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Xian He,1,2 Xin Ran,1 Dan Liang,2 Hongxia Fan,3 Yuping Ran1 1Department of Dermatovenereology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Allergy, Chengdu First People’s Hospital, Chengdu, People’s Republic of China; 3Department of Ultrasonic, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Yuping Ran, Tel +8618980601697, Email ranyuping@vip.sina.comAbstract: An infantile hemangioma is a congenital benign tumor formed by the proliferation of vascular cells during the embryonic stage. It is more common in the skin but can also occur in the mucous membranes, liver, brain and muscle. Hepatic hemangioma appears to be a benign tumor; however, it may lead to poor outcomes because of severe complications, such as high-output cardiac failure. The main treatment of hepatic hemangioma in infants is oral drugs, such as propranolol and glucocorticoids, but the clinical response is not always satisfactory. We describe a rare case of a 2-month-old boy who presented with infantile cutaneous and hepatic hemangiomas. By using dermoscopy and observations of the abdominal color Doppler ultrasound, after 9 months of oral treatment with itraconazole solution, the infantile cutaneous hemangioma complicated with hepatic hemangioma was eventually cured. There was no liver or kidney function damage during the whole treatment period. Itraconazole oral solution for the treatment of infantile cutaneous hemangioma complicated with hepatic hemangioma showed good efficacy, compliance, and safety in this case.Keywords: infantile hemangioma, cutaneous, hepatic, itraconazole oral solution, dermoscopy, color ultrasonic

Hong Wang,1,&ast; Tao Yang,2,&ast; Xiaodan Yu,3,&ast; Zhihong Chen,4 Yajuan Ran,5 Jiajia Wang,6 Guangming Dai,1 Huojin Deng,7 Xinglong Li,8 Tao Zhu8 1Respiratory Medicine, First People’s Hospital of Suining City, Suining, 629000, Sichuan, People’s Republic of China; 2Thoracic Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 3Respiratory Medicine, Fifth People’s Hospital of Chengdu, Chengdu, 610000, Sichuan, People’s Republic of China; 4Respiratory Medicine, Zhongshan Hospital of Fudan University, Shanghai, 20032, People’s Republic of China; 5Pharmacy Department, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 6Rheumatology Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 7Respiratory Medicine, ZhuJiang Hospital of Southern Medical University, Guangzhou, Guangdong, 510280, People’s Republic of China; 8Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Zhu, Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China, Tel +86 23 63693094, Email zhutao063020@163.comBackground/Purpose: A patient’s length of hospital stay (LHS) is associated with the severity and outcome of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Therefore, identification of patients with prolonged LHS at an early stage can potentially reduce the risk of adverse events and treatment costs in patients with AECOPD. Therefore, this study aimed to explore the independent predictors of prolonged LHS in AECOPD patients.Patients and Methods: This multicenter cross-sectional study was conducted at two tertiary hospitals between January 2019 and August 2020. Demographic data, underlying diseases, symptoms, and laboratory findings were collected. Univariate analysis was used to identify variables with significant differences. A collinearity diagnostic was applied to the selected variables before the establishment of the regression model. Ordinal logistic regression was performed to explore the independent risk factors for prolonged LHS in patients with AECOPD.Results: In total, 598 patients with AECOPD were screened. Finally, the LHS of 111, 218, and 100 patients was < 7, 7– 10, and ≥ 11 days, respectively. Significant differences in the 12 variables were found in the univariate analysis. Because collinearities among white blood cells (WBC), neutrophils (NS), and NS% were observed, WBC and NS% were excluded. Subsequently, an ordinal logistic regression model identified that rates of hypertension and chronic cor pulmonale (CCP), neutrophil–lymphocyte ratio (NLR), and erythrocyte sedimentation rate (ESR) were independent predictors of prolonged LHS in AECOPD patients.Conclusion: Collectively, our results showed that inflammatory status, hypertension, and CCP were independently associated with LHS in patients with AECOPD. These data indicate that early and appropriate administration of antibiotics and anti-inflammatory drugs is essential for reducing LHS. Hypertension and CCP were independent predictors of worse outcomes in patients with AECOPD. Therefore, advanced management and care should be provided to AECOPD patients with hypertension and/or CCP on admission.Keywords: acute exacerbation of chronic obstructive pulmonary disease, chronic cor pulmonale, erythrocyte sedimentation rate, hypertension, length of hospital stay, neutrophil–lymphocyte ratio

