Search

Abstract The expression of tsRNA in white adipose tissue (WAT) of VD deficiency male mice with obesity has not been reported. The healthy male C57BL/6J mice aged 4-6 weeks were divided into 4 groups according to the VD3 and fat energy supplement in daily diets. The qPCR verification further demonstrated that tRF5-20-HisGTG-3 were significantly up-regulated and mt-tRF3a-ProTGG was significantly down-regulated not only in HFVDD vs HFVDS, but aslo in HFVDD vs ConVDS. tRF5-22-CysGCA-27 were significantly up-regulated and mt-5'tiRNA-32-SerTGA, mt-5'tiRNA-33-SerTGA and mt-5'tiRNA-33-AlaTGC was significantly down-regulated only in HFVDD vs ConVDS. Enrichment analysis of the qPCR verified DE tsRNAs showed that the 3 up-regulated tsRNAs seemed to be associated with FoxO signaling pathway, GnRH secretion, 2−Oxocarboxylic acid metabolism, Autophagy-animal, Glucagon and insulin signaling pathway, while 4 down-regulated tsRNA seemed to be associated with cell communication, primary metabolic process, metabolic process, response to stimulus, multicellular organismal process, cellular metabolic process, cellular process and biological regulation. The tsRNAs were differentially expressed in VD deficiency with obesity, especially tRF5-20-HisGTG-3, tRF5-22-CysGCA-27, tRF3a-GlyGCC-1, mt-5'tiRNA-33-AlaTGC, mt-5'tiRNA-33-SerTGA, mt-5'tiRNA-32-SerTGA and mt-tRF3a-ProTGG. These tsRNAs seemed to be associated with FoxO signaling pathway, GnRH secretion, 2−oxocarboxylic acid metabolism, autophagy, glucagon and insulin signaling pathway, metabolic process and biological regulation.

Abstract Wide-Field Small Aperture Telescopes (WFSAT) are widely used for surveilling space objects. Due to their wide-field of view (FOV) characteristics, these telescopes can cover a large areas of the sky at once, improving observation efficiency. However, a wide-field optical telescope is highly sensitive to external stray light (such as moonlight and thin clouds), which can significantly reduce the quality of observation data. In severe cases, it can cause the telescope to malfunction and inaccurately position the object. In response to this problem, this paper proposes a model for suppressing stray light in astronomical images based on deep learning: the Pyramid Deformable Large Kernel Attention (PD-LKA) Model. This model expands the receptive field through a pyramid structure, captures multi-scale features, and improves the model’s robustness to various scales of stray light interference. Meanwhile, through the Deformable Large Kernel Attention (D-LKA), the model can more accurately locate and enhance the feature extraction ability in areas affected by stray light interference, thereby better suppressing stray light.Using simulated astronomical image pairs to train the model, the tests achieved a PSNR of up to 32.540 and an SSIM of up to 0.938. Finally, the model is applied to a image sequence with real stray light interference. The restored images undergo astronomical positioning and orbital association processing. The results show that the positioning accuracy of the object is better than 5 arcseconds. This indicates that the model proposed in this paper not only recovers the object and background stars but also effectively preserves their gray values, shapes, and positional information.

Abstract Background Diminished ovarian reserve (DOR) is clinically characterized by a decrease in the number of available ovarian follicles and a decline in the quality of oocytes, accompanied by hormonal changes. Low quality of DOR oocyte leads to impaired embryo development, an increased risk of aneuploid pregnancies and miscarriages. However, the specific pathogenic mechanism remains unclear, posing a significant challenge for assisted reproductive technology. Methods For the first time, our study employed single-cell RNA sequencing to reveal the altered transcriptomic landscape of DOR oocytes at GV stage after ovarian stimulation. Differentially expressed genes analysis (DEGs), functional enrichment analysis, weighted gene co-expression network analysis (WGCNA) and protein-protein interactions network analysis were performed. Results We found 132 up-regulated genes and 466 down-regulated genes in DOR oocytes, with the down-regulated genes primarily enriched in mitochondrial function and translation. Hub genes, identified through integrated analysis of WGCNA and DEGs, were further validated in DOR and control oocytes using RT-qPCR. By utilizing hub genes and employing transcription factor enrichment tools, it had been predicted that pleomorphic adenoma gene 1 (PLAG1) played a crucial role as a transcriptional regulatory factor in DOR oocytes. Additionally, we conformed the PLAG1-IGF2 axis was dysregulated in DOR oocytes. Conclusions Transcriptome analysis revealed that DOR oocytes exhibited mitochondrial dysfunction and translational defects, and the PLAG1-IGF2 axis might be a potential contributor for the low quality of DOR oocytes.

Abstract The ovary is crucial for female reproduction and health, as it generates oocytes and secretes sex hormones. Transplantation of mesenchymal stem cells (MSCs) has been shown to alleviate pathological ovarian aging. However, it is unclear whether MSCs could benefit the naturally aging ovary. In this study, we first examined the dynamics of ovarian reserve of Chinese women during perimenopause. Using a naturally aging cynomolgus monkey (Macaca fascicularis) model, we found that transplanting human embryonic stem cells-derived MSC-like cells, which we called M cells, into the aging ovaries significantly decreased ovarian fibrosis and DNA damage, enhanced secretion of sex hormones and improved fertility. Encouragingly, a healthy baby monkey was born after M-cell transplantation. Moreover, single-cell RNA sequencing analysis and in vitro functional validation suggested that apoptosis, oxidative damage, inflammation, and fibrosis were mitigated in granulosa cells and stromal cells following M-cell transplantation. Altogether, these findings demonstrate the beneficial effects of M-cell transplantation on aging ovaries and expand our understanding of the molecular mechanisms underlying ovarian aging and stem cell-based alleviation of this process.

Abstract The continued increase in demand for food is such that flood-irrigation-based agricultural techniques are not expected to change in the future. Consequently, in cultivated areas dominated by river terraces that experience neotectonic movements, catastrophes caused by earthquakes that trigger material liquefaction may continue to occur. Among such catastrophes, low-angle, ultra-long-distance landslides induced by synergistic effects of tectonic and human activities are events that are not fully understood but can potentially be mitigated. A landslide-mudflow that occurred on December 18, 2023, during an Ms 6.2 earthquake in Jishishan, China, on the tertiary terrace of the Yellow River. We reveal the causal mechanisms by which geomorphology, tectonics, and human activities controlled the landslide-mudflow, and outline a new, potentially widespread, dual liquefaction layer-dominated failure mode for earthquake-induced landslides on river terraces. Our findings serve as a warning that urgent landslide-potential assessments should be conducted across river terrace irrigation areas in tectonically active regions.

Abstract Background Hemsleya Chinensis is a perennial plant in the Cucurbitaceae family containing antibacterial and anti-inflammatory compounds. The lack of genetic transformation systems makes it difficult to verify the functions of genes controlling important traits and conduct molecular breeding in H. chinensis. Results Highly efficient calli were induced on MS medium added 1.5 mg·L− 1 6-benzylaminopurine (6-BA) and 0.02 mg·L− 1 1-naphthylacetic acid (NAA) with high efficiency (> 95%). The frequency of shoot induction was increased to 90% with a plant growth regulator combination of 1.5 mg·L− 1 6-BA and 0.1 mg·L− 1 NAA. Our results also showed that 100% of shoot regeneration was achieved in a shoot regeneration medium. Additionally, more than 92% of kanamycin-resistant plants were confirmed. Furthermore, we achieved 42% genome editing efficiency by applying this transformation method to HcOSC6, a gene that catalyzes the formation of cucurbitadienol. HPLC analysis showed OE-HcOSC6 lines exhibited significantly higher cucurbitadienol levels than the genome-edited lines. Transcriptomic analysis revealed that some downstream genes related to cucurbitadienol biosynthesis, such as HcCYP87D20, HcCYP81Q58, and HcSDR34, were up-regulated in OE lines and down-regulated in mutants. Conclusions Here, we established a process for regeneration, transformation, and genome editing of H. chinensis using stem segments. This provides valuable insight into the underlying molecular mechanisms of medicinal compound production. By combining high-efficiency tissue culture, transformation, and genome editing systems, we provide a powerful platform that supports functional research on molecular mechanisms of secondary metabolism.

