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Abstract The controversy surrounding whether serum total cholesterol is a risk factor for the graded progression of knee osteoarthritis (KOA) has prompted this study to develop an authentic prediction model using a machine learning (ML) algorithm. The objective was to investigate whether serum total cholesterol plays a significant role in the progression of KOA. This cross-sectional study utilized data from the public database DRYAD. LASSO regression was employed to identify risk factors associated with the graded progression of KOA. Additionally, six ML algorithms were utilized in conjunction with clinical features and relevant variables to construct a prediction model. The significance and ranking of variables were carefully analyzed. The variables incorporated in the model include JBS3, Diabetes, Hypertension, HDL, TC, BMI, SES, and AGE. Serum total cholesterol emerged as a significant risk factor for the graded progression of KOA in all six ML algorithms used for importance ranking. XGBoost algorithm was based on the combined best performance of the training and validation sets. The ML algorithm enables predictive modeling of risk factors for the progression of the KOA K–L classification and confirms that serum total cholesterol is an important risk factor for the progression of KOA.

Abstract Dental calculus severely affects the oral health of humans and animal pets. Calculus deposition affects the gingival appearance and causes inflammation. Failure to remove dental calculus from the dentition results in oral diseases such as periodontitis. Apart from adversely affecting oral health, some systemic diseases are closely related to dental calculus deposition. Hence, identifying the mechanisms of dental calculus formation helps protect oral and systemic health. A plethora of biological and physicochemical factors contribute to the physiological equilibrium in the oral cavity. Bacteria are an important part of the equation. Calculus formation commences when the bacterial equilibrium is broken. Bacteria accumulate locally and form biofilms on the tooth surface. The bacteria promote increases in local calcium and phosphorus concentrations, which triggers biomineralization and the development of dental calculus. Current treatments only help to relieve the symptoms caused by calculus deposition. These symptoms are prone to relapse if calculus removal is not under control. There is a need for a treatment regime that combines short-term and long-term goals in addressing calculus formation. The present review introduces the mechanisms of dental calculus formation, influencing factors, and the relationship between dental calculus and several systemic diseases. This is followed by the presentation of a conceptual solution for improving existing treatment strategies and minimizing recurrence.

Abstract We construct rotating hybrid axion-miniboson stars (RHABSs), which are asymptotically flat, stationary, axially symmetric solutions of (3+1)-dimensional Einstein–Klein–Gordon theory. RHABSs consist of an axion field (ground state) and a free complex scalar field (first excited state). The solutions of RHABSs have two types of nodes, including $$^1S^2S$$ 1 S 2 S state and $$^1S^2P$$ 1 S 2 P state. For different axion decay constants $$f_a$$ f a , we present the mass M of RHABSs as a function of the synchronized frequency, as well as the nonsynchronized frequency, and explore the mass M versus the angular momentum J for the synchronized frequency and the nonsynchronized frequency, respectively. Furthermore, we study the effect of axion decay constant $$f_a$$ f a and free scalar field mass $$\mu _f$$ μ f on the existence domain of the synchronized frequency $$\omega $$ ω .

Reducing the oral bioavailability of metal contaminants including As, Cd, , and Pb in foods can protect human health. Studies showed reduced metal bioavailability with elevated Ca and Fe intake; however, the effectiveness of enhancing food Ca and Fe bioavailability remains unknown. Based on a mouse bioassay and using metal accumulation in mouse tissues (kidneys and liver) as the bioavailability endpoint, this study investigated the roles of casein phosphopeptides (CPP, food nutrition fortifier) in lowering the As, Cd, and Pb bioavailability from consuming a metal-contaminated wheat. The CPP amendment at 0.10–0.50% in wheat promoted its Ca bioavailability, causing 33–62% and 59–80% decreases in the gene expression encoding for duodenal Ca and phosphate transporters in mice. This limited transcellular transport of Cd2+ and inorganic arsenate via Ca and phosphate transporters respectively, thus leading to 27% and 34% decreases in Cd and As contents in mouse kidneys fed with wheat at 0.50% CPP amendment. In addition, CPP promoted the colonization of Feacalibaculum and Bifidobacterium in mouse gut, likely promoting As excretion in feces by 81–112%. In contrast to As, and Cd, CPP failed to reduce Pb contents in mouse tissue after consuming CPP-amended wheat, probably by elevating wheat-Pb solubility in the intestinal fluid by 48–136%. However, co-amendment of 0.30% CPP and 500 ​μg ​g−1 Ca as Ca gluconate lowered the As, Cd, and Pb contents in mouse kidneys by 38–71%. The data indicate that fortifying Ca together with CPP in wheat can reduce human exposure to multi-metals via dietary intake.

The widespread use of copper and tetracycline as growth promoters in the breeding industry poses a potential threat to environmental health. Nevertheless, to the best of our knowledge, the potential adverse effects of copper and tetracycline on the gut microbiota remain unknown. Herein, mice were fed different concentrations of copper and/or tetracycline for 6 weeks to simulate real life–like exposure in the breeding industry. Following the exposure, antibiotic resistance genes (ARGs), potential pathogens, and other pathogenic factors were analyzed in mouse feces. The co-exposure of copper with tetracycline significantly increased the abundance of ARGs and enriched more potential pathogens in the gut of the co-treated mice. Copper and/or tetracycline exposure increased the abundance of bacteria carrying either ARGs, metal resistance genes, or virulence factors, contributing to the widespread dissemination of potentially harmful genes posing a severe risk to public health. Our study provides insights into the effects of copper and tetracycline exposure on the gut resistome and potential pathogens, and our findings can help reduce the risks associated with antibiotic resistance under the One Health framework.

