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Abstract Background The prevalence of oral diseases is subject to change over time. In 2021, Guangdong Province conducted its fourth survey assessing the oral health status of individuals aged 65–74. Materials and methods Evaluation criteria and potential influencing factors were identified. A sample of residents aged 65–74 from 13 designated monitoring sites in Guangdong Province was randomly selected for the study. Spearman correlation analysis was employed to investigate the clinical correlation between influencing factors and evaluation criteria. Negative binomial and zero-inflated negative binomial regression models were utilized to examine the factors influencing caries prevalence. In contrast, logistic regression was employed to identify the risk factors for caries occurrence. A p-value of ≤0.05 was considered statistically significant. Results The prevalence of caries rate of crowns, roots, and teeth were 76.36%, 52.25%, and 79.2%, respectively. Individuals with periodontal pockets exhibited a significantly higher risk of root caries. The presence of dental calculus significantly exacerbated the occurrence of crown, root, and dental caries, and increased the risk of crown and dental caries. Consuming sweet foods once or more a week notably increased the average root decayed score (D of roots), the prevalence rate of root caries, and the D score of the Decayed, Missing, and Filled teeth [DMFT] index in individuals already afflicted with this condition. Similarly, the consumption of sweetened drinks significantly elevated the risk of crown and root caries, exacerbating overall caries progression. Frequencies of manual toothbrush and toothpick cleaning showed a negative correlation with average tooth missing score (MT). In contrast, the frequency of manual/electric toothbrush and toothpick cleaning was negatively correlated with the DMFT index. Engaging in dental diagnosis and treatment behaviors significantly increased the number of filled crowns (F), MT, and DMFT scores while reducing the prevalence of dental caries. Conclusions In Guangdong Province, caries prevalence among older individuals aged 65–74 remains substantial. Relevant professionals and institutions must provide comprehensive guidance and assistance to the older population, emphasizing the importance of reducing the consumption of sweets and sweetened beverages, adopting correct tooth brushing techniques and frequency (at least twice daily), timely treatment of periodontal diseases, conducting regular epidemiological caries surveys, and addressing economic barriers to accessing caries diagnosis and treatment services.

Abstract Nanotechnology has contributed important innovations to medicine and dentistry, and has also offered various applications to the field of orthodontics. Intraoral appliances must function in a complex environment that includes digestive enzymes, a diverse microbiome, mechanical stress, and fluctuations of pH and temperature. Nanotechnology can improve the performance of orthodontic brackets and archwires by reducing friction, inhibiting bacterial growth and biofilm formation, optimizing tooth remineralization, improving corrosion resistance and biocompatibility of metal substrates, and accelerating or decelerating orthodontic tooth movement through the application of novel nanocoatings, nanoelectromechanical systems, and nanorobots. This comprehensive review systematically explores the orthodontic applications of nanotechnology, particularly its impacts on tooth movement, antibacterial activity, friction reduction, and corrosion resistance. A search across PubMed, the Web of Science Core Collection, and Google Scholar yielded 261 papers, of which 28 met our inclusion criteria. These selected studies highlight the significant benefits of nanotechnology in orthodontic devices. Recent clinical trials demonstrate that advancements brought by nanotechnology may facilitate the future delivery of more effective and comfortable orthodontic care.

Abstract Background Patients with knee osteoarthritis (KOA) are at high risk for falls, which is attributed to their impaired balance control. Identifying factors associated with balance control facilitates the development of precise KOA rehabilitation programs. This study was to investigate the correlations of balance control with proprioception, plantar tactile sensation (PTS), pain, joint range of motion (ROM), and strength among older adults with and without KOA, as well as the magnitudes and sequence of correlation of these factors to balance control. Methods A total of 240 older adults with (n = 124, female: 84, age: 68.8 ± 4.0 years) and without (n = 116, female: 64, age: 67.9 ± 3.5 years) KOA were recruited and assigned to the KOA and control groups. Their proprioception, PTS, pain, ROM, and strength were measured. Pearson or Spearman correlations were used to test whether they were significantly related to their Berg Balance Scale (BBS), and factor analysis and multivariate linear regression were used to determine the degrees of correlation between each factor and the BBS. Results Compared to the control group, the KOA group had lower BBS score, larger proprioception and PTS thresholds, smaller ROM, and less strength (p: 0.008,

Drug combinations have emerged as a promising therapeutic approach in cancer treatment, aimed at overcoming drug resistance and improving the efficacy of monotherapy regimens. However, identifying effective drug combinations has traditionally been time-consuming and often dependent on chance discoveries. Therefore, there is an urgent need to explore alternative strategies to support experimental research. In this study, we propose network-based prediction models to identify potential drug combinations for 11 types of cancer. Our approach involves extracting 55,299 associations from literature and constructing human protein interactomes for each cancer type. To predict drug combinations, we measure the proximity of drug-drug relationships within the network and employ a correlation clustering framework to detect functional communities. Finally, we identify 61,754 drug combinations. Furthermore, we analyze the network configurations specific to different cancer types and identify 30 key genes and 21 pathways. The performance of these models is subsequently assessed through in vitro assays, which exhibit a significant level of agreement. These findings represent a valuable contribution to the development of network-based drug combination design strategies, presenting potential solutions to overcome drug resistance and enhance cancer treatment outcomes.

Abstract Background Prior studies reported that elevated asprosin level was associated with obesity in adults and animal models. However, the relationship between asprosin level and children with obeisty remains controversial. The aim of our analysis was to systematically review available literatures linking asprosin and children with obesity for a comprehensive understanding of the relationship between circulating asprosin level and obesity in children. Methods Eight databases were gleaned for studies published up to January 2024. Standard mean difference with 95% confidence interval (CI) and Fisher’s Z transformation was calculated to evaluate the relationship between asprosin level and children with obesity using the Review Manager 5.4 Software. Other indicators were measured via mean difference with 95% CI. Results Six observational studies were included both in systematic review and meta-analysis. The current evidence indicated that no significant difference was observed in the level of circulating asprosin between the children with and without obesity (SMD = 0.37; 95% CI:—0.22–0.95, p = 0.22). However, Fisher’s Z transformation suggested the positive association of circulating asprosin levels and clinical index measuring the degree of obesity: total cholesterol (Fisher’s Z: 0.11, 95% CI: 0.02–0.20, p = 0.02). Conclusions Circulating asprosin level was not independently related to childhood obesity currently. More rigorous longitudinal researches were required to disentangle the causations. However, the positive association of asprosin levels and total cholesterol indicated that asprosin might get involved in the lipid-metabolism of childhood obesity, asprosin might be a prospective bio-index and targeted treatment of total cholesterol metabolism besides the role of glucogenic and orexigenic. Trial registration Prospero ID: CRD42023426476.

ABSTRACTEffectiveness of heterologous booster regimes with ad5 vectored COVID-19 vaccine in a large, diverse population during the national-scale outbreak of SARS-CoV-2 omicron predominance in China has not been reported, yet. We conducted a large-scale cohort-control study in six provinces in China, and did a retrospective survey on the COVID-19 attack risk during this outbreak. Participant aged ≥18 years in five previous trials who were primed with 1 to 3 doses of ICV received heterologous booster with either intramuscular or orally inhaled ad5 vectored COVID-19 vaccine were included in the heterologous-trial cohort. We performed propensity score-matching at a ratio of 1:4 to match participants in the heterologous-trial cohort individually with the community individuals who received three-dose of ICV as a control (ICV-community cohort). From February 4 to April 10, 2023, 41504 (74.5%) of 55710 individuals completed the survey. The median time since the most recent vaccination to the onset of the symptoms of COVID-19 was 303.0 days (IQR 293.0-322.0). The attack rate of COVID-19 in the heterologous-trial cohort was 55.8%, while that in the ICV-community cohort was 64.6%, resulting in a relative effectiveness of 13.7% (95% CI 11.9 to 15.3). In addition, a higher relative effectiveness against COVID-19 associated outpatient visits, and admission to hospital was demonstrated, which was 25.1% (95% CI 18.9 to 30.9), and 48.9% (95% CI 27.0 to 64.2), respectively. The heterologous booster with ad5 vectored COVID-19 vaccine still offered some additional protection in preventing COVID-19 breakthrough infection versus homologous three-dose regimen with ICV, 10 months after vaccination.