Abstract Cyclodehydrogenation is an important ring-formation reaction that can directly produce planar-conjugated carbon-based nanomaterials from nonplanar molecules. However, inherently high C–H bond energy necessitates a high temperature during dehydrogenation, and the ubiquity of C − H bonds in molecules and small differences in their bond energies hinder the selectivity of dehydrogenation. Here, we report a room-temperature cyclodehydrogenation reaction on Au(111) via radical addition of open-shell resonance structures and demonstrate that radical addition significantly decreases cyclodehydrogenation temperature and further improves the chemoselectivity of dehydrogenation. Using scanning tunneling microscopy and non-contact atomic force microscopy, we visualize the cascade reaction process involved in cyclodehydrogenation and determine atomic structures and molecular orbitals of the planar acetylene-linked oxa-nanographene products. The nonplanar intermediates observed during progression annealing, combined with density functional theory calculations, suggest that room-temperature cyclodehydrogenation involves the formation of transient radicals, intramolecular radical addition, and hydrogen elimination; and that the high chemoselectivity of cyclodehydrogenation arises from the reversibility and different thermodynamics of radical addition step.

Abstract Ligand-protected metal nanoclusters provide an ideal platform for investigating photoredox catalysis. The central challenge is balancing their stability and catalytic activity. Here we show a photochemical reduction–oxidation cascade method for synthesizing an Au8Cu6 nanocluster, which features a robust structure and active surface. Photoredox catalytic activity of Au8Cu6 is developed for the functionalization of alkynes under oxidative conditions. Mechanism studies based on the precise structure reveal the catalytic process of the Au8Cu6 nanocluster. Oxidant-dependent selectivity of Au8Cu6 catalysis is developed for chemodivergent synthesis of mono- and di-functionalized products in high efficiency. The results will stimulate more research on metal nanocluster synthesis and catalysis.

Abstract Background MADS-box transcription factors have been shown to be involved in multiple developmental processes, including the regulation of floral organ formation and pollen maturation. However, the role of the MADS-box gene family in floral development of the alpine plant species Coptis teeta Wall, which is widely used in Traditional Chinese Medicine (TCM), is unknown. Results Sixty-six MADS-box genes were identified in the C. teeta genome. These genes were shown to be unevenly distributed throughout the genome of C. teeta. The majority of which (49) were classified as type I MADS-box genes and were further subdivided into four groups (Mα, Mβ, Mγ and Mδ). The remainder were identified as belonging to the type II MADS-box gene category. It was observed that four pairs of segmental and tandem duplication had occurred in the C. teeta MADS-box gene family, and that the ratios of Ka/Ks were less than 1, suggesting that these genes may have experienced purifying selection during evolution. Gene expression profiling analysis revealed that 38 MADS-box genes displayed differential expression patterns between the M and F floral phenotypes. Sixteen of these MADS-box genes were further verified by RT-qPCR. The 3D structure of each subfamily gene was predicted, further indicating that MADS-box genes of the same type possess structural similarities to the known template. Conclusions These data provide new insights into the molecular mechanism of dichogamy and herkogamy formation in C. teeta and establish a solid foundation for future studies of the MADS-box genes family in this medicinal plant species.

Abstract Background Leaves are important sites for photosynthesis and can convert inorganic substances into organic matter. Photosynthetic performance is an important factor affecting crop yield. Leaf colour is closely related to photosynthesis, and leaf colour mutants are considered an ideal material for studying photosynthesis. Results We obtained a yellow-green leaf mutant jym165, using ethyl methane sulfonate (EMS) mutagenesis. Physiological and biochemical analyses indicated that the contents of chlorophyll a, chlorophyll b, carotenoids, and total chlorophyll in the jym165 mutant decreased significantly compared with those in Jiyu47 (JY47). The abnormal chloroplast development of jym165 led to a decrease in net photosynthetic rate and starch content compared with that of JY47. However, quality traits analysis showed that the sum of oil and protein contents in jym165 was higher than that in JY47. In addition, the regional yield (seed spacing: 5 cm) of jym165 increased by 2.42% compared with that of JY47 under high planting density. Comparative transcriptome analysis showed that the yellow-green leaf phenotype was closely related to photosynthesis and starch and sugar metabolism pathways. Genetic analysis suggests that the yellow-green leaf phenotype is controlled by a single recessive nuclear gene. Using Mutmap sequencing, the candidate regions related of leaf colour was narrowed to 3.44 Mb on Chr 10. Conclusions Abnormal chloroplast development in yellow-green mutants leads to a decrease in the photosynthetic pigment content and net photosynthetic rate, which affects the soybean photosynthesis pathway and starch and sugar metabolism pathways. Moreover, it has the potentiality to increase soybean yield under dense planting conditions. This study provides a useful reference for studying the molecular mechanisms underlying photosynthesis in soybean.

Intracellular delivery of biologicals such as peptides, proteins, and nucleic acids presents a great opportunity for innovative therapeutics. However, the endosome entrapment remains a major bottleneck in the intracellular delivery of biomacromolecules, largely limiting their therapeutic potential. Here, we converted a cell-penetrating peptide (CPP), low molecular weight protamine (LMWP), to endosomal escape peptides (EEPs) by masking LMWP with a pH-responsive counter-ionic peptide. The resulting masked CPPs (mLMWP and mLMWP2) effectively promoted the escape of peptide/protein cargoes from endosomes into the cytoplasm. Consequential lysosome repair and lysophagy were initiated upon the endolysosomal leakage. Minimal reactive oxygen species (ROS) elevation or cell death was observed. Based on mLMWP2, we constructed an intracellular protein delivery system containing an antibody as a targeting module, mLMWP2 as an endosomal escape module, and the desired protein cargo. With the HER2-targeting delivery system, we efficiently translocated cyclization recombination enzyme (Cre) and BH3-interacting domain death agonist (BID) into the cytosol of HER2+ cells to exert their biological activity. Thereby, the modular delivery system shows its potential as a promising tool for scientific studies and therapeutic applications.

Abstract Background Chronic osteomyelitis is a highly prevalent and severe orthopaedic complication, representing a critical unresolved issue. The clinical symptoms of osteomyelitis are influenced by various factors, including geography, lifestyle, and pre-existing medical conditions.This study aims to provide theoretical basis for treatment and prevention of osteomyelitis by investigating and analyzing clinical features and pathogen distribution among 282 patients with chronic tibial osteomyelitis in xinjiang. Methods A total of 282 patients with chronic tibial osteomyelitis from January 1, 2012 to January 1, 2022 in the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed. All data were collected from electronic medical record (EMR) system including demographics, etiology, risk factors, osteomyelitis location and clinical classification. Results Farmers, students, unemployed and retirees accounted for a relatively large proportion of the 282 patients. There were 233 males and 49 females with a gender ratio of 4.75:1. The average age was 40.21 ± 15.68 years and was mainly concentrated in 41–50 years, specifically, the mean age of females was slightly older than that of males. Education level was mostly primary and secondary school education, and illiteracy. Risk factors of chronic tibial osteomyelitis included history of smoking and drinking, history of multiple repeated surgeries, and impaired immunity. Frequent clinical symptoms were in the order of pain, local swelling, pus discharge and skin ulceration. Among all inflammatory markers, proportion of positive results were 30.85%, 59.93% and 53.90% for white blood cell (WBC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), respectively. Positive rate of pathogenic microorganism culture was low and the three most common bacteria were Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli). The most frequent site of infection was middle tibia. According to Cierny-Mader osteomyelitis classification, the most common types were type IIIA, IVA and IIA. Conclusion Number of visits due to chronic osteomyelitis increased year by year, with young and middle-aged male farmers and low education level as the main groups. Smoking and drinking were two considerable risk factors that should be attached to a great importance. No significant increase was found in inflammatory markers and lower positive rate of pathogenic microorganism culture was observed. Multi-drug resistant bacteria were common and S. aureus remained the most frequent pathogen. Elevated ESR had certain diagnostic value for osteomyelitis. Type III and type IV osteomyelitis accounted for a large proportion which posed great challenges for clinical diagnosis and treatment.

