Search

Background: STIL is an important cell cycle-regulating protein specifically recruited to the mitotic centrosome to promote the replication of centrioles in dividing cells. However, the potential role of STIL in the regulation of the biological functions of triple-negative breast cancer remains still unclear. Methods: We screened for differentially expressed STIL in the Cancer Genome Atlas database. The expression of STIL protein in 10 pairs of breast cancer tissues and adjacent normal tissues was further assessed by western blotting. Functionally, the knockdown and overexpression of STIL have been used to explore the effects of STIL on breast cancer cell proliferation, migration, and invasion. Mechanistically, RNA-seq, dual-luciferase reporter assay, chromatin immunoprecipitation assay, mass spectrometry, immunoprecipitation assay, and DNA pull-down assay were performed. Results: Breast cancer tissues and cells have higher STIL expression than normal tissues and cells. STIL knockdown impairs breast cancer cell growth, migration, and invasion, whereas STIL overexpression accelerates these processes. STIL promotes breast cancer progression by regulating FANCD2 expression, and exploration of its molecular mechanism demonstrated that STIL interacts with KLF16 to regulate the expression of FANCD2. Conclusions: Collectively, our findings identified STIL as a critical promoter of breast cancer progression that interacts with KLF16 to regulate Fanconi anemia pathway protein FANCD2. In summary, STIL is a potential novel biomarker and therapeutic target for breast cancer.

Background: Brain metastasis (BM) is a prevalent form of metastasis in lung adenocarcinoma (LUAD), necessitating investigations into the underlying mechanisms. Interleukin 34 (IL-34) and its receptors, macrophage colony-stimulating factor-1 receptor (CSF-IR), Syndecan-1 (SDC-1), and protein-tyrosine phosphatase zeta receptor (PTPRZ1), are known to play pivotal roles in the metastasis of malignant tumors, thereby holding promise as potential biomarkers for studying BM in LUAD. Methods: We performed immunohistochemistry to analyze the expression of IL-34, CSF-1R, SDC-1, and PTPRZ1 in 10 pairs of LUAD primary tissues and BMs, along with 96 unpaired primary tissues and 68 unpaired BMs. Subsequently, we evaluated the association between protein expression and the occurrence of BM. Furthermore, Kaplan-Meier survival curve analysis was conducted on both network and clinical data to explore the association between protein expression and patient prognosis and survival. Results: At the protein level, the expression of IL-34 and its receptors showed significant variation between paired primary tumors and BMs in 10 LUAD patients. The levels of IL-34, CSF-1R, and SDC-1 expression are typically elevated in brain metastatic lesions of LUAD compared to primary LUAD tumors. Furthermore, patients with high CSF-1R expression in primary LUAD are at a greater risk of developing brain metastases. High expression of IL-34 and CSF-1R in primary LUAD lesions indicated poor disease-free survival (DFS) and overall survival (OS), while high expression of SDC-1 indicated poor OS. Cox multivariate analysis further revealed that CSF-1R and IL-34+CSF-1R positivity independently affected LUAD OS. These findings were further substantiated in unpaired samples. Conclusions: Our results indicate significant alterations in the expression of IL-34 and its receptors, CSF-1R and SDC-1, between LUAD primary lesions and BMs, with increased expression observed in BMs. LUAD patients with positive CSF-1R expression in primary lesions exhibited a higher likelihood of developing BM, and high expression of IL-34, CSF-1R, and SDC-1 correlated with poor prognosis. These findings contribute novel insights towards identifying potential treatment or diagnostic targets for metastatic LUAD.

Summary: Lunar-based equipment plays a vital role in the exploration of the moon because it undertakes the tasks of moving, transporting, digging, and so on. In order to control the gait of lunar-based equipment more precisely and guarantee mobile stability, the contact mechanism between its foot and lunar soil is worthy of in-depth study. In this paper, a contact model is proposed to predict the stress, strain, and displacement both on the contact surface and in the lunar soil when the foot is under vertical load. The axial stress in the proposed contact model is verified through the experiment and its accuracy in the lunar equipment is verified through simulation. The error is in a reasonable range and the influence depth of load conforms to the experiment results. This paper provides a relatively accurate model to describe the contact force between the lunar-based equipment’s foot and the lunar soil and will promote the research of lunar exploration.

Increasing evidences have revealed a close relationship between various environmental exposures and reproductive health. The real-world complex exposure scenario along with intricate interactions effects of these exposures has high demands of exposome-wide association studies for human risk assessment. With the development of exposomic studies, applying hair exposome to link environmental factors and reproductive health outcomes has obvious potential advantages. However, the reliability of utilizing hair to characterize exposome is always of high concern for researchers. In this review, we briefly summarized studies about the effects of environmental exposures on several typical reproductive health outcomes, described state-of-the-art situation of applying hair exposome for reproductive health risk assessment, elucidated the advantages (e.g., containing abundant exposure factors, low expenses for sampling, and tracing exposure history), and proposed the unsolved issues in this area. We also conducted a comprehensive discussion about the reliability of various hair biomarkers and primarily established the biomarker databases. Finally, a standardized framework on using hair exposome for reproductive health study was proposed to provide fundamental approach for future studies. We concluded that it is promising to apply hair exposome to evaluate the effects of the environmental factors on human reproductive health.

A suspension of copper oxide nanoparticles (CuO NPs) is a mixture of dissolved and particulate Cu, the relative proportions of which highly depend on the water chemistry. However, the relationship between different proportions of particulate and dissolved Cu and the overall toxicity of CuO NPs is still unknown. This study investigated the response of Chlorella vulgaris to CuO NPs at varying solution pH and at different tannic acid (TA) additions, with a focus on exploring whether and how dissolved and particulate Cu contribute to the overall toxicity of CuO NPs. The results of the exposure experiments demonstrated the involvement of both dissolved and particulate Cu in inducing toxicity of CuO NPs, and the inhibition of CuO NPs on cell density of Chlorella vulgaris was found to be significantly (p

This study aimed to investigate the impact of different curing regimes on the strength of magnesium silicate hydrate cement (MSHC). The study employed various microscopic tests, including XRD, TG, SEM, and MIP, to analyze the underlying mechanisms. The research findings demonstrated that the use of short-term high-temperature curing under the two-stage variable temperature curing regime (TTC) significantly enhanced the early strength of MSHC, with a 3d strength exceeding 30 MPa. In contrast, under standard curing (SC), the strength was only around 2 MPa. The samples subjected to TTC did not exhibit the strength retrogression phenomenon observed under high-temperature curing in previous research, and a high-temperature curing duration of 48 h was found to be more beneficial for the strength development of MSHC. However, from a long-term perspective, the late-stage strength of the TTC samples was lower than that of the SC samples. Microscopic tests revealed that increasing the curing temperature substantially improved the early hydration degree of MSHC, reduced its porosity, and resulted in a more compact cement matrix, thereby enhancing the early strength. Under TTC, hydration continued in the later stage, leading to a decrease in porosity and promoting further strength growth. However, in the long-term, the microstructure of the TTC samples became loose, and the interface connection between silica particles and gel weakened. Compared to the SC samples, the TTC samples exhibited higher porosity, resulting in lower long-term strength.

