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The excavation of deep foundation pits can cause variations in the displacement and stress fields of surrounding soils, which hence induces adverse effects on adjacent structures. This study presents a two-stage method to quantify the impact of the excavation of a deep foundation pit on the adjacent double-curved arch bridge in the historical city of Nanjing, Southeastern China. The entire process of the foundation pit excavation was simulated and the induced deformation of the arch foot was obtained in the first stage by hardening soil model with small-strain stiffness. Then, the obtained deformation of the arch foot was applied to the bridge structure as a displacement boundary in the second stage to calculate the internal forces and deformations of the double-curved arch bridge structure. The tensile strength of concrete is taken as the limit value of the tensile stress of the double-curved arch bridge. The limit values of arch foot displacement under four evaluation conditions are obtained by step loading calculation. The present results provide construction guidance and safety warning for the process of foundation pit excavation adjacent to double-curved arch bridges for historical preservation.

Abstract Background Recent years, exosomes have been increasing used to treat diseases, but there is little research on how exosomes affect the metabolism of the body after entering. Therefore, in this study, we discussed the changes of metabolic spectrum and determined the differentially expressed metabolites in the serum of cynomolgus monkeys after injecting exosomes. Six cynomolgus monkeys were divided into control group and exosomes group. After intravenous injection of exosomes, the peripheral blood serum of cynomolgus monkeys was collected at baseline, day 1, day 7 and day 14 respectively. An ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based non-targeted metabolomics platform was used to detect the metabolites. The metabolic spectra of two groups of cynomolgus monkeys were identified and compared, and the time series changes of metabolites in exosomes were described. Results The results showed that there was significant difference in metabolic spectrum between the two groups. 45, 114, 49, 39 differentially expressed metabolites were identified in baseline, day 1, day 7, and day 14, respectively. 6-hydroxydopamine, a metabolite related to the regulation of nerve function, was also found. Tryptophan metabolism, choline metabolism in cancer, porphyrin and chlorophyll metabolism were involved in day 1. Sphingolipid metabolism and histidine metabolism were involved in day 7. Three pathways, including choline metabolism, sphingolipid metabolism and biotin metabolism in cancer were involved in day 14. Through time series analysis, it was found that the level of propionylcarnitine and biliverdin increased on day 1 after inoculation with exosomes, while the level of hippuric acid decreased. These changes of immune-related metabolites suggested that exosomes might participate in the immunoregulation reaction after entering the body of cynomolgus monkeys. Conclusions In our current study, we found that exosomes injected intravenously affect the changes of metabolites and metabolic pathways in cynomolgus monkeys. Intravenous injection of exosomes may affect the metabolite 6-hydroxydopamine, sphingolipid metabolic pathway, and choline metabolic in cancer pathway, which is of some significance for the treatment of Parkinson’s disease. In addition, exosomes may also affect the immune-related metabolites in vivo, such as propionylcarnitine, biliverdin, hippuric acid metabolites, as well as tryptophan metabolism pathway, sphingolipid metabolism pathway involved in immune regulation, which is of great significance for the future study of immune-regulatory mechanisms of exosomes.

Abstract Efficiently mixed conduction between ionic and electronic charges stands to revolutionize the studies in organic electrochemical transistors (OECTs). However, inefficient ion transport due to the long-range injection and migration process in the bulk film presents challenges for enhancing the steady and transient performance of OECTs. In this work, we proposed a lateral intercalation-assisted ion transport strategy to assist volumetric ion charging, by introducing a striped microstructure in the conductive channel. By precisely adjusting the ratio of lateral area (RoL), the electrical performance, indicated by the maximum transconductance versus response time (G m,max/τ), increases progressively by over 600%. We further unveiled the mechanism for the enhanced doping uniformity and increased volume capacitance at the lateral area. Based on the universality investigation, we uncovered the effects of molecular stacking on ionic lateral intercalation transport, contributing to the high-performance OECTs and the bio-applications in the recording of dynamic electrocardiography (ECG) signals with distinct features.

Abstract The progression and outcome of bladder cancer (BLCA) are critically affected by the propensity of tumor metastasis. Our previous study revealed that activation of the mevalonate (MVA) pathway promoted migration of BLCA cells; however, the exact mechanism is unclear. Here we show that elevated expression of MVA pathway enzymes in BLCA cells, correlating with poorer patient prognosis by analyzing single-cell and bulk-transcriptomic datasets. Inhibition of the MVA pathway, either through knockdown of farnesyl diphosphate synthase (FDPS) or using inhibitors such as zoledronic acid or simvastatin, led to a marked reduction in BLCA cell migration. Notably, this effect was reversed by administering geranylgeranyl pyrophosphate (GGPP), not farnesyl pyrophosphate (FPP) or cholesterol, indicating the specificity of geranylgeranylation for cell motility. Moreover, we found that RhoB, a Rho GTPase family member, was identified as a key effector of the impact of the MVA pathway on BLCA metastasis. The post-translational modification of RhoB by GGPP-mediated geranylgeranylation influenced its protein stability through the ubiquitin-proteasome pathway. Additionally, overexpression of RhoB was found to block the membrane translocation of integrin β1 in BLCA cells. In summary, our findings underscore the role of the MVA pathway in BLCA metastasis, providing insights into potential therapeutic targets of this malignancy.

Abstract Cell-derived extracellular vesicles (EVs), which carry diverse biomolecules such as nucleic acids, proteins, metabolites, and lipids reflecting their cell of origin, are released under both physiological and pathological conditions. EVs have been demonstrated to mediate cell-to-cell communication and serve as biomarkers. EV-associated DNA (EV-DNA) comprises genomic and mitochondrial DNA (i.e., gDNA and mtDNA) fragments. Some studies have revealed that EV-DNA can represent the full nuclear genome and mitochondrial genome of parental cells. Furthermore, DNA fragments loaded into EVs are stable and can be transferred to recipient cells to regulate their biological functions. In this review, we summarized and discussed EV-DNA research advances with an emphasis on EV-DNA detection at the population-EV and single-EV levels, gene transfer-associated biological functions, and clinical applications as biomarkers for disease liquid biopsy. We hope that this review will provide potential directions or guidance for future EV-DNA investigations.

Abstract Pancreatic cancer is one of the most malignant tumors with the highest mortality rates, and it currently lacks effective drugs. Aptamer-drug conjugates (ApDC), as a form of nucleic acid drug, show great potential in cancer therapy. However, the instability of nucleic acid-based drugs in vivo and the avascularity of pancreatic cancer with dense stroma have limited their application. Fortunately, VNP20009, a genetically modified strain of Salmonella typhimurium, which has a preference for anaerobic environments, but is toxic and lacks specificity, can potentially serve as a delivery vehicle for ApDC. Here, we propose a synergistic therapy approach that combines the penetrative capability of bacteria with the targeting and toxic effects of ApDC by conjugating ApDC to VNP20009 through straightforward, one-step click chemistry. With this strategy, bacteria specifically target pancreatic cancer through anaerobic chemotaxis and subsequently adhere to tumor cells driven by the aptamer’s specific binding. Results indicate that this method prolongs the serum stability of ApDC up to 48 h and resulted in increased drug concentration at tumor sites compared to the free drugs group. Moreover, the aptamer’s targeted binding to cancer cells tripled bacterial colonization at the tumor site, leading to increased death of tumor cells and T cell infiltration. Notably, by integrating chemotherapy and immunotherapy, the effectiveness of the treatment is significantly enhanced, showing consistent results across various animal models. Overall, this strategy takes advantage of bacteria and ApDC and thus presents an effective synergistic strategy for pancreatic cancer treatment.