Abstract The NOD2 signaling pathway, which plays an important role in the mechanisms of inflammatory bowel disease (IBD) development, has been closely associated with ubiquitination. It was revealed in this study that NOD2 receptor activation could obviously affect the expression of 19 ubiquitination-related genes, with N4BP3 being the most prominently expressed and upregulated. In addition, N4BP3 knockdown was found to reduce the mRNA levels of MDP-induced inflammatory factors, while N4BP3 overexpression elevated their mRNA levels as well as the levels of phospho-ERK1/2, phospho-JNK, phospho-P38 and phospho-NF-κB P65 proteins. Immunoprecipitation tests showed that N4BP3 could pull down RIPK2 and promote its K63-linked ubiquitination. In human tissue specimen assays and mouse experiments, we found that the expression of N4BP3 was significantly elevated in Crohn’s disease (CD) patients and IBD mice, and N4BP3 knockdown reduced the dextran sulfate sodium-induced pathological score and the expression of inflammatory factors in the mouse colon tissue. In conclusion, N4BP3 is able to interact with RIPK2 and promote its K63-linked ubiquitination, to further promote the NOD2-MAPK/NF-κB pathway, thereby increasing promoting the release of inflammation factors and the degree of IBD inflammation.

Abstract Background The aim was to assess the knowledge, attitudes, and practices (KAPs) of endoscopy among gastroenterologists in the diagnosis and management of IBD in China. Methods A multicenter cross-sectional KAP study was performed. The questionnaire was developed and improved using feedback and opinions from a team of experienced IBD specialist professors and then distributed and collected online. In addition, eight fellow gastroenterologists participated in an IBD endoscopy training program were asked to review endoscopic images, and the consistency of the endoscopic scores before and after training was calculated. Results A total of 193 participants from 12 provincial-level administrative regions encompassing both the Northern and Southern parts of China completed the study questionnaire. The median age of the participants was 40 (36, 45) years, with the majority being female (70.5%). The median professional experience as gastroenterologists was 11 (7, 17) years, while the median experience as endoscopists was 8 (3, 15) years. The median knowledge score was 8 out of 10 points for single-choice questions; however, most gastroenterologists believed that some concepts in these endoscopic indices were vague, including those regarding deep ulcerations, ulcerated surfaces, affected surfaces and narrowing in open-answer questions. The UCEIS and SES-CD were considered most consistent with clinical activity score in the evaluation of UC and CD, respectively. IBD subspecialists and gastroenterologists who had previously received IBD endoscopy screening training were more likely to use endoscopic indices (p

Abstract Purpose To compare clinical outcomes of transjugular intrahepatic portosystemic shunt (TIPS) created with the single covered-uncovered stent (Viatorr TIPS Endoprosthesis) versus covered stent (Fluency) versus a combination of covered and uncovered stent. Materials and methods From May 2016 and July 2019, a total of 180 liver cirrhosis patients with recurrent variceal bleeding underwent TIPS creation with single covered-uncovered stent (n = 63) or covered stent (n = 41) or a covered and uncovered stent combination (n = 76). Shunt dysfunction, rebleeding, overt hepatic encephalopathy and mortality was estimated using the Kaplan–Meier method and compared with the log-rank test. Results The difference of baseline characteristics among these three groups were not significant. The included patients had a median age of 51 years (IQR 43–61), and 101 (56.1%) were men. The 1-year and 2-year shunt dysfunction rates were 1.6% and 3.2% in the single covered-uncovered stent group, 7.3% and 7.3% in the covered stent group and 5.3% and 6.6% in the combination group, respectively. There was no significant difference among groups [Hazard Ratio (HR) (95%CI): 1 vs 2.29 (0.38 − 13.72) vs 2.10 (0.41 − 10.83); P = 0.913]. No significant differences in the incidence of all-cause rebleeding were observed between the groups at 1 year (Viatorr vs Fluency vs combination: 11.1% vs 17.1% vs 10.5%) as well as 2 years (15.9% vs 17.1% vs 11.8%), with the HR (95%CI) being 1 vs 1.27 (0.5—3.21) vs 0.74 (0.30–1.82); P = 0.475). The 1-year and 2-year incidence of overt hepatic encephalopathy were 30.2% and 30.2% in the single covered-uncovered stent group, 22.0% and 22.0% in the covered stent group and 25.0% and 25.0% in the combination group, respectively. However, there was no significant difference among these three groups (P = 0.402). In addition, there was no significant difference in the 1-year and 2-year mortality (6.3% and 7.9% vs. 4.9% and 9.8% vs. 6.6% and 9.2%, P = 0.606). Conclusion No significant difference was observed among different stent groups. Fluency covered stent and the generic bare stent/Fluency covered stent was not an unreasonable alternative to the Viatorr stent for TIPS creation.

The effect of the void shape on cut blasting is investigated by establishing a damage analysis model for a void using an improved calculation formula for stress on the wall of the void. Additionally, an optimization scheme is provided for the “square void cutting theoretical model.” The vibration effect of the rock mass outside the excavation area is simultaneously monitored, and its validity is substantiated through experimental and simulation-based verification. The findings indicate that the variation of q2sinθ over time aligns with the dynamic loading process of wall stress in holes. Under the influence of longitudinal waves, thin-walled circular damage occurs, and tensile effects from reflected waves are influenced by impedance. In a square void cutting model, two-stage stress waves cause tensile shear damage and inward collapse in the rock mass along hole walls. The explosive energy generated by square holes significantly contributes to fragmentation of rock masses. The circular empty-hole cutting model generates significant vibrations in central areas due to resistance. Vibration velocity in 45° direction for circular holes is lower than that for square voids outside cuts while vibration velocity remains equivalent between circular and square holes at 90° direction.

Abstract Helicobacter pylori (H. pylori) is one of the most common bacterial infections in the world, and its key virulence component CagA is the leading cause of gastric cancer. Mitophagy is a form of selective autophagy that eliminates damaged mitochondria and is essential for some viruses and bacteria to evade the immune system. However, the mechanisms by which CagA mediates H. pylori-induced mitophagy and NLRP3 inflammasome activation remain elusive. In this study, we reported that H. pylori primarily uses its CagA to induce mitochondrial oxidative damage, mitochondrial dysfunction, dynamic imbalance, and to block autophagic flux. Inhibition of mitophagy led to an increase in NLRP3 inflammasome activation and apoptosis and a decrease in the viability of H. pylori-infected cells. Our findings suggested that H. pylori induces mitochondrial dysfunction and mitophagy primarily via CagA. It reduces NLRP3 inflammasome activation to evade host immune surveillance and increases the survival and viability of infected cells, potentially leading to gastric cancer initiation and development. Our findings provide new insights into the pathogenesis of H. pylori-induced gastric cancer, and inhibition of mitophagy may be one of the novel techniques for the prevention and treatment of this disease.

Abstract Hypopharyngeal carcinoma is one of the malignant tumors of the head and neck with a particularly poor prognosis. Recurrence and metastasis are important reasons for poor prognosis of hypopharyngeal cancer patients, and malignant proliferation, migration, and invasion of tumor cells are important factors for recurrence and metastasis of hypopharyngeal cancer. Therefore, elucidating hypopharyngeal cancer cells’ proliferation, migration, and invasion mechanism is essential for improving diagnosis, treatment, and prognosis. Plasmacytoma Variant Translocation 1 (PVT1) is considered a potential diagnostic marker and therapeutic target for tumors. However, it remains unclear whether PVT1 is related to the occurrence and development of hypopharyngeal cancer and its specific mechanism. In this study, the promoting effect of PVT1 on the proliferation, migration, and invasion of hypopharyngeal carcinoma FaDu cells was verified by cell biology experiments and animal studies, and it was found that PVT1 inhibited the expression of TGF-β, suggesting that PVT1 may regulate the occurrence and development of hypopharyngeal carcinoma FaDu cells through TGF-β.

