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Because basalt formation is rich in calcium, magnesium, iron and other bivalent metal elements, it can transform injected CO2 into carbonate rock through efficient mineralization reaction, so as to achieve a safe and effective permanent storage of CO2. However, the research on the mechanism of CO2 mineralization and storage is incomplete, and most studies ignore the effect of diffusion on the mechanism of CO2 mineralization. By conducting experiments with the sand grains being filled in the tube or scatted in a beaker, the CO2-water-rock reactions with different minerals, different particle sizes and different reaction time are investigated. The rock samples after the reaction are analyzed by multi-dimensional analysis, including Raman spectra, inorganic carbon content and SEM-EDS, thus clarifying the importance of diffusion in the CO2 mineralization and the spatio-temporal evolution of CO2 mineralization products under diffusion control. At the same time, the numerical simulation model of the tube filling experiment is established by TOUGHREACT, and the accuracy of the numerical simulation model is ensured by fitting the physical experiment results. On this basis, more studies on the law of the influencing factors are carried out, and the mechanistic explanation for the physical experimental phenomena is provided. The results of physical experiment and numerical simulation show that: ① For the experiment carried out with olivine grains scattered at the bottom of beaker, no diffusion occurred. At this situation, after 14 days’ reaction, no mineral carbonation was observed. Meanwhile, after 28 days marginal amount of magnesite was observed. ② In contrast, in the filled tubes, under the control of diffusion, the main precipitates in the olivine filled tube are magnesite, and the precipitates in the natural basalt filled tube are mainly calcite and siderite, with magnesite as auxiliary. At the same mineral particle size and the same reaction time, the CO2 mineralization rate in natural basalt is much smaller than that of olivine, because olivine has the fastest dissolution rate compared with other constituent minerals of basalt. ③ In olivine or basalt filled tubes, the carbonate precipitates are distributed ununiformly along the filled tubes. The root cause of this phenomenon is explained by numerical simulation, i.e., under the control of diffusion, there are concentration gradients of pH, DIC and bivalent metal cations in the packed bed, and the concentration gradients are different in different directions. ④ The specific mineral surface has a significant influence on the CO2-water-rock reaction, which not only affects the mineralization efficiency but also affects the spatial distribution of the mineralized products, and finally affects the porosity distribution of the porous media after the reaction. ⑤ Compared with pressure, temperature has more influence on CO2 mineralization. The precipitation of calcite, siderite and carbonate increases significantly when the temperature increases from 65 ℃ to 85 ℃, but only the precipitation of magnesite increases significantly when the temperature increases from 85 ℃ to 100 ℃. The pressure has little effect on the formation of calcite precipitate, but has no effect on the formation of magnesite and siderite.

Background: Hyperbaric oxygen therapy (HBOT), which is widely used in clinical practice, is aimed at improving nerve function impairment after brain injury. Meanwhile, the effects of music therapy on brain function are unclear. This retrospective study was conducted to explore the application effect of HBOT combined with music therapy on patients suffering from aneurysmal subarachnoid hemorrhage (aSAH). Methods: For this retrospective study, 130 patients with aSAH after HBOT were selected from our hospital from June 2021 to June 2022. The patients were divided into the observation (n = 70) and control (n = 60) groups based on whether they received music therapy. Comparisons were made on general demographic data, blood flow rate in median cerebral artery (MCA), cerebral vasospasm (CVS), National Institutes of Health Stroke Scale (NIHSS), activities of daily living (ADL) score, Self-Rating Depressive Scale (SDS), and Self-Rating Anxiety Scale (SAS) of patients. Results: Baseline data between the two groups showed no statistically significant difference (P > 0.05). After management, patients in the observation group presented significantly lower SAS and SDS scores (P < 0.05), lower blood flow rate in MCA, CVS and NIHSS scores (P < 0.05), and higher ADL scores than the control group (P < 0.05). Conclusions: The combination of HBOT and music therapy can considerably improve cerebral neurological deficits, slow down cerebral arterial blood flow, promote the recovery of postoperative cerebral function in aSAH patients, and improve anxiety and depression and the patients’ ADL.

Supercapacitors (SCs) are considered promising energy storge systems because of their outstanding power density, fast charge and discharge rate and long-term cycling stability. The exploitation of cheap and efficient electrode materials is the key to improve the performance of supercapacitors. As the battery-type materials, transition metal phosphides (TMPs) possess high theoretical specific capacity, good electrical conductivity and superior structural stability, which have been extensively studied to be electrode materials for supercapacitors. In this review, we summarize the up-to-date progress on TMPs materials from diversified synthetic methods, diverse nanostructures and several prominent TMPs and their composites in application of supercapacitors. In the end, we also propose the remaining challenges toward the rational discovery and synthesis of high-performance TMP electrodes materials for energy storage.

Whole genome doublings (WGD), a hallmark of human cancer, is pervasive in breast cancer patients. However, the molecular mechanism of the complete impact of WGD on survival and treatment response in breast cancer remains unclear. To address this, we performed a comprehensive and systematic analysis of WGD, aiming to identify distinct genetic alterations linked to WGD and highlight its improvement on clinical outcomes and treatment response for breast cancer. A linear regression model along with weighted gene co-expression network analysis (WGCNA) was applied on The Cancer Genome Atlas (TCGA) dataset to identify critical genes related to WGD. Further Cox regression models with random selection were used to optimize the most useful prognostic markers in the TCGA dataset. The clinical implication of the risk model was further assessed through prognostic impact evaluation, tumor stratification, functional analysis, genomic feature difference analysis, drug response analysis, and multiple independent datasets for validation. Our findings revealed a high aneuploidy burden, chromosomal instability (CIN), copy number variation (CNV), and mutation burden in breast tumors exhibiting WGD events. Moreover, 247 key genes associated with WGD were identified from the distinct genomic patterns in the TCGA dataset. A risk model consisting of 22 genes was optimized from the key genes. High-risk breast cancer patients were more prone to WGD and exhibited greater genomic diversity compared to low-risk patients. Some oncogenic signaling pathways were enriched in the high-risk group, while primary immune deficiency pathways were enriched in the low-risk group. We also identified a risk gene, ANLN (anillin), which displayed a strong positive correlation with two crucial WGD genes, KIF18A and CCNE2. Tumors with high expression of ANLN were more prone to WGD events and displayed worse clinical survival outcomes. Furthermore, the expression levels of these risk genes were significantly associated with the sensitivities of BRCA cell lines to multiple drugs, providing valuable insights for targeted therapies. These findings will be helpful for further improvement on clinical outcomes and contribution to drug development in breast cancer.