Introduction: Chronic psychological stress is a well-established risk factor for breast cancer development. Si-Ni-San (SNS) is a classical traditional Chinese medicine formula prescribed to psychological disorder patients. However, its action effects, molecular mechanisms, and bioactive phytochemicals against breast cancer are not yet clear. Objectives: This study aimed to explore the modulatory mechanism and bioactive compound of SNS in regulating estrogen metabolism during breast cancer development induced by chronic psychological stress. Methods: Mouse breast cancer xenograft was used to determine the effect of SNS on breast cancer growth and metastasis. Metabolomics analysis was conducted to discover the impact of SNS on metabolic profile changes in vivo. Multiple molecular biology experiments and breast cancer xenografts were applied to verify the anti-metastatic potentials of the screened bioactive compound. Results: SNS remarkably inhibited chronic psychological stress-induced breast cancer growth and metastasis in the mouse breast cancer xenograft. Meanwhile, chronic psychological stress increased the level of cholic acid, accompanied by the elevation of estradiol. Mechanistic investigation demonstrated that cholic acid activated farnesoid X receptor (FXR) expression, which inhibited hepatocyte nuclear factor 4α (HNF4α)-mediated estrogen sulfotransferase (EST) transcription in hepatocytes, and finally resulting in estradiol elevation. Notably, SNS inhibited breast cancer growth by suppressing estradiol level via modulating FXR/EST signaling. Furthermore, luciferase-reporting gene assay screened naringenin as the most bioactive compound in SNS for triggering EST activity in hepatocytes. Interestingly, pharmacokinetic study revealed that naringenin had the highest absorption in the liver tissue. Following in vivo and in vitro studies demonstrated that naringenin inhibited stress-induced breast cancer growth and metastasis by promoting estradiol metabolism via FXR/EST signaling. Conclusion: This study not only highlights FXR/EST signaling as a crucial target in mediating stress-induced breast cancer development, but also provides naringenin as a potential candidate for breast cancer endocrine therapy via promoting estradiol metabolism.

Background: Banxia Xiexin decoction (BXD) is a classic traditional Chinese medicine (TCM) formula clinically used to treat chronic gastritis, gastric ulcers, gastric cancer, and many other gastrointestinal diseases. Long noncoding RNAs (lncRNAs) have been shown to play an important role in maintaining the malignant phenotype of tumors. However, no relevant studies have shown whether Banxia Xiexin decoction regulates and controls lncRNA TUC338, and the effect of TUC338 on the regulation of gastric cancer invasion and metastasis remains unclear. Purpose: To investigate the ability of the traditional Chinese medicine (TCM) Banxia Xiexin decoction (BXD) to inhibit the migration and invasion of human gastric cancer AGS cells by regulating the long noncoding RNA (lncRNA) TUC338. Methods: UHPLC‒MS/MS was used to analyze the chemical components of BXD. MTT was performed to determine the effects of BXD on the proliferation of AGS cells. qRT‒PCR was used to determine the expression of lncRNA TUC338 in gastric cancer tissues, paracarcinoma tissues, AGS human gastric cancer cells and GES-1 normal gastric mucosa cells and to evaluate the effects of BXD on the expression of lncRNA TUC338 in AGS cells. Lentiviral transfection was used to establish human gastric cancer AGS cells with knocked down lncRNA TUC338 expression. The effects of lncRNA TUC338 knockdown on the migration and invasion of AGS cells were observed by a scratch assay and Transwell migration assay, respectively. Western blotting was performed to analyze the effects of lncRNA TUC338 knockdown on epithelial-to-mesenchymal transition (EMT) in AGS cells. We performed quality control on three batches of BXD. We used UHPLC‒MS/MS to control the quality of three random batches of BXD used throughout the study. Results: Ninety-five chemical components were identified from the water extract of BXD, some of which have anticancer effects. The expression of TUC.338 in gastric cancer tissues was higher than that in para-carcinoma tissues. BXD inhibited the invasion and migration of gastric cancer cells by inhibiting the expression of lncRNA TUC338, which reduced EMT. After knockdown of lncRNA TUC338, the migration and invasion of AGS cells were reduced; the expression of the EMT-related protein E-cadherin was increased, and the expression of N-cadherin and vimentin was reduced. Conclusions: The present results suggest that BXD has potential as an effective treatment for gastric cancer through the inhibition of lncRNA TUC338 expression.

Mammalian apurinic/apyrimidinic endonuclease 1 (APE1, APEX1) is a multifunctional enzyme that maintains cellular homeostasis. It is involved in the base excision repair (BER) pathway and plays a key role in radiation-induced DNA damage response. However, the relationship between APE1-driven radiation resistance and pyroptosis in lung adenocarcinoma (LUAD) cells and the underlying molecular mechanisms remain unclear. We found that APE1 was significantly upregulated in LUAD tissues compared to para-carcinoma tissues and promoted the proliferation and invasion of LUAD cells in vitro and in vivo. Mechanistically, APE1 inhibited pyroptosis by inactivating the interferon gene stimulator (STING) pathway via direct interaction with AIM2 and DDX41, as detected by RNA-seq and co-immunoprecipitation. APE1 protects LUAD cells against radiation-induced damage and induces radio-resistance by targeting the STING pathway. It can induce pyroptosis and is negatively regulated by interactions with AIM2 and DDX41. Therefore, APE1 inhibitors should be considered to enhance the radiosensitivity of LUAD cells and improve patient prognosis and therapeutic outcomes. Thus, APE1 play a role in the tumor immune microenvironment and in tumor immunotherapy.

