The Protocol of Ultrasonic Backscatter Measurements of Musculoskeletal Properties.

This study aims to introduce the protocol for ultrasonic backscatter measurements of musculoskeletal properties based on a novel ultrasonic backscatter bone diagnostic (UBBD) instrument. Dual-energy X-ray absorptiometry (DXA) can be adopted to measure bone mineral density (BMD) in the hip, spine, legs and the whole body. The muscle and fat mass in the legs and the whole body can be also calculated by DXA body composition analysis. Based on the proposed protocol for backscatter measurements by UBBD, ultrasonic backscatter signals can be measured in vivo, deriving three backscatter parameters [apparent integral backscatter (AIB), backscatter signal peak amplitude (BSPA) and the corresponding arrival time (BSPT)]. AIB may provide important diagnostic information about bone properties. BSPA and BSPT may be important indicators of muscle and fat properties. The standardized backscatter measurement protocol of the UBBD instrument may have the potential to evaluate musculoskeletal characteristics, providing help for promoting the application of the backscatter technique in the clinical diagnosis of musculoskeletal disorders (MSDs), such as osteoporosis and muscular atrophy.

Hepatic steatosis predicts metachronous liver metastasis in colorectal cancer patients: a nested case-control study and systematic review.

Nearly twenty-five percent of colorectal cancer (CRC) patients develop metachronous colorectal liver metastasis (CRLM) after curative surgery. Hepatosteatosis is the most prevalent liver condition worldwide, but its impact on the incidence of metachronous CRLM is understudied. In the present study, we aimed to investigate the predictive value of hepatic steatosis on the development of metachronous CRLM. First, a nested case-control study was conducted, enrolling stage I to III CRC patients in the National Colorectal Cancer Cohort (NCRCC) database. Metachronous CRLM patients and recurrence-free patients were matched via propensity-score matching. Fatty liver was identified based on treatment-naïve CT scans and the degree of hepatic fibrosis was scored. Multivariable analysis was conducted to investigate the association between fatty liver and metachronous CRLM. In our database, a total of 414 patients were included. Metachronous CRLM patients had considerably higher rates of hepatic steatosis (30.9% versus 15.9%, P<0.001) and highly fibrotic liver (11.6% versus 2.9%, P=0.001) compared to recurrence-free patients. Multivariable analysis showed that fatty liver (odds ratios [OR]=1.99, 95% confidence interval [CI] 1.19-3.30, P=0.008) and fibrotic liver (OR=4.27, 95% CI 1.54-11.81, P=0.005) were associated with high risk of metachronous CRLM. Further, a systematic literature review was performed to assess available evidence on the association between hepatosteatosis and development of metachronous CRLM. In the systematic review, 1815 patients were pooled from eligible studies, and hepatic steatosis remained a significant risk factor for metachronous CRLM (OR=1.90, 95% CI 1.35-2.66, P<0.001, I2=25.3%). In conclusion, our data suggest that patients with a steatotic liver and a high fibrosis score at CRC diagnosis have elevated risk of developing metachronous CRLM.

GroEL triggers NLRP3 inflammasome activation through the TLR/NF-κB p-p65 axis in human periodontal ligament stem cells.

The interaction between bacteria and the host plays a vital role in the initiation and progression of systemic diseases, including gastrointestinal and oral diseases, due to the secretion of various virulence factors from these pathogens. GroEL, a potent virulence factor secreted by multiple oral pathogenic bacteria, is implicated in the damage of gingival epithelium, periodontal ligament, alveolar bone and other peripheral tissues. However, the underlying biomechanism is still largely unknown. In the present study, we verify that GroEL can trigger the activation of NLRP3 inflammasome and its downstream effector molecules, IL-1ß and IL-18, in human periodontal ligament stem cells (hPDLSCs) and resultantly induce high activation of gelatinases (MMP-2 and MMP-9) to promote the degradation of extracellular matrix (ECM). GroEL-mediated activation of the NLRP3 inflammasome requires the participation of Toll-like receptors (TLR2 and TLR4). High upregulation of TLR2 and TLR4 induces the enhancement of NF-κB (p-p65) signaling and promotes its nuclear accumulation, thus activating the NLRP3 inflammasome. These results are verified in a rat model with direct injection of GroEL. Collectively, this study provides insight into the role of virulence factors in bacteria-induced host immune response and may also provide a new clue for the prevention of periodontitis.