LoRa (long-range) is an emerging low-power wide-area network technology. Facing challenges such as frequency selective fading multipath channels, existing LoRa schemes are subjected to issues like low data rates and high system complexity. To address these issues, a multi-mode LoRa (MM-LoRa-Mod) based modulation scheme was proposed. The frequency shifts of the multiple multiplexed chirp signals for information transmission were utilized in this scheme, thereby significantly enhancing data rates. Additionally, for underwater acoustic communication scenarios, a low-complexity non-coherent detection algorithm for MM-LoRa-Mod was introduced. Through the evaluation of MM-LoRa-Mod’s bit error rate performance in multipath channels, Watermark underwater acoustic channels, and shallow water acoustic channels, excellent anti-multipath fading and anti-Doppler frequency shift capabilities were demonstrated, indicating the high reliability of MM-LoRa-Mod in underwater acoustic communication scenarios.

Abstract The need for equitable access to primary healthcare services in the current global context has attracted widespread attention, prompting nations to continuously enhance their grassroots medical service levels. In response, China launched the "Healthy China" initiative, which prioritizes the enhancement of national health as a core goal of the healthcare system and uses this opportunity to deepen reforms aimed at strengthening primary care. However, in remote and rural areas, the optimization of medical resource allocation and the achievement of balanced service development remain critical challenges owing to limited resources. This study selected Liannan Yao Autonomous County, which is situated in the northwestern corner of Guangdong Province, as a case study due to its remote mountainous location, underdeveloped economy, and minority region characteristics. Through field research and interviews, this study thoroughly explored the needs of both supply and demand, factoring in elements such as the service capability of healthcare facilities and residents' travel thresholds to enhance the two-step floating catchment area model, thus making it more applicable to remote villages. By integrating electric bikes and cars, which are the primary means of transportation in rural areas, this study conducted a thorough analysis and comparison of the accessibility of medical services in Liannan Yao Autonomous County (Liannan County) . The results reveal significant disparities in healthcare accessibility, an uneven distribution of medical resources, and varying impacts of transportation conditions and facility service capabilities on accessibility. Notably, the study revealed that improving transportation conditions alone has limited effects in rural areas; the key lies in balancing medical service capabilities and the rationality of overall layouts. From the perspectives of equity and efficiency, this study employs the equitable coverage model and the efficiency-driven model to construct two scenarios, comparing accessibility changes in Liannan County under both conditions and proposing strategies to improve the spatial layout of local healthcare facilities. This research not only deepens the understanding of healthcare service accessibility in rural areas but also provides a scientific basis for optimizing resource allocation and enhancing primary medical services, offering valuable guidance and reference for Liannan County and other similar rural regions.

Abstract In this study, we dynamically monitored the glomerular filtration rate and other assessment of renal function and markers of injury in various mice models of acute kidney injury. Male C57BL/6 mice were utilized to establish acute kidney injury models of sepsis, ischemia reperfusion, cisplatin, folic acid, aristolochic acid and antibiotic. In addition to the real time glomerular filtration rate, renal LCN-2 and HAVCR-1 mRNA expression levels, and serum creatinine, urea nitrogen and cystatin c levels were also used to evaluate renal function. In addition, the protein levels of LCN-2 and HAVCR-1 in renal, serum and urine were measured. Our results demonstrated that the changes in biomarkers always lagged the real time glomerular filtration rate during the progression and recovery of renal injury. Cystatin-c can reflect renal injury earlier than other markers, but it remains higher in the recovery stage. Perhaps the glomerular filtration rate does not reflect the greater injury caused by vancomycin plus piperacillin.

Bone metabolism is a dynamic balance between bone formation and absorption regulated by osteoblasts/osteoclasts. Bone metabolic disorders can lead to metabolic bone disease. Osteoporosis (OP), osteoarthritis (OA) and femoral head necrosis (ONFH) are common metabolic bone diseases. At present, the treatment of metabolic bone disease is still mainly to relieve pain and improve joint function. However, surgical treatment does not apply to the vast majority of high-risk groups, including postmenopausal women, patients with diabetes, cirrhosis, etc. Exosomes (Exos) are nanoscale membrane vesicles that are released by almost all cells. Exos are rich in a variety of bioactive substances, such as non-coding RNAs, nucleic acids, proteins and lipids. In view of the structure of Exos, it can protect the biologically active molecules can be smoothly delivered to the target cells and involved in the regulation of cell function. In this review, we focus on the regulation mechanism and function of bone homeostasis mediated by exosomal ncRNAs (Exos-ncRNAs), including macrophage polarization, autophagy, angiogenesis, signal transduction and competing endogenous RNA (ceRNA). We summarized the therapeutic strategies and potential drugs of Exos-ncRNAs in metabolic bone disease. Moreover, we discussed the shortcomings and potential research directions of Exos as carrier to deliver ncRNAs to play a role.

ABSTRACT The Hadal Zone is acknowledged for its extreme environmental conditions, especially high hydrostatic pressures. The dominant scavengers in the Hadal Zone, Hadal amphipods, fulfill vital roles in the Hadal food web and ecological niches. However, research on the gut microbiota of amphipods related to ecological functions and environmental adaptation is still limited. Here, we used 16S rRNA sequencing technology and a culture-dependent method to analyze the composition of the gut microbiota in Amphipoda living in the Mariana Trench. A total of 16 bacterial genera were identified. Among them, Firmicutes and Proteobacteria were the predominant phyla. The adaptability of gut probiotics to the environment was investigated. Pediococcus pentosaceus XY62 was picked up as the representative strain to elucidate the ecological functions of gut microbes in amphipods. The ProBio database and the K-B agar diffusion method indicated that P. pentosaceus XY62 exhibited the highest probiotic activity compared with all other isolated strains. Specific metabolic pathways and transporter systems that contribute to a range of environmental adaptation strategies have been revealed by genomic analysis of P. pentosaceus XY62. The environmental response genes and a specialized KDP transport system allow it to adapt to the challenging conditions of the Hadal Zone. In addition, the presence of antibacterial compounds and antibiotic resistance genes, as well as the ability to form a biofilm, facilitated the successful colonization of P. pentosaceus XY62 in the gut environment.IMPORTANCEAmphipods are widely distributed in the Hadal trenches, and the study of their gut microbes has garnered considerable scientific interest. Our research breaks away from traditional omics approaches, innovatively combining sequencing technologies with culture-dependent methods to analyze the gut microbiome structure of amphipods from the Mariana Trench. This not only complements the current omics-dominated field but also paves the way for future resource development of extreme microbes. Furthermore, by conducting genomic analyses and functional validations on a representative strain, we have uncovered its probiotic effects and strategies for adapting to extreme environments. This provides new insights into the theoretical study of the ecological functions of deep-sea bacteria. Overall, our findings offer a fresh perspective on the microbial community structure and environmental adaptation strategies of gut microorganisms in the Hadal Zone.

With the rapid development of synthetic biology and genomic research, the demand for high-throughput DNA synthesis has been steadily increasing. Inkjet printing technology has gradually emerged as an ideal method for customized oligonucleotide synthesis due to its high precision and flexibility. However, the traditional solvent acetonitrile (ACN), due to its low viscosity and high permeability, fails to meet the stability requirements for inkjet head operation, resulting in unstable droplet formation that affects synthesis accuracy and efficiency. This study proposes propylene carbonate (PC) as a novel solvent for inkjet DNA synthesis, comparing the stability of inkjet droplets and the performance of oligonucleotide synthesis between PC and ACN, while further optimizing the concentrations of phosphoramidite monomers and activator. Experimental results indicate that the PC solvent not only exhibits good inkjet stability but also significantly enhances the purity of oligonucleotide synthesis products and stepwise coupling efficiency under optimal conditions. When synthesizing a target sequence of 30 nucleotides, a stepwise coupling efficiency of 99.01 % was achieved. This study achieved a new DNA synthesis reagent formulation that supports inkjet-based DNA synthesis and exhibits excellent coupling efficiency. This research outcome is expected to promote the further development of high-throughput DNA synthesis using inkjet technology.