BackgroundWe aimed to evaluate the efficacy, safety, and immunogenicity of a SARS-CoV-2 mRNA vaccine (Omicron BA.5) LVRNA012 given as the booster in immunized but SARS-CoV-2 infection-free adults in China.MethodsThis is a single-center, randomized, double-blind, placebo-controlled phase 3 clinical trial enrolling healthy adult participants (≥18 years) who had completed two or three doses of inactivated COVID-19 vaccines at least 6 months before, in Bengbu, Anhui province, China. Eligible participants were randomly assigned (1:1) to receive a booster intramuscular vaccination with an LVRNA012 vaccine (100ug) or placebo. The primary endpoint was the protective efficacy of a booster dose of the LVRNA012 vaccine or placebo against symptomatic COVID-19 of any severity 14 days after vaccination. Laboratory-confirmed COVID-19 infections were identified from 14 days to 180 days after intervention, with active surveillance for symptomatic illness 8 times per month between 7 to 90 days and at least once per month between 90 to 180 days after intervention.Results2615 participants were recruited and randomly assigned in a 1:1 ratio to either the vaccine group (1308) or the placebo group (1307). A total of 141 individuals (46 in the LVRNA012 group and 95 in the placebo group) developed symptomatic COVID-19 infection 14 days after the booster immunization, showing a vaccine efficacy of 51.9% (95% CI, 31.3% to 66.4%). Most infections were detected 90 days after intervention during a period when XBB was prevalent in the community. Adverse reactions were reported by 64% of participants after the LVRNA012 vaccination, but most of them were mild or moderate. The booster vaccination with the LVRNA012 mRNA vaccine could significantly enhance neutralizing antibody titers against the Omicron variant XBB.1.5 (GMT 132.3 [99.8, 175.4]) than did those in the placebo group (GMT 12.5 [8.4, 18.7]) at day 14 for the previously immunized individuals.ConclusionThe LVRNA012 mRNA vaccine is immunogenic, and shows robust efficacy in preventing COVID-19 during the omicron-predominate period.Clinical trial registrationClinicalTrials.gov, identifier NCT05745545.

Ovarian mucinous tumors with sarcomatous mural nodules are rare. Sarcomatous nodules have a bad prognosis. Its diagnosis and treatment are controversial.It is still controversial whether malignant mural nodules represent a dedifferentiated form of mucinous tumors or collisional tumors. This is a case report of a 32-year-old female diagnosed with ovarian mucinous tumor recurred as a mucinous carcinoma combined with sarcomatoid and undifferentiated sarcoma mural nodules after surgery and chemotherapy. The primary lesion did not have a sarcomatous component after comprehensive sampling and repeated review, while the recurrent lesion had a predominantly sarcomatous component. The patient received a second operation and postoperative chemotherapy plus Anlotinib with no progression at 16 months of follow-up. Primary mucinous carcinoma and sarcomatous mural nodules revealed the same K-RAS mutation(c.35G>T, pG12V), TP53 mutation (c.817C>T, p.R273C), MLL2 mutation(c.13450C>T, p.R4484) and NF1 mutation(c.7876A>G, p.S2626G). We present a comprehensive analysis on morphologic characteristics, molecular detection results, clinical management, and prognosis of ovarian mucinous tumors with mural nodules of sarcomatoid and undifferentiated sarcoma. Mutation sharing between primary mucinous carcinoma and recurrent sarcomatous nodules supports monoclonal origin of primary and recurrent tumors, suggesting a tendency for sarcomatous differentiation during the progression of epithelial tumors. Malignant mural nodules represent dedifferentiation in mucinous ovarian tumors rather than collision of two different tumor types. Therefore, it is imperative to conduct comprehensive sampling, rigorous clinical examination, and postoperative follow-up in order to thoroughly evaluate all mural nodules of ovarian mucinous tumors due to their potential for malignancy and sarcomatous differentiation.

Abstract Colorectal cancer is one of the most common malignancies worldwide. Although initially effective, patients who receive chemotherapy ultimately experience various complications and develop chemo-resistance, leading to cancer recurrence. Therefore, we aimed to find a drug with good efficacy and low toxicity that could enhance the treatment with 5-Fluorouracil (a commonly used clinical drug) and reduce its dosing. Corilagin, an anti-tumor natural product, has received widespread attention. Glucose regulated protein 78 (GRP78) is overexpressed in colorectal cancer cells and plays a key role in the proliferation, migration and drug resistance of cancer cells. Importantly, GRP78 can affect the apoptosis induced by 5-fluorouracil in CRC cells. In the present study, we determined the synergistic anti-tumor activity of the combination treatment by cell proliferation assay, apoptosis assay, fluorescent staining, cell cycle analysis, WB and PCR assays. This synergistic effect was associated with S-phase blockade, intracellular reactive oxygen species production and downregulation of GRP78. Taken together, our results indicate that Corilagin acts as a potentiator of 5-fluorouracil and may have therapeutic potential for patients with CRC.

Abstract The human bone marrow mesenchymal stem cells (hBMSCs) undergo intense osteogenic differentiation, a crucial bone formation mechanism. Evidence from prior studies suggested an association between long noncoding RNAs (lncRNAs) and the osteogenic differentiation of hBMSCs. However, precise roles and molecular mechanisms are still largely unknown. In this work, we report for the first time that lncRNA KCNMA1 antisense RNA 1 (KCNMA1-AS1) plays a vital role in regulating hBMSCs’ osteogenic differentiation. Here, it was observed that the KCNMA1-AS1 expression levels were significantly upregulated during osteogenic differentiation. In addition, KCNMA1-AS1 overexpression enhanced in vitro osteogenic differentiation of hBMSCs and in vivo bone formation, whereas knockdown of KCNMA1-AS1 resulted in the opposite result. Additionally, the interaction between KCNMA1-AS1 and mothers against decapentaplegic homolog 9 (SMAD9) was confirmed by an RNA pull-down experiment, mass spectrometry, and RIP assay. This interaction regulated the activation of the SMAD9 signaling pathway. Moreover, rescue assays demonstrated that the inhibitor of the SMAD9 signaling pathway reversed the stimulative effects on osteogenic differentiation of hBMSCs by KCNMA1-AS1 overexpression. Altogether, our results stipulate that KCNMA1-AS1 promotes osteogenic differentiation of hBMSCs via activating the SMAD9 signaling pathway and can serve as a biomarker and therapeutic target in treating bone defects.

Xuanwei ham is a traditional fermented meat product in China with a unique production process and excellent-quality reputation at home and abroad. To reveal the microbial community succession of Xuanwei ham at different post-ripening times (W1-4) and its relationship with flavour formation, the microbial community, free amino acids, and volatile flavour compounds (VOCs) were analysed by high-throughput sequencing, liquid chromatography (LC), and gas chromatography–mass spectrometry (GC-MS), respectively. A total of 25 free amino acids were detected, among which W3 contained the fewest, and most were generally lower than in hams in the other three years. Fifty-nine VOCs were detected, among which 17 were esters, and the highest ester content was found in W4. Analysis of the bacterial community composition revealed that the bacterial community composition of ham samples from W3 and other years differed greatly, and at the gate level, the dominant bacterial group of Xuanwei ham from different years was Pseudomonadota. At the genus level, the most abundant genera in W1, W2, and W4 were all dominated by Sarocladium, Klebsiella, and Vibrio, with Klebsiella being the most abundant in W1. The most abundant genus in W3 was Vibrio, and the second most dominant genera were Sarocladium and Gammaretrovirus. In short, this study provides a theoretical basis for the storage, quality, and improvement of Xuanwei ham.

