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Abstract Efficient harnessing of solar energy presents a significant challenge in environmental cleanup efforts. This study develops a highly effective carbon quantum dots-modified hollow core-shell TiO2-LaFeO3 heterojunction photocatalyst (CDs-TLFO). Structural analysis confirmed that nanosheets are loaded with CQDs, forming a hollow core-shell structure with intimate interconnection. Photocatalytic experiments reveal that CDs-TLFO degrads tetracycline hydrochloride (TC) 2.02 times faster than TLFO alone, and significantly outperformes h-TiO2 and LaFeO3 (11.28 and 2.78 times, respectively). This enhancement is attributed to CQDs acting as electron acceptors with upconversion properties, enhancing the separation of e–-h+ pairs and boosting visible light absorption. Integration of CQDs onto the TLFO surface creates numerous active sites and enhances visible light absorption. SEM and TEM tests confirm that the catalyst has a hollow core-shell structure. ESR tests and radical trapping experiments indicate that the high degradation efficiency of the catalyst mainly owns to the synergistic effect of hydroxyl radicals (·OH) and superoxide radicals (·O2 −). The reusability and stability of the catalysts are investigated, potential TC degradation pathways are proposed as well as the photocatalytic reaction mechanism is revealed. This research introduces promising avenues for environmental cleanup and offers a straightforward, energy-efficient, and environmentally friendly method for producing CDs-TLFO heterojunction materials with superior photocatalytic capabilities.

Abstract This study proposes a novel topology with bi‐stable controlling for wireless charging system (WCS). The advantage of the proposal is that a desired charging current can be directly output from rectifier without requiring charging current manager, thereby greatly simplifying the structure of the receiver. The proposed topology not only improves the transmission efficiency of system, but also reduces the loss and heat dissipation in the receiver. The principle of the topology is outlined and the circuitry model and control strategy are established and analyzed in detail. The innovation of this method lies in treating the coupler as a current transformer, which enables more direct and simpler controlling of the charging current. The experiment is conducted to verify that when the peak charging current is increased from 5A to 10A, the system efficiency is increased up to 82.0% and the receiver efficiency up to 96.7%. Both computational simulation and experimental validation have confirmed the feasibility of the proposed method. Compared with conventional WCS topology with compensation, the proposed method improves the system efficiency by 3% and the receiver efficiency by 5%, which is more suitable for practical applications where compact and light‐weight receiver is required.

Abstract Traffic information is crucial for managing transportation and city planning, but obtaining national-scale data is difficult due to privacy concerns. Consequently, most current traffic datasets have limitations in terms of time and location coverage, leading to a lack of comprehensive public access to national traffic data. To address this issue, a multi-source highway traffic dataset has been created, featuring 2042 sensors in New Zealand over a 9-year period with 15-minute intervals and accompanying metadata. The dataset includes data of both light-duty and heavy-duty vehicles, as well as weather information like temperature and precipitation. This dataset has diverse potential research applications such as traffic flow prediction and congestion management.

Abstract Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis that can lead to joint deformities. To date, more than 18 million individuals worldwide have been diagnosed with RA, making it one of the most prevalent autoimmune diseases globally and posing a significant threat to public health and safety. Due to the complex pathogenesis of the disease, which involves autoimmunity, genetics, inflammation and oxidative stress in the body’s tissues, the current drug therapy generally targets a single molecule, and effective and efficient drugs involving multiple levels and targets are lacking; thus, there is an urgent need for high-quality research and treatment in this field. Nuclear transcription factor erythroid 2-associated factor 2 (Nrf2) plays a crucial role in cellular resistance to oxidative stress and electrophilic attacks and is a potential pharmacological target for chronic disease treatment. While currently no drugs that target Nrf2 have been approved specifically for RA treatment, such an approach holds great significance. In recent years, the use of natural products to treat RA and other chronic conditions has become increasingly widespread because of their superior efficacy and minimal side effects. Therefore, this article provides a review of the mechanism of Nrf2 in RA and summarizes natural products that target Nrf2 and its associated pathways in the treatment of RA, aiming to offer new insights and strategies for the prevention and management of RA. Graphical abstract

Abstract ENO1, also called 2-phospho-D-glycerate hydrolase in cellular glycolysis, is an enzyme that converts 2-phosphoglycerate to phosphoenolpyruvate and plays an important role in the Warburg effect. In various tumors, ENO1 overexpression correlates with poor prognosis. ENO1 is a multifunctional oncoprotein that, when located on the cell surface, acts as a “moonlighting protein” to promote tumor invasion and metastasis. When located intracellularly, ENO1 facilitates glycolysis to dysregulate cellular energy and sustain tumor proliferation. Additionally, it promotes tumor progression by activating oncogenic signaling pathways. ENO1 is a tumor biomarker and represents a promising target for tumor therapy. This review summarizes recent advances from 2020 to 2024 in understanding the relationship between ENO1 and tumors and explores the latest targeted therapeutic strategies involving ENO1.

Abstract Coenzyme Q10 (CoQ10) is the most consumed dietary supplement and mainly biosynthesized by aerobic fermentation of Rhodobacter sphaeroides (R. sphaeroides). Oxygen supply was identified as a bottleneck for improving CoQ10 yield in R. sphaeroides. In this study, a precise regulation strategy based on dielectric spectroscopy (DS) was applied to further improve CoQ10 biosynthesis by R. sphaeroide. First, a quantitative response model among viable cells, cell morphology, and oxygen uptake rate (OUR) was established. DS could be used to detect viable R. sphaeroides cells, and the relationship among cell morphology, CoQ10 biosynthesis, and OUR was found to be significant. Based on this model, the online specific oxygen consumption rate (QO2) control strategy was successfully applied to the CoQ10 fermentation process. QO2 controlled at 0.07 ± 0.01 × 10− 7mmol/cell/h was most favorable for CoQ10 biosynthesis, resulting in a 28.3% increase in CoQ10 production. Based on the multi-parameters analysis and online QO2 control, a precise online nutrient feeding strategy was established using conductivity detected by DS. CoQ10 production was improved by 35%, reaching 3384 mg/L in 50 L bioreactors. This online control strategy would be effectively applied for improving industrial CoQ10 production, and the precise fermentation control strategy could also be applied to other fermentation process.

Abstract Accurate postoperative assessment is critical for optimizing 131I therapy in patients with papillary thyroid cancer (PTC). This study aimed to develop a pathology model utilizing postoperative digital pathology slides to predict lymph node and/or distant metastases on post-therapeutic 131I scan after initial 131I treatment in PTC patients. A retrospective analysis was conducted on 229 PTC patients who underwent total or near-total thyroidectomy and subsequent 131I treatment after levothyroxine (LT4) withdrawal between January 2022 and August 2023. The pathology model was developed through two stages: patch-level prediction and WSI-level prediction. The clinical model was constructed using statistically significant variables identified from univariate and multivariate logistic regression analysis. Of the 229 patients, 19.6% (45/229) exhibited 131I-avid metastatic foci in post-therapeutic 131I scan. Multifactorial analysis identified stimulated thyroglobulin (sTg) as the sole independent risk factor. The AUC of the pathology model in the training and test cohorts were 0.976 (95% CI 0.948–1.000) and 0.805 (95% CI 0.660–0.951), respectively, which were significantly higher than the clinical model (AUC 0.652 and 0.548, Pall