Yu Ran, Qiang Yi, Cong Li Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Cong LiDepartment of Gynecology, The First Affiliated Hospital of Chongqing Medical University, No. 1 YouYi Road, YuZhong District, Chongqing, People’s Republic of ChinaTel +8615334506105Fax +86023 89011080Email b05104@126.comPurpose: To explore the value of anti-Mullerian hormone (AMH) in patients with polycystic ovary syndrome (PCOS) with different phenotypes and ages, and to identify the relationship between hyperandrogenism (HA) and polycystic ovary morphology (PCOM), in a Chinese cohort.Methods: A total of 2262 women (1631 with PCOS and 631 controls) were enrolled. The serum AMH and total testosterone (TT) were analyzed, the AMH levels of each subgroup were compared, and the value of each phenotype and age group of patients with PCOS was evaluated.Results: The level of AMH in women with PCOS (mean±SD, 8.63± 4.73 ng/mL) was higher than that in controls (5.57± 3.31 ng/mL) (P< 0.01). The level of AMH in the PCOM subgroup (11.19± 6.4 ng/mL) was significantly higher than that in the HA subgroup (8.58± 4.74 ng/mL) (P< 0.01), and both were higher than that in controls (P< 0.01). AMH was higher in PCOS patients than in controls, but the same values were found in subgroups of PCOS patients under 30 years old.Conclusion: AMH changed in different subgroups of PCOS, which was the possible reason why AMH was not a diagnostic indicator. However, AMH could help to differentiate between clinical subgroups, as it was strongly related with PCOM but not with HA. AMH changed substantially with age, but was stable in PCOS patients under 30 years old.Keywords: anti-Mullerian hormone, polycystic ovary syndrome, hyperandrogenism, polycystic ovary morphology

Qiang Yi, Yu Ran, Cong Li Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Cong Li No. 1 YouYi Road, YuZhong District, Chongqing 400010, People’s Republic of ChinaTel +8615334506105Fax +8623 89011080Email b05104@126.comObjective: To investigate whether patients with epithelial ovarian cancer were affected by delayed chemotherapy during the coronavirus disease pandemic in 2020.Materials and Methods: A delay of more than 21 days in the planned chemotherapy was defined as “delayed chemotherapy.” Forty-five patients with epithelial ovarian, fallopian tube, and peritoneal cancer were delayed between January 1 and March 30, 2020 in the First Affiliated Hospital of Chongqing Medical University. Thirty-two cases were enrolled in this study. Neoadjuvant chemotherapy was used in 8 cases; palliative chemotherapy was used in 5 cases; and maintenance chemotherapy was used in 19 cases. Data included age, pathological type, surgical pathological stage, chemotherapy time and CA125 levels were collected. The half-life of CA125 and the decrease in CA125 levels before and after delayed chemotherapy were calculated.Results: No patient got coronavirus disease. Compared with patients of ovarian cancer, fallopian tube epithelial cancer and peritoneal epithelial cancer in the same periods in 2019, the half-life of CA125 in neoadjuvant chemotherapy group and recurrence chemotherapy group were more than 20 days, but there was no significant difference. Only when the delayed chemotherapy took place before CA125 turned negative, accompanied by an interval of more than 60 days, the CA125 half-life and the decreased range of CA125 were totally affected.Conclusion: There was no evidence to support that once chemotherapy was delayed it would influence the decrease of CA125, but whether it would affect the long-term effects such as recurrence and five-year survival rate remains to be further followed up.Keywords: epithelial ovarian cancer, CA125, delayed chemotherapy, half-life