Backscatter measurement of cancellous bone using the ultrasound transit time spectroscopy.

Recently, ultrasound transit time spectroscopy (UTTS) was proposed as a promising method for bone quantitative ultrasound measurement. Studies have showed that UTTS could estimate the bone volume fraction and other trabecular bone structure in ultrasonic through-transmission measurements. The goal of this study was to explore the feasibility of UTTS to be adapted in ultrasonic backscatter measurement and further evaluate the performance of backscattered ultrasound transit time spectrum (BS-UTTS) in the measurement of cancellous bone density and structure. First, taking ultrasonic attenuation into account, the concept of BS-UTTS was verified on ultrasonic backscatter signals simulated from a set of scatterers with different positions and intensities. Then, in vitro backscatter measurements were performed on 26 bovine cancellous bone specimens. After a logarithmic compression of the BS-UTTS, a linear fitting of the log-compressed BS-UTTS versus ultrasonic propagated distance was performed and the slope and intercept of the fitted line for BS-UTTS were determined. The associations between BS-UTTS parameters and cancellous bone features were analyzed using simple linear regression. The results showed that the BS-UTTS could make an accurate deconvolution of the backscatter signal and predict the position and intensity of the simulated scatterers eliminating phase interference, even the simulated backscatter signal was with a relatively low signal-to-noise ratio. With varied positions and intensities of the scatterers, the slope of the fitted line for the log-compressed BS-UTTS versus ultrasonic propagated distance (i.e., slope of BS-UTTS for short) yield a high agreement (r2 = 99.84%-99.96%) with ultrasonic attenuation in simulated backscatter signal. Compared with the high-density cancellous bone, the low-density specimen showed more abundant backscatter impulse response in the BS-UTTS. The slope of BS-UTTS yield a significant correlation with bone mineral density (r = 0.87; p < 0.001), BV/TV (r = 0.87; p < 0.001), and cancellous bone microstructures (r up to 0.87; p < 0.05). The intercept of BS-UTTS was also significantly correlated with bone densities (r = -0.87; p < 0.001) and trabecular structures (|r|=0.43-0.80; p < 0.05). However, the slope of the BS-UTTS underestimated attenuation when measurements were performed experimentally. In addition, a significant non-linear relationship was observed between the measured attenuation and the attenuation estimated by the slope of the BS-UTTS. This study demonstrated that the UTTS method could be adapted to ultrasonic backscatter measurement of cancellous bone. The derived slope and intercept of BS-UTTS could be used in the measurement of bone density and microstructure. The backscattered ultrasound transit time spectroscopy might have potential in the diagnosis of osteoporosis in the clinic.

Super-resolution reconstruction of ultrasound image using a modified diffusion model.

OBJECTIVE: This study aims to perform super-resolution (SR) reconstruction of ultrasound images using a modified diffusion model, designated as the Diffusion Model for Ultrasound Image Super-Resolution (DMUISR). SR involves converting low-resolution images to high-resolution ones, and the proposed model is designed to enhance the suitability of diffusion models for this task in the context of ultrasound imaging. APPROACH: DMUISR incorporates a multi-layer self-attention (MLSA) mechanism and a wavelet-transform based low-resolution image (WTLR) encoder to enhance its suitability for ultrasound image SR tasks. The model takes interpolated and magnified images as input and outputs high-quality, detailed SR images. The study utilized 1,334 ultrasound images from the public fetal head-circumference dataset (HC18) for evaluation. MAIN RESULTS: Experiments were conducted at 2×, 4×, and 8× magnification factors. DMUISR outperformed mainstream ultrasound SR methods (Bicubic, VDSR, DECUSR, DRCN, REDNet, SRGAN) across all scales, providing high-quality images with clear structures and rich detailed textures in both hard and soft tissue regions. DMUISR successfully accomplished multiscale SR reconstruction while suppressing over-smoothing and mode collapse problems. Quantitative results showed that DMUISR achieved the best performance in terms of learned perceptual image patch similarity (LPIPS), with a significant decrease of over 50% at all three magnification factors (2×, 4×, and 8×), as well as improvements in peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM). Ablation experiments validated the effectiveness of the MLSA mechanism and WTLR encoder in improving DMUISR's SR performance. Furthermore, by reducing the number of diffusion steps, the computational time of DMUISR was shortened to nearly one-tenth of its original while maintaining image quality without significant degradation. SIGNIFICANCE: This study demonstrates that the modified diffusion model, DMUISR, provides superior performance for SR reconstruction of ultrasound images and has potential in improving imaging quality in the medical ultrasound field.

