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Abstract To compare the safety and effectiveness of the combination of intelligent intrarenal pressure control platforms and flexible end ureteral access sheath combined with flexible ureteroscopic lithotripsy (FURL) for the treatment of renal stones less than 2 cm with day case mode. From November 2023 to July 2024, a prospective, randomized, double-blind, parallel-controlled study was conducted to recruit 60 patients with upper urinary tract calculi measuring ≤ 2 cm in longest diameter. A total of 60 eligible patients were consecutively enrolled. Based on a pre-generated random number table and allocation scheme using SPSS 27.0, patients were assigned to either the intelligent pressure control group (IFURL, n = 30) or the head bending group (BFURL, n = 30). Blinding measures were implemented for patients, data collectors, statisticians, and analysts, with the allocation results disclosed to the surgeons prior to the start of the procedure in the operating room. The operation duration for IFURL and BFURL was 52.50 (48.00, 60.00) vs. 46.00 (36.00, 56.25), respectively (p = 0.047). Stone free rate (SFR) on the first postoperative day was 73.33% vs. 93.33% for IFURL and BFURL, respectively (p = 0.038). While, SFR was no significant difference between the two groups after two months(90.00% vs. 96.67%, p = 0.301). One patient in IFURL was readmitted after discharge due to fever 2 days post-discharge, and improved after 2 days of anti-infection treatment. One patient in BFURL was readmitted due to lumbar and abdominal pain from urine extravasation, which improved after 3 days of anti-infection treatment. SFR of one-month post-surgery for renal calculi ≤ 2 cm treated with intelligent pressure control and flexible UAS combined with FURL in day surgery mode was similar, with low infection-related complications and rehospitalization rates, showing no statistical difference. However, the overall hospitalization costs for the BFURL was lower than IFURL.

Abstract To meet the comprehensive requirements of drivers for Human-Computer Interaction (HCI) during operation and to enhance situation awareness (SA), this paper proposes a design and evaluation method for flight simulator HCI interfaces grounded in SA. Firstly, the widely adopted Endsley’s SA model, which comprehensively covers processes relevant to individual drivers was selected as the foundational framework. The study concentrates on flight, cruise, and landing scenarios within the simulator, analyzing and restructuring the information architecture of the HCI interface. Secondly, a self-assessment scale was developed based on the three-level model of information processing for SA to measure drivers’ SA cognitive levels. The core scenarios of the simulation training were analyzed to establish a design-making process. Thirdly, invite participants were invited to engage in simulated driving sessions on the flight simulator, where their SA cognitive levels were assessed. An analysis of detail features was performed on samples with high SA cognitive levels. Subsequently, drivers’ requirements for the control layout features of the HCI interface design were gathered through surveys. The design detail features of the HCI interface associated with high SA cognitive levels were identified and synthesized into four distinct dimensions to guide the detailed design process. Finally, participants engaged in simulated driving using the finalized interface design, and their SA cognitive levels were reassessed. The results demonstrated that the HCI interface design derived from this method significantly improved SA cognitive levels compared to the original design.

Abstract Our study aimed to retrospectively analyze the patients who underwent the combination of negative pressure equipment and RIRS(NP-RIRS) for renal stones, and identified new high-risk factors related to infection. 456 patients with renal stones ≤ 3 cm underwent NP-RIRS in our department, from January 2022 to October 2023. All patients were divided into non-infection group(NIRIRS group) and infection group(IRIRS group) based on infection complications during the perioperative period. Establish a receiver operating characteristic curve(ROC curve)based on variables with statistical differences, and use the Jordan index to find the optimal cutoff value. Classify the data into two categories based on the best truncation value, and perform binary logistic regression analysis on the classified data. In the IRIRS group, there were 10 cases of fever (2.92%), 2 cases of sepsis (0.58%), and no cases of septic shock or death. The length and the CT value of the stone were 16 (13,21) vs. 22 (19,24) (p

ObjectiveThis study was to employ 18F-flurodeoxyglucose (FDG-PET) to evaluate the resting-state brain glucose metabolism in a sample of 46 patients diagnosed with disorders of consciousness (DoC). The aim was to identify objective quantitative metabolic indicators and predictors that could potentially indicate the level of awareness in these patients.MethodsA cohort of 46 patients underwent Coma Recovery Scale-Revised (CRS-R) assessments in order to distinguish between the minimally conscious state (MCS) and the unresponsive wakefulness syndrome (UWS). Additionally, resting-state FDG-PET data were acquired from both the patient group and a control group consisting of 10 healthy individuals. The FDG-PET data underwent reorientation, spatial normalization to a stereotaxic space, and smoothing. The normalization procedure utilized a customized template following the methodology outlined by Phillips et al. Mean cortical metabolism of the overall sample was utilized for distinguishing between UWS and MCS, as well as for predicting the outcome at a 1-year follow-up through the application of receiver operating characteristic (ROC) analysis.ResultsWe used Global Glucose Metabolism as the Diagnostic Marker. A one-way ANOVA revealed that there was a statistically significant difference in cortical metabolic index between two groups (F(2, 53) = 7.26, p