Yu Ran, Qiang Yi, Cong Li Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing City, People’s Republic of ChinaCorrespondence: Cong LiDepartment of Gynecology, The First Affiliated Hospital of Chongqing Medical University, YuZhong District, Chongqing City 400010, People’s Republic of ChinaTel +8615334506105Fax +86(23) 89011080Email b05104@126.comObjective: To analyze the status of insulin resistance and hyperlipidemia in the regulation of menstrual cycle in patients undergoing sleeve gastrectomy (LSG).Materials and Methods: Retrospective analysis of a typical metabolic syndrome population: 65 cases of sexually mature women underwent weight reduction surgery from January 2015 to June 2018, and for 35 of these cases we collected all clinical data including age, menstrual status, body mass index (BMI), waist-to-hip ratio (WHR), blood lipid level, homeostasis model assessment in insulin resistance (HOMA-IR) and free androgen index (FAI). Sixteen of these patients had menstrual disorder that was characterized by oligomenorrhea and their menstrual cycle was > 2 months or < 24 days before operation, while their menstrual cycle recovered approximately 1 month to one year after sleeve gastrectomy.Results: The age of our 35 patients with metabolic syndrome was 15– 40 years; 19 cases were in the menstrual regularity group and 16 cases in the menstrual disorder group. On analysis of metabolic factors in the two groups, only BMI and FAI distribution in the two groups were statistically different, while lipid levels and insulin resistance levels for abnormal menstrual cycle were not statistically significant. The analysis of blood lipid components showed that high triglyceride levels and high cholesterol levels increased the occurrence of menstrual disorders.Conclusion: BMI can be used as one of the important metabolic indicators of menstrual disorders in patients with metabolic syndrome. Excess androgen can increase the occurrence of menstrual disorders, leading to polycystic ovarian syndrome (PCOS). Although insulin resistance is universal in patients with metabolic syndrome, it is not a specific factor that affects menstrual cycle. Hyperlipidemia, especially triglyceride composition, may be one of the driving factors of menstrual disorder.Keywords: sleeve gastrectomy, metabolic syndrome, menstrual cycle, hyperlipidemia

Xi Zhang,1 Yuge Ran,1 Kunjie Wang,2 Yuanxue Zhu,2 Jinghua Li3 1Department of Radiation Oncology, 2Department of Medical Oncology, 3Department of Hepatobiliary Surgery, Affiliated Hospital of Hebei University, Baoding, People’s Republic of China Purpose: Anti-programmed cell death receptor-1 (PD-1) antibodies have demonstrated antitumor activity in many cancer entities. Hepatic adverse events (AEs) are one of its major side effects, but the overall risks have not been systematically evaluated. Thus, we conducted this meta-analysis to investigate the overall incidence and risk of developing hepatic AEs in cancer patients treated with PD-1 inhibitors. Methods: PubMed, Embase, and oncology conference proceedings were searched for relevant studies. Eligible studies were randomized controlled trials of cancer patients treated with PD-1 inhibitors with adequate data on hepatic AEs. Results: A total of nine randomized controlled trials with a variety of solid tumors were eligible for the meta-analysis. The use of PD-1 inhibitors significantly increased the risk of developing all-grade hepatic AEs but not for high-grade hepatic AEs in comparison with chemotherapy or everolimus control. Additionally, the risk of all-grade and high-grade hepatic AEs with a nivolumab/ipilimumab combination was substantially higher than ipilimumab. No significant differences in the risk of all-grade and high-grade hepatic AEs were found between PD-1 inhibitors monotherapy and ipilimumab. Conclusion: While the use of PD-1 inhibitors is associated with an increased risk of developing hepatic AEs in cancer patients, this is primarily for lower grade events. Keywords: cancer, hepatic toxicities, PD-1 inhibitors, meta-analysis

We present RASPA3, a molecular simulation code for computing adsorption and diffusion in nanoporous materials and thermodynamic and transport properties of fluids. It implements force field based classical Monte Carlo/molecular dynamics in various ensembles. In this article, we introduce the new additions and changes compared to RASPA2. RASPA3 is rewritten from the ground up in C++23 with speed and code readability in mind. Transition-matrix Monte Carlo is added to compute the density of states and free energies. The Monte Carlo code for rigid molecules is based on quaternions, and the atomic positions needed in the energy evaluation are recreated from the center of mass position and quaternion orientation. The expanded ensemble methodology for fractional molecules, with a scaling parameter λ between 0 and 1, now also keeps track of analytic expressions of dU/dλ, allowing independent verification of the chemical potential using thermodynamic integration. The source code is freely available under the MIT license on GitHub. Using this code, we compare four Monte Carlo (MC) insertion/deletion techniques: unbiased Metropolis MC, Configurational-Bias Monte Carlo (CBMC), Continuous Fractional Component MC (CFCMC), and CB/CFCMC. We compare particle distribution shapes, acceptance ratios, accuracy and speed of isotherm computation, enthalpies of adsorption, and chemical potentials, over a wide range of loadings and systems, for the grand canonical ensemble and for the Gibbs ensemble. [ABSTRACT FROM AUTHOR]

