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The abandoned roadways (ARs) in front of the longwall face catastrophic instability will seriously hamper mining progress, which is a complicated process related to the stress environment, the roadway section, and the mechanical properties of the surrounding rock. The cusp catastrophe theory is employed to establish a state identification model for the irregular coal pillar-roof system (CPRS) formed by the ARs and re-mining entries. To begin, the state discrimination equation (Δp) for the gradual CPRS is derived, and the critical value at which the system transitions into an unstable state under quasi-static conditions is determined. The results indicated that when 16.49 m ≤ L ≤ 22.63 m (L denotes the equivalent span of the intersection roof) and 0

Abstract Background To explore the potential impact of lymphovascular invasion (LVI) on overall survival (OS) of pN0 stage gastric cancer (GC) after curative resection. Methods A total of 497 GC patients who underwent curative gastrectomy and postoperative pathology proved negative lymph node metastasis between January 2015 and December 2018 in our center were enrolled in this study. All patients were divided into two groups according to the status of LVI. Their clinical and pathological features were compared and potential prognostic factors were analyzed using the propensity score matching analysis (PSM). Results Ninety-nine (19.9%) patients had LVI. The presence of LVI was associated with significantly worse survival outcomes in both the overall and PSM cohorts (χ2 = 19.635, p

Objective: The aim of the study was to introduce the development of forensic pathology for social-oriented forensic-identification institutions, using the Academy of Forensic Science as an example. Methods: Cases were collected from the Forensic Pathology Section of the Academy of Forensic Science and classified and organized according to gender, source, type, manner of death, and virtual autopsies of the cases over the years. Descriptive statistical analyses were performed using SPSS and Excel tables so as to summarize forensic pathology for social-oriented services. Results: A total of 12,161 cases were collected from the forensic pathology department; the most cases were from the People’s Public Security sources, and the fewest cases were from the Department of Health; the most cases were commissioned for the examination of cadaver surface in forensic medicine (8323 cases), and the fewest were for injury examination (72 cases) and diatom examination (78 cases); there were a total of 322 cases of virtual autopsy examination during the 11-year period, of which 33 cases were performed for target-organ arteriography; the highest number of cases for accidental death examinations (8122 cases). Conclusion: The Academy of Forensic Science and other social-service-oriented identification organizations undertake identification work on cases commissioned to them by the local and local people’s public security, people’s procuratorates, and people’s court systems. Virtual autopsy technology and other new technologies, new methods, and new standards to make up for the shortcomings of the traditional autopsy, to provide identification and research support, and subsequent prospective research to provide a database.

Background: This study evaluates the noninvasive virtual autopsy (virtopsy), which uses imaging technologies like computed tomography (CT) and magnetic resonance imaging to examine deceased internal structures, as an alternative to traditional autopsies due to its less invasive nature and greater family acceptance. Aims and Objectives: The aim was to assess virtopsy’s effectiveness by comparing it with traditional autopsies in 322 cases from the Academy of Forensic Science in China over a decade, focusing on various anatomical regions and tissues. Materials and Methods: Postmortem computed tomography (PMCT) and PMCT angiography (PMCTA) were performed on 204 cadavers before traditional autopsies, with the agreement between virtopsy and autopsy findings assessed using Cohen kappa values. Results: Virtopsy showed higher sensitivity in detecting fractures, particularly in hard-to-access bones, but was less sensitive to rib fractures. Autopsy was more effective for intracranial injuries and organ pathologies, while PMCTA excelled at revealing vascular lesions and injuries. Conclusion: Virtopsy is effective for certain tissues and organs, serving as an auxiliary and guiding tool in traditional autopsies, thus enhancing forensic diagnosis and case resolution.

Abstract Background Epidemiological and other studies have shown correlations among major depressive disorder (MDD), anxiety disorder (AXD) and constipation. However, no consensus has been reached regarding their interdependence and pathogenesis. Herein, we sought to further explore the causal associations between them. Methods Bidirectional two-sample Mendelian randomization (MR) analysis was performed to confirm the causal link between MDD, AXD and constipation. Genetic instrumental variables for MDD, AXD, and constipation were obtained from publicly available genome-wide association studies (GWASs). In this MR analysis, inverse variance weighting (IVW) was used as the primary analysis method to evaluate the causal effect. Additionally, we employed Cochran’s Q test, MR‒Egger intercept and MR-PRESSO analysis to examine heterogeneity and pleiotropy. Moreover, leave-one-out analysis was employed to investigate the stability of the associations. Finally, a reverse analysis of Mendelian randomization was conducted. Results The results revealed a causal relationship between MDD and an increased risk of constipation (p = 0.0001), whereas AXD (p = 8.52 × 10–1) did not increase the risk of constipation. In the inverse MR analysis, no causal associations were found (constipation to MDD: p = 9.37 × 10–1; constipation to AXD: p = 8.51 × 10–1). Conclusion This MR study revealed genetic evidence supporting a causal relationship between MDD and constipation.