Hydrogen-Bond-Network Breakdown Boosts Selective CO2 Photoreduction by Suppressing H2 Evolution.

Conventional strategies for highly efficient and selective CO2 photoreduction focus on the design of catalysts and cocatalysts. In this study, we discover that hydrogen bond network breakdown in reaction system can suppress H2 evolution, thereby improving CO2 photoreduction performance. Photosensitive poly(ionic liquid)s are designed as photocatalysts owing to their strong hydrogen bonding with solvents. The hydrogen bond strength is tuned by solvent composition, thereby effectively regulating H2 evolution (from 0 to 12.6 mmol g-1 h-1). No H2 is detected after hydrogen bond network breakdown with trichloromethane or tetrachloromethane as additives. CO production rate and selectivity increase to 35.4 mmol g-1 h-1 and 98.9 % with trichloromethane, compared with 0.6 mmol g-1 h-1 and 26.2 %, respectively, without trichloromethane. Raman spectroscopy and theoretical calculations confirm that trichloromethane broke the systemic hydrogen bond network and subsequently suppressed H2 evolution. This hydrogen bond network breakdown strategy may be extended to other catalytic reactions involving H2 evolution.

Characterization and application of in situ curcumin/ZNP hydrogels for periodontitis treatment.

BACKGROUND: Periodontitis is a chronic inflammatory disease that occurs in tooth-supporting tissues. Controlling inflammation and alleviating periodontal tissue destruction are key factors in periodontal therapy. This study aimed to develop an in situ curcumin/zinc oxide (Cur/ZNP) hydrogel and investigate its characteristics and effectiveness in the treatment of periodontitis. METHODS: Antibacterial activity and cytotoxicity assays were performed in vitro. To evaluate the effect of the in situ Cur/ZNP hydrogel on periodontitis in vivo, an experimental periodontitis model was established in Sprague‒Dawley rats via silk ligature and inoculation of the maxillary first molar with Porphyromonas gingivalis. After one month of in situ treatment with the hydrogel, we examined the transcriptional responses of the gingiva to the Cur/ZNP hydrogel treatment and detected the alveolar bone level as well as the expression of osteocalcin (OCN) and osteoprotegerin (OPG) in the periodontal tissues of the rats. RESULTS: Cur/ZNPs had synergistic inhibitory effects on P. gingivalis and good biocompatibility. RNA sequencing of the gingiva showed that immune effector process-related genes were significantly induced by experimental periodontitis. Carcinoembryonic antigen-related cell adhesion molecule 1 (Ceacam1), which is involved in the negative regulation of bone resorption, was differentially regulated by the Cur/ZNP hydrogel but not by the Cur hydrogel or ZNP hydrogel. The Cur/ZNP hydrogel also had a stronger protective effect on alveolar bone resorption than both the Cur hydrogel and the ZNP hydrogel. CONCLUSION: The Cur/ZNP hydrogel effectively inhibited periodontal pathogenic bacteria and alleviated alveolar bone destruction while exhibiting favorable biocompatibility.

A cascading learning method with SegFormer for radiographic measurement of periodontal bone loss.

OBJECTIVE: Marginal alveolar bone loss is one of the key features of periodontitis and can be observed via panoramic radiographs. This study aimed to establish a cascading learning method with deep learning (DL) for precise radiographic bone loss (RBL) measurements at specific tooth positions. MATERIALS AND METHODS: Through the design of two tasks for tooth position recognition and tooth semantic segmentation using the SegFormer model, specific tooth's crown, intrabony portion, and suprabony portion of the roots were obtained. The RBL was subsequently measured by length through these three areas using the principal component analysis (PCA) principal axis. RESULTS: The average intersection over union (IoU) for the tooth position recognition task was 0.8906, with an F1-score of 0.9338. The average IoU for the tooth semantic segmentation task was 0.8465, with an F1-score of 0.9138. When the two tasks were combined, the average IoU was 0.7889, with an F1-score of 0.8674. The correlation coefficient between the RBL prediction results based on the PCA principal axis and the clinicians' measurements exceeded 0.85. Compared to those of the other two methods, the average precision of the predicted RBL was 0.7722, the average sensitivity was 0.7416, and the average F1-score was 0.7444. CONCLUSIONS: The method for predicting RBL using DL and PCA produced promising results, offering rapid and reliable auxiliary information for future periodontal disease diagnosis. CLINICAL RELEVANCE: Precise RBL measurements are important for periodontal diagnosis. The proposed RBL-SF can measure RBL at specific tooth positions and assign the bone loss stage. The ability of the RBL-SF to measure RBL at specific tooth positions can guide clinicians to a certain extent in the accurate diagnosis of periodontitis.