Abstract Background The risk of cervical cancer progression in high-risk human papillomavirus (HR-HPV)-positive women is associated with cervical lesion severity and molecular heterogeneity. Classification systems based on p16 and Ki67 expression cumulative scores (0–3 each)—p16/Ki67 collectively known as an immunoscore [IS]—are an accurate and reproducible method for grading cervical intraepithelial neoplasia (CIN) lesions. Meanwhile, DNA methylation is an early event in the development of cervical cancer. Hence, this study evaluated the relationship among CIN, p16/Ki-67 IS, and PAX1/ZNF582 methylation. Methods In this study, 414 HPV-positive paraffin-embedded specimens were collected, and PAX1/ZNF582 methylation and the p16/ki67 IS were determined. A total of 43 invalid samples were excluded and 371 were included in the statistical analyses. There were 103 cervicitis, 95 CIN1, 71 CIN2, 89 CIN3, and 13 squamous cell carcinoma (SCC) cases. The association between PAX1/ZNF582 methylation and p16/Ki6 immunohistochemical staining scores was analyzed. Results The ΔCp of PAX1 m (PAX1 methylation) and ZNF582 m (ZNF582 methylation) decreased with cervical lesion severity (Cuzick trend test, all P

Abstract The halo-shape technique (HST) is an emerging approach for implanting a leadless pacemaker in scoliosis patients in recent years. Severe scoliosis and humpback made it challenging to push the tip of the delivery catheter towards the ventricular septum using the conventional gooseneck-shape technique. The feasibility and safety of the use of HST in an octogenarian with severe dextroscoliosis and humpback have not been well-assessed. Here, we report a case of high-degree atrioventricular block octogenarian with severe dextroscoliosis and humpback who successfully received a leadless pacemaker implantation using HST. Procedure-related complications were not observed, and the electrical parameters were stable at 6-month follow-up.

Highlights “Zero-strain” NiNb2O6 fibers with nanosized primary particles are explored as an all-climate anode material with comprehensively good Li+-storage properties. The almost completely opposite volume changes of electrochemical inactive NiO6 octahedra and active NbO6 octahedra are achieved through reversible O movement, leading to the “zero-strain” behavior of NiNb2O6 with minor unit-cell-volume change and excellent cyclability in a broad temperature range. The gained insight can provide guide for the exploration of high-performance energy-storage materials working at harsh temperatures.

Abstract Background In this study, we explored the impact of hypothyroidism and thyroid hormone replacement therapy on the risk of developing cardiovascular diseases, including myocardial infarction, heart failure, and cardiac death, via Mendelian randomization analysis. Methods Genetic instrumental variables related to hypothyroidism, levothyroxine treatment (refer to Participants were taking the medication levothyroxine sodium) and adverse cardiovascular events were obtained from a large publicly available genome-wide association study. Two-sample Mendelian randomization analysis was performed via inverse-variance weighting as the primary method. To ensure the reliability of our findings, we performed MR‒Egger regression, Cochran’s Q statistic, and leave-one-out analysis. Additionally, multivariable Mendelian randomization was employed to regulate confounding factors, including systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), diabetes, cholesterol, low-density lipoprotein (LDL), triglycerides and metformin. A mediation analysis was conducted to assess the mediating effects on the association between exposure and outcome by treating atrial fibrillation and stroke as mediator variables of levothyroxine treatment and bradycardia as mediator variables of hypothyroidism. Results Genetically predicted hypothyroidism and levothyroxine treatment were significantly associated with the risk of experiencing myocardial infarction [levothyroxine: odds ratio (OR) 3.75, 95% confidence interval (CI): 1.80–7.80; hypothyroidism: OR: 15.11, 95% CI: 2.93–77.88]. Levothyroxine treatment was also significantly related to the risk of experiencing heart failure (OR: 2.16, 95% CI: 1.21–3.88). However, no associations were detected between hypothyroidism and the risk of experiencing heart failure or between hypothyroidism or levothyroxine treatment and the risk of experiencing cardiac death. After adjusting for confounding factors, the results remained stable. Additionally, mediation analysis indicated that atrial fibrillation and stroke may serve as potential mediators in the relationships between levothyroxine treatment and the risk of experiencing heart failure or myocardial infarction. Conclusion The results of our study suggest a positive association between hypothyroidism and myocardial infarction and highlight the potential effects of levothyroxine treatment, the main thyroid hormone replacement therapy approach, on increasing the risk of experiencing myocardial infarction and heart failure.

Abstract The aim of this study was to investigate the effect of zoledronic acid (ZA) on postoperative healing and functional rehabilitation in osteoporotic patients with rotator cuff (RC) injury. 96 Patients were divided into three groups according to bone mineral density and ZA use (Group A: normal BMD; Group B: osteoporosis and intravenous ZA use; Group C: osteoporosis, without ZA use). Radiologic, functional and Serological outcomes were evaluated 6 months after surgery. The functional scores in all groups exhibited significant improvement 6 months after surgery. Inter-group comparison showed that Constant Shoulder joint function Score (CSS) of group A not significantly differing from that of group B, the other indicators were significantly better than those of group B and C. There were no significant differences in shoulder forward flexion, abductive Range of Motion between group B and C. Other indicators of group B were significantly improved compared to group C. The retear rate in group C (30.3%, 10/33) was higher than group A (6.1%, 2/33) and group B (13.3%, 4/30). In conclusion, the application of ZA can significantly reduce the rate of RC retear in elderly patients with osteoporosis after surgery, which is significant for postoperative shoulder joint functional rehabilitation.

AbstractAs a processed product of traditional Chinese medicine Curcumae Radix, Curcumae Radix Carbonisata (CRC) has been widely used in the treatment of liver diseases in ancient medical books. In this study, novel carbon dots (CDs) extending from 1.0 to 4.5 nm were separated from fluid extricates of CRC. Meanwhile, a liver fibrosis model induced by carbon tetrachloride (CCl4) was utilized to determine the inhibitory effects of CRC-CDs against liver fibrosis. The results exhibited the CRC-CDs with a quantum yield of 1.34% have a significant inhibitory effect on CCl4-induced liver fibrosis, as demonstrated by improving hepatocyte degeneration and necrosis, inflammatory cell infiltration and fibrotic tissue hyperplasia, downregulating the levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA), triglyceride (TG), tumour necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β in the serum, upregulating the contents of superoxide dismutase (SOD), reduced glutathione (GSH), and downregulating the concentration of malondialdehyde (MDA), which lays an important foundation for the development of CRC-CDs as a novel drug for the treatment of liver fibrosis, and provide a certain experimental basis for the clinical application of CRC-CDs in the future.

AbstractChinese herbs contain substances that regulate female hormones. Our study confirmed that Zingiberis rhizoma carbonisata contains Zingiberis rhizoma-based carbon dots (ZR-CDs), which exert regulatory effects on serum oestradiol and FSH in mice and show impacts on endometrial growth and follicular development that potentially affect the ability of female fertility. ZR-CDs were characterized to clarify the microstructure, optical features, and functional group characteristics. It shows that ZR-CDs are spherical carbon nanostructures ranging from 0.97 to 2.3 nm in diameter, with fluorescent properties and a surface rich in functional groups. We further investigated the impact of ZR-CDs on oestradiol and FSH in serum, growth, and the development of ovarian and uterine using normal female mice and exogenous oestradiol intervention model. It was observed that ZR-CDs accelerated oestrogen metabolism and attenuated oestradiol-induced endometrial hyperplasia. Simultaneously, ZR-CDs triggered an increase in FSH, even in the presence of high-serum oestradiol that inhibits FSH secretion. Our findings suggest that ZR-CDs could be a potential therapeutic treatment for anovulatory menstruation.

Abstract Background The aim of this research is to prospectively investigate the diagnostic performance of intravoxel incoherent motion (IVIM) using the integrated slice-specific dynamic shimming (iShim) technique in staging primary esophageal squamous cell carcinoma (ESCC) and predicting presence of lymph node metastases from ESCC. Methods Sixty-three patients with ESCC were prospectively enrolled from April 2016 to April 2019. MR and IVIM using iShim technique (b = 0, 25, 50, 75, 100, 200, 400, 600, 800 s/mm2) were performed on 3.0T MRI system before operation. Primary tumour apparent diffusion coefficient (ADC) and IVIM parameters, including true diffusion coefficient (D), pseudodiffusion coefficient (D*), pseudodiffusion fraction (f) were measured by two independent radiologists. The differences in D, D*, f and ADC values of different T and N stages were assessed. Intraclass correlation coefficients (ICCs) were calculated to evaluate the interobserver agreement between two readers. The diagnostic performances of D, D*, f and ADC values in primary tumour staging and prediction of lymph node metastasis of ESCC were determined using receiver operating characteristic (ROC) curve analysis. Results The inter-observer consensus was excellent for IVIM parameters and ADC (D: ICC = 0.922; D*: ICC = 0.892; f: ICC = 0.948; ADC: ICC = 0.958). The ADC, D, D* and f values of group T1 + T2 were significantly higher than those of group T3 + T4a [ADC: (2.55 ± 0.43) ×10− 3 mm2/s vs. (2.27 ± 0.40) ×10− 3 mm2/s, t = 2.670, P = 0.010; D: (1.82 ± 0.39) ×10− 3 mm2/s vs. (1.53 ± 0.33) ×10− 3 mm2/s, t = 3.189, P = 0.002; D*: 46.45 (30.30,55.53) ×10− 3 mm2/s vs. 32.30 (18.60,40.95) ×10− 3 mm2/s, z=-2.408, P = 0.016; f: 0.45 ± 0.12 vs. 0.37 ± 0.12, t = 2.538, P = 0.014]. The ADC, D and f values of the lymph nodes-positive (N+) group were significantly lower than those of lymph nodes-negative (N0) group [ADC: (2.10 ± 0.33) ×10− 3 mm2/s vs. (2.55 ± 0.40) ×10− 3 mm2/s, t=-4.564, P

