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Recently, topological data analysis has become a trending topic in data science and engineering. However, the key technique of topological data analysis, i.e., persistent homology, is defined on point cloud data, which does not work directly for data on manifolds. Although earlier evolutionary de Rham-Hodge theory deals with data on manifolds, it is inconvenient for machine learning applications because of the numerical inconsistency caused by remeshing the involving manifolds in the Lagrangian representation. In this work, we introduced persistent de Rham-Hodge Laplacian, or persistent Hodge Laplacian (PHL), as an abbreviation for manifold topological learning. Our PHLs were constructed in the Eulerian representation via structure-persevering Cartesian grids, avoiding the numerical inconsistency over the multi-scale manifolds. To facilitate the manifold topological learning, we proposed a persistent Hodge Laplacian learning algorithm for data on manifolds or volumetric data. As a proof-of-principle application of the proposed manifold topological learning model, we considered the prediction of protein-ligand binding affinities with two benchmark datasets. Our numerical experiments highlighted the power and promise of the proposed method.

Summary: Background: The worldwide geographical and temporal variation in the prevalence of diabetes represents a challenge, but also an opportunity for gaining etiological insights. Encompassing the bulk of East Asians, a large and distinct proportion of the world population, China can be a source of valuable epidemiological insights for diabetes, especially in early life, when pathophysiology begins. We carried out a nationwide, epidemiological survey of Prevalence and Risk of Obesity and Diabetes in Youth (PRODY) in China, from 2017 to 2019, to estimate the population-based prevalence of diagnosed pediatric diabetes and screen for undiagnosed pediatric type 2 diabetes (T2D). Methods: PRODY was a nation-wide, school population-based, cross-sectional, multicenter survey by questionnaire, fasting urine glucose test and simple oral glucose tolerance test (s-OGTT), among a total number of 193,801 general-population children and adolescents (covered a pediatric population of more than 96.8 million), aged 3–18, from twelve provinces across China. The prevalence of the self-reported pediatric diabetes, the proportion of subtypes, the crude prevalence of undiagnosed T2D and prediabetes in general juvenile population and the main risk factors of type 1 (T1D) and type 2 (T2D) diabetes had been analyzed in the study. Findings: The prevalence of all self-reported pediatric diabetes was estimated at 0.62/1000 (95% CI: 0.51–0.74), with T1D at 0.44/1000 (95% CI: 0.35–0.54) and T2D at 0.18/1000 (95% CI: 0.13–0.25). For undiagnosed T2D, the crude prevalence was almost ten-fold higher, at 1.59/1000, with an estimated extra 28.45/1000 of undiagnosed impaired glucose tolerance (IGT) and 53.74/1000 of undiagnosed impaired fasting glucose (IFG) by s-OGTT screening. Maternal diabetes history is the major risk factors for all subtypes of pediatric diabetes in China. Interpretation: The PRODY study provides the first population-based estimate of the prevalence of pediatric diabetes China and reveals a magnitude of the problem of undiagnosed pediatric T2D. We propose a practical screening strategy by s-OGTT to address this serious gap. Funding: The National Key Research and Development Programme of China, Key R&D Program of Zhejiang, the National Natural Science Foundation of China and the Zhejiang Provincial Key Disciplines of Medicine, Key R&D Program Projects in Zhejiang Province.

We identified a novel mouse plasmacytoid dendritic cell (pDC) lineage derived from the common lymphoid progenitors (CLPs) that is dependent on expression of Bcl11a. These CLP-derived pDCs, which we refer to as ‘B-pDCs’, have a unique gene expression profile that includes hallmark B cell genes, normally not expressed in conventional pDCs. Despite expressing most classical pDC markers such as SIGLEC-H and PDCA1, B-pDCs lack IFN-α secretion, exhibiting a distinct inflammatory profile. Functionally, B-pDCs induce T cell proliferation more robustly than canonical pDCs following Toll-like receptor 9 (TLR9) engagement. B-pDCs, along with another homogeneous subpopulation of myeloid-derived pDCs, display elevated levels of the cell surface receptor tyrosine kinase AXL, mirroring human AXL+ transitional DCs in function and transcriptional profile. Murine B-pDCs therefore represent a phenotypically and functionally distinct CLP-derived DC lineage specialized in T cell activation and previously not described in mice.

Abstract Background Patients with Turner syndrome (TS) face an increased risk of developing aortic dilatation (AD), but diagnosing AD in children presents greater complexity compared to adults. This study aimed to investigate the application of various assessment indicators of AD in Chinese children and adolescents with TS. Methods This study included TS patients admitted to Shenzhen Children’s Hospital from 2017 to 2022. Cardiovascular lesions were diagnosed by experienced radiologists. Patients without structural heart disease were divided into different body surface area groups, then the Chinese TS population Z-score (CHTSZ-score) of the ascending aorta was calculated and compared with other indicators such as aortic size index (ASI), ratio of the ascending to descending aortic diameter (A/D ratio), and TSZ-score (Quezada’s method). Results A total of 115 TS patients were included, with an average age of 10.0 ± 3.7 years. The incidences of the three most serious cardiovascular complications were 9.6% (AD), 10.4% (coarctation of the aorta, CoA), and 7.0% (bicuspid aortic valve, BAV), respectively. The proportion of developing AD in TS patients aged ≥ 10 years was higher than that in those

We demonstrate a compact ion beam device capable of accelerating H+ and D+ ions up to 75 keV energy, onto a solid target, with sufficient beam current to study fusion reactions. The ion beam system uses a microwave driven plasma source to generate ions that are accelerated to high energy with a direct current (DC) acceleration structure. The plasma source is driven by pulsed microwaves from a solid-state radiofrequency (RF) amplifier, which is impedance matched to the plasma source chamber at the S-band frequency in the range of 2.4–2.5 GHz. The plasma chamber is held at high positive DC potential and is isolated from the impedance matching structure (at ground potential) by a dielectric-filled gap. To facilitate the use of high-energy-particle detectors near the target, the plasma chamber is biased to a high positive voltage, while the target remains grounded. A target loaded with deuterium is used to study D-D fusion and a B4C or LaB6 target is used to study p-11B fusion. Detectors include solid-state charged particle detector and a scintillation fast neutron detector. The complete ion beam system can fit on a laboratory table and is a useful tool for teaching undergraduate and graduate students about the physics of fusion.

BackgroundThe correlation between oxidative stress and female infertility pathogenesis was established, and the oxidative balance score (OBS) can serve as a measure of overall oxidative stress burden within an individual. Prior reports have not addressed the relationship between OBS and female infertility. This study endeavors to investigate the association between infertility risk in female and OBS.MethodsThe analysis focused on data from the National Health and Nutrition Examination Survey 2013-2018. OBS was determined from 16 dietary components and 4 lifestyle components. Multivariate logistic regression was employed to investigate the relationship between OBS and female infertility. Further stratified analysis was conducted to examine the associations across various subgroups. To elucidate the dose-response relationship between infertility risk in female and OBS, a restricted cubic spline function was employed.ResultsThe study included a total of 1410 participants. Through weighted multivariable logistic regression analysis, we observed a consistent inverse correlation between OBS and the risk of female infertility [OR (95% CI) = 0.97 (0.95, 0.99), p = 0.047]. When participants were segregated into quartiles based on OBS, those in the highest quartile had a 61% [OR (95% CI) = 0.39 (0.2, 0.79), p = 0.01] reduced risk of infertility compared to those in the lowest quartile of OBS. A trend test assessing OBS by quartile also revealed the relationship between OBS and female infertility. This correlation remained constant across both dietary and lifestyle OBS. Additionally, lifestyle OBS and female infertility exhibited a nonlinear association. A sensitivity analysis verified the consistency of our findings.ConclusionThe study found that a higher OBS is associated with a lower prevalence of female infertility. These results emphasized the potential role of oxidative homeostasis in the pathogenesis of infertility and highlighted the importance of follow-up studies and prevention strategies.