Abstract N4-acetylcytidine (ac4C) is a post-transcriptional RNA modification that regulates in various important biological processes. However, its role in human cancer, especially lymph node metastasis, remains largely unknown. Here, we demonstrated N-Acetyltransferase 10 (NAT10), as the only known “writer” of ac4C mRNA modification, was highly expressed in head and neck squamous cell carcinoma (HNSCC) patients with lymph node metastasis. High NAT10 levels in the lymph nodes of patients with HNSCC patients are a predictor of poor overall survival. Moreover, we found that high expression of NAT10 was positively upregulated by Nuclear Respiratory Factor 1 (NRF1) transcription factor. Gain- and loss-of-function experiments displayed that NAT10 promoted cell metastasis in mice. Mechanistically, NAT10 induced ac4C modification of Glycosylated Lysosomal Membrane Protein (GLMP) and stabilized its mRNA, which triggered the activation of the MAPK/ERK signaling pathway. Finally, the NAT10-specific inhibitor, remodelin, could inhibit HNSCC tumorigenesis in a 4-Nitroquinoline 1-oxide (4NQO)-induced murine tumor model and remodel the tumor microenvironment, including angiogenesis, CD8+ T cells and Treg recruitment. These results demonstrate that NAT10 promotes lymph node metastasis in HNSCC via ac4C-dependent stabilization of the GLMP transcript, providing a potential epitranscriptomic-targeted therapeutic strategy for HNSCC.

ObjectiveTo construct an evaluation framework for prioritizing the inclusion of non-program vaccines into planned immunization of Shenzhen city. MethodsAfter developing a preliminary evaluation framework with literature studies, we conducted two rounds of Delphi consultation among 15 experts for screening relevant indicators and modifying the framework during March – July 2022. The weight of each indicator in the framework was calculated using analytic hierarchy process. ResultsThe active coefficients for the two rounds of expert consultation were 100% and 86.67% and the expert authority index was 0.84 for the two rounds of consultation. The concordance coefficients for the experts′ comprehensive evaluation scores of all indicators ranged between 0.199 – 0.465 (P < 0.05) and 0.253 – 0.442 (P < 0.05) in the first and second consultation. Totally 4 primary, 13 secondary and 34 tertiary indicators were included in the finally established evaluation framework for assessing the priority of a non-program vaccine to be included into planned immunization on 4 dimensions: disease impact (disease burden, economic burden, prevention urgency), vaccine effect (safety, efficacy, related attributes), vaccination feasibility (policy making, fund, vaccine supply, human resource, surveillance), and cost-effectiveness (economic and social benefit). The combined weights were between 0.003 and 0.279 for all the indicators. ConclusionThe established evaluation framework is innovative and reliable and could provide a reference tool in selecting a vaccine to be included into Shenzhen municipal immunization program.

Abstract Chronic prostatic inflammation promotes cell survival and fibrosis, leading to benign prostatic hyperplasia (BPH) with aggravated urinary symptoms. It is investigated whether yes‐associated protein 1 (YAP1), an organ size controller and mechanical transductor, is implicated in inflammation‐induced BPH. The correlation between YAP1 expression and fibrosis in human and rat BPH specimens is analyzed. Furthermore, the effects of YAP1 activation on prostatic cell survival and fibrosis, as well as the underlying mechanism, are also studied. As a result, total and nuclear YAP1 expression, along with downstream genes are significantly upregulated in inflammation‐associated human and rat specimens. There is a significant positive correlation between YAP1 expression and the severity of fibrosis or clinical performance. YAP1 silencing suppresses cell survival by decreasing cell proliferation and increasing apoptosis, and alleviates fibrosis by reversing epithelial‐mesenchymal transition (EMT) and extracellular matrix (ECM) deposition in prostatic BPH‐1 and WPMY‐1 cells. Mechanistically, inflammatory stimulus and rigid matrix stiffness synergistically activate the RhoA/ROCK1 pathway to provoke cytoskeleton remodeling, thereby promoting YAP1 activation to exacerbate BPH development. Overall, inflammation‐triggered mechanical stiffness reinforcement activates the RhoA/ROCK1/F‐actin/YAP1 axis, thereby promoting prostatic cell survival and fibrosis to accelerate BPH progression.

Accumulation of the heavy metal Cadmium (Cd) in the ovaries and placenta can affect the structure and function of these organs and induce female reproductive toxicity. This toxicity may be due to Cd’s similarity to estrogen and its ability to disrupt endocrine systems. However, the exact molecular mechanism by which Cd causes reproductive toxicity at the transcriptome level remains poorly understood. Hence, this study aimed to observe Cd-induced reproductive damage at the gene level, scrutinize the repercussions of Cd exposure on oogenesis, and explicate the putative pathogenesis of Cd-induced oogenesis based on Caenorhabditis elegans (C. elegans) as an in vivo model. The results showed that Cd exposure significantly decreased the number of offspring and prolonged the reproductive span of C. elegans. Cd exposure also reduced the number of cells in mitosis and the pachytene and diakinesis stages of meiosis, thereby disrupting oogenesis. Combined with transcriptional sequencing and bioinformatics analysis, a total of 3167 DEmRNAs were identified. Regarding gene expression, cul-6, mum-2, and vang-1 were found to be related to Cd-induced reproductive toxicity, and their competing endogenous RNA networks were constructed. We observed that mutations of mom-2 and vang-1 in the Wnt pathway could induce susceptibility to Cd-caused meiosis injury. In conclusion, the results indicated that Cd could impair the oogenesis of C. elegans and the Wnt pathway might serve as a protective mechanism against Cd reproductive toxicity. These findings contribute to a better understanding of the damaging effects and molecular biological mechanisms of Cd on the human reproductive system.

Highlights History and benefits of zinc ion hybrid capacitors are introduced. Carbon materials with different dimensions are developed for the cathodes. Relationship between carbon structures and capacitive performances are discussed. Current collectors and separators are firstly showcased and summarized.

BackgroundAlternative splicing events (ASEs) are vital causes of tumor heterogeneity in genitourinary tumors and many other cancers. However, the clinicopathological relevance of ASEs in cancers has not yet been comprehensively characterized.MethodsBy analyzing splicing data from the TCGA SpliceSeq database and phenotype data for all TCGA samples from the UCSC Xena database, we identified differential clinical feature-related ASEs in 33 tumors. CIBERSORT immune cell infiltration data from the TIMER2.0 database were used for differential clinical feature-related immune cell infiltration analysis. Gene function enrichment analysis was used to analyze the gene function of ASEs related to different clinical features in tumors. To reveal the regulatory mechanisms of ASEs, we integrated race-related ASEs and splicing quantitative trait loci (sQTLs) data in kidney renal clear cell carcinoma (KIRC) to comprehensively assess the impact of SNPs on ASEs. In addition, we predicted regulatory RNA binding proteins in bladder urothelial carcinoma (BLCA) based on the enrichment of motifs around alternative exons for ASEs.ResultsAlternative splicing differences were systematically analyzed between different groups of 58 clinical features in 33 cancers, and 30 clinical features in 24 cancer types were identified to be associated with more than 50 ASEs individually. The types of immune cell infiltration were found to be significantly different between subgroups of primary diagnosis and disease type. After integrating ASEs with sQTLs data, we found that 63 (58.9%) of the race-related ASEs were significantly SNP-correlated ASEs in KIRC. Gene function enrichment analyses showed that metastasis-related ASEs in KIRC mainly enriched Rho GTPase signaling pathways. Among those ASEs associated with metastasis, alternative splicing of GIT2 and TUBB3 might play key roles in tumor metastasis in KIRC patients. Finally, we identified several RNA binding proteins such as PCBP2, SNRNP70, and HuR, which might contribute to splicing differences between different groups of neoplasm grade in BLCA.ConclusionWe demonstrated the significant clinical relevance of ASEs in multiple cancer types. Furthermore, we identified and validated alternative splicing of TUBB3 and RNA binding proteins such as PCBP2 as critical regulators in the progression of urogenital cancers.

