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Objective: To explore the effects of Agaricus bisporu-derived glucosamine hydrochloride (GAH) on hepatocellular carcinoma (HCC). Methods: A zebrafish liver cancer and vascular double transgenic model, Tg (flk:mCherry;krasG12V) was induced using a 60 mg/mL doxycycline hydrochloride solution. Larvae were traced and observed for the development of liver cancer from 5 d to 10 d using laser confocal microscopy. Different concentrations of GAH were added during Dox induction, larvae in Control group (Ctr), modeling group (Dox), Dox+0.1% GAH group and Dox+0.3% GAH group (Dox) were analyzed under laser confocal microscopy to observe the effect of GAH on liver cancer and tumor vascular growth. The effect of GAH on the mRNA and protein expression of HCC and vascular-related regulatory factors (prmt5, tiam1, kat5, vegfaa, vegfr2, tgf-β1) was analyzed via qPCR and ELISA assays. Finally, the correlations between tgf-β1, prmt5, tiam1, kat5, vegfaa and vegfr2 were validated through TIMER2 online bioinformatics analysis tool. Results: Continuous induction of Dox facilitated the emergence of HCC. Compared with the Dox model group, the growth and invasion of HCC were significantly inhibited after GAH treatment (P

Increasing customer apprehensions regarding the security and nutritional value of agricultural goods are compelling governments and industries to implement traceable, transparent, and reputable logistics management systems. Blockchain-based agricultural logistics management systems guarantee the permanence of data once it is uploaded but cannot cope with the risk of data being falsified before uploading to the blockchain. In this work, we developed a collaborative game model between government bodies and agricultural enterprises based on the evolutionary game theory and explored the influencing factors of enterprises following the rules to share the real traceability information through numerical simulation using MATLAB. The findings show that government incentives and penalties promote positive behavior, and consumer and media supervision contribute to supply chain transparency, but firms tend to share truthful information only when it benefits them. This study builds upon existing research on the impact of social variables on both members' decision-making behavior. It highlights the positive roles of consumers and the media in the supervision of agricultural product traceability, which can help to raise public awareness of social responsibility and thus promote positive interaction in the market.

Abstract Background Widespread neuropathic pain usually affects a wide range of body areas and inflicts huge suffering on patients. However, little is known about how it happens and effective therapeutic interventions are lacking. Methods Widespread neuropathic pain was induced by partial infraorbital nerve transection (p-IONX) and evaluated by measuring nociceptive thresholds. In vivo/vitro electrophysiology were used to evaluate neuronal activity. Virus tracing strategies, combined with optogenetics and chemogenetics, were used to clarify the role of remodeling circuit in widespread neuropathic pain. Results We found that in mice receiving p-IONX, along with pain sensitization spreading from the orofacial area to distal body parts, glutamatergic neurons in the ventral posteromedial nucleus of the thalamus (VPMGlu) were hyperactive and more responsive to stimulations applied to the hind paw or tail. Tracing experiments revealed that a remodeling was induced by p-IONX in the afferent circuitry of VPMGlu, notably evidenced by more projections from glutamatergic neurons in the dorsal column nuclei (DCNGlu). Moreover, VPMGlu receiving afferents from the DCN extended projections further to glutamatergic neurons in the posterior insular cortex (pIC). Selective inhibition of the terminals of DCNGlu in the VPM, the soma of VPMGlu or the terminals of VPMGlu in the pIC all alleviated trigeminal and widespread neuropathic pain. Conclusion These results demonstrate that hyperactive VPMGlu recruit new afferents from the DCN and relay the extra-cephalic input to the pIC after p-IONX, thus hold a key position in trigeminal neuropathic pain and its spreading. This study provides novel insights into the circuit mechanism and preclinical evidence for potential therapeutic targets of widespread neuropathic pain.

Abstract With the rapid spread of the novel coronavirus (COVID-19), a sustained global pandemic has emerged. Globally, the cumulative death toll is in the millions. The rising number of COVID-19 infections and deaths has severely impacted the lives of people worldwide, healthcare systems, and economic development. We conducted a retrospective analysis of the characteristics of COVID-19 patients. This analysis includes clinical features upon initial hospital admission, relevant laboratory test results, and imaging findings. We aimed to identify risk factors for severe illness and to construct a predictive model for assessing the risk of severe COVID-19. We collected and analyzed electronic medical records of confirmed COVID-19 patients admitted to the Affiliated Hospital of Jiangsu University (Zhenjiang, China) between December 18, 2022, and February 28, 2023. According to the WHO diagnostic criteria for the novel coronavirus, we divided the patients into two groups: severe and non-severe, and compared their clinical, laboratory, and imaging data. Logistic regression analysis, the least absolute shrinkage and selection operator (LASSO) regression, and receiver operating characteristic (ROC) curve analysis were used to identify the relevant risk factors for severe COVID-19 patients. Patients were divided into a training cohort and a validation cohort. A nomogram model was constructed using the “rms” package in R software. Among the 346 patients, the severe group exhibited significantly higher respiratory rates, breathlessness, altered consciousness, neutrophil-to-lymphocyte ratio (NLR), and lactate dehydrogenase (LDH) levels compared to the non-severe group. Imaging findings indicated that the severe group had a higher proportion of bilateral pulmonary inflammation and ground-glass opacities compared to the non-severe group. NLR and LDH were identified as independent risk factors for severe patients. The diagnostic performance was maximized when NLR, respiratory rate (RR), and LDH were combined. Based on the statistical analysis results, we developed a COVID-19 severity risk prediction model. The total score is calculated by adding up the scores for each of the twelve independent variables. By mapping the total score to the lowest scale, we can estimate the risk of COVID-19 severity. In addition, the calibration plots and DCA analysis showed that the nomogram had better discrimination power for predicting the severity of COVID-19. Our results showed that the development and validation of the predictive nomogram had good predictive value for severe COVID-19.

Abstract Complex coumarins (CCs) represent characteristic metabolites found in Apiaceae plants, possessing significant medical value. Their essential functional role is likely as protectants against pathogens and regulators responding to environmental stimuli. Utilizing genomes and transcriptomes from 34 Apiaceae plants, including our recently sequenced Peucedanum praeruptorum, we conduct comprehensive phylogenetic analyses to reconstruct the detailed evolutionary process of the CC biosynthetic pathway in Apiaceae. Our results show that three key enzymes – p-coumaroyl CoA 2’-hydroxylase (C2’H), C-prenyltransferase (C-PT), and cyclase – originated successively at different evolutionary nodes within Apiaceae through various means of gene duplications: ectopic and tandem duplications. Neofunctionalization endows these enzymes with novel functions necessary for CC biosynthesis, thus completing the pathway. Candidate genes are cloned for heterologous expression and subjected to in vitro enzymatic assays to test our hypothesis regarding the origins of the key enzymes, and the results precisely validate our evolutionary inferences. Among the three enzymes, C-PTs are likely the primary determinant of the structural diversity of CCs (linear/angular), due to divergent activities evolved to target different positions (C-6 or C-8) of umbelliferone. A key amino acid variation (Ala161/Thr161) is identified and proven to play a crucial role in the alteration of enzymatic activity, possibly resulting in distinct binding forms between enzymes and substrates, thereby leading to different products. In conclusion, this study provides a detailed trajectory for the establishment and evolution of the CC biosynthetic pathway in Apiaceae. It explains why only a portion, not all, of Apiaceae plants can produce CCs and reveals the mechanisms of CC structural diversity among different Apiaceae plants.