Summary: Blood microbiome signatures in patients with type 1 diabetes (T1D) remain unclear. We profile blood microbiome using 16S rRNA gene sequencing in 77 controls and 64 children with new-onset T1D, and compared it with the gut and oral microbiomes. The blood microbiome of patients with T1D is characterized by increased diversity and perturbed microbial features, with a significant increase in potentially pathogenic bacteria compared with controls. Thirty-six representative genera of blood microbiome were identified by random forest analysis, providing strong discriminatory power for T1D with an AUC of 0.82. PICRUSt analysis suggested that bacteria capable of inducing inflammation were more likely to enter the bloodstream in T1D. The overlap of the gut and oral microbiome with the blood microbiome implied potential translocation of bacteria from the gut and oral cavity to the bloodstream. Our study raised the necessity of further mechanistic investigations into the roles of blood microbiome in T1D.

Endochondral ossification is the process by which cartilage is mineralized into bone, and is essential for the development of long bones. Osteocalcin (OCN), a protein abundant in bone matrix, also exhibits high expression in chondrocytes, especially hypertrophic chondrocytes, while its role in endochondral ossification remains unclear. Utilizing a new CRISPR/Cas9-mediated bglap–bglap2 deficiency (OCNem) mouse model generated in our laboratory, we provide the first evidence of OCN’s regulatory function in chondrocyte differentiation and endochondral ossification. The OCNem mice exhibited significant delays in primary and secondary ossification centers compared to wild-type mice, along with increased cartilage length in growth plates and hypertrophic zones during neonatal and adolescent stages. These anomalies indicated that OCN deficiency disturbed endochondral ossification during embryonic and postnatal periods. Mechanism wise, OCN deficiency was found to increase chondrocyte differentiation and postpone vascularization process. Furthermore, bone marrow mesenchymal stromal cells (BMSCs) from OCNem mice demonstrated an increased capacity for chondrogenic differentiation. Transcriptional network analysis implicated that BMP and TGF-β signaling pathways were highly affected in OCNem BMSCs, which is closely associated with cartilage development and maintenance. This elucidation of OCN’s function in chondrocyte differentiation and endochondral ossification contributes to a more comprehensive understanding of its impact on skeletal development and homeostasis.

Abstract The integration of nano-semiconductors into electromagnetic wave absorption materials is a highly desirable strategy for intensifying dielectric polarization loss; achieving high-attenuation microwave absorption and realizing in-depth comprehension of dielectric loss mechanisms remain challenges. Herein, ultrafine oxygen vacancy-rich Nb2O5 semiconductors are confined in carbon nanosheets (ov-Nb2O5/CNS) to boost dielectric polarization and achieve high attenuation. The polarization relaxation, electromagnetic response, and impedance matching of the ov-Nb2O5/CNS are significantly facilitated by the Nb2O5 semiconductors with rich oxygen vacancies, which consequently realizes an extremely high attenuation performance of − 80.8 dB (> 99.999999% wave absorption) at 2.76 mm. As a dielectric polarization center, abundant Nb2O5–carbon heterointerfaces can intensify interfacial polarization loss to strengthen dielectric polarization, and the presence of oxygen vacancies endows Nb2O5 semiconductors with abundant charge separation sites to reinforce electric dipole polarization. Moreover, the three-dimensional reconstruction of the absorber using microcomputer tomography technology provides insight into the intensification of the unique lamellar morphology regarding multiple reflection and scattering dissipation characteristics. Additionally, ov-Nb2O5/CNS demonstrates excellent application potential by curing into a microwave-absorbing, machinable, and heat-dissipating plate. This work provides insight into the dielectric polarization loss mechanisms of nano-semiconductor/carbon composites and inspires the design of high-performance microwave absorption materials.

Abstract Phthalate esters (PAEs) may act as estrogen receptor agonists, and their relationship with precocious puberty is a global health concern. However, their role in isolated premature thelarche (IPT) progression remains unclear. We conducted a cohort study investigating the relationship between IPT progression and urinary PAE metabolites. Girls with IPT aged 6–8 years were regularly followed up every three months for one year. Clinical data and urine PAE metabolite levels were collected. Participants who progressed to central precocious puberty (CPP) or early puberty (EP) had significantly higher ovarian volume, breast Tanner stage, and levels of the creatinine-adjusted urinary secondary oxidized di-2-ethylhexyl phthalate (DEHP) metabolites (Σ4DEHP). Breast Tanner stage (odds ratio [OR] = 7.041, p = 0.010), ovarian volume (OR = 3.603, p = 0.019), and Σ4DEHP (OR = 1.020, p = 0.005) were independent risk factors for IPT progression. For each 10 µg/g/Cr increase in the urine level of Σ4DEHP, the risk of progression from IPT to CPP/EP within one year increased by 20%. This study demonstrated that the breast Tanner stage, ovarian volume, and Σ4DEHP in urine were independent risk factors for IPT progression, and Σ4DEHP may be associated with the progression of IPT to CPP or EP.

Bamboo forest healthcare tourism is a practical and sustainable management model that utilizes the medicinal functions of bamboo. However, the mechanism and potential functions of bamboo’s healthcare functions are still unclear. In this study, the volatile organic compounds (VOCs) that are the core factor of bamboo forest healthcare were analyzed. The foliar VOCs of eight bamboo species, including Pleioblastus amarus (Keng) P. C. Keng, Pleioblastus maculatus (McClure) C. D. Chu et C. S. Chao, Pleioblastus juxianensis T. H. Wen, C. Y. Yao et S. Y. Chen, Acidosasa chienouensis (T. H. Wen) C. S. Chao et T. H. Wen, Pseudosasa amabilis (McClure) P. C. Keng ex S. L. Chen et al., Pseudosasa amabilis (McClure) Keng f., Phyllostachys rubromarginata McClure, and Phyllostachys hirtivagina G. H. Lai were qualitatively and semi-quantitatively analyzed by headspace solid-phase microextraction (HS-SPME)–gas chromatography–mass spectrometry (GC-MS). Screening compounds by aroma vitality value (OAV) determined the key aromas. The results showed that a total of 40 VOCs were identified from the leaves of the eight bamboo species. The compounds with relatively high content were (Z)-3-Hexen-1-ol, (E)-2-Hexen-1-ol, 1-Hexanol, (E, E)-2,4-Hexadienal, Limonene, and so on. The commonality of different bamboo species was that the dominant groups consisted of alcohols and aldehydes. The significant differences in leaf VOCs among species presented classification. Pleioblastus amarus, Acidosasa chienouensis, Pseudosasa amabilis, and Phyllostachys rubromarginata were noticeably clustered together. The aroma of bamboo leaves is a combination of grassy, fruity, and piney notes by 24 VOCs. The key aroma from Pleioblastus amarus is leaf alcohol, which contributes to the grassy scent, while the piney aroma is dominant in Pseudosasa amabilis and Phyllostachys rubromarginata. The study provides a reference value for enriching the chemical information of subtropical bamboo and developing the functional potential of bamboo forest healthcare tourism.

Introduction: The advancement and advocacy of the 3R principle and safety evaluation and risk assessment technology has given rise to an innovative method on a global scale, which known as the Next Generation Risk Assessment (NGRA). This progressive approach adopts a tiered assessment strategy based on prepositive hypothesis and exposure analysis. Unlike traditional risk assessment methods that rely on toxicological endpoint animal tests, NGRA lays emphasis on evaluating the exposure process by outlining the mechanisms and significant key events leading to adverse outcomes. The NGRA process entails prioritizing the robust high-throughput screening and prediction tools to enhance the accuracy, efficiency, and relevance of the assessment. Result: This review provides an overview of the principles, framework, and tools of NGRA as recommended by the International Cosmetics Regulatory Cooperation Organization (ICCR). Furthermore, the review encompasses published case studies of cosmetics ingredients and elucidates the potential applications and technical challenges associated with NGRA while considering the extant safety evaluation requirements for cosmetics ingredients in China. Moreover, the review synthesizes a selection of case studies of cosmetics ingredients and hope to proffer implications for the assessment of risk in traditional Chinese medicine. Conclusion: It was hoped to help researchers to investigate novel techniques of safety risk assessment and propose research concepts for both cosmetics and traditional Chinese medicine.