Ischemia brain injury is closely associated with the gut microbiota. Polysaccharides, as a typical prebiotic, have been extensively employed in stroke treatment. In our previous study, Pueraria lobata polysaccharide (PLP-3) with antioxidant activity was prepared via water extraction and alcohol precipitation combined with ultrasonic degradation. In this study, the effects of PLP-3 on ischemia brain injury and its regulatory effects on the gut microbiota were further investigated. The results demonstrated that PLP-3 effectively reduced the infarct area, improves neurological function, and alleviates neuronal damage of cerebral ischemia injury. Mechanistically, PLP-3 significantly reduces serum LPS levels in MCAO mice, inhibiting TLR-4 activation in brain tissue and thereby reducing IL-1β and TNF-α levels. Meanwhile, PLP-3 significantly repaired the intestinal barrier injury by increasing the expression of tight junction proteins (ZO-1 and Occludin) and increasing the number of goblet cells. Additionally, the structure and composition of gut microbiota in MCAO mice after PLP-3 intervention, were also significantly changed, especially the enrichment of Lactobacillus and the reduction of Corynebacterium and Staphylococcus. At the same time, short chain fatty acid, metabolites of gut microbiota, were also significantly increased and significantly correlated with the abundance of Lactobacillus. Moreover, LC-MS untargeted metabolomics revealed that PLP-3 significantly improves the intestinal metabolic profile after cerebral ischemia injury, upregulating the amino acid biosynthesis pathway and enriching amino acids such as glutamine and arginine, as well as neuroprotective flavonoids such as fisetin and liquiritigenin. These results suggested that PLP-3 could protect mice from cerebral ischemia–reperfusion injury by regulating gut microbiota and repairing gut barrier, inhibiting brain LPS/TLR4/MyD88 inflammatory pathway, therefore we provide a theoretical basis for PLP-3 as a functional food to prevent ischemic brain injury.

Background: Retinal sublayer thickness is associated with both ophthalmic and neurodegenerative diseases, serving as a valuable biomarker. Despite the established role of diet in chronic disease prevention, the relationship between healthy dietary patterns and retinal sublayer thickness remains underexplored. Objective: This study aims to investigate the associations between four commonly used diet assessment scores and retinal sublayer thickness in a large-scale population. Methods: This study utilized data from the UK Biobank, including 13,993 participants with complete optical coherence tomography (OCT) measurements and dietary assessments. The dietary patterns analyzed were the Alternate Mediterranean Diet (AMED), Anti-Empirical Dietary Inflammatory Index (AEDII), Alternate Healthy Eating Index-2010 (AHEI-2010), and Healthful Plant-Based Diet Index (HPDI). Retinal sublayers measured included macular retinal nerve fiber layer (mRNFL), macular ganglion cell-inner plexiform layer (mGCIPL), macular ganglion cell complex (mGCC), retinal pigment epithelium (mRPE), the outer nuclear layer of the central subfield (ONL), photoreceptor inner segment of the central subfield (IS) and total macular thickness. Multivariable linear regression models adjusted for demographics, ophthalmic measurements, and lifestyle factors were employed to examine associations. Mediation analysis was applied to explore the potential mediation effect of several blood biochemical indicators in simple mediation models. Results: Higher HPDI scores were significantly associated with increased central retinal macular thickness (β = 0.106, p = 0.001), mGCIPL thickness (β = 0.017, p = 0.033), mRPE (β = −0.012, p = 0.161), ONL (β = 0.044, p = 0.003), IS (β = 0.003, p = 0.005) and mGCC thickness (β = 0.027, p = 0.025). In contrast, the AMED, AEDII, and AHEI-2010 scores did not show consistent associations with retinal sublayer thickness except ONL and IS. The mediation analysis revealed that cholesterol acted as a suppressor variable, partially mediating the relationship between HPDI and retinal sublayer thickness. Sensitivity analyses indicated that the associations between HPDI and retinal sublayer thickness were more pronounced in younger individuals and females. Additionally, the variability in associations across different age and sex subgroups highlighted the potential influence of demographic factors on dietary impacts. Conclusion: The study findings suggest that adherence to a healthful plant-based diet may confer neuroprotective benefits, particularly for retinal ganglion cell health. This large-scale population-based study underscores the potential role of diet in mitigating early neurodegenerative changes detectable through non-invasive retinal imaging. Further longitudinal research is needed to establish causal relationships and elucidate the underlying mechanisms between diet and retinal health.

Fully Homomorphic Encryption (FHE) allows computations to be performed directly on encrypted data without decryption. Despite its great theoretical potential, the computational overhead remains a major obstacle for practical applications. To address this challenge, hardware acceleration has emerged as a promising approach, aiming to achieve real-time computation across a wider range of scenarios. In line with this, our research focuses on designing and implementing a Graphic Processing Unit (GPU)-based accelerator for the third generation FHEW/TFHE bootstrapping scheme, which features smaller parameters and bootstrapping keys particularly suitable for GPU architectures compared to the other generations. In summary, our accelerator offers improved efficiency, scalability, and flexibility for extensions, e.g., functional bootstrapping (Liu et al., Asiacrypt 2022), compared to current state-of-the-art solutions. We evaluate our implementation and demonstrate substantial speedup in the single-GPU setting, our bootstrapping achieves an 18x - 20x speedup compared to a 64-thread server-class CPU; by using 8 GPUs, the throughput can be further improved by 7x compared to the single-GPU implementation, confirming the scalability of our design. Furthermore, compared to the SoTA GPU solution TFHE-rs, we achieve a maximum speedup of 1.69x in AND gate evaluation. Finally, we benchmark several private machine learning applications, showing real-time solutions for (1) encrypted neural network inference for MNIST in 0.04 seconds per image, which is the fastest implementation to our knowledge.(2) private decision trees in 0.38 seconds for Iris dataset, where as prior 16 cores CPU implementation (Lu et al., IEEE S&P 2021) required 1.87 seconds; These results highlight the effectiveness and efficiency of our GPU-acceleration in real-world applications. As a technical highlight, we design a novel parallelization strategy tailored for FHEW/TFHE bootstrapping, allowing an automated optimization that partitions bootstrapping into multiple GPU thread blocks. This is necessary for FHEW/TFHE bootstrapping with scalable parameters, where the whole bootstrapping process may not fit into a single thread block. With this, our accelerator can support a broader range of parameters, making it ideal for upcoming privacy-preserving applications.

Abstract Bladder cancer (BLCA) is a prevalent cancer with high case‐fatality rates and a substantial economic burden worldwide. Understanding its molecular underpinnings to guide clinical management is crucial. Ferroptosis, a recently described non‐apoptotic form of cell death, is initiated by the lethal accumulation of iron‐dependent lipid peroxidation products. Despite growing interest, the roles and vulnerabilities determining ferroptosis sensitivity in BLCA remain unclear. Re‐analysis of single‐cell RNA data reveals a decrease in high‐ferroptosis cancer cells as BLCA advances. USP52/PAN2 is identified as a key regulator of ferroptosis in BLCA through an unbiased siRNA screen targeting 96 deubiquitylases (DUBs). Functionally, USP52 depletion impedes glutathione (GSH) synthesis by promoting xCT protein degradation, increasing lipid peroxidation and ferroptosis susceptibility, thus suppressing BLCA progression. Mechanistically, USP52 interacts with xCT and enzymatically cleaves the K48‐conjugated ubiquitin chains at K4 and K12, enhancing its protein stability. Clinical BLCA samples demonstrate a positive correlation between USP52 and xCT expression, with high USP52 levels associated with aggressive disease progression and poor prognosis. In vivo, USP52 depletion combined with ferroptosis triggers imidazole ketone Erastin (IKE) synergistically restrains BLCA progression by inducing ferroptosis. These findings elucidate the role of the USP52‐xCT axis in BLCA and highlight the therapeutic potential of targeting USP52 and ferroptosis inducers in BLCA.