In pursuit of reliable and efficient industrial microbes, this study integrates cutting-edge systems biology tools with Halomonas bluephagenesis TD01, a robust halophilic bacterium. We generated the complete and annotated circular genome sequence for this model organism, constructed and meticulously curated a genome-scale metabolic network, achieving striking 86.32% agreement with Biolog Phenotype Microarray data and visualize the network via an interactive Electron/Thrift server architecture. We then analyzed the genome-scale network using vertex sampling analysis (VSA) and found that productions of biomass, polyhydroxyalkanoates (PHA), citrate, acetate, and pyruvate are mutually competing. Recognizing the dynamic nature of H. bluephagenesis TD01, we further developed and implemented the hyper-cube-shrink-analysis (HCSA) framework to predict effects of nutrient availabilities and metabolic reactions in the model on biomass and PHA accumulation. We then, based on the analysis results, proposed and validate multi-step feeding strategies tailored to different fermentation stages. This integrated approach yielded remarkable results, with fermentation culminating in a cell dry weight of 100.4 g/L and 70% PHA content, surpassing previous benchmarks. Our findings exemplify the powerful potential of system-level tools in the design and optimization of industrial microorganisms, paving the way for more efficient and sustainable bio-based processes.

ABSTRACTChanges in water content dynamics can serve as predictive indicators for catastrophic transitions in vegetation tipping elements. Vegetation water content is a rapidly changing parameter with sub-daily fluctuations, and current space-borne sensors fall short of providing adequate spatiotemporal coverage for effective analysis. The Moon-based Earth observation, i.e. Synthetic Aperture Radar has recently showcased prolonged durations, rapid revisiting rates, and extensive monitoring capabilities with a decent spatial resolution (10-100 m). This opens up new possibilities for vegetation water content monitoring which has not yet been discussed. The study has assessed its monitoring capability in four critical vegetation tipping elements and considered both overall temporal observation availability fraction and diurnal variation acquisition. The results indicate that Amazon and Sahelian regions can be observed for ∼30% of a nutation period (∼18.6 years). Diurnal variations in water content can be captured with a 1-hour interval every 16–23 days for the Amazon and Sahelian regions. For polar tundra and boreal regions, continuous observation spanning 7–12 h can be achieved. These outstanding characteristics offer a deeper understanding of water content dynamics in vegetation tipping elements, which will enhance our prediction for their critical transitions.

Abstract Background Intussusception presents a significant emergency that often necessitates bowel resection, leading to severe complications and management challenges. This study aims to investigate and establish a scoring system to enhance the prediction of bowel resection necessity in pediatric intussusception patients. Methods This retrospective study analyzed 660 hospitalized patients with intussusception who underwent surgical management at a pediatric hospital in Southwest China from April 2008 to December 2020. The necessity of bowel resection was assessed and categorized in this cohort. Variables associated with bowel resection were examined using univariate and multivariate logistic regression analyses. Based on these analyses, a scoring system was developed, grounded on the summation of the coefficients (β). Results Among the 660 patients meeting the inclusion criteria, 218 required bowel resection during surgery. Bowel resection occurrence was linked to an extended duration of symptoms (Odds Ratio [OR] = 2.14; 95% Confidence Interval [CI], 1.03–5.23; P = 0.0015), the presence of gross bloody stool (OR = 8.98; 95% CI, 1.76–48.75, P

Summary: Energy crops play a vital role in meeting future energy and chemical demands while addressing climate change. However, the idealization of low-carbon workflows and careful consideration of cost-benefit equations are crucial for their more sustainable implementation. Here, we propose tobacco as a promising energy crop because of its exceptional water solubility, mainly attributed to a high proportion of water-soluble carbohydrates and nitrogen, less lignocellulose, and the presence of acids. We then designed a strategy that maximizes biomass conversion into bio-based products while minimizing energy and material inputs. By autoclaving tobacco leaves in water, we obtained a nutrient-rich medium capable of supporting the growth of microorganisms and the production of bioproducts without the need for extensive pretreatment, hydrolysis, or additional supplements. Additionally, cultivating tobacco on barren lands can generate sufficient biomass to produce approximately 573 billion gallons of ethanol per year. This approach also leads to a reduction of greenhouse gas emissions by approximately 76% compared to traditional corn stover during biorefinery processes. Therefore, our study presents a novel and direct strategy that could significantly contribute to the goal of reducing carbon emissions and global sustainable development compared to traditional methods.