Abstract Objective This research aimed to delineate the pharmacological mechanisms of 7-Hydroxycoumarin (7-HC) on ulcerative colitis (UC) employing network pharmacology and experimental validation. Methods To investigate the therapeutic effects of 7-HC on UC, a UC mouse model was established through the unrestricted intake of 3.0% dextran sulfate sodium (DSS) in their drinking water. Subsequently, we predicted the core targets and signaling pathways of 7-HC for the treatment of UC using the network pharmacology approach. Finally, the insights gained from network pharmacology were further validated by molecular docking, molecular dynamics simulation as well as in vivo experiments. Results Administering 7-HC orally to mice with UC led to a marked improvement in colitis indicators. Furthermore, 7-HC significantly lowered the levels of inflammatory cytokines (TNF-α, IL-1β) in the colon and modulated oxidative stress markers (MPO, SOD). Subsequent studies identified 2 core targets (AKT1 and EGFR) in the colon of UC mice that were inhibited by 7-HC. Network pharmacology and experimental validation showed that 7-HC can reduce the expression of MAPK pathway markers P38, JNK, ERK, and their phosphorylation; 7-HC can also ameliorate UC by regulating the gut microbiome. Conclusion 7-HC demonstrates considerable efficacy in alleviating UC in mice, primarily through substantial diminution of tissue inflammation and oxidative stress. This is the first time that 7-HC has been found to treat UC by inhibiting the MAPK pathway and modulating the gut microbiota, providing a fresh perspective on the pharmacological mechanisms through which 7-HC operates in the management of UC.

Abstract Low temperatures are a key factor affecting the growth, development, and geographical distribution of prickly ash. This study investigated the impact of ecological and geographical factors on the freezing tolerance of prickly ash germplasm. Thirty-seven germplasm samples from 18 different origins were collected, and their freezing tolerance was comprehensively evaluated. The correlation between freezing tolerance and the ecological and geographical factors of their origins was also analyzed. Significant differences in freezing tolerance were observed among germplasm from different origins. The semi-lethal temperature of the germplasm ranged from − 12.37 to 1.08 °C. As temperatures decreased, the relative conductivity (REC) and catalase (CAT) activity of the germplasm gradually increased, while soluble sugar (SS), soluble protein (SP), free proline (Pro), and Peroxidase (POD) activities decreased and then increased. Superoxide dismutase (SOD) activity initially increased and then decreased. A comprehensive evaluation of freezing tolerance was conducted using a logistic equation, membership function, and cluster analysis. Germplasm from Tongchuan and Hancheng (Shaanxi Province, China), Asakura (Japan), and Yuncheng (Shanxi Province, China) exhibited the highest freezing tolerance, whereas those from Rongchang (Chongqing Municipality, China), Qujing (Yunnan Province, China), and Honghe (Yunnan Province, China) had the lowest. The correlation analysis revealed a significant positive correlation between freezing tolerance and latitude, and a significant negative correlation with the temperature of origin. Germplasm from higher latitudes showed higher SS content, SOD and CAT activities, stronger antioxidant enzyme activity, and better freezing tolerance compared to those from lower latitudes. REC was lower in germplasm originating from low-temperature areas than in those from high-temperature areas. Additionally, SP, Pro content, SOD, and POD activities were higher, indicating effective scavenging of active oxygen free radicals. No significant correlation was found between altitude and longitude of origin and freezing tolerance. However, at similar latitudes, prickly ash from higher altitudes displayed higher antioxidant enzyme activity and stronger freezing tolerance compared to those from lower altitudes. These findings provide a scientific basis for breeding prickly ash cultivars suited to different ecological regions.

Abstract Although observational clinical studies have established an association between Intestinal Diseases (IDS) and Anal Diseases (ADS), the causal relationship is still not fully understood due to the limitations of observational studies. Genome-wide association study (GWAS) statistical data for IDS and ADS were obtained from publicly available databases. To assess the causal effects of IDS on ADS, we conducted Mendelian randomization analysis. The inverse variance weighted method indicated that Inflammatory bowel disease (IBD) had a significant causal relationship with three kinds of ADS: Anorectal abscess (ARB), Haemorrhoidal disease (HEM), and Fissure and fistula of anal and rectal regions (FISSANAL). Crohn’s disease (CD) and Ulcerative colitis (UC) also showed significant causal effects with three ADS: ARB, HEM, and FISSANAL. Furthermore, a potential link between CD and BNA(Benign neoplasm of anus and anal canal), Irritable bowel syndrome (IBS) and HEM, Colorectal cancer (CRC) and BNA, and Celiac disease and MNA (Malignant neoplasm of anus and anal canal) was observed. This comprehensive MR analysis highlight the significant and increased risk of common Anal Diseases (ARB, FISSANAL, and HEM) in patients with IBD, CD, and UC. Additionally, potential positive causal associations emerged between IBS and HEM, CRC and BNA, as well as between celiac disease and MNA.