Abstract Background Ulcerative colitis (UC) is a chronic intestinal inflammation, resulting in a global healthcare challenge with no real specific medicine. Natural medicines are recognized as a potential clinical alternative therapy, but their applications are limited by poor solubility and low bioavailability. Results In this work, inspired by the natural medicines of ancient China, novel functional carbon dots derived from Magnetite and Medicated Leaven (MML-CDs) were synthesized by hydrothermal method, and confirmed their ultrasmall nano-size (3.2 ± 0.6 nm) and Fe doped surface structure, thereby with excellent gastrointestinal stability, remarkable capabilities in eliminating ROS, and highly biocompatibility. With no external stimuli, the oral administration of MML-CDs demonstrated obvious alleviation to UC. Further experiments pointed that MML-CDs could improve hemostasis capability, suppress inflammation reactions and oxidative stress, and up-regulate the expression of tight junction proteins. Furthermore, MML-CDs also showed well regulation in the dysbiosis of intestinal flora. Conclusion Overall, above evidence reveals that green-synthesized MML-CDs can significantly alleviate intestinal bleeding, inhibit colon inflammation, and repair colonic barrier damage, further regulating intestinal flora and intestinal inflammation microenvironment. Our findings provide an efficient oral administration of MML-CDs as a novel therapy strategy for ulcerative colitis. Graphical Abstract

Abstract Background Melanoma is a highly aggressive form of skin cancer. The existence of cancer stem cells (CSCs) and tumor immune evasion are two major causes of melanoma progression, but no effective treatment has been found at present. Astragalus polysaccharide (APS) is a principal active component derived from Astragalus membranaceus, showing anti-tumor effects in various tumors including melanoma. However, the underlying mechanism is still unclear. Methods The regulation of APS on self-renewal ability and CSC markers expression in melanoma stem cells (MSCs) was measured by tumor sphere formation and tumorigenicity assays, RT-qPCR, and western blot. Flow cytometry was conducted to evaluate the activation of immune system by APS in melanoma mice. Further, the mechanism was explored based on PD-L1 overexpression and knock-down B16 cells. Results APS attenuated the tumor sphere formation of MSCs in vitro as well as the tumorigenicity in vivo. It also decreased the expression of CD133, BMI1 and CD47. Based on the PD-L1 overexpression and knock-down B16 cells, it was confirmed that APS inhibited the induction of MSCs by down-regulating PD-L1 expression. Meanwhile, APS increased the infiltration of CD4+ and CD8+T cells in tumor tissues because of its inhibitory effect on PD-L1. Conclusions APS inhibited MSC induction and overcame tumor immune evasion through reducing PD-L1 expression. This study provided compelling evidence that APS could be a prospective therapeutic agent for treating melanoma.

Abstract Background Accumulating evidence suggests that cardiovascular diseases and breast cancer share a number of common risk factors, however, evidence on the association between cardiovascular health (CVH) and breast cancer is limited. The present study aimed to assess the association of CVH, defined by Life’s Essential 8 (LE8) and genetic risk with breast cancer incidence and mortality among premenopausal and postmenopausal women. Methods We used data from the UK Biobank and conducted the multivariate Cox proportional-hazards models to examine associations of LE8 score and genetic risk with breast cancer incidence and mortality. Date on LE8 score was collected between 2006 and 2010 and composed of eight components, including behavioral metrics (diet, tobacco or nicotine exposure, physical activity, and sleep health), and biological metrics (body mass index, blood lipids, blood glucose, and blood pressure). The polygenic risk score (PRS) was calculated as the sum of effect sizes of individual genetic variants multiplied by the allele dosage. Results A total of 150,566 premenopausal and postmenopausal women were included. Compared to postmenopausal women with low LE8 score, those with high LE8 score were associated with 22% lower risk of breast cancer incidence (HR: 0.78, 95% CI: 0.70–0.87) and 43% lower risk of breast cancer mortality (HR: 0.57, 95% CI: 0.36–0.90). By contrast, we did not observe the significant association among premenopausal women. Further analyses stratified by PRS categories showed that high LE8 score was associated with 28% and 71% decreased risk of breast cancer incidence (HR: 0.72, 95% CI: 0.60–0.87) and mortality (HR: 0.29, 95% CI: 0.10–0.83) compared to low LE8 score among high genetic risk groups, but no significant associations were found among low genetic risk groups. Furthermore, compared with postmenopausal women with high LE8 score and low genetic risk, those with low LE8 score and high genetic risk were associated with increased risk of breast cancer incidence (HR: 6.26, 95% CI: 4.43–8.84). Conclusions The present study suggests that better CVH is a protective factor for both breast cancer incidence and mortality among postmenopausal women. Moreover, the risk of developing breast cancer caused by high genetic susceptibility could be largely offset by better CVH.

Water is the important medium of the tea infusions, which plays a crucial role in the development of tea quality. Tooma sinensis (TS) fermented tea was brewed with tap water, mineral water and purified water. The physicochemical indexes, biochemical components, antioxidant activity and flavor compounds of three types tea infusions were analyzed using ultraviolet spectrophotometer, electronic tongue and gas chromatography-mass spectrometry (GC-MS) to elucidate the influence of different brewing water on the quality of TS fermented tea infusions. The results demonstrated that the quality and antioxidant activity of TS fermented tea infusions were significant influenced by different brewing water (P

Abstract Peripheral arterial diseases (PAD) have been reported to be the leading cause for limb amputations, and the current therapeutic strategies including antiplatelet medication or intervene surgery are reported to not clinically benefit the patients with high-grade PAD. To this respect, revascularization based on angiogenetic vascular endothelial growth factor (VEGF) gene therapy was attempted for the potential treatment of critical PAD. Aiming for transcellular delivery of VEGF-encoding plasmid DNA (pDNA), we proposed to elaborate intriguing virus-like DNA condensates, wherein the supercoiled rigid micrometer-scaled plasmid DNA (pDNA) could be regulated in an orderly fashion into well-defined nano-toroids by following a self-spooling process with the aid of cationic block copolymer poly(ethylene glycol)-polylysine at an extraordinary ionic strength (NaCl: 600 mM). Moreover, reversible disulfide crosslinking was proposed between the polylysine segments with the aim of stabilizing these intriguing toroidal condensates. Pertaining to the critical hindlimb ischemia, our proposed toroidal VEGF-encoding pDNA condensates demonstrated high levels of VEGF expression at the dosage sites, which consequently contributed to the neo-vasculature (the particularly abundant formation of micro-vessels in the injected hindlimb), preventing the hindlimb ischemia from causing necrosis at the extremities. Moreover, excellent safety profiles have been demonstrated by our proposed toroidal condensates, as opposed to the apparent immunogenicity of the naked pDNA. Hence, our proposed virus-like DNA condensates herald potentials as gene therapy platform in persistent expressions of the therapeutic proteins, and might consequently be highlighted in the management of a variety of intractable diseases.