Sixty-three patients admitted to 5 hospitals in 2014–2020 for the treatment of severe hypertensive brainstem hemorrhage by CT-guided and bone marker-oriented transcerebellar aspiration were enrolled in this study. The puncture accuracy, duration of hematoma removal, tracheal decannulation, postoperative complications, postoperative consciousness recovery time, Glasgow Outcome Scale (GOS) score, and prognosis outcome at follow-up were retrospectively analyzed. Additionally, the relationship between admission Glasgow Coma Scale (GCS) score and GOS score, and between hematoma volume and prognosis of patients was analyzed at follow-up. Results showed that CT localization–based and bone marker oriented transcerebellar hematoma aspiration in the treatment of severe hypertensive brainstem hemorrhage ensures high puncture accuracy, relatively low surgery risk, and good prognosis. The prognosis relates to the state of consciousness and hematoma volume.

Phosphate oxygen isotope analysis is an effective tool for investigating phosphorus migration and transformation in water bodies. Unfortunately, current pretreatment methods for this technology are significantly limited due to their demanding sample amount requirements, complex operation, and limited scope of application. In order to enhance the efficiency of the pretreatment process, hydrated zirconia was synthesized through liquid-phase precipitation. Zeolite, D001 macroporous resin, activated carbon, and ceramsite were chosen as possible candidate materials for loading purposes. The optimal zirconium loading material was identified through a combination of field enrichment and laboratory elution experiments. The ideal in situ enrichment duration, material dosages, and elution time were ascertained using response surface methodology. The findings showed that D001 resin exhibited superior selective adsorption and elution capacity for phosphate. The response surface optimization yielded the optimal parameters for the in situ phosphate-enrichment blanket: a mass of 13 g for zirconium-loaded D001 resin, an enrichment period of 360 min, and an elution period of 853 min. The attainment of a bright yellow Ag3PO4 solid after purification served as proof of the reliability of the optimization method. The obtained results provide a fundamental basis for the preparation and application of phosphate oxygen isotope analysis in freshwater ecosystem. HIGHLIGHTS In situ phosphate-enrichment method was used to optimize the existing phosphate oxygen isotope pretreatment method.; An in situ phosphate-enrichment device for freshwater was designed.; Response surface methodology was used to optimize the production and operation parameters of in situ phosphate-enrichment unit.; We replaced NH4NO3 with HNO3 and NH3 H2O solution to make the experiments safer.;

Cardiovascular disease (CVD) represents a substantial global health challenge, with its impact on mortality and morbidity rates surpassing that of cancer. The present study was designed to explore the cardioprotective properties of anthocyanin (ACN), a compound derived from black barley, against oxidative stress-induced damage in myocardial cells and to uncover the molecular mechanisms at play. Utilizing both in vitro and in vivo experimental models, our findings indicate that ACN notably reduced cell damage caused by oxidative stress and effectively prevented apoptosis. High-throughput RNA sequencing analysis has shed light on the mechanism by which ACN achieves its antioxidative stress effects, implicating the PTEN-Akt signaling pathway. ACN was found to modulate PTEN expression levels, which in turn influences the Akt pathway, leading to a reduction in apoptotic processes. This novel insight lays the groundwork for the potential clinical utilization of ACN in the management of CVD. While this study has shed light on some of the functions of ACN, it is important to recognize that natural compounds often interact with multiple molecular targets and engage in intricate signaling cascades. Future research endeavors will concentrate on further elucidating the regulatory mechanisms by which ACN influences PTEN expression, with the goal of enhancing our comprehension and expanding the therapeutic potential of ACN in the treatment of cardiovascular conditions.

Abstract Super-resolution structured illumination microscopy (SR-SIM) has become a widely used nanoscopy technique for rapid, long-term, and multi-color imaging of live cells. Precise but troublesome determination of the illumination pattern parameters is a prerequisite for Wiener-deconvolution-based SR-SIM image reconstruction. Here, we present a direct reconstruction SIM algorithm (direct-SIM) with an initial spatial-domain reconstruction followed by frequency-domain spectrum optimization. Without any prior knowledge of illumination patterns and bypassing the artifact-sensitive Wiener deconvolution procedures, resolution-doubled SR images could be reconstructed by direct-SIM free of common artifacts, even for the raw images with large pattern variance in the field of view (FOV). Direct-SIM can be applied to previously difficult scenarios such as very sparse samples, periodic samples, very small FOV imaging, and stitched large FOV imaging.

Salinity is a major factor limiting rice productivity, and developing salt-tolerant (ST) varieties is the most efficient approach. Seventy-eight ST introgression lines (ILs), including nine promising lines with improved ST and yield potential (YP), were developed from four BC2F4 populations from inter-subspecific crosses between an elite Geng (japonica) recipient and four Xian (indica) donors at the Institute of Crop Sciences, Chinese Academy of Agricultural Sciences. Genome-wide characterization of donor introgression identified 35 ST QTLs, 25 of which harbor 38 cloned ST genes as the most likely QTL candidates. Thirty-four are Xian-Geng differentiated ones with the donor (Xian) alleles associated with ST, suggesting differentiated responses to salt stress were one of the major phenotypic differences between the two subspecies. At least eight ST QTLs and many others affecting yield traits were identified under salt/non-stress conditions. Our results indicated that the Xian gene pool contains rich ‘hidden’ genetic variation for developing superior Geng varieties with improved ST and YP, which could be efficiently exploited by selective introgression. The developed ST ILs and their genetic information on the donor alleles for ST and yield traits would provide a useful platform for developing superior ST and high-yield Geng varieties through breeding by design in the future.

Due to unique patient characteristics, prosthetic sockets cannot be included in a standardised testing protocol as the rest major parts of the prosthesis. This makes the mechanical assessment of the socket a difficult process, which still remains crucial, especially nowadays, when new manufacturing technologies, such as additive manufacturing, are gaining ground in the field. In this study, a prototype testing rig was developed according to BS EN ISO 10328 standard, able to recreate the loading conditions of the early stance of the amputee gait on a paediatric transfemoral socket. The load requirements suggested in the standard were recalculated for the case of a 14-year-old male user with their weight in the 98th percentile. A variety of above-knee prosthetic sockets were produced with PLA and carbon-fibre reinforced nylon, using a commercial 3D printer. The sockets were tested under compressive load employing a plaster limb manikin. Video image processing was used to accurately capture the load-displacement relation of the sockets.

Green development efficiency (GDE) is an important criterion for measuring the level of green development. GDE considers not only economic development efficiency but also environmental costs. In China, marine fish culture, as one of the pillar industries of mariculture, promotes green development and industrial transformation and upgradation. Based on data from the field surveys of marine fish farmers (2017–2019) and the China Fishery Statistical Yearbook (2018–2020), this study establishes an evaluation index system and uses the super-slack-based measure model (Super-SBM) to evaluate the GDE of marine fish culture. The results show that the average GDE of marine fish culture in China was 0.9529, which was in an inefficient state. As for culture species, golden pompano (Trachinotus ovatus) and cobia (Rachycentron canadum) were the two species farmed in an efficient state, with a GDE of 1.2107 and 1.0659, respectively. Regarding culture modes, green modes (offshore cage aquaculture, industrial recirculating aquaculture, and engineering pond aquaculture) were in an efficient state, with a GDE of 1.2310, 1.0827, and 1.0401, respectively. Traditional modes (industrial flow-through aquaculture, ordinary cage aquaculture, and ordinary pond aquaculture) were in an inefficient state, with their GDE being 0.9884, 0.8746, and 0.8248, respectively. Green modes have higher GDE than traditional modes. In contrast, the production and culture areas of green modes were less than those of traditional modes because the profits of the same species in green modes were lower than those in traditional modes. The results of this study present an objective assessment of the GDE of marine fish culture in China and provide valuable insights for analyzing the mechanisms to improve the GDE of marine fish culture.