Coumarins, derived from the phenylpropanoid pathway, represent one of the primary metabolites found in angiosperms. The alignment of the tetrahydropyran (THP) and tetrahydrofuran (THF) rings with the lactone structure results in the formation of at least four types of complex coumarins. However, the mechanisms underlying the structural diversity of coumarin remain poorly understood. Here, we report the chromosome-level genome assembly of Notopterygium incisum, spanning 1.64 Gb, with a contig N50 value of 22.7 Mb and 60,021 annotated protein-coding genes. Additionally, we identified the key enzymes responsible for shaping the structural diversity of coumarins, including two p-coumaroyl CoA 2′-hydroxylases crucial for simple coumarins basic skeleton architecture, two UbiA prenyltransferases responsible for angular or linear coumarins biosynthesis, and five CYP736 cyclases involved in THP and THF ring formation. Notably, two bifunctional enzymes capable of catalyzing both demethylsuberosin and osthenol were identified for the first time. Evolutionary analysis implies that tandem and ectopic duplications of the CYP736 subfamily, specifically arising in the Apiaceae, contributed to the structural diversity of coumarins in N. incisum. Conclusively, this study proposes a parallel evolution scenario for the complex coumarin biosynthetic pathway among different angiosperms and provides essential synthetic biology elements for the heterologous industrial production of coumarins.

Objective: The extraction process of alkali-extracted abalone viscera polysaccharides (Aavp) was optimized, and the preventive and repair effects of purified Aavp on H2O2 oxidative damage on L929 cells were studied to provide a reference for the development and application of Aavps. Methods: Crude Aavp was obtained by hot alkali extraction followed by alcohol precipitation, and its extraction process was optimized by the response surface method. The preventive and repair abilities of H2O2 oxidative damage on L929 cells were analyzed. Resulst: The optimum extraction conditions of crude Aavps were as follows: Solid-liquid ratio of 1:150 g/mL, extraction time of 2 h, and extraction temperature of 70 ℃. Under these optimal conditions, the yield of crude Aavp was 8.57%. In the prevention test of H2O2 oxidative damage on L929 cells, different doses of purified Aavp (20, 50 and 100 μg/mL) had a significant preventive effect on L929 cell oxidative damage (P

Abstract To investigate the effect and safety of percutaneous endovascular angioplasty (PEA) with optional stenting for the treatment of severe stenosis or occlusion of subclavian artery, patients with severe stenosis ≥ 70% or occlusion of subclavian artery treated with PEA were retrospectively enrolled. The clinical data were analyzed. A total of 222 patients were retrospectively enrolled, including 151 males (68.0%) and 71 females (32.0%) aged 48–86 (mean 63.9 ± 9.0) years. Forty-seven (21.2%) patients had comorbidities. Subclavian artery stenosis ≥ 70% was present in 201 (90.5%) patients and complete subclavian occlusion in 21 (9.5%) cases. Angioplasty was successfully performed in all (100%) patients. Balloon-expandable stents were used in 190 (85.6%) cases, and self-expandable stents in 20 (9.0%) cases. Only 12 (5.4%) cases were treated with balloon dilation only. Among 210 patients treated with stent angioplasty, 71 (33.8% or 71/210) cases underwent balloon pre-dilation, 139 (66.2% or 139/210) had direct deployment of balloon-expandable stents, and 2 (1.0% or 2/210) experienced balloon post-dilation. Distal embolization protection devices were used in 5 (2.3% or 5/222) cases. Periprocedural complications occurred in 3 (1.4%) patients, including aortic dissection in 2 (0.9%) cases and right middle cerebral artery embolism in 1 (0.5%). No hemorrhage occurred. Among 182 (82.0%) patients with 6-month follow-up, restenosis > 70% occurred in 1 (0.5%) patient, and among 68 (30.6%) patients with 12-month follow-up, restenosis > 70% took place in 11 (16.2%) patients. Percutaneous endovascular angioplasty can be safely and efficiently performed for the treatment of severe stenosis ≥ 70% or occlusion of subclavian artery.

Natural killer (NK) cells are cytotoxic immune cells that can eliminate target cells without prior stimulation. Human induced pluripotent stem cells (iPSCs) provide a robust source of NK cells for safe and effective cell-based immunotherapy against aggressive cancers. In this in vitro study, a feeder-free iPSC differentiation was performed to obtain iPSC-NK cells, and distinct maturational stages of iPSC-NK were characterized. Mature cells of CD56bright CD16bright phenotype showed upregulation of CD56, CD16, and NK cell activation markers NKG2D and NKp46 upon IL-15 exposure, while exposure to aggressive atypical teratoid/rhabdoid tumor (ATRT) cell lines enhanced NKG2D and NKp46 expression. Malignant cell exposure also increased CD107a degranulation markers and stimulated IFN-γ secretion in activated NK cells. CD56bright CD16bright iPSC-NK cells showed a ratio-dependent killing of ATRT cells, and the percentage lysis of CHLA-05-ATRT was higher than that of CHLA-02-ATRT. The iPSC-NK cells were also cytotoxic against other brain, kidney, and lung cancer cell lines. Further NK maturation yielded CD56−ve CD16bright cells, which lacked activation markers even after exposure to interleukins or ATRT cells - indicating diminished cytotoxicity. Generation and characterization of different NK phenotypes from iPSCs, coupled with their promising anti-tumor activity against ATRT in vitro, offer valuable insights into potential immunotherapeutic strategies for brain tumors.

Malignant tumors are a category of diseases that possess invasive and metastatic capabilities, with global incidence and mortality rates remaining high. In recent years, the pivotal role of fibrosis in tumor progression, drug resistance, and immune evasion has increasingly been acknowledged. Fibrosis enhances the proliferation, migration, and invasion of tumor cells by modifying the composition and structure of the extracellular matrix, thereby offering protection for immune evasion by tumor cells. The activation of cancer-associated fibroblasts (CAFs) plays a significant role in this process, as they further exacerbate the malignant traits of tumors by secreting a variety of cytokines and growth factors. Anti-fibrotic tumor treatment strategies, including the use of anti-fibrotic drugs and inhibition of fibrosis-related signaling pathways such as Transforming Growth Factor-β (TGF-β), have demonstrated potential in delaying tumor progression and improving the effectiveness of chemotherapy, targeted therapy, and immunotherapy. In the future, by developing novel drugs that target the fibrotic microenvironment, new therapeutic options may be available for patients with various refractory tumors.