Background: Taxane-induced peripheral neuropathy (TIPN) is a debilitating adverse effect of cancer treatments with taxanes which may require a reduction or discontinuation chemotherapy and affect clinical and survival outcomes. A number of factors have contributed to the increasing prevalence of TIPN. Nonetheless, limited knowledge exists of potential prechemotherapy blood-based biochemical factors associated with TIPN development. Methods: We recruited breast cancer patients at seven cancer institutions in China. Participants aged 18 years or older with stage I to III breast cancer who scheduled to undergo primary neoadjuvant and adjuvant chemotherapy with taxanes were eligible. Eligible patients underwent patient-reported neuropathy assessments using the EORTC-CIPN20 questionnaire. Patients completed the questionnaire before commencing treatment and after every cycle. For every patient, we selected the highest TIPN toxicity score for analysis since the first cycle. The posttreatment TIPN severity was compared with blood-based biochemical factors within 30 days before commencing treatment. Independent samples t tests, Mann-Whitney U tests and linear regression were used to identify blood-based and clinical associations with TIPN development. Results: The study included 873 breast cancer participants who received paclitaxel, docetaxel or nanoparticle albumin-bound (nab)-paclitaxel. In the whole cohort, factors associated with higher TIPN toxicity scores were higher cumulative chemotherapy dose (β = 0.005; 95% CI, 0.004 to 0.006; P

In order to investigate the characteristics of rock and rock-like materials during the fracture process, notched semi-circular bending (SCB) experiments of 3 rocks and 2 rock-like materials were conducted in this paper. The process of the crack mouth opening was measured with a clip gauge. Acoustic emission was used to analyze the damage and failure mode of the specimens. Meanwhile, the fracture process zone (FPZ) was analyzed with the digital image correlation (DIC). Finally, the differences in the fracture process between rocks and rock-like materials were observed with a polarized microscope, and the formation mechanism of FPZ was discussed. The results indicate that the sequence from brittleness to plasticity is gypsum, marble, granite, concrete and fine sandstone. The crack opening velocity of gypsum, marble, and granite reaches 0.02–0.025 mm/s, far exceeding that of sandstone and concrete at 0.003 mm/s and 0.005 mm/s. The stronger the brittleness of geomaterials, the less significant their acoustic emission effect. Only a few acoustic emissions occur during the fracture process of gypsum with 8 hits. Its fracture occurs instantaneously rather than through a process of damage to fracture and the failure mode is tensile failure. Sandstone has the strongest plasticity, with a large count of acoustic emissions before and after fracture, with a hit number of 5062, which is 630 times of pure gypsum. The fracture is a process of damage accumulation with 94% of sandstone, 89% of concrete, 80% of granite, and 60% of marble showing a tensile and shear failure mode except gypsum. In addition, the stronger the brittleness of geomaterials, the smaller their FPZ size. The FPZ of gypsum is only about 3 mm, which can be considered as lacking, while other materials are about 6–11 mm. The formation of FPZ depends on whether an interlocking structure can be formed inside the material, which is related to the base material and crystalline or aggregate particle size.

Graphene hydrogel (GH) and aerogel (GA) have great application potential as highly effective adsorbents, but the accessibility of their adsorption sites have not yet been identified, restricting our understanding on the adsorption mechanisms and manufacturing. This study comparatively studied the adsorption characteristics of bisphenol A (BPA) and naphthalene (NAP) on GH and GA, focussing on the accessibility of the adsorption sites. The adsorption of BPA on GA was much lower but faster than that on GH. NAP adsorption on GA was very close to that on GH but faster than that on the latter. Considering that NAP is volatilisable, we speculate that some unwetted sites in the air-enclosed pores are available to it, but not to BPA. We applied ultrasonic and vacuum treatments to remove the air in GA pores, which was verified using a CO2 replacement experiment. BPA adsorption was greatly enhanced but slowed, while that of NAP was not enhanced. This phenomenon suggested that some inner pores became accessible in the aqueous phase after air removal from pores. The enhanced accessibility of air-enclosed pores was verified by the increased relaxation rate of surface-bounded water on GA, based on a 1H NMR relaxation analysis. This study highlights that the accessibility of adsorption site plays a crucial role for the adsorption properties of carbon-based aerogel. The volatile chemicals may be quickly adsorbed in the air-enclosed pores, which be useful for immobilizing volatile contaminants.

Summary: N6-adenine DNA methylation (6mA), a rediscovered epigenetic mark in eukaryotic organisms, diversifies in abundance, distribution, and function across species, necessitating its study in more taxa. Paramecium bursaria is a typical model organism with endosymbiotic algae of the species Chlorella variabilis. This consortium therefore serves as a valuable system to investigate the functional role of 6mA in endosymbiosis, as well as the evolutionary importance of 6mA among eukaryotes. In this study, we report the first genome-wide, base pair-resolution map of 6mA in P. bursaria and identify its methyltransferase PbAMT1. Functionally, 6mA exhibits a bimodal distribution at the 5′ end of RNA polymerase II-transcribed genes and possibly participates in transcription by facilitating alternative splicing. Evolutionarily, 6mA co-evolves with gene age and likely serves as a reverse mark of endosymbiosis-related genes. Our results offer new insights for the functional diversification of 6mA in eukaryotes as an important epigenetic mark.

People generally spend most of their time indoors, making indoor air quality be of great significance to human health. Large spatiotemporal heterogeneity of indoor air pollution can be hardly captured by conventional filter-based monitoring but real-time monitoring. Real-time monitoring is conducive to change air assessment mode from static and sparse analysis to dynamic and massive analysis, and has made remarkable strides in indoor air evaluation. In this review, the state of art, strengths, challenges, and further development of real-time sensors used in indoor air evaluation are focused on. Researches using real-time sensors for indoor air evaluation have increased rapidly since 2018, and are mainly conducted in China and the USA, with the most frequently investigated air pollutants of PM2.5. In addition to high spatiotemporal resolution, real-time sensors for indoor air evaluation have prominent advantages in 3-dimensional monitoring, pollution peak and source identification, and short-term health effect evaluation. Huge amounts of data from real-time sensors also facilitate the modeling and prediction of indoor air pollution. However, challenges still remain in extensive deployment of real-time sensors indoors, including the selection, performance, stability, as well as calibration of sensors. In future, sensors with high performance, long-term stability, low price, and low energy consumption are welcomed. Furthermore, more target air pollutants are also expected to be detected simultaneously by real-time sensors in indoor air monitoring.