Abstract Background Osteogenesis imperfecta (OI) is a genetic disorder characterized by low bone mass, bone fragility and short stature. There is a significant gap in knowledge regarding the growth patterns across different types of OI, and the prediction of height in individuals with OI was not adequately addressed. In this study, we described the growth patterns and predicted the height of individuals with OI employing multiple machine learning (ML) models. Accurate height prediction enables effective monitoring and facilitates the development of personalized intervention plans for managing OI. Method This study included cross-sectional data for 323 participants with OI, and the median height Z-score for OI types I, III and IV were − 0.62 (-5.93 ~ 3.24), -3.97 (-10.44 ~ -0.02) and − 1.64 (-6.67 ~ 2.44), respectively. Based on the cross-sectional data of participants, the height curves across different gender and OI types were plotted and compared. Subsequently, feature selection techniques, specifically the filter and wrapper methods, were employed to identify predictive factors for the height of participants. Finally, multiple machine learning (ML) models were constructed for height prediction, and the performance of each model was systematically evaluated. Results The analysis of height curves revealed that male with OI are significantly taller than female with OI from the age of 14 (p = 0.045), individuals with OI type III are statistically shorter than those with OI types I and IV starting from 3 years old (p = 0.006), and those with OI type IV are statistically shorter than those with OI type I from the age of 10 (p = 0.028). The application of filter and wrapper methods identified gender (p = 0.001), age (p

Abstract Hyperglycemia and diabetes are common metabolic disorders. It is considered a safe and effective strategy to screen active ingredients from food and herbs for controlling blood sugar levels. Quinic acid (QA) is a natural polyphenolic acid with various health‐promoting properties. In this study, QA was found to exhibit a potent inhibitory effect on α‐glucosidase activity, with a half maximal inhibitory concentration (IC50) of 5.46 mM. This inhibitory property surpassed that of three common organic acids including gallic acid, malic acid, and citric acid. A combination of 25% acarbose (0.5 mM) and 75% QA (5 mM) (v/v) exhibited synergistic inhibition of α‐glucosidase activity. Enzyme kinetics, fluorescence spectra, and molecular docking analyses indicated that QA acted as an uncompetitive inhibitor of α‐glucosidase, with hydrogen bonds playing a key role in the intermolecular interactions. Moreover, QA was found to effectively inhibit three major nonenzymatic glycation products including advanced glycosylation end products (AGEs), fructosamine, and α‐dicarbonyl in a dose‐dependent manner, outperforming the positive control aminoguanidine (AG) within the tested concentration range. Utilizing a Caco‐2 cell model, QA demonstrated the ability to inhibit the transmembrane absorption of glucose. This study highlighted QA as a promising food functional factor that had been overlooked in the past, offering potential benefits in improving hyperglycemia, diabetes, and associated complications through the inhibition of α‐glucosidase, nonenzymatic glycosylation, and glucose uptake.

Abstract Background Camellia nitidissima Chi is a popular ornamental plant because of its golden flowers, which contain flavonoids and carotenoids. To understand the regulatory mechanism of golden color formation, the metabolites of C. nitidissima petals at five different developmental stages were detected, a proteome map of petals was first constructed via tandem mass tag (TMT) analysis, and the accuracy of the sequencing data was validated via parallel reaction monitoring (PRM). Results Nineteen color components were detected, and most of these components were carotenoids that gradually accumulated, while some metabolites were flavonoids that were gradually depleted. A total of 97,647 spectra were obtained, and 6,789 quantifiable proteins were identified. Then, 1,319 differentially expressed proteins (DEPs) were found, 55 of which belong to the flavonoid and carotenoid pathways, as revealed by pairwise comparisons of protein expression levels across the five developmental stages. Notably, most DEPs involved in the synthesis of flavonoids, such as phenylalanine ammonium lyase and 4-coumarate-CoA ligase, were downregulated during petal development, whereas DEPs involved in carotenoid synthesis, such as phytoene synthase, 1-deoxy-D-xylulose-5-phosphate synthase, and β-cyclase, tended to be upregulated. Furthermore, protein‒protein interaction (PPI) network analysis revealed that these 55 DEPs formed two distinct PPI networks closely tied to the flavonoid and carotenoid synthesis pathways. Phytoene synthase and chalcone synthase exhibited extensive interactions with numerous other proteins and displayed high connectivity within the PPI networks, suggesting their pivotal biological functions in flavonoid and carotenoid biosynthesis. Conclusion Proteomic data on the flavonoid and carotenoid biosynthesis pathways were obtained, and the regulatory roles of the DEPs were analyzed, which provided a theoretical basis for further understanding the golden color formation mechanism of C. nitidissima.

Abstract Objective This study aimed to identify risk factors contributing to the early onset of patellofemoral osteoarthritis (PFOA) within the first two years following anterior cruciate ligament reconstruction (ACLR) using a hamstring tendon autograft. Methods Participants aged 18 to 40 who had undergone ACLR within the past two years were included in this study, along with a control group of healthy volunteers. Magnetic resonance imaging (MRI) data were obtained preoperatively, at two years postoperatively, and from the control group. T-tests were used to assess differences in patellofemoral alignment (PA) and trochlear morphology (TM) between the pre- and post-ACLR patients and healthy controls. The incidence of PFOA was recorded, and associations between PA, TM, and clinical parameters were evaluated in patients with and without PFOA. Logistic regression analysis was conducted to identify potential risk factors for PFOA development. Results A total of 177 patients, with a mean follow-up period of 22.17 ± 5.09 months and a mean age of 26.4 ± 5.6 years, were included in the study. Following ACL injury, significant alterations in patellar tilt angle (PTA), tuberositas tibae-trochlear groove distance (TT-TG), Insall-Salvati ratio (ISR), and static anterior tibial translation (SATT) were observed compared to the control group. Postoperatively, deviations in PTA and SATT remained significant when compared to healthy controls. Of the 177 patients, 68 (38.42%) developed early-onset PFOA. Factors associated with the early onset of PFOA included age at the time of surgery, the interval between injury and surgery, PTA, bisect offset (BO), sulcus angle (SA), thigh circumference, SATT, and partial meniscectomy. Conclusion Significant differences in PTA, TT-TG, ISR, and SATT were identified between patients who underwent ACLR and healthy controls. Postoperatively, there was no correction in PTA or SATT, which remained significantly altered. Factors such as age at the time of surgery, PTA, BO, SA, ISR, SATT, thigh circumference, partial meniscectomy, and the time interval between injury and surgery were associated with the early onset of PFOA within two years post-ACLR. These findings may aid in the prevention of PFOA by identifying individuals at higher risk for early development.

To solve the problem of poor thermal stability of the current D-allulose 3-epimerase (DAEase), the ancestor sequences of DAEase with different catalytic domains were reconstructed by big data mining, reasonable modification and ancestor sequence reconstruction (ASR) strategy under the guidance of phylogenetic information. The expression vectors of the ancestor sequences were constructed, and DAEase A13 with significantly enhanced thermal stability was screened by recombinant expression and molecular docking, and its enzymatic properties were characterized. In addition, the molecular mechanism of thermal stability enhancement of DAEase A13 was revealed based on structural analysis and molecular dynamics. The results showed that the half-life of A13 constructed based on ASR strategy could reach 8.4 h at 70 ℃, indicating that its thermal stability was significantly enhanced compared with that of wild-type (WT) enzyme. The maximum conversion rate of A13 reached 31%, indicating that the catalytic activity of A13 was slightly higher than that of WT enzyme. The structural and molecular dynamics analysis revealed that the increase in hydrogen bonding and hydrophobic interaction in ASR A13 was the main factor responsible for maintaining the stability of the enzyme's molecular structure at high temperatures. The results showed that ASR strategy could modify DAEases to enhance the stability, activity or hybridity, which could provide superior biocatalyst sources for various industrial applications of functional sugars.