Background: Heart failure (HF) is a condition caused by a malfunction of the heart's pumping function. The single-point insulin sensitivity estimator (SPISE) index is a novel indicator for assessing insulin resistance in humans. However, the connection between the SPISE index and the risk of HF in the elderly is unknown. Therefore, our study aims to evaluate the connection between the SPISE index and HF in older adults. Methods: The study was based on data collected from the 1999–2020 National Health and Nutrition Examination Survey database and included 6165 participants aged ≥60 years. The multivariable linear regression model and the smooth fitting curve model were applied to investigate the connection between the SPISE index and HF in the elderly. Furthermore, the subgroup analysis was performed to investigate the interactive factors. Results: In this study, the mean age of the population was 69.38 years. After adjusting for all covariates, we observed that the SPISE index was inversely related to the prevalence of HF (OR = 0.87, 95 % CI = 0.80–0.94, P

IntroductionEndoglucanase (EG) and cellobiohydrolase (CBH) which produced by microorganisms, have been widely used in industrial applications.MethodsIn order to construct recombinant bacteria that produce high activity EG and CBH, in this study, eg (endoglucanase) and cbh (cellobiohydrolase) were cloned from the rumen microbial genome of yak and subsequently expressed independently and co-expressed within Lactococcus lactis NZ9000 (L. lactis NZ9000).ResultsThe recombinant strains L. lactis NZ9000/pMG36e-usp45-cbh (L. lactis-cbh), L. lactis NZ9000/pMG36e-usp45-eg (L. lactis-eg), and L. lactis NZ9000/pMG36e-usp45-eg-usp45-cbh (L. lactis-eg-cbh) were successfully constructed and demonstrated the ability to secrete EG, CBH, and EG-CBH. The sodium carboxymethyl cellulose activity of the recombinant enzyme EG was the highest, and the regenerated amorphous cellulose (RAC) was the specific substrate of the recombinant enzyme CBH, and EG-CBH. The optimum reaction temperature of the recombinant enzyme CBH was 60°C, while the recombinant enzymes EG and EG-CBH were tolerant to higher temperatures (80°C). The optimum reaction pH of EG, CBH, and EG-CBH was 6.0. Mn2+, Fe2+, Cu2+, and Co2+ could promote the activity of CBH. Similarly, Fe2+, Ba2+, and higher concentrations of Ca2+, Cu2+, and Co2+ could promote the activity of EG-CBH. The addition of engineered strains to whole-plant corn silage improved the nutritional quality of the feed, with the lowest pH, acid detergent fiber (ADF), and neutral detergent fiber (NDF) contents observed in silage from the L. lactis-eg group (p

Abstract To investigate the significance of atherosclerotic plaque location in hybrid surgery comprising both endovascular recanalization approaches and carotid endarterectomy for symptomatic atherosclerotic non-acute long-segment occlusion of the internal carotid artery (ICA), 162 patients were enrolled, including 120 (74.1%) patients in the proximal plaque group and 42 (25.9%) in the distal plaque group. Surgical recanalization was performed in all patients, with successful recanalization in 119 (99.2%) patients in the proximal and 39 (92.9%) in the distal plaque group. The total successful recanalization rate was 97.5% (158/162) with a failure rate of 2.5% (4/162). Periprocedural complications occurred in 5 (4.2% or 5/120) patients in the proximal plaque group, including neck infection in two (1.7%), recurrent nerve injury in 1 (0.8%), and laryngeal edema in 2 (1.7%), and 2 (4.8%) in the distal plaque group, including femoral puncture infection in 2 (4.8%). No severe complications occurred in either group. Univariate analysis showed plaque location was a significant (P = 0.018) risk factor for successful recanalization, and multivariate analysis indicated that the plaque location remained a significant independent risk factor for recanalization success (P = 0.017). In follow-up 6–48 months after the recanalization surgery, reocclusion occurred in two (2.8%) patients in the proximal plaque group and 4 (13.3%) in the distal plaque group. In conclusion, although hybrid surgery achieves similar outcomes in patients with ICA occlusion caused by either proximal or distal atherosclerotic plaques, plaque location may be a significant risk factor for successful recanalization of symptomatic non-acute long-segment ICA occlusion.

Abstract This study aimed to evaluate the association between low-density lipoprotein cholesterol (LDL-C) and serum uric acid to serum creatinine (SUA/SCr) ratio in male gout patients at different BMIs. This real-world study included 956 male gout patients aged 18–83 years. We retrospectively analyzed the medical records of Chinese male gout patients from 2017 to 2019. The correlation between LDL-C and SUA/SCr was tested after adjusting for confounding factors. We found a nonlinear relationship between LDL-C and SUA/SCr in the whole study population. Stratification analysis showed that there was actually a nonlinear relationship between LDL-C and SUA/SCr in men with a BMI of 24–28, the inflection point of LDL-C was 1.8 mmol/L, when LDL-C was greater than 1.8 mmol/L, there was a positive correlation between LDL-C levels and SUA/SCr (β = 0.67, 95% CI 0.35–0.98, P

Abstract Sleep, locomotor and social activities are essential animal behaviors, but their reciprocal relationships and underlying mechanisms remain poorly understood. Here, we elicit information from a cutting-edge large-language model (LLM), generative pre-trained transformer (GPT) 3.5, which interprets 10.2–13.8% of Drosophila genes known to regulate the 3 behaviors. We develop an instrument for simultaneous video tracking of multiple moving objects, and conduct a genome-wide screen. We have identified 758 fly genes that regulate sleep and activities, including mre11 which regulates sleep only in the presence of conspecifics, and NELF-B which regulates sleep regardless of whether conspecifics are present. Based on LLM-reasoning, an educated signal web is modeled for understanding of potential relationships between its components, presenting comprehensive molecular signatures that control sleep, locomotor and social activities. This LLM-aided strategy may also be helpful for addressing other complex scientific questions.

Convolutional neural networks (CNNs) play a prominent role in solving problems in various domains such as pattern recognition, image tasks, and natural language processing. In recent years, neural architecture search (NAS), which is the automatic design of neural network architectures as an optimization algorithm, has become a popular method to design CNN architectures against some requirements associated with the network function. However, many NAS algorithms are characterised by a complex search space which can negatively affect the efficiency of the search process. In other words, the representation of the neural network architecture and thus the encoding of the resulting search space plays a fundamental role in the designed CNN performance. In this paper, to make the search process more effective, we propose a novel compact representation of the search space by identifying network blocks as elementary units. The study in this paper focuses on a popular CNN called DenseNet. To perform the NAS, we use an ad-hoc implementation of the particle swarm optimization indicated as PSO-CNN. In addition, to reduce size of the final model, we propose a segmentation method to cut the blocks. We also transfer the final model to different datasets, thus demonstrating that our proposed algorithm has good transferable performance. The proposed PSO-CNN is compared with 11 state-of-the-art algorithms on CIFAR10 and CIFAR100. Numerical results show the competitiveness of our proposed algorithm in the aspect of accuracy and the number of parameters.

Abstract Cirsium japonicum contains a variety of medicinal components with good clinical efficacy. With the rapid changes in global climate, it is increasingly important to study the distribution of species habitats and the factors influencing their adaptability. Utilizing the MaxEnt model, we forecasted the present and future distribution regions of suitable habitats for C. japonicum under various climate scenarios. The outcome showed that under the current climate, the total suitable area of C. japonicum is 2,303,624 km2 and the highly suitable area is 79,117 km2. The distribution of C. japonicum is significantly influenced by key environmental factors such as temperature annual range, precipitation of the driest month, and precipitation of the wettest month. In light of future climate change, the suitable habitat for C. japonicum is anticipated to progressively relocate toward the western and northern regions, leading to an expansion in the total suitable area. These findings offer valuable insights into the conservation, sustainable utilization, and standardized cultivation of wild C. japonicum resources.