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of kidney transplantation, and whole-body 18F- FDG PET/CT imaging plays a key role in patients with PTLD. This article reports three cases of 18F-FDG PET/CT manifestations of gastric, prostate, and pulmonary lymphomas after kidney transplantation, all of which showed local lesions without involvement of adjacent or distant lymph nodes and lymphoid node organs. All patients were treated with a reduced dose of R–CHOP and were generally in a good condition after discharge. Early diagnosis and reasonable treatment are key factors in achieving a better prognosis in patients with PTLD, and whole-body 18F-FDG PET/CT imaging plays an important role in the diagnosis and monitoring of PTLD.

Inhalation exposure to polycyclic aromatic hydrocarbons (PAHs) from indoor solid fuel combustion poses a high health risk, and PAHs bound to particles with smaller sizes (e.g., PM1.0, aerodynamic diameter ≤ 1.0 µm) should be of particular concern since they can penetrate deep into pulmonary alveoli. However, PAHs bound to PM1.0 was less studied compared with PAHs in total suspended particles or PM2.5. In this study, multiple provincial field measurements were conducted to investigate 28 PAHs bound to PM1.0 in rural Chinese homes. Daily averaged PM1.0-PAH28 concentrations ranged from 27 ng/m3 to 3795 ng/m3 (median: 233 ng/m3) and from 10 ng/m3 to 2978 ng/m3 (median: 87 ng/m3) in indoor and outdoor air, respectively. Higher concentrations were found in northern China in winter due to increased solid fuels consumption for space heating. The ambient pollution was lower during the non-heating season in Eastern China, where clean energy was preferred. Highly toxic congeners were more abundant in indoor air compared with outdoor air. The results of source apportionment revealed that solid fuel combustion was the primary contributor to rural household PM1.0-PAHs, but other sources such as vehicles cannot be overlooked. The transition to cleaner energy can reduce the indoor PM1.0-PAH28 and BaPeq-28 concentrations by 87% and 98%, respectively, and more efficient reduction was observed for highly toxic congeners. The estimated Incremental Lifetime Cancer Risk (ILCR) based on PM1.0-PAH28 ranged from 4.6 × 10−5 to 3.4 × 10−2, far exceeding the acceptable level of 10−6. Over 60% of the ILCR could be attributed to inhalation exposure during childhood and adolescence.

Introduction: Longxuetongluo Capsule (LTC) is wildly applied to treat ischemic stroke in clinical practice in China. However, the pharmacological mechanism of LTC on ischemic stroke is still unstated. Objective: Our research was designed to study the protective effect of LTC against cerebral ischemia–reperfusion (I/R) injury and reveal the underlying mechanism both in vivo and in vitro. Methods: PC12 cells treated with glucose deprivation/reperfusion (OGD/R) were used to simulate in vitro ischemia/reperfusion (I/R) injury. The cell viability, apoptosis rate, and protein expressions of PC12 cells were evaluated. In vivo validation of the protective effect of LTC was carried out by middle cerebral artery occlusion (MCAO)/reperfusion treatment, and the underlying mechanism of its anti-apoptosis ability was further revealed by immunohistochemistry staining and Western blotting. Results: In the current study, we observed that LTC effectively inhibited oxygen-glucose deprivation/reperfusion (OGD/R) induced apoptosis of PC12 cells through suppressing the cleavage of poly ADP-ribose polymerase (PARP), caspase-3, and caspase-9. Further investigation revealed that OGD/R insult remarkably triggered the endoplasmic reticulum stress responses (ER stress) to induce PC12 cell apoptosis. LTC treatment alleviated OGD/R induced ER stress by inhibiting the activation of protein kinase RNA (PKR)-like ER kinase (PERK)/eukaryotic translation initiation factor 2 (eIF2α) and inositol requiring enzyme 1 (IRE1)/tumor necrosis factor receptor-associated factor 2 (TRAF2) pathways. Additionally, LTC also restrained the OGD/R-induced PC12 cell apoptosis by reversing the activated mitogen-activated protein kinase (MAPK) through IRE1/TRAF2 pathway. Animal studies demonstrated LTC significantly restricted the infarct region induced by middle cerebral artery occlusion (MCAO)/reperfusion, the activation of ER stress and apoptosis of neuronal cells had also been suppressed by LTC in the penumbra region. Conclusion: LTC protects the cerebral neuronal cell against ischemia/reperfusion injury through ER stress and MAPK-mediated mechanisms.

Multilineage differentiating stress enduring cells (Muse cells), double positive for SSEA-3 and CD105, can be isolated by fluorescence-activated cell sorting (FACS) or sever cellular conditions from dermal fibroblasts, bone marrow stem cells (BMSCs), adipose tissue derived stem cells (ADSCs), fresh bone marrow and liposuction fat. When cultured in a single-cell suspension, Muse cells can grow into characteristic cell clusters. Muse cells maintain pluripotency as evidenced by pluripotent markers in vitro. Besides, Muse cells have no tumorigenesis up to 6 months in SCID mice. Muse cells differentiate into cells representative of all three germ layers both spontaneously and under specific induction. In comparison to mesenchymal stem cells (MSCs), Muse cells show higher homing and migration capabilities to damaged sites which is predominantly attributed to S1P–S1PR2 axis. The regenerative effects of Muse cells have been demonstrated by many models in vivo or in vitro, including stroke, intracerebral hemorrhage, myocardial infarction, aortic aneurysm, lung injuries, liver fibrosis, focal segmental glomerulosclerosis, osteochondral defects and skin ulcer. In general, migration, differentiation and paracrine play a pivotal role in the regeneration capability. Here we review the isolation, core properties, preclinical studies as well as the underling molecular and cellular details to highlight their regenerative potential.