BackgroundMultidrug resistance in bacteria is a serious problem in organ transplantations. This study aimed to identify risk factors and establish a predictive model for screening deceased organ donors for multidrug-resistant (MDR) bacteria.MethodsA retrospective cohort study was conducted at the First Affiliated Hospital of Zhejiang University School of Medicine from July 1, 2019 to December 31, 2022. The univariate and multivariate logistic regression analysis was used to determine independent risk factors associated with MDR bacteria in organ donors. A nomogram was established based on these risk factors. A calibration plot, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to estimated the model.ResultsIn 164 organ donors, the incidence of MDR bacteria in culture was 29.9%. The duration of antibiotic use ≥3 days (odds ratio [OR] 3.78, 95% confidence interval [CI] 1.62–8.81, p=0.002), length of intensive care unit (ICU) stay per day(OR 1.06, 95% CI 1.02–1.11, p=0.005) and neurosurgery (OR 3.31, 95% CI 1.44–7.58, p=0.005) were significant independent predictive factors for MDR bacteria. The nomogram constructed using these three predictors displayed good predictive ability, with an area under the ROC curve value of 0.79. The calibration curve showed a high consistency between the probabilities and observed values. DCA also revealed the potential clinical usefulness of this nomogram.ConclusionsThe duration of antibiotic use ≥3 days, length of ICU stay and neurosurgery are independent risk factors for MDR bacteria in organ donors. The nomogram can be used to monitor MDR bacteria acquisition risk in organ donors.

BackgroundTesticular germ cell tumor (TGCT) is the most common tumor in young men, but molecular signatures, especially the alternative splicing (AS) between its subtypes have not yet been explored.MethodsTo investigate the differences between TGCT subtypes, we comprehensively analyzed the data of gene expression, alternative splicing (AS), and somatic mutation in TGCT patients from the TCGA database. The gene ontology (GO) enrichment analyses were used to explore the function of differentially expressed genes and spliced genes respectively, and Spearman correlation analysis was performed to explore the correlation between differential genes and AS events. In addition, the possible patterns in which AS regulates gene expression were elaborated by the ensemble database transcript atlas. And, we identified important transcription factors that regulate gene expression and AS and functionally validated them in TGCT cell lines.ResultsWe found significant differences between expression and AS in embryonal carcinoma and seminoma, while mixed cell tumors were in between. GO enrichment analyses revealed that both differentially expressed and spliced genes were enriched in transcriptional regulatory pathways, and obvious correlation between expression and AS events was determined. By analyzing the transcript map and the sites where splicing occurs, we have demonstrated that AS regulates gene expression in a variety of ways. We further identified two pivot AS-related molecules (SOX2 and HDAC9) involved in AS regulation, which were validated in embryonal carcinoma and seminoma cell lines. Differences in somatic mutations between subtypes are also of concern, with our results suggesting that mutations in some genes (B3GNT8, CAPN7, FAT4, GRK1, TACC2, and TRAM1L1) occur only in embryonal carcinoma, while mutations in KIT, KARS, and NRAS are observed only in seminoma.ConclusionsIn conclusion, our analysis revealed the differences in gene expression, AS and somatic mutation among TGCT subtypes, providing a molecular basis for clinical diagnosis and precise therapy of TGCT patients.

Agouti-related protein (AgRP) is a neuropeptide synthesized by AgRP/NPY neurons and transcribed as 132 amino acids in humans and 142 amino acids (AgRP1) in Japanese seabass (Lateolabrax maculatus) fish. AgRP neurons are activated by hormonal signals of energy deficits and inhibited by signals of energy surpluses and have been demonstrated to have the ability to sense the dynamics of blood glucose concentrations as the “glucose sensor” in mammals. It is widely recognized that AgRP is an endogenous antagonist of the melanocortin-3 and -4 receptors (MC3R and MC4R) in the hypothalamus, exhibiting potent orexigenic activity and control of energy homeostasis. Most fish, especially carnivorous fish, cannot make efficient use of carbohydrates. When carbohydrates like corn or wheat bran are added as energy sources, they often cause feeding inhibition and metabolic diseases. When fishmeal is replaced by plant protein, this does not completely eliminate carbs, limiting the utilization of carbohydrates and plant proteins in aquaculture. Our previous study showed that AgRP, and not neuropeptide Y (NPY) is the principal protein molecule that correlates well with feeding behavior in Japanese seabass from anorexia to adaptation. The Ghrelin/Leptin-mTOR-S6K1-NPY/AgRP/POMC feed intake regulatory pathway responds to the plant-oriented protein which contains glucose. However, its regulatory function and mechanism are still not clear. This review offers an integrative overview of how glucose signals converge on a molecular level in AgRP neurons of the arcuate nucleus of the hypothalamus. This is in order to control fish food intake and energy homeostasis.

Supercapacitors (SCs) have attracted extensive attention due to their ultrahigh power density, fast charging/discharging rate, excellent electrochemical stability and environmental friendliness. Currently, the main commercial electrode materials for SCs are carbon materials in term of low cost, excellent conductivity, large specific surface area and good electrochemical stability. Recently, various dimensional carbon materials including zero dimensional (0D) carbon materials (nanosphere, dot etc.), 1D carbon materials (nanotube, nanofiber etc.), 2D carbon materials (nanosheet) as well as 3D carbon materials have been developed for SCs. Carbon materials with different spatial dimensions have their unique properties when used as the electrode materials for SCs. In this review, recent advances in the fabrication of different dimensional carbons for SCs are summarized. Several key issues for enhancing the electrochemical properties of carbon-based SCs and some mutual relationships among various influence parameters are reviewed, and challenges and perspectives in this field are also discussed.