In ophthalmology, the quality of fundus images is critical for accurate diagnosis, both in clinical practice and in artificial intelligence (AI)-assisted diagnostics. Despite the broad view provided by ultrawide-field (UWF) imaging, pseudocolor images may conceal critical lesions necessary for precise diagnosis. To address this, we introduce UWF-Net, a sophisticated image enhancement algorithm that takes disease characteristics into consideration. Using the Fudan University ultra-wide-field image (FDUWI) dataset, which includes 11 294 Optos pseudocolor and 2415 Zeiss true-color UWF images, each of which is rigorously annotated, UWF-Net combines global style modeling with feature-level lesion enhancement. Pathological consistency loss is also applied to maintain fundus feature integrity, significantly improving image quality. Quantitative and qualitative evaluations demonstrated that UWF-Net outperforms existing methods such as contrast limited adaptive histogram equalization (CLAHE) and structure and illumination constrained generative adversarial network (StillGAN), delivering superior retinal image quality, higher quality scores, and preserved feature details after enhancement. In disease classification tasks, images enhanced by UWF-Net showed notable improvements when processed with existing classification systems over those enhanced by StillGAN, demonstrating a 4.62% increase in sensitivity (SEN) and a 3.97% increase in accuracy (ACC). In a multicenter clinical setting, UWF-Net-enhanced images were preferred by ophthalmologic technicians and doctors, and yielded a significant reduction in diagnostic time ((13.17 ± 8.40) s for UWF-Net enhanced images vs (19.54 ± 12.40) s for original images) and an increase in diagnostic accuracy (87.71% for UWF-Net enhanced images vs 80.40% for original images). Our research verifies that UWF-Net markedly improves the quality of UWF imaging, facilitating better clinical outcomes and more reliable AI-assisted disease classification. The clinical integration of UWF-Net holds great promise for enhancing diagnostic processes and patient care in ophthalmology.

Abstract Background Lychee seeds were fermented by three kinds of bacteria (Lactobacillus plantarum, Saccharomyces cerevillus and ganoderma lucidum mycelium), and two effective strains were selected by two indexes of activity content and antioxidant, so as to further verify whether lychee seeds have waste multiplication effect and can protect cells damaged by oxidation from anti-inflammatory, anti-aging and safety. Results The contents of polyphenols, flavonoids and proteins in the solution fermented by Ganoderma lucidum mycelium did not increase, thus affecting the antioxidant capacity of the solution was far less than that of the water extract. The active content of the other two fermentation solutions was higher than that of the water extract, and the ability of scavenging free radicals of the two solutions increased with the increase of the volume fraction. At the cellular level, the two fermentation solutions showed repair effects on UVA-induced damaged cells. The contents of type I collagen (COL-1), total antioxidant capacity and ELN were increased, the contents of reactive oxygen species and MDA were decreased, and the expressions of inflammatory factors IL-6, TNF-a, iNOS and COX-2 were decreased in HaCaT cells. From the gene level, the mRNA contents of IL-6, TNF-a, Caspase-3, Caspase-9, Bax and Bcl were significantly decreased. The test of chick embryo chorioallantoic membrane (HTET CAM) showed that there was no bleeding and litchi seed fermentation liquid was not irritating. Conclusions Therefore, two kinds of litchi seed fermentation can be used as natural plant raw materials for cosmetics, and have strong antioxidant, anti-inflammatory and anti-aging functions on skin, and also have good human safety. Graphical Abstract

IntroductionIn the excavation engineering of tunnels and mines in the western cold region, the unloading failure zone is mainly caused by stress release. This study aimed to investigate the deformation and failure mechanism of frozen weakly cemented sandstone (FWCS) when the initial principal stress σ3 was 3, 6, or 10 MPa.MethodsA conventional triaxial compression test and a triaxial unloading test with an unloading rate of 0.05 MPa/s were carried out. Based on the experimental data and mathematical analysis methods, the non-linear criterion was constructed and analyzed. The microfracture characteristics of the damaged surface were studied by scanning electron microscopy (SEM).ResultsThe results show that compared with conventional triaxial compression and room temperature triaxial compression tests, the strength and plastic deformation characteristics of FWCS during unloading were significantly weakened, with transverse deformation and volume strain increased, showing obvious dilatancy characteristics. Unloading reduced the cohesion of FWCS, increased the internal friction angle, and increased the risk of rock failure. Macroscopic and microscopic analysis revealed the failure mechanism of FWCS. The unloading stress ratio was introduced to establish relationships. A non-linear criterion based on the Mohr–Coulomb strength criterion was established, with the power function strength criterion being more accurate in describing the failure of FWCS.DiscussionThis study provides valuable insights into the mechanical properties and failure mechanism of FWCS under unloading conditions, which is beneficial for the excavation engineering of tunnels and mines in the western cold region.