Background The novel COVID-19 was rapidly spreading and was highly contagious. COVID-19 caused over 6 million deaths worldwide, with high mortality rates, particularly in severe cases.Objective This study aimed to investigate whether serum albumin-neutrophil count to lymphocyte count ratio (NLR) score (ANS) could be used as a prognostic indicator of COVID-19 severity.Design A retrospective study.Participants Based on the WHO diagnostic criteria, patients were classified as either non-severe (n=270) or severe (n=100).Primary and secondary outcome measures NLR, serum albumin level and ANS.Main results The NLR of patients with severe disease was significantly higher than that of those with non-severe disease. Serum albumin levels were significantly lower in patients with severe disease than in those with non-severe disease. The cut-off values representing the maximum potential effectiveness of serum albumin and NLR were 33.5 g/L and 8.25, respectively, according to the Youden index. In patients with severe COVID-19, we observed that the serum albumin level, NLR and ANS were independent prognostic indicators of severe COVID-19 using logistic analysis. The relative risk of severe COVID-19 was 7.65 (95% CI 3.72 to 15.75, p

Background: Dihydroartemisinin (DHA), a derivative of Artemisia annua, has been shown to possess anti-inflammatory properties. Besides, Yes-associated protein 1 (YAP1) plays a crucial role in maintaining liver homeostasis. Methods: This study used Yap1Flox/Flox, Albumin-Cre mice with hepatocyte-specific Yap1 knockout (referred to as Yap1LKO) and their control mice (Yap1Flox/Flox, referred to as Yap1Flox). The effect of Yap1 on lipid metabolism homeostasis was investigated through non-targeted metabolomic analysis of mouse liver. Subsequently, DHA was administered to Yap1LKO mice to assess its potential as a treatment. Liver pathology was evaluated via H&E staining, and the levels of AST, ALT, and TG were quantified using biochemical assays. The contents of arachidonic acid (AA), prostaglandin E1 (PGE1), and leukotrienes (LT) in the liver were measured using ELISA, while the protein expressions of PLIN2, 5-lipoxygenase (5-LOX), and cyclooxygenase-2 (COX-2) were analyzed through IHC staining. Results: Hepatocyte-specific Yap1 knockout activated the AA metabolic pathway, resulting in increased elevated levels of AA, PGE1, and LT levels, along with inflammatory cytokine infiltration. DHA mitigated the elevation of metabolites such as PGE1 and LT caused by the AA metabolic pathway activation by down-regulating the levels of COX-2 and 5-LOX in the liver of Yap1LKO mice. Moreover, it alleviated the accumulation of lipid vacuoles and reduced triglyceride (TG) and perilipin-2 (PLIN2) levels in the liver of Yap1LKO mice. Conclusions: Excessively low YAP1 expression induces liver inflammation and disturbances in lipid metabolism, whereas DHA modulated AA metabolism and mitigated liver inflammation by inhibiting the activation of 5-LOX and COX-2.

Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory disease. Psoralen (PSO) is the main pharmacological component identified from Bu-Shen-Fang-Chuan formula which has been traditionally used in treatment of COPD, yet its efficacy in COPD inflammation were unreported. In this study, we aimed to elucidate the anti-inflammatory potential of PSO in COPD and unravel the underlying mechanisms, focusing on T lymphocyte recruitment and the modulation of chemokines, namely monokine induced by interferon-gamma (CXCL9), interferon inducible protein 10 (CXCL10), and interferon inducible T-Cell alpha chemoattractant (CXCL11). In vitro, RAW264.7 was stimulated by interferon (IFN)-γ + cigarette smoke extract (CSE) and were treated with PSO (2.5, 5, 10 μM), then the levels of chemokines and the activation of Janus kinase (JAK)/Signal transducer and activator of transcription 1 (STAT1) pathway were analyzed by real time PCR and western blot. In vivo, a murine model was established by intraperitoneal injection of CSE on day 1, 8, 15, and 22, then treated with PSO (10 mg/kg). Our experiments in vitro illustrated that PSO reduced the levels of CXCL9, CXCL10, and CXCL11, and decreased the protein phosphorylation levels of JAK2 and STAT1. Additionally, PSO effectively improved inflammatory infiltration and decreased the proportion of CD8+ T cells in CSE-exposed mice. Furthermore, PSO reduced the levels of CXCL9, CXCL10, and CXCL11 in bronchoalveolar lavage fluid (BALF) and lung tissue, and decreased the protein phosphorylation levels of JAK2 and STAT1. In conclusion, our results revealed the therapeutic potential of PSO for COPD inflammation, possibly mediated through the regulation of CD8+ T cell recruitment and chemokines via the JAK2/STAT1 signaling pathway.

Abstract Brexucabtagene autoleucel CAR-T therapy is highly efficacious in overcoming resistance to Bruton’s tyrosine kinase inhibitors (BTKi) in mantle cell lymphoma. However, many patients relapse post CAR-T therapy with dismal outcomes. To dissect the underlying mechanisms of sequential resistance to BTKi and CAR-T therapy, we performed single-cell RNA sequencing analysis for 66 samples from 25 patients treated with BTKi and/or CAR-T therapy and conducted in-depth bioinformatics™ analysis. Our analysis revealed that MYC activity progressively increased with sequential resistance. HSP90AB1 (Heat shock protein 90 alpha family class B member 1), a MYC target, was identified as early driver of CAR-T resistance. CDK9 (Cyclin-dependent kinase 9), another MYC target, was significantly upregulated in Dual-R samples. Both HSP90AB1 and CDK9 expression were correlated with MYC activity levels. Pharmaceutical co-targeting of HSP90 and CDK9 synergistically diminished MYC activity, leading to potent anti-MCL activity. Collectively, our study revealed that HSP90-MYC-CDK9 network is the primary driving force of therapeutic resistance.

In this paper, we study eight single-machine scheduling problems with rejection and position-dependent parameters. We consider two position-dependent parameters as follows: (1) position-dependent weights and (2) position-dependent processing times. In addition, we also introduce a weight-modifying activity or a rate-modifying activity into our problems. In the first six problems, the task is to minimize the sum of the total weighted completion time of accepted jobs and the total rejection cost of rejected jobs. We show that all six problems can be solved in polynomial time. In the last two problems, the task is to minimize the total weighted completion time of accepted jobs under the constraint that the total rejection cost of rejected jobs can not exceed a given upper bound. We show that these two problems are binary NP-hard and each problem admits an FPTAS.