Research on the geological process of the Xing’an - Mongolia Orogenic Belt has attracted the attention of scholars both domestically and internationally. Its genesis and tectonic location may help revealing the geological processes asscoaited with the evolution of the Xing’an - Mongolia Orogenic Belt. This study focuses on the development of the Permian granitic complex in Jielin Ranch, and we conduct systematic geological, petrographic, zircon U-Pb chronology, Hf isotope, and geochemical tracing of rock elements for evidence. The results show that the granitic complex is mainly composed of monzogranite and syenogranite, which obtained zircon U-Pb ages of 291.1 ± 1.1 Ma and 260.8 ± 1.1 Ma, respectively. The monzogranite and syenogranite are all acidic and aluminum rich rocks, and the monzogranite is a potassium rich, high potassium calcium alkaline rock series with relatively low REE content, high degree of fractionation, and insignificant europium anomalies, enriched with LILE (Rb, Th, U, K), deficient elements such as Ba, Sr, Nb, Ti, and P, εHf(t) values are from +4.1 to +7.0 (TDM2=1130–920 Ma). Geochemistry shows that the monzogranite belongs to high fractionation of I-type granite, which formed in a subduction-compressional or extension tectonic environment, and Middle Neoproterozoic lower crust rocks as the major source material of magma. The syenogranite is a potassium high potassium transitional rock series with a high rare earth content (214 × 10−6∼325 × 10−6), low LREE/HREE (2.54–6.41), δEu (0.04–0.15) and the typical “four component effect” fractionation mode is enriched in large ion lithophilic elements such as Rb, Th, K, and strongly depleted in elements such as Ba, Sr, Nb, Ta, Ti, P, εHf(t) values are from +4.2 to +8.6 (TDM2=738–1228 Ma), suggesting the characteristics of an “A2 type” granite. The magma originated from partial melting of the lower crust of the Middle and Neoproterozoic with the participation of mantle derived melts, and was formed in a back-arc extensional environment. This suggests that the study area experienced a subduction-compressional or extension tectonic environment during the early Permian and a brief backarc extension process in the late Permian.

Abstract To compare the safety and effectiveness of the combination of intelligent intrarenal pressure control platforms (IPCP) and flexible ureteral access sheath (FUAS) combined with retrograde intrarenal surgery (RIRS) for the treatment of renal stones less than 2 cm. We retrospectively collected 383 patients with renal stones who underwent RIRS in our department from June 2022 to October 2023. Inclusion criteria: stone length or the sum of multiple stone lengths ≤ 2 cm. Finally, 99 cases were included and divided into an IPCP group (n = 40) and FUAS group (n = 59) based on surgical methods. The main endpoint was the stone-free rate (SFR) at third months after surgery, with no residual stones or stone fragments less than 2 mm defined as stone clearance. The secondary endpoints were surgical time and perioperative complications, including fever, sepsis, septic shock, and perirenal hematoma. There was no statistically significant difference in general information between the two groups, including age, gender, body mass index, comorbidities, stone side, stone location, stone length, urine bacterial culture, and hydronephrosis. The operation time for IPCP group and FUAS group was 56.83 ± 21.33 vs 55.47 ± 19.69 min (p = 0.747). The SFR of IPCP group and FUAS group on the first postoperative day was 75.00% vs 91.50% (p = 0.024). The SFR was 90.00% vs 94.90% in the third month (p = 0.349).In IPCP group, there were 11 cases with stones located in the lower renal calyces and 17 cases in FUAS group. The SFR of the two groups on the first day and third months after surgery were 45.50% vs 88.20% (p = 0.014) and 63.60% vs 94.10% (p = 0.040), respectively, with statistical differences. For kidney stones ≤ 2 cm, there was no difference in SFR and the incidence of infection-related complications between IPCP and FUAS combined with RIRS, both of which were superior to T-RIRS. For lower renal caliceal stones, FUAS has a higher SFR compared to IPCP.

Abstract Glioblastoma (GBM) cells require large amounts of iron for tumor growth and progression, which makes these cells vulnerable to destruction via ferroptosis induction. Mitochondria are critical for iron metabolism and ferroptosis. Sirtuin-3 (SIRT3) is a deacetylase found in mitochondria that regulates mitochondrial quality and function. This study aimed to characterize SIRT3 expression and activity in GBM and investigate the potential therapeutic effects of targeting SIRT3 while also inducing ferroptosis in these cells. We first found that SIRT3 expression was higher in GBM tissues than in normal brain tissues and that SIRT3 protein expression was upregulated during RAS-selective lethal 3 (RSL3)-induced GBM cell ferroptosis. We then observed that inhibition of SIRT3 expression and activity in GBM cells sensitized GBM cells to RSL3-induced ferroptosis both in vitro and in vivo. Mechanistically, SIRT3 inhibition led to ferrous iron and ROS accumulation in the mitochondria, which triggered mitophagy. RNA-Sequencing analysis revealed that upon SIRT3 knockdown in GBM cells, the mitophagy pathway was upregulated and SLC7A11, a critical antagonist of ferroptosis via cellular import of cystine for glutathione (GSH) synthesis, was downregulated. Forced expression of SLC7A11 in GBM cells with SIRT3 knockdown restored cellular cystine uptake and consequently the cellular GSH level, thereby partially rescuing cell viability upon RSL3 treatment. Furthermore, in GBM cells, SIRT3 regulated SLC7A11 transcription through ATF4. Overall, our study results elucidated novel mechanisms underlying the ability of SIRT3 to protect GBM from ferroptosis and provided insight into a potential combinatorial approach of targeting SIRT3 and inducing ferroptosis for GBM treatment.