Abstract Purpose The mechanism of chemo‐resistance in small cell lung cancer (SCLC) is unclear. This study aims to explore the resistance‐related genomic profiles of residual tumors after neo‐adjuvant chemotherapy (NAC) in SCLC through the whole‐exome sequencing (WES). Experimental design A total of 416 limited diseases (LD) SCLC patients underwent surgery were retrospectively analyzed, of which 40 patients received NAC. Then we selected 29 patients undergoing NAC (n = 19) and chemotherapy naïve (CTN, n = 10) to perform WES sequence with formalin‐fixed paraffin‐embedded samples including tumor and paired para‐tumor. Results In total, single nucleotide variation and mutation rate were similar between NAC and CTN groups. The mutation signatures were significantly discrepant between NAC and CTN groups, as well as among patients with partial response (PR), stable disease (SD), and progressive disease. There were more copy number variation deletions in NAC group compared with CTN group. The inactivation of TP53 and RB1 were the most significantly events in both NAC and CTN groups. RB1 nonsense mutations were recurrent in NAC group (9/19 vs. 0/9, 47.4% vs. 0%) with favorable survival, while the frame‐shift deletions were frequent in CTN group (3/9 vs. 3/19, 33.3% vs.15.8%). Integrated function enrichment revealed that the frequently mutant genes were involved in cell cycle, metabolic reprogramming, and oncogenic signaling pathways in NAC group, such as BTG2 pathway, glycolysis in senescence and P53 pathway. A total of 27 genes presented frequently mutant in NAC group and might played a positive role in drug resistance. Multiple genes including BRINP3, MYH6, ST18, and PCHD15, which were associated with prognosis, occurred mutant frequently in PR and SD groups. Conclusion Residual tumors after neo‐adjuvant therapy exhibited different mutation signature spectrum. Multiple genes including RB1 nonsense mutations, BRINP3, MYH6, ST18, and PCHD15 were with frequent mutation in residual tumors, which might participate chemo‐resistance and influenced the prognosis in patients with limited disease SCLC.

Abstract Polycystic ovary syndrome (PCOS), a common reproductive endocrine disease, has clinically heterogeneous characteristics. Recently, cuproptosis causes several diseases by killing cells. Hence, we aimed to explore cuproptosis-related molecular clusters in PCOS and construct a prediction model. Based on the GSE5090, GSE43264, GSE98421, and GSE124226 datasets, an analysis of cuproptosis regulators and immune features in PCOS was conducted. In 25 cases of PCOS, the molecular clusters of cuproptosis-related genes and the immune cell infiltration associated with PCOS were investigated. Weighted gene co-expression network analysis was used to identify differentially expressed genes within clusters. Next, we compared the performance of the random forest model, support vector machine model, generalized linear model, and eXtreme Gradient Boosting for deciding the optimum machine model. Validation of the predictive effectiveness was accomplished through nomogram, calibration curve, decision curve analysis, and using other two datasets. PCOS and non-PCOS controls differed in the dysregulation of cuproptosis-related genes and the activation of immunoreaction. Two cuproptosis-related molecular clusters associated with PCOS were identified. Significant heterogeneity was noted in immunity between the two clusters based on the analysis of immune infiltration. The immune-related pathways related to cluster-specific differentially expressed genes in Cluster1 were revealed by functional analysis. With a relatively low residual error and root mean square error and a higher area under the curve (1.000), the support vector machine model demonstrated optimal discriminative performance. An ultimate 5-gene-based support vector machine model was noted to perform satisfactorily in the other two validation datasets (area under the curve = 1.000 for both). Moreover, the nomogram, calibration curve, and decision curve analysis showed that PCOS subtypes can be accurately predicted. Our study results helped demonstrate a comprehensive understanding of the complex relationship between cuproptosis and PCOS and establish a promising prediction model for assessing the risk of cuproptosis in patients with PCOS.

Abstract Background Growth chart is a valuable clinical tool to monitor the growth and nutritional status of children. A growth chart widely used in China is based on the merged data sets of national surveys in 2005. We aimed to establish an up-to-date, complete growth curve for urban Chinese children and adolescents with a full range of ages. Methods Using data collected in a large-scale, cross-sectional study (Prevalence and Risk factors for Obesity and Diabetes in Youth (PRODY), 2017–2019), we analyzed 201,098 urban children aged 3 to 18 years from 11 provinces, autonomous regions, and municipalities that are geographically representative of China. All participants underwent physical examinations. Sex-specific percentiles of height-for-age and weight-for-age were constructed by Generalized Additive Models for Location Scale and Shape (GAMLSS) model. We also compared the median values of height-for-age or weight-for-age between our growth chart and the established growth reference using Welch-Satterthwaite T-Test. Results Consistent with the established growth reference, we observed that the P50 percentile of height-for-age reached plateaus at the age of 15 years (172 cm) and 14 years (160 cm) for boys and girls, respectively. In addition, boys aged 10 ~ 14 years and girls aged 10 ~ 12 years exhibited the most dramatic weight difference compared to those of other age groups (19.5 kg and 10.3 kg, respectively). However, our growth chart had higher median values of weight-for-age and height-for-age than the established growth reference with mean increases in weight-for-age of 1.36 kg and 1.17 kg for boys and girls, respectively, and in height-for-age of 2.9 cm and 2.6 cm for boys and girls, respectively. Conclusions Our updated growth chart can serve as a reliable reference to assess the growth and nutritional status in urban Chinese children throughout the entire childhood.

Abstract Although unmanned aerial vehicle (UAV) relay can provide auxiliary communication due to its flexible mobility, it is vulnerable to jamming attacks. This paper considers the UAV relay anti‐jamming communication issue under the threat of a malicious jammer with beam‐forming jamming capability. To prevent the relay link from deteriorating, UAV trajectory adjustment and transmission mode switching between half‐duplex and full‐duplex are two available schemes, while they will incur the additional flying costs and continuous mode switching, respectively. To balance the trade‐off between trajectory optimization and mode selection, this paper investigates the joint trajectory optimization and mode selection anti‐jamming approach. First, an anti‐jamming utility considering the cost‐efficient and end‐to‐end capacity gains is designed. Second, to model the bounded rationality of both the UAV relay and the jammer due to the adversarial context, a biased Stackelberg game to analyse the competitive system interactions is proposed. Moreover, the existence of Stackelberg equilibrium (SE) in the problem is proved. Finally, a joint mode selection and trajectory optimization (JMSTO) algorithm based on the multi‐armed bandit is proposed to obtain the SE. It is further demonstrated that the JMSTO algorithm has a logarithmic regret. The results show that our proposed JMSTO algorithm is superior to non‐joint optimization methods.

Abstract Background Primary generalized glucocorticoid hypersensitivity (PGGH) is a very rare disease caused by terminal organ hypersensitivity to glucocorticoids for which the aetiology is unknown. The incidence of PGGH is extremely rare, especially in children. To date, the literatures about the etiology, prognosis and treatment of PGGH are scarce. Aim of the study is describing the cases of two Chinese children with infantile-onset PGGH in one family, one of whom died and one who was treated with mifepristone. They are the two youngest children with PGGH reported in the literature. Case presentation Two siblings with infantile-onset PGGH were affected in this family. The main manifestations of patient 1 were typical Cushing’s syndrome-like manifestations, significantly aggravated symptoms after physiological doses of glucocorticoids and very low levels of serum cortisol and adrenocorticotropin hormone (ACTH) during attacks. After being diagnosed with PGGH, he was given guidance to avoid glucocorticoids and took mifepristone therapy for 5 months, and his symptoms improved. Patient 2 was the younger brother of patient 1, with similar manifestations to his brother at the age of 4 months. Patient 2 ultimately died at the age of 9 months. Conclusion PGGH is a very rare disease that can lead to death if not diagnosed and treated in a timely manner. This article describes the cases of the two youngest children with PGGH reported in the literature, one of whom improved after mifepristone treatment, and increases the knowledge of the clinical manifestations of and the treatment experience in PGGH.