Persistent Hyperkeratotic Plaques on a Man's Genitogluteal Area.

A man in his 40s presented with a 10-year history of pruritic lesions on the scrotum and buttock. What is your diagnosis?

Tumor-derived Exosomal ENO2 Modulates Polarization of Tumor-associated Macrophages through Reprogramming Glycolysis to Promote Progression of Diffuse Large B-cell Lymphoma.

Macrophages can be polarized into functional classically activated (M1) or alternatively activated (M2) phenotype. Tumor-associated macrophages (TAMs) mainly exhibit M2 phenotype. Previous works determined that up-regulation of enolase 2 (ENO2) in diffuse large B-cell lymphoma (DLBCL) cells can promote macrophages to an M2-like phenotype, thereby consequently promoting the progression of DLBCL. Exosomes are a subset of extracellular vesicles, carrying various bioactive molecules, mediate signals transduction and regulate immune cells. In our study, we investigated the role and related mechanisms of DLBCL-derived exosomal ENO2 in regulating macrophage polarization during DLBCL progression via bioinformatics analysis and a series of experiments. The results of bioinformatics analysis indicated that high expression of ENO2 was positively correlated with DLBCL progression and macrophages M2/M1 ratio. ENO2 protein levels were increased in the exosomes of the sera of DLBCL patients and DLBCL cells. Moreover, the DLBCL-derived exosomes were assimilated by macrophages and then regulated macrophage polarization. The results of in vitro and in vivo experiments showed that DLBCL-derived exosomal ENO2 modulated macrophages polarization (increased M2 phenotype and decreased M1 phenotype), thereby promoting DLBCL proliferation, migration, and invasion. We then revealed that the modulation of macrophages polarization by DLBCL-derived exosomal ENO2 depended on glycolysis and was promoted through GSK3ß/ß-catenin/c-Myc signaling pathway. These findings suggested that DLBCL-derived exosomal ENO2 accelerated glycolysis via GSK3ß/ß-catenin/c-Myc signaling pathway to ultimately promote macrophages to an M2-like phenotype, which can promote the proliferation, migration and invasion of DLBCL, suggesting that exosomal ENO2 may be a promising therapeutic target and prognostic biomarker for DLBCL.

Primary Surgery Followed by Selective Chemoradiotherapy Versus Preoperative Chemoradiotherapy Followed by Surgery for Locally Advanced Rectal Cancer: A Randomized Clinical Trial.

PURPOSE: The aim of this work was to determine whether locally advanced rectal cancer (LARC) with negative mesorectal fascia (MRF) predicted by magnetic resonance imaging (MRI) can be excluded from preoperative radiation therapy treatment. METHODS AND MATERIALS: This multicenter, open-label, non-inferiority, randomized clinical trial enrolled patients with LARC within 6 to 12 cm from the anal verge and with negative MRI-predicted MRF. Participants were randomized to the intervention group (primary surgery, in which the patients with positive pathologic [CRM] circumferential margins were subjected to chemoradiotherapy [CRT] and those with negative CRM underwent adjuvant chemotherapy according to pathologic staging) or the control group (preoperative CRT, in which all patients underwent subsequent surgery and adjuvant chemotherapy). The primary endpoint was 3-year disease-free survival (DFS). RESULTS: A total of 275 patients were randomly assigned to the intervention (n = 140) and control (n = 135) groups, in which 33.57% and 28.15% patients were at clinical T4 stage and 85.92% and 80.45% patients were at "bad" or "ugly" risk in the intervention and control groups, respectively. There were 2 patients (1.52%) and 1 patient (0.77%) with positive CRM in the intervention and control groups, respectively (P > .05). The non-adherence rates for the intervention and control groups were 3.6% and 23.7%, respectively. After a median follow-up of 34.6 months (IQR, 18.2-45.7), 43 patients had positive events (28 patients and 15 patients in the intervention and control groups, respectively). There were 6 patients (4.4%) with local recurrence in the intervention group and none in the control group, which led to the termination of the trial. The 3-year DFS rate was 81.82% in the intervention group (95% CI, 78.18%-85.46%) and 85.37% in the control group (95% CI, 81.75%-88.99%), with a difference of -3.55% (95% CI, -3.71% to -3.39%; hazard ratio, 1.76; 95% CI, 0.94-3.30). In the per-protocol data set, the difference between 3-year DFS rates was -5.44% (95% CI, -5.63% to -5.25%; hazard ratio, 2.02; 95% CI, 1.01-4.06). CONCLUSIONS: Based on the outcomes of this trial, in patients with LARC and MRI-negative MRF, primary surgery could negatively influence their DFS rates. Therefore, primary surgery was an inferior strategy compared with preoperative CRT followed by surgery and cannot be recommended for patients with LARC.