Abstract Triple negative breast cancer (TNBC) has the characteristics of low immune cell infiltration, high expression of tumor programmed death ligand 1 (PD-L1), and abundant cancer stem cells. Systemic toxicity of traditional chemotherapy drugs due to poor drug selectivity, and chemotherapy failure due to tumor drug resistance and other problems, so it is particularly important to find new cancer treatment strategies for TNBC with limited treatment options. Both the anti-tumor natural drugs curcumin and ginsenoside Rg3 can exert anti-tumor effects by inducing immunogenic cell death (ICD) of tumor cells, reducing PD-L1 expression, and reducing cancer stem cells. However, they have the disadvantages of poor water solubility, low bioavailability, and weak anti-tumor effect of single agents. We used vinyl ether bonds to link curcumin (Cur) with N-O type zwitterionic polymers and at the same time encapsulated ginsenoside Rg3 to obtain hyperbranched zwitterionic drug-loaded micelles OPDEA-PGED-5HA@Cur@Rg3 (PPH@CR) with pH response. In vitro cell experiments and in vivo animal experiments have proved that PPH@CR could not only promote the maturation of dendritic cells (DCs) and increase the CD4+ T cells and CD8+ T cells by inducing ICD in tumor cells but also reduce the expression of PD-L1 in tumor tissues, and reduce cancer stem cells and showed better anti-tumor effects and good biological safety compared with free double drugs, which is a promising cancer treatment strategy.

Abstract Background To evaluate a novel intraoperative localization technique utilizing temporary pulmonary arteriovenous occlusion for enhancing the precision of sublobar resections in early‐stage NSCLC. Methods Conducted from January to November 2023, this study involved 140 patients. During the surgery, key pulmonary vessels were identified using preoperative three‐dimensional (3D) imaging and temporarily occluded with noninvasive clamps to isolate the target lung segment. Following vascular occlusion, indocyanine green (ICG) was administered intravenously to precisely delineate the resection margins. After visually confirming the marked areas, the clamps were released, and a targeted partial resection was performed on the delineated segment. Surgical data, including operation times, surgical margins, and hospitalization costs, were collected and compared with those from a historical control group of 110 patients who underwent traditional pulmonary wedge resections. Results In the study group, the median surgical margin achieved was 16 mm, which was statistically significant compared to 15 mm in the control group (p

Abstract Background Multidrug-resistant organisms (MDRO) pose a significant threat to public health. Intensive Care Units (ICU), characterized by the extensive use of antimicrobial agents and a high prevalence of bacterial resistance, are hotspots for MDRO proliferation. Timely identification of patients at high risk for MDRO can aid in curbing transmission, enhancing patient outcomes, and maintaining the cleanliness of the ICU environment. This study focused on developing a machine learning (ML) model to identify patients at risk of MDRO during the initial phase of their ICU stay. Methods Utilizing patient data from the First Medical Center of the People’s Liberation Army General Hospital (PLAGH-ICU) and the Medical Information Mart for Intensive Care (MIMIC-IV), the study analyzed variables within 24 h of ICU admission. Machine learning algorithms were applied to these datasets, emphasizing the early detection of MDRO colonization or infection. Model efficacy was evaluated by the area under the receiver operating characteristics curve (AUROC), alongside internal and external validation sets. Results The study evaluated 3,536 patients in PLAGH-ICU and 34,923 in MIMIC-IV, revealing MDRO prevalence of 11.96% and 8.81%, respectively. Significant differences in ICU and hospital stays, along with mortality rates, were observed between MDRO positive and negative patients. In the temporal validation, the PLAGH-ICU model achieved an AUROC of 0.786 [0.748, 0.825], while the MIMIC-IV model reached 0.744 [0.723, 0.766]. External validation demonstrated reduced model performance across different datasets. Key predictors included biochemical markers and the duration of pre-ICU hospital stay. Conclusions The ML models developed in this study demonstrated their capability in early identification of MDRO risks in ICU patients. Continuous refinement and validation in varied clinical contexts remain essential for future applications.

The cuticular wax, acting as the ultimate defense barrier, is essential for the normal morphogenesis of plant organs. Despite this importance, the connection between wax composition and leaf development has not been thoroughly explored. In this study, we characterized a new maize mutant, ragged leaf4 (rgd4), which exhibits crinkled and ragged leaves starting from the sixth leaf stage. The phenotype of rgd4 is conferred by ZmCER1, which encoding an aldehyde decarbonylase involved in wax biosynthesis. ZmCER1 function deficient mutant displayed reduced cuticular wax density and disordered bulliform cells (BCs), while ZmCER1 overexpressing plants exhibited the opposite effects, indicating that ZmCER1 regulates cuticular wax biosynthesis and BCs development. Additionally, as the density of cuticular wax increased, the water loss rate of detached leaf decreases, suggesting that ZmCER1 is positively correlated with plant drought tolerance.

Abstract Helicobacter pylori (H. pylori), together with its CagA, has been implicated in causing DNA damage, cell cycle arrest, apoptosis, and the development of gastric cancer. Although lncRNA H19 is abundantly expressed in gastric cancer and functions as a pro-oncogene, it remains unclear whether lncRNA H19 contributes to the oncogenic process of H. pylori CagA. This study investigates the role of H19 in the DNA damage response and malignancy induced by H. pylori. It was observed that cells infected with CagA+ H. pylori strain (GZ7/cagA) showed significantly higher H19 expression, resulting in increased γH2A.X and p-ATM expression and decreased p53 and Rad51 expression. Faster cell migration and invasion was also observed, which was reversed by H19 knockdown in H. pylori. YWHAZ was identified as an H19 target protein, and its expression was increased in H19 knockdown cells. GZ7/cagA infection responded to the increased YWHAZ expression induced by H19 knockdown. In addition, H19 knockdown stimulated cells to enter the G2-phase and attenuated the effect of GZ7/cagA infection on the cellular S-phase barrier. The results suggest that H. pylori CagA can upregulate H19 expression, participate in the DNA damage response and promote cell migration and invasion, and possibly affect cell cycle arrest via regulation of YWHAZ.

Abstract Sysmex DI-60 enumerates and classifies leukocytes. Limited research has evaluated the performance of Sysmex DI-60 in abnormal samples, and most focused on leukopenic samples. We evaluate the efficacy of DI-60 in determining white blood cell (WBC) differentials in normal and abnormal samples in different WBC count. Peripheral blood smears (n = 166) were categorised into normal control and disease groups, and further divided into moderate and severe leucocytosis, mild leucocytosis, normal, mild leukopenia, and moderate and severe leukopenia groups based on WBC count. DI-60 preclassification and verification and manual counting results were assessed using Bland–Altman and Passing–Bablok regression analyses. The Kappa test compared the concordance in the abnormal cell detection between DI-60 and manual counting. DI-60 exhibited notable overall sensitivity and specificity for all cells, except basophils. The correlation between the DI-60 preclassification and manual counting was high for segmented neutrophils, band neutrophils, lymphocytes, and blasts, and improved for all cell classes after verification. The mean difference between DI-60 and manual counting for all cell classes was significantly high in moderate and severe leucocytosis (WBC > 30.0 × 109/L) and moderate and severe leukopenia (WBC

Abstract The mid-Piacenzian warm period (MPWP, ~3.264–3.025 Ma) has gained widespread interest due to its partial analogy with future climate. However, quantitative data–model comparison of East Asian Summer Monsoon (EASM) precipitation during the MPWP is relatively rare, especially due to problems in decoding the imprint of physical processes to climate signals in the records. In this study, pollen-based precipitation records are reconstructed and compared to the multi-model ensemble mean of the Pliocene Model Intercomparison Project Phase 2 (PlioMIP2). We find spatially consistent precipitation increase in most simulations but a spatially divergent change in MPWP records. We reconcile proxy data and simulation by decomposing physical processes that control precipitation. Our results 1) reveal thermodynamic control of an overall enhancement of EASM precipitation and 2) highlight a distinct control of thermodynamic and dynamical processes on increases of tropical and subtropical EASM precipitation, reflecting the two pathways of water vapor supply that enhance EASM precipitation, respectively.

Abstract Background Clear cell renal cell carcinoma (ccRCC) is a common disease in the urinary system, with a high incidence and poor prognosis in advanced stages. Although γ-interferon-inducible protein 16 (IFI16) has been reported to play a role in various tumors, its involvement in ccRCC remains poorly documented, and the molecular mechanisms are not yet clear. Methods We conducted bioinformatics analysis to study the expression of IFI16 in ccRCC using public databases. Additionally, we analyzed and validated clinical specimens that we collected. Subsequently, we explored the impact of IFI16 on ccRCC cell proliferation, migration, and invasion through in vitro and in vivo experiments. Furthermore, we predicted downstream molecules and pathways using transcriptome analysis and confirmed them through follow-up experimental validation. Results IFI16 was significantly upregulated in ccRCC tissue and correlated with poor patient prognosis. In vitro, IFI16 promoted ccRCC cell proliferation, migration, and invasion, while in vivo, it facilitated subcutaneous tumor growth and the formation of lung metastatic foci. Knocking down IFI16 suppressed its oncogenic function. At the molecular level, IFI16 promoted the transcription and translation of IL6, subsequently activating the PI3K/AKT signaling pathway and inducing epithelial-mesenchymal transition (EMT). Conclusion IFI16 induced EMT through the IL6/PI3K/AKT axis, promoting the progression of ccRCC.