Trace elements have various physiochemical functions in humans and are associated with the occurrence of preterm birth (PB). However, their mixed effects on PB risk have rarely been studied. We aimed to investigate the associations between hair levels of trace elements and PB risk among pregnant women. A nested case-control study with a prospective cohort was conducted in Beijing City, China. We included 82 women who had a PB [total PB (tPB)] as cases [including 40 with a spontaneous PB (SPB)] and 415 who had a term delivery as controls. Hair levels of the concerned trace elements were measured including endocrine disrupting metal(loid)s [EDMs; lead, mercury (Hg), arsenic, and cadmium] and nutritional trace metal(loid)s [NTMs; zinc (Zn), iron (Fe), copper, and selenium]. Logistic regression analysis was performed to estimate the odds ratios (ORs) for PB. Bayesian kernel machine regression (BKMR) was used to assess the associations between mixed exposure to the trace elements and PB risk. Significantly lower maternal hair concentrations of Zn and Fe were observed in the SPB cases than in the controls, whereas no differences for the other trace elements. Single-element modeling results suggested second-quartile Hg maternal hair concentrations, third-quartile Zn concentrations, and fourth-quartile Fe concentrations were associated with a reduced risk of tPB with adjusted ORs of 0.43 [95% confidence interval (CI): 0.21–0.87], 0.38 (95% CI: 0.18–0.82), and 0.48 (95% CI: 0.24–0.98), respectively, compared to first-quartile values. Similar results were obtained for SPB. According to the BKMR models, hair NTMs were significantly, monotonously, and inversely associated with the risk of SPB, after controlling for covariates and levels of the four EDMs. Fe and Zn contributed the most strongly to the association. We concluded that maternal higher levels of NTMs, especially Fe and Zn, may reduce the risk of PB.

Background: Exposure to environmental endocrine disruptors (EDCs) may lead to abnormal glucose metabolism and, potentially, gestational diabetes mellitus (GDM). Objective: We investigated the association between five endocrine-disrupting heavy metals (EDHMs), i.e., arsenic (As), cadmium (Cd), lead (Pb), mercury (Hg), and tin (Sn), in maternal hair and the risk of GDM. Methods: We conducted a nested case-control study including 335 GDM cases and 343 controls without GDM based on a prospective birth cohort established in Beijing, China. Concentrations of EDHMs were analyzed in maternal hair. Log-binomial regression and multiple linear regression were used to estimate the associations between the hair concentrations of single metals and the risk of GDM, while weighted quantile sum (WQS) regression for their mixed effects. Results: The median concentrations of Hg (0.442 vs. 0.403 μg/g) and Sn (0.171 vs. 0.140 μg/g) in the case group were significantly higher than those in the control group. No differences were found between the two groups for the other three metals. After adjusting for confounders, the prevalence ratio (PR; highest vs. lowest tertile) of GDM risk for Hg was 1.27 (95% confidence interval [CI]: 1.05–1.54), while that for Sn was 1.26 (95% CI: 1.04–1.53). Among women with a body mass index

Mutations of the Treacle Ribosome Biogenesis Factor 1 (TCOF1) gene can lead to Treacher Collins syndrome (TCS). In present study, the peripheral blood mononuclear cells (PBMCs) of a 33-year-old male TCS patient with the heterozygous TCOF1 mutation c.1966_1969dup (p.Ser657Trpfs*25) were reprogrammed into induced pluripotent stem cells (iPSCs) named PSHi002-A through episomal plasmids encoding hOCT4, hSOX2, hNANOG, hLIN28, hKLF4, and hL-MYC. The established iPSC line expressed pluripotent markers, had a normal karyotype (46, XY), and can be differentiated into the three germ layers in vivo.

Beta-Glucans are commonly used health supplements for humans and animals. They represent a promising avenue to help combat many widespread health concerns including intestinal upset and inflammation. These beneficial effects may be different from species to species and between different cell types and therefore it is important to examine the mechanisms in any species or cell type for which this supplement may be used in. In this study we have shown that pure Beta-Glucans and the less processed yeast cell wall extracts significantly enhance cell migration in a porcine intestinal cell model, potentially through activation of the ELK1 pathway. The expression of migration-related genes was also seen to be significantly increased in response to Beta-Glucan treatment. Our data suggests that Beta-Glucans activate the CD22 receptor in the pig intestine, which has the potential to reduce inflammation. Overall, we found a novel mechanism through which Beta-Glucans exert their effects in the pig intestinal cell model.

Congenital microtia is a malformation of the middle and external ear. Duplications involving the ECR, an ear-specific long-range enhancer of HMX1, lead to ear malformation in different species. Use of electroporation of episomal plasmids encodes OCT4, SOX2, NANOG, LIN28, KLF4, and LMYC into peripheral blood mononuclear cells (PBMCs), we generated an induced pluripotent stem cell (iPSCs) line of a microtia patient carrying the duplication involving ECR. The iPSCs express pluripotency markers, have the potential to differentiate into three germ layers, and show the normal karyotype. This patient-specific iPSC will be used for modeling the pathophysiology of ear malformation.

Fibrous dysplasia of bone (FDB) was a condition that the normal bone tissue was replaced by benign hyperplastic fibrous tissue; these patients may present with pain, swelling, or pathological fracture. The imaging findings of FDB on CT or MR images have been documented previously, however it was usually misdiagnosed as primary bone malignancy or metastatic tumor due to lack of specificity in routine radiographic examinations. Furthermore, the most common affected sites were extremities, pelvis, femur and craniofacial bones, and the spine is less involved. Here we reported a case with thoracic FD, she presented with chest and back pain for 9 years, the 18F-FDG PET/CT examination revealed abnormal hypermetabolic foci at 8th and 9th vertebrae, and the right ninth posterior ribs; Histopathological examination showed fibrous dysplasia, and she was discharged 1 week later, and was in good health during follow up.

Hair metal(loid)s are often measured as biomarkers to evaluate population internal exposure, however, hair samples could be easily contaminated by ambient particulate matter (PM) pollution. Here, we evaluated the potential external interference from ambient PM pollution on using hair metal(loid)s for population biomarker-based exposure assessment. The raw hair samples were strictly washed and placed under various indoor and outdoor scenarios for ~6 months at sites with high PM pollution. The contaminated hair was then washed using the same method. A total of 33 hair elements were quantified by inductively coupled plasma–mass spectrometry. The surface residual PM on hair after washing was observed by scanning electron microscopy. In addition, we chose a practical exposure scenario including 77 housewives in Shanxi Province, China for validation. The results for the hair exposure experiment revealed that external contamination of some elements that had relatively high concentrations in hair was generally mild in both indoor and outdoor exposure scenarios (i.e., Zn, Mg, Se, Fe, Sr, Ti, Mn, Sn, Ge, U, Co, Mo, and As). A relatively higher external contamination of other elements (e.g., Al, Cr, Pb, Cd, Li, and most rare earth elements (REEs)) was observed, especially for those elements with relatively low hair concentrations (e.g., Cd, and REEs) in the outdoor environment. This finding was due mainly to some small ambient PM not being fully removed by the current washing strategy when the hair sample was heavily contaminated. However, results from practical exposure scenario of the housewives showed that there were overall no significant differences of hair metal(loid)s between the housewives using coal and clean energy for cooking. We concluded that the external interference on hair internal metal(loid) analysis could be negligible when hair was efficiently washed, especially for population with relatively longer indoor activities. It is therefore promising to use hair analysis for their population exposure assessment. Keywords: Hair, Metal(loid), Element, External contamination, Reliability