With the resurgence of electrosynthesis in organic chemistry, there is a significant increase in the number of routes available for late-stage functionalization (LSF) of drugs. Electrosynthetic methods, which obviate the need for hazardous chemical oxidants or reductants, offer unprecedented control of reactions through the continuous variation of the applied potential and the possibility of combination with photochemical processes. This capability is a substantial advantage for performing electrochemical or photoelectrochemical LSF. Ultimately, these protocols are poised to become a vital component of the medicinal chemist's toolkit. In this review, we discuss electrochemical protocols that have been demonstrated to be applicable for the LSF of pharmaceutical drugs, their derivatives, and natural substrates. We present and analyze representative examples to illustrate the potential of electrochemistry or photoelectrochemistry for the LSF of valuable molecular scaffolds.

Abstract Phytopathogens often secrete effectors to enhance their infection of plants. In the case of Sclerotinia sclerotiorum, a necrotrophic phytopathogen, a secreted protein named SsPEIE1 (Sclerotinia sclerotiorum Plant Early Immunosuppressive Effector 1) plays a crucial role in its virulence. During the early stages of infection, SsPEIE1 is significantly up-regulated. Additionally, transgenic plants expressing SsPEIE1 exhibit increased susceptibility to different phytopathogens. Further investigations revealed that SsPEIE1 interacts with a plasma membrane protein known as hypersensitive induced reaction (HIR) that dampens immune responses. SsPEIE1 is required for S. sclerotiorum virulence on wild-type Arabidopsis but not on Arabidopsis hir4 mutants. Moreover, Arabidopsis hir2 and hir4 mutants exhibit suppressed pathogen-associated molecular pattern-triggered reactive oxygen species (ROS) bursts and salicylic acid (SA)-associated immune gene induction, all of which are phenocopied by the SsPEIE1 transgenic plants. We find that the oligomerization of AtHIR4 is essential for its role in mediating immunity, and that SsPEIE1 inhibits its oligomerization through competitively binding to AtHIR4. Remarkably, both Arabidopsis and rapeseed plants overexpress AtHIR4 display significantly increased resistance to S. sclerotiorum. In summary, these results demonstrate that SsPEIE1 inhibits AtHIR4 oligomerization-mediated immune responses by interacting with the key immune factor AtHIR4, thereby promoting S. sclerotiorum infection.

Abstract The concerns on the function of Transmembrane protein 173 (TMEM173)-dependent innate immunity in prevention and management of cancers has recently been increased. The role of TMEM173 in predicting the prognosis and response to treatment in lung adenocarcinoma (LUAD) remain unclear. Our study revealed that TMEM173 expression was significantly differential in various tumors and the related prognosis was heterogeneous. Further investigation discovered that the expression level of TMEM173 in LUAD tissues was significantly decreased and high TMEM173 expression is associated with better overall survival in LUAD patients. TMEM173 was mainly enriched in immune response-regulating signaling pathway, T cell activation and cell cycle G2/M phase. Furthermore, it was found that TMEM173 expression was positively related to markers and infiltration levels of tumor-infiltrating immune cells. TMEM173 could predict response to targeted therapy, chemotherapy and immunotherapy in LUAD patients. In vitro TMEM173 knockdown decreased the percentage of G2 phase cells, contributing to the increased growth of lung cancer cells. These results implied that TMEM173 might be a prognostic biomarker and a potential target of precision therapy for LUAD patients.

The Lower Silurian Longmaxi Formation is a major horizon for shale gas development in the Changning block in Sichuan Basin. In this study, the fracture features in the Longmaxi Formation in the Changning block were investigated through outcrop observation, core description, inclusion testing, and Fullbore Formation MicroImage logging. The results showed that tectogenetic shear fractures dominated the Longmaxi Formation, with maximum principal stress in the SSW, NW, and NE directions. According to fracture features and stress analysis, three phases of faults were generated by tectonic movements after the buried depth reached a maximum in the study area: phase 1 nearly EW-trending faults formed in the middle-late Yanshanian, phase 2 NE-trending faults formed from the end of the Yanshanian to the early Himalayan, and phase 3 NW-trending faults formed from the middle Himalayan to the present. According to the regression analysis of the tested shale gas production and faults, the faults with a throw of > 200 m could have a great effect on gas production, and high-yield wells were generally located over 1 km away from faults. Based on the dissection of tectonic styles and typical wells drilled in the Changning block, three shale gas accumulation models were established: wide gentle syncline + internal smalxl fault, subdued anticline + large fault, and slope + internal fault. The study reveals the mechanism of fault influence on shale gas accumulation in the Longmaxi Formation in the Changning block and provides a reference for efficient shale gas production in the Sichuan Basin.

In this research, we aimed to construct a novel planting pattern for faba bean and maize with high-efficiency utilization of climate resources for application in production. We incorporated relay intercropping in two triple-crop planting patterns, namely faba bean/maize-maize and faba bean/maize-soybean. A field experiment was conducted to compare the annual yield, utilization efficiency of climatic resources and economic benefits among these two triple-crop planting patterns and the conventional faba bean – maize double-cropping system at Nantong, Jiangsu, China, from 2016 to 2020. Compared with the conventional double-cropping system, the faba bean/maize-maize triple-crop planting pattern resulted in significantly increased annual yield by 7,392 kg hm−2 to 10,519 kg hm−2, and increased annual biomass by 5,342 kg hm−2 to 7,172 kg hm−2.The triple-crop planting patterns increased the annual economic benefit by 12,195 RMB hm−2 and 15,680 RMB hm−2, respectively. The faba bean/maize-maize triple-crop planting pattern increased the annual radiation production efficiency by 0.18 g·MJ−1 to 0.31 g·MJ−1, the annual temperature production efficiency by 2.70 kg·hm−2·°C−1 to 3.78 kg·hm−2·°C−1, and the annual precipitation production efficiency by 4.55 kg·mm−1·hm−2 to 7.20 kg·mm−1·hm−2. Considering the yields, resource-use efficiency, and economic benefits, the triple-cropping planting patterns show promise as multi-crop systems to achieve high yields and high resource-use efficiency in the Yangtze River Delta region. These results demonstrate the use of a new relay intercropping planting pattern for use in crop production and represent a theoretical contribution to the development of efficient agricultural production.

Abstract Tissue interfaces are essential for development and their disruption often leads to diseases such as tumor invasion. Here, we combine experiments, theoretical modeling, and numerical simulations to quantify the morphodynamics of interface in a biphasic system composed of Madin Darby canine kidney (MDCK) and mouse myoblast (C2C12) cells. We show that cellular activity regulates the interface morphodynamics and drives wave propagation along the interface. Based on the dispersion relationship, we identify that the wave dynamics results from the activity-mediated instability of the interface and coherent flow. It is found that the topological defects accumulate around and destabilize the interface and +1/2 topological defects are more likely to aggregate in MDCK cell clusters. A biphasic active nematic theory is employed to reproduce our experimental observations and decipher the underlying mechanisms. These findings provide physical insights into the interfacial evolution that could be implicated in tissue morphogenesis and tumor invasion.