Mitochondria are important organelles that regulate cellular energy and biosynthesis, as well as maintain the body’s response to environmental stress. Their dynamics and autophagy influence occurrence of cellular function, particularly under stressful conditions. They can generate reactive oxygen species (ROS) which is a major contributor to inflammatory diseases such as ulcerative colitis (UC). In this review, we discuss the key effects of mitochondrial dynamics and mitophagy on the pathogenesis of UC, with a particular focus on the cellular energy metabolism, oxidative stress, apoptosis, and immunoinflammatory activities. The therapeutic efficacy of existing drugs and phytochemicals targeting the mitochondrial pathway are discussed to reveal important insights for developing therapeutic strategies for treating UC. In addition, new molecular checkpoints with therapeutic potential are identified. We show that the integration of mitochondrial biology with the clinical aspects of UC may generate ideas for enhancing the clinical management of UC.

Abstract This study aimed to reveal the diversity and variation in panicle traits of the Chinese prickly ash and clarify their influence on the its systematic classification to provide a theoretical basis and technical support for the efficient utilization of Chinese prickly ash germplasm resources and breeding. Sixteen panicle traits were identified from 35 Chinese prickly ash germplasm resources from 2021 to 2022. The diversity of these panicle traits and their role in the plant’s systematic classification were studied using variance, correlation, cluster, and principal component analyses. Cluster analysis showed that the 35 Chinese prickly ash germplasm resources could be divided into two groups with Euclidean distances of 25. Further analysis showed that yield traits such as panicle length, panicle width, primary branching, grain number per panicle, and grain weight per panicle were significantly positively correlated with grain chlorophyll content, while grain anthocyanin content was negatively correlated with both panicle (panicle length, panicle width, panicle length to width ratio, primary branching, grain number per panicle, and grain weight per panicle) and grain characteristics (single grain weight, thousand-grain weight, grain length, grain width and fruit shape index). In conclusion, Chinese prickly ash germplasms have diverse panicle traits. Z. armatum has dark green grains, long and wide panicles, a long conical shape, many primary branches, high grain weight, and high grain number per panicle. In contrast, Z. bungeanum has bright red seeds, a panicle width larger than its length, short and conical panicles, a small number of primary branches, and low grain weight per panicle and number of grains per panicle. Overall, Z. armatum had a significant yield advantage over Z. bungeanum.

Abstract Ulcerative colitis (UC) is a persistent inflammatory condition that specifically targets the colon and rectum. Existing therapies fail to adequately address the clinical requirements of people suffering from this ailment. Despite the acknowledged potential of nanomedicines in the field of anti-inflammatory treatment, their widespread use in clinical settings is impeded by their expensive nature and the uncertainty surrounding their safety profiles. This study illustrates that two naturally occurring phytochemicals, Costunolide (COS) and Glycyrrhizic acid (GA), form carrier-free, multifunctional spherical nanoparticles (NPs) through noncovalent interactions, such as π–π stacking and hydrogen bonding. The COS-GA NPs displayed a synergistic anti-inflammatory effect, providing much more evidently improved therapeutic benefits for dextran sodium sulfate (DSS)-induced UC mice due to more effective reduction in inflammation and oxidative stress than did equal dosages of COS or GA used alone. In addition, COS-GA NPs have biocompatibility and biosafety properties unique to them. This study will serve as affirmation of the potential of COS-GA NPs as innovative natural anti-inflammatory and antioxidant activities and also such agents as drug discovery in UC, leading possibly to better outcomes in people living with this disabling condition.

Abstract Background This study aimed to evaluate the effect of foraminoplasty using large-channel endoscopy during TESSYS on the biomechanics of the lumbar spine. Methods A complete lumbar spine model, M1, was built using 3D finite elements, and models M2 and M3 were constructed to simulate the intraoperative removal of the superior articular process of L5 using a trephine saw with diameters of 5 mm and 8.5 mm, respectively, and applying normal physiological loads on the different models to simulate six working conditions—anterior flexion, posterior extension, left-right lateral bending, and left-right rotation—to investigate the displacement and facet joint stress change of the surgical segment, and the disc stress change of the surgical and adjacent segments. Results Compared with the M1 model, the M2 and M3 models showed decreased stress at the L4-5 left FJ and a significant increase in stress at the right FJ in forward flexion. In the M2 and M3 models, the L4-5 FJ stresses were significantly greater in left lateral bending or left rotation than in right lateral bending or right rotation. The right FJ stress in M3 was greater during left rotation than that in M2, and that in M2 was greater than that in M1. The L4-5disc stress in the M3 model was greater during posterior extension than that in the M1 and M2 models. The L4-5disc stress in the M3 model was greater in the right rotation than in the M2 model, and that in the M2 model was greater than that in the M1 model. Conclusion Foraminoplasty using large-channel endoscopy could increase the stress on the FJ and disc of the surgical segment, which suggested unnecessary and excessive resection should be avoided in PTED to minimize biomechanical disruption.