Abstract The abrasive water-jet (AWJ) erosion process involves the complex interaction between fluid medium, abrasive particles and solid material, which brings great challenges to the establishment of numerical model. Because traditional grid-based methods are not suitable for the problems of local deformation and material removal, the meshfree method smoothed particle hydrodynamics (SPH), based on the unresolved coupling and the discrete element method (DEM), is adopted to establish the model for AWJ study. The fluid medium is treated as a weakly compressible viscous liquid, the solid material is treated as an elastic-plastic material, and the abrasives are treated as rigid bodies. The fluid and solid phases are discretized with SPH particles, and the abrasives are described with DEM particles. The Johnson-Cook (J-C) and Johnson-Holmquist-II (JH-2) constitutive models are used to describe the stress-strain behavior of ductile and brittle materials, respectively. The effectiveness of the numerical model is further verified by AWJ impact experiments. The plastic deformation and cumulative failure characteristics of ductile materials, and the crack formation and propagation characteristics of brittle materials are systematically analyzed. The results provide insight for the AWJ research and lay a foundation for investigation of other complex fluid-particle flow in a numerical way.

【Objective】 Subsurface drip fertigation is an irrigation technique to simultaneously deliver water and dissolved nutrients into the root zone. Its efficacy depends on many factors. In this paper, we investigate the combined effect of phosphate fertilizer types and dripline depth on distribution of nitrogen and phosphorus in soil and grain yield of maize. 【Method】 The experiments were conducted in tanks grown with maize in a rain shelter, using two types of fertilizers: ammonium polyphosphate (APP, P1) and monoammonium phosphate (MAP, P2). The control is no fertilization (CK). The driplines were buried at the depths of 0 cm (D1) and 15 cm (D2). In each treatment, we measured the spatial variation of nitrogen and phosphate, as well as grain yield. 【Result】 Nitrogen applied in the drip fertigation can move to the edge of the maize roots and accumulate there, while the phosphorus was absorbed by soil. The polymerized phosphate fertilizer (P1) weakened soil adsorption and fixation compared to the normal phosphate fertilizer (P2). Soil available phosphorus content in the APP was 15% higher than that in MAP. Irrigation facilitated phosphorus movement in soil and improved uniformity of its distribution, with the bioavailable phosphorus in D2 being 17% higher than in D1. Phosphorus application significantly promoted root growth, with the root length density at the jointing stage being 35% and 19% higher in P1 and P2 than in CK, respectively. It was also found that D2 increased root length density by 12%, compared to D1. Phosphorus application increased bioavailable phosphorus and root length density. This in turn enhanced dry matter accumulation and root uptake of nitrogen and phosphorus, thereby increasing the final grain yield. P1 increased the grain yield by 3% compared to P2, and 21% compared to CK. 【Conclusion】 Our results showed that subsurface fertigation using APP reduced soil phosphorus adsorption, which in turn promoted maize growth and increased the final grain yield.