Abstract The authors aimed to investigate the association between outdoor light at night (LAN) intensity and blood pressure. The study included 13 507 participants aged 45 and above from the 2011–2012 China Health and Retirement Longitudinal Study baseline survey. Blood pressure measurements were obtained by averaging the last two readings recorded (three measurements with an interval of 45–60 s between each measurement) during the survey. Outdoor LAN intensity was assessed using Defense Meteorological Satellite Program data. The study categorized participants based on quartiles of outdoor LAN intensity and employed statistical methods like linear regression, restricted cubic splines, and logistic models to analyze the connections. After adjusting for potential confounding factors, higher levels of outdoor LAN intensity were associated with increase in systolic blood pressure (0.592 mmHg/interquartile range [IQR], 95% confidence interval [CI]: 0.027,1.157), diastolic blood pressure (0.853 mmHg/IQR, 95% CI: 0.525,1.180) and mean arterial pressure (0.766 mmHg/IQR, 95% CI: 0.385,1.147). Interestingly, the relationship between LAN intensity and odds of hypertension followed a non‐linear pattern, resembling a reverse “L” shape on cubic splines. Participants with the highest quartile of outdoor LAN intensity had 1.31‐fold increased odds of hypertension (95% CI: 1.08–1.58) compared to the lowest quartile. Additionally, there was an observable trend of rising odds for high‐normal blood pressure with higher levels of LAN intensity in the crude model, but no statistically significant differences were observed after adjusting for confounding factors. In conclusion, this study underscores a significant connection between outdoor LAN intensity and the prevalence of hypertension.

This study designs and develops a wearable exoskeleton piano assistance system for individuals recovering from neurological injuries, aiming to help users regain the ability to perform complex tasks such as playing the piano. While soft robotic exoskeletons have proven effective in rehabilitation therapy and daily activity assistance, challenges remain in performing highly dexterous tasks due to structural complexity and insufficient motion accuracy. To address these issues, we developed a modular division method based on multi-domain mapping and a top-down process model. This method integrates the functional domain, structural domain, and user needs domain, and explores the principles and methods for creating functional construction modules, overcoming the limitations of traditional top-down approaches in design flexibility. By closely combining layout constraints with the design model, this method significantly improves the accuracy and efficiency of module configuration, offering a new path for the development of piano practice assistance devices. The results demonstrate that this device innovatively combines piano practice with rehabilitation training and through the introduction of ontological modeling methods, resolves the challenges of multidimensional needs mapping. Based on five user requirements (P), we calculated the corresponding demand weight (K), making the design more aligned with user needs. The device excels in enhancing motion accuracy, interactivity, and comfort, filling the gap in traditional piano assistance devices in terms of multi-functionality and high adaptability, and offering new ideas for the design and promotion of intelligent assistive devices. Simulation analysis, combined with the motion trajectory of the finger’s proximal joint, calculates that 60° is the maximum bending angle for the aforementioned joint. Physical validation confirms the device’s superior performance in terms of reliability and high-precision motion reproduction, meeting the requirements for piano-assisted training. Through multi-domain mapping, the top-down process model, and modular design, this research effectively breaks through the design flexibility and functional adaptability bottleneck of traditional piano assistance devices while integrating neurological rehabilitation with music education, opening up a new application path for intelligent assistive devices in the fields of rehabilitation medicine and arts education, and providing a solution for cross-disciplinary technology fusion and innovative development.

The 3D printing method based on digital light processing (DLP) technology can transform liquid resin materials into complex 3D models. However, due to the limitations of digital micromirror device (DMD) specifications, the normal DLP 3D printing method (NDPM) cannot simultaneously process large-size and small-feature parts. Therefore, a scalable DLP 3D printing method (SDPM) was proposed. Different printing resolutions for a part were designed by changing the distance between the projector and the molding liquid level. A scalable DLP printer was built to realize the printing resolution requirements at different sizes. A series of experiments were performed. Firstly, the orthogonal experimental method was used, and the minimum and maximum projection distances were obtained as 20.5 cm and 30.5 cm, respectively. Accordingly, the layer thickness, exposure time, and waiting leveling time were 0.08 mm, 3 s, and 6 s and 0.08 mm, 7 s, and 10 s. Secondly, single-layer column feature printing was finished, which was shown to have two minimum printing resolutions of 101 μm and 157 μm at a projection distance of 20.5 cm and 30.5 cm. Thirdly, a shape accuracy test was conducted by using the SDPM. Compared with the NDPM, the shape accuracy of the small-feature round, diamond, and square parts was improved by 49%, 42%, and 2%, respectively. This study verified that the SDPM can build models with features demonstrating high local shape accuracy.