Substantial removal of four pesticide residues in three fruits with ozone microbubbles.

Developing a straightforward method to remove pesticide residues from fruits is essential for food safety. In this study, ozone microbubble treatment was performed on three fruits (strawberry, cherry, and apricot) to remove four pesticide residues (emamectin benzoate, azoxystrobin, boscalid, and difenoconazole) while comparing removal efficiency. The concentration of hydroxyl radicals in different washing orientations was homogeneous at a concentration ranging between 8.9 and 10.2 µmol·L-1. Under long washing time (18 min), strawberry, cherry, and apricot obtained higher removal rates of 51 %∼65 %, 51 %∼59 % and 24 %∼70 %, respectively. Moreover, scanning electron microscopy (SEM) and contact angle (CA) revealed that apricot has better hydrophobicity, leading to a higher pesticide removal of 45 âˆ¼ 84 % with less water and more vigorous washing. Notably, vitamin C content in fruits remain largely unchanged following ozone microbubble treatment. This study demonstrated the effectiveness of ozone microbubble treatment as pollution-free method for enhancing food safety by removing pesticide residues on fruits.

MXene-Derived Na+ -Pillared Vanadate Cathodes for Dendrite-Free Potassium Metal Batteries.

Cation-intercalated vanadates, which have considerable promise as the cathode for high-performance potassium metal batteries (PMBs), suffer from structural collapse upon K+ insertion and desertion. Exotic cations in the vanadate cathode may ease the collapse, yet their effect on the intrinsic cation remains speculative. Herein, a stable and dendrite-free PMB, composed of a Na+ and K+ co-intercalated vanadate (NKVO) cathode and a liquid NaK alloy anode, is presented. A series of NKVO with tuneable Na/K ratios are facilely prepared using MXene precursors, in which Na+ is testified to be immobilized upon cycling, functioning as a structural pillar. Due to stronger ionic bonding and lower Fermi level of Na+ compared to K+ , moderate Na+ intercalation could reduce K+ binding to the solvation sheath and favor K+ diffusion kinetics. As a result, the MXene-derived Na+ -pillared NKVO exhibits markedly improved specific capacities, rate performance, and cycle stability than the Na+ -free counterpart. Moreover, thermally-treated carbon paper, which imitates the microscopic structure of Chinese Xuan paper, allows high surface tension liquid NaK alloy to adhere readily, enabling dendrite-free metal anodes. By clarifying the role of foreign intercalating cations, this study may lead to a more rational design of stable and high-performance electrode materials.

Low-Intensity Pulsed Ultrasound Promotes the Repair of Achilles Tendinopathy by Downregulating the JAK/STAT Signaling Pathway in Rabbits.

Tendinopathy is a complex tendon injury or pathology outcome, potentially leading to permanent impairment. Low-intensity pulsed ultrasound (LIPUS) is emerging as a treatment modality for tendon disorders. However, the optimal treatment duration and its effect on tendons remain unclear. This study aims to investigate the efficacy of LIPUS in treating injured tendons, delineate the appropriate treatment duration, and elucidate the underlying treatment mechanisms through animal experiments. Ninety-six three-month-old New Zealand white rabbits were divided into normal control (NC) and model groups. The model group received Prostaglandin E2 (PGE2) injections to induce Achilles tendinopathy. They were then divided into model control (MC) and LIPUS treatment (LT) groups. LT received LIPUS intervention with a 1-MHz frequency, a pulse repetition frequency (PRF) of 1 kHz, and spatial average temporal average sound intensity ( [Formula: see text]) of 100 mW/cm2. MC underwent a sham ultrasound, and NC received no treatment. Assessments on 1, 4, 7, 14, and 28 days after LT included shear wave elastography (SWE), mechanical testing, histologic evaluation, ribonucleic acid sequencing (RNA-seq), polymerase chain reaction (PCR), and western blot (WB) analysis. SWE results showed that the shear modulus in the LT group was significantly higher than that in the MC group after LT for seven days. Histological results demonstrated improved tendon tissue alignment and fibroblast distribution after LT. Molecular analyses suggested that LIPUS may downregulate the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway and regulate inflammatory and matrix-related factors. We concluded that LT enhanced injured tendon elasticity and accelerated Achilles tendon healing. The study highlighted the JAK/STAT signaling pathway as a potential therapeutic target for LT of Achilles tendinopathy, guiding future research.