Microtia is a congenital external ear malformation that can seriously influence the psychological and physiological well-being of affected children. The successful regeneration of human ear-shaped cartilage using a tissue engineering approach in a nude mouse represents a promising approach for auricular reconstruction. However, owing to technical issues in cell source, shape control, mechanical strength, biosafety, and long-term stability of the regenerated cartilage, human tissue engineered ear-shaped cartilage is yet to be applied clinically. Using expanded microtia chondrocytes, compound biodegradable scaffold, and in vitro culture technique, we engineered patient-specific ear-shaped cartilage in vitro. Moreover, the cartilage was used for auricle reconstruction of five microtia patients and achieved satisfactory aesthetical outcome with mature cartilage formation during 2.5 years follow-up in the first conducted case. Different surgical procedures were also employed to find the optimal approach for handling tissue engineered grafts. In conclusion, the results represent a significant breakthrough in clinical translation of tissue engineered human ear-shaped cartilage given the established in vitro engineering technique and suitable surgical procedure. This study was registered in Chinese Clinical Trial Registry (ChiCTR-ICN-14005469).

Human enterovirus 71 (EV71) is the main causative pathogen of hand, foot, and mouth disease (HFMD) in children. The epidemic of HFMD has been a public health problem in Asia-Pacific region for decades, and no vaccine and effective antiviral medicine are available. Curcumin has been used as a traditional medicine for centuries to treat a diversity of disorders including viral infections. In this study, we demonstrated that curcumin showed potent antiviral effect again EV71. In Vero cells infected with EV71, the addition of curcumin significantly suppressed the synthesis of viral RNA, the expression of viral protein, and the overall production of viral progeny. Similar with the previous reports, curcumin reduced the production of ROS induced by viral infection. However, the antioxidant property of curcumin did not contribute to its antiviral activity, since N-acetyl-l-cysteine, the potent antioxidant failed to suppress viral replication. This study also showed that extracellular signal-regulated kinase (ERK) was activated by either viral infection or curcumin treatment, but the activated ERK did not interfere with the antiviral effect of curcumin, indicating ERK is not involved in the antiviral mechanism of curcumin. Unlike the previous reports that curcumin inhibited protein degradation through ubiquitin–proteasome system (UPS), we found that curcumin had no impact on UPS in control cells. However, curcumin did reduce the activity of proteasomes which was increased by viral infection. In addition, the accumulation of the short-lived proteins, p53 and p21, was increased by the treatment of curcumin in EV71-infected cells. We further probed the antiviral mechanism of curcumin by examining the expression of GBF1 and PI4KB, both of which are required for the formation of viral replication complex. We found that curcumin significantly reduced the level of both proteins. Moreover, the decreased expression of either GBF1 or PI4KB by the application of siRNAs was sufficient to suppress viral replication. We also demonstrated that curcumin showed anti-apoptotic activity at the early stage of viral infection. The results of this study provide solid evidence that curcumin has potent anti-EV71 activity. Whether or not the down-regulated GBF1 and PI4KB by curcumin contribute to its antiviral effect needs further studies.

Void drift between subchannels in a rod bundle is a crucial phenomenon affecting the calculation accuracy of thermal-hydraulic parameters in SMRs. It holds significant importance in enhancing the precision of safety analysis for SMRs. Existing research on experiment and model of void drift between rod bundle subchannels is relatively rare, and the accuracy of model calculations requires improvement. In this study, experiments on gas-liquid two-phase non-equilibrium flow were conducted to measure the redistribution of two-phase flow induced by void drift in a 1 × 2 rod bundle. The experiment results indicated that in bubby flow regime with void fraction less than 0.3, the void diffusion coefficient showed little variation with changes in void fraction. However, in slug flow and annular flow regimes with void fraction exceeding 0.3, the void diffusion coefficient significantly increased with an increase in void fraction. Furthermore, a new void drift model was developed and validated based on a subchannel code. The overall predicted uncertainty for the outlet void fraction in the rod bundle benchmark was less than 13%.

The ABCC1 gene belongs to the ATP-binding cassette membrane transporter superfamily, which plays a crucial role in the efflux of various endogenous and exogenous substances. Mutations in ABCC1 can result in autosomal dominant hearing loss. However, the specific roles of ABCC1 in auditory function are not fully understood. Through immunofluorescence, we found that ABCC1 was expressed in microvascular endothelial cells (ECs) of the stria vascularis (StV) in the murine cochlea. Then, an Abcc1 knockout mouse model was established by using CRISPR/Cas9 technology to elucidate the role of ABCC1 in the inner ear. The ABR threshold did not significantly differ between WT and Abcc1−/− mice at any age studied. After noise exposure, the ABR thresholds of the WT and Abcc1−/− mice were significantly elevated. Interestingly, after 14 days of noise exposure, ABR thresholds largely returned to pre-exposure levels in WT mice but not in Abcc1−/− mice. Our subsequent experiments showed that microvascular integrity in the StV was compromised and that the number of outer hair cells and the number of ribbons were significantly decreased in the cochleae of Abcc1−/− mice post-exposure. Besides, the production of ROS and the accumulation of 4-HNE significantly increased. Furthermore, StV microvascular ECs were cultured to elucidate the role of ABCC1 in these cells under glucose oxidase challenge. Notably, 30 U/L glucose oxidase (GO) induced severe oxidative stress damage in Abcc1−/− cells. Compared with WT cells, the ROS and 4-HNE levels and the apoptotic rate were significantly elevated in Abcc1−/− cells. In addition, the reduced GSH/GSSG ratio was significantly decreased in Abcc1−/− cells after GO treatment. Taken together, Abcc1−/− mice are more susceptible to noise-induced hearing loss, possibly because ABCC1 knockdown compromises the GSH antioxidant system of StV ECs. The exogenous antioxidant N-acetylcysteine (NAC) may protect against oxidative damage in Abcc1−/− murine cochleae and ECs.