Background/Objective: The deleterious effects of chronic spinal cord injury (SCI) on the skeleton in rats, especially the lower extremities, has been proved previously. However, the long-term skeletal changes after SCI in non-human primates (NHP) have been scarcely studied. This study aimed to evaluate the bone loss in limbs and vertebrae and the bone metabolic changes in NHP after unilateral cervical spinal cord contusion injury. Methods: Twelve Macaca fascicularis were randomly divided into the SCI (n=8) and the Sham (n=4) groups. The SCI models were established using hemi-contusion cervical spinal cord injury on fifth cervical vertebra (C5), and were further evaluated by histological staining and neurophysiological monitoring. Changes of bone microstructures, bone biomechanics, and bone metabolism markers were assessed by micro-CT, micro-FEA and serological kit. Results: The NHP hemi-contusion cervical SCI model led to consistent unilateral limb dysfunction and potential plasticity in the face of loss of spinal cord. Furthermore, the cancellous bone mass of ipsilateral humerus and radius decreased significantly compared to the contralateral side. The bone volume fraction of humerus and radius were 17.2% and 20.1% on the ipsilateral while 29.0% and 30.1% on the contralateral respectively. Similarly, the thickness of the cortical bone in the ipsilateral forelimbs was significantly decreased, as well as the bone strength of the ipsilateral forelimbs. These changes were accompanied by diminished concentration of osteocalcin and total procollagen type 1 N-terminal propeptide (t-P1NP) as well as increased level of β-C-terminal cross-linking telopeptide of type 1collagen (β-CTX) in serological testing. Conclusions: The present study demonstrated that hemi-SCI induced loss of bone mass and compromised biomechanical performance in ipsilateral forelimbs, which could be indicated by both muscle atrophy and serological changes of bone metabolism, and associated with a consistent loss of large-diameter cells of sensory neurons in the dorsal root ganglia. The Translational potential of this Article: Our study, for the first time, demonstrated the bone loss in limbs and vertebrae as well as the bone metabolic changes in non-human primates after unilateral spinal cord injury (SCI). This may help to elucidate the role of muscle atrophy, serological changes and loss of sensory neurons in the mechanisms of SCI-induced osteoporosis, which would be definitely better compared with rodent models.

ABSTRACT Root-associated microorganisms are widely recognized as playing an important role in mitigating stress-induced damage to plants, but the responses of rhizosphere microbial communities after inoculation and their relationship with plant responses remain unclear. In this study, the bacterium Providencia vermicola BR68 and the fungus Sarocladium kiliense FS18 were selected from among 91 strains isolated from the halophyte Suaeda salsa to interact with maize seedlings under salt stress. The results showed that compared with NaCl-only treatment, inoculation with strains BR68 and FS18 significantly improved the growth, net photosynthetic rate, and antioxidant enzyme activities of maize; significantly reduced proline content and generation rate of reactive oxygen species (ROS); and alleviated oxidative stress and osmotic stress. Moreover, inoculation with these two strains increased the activities of soil microbiome enzymes such as sucrase, catalase, and fluorescein diacetate hydrolase, which improved maize physiologies and promoted maize growth under salt stress. In addition, these inoculated strains significantly affected the abundance of certain genera, and the correlation trends for these genera with soil properties and maize physiologies were similar to those of these inoculated strains. Strain BR68 was indirectly associated with bacterial communities through BR-specific biomarkers, and bacterial communities and soil properties explained most of the variation in maize physiologies and growth. Inoculation of strain FS18 was directly associated with variations in soil properties and maize physiologies. The two strains improved maize growth under salt stress and alleviated stress damage in maize in different ways. The links among salt-tolerant microorganisms, soil, and plants established in this study can inform strategies for improving crop cultivation in salinized lands. IMPORTANCE This study demonstrates that halophyte root-associated microorganisms can promote crop tolerance to salt stress and clarify the mechanism by which the strains work in rhizosphere soil. The links among salt-tolerant microorganisms, soil, and plants established in this study can inform strategies for improving crop cultivation in salinized lands.

Abstract Circular RNAs (circRNAs), which are single-stranded closed-loop RNA molecules lacking terminal 5′ caps and 3′ poly(A) tails, are attracting increasing scientific attention for their crucial regulatory roles in the occurrence and development of various diseases. With the rapid development of high-throughput sequencing technologies, increasing numbers of differentially expressed circRNAs have been identified in bladder cancer (BCa) via exploration of the expression profiles of BCa and normal tissues and cell lines. CircRNAs are critically involved in BCa biological behaviours, including cell proliferation, tumour growth suppression, cell cycle arrest, apoptosis, invasion, migration, metastasis, angiogenesis, and cisplatin chemoresistance. Most of the studied circRNAs in BCa regulate cancer biological behaviours via miRNA sponging regulatory mechanisms. CircRNAs have been reported to be significantly associated with many clinicopathologic characteristics of BCa, including tumour size, grade, differentiation, and stage; lymph node metastasis; tumour numbers; distant metastasis; invasion; and recurrence. Moreover, circRNA expression levels can be used to predict BCa patients’ survival parameters, such as overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). The abundance, conservation, stability, specificity and detectability of circRNAs render them potential diagnostic and prognostic biomarkers for BCa. Additionally, circRNAs play crucial regulatory roles upstream of various signalling pathways related to BCa carcinogenesis and progression, reflecting their potential as therapeutic targets for BCa. Herein, we briefly summarize the expression profiles, biological functions and mechanisms of circRNAs and the potential clinical applications of these molecules for BCa diagnosis, prognosis, and targeted therapy.

Summary: Organs-on-chips are microfluidic devices for cell culturing to simulate tissue-level or organ-level physiology and recapitulate their microenvironment, providing new and significant solutions other than traditional animal tests. In vitro testing platforms for ocular biological studies have been increasingly used in preclinical efficacy and toxicity prediction. Here, we developed a microfluidic platform consisting of human corneal cells and porous membrane, replicating the multi-scale structural organization and biological phenotype. We verified the fully integrated human cornea’s barrier effects on the chip. Moreover, we found that extracellular vesicles derived from bone marrow-derived mesenchymal stem cells can significantly accelerate the mild corneal epithelial wound healing, and the decreased expression of matrix metallopeptidase-2 protein indicated that this method effectively inhibits corneal inflammation and angiogenesis. This work improves our ability to simulate the interaction between the human cornea and the external world in vitro and contributes to the future development of new screening platforms for biopharmaceuticals.

(1) Background: Currently, residents ≥ 60 and ≥65 years old in Beijing, China, are eligible for free influenza and pneumococcal polysaccharide vaccines (PPSV23), respectively. The present study aimed to assess the cost-effectiveness of current and alternative strategies of dual influenza and PPSV23 vaccination among the elderly in Beijing. (2) Methods: We developed a Markov state-transition model to compare the costs and the quality-adjusted life years (QALYs) associated with four influenza and PPSV23 vaccination strategies among the elderly in Beijing. The strategies were as follows: (1) no vaccination; (2) only flu vaccine for people ≥ 60 years old; (3) flu vaccine for people ≥ 60 years old and PPSV23 for people ≥ 65 years old; and (4) dual influenza vaccines and PPSV23 for people ≥ 60 years old. Incremental costs and QALYs were quantified to determine the optimal option. If dominant strategies emerged, the Chinese gross domestic product per capita in 2021 (80,976 CNY) was used as the willingness-to-pay (WTP) threshold to covert QALYs into the monetary equivalent. (3) Results: The current program saved costs and increased QALYs compared to no vaccination or flu vaccine-only strategies. However, extending free PPSV23 to people ≥ 60 years old saved 0.35 CNY additionally while increasing QALYs marginally compared with the current policy. Results were robust in all sensitivity analyses. (4) Conclusion: Beijing’s current dual influenza and pneumococcal vaccination program was cost-effective among the elderly compared with the preceding policies of no vaccination and flu-only immunization programs. However, the program can further save money while enhancing the population health by extending PPSV23 to all people ≥ 60 years old.