Abstract Objectives Pulmonary neuroendocrine neoplasms (NENs) are the most frequent cause of ectopic adrenocorticotropic hormone syndrome (EAS); lung infection is common in EAS. An imaging finding of infection in EAS patients can mimic NENs. This retrospective study investigated EAS-associated pulmonary imaging indicators. Methods Forty-five pulmonary NENs and 27 tumor-like infections from 59 EAS patients (45 NEN and 14 infection patients) were included. Clinical manifestations, CT features, 18F-FDG, or 68Ga-DOTATATE-PET/CT images and pathological results were collected. Results High-sensitivity C-reactive protein (p

Abstract Objective To develop preoperative nomograms using risk factors based on clinicopathological and MRI for predicting the risk of positive surgical margin (PSM) after radical prostatectomy (RP). Patients and methods This study retrospectively enrolled patients who underwent prostate MRI before RP at our center between January 2015 and November 2022. Preoperative clinicopathological factors and MRI-based features were recorded for analysis. The presence of PSM (overall PSM [oPSM]) at pathology and the multifocality of PSM (mPSM) were evaluated. LASSO regression was employed for variable selection. For the final model construction, logistic regression was applied combined with the bootstrap method for internal verification. The risk probability of individual patients was visualized using a nomogram. Results In all, 259 patients were included in this study, and 76 (29.3%) patients had PSM, including 40 patients with mPSM. Final multivariate logistic regression revealed that the independent risk factors for oPSM were tumor diameter, frank extraprostatic extension, and annual surgery volume (all p

Abstract Recent studies have suggested that mRNA internal m7G and its writer protein METTL1 are closely related to cell metabolism and cancer regulation. Here, we identify that IGF2BP family proteins IGF2BP1-3 can preferentially bind internal mRNA m7G. Such interactions, especially IGF2BP3 with m7G, could promote the degradation of m7G target transcripts in cancer cells. IGF2BP3 is more responsive to changes of m7G modification, while IGF2BP1 prefers m6A to stabilize the bound transcripts. We also demonstrate that p53 transcript, TP53, is m7G-modified at its 3’UTR in cancer cells. In glioblastoma, the methylation level and the half lifetime of the modified transcript could be modulated by tuning IGF2BP3, or by site-specific targeting of m7G through a dCas13b-guided system, resulting in modulation of cancer progression and chemosensitivity.

Abstract BF/C2 is a crucial molecule in the coagulation complement cascade pathway and plays a significant role in the immune response of grass carp through the classical, alternative, and lectin pathways during GCRV infection. In vivo experiments demonstrated that the mRNA expression levels of BF/C2 (A, B) in grass carp positively correlated with GCRV viral replication at various stages of infection. Excessive inflammation leading to death coincided with peak levels of BF/C2 (A, B) mRNA expression and GCRV viral replication. Correspondingly, BF/C2 (A, B) recombinant protein, CIK cells and GCRV co-incubation experiments yielded similar findings. Therefore, 3 h (incubation period) and 9 h (death period) were selected as critical points for this study. Transcriptome sequencing analysis revealed significant differences in the expression of BF/C2A and BF/C2B during different stages of CIK infection with GCRV and compared to the blank control group (PBS). Specifically, the BF/C2A_3 and BF/C2A_9 groups exhibited 2729 and 2228 differentially expressed genes (DEGs), respectively, with 1436 upregulated and 1293 downregulated in the former, and 1324 upregulated and 904 downregulated in the latter. The BF/C2B_3 and BF/C2B_9 groups showed 2303 and 1547 DEGs, respectively, with 1368 upregulated and 935 downregulated in the former, and 818 upregulated and 729 downregulated in the latter. KEGG functional enrichment analysis of these DEGs identified shared pathways between BF/C2A and PBS groups at 3 and 9 h, including the C-type lectin receptor signaling pathway, protein processing in the endoplasmic reticulum, Toll-like receptor signaling pathway, Salmonella infection, apoptosis, tight junction, and adipocytokine signaling pathway. Additionally, the BF/C2B groups at 3 and 9 h shared pathways related to protein processing in the endoplasmic reticulum, glycolysis/gluconeogenesis, and biosynthesis of amino acids. The mRNA levels of these DEGs were validated in cellular models, confirming consistency with the sequencing results. In addition, the mRNA expression levels of these candidate genes (mapk1, il1b, rela, nfkbiab, akt3a, hyou1, hsp90b1, dnajc3a et al.) in the head kidney, kidney, liver and spleen of grass carp immune tissue were significantly different from those of the control group by BF/C2 (A, B) protein injection in vivo. These candidate genes play an important role in the response of BF/C2 (A, B) to GCRV infection and it also further confirmed that BF/C2 (A, B) of grass carp plays an important role in coping with GCRV infection.

BACKGROUND AND OBJECTIVES: Current treatment strategies for elderly patients with acute lower limb ischemia (ALLI) have no definitive effect, and studies have reported no definitive prognostic factors that reflect poor outcomes among patients with ALLI. Therefore, reliable clinical indicators that can accurately predict outcomes and guide the choice of treatment options are needed. This study aimed to identify prognostic factors among the elderly patients who underwent endovascular treatment for ALLI. DESIGN: Retrospective. MATERIALS AND METHODS: From January 2011 to December 2020, 270 patients (281 limbs; 124 males; mean age: 84.8 years [range, 80–102 years]) underwent endovascular therapy for ALLI, including acute limb arterial embolism (191 limbs) and acute exacerbation of chronic ischemia (90 limbs). Factors identified through univariate analysis (P < 0.1) and other variables considered likely to have important prognostic value were tested in a logistic regression model for symptom improvement, major amputation, and all-cause mortality. RESULTS: The mean age of the patients was 84.8 years, 54.1% were female, and hypertension (69.0%) was the most common coexisting disease. Patients in the acute group exhibited higher rates of atrial fibrillation (45.5% vs. 24.4%; P = 0.001) and chronic renal failure (15.2% vs. 6.7%; P = 0.044) than the acute-on-chronic group. The acute group exhibited significantly higher plasma D-dimer levels than the acute-on-chronic group (1.59 vs. 1.06; P < 0.001). In the acute group, 145 (75.9%) limbs had preacute Rutherford Classification (RC) of Grade I. In the acute-on-chronic group, 47 (52.2%) limbs had symptom duration of 7–14 days, and 84 (93.3%) limbs were diagnosed with arteriosclerosis obliterans. Most patients opted for antiplatelet therapy, particularly those in the acute-on-chronic group. Multivariate logistic regression analysis revealed that onset time, hypertension, white blood cell (WBC) count, and lesion nature were independent factors for postoperative symptom improvement, whereas hypertension, WBC count, and preacute RC grade were independent factors for amputation at 3 months postoperatively. CONCLUSIONS: WBC count was a major risk factor for postoperative symptom improvement and amputation within 3 months among elderly patients; the higher the WBC count, the higher the risk for amputation. In addition, among patients >80 years of age, early surgery could significantly improve the prognosis of ALLI, regardless of the procedure used to restore blood supply.