Abstract Background The cumulative live birth rate (CLBR) has been regarded as a key measure of in vitro fertilization (IVF) success after a complete treatment cycle. Women undergoing IVF face great psychological pressure and financial burden. A predictive model to estimate CLBR is needed in clinical practice for patient counselling and shaping expectations. Methods This retrospective study included 32,306 complete cycles derived from 29,023 couples undergoing IVF treatment from 2014 to 2020 at a university-affiliated fertility center in China. Three predictive models of CLBR were developed based on three phases of a complete cycle: pre-treatment, post-stimulation, and post-treatment. The non-linear relationship was treated with restricted cubic splines. Subjects from 2014 to 2018 were randomly divided into a training set and a test set at a ratio of 7:3 for model derivation and internal validation, while subjects from 2019 to 2020 were used for temporal validation. Results Predictors of pre-treatment model included female age (non-linear relationship), antral follicle count (non-linear relationship), body mass index, number of previous IVF attempts, number of previous embryo transfer failure, type of infertility, tubal factor, male factor, and scarred uterus. Predictors of post-stimulation model included female age (non-linear relationship), number of oocytes retrieved (non-linear relationship), number of previous IVF attempts, number of previous embryo transfer failure, type of infertility, scarred uterus, stimulation protocol, as well as endometrial thickness, progesterone and luteinizing hormone on trigger day. Predictors of post-treatment model included female age (non-linear relationship), number of oocytes retrieved (non-linear relationship), cumulative Day-3 embryos live-birth capacity (non-linear relationship), number of previous IVF attempts, scarred uterus, stimulation protocol, as well as endometrial thickness, progesterone and luteinizing hormone on trigger day. The C index of the three models were 0.7559, 0.7744, and 0.8270, respectively. All models were well calibrated (p = 0.687, p = 0.468, p = 0.549). In internal validation, the C index of the three models were 0.7422, 0.7722, 0.8234, respectively; and the calibration P values were all greater than 0.05. In temporal validation, the C index were 0.7430, 0.7722, 0.8234 respectively; however, the calibration P values were less than 0.05. Conclusions This study provides three IVF models to predict CLBR according to information from different treatment stage, and these models have been converted into an online calculator ( https://h5.eheren.com/hcyc/pc/index.html#/home ). Internal validation and temporal validation verified the good discrimination of the predictive models. However, temporal validation suggested low accuracy of the predictive models, which might be attributed to time-associated amelioration of IVF practice.

Beef is rich in nutrients and is one of the favored meats among consumers. Market price, consumer willingness to buy and satisfaction are affected by the quality of beef, so it is important to test the quality of beef. At present, traditional beef quality testing methods have the problems of time-consuming, sample damage and complex operation. Recently, non-destructive testing technology has been widely used in beef quality testing because of its advantages of rapidity, high efficiency, non-destructive and environment-friendly. This paper summarises the progress of non-destructive testing technology in beef quality analysis (sensory quality, nutritional quality and other quality), and systematically describes the principles of non-destructive testing techniques such as near-infrared spectroscopy, Raman spectroscopy, hyperspectral imaging, E-tongue and E-nose. The progress of non-destructive testing techniques in beef quality analysis within the last five years is discussed in detail. The existing problems of non-destructive testing technology in beef quality analysis are put forward, and the future application prospect is prospected. It hopes to provide a reference for the research and application of non-destructive testing technology for beef quality.

The administration of T cells that have been modified to carry chimeric antigen receptors (CARs) aimed at B cells has been an effective strategy in treating B cell malignancies. This breakthrough has spurred the creation of CAR T cells intended to specifically reduce or alter the faulty immune responses associated with autoimmune disorders. Early positive outcomes from clinical trials involving CAR T cells that target the B cell protein CD19 in patients suffering from autoimmune diseases driven by B cells have been reported. Additional strategies are being developed to broaden the use of CAR T cell therapy and enhance its safety in autoimmune conditions. These include employing chimeric autoantireceptors (CAAR) to specifically eliminate B cells that are reactive to autoantigens, and using regulatory T cells (Tregs) engineered to carry antigen-specific CARs for precise immune modulation. This discussion emphasizes key factors such as choosing the right target cell groups, designing CAR constructs, defining tolerable side effects, and achieving a lasting immune modification, all of which are critical for safely integrating CAR T cell therapy in treating autoimmune diseases.

The agglomeration of nano carbon black (NCB), driven by its high specific surface energy, limits the fundamental performance of cementitious materials and hinders the broader application of functional cementitious materials in engineering domains. NCB-modified cement (NC) has a low snow-melting efficiency, resulting in high energy consumption and excessive CO2 emissions. Herein, this study innovatively proposed a method of using dispersants to overcome the above issue and systematically introduced the effects of three dispersants, polycarboxylic acid superplasticizer (PCE), tannic acid (TA), and sodium dodecyl sulfate (SDS), on NC. The dispersity of dispersant-NCB suspension was analyzed firstly, and then the performance of fresh paste, mechanical properties, resistivity, snow-melting speed and LCA of NC were explored. Experimental results indicated that, in terms of suspension stability, SDS was the most effective, followed by TA, while PCE exhibited the least efficacy. Furthermore, all three dispersants improved the fluidity of NC to varying degrees. However, PCE and TA demonstrated a retardation effect on the setting time, whereas SDS facilitated a reduction in the setting time of NC. From the point of view of mechanical properties, the use of these dispersants not only augmented the mechanical strength of the NC but also decreased its electrical resistivity. The uniform dispersion of SDS at the microstructural level of NCB had also been found. When the PCE content is 0.2%, TA content is 0.4%, and SDS content is 0.4%, the mechanical strength and resistivity of NC were the best. NC with dispersant TA melted snow three times faster than the control group, reducing snow-melting energy consumption. Moreover, LCA analysis showed that the addition of dispersants also reduced carbon emissions.

Blood-brain barrier (BBB) breakdown, an early hallmark of multiple sclerosis (MS), remains crucial for MS progression. Our previous works have confirmed that Astragalus polysaccharides (APS) can significantly ameliorate demyelination and disease progression in experimental autoimmune encephalomyelitis (EAE) mice. However, it remains unclear whether APS protects BBB and the potential mechanism. In this study, we found that APS effectively reduced BBB leakage in EAE mice, which was accompanied by a decreased level of endothelial-to-mesenchymal transition (EndoMT) in the central nervous system (CNS). We further induced EndoMT in the mouse brain endothelial cells (bEnd.3) by interleukin-1β (IL-1β) in vitro. The results showed that APS treatment could inhibit IL-1β-induced EndoMT and endothelial cell dysfunction. In addition, the transcription factor ETS1 is a central regulator of EndoMT related to the compromise of BBB. We tested the regulation of APS on ETS1 and identified the expression of ETS1 was upregulated in both EAE mice and bEnd.3 cells by APS. ETS1 knockdown facilitated EndoMT and endothelial cell dysfunction, which completely abolished the regulatory effect of APS. Collectively, APS treatment could protect BBB integrity by inhibiting EndoMT, which might be associated with upregulating ETS1 expression. Our findings indicated that APS has potential value in the prevention of MS.

Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) is prevalent and increasingly reported. Its diagnosis traditionally follows the Kidney Disease: Improving Global Outcomes (KDIGO) AKI criteria. However, little evidence supports its appropriateness for cardiac surgery patients, particularly regarding the subtle serum creatinine change (ΔSCr) that defines mild AKI. Objectives: The purpose of the study was to investigate the ΔSCr threshold specific to CSA-AKI and compare its impact on CSA-AKI incidence and prognosis with the KDIGO AKI criteria threshold. Methods: A 10-year coronary surgery cohort with serial perioperative SCr measurements was retrospectively analyzed. The relationship and prognostically significant threshold of 48-hour absolute ΔSCr with 30-day mortality were explored using multivariate restricted cubic spline analysis and receiver-operating characteristic curve analysis. AKI incidence and prognostic value were compared between adopting the KDIGO or new thresholds. Results: Among 37,706 patients, 20,290 (53.8%) developed KDIGO-defined AKI. For stage-1 AKI (18,835, 49.9%), the majority (75.2%) were solely attributed to the KDIGO absolute criterion (48-hour ΔSCr ≥0.3 mg/dL). The 48-hour ΔSCr threshold associated with an adjusted odds ratio ≥1.00 for 30-day mortality was 0.549 mg/dL. A similar threshold (0.553 mg/dL) was also identified based on the Youden index cutoff. Applying the 0.55 mg/dL threshold to define stage 1 CSA-AKI, the overall and stage-1 CSA-AKI incidence decreased to 21.0% and 17.2%, with 27.7% of the stage-1 CSA-AKI solely attributed to the new criterion. The prognostic value for AKI defined by this new threshold was significantly higher than the KDIGO criteria. Conclusions: A cardiac surgery-specific ΔSCr threshold in defining AKI was notably higher compared with the current general AKI definition.

Abstract Exosomes, a specific subset of extracellular vesicles, have diverse functions in various biological processes. In the field of cancer research, there has been a growing interest in the potential of exosomes to act as versatile vehicles for targeted tumor imaging and therapy. In this study, we constructed a targeted delivery platform using hypoimmunogenic exosomes by genetically modifying β2‐microglobulin knocking‐out HEK‐293F cells to express a fusion protein, referred to as αMUC1‐Exo, which comprises the exosomal membrane‐enriched platelet‐derived growth factor receptor, intracellular nanoluciferase, and extracellular anti‐MUC1 single‐chain variable fragment. The findings of this study indicate that αMUC1‐Exos exhibited notable drug delivery properties toward MUC1‐positive pancreatic cancer cells, resulting in a substantial inhibition of tumor growth. Moreover, these exosomes demonstrated a high level of biosafety and the absence of any adverse effects. The application of engineered exosomes as a vehicle for drug delivery holds promise for enhancing the immunogenicity of neoplastic cells following treatment, thereby inducing antitumor immune memory in mice with intact immune systems, and also improving the response to anti‐PD1 therapy. This approach utilizing engineered exosomes for Gemcitabine administration holds promise as a potential strategy for overcoming drug resistance in pancreatic carcinoma thereby improving the overall treatment efficacy.

Abstract Electronic tattoo, capable of imperceivably acquiring bio‐electrical signals from the body, is broadly applied in healthcare and human‐machine interface. Tattoo substrate, the foundation of electronic tattoo, is expected to be mechanically mimetic to skin, adhesive, and breathable, and yet remains highly challenging to achieve. Herein, the study mimics human skin and design a breathable, adhesive, and mechanically skin‐like super tattoo substrate based on an ultra‐thin film (≈2 µm). Similar to skin, super tattoo demonstrates strain‐adaptive stiffening properties with high tear energy (5.4 kJ·m−2) and toughness (1.3 MJ·m−3). Superior to skin, it exhibits high adhesion, ionic conductivity, and permeability. A variety of conductive electrodes can be processed on it, showing the universality toward an ideal platform for electronic tattoo with stable and low contact impedance. Super tattoo‐based electrodes can imperceivably and accurately monitor weak electromyography (EMG) of swallowing on the junction, providing effective guidance for rehabilitation training of dysphagia.

Abstract Gut microbiota dysbiosis has been implicated in rheumatoid arthritis (RA) and influences disease progression. Although molecular and culture‐independent studies revealed RA patients harbored a core microbiome and had characteristic bacterial species, the lack of cultured bacterial strains had limited investigations on their functions. This study aimed to establish an RA‐originated gut microbial biobank (RAGMB) that covers and further to correlates and validates core microbial species on clinically used and diagnostic inflammation and immune indices. We obtained 3200 bacterial isolates from fecal samples of 20 RA patients with seven improved and 11 traditional bacterial cultivation methods. These isolates were phylogenetically identified and selected for RAGMB. The RAGMB harbored 601 bacterial strains that represented 280 species (including 43 novel species) of seven bacterial phyla. The RAGMB covered 93.2% at species level of medium‐ and high‐abundant (relative abundances ≥0.2%) RA gut microbes, and included four rare species of the phylum Synergistota. The RA core gut microbiome was defined and composed of 20 bacterial species. Among these, Mediterraneibacter tenuis and Eubacterium rectale were two species that statistically and significantly correlated with clinically used diagnostic indices such as erythrocyte sedimentation rate (ESR) and IL‐10. Thus, M. tenuis and E. rectale were selected for experimental validation using DSS‐treated and not DSS‐treated mice model. Results demonstrated both M. tenuis and E. rectale exacerbated host inflammatory responses, including shortened colon length and increased spleen weight, decreased IL‐10 and increased IL‐17A levels in plasma. Overall, we established the RAGMB, defined the RA core microbiome, correlated and demonstrated core microbial species effected on host inflammatory and immune responses. This work provides diverse gut microbial resources for future studies on RA etiology and potential new targets for new biomedical practices.

BackgroundOver the past 23 years, there has been a thorough analysis of literature concerning nutritional interventions, nutrients, and feeding approaches related to stroke. Furthermore, a scientific knowledge map was established, elucidating the current state of research, examining its development and trends, and offering new research viewpoints for the future. This study aimed to investigate global and emerging research trends in nutritional interventions for stroke from 2000 to 2023 through bibliometric analysis.MethodsA bibliometric analysis of literature from the Core Collection of Scientific Networks for the years 2000–2022 was conducted. CiteSpace, VOSviewer, and bibliometric graphical software were used to identify major contributors to publications, including authors, countries, institutions, journals, references, and keywords.ResultsThe bibliometric analysis yielded a total of 464 publications. This is a gradually increasing number in terms of the number of publications during the study period. China had the highest number of publications. Clinical Nutrition” was the journal with the highest number of relevant publications, and the most commonly used keywords were “stroke,” “nutrition” and “malnutrition.”ConclusionThese analyses reveal research trends in nutritional therapy for stroke from 2000 to 2023 and point to prospective research frontiers. This study provides a deeper understanding of what nutritional treatment of stroke entails and provides guidance and support for future research in this area.

BackgroundThe clinical phenotypes of 16p13.11 microduplication syndrome have been extensively reported in previous studies, mostly about adults and children, with limited information available on fetal cases. This study aims to explore the genotype-phenotype correlation of fetuses with 16p13.11 microduplication syndrome and analyze the characteristics of prenatal diagnosis indications and provide clinical information for prenatal and postnatal genetic counseling.MethodsWe conducted a retrospective analysis of 3,451 pregnant women who underwent invasive prenatal diagnosis for SNP array between January 2018 and December 2022 at the Jinan Maternal and Child Health Hospital. Descriptive statistical analysis was performed on the prenatal diagnosis indications, pedigree analysis, pregnancy outcomes and postnatal follow-up of 15 fetuses with 16p13.11 microduplication syndrome.ResultsSNP array revealed that 15 fetuses had duplications in the 16p13.11 region with varying prenatal diagnosis indications. Among the cases, 6/15 exhibited ultrasound abnormalities, 5/15 had abnormal chromosomal copy number variations as indicated by non-invasive prenatal testing (NIPT), one case involved advanced maternal age, and 3/15 had other abnormalities. 16p13.11 microduplication syndrome was closely related to ultrasound abnormalities, especially structural abnormalities and soft marker anomalies (abnormal ultrasonic soft indicators), while the indication of NIPT could improve the detection rate of copy number variations (CNVs) in this region. Only 7/15 fetuses underwent pedigree verification, with one case of de novo 16p13.11 microduplication, and the others inherited from one parent. Pregnancy was terminated in 2/15 cases and the outcome of one case is unknown due to loss to follow-up. Among the remaining cases, only one case exhibited a ventricular septal defect, while another presented with omphalocele. No other obvious abnormalities were reported postnatally.ConclusionThe prenatal phenotypes of fetuses with 16p13.11 microduplication were highly associated with ultrasound abnormalities but lacked specificity. Comprehensive genetic tracing, outcome analysis, and follow-up are essential for providing accurate prenatal and postnatal genetic counseling.