Here, by performing multi-omics microbiome analyses in a cohort of children with new-onset T1D, the authors characterize altered microbial functional and metabolic traits involved in T1D, which they validate in animal experiments, together providing potential avenues for microbiome-based interventions.

Abstract Estrogen can promote the acceleration of bone maturation and phthalate esters (PAEs) have estrogen-mimicking effects. We investigated whether PAEs are associated with the acceleration of bone age (BA) in girls with early onset of puberty (EOP). This case–control study enrolled 254 girls with EOP from the Endocrinology Department at Shenzhen Children’s Hospital between December 2018 and August 2019. Ultra-performance liquid chromatography and tandem mass spectrometry were used to analyze the 10 metabolites of PAEs (mPAEs) in urine samples. BA was measured using an artificial intelligence system. BA exceeding the chronological age (CA) by > 2 years (BA-CA ≥ 2 years) was referred to as significant BA advancement. Participants were divided into groups A (BA-CA ≥ 2 years; case group) and B (BA-CA 0.05). Our findings suggested that MEP was positively associated with BA advancement in girls with EOP. Exposure to PAEs may promote accelerated bone maturation.

Supercapacitors (SCs) are becoming new candidates in the field of sustainable energy supply. Nevertheless, the unsatisfactory energy density due to the narrow voltage window of the supercapacitor is the main barrier to its practical application. Developing appropriate electrode materials to improve the electrochemical performance of SCs and broaden the operating voltage of supercapacitors are imperative. Herein, compatible interfacial engineering wood-derived nanostructured electrodes for aqueous asymmetric supercapacitors (AASCs) are demonstrated. The 3D carbonized wood matrix serves as a high specific surface area current collector and a porous host for the high capacitive active substance, which is composed of manganese dioxide (MnO2) nanowires and polyaniline (PANI) nanoparticles grown uniformly on the porous wall of aligned microchannels (CW@MnO2 and CW@PANI). The resulting electrochemical exchange reactive sites enable the positive electrode to deliver a high areal capacitance of 729 mF cm−2 at 1 mA cm−2 (369 F g−1 at 0.5 A g−1). The negative electrode delivers a high areal capacitance of 1721 mF cm−2 at 1 mA cm−2 (848 F g−1 at 0.5 A g−1). The areal capacitance of two electrodes is superior to most reported supercapacitor electrodes. Additionally, the assembled CW@MnO2//CW@PANI AASC achieves a desirable energy density (170.84 μWh cm−2 at a power density of 0.5 mW cm−2) because a considerable work function difference between electrodes achieved a 2 V wide voltage window. The results of this study provide a critical benchmark and optimistic incentives to adopt natural hierarchical structures to enhance the performance of new-generation energy-related systems.

The present study explores a three-dimensional deformation monitoring method for the better delineation of the surface subsidence range in coal mining by combining the mining subsidence law with the geometries of SAR imaging. The mining surface subsidence of the filling working face in Shandong, China, from March 2018 to June 2021, was obtained with 97 elements of Sentinel-1A data, the small baseline subset (SBAS) technique, and the proposed method, respectively. By comparison with the ground leveling of 46 observation stations, it is shown that the average standard deviation of the SBAS monitoring results is 10.3 mm; with this deviation, it is difficult to satisfy the requirements for the delimitation of the mining impact area. Meanwhile, the average standard deviation of the vertical deformation obtained by the proposed method is 6.2 mm. Compared to the SBAS monitoring accuracy, the monitoring accuracy of the proposed method is increased by 39.8%; thus, it meets the requirements for the precise delineation of the surface subsidence range for backfill mining.

Abstract Background To evaluate the effectiveness of individualized-dose polyethylene glycol recombinant human growth hormone (PEG-rhGH) for short stature. Methods This real-world study enrolled children with short stature in 19 hospitals throughout China. They were treated with PEG-rhGH for 6 months. The starting dosage ranged from 0.10 to 0.20 mg/kg/week. The primary outcome was the change in height standard deviation score (ΔHt SDS). Results Five hundred and ten patients were included and grouped based on dosage as A (0.10–0.14 mg/kg/week), B (0.15–0.16 mg/kg/week), C (0.17–0.19 mg/kg/week), and D (0.20 mg/kg/week). The mean 6-month ΔHt SDS for the total cohort was 0.49 ± 0.27, and the means differed among the four dose groups (P = 0.002). The ΔHt SDS was lower in group A than in groups B (LSM difference [95%CI], -0.09 [-0.17, -0.01]), C (LSM difference [95%CI], -0.10 [-0.18, -0.02]), and D (LSM difference [95%CI], -0.13 [-0.21, -0.05]) after adjusting baseline covariates. There were no significant differences among groups B, C, and D. When the baseline IGF-1 was 0 SDS, the △Ht SDS was not different among the four groups (P = 0.931 and P = 0.400). In children with baseline IGF-1 SDS of -2 ~ 0 SDS, a higher dosage was associated with a better treatment effect (P = 0.003), and the △Ht SDS was lower in older children than in younger ones (P

Background and objectiveWith a worldwide trend to earlier age of onset of puberty, the prevalence of early-onset puberty (EP) among girls has increased. The impact of EP on the pattern of linear growth and bone maturation is unclear. Accordingly, the objective of our study was to describe this pattern for girls with EP in Shenzhen, China.MethodsA total of 498 untreated girls diagnosed with EP at Shenzhen Children's Hospital, China, between January 2016 and December 2021. A total of 1,307 anthropometric measurements and 1,307 left-hand radiographs were available for analysis. Artificial intelligence (AI) was used to determine bone age (BA). Participants were classified into groups according to chronological age (CA) and BA. The pattern of linear growth (height) and progression of bone maturation was described between groups using the Lambda-Mu-Sigma (LMS) method. Published height-for-CA and height-for-BA norm references for a healthy Chinese population were used for age-appropriate comparisons.ResultsThe mean CA of appearance of first pubertal signs (breast buds) was 8.1 ± 0.5 years. Compared to norm-referenced data, girls with EP were significantly taller at a CA of 7–10 years. This was followed by a slowing in linear growth after a CA of 10 years, with 71 girls with EP having already achieved their target adult height. From 7 to 10 years of BA, the linear growth was slower in the EP group compared to norm-reference values. This was followed by a period of catch-up growth at 11.2 years of BA, with growth curves approaching norm-referenced values. The BA progressed rapidly from 7 to 8 years of age in about half of the girls with EP (median ΔBA/ΔCA >1.9), slowing, thereafter, until the period of catch-up growth at 11.2 years of BA.ConclusionsBA provides a more reliable reference than CA to assess growth parameters among girls with EP. Our limited data set does indicate that EP does not negatively impact final adult height. Therefore, the growth curves from our study are relevant, providing a reference for pediatricians in this clinical population and, thus, preventing over-treatment for EP.

Abstract Background Adaptive resistance and side effects of sorafenib treatment result in unsatisfied survival of patients with hepatocellular carcinoma (HCC). Palmitoyl-protein thioesterase 1 (PPT1) plays a critical role in progression of various cancers. However, its role on prognosis and immune infiltrates in HCC remains unclarified. Methods By data mining in the Cancer Genome Atlas databases, the role of PPT1 in HCC were initially investigated. Furthermore, HCC cell lines Hep 3B and Hep 1-6 were treated with DC661 or siRNA against PPT1. The biological function of PPT1 was determined by CCK-8 test, colony formation assay, TUNEL staining, immunofluorescence staining, Western blot test, and PI-Annexin V apoptosis assays in vitro. Animal models of subcutaneous injection were applied to investigate the therapeutic role of targeting PPT1. Results We found that PPT1 levels were significantly upregulated in HCC tissues compared with normal tissues and were significantly associated with a poor prognosis. Multivariate analysis further confirmed that high expression of PPT1 was an independent risk factor for poor overall survival of HCC patients. We initially found that PPT1 was significantly upregulated in sorafenib-resistant cell lines established in this study. Upon sorafenib treatment, HCC cells acquired adaptive resistance by inducing autophagy. We found that DC661, a selective and potent small-molecule PPT1-inhibitor, induced lysosomal membrane permeability, caused lysosomal deacidification, inhibited autophagy and enhanced sorafenib sensitivity in HCC cells. Interestingly, this sensitization effect was also mediated by the induction mitochondrial pathway apoptosis. In addition, the expression level of PPT1 was associated with the immune infiltration in the HCC tumor microenvironment, and PPT1 inhibitor DC661 significantly enhanced the anti-tumor immune response by promoting dendritic cell maturation and further promoting CD8+ T cell activation. Moreover, DC661 combined with sorafenib was also very effective at treating tumor models in immunized mice. Conclusions Our findings suggest that targeting PPT1 with DC661 in combination with sorafenib might be a novel and effective alternative therapeutic strategy for HCC.