Objective: Alkali-extracted polysaccharides from Abalone viscera (Aavp) were isolated and purified. The structure and antioxidant activity of Aavp were studied, which would provide a reference for developing and applying polysaccharides. Methods: The crude alkali-extracted polysaccharide was prepared by hot alkali extraction and alcohol precipitation. After the purification of DEAE sepharose fast flow and sephacryl S-400 HR, the purified polysaccharide was obtained and subjected to the structural analysis and antioxidant activity assay, such as Gas chromatography (GC), high-performance liquid chromatography (HPLC), infrared spectroscopy (IR), and thermogravimetric analyzer (TGA), etc. Result: Four kinds of components (Aavp Ia, Aavp Ib, Aavp IIa, and Aavp IIb) were obtained from the crude polysaccharide. Because of the highest yield, Aavp IIa was selected for further structural analysis. Aavp IIa was composed of xylose and galactose, with a relative molecular weight of 166513 Da. IR characterized the α-glycosidic bond configuration. The composition of Aavp IIa was possible as follows: The molar percentage of the galactose 1→4 glycosidic bond was 11.81%, the galactose 1→3 glycosidic bond was 34.14%, and the galactose 1→2 glycosidic bond was 10.14%. The molar percentage of the xylose 1→3 glycosidic bond was 33.85%, and the 1→2 and 1→4 glycosidic bond was 10.06%. Thermogravimetric analysis showed that Aavp IIa was broken and decomposed at 226.4~332.6 °C, and the thermal weight loss rate was 43.65%. Antioxidant experiments showed that Aavp IIa had a scavenging rate of 85.89% for superoxide anion radicals and 62.17% for DPPH radicals, respectively, presenting a certain antioxidant activity. Conclusion: Aavp is a heteropolysaccharide with specific antioxidant activity.

Abstract Background Bacterial vaginosis (BV) is a widely occurring vaginal inflammation in women of childbearing age caused by dysbiosis of the vaginal flora. Few studies have investigated the effect of serum carotenoids on the development and pathogenesis of BV. This study thus aimed to explore the correlation between serum carotenoids and BV in American women. Method The analysis included 1252 participants with BV from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2004. Multiple logistic regression was conducted to explore the correlation between BV and serum carotenoids, while smooth curve fitting was utilized to examine potential nonlinear correlations. Furthermore, stratified subgroup analyses and sensitivity analyses were conducted. ORs reflected the correlation between BV and serum carotenoids. Result Results of multiple logistic regression indicated that total serum carotenoids and BV had an inverse correlation. In the fully adjusted model II, the quartile with the highest levels of α-carotene and β-cryptoxanthin had a substantially lower incidence of BV. Smooth curve fitting revealed a significant negative linear correlation between serum carotenoids and the incidence of BV. The negative correlation between serum carotenoids and BV was relatively stable in stratified analyses. Moreover, in sensitivity analyses, the association between serum carotenoids and BV persisted, and β-carotene became significantly negatively correlated with BV. Conclusion This study found an inverse correlation between serum carotenoids and the prevalence of BV.

Neural architecture search (NAS), a promising method for automated neural architecture design, is often hampered by its overwhelming computational burden, especially the architecture evaluation process in evolutionary neural architecture search (ENAS). Although there are surrogate models based on regression or ranking to assist or replace the neural architecture evaluation process in ENAS to reduce the computational cost, these surrogate models are still affected by poor architectures and are not able to accurately find good architectures in a search space. To solve the above problems, we propose a novel surrogate-assisted NAS approach, which we call the similarity surrogate-assisted ENAS with dual encoding strategy (SSENAS). We propose a surrogate model based on similarity measurement to select excellent neural architectures from a large number of candidate architectures in a search space. Furthermore, we propose a dual encoding strategy for architecture generation and surrogate evaluation in ENAS to improve the exploration of well-performing neural architectures in a search space and realize sufficiently informative representations of neural architectures, respectively. We have performed experiments on NAS benchmarks to verify the effectiveness of the proposed algorithm. The experimental results show that SSENAS can accurately find the best neural architecture in the NAS-Bench-201 search space after only 400 queries of the tabular benchmark. In the NAS-Bench-101 search space, it can also get results that are comparable to other algorithms. In addition, we conducted a large number of experiments and analyses on the proposed algorithm, showing that the surrogate model measured via similarity can gradually search for excellent neural architectures in a search space.

Abstract Background Auxin transcription factor (ARF) is an important transcription factor that transmits auxin signals and is involved in plant growth and development as well as stress response. However, genome-wide identification and responses to abiotic and pathogen stresses of the ARF gene family in Cucurbita pepo L, especially pathogen stresses, have not been reported. Results Finally, 33 ARF genes (CpARF01 to CpARF33) were identified in C.pepo from the Cucurbitaceae genome database using bioinformatics methods. The putative protein contains 438 to 1071 amino acids, the isoelectric point is 4.99 to 8.54, and the molecular weight is 47759.36 to 117813.27 Da, the instability index ranged from 40.74 to 68.94, and the liposoluble index ranged from 62.56 to 76.18. The 33 genes were mainly localized in the nucleus and cytoplasm, and distributed on 16 chromosomes unevenly. Phylogenetic analysis showed that 33 CpARF proteins were divided into 6 groups. According to the amino acid sequence of CpARF proteins, 10 motifs were identified, and 1,3,6,8,10 motifs were highly conserved in most of the CpARF proteins. At the same time, it was found that genes in the same subfamily have similar gene structures. Cis-elements and protein interaction networks predicted that CpARF may be involved in abiotic factors related to the stress response. QRT-PCR analysis showed that most of the CpARF genes were upregulated under NaCl, PEG, and pathogen treatment compared to the control. Subcellular localization showed that CpARF22 was localized in the nucleus. The transgenic Arabidopsis thaliana lines with the CpARF22 gene enhanced their tolerance to salt and drought stress. Conclusion In this study, we systematically analyzed the CpARF gene family and its expression patterns under drought, salt, and pathogen stress, which improved our understanding of the ARF protein of zucchini, and laid a solid foundation for functional analysis of the CpARF gene.

In this article, a novel method is proposed to investigate the $ H_{\infty} $ state observer design problem for genetic regulatory networks with time-varying delays and disturbances. First, the structure of the desired state observer is constructed, and the parameterized bounds of the error system solutions are given. Then, a bounded real lemma is established to provide the existence of the state observer and ensure that the error system is globally exponentially stable at an $ H_{\infty} $ performance level. Third, based on the obtained bounded real lemma, the explicit expressions of the $ H_{\infty} $ state observer can be obtained by solving several matrix inequalities. The effectiveness of the proposed novel observer design method is illustrated via a numerical example.

In this study, (diamond + TiC) reinforced Ti6Al4V titanium matrix composites (DT-TMCs) were fabricated using the directed energy deposition (DED) technique to enhance multiple properties of the Ti6Al4V alloy. The phase composition, microstructure, microhardness, wear resistance, and thermal conductivity of the composites were investigated. The findings demonstrate that the DT-TMCs consist of diamond, in-situ formed TiC (including eutectic TiC and primary TiC), α-Ti and β-Ti. The formation of in-situ TiC is attributed to the partial dissolution of the diamond into the Ti6Al4V matrix during the DED process. The superior hardness of in-situ TiC, compared to that of Ti6Al4V alloy, plays a pivotal role in enhancing the overall hardness of the DT-TMCs. Owing to the high hardness and excellent thermal conductivity of diamond, the wear resistance and thermal conductivity of the DT-TMCs are superior to those of the unmodified Ti6Al4V alloy. With the diamond volume fraction increasing from 0% to 15%, the microhardness of the DT-TMCs raises from 333.99 HV0.2 to 438.15 HV0.2, the wear rate decreases from 207.514 × 10−5 mm³·N−1·m−1 to 2.256 × 10−5 mm³·N−1·m−1, and the thermal conductivity increases from 6.686 W·m−1·K−1 to 13.613 W·m−1·K−1. Additionally, the in-situ TiC exhibits superior thermal conductivity compared to the Ti6Al4V alloy, which also contributes to the improved thermal conductivity of the DT-TMCs.