Perineural invasion (PNI), the neoplastic invasion of nerves, is an often overlooked pathological phenomenon in cervical cancer that is associated with poor clinical outcomes. The occurrence of PNI in cervical cancer patients has limited the promotion of Type C1 surgery. Preoperative prediction of the PNI can help identify suitable patients for Type C1 surgery. However, there is a lack of appropriate preoperative diagnostic methods for PNI, and its pathogenesis remains largely unknown. Here, we dissect the neural innervation of the cervix, analyze the molecular mechanisms underlying the occurrence of PNI, and explore suitable preoperative diagnostic methods for PNI to advance the identification and treatment of this ominous cancer phenotype.

Background and objectivesInitial shunt failure following ventriculoperitoneal (VP) shunt surgery has a significant impact on the working time of the shunt. However, there are few studies regarding factors affecting VP shunt longevity. Hence, in this study, we aimed to build a nomogram to predict the longevity of the replacement VP shunt in patients with initial shunt failure.MethodsFrom 2011 to 2021, 142 patients with initial VP failure who underwent VP shunt revision were enrolled and relevant clinical and demographic factors were analyzed. Univariate and multivariate Cox proportional hazard regression models were used to choose predictors, and a nomogram was constructed using nine independent prognostic variables: sex, age, hydrocephalus type, intensive care unit admission, tracheostomy, decompressive craniectomy, craniotomy, lumbar cisterna drainage, and ventricular drainage. The prediction models’ discrimination, accuracy, calibration, and clinical value were evaluated using Harrell’s C-index, a calibration plot, and decision curve analysis.ResultsAt 1 month, 3 months, and 5 years, the nomogram’s C-index was 0.680, 0.708, and 0.694, respectively. The nomogram’s calibration plot provided a good fit for the overall prediction over the course of 1 year. Decision curve analysis predicted that 1–3 months after surgery will yield good net benefits between 30 and 50% probability thresholds.ConclusionA preoperative nomogram may be an effective tool for assessing VP shunt longevity after initial VP shunt placement.

Abstract As a model of the combination of nostalgia and creative products, ethnic cultural heritage carry the function of shaping and spreading geo-culture. Its unique geo-cultural context, as a link, shows the historical inheritance of local culture. The deep deconstruction of its emotional identity helps to strengthen this identity and stimulate more cultural and creative designs with national and local characteristics. While culture prospers, the local cultural and creative economy is strengthened and cultural confidence and national self-confidence are further enhanced. Based on the New Year paintings of Wuqiang in Hebei, which have a strong folk vernacular and geo-cultural character in northern China, in the process of using the reconstructed pattern elements for clothing design, 156 questionnaires were collected through questionnaire interviews and fsQCA was used to analyze the emotional identity of products with high geo-cultural recognition. The study finds that while the injection of regional culture plays a role in the development of products, people's emotional identification with vernacular cultural and creative products actually depends on a combination of causal paths, with beauty and elegance more important than place and humanity as commonly believed to reflect geographic cultural identity. fsQCA was used to analyze the emotional identity of products with high geo-cultural recognition. And understand the emotional components of vernacular cultural products and how emotional factors influence people's identities.

Abstract As a terpenoids natural product isolated from the plant Thunder God Vine, Celastrol is widely studied for its pharmacological activities, including anti-tumor activities. The clinical application of Celastrol is strictly limited due to its severe side effects, whereas previously revealed targets and mechanism of Celastrol seldom reduce its in vivo toxicity via structural optimization. Target identification has a far-reaching influence on the development of innovative drugs, and omics data has been widely used for unbiased target prediction. However, it is difficult to enrich target of specific phenotype from thousands of genes or proteins, especially for natural products with broad promising activities. Here, we developed a text-mining-based web-server tool to enrich targets from omics data of inquired compounds. Then peroxiredoxin 1 (PRDX1) was identified as the ROS-manipulating target protein of Celastrol in colorectal cancer. Our solved high-resolution crystal structure revealed the unique covalent binding mode of Celastrol with PRDX1. New derivative compound 19-048 with improved potency against PRDX1 and selectivity towards PRDX2~PRDX6 were synthesized based on crystal structure analysis. Both Celastrol and 19-048 effectively suppressed the proliferation of colorectal cancer cells. The anti-tumor efficacy of Celastrol and 19-048 was significantly diminished on xenograft nude mice bearing PRDX1 knock-down colorectal cancer cells. Several downstream genes of p53 signaling pathway were dramatically up-regulated with Celastrol or 19-048 treatment. Our findings reveal that the side effects of Celastrol could be reduced via structural modification, and PRDX1 inhibition is promising for the treatment of colorectal cancer.