Magnetic fluids, a new type of energy transfer fluid with tunable properties, have garnered significant interest from researchers worldwide. Hybrid magnetic fluids prepared by adding different types of nanoparticles exhibit superior thermophysical properties and functional characteristics. In this paper, we prepared a water-based magnetic fluid loaded with multi-walled carbon nanotubes (MCNTs), silver (Ag), and copper (Cu) to enhance thermal conductivity. Using a transient double hot-wire method, we designed and built an experimental measurement system for the thermal conductivity of magnetic fluids with an average measurement error of less than 5%. We studied the thermal conductivity of hybrid magnetic fluids under different conditions and evaluated the advantages and disadvantages of various models, including the Maxwell model, H&C model, Tim model, Y&C model, and Evans model. Our results show that MF+MCNTs, MF+Ag, and MF+Cu nanofluids can all improve the thermal conductivity of the carrier fluid, with MF+MCNTs exhibiting the best improvement effect of 10.93%. Among the five models evaluated, the Evans model had the best predictive effect with a deviation range within 5%. This work provides theoretical and practical reference for enhancing the thermal conductivity of magnetic fluids and provides a more accurate theoretical model for calculating the thermal conductivity of hybrid magnetic fluids.

Ultra-precise actuation at extremely low speeds over a broad range is a major challenge for advanced manufacturing. A novel two-axis differential micro-feed system (TDMS) has been proposed recently to overcome the low-speed crawling of the worktable. However, due to the diversity of the force states of the TDMS, the methods for identification identifyingof friction parameters traditionally (like the all -components identification method, ACIM) didn’t did not perform well. And many studies on the performance of the pre-sliding phase of the TDMS are missing. Therefore, a novel whole-system identification method (WSIM) based on the TDMS was proposed in this paper to precisely identify the friction parameters under different states of motion. The generalized Maxwell sliding (GMS) friction model was also applied to improve the accurate description of the pre-sliding. A novel corrected Stribeck curve based on the TDMS (TDMSSC) was proposed under the uniqueness of the TDMS structure. Control experiments showedn that the WSIM has higher precision and stability rather thancompared torather than the ACIM, and the correction of the Stribeck curve for the TDMS makes a contribution to the performance. This method significantly improves the accuracy and stability of the machine tool drive system.

Abstract Ferromagnetic alloys/carbon composites with excellent electrical and magnetic properties are highly desirable as electromagnetic wave absorption materials, but achieving high‐attenuation performance in C‐band (4–8 GHz) remains a challenge. Herein, a direct carbothermal reduction of organic gluconate solid‐solution precursor method is developed to synthesize ferromagnetic Fe‐Co‐Ni alloy/carbon composites, which realize high‐attenuation electromagnetic wave absorption in C‐band. By virtue of Fe, Co, and Ni elements homogeneously dispersing at the molecular level in the solid‐solution precursor with the regulated mole ratio, serial FeCo2Ni/C, Co7Fe3/C, FeNi3/C, and Co3Ni/C composites can be deliberately prepared. First‐principles calculations and off‐axis electron holograms can clearly unravel that these Fe‐Co‐Ni alloys could perform as excellent dielectric‐magnetic complementary loss units to trigger synergistic electronic dipole polarization oscillation, magnetic moment resonance, and magnetic coupling interaction. Meanwhile, the rich alloy–carbon interfaces and conductive carbon skeleton can facilitate delightful interfacial polarization and conductive loss. Combining these positive electromagnetic energy dissipation characteristics, FeCo2Ni/C with strengthened dipole polarization oscillation and outstanding impedance matching realizes an extremely high‐attenuation absorption performance with a minimum reflection loss of −82.2 dB at 5.21 GHz. This work provides a feasible and flexible insight into producing magnetic‐dielectric complementary Fe‐Co‐Ni alloys/carbon composites with various alloy compositions as excellent electromagnetic wave absorbers.

The children's gut microbiota, associated with the development of obesity, is in maturation. The impact of obesity on the gut microbiota in childhood could have a more significant effect than on adulthood and eventually be lifelong lasting, but it has been rarely studied. Aimed to discover the difference in gut microbiota between children and adults with obesity, we collected published amplicon sequencing data from National Center for Biotechnology Information (NCBI) and re-analyzed them using a uniform bioinformatic pipeline, as well as predicted the obesity using gut microbiota based on the random forest model. Summarizing common points among these cohorts, we found that the gut microbiota had a significant difference between children with and without obesity, but this difference was not observed in adult cohorts. Based on the random forest model, it was more challenging to predict childhood obesity using gut microbiota than adulthood obesity. Our results suggest that gut microbiota in childhood is more easily affected than in adulthood. Early intervention for childhood obesity is essential to improve children's health and lifelong gut microbiota-related health.

Immune checkpoint blockade (ICB) therapy has emerged as a promising approach for the treatment of hepatocellular carcinoma (HCC), especially for advanced and metastatic tumors. However, many HCC patients do not respond due to low tumor antigen exposure and the highly immunosuppressive tumor microenvironment (ITM). Chemotherapy and photodynamic therapy are considered to be effective methods for eliciting anti-tumor immune responses. Here, we developed a light-triggered nanoplatform Ce6@PMTKP for combination chemo-photodynamic therapy and the potentiation of ICB therapy. The Ce6@PMTKP micelles entrapped Ce6 for photodynamic therapy, while PMTKP contains the ROS-sensitive paclitaxel (PTX) polymeric prodrug for chemotherapy. The Ce6@PMTKP micelles showed excellent tumor accumulation and light-triggered drug release. Compared with chemotherapy or photodynamic therapy alone, the combination therapy mediated by Ce6@PMTKP was found to be more effective in the elimination of tumors, induction of immunogenic cell death, and the promotion of dendritic cell maturation and cytotoxic T lymphocytes infiltration, thus mitigating ITM immunosuppression. When combined with anti-PD-L1 immunotherapy, the Ce6@PMTKP micelles induced complete regression of primary tumors and effectively inhibited distant metastatic tumors by enhancing anti-tumor immune responses.

Abstract Study design Retrospective case series. Objectives This study aimed to determine the prevalence and risk factors for orthostatic hypotension (OH) in adolescents undergoing posterior spinal fusion for spinal deformity correction. Methods The data of 282 consecutive adolescents who underwent posterior spinal fusion for spinal deformity correction in our center over 12 months were retrieved. Patient characteristics, including whether laminectomy or osteotomy was performed during the surgery, the occurrence of postoperative nausea and vomiting (PONV), perioperative hemoglobin albumin changes, perioperative blood transfusion, length of bed rest, willingness to ambulate, length of postoperative exercises of the lower limbs, and length of hospital stay, were collected and compared statistically between patients who did and did not develop postoperative OH. Results Of 282 patients, 197 (69.86%) developed OH postoperatively, and all cases completely resolved 5 days after the first out-of-bed exercises. Significant differences in the incidence of PONV, the willingness to ambulate and the length of postoperative exercises of the lower limbs were observed. The mean length of hospital stay of the patients with OH was longer than that of the patients without OH. Conclusion Our study suggests that temporary OH is a common manifestation following posterior spinal fusion for spinal deformity correction in adolescents. Postoperative OH may increase the length of hospital stay in these patients. Patients with PONV, who are not willing to ambulate and who perform postoperative lower limb exercises for a shorter time are more likely to have OH.