【Objective】In the Low Earth Orbit (LEO) satellite Internet of Things (IoT) scenario, the time delay and power consumption requirements of Narrowband (NB) -IoT terminal in wide coverage area vary due to different business scenarios. However, the ground NB-IoT terminal with a single business scenario adopts a fixed working state timer parameter configuration method, which cannot meet the needs of time delay and power consumption for multi-scenario terminals in large geographical areas of LEO satellite IoT.【Methods】In response to the wide coverage characteristics of LEO satellite IoT, the problem of different delay and power consumption requirements for terminal multi-scenario application services in LEO satellite IoT scenarios, this article proposes a method based on a simplified interaction process and Markov chain model for terminal work state switching. The method uses system downlink delay and terminal power consumption as Non-dominated Sorting Genetic Algorithms-Ⅱobjective functions to obtain a set of Pareto optimal solutions for multiple scenario frontiers. Furthermore, it selects working state timer parameters from the Pareto frontier to configure terminals online that meet different scenario delay and power consumption requirements.【Results】The simulation results show that the multi-objective optimization method proposed in this paper can globally optimize the timing parameters of the working state timer, and overcome the shortcomings of traditional methods such as exhaustive search falling into local optima. Additionally, it has been verified that simplifying the random access interaction process can effectively reduce terminal delay and power consumption.【Conclusion】The multi-objective optimization method proposed in this paper can obtain the working state timer parameters of the terminal in various scenarios of LEO satellite IoT.

Abstract Due to the increasing power system capacity, the interruption of large fault currents has gradually become a major challenge in power systems. At the moment, such currents are interrupted mainly via circuit breakers based on the method of active current commutation. However, these types of circuit breakers tend to be costly and oversized. One possible alternative—a fuse‐based circuit breaker with current commutation process enhanced by an external transverse magnetic field (ETMF)—is proposed by the authors. Its main advantage lies in the fast current commutation achieved by an ETMF‐enhanced three‐stage increase of the vacuum arc voltage. The study of the current commutation process is mainly represented by the authors, and the influencing factors of the current commutation—contact opening speed and ETMF current—are discussed. At last, the proposed circuit breaker is verified by an experiment, whose results show that a short‐circuit current of 42 kA can be interrupted within just 2 ms.

Abstract Smart gloves are in high demand for entertainment, manufacturing, and rehabilitation. However, designing smart gloves has been complex and costly due to trial and error. We propose an open simulation platform for designing smart gloves, including optimal sensor placement and deep learning models for gesture recognition, with reduced costs and manual effort. Our pipeline starts with 3D hand pose extraction from videos and extends to the refinement and conversion of the poses into hand joint angles based on inverse kinematics, the sensor placement optimization based on hand joint analysis, and the training of deep learning models using simulated sensor data. In comparison to the existing platforms that always require precise motion data as input, our platform takes monocular videos, which can be captured with widely available smartphones or web cameras, as input and integrates novel approaches to minimize the impact of the errors induced by imprecise motion extraction from videos. Moreover, our platform enables more efficient sensor placement selection. We demonstrate how the pipeline works and how it delivers a sensible design for smart gloves in a real-life case study. We also evaluate the performance of each building block and its impact on the reliability of the generated design.

Abstract Purpose The study aimed to investigate the potential influence of COVID-19 infection on embryo implantation and early development in women undergoing frozen embryo transfer (FET), with a specific focus on infections occurring at different periods around FET. Methods A retrospective analysis was performed on women who had undergone FET during a period marked by a significant surge in COVID-19 infection in Shanghai. All enrolled women experienced their first documented COVID-19 infection around the time of FET, ensuring that infections did not occur prior to oocyte retrieval. Participants were categorized into six groups based on the timing of infection: uninfected, ≥ 60 days,

BackgroundThe current research aimed to demonstrate the independent association between preoperative severe asymptomatic carotid artery stenosis (ACAS) and severe multi-organ dysfunction after off-pump coronary artery bypass grafting (OPCAB), which may further indicate the relationship between severe ACAS and adverse 30-day postoperative outcomes of patients undergoing OPCAB.MethodsThis was a single-center, retrospective observational study including patients without a history of stroke or Transient Ischemic Attacks (TIA) (asymptomatic), who underwent for an isolated OPCAB in the center for operative treatment of coronary artery disease of Beijing Anzhen Hospital from January 2020 to December 2021. All enrolled patients underwent carotid artery ultrasound prior to OPCAB. The information was extracted independently by two authors of the study from the medical records. Both univariate and multivariate analyses were conducted.ResultsA total of 562 patients met the inclusion criteria for the current study. 63 (11.2%) suffered from severe ACAS. The Sequential Organ Failure Assessment (SOFA) maximum in the severe ACAS group was significantly higher than that in the non-severe ACAS group (9.76 ± 3.03 vs. 7.75 ± 2.96, p

Abstract Background Preeclampsia, one of the most lethal pregnancy-related diseases, is associated with the disruption of uterine spiral artery remodeling during placentation. However, the early molecular events leading to preeclampsia remain unknown. Results By analyzing placentas from preeclampsia, non-preeclampsia, and twin pregnancies with selective intrauterine growth restriction, we show that the pathogenesis of preeclampsia is attributed to immature trophoblast and maldeveloped endothelial cells. Delayed epigenetic reprogramming during early extraembryonic tissue development leads to generation of excessive immature trophoblast cells. We find reduction of de novo DNA methylation in these trophoblast cells results in selective overexpression of maternally imprinted genes, including the endoretrovirus-derived gene PEG10 (paternally expressed gene 10). PEG10 forms virus-like particles, which are transferred from the trophoblast to the closely proximate endothelial cells. In normal pregnancy, only a low amount of PEG10 is transferred to maternal cells; however, in preeclampsia, excessive PEG10 disrupts maternal vascular development by inhibiting TGF-beta signaling. Conclusions Our study reveals the intricate epigenetic mechanisms that regulate trans-generational genetic conflict and ultimately ensure proper maternal–fetal interface formation.

Abstract The fluorescent light-up aptamer RhoBAST, which binds and activates the fluorophore–quencher conjugate tetramethylrhodamine-dinitroaniline with high affinity, super high brightness, remarkable photostability, and fast exchange kinetics, exhibits excellent performance in super-resolution RNA imaging. Here we determine the co-crystal structure of RhoBAST in complex with tetramethylrhodamine-dinitroaniline to elucidate the molecular basis for ligand binding and fluorescence activation. The structure exhibits an asymmetric “A”-like architecture for RhoBAST with a semi-open binding pocket harboring the xanthene of tetramethylrhodamine at the tip, while the dinitroaniline quencher stacks over the phenyl of tetramethylrhodamine instead of being fully released. Molecular dynamics simulations show highly heterogeneous conformational ensembles with the contact-but-unstacked fluorophore–quencher conformation for both free and bound tetramethylrhodamine-dinitroaniline being predominant. The simulations also show that, upon RNA binding, the fraction of xanthene-dinitroaniline stacked conformation significantly decreases in free tetramethylrhodamine-dinitroaniline. This highlights the importance of releasing dinitroaniline from xanthene tetramethylrhodamine to unquench the RhoBAST–tetramethylrhodamine-dinitroaniline complex. Using SAXS and ITC, we characterized the magnesium dependency of the folding and binding mode of RhoBAST in solution and indicated its strong structural robustness. The structures and binding modes of relevant fluorescent light-up aptamers are compared, providing mechanistic insights for rational design and optimization of this important fluorescent light-up aptamer-ligand system.