In the original publication [...]

ObjectiveAtypical polypoid adenomyoma (APA) is a rare benign tumor frequently diagnosed in young women that may coexist with or progress to atypical endometrial hyperplasia (EAH) or endometrioid endometrial carcinoma (EEC). This study aimed to investigate which subset of patients with APA are prone to concurrent or subsequent EAH or EEC, evaluate the necessity of progestin treatment in patients with APA only after achieving a complete response (CR) through hysteroscopic lesion resection, and assess the impact of concurrent APA on the fertility-preserving treatment of EAH or EEC.MethodsThis retrospective single-center study analyzed 86 patients with APA treated at the Obstetrics and Gynecology Hospital of Fudan University between January 2010 and October 2021. Patients with EAH or EEC only who underwent fertility-preserving treatment during the same period were matched in a 2:1 ratio with patients with concurrent APA and EAH or EEC. The clinicopathological characteristics, treatments, and prognosis were analyzed.ResultsThe median patient age was 31 years (range 21–47 years). Among the 86 included patients, nine underwent total hysterectomy, 62 received conservative treatment, and the remaining 15 were lost to follow-up. A comparison of the 16 patients with APA only versus the 58 patients with APA and concurrent or subsequent EAH or EEC revealed that a homeostasis model assessment of insulin resistance (HOMA-IR) of > 2.2 (P = 0.047) and high-density lipoprotein (HDL) concentration of < 1.2 mmol/L (P = 0.028) were independent risk factors for EAH or EEC in patients with APA. Among the 17 patients with APA only who received conservative treatment and achieved a CR after hysteroscopic lesion resection, 13 received hormone treatment for a median duration of 6.3 months. The median follow-up time for these 17 patients was 49.0 months, during which no recurrence of APA was observed, but six patients developed endometrial hyperplastic diseases. Regarding the impact of concurrent APA on fertility-preserving treatment for EAH or EEC, the median time to achieve a CR was 24.0 weeks (95% confidence interval [CI]: 23.0–40.4) in the APA group and 26.0 weeks (95% CI: 24.3–32.3) in the non-APA group (P = 0.424). There were no significant differences between the two groups in the outcomes of fertility-preserving treatment.ConclusionPatients with APA only may still develop endometrial hyperplastic diseases after complete resection of the lesion under hysteroscopy to achieve a CR, particularly those with a HOMA-IR of > 2.2 or HDL concentration of < 1.2 mmol/L. Concurrent APA did not affect the efficacy of fertility-preserving treatment in patients with EAH or EEC.

Abstract Ependymin‐related protein 1 (EPDR1) has been found in the secretory body of adipocytes where it plays a role in lipid binding, transportation, and catabolism. The aim of this study was to investigate serum EPDR1 levels in children with obesity and normal‐weight children and to compare the levels of EPDR1 between children with obesity, with and without metabolic‐associated fatty liver disease (MAFLD). Thirty‐four normal‐weight children and 49 children with obesity (15 with MAFLD) were included in the study. Circulating EPDR1, IL‐1β, and TNF‐α were measured using enzyme‐linked immunosorbent assays. Anthropometric and biochemical measurements related to obesity, blood lipids, and insulin resistance were performed on all participants. The serum EPDR1 levels of children with obesity were significantly higher than those of the control group. There was no difference in EPDR1 levels between the patients with and without MAFLD. Circulating EPDR1 was positively correlated with body mass index (BMI), BMI z‐score, insulin, glucose, homeostatic model assessment insulin resistance index (HOMA‐IR), triglycerides, white blood cells, and neutrophils. Binary logistic regression analysis showed a significant increase in the odds ratio of obesity with increasing EPDR1 levels. EPDR1 is strongly associated with obesity and may also be associated with metabolic disorders. This trial is registered with ChiCTR2300070951.

As ferroelectric materials, lithium tantalate and lithium niobate share similar material characteristics, such as a high Pockels effect and nonlinear optical coefficients. When compared to lithium niobate, lithium tantalate offers a higher optical damage threshold, a broader transparent window, and lower birefringence, making it a promising candidate for high-performance electro-optical photonic integrated devices. In this study, we design and successfully fabricate micro-ring resonators on an acoustic-grade lithium-tantalate-on-insulator wafer, demonstrating their tunability and dynamic modulation capabilities. Experimental results indicate that the achieved thin-film lithium tantalate based micro-ring resonator exhibits an intrinsic Q-factor of 8.4 × 105, corresponding to a waveguide propagation loss of 0.47 dB/cm and a tuning efficiency of 1.94 pm/V. More importantly, as compared to those based on thin-film lithium niobate, a much weaker photorefractive effect and drift phenomenon around the 1550 nm wavelength under a direct-current drive are observed in the present fabricated thin-film lithium tantalate micro-rings with a silicon oxide over-cladding and a tuning electrode on top.

IntroductionThe brown planthopper (BPH) poses a significant threat to rice production in Asia. The use of resistant rice varieties has been effective in managing this pest. However, the adaptability of BPH to resistant rice varieties has led to the emergence of virulent populations, such as biotype Y BPH. YHY15 rice, which carries the BPH resistance gene Bph15, exhibits notable resistance to biotype 1 BPH but is susceptible to biotype Y BPH. Limited information exists regarding how resistant rice plants defend against BPH populations with varying levels of virulence.MethodsIn this study, we integrated miRNA and mRNA expression profiling analyses to study the differential responses of YHY15 rice to both avirulent (biotype 1) and virulent (biotype Y) BPH.ResultsYHY15 rice demonstrated a rapid response to biotype Y BPH infestation, with significant transcriptional changes occurring within 6 hours. The biotype Y-responsive genes were notably enriched in photosynthetic processes. Accordingly, biotype Y BPH infestation induced more intense transcriptional responses, affecting miRNA expression, defenserelated metabolic pathways, phytohormone signaling, and multiple transcription factors. Additionally, callose deposition was enhanced in biotype Y BPH-infested rice seedlings.DiscussionThese findings provide comprehensive insights into the defense mechanisms of resistant rice plants against virulent BPH, and may potentially guide the development of insect-resistant rice varieties.

Groundwater is one of the important freshwater resources on Earth and is closely related to human activities. As a good biological vector, a more diverse repertory of antibiotic resistance genes in the water environment would have a profound impact on human medical health. Therefore, this study conducted a metagenomic sequencing analysis of water samples from groundwater monitoring points in the middle and lower reaches of the Yangtze River to characterize microbial community composition and antibiotic resistance in the groundwater environment. Our results show that different microbial communities and community composition were the driving factors in the groundwater environment, and a diversity of antibiotic resistance genes in the groundwater environment was detected. The main source of antibiotic resistance gene host was determined by correlation tests and analyses. In this study, metagenomics was used for the first time to comprehensively analyze microbial communities in groundwater systems in the middle and lower reaches of the Yangtze River basin. The data obtained from this study serve as an invaluable resource and represent the basic metagenomic characteristics of groundwater microbial communities in the middle and lower reaches of the Yangtze River basin. These findings will be useful tools and provide a basis for future research on water microbial community and quality, greatly expanding the depth and breadth of our understanding of groundwater.