Background: Small cell lung cancer (SCLC) transformation had previously been reported mainly in epidermal growth factor receptor (EGFR) mutant adenocarcinoma. However, the underlying genomic profile remains unclear. Our study aimed to find the evolution and genotypic characteristic of SCLC transformation. Methods: Thirty-one SCLC transformation patients who were initially diagnosed as non-small cell lung cancer (NSCLC) patients were included. Whole exome sequencing (WES) of both primary and transformed re-biopsy lesions was conducted on 12 patients. Clinical characteristics were analyzed using R software (v.3.6.1). Results: Our study included 31 patients, of whom, three had lung squamous cell carcinoma, 6 patients did not carry EGFR mutations, and 30 patients received chemotherapy for SCLCs. The disease control rate (DCR) was 96.7%, and the median progression-free survival (PFS) was 4.03 months. The median time to transformation was 33.07 months, and the median overall survival (OS) was 62.08 months. Somatic mutation analysis showed that besides TP53, RB1, and EGFR, there was a high occurrence of mutations to CSMD3 and ADAMTS19, especially in the EGFR-wild type (EGFR-wt) group. Concerning mutational signature, the EGFR-mutant (EGFR-mut) transformed group favored an apolipoprotein B (APOBEC) mRNA editing catalytic polypeptide-like-associated mutation pattern (P = 0.16). DNA damage repair (DDR)-related signatures were significantly enriched in the EGFR-wt transformed group (P = 0.034). Additionally, clonal evolution analysis revealed that all patients had the same main trunk genes in the phylogenetic tree. Transformed SCLCs are not sensitive to immunotherapy, possibly due to increased tumor heterogeneity. Conclusions: Our results indicate that the EGFR-wt patients could also transform to SCLCs, but they have different genetic features with EGFR-mut patients. SCLC-transformed patients respond to classical chemotherapy and have a better prognosis than those with classical SCLCs.

Summary: The human gut-on-a-chip has demonstrated in vivo-relevant cellular fidelity and physiological functions of Caco-2 intestinal epithelium compared to its static cultures. However, transcriptomic dynamics that controls the morphogenic and mechanodynamic perturbation of Caco-2 epithelium in a microphysiological culture remain elusive. Single-cell transcriptomic analysis revealed that a gut-on-a-chip culture drives three clusters that illustrate distinct gene expressions and their spatial representation in three-dimensional (3D) epithelial layers. A pseudotemporal trajectory analysis elucidated the evolutionary transition from a homogeneous ancestral genotype in Transwell cultures into heterogeneous transcriptomes in gut-on-a-chip cultures, verified in cell cycle perturbation, cytodifferentiation, and intestinal functions in digestion, transport, and drug metabolism. Furthermore, the inversed transcriptomic signature of oncogenes and tumor-suppressor genes of Caco-2 cells confirmed that gut-on-a-chip cultures induce post-mitotic reprogramming of cancer-associated genes. Our study suggests that a physiological gut-on-a-chip culture induces the transcriptomic perturbation of Caco-2 epithelium to elicit in vivo-relevant morphogenesis and restoration of normal physiological functions.

Background and Aim The relationship between the oral microbiota and type 1 diabetes (T1D) remains unclear. We aimed to evaluate the variations in the oral microbiome in T1D and identify potentially associated bacterial factors.Methods We performed high-throughput sequencing of the V3-V4 area of the 16S rRNA gene to profile the oral bacterial composition of 47 healthy children (CON group), 46 children with new-onset T1D in the acute phase (NT1D group), and 10 children with T1D in the chronic phase receiving insulin treatment (CT1D group). Multivariate statistical analysis of sequencing data was performed.Results Compared to the CON group, the NT1D group was characterized by decreased diversity and increased abundance of genera harboring opportunistic pathogens, while this trend was partially reversed in the CT1D group. Differential genera between groups could distinguish the NT1D group from the CON group (AUC = 0.933) and CT1D group (AUC = 0.846), respectively. Moreover, T1D-enriched genera were closely correlated with HbA1c, FBG and WBCs levels.Conclusion Our results showed that the acute phase of T1D was characterized by oral microbiota dysbiosis, which could be partially ameliorated via glycemic control. The possible role of oral microbiota dysbiosis on oral health and systemic metabolic status in T1D warrants further mechanistic investigation.

Abstract The flow state of oil film in the hydrostatic lead screw directly affects the transmission performance of the screw pair. The static and dynamic characteristics of a new type of double driven hydrostatic screw-nut pair (DDHSNP) are studied under different motion modes. The boundary condition of navier slip model is introduced into the lubricating mathematical model of DDHSNP, and the influences of boundary slip on the axial bearing capacity, axial stiffness and damping coefficient in micro scale are researched by finite difference method. The results show that when the motor runs at high speed (the rotating speed range of the screw and nut driven motor is 1000–9000 rpm), the existence of boundary slip leads to a improvement of the axial bearing capacity and stiffness coefficient of DDHSNP in the case of single-drive operation and dual-drive differential feed (the range of rotation difference is 10–100 rpm), which is more obvious under the single-drive mode. The increase rate of stiffness coefficient induced by boundary slip is much larger than that of bearing capacity. In addition, the boundary slip has little effect on the damping coefficient of DDHSNP in either single drive operation or dual drive differential operation.

Abstract Background Hepatocellular carcinoma (HCC) is a common malignant tumor with high rate of metastasis and recurrence. Although immune checkpoint blockade (ICB) has emerged as a promising type of immunotherapy in advanced HCC, treatment with ICB alone achieves an objective remission rate less than 20%. Thus, combination therapy strategies is needed to improve the treatment response rate and therapeutic effect. Methods A light-triggered disassembly of nanoplatform (TB/PTX@RTK) co-loaded an aggregation induced emission (AIE) photosensitizer (TB) and paclitaxel (PTX) was prepared for on-command drug release and synergistic chemo-photodynamic therapy (chemo-PDT). Nano-micelles were characterized for drug loading content, hydrodynamic size, absorption and emission spectra, reactive oxygen species production, and PTX release from micelles. The targeted fluorescence imaging of TB/PTX@RTK micelles and the synergistic anti-tumor efficacy of TB/PTX@RTK micelles-mediated chemo-PDT combined with anti-PD-L1 were assessed both in vitro and in vivo. Results The TB/PTX@RTK micelles could specifically accumulate at the tumor site through cRGD-mediated active target and facilitate image-guided PDT for tumor ablation. Once irradiated by light, the AIE photosensitizer of TB could produce ROS for PDT, and the thioketal linker could be cleaved by ROS to precise release of PTX in tumor cells. Chemo-PDT could not only synergistically inhibit tumor growth, but also induce immunogenic cell death and elicit anti-tumor immune response. Meanwhile, chemo-PDT significantly upregulated the expression of PD-L1 on tumor cell surface which could efficiently synergize with anti-PD-L1 monoclonal antibodies to induce an abscopal effect, and establish long-term immunological memory to inhibit tumor relapse and metastasis. Conclusion Our results suggest that the combination of TB/PTX@RTK micelle-mediated chemo-PDT with anti-PD-L1 monoclonal antibodies can synergistically enhance systemic anti-tumor effects, and provide a novel insight into the development of new nanomedicine with precise controlled release and multimodal therapy to enhance the therapeutic efficacy of HCC. Graphical Abstract

Abstract Background Contradictory opinions about whether early correction and fusion surgeries should be performed for congenital scoliosis (CS) patients at a young age exist. The objectives of this study were to analyze the association between patient characteristics and fusion-surgery outcomes in CS patients treated with spinal correction and fusion surgeries and to report risk factors for extended length of stay (LOS), more estimated blood loss (EBL), longer fused segments and higher medical costs. Methods We analyzed data of 1,207 CS inpatients treated with fusion surgeries in our institute from January 2010 - December 2019. All patients underwent spinal X-ray, CT, MRI, echocardiogram and urogenital ultrasound. We analyzed demographic and clinical information and outcome measures, including LOS, EBL, fused segments and medical costs. Results Age at fusion (OR = 1.053; p