Abstract Bridging the gap between genotype and phenotype in GWAS studies is challenging. A multitude of genetic variants have been associated with immune-related diseases, including cancer, yet the interpretability of most variants remains low. Here, we investigate the quantitative components in the T cell receptor (TCR) repertoire, the frequency of clusters of TCR sequences predicted to have common antigen specificity, to interpret the genetic associations of diverse human diseases. We first developed a statistical model to predict the TCR components using variants in the TRB and HLA loci. Applying this model to over 300,000 individuals in the UK Biobank data, we identified 2309 associations between TCR abundances and various immune diseases. TCR clusters predicted to be pathogenic for autoimmune diseases were significantly enriched for predicted autoantigen-specificity. Moreover, four TCR clusters were associated with better outcomes in distinct cancers, where conventional GWAS cannot identify any significant locus. Collectively, our results highlight the integral role of adaptive immune responses in explaining the associations between genotype and phenotype.

Primula meishanensis K.Huang & Z.X.Fu, sp. nov., a new species of Primulaceae from Meishan City, Sichuan Province, China, is described and illustrated. The morphological data and phylogenetic analysis, based on the complete chloroplast genome, suggest that Primula meishanensis is a separate species closely related to Primula dejuniana. The complete chloroplast genome of Primula meishanensis was 152,175 bp and the complete chloroplast genome of Primula dejuniana was 151,988 bp. The new species differs from the latter by the solitary scape, the length of petiole, acute leaf blade apex and pin flower. The distribution map, morphological comparison of related species and conservation status of the new species are also provided.

Abstract Accurate and efficient identification of water inrush sources, as one of the three critical elements of mine water hazards, is crucial for mine water management. To identify the sources of mine water inrush effectively, a model named HBA-CatBoost is introduced. This model is established on the hybrid bat algorithm (HBA)-optimized category feature gradient boosting tree (CatBoost), and the shapley additive explanation (SHAP) method is employed to elucidate the model’s decision-making process. Given the prevalent occurrence of water hazards in coal seam roofs and floors in the northern Guizhou coalfield, coupled with the challenges in pinpointing water inrush sources in mines, the HBA-CatBoost model is tested at the Longfeng Coal Mine in northern Guizhou to validate its practicality. Comparative analysis with the HBA-RF, HBA-XGBoost, CatBoost, RF, and XGBoost models demonstrates that the hybrid bat algorithm significantly enhances the classification performance of the CatBoost model, resulting in improved convergence speed and classification accuracy. The HBA-CatBoost model outperforms the aforementioned models in terms of classification effectiveness, achieving accuracy, recall, precision, and F1 scores of 96.43%, 97.22%, 96.43%, and 96.61%, respectively. The SHAP method elucidates the decision mechanism of the optimal HBA-CatBoost model, highlighting the significance of sample features and bolstering the model’s credibility. These outcomes underscore the superior performance of the HBA-CatBoost model and its potential for effectively identifying water inrush sources in mines.

Abstract Purpose Vision-threatening diabetic retinopathy (VTDR) included severe non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR) and clinically significant diabetic macular edema (DME). To compare the axial length (AL) and assess its influence on VTDR across different ages. Methods A retrospective cohort study. Medical chart review was performed in 736 consecutive patients with VTDR. The patients were divided into young (≤ 45 years) and elderly group (> 45 years) based on their age at the diagnosis of VTDR. After at least one year of standardized treatments, all eligible patients were followed up. The main outcome measures included the presence of tractional retinal detachment (TRD) involving foveal, final best-corrected visual acuity (BCVA), the development of neovascular glaucoma (NVG), and recurrent vitreous hemorrhage (VH) post-vitrectomy. ALs were compared between two age groups. The impact of AL on clinical outcomes was determined by logistic analyses after controlling for systemic parameters. Results The study included 144 patients ≤ 45 years and 592 patients > 45 years. Young patients had significantly longer AL than elderly participants (23.9 mm vs 23.0 mm, p

Abstract Background In addition to their classic genomic effects, glucocorticoids also manifest rapid non genomic effects. We speculate that dexamethasone has the potential prompt onset of analgesic effects. The objective of this study is to investigate the influence of a single preoperative dose of dexamethasone on the half maximal effective concentration (EC50) of remifentanil when combined with dexmedetomidine for pain relief during pancreatic extracorporeal shockwave lithotripsy (P-ESWL). Methods A total of 60 patients undergoing P-ESWL were enrolled and randomized at 1:1 ratio into the dexamethasone (DXM) group and the placebo group. Before anesthesia induction, patients in DXM group received an intravenous injection of 8 mg dexamethasone, while subjects in placebo group received an equal dose of physiological saline. Monitored anesthesia care (MAC) was performed based on remifentanil in combination with dexmedetomidine. Remifentanil was administered by TCI with an initial target concentration of 2.5 µg/mL for both groups. A positive response was defined as that VAS score > 3 by the patient at any time during the procedure. Subsequent target concentrations were adjusted by Dixon up-down sequential method, where dose modifications were performed by 0.3 ng/mL intervals, based on the response of the previous patient. The EC50 of remifentanil for pain relief during P-ESWL treatment was calculated using Dixon’s up-and-down method. Hemodynamic variables, oxygen saturation and adverse events were also recorded. Results Dixon up-and-down method revealed that the EC50 of remifentanil was significantly higher in placebo group (2.65 ± 0.28 ng/mL) than in DXM group (2.02 ± 0.23 ng/ml) (P 0.05). Less adverse events occurred in DXM group, including the incidence of postoperative nausea and vomiting (PONV) and analgesia requirement with in the first 24 h following the procedure at ward. Conclusion Dexamethasone exerted analgesic effects with a rapid onset, and patients received dexamethasone 8 mg preoperative had a lower required EC50 of remifentanil during P-ESWL. It is also associated with reduced PONV in addition to reduced postoperative analgesic consumption in the first postoperative 24 h. Trial registration Registered in the Chinese Clinical Trial Registry (ChiCTR2300078171) on 30/11/2023.

Abstract Background Diabetic nephropathy (DN) has been a major factor in the outbreak of end-stage renal disease for decades. As the underlying mechanisms of DN development remains unclear, there is no ideal methods for the diagnosis and therapy. Objective We aimed to explore the key genes and pathways that affect the rate progression of DN. Methods Nanopore-based full-length transcriptome sequencing was performed with serum samples from DN patients with slow progression (DNSP, n = 5) and rapid progression (DNRP, n = 6). Results Here, transcriptome proclaimed 22,682 novel transcripts and obtained 45,808 simple sequence repeats, 1,815 transcription factors, 5,993 complete open reading frames, and 1,050 novel lncRNA from the novel transcripts. Moreover, a total of 341 differentially expressed transcripts (DETs) and 456 differentially expressed genes (DEGs) between the DNSP and DNRP groups were identified. Functional analyses showed that DETs mainly involved in ferroptosis-related pathways such as oxidative phosphorylation, iron ion binding, and mitophagy. Moreover, Functional analyses revealed that DEGs mainly involved in oxidative phosphorylation, lipid metabolism, ferroptosis, autophagy/mitophagy, apoptosis/necroptosis pathway. Conclusion Collectively, our study provided a full-length transcriptome data source for the future DN research, and facilitate a deeper understanding of the molecular mechanisms underlying the differences in fast and slow progression of DN.