Objective: To investigate the neuroprotective effects of trihydroxyethyl rutin in rats with cervical spinal cord hemi-contusion.Methods: Adult male Sprague–Dawley rats were subjected to hemi-contusion at a stroke depth of 1.2 mm, and then intraperitoneally injected with 50 or 100 mg/kg trihydroxyethyl rutin per day for 12 weeks (T50 and T100 groups, respectively). Changes in somatosensory evoked potentials (SEPs), motor evoked potentials (MEPs), and behavior were continuously monitored. At 12 weeks post-injury, immunohistochemical staining was performed to assess changes in cervical spinal cord microvascular morphology. Magnetic resonance imaging (MRI) scans were performed to examine end-stage injury in the cervical spinal cord, and Eriochrome cyanine-stained slices of spinal cord tissue were evaluated for injury.Results: There were no significant differences in biomechanical parameters among the spinal cord injury, T50 and T100 rat groups. At 3 days-post-injury, there was a significant decrease in grip strength. At 12 weeks post-injury, grip strength recovery was significantly better in the T50 and T100 groups than in the injury group. Compared with the injury group, the total limb placement frequency was significantly higher in the T50 group at 2, 4, 6, 10, and 12 weeks post-injury and in the T100 group at 2, 6, 8, and 10 weeks post-injury. Ipsilateral SEPs and MEPs were dynamic, increasing in latency and decreasing in amplitude in the injury compared with sham group. MRI scanning demonstrated that the coronal, sagittal, and transversal lesion areas were smaller in the T50 and T100 groups than in the injury group. Microvascular density showed a greater reduction in the injury group compared with the T50 and T100 groups. Eriochrome cyanine staining showed that the ipsilateral side, residual parenchyma, and gray matter areas were larger in the T50 and T100 groups than in the injury group.Conclusion: Trihydroxyethyl rutin exhibits robust neuroprotective effects, improving limb motor function and nerve electrophysiological parameters after spinal cord injury, maintaining microvascular density, and reducing the area of injury and degree of demyelination.

The role of the human–computer interaction (HCI) system in college students’ oral English learning is discussed to analyze the current situation of college students’ oral English based on the HCI simulation system. The purpose is to study the oral education of college students. First, the theories of educational psychology, the HCI system, and the current situation of college students’ oral English learning are elaborated. Meanwhile, in oral English teaching, teachers use support vector machines and multimodal fusion intention perception methods in set theory to realize the interactive teaching between students and machines; then, the HCI simulation of oral English is explained. The current situation of college students’ oral English learning is analyzed by a questionnaire from the perspective of educational psychology. Finally, the HCI system in college students’ oral English learning is explored based on the learning level detection. The results show that 12% of college students are unqualified in oral English; 25% of them think their oral English level is medium; most of college students’ English learning anxiety is related to English progress anxiety; 18% of the students believe that they will study oral English for life; 32% of the students think that they have more opportunities to learn English at ordinary times; and most of the students learn English through English movies and songs outside of class. What attracts college students to learn oral English through the HCI system is that learning is not limited by time and space. Most students believe that their English level is good and hope that learning anxiety can be reduced through HCI systems. The strategies of college students’ oral English education with an HCI simulation system are evaluated based on the perspective of educational psychology, providing a research basis for oral English education in other regions and even the whole country to facilitate the better development of oral English education.

BackgroundDonor-derived human parvovirus B19 (B19V) infections are rarely reported. Thus, its incidence in kidney transplantation is still unknown due to lack of surveillance studies. Similarly, whether the donor needs to be routinely screened for B19V and whether the kidneys from those with B19V DNAemia could be accepted also remain unknown.MethodsThis retrospective study aims to evaluate the donor-derived B19V infections occurring in 823 living and 1,225 deceased donor kidney transplantations from January 2016 to December 2020. The serum viral load of living donors and their corresponding recipients was evaluated before and after transplantation. Meanwhile, for the deceased donor kidney transplantation, the serum viral load of recipients was only tested after transplantation; if recipients of a deceased donor subsequently developed B19V infection, the serum viral load of recipients and their corresponding donors before transplantation would then be further traced.ResultsA total of 15 living donors were B19V DNAemia positive before the donation, of which B19V DNAemia occurred in three corresponding recipients. In deceased donor kidney transplantation, DNAemia occurred simultaneously in 18 recipients and their corresponding nine donors. A progressive decline in hemoglobin and reticulocyte count could be observed in one living donor recipient and other 11 deceased donor recipients, which were all well controlled by treatment eventually.ConclusionThe incidence of donor-derived B19V infection was 0.4% and 1.5% in living and deceased kidney transplantations, respectively. B19V was seemingly unnecessary to be routinely screened for the donor. Moreover, kidneys of the donors with B19V infection were acceptable.

Objective To analyse the epidemiological characteristics of family clusters of COVID-19 and the three stages of the comprehensive non-pharmaceutical interventions and measures implemented in Shenzhen.Methods The epidemic curve of COVID-19 was drawn and the impact of the comprehensive non-pharmaceutical interventions and measures was analysed by the different periods of the epidemic.Results A total of 427 cases (417 confirmed cases and 10 asymptomatic infectious cases) were reported in Shenzhen, of which 259 (60.7%) were clustered cases. 97 cluster events were drawn and most cluster events (97.3%) occurred in families. There were three stages of the COVID-19 epidemic in Shenzhen. The epidemic increased rapidly, but the peak lasted for a short time, while the decline in incidence was rapid and large.Conclusions Family clusters were the main feature of the COVID-19 outbreak in Shenzhen in 2020, and the Shenzhen government rolled out a quick response to the epidemic. Non-pharmaceutical interventions and measures were proven to have effectively contained community transmission, limit the transmission to aggregation and reduce the scale of transmission within a household.