Antimicrobial efficacy of aloe-emodin mediated photodynamic therapy against antibiotic-resistant Pseudomonas aeruginosa in vitro.

Multidrug-resistant Pseudomonas aeruginosa is a common pathogen that causes topical infections following burn injuries. Antimicrobial photodynamic therapy (aPDT) has emerged as a promising approach for treating antibiotic-resistant bacterial infections. The objective of this study was to evaluate the aPDT efficacy of aloe-emodin (AE), which is a photosensitizer extracted from traditional Chinese herbs, on antibiotic-sensitive and antibiotic-resistant P. aeruginosa in vitro. In this study, we confirmed the effectiveness of AE-mediated aPDT against both standard and MDR P. aeruginosa, explored the effects of irradiation time and AE concentration on bacterial survival in AE-mediated aPDT, and observed the structural damage of P. aeruginosa by using transmission electron microscope. Our results showed that neither AE nor light irradiation alone caused cytotoxic effects on P. aeruginosa. However, AE-mediated aPDT effectively inactivated both antibiotic-sensitive and antibiotic-resistant P. aeruginosa. The transmission electron microscope investigation showed that aPDT mediated by AE primarily caused damage to the cytoplasm and cell membrane. Our findings suggest that AE is a photosensitizer in the aPDT of MDR P. aeruginosa-caused topical infections following burn injuries. Future investigations will concentrate on the safety and efficacy of AE-mediated aPDT in animal models and clinical trials.

Salivary Proteome and Intact N-Glycopeptides Analysis Reveal Specific Signatures in Periodontitis.

Periodontitis is a prevalent oral inflammatory disease that can result in tooth loss and is closely linked to type 2 diabetes (T2D). In this study, we analyzed the salivary proteome and intact N-glycopeptides (IGPs) of individuals with mild-moderate, severe, aggressive periodontitis, and periodontitis with T2D, including those treated with antidiabetic drugs, to identify specific signatures associated with the disease. Our results revealed that salivary proteins and glycoproteins were altered in all periodontitis groups (PRIDE ID: 1-20230612-72345), with fucose- and sialic acid-containing N-glycans showing the greatest increase. Additionally, differentially expressed proteins were classified into 9 clusters, including those that were increased in all periodontitis groups and those that were only altered in certain types of periodontitis. Interestingly, treatment with antidiabetic drugs reversed many of the changes observed in the salivary proteome and IGPs in T2D-related periodontitis, suggesting a potential therapeutic approach for managing periodontitis in patients with T2D. Consistent with MS/MS results, the expression of salivary IGHA2 and Fucα1-3/6GlcNAc (AAL) was significantly increased in MP. These findings provide new insights into the pathogenesis of periodontitis and highlight the potential of salivary biomarkers for diagnosis, prognosis, and monitoring of disease progression and treatment response.

Reconstruction of ENSO variability using the standardized growth index of a Tridacna shell from Yongshu Reef, South China Sea.