Abstract Previous studies have supported a tumor‐suppressive role of semaphorin 3A (SEMA3A) in several tumors including oral squamous cell carcinoma (OSCC). However, in‐depth characterization of the role of SEMA3A in OSCC and the underlying molecular mechanisms is lacking. Gene and protein expressions were detected using quantitative real‐time PCR, western blot assay, and immunohistochemistry. OSCC cell metastasis was evaluated using Transwell and angiogenesis of human umbilical vein endothelial cells (HUVECs) was determined using tube formation assay. The interactions among molecules were predicted using bioinformatics analysis and validated using luciferase activity experiment and RNA immunoprecipitation assay. Pulmonary metastasis was evaluated using hematoxylin and eosin staining after constructing a lung metastasis tumor model in mice. SEMA3A expression was decreased in OSCC cells and its overexpression led to suppression of epithelial‐mesenchymal transition (EMT), migration, and invasion of OSCC cells and angiogenesis of HUVECs. miR‐32‐5p was identified as an upstream molecule of SEMA3A and long non‐coding RNA NR2F2 antisense RNA 1 (NR2F2‐AS1) was validated as an upstream gene of miR‐32‐5p. Further experiments revealed that the inhibitory effects of NR2F2‐AS1 overexpression on EMT, migration, invasion of OSCC cells, and angiogenesis of HUVECs as well as tumor growth and metastasis in mice were mediated via the miR‐32‐5p/SEMA3A axis. To conclude, NR2F2‐AS1 may attenuate OSCC cell metastasis and angiogenesis of HUVECs and suppress tumor growth and metastasis in mice via the miR‐32‐5p/SEMA3A axis.

Abstract In recent years, multi‐view clustering (MVC) has had significant implications in the fields of cross‐modal representation learning and data‐driven decision‐making. Its main objective is to cluster samples into distinct groups by leveraging consistency and complementary information among multiple views. However, the field of computer vision has witnessed the evolution of contrastive learning, and self‐supervised learning has made substantial research progress. Consequently, self‐supervised learning is progressively becoming dominant in MVC methods. It involves designing proxy tasks to extract supervisory information from image and video data, thereby guiding the clustering process. Despite the rapid development of self‐supervised MVC, there is currently no comprehensive survey analysing and summarising the current state of research progress. Hence, the authors aim to explore the emergence of self‐supervised MVC by discussing the reasons and advantages behind it. Additionally, the internal connections and classifications of common datasets, data issues, representation learning methods, and self‐supervised learning methods are investigated. The authors not only introduce the mechanisms for each category of methods, but also provide illustrative examples of their applications. Finally, some open problems are identified for further investigation and development.

Abstract The innate immune system is the first responder to infectious agents, cellular debris, and cancerous growths. This system plays critical roles in the antitumor immune responses by boosting and priming T cell-mediated cytotoxicity but is understudied due to the complexity and redundancy of its various downstream signaling cascades. We utilized a mathematical tool to holistically quantify innate immune signaling cascades and immunophenotype over 8,000 tumors from The Cancer Genome Atlas (TCGA). We found that innate immune activation was predictive of patient mortality in a subset of cancers. Further analysis identified PHF genes as transcripts that were associated with genomic stability and innate activation. Knockdown of PHF gene transcripts in vitro led to an increase in cell death and IFNB1 expression in a cGAS-dependent manner, validating PHF genes as potential anti-tumor targets. We also found an association between innate immune activation and both tumor immunogenicity and intratumor microbes, which highlights the versatility of this model. In conclusion, interrogating activation of innate immune signaling cascades demonstrated the importance of studying innate signaling in cancer and broadened the search for new therapeutic adjuvants.

Abstract Background Junior OB/GYN residents lack opportunities for fundamental surgical skills training of cesarean section, and most OB/GYN residents lack the experience of cervical laceration suturing due to its low incidence. Methods A porcine stomach simulation model was designed for obstetrics surgical training. The surface of the stomach simulated the uterus, and the pylorus and cardia simulated the cervical canal. Experience Materials are available from the nearby market. The total cost of the model is￥41. This model can be used in the training in uterus incision and repair of cesarean section and training in cervical laceration suturing. Conclusion The porcine stomach simulation model is pragmatic and realistic. They can be applied in the OB/GYN skill courses to introduce the fundamental obstetrics process to medical students and residents.

Abstract T cell senescence alters the homeostasis of distinct T cell populations and results in decayed adaptive immune protection in older individuals, but a link between aging and dynamic T cell clone changes has not been made. Here, using a newly developed computational framework, Repertoire Functional Units (RFU), we investigate over 6500 publicly available TCR repertoire sequencing samples from multiple human cohorts and identify age-associated RFUs consistently across different cohorts. Quantification of RFU reduction with aging reveals accelerated loss under immunosuppressive conditions. Systematic analysis of age-associated RFUs in clinical samples manifests a potential link between these RFUs and improved clinical outcomes, such as lower ICU admission and reduced risk of complications, during acute viral infections. Finally, patients receiving bone marrow transplantation show a secondary expansion of the age-associated clones upon stem cell transfer from younger donors. Together, our results suggest the existence of a ‘TCR clock’ that could reflect the immune functions in aging populations.

Abstract Background The persistent destructive power of cancer-related fatigue (CRF) has been regarded as the biggest influencing factor affecting the postoperative physical and mental health of patients with cervical cancer. During this process, patients might also experience different feelings of disease-related psychological. Therefore, this study aimed to adopt mindfulness-based stress reduction (MBSR) to intervene in patients with cervical cancer, and conducted follow-up for 3 and 6 months to observe the effects of changes in CRF, uncertainty in illness, coping styles, sense of coherence (SOC), and perceived social support (PSS). Methods A randomized controlled trial was conducted in ShengJing Hospital of China Medical University. A total of 102 patients were selected, and 78 patients completed the whole process, including 40 in the experimental group and 38 in the control group. Data were collected according to Cancer Fatigue Scale, Medical Coping Modes Questionnaire, Multidimensional Scale of Perceived Social Support, and Sense of Coherence-13. The change trend and difference of the two groups of research data were compared by repeated measurement analysis of variance. Bonferroni test was used for multiple tests between groups. Results The CRF, SOC, and coping styles of the MBSR group showed a decreasing trend (P

Abstract The activation of nuclear factor erythroid 2–related factor 2 (NRF2) has been observed in various cancers. Yet its exact contribution to the development of head and neck squamous cell carcinoma (HNSCC) remains undetermined. We previously found that NRF2 signaling is critical for the differentiation of squamous basal progenitor cells, while disruption of NRF2 causes basal cell hyperplasia. In this study, we revealed a correlation between elevated NRF2 activity and poor outcomes in HNSCC patients. We demonstrated that NRF2 facilitates tumor proliferation, migration, and invasion, as evidenced by both in vitro and in vivo studies. Significantly, NRF2 augments the expression of the antioxidant enzyme GPX2, thereby enhancing the proliferative, migratory, and invasive properties of HNSCC cells. Activation of GPX2 is critical for sustaining cancer stem cells (CSCs) by up-regulating NOTCH3, a key driver of cancer progression. These results elucidate that NRF2 regulates HNSCC progression through the NRF2-GPX2-NOTCH3 axis. Our findings proposed that pharmacological targeting of the NRF2-GPX2-NOTCH3 axis could be a potential therapeutic approach against HNSCC.