Objective To explore the inhibitory effect of berberine （BBR） on contrast-induced nephropathy （CIN） and clarify the underlying mechanism. Methods Sprague-Dawley （SD） rats were utilized for constructing a rat CIN model. BBR treatment group （M+B） received a gavage of 200 mg/kg BBR while control group （Con） and model group （Mod） had an oral intake of the same volume of normal saline. Human kidney cortex proximal tubule epithelial cells （HK-2） were utilized for constructing a CIN cell model in vitro. No special treatment was offered to HK-2 cells in Con group. HK-2 cells in Mod group were treated with 50 g/L ioversol for 24 h and HK-2 cells in M+B group 50 g/L ioversol and 30 μmol/L BBR for 24 h. Akt agonist （SC79） and Akt inhibitor （MK2206） were utilized for confirming the effect of BBR on protein kinase B-forkhead box O3-nuclear factor erythroid 2-related factor 2 （Akt-Foxo3a-Nrf2） regulatory axis. Serum creatinine （Scr） detection and hematoxylin-eosin （HE） stain were employed for evaluating renal injury in rats. Annexin V-propidium iodide （annexin V-PI） stain was used for detecting cell apoptosis. And Western blot was utilized for detecting the protein expression of Akt-Foxo3a-Nrf2 axis.Results The level of Scr was higher in Mod group than that in Con group [（58.83 ± 7.96）μmol/L vs （23.52 ± 0.78）μmol/L，P＜0.05]. And it was lower in M+B group than that in Mod group [（39.64 ± 2.52）μmol/L vs （58.83 ± 7.96）μmol/L，P＜0.05]. HE stain indicated that kidney morphology was normal and renal tubular epithelial cells remained intact in Con group. In Mod group， structure of renal tubules was disarrayed with diffuse death of epithelial cells and obvious vacuolar degeneration of renal tubular epithelial cells. In M+B group， morphology of renal tubules was partially restored and vacuolar degeneration of renal tubule epithelial cells and cell death lessened. Western blot results indicated that， as compared with Con group， the expression of phospho-protein kinase B （p-Akt） was up-regulated in CIN rats and ioversol treated HK-2 cells. And the difference was statistically significant （P＜0.05）. In M+B group， the expression of p-Akt dropped as compared with Mod group （P＜0.05）. Annexin V-PI apoptosis assay indicated that， as compared with Con group， cell apoptosis spiked in Mod group [（12.65 ± 1.25）% vs （27.44 ± 0.73）%，P＜0.05]. As compared with Mod group， cell apoptosis declined in M+B group [（27.44 ± 0.73）% vs （24.81 ± 0.49）%，P＜0.05]. As compared with M+B group， cell apoptosis rose in BBR plus SC79 treatment group [（24.81 ± 0.49）% vs （27.50 ± 0.35）%，P＜0.05]. As compared with Mod group， cell apoptosis declined in MK2206 treatment group [（27.65 ± 0.56）% vs （25.20 ± 0.64）%，P＜0.05]. As compared with M+B group， MK2206 plus BBR further reduced ioversol-induced HK-2 cell apoptosis [（24.51 ± 0.52）% vs （21.24 ± 0.99）%，P＜0.05]. Conclusion BBR may suppress CIN in vivo and in vitro through regulating Akt-Foxo3a-Nrf2 axis in a p-Akt dependent mode.

Coordination compounds of polydentate nitrogen ligands with metals are used extensively in research areas such as catalysis, and as models of complex active sites of enzymes in bioinorganic chemistry. Tris(2-pyridylmethyl)amine (TPA) is a tripodal tetradentate ligand that is known to form coordination compounds with metals, including copper, iron and zinc. The related compound, tris[(6-bromopyridin-2-yl)methyl]amine (TPABr3), C18H15Br3N4, which possesses a bromine atom on the 6-position of each of the three pyridyl moieties, is also known but has not been heavily investigated. The molecular structure of TPABr3 as determined by X-ray diffraction is reported here. The TPABr3 molecule belongs to the triclinic, P\overline{1} space group and displays interesting intermolecular Br...Br interactions that provide a stabilizing influence within the molecule.

Objective To understand the establishment and application experience of whole-course management nursing path for lymphoma patients by navigation nurses, and to provide reference for the construction of whole-course management for lymphoma patients. Methods In November 2023, a purposive sampling method was used to select 11 navigation nurses for lymphoma management in the Department of Lymphatic Hematology and Pediatric Medicine at the Guangxi Medical University Cancer Hospital for semi-structured interviews. The Colaizzi 7-step method was used to organize and analyze the dataResults The application experience of navigation nurses can be summarized into three main themes and four sub themes: recognizing the importance of managing nursing paths throughout the entire process (perceiving the value of professional roles), real work emotional experiences (positive feedback, negative psychological feelings), and factors affecting long-term career development (challenges in ensuring the quality of specialized practice). Conclusion Navigation nurses play an indispensable role in the overall management of lymphoma. Valuing their establishment and application experience in the management of nursing paths throughout the entire process can further enhance the value of full-time nursing, thereby increasing their work engagement, initiative, and creativity, and better playing the role of navigation nurses in the overall management of lymphoma; Ultimately achieving high-quality development of the hospital's dedicated nursing team. (目的 了解导航护士对淋巴瘤患者全程管理护理路径建立及应用体验, 为实施淋巴瘤患者全程管理的建设提供参考依据。方法 于2023年11月在广西医科大学附属肿瘤医院淋巴血液及儿童内科采用目的抽样法选取淋巴瘤全程管理的导航护士11名进行半结构式访谈, 并采用Colaizzi的七步资料分析法进行资料整理与分析。结果 导航护士的应用体验可归纳为3大主题4个次主题: 认可全程管理护理路径的重要性(感知专业角色价值), 真实工作情感体验(正性反馈、负性心理感受)和职业长远发展影响因素(专科实践质量保障挑战)。结论 导航护士在全程管理工作中发挥着不可或缺的作用, 重视其在全程管理护理路径的建立及应用体验, 可进一步发挥专职护理价值, 进而增强其工作投入度、主动性与创造力, 更好地发挥导航护士在淋巴瘤全程管理的作用; 最终实现医院专职护理队伍高质量发展。)