Phosphate oxygen isotope (δ18OP) technique is an effective tool to identify the source and transformation process of phosphorus. The poor applicability of existing δ18OP pretreatment methods for sediments hindered the large-scale application of δ18OP technology. This paper presents an optimization framework for the pretreatment of sediment δ18OP samples based on large-scale applications, using the Fuyang River Basin as a case study. The typical channel landscape outflow lake, South Lake, was selected as the most favorable point for assessing the applicability and optimizing the mainstream δ18OP pretreatment method, which was achieved by clarifying the sediment environmental characteristics of South Lake. To evaluate the suitability of the Blake and McLaughlin methods in South Lake, a comparative study was carried out based on five dimensions: phosphorus recovery rate, removal efficiency of organic matter, removal efficiency of extraction liquid impurity ion, experimental time, and reagent consumption cost. The findings demonstrated that the Blake method outperformed the McLaughlin method across all five dimensions. Based on the environmental characteristics of the sediments of South Lake, the Blake method was optimized from two perspectives, namely the substitution of reagents and adjustment and optimization of experimental procedures. This resulted in an enhancement of phosphorus recovery and organic matter removal efficiency, while also reducing the experimental time required. The optimized method also yielded satisfactory results when applied to the entire watershed. This research paper can thus offer valuable technical support for the widespread application of sediment δ18OP technology.

Background: Periodontits (PD) and Alzheimer’s disease (AD) are both associated with ageing and clinical studies increasingly evidence their association. However, specific mechanisms underlying this association remain undeciphered, and immune-related processes are purported to play a signifcant role. The accrual of publicly available transcriptomic datasets permits secondary analysis and the application of data-mining and bioinformatic tools for biological discovery.Aim: The present study aimed to leverage publicly available transcriptomic datasets and databases, and apply a series of bioinformatic analysis to identify a robust signature of immune-related signature of PD and AD linkage.Methods: We downloaded gene-expresssion data pertaining PD and AD and identified crosstalk genes. We constructed a protein-protein network analysis, applied immune cell enrichment analysis, and predicted crosstalk immune-related genes and infiltrating immune cells. Next, we applied consisent cluster analysis and performed immune cell bias analysis, followed by LASSO regression to select biomarker immune-related genes.Results: The results showed a 3 gene set comprising of DUSP14, F13A1 and SELE as a robust immune-related signature. Macrophages M2 and NKT, B-cells, CD4+ memory T-cells and CD8+ naive T-cells emerged as key immune cells linking PD with AD.Conclusion: Candidate immune-related biomarker genes and immune cells central to the assocation of PD with AD were identified, and merit investigation in experimental and clinical research.

Summary: The atomically precise metal electrocatalysts for driving CO2 reduction reactions are eagerly pursued as they are model systems to identify the active sites, understand the reaction mechanism, and further guide the exploration of efficient and practical metal nanocatalysts. Reported herein is a nanocluster-based electrocatalyst for CO2 reduction, which features a clear geometric and electronic structure, and more importantly excellent performance. The nanocatalysts with the molecular formula of [Ag17Cu10(dppm)4(PhC≡C)20H4]3+ have been obtained in a facile way. The unique metal framework of the cluster, with silver, copper, and hydride included, and dedicated surface structure, with strong (dppm) and labile (alkynyl) ligands coordinated, endow the cluster with excellent performance in electrochemical CO2 reduction reaction to CO. With the atomically precise electrocatalysts in hand, not only high reactivity and selectivity (Faradaic efficiency for CO up to 91.6%) but also long-term stability (24 h), are achieved.

Neuropeptides are endogenous active substances within the central and peripheral nervous systems that play important roles in a wide range of brain functions, including metabolism, food intake, social behavior, reproduction, learning, sleep, and wakefulness. This article reviews recent advances in the involvement of neuropeptides in vascular dementia. Neuropeptides are present in the brain as chemical signals and last for nearly 50 years. Peptide hormones are chemical signals of the endocrine system. Thus, neuropeptides are the most diverse class of signaling molecules in the brain, involving the genomes of many mammals, encoding neuropeptide precursors and many bioactive neuropeptides. Here the aim is to describe the recent advances in classical neuropeptides, as well as putative neuropeptides from other families, in the control of or as diagnostic tools for vascular dementia. Additionally, its molecular mechanisms are described to explore new avenues of treatment and early diagnosis, as there is increasing evidence that dysregulation of vascular processes is associated with different pathological conditions.

Abstract CD80 is an important co‐stimulatory molecule that participates in the immune response. Soluble CD80 can induce T cell activation and overcome PDL1‐mediated immune suppression. In this study, we aimed to construct recombinant Lactococcus lactis for oral delivery of the soluble CD80 (hsCD80) protein or the fusion protein containing the cholera toxin B subunit (CTB) and hsCD80 (CTB‐hsCD80) under the control of the nisin‐inducible expression system. The recombinant L. lactis expressed and secreted hsCD80 or CTB‐hsCD80 fusion proteins after induction by nisin in vitro and in the enteric cavity. Additionally, the CTB‐hsCD80 fusion protein showed uptake by intestinal epithelial cells, was cleaved by the furin protease, and was released as free hsCD80 protein into the blood circulation. Orally administered hsCD80 and CTB‐hsCD80 containing L. lactis increased the proportion of activated T cells in the spleen and intestinal epithelium, inhibited tumor growth, and prolonged the survival of tumor‐bearing mice. The hsCD80‐containing L. lactis showed greater therapeutic effects on primary colonic adenoma in APCmin/− mice and completely suppressed tumor growth. Further, recombinant CTB‐hsCD80 in L. lactis was more efficient than hsCD80‐containing bacteria in inhibiting the growth of xenografted colon cancer and melanoma cells. hsCD80 engineered probiotics may serve as a promising new approach for antitumor immunotherapy, especially for colorectal cancer.

RNA splicing refers to a process by which introns of a pre-mRNA are excised and the exons at both ends are joined together. Chloroplast introns are inherently self-splicing ribozymes, but over time, they have lost self-splicing ability due to the degeneration of intronic elements. Thus, the splicing of chloroplast introns relies heavily on nuclear-encoded splicing factors, which belong to diverse protein families. Different splicing factors and their shared intron targets are supposed to form ribonucleoprotein particles (RNPs) to facilitate intron splicing. As characterized in a previous review, around 14 chloroplast intron splicing factors were identified until 2010. However, only a few genetic and biochemical evidence has shown that these splicing factors are required for the splicing of one or several introns. The roles of splicing factors are generally believed to facilitate intron folding; however, the precise role of each protein in RNA splicing remains ambiguous. This may be because the precise binding site of most of these splicing factors remains unexplored. In the last decade, several new splicing factors have been identified. Also, several splicing factors were found to bind to specific sequences within introns, which enhanced the understanding of splicing factors. Here, we summarize recent progress on the splicing factors in land plant chloroplasts and discuss their possible roles in chloroplast RNA splicing based on previous studies.

Abstract The application of radiogenomics in oncology has great prospects in precision medicine. Radiogenomics combines large volumes of radiomic features from medical digital images, genetic data from high-throughput sequencing, and clinical-epidemiological data into mathematical modelling. The amalgamation of radiomics and genomics provides an approach to better study the molecular mechanism of tumour pathogenesis, as well as new evidence-supporting strategies to identify the characteristics of cancer patients, make clinical decisions by predicting prognosis, and improve the development of individualized treatment guidance. In this review, we summarized recent research on radiogenomics applications in solid cancers and presented the challenges impeding the adoption of radiomics in clinical practice. More standard guidelines are required to normalize radiomics into reproducible and convincible analyses and develop it as a mature field.

Data-driven method has gained its popularity in fault detection. Conventional methods are associated with one-single-layer process monitoring. Information extracted by such a method may not be sufficient to detect some faults for complicated process systems. Inspired by the deep learning conception, a multi-layer fault detection method, namely Deep Principal Component Analysis (DePCA) was proposed previously in the literature. DePCA has the capability to extract deep features for a process resulting in better fault detection performance. However, it assumes that the value of the variable at each moment is unrelated, which is not suitable for complex nonlinear dynamic system. To address the concerns, by adopting dynamic PCA to extract dynamic features, a new deep approach, namely Deep Dynamic Principal Component Analysis (DeDPCA), is proposed. In the new approach, both Dynamic feature and nonlinear feature can be extracted in different layers so that more process faults can be detected. A Tennessee Eastman process case study was then employed for application and validation of the DeDPCA, which indicates the proposed method is suitable for monitoring complex dynamic nonlinear processes.