Delineating the cellular composition of tumour boundaries in spatial transcriptomics (ST) data is challenging. Here, the authors develop Cottrazm to integrate ST with histological imaging and single-cell data, identify the malignant and non-malignant tissue boundaries, deconvolute cell-type composition, and reconstruct cell type-specific gene expression profiles.

Abstract Background Cervical cancer (CC) is the 3rd most common cancer in women and the 4th leading cause of deaths in gynaecological malignancies, yet the exact progression of CC is inconclusive, mainly due to the high complexity of the changing tumour microenvironment (TME) at different stages of tumorigenesis. Importantly, a detailed comparative single-nucleus transcriptomic analysis of tumour microenvironment (TME) of CC patients at different stages is lacking. Methods In this study, a total of 42,928 and 29,200 nuclei isolated from the tumour tissues of stage-I and II CC patients and subjected to single-nucleus RNA sequencing (snRNA-seq) analysis. The cell heterogeneity and functions were comparatively investigated using bioinformatic tools. In addition, label-free quantitative mass spectrometry based proteomic analysis was carried out. The proteome profiles of stage-I and II CC patients were compared, and an integrative analysis with the snRNA-seq was performed. Results Compared with the stage-I CC (CCI) patients, the immune response relevant signalling pathways were largely suppressed in various immune cells of the stage-II CC (CCII) patients, yet the signalling associated with cell and tissue development was enriched, as well as metabolism for energy production suggested by the upregulation of genes associated with mitochondria. This was consistent with the quantitative proteomic analysis that showed the dominance of proteins promoting cell growth and intercellular matrix development in the TME of CCII group. The interferon-α and γ responses appeared the most activated pathways in many cell populations of the CCI patients. Several collagens, such as COL12A1, COL5A1, COL4A1 and COL4A2, were found significantly upregulated in the CCII group, suggesting their roles in diagnosing CC progression. A novel transcript AC244205.1 was detected as the most upregulated gene in CCII patients, and its possible mechanistic role in CC may be investigated further. Conclusions Our study provides important resources for decoding the progression of CC and set the foundation for developing novel approaches for diagnosing CC and tackling the immunosuppressive TME.

In this study, we reported a complex-signal-based optical coherence tomography angiography (OCTA) method, called complex correlated phase gradient variance (CCPGV), for mapping high-quality microvascular images. The performance of the newly proposed algorithm is benchmarked against the previously reported phase-resolved Doppler variance, complex differential variance (CDV), and split-spectrum amplitude and phase-gradient angiography (SSAPGA), by both tissue phantoms experiments and in vivo human skin measurements. Compared to the phase-resolved Doppler variance, CCPGV can intrinsically reject undesirable phase shifts caused by bulk motion and trigger jitter. In contrast to CDV and SSAPGA, which are insensitive to phase instability, CCPGV can provide superior motion contrast, as demonstrated by ∼1.4 and 3 times higher contrast in phantom experiments respectively. An increase of 27.3% and 106.3% were found in vivo experiments for CCPGV, making it easier to distinguish vessels from the background static. Benefiting from the advantages, more vessels and better connectivity can be visualized in the en-face angiogram processed by the CCPGV method. We believe that our method will benefit the biomedical community to some extent in disease diagnosis and monitoring.

ABSTRACT Caerin 1 is a family of host defense peptides with antimicrobial properties originally isolated from the Australian tree frog. Both caerin 1.1 and caerin 1.9 have been demonstrated to inhibit infections caused by multiple antibiotic-resistant bacteria, both in vitro and in vivo. In this current study, we conducted a comparison of the minimum inhibitory concentrations of caerin 1.1 and caerin 1.9 (referred to as caerin 1.1/1.9) with commonly used antibiotics against various bacteria, including Staphylococcus aureus, Copper-Green Pseudomonas aeruginosa, Acinetobacter baumannii, and Streptococcus haemolyticus. Our findings reveal that caerin 1.1/1.9 not only prevent the formation of biofilms by A. baumannii but also exhibit a therapeutic effect on established biofilms. Furthermore, our study demonstrates that caerin 1.1/1.9 significantly inhibit the growth of methicillin-resistant Staphylococcus aureus (MRSA) strains in a murine skin infection model. A quantitative proteomic analysis conducted as part of our study indicates that caerin 1.1/1.9 primarily activate oxidative phosphorylation pathways, along with several pathways associated with tissue repair and growth. These findings were observed in comparison to untreated tissues that were infected with MRSA in mice. In summary, our research outcomes suggest that caerin 1.1/1.9 exhibit the potential to serve as promising drug candidates for treating complicated antibiotic-resistant bacterial infections in humans. IMPORTANCE Caerin 1.1 and caerin 1.9, natural antimicrobial peptides derived from tree frogs, have demonstrated the ability to inhibit the growth of antibiotic-resistant bacteria, comparable to certain widely used antibiotics. Additionally, these peptides exhibit the capacity to prevent or treat biofilms formed by bacteria in conjunction with bodily components. The mechanisms underlying their antibacterial effects were investigated through a mouse model of bacterial skin infection, utilizing proteomic analysis as a technological approach.