Abstract Background Shear Wave Elastography (SWE) offers quantitative insights into the hardness and elasticity characteristics of tissues. The objective of this study is to investigate the correlation between SWE of the menisci and MRI-assessed degenerative changes in the menisci, with the aim of providing novel reference source for improving non-invasive evaluation of meniscal degenerative alterations. Methods The participants in this study were selected from patients who underwent knee joint MRI scans at our hospital from February 2023 to February 2024. The anterior horns of both the medial and lateral menisci were evaluated using SWE technique. The differences in elastic values of meniscus among different MRI grades were compared. The correlation between elastic values and MRI grades, as well as various parameters, was analyzed. Using MRI Grade 3 as the gold standard, the optimal cutoff value for meniscal tear was determined. The intraclass correlation coefficient (ICC) was employed to evaluate the reliability of repeated measurements performed by the same observer. Results A total of 104 female participants were enrolled in this study, with 152 lateral menisci (LM) and 144 medial menisci (MM) assessed. For the male group, 83 individuals were included, with 147 LM and 145 MM evaluated. The results demonstrated statistically significant differences in the elasticity values of the menisci at the same anatomical sites across different MRI grades (P 0.79). Conclusions The meniscal elasticity values measured by SWE exhibit a significant positive correlation with the grades of degeneration assessed by MRI. Furthermore, the elasticity values of the meniscus are found to increase with advancing age and elevated BMI.

Abstract Astrocytes, the predominant glial cells in the central nervous system, play essential roles in maintaining brain function. Reprogramming induced pluripotent stem cells (iPSCs) to become astrocytes through overexpression of the transcription factors, NFIB and SOX9, is a rapid and efficient approach for studying human neurological diseases and identifying therapeutic targets. However, the precise differentiation path and molecular signatures of induced astrocytes remain incompletely understood. Accordingly, we performed single-cell RNA sequencing analysis on 64,736 cells to establish a comprehensive atlas of NFIB/SOX9-directed astrocyte differentiation from human iPSCs. Our dataset provides detailed information about the path of astrocyte differentiation, highlighting the stepwise molecular changes that occur throughout the differentiation process. This dataset serves as a valuable reference for dissecting uncharacterized transcriptomic features of NFIB/SOX9-induced astrocytes and investigating lineage progression during astrocyte differentiation. Moreover, these findings pave the way for future studies on neurological diseases using the NFIB/SOX9-induced astrocyte model.

Abstract Background The development of the human vermiform appendix at the cellular level, as well as its function, is not well understood. Appendicitis in preschool children, although uncommon, is associated with a high perforation rate and increased morbidity. Methods We performed single-cell RNA sequencing (scRNA-seq) on the human appendix during fetal and pediatric stages as well as preschool-age inflammatory appendices. Transcriptional features of each cell compartment were discussed in the developing appendix. Cellular interactions and differentiation trajectories were also investigated. We compared scRNA-seq profiles from preschool appendicitis to those of matched healthy controls to reveal disease-associated changes. Bulk transcriptomic data, immunohistochemistry, and real-time quantitative PCR were used to validate the findings. Results Our analysis identified 76 cell types in total and described the cellular atlas of the developing appendix. We discovered the potential role of the BMP signaling pathway in appendiceal epithelium development and identified HOXC8 and PITX2 as the specific regulons of appendix goblet cells. Higher pericyte coverage, endothelial angiogenesis, and goblet mucus scores together with lower epithelial and endothelial tight junction scores were found in the preschool appendix, which possibly contribute to the clinical features of preschool appendicitis. Preschool appendicitis scRNA-seq profiles revealed that the interleukin-17 signaling pathway may participate in the inflammation process. Conclusions Our study provides new insights into the development of the appendix and deepens the understanding of appendicitis in preschool children. Graphical Abstract

