respectively. A joint effect of genetic risk and PhenoAgeAccel was observed on overall cancer risk, with HRs of 2.29 (2.10-2.51) for men and 1.94 (1.78-2.11) for women with high genetic risk and older PhenoAge compared with those with low genetic risk and younger PhenoAge. PhenoAgeAccel was negatively associated with the number of healthy lifestyle factors (Beta = -1.01 in men, p<0.001; Beta = -0.98 in women, p<0.001). Conclusions: Within and across genetic risk groups, older PhenoAge was consistently related to an increased risk of incident cancer with adjustment for chronological age and the aging process could be retarded by adherence to a healthy lifestyle. Funding: This work was supported by the National Natural Science Foundation of China (82230110, 82125033, 82388102 to GJ; 82273714 to MZ); and the Excellent Youth Foundation of Jiangsu Province (BK20220100 to MZ).

Age is a major risk factor for cancer. Other factors, such as lifestyle or environmental exposures, may increase or mitigate cancer risks. Biological age, which considers accelerated aging processes, may, however, better predict cancer risk than chronological age. Some scientists propose using biological aging measures as an alternative for assessing cancer and other age-related disease risks, as these markers may provide a more accurate assessment of the various factors contributing to cancer risk. PhenoAge, a measure of biological aging processes in the body, could provide an alternative way to assessing aging-related cancer risks. This tool utilizes an individual's chronological age and nine biomarkers of aging processes. It has the potential to identify individuals whose aging process is accelerated compared to their peers, potentially indicating an increased cancer risk. This information may empower them to make lifestyle changes that could significantly reduce their risk. To assess the suitability of PhenoAge, Bian, Ma et al. used nine clinical chemistry biomarkers and chronological age to calculate PhenoAge in 374,463 participants from the UK Biobank. Their findings revealed that people with older PhenoAges ­ regardless of their genetic risk profiles ­ have an increased risk of cancer. Individuals with higher PhenoAge scores, indicating accelerated biological aging, had a roughly 25 percent higher risk of developing cancer. Individuals with both a high genetic risk and higher PhenoAge score had roughly double the risk of cancer. People with lower PhenoAges were more likely to have healthier lifestyles. These results suggest that adopting healthier lifestyles may slow the aging process and reduce cancer risk. While the analyses conducted by Bian, Ma et al. provide promising insights, they also underscore the need for further research. PhenoAge may offer a way to assess biological aging and identify individuals at higher risk of cancer. Those with higher PhenoAge scores may benefit from earlier cancer screening, and adopting a healthier lifestyle could potentially slow down the aging process and reduce their cancer risk. However, more studies in more diverse cohorts of people are needed to confirm that PhenoAge is a reliable marker for cancer risk and to test interventions to slow aging and reduce cancer risks in individuals with accelerated aging.

Estimating Rotational Acceleration in Shoulder and Elbow Joints Using a Transformer Algorithm and a Fusion of Biosignals.

In the present study, we used a transformer model and a fusion of biosignals to estimate rotational acceleration in elbow and shoulder joints. To achieve our study objectives, we proposed a mechanomyography (MMG) signal isolation technique based on a variational mode decomposition (VMD) algorithm. Our results show that the VMD algorithm delivered excellent performance in MMG signal extraction compared to the commonly used technique of empirical mode decomposition (EMD). In addition, we found that transformer models delivered estimates of joint acceleration that were more precise than those produced by mainstream time series forecasting models. The average R2 values of transformer are 0.967, 0.968, and 0.935, respectively. Finally, we found that using a fusion of signals resulted in more precise estimation performance compared to using MMG signals alone. The differences between the average R2 values are 0.041, 0.053, and 0.043, respectively. Taken together, the VMD isolation method, the transformer algorithm and the signal fusion technique described in this paper can be seen as supplying a robust framework for estimating rotational acceleration in upper-limb joints. Further study is warranted to examine the effectiveness of this framework in other musculoskeletal contexts.

Mechanical energy triggered piezo-catalyzation of Bi2WO6 nanoplates on ferrate (Fe(VI)) oxidation in alkaline media: Performance and mechanism.