Abstract Background The emergence of plasmid-mediated mobile colistin resistance (mcr) gene poses a great challenge to the clinical application of polymyxins. To date, mcr-1 to mcr-10 have been found in animals, humans, and the environment. Among them, mcr-8 was first identified in Klebsiella pneumoniae (K. pneumoniae) of swine origin, and then mcr-8.1 to mcr-8.5 were successively identified. Notably, K. pneumoniae is the major host of the mcr-8 gene in both animals and humans. This study aims to explore the characteristics of K. pneumoniae strains carrying the mcr-8 gene and tmexCD1-toprJ1 gene cluster and investigate the correlation between these two antibiotic resistance genes. Methods The isolates from the poultry farms and the surrounding villages were identified by mass spectrometer, and the strains positive for mcr-1 to mcr-10 were screened by polymerase chain reaction (PCR). The size of the plasmid and the antimicrobial resistance genes carried were confirmed by S1-nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern hybridization, and the transferability of the plasmid was verified by conjugation experiments. Antimicrobial susceptibility testing (AST) and whole genome sequencing (WGS) were used to characterize the strains. Results Two K. pneumoniae isolates (KP26 and KP29) displaying polymyxin resistance were identified as mcr-8 gene carriers. Besides that, tigecycline-resistant gene cluster tmexCD1-toprJ1 was also found on the other plasmid which conferred strain resistance to tigecycline. Through epidemiological analysis, we found that the mcr-8 gene has dispersed globally, circulating in the human, animals, and the environment. Furthermore, our analysis suggests that the coexistence of mcr-8 and tmexCD1-toprJ1 on a single plasmid might evolved through plasmid recombination. Conclusions Although the mcr-8 and tmexCD1-toprJ1 gene clusters in the two strains of K. pneumoniae in this study were on two different plasmids, they still pose a potential threat to public health, requiring close monitoring and further study.

Abstract Background According to the 5th edition of the Japanese Guidelines for the Treatment of Gastric Cancer, proximal gastrectomy is recommended for patients with early upper gastric cancer who can retain the distal half of the residual stomach after R0 resection. However, a large number of recent clinical studies suggest that surgical indications for proximal gastrectomy in the guidelines may be too narrow. Therefore, this meta-analysis included patients with early and advanced gastric cancer and compared short- and long-term postoperative outcomes between the two groups. At the same time, we only had high-quality clinical studies such as propensity score-matched studies and randomized controlled trials, which made our research more authentic and credible. Methods Data were retrieved from PubMed, EMBASE, Medline, and Cochrane Library up to June 2023, and included treatment outcomes after proximal gastrectomy with double-tract reconstruction and total gastrectomy with Roux-en-Y reconstruction. The primary results were Early-phase complications(Anastomotic leakage, Anastomotic bleeding, Abdominal abscess, Abdominal infection, Pulmonary infection, Incision infection, Intestinal obstruction, Dumping syndrome, Pancreatic fistula), Late-phase complications(Intestinal obstruction, Anastomosis stricture, Dumping syndrome, Reoperation, Internal hernia, Incidence of endoscopic gastroesophageal reflux), Serious complications (≥ Grade III C-D score), Quality of life[Gastroesophageal reflux symptom evaluation (Visick score)(≥ III), Los Angeles classification(C or D)], Nutritional status(Hemoglobin, Receipt of vitamin B12 supplementation), Oncologic Outcomes(The 5-year overall survival rates). Secondary outcomes were surgical outcomes (Operative time, Estimated blood loss, Postoperative hospital stay, Number of harvested lymph nodes, Gas-passing, Postoperative mortality).The Cochrane risk-of-bias tool and Newcastle‒Ottawa scale were used to assess the quality of the included studies. Results After screening, 11 studies were finally included, including 1154 patients. Results from the combined literature showed that total gastrectomy had a significant advantage over proximal gastrectomy with double-tract reconstruction in mean operating time (MD = 4.92, 95% CI: 0.22∼9.61 P = 0.04). However, meta-analysis results showed that Hemoglobin (MD = 7.12, 95% CI:2.40∼11.84, P = 0.003) and Receipt of vitamin B12 supplementation (OR = 0.12, 95% CI:0.05∼0.26, P

The load-bearing performance (LBP) of pumpable supports (PPS) is crucial for the stability of longwall pre-driven recovery room (PRR) surrounding rock. However, the unbalanced bearing coefficient (UBC)of the PPS (undertaking unequal load along the mining direction) has not been investigated. A mechanical model of the PRR was established, considering the main roof cantilever beam structure, to derive an assessment formula for the load, the failure criteria, and the UBC of the PPS. Subsequently, the generation mechanisms, and influencing factors of the UBC were revealed. Global sensitivity analysis shows that the main roof hanging length (l2) and the spacing between the PPS (r) significantly impact the UBC. A novel design of the PPS and the coupling control technology were proposed and applied to reduce the UBC of the PPS in the adjacent longwall PRR. Monitor results showed no failure of the PPS at the test site, with the UBC (ζ) reduced to 1.1 consistent with the design value (1.15) basically, fully utilizing the collaborative LBP of the PPS. Finally, the maximum roof-to-floor convergence of the PRR was 234 mm, effectively controlling the stability of the surrounding rock of the PRR and ensuring the mining equipment recovery.