Although carbon disulphide (CS2) is an old fumigant, the possibility of reintroducing it is supported by new data from Australia, and by published Egyptian and Chinese data which is not widely known. The data covers grain quality, natural emissions and residues in processed food. Egyptian data shown that CS2 has no effect on the germination and plumule length of rice even at high doses (400 mg/m3). Chinese data has shown that CS2, at high doses (200 mg/m3), has no effect on the germination of a large number of seeds, including malting barley, wheat and maize, sorghum, cotton, carrot etc. This is supported by current Australian data (150 mg/m3) on germination and plumule length of wheat, barley and chickpeas. Australian data from the Stored Grain Research Laboratory (SGRL) commercial scale trial showed that all tested insects are killed by CS2 at a range of C´T (concentration´time) values of 1 000~1 500 mg·h·L–1 and has no effect on the quality of end products of wheat. The sorption of carbon disulphide on grain is lower than that for methyl bromide, and is mainly physical in origin. It leaves residues on grain, but these are extensively degraded during storage and processing. Remaining residues of CS2 are reduced during cleaning and conditioning of wheat before milling. Residues of CS2 are progressively reduced during the milling and baking processes. For example, wheat was treated at 27 g/m3 of CS2 for 6 days in sealed farm bin and then aired for 24 hours. Cleaning reduced residues from 6.7 to 4.6 mg/kg, and conditioning reduced residues from 4.6 to 2.2 mg/kg before milling. They are further reduced during milling, and further still during formation of noodles (even before cooking), pasta and bread. Residues in processed products were indistinguishable by current methods of analysis (limits of quantification were

Ethyl formate and carbonyl sulfide are potential stored product fumigants. They are present naturally in the atmosphere, plants and soil. Natural levels of ethyl formate and carbonyl sulfide in newly harvested grain and stored wheat, barley, oats and canola are varied with the commodity, temperature, moisture content and the period of storage. The values ranged from 0.5~2.0 mg/kg for ethyl formate and 0.02~1.0 mg/kg for carbonyl sulfide. Ethyl formate and carbonyl sulfide were naturally present in grains at harvest, increased during the first 4~5 months of storage, and then began to decline, particularly at grain temperatures greater than 20 ℃ and moisture contents of grain and canola greater than 9.5% and 5%. This information on natural levels is relevant to the establishment of Maximum Residue Limits (MRL) and to market acceptance of ethyl formate and carbonyl sulfide as fumigants for stored products.

Abstract The α-Aurora kinase is a crucial regulator of spindle microtubule organization during mitosis in plants. Here, we report a post-mitotic role for α-Aurora in reorganizing the phragmoplast microtubule array. In Arabidopsis thaliana, α-Aurora relocated from spindle poles to the phragmoplast midzone, where it interacted with the microtubule cross-linker MAP65-3. In a hypomorphic α-Aurora mutant, MAP65-3 was detected on spindle microtubules, followed by a diffuse association pattern across the phragmoplast midzone. Simultaneously, phragmoplast microtubules remained belatedly in a solid disk array before transitioning to a ring shape. Microtubules at the leading edge of the matured phragmoplast were often disengaged, accompanied by conspicuous retentions of MAP65-3 at the phragmoplast interior edge. Specifically, α-Aurora phosphorylated two residues towards the C-terminus of MAP65-3. Mutation of these residues to alanines resulted in an increased association of MAP65-3 with microtubules within the phragmoplast. Consequently, the expansion of the phragmoplast was notably slower compared to wild-type cells or cells expressing a phospho-mimetic variant of MAP65-3. Moreover, mimicking phosphorylation reinstated disrupted MAP65-3 behaviors in plants with compromised α-Aurora function. Overall, our findings reveal a mechanism in which α-Aurora facilitates cytokinesis progression through phosphorylation-dependent restriction of MAP65-3 associating with microtubules at the phragmoplast midzone.

Abstract Purpose The purpose of this study was to compare the preoperative anxiety, aqueous humor monocyte chemoattractant protein-1 (MCP-1) concentration, intraoperative pain, and degree of cooperation of the first eye implantable collamer lens (ICL) surgery with the second eye surgery, of the 1-day interval group with the 1-week interval group, and to investigate the possible causes of these differences, as well as to determine the appropriate interval between bilateral eye ICL surgeries. Method The study was a prospective observational study. A total of 120 patients who underwent bilateral ICL surgery at the Department of Ophthalmology, West China Fourth Hospital, Sichuan University, from July to September 2023, were enrolled. The patients were divided into a 1-day interval group and a 1-week interval group. The ICL surgery was performed on both eyes according to the schedule. Anxiety levels, aqueous humor MCP1, cooperativeness, surgical time, pain and satisfaction, and patients’ estimations of the time spent in the operation were recorded for each eye. The patients were instructed to recall the intraoperative pain of the first eye surgery after the operation of the second eye. Statistical analyses (two independent samples t-test,two paired samples t-test, the rank-sum test, the chi-square test, non-parametric test with multiple independent samples) were performed to compare the differences between each score in both eyes and two groups. Furthermore, we examined the relationship between pain levels and the reproductive history of the patients. Results In the 1-day interval group, male/female is 22/52, average age is 25.24±5.00. In the 1-week interval group, male/female is 17/29, average age is 25.39±5.57. There was no statistically significant difference between the two groups. In both groups, patients were less nervous, had significantly more pain, had less surgical satisfaction, had a longer estimated operative time, and had elevated preoperative MCP1 during the second eye operation. In the second eye surgery, the patient’s cooperation worsened, but it did not lead to an increase in surgical time. A significant proportion of patients, particularly in the 1-week interval group, recalled experiencing reduced pain during the first eye surgery. The 1-week interval group had a higher difference in all indicators between the bilateral surgeries. In the second eye surgery, patients in the 1-week interval group experienced more severe pain, less cooperation, longer estimated operation duration, and a greater MCP1 than those in the 1-day interval group. Conclusion Patients undergoing second eye ICL surgery had decreased nervousness, increased pain, decreased cooperation, and satisfaction, and increased MCP1 compared to the first eye surgery. It is recommended that an interval of about one week should be avoided between bilateral surgeries when developing a surgical schedule to improve patients’ cooperation, satisfaction, and comfort.

Abstract The aim of this study was to develop a dynamic nomogram combining clinical and imaging data to predict malignant brain edema (MBE) after endovascular thrombectomy (EVT) in patients with large vessel occlusion stroke (LVOS). We analyzed the data of LVOS patients receiving EVT at our center from October 2018 to February 2023, and divided a 7:3 ratio into the training cohort and internal validation cohort, and we also prospectively collected patients from another stroke center for external validation. MBE was defined as a midline shift or pineal gland shift > 5 mm, as determined by computed tomography (CT) scans obtained within 7 days after EVT. A nomogram was constructed using logistic regression analysis, and its receiver operating characteristic curve (ROC) and calibration were assessed in three cohorts. A total of 432 patients were enrolled in this study, with 247 in the training cohort, 100 in the internal validation cohort, and 85 in the external validation cohort. MBE occurred in 24% (59) in the training cohort, 16% (16) in the internal validation cohort and 14% (12) in the external validation cohort. After adjusting for various confounding factors, we constructed a nomogram including the clot burden score (CBS), baseline neutrophil count, core infarct volume on CTP before EVT, collateral index, and the number of retrieval attempts. The AUCs of the training cohorts were 0.891 (95% CI 0.840–0.942), the Hosmer–Lemeshow test showed good calibration of the nomogram (P = 0.879). And our nomogram performed well in both internal and external validation data. Our nomogram demonstrates promising potential in identifying patients at elevated risk of MBE following EVT for LVOS.