Liver diseases have long been a prevalent cause of morbidity and mortality, and their development and progression involve multiple vital organs throughout the body. Recent studies on the oral–gut–liver axis have revealed that the oral microbiota is associated with the pathophysiology of chronic liver diseases. Since interventions aimed at regulating oral biological disorders may delay the progress of liver disease, it is crucial to better comprehend this process. Oral bacteria with potential pathogenicity have been extensively studied and are closely related to several types of chronic liver diseases. Therefore, this review will systemically describe the emerging role of oral pathogenic bacteria in common liver diseases, including alcoholic liver disease (ALD), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), cirrhosis, autoimmune liver diseases (AILD), and liver cancer, and bring in new perspectives for future research.

Abstract Background The aim of this study was to detect potential crosstalk genes, pathways and immune cells between periodontitis and chronic obstructive pulmonary disease (COPD). Methods Chronic periodontitis (CP, GSE156993) and COPD (GSE42057, GSE94916) datasets were downloaded. Differential expressed genes (DEGs; p 0.5 and p-value

Enhancing the wicking/evaporative functionality of materials by surface nano/microstructuring is a key approach in creating advanced technologies based on the liquid–vapor phase change, particularly in the field of power generation for substantial fuel savings and reducing global greenhouse gas pollution. Despite the technological importance, the capillary flow of a liquid undergoing intensive evaporation on a hot nano/microstructured surface is not well understood. During the capillary flow on a nano/microstructured surface, water confinement undergoes a dramatical spatiotemporal change. The evaporation mechanisms of water confined in capillary nano/microstructures fundamentally depend on the scale of liquid confinement, making the dynamics of water confinement one of the basic characteristics in spreading/evaporation behavior of water on a hot capillary surface. Here, we develop an experimental technique for studying the water film confinement dynamics based on different optical footprints of nanoscale and microscale water confinements found in our work. We study both water film confinement dynamics and traditional capillary flow/receding dynamics of a water drop in a highly hierarchical capillary surface nano/microstructure created in our work using femtosecond laser processing. For the first time, we obtain the spatiotemporal map of water nano/microstructural confinements that provides basic data for the identification of evaporation mechanisms. The obtained results give important guidelines for engineering advanced materials with an efficient wicking/evaporative functionality.

Introduction: Triple-negative breast cancer (TNBC) usually has a poor prognosis. Although the immunotherapy of TNBC has achieved great progress, only a few patients can benefit from the current treatment. CD47 is widely expressed on the surface of TNBC cells and may become an immune checkpoint for TNBC treatment. Nevertheless, increasingly more attention has been paid to systemic side effects since the ubiquitous expression of CD47 on normal cells. The toll-like receptor (TLR) agonist resiquimod (R848) can activate dendritic cells (DCs) and promote the maturation of immune cells in the tumor microenvironment, which further enhances the tumor inhibition ability of the immune system and synergizes with CD47 small interfering RNA (siRNA) for TNBC therapy. However, ideal delivery platforms such as nanocarriers are still needed because its weakness of hydrophobicity.Methods: In order to improve efficacy and reduce toxicity, R848 and siCD47 were entrapped in amphiphilic PEG-PLGA nanoparticles by double emulsification and stable nanoparticles NP/R848/siCD47 were generated to investigate their anti-tumor effects in a TNBC tumor-bearing mouse model.Results: Here, we show that PEG-PLGA nanoparticles are effective nanocarriers that can safely and effectively deliver siCD47 and R848 to tumor tissue, as demonstrated by retarded tumor growth. Mechanistically, downregulation of CD47 expression and activation of DCs took part in promoting the immune response of cytotoxic T cells (CTLs). Meanwhile, a decrease of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) indicated the modulating of the tumor immune microenvironment.Discussion: To our best knowledge, our study pioneered co-delivery system for hydrophilic siCD47 and hydrophobic R848. It can maximize break tumor immune escape caused by CD47 and simultaneously enhance antigen presentation by activating DCs for effector T cell killing while regulating the tumor microenvironment as expected. Not only does it conform to the reports of previous basic research, but also it can break the bottleneck of their clinical application hopefully. Collectively, our findings could lay the foundation for future therapeutic strategies of TNBC.

Abstract Background Serum ceruloplasmin is one of the major diagnostic parameters for Wilson’s disease (WD). Age and gender difference of serum ceruloplasmin remain controversy. This study aims to assess diagnostic value of serum ceruloplasmin level for WD in children up to age of 15 years. Methods Serum ceruloplasmin levels were measured in 317 WD patients, 21 heterozygotes, 372 healthy control children and 154 non-WD patients with other liver diseases. Receiver operating characteristic (ROC) curve was used to determine the diagnostic accuracy of serum ceruloplasmin for WD in children. Results Among healthy controls, serum ceruloplasmin level was slightly low in the infants younger than 6 months, and then maintained from 26 to 33 mg/dl after age of 6 months. A total of 8.1% of healthy children had levels of serum ceruloplasmin 20 mg/dL. Serum ceruloplasmin levels had gender difference, being higher in healthy boys than healthy girls, and higher in asymptomatic WD boys than asymptomatic WD girls (p

Aquaculture plays an important role in fishery structure and economy in China. At present, fishery industry is in a period of transformation from elements-driven to innovation-driven, which has put forward higher requirements for the transformation and upgrading of the aquaculture. This study was based on industry evolution path and running mechanism, from the aspects of resources, technology, market, system, by using the index data from 1998 to 2019, through the grey relation analysis and ridge regression analysis, to explore the factors affecting the evolution of industry and study the effects of different factors on the degree of influence on the development of the aquaculture evolution, to promote the development of China's aquaculture industry and strengthen the competitiveness of aquaculture to provide theoretical support. The results showed that the per capita consumption of aquatic products of urban residents had the greatest impact on the evolution of China's aquaculture. The GDP and output per unit area had significant impact, and the expenditure of aquatic technology promotion had the least impact. Therefore, to promote the transformation and upgrading in China's aquaculture, the following suggestions were put forward that we should promote the leading and management about aquatic product consumption, expand domestic and international consumer market, increase investment in science and technology and develop breeding technology, strengthen resource protection and promote green development and resolve the problems about quality and safety of aquaculture products.

ObjectiveTo identify the genetic linkage mechanisms underlying Parkinson’s disease (PD) and periodontitis, and explore the role of immunology in the crosstalk between both these diseases.MethodsThe gene expression omnibus (GEO) datasets associated with whole blood tissue of PD patients and gingival tissue of periodontitis patients were obtained. Then, differential expression analysis was performed to identify the differentially expressed genes (DEGs) deregulated in both diseases, which were defined as crosstalk genes. Inflammatory response-related genes (IRRGs) were downloaded from the MSigDB database and used for dividing case samples of both diseases into different clusters using k-means cluster analysis. Feature selection was performed using the LASSO model. Thus, the hub crosstalk genes were identified. Next, the crosstalk IRRGs were selected and Pearson correlation coefficient analysis was applied to investigate the correlation between hub crosstalk genes and hub IRRGs. Additionally, immune infiltration analysis was performed to examine the enrichment of immune cells in both diseases. The correlation between hub crosstalk genes and highly enriched immune cells was also investigated.ResultsOverall, 37 crosstalk genes were found to be overlapping between the PD-associated DEGs and periodontitis-associated DEGs. Using clustering analysis, the most optimal clustering effects were obtained for periodontitis and PD when k = 2 and k = 3, respectively. Using the LASSO feature selection, five hub crosstalk genes, namely, FMNL1, MANSC1, PLAUR, RNASE6, and TCIRG1, were identified. In periodontitis, MANSC1 was negatively correlated and the other four hub crosstalk genes (FMNL1, PLAUR, RNASE6, and TCIRG1) were positively correlated with five hub IRRGs, namely, AQP9, C5AR1, CD14, CSF3R, and PLAUR. In PD, all five hub crosstalk genes were positively correlated with all five hub IRRGs. Additionally, RNASE6 was highly correlated with myeloid-derived suppressor cells (MDSCs) in periodontitis, and MANSC1 was highly correlated with plasmacytoid dendritic cells in PD.ConclusionFive genes (i.e., FMNL1, MANSC1, PLAUR, RNASE6, and TCIRG1) were identified as crosstalk biomarkers linking PD and periodontitis. The significant correlation between these crosstalk genes and immune cells strongly suggests the involvement of immunology in linking both diseases.