Abstract The transformative role of artificial intelligence (AI) in various fields highlights the need for it to be both accurate and fair. Biased medical AI systems pose significant potential risks to achieving fair and equitable healthcare. Here, we show an implicit fairness learning approach to build a fairer ophthalmology AI (called FairerOPTH) that mitigates sex (biological attribute) and age biases in AI diagnosis of eye diseases. Specifically, FairerOPTH incorporates the causal relationship between fundus features and eye diseases, which is relatively independent of sensitive attributes such as race, sex, and age. We demonstrate on a large and diverse collected dataset that FairerOPTH significantly outperforms several state-of-the-art approaches in terms of diagnostic accuracy and fairness for 38 eye diseases in ultra-widefield imaging and 16 eye diseases in narrow-angle imaging. This work demonstrates the significant potential of implicit fairness learning in promoting equitable treatment for patients regardless of their sex or age.

Abstract Radiotherapy combined with immune checkpoint blockade holds great promise for synergistic antitumor efficacy. Targeted radionuclide therapy delivers radiation directly to tumor sites. LNC1004 is a fibroblast activation protein (FAP)-targeting radiopharmaceutical, conjugated with the albumin binder Evans Blue, which has demonstrated enhanced tumor uptake and retention in previous preclinical and clinical studies. Herein, we demonstrate that 68Ga/177Lu-labeled LNC1004 exhibits increased uptake and prolonged retention in MC38/NIH3T3-FAP and CT26/NIH3T3-FAP tumor xenografts. Radionuclide therapy with 177Lu-LNC1004 induced a transient upregulation of PD-L1 expression in tumor cells. The combination of 177Lu-LNC1004 and anti-PD-L1 immunotherapy led to complete eradication of all tumors in MC38/NIH3T3-FAP tumor-bearing mice, with mice showing 100% tumor rejection upon rechallenge. Immunohistochemistry, single-cell RNA sequencing (scRNA-seq), and TCR sequencing revealed that combination therapy reprogrammed the tumor microenvironment in mice to foster antitumor immunity by suppressing malignant progression and increasing cell-to-cell communication, CD8+ T-cell activation and expansion, M1 macrophage counts, antitumor activity of neutrophils, and T-cell receptor diversity. A preliminary clinical study demonstrated that 177Lu-LNC1004 was well-tolerated and effective in patients with refractory cancers. Further, scRNA-seq of peripheral blood mononuclear cells underscored the importance of addressing immune evasion through immune checkpoint blockade treatment. This was emphasized by the observed increase in antigen processing and presentation juxtaposed with T cell inactivation. In conclusion, our data supported the efficacy of immunotherapy combined with 177Lu-LNC1004 for cancer patients with FAP-positive tumors.

Abstract Developing superporous hemostatic sponges with simultaneously enhanced permeability and mechanical properties remains challenging but highly desirable to achieve rapid hemostasis for non-compressible hemorrhage. Typical approaches to improve the permeability of hemostatic sponges by increasing porosity sacrifice mechanical properties and yield limited pore interconnectivity, thereby undermining the hemostatic efficacy and subsequent tissue regeneration. Herein, we propose a temperature-assisted secondary network compaction strategy following the phase separation-induced primary compaction to fabricate the superporous chitosan sponge with highly-interconnected porous structure, enhanced blood absorption rate and capacity, and fatigue resistance. The superporous chitosan sponge exhibits rapid shape recovery after absorbing blood and maintains sufficient pressure on wounds to build a robust physical barrier to greatly improve hemostatic efficiency. Furthermore, the superporous chitosan sponge outperforms commercial gauze, gelatin sponges, and chitosan powder by enhancing hemostatic efficiency, cell infiltration, vascular regeneration, and in-situ tissue regeneration in non-compressible organ injury models, respectively. We believe the proposed secondary network compaction strategy provides a simple yet effective method to fabricate superporous hemostatic sponges for diverse clinical applications.

Objectives There are differing opinions and findings about the accuracy of self-reported data. This study sought to assess the accuracy of self-reported height, weight, and waist circumference (WC) data among adult residents in poor, rural areas of China. Methods Multi-stage stratified cluster random sampling was used to sample rural adult residents in Jinzhai County. Intraclass correlations (ICCs), Bland-Altman plots with limits of agreements (LOAs), and Cohen’s kappa were used to examine the accuracy of self-reported data. Multiple linear regression was used to explore the effect of demographic and socioeconomic variables. Results Height was over-reported by an average of 0.67 cm, weight and WC were both under-reported, by an average of 0.004 kg and 1.09 cm, respectively. The ICC for height was 0.92, the ICC for weight was 0.93, and the ICC for WC was 0.93. Bland-Altman plots showed no trend in variability with increasing height, weight, and WC, but 95% of the LOAs were wide, especially for WC. The percentage agreement (kappa) for BMI was 82.10% (0.71), and the percentage agreement for WC was 83.56% (0.66). Overall, obesity, overweight, and increased WC were underestimated by 0.56%, 2.64%, and 6.89%, respectively. Assessments of which demographic and socioeconomic factors were associated with statistically significant differences between self-reported and measured data showed that education (junior school vs. primary or below: β = −0.56, 95% CI [−1.01 to −0.11]) and occupation (others vs. professionals: β = 2.16, 95% CI [0.62–3.70]) were associated with differences between measured and self-reported height; occupation (industrial and commercial service vs. professionals: β = 1.57, 95% CI [0.52–2.61]) was associated with differences between measured and self-reported weight; and gender (women vs. men: β = −1.74, 95% CI [−2.51 to −0.97]) and age (60– vs. 18–44: β = −1.62, 95% CI [−2.88 to −0.36]) were associated with differences between measured and self-reported WC. Conclusions Self-reported height and weight were shown to be reliable in poor, rural areas of China, but self-reported WC should be used with caution. To improve the accuracy of self-reported data, certain subgroups should be targeted for educational interventions.