In recent years, large-scale point cloud semantic segmentation has been widely applied in various fields, such as remote sensing and autonomous driving. Most existing point cloud networks use local aggregation to abstract unordered point clouds layer by layer. Among these, position embedding serves as a crucial step. However, current methods of position embedding have limitations in modeling spatial relationships, especially in deeper encoders where richer spatial positional relationships are needed. To address these issues, this paper summarizes the advantages and disadvantages of mainstream position embedding methods and proposes a novel Hybrid Offset Position Encoding (HOPE) module. This module comprises two branches that compute relative positional encoding (RPE) and offset positional encoding (OPE). RPE combines explicit encoding to enhance position features through attention, learning position bias implicitly, while OPE calculates absolute position offset encoding by considering differences with grouping embeddings. These two encodings are adaptively mixed in the final output. The experiment conducted on multiple datasets demonstrates that our module helps the deep encoders of the network capture more robust features, thereby improving model performance on various baseline models. For instance, PointNet++ and PointMetaBase enhanced with HOPE achieved mIoU gains of 2.1% and 1.3% on the large-scale indoor dataset S3DIS area-5, 2.5% and 1.1% on S3DIS 6-fold, and 1.5% and 0.6% on ScanNet, respectively. RandLA-Net with HOPE achieved a 1.4% improvement on the large-scale outdoor dataset Toronto3D, all with minimal additional computational cost. PointNet++ and PointMetaBase had approximately only a 0.1 M parameter increase. This module can serve as an alternative for position embedding, and is suitable for point-based networks requiring local aggregation.

Amidst the dual challenges of energy shortages and global warming, photovoltaic (PV) power generation has emerged as a critical technology due to its efficient utilization of solar energy. Rooftops, as underutilized spaces, are ideal locations for installing solar panels, avoiding the need for additional land. However, the accurate and generalized segmentation of large-scale PV panel images remains a technical challenge, primarily due to varying image resolutions, large image scales, and the significant imbalance between foreground and background categories. To address these challenges, this paper proposes a novel model based on the Res2Net architecture, an enhanced version of the classic ResNet optimized for multi-scale feature extraction. The model integrates Spatial Feature Reconstruction and multi-scale feature aggregation modules, enabling effective extraction of multi-scale data features and precise reconstruction of spatial features. These improvements are particularly designed to handle the small proportion of PV panels in images, effectively distinguishing target features from redundant ones and improving recognition accuracy. Comparative experiments conducted on a publicly available rooftop PV dataset demonstrate that the proposed method achieves superior performance compared to mainstream techniques, showcasing its effectiveness in precise PV panel segmentation.

Indoor point clouds often present significant challenges due to the complexity and variety of structures and high object similarity. The local geometric structure helps the model learn the shape features of objects at the detail level, while the global context provides overall scene semantics and spatial relationship information between objects. To address these challenges, we propose a novel network architecture, PointMSGT, which includes a multi-scale geometric feature extraction (MSGFE) module and a global Transformer (GT) module. The MSGFE module consists of a geometric feature extraction (GFE) module and a multi-scale attention (MSA) module. The GFE module reconstructs triangles through each point’s two neighbors and extracts detailed local geometric relationships by the triangle’s centroid, normal vector, and plane constant. The MSA module extracts features through multi-scale convolutions and adaptively aggregates features, focusing on both local geometric details and global semantic information at different scale levels, enhancing the understanding of complex scenes. The global Transformer employs a self-attention mechanism to capture long-range dependencies across the entire point cloud. The proposed method demonstrates competitive performance in real-world indoor scenarios, with a mIoU of 68.6% in semantic segmentation on S3DIS and OA of 86.4% in classification on ScanObjectNN.

Dupilumab was approved for the treatment of several dermatologic immune-mediated inflammatory diseases, such as atopic dermatitis and bullous pemphigoid; whereas omalizumab is the first biological agent which was approved to treat chronic spontaneous urticaria. None of the published meta-analyses has provided the sufficient data regarding the safety of these two biologics, especially regarding their potential serious adverse events (SAEs). The aim of this study was, to comprehensively evaluate the safety of the two biologics dupilumab and omalizumab. In this study, we included 32 randomized trials, and performed meta-analyses on 113 types of SAEs regarding dupilumab and 61 types of SAEs regarding omalizumab. We identified that: (1) use of dupilumab was significantly associated with the lower incidence of atopic dermatitis, while use of omalizumab was significantly associated with the lower incidence of asthma; and (2) use of dupilumab was not significantly associated with the incidences of 112 other kinds of SAEs including various infectious diseases, while use of omalizumab was not significantly associated with the incidences of 60 other kinds of SAEs including various infectious diseases. This meta-analysis for the first time assessed the association between use of dupilumab or omalizumab and incidences of various SAEs, and identified that neither dupilumab use nor omalizumab use was associated with the increased risks of any SAEs including various infectious diseases. These findings further confirm the general safety of the two biologics dupilumab and omalizumab. This informs clinicians that there is no need to worry too much about the safety issues of these two biologics.

BackgroundIschaemic heart failure with reduced ejection fraction (HFrEF) caused by coronary artery disease accounts for the largest proportion of heart failure cases with the worst prognosis. Coronary artery bypass grafting (CABG) is the most effective treatment for ischaemic HFrEF. On-pump and off-pump are the two surgical methods used for CABG. Whether patients with HFrEF should undergo on- or off-pump CABG is controversial in coronary heart disease surgery. The left ventricular end-systolic volume index (LVSEVI) is the gold standard for evaluating the severity of left ventricular remodelling; however, its effect on the perioperative risk and long-term survival rate of patients with HFrEF undergoing CABG remains unclear.MethodsThis single centre prospective cohort analysis included 118 coronary heart disease patients with symptoms and signs of heart failure and a left ventricular ejection fraction (LVEF) of

Abstract Background This study evaluates the efficacy of a nomogram for predicting the pathology upgrade of apical prostate cancer (PCa). Methods A total of 754 eligible patients were diagnosed with apical PCa through combined systematic and magnetic resonance imaging (MRI)‐targeted prostate biopsy followed by radical prostatectomy (RP) were retrospectively identified from two hospitals (training: 754, internal validation: 182, internal–external validation: 148). A nomogram for the identification of apical tumors in high‐risk pathology upgrades through comparing the results of biopsy and RP was established incorporating statistically significant risk factors based on univariable and multivariable logistic regression. The nomogram's performance was assessed via the receiver operating characteristic (ROC) curve, calibration plots, and decision curve analysis (DCA). Results Univariable and multivariable analysis identified age, targeted biopsy, number of targeted cores, TNM stage, and the prostate imaging‐reporting and data system score as significant predictors of apical tumor pathological progression. Our nomogram, based on these variables, demonstrated ROC curves for pathology upgrade with values of 0.883 (95% CI, 0.847–0.929), 0.865 (95% CI, 0.790–0.945), and 0.840 (95% CI, 0.742–0.904) for the training, internal validation and internal–external validation cohorts respectively. Calibration curves showed good consistency between the predicted and actual outcomes. The validation groups also showed great generalizability with the calibration curves. DCA results also demonstrated excellent performance for our nomogram with positive benefit across a threshold probability range of 0–0.9 for the training and internal validation group, and 0–0.6 for the internal–external validation group. Conclusion The nomogram, integrating clinical, radiological, and pathological data, effectively predicts the risk of pathology upgrade in apical PCa tumors. It holds significant potential to guide clinicians in optimizing the surgical management of these patients.