Cu–15Ni–8Sn-xNb alloys (x = 0, 0.2, 0.6 wt%) were prepared using a medium-frequency induction melting furnace. The effect of Nb addition on grain refinement and inhibition of discontinuous precipitation (DP) in Cu–15Ni–8Sn alloys was systematically studied to elucidate the mechanism by which microstructural characteristics contribute to strength improvement. The results indicate that the increase the Nb content from 0 to 0.6 wt% reduces the average grain size of the as-cast alloy from approximately 524.8 μm to approximately 81.3 μm, and significantly decreases the lamellar transition structure region (α+γ). During solution treatment, dispersed needle-like NbNi3 phases were observed in the Cu–15Ni–8Sn-0.2Nb alloy. After aging, the DP growth rate in the Cu–15Ni–8Sn-0.2Nb alloy was notably slower than those of the other alloys. This was attributed to NbNi3 phases at the grain boundaries hindering DP nucleation, with intragranular NbNi3 phases inhibiting DP growth. The phase transformation order of the solid solution Cu–15Ni–8Sn-0.2Nb at 673 K aging is: spinodal structure → D022 ordered phase → L12 ordered phase → DP. The hardness and tensile strength of the Cu–15Ni–8Sn-0.2Nb alloy peaked at 338.3 HV and 725.42 MPa, respectively, after aging for 120 min. Using the Johnson–Mehl–Avrami–Kolmogorov (JMAK) and Arrhenius equations, the activation energies of DP in Cu–15Ni–8Sn-xNb (x = 0, 0.2, 0.6 wt%) alloys were calculated to be 93.19, 148.64, and 98.33 kJ/mol, respectively. These values suggest that the diffusion of DP atoms in the Nb-containing alloys is hindered, which effectively inhibits DP formation.

Abstract Mixed emotions have attracted increasing interest recently, but existing datasets rarely focus on mixed emotion recognition from multimodal signals, hindering the affective computing of mixed emotions. On this basis, we present a multimodal dataset with four kinds of signals recorded while watching mixed and non-mixed emotion videos. To ensure effective emotion induction, we first implemented a rule-based video filtering step to select the videos that could elicit stronger positive, negative, and mixed emotions. Then, an experiment with 80 participants was conducted, in which the data of EEG, GSR, PPG, and frontal face videos were recorded while they watched the selected video clips. We also recorded the subjective emotional rating on PANAS, VAD, and amusement-disgust dimensions. In total, the dataset consists of multimodal signal data and self-assessment data from 73 participants. We also present technical validations for emotion induction and mixed emotion classification from physiological signals and face videos. The average accuracy of the 3-class classification (i.e., positive, negative, and mixed) can reach 80.96% when using SVM and features from all modalities, which indicates the possibility of identifying mixed emotional states.

Abstract Glioblastoma (GBM) is the most common brain tumor and remains incurable. Primary GBM cultures are widely used tools for drug screening, but there is a lack of genomic and pharmacological characterization for these primary GBM cultures. Here, we collect 50 patient-derived glioma cell (PDGC) lines and characterize them by whole genome sequencing, RNA sequencing, and drug response screening. We identify three molecular subtypes among PDGCs: mesenchymal (MES), proneural (PN), and oxidative phosphorylation (OXPHOS). Drug response profiling reveals that PN subtype PDGCs are sensitive to tyrosine kinase inhibitors, whereas OXPHOS subtype PDGCs are sensitive to histone deacetylase inhibitors, oxidative phosphorylation inhibitors, and HMG-CoA reductase inhibitors. PN and OXPHOS subtype PDGCs stably form tumors in vivo upon intracranial transplantation into immunodeficient mice, whereas most MES subtype PDGCs fail to form tumors in vivo. In addition, PDGCs cultured by serum-free medium, especially long-passage PDGCs, carry MYC/MYCN amplification, which is rare in GBM patients. Our study provides a valuable resource for understanding primary glioma cell cultures and clinical translation and highlights the problems of serum-free PDGC culture systems that cannot be ignored.