We present the current state of the art in micro-transfer printing for heterogeneously integrated silicon photonic integrated circuits. The versatility of the technology is highlighted, as is the way ahead to make this technology a key enabler for next-generation photonic systems-on-chip.

pH-sensitive fluorescent proteins have revolutionized the field of cellular imaging and physiology, offering insight into the dynamic pH changes that underlie fundamental cellular processes. This comprehensive review explores the diverse applications and recent advances in the use of pH-sensitive fluorescent proteins. These remarkable tools enable researchers to visualize and monitor pH variations within subcellular compartments, especially mitochondria, shedding light on organelle-specific pH regulation. They play pivotal roles in visualizing exocytosis and endocytosis events in synaptic transmission, monitoring cell death and apoptosis, and understanding drug effects and disease progression. Recent advancements have led to improved photostability, pH specificity, and subcellular targeting, enhancing their utility. Techniques for multiplexed imaging, three-dimensional visualization, and super-resolution microscopy are expanding the horizon of pH-sensitive protein applications. The future holds promise for their integration into optogenetics and drug discovery. With their ever-evolving capabilities, pH-sensitive fluorescent proteins remain indispensable tools for unravelling cellular dynamics and driving breakthroughs in biological research. This review serves as a comprehensive resource for researchers seeking to harness the potential of pH-sensitive fluorescent proteins.

ObjectivesReal-world data indicated that some endometrial atypical hyperplasia (EAH) and early endometrial carcinoma (EEC) patients of fertility preservation had a normal ovarian reserve, while some had a decreased ovarian reserve (DOR). This study was designed to investigate the effect of baseline ovarian reserve on the treatment of EAH and EEC patients who ask for preservation of fertility.MethodsThis was a prospective cohort study conducted at a single university-affiliated fertility center. A total of 102 EAH and EEC patients who received fertility-preserving treatment between March 2019 and August 2020 were included and divided into a DOR group (n=22) and a non-DOR group (n=80).ResultsThe 32-week CR rate of the non-DOR group was significantly higher than that of the DOR group (60.3% vs. 33.3%, P =0.028). The DOR group had a longer treatment duration to achieve CR than the non-DOR group (40.07 vs. 29.71 weeks, P=0.008, HR: 0.54, 95% CI: 0.36–0.86). Multivariate logistic regression analyses demonstrated that DOR (OR: 0.35, 95% CI: 0.13–0.99, P=0.049) and BMI ≥25 kg/m2 (OR: 0.40, 95% CI: 0.17–0.92, P=0.031) were negatively associated with 32-week CR.ConclusionsDecreased baseline ovarian reserve is negatively correlated with the efficacy of fertility-preserving treatment in EAH and EEC patients, as this group has a lower CR rate and a longer treatment duration to achieve CR than those without DOR.

Objective To estatblish a real-time fluorescence imaging method for observing arterial blood spiral laminar flow. Methods Sprague Dawley rats were randomly divided into vein angiography group (femoral vein injection, 1 mL/kg) and low-dose arteriography group (abdominal aortic injection, 0.1 mL/kg). The low-dose arteriography group was further divided into fluorescein sodium group, rhodamine B group, FITC-dextran group and quantum dot group (n=7 for each group). The dynamic images were captured with high-speed camera. The fluorescence region was calibrated by image threshold segmentation algorithm and morphological post-processing algorithm. The axial velocity and tangential velocity of helical blood flow in rat femoral artery were measured, and the screw pitch and shear force were calculated. Results Compared with the vein angiography group, the low-dose arteriography group clearly showed the clockwise spiral laminar flow in the femoral artery of rats. In the FITC-dextran group, the axial velocity of blood spiral laminar flow was (198.4±112.7)mm/s, and the tangential velocity was(3.3±0.8)mm/s.The screw pitch was (126.1±76.3)mm, and the shear force was (9.5±5.6)Pa. The injections were repeated three times for each rat, and there was no significant difference among each injection. Conclusions Real-time fluorescence imaging can be used to observe arterial blood spiral laminar flow in vivo and to quantitatively analyze the hemodynamic characteristics of spiral laminar flow.

The precise wake model is crucial for accurately estimating wind farm loads and power, playing a key role in wake control within wind farms. This study proposes a segmented dual-Gaussian wake model, which is built upon existing dual-Gaussian wake models but places greater emphasis on the influence of initial wake generation and evolution processes on the wind speed profile in the near-wake region. The enhanced model optimizes the wake speed profile in the near-wake region and improves the accuracy of wake diffusion throughout the entire flow field. Furthermore, the optimized dual-Gaussian wake model is utilized to estimate the power output and blade root vibration loads in offshore wind farms. Through comparative analysis of high-fidelity simulation results and actual measurement data, the accuracy of the optimized dual-Gaussian wake model is validated. This approach offers high computational efficiency and provides valuable insights for load fluctuations and power estimation, thereby advancing the development of wake control strategies rapidly.

With the continuous warming of the global climate, expanding the use of renewable energy has become one of the main social responsibilities. However, as the number of installed wind turbines and their physical dimensions continue to increase, the issue of generated noise has become increasingly significant in influencing the acceptance and endorsement of wind power projects by neighboring communities. In this paper, we investigated the noise generated by two wind turbine units with rated powers of 1.5 MW and 4.5 MW and analyzed the variations in low-frequency noise during their operation and shutdown periods. This research shows that the power of a single unit has a significant impact on the low-frequency noise emitted into the environment. Compared with 1.5 MW wind turbines, 4.5 MW wind turbines generate more low-frequency noise when operating at the same wind speed. Further analysis of the narrowband frequency spectra and one-third octave spectra of the measured noise indicates that the low-frequency noise from the 4.5 MW wind turbine increases significantly in the range of approximately 80 Hz to 300 Hz, with more pronounced variations below 250 Hz corresponding to changes in wind speed. However, the overall variations in low-frequency noise with wind speed are not as notable as those observed for the 1.5 MW wind turbine. Due to the relatively weak attenuation of low-frequency noise in the atmosphere, the higher low-frequency content of large wind turbines may cause more distress to residents near wind farms. The result of this study emphasizes that in the planning and design of wind power projects, in addition to considering the efficiency of single-unit power generation and the contribution of renewable energy, it is also necessary to pay full attention to noise emission issues to ensure that the project is widely supported and accepted in the community.