Lianhua Qingke tablets, a patented traditional Chinese medicine that has validated clinical efficacy for treating cough caused by severe acute respiratory syndrome coronavirus 2 infection, lack rigorous evidence-based research evaluating their effect on long coronavirus disease (COVID) cough. A randomized, double-blind, placebo-controlled, multicenter clinical study was conducted among patients with long COVID cough from 19 hospitals and 23 community health centers in China. Patients were randomized 1:1 to receive either Lianhua Qingke tablets or placebo orally for 14 days (four tablets, 1.84 g, three times a day). The primary endpoint indicator was the disappearance of cough, with the remission of cough also considered. Among 482 randomized patients, 480 (full analysis set 480; per-protocol set 470; safety set 480) were included in the primary analysis. According to the full analysis, the time until cough disappearance was significantly shorter in the trial group than in the control group, with a significant increase in the 14-day cough disappearance rate. Accordingly, the time to cough remission was significantly shorter in the trial group than in the control group. The change in the total symptom score was significantly greater in the trial group than in the control group on days 7 and 14, consistent with the results indicated by the visual analog scale (VAS) and cough evaluation test (CET) scores. No serious adverse events were recorded during the study. Lianhua Qingke tablets significantly improved the clinical symptoms of patients with long COVID cough.

Abstract Objective The aim of this study was to evaluate the effectiveness and safety of the nine most widely studied Vonoprazan (VPZ)-based treatment regimens along with traditional Proton pump inhibitor (PPI)-based treatment regimens in eradicating Helicobacter pylori (H. pylori) infection. Design Through searching PubMed, Embase, Cochrane Library, Web of Science, we exclusively included randomized controlled trials (RCTs) to investigate the efficacy of VPZ-based and PPI-based therapies for H. pylori infection. The included studies were evaluated for methodological quality using the Cochrane bias risk assessment tool, and the data analysis software was used to analyze the data accordingly. Results The RCTs were collected from the earliest available date up to August 2023. Twenty-one RCTs were included, with a total sample size of 5481. The results of the network meta-analysis showed that the eradication rate of the VPZ-based quadruple 14-day (VPZ-Q14) treatment regimen in Intention-to-treat (ITT) analysis was the highest (SUCRA: 0.874); The eradication rate of the VPZ-based quadruple 10-day (VPZ-Q10) treatment plan in Per-protocol (PP) analysis was the highest (SUCRA: 0.849). All regimens were well tolerated without significant differences. According to the probability ranking of safety, high-dose VPZ-based dual 14-day therapy (H-VPZ-D14) ranked first in SUCRA, reaching 0.952. This indicates that H-VPZ-D14 treatment is the safest with a relatively low incidence of adverse effect. Therefore, VPZ-based therapies not only have a higher eradication rate, but also possess satisfactory safety. Conclusion Compared with traditional PPI-based therapies, VPZ-based therapies have shown superior eradication effects. Based on the Ranking Plot of the Network, the VPZ-Q14 or VPZ-Q10 treatment regimen for H. pylori has a higher eradication rate and acceptable differences compared to other treatment regimens. In addition, for regions with high antibiotic resistance rates, we recommend a 14-day quadruple therapy with bismuth based on VPZ.

Abstract Multi-functional cysteine-targeting covalent warheads possess significant therapeutic potential in medicinal chemistry and chemical biology. Herein, we present novel unsaturated and asymmetric ketone (oxazolinosene) scaffolds that selectively conjugate cysteine residues of peptides and bovine serum albumin under normal physiological conditions. This unsaturated saccharide depletes GSH in NCI-H1299 cells, leading to anti-tumor effects in vitro. The acetyl group of the ketal moiety on the saccharide ring can be converted to other carboxylic acids in a one-pot synthesis. In this way, the loaded acid can be click-released during cysteine conjugation, making the oxazolinosene a potential multifunctional therapeutic agent. The reaction kinetic model for oxazolinosene conjugation to GSH is well established and was used to evaluate oxazolinosene reactivity. The aforementioned oxazolinosenes were stereoselectively synthesized via a one-step reaction of nitriles with saccharides and conveniently converted into a series of α, β-unsaturated ketone N-glycosides as prevalent synthetic building blocks. The reaction mechanisms of oxazolinosene synthesis were investigated through calculations and validated with control experiments. Overall, these oxazolinosenes can be easily synthesized and developed as cysteine-targeted covalent warheads carrying useful click-releasing groups.

Abstract Background The pretherapeutic differentiation of subtypes of primary intracranial germ cell tumours (iGCTs), including germinomas (GEs) and nongerminomatous germ cell tumours (NGGCTs), is essential for clinical practice because of distinct treatment strategies and prognostic profiles of these diseases. This study aimed to develop a deep learning model, iGNet, to assist in the differentiation and prognostication of iGCT subtypes by employing pretherapeutic MR T2-weighted imaging. Methods The iGNet model, which is based on the nnUNet architecture, was developed using a retrospective dataset of 280 pathologically confirmed iGCT patients. The training dataset included 83 GEs and 117 NGGCTs, while the retrospective internal test dataset included 31 GEs and 49 NGGCTs. The model’s diagnostic performance was then assessed with the area under the receiver operating characteristic curve (AUC) in a prospective internal dataset (n = 22) and two external datasets (n = 22 and 20). Next, we compared the diagnostic performance of six neuroradiologists with or without the assistance of iGNet. Finally, the predictive ability of the output of iGNet for progression-free and overall survival was assessed and compared to that of the pathological diagnosis. Results iGNet achieved high diagnostic performance, with AUCs between 0.869 and 0.950 across the four test datasets. With the assistance of iGNet, the six neuroradiologists’ diagnostic AUCs (averages of the four test datasets) increased by 9.22% to 17.90%. There was no significant difference between the output of iGNet and the results of pathological diagnosis in predicting progression-free and overall survival (P = .889). Conclusions By leveraging pretherapeutic MR imaging data, iGNet accurately differentiates iGCT subtypes, facilitating prognostic evaluation and increasing the potential for tailored treatment. Graphical Abstract

Interactions between bone cells and neurocytes are crucial for endosseous nerve and ensuing bone regeneration. However, absence of neural stem cells in bone makes the innervation of implant osseointegration a major challenge. Herein, a nanorod-like array of sodium hydrogen titanate (ST) co-doped with Co2+ and Co3+, namely STCh that behaves as a reactive oxygen species (ROS)-scavenging enzyme, was hydrothermally formed on Ti substrate. We show that the doped Co2+ and Co3+ locate at TiO6 octahedral interlayers and within octahedra of STCh lattice, appearing releasable and un-releasable, respectively, leading to an increase in Co3+/Co2+ ratio and enzyme activity of the array with immersion. The nanoenzyme-released Co2+ triggers macrophages (MΦs) towards M1 phenotype, then the nanoenzyme scavenges extracellular ROS inducing M1-to-M2 transition. The neurogenic factors secreted by STCh-regulated MΦs, in combination with the released Co2+, promote mesenchymal stem cells to differentiate into neurons and Schwann cells compared to sole Co2+and ST. STCh array greatly enhances nerve reconstruction, type-H capillary formation and ensuing osseointegration in normal rat bone, and antibacteria via engulfing S. aureus by MΦs and osteogenesis in infective case. This nanoenzyme provides an alternative strategy to orchestrate endosseous nerve regeneration for osseointegration without loading exogenous neurotrophins in implants.