Diabetic nephropathy (DN) is a common and serious complication of diabetes, contributing significantly to patient mortality. Complication of DN (CDN) ranks as the second leading cause of end-stage renal disease globally. To address this, understanding the genetic regulation underlying DN is crucial for personalized treatment strategies. In this study, we identified genes and lncRNAs associated with diabetes and diabetic nephropathy constructing a DN-related lncRNA–mRNA network (DNLMN). This network, characterized by scale-free biomolecular properties, generated through the study of topological properties, elucidates key regulatory interactions. Enrichment analysis of important network modules revealed critical biological processes and pathways involved in DN pathogenesis. In the second step, we investigated the differential expression and co-expression of hub nodes in diseased and normal individuals, identifying lncRNA-mRNA relationships implicated in disease regulation. Finally, we gathered DN-related single nucleotide polymorphisms (SNPs) and lncRNAs from the LincSNP 3.0 database. The DNLMN encompasses SNP-associated lncRNAs, and transcription factors (TFs) linked to differentially expressed lncRNAs between diseased and normal samples. These results underscore the significance of biomolecular networks in disease progression and highlighting the role of biomolecular variability contributes to personalized disease phenotyping and treatment.

Abstract While the anaerobic-anoxic-oxic (AAO) process is the most widely applied biological wastewater treatment process in municipal wastewater treatment plants (WWTPs), it struggles to meet the increasing demands on biological toxicity control of the treated effluent. To tackle this challenge, this study develops machine learning (ML)-based models for optimizing the AAO treatment process towards improving its toxicity reduction efficacy for the effluent. The water quality parameters, treatment process parameters, and biological toxicity information (based on the nematode bioassay) of the effluent collected from 122 WWTPs in China are used to train the models. The validated models accurately predict the effluent’s quality parameters (average R2 = 0.81) and the biological toxicity reduction ratio of treatment process (R2 = 0.86). To further improve the toxicity reduction, we developed a multiple objective optimization framework to optimize the AAO process via unit process recombination. In the short-range unit combination, the toxicity reduction ratio of the four-unit combined processes (up to 79.8% of anaerobic-aerobic-anaerobic-aerobic) is significantly higher than others. After optimization, it helps to improve the average toxicity reduction efficacy of 122 WWTPs from 48.6% to 70.7%, with a maximum of 87.5%. The methodologies and findings derived from this work are expected to provide the foundation for the optimization, expansion, and technical transformation of biological wastewater treatment in WWTPs.

Objective To investigate the radiosensitizating effect of quercetin (QU) loaded manganese dioxide nanoparticles [Mn(QU)] on breast cancer cell line 4T1 and tumour-bearing mice. Methods Manganese dioxide (MnO2) nanoparticles were synthesized by oleic acid template method. The morphology and chemical composition of MnO2 nanoparticles were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy. Then QU nanomaterials were encapsulated by using physical adsorption. The composition was characterized by ultraviolet spectrophotometer, and the ability of Mn(QU) nanoparticles reacting with different doses of hydrogen peroxide to produce oxygen at different pH values was detected by dissolved oxygen analyzer. CCK-8 assay was employed to detect the effects of different concentrations of Mn(QU) nanoparticles on the viability of 4T1 cells. Colony formation, γ-H2AX fluorescence staining, ROS fluorescence staining, LIVE/DEAD cell viability assay and flow cytometry were used to evaluate the radiosensitizing and pro-apoptotic effects of Mn(QU) nanoparticles on 4T1 cells. Finally, the effect of Mn(QU) nanoparticles combined with radiotherapy on tumor growth inhibition was evaluated in mouse model of 4T1 cell transplanted tumor. Results MnO2 nanoparticles with particle size of about 120 nm were successfully synthesized and encapsulated with QU. The oxygen generation capacity of the prepared Mn(QU) nanoparticles reacting with hydrogen peroxide was negatively correlated with pH value and positively with hydrogen peroxide concentration. The results of cell experiments showed that Mn(QU) nanoparticles at a concentration of 50 μg/mL had no obvious toxicity to 4T1 cells, but could significantly enhance the X-ray-induced killing effect on 4T1 cells, at a radiotherapy sensitization ratio of 1.61, improve DNA double-strand breaks and ROS production, and induce apoptosis of 4T1 cells. The results of tumor xenograft model experiment indicated that the inhibition of tumor volume was Mn(QU) nanoparticles combined with radiotherapy>MnO2 nanoparticles combined radiotherapy>QU combined radiotherapy>Radiotherapy>Control. Conclusion Mn(QU) nanoparticles combined with radiotherapy can significantly inhibit the proliferation and show radiosensitization of breast cancer 4T1 cells, and also exert a significant inhibitory effect on the growth of the transplanted tumor.