Abstract Background context Pedicle screw loosening is a common complication after spine surgeries. Traditionally, it was assessed by radiological approaches, both X-ray and CT (computed tomography) scan, while reports using mechanical method to study screw loosening after spine surgery are rare. The primary objective was to study the prevalent of pedicle screw loosening according to extraction torque during screw removal surgery and access the sensitivity and specificity of both X-ray and CT scan for diagnosing screw loosening. The second objective was to identify the risk factors for low extraction torque of pedicle screw that might lead to loosening. Methods Thirty-three patients who underwent pedicle screw removal surgery after at least 2 years from primary surgery were evaluated preoperatively for fixation stability by X-ray and CT scan. In total, 236 screws were taken out, and the extraction torque data was recorded and analyzed to identify the sensitivity and specificity of both imaging studies for screw loosening. Furthermore, risk factors that might contribute to low extraction torque were also studied. Results The mean extraction torque of removed screws was 1.55 ± 1.00 Nm; a torque force of less than 1.02 Nm was used to define a screw as loosened. According to such criterion, the loosening rate was found to be 33%. X-ray had a sensitivity of 24% and a specificity of 98%, while CT scan had a sensitivity of 22% and a specificity of 96%. Extraction torque of pedicle screws inserted in fractured vertebrae was significantly lower than those in non-fractured vertebrae (p = 0.009); meanwhile, screws of non-fusion surgery had lower extraction torque when compared to those in fusion surgery (p = 0.001). BMD (bone mineral density) and age had low but significant linear relationship with screw extraction torque (p = 0.01, R 2 = 0.304; p = 0.045, R 2 = 0.123). Conclusions Our findings showed that both X-ray and CT scan had high specificity for screw loosening detection, but their sensitivities were relatively low. Surgeons needed to be more cautious when assessing screw loosening merely according to radiological examination, and aware of that screws in fractured vertebrae or non-fusion surgery were vulnerable to loosening.

Dysregulation of transcription factors contributes to the carcinogenesis and progression of cancers. However, their roles in clear cell renal cell carcinoma remain largely unknown. This study aimed to evaluate the clinical significance of TFs and investigate their potential molecular mechanisms in ccRCC. Data were accessed from the cancer genome atlas kidney clear cell carcinoma cohort. Bioinformatics algorithm was used in copy number alterations mutations, and differentially expressed TFs’ analysis. Univariate and multivariate Cox regression analyses were performed to identify clinically significant TFs and construct a six-TF prognostic panel. TFs’ expression was validated in human tissues. Gene set enrichment analysis (GSEA) was utilized to find enriched cancer hallmark pathways. Functional experiments were conducted to verify the cancer-promoting effect of BARX homeobox 1 (BARX1) and distal-less homeobox 4 (DLX4) in ccRCC, and Western blot was performed to explore their downstream pathways. As for results, many CNAs and mutations were identified in transcription factor genes. TFs were differentially expressed in ccRCC. An applicable predictive panel of six-TF genes was constructed to predict the overall survival for ccRCC patients, and its diagnostic efficiency was evaluated by the area under the curve (AUC). BARX1 and DLX4 were associated with poor prognosis, and they could promote the proliferation and migration of ccRCC. In conclusion, the six-TF panel can be used as a prognostic biomarker for ccRCC patients. BARX1 and DLX4 play oncogenic roles in ccRCC via promoting proliferation and epithelial–mesenchymal transition. They have the potential to be novel therapeutic targets for ccRCC.

Protecting white matter is one of the key treatment strategies for spinal cord injury (SCI), including alleviation of myelin loss and promotion of remyelination. Rapamycin has been shown neuroprotective effects against SCI and cardiotoxic effects while enhancing autophagy. However, specific neuroprotection of rapamycin for the white matter after cervical SCI has not been reported. Therefore, we aim to evaluate the role of rapamycin in neuroprotection after hemi-contusion SCI in mice. Forty-six 8-week-old mice were randomly assigned into the rapamycin group (n = 16), vehicle group (n = 16), and sham group (n = 10). All mice of the rapamycin and vehicle groups received a unilateral contusion with 1.2-mm displacement at C5 followed by daily intraperitoneal injection of rapamycin or dimethyl sulfoxide solution (1.5 mg⋅kg–1⋅day–1). The behavioral assessment was conducted before the injury, 3 days and every 2 weeks post-injury (WPI). The autophagy-related proteins, the area of spared white matter, the number of oligodendrocytes (OLs) and axons were evaluated at 12 WPI, as well as the glial scar and the myelin sheaths formed by Schwann cells at the epicenter. The 1.2 mm contusion led to a consistent moderate–severe SCI in terms of motor function and tissue damage. Rapamycin administration promoted autophagy in spinal cord tissue after injury and reduced the glial scar at the epicenter. Additionally, rapamycin increased the number of OLs and improved motor function significantly than in the vehicle group. Furthermore, the rapamycin injection resulted in an increase of Schwann cell-mediated remyelination and weight loss. Our results suggest that rapamycin can enhance autophagy, promote Schwann cell myelination and motor function recovery by preserved neural tissue, and reduce glial scar after hemi-contusive cervical SCI, indicating a potential strategy for SCI treatment.

ObjectiveTo investigate the effects of ketogenic metabolism on macrophage polarization, inflammation inhibition, and function recovery after acute spinal cord injury (SCI) in rats.MethodsSixty-four adult male Sprague–Dawley rats were randomly and equally divided into sham, standard diet (SD), ketone diet (KD), and 1, 3-butanediol (BD) groups. All animals underwent C5 unilateral laminectomy, whereas the SD, KD, and BD groups underwent C5 spinal cord hemi-contusion. The impact rod with a diameter of 1.5 mm was aligned 22.5° to the left and 1.4 mm to the midline, and then triggered to deliver a set displacement of 1.5 mm at a speed of 100 mm/s. The gene expression of inflammatory factors as well as the protein expression of inducible nitric oxide synthase, arginase-1, and inflammatory factors were measured at 1 week post-injury. Serum ketone and behavior were evaluated every second week for 12 weeks. Then, histological analyses of the gray and white matter at the epicenter were conducted at 12 weeks post-injury.ResultsThe serum ketone levels of the KD and BD groups were significantly increased when compared with the SD group. The gene and protein expression of TNF-α and IL-1β tended to increase after the SCI, but were inhibited in the KD and BD groups. The protein expression of inducible nitric oxide synthase, marker of M1 macrophage, was inhibited in the KD and BD groups; on the other hand, the expression of arginase-1, marker of M2 macrophage, was boosted in the KD and BD groups. The usage of the ipsilateral forelimb was higher in the KD group than in the SD group. The hemi-contusive injury resulted in an obvious ipsilateral lesion area at the epicenter, and there was no significant difference between groups regarding the lesion size. However, the spared gray matter area was significantly greater in the KD group than in the SD and BD groups.ConclusionThe present study suggests that ketogenic metabolism promotes macrophage polarization to M2, inhibits an inflammatory response, and alleviates the loss of gray matter after SCI. A higher ketone level, such as that induced by the ketogenic diet, seems to benefit function recovery after SCI.