We admitted a 41-year-old man with a chief complaint of multiple nodules found in the scrotum, accompanied by itching discomfort, occasionally some nodules discharged white secretions. Physical examination revealed extensive nodules of scrotal skin, approximately 2.0 cm in diameter in the largest, grayish white, textured hard, no pain, no breakdown of skin. Due to the wide distribution of scrotal nodules in this patient, there was a large deletion in the scrotal skin after intraoperative removal of all nodules; the skin was submitted to V and Z-sutures, and the scrotum was finally successfully reconstructed.

In this work, polydopamine (PDA) was used to facilitate the reduction of silver nitrate (AgNO3) to silver nanoparticles (AgNPs) and the simultaneous loading on waste silk fabrics (PDA-SF/AgNPs). The removal activity of the obtained composite PDA-SF/AgNPs on different dyes in the presence of hydrogen peroxide (H2O2) and potassium peroxymonosulfate (PMS) was compared. The effects of reaction temperature, H2O2/PMS dosage, dye concentration, composite dosage, electrolyte concentration and time in two catalyst systems on the dye removal were discussed. The results showed the dye removal of Telon Red A2R reached 81% and 95% in 30–50 min in PDA-SF/AgNPs-H2O2 and PDA-SF/AgNPs-PMS system, respectively. Quenching experiments demonstrated that ·OH, ·O2– and SO4-· were produced during the degradation process, and the possible degradation pathway of Telon Red A2R were analyzed by HPLC-MS. In addition, the kinetic study indicated that the removal of dye followed quasi-second-order adsorption kinetics. These findings suggest that fabric-based composites have great potential and applications in catalysis and treatment of wastewater.

To address the challenge of achieving both temporal consistency and spatial continuity in Earth observation data of polar regions, this paper proposes an innovative concept of Moon-based/Highly Elliptical Orbit (HEO) Spaceborne Bistatic Synthetic Aperture Radar (MH-BiSAR), with transmitters on the Moon and receivers on HEO satellites. By utilizing ephemeris data and an orbit propagator, this study explores MH-BiSAR’s geometric coverage capabilities in polar regions and conducts a preliminary analysis of its characteristics. The findings reveal that MH-BiSAR could provide continuous multi-day revisit observations of polar regions within each sidereal month, presenting a significant advantage for monitoring high-dynamic and large-scale scientific phenomena, such as polar sea ice observations. This innovative observational method offers a new perspective for polar monitoring and is expected to deepen our understanding of polar phenomena.

Traumatic brain injury (TBI) is a serious neurological disorder with increasing worldwide incidence. Emerging evidence has shown a significant therapeutic role of mesenchymal stem cells (MSCs) derived exosomes on traumatic brain injury with broad application prospects as a cell-free therapy. However, a comprehensive understanding of its underlying mechanism remained elusive. In this study, umbilical cord mesenchymal stem cells (UCMSCs)-derived exosomes (UC-MSCs-Exo) were isolated by ultracentrifugation and injected intraventricularly in a rat model of TBI. Our results showed that UC-MSCs-Exo promoted functional recovery and reduced neuronal apoptosis in TBI rats. Moreover, UC-MSCs-Exo inhibited the activation of microglia and astrocytes during brain injury, thereby promoting functional recovery. However, the effect of UC-MSCs-Exo on the content of plasma inflammatory factors in rats was not significant. Collectively our study suggested that UC-MSCs-Exo promotes the recovery of neurological function in TBI rats by inhibiting the activation of microglia and astrocytes, providing a theoretical basis for new therapeutic strategies for central nervous system diseases.

Abstract Mitophagy is a vital process that controls mitochondria quality, dysregulation of which can promote cancer. Oncoprotein mucin 1 (MUC1) targets mitochondria to attenuate drug-induced apoptosis. However, little is known about whether and how MUC1 contributes to mitochondrial homeostasis in cancer cells. We identified a novel role of MUC1 in promoting mitophagy. Increased mitophagy is coupled with the translocation of MUC1 to mitochondria, where MUC1 interacts with and induces degradation of ATPase family AAA domain-containing 3A (ATAD3A), resulting in protection of PTEN-induced kinase 1 (Pink1) from ATAD3A-mediated cleavage. Interestingly, MUC1-induced mitophagy is associated with increased oncogenicity of cancer cells. Similarly, inhibition of mitophagy significantly suppresses MUC1-induced cancer cell activity in vitro and in vivo. Consistently, MUC1 and ATAD3A protein levels present an inverse relationship in tumor tissues of breast cancer patients. Our data validate that MUC1/ATAD3A/Pink1 axis-mediated mitophagy constitutes a novel mechanism for maintaining the malignancy of cancer cells, providing a novel therapeutic approach for MUC1-positive cancers.