Background: Desert hedgehog (DHH), as a member of the Hedgehog (HH) family, is mainly involved in testicular development and peripheral nerve sheath formation. A DHH variant has been identified in patients with 46, XY gonadal dysgenesis (46, XY GD) with or without neuropathy, but few reports mention the involvement of other complications.Case presentation: Here, we report a Chinese female patient who was hospitalized at 14.3 years old due to slow breast development for more than 1 year. She had a female genitalia phenotype and breast development started at 13 years old but progressed slowly. She was not yet menarche on admission, and she had intermittent muscle cramps in her hands and feet. Her karyotype analysis was 46, XY and the SRY gene was positive. Surgical exploration revealed no uterus or ovaries, and the pathology of bilateral gonads was dysplastic testis tissue, which was consistent with partial gonadal dysgenesis (PGD). Genetic analysis identified a homozygous pathogenic variant in DHH exon 3 (c.1027T>C, p. Cys343Arg). During the 6-year follow-up, she received estrogen replacement therapy, resulting in breast development progression without gender dysphoria. However, her peripheral neuropathy became more obvious, and a nerve conduction study (NCS) indicated decreased nerve conduction velocity and action potential. In addition, she also suffered complications such as obesity, insulin resistance, fatty liver, and gastric ulcers.Conclusion: In the present study, we reported a case of 46, XY GD with minifascicular neuropathy caused by a DHH homozygous variant, and we summarized the reported cases worldwide. For the first time in such patients, we showed a comparison of NCS changes with age as well as the presence of multiple complications not previously reported.

Paclitaxel-triethylenetetramine hexaacetic acid conjugate (PTX-TTHA), a novel semi-synthetic taxane, is designed to improve the water solubility and cosolvent toxicity of paclitaxel in several aminopolycarboxylic acid groups. In this study, the in vitro and in vivo antitumor effects and mechanisms of PTX-TTHA against triple-negative breast cancer (TNBC) and its intravenous toxicity were evaluated. Results showed the water solubility of PTX-TTHA was greater than 5 mg/mL, which was about 7140-fold higher than that of paclitaxel (5 nmol/L) could significantly inhibit breast cancer proliferation and induce apoptosis by stabilizing microtubules and arresting the cell cycle in the G2/M phase in vitro, with its therapeutic effect and mechanism similar to paclitaxel. However, when the MDA-MB-231 cell-derived xenograft (CDX) tumor model received PTX-TTHA (13.73 mg/kg) treatment once every 3 days for 21 days, the tumor inhibition rate was up to 77.32%. Furthermore, PTX-TTHA could inhibit tumor proliferation by downregulating Ki-67, and induce apoptosis by increasing pro-apoptotic proteins (Bax, cleaved caspase-3) and TdT-mediated dUTP nick end labeling (TUNEL) positive apoptotic cells, and reducing anti-apoptotic protein (Bcl-2). Moreover, PTX-TTHA demonstrated no sign of acute toxicity on vital organs, hematological, and biochemical parameters at the limit dose (138.6 mg/kg, i.v.). Our study indicated that PTX-TTHA showed better water solubility than paclitaxel, as well as comparable in vitro and in vivo antitumor activity in TNBC models. In addition, the antitumor mechanism of PTX-TTHA was related to microtubule regulation and apoptosis signaling pathway activation.

Magnetic fluids, as smart nanomaterials, have been successfully used in sealing applications and other fields. However, the temperature of magnetic fluids in the sealing gap is a key factor affecting sealing performances, limiting their application in high-speed sealing fields. Since obtaining a direct measurement of the magnetic fluid’s temperature is difficult, due to the small clearance, accurately calculating the maximum temperature of the magnetic fluid layer in high-speed seals is crucial. Herein, a mathematical model for calculating the maximum temperature of the magnetic fluid layer was established, by using a reasonable simplification of high-speed sealing conditions, and the calculation formula was modified by studying the rheological properties of the diester-based magnetic fluid. The results suggest that the calculation of the maximum temperature is influenced by viscous dissipation, and both are related to the rheological characteristics of magnetic fluids. When the influence of rheological properties is ignored, the calculation results are not accurate for higher-velocity seals, but the calculation model applies to lower-velocity seals. When the influence of rheological properties is considered, the calculation results obtained by the corrected formula are more accurate, and they are applicable to both lower- and higher-velocity seals. This work can help us more accurately and conveniently estimate the maximum temperature of magnetic fluids in high-speed seal applications, which is of theoretical and practical research significance for determining sealing performances and thermal designs.

Abstract Purpose To analyze how pedicle subtraction osteotomy (PSO) treatment of severe Scheuermann thoracolumbar kyphosis (STLK) using pedicle screw instrumentation affects sagittal spinopelvic parameters. Background The medical literature on the post-surgical effects of treatments such as Ponte osteotomy is limited, but suggests few effects on spinopelvic profiles. Currently, there is no research regarding changes in sagittal spinopelvic alignment upon PSO treatment in STLK patients. Methods We performed a retrospective study on 11 patients with severe STLK. These patients underwent posterior-only correction surgeries with PSO and pedicle screw instrumentation between 2012 to 2017 in a single institute. Patients were measured for the following spinopelvic parameters: global kyphosis (GK), thoracic kyphosis (TK), thoracolumbar kyphosis (TL), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tile (PT), sacral slope (SS), and administered a Scoliosis Research Society-22 questionnaire (SRS-22) pre-operation, post-operation and at final follow-up. Results GK improved from a median of 74.1° to 40.0° after surgery, achieving a correction rate of 48.8% with a median correction loss of 0.8°. TK, TL and LL all showed significant difference (P

Abstract Background Noonan syndrome is an inherited disease involving multiple systems. More than 15 related genes have been discovered, among which LZTR1 was discovered recently. However, the pathogenesis and inheritance pattern of LZTR1 in Noonan syndrome have not yet been elucidated. Case presentation We herein describe a family with LZTR1-related Noonan syndrome. In our study, the proband, sister, mother, maternal aunt and grandmother and female cousin showed the typical or atypical features of Noonan syndrome. Only 3 patients underwent the whole-exome sequencing analysis and results showed that the proband as well as her sister inherited the same heterozygous LZTR1 variant (c.1149 + 1G > T) from their affected mother. Moreover, the proband accompanied by growth hormone deficiency without other associated variants. Conclusion In a Chinese family with Noonan syndrome, we find that the c.1149 + 1G > T variant in LZTR1 gene shows a different autosomal dominant inheritance from previous reports, which changes our understanding of its inheritance and improves our understanding of Noonan syndrome.

Abstract Background It is showed that inflammation is causative factor for PCOS, leading to a decline in ovarian fertility. Previous studies have reported that tea consumption can reduce the incidence of ovarian cancer. We speculate that catechins from oolong tea (Camellia sinensis (L.) O. Kuntze) may have a potential therapeutic effect on PCOS. This study aims to investigate the effects of oolong tea catechins on the uterus of polycystic ovary syndrome (PCOS) mice induced by insulin combined with human chorionic gonadotropin (hCG). Methods Sixty female mice were divided into 6 groups (n = 10): model, model + Metformin 200 mg/kg, model + catechins 25 mg/kg, model + catechins 50 mg/kg, and model + catechins 100 mg/kg. Another forty female mice were divided into 4 groups (n = 10): control, control + catechins 100 mg/kg, model, and model + catechins 100 mg/kg. Ovarian and uterine weight coefficients, sex hormone levels, glucose metabolism and insulin resistance, and ovarian and uterine pathology were examined. Changes in NF-κB-mediated inflammation, MMP2 and MMP9 expressions, and STAT3 signaling were evaluated in the uterus of mice. Results Catechins could effectively reduce the ovarian and uterine organ coefficients, reduce the levels of E2, FSH and LH in the blood and the ratio of LH/FSH, and improve glucose metabolism and insulin resistance in PCOS mice induced by insulin combined with hCG. In addition, catechins could significantly down-regulated the expression of p-NF-κB p65 in the uterus and the protein expressions of the pro-inflammatory factors (IL-1β, IL-6, and TNF-α). The expressions of mmp2 and mmp9 associated with matrix degradation in uterine tissue were also significantly down-regulated by catechins. Further, catechins significantly reduced the expression of p-STAT3 and increased the expression of p-IRS1 and p-PI3K in the uterus of PCOS mice. Conclusion Catechins from oolong tea can alleviate ovarian dysfunction and insulin resistance in PCOS mice by inhibiting uterine inflammation and matrix degradation via inhibiting p-STAT3 signaling.