Background and Objectives. Back pains associated with osteoporotic vertebral compression fractures (OVCFs) may arise not just from vertebral body but also from posterior elements. Percutaneous vertebroplasty (PVP) and facet blocking (FB) combined therapy would relieve pain better, but it has not been elucidated. The purpose of this retrospective study was to compare the treatment effects of PVP and FB combined therapy with PVP alone in OVCFs patients. Methods. Clinical and radiological data of 204 patients were reviewed. The patients were divided into Group A (PVP alone) and Group B (PVP and FB combined therapy) according to treatments. Back pain was evaluated with Visual Analog Scale (VAS) and Oswestry Disability Index (ODI). The operation, fluoroscopic exposure time, and bone cement leakage were recorded. The χ2 test, Student’s t-test, and repeated measures analysis of variance were used to compare the differences between the two groups. Results. There were 125 patients in Group A and 79 patients in Group B. Their baseline characteristics were similar (P>0.05). The mean VAS scores of Group A and Group B were 7.03 and 7.21 at admission, 4.7 and 3.2 at 1 day after operation, 4.0 and 3.0 at 3 months, and 2.2 and 2.2 at 12 months after operation, respectively. The mean ODI scores of Group A and Group B were 30.9 and 29.8 at admission, 17.6 and 17.7 at 3 months, and 10.5 and 10.9 at 12 months after operation, respectively. The mean operation time and fluoroscopic exposure time of Group A (35.6 minutes and 7.2 seconds, respectively) was significantly shorter than that of Group B (45.7 minutes and 11.7 seconds, respectively, P

Purpose: The aim of this study is to evaluate the impact of plating level on the loss of cervical lordosis (LCL) after laminoplasty with skipped-level plating. Methods: This retrospective study included patients who underwent alternative skipped-level plating laminoplasty from C3 to C6. Patients were divided into two groups according to the plating level. Group 1 had miniplate fixed at C3 and C5 (C3/C5 group), while patients in group 2 were fixed at C4 and C6 (C4/C6 group). The outcome of interest was the difference of LCL between the two groups; meanwhile, kyphosis development after laminoplasty was also compared. Results: A total of 70 patients were included in our study with a mean age of 60.44 ± 9.97 years. The median follow-up was 15 (12, 16) months. Median lordosis was 15.43° (9.35°, 22.23°) before surgery and 9.88° (4.15°, 18.94°) after, with a median LCL of 4.48° (−0.66°, 8.11°). There were 17 patients in the C3/C5 group, whereas 53 patients in the C4/C6 group. While preoperative C2–C7 Cobb’s angle was comparable between the two groups (15.32° (9.73°, 23.84°) vs. 15.51° (9.03°, 21.70°), p = 0.864), there were statistical differences regarding postoperative C2–C7 Cobb’s angle (6.54° (2.49°, 16.42°) vs. 10.62° (5.89°, 18.85°), p = 0.006) and LCL (4.74° (4.17°, 12.03°) vs. 4.07° (−1.89°, 6.69°), p = 0.034) between the C3/C5 group and the C4/C6 group. In all, 94.1% (16 of 17) of patients showed some degree of LCL after laminoplasty in the C3/C5 group, which was significantly higher when compared with 64.2% (34 of 52) of C4/C6 group ( p = 0.038). Before surgery, there were no kyphosis patients in either the C3/C5 group or the C4/C6 group. Postoperatively, four patients (23.5%) developed kyphotic alignment in the C3/C5 group, but only one (1.9%) in the C4/C6 group ( p = 0.013). Conclusions: Cervical alignment was compromised after laminoplasty. When alternative skipped-level plating is adopted in laminoplasty from C3 to C6, plating at C4/C6 may better preserve cervical lordosis than plating at C3/C5 after surgery.

An 8-week feeding trial was conducted to investigate the effects of high-starch diets and the supplementation of an olive extract (OE) on the growth performance, liver health and lipid metabolism of largemouth bass (Micropterus salmoides). Four isonitrogenous and isolipidic diets were prepared: two basal diets containing low (9.0%) and high (14.4%) levels of starch (named as LS and HS), and 0.125% OE was supplemented to each basal diet (named LSOE and HSOE). The results show that high-starch diets had significant negative effects on growth performance, with lower FR, SGR and higher FCR, whereas OE significantly lowered FCR, determined by two-way ANOVA analysis. High-starch diets induced oxidative stress, inflammatory response and liver function injury, with significant increases in the content of plasmatic AKP, AST, ALT, hepatic SOD and MDA, and up-regulation of hepatic TNFα, IL1β, and TGFβ1 gene expression. In addition, a high-starch diet decreased the phosphorylation of AMPK and upregulated the expression of SREBP, together with higher hepatic liver lipid and HSI. The oxidative stress and lipid metabolism disorders indicate metabolic liver disease (MLD) of largemouth bass fed high-starch diets. Feeding on OE-supplemented diets increased the hepatic antioxidant capacity by decreasing the content of MDA and SOD. Fish fed the HSOE diet had an activated phosphorylation of JNK and decreased expression of pro-inflammatory IL1β compared with those fed the HS diet, which strongly indicated that the degree of inflammatory responses was reduced after OE supplementation. Interestingly, this study demonstrated that OE regulates hepatic lipid metabolism in fish by inhibiting the expression of hepatic lipogenesis genes (ACC1 and FASN) and promoting lipolysis (ATGL) and β-oxidation (CPT1α) to prevent TG accumulation. In conclusion, high-starch feed induced oxidative stress and lipid metabolic disorder of largemouth bass, while supplementation with OE improved its antioxidant capacity, anti-inflammatory responses and lipid metabolism. However, hepatic histopathological results suggested that OE supplementation could not completely repair the MLD caused by the high level of starch in largemouth bass.

Background/Aims: Pancreatic cancer (PC) is an aggressive malignancy with a poor survival rate. Despite advances in the treatment of PC, the efficacy of therapy is limited by the development of chemoresistance. Here, we examined the role of microRNA-29c (miR-29c) and the involvement of autophagy and apoptosis in the chemoresistance of PC cells in vivo and in vitro. Methods: We employed qRT-PCR, western blot and immunofluorescence to examine the expression level of miR-29c, USP22 and autophagy relative protein. In addition, we used MTT assay to detect cell proliferation and transwell assay to measure migration and invasiveness. The apoptosis was determined using annexin V-FITC/PI apoptosis detection kit by flow cytometry. Luciferase reporter assays confirmed the relationship between USP22 and miR-29c. Results: miR-29c overexpression in the PC cell line PANC-1 enhanced the effect of gemcitabine on decreasing cell viability and inducing apoptosis and inhibited autophagy, as shown by western blotting, immunofluorescence staining, colony formation assays, and flow cytometry. Ubiquitin specific peptidase (USP)-22, a deubiquitinating enzyme known to induce autophagy and promote PC cell survival, was identified as a direct target of miR-29c. USP22 knockdown experiments indicated that USP22 suppresses gemcitabine-induced apoptosis by promoting autophagy, thereby increasing the chemoresistance of PC cells. Luciferase reporter assays confirmed that USP22 is a direct target of miR-29c. A xenograft mouse model demonstrated that miR-29c increases the chemosensitivity of PC in vivo by downregulating USP22, leading to the inhibition of autophagy and induction of apoptosis. Conclusions: Taken together, these findings reveal a potential mechanism underlying the chemoresistance of PC cells mediated by the regulation of USP22-mediated autophagy by miR-29c, suggesting potential targets and therapeutic strategies in PC.