Piezo-electricity, as a unique physical phenomenon, demonstrates high effectiveness in capturing the environmental mechanical energy into polarization charges, offering the possibility to activate the advanced oxidation processes via the electron pathway. However, information regarding the intensification of Fe(VI) through piezo-catalysis is limited. Therefore, our study is the first to apply Bi2WO6 nanoplates for piezo-catalyzation of Fe(VI) to enhance bisphenol A (BPA) degradation. Compared to Fe(VI) alone, the Fe(VI)/piezo/Bi2WO6 system exhibited excellent BPA removal ability, with the degradation rate increased by 32.6% at pH 9.0. Based on the experimental and theoretical results, Fe(VI), Fe(V), Fe(IV) and •OH were confirmed as reaction active species in the reaction, and the increased BPA removal mainly resulted from the enhanced formation of Fe(IV)/Fe(V) species. Additionally, effects of coexisting anions (e.g., Cl-, NO3-, SO42- and HCO3-), humic acid and different water matrixes (e.g., deionized water, tap water and lake water) on BPA degradation were studied. Results showed the Fe(VI)/piezo/Bi2WO6 system still maintained satisfactory BPA degradation efficiencies under these conditions, guaranteeing future practical applications in surface water treatment. Furthermore, the results of intermediates identification, ECOSAR calculation and cytotoxicity demonstrated that BPA degradation by Fe(VI)/piezo/Bi2WO6 posed a diminishing ecological risk. Overall, these findings provide a novel mechanical energy-driven piezo-catalytic approach for Fe(VI) activation, enabling highly efficient pollutant removal under alkaline condition.

Red ginseng ameliorates lipotoxicity-induced renal fibrosis in hyperuricemia mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic kidney disease can be caused by numerous diseases including obesity and hyperuricemia (HUA). Obesity may exacerbate the renal injury caused by HUA. Red ginseng, a steamed products of Panax ginseng Meyer root, is known for its remarkable efficacy in improving metabolic syndrome, such as maintaining lipid metabolic balance. However, the role of red ginseng on hyperuricemia-induced renal injury in obese cases remains unclear. AIM OF THE STUDY: This study aimed to investigate the action of red ginseng extract (RGE) on lipotoxicity-induced renal injury in HUA mice. MATERIALS AND METHODS: A high-fat diet (HFD)-induced obesity model was employed to initially investigate the effects of RGE on body weight, TC, OGTT, renal lipid droplets, and renal function indices such as uric acid, creatinine, and urea nitrogen. Renal structural improvement was demonstrated by H&E staining. Subsequently, an animal model combining obesity and HUA was established to further study the impact of RGE on OAT1 and ACC1 expression levels. The mechanisms underlying renal injury regulation by RGE were postulated on the basis of RNA sequencing, which was verified by immunohistochemical (including F4/80, Ki67, TGF-ß1, α-SMA, and E-cadherin), Masson, and Sirius red staining. RESULTS: RGE modulated HFD-induced weight gain, glucose metabolism, and abnormalities of uric acid, urea nitrogen, and creatinine. RGE alleviated the more severe renal histopathological changes induced by obesity combined with HUA, with down-regulated the protein levels of ACC1, F4/80, Ki67, TGF-ß1, and α-SMA, and up-regulated OAT1 and E-cadherin. CONCLUSIONS: RGE has ameliorative effects on chronic kidney disease caused by obesity combined with HUA by maintaining lipid balance and reducing renal inflammation and fibrosis.

Effect of moxibustion combined with intraperitoneal injection of benazepril on endoplasmic reticulum stress-related protein phosphorylation in rats with chronic heart failure. / è‰¾ç¸è”åˆè´é‚£æ™®åˆ©å¯¹æ ¢æ€§å¿ƒåŠ›è¡°ç«­å¤§é¼ å¿ƒè‚Œå† è´¨ç½‘åº”æ¿€ç›¸å ³è›‹ç™½ç£·é ¸åŒ–è¡¨è¾¾çš„å½±å“.

OBJECTIVES: To observe the effect of moxibustion at "Xinshu"(BL15) and "Feishu"(BL13) combined with intraperitoneal injection of benazepril on cardiac function and phosphorylation of protein kinase R-like endoplasmic reticulum kinase (PERK) and eukaryotic initiation factor 2α (elF2α) proteins in myocardium of rats with chronic heart failure (CHF), so as to explore its potential mechanism underlying improvement of CHF. METHODS: A total of 42 male SD rats were randomly assigned to blank control (n=10), CHF model (n=7), medication (benazepril, n=8), moxibustion (n=8) and moxibustion+benazepril (n=9) groups, after cardiac ultrasound model identification and elimination of the dead. The CHF model was established by intraperitoneal injection of doxorubicin hydrochloride (DOX), once every week for 6 weeks. Mild moxibustion was applied to bilateral BL15 and BL13 regions for 20 min, once daily for 3 weeks. The rats of the medication group and moxibustion+benazepril group (benazepril was given first, followed by moxibustion) received intraperitoneal injection of benazepril (0.86 mg/kg) solution once daily for 3 weeks . The cardiac ejection fraction (EF) and left ventricular fractional shortening (FS) were measured using echocardiography. Histopathological changes of the cardiac muscle tissue were observed under light microscope after hematoxylin-eosin (H.E.) staining. Serum contents of B-type brain natriuretic peptide (BNP) and angiotensin Ⅱ (AngⅡ) were measured by enzyme-linked immunosorbent assay (ELISA). The expressions of phospho-PERK (p-PERK) and phospho-elF2α (p-elF2α) in the myocardium were detected by Western blot. RESULTS: Compared with the blank control group, the EF and FS of the left cardiac ventricle were significantly decreased (P<0.01), while the contents of serum BNP and AngⅡ, and expression levels of p-PERK and p-eIF2α significantly increased in the model group (P<0.01). In comparison with the model group, both the decreased EF and FS and the increased BNP and AngⅡ contents as well as p-PERK and p-elF2α expression levels were reversed by moxibustion, medication and moxibustion+benazepril (P<0.01). The effects of moxibustion+benazepril were markedly superior to those of simple moxibustion and simple medication in raising the levels of EF and FS rate and in down-regulating the contents of BNP, Ang Ⅱ, levels of p-PERK and p-elF2α (P<0.01, P<0.05). Outcomes of H.E. staining showed irregular arrangement of cardiomyocytes, cell swelling, vacuole and inflammatory infiltration in the model group, which was relatively milder in the 3 treatment groups. The effects of moxibustion+benazepril were superior to those of moxibustion or benazepril. CONCLUSIONS: Moxibustion combined with Benazepril can improve the cardiac function in CHF rats, which may be related to its functions in down-regulating the expression levels of myocardial p-PERK and p-elF2α to inhibit endoplasmic reticulum stress response.