When tunnel boring machines (TBMs) excavate through jointed rock masses, the cutting efficiency is strongly affected by the shear strength of joints, the mechanism of which, however, remains poorly understood. In this study, a series of disc-cutter indentation tests were conducted on granite rock mass specimens with different joint shear strengths. During the indentation, the cracking process was recorded by a digital image correlation (DIC) system. The deformation and strength of specimens, cracking behavior, rock breakage mode and cutting efficiency were quantitatively investigated. In addition, to investigate the combined effects of joint shear strength, orientation and spacing on the rock breakage mechanism, numerical rock mass models were established based on a particle flow code PFC2D. Experimental results reveal that the cracking of primary and secondary cracks changes from the mixed shear-tensile to tensile mode in the initial stage, while the joint shear strength does not affect the cracking mode in the subsequent propagation process. The rock breakage mode is classified to an internal block breakage mode, a cross-joint breakage mode and a cutters-dependent breakage mode. The cross-joint breakage mode is optimal for improving the cutting efficiency. Numerical simulation results reveal that the increase in the joint shear strength changes the internal block breakage mode to cross-joint breakage mode for rock masses of particular ranges of joint orientation and spacing. These findings provide basis for improving the TBM cutting efficiency through jointed rock masses.

Extrachromosomal circular DNA (eccDNA) has recently gained increasing attention due to its significant role in cancer and other pathophysiologic states. The majority of circular DNAs detected by Circle-seq are small-size eccDNAs with enigmatic functions. One major technical hurdle is to synthesize eccDNA for functional identification. Here, we describe CAES (Circle-seq based Artificial EccDNA Synthesis), a promising and reliable method for artificial eccDNA synthesis. Eight eccDNAs carrying different microRNA genes (eccMIR) found in gastric cancer tissues, ranging from 329 bp to 2189 bp in size, were created utilizing the CAES method. Exonuclease V and single restriction-endonuclease digestion identified the circular structure of synthetic eccDNAs. The DNA circularization efficiency afforded by CAES ranged from 15.6% to 31.1%, which was negatively correlated with the eccDNA length. In addition, we demonstrated that CAES-synthesized eccMIRs can express both miRNA-3p and − 5p molecules efficiently independent of a canonical promoter in human cell lines. Further assays proved that these eccMIRs were functional as they were able to repress the luciferase gene containing a miRNA-target sequence in the 3′UTR as well as the endogenous mRNA targets. Finally, kinetics study revealed that eccDNA exhibited a decay rate similar to the standard plasmids and linear DNA in cultured cells. Together, this study offers a rapid and convenient method for Circle-seq users to synthesize artificial eccDNAs. It also demonstrates the promising potential of eccMIR as a bacterial DNA-free vector for safe and robust miRNA overexpression in both basic research and therapeutic applications.

Exogenous gibberellic acid was applied to regulate fruit growth of grapes to acquire high quality seedless berries. The vascular bundles provide the pathway of water and nutrient transport into the fruit and play an important role in berry growth and sugar accumulation. Therefore, changes in berry size and quality are closely related to the structure and function of the vascular tissue. In this study, 10-year-old “Shine Muscat” grape vines were treated with GA3 in grapevine production. Based on previous research and experimental environmental conditions, four treatments were applied: elongating cluster（5 mg L−1 GA3 on Apr. 28）+ seedless（25 mg L−1 GA3 on May. 24）+ expanding（50 mg L−1 GA3 on Jun. 7） (T1), seedless（25 mg L−1 GA3 on May. 24）+ expanding（50 mg L−1 GA3 on Jun. 7） (T2), expanding（50 mg L−1 GA3 on Jun. 7） (T3) and water (CK). Compared to CK, all fruits treated with GA3 had greater berry size. In addition, GA3 treated grapes had greater vascular bundle areas, including the areas of both phloem and xylem, as well as a greater number of vessels compared to control fruit. During the first rapid growth stage, water transport into the grape was rapid and did not differ among treatments. During veraison, the water transport rate among the four treatments differed, and the rank of speed was T2>T3>CK>T1. Therefore, we found that GA3 treatment can significantly promote the differentiation of vascular tissues and improve water transport capacity and phloem sugar unloading; T2 promoted the development of vascular bundles, enhanced water transport speed and phloem sugar unloading of fruit after veraison, and increased berry size.

Word of mouth (WOM) is crucial in customers’ purchasing decisions and affects companies’ long-term profits. This study examines the long-term trends in companies’ dynamic pricing and profits by using the Hamiltonian function method and dynamic simulation to construct a dynamic equation. It takes into account the intensity of word of mouth faced by companies and analyzes the level of publicity and consumers’ predictions of product quality. In this paper, we also discuss the interactive processes between WOM and advertising levels, the two most prominent market factors, and their ultimate impact on companies. The experimental results show that elevated levels of external advertising can potentially prompt companies to establish higher product pricing strategies, particularly in scenarios where the intensity of word of mouth is pronounced. In the initial phases of market development, the saturation level of consumers within the market exerts a negligible influence on companies’ long-term profit margins. Conversely, the rate of natural attrition from consumers’ upper threshold of product quality expectations distinctly impacts companies’ profitability.

Abstract Osteoarthritis (OA) is a chronic degenerative disease characterized by articular cartilage destruction and subchondral bone reconstruction in the early stages. Bergenin (Ber) is a cytoprotective polyphenol found in many medicinal plants. It has been proven to have anti-inflammatory, antioxidant, and other biological activities, which may reveal its potential role in the treatment of OA. This study aimed to determine the potential efficacy of Ber in treating OA and explore the possible underlying mechanism through network pharmacology and validation experiments. The potential co-targets and processes of Ber and OA were predicted by using network pharmacology, including a Venn diagram for intersection targets, a protein‒protein interaction (PPI) network to obtain key potential targets, and GO and KEGG pathway enrichment to reveal the probable mechanism of action of Ber on OA. Subsequently, validation experiments were carried out to investigate the effects and mechanisms of Ber in treating OA in vitro and vivo. Ber suppressed IL-1β-induced chondrocyte apoptosis and extracellular matrix catabolism by inhibiting the STAT3, NF-κB and Jun signalling pathway in vitro. Furthermore, Ber suppressed the expression of osteoclast marker genes and RANKL-induced osteoclastogenesis. Ber alleviated the progression of OA in DMM-induced OA mice model. These results demonstrated the protective efficacy and potential mechanisms of Ber against OA, which suggested that Ber could be adopted as a potential therapeutic agent for treating OA.

Abstract Sulfur deposition can result in an increase in the wall thickness of high-sulfur natural gas gathering pipelines, leading to issues like unstable pipeline flow. It is crucial to reveal the aggregation of sulfur particles at key locations of high-sulfur natural gas gathering pipelines to predict the location and amount of sulfur deposition in the pipelines. In this paper, the Euler–PBM (Population balance model) coupling is used to establish a numerical simulation model of gas–solid two-phase pipe flow accompanied by sulfur particle agglomeration in the pipe bends, focusing on the influence of sulfur particle volume fraction, pipe inclination angle and inlet flow velocity on sulfur particles agglomeration behavior. The results show that the sulfur particles have a significant agglomeration effect at the bend of the collecting pipeline, and the agglomeration growth occurs to different degrees throughout the bend, and the main area of sulfur particles agglomeration is near the top wall of the pipeline, followed by other areas near the wall of the pipeline. When the inlet volume fraction of sulfur particles was increased from 0.05 to 0.25%, and the inclination angle of the pipe was increased from 30° to 90°, the distribution range of sulfur particle size after agglomeration became wider, and the maximum size of sulfur particles was 187.56 μm, and the effect of sulfur particle agglomeration was enhanced; the inlet flow rate was increased from 3.0 to 9.0 m/s, and the reduction range of sulfur particle size after agglomeration was 5.68–9.87 μm. The maximum particle size of sulfur particles also decreased, and the effect of sulfur particle agglomeration was weakened.