Abstract The exploration of antibiotic‐independent phototherapy strategies for the treatment of bacterial biofilm infections has gained significant attention. However, efficient eradication of bacterial biofilms remains a challenge. Herein, a self‐regulated phototheranostic nanosystem with single wavelength‐triggered photothermal therapy (PTT)/photodynamic therapy (PDT) transformation and oxygen supply for multimodal synergistic therapy of bacterial biofilm infections is presented. This approach combines a eutectic mixture of natural phase‐change materials (PCMs) and an aggregation‐induced emission (AIE) phototheranostic agent TPA‐ICN to form colloidally stable nanopartcicles (i.e. AIE@PCM NPs). The reversible solid−liquid phase transition of PCMs facilitates the adaptive regulation of the aggregation states of TPA‐ICN, enabling a switch between the energy dissipation pathways for enhanced PDT in solid PCMs or enhanced PTT in liquid PCMs. Additionally, oxygen‐carrying thermoresponsive nanoparticles are also introduced to alleviate the hypoxic microenvironment of biofilms by releasing oxygen upon heating by AIE@PCM NPs with enhanced PTT. The nanosystem exhibits outstanding therapeutic efficacy against bacterial biofilms both in vitro and in vivo, with an antibacterial efficiency of 99.99%. This study utilizes a self‐regulated theranostic nanoplatform with adaptive PTT/PDT transformation via the phase transition of PCMs and heat‐triggered oxygen release, holding great promise in the safe and efficient treatment of bacterial biofilm infections.

The viral genome titer is a crucial indicator for the clinical dosing, manufacturing, and analytical testing of recombinant adeno-associated virus (rAAV) gene therapy products. Although quantitative PCR and digital PCR are the common methods used for quantifying the rAAV genome titer, they are limited by inadequate accuracy and robustness. The clustered regularly interspaced short palindromic repeat (CRISPR)-Cas12a biosensor is being increasingly used in virus detection; however, there is currently no report on its application in the titer determination of gene therapy products. In the present study, an amplification-free CRISPR-Cas12a assay was developed, optimized, and applied for rAAV genome titer determination. The assay demonstrated high precision and accuracy within the detection range of 4 × 109 and 1011 vg/mL. No significant difference was observed between the Cas12a and qPCR assay results (p

Ecosystem services are crucial for human survival and development. Changes in land use can lead to alterations in ecosystem service functions. However, the mechanism of how land use changes resulting from underground coal mining affect ecosystem service remains unclear, especially in areas with high groundwater levels. To address this issue, we studied the spatiotemporal in land use change in Jining City from 2000 to 2020 and employed Markov-PIM (probability integration method)-PLUS (Patch-generate Land Use Simulation) model to simulate land use change and ecosystem service values (ESV) in Jining City by 2030 under four different scenarios. The results indicate that from 2000 to 2020, the area of ecological space increased by 169.99 km2, and the area of living space expanded by 775.28 km2, while the area of production space decreased by 945.27 km2, conversely. These changes led to a 3 million yuan increase in total ESV. From 2020 to 2030, there was a marked decline in ESV under both natural development (ND) and living space preference (LSP) scenarios, with decreases of 0.59 billion yuan and 1.38 billion yuan, respectively. In contrast, in production space preference (PSP) and ecological space preference (ESP) scenarios, ESV increase by 0.22 billion yuan and 0.34 billion yuan. The ESP scenario is an effective strategy to strengthen environmental protection, significantly improve the ESV level of Jining City and meet the development goals of Jining City. Finally, the study concludes with recommendations like comprehensive management, industrial upgrading, and collaborative development for optimizing Jining City's future land use and enhance ESV for urban development.

BackgroundWhile several studies have noted a higher SII correlates with multiple diseases, research on the association between SII and cataract remains limited. Our cross-sectional study seeks to examine the association between SII and cataract among outpatient US adults.MethodsThis compensatory cross-sectional study utilized NHANES data from 1999 to 2008 cycles, conducting sample-weighted multivariate logistic regression and stratified analysis of subgroups.ResultsAmong 11,205 adults included in this study (5,571 [46.2%] male; 5,634 [53.8%] female), 2,131 (15.2%) had cataract and 9,074 (84.8%) did not have cataract. A fully adjusted model showed that SII higher than 500 × 109/L was positively correlated with an increased risk of cataracts among women (OR, 1.27; 95% CI, 1.02–1.59) (p = 0.036). However, no difference was found in the men subgroup, and there was no significant interaction between SII and sex.ConclusionOur results indicated that a SII higher than 500 × 109/L was positively correlated with an increased risk of cataracts in women. This study is the first to specifically investigate the impact of a high SII on cataract risk in outpatient adults in the United States. By effectively addressing inflammation, it is possible to mitigate cataract progression and significantly enhance patient outcomes.