Thread-structural microneedles loaded with engineered exosomes for annulus fibrosus repair by regulating mitophagy recovery and extracellular matrix homeostasis.

Low back pain is among the most grave public health concerns worldwide and the major clinical manifestation of intervertebral disc degeneration (IVDD). The destruction of annulus fibrosus (AF) is the primary cause of IVDD. A sustainable and stable treatment system for IVDD is lacking because of the special organizational structure and low nutrient supply of AF. We here found that IVDD results in the impaired mitochondrial function of AF tissue, and mitochondrial autophagy (mitophagy) plays a protective role in this process. We therefore reported a thread-structural microneedle (T-MN) matching the ring structure of AF. Based on the adsorption effect of laminin, our T-MN could load with bone marrow mesenchymal stem cell-derived exosomes to envelope the regulating mitophagy microRNA (miRNA 378), named as T-MN@EXO@miR-378. In general, we offered in situ locking in the defect site of AF to prevent nucleus pulposus leakage and promoted AF repair. The design of the thread structure was aimed at bionically matching the layered AF structure, thereby providing stronger adhesion. The T-MN@EXO@miR-378 effectively attached to AF and slowly released therapeutic engineered exosomes, and prevented IVDD progression by restoring mitophagy, promoting AF cell proliferation and migration, and inhibiting the pathological remodeling of the extracellular matrix. This functional system can be used as an excellent tool for sustained drug release and has a certain prospect in substituting the conventional treatment of IVDD.

Validation of LymphGen classification on a 400-gene clinical next-generation sequencing panel in diffuse large B-cell lymphoma: real-world experience from a cancer center.

Not available.

Randomized Experiments to Reduce Overuse of Health Care: A Scoping Review.

OBJECTIVE: Health care overuse is pervasive in countries with advanced health care delivery systems. We hypothesize that effective interventions to reduce low-value care that targets patients or clinicians are mediated by psychological and cognitive processes that change behaviors and that interventions targeting these processes are varied. Thus, we performed a scoping review of experimental studies of interventions, including the interventions' objectives and characteristics, to reduce low-value care that targeted psychological and cognitive processes. METHODS: We systematically searched databases for experimental studies of interventions to change cognitive orientations and affective states in the setting of health care overuse. Outcomes included observed overuse or a stated intention to use services. We used existing frameworks for behavior change and mechanisms of change to categorize the interventions and the mediating processes. RESULTS: Twenty-seven articles met the inclusion criteria. Sixteen studied the provision of information to patients or clinicians, with most providing cost information. Six studies used educational interventions, including the provision of feedback about individual practice. Studies rarely used counseling, behavioral nudges, persuasion, and rewards. Mechanisms for behavior change included gain in knowledge or confidence and motivation by social norms. CONCLUSIONS: In this scoping review, we found few experiments testing interventions that directly target the psychological and cognitive processes of patients or clinicians to reduce low-value care. Most studies provided information to patients or clinicians without measuring or considering mediating factors toward behavior change. These findings highlight the need for process-driven experimental designs, including trials of behavioral nudges and persuasive language involving a trusting patient-clinician relationship, to identify effective interventions to reduce low-value care.

Histatin 5-Inspired Short-Chain Peptides Selectively Combating Pathogenic Fungi with Multifaceted Mechanisms.