Objective: The high incidence of Tension-type headache (TTH) has led to significant social and economic challenges. Given the widespread use of Chinese patent medicines (CPM) for TTH patients, this study aim to evaluate the efficacy of different CPMs in treating TTH by network meta-analysis. Methods: Eight databases were conducted to identify CPMs-related randomized controlled trials (RCTs) from database inception date to August 2023. The primary outcome was clinical efficiency rate. The secondary outcomes were numerical rating scale (NRS), frequency of headache, duration of headache, hamilton anxiety scale (HAMA), hamilton depression Scale (HAMD) and adverse reactions. ROB 2.0 were used for quality evaluation. Stata 15.1 and R 3.5.3 software were used for Bayesian network meta-analysis. Results: A total of forty-one RCTs were included, involving 3,996 patients and 8 CPMs. The network meta-analysis revealed that Shugan Jieyu capsule plus western medicine (WM) was the best choice of CPM for improving clinical efficiency rate [vs. WM: relative risk (RR) = 7.31, 95 % confidence interval (CI): (1.65, 56.71)]. Yangxue Qingnao granule plus WM was superior to other therapeutic combinations in reducing duration of headache [vs. WM: MD = 1.05, 95%CI(0.74, 1.40)]. Jieyu pill plus WM might have best effect in reducing HAMD [vs. WM: MD = 7.15, 95%CI(-3.77, 18.14)], HAMA scores [vs. WM: MD = −7.41, 95%CI(-13.39, −1.42)], and NRS scores [vs. WM: mean difference (MD) = 2.01, 95%CI(1.47, 2.55)]. In terms of the frequency of headache, although Yangxue Qingnao granule plus WM and Toutong-ning capsule plus WM performed best, the optimal CPMs in reducing the frequency of headache remain to be further explored. Furthermore, due to the limited safety evidence available, reliable safety conclusions could not be drawn. Conclusion: CPM can effectively improve headache symptoms, clinical efficiency, and quality of life in patients with TTH. However, research with high quality and large sample sizes is needed for further investigation due to the limitations of this study.

The undulating appearance of 3D-printed concrete (3DPC) is an essential feature that impacts the integrity and stability of the multilayer structure, yet the related evaluation parameters have rarely been proposed. This study proposed a quantitative evaluation and parameters through the on-site 3D scan technology to impel a direct and precise understanding of the surface quality of 3DPC, especially concrete with coarse aggregates. Firstly, 8-layer 3DPC walls are produced at four different printer printing rates and then 3D scanned. After point cloud correction, noise reduction, and 2D processing onto acquired points cloud, the evaluation parameters for evaluating 3DPC surface characteristics are defined and calculated. Results indicate that a higher 3D printer printing rate helps reduce surface fluctuation of 3DPC multilayer structures but disfavor the vertical flatness, of which the linear relationship between the parameters and the printing speed of the printer is explored and discussed. Recommendation of 3DPC straight wall structures controlled to surface defects ratio within 2% and slope within 0.2% is suggested. These conclusions provide precise external surface quality control and treatment basements that contribute to improving the practical application of 3DPC.

Lipopolysaccharide (LPS)-triggered damage in human dental pulp cells (hDPCs) is associated with the progression of gingivitis, which is inflammation of the gingival tissue. Nesfatin-1 is a peptide secreted by neurons and peripheral tissues. Here, we report a novel property of Nesfatin-1 in ameliorating LPS-induced inflammatory response and senescence in hDPCs. First, we demonstrate that Nesfatin-1 repressed LPS-triggered expression of inflammatory factors. Secondly, Nesfatin-1 restored telomerase activity and the expression of human telomerase reverse transcriptase (hTERT) and telomeric repeat binding factor 2 (TERF2) against LPS. Senescence-associated β-galactosidase (SA-β-gal) staining assay revealed that Nesfatin-1 attenuated LPS-induced cellular senescence in hDPCs. We also found that Nesfatin-1 increased telomerase activity in LPS-challenged hDPCs. It is also shown that Nesfatin-1 reduced the expression of plasminogen activator inhibitor-1 (PAI-1) and p16. Additionally, LPS stimulation reduced the expression of SIRT1, which was rescued by Nesfatin-1. However, the silencing of sirtuin1 (SIRT1) abrogated the protective property of Nesfatin-1 in preventing cellular senescence, implying that the function of Nesfatin-1 is regulated by SIRT1. Taken together, our findings suggest that Nesfatin-1 might possess a protective effect against gingivitis.

The purpose of this study was to investigate the effect of Treg/Th1 imbalance in cadmium-induced lung injury and the potential protective effect of astilbin against cadmium-induced lung injury in chicken. Cadmium exposure significantly decreased T-AOC and GSH-Px levels and SOD activity in the chicken lung tissues. In contrast, it significantly increased the MDA and NO levels. These results indicate that cadmium triggers oxidative stress in lungs. Histopathological analysis revealed that cadmium exposure further induced infiltration of lymphocytes in the chicken lungs, indicating that cadmium causes pulmonary damage. Further analysis revealed that cadmium decreased the expression of IL-4 and IL-10 but increased those of IL-17, Foxp3, TNF-α, and TGF-β, indicating that the exposure of cadmium induced the imbalance of Treg/Th1. Moreover, cadmium adversely affected chicken lung function by activating the NF-kB pathway and inducing expression of genes downstream to these pathways (COX-2, iNOS), associated with inflammatory injury in the lung tissue. Astilbin reduced cadmium-induced oxidative stress and inflammation in the lungs by increasing antioxidant enzyme activities and restoring Treg/Th1 balance. In conclusion, our results suggest that astilbin treatment alleviated the effects of cadmium-mediated lung injury in chickens by restoring the Treg/Th1 balance.