Introduction Premenopausal and postmenopausal osteoporosis and associated fragility fractures are major public health problems. Exercise, especially moderate-to-high-intensity impact exercise, has been recommended as an effective, low-cost non-pharmacological strategy for bone strength improvement; however, evidence on fracture risk is limited. In addition, maintaining regular training is currently a problem. Therefore, this study aims to conduct a randomised controlled trial of moderate-to-high-intensity tele-exercise intervention using a tele-rehabilitation app and quantify its effects on vertical fracture and fall prevention in women at high risk of osteoporotic fractures.Methods and analysis In this multicentre, randomised controlled trial, 794 women at high risk of osteoporotic fractures will be recruited and randomised into either the tele-exercise rehabilitation or control group. Participants in the control group will receive routine remote rehabilitation, while those in the intervention group will be provided with a 6-month tele-exercise rehabilitation. The primary outcomes are the percentage of participants with one or more new vertebral fractures and incidence of falls. Intention-to-treat, full analysis set and per-protocol approaches will be used for outcome analyses.Ethics and dissemination The study was approved by the biomedical research ethics committee of the West China Hospital of Sichuan University (2021-579). Written informed consent will be obtained from each participant after agreeing to participate in the study. The study findings will be presented at national and international scientific conferences and published in peer-reviewed journals. Results are propagated regardless of the magnitude or direction of the impact. Authorship is assigned according to authorship guidelines as defined by the International Board of Medical Journal Editors, and each author’s role is based on journal requirements for publication.Trial registration number The study was registered with the Chinese Clinical Trial Registry (ChiCTR2200058780) prior to recruitment (May 2022).

Abstract Introduction Genome sequence plays an important role in both basic and applied studies. Gossypium raimondii, the putative contributor of the D subgenome of upland cotton (G. hirsutum), highlights the need to improve the genome quality rapidly and efficiently. Methods We performed Hi-C sequencing of G. raimondii and reassembled its genome based on a set of new Hi-C data and previously published scaffolds. We also compared the reassembled genome sequence with the previously published G. raimondii genomes for gene and genome sequence collinearity. Result A total of 98.42% of scaffold sequences were clustered successfully, among which 99.72% of the clustered sequences were ordered and 99.92% of the ordered sequences were oriented with high-quality. Further evaluation of results by heat-map and collinearity analysis revealed that the current reassembled genome is significantly improved than the previous one (Nat Genet 44:98–1103, 2012). Conclusion This improvement in G. raimondii genome not only provides a better reference to increase study efficiency but also offers a new way to assemble cotton genomes. Furthermore, Hi-C data of G. raimondii may be used for 3D structure research or regulating analysis.

BackgroundWith the popularization of electronic health records in China, the utilization of digitalized data has great potential for the development of real-world medical research. However, the data usually contains a great deal of protected health information and the direct usage of this data may cause privacy issues. The task of deidentifying protected health information in electronic health records can be regarded as a named entity recognition problem. Existing rule-based, machine learning–based, or deep learning–based methods have been proposed to solve this problem. However, these methods still face the difficulties of insufficient Chinese electronic health record data and the complex features of the Chinese language. ObjectiveThis paper proposes a method to overcome the difficulties of overfitting and a lack of training data for deep neural networks to enable Chinese protected health information deidentification. MethodsWe propose a new model that merges TinyBERT (bidirectional encoder representations from transformers) as a text feature extraction module and the conditional random field method as a prediction module for deidentifying protected health information in Chinese medical electronic health records. In addition, a hybrid data augmentation method that integrates a sentence generation strategy and a mention-replacement strategy is proposed for overcoming insufficient Chinese electronic health records. ResultsWe compare our method with 5 baseline methods that utilize different BERT models as their feature extraction modules. Experimental results on the Chinese electronic health records that we collected demonstrate that our method had better performance (microprecision: 98.7%, microrecall: 99.13%, and micro-F1 score: 98.91%) and higher efficiency (40% faster) than all the BERT-based baseline methods. ConclusionsCompared to baseline methods, the efficiency advantage of TinyBERT on our proposed augmented data set was kept while the performance improved for the task of Chinese protected health information deidentification.

Adaptation is the process by which bone responds to changes in loading environment and modulates its properties and spatial organization to meet the mechanical demands. Adaptation in trabecular bone is achieved through increase in bone mass and alignment of trabecular-bone morphology along the loading direction. This transformation of internal microstructure is governed by mechanical stimuli sensed by mechanosensory cells in the bone matrix. Realisation of adaptation in the form of local bone-resorption and -formation activities as a function of mechanical stimuli is still debated. In silico modelling is a useful tool for simulation of various scenarios that cannot be investigated in vivo and particularly well suited for prediction of trabecular bone adaptation. This progress report presents the recent advances in in silico modelling of mechanoregulated adaptation at the scale of trabecular bone tissue. Four well-established bone-adaptation models are reviewed in terms of their recent improvements and validation. They consider various mechanical factors: (i) strain energy density, (ii) strain and damage, (iii) stress nonuniformity and (iv) daily stress. Contradictions of these models are discussed and their ability to describe adequately a real-life mechanoregulation process in bone is compared.

Background: Accurate target identification of small molecules and downstream target annotation are important in pharmaceutical research and drug development.Methods: We present TAIGET, a friendly and easy to operate graphical web interface, which consists of a docking module based on AutoDock Vina and LeDock, a target screen module based on a Bayesian–Gaussian mixture model (BGMM), and a target annotation module derived from >14,000 cancer-related literature works.Results: TAIGET produces binding poses by selecting ≤5 proteins at a time from the UniProt ID-PDB network and submitting ≤3 ligands at a time with the SMILES format. Once the identification process of binding poses is complete, TAIGET then screens potential targets based on the BGMM. In addition, three medical experts and 10 medical students curated associations among drugs, genes, gene regulation, cancer outcome phenotype, 2,170 cancer cell types, and 73 cancer types from the PubMed literature, with the aim to construct a target annotation module. A target-related PPI network can be visualized by an interactive interface.Conclusion: This online tool significantly lowers the entry barrier of virtual identification of targets for users who are not experts in the technical aspects of virtual drug discovery. The web server is available free of charge at http://www.taiget.cn/.

As a key component of a drip irrigation system, the performance of drip irrigation emitters is determined by the flow channel structures and parameters. In this paper, a novel Y-shaped labyrinth-channel emitter was proposed, and the influence of the hydraulic performance was researched under different waist-arc angles (α) and ratios of crown height to chord length (a:b). The flow characteristics and energy dissipation mechanisms of water in the emitter were analyzed by using fluid dynamics software. The analysis showed that, keeping the ratio of crown height to chord length unchanged and with an increase in the waist-arc angle from 90° to 180°, the pressure-drop ratio before and after the water flow through the vortex area increased, and the hydraulic performance of the emitter was improved, specifically: the design flow could be reduced by 6.02–26.7%, and the slope of the curve could be reduced by 9.83–28.1%. The smaller the ratio of crown height to chord length, the weaker the influence of waist-arc angle was on the design flow and hydraulic performance. Keeping the waist-arc angle unchanged, there was a decrease in the ratio of crown height to chord length from 6:30 to 1:30, the vortex strength inside the emitter channel increased, and the hydraulic performance was improved: the design flow could be reduced by 7.56–23.5%, and the slope of the curve could be reduced by 5.43–20.5%. The bigger the waist-arc angle, the weaker the influence of the ratio of crown height to chord length was on the design flow and the hydraulic performance, even to the point of having no effect. When the Y-shaped emitter was close to the pressure-flow curve slope of the commonly-used triangular-channel emitter, the hydraulic performance of the two was similar, and the former could increase the channel width by 25%, as compared to the latter, or shorten the channel length by 44.3%. The results showed that the Y-shaped emitter had better hydraulic performance compared with the triangular-flow-channel emitter commonly used today. Therefore, the Y-shaped emitter has broad application prospects in water-saving irrigation.