Short-chain antifungal peptides (AFPs) inspired by histatin 5 have been designed to address the problem of antifungal drug resistance. These AFPs demonstrate remarkable antifungal activity, with a minimal inhibitory concentration as low as 2 µg mL-1 . Notably, these AFPs display a strong preference for targeting fungi rather than bacteria and mammalian cells. This is achieved by binding the histidine-rich domains of the AFPs to the Ssa1/2 proteins in the fungal cell wall, as well as the reduced membrane-disrupting activity due to their low amphiphilicity. These peptides disrupt the nucleus and mitochondria once inside the cells, leading to reactive oxygen species production and cell damage. In a mouse model of vulvovaginal candidiasis, the AFPs demonstrate not only antifungal activity, but also promote the growth of beneficial Lactobacillus spp. This research provides valuable insights for the development of fungus-specific AFPs and offers a promising strategy for the treatment of fungal infectious diseases.

A Cyclical Magneto-Responsive Massage Dressing for Wound Healing.

Tissue development is mediated by a combination of mechanical and biological signals. Currently, there are many reports on biological signals regulating repair. However, insufficient attention is paid to the process of mechanical regulation, especially the active mechanical regulation in vivo, which has not been realized. Herein, a novel dynamically regulated repair system for both in vitro and in vivo applications is developed, which utilizes magnetic nanoparticles as non-contact actuators to activate hydrogels. The magnetic hydrogel can be periodically activated and deformed to different amplitudes by a dynamic magnetic system. An in vitro skin model is used to explore the impact of different dynamic stimuli on cellular mechano-transduction signal activation and cell differentiation. Specifically, the effect of mechanical stimulation on the phenotypic transition of fibroblasts to myofibroblasts is investigated. Furthermore, in vivo results verify that dynamic massage can simulate and enhance the traction effect in skin defects, thereby accelerating the wound healing process by promoting re-epithelialization and mediating dermal contraction.

The association between METS-IR, an indirect index for insulin resistance, and lung cancer risk.

BACKGROUND: Insulin resistance has been reported to increase the risk of breast, prostate and colorectal cancer. However, the role of insulin resistance and its interaction with genetic risk in the development of lung cancer remains controversial. Therefore, we aimed to explore the association between a novel metabolic score for insulin resistance (METS-IR) and lung cancer risk. METHODS: A total of 395 304 participants without previous cancer at baseline were included. The Cox proportional hazards regression model was performed to investigate the association between METS-IR and lung cancer risk. In addition, a Mendelian randomization analysis was also performed to explore the causal relationship. The joint effects and additive interactions between METS-IR and polygenetic risk score (PRS) of lung cancer were also investigated. RESULTS: During a median follow-up of 11.03 years (Inter-quartile range (IQR): 10.30-11.73), a total of 3161 incident lung cancer cases were diagnosed in 395 304 participants. There was a significant association between METS-IR and lung cancer risk, with an HR of 1.28 (95% CI: 1.17-1.41). Based on the Mendelian randomization analysis, however, no causal associations were observed. We observed a joint effect but no interaction between METS-IR and genetic risk. The lung cancer incidence was estimated to be 100.42 (95% CI: 91.45-109.38) per 100 000 person-year for participants with a high METS-IR and PRS, while only 42.76 (95% CI: 36.94-48.59) with low METS-IR and PRS. CONCLUSIONS: High METS-IR was significantly associated with an increased risk of lung cancer. Keeping a low level of METS-IR might help reduce the long-term incident risk of lung cancer.

Bromide triggers efficient peroxymonosulfate activation for phosphonate degradation.

Phosphonates have received a widespread attention in wastewater treatment due to their potential threat to the water environment. Advanced oxidation processes (AOPs) are feasible methods to degrade phosphonates, and most of the coexisting substances in water show a negative factor during their oxidation. However, the effect of bromide (Br-) on the degradation of phosphonates in peroxymonosulfate (PMS) activation is still unclear. Herein, using 1-hydroxyethane 1,1-diphosphonic acid (HEDP) as a target phosphonate, Br- could remarkably enhance the degradation of HEDP in PMS activation compared to the PMS alone. Under the condition of pH = 7.0, the optimal degradation efficiency of HEDP is 84.8% in the PMS/Br- process after 30-min reaction, whereas no significant oxidation is obtained in the PMS/I- and PMS/Cl- processes. Multiple experiments (i.e., electron paramagnetic resonance (EPR), radical quenching experiments and chemical probs) confirm that free bromine, SO4•- and HO• paly a minor role in HEDP removal, and bromine radical species make a dominant responsible for HEDP oxidation. Additionally, NO3-, SO42-, Cl-, and HCO3- have a little effect on the degradation of HEDP, but the HEDP removal is greatly inhibited in the presence of humic acid (HA). However, the degradation efficiency of HEDP using PMS/Br- process in river and sewage is a much higher than UV/persulfate (PDS) and UV/H2O2 processes. This study provides a new sight into the effect of Br- on the degradation phosphonates in PMS activation process.