The instability of plastic flow in medium manganese steel was investigated through uniaxial tensile tests conducted at room temperature across various strain rates. The Portvin-Le Chatelier (PLC) effect was analyzed using statistical methods and a multifractal approach. The findings indicate that the zigzag stress–strain curves associated with instability plastic flow exhibit typical multifractal characteristics. Furthermore, the multifractal analysis quantifies the influence of strain rate and initial phase composition on the instability characteristics of the stress–strain curves. Specifically, it was observed that lower strain rates and austenite content correspond to a chaotic state, whereas higher strain rates and austenite content result in self-organizing critical dynamics. Finally, the underlying physical mechanisms driving these differing modes of behavior are discussed, with a focus on their relationship to strain rate and the initial austenitic phase fraction.

Background Bridges are vital construction infrastructures that almost every nation needs in order to function. Climate change is a significant issue, that especially affects the construction industry. It is very important that bridges are able to withstand the impacts of climate change and adaptation measures will be required to achieve this. Methods The digital twin will be developed using BIM to manage the climate change adaptation measures for the bridges. A 6D BIM model will be created that includes the 3D Revit model of a bridge featuring climate change measures, the climate change adaptation measures timeline schedule, climate change adaptation cost estimation, and carbon emission estimation, which will be produced using Revit software, Navisworks, and Granta EduPack. The results will show how 6D BIM can be used to support the adaptation of bridges to the effects of climate change. Results The findings underscore the efficacy of 6D BIM in enhancing bridge resilience against climate change impacts. The 3D model demonstrates integration of adaptation measures without compromising bridge functionality. Moreover, the 4D model's timeline scheduling facilitates hazard anticipation, project planning, communication enhancement, collaborative efforts, and project visualization. Cost estimations from the 5D model reveal varying costs among adaptation measures, while the 6D model highlights differences in carbon footprints. These BIM dimensions enable stakeholders to analyse effects on project costs and energy consumption, aiding sustainability and cost-efficiency considerations. Conclusions The study exhibits the literature review analysis, the risk assessment, research on climate change adaptation strategies, and implementation using Revit 2022, Navisworks 2022, and Granta EduPack software. By contributing to the adaptation of bridges to climate change effects, the research has provided valuable insights and practical implications for enhancing bridge resilience globally.

Background Accessory breast plasma cell mastitis (PCM) is uncommon in clinical practice with rare reports. Objective To investigate the clinical characteristics, diagnostic methods and the traditional Chinese medicine (TCM) clinical efficacy of accessory breast PCM. Methods The clinical diagnosis and treatment data of 15 patients with accessory breast PCM admitted to Beijing Hospital of Traditional Chinese Medicine, Capital Medical University from January 2017 to December 2021 were analyzed retrospectively, the general information, diagnostic methods, treatment methods and outcomes of 15 cases with accessory breast PCM were summarized. Results A total of 15 female patients of childbearing age with accessory breast PCM were included in this paper, with onset within 2-5 years after pregnancy. The etiology was complex and the course of accessory breast PCM was protracted, which was similar to breast PCM in pathogenetic characteristics, using pathological examination results as gold standard for diagnosis. After the combination of internal and external treatment of TCM, the symptoms of 15 patients were relieved, local lesions disappeared, and there was no recurrence after six months of follow-up. Conclusion Accessory breast PCM is rare in clinical practice, which is easy to be misdiagnosed or missed, and difficult to be treated clinically. The combination of internal and external treatment of TCM has a significant effect on accessory breast PCM.

The Gibberellic Acid-stimulated Arabidopsis (GASA) gene family is involved in the regulation of gene expression and plant growth, development, and stress responses. To investigate the function of loquat GASA genes in the growth and developmental regulation of plants, a loquat EjGASA6 gene homologous to Arabidopsis AtGASA6 was cloned. EjGASA6 expression was induced by gibberellin, and ectopic transgenic plants containing this gene exhibited earlier bloom and longer primary roots since these phenotypic characteristics are related to higher gibberellin content. Transcriptome analysis and qRT-PCR results showed that the expression levels of GA3ox1 and GA20ox1, which encode key enzymes in gibberellin biosynthesis, were significantly increased. Furthermore, we confirmed that EjGASA6 could promote the expression of GA20ox1 via the luciferase reporter system. Overall, our results suggest that EjGASA6 promotes blooming and main-root elongation by positively regulating gibberellin biosynthesis. These findings broaden our understanding of the role of GASAs in plant development and growth, and lay the groundwork for future research into the functions of EjGASA6 in regulating loquat growth and development.