Abstract Background Hepatic epithelioid hemangioendothelioma (HEHE) is an extremely rare borderline tumor of vascular endothelial origin. Laparoscopic resection of HEHE has never been reported. Methods The clinical data of eleven patients with HEHE (4 women and 7 men) who were diagnosed and treated at the Union Hospital (Wuhan, China), and Wuhan Asia General Hospital (Wuhan, China), between March 2012 and July 2020 were analyzed retrospectively. Results The mean age of HEHE patients was 42.4 ± 13.9 years (range 22–67 years). All patients underwent laparoscopic surgery alone or in combination with radiofrequency ablation. Most tumors showed aggressive growth or metastasis. By immunohistochemistry, tumor cells were positive for CD31, CD34, ERG, PCK, FLi-1, TFE-3, and Ki-67 (labeling index range, 5–15%). In one of the patients, the tumor was accompanied by partial necrosis with a local appearance of epithelioid angiosarcoma. Postoperative adjuvant treatment included chemotherapy, sorafenib, and Huaier granule. As of July 2020, the median follow-up duration was 36 months (range, 9–60 months), with 2 (18.2%) patients experiencing tumor recurrence. Conclusions This is the first report of laparoscopic hepatectomy of HEHE. Curative laparoscopic hepatectomy might be an acceptable treatment for appropriate HEHE patients.

Abstract Background In isolated premature thelarche (IPT) girls, bone age (BA) is considered consistent with chronological age. However, some IPT girls confirmed by gonadotropin-releasing hormone (GnRH) stimulation test could show another trend. We analysed BA and possible potentiating factors in a selected group of girls aged 4–8 years with IPT. Methods IPT girls confirmed by GnRH stimulation test aged 4–8 years hospitalized from January 2015 to April 2018 at Shenzhen Children’s Hospital were included in this retrospective study. They were divided into two groups with advanced BA of 2 years as the cut-off. Body mass index (BMI) and hormone levels were the main outcome measures, and regression analysis was used to identify independent risk factors. IPT girls were divided into subgroups according to the levels of BMI standard deviation score (SDS), insulin-like growth factor-1 (IGF-1) SDS and dehydroepiandrosterone sulfate (DHEAS) SDS for comparisons of advanced BA. Results Overall, 423 subjects were included and classified into the advanced BA group (48.7%, n = 206) and control group (51.3%, n = 217). The advanced BA group had significantly higher BMI SDS, serum DHEAS SDS, IGF-1 SDS, androstenedione and fasting insulin and significantly lower sex hormone binding globulin (all p

Background. Endometrial cancer (EC) is a common tumor of the genital tract that affects the female reproductive system but with only limited treatment options. We aimed to discover new prognostic biomarkers for EC. Methods. We used mRNA-seq data to detect differentially expressed genes (DEGs) between EC and control tissues. Detailed clinicopathological information was collected, and changes in the mRNA and protein levels of hub DEGs were analyzed in EC. Copy number variation (CNV) was also evaluated for its association with the pathogenesis of EC. Gene set enrichment analysis (GSEA) was conducted to enrich significant pathways driven by the hub genes. Cox regression analysis was used to select variables to create a nomogram. The nomogram was calibrated by applying the concordance index (C-index), and net benefits of the nomogram at different threshold probabilities were quantified using decision curve analysis (DCA). Results. Differential expression analysis identified 24 DEGs as potential risk factors for EC. Survival analysis revealed that TPX2 expression was related to worsening overall survival in patients with advanced EC. A high CNV was associated with the overexpression of TPX2; this suggested that modifications in the cell-cycle pathway might be crucial in the advancement of EC. Moreover, an individualized nomogram was developed for TPX2 incorporating clinical factors; this was also evaluated for its ability to predict EC. Calibration and DCA analyses confirmed the robustness and clinical usefulness of the nomogram. Conclusion. We offer novel insights into the pathogenesis and molecular mechanisms of EC. The overexpression of TPX2 was related to a poorer prognosis and could serve as a biomarker for predicting prognostic outcomes in EC patients.

Abstract In this letter, the problem of jamming data prediction in wireless communications is investigated. Both time and frequency domains are considered to construct the multi‐domain historical jamming data tensor. Besides, due to the perceiver's limited ability, false alarm data and missing detection data are considered. Two neural network prediction models are proposed to predict the jammers' future actions based on deep learning techniques. One is the multi‐variate long‐short‐term‐memory (multi‐variate LSTM) model, and the other is the 2‐D convolutional long‐short‐term‐memory model. Simulation results show that the proposed models have better prediction accuracy and robustness than the benchmark method.

A new method is proposed to solve the hydrodynamics performances of a fluid lubricated screw-nut pair using FLUENT. Before the simulations, the Computational Fluid Dynamics (CFD) model of the gap flow field is built, based on some approximation rules. During the simulations, the dynamic mesh technology is employed to realize the real-time update of the grids of the computational domain. For a given velocity perturbation, the stiffness and damping coefficients of the system are solved using the finite difference method, and the influences of the perturbations on the system are compared among different ranges. With the fluid–solid interaction and the real-time restriction of the restrictors considered, the system is solved under different loading conditions. A more accurate solution method for the dynamic stiffness and damping coefficients is provided, and the dynamics characteristics of the system after loading are analyzed. On this basis, a qualitative and quantitative comparison is carried out between the method based on the simplified Reynolds equation and the proposed method in this paper, showing the latter superiorities in illustrating the field. A general understanding of the dynamics properties under different loading conditions of the system is obtained through this research, providing a basis for the precision control of the system in the future research.

This paper investigates the transmission performance of a novel dual-drive hydrostatic lead screw micro-nano feed system (DDHLS) that can obtain extremely low speed. Firstly, the oil film liquid friction of hydrostatic transmission is modelled, and the calculation model of oil film dynamic friction is proposed based on the variable viscosity theory. Secondly, on this basis, combined with the LuGre friction model, a novel all-components refinement friction identification method (ACRFIM) for DDHLS was developed. The friction parameters of the feed drive components such as LM guide and hydrostatic lead screw can be identified independently using the proposed method, ensuring precise friction force modelling in all components. Then, an all-component adaptive friction compensation control algorithm (AACA) was designed by introducing the temperature and disturbance influence factors into the friction model and considering the influence of the dynamic friction of liquid. The experiments illustrate that the calculation accuracy of the oil film friction model based on the variable viscosity theory is substantially improved. DDHLS can effectively suppress the adverse effects of nonlinear friction, and the proposed AACA has an obvious compensation effect for the friction of the time-varying system.

Aortic dissection (AD) is a fatal cardiovascular acute disease with high incidence and mortality, and it seriously threatens patients’ lives and health. The pathogenesis of AD mainly includes vascular inflammation, extracellular matrix degradation, and phenotypic conversion as well as apoptosis of vascular smooth muscle cells (VSMCs); however, its detailed mechanisms are still not fully elucidated. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are an emerging class of RNA molecules without protein-coding ability, and they play crucial roles in the progression of many diseases, including AD. A growing number of studies have shown that the dysregulation of ncRNAs contributes to the occurrence and development of AD by modulating the expression of specific target genes or the activity of related proteins. In addition, some ncRNAs exhibit great potential as promising biomarkers and therapeutic targets in AD treatment. In this review, we systematically summarize the recent findings on the underlying mechanism of ncRNA involved in AD regulation and highlight their clinical application as biomarkers and therapeutic targets in AD treatment. The information reviewed here will be of great benefit to the development of ncRNA-based therapeutic strategies for AD patients.