Abstract Structured illumination microscopy (SIM) has become a widely used tool for insight into biomedical challenges due to its rapid, long-term, and super-resolution (SR) imaging. However, artifacts that often appear in SIM images have long brought into question its fidelity, and might cause misinterpretation of biological structures. We present HiFi-SIM, a high-fidelity SIM reconstruction algorithm, by engineering the effective point spread function (PSF) into an ideal form. HiFi-SIM can effectively reduce commonly seen artifacts without loss of fine structures and improve the axial sectioning for samples with strong background. In particular, HiFi-SIM is not sensitive to the commonly used PSF and reconstruction parameters; hence, it lowers the requirements for dedicated PSF calibration and complicated parameter adjustment, thus promoting SIM as a daily imaging tool.

Background: Drug resistance and recurrence often develop during the treatment of muscle-invasive bladder cancer (MIBC). The existence of cancer stem cells (CSCs) in MIBC makes the formulation of effective treatment strategies extremely challenging. We aimed to use single-cell RNA sequencing approaches to identify CSCs and evaluate their molecular characteristics and to discover possible therapeutic measures.Methods: GEO data sets GSE130001 and GSE146137 were used to construct an expression matrix. After cells were identified by type, malignant epithelial cells inferred by InferCNV were extracted for stemness evaluation. The subset of cells with the highest stemness was subjected to weighted gene coexpression network analysis (WGCNA) and pseudotime analysis to identify key genes. In addition, we predicted drug sensitivity relationships for key genes in CTD and predicted the correlation between drugs and survival through siGDC.Results: We found that there were some CSCs in MIBC samples. The CSC population was heterogeneous during tumor development and was divided into quiescent and proliferating CSCs. We identified DBI as the key gene in quiescent CSCs. Analysis of a TCGA data set showed that higher DBI expression indicated higher histological grade. In addition, we predicted that acetaminophen can reduce DBI expression, thereby reducing the stemness of CSCs. Thus, we identified a potential new use of acetaminophen.Conclusion: We systematically explored CSCs in tumors and determined that DBI may be a key gene and potential therapeutic target in quiescent CSCs. In addition, we confirmed that acetaminophen may be a candidate drug targeting CSCs, improving our understanding of CSC-targeting therapeutic strategies.

AimThis study aims to identify pyroptosis-related genes (PRGs), their functional immune characteristics, and distinct pyroptosis-related clusters in periodontitis.MethodsDifferentially expressed (DE)-PRGs were determined by merging the expression profiles of GSE10334, GSE16134, and PRGs obtained from previous literatures and Molecular Signatures Database (MSigDB). Least absolute shrinkage and selection operator (LASSO) regression was applied to screen the prognostic PRGs and develop a prognostic model. Consensus clustering was applied to determine the pyroptosis-related clusters. Functional analysis and single-sample gene set enrichment analysis (ssGSEA) were performed to explore the biological characteristics and immune activities of the clusters. The hub pyroptosis-related modules were defined using weighted correlation network analysis (WGCNA).ResultsOf the 26 periodontitis-related DE-PRGs, the highest positive relevance was for High-Mobility Group Box 1 (HMGB1) and SR-Related CTD Associated Factor 11 (SCAF11). A 14-PRG-based signature was developed through the LASSO model. In addition, three pyroptosis-related clusters were obtained based on the 14 prognostic PRGs. Caspase 3 (CASP3), Granzyme B (GZMB), Interleukin 1 Alpha (IL1A), IL1Beta (B), IL6, Phospholipase C Gamma 1 (PLCG1) and PYD And CARD Domain Containing (PYCARD) were dysregulated in the three clusters. Distinct biological functions and immune activities, including human leukocyte antigen (HLA) gene expression, immune cell infiltration, and immune pathway activities, were identified in the three pyroptosis-related clusters of periodontitis. Furthermore, the pink module associated with endoplasmic stress-related functions was found to be correlated with cluster 2 and was suggested as the hub pyroptosis-related module.ConclusionThe study identified 14 key pyroptosis-related genes, three distinct pyroptosis-related clusters, and one pyroptosis-related gene module describing several molecular aspects of pyroptosis in the pathogenesis and immune micro-environment regulation of periodontitis and also highlighted functional heterogeneity in pyroptosis-related mechanisms.

Immune microenvironment is implicated in cancer progression. However, the role of immune microenvironment in bladder cancer has not been fully explored. Open-accessed datasets GSE120736, GSE128959, GSE13507, GSE31684, GSE32548, GSE48075, GSE83586, and The Cancer Genome Atlas (TCGA) database were enrolled in our study. Single-sample gene set enrichment analysis (ssGSEA) was used to quantify 53 immune terms in combined BLCA cohorts. The top 10 important immune terms were identified through random forest algorithm for model establishment. Our model showed satisfactory efficacy in prognosis prediction. Furthermore, we explored clinical and genomic feature differences between high- and low-risk groups. The results indicated that the patients in the high-risk group might be associated with worse clinical features. Gene set enrichment analysis showed that epithelial–mesenchymal translational, mTORC1 signaling, mitotic spindle, glycolysis, E2F target, and G2M checkpoint pathways were aberrantly activated in high-risk patients, partially explaining its worse prognosis. Patients in the low-risk group showed better immunotherapy response according to TIDE and TCIA analysis, indicating that our model could effectively predict the immunotherapy response rate. KCNH4, UGT1A1, TPO, SHANK1, PITX3, MYH1, MYH13, KRT3, DEC1, and OBP2A genes were identified as feature genes in the high- and low-risk patients. CMAP analysis was performed to identify potential compounds targeting the riskscore.

ObjectiveTo investigate the mechanisms of super-enhancer-associated LINC01485/miR-619-5p/RUNX2 signaling axis involvement in osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs).MethodsOsteogenic differentiation of hBMSCs was induced in vitro. The expression levels of LINC01485 and miR-619-5p during osteogenesis were measured using quantitative real-time polymerase chain reaction (qRT-PCR). Osteogenic differentiation was examined by qRT-PCR, western blot, alkaline phosphatase (ALP) staining, ALP activity measurement, and Alizarin Red S (ARS) staining assays. Thereafter, the effects of LINC01485 and miR-619-5p on osteogenic differentiation of hBMSCs were evaluated by performing loss- and gain-of-function experiments. Subsequently, a fluorescence in situ hybridization (FISH) assay was employed to determine the cellular localization of LINC01485. Bioinformatics analysis, RNA antisense purification (RAP) assay, and dual-luciferase reporter assays were conducted to analyze the interactions of LINC01485, miR-619-5p, and RUNX2. Rescue experiments were performed to further delineate the role of the competitive endogenous RNA (ceRNA) signaling axis consisting of LINC01485/miR-619-5p/RUNX2 in osteogenic differentiation of hBMSCs.ResultsThe expression of LINC01485 was up-regulated during osteogenic differentiation of hBMSCs. The overexpression of LINC01485 promoted osteogenic differentiation of hBMSCs by up-regulating the expression of osteogenesis-related genes [e.g., runt-related transcription factor 2 (RUNX2), osterix (OSX), collagen type 1 alpha 1 (COL1A1), osteocalcin (OCN), and osteopontin (OPN)], and increasing the activity of ALP. ALP staining and ARS staining were also found to be increased upon overexpression of LINC01485. The opposing results were obtained upon LINC01485 interference in hBMSCs. miR-619-5p was found to inhibit osteogenic differentiation. FISH assay displayed that LINC01485 was mainly localized in the cytoplasm. RAP assay results showed that LINC01485 bound to miR-619-5p, and dual-luciferase reporter assay verified that LINC01485 bound to miR-619-5p, while miR-619-5p and RUNX2 bound to each other. Rescue experiments illustrated that LINC01485 could promote osteogenesis by increasing RUNX2 expression by sponging miR-619-5p.ConclusionLINC01485 could influence RUNX2 expression by acting as a ceRNA of miR-619-5p, thereby promoting osteogenic differentiation of hBMSCs. The LINC01485/miR-619-5p/RUNX2 axis might comprise a novel target in the bone tissue engineering field.