Abstract Intratumor heterogeneity (ITH) of bladder cancer (BLCA) contributes to therapy resistance and immune evasion affecting clinical prognosis. The molecular and cellular mechanisms contributing to BLCA ITH generation remain elusive. It is found that a TM4SF1‐positive cancer subpopulation (TPCS) can generate ITH in BLCA, evidenced by integrative single cell atlas analysis. Extensive profiling of the epigenome and transcriptome of all stages of BLCA revealed their evolutionary trajectories. Distinct ancestor cells gave rise to low‐grade noninvasive and high‐grade invasive BLCA. Epigenome reprograming led to transcriptional heterogeneity in BLCA. During early oncogenesis, epithelial‐to‐mesenchymal transition generated TPCS. TPCS has stem‐cell‐like properties and exhibited transcriptional plasticity, priming the development of transcriptionally heterogeneous descendent cell lineages. Moreover, TPCS prevalence in tumor is associated with advanced stage cancer and poor prognosis. The results of this study suggested that bladder cancer interacts with its environment by acquiring a stem cell‐like epigenomic landscape, which might generate ITH without additional genetic diversification.

Cordyceps chanhua is a well-known edible and medicinal mushroom with a long history of use in China, and it contains a variety of secondary metabolites with interesting bioactive ingredients. However, recent researches have mainly focused on cultivation conditions, secondary metabolite compositions and pharmacological activities of C. chanhua, the lack of an efficient and stable genetic transformation system has largely limited further research on the relationship between secondary metabolites and biosynthetic gene clusters in C. chanhua. In this study, single-factor experiments were used to compare the effects of different osmotic stabilizers, enzyme concentrations and enzyme digestion times on protoplast yield, and we found that the highest yield of 5.53 × 108 protoplasts/mL was obtained with 0.7 M mannitol, 6 mg/mL snail enzyme and 4 h of enzyme digestion time, and the regeneration rate of protoplasts was up to approximately 30% using 0.7 M mannitol as an osmotic stabilizer. On this basis, a PEG-mediated genetic transformation system of C. chanhua was successfully established for the first time, which lays the foundation for further genetic transformation of C. chanhua.

The Well Mitan-1 has achieved a major breakthrough in the exploration of Ordovician subsalt natural gas in the mid-eastern Ordos Basin, demonstrating a high-yield industrial gas flow in fourth member of the Majiagou Formation of Ordovician (O1m4). Despite this success, there are ongoing disputes regarding the origin of the natural gas found in Well Mitan-1. Measured results show that the natural gas in Well Mitan-1 is mainly composed of alkane gas (95.18 %). The gas drying coefficient (C1/C1-5) is measured at 0.947, and the H2S content is 3.49 %, with a small amount of N2 and CO2 in the non-hydrocarbon gas. The carbon isotopic compositions of methane, ethane, and propane in the natural gas are −45.5 ‰, −26.4 ‰, and −24.3 ‰, respectively. Based on the regional geological background, the characteristics of potential source rocks and the geochemical characteristics of natural gas, it is considered that the natural gas in Well Mitan-1 is self-generated and self-accumulated oil-associated gas in Ordovician subsalt carbonate rocks. However, certain geochemical anomalies, such as the lighter methane carbon isotope value (δ13C1) and coal-type gas characteristics in ethane carbon isotope (δ13C2), raise questions. Further insights from thermal simulation experiments on hydrocarbon generation and the analysis of residual gas in rocks suggest a close relationship between the special geochemical characteristics of Well Mitan-1 and the presence of gypsum rocks. The ubiquitous gypsum rock serves a dual purpose: acting as an effective caprock, facilitating the retention of early-generated natural gas, and promoting the generation of heavy hydrocarbon gases (C2+) and H2S. The relatively low H2S content (less than 5 %) and higher C2+ content indicate that thermochemical sulfate reduction (TSR), if present, is not strong enough to significantly impact methane. The δ13C2 is identified as a potentially sensitive parameter for identifying TSR.

Abstract PRKN is a key gene involved in mitophagy in Parkinson’s disease. However, recent studies have demonstrated that it also plays a role in the development and metastasis of several types of cancers, both in a mitophagy-dependent and mitophagy-independent manner. Despite this, the potential effects and underlying mechanisms of Parkin on bladder cancer (BLCA) remain unknown. Therefore, in this study, we investigated the expression of Parkin in various BLCA cohorts derived from human. Here we show that PRKN expression was low and that PRKN acts as a tumor suppressor by inhibiting the proliferation and migration of BLCA cells in a mitophagy-independent manner. We further identified Catalase as a binding partner and substrate of Parkin, which is an important antioxidant enzyme that regulates intracellular ROS levels during cancer progression. Our data showed that knockdown of CAT led to increased intracellular ROS levels, which suppressed cell proliferation and migration. Conversely, upregulation of Catalase decreased intracellular ROS levels, promoting cell growth and migration. Importantly, we found that Parkin upregulation partially restored these effects. Moreover, we discovered that USP30, a known Parkin substrate, could deubiquitinate and stabilize Catalase. Overall, our study reveals a novel function of Parkin and identifies a potential therapeutic target in BLCA.

Abstract Disulfidptosis (DSP), a form of cell death caused by disulphide stress, plays an important role in tumour progression. However, the mechanisms by which DSP regulates the tumour microenvironment remain unclear. Thus, we analysed the transcriptome profiles and clinical data, which were obtained from the TCGA database, of 540 patients with colorectal cancer. Compared with the patients with low DSP expression, those with high DSP expression exhibited significantly better survival outcomes; lower stromal and ESTIMATE scores; significantly higher numbers of CD4+ T cells, M2 macrophages, dendritic cells, and neutrophils; higher expression of immune checkpoint-related genes; and lower Tregs and HLA-DQB2 levels. A prognostic signature established based on DSP-related genes demonstrated an increase in risk score with a higher clinical stage. Risk scores negatively correlated with dendritic cells, eosinophils, and CD4+ T cells and significantly positively correlated with Treg cells. Patients with higher risk scores experienced significantly worse survival outcomes and immunotherapy non-response. Our nomogram model, combining clinicopathological features and risk scores, exhibited robust prognostic and predictive power. In conclusion, DSP-related genes actively participated in regulating the tumour microenvironment. Thus, they can serve as biomarkers to provide targeted treatment for colorectal cancer.

Abstract Background In recent years, mobile psychological interventions have proven effective in reducing self-injury and suicide-related behaviors. Therefore, it is essential to continually enhance the user experience and address patients' needs to facilitate the development of mobile mental health interventions. Identifying patients with mobile mental health needs can be challenging for mental health professionals. To address this, we conducted a systematic review of qualitative research to synthesize the needs of patients engaged in self-injury and suicide-related behaviors for mobile and internet-based psychological interventions. Methods This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) and the Enhancing Transparency in Reporting the Synthesis of Qualitative Research statement (ENTREQ). We explored 11 databases and synthesized the results using thematic analysis. Results Sixteen qualitative and mixed-method studies were included. The study found that the needs of patients with self-injury and suicide-related behaviors for mobile psychological intervention included therapy, technology, culture, privacy, communication, emotional support, personalization, and self-management. Consistent with the Technology Acceptance Model (TAM), the needs of patients with self-injury and suicide-related behaviors are influenced by the perceived ease of use and perceived usefulness of the mobile intervention. However, the findings also highlight the importance and unmet needs of peer support, communication, self-management, and empowerment in using mobile psychological interventions for patients with self-injury and suicide-related behaviors. Conclusions Studies in this area have shown that the needs of patients with self-harm and suicide-related behaviors cover multiple stages, including basic therapeutic and technical needs and advanced emotional needs. This complexity makes it challenging to address the needs of patients engaged in self-injury and suicide-related behaviors through digital interventions. In the future, mental health professionals should be encouraged to participate in multidisciplinary collaborations to expand the use of digital interventions, enhancing remote self-management for patients and providing new strategies for the ongoing care of psychiatric patients. We registered the review protocol on PROSPERO (CRD42022324958).