Abstract Hypoxia inducible factor‐1α (HIF‐1α) plays a critical role in cellular adaptation to hypoxia and it is a potential therapeutic target for anti‐cancer drugs. Applying high‐throughput screening, here it is found that HI‐101, a small molecule containing an adamantaniline moiety, effectively reduces HIF‐1α protein expression. With the compound as a hit, a probe (HI‐102) is developed for target identification by affinity‐based protein profiling. The catalytic β subunit of mitochondrial FOF1‐ATP synthase, ATP5B, is identified as the binding protein of HI‐derivatives. Mechanistically, HI‐101 promotes the binding of HIF‐1α mRNA to ATP5B, thus inhibiting HIF‐1α translation and the following transcriptional activity. Further modifications of HI‐101 lead to HI‐104, a compound with good pharmacokinetic properties, exhibiting antitumor activity in MHCC97‐L mice xenograft model, and HI‐105, the most potent compound with an IC50 of 26 nm. The findings provide a new strategy for further developing HIF‐1α inhibitors by translational inhibition through ATP5B.

Perineural invasion (PNI) is a pathological feature of many cancers associated with poor outcomes, metastases, and recurrence. In relation to ovarian cancer (OC), there is no information about PNI’s role and mechanisms. Our study found that patients with PNI-positive symptoms had significantly shorter overall survival (OS) time than patients with PNI-negative symptoms. Multivariate analyses demonstrated that PNI represented a substantial independent prognostic factor in OC patients. At the transcriptome level, it is noteworthy that PNI positivity was negatively correlated with the degree of infiltration of immune killer cells in OC tumor tissues, including macrophage, central memory CD4 T-cell, natural killer cells, monocyte, and central memory CD4 T-cell. The results of this study revealed that TAS2Rs proteins were markedly upregulated in PNI-positive OC tissues and predicted poor prognoses. Moreover, Immunohistochemical analysis demonstrated that the TAS2R10 protein was associated with poor prognoses and PNI in OC. Consequently, we found for the first time that PNI was a powerful predictor of poor prognosis in OC and analyzed its expression pattern and some preliminary biochemical characterization, providing new clues for guiding clinical prevention and treatment of OC.

The adenomatous polyposis coli (APC)–Asef protein interaction is essential for colorectal cancer metastasis. Here, the authors present the rational design of a sensitivity-enhanced tracer for fluorescence polarization assays, enabling them to discover more efficient APC–Asef interaction inhibitors.

Traditional textile dyeing uses chemical pigments and dyes, which consumes a large amount of water and causes serious environmental pollution. Structural color is an essential means of achieving green dyeing of textiles, and thin-film interference is one of the principles of structural coloring. In the assembly of structural color films, it is necessary to introduce dark materials to suppress light scattering and improve the brightness of the fabric. In this study, the conditions for the generation of nanofilms of catechin (CC) at the gas–liquid interface were successfully investigated. At the same time, environmentally friendly colored silk fabrics were novelly prepared using polycatechin (PCC) structural color films. In addition, it was found that various structural colors were obtained on the surface of silk fabrics by adjusting the time. Meanwhile, the color fastness of the structural colored fabrics was improved by introducing polyvinylpyrrolidone (PVP) to form a strong hydrogen bond between the fabric and catechin. PCC film is uniform and smooth, with a special double-layer structure, and can be attached to the surface of silk fabrics, giving the fabrics special structural colors. Through the thin-film interference formed between the visible light and the PCC film, the silk fabrics obtain bright, controllable, and uniform structural colors. This method is easy to operate and provides a new way of thinking for environmental-protection-oriented coloring of fabrics.

When active noise control technology is applied to traffic noise control, additional sources are often added to the facade of the barrier, and error sensors are placed in the protected area. The noise reduction effect in the area without error sensors is often ignored. In this paper, the effect of the additional source configuration on the sound field in the space without error sensors is researched. By analyzing the directivity and distribution of the sound field at the top of the barrier under various conditions, it is believed that the optimal location of the additional source is related to the height of the primary source and the barrier. An approximate model is established to evaluate the optimal location of the additional source for achieving a good noise reduction effect in a large space. Experiments are also carried out to verify the model. The conclusions are beneficial for improving the noise reduction effect in the area higher than the barrier and without error microphones.