This paper presents the design of a real-time direction judgment system for a sub-nanometer scale grating ruler based on field-programmable gate array (FPGA) technology. On the basis of the working principle of the grating ruler reading head, the characteristics of the grating ruler phase signal are analyzed. In view of the frequency uncertainty and nonlinear error of grating scale phase signal laser, a preprocessing structure based on biorthogonal lock-in amplifier is designed. Aiming at the problem of low data update rate and insensitivity to direction switching in short stroke of traditional grating direction judgment method, a real-time direction judgment method is proposed. On the FPGA platform, the signal generator is used to simulate the actual photoelectric signal of grating ruler, and the calibration experimental platform of electrical analog signal is built to verify the effect of the real-time direction judgment system on the FPGA platform. The results show that compared with the traditional direction judgment system, the data update rate is improved by 256-fold. Moreover, a method for using the result of the direction judgment system to compensate the count value of the electronic subdivision when the object is moving backward is proposed.

Effective and inexpensive electrocatalysts are significant to improve the performance of oxygen evolution reaction. Facing the bottleneck of slow kinetics of oxygen evolution reaction, it is highly desirable to design the electrocatalyst with high activity, good conductivity, and satisfactory stability. In this work, nickel foam supported hierarchical Co9S8–Ni3S2 composite hollow microspheres were derived from in situ-generative MOF precursors and the subsequent sulfurization process by a simple two-step solvothermal method. The composite microspheres were directly grown on nickel foam without any binder, and nickel foam was used as the nickel source and support material. The morphology and constitution of the series self-supported electrodes were characterized by SEM, TEM, XRD, XPS, and Raman, respectively. The unique porous architecture enriched the electrode with sufficient active surface and helped to reactants and bubble evolved during electrochemical water oxidation. Through tuning the concentration of cobalt source and ligand, the content ratio of Co9S8 and Ni3S2 can be modulated. The heterostructures not only afford active interfaces between the phases but also allow electronic transfer between Co9S8 and Ni3S2. The optimized Co9S8-Ni3S2/NF-0.6 electrode with the highest electrochemical surface area and conductivity shows the best OER performance among the series electrodes in 1 M KOH solution. The overpotential of Co9S8-Ni3S2/NF-0.6 is only 233 mV when the current density is 10 mA cm−2, and corresponding Tafel slope is 116.75 mV dec−1. In addition, the current density of Co9S8-Ni3S2/NF-0.6 electrocatalyst hardly decreased during the 12 h stability measurement. Our approach in this work may provide the future rational design and synthesis of satisfactory OER electrocatalysts.

To extract the weak fault features hidden in strong background interference in the event of the early failure of rolling bearings, a two-stage based method is proposed. The broadband noise elimination ability of an adaptive morphological filter (AMF) and the superior capability of a frequency band selection (FBS) strategy for fault transient location identification are comprehensively utilized by the proposed method. Firstly, the AMF with a simple theory and high calculation efficiency is used as a preprocessing program to enhance the fault transient features. Then, the proposed FBS strategy based on the sparsity index (SI) is utilized to further handle the filtered signal processed by the AMF. Finally, the constructed optimum bandpass filter based on the analysis result of the FBS is used to further filter the handled signal processed by AMF and envelope spectral analysis is applied on the last filtered signal to realize the ideal fault feature extraction effect. Compared with the other traditional FBS methods based on kurtosis or the other index, the proposed FBS strategy based on SI has strong robustness to noise. One experimental signal and one engineering vibration signal are used, respectively, to verify the feasibility of the proposed method.

Emerging evidence indicates that microRNAs play a pivotal role in neural remodeling after spinal cord injury (SCI). This study aimed to investigate the mechanisms of miR-135a-5p in regulating the functional recovery of SCI by impacting its target genes and downstream signaling. The gene transfection assay and luciferase reporter assay confirmed the target relationship between miR-135a-5p and its target genes (specificity protein 1 [SP1] and Rho-associated kinase [ROCK]1/2). By establishing the H2O2-induced injury model, miR-135a-5p transfection was found to inhibit the apoptosis of PC12 cells by downregulating the SP1 gene, which subsequently induced downregulation of pro-apoptotic proteins (Bax, cleaved caspase-3) and upregulation of anti-apoptotic protein Bcl-2. By measuring the neurite lengths of PC12 cells, miR-135a-5p transfection was found to promote axon outgrowth by downregulating the ROCK1/2 gene, which subsequently caused upregulation of phosphate protein kinase B (AKT) and phosphate glycogen synthase kinase 3β (GSK3β). Use of the rat SCI models showed that miR-135a-5p could increase the Basso, Beattie, and Bresnahan (BBB) scores, indicating neurological function recovery. In conclusion, the miR-135a-5p-SP1-Bax/Bcl-2/caspase-3 and miR-135a-5p-ROCK-AKT/GSK3β axes are involved in functional recovery of SCI by regulating neural apoptosis and axon regeneration, respectively, and thus can be promising effective therapeutic strategies in SCI.

BackgroundPeriodontal disease has been associated with gestational complications and both conditions have a high prevalence in rural populations from developing regions. A cross-sectional study was carried out to explore the relationship between periodontal inflamed surface area (PISA), blood pressure (BP), and, serum uric acid levels (UA) in a group of rural North Chinese pregnant women in the third trimester of pregnancy.MethodsThree hundred and thirty-five rural women aged 20–34 years, with normal body mass index (BMI) were examined in a cross-sectional study during their third trimester of gestation. Exclusion criteria were history of pregnancy complications, multiple pregnancy, smoking habits, diabetes, hypertension or any known infectious disease. Socio-demographic variables, including age and socioeconomic status (SES), systolic blood pressure (SBP) and diastolic blood pressure (DBP) readings, serum UA levels, and PISA values were recorded. A structural equation model was implemented with two constructed latent variables including “Dem” (comprising of age and SES category to represent unobserved demographic variables) and, “BP” (comprising of SBP and DBP to account for measurement error and lack of multiple BP readings). The model accounted for co-variance of BP and UA, and implemented simultaneous regressions for BP and UA as outcomes, upon Dem and PISA values as exogenous variables.ResultsThe median PISA score was 1,081.7 (IQR = 835.01), reflecting high levels of periodontal inflammation in the sample. SEM showed a significant association of PISA with BP (estimate = 0.011, 95% CI = 0.009–0.012 p < 0.001) and UA (estimate = 0.001, 95% CI = 0.001–0.001, p < 0.001).ConclusionHigher PISA values were significantly associated with higher blood pressure and uric acid levels among rural pregnant women in a cross-sectional sample from a center in North China after accounting for a latent demographic construct derived from age and SES.

Three new polyketide dimers named huoshanmycins A‒C (1–3) were isolated from a plant endophytic Streptomyces sp. HS-3-L-1 in the leaf of Dendrobium huoshanense, which was collected from the Cultivation base in Jiuxianzun Huoshanshihu Co., Ltd. The dimeric structures of huoshanmycins were composed of unusual polyketides SEK43, SEK15, or UWM4, with a unique methylene linkage. Their structures were elucidated through comprehensive 1D-/2D-NMR and HRESIMS spectroscopic data analysis. The cytotoxicity against MV4-11 human leukemia cell by the Cell Counting Kit-8 (CCK8) method was evaluated using isolated compounds with triptolide as positive control (IC50: 1.1 ± 0.4 μM). Huoshanmycins A and B (1, 2) displayed moderate cytotoxicity with IC50 values of 32.9 ± 7.2 and 33.2 ± 6.1 μM, respectively.