Abstract Background DNA methylation has been identified to be widely associated to complex diseases. Among biological platforms to profile DNA methylation in human, the Illumina Infinium HumanMethylation450 BeadChip (450K) has been accepted as one of the most efficient technologies. However, challenges exist in analysis of DNA methylation data generated by this technology due to widespread biases. Results Here we proposed a generalized framework for evaluating data analysis methods for Illumina 450K array. This framework considers the following steps towards a successful analysis: importing data, quality control, within-array normalization, correcting type bias, detecting differentially methylated probes or regions and biological interpretation. Conclusions We evaluated five methods using three real datasets, and proposed outperform methods for the Illumina 450K array data analysis. Minfi and methylumi are optimal choice when analyzing small dataset. BMIQ and RCP are proper to correcting type bias and the normalized result of them can be used to discover DMPs. R package missMethyl is suitable for GO term enrichment analysis and biological interpretation.

Oxidative stress is a possible pathogenesis of hyperalgesia. Advanced oxidation protein products (AOPPs), a new family of oxidized protein compounds, have been considered as a novel marker of oxidative stress. However, the role of AOPPs in the mechanism of hyperalgesia remains unknown. Our study aims to investigate whether AOPPs have an effect on hyperalgesia and the possible underlying mechanisms. To identify the AOPPs involved, we induced hyperalgesia in rats by injecting complete Freund’s adjuvant (CFA) in hindpaw. The level of plasma AOPPs in CFA-induced rats was 1.6-fold in comparison with what in normal rats (P

Automatic mechanical transmission (AMT) with a gearshift assistant mechanism is a novel transmission architect concept aiming to improve the torque interruption and driveline jerk of AMT. During the shifting process, the shifting performance deteriorates as the varying road gradient and the friction coefficient worsen the coupling effect between the motor torque and the clutch friction torque. This paper focuses on improving the controller’s robustness of AMT with a gearshift assistant mechanism against the perturbed parameters during the stage of torque gap filling. In this paper, a detailed powertrain simulation model was presented. Based on a decoupling controller and a disturbance compensator, proportional-integral-differential (PID) controllers are applied to enhance the robustness and the decoupling effect. The PID parameters are automatically tuned by employing the Nelder-Mead method. In the tuning process, a cost function was established to demonstrate the outputs’ reference tracking performance, and the PID parameters are tuned by minimizing the cost function. Finally, the tuned parameters are stored in PID maps to make them adjustable online. Simulation results show that with the perturbed parameters well estimated, the upshift process was successful and the torque filling effect was also acceptable. The proposed transmission is a promising structure for industry applications.

Despite its rare incidence worldwide, penile squamous cell carcinoma (PeSCC) still presents with significant morbidity and mortality due to the limited treatment options for advanced patients, especially those in developing countries. The program death-1 (PD-1)/PD-1 ligand (PD-L1) axis has been demonstrated to play an important role in tumor immune escape, and immunotherapies targeting this pathway have shown great success in certain cancer types. Here, we analyzed the expression pattern of PD-L1 in tumor cells and tumor-infiltrating lymphocytes (TILs) in PeSCC with a multi-center cohort. We found that the majority of PeSCCs (53.4%) were PD-L1-positive and that high PD-L1 expression in tumor cells was associated with a poor prognosis. Notably, PD-L1 expression in tumor cells was significantly associated with the extent of TILs and CD8+ TILs. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) showed that PD-L1 was positively correlated with interferon-gamma (IFNγ) and CD8+ gene expression. Moreover, we defined the constitutive and inducible surface expression of PD-L1 in newly established primary PeSCC cell lines. Interestingly, two PeSCC cell lines had high intrinsic PD-L1 expression. Another cell line showed low PD-L1 expression, but the PD-L1 expression could be induced by IFNγ stimulation. Overall, our data showed that high PD-L1 expression in penile tumor cells indicated a poor prognosis. The upregulation of PD-L1 in PeSCC included both extrinsic and intrinsic mechanisms. These findings indicated that the PD-1/PD-L1 axis might be a potential therapeutic target for patients with penile squamous cell carcinoma.

Signal generators are widely used in experimental courses of universities. However, most of the commercial tests signal generators are expensive and bulky. In addition, a majority of them are in a fixed working mode with many little-used signals. In order to improve this situation, a small sized and highly accurate economic signal generator based on DDS technology has been developed, which is capable of providing wave signals commonly used in experiments. Firstly, it is introduced the basic principles of DDS and is determined the overall scheme of the signal generator. Then, it proposes a design of the hardware, which include power supply module, display module, keyboard module, waveform generating module based on DDS chip, and the minimum system module based on C8051F010. The signal generator was designed to output sine and square waveforms, and the other achieved performances included the frequency range 0.1 Hz–12.5 MHz, the frequency resolution 0.05 Hz–0.1 Hz, the output amplitude 1.0–4.5 V, the frequency accuracy Kfmin=94.12% and Kfmax=99.99%, and the signal distortion RTHDmin=0.638% and RTHDmax=11.67%.

With the development of space technology and the performance of remote sensors, high-resolution satellites are continuously launched by countries around the world. Due to high efficiency, large coverage and not being limited by the spatial regulation, satellite imagery becomes one of the important means to acquire geospatial information. This paper explores geometric processing using satellite imagery without ground control points (GCPs). The outcome of spatial triangulation is introduced for geo-positioning as repeated observation. Results from combining block adjustment with non-oriented new images indicate the feasibility of geometric positioning with the repeated observation. GCPs are a must when high accuracy is demanded in conventional block adjustment; the accuracy of direct georeferencing with repeated observation without GCPs is superior to conventional forward intersection and even approximate to conventional block adjustment with GCPs. The conclusion is drawn that taking the existing oriented imagery as repeated observation enhances the effective utilization of previous spatial triangulation achievement, which makes the breakthrough for repeated observation to improve accuracy by increasing the base-height ratio and redundant observation. Georeferencing tests using data from multiple sensors and platforms with the repeated observation will be carried out in the follow-up research.

An association between cholecystectomy and metabolic syndrome has not been fully established. Here we analyzed the association between cholecystectomy and metabolic syndrome in a Chinese population of 5672 subjects who undergone annual health checkups at the First Affiliated Hospital, College of Medicine, Zhejiang University between January 2011 and December 2012. The prevalences of gallstones, cholecystectomy and metabolic syndrome were 6.0%, 3.6%, and 32.5%, respectively. The prevalence of metabolic syndrome was significantly higher in subjects with a history of cholecystectomy (63.5%) than in those with gallstones (47.0%) or in those without gallstone disease (30.3%; P