Objective: To explore the preventive effect of electroacupuncture pretreatment on stroke in rats by inhibiting ferroptosis and oxidative stress. Methods: Rats were randomly assigned to the sham, middle cerebral artery occlusion/reperfusion (MCAO/R), MCAO/R + EP, MCAO/R + EP + erastin, and MCAO/R + EP + ferrostatin 1 groups. Daily electroacupuncture was performed 2 weeks before establishing the MCAO/R model utilizing the modified Zea Longa suture method. Rats were sacrificed 1 day after reperfusion, and brain tissues were collected. They were prepared for hematoxylin and eosin staining, prussian blue staining, transmission electron microscope. Measurement of total iron levels using a commercial kit, detection of malondialdehyde (MDA) and superoxide dismutase (SOD) levels by ELISA, and examination of 15-lox2, GPX4, SLC7A11, ACSL4, and TFR1 by western blotting. Results: Compared with sham rats, cerebral infarction size was dramatically larger in MCAO/R rats. Moreover, the MCAO/R group displayed damaged mitochondria with a disarranged structure of cristae; free iron, total iron levels, and oxidative stress were significantly higher. Cerebral pathological lesions, oxidative stress, total iron levels, and protein levels of ACSL4, TFR1, and 15-lox2 were significantly reduced in the MCAO/R + EP and MCAO/R + EP + ferrostatin 1 groups, while the protective effect of electroacupuncture pretreatment on cerebral ischemia-reperfusion injury was inhibited by treatment with the ferroptosis activator erastin. Conclusion: Electroacupuncture pretreatment can protect rats from cerebral ischemia-reperfusion injury by reducing the area of cerebral infarction and inhibiting ferroptosis and oxidative stress.

Context: Shenyu Ningshen (SYNS) tablet is the first pure Chinese medicinal small compound preparation approved for clinical trials for the treatment of depression in China. Clinical experiments confirmed that the formulation had a significant Improvement effect against depression due to the deficiency of both qi and yin. Our previous study showed that SYNS could effectively inhibit the inflammatory response in a depression model. Aim of the study: The purpose of this study was to investigate the protective effects of SYNS on neurons and explore whether the underlying mechanism was associated with A1s. Materials and methods: The depression model of solitary raising-chronic restraint stress (CRS) rats was established; body weight examination, sugar water preference test, open field test, and histological analysis were performed to preliminarily verify the efficacy of the formulation. Subsequently, neuronal nucleus (NeuN) and synaptic-associated proteins (MAP2 and PSD95) were labeled, and the protective effect of SYNS on hippocampal neurons was observed based on the fluorescence intensity of the above indicators. Western blotting, histological examination, and immunofluorescence were used to evaluate the inhibitory effects of SYNS on neuroinflammation and activation of A1s in CRS depression model. Results: SYNS improved behavioral indicators such as weight loss, pleasure loss, and reduced exercise volume in CRS rat model. SYNS restored the CRS-induced histopathological changes in the hippocampus. SYNS showed a certain degree of protective effect on synapses. Further, SYNS inhibited the activation of A1s by inhibiting neuroinflammatory factors in the hippocampus. Conclusion: Our results showed that SYNS had a certain degree of neuroprotective effect, which might be related to its inhibition of the inflammatory response and A1s.

Background: Although many experiments and clinical studies have proved the link between the expression of CDKN3 and human tumors, we have not been able to identify any bioinformatics study in which the extensive tumor-promoting effect of CDKN3 was systematically analyzed. Objective: Explore the extensive tumor-promoting effects of CDKN3 and review the research progress of CDKN3 in cancer. Methods: We systematically reviewed the literature on CDKN3 and tumors. We explored the potential tumor-promoting effects of CDKN3 on different tumors in the TCGA database and the GTEx database using multiple platforms and websites. We studied the expression level of CDKN3, survival, prognosis, diagnosis, genetic variation, immune infiltration, and enrichment analysis using databases such as TIMER 2.0, GEPIA2, cBioPortal, and STRING. Results: We found that CDKN3 is highly expressed in most tumors. The expression of CDKN3 is closely related to the prognosis of some tumors. And CDKN3 may have diagnostic value. The conclusion of our literature review is roughly the same, but there are differences, which are worthy of further study. Moreover, CDKN3 may be related to immune cell infiltration in tumor tissues. The genetic alteration of LUAD, STAD, SARC, PCPG, and ESCA with ''Amplification'' as the main type. In addition, through enrichment analysis, we found that CDKN3 affects tumors mainly through the control of the cell cycle and mitosis. Conclusion: CDKN3 is highly expressed in most tumor tissues and has a statistical correlation with survival prognosis. It has extensive tumor-promoting effects that may be related to mechanisms such as immune infiltration.

Halobenzoquinones (HBQs) were recently discovered as an emerging class of drinking water disinfection byproducts with carcinogenic concern. However, the molecular mechanism underlying HBQs-induced DNA damage is not clear. In this study, we integrated in vitro genotoxicity, computational toxicology, and the quantitative toxicogenomic analysis of HBQs on DNA damage/repair pathways in human bladder epithelial cells SV-HUC-1. The results showed that HBQs could induce cytotoxicity with the descending order as 2,6-DIBQ > 2,6-DCBQ ≈ 2,6-DBBQ. Also, HBQs can increase DNA damage in SV-HUC-1 cells and thus generate genotoxicity. However, there is no significant difference in genotoxicity among the three HBQs. The results of molecular docking and molecular dynamics simulation further confirmed that HBQs had high binding fractions and stability to DNA. Toxicogenomic analysis indicated that HBQs interfered with DNA repair pathways, mainly affecting base excision repair, nucleotide excision repair and homologous recombination repair. These results have provided new insights into the underlying molecular mechanisms of HBQs-induced DNA damage, and contributed to the understanding of the relationship between exposure to DBPs and risks of developing bladder cancer.

The cochlear implant (CI), an advanced electronic device replacing the entire cochlear function, is the ultimate treatment for over 466 million people with disabling hearing loss. Infection after cochlear implantation is a common and worrisome complication despite the routine administration of the antibiotic. The bacterial biofilms formed on the surface of CI are the main cause of antibiotic failure. To solve this problem, we developed a copper-containing zwitterionic coating consisting of anti-adherent poly sulfobetaine methacrylate (PSB) and steadfast polydopamine (PDA). CuSO4/H2O2. was added to accelerate this co-deposition reaction and enhance the anti-bacterial property. The preparation method was simple, rapid, and suitable for clinical use. In our in vitro and in vivo studies, the PSB/PDA(Cu) coating showed high biocompatibility, and conferred CI implants excellent anti-inflammatory, strong anti-bacterial effects, and great anti-biofilm properties to representative Gram-positive and Gram-negative bacteria. These findings implied that the PSB/PDA(Cu) coating was a unique anti-bacterial strategy for enhancing CI performance.