Abstract The free-field switching of the perpendicular magnetization by the out-of-plane polarized spin current induced spin-orbit torque makes it a promising technology for developing high-density memory and logic devices. The materials intrinsically with low symmetry are generally utilized to generate the spin current with out-of-plane spin polarization. However, the generation of the out-of-plane polarized spin current by engineering the symmetry of materials has not yet been reported. Here, we demonstrate that paramagnetic CaRuO3 films are able to generate out-of-plane polarized spin current by engineering the crystal symmetry. The non-uniform oxygen octahedral tilt/rotation along film’s normal direction induced by oxygen octahedral coupling near interface breaks the screw-axis and glide-plane symmetries, which gives rise to a significant out-of-plane polarized spin current. This spin current can drive field-free spin-orbit torque switching of perpendicular magnetization with high efficiency. Our results offer a promising strategy based on crystal symmetry design to manipulate spin current and could have potential applications in advanced spintronic devices.

Abstract Background Clear cell odontogenic carcinoma (CCOC) is an odontogenic carcinoma characterized by sheets and islands of vacuolated and clear cells. The diagnosis of atypical CCOC can pose a challenge when tumor cells deviate from their characteristic clear morphology, even with the aid of genetic profiling for CCOC identification. Case presentation In this manuscript, we detailed the inaugural instance of a recurrently recurring clear cell odontogenic carcinoma (CCOC) with pronounced squamous differentiation in a 64-year-old male. The primary tumor in this individual initially displayed a biphasic clear cell phenotype. However, subsequent to the third recurrence, the clear tumor cells were entirely supplanted by epidermoid cells characterized by eosinophilic cytoplasm, vesicular chromatin, and prominent nucleoli. Notable aggressive attributes such as necrosis, conspicuous cytological malignancy, perineural dissemination, and vascular invasion were noted. Additionally, the tumor progressed to manifest lung metastases. The tumor cells exhibited positive immunoreactivity for AE1/AE3, KRT19, Pan-CK, EMA, P40, P63, CK34βE12, and P53, while they tested negative for CK35βH11, KRT7, S-100, and neuroendocrine markers. The Ki-67 proliferation index was calculated at an average of 15%. Furthermore, FISH analysis unveiled the presence of the EWSR1::ATF1 gene fusion. Conclusions This case illustrated a rare and aggressive case of CCOC characterized by significant squamous differentiation upon recurrence of the tumor.

Abstract Background Systemic conversion therapy provides patients with initially unresectable hepatocellular carcinoma (HCC) the chance to salvage radical liver resection and superior survival outcomes, but the optimal conversion strategy is unclear. Methods A systematic literature search was conducted on PubMed, EMBASE, Web of Science, Scopus, and the Cochrane Library between 2007 and 2024 focusing on studies reporting conversion therapy for HCC. The treatment groups were divided into Tyrosine kinase inhibitors (TKI), TKI plus loco-regional therapy (LRT), TKI plus anti-PD-1 therapy (TKI + PD-1), TKI + PD-1 + LRT, immune checkpoint inhibitors (ICI) plus LRT, and Atezolizumab plus bevacizumab (A + T) groups. The conversion to surgery rate (CSR), objective response rate (ORR), grade ≥ 3 treatment-related adverse events (AEs), overall survival (OS) and progression-free survival (PFS) were analyzed. Results 38 studies and 4,042 patients were included. The pooled CSR were 8% (95% CI, 5-12%) in TKI group, 13% (95% CI, 8-19%) in TKI + LRT group, 28% (95% CI, 19-37%) in TKI + PD-1 group, 33% (95% CI, 25-41%) in TKI + PD-1 + LRT group, 23% (95% CI, 1-46%) in ICI + LRT group, and 5% (95% CI, 3-8%) in A + T group, respectively. The pooled HR for OS (0.45, 95% CI, 0.35–0.60) and PFS (0.49, 95% CI, 0.35–0.70) favored survival benefit of conversion surgery. Subgroup analysis revealed that lenvatinib + PD-1 + LRT conferred higher CSR of 35% (95% CI, 26-44%) and increased ORR of 70% (95% CI, 56-83%). Conclusions The current study indicates that TKI + PD-1 + LRT, especially lenvatinib + PD-1 + LRT, may be the superior conversion therapy with a manageable safety profile for patients with initially unresectable HCC. The successful conversion therapy favors the superior OS and PFS compared with systemic treatment alone. Trial registration International prospective register of systematic reviews (PROSPERO) (registration code: CRD 42024495289).

Abstract Postpartum post-traumatic stress disorder (PP-PTSD) is a severe mental disorder worldwide. In recent years, some studies have reported that PP-PTSD stems from birth trauma. The present study was dedicated in finding ways to predict the occurrence of emergency caesarean section (ECS), trying to analyze the methods to reduce incidence of PP-PTSD on this basis, further exploring the neuroimaging changes in PP-PTSD. A total of 245 primiparas with intention of vaginal delivery were recruited. The internal tocodynamometry measurement was performed during labor for all mothers, and respectively taken at 3–5 cm, 5–8 cm, and 8–10 cm of cervical dilation. The receiver operating characteristic (ROC) curve and Binary logistic regression analyses were also performed to identify fetal head descending thrust that might help in the prediction of ECS. Resting-state magnetic resonance imaging (MRI) was performed on 26 patients diagnosed with PP-PTSD of 245 mothers, the amplitude of low-frequency fluctuations (ALFF) technology was used to observe the spontaneous neural activity of all PP-PTSD patients and correlation analyses were performed. We found that the natural delivery rate of mothers with fetal head descending thrust

Abstract Background Loneliness and social isolation have been found to be associated with various health-related outcomes. Our study aimed to evaluate the association of loneliness and social isolation with the risk of glaucoma. Methods A total of 373,330 participants from the UK Biobank without glaucoma at recruitment were included in this study. Self-reported questionnaires were used to define loneliness and social isolation. Incident glaucoma events were identified by hospital inpatient admissions and self-reported data. COX proportional hazards models adjusted for sociodemographic, lifestyle, and health-related factors were used to estimate hazard ratios (HRs) and 95% CIs. Results During a median follow-up of 13.1 (interquartile range: 12.3–13.9) years, 6,489 participants developed glaucoma. After adjusting for confounding factors, loneliness (yes vs. no: adjusted HR: 1.16; 95% CI: 1.04–1.30; P = 0.009) and social isolation (yes vs. no: adjusted HR: 1.08; 95% CI: 1.01–1.16; P = 0.033) were associated with an increased risk of glaucoma. Conclusions In this population-based prospective cohort study, loneliness and social isolation were associated with a higher risk of glaucoma.

To further develop a protein-polysaccharide composite fat replacer in low-fat meat products, this used pumpkin seed protein (PSP) and carrageenan to prepare a composite emulsion fat replacer, and added it to myofibrillar protein (MP) to form heat induced gel. The effects of the composite emulsion formed by PSP and carrageenan at various additive amounts on the properties of MP gels were investigated through the determination of gel moisture distribution, textural properties, microstructure, rheological properties, and other indexes. The results showed that when PSP and carrageenan composite emulsion was added at 50%, the water-holding properties and strength of the gel significantly improved (P