El Niño-Southern Oscillation (ENSO) is the strongest signal of global interannual climate anomaly and reconstructing past ENSO variations using high-resolution paleoclimate archives can improve our understanding of ENSO variability, as well as improve our ability to predict future climate changes. Here, a daily resolution standardized growth index (SGI) was established using a giant clam (Tridacna spp.) shell specimen MD2 (life span: 1994-2013 CE), collected from the Yongshu Reef, southern South China Sea (SCS). The cross-spectral and correlation analysis indicated that the SGI variation of MD2 was strongly influenced by ENSO variability on an interannual timescale. Tridacna spp. is in symbiosis with zooxanthellae, and its growth index is usually modulated by the photosynthetic efficiency of zooxanthellae. During the El Niño (La Niña) period, the convective anomalies stimulated in western Pacific would increase (decrease) the effective solar radiation on Yongshu Reef, and in turn influence the photosynthesis rate of zooxanthellae and enzyme activity for the calcification site and thus the SGI of giant clam MD2. The SGI can explain 54.7 % of ENSO variance, demonstrating the potential for Tridacna SGI in ENSO reconstruction. Compared with conventional ENSO reconstruction using high-resolution geochemical proxies, the method of giant clam SGI is rapid and economical.

Polymyxin B-targeted liposomal photosensitizer cures MDR A. baumannii burn infections and accelerates wound healing via M1/M2 macrophage polarization.

Multidrug-resistant (MDR) Acinetobacter baumannii infections pose a significant challenge in burn wound management, necessitating the development of innovative therapeutic strategies. In this work, we introduced a novel polymyxin B (PMB)-targeted liposomal photosensitizer, HMME@Lipo-PMB, for precise and potent antimicrobial photodynamic therapy (aPDT) against burn infections induced by MDR A. baumanni. HMME@Lipo-PMB-mediated aPDT exhibited enhanced antibacterial efficacy by specifically targeting and disrupting bacterial cell membranes, and generating increased intracellular ROS. Remarkably, even at low concentrations, this targeted approach significantly reduced bacterial viability in vitro and completely eradicated burn infections induced by MDR A. baumannii in vivo. Additionally, HMME@Lipo-PMB-mediated aPDT facilitated burn infection wound healing by modulating M1/M2 macrophage polarization. It also effectively promoted acute inflammation in the early stage, while attenuated chronic inflammation in the later stage of wound healing. This dynamic modulation promoted the formation of granulation tissue, angiogenesis, and collagen regeneration. These findings demonstrate the tremendous potential of HMME@Lipo-PMB-mediated aPDT as a promising alternative for the treatment of burn infections caused by MDR A. baumannii.

Prediction of the Fatigue Strength of Steel Based on Interpretable Machine Learning.

Most failures in steel materials are due to fatigue damage, so it is of great significance to analyze the key features of fatigue strength (FS) in order to improve fatigue performance. This study collected data on the fatigue strength of steel materials and established a predictive model for FS based on machine learning (ML). Three feature-construction strategies were proposed based on the dataset, and compared on four typical ML algorithms. The combination of Strategy Ⅲ (composition, heat-treatment, and atomic features) and the GBT algorithm showed the best performance. Subsequently, input features were selected step by step using methods such as the analysis of variance (ANOVA), embedded method, recursive method, and exhaustive method. The key features affecting FS were found to be TT, mE, APID, and Mo. Based on these key features and Bayesian optimization, an ML model was established, which showed a good performance. Finally, Shapley additive explanations (SHAP) and symbolic regression (SR) are introduced to improve the interpretability of the prediction model. It had been discovered through SHAP analysis that TT and Mo had the most significant impact on FS. Specifically, it was observed that 160 < TT < 500 and Mo > 0.15 was beneficial for increasing the value of FS. SR was used to establish a significant mathematical relationship between these key features and FS.

Estimating the economic burden of colorectal cancer in China, 2019-2030: A population-level prevalence-based analysis.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide. Comprehensive data on the economic burden of CRC at a population-level is critical in informing policymaking, but such data are currently limited in China. METHODS: From a societal perspective, the economic burden of CRC in 2019 was estimated, including direct medical and nonmedical expenditure, disability, and premature-death-related indirect expenditure. Data on disease burden was taken from the GBD 2019 and analyzed using a prevalence-based approach. The per-person direct expenditure and work loss days were from a multicenter study; the premature-death-related expenditure was estimated using a human capital approach. Projections were conducted in different simulated scenarios. All expenditure data were in Chinese Yuan (CNY) and discounted to 2019. RESULTS: In 2019, the estimated overall economic burden of CRC in China was CNY170.5 billion (0.189% of the local GDP). The direct expenditure was CNY106.4 billion (62.4% of the total economic burden), 91.4% of which was a direct medical expenditure. The indirect expenditure was CNY64.1 billion, of which 63.7% was related to premature death. The predicted burden would reach CNY560.0 billion in 2030 given constant trends for disease burden; however, it would be alternatively reduced to