BackgroundThe molecular classification of endometrial cancer has previously been shown to be associated with clinical outcomes. However, there are insufficient data to support the routine use of molecular classification for the treatment of patients seeking fertility preservation.MethodsHere, we retrospectively investigated 90 patients received fertility-sparing treatment. We used a next generation sequencing (NGS) panel to classify these patients into four subtypes. All patients received hormonal therapy combined with hysteroscopy. Therapeutic effects were evaluated by hysteroscopy every three months during the treatment.ResultsPatients with POLE mutations had the highest disease progression rate (50.0%, P=0.013), while the microsatellite instability-high (MSI-H) group had the highest recurrence rate (50.0%, P=0.042). PIK3CA mutation (hazard ratio (HR): 0.61; 95% confidence interval (CI): 0.37–0.99; P=0.046), overweight (HR: 0.56; 95% CI: 0.32–0.96; P=0.033) and obesity (HR: 0.44; 95% CI: 0.20–0.95; P=0.036) were associated with a significantly lower cumulative complete response (CR) rate. The combination of gonadotropin-releasing hormone analogues (GnRH-a) and letrozole (HR: 3.43; 95% CI: 1.81–6.52; P< 0.001) was associated with a significantly higher cumulative CR rate. KRAS mutation was significantly associated with disease progression (P=0.002). In wild-type TP53 patients, PTEN and PIK3CA mutations significantly prolonged the duration of treatment to achieve CR (log rank P=0.034; P=0.018).ConclusionThe implementation of molecular classification for EC patients undergoing fertility-sparing treatment is promising and can facilitate the selection of appropriate medical regimes to achieve better outcomes in patients with EC who require fertility preservation treatment.

To investigate the advancements of artificial intelligence techniques in the realm of library and information subject, we have chosen the Latent Dirichlet Allocation method as a case study to explore its current study status and implementations. Traditional theme mining analyses utilize methods such as word frequency statistics, co-occurrence analysis, community detection, and citation analysis to capture external quantitative features of words or documents. In contrast, the Latent Dirichlet Allocation theme modelling method employs a three-layer Bayesian structure of document-topic-word to describe the themes of documents and the semantic relationships among words, enabling a better exploration of latent semantic information in text. This method plays a pivotal role in fine-grained knowledge extraction and analysis. We systematically review more than a decade of relevant literature in the realm about library and information subject. Through content analysis, we construct an analytical architecture for the implementation of the Latent Dirichlet Allocation method. This architecture, viewed from the perspective of the implementation process of Latent Dirichlet Allocation, comprehensively summarizes the core stages and technical challenges, including text pre-processing, model construction (i.e., theme model selection and optimal theme number determination), and model solving. Additionally, we provide a comprehensive overview of the current study status of the Latent Dirichlet Allocation method across various implementation domains, such as theme exploration, knowledge organization, academic evaluation, sentiment analysis, and recommendation study. Our findings indicate that the Latent Dirichlet Allocation method has formed a mature analytical process in the realm of library and information subject, with ongoing growth in study interest.

Autophagy has been typically associated with resistance to cancer therapy, and autophagy inhibitors have been explored in cancer. Here, the authors investigate autophagy signatures and their association with drug response in cancer, and find that autophagy induction can actually sensitise cancer cells to therapy.

Protein kinase-mediated phosphorylation plays a critical role in many biological processes. Here the authors develop a trans-omics-based algorithm called Central Kinase Inference to integrate quantitative transcriptomic and phosphoproteomic data, finding that PIM1 promotes hepatic conversion by suppressing reprogramming-induced ferroptosis and cell cycle arrest.

Accurate accounting of indirect carbon emissions from electricity is conducive to motivating market entities to proactively and voluntarily reduce emissions, fairly promoting regional emissions reductions, and accelerating the formation of green and low-carbon consumption models. Based on the analysis of the problems faced by China's power carbon emission accounting, this paper considers different transaction types such as market-based electricity consumption, priority power purchase, and power grid agency power purchase, and proposes an indirect carbon emission accounting method for enterprise power sources based on power transaction data. The effectiveness of the proposed model and method is verified through case calculations for high-energy-consuming enterprises. The method proposed in this article can accurately describe the power consumption structure of enterprises and effectively encourage market entities to proactively and voluntarily reduce emissions.

Super-hydrophilic and oleophobic functional materials can prevent pollution or adsorption by repelling oil, and have good circulation. However, traditional strategies for preparing these functional materials either use expensive fabrication machines or contain possibly toxic organic polymers, which may prohibit the practical application. The research of multifunctional ZnO microstructures or nanoarrays thin films with super-hydrophilic, antifouling, and antibacterial properties has not been reported yet. Moreover, the exploration of underwater oleophobic and self-cleaning antifouling properties in ZnO micro/nanostructures is still in its infancy. Here, we prepared ZnO microstructured films on fluorine-doped tin oxide substrates (F-ZMF) for the development of advanced self-cleaning type super-hydrophilic and oleophobic materials. With the increase of the accelerators, the average size of the F-ZMF microstructures decreased. The F-ZMF shows excellent self-cleaning performance and hydrophilic (water contact angle ≤ 10°) and oleophobic characteristics in the underwater antifouling experiment. Under a dark condition, F-ZMF-4 showed good antibacterial effects against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) with inhibition rates of 99.1% and 99.9%, respectively. This study broadens the application scope of ZnO-based material and provides a novel prospect for the development of self-cleaning super-hydrophilic and oleophobic materials.

Cancer cells, especially cancer stem cells (CSCs), share many molecular features with induced pluripotent stem cells (iPSCs) that enable the derivation of induced pluripotent cancer cells by reprogramming malignant cells. Conversely, normal iPSCs can be converted into cancer stem-like cells with the help of tumor microenvironment components and genetic manipulation. These CSC models can be utilized in oncogenic initiation and progression studies, understanding drug resistance, and developing novel therapeutic strategies. This review summarizes the role of pluripotency factors in the stemness, tumorigenicity, and therapeutic resistance of cancer cells. Different methods to obtain iPSC-derived CSC models are described with an emphasis on exposure-based approaches. Culture in cancer cell-conditioned media or cocultures with cancer cells can convert normal iPSCs into cancer stem-like cells, aiding the examination of processes of oncogenesis. We further explored the potential of reprogramming cancer cells into cancer-iPSCs for mechanistic studies and cancer dependencies. The contributions of genetic, epigenetic, and tumor microenvironment factors can be evaluated using these models. Overall, integrating iPSC technology into cancer stem cell research holds significant promise for advancing our knowledge of cancer biology and accelerating the development of innovative and tailored therapeutic interventions.

Glucosamine hydrochloride (GAH) is a natural component of glycoproteins present in almost all human tissues and participates in the construction of human tissues and cell membranes. GAH has a wide range of biological activities, particularly in anti-inflammatory and osteogenic damage repair. At present, little is known about how GAH functions in angiogenesis. To determine the role of GAH on vascular development and impairment repair, we used the inhibitors VRI, DMH1, and dorsomorphin (DM) to construct vascular-impaired models in Tg(kdrl: mCherry) transgenic zebrafish. We then treated with GAH and measured its repair effects on vascular impairment through fluorescence intensity, mRNA, and protein expression levels of vascular-specific markers. Our results indicate that GAH promotes vascular development and repairs impairment by regulating the vascular endothelial growth factor (VEGF) signaling pathway through modulation of bone morphogenetic protein (BMP) signaling. This study provides an experimental basis for the development of GAH as a drug to repair vascular diseases.