AIM:To investigate the neuroprotective effect of 17β-estradiol(E2)on retina light damage in BALB/c and C57BL/6 mice and provide experimental data for the successful construction of a research model for E2 against retinal light damage.METHODS:Totally 40～45 adult female BALB/c or C57BL/6 mice were divided into six groups, 6 for each group: normal control, ovariectomized control, ovariectomized light(mice were stimulated with continuous white light at 10000 lx for 4, 8, 12, 16, and 24h after 14d of ovariectomy), intravitreal administration sham operation, saline and E2 pre-treatment groups(2μL saline or 10-5mol/L E2 were intravitreal injected respectively after 14d of ovariectomy operation and 24h of dark adaptation). The morphological and functional changes of the retina were detected by paraffin section HE staining, TUNEL staining and electroretinogram.RESULTS:In the ovariectomized light group, the thickness of the inner/outer nuclear layer decreased significantly from the 4h stimulation of 10000 lx white light group. Intravitreal administration of E2 significantly inhibited the apoptosis of retinal cells in the two strains of mice(P

Myofibroblastic sarcoma (MS) is a malignant tumor of soft tissue or bone that can occur in children or adults, with a high rate of recurrence and metastasis. We report a case of low-grade malignant MS of the left shoulder, diagnosed based on pathological examination and immunohistochemical staining. However, the patient had unexplained pleural maculopathy. The patient passed away 6 months after the diagnosis of myofibroblast sarcoma due to multiple metastases throughout the sarcoma. Combined with the patient’s history, ancillary findings, and after MDT discussion, the patient was ultimately considered to have a high probability of myofibroblast sarcoma combined with pleural maculopathy. In conclusion, when a patient is diagnosed with myofibroblast sarcoma in combination with pleural macula, in the absence of other causative factors, a deep tissue biopsy of the pleura should be actively performed to confirm the diagnosis.

Background: Mesenchymal stem cells (MSCs) are considered a promising therapeutic strategy for rheumatoid arthritis (RA), but the current clinical results are varied. This study is to analyze the therapeutic effect of cell-based strategies on RA. Materials and Methods: The searches were performed with public databases from inception to June 17, 2021. Randomized controlled trials researching cell-based therapies in RA patients were included. Results: Eight studies, including 480 patients, were included in the analysis. The results showed that compared to the control, MSC treatment significantly reduced the disease activity score (DAS) at the second standardized mean difference (SMD): −0.70; 95% confidence interval (CI): −1.25, −0.15; P = 0.01) and 3rd month (SMD: −1.47; 95% CI: −2.77, −0.18; P < 0.01) and significantly reduced the rheumatoid factor (RF) level at the first (SMD: −0.38; 95% CI: −0.72, −0.05; P = 0.03) and 6th months (SMD: −0.81; 95% CI: −1.32, −0.31; P < 0.01). In the network meta-analysis, MSCs combined with interferon-γ (MSC_IFN) had a significant effect on increasing the American college of rheumatology criteria (ACR) 20, ACR50, and DAS

Seven possible ultra-low-mass and small-radius white dwarfs have been recently identified, with masses ranging from ∼0.02 M⊙ to ∼0.08 M⊙ and radii ranging from ∼ 4,270 km to 10670 km. The mass–radius measurements of these white dwarfs pose challenges to traditional white dwarf models, assuming they are mostly made of nuclei lighter than 56Fe. In this work, we consider the possibility that those white dwarfs are made of heavier elements. Due to the small charge-to-mass ratios in heavy elements, the electron number density in white dwarf matter is effectively reduced, which reduces the pressure with additional contributions of lattice energy and electron polarization corrections. This consequently leads to white dwarfs with much smaller masses and radii, which coincide with the seven ultra-low-mass and small-radius white dwarfs. The mass of the most massive white dwarfs is effectively reduced and could possibly account for the sub-Chandrasekhar progenitors in underluminous Type Ia supernovae. The corresponding equation of state and matter contents of dense stellar matter with and without reaching the cold-catalyzed ground state are presented, which are obtained using the latest Atomic Mass Evaluation (AME 2020). Further observations are necessary to unveil the actual matter contents in those white dwarfs via, e.g., spectroscopy, asteroseismology, and the discoveries of other ultra-low-mass and small-radius white dwarfs.

Compact stars have been perceived as natural laboratories of matter at an extremely high density. The uncertainties of the equation of state (EOS) of matter can be constrained by observing compact stars. In this review, we investigate the EOSs, global structure, and elastic properties of compact stars. We focus in detail on how to constrain the above properties of compact stars via asteroseismology. Observations that include studies of quasi-periodic oscillations from giant flares of soft gamma-ray repeaters and gravitational waves provide information about the elastic properties and internal compositions of compact stars.

Abstract Background The aim of the present study was to compare the clinical efficacy of arthroscopic-assisted fixation using the Tight-rope system and clavicular hook plate fixation in the treatment of Neer IIB distal clavicle fractures. Methods We enrolled 48 consecutive patients with Neer IIB distal clavicle fractures who were treated at our institution from February 2016 and August 2020. These patients were divided into 2 groups based on the fixation method (16 cases with Tight-rope system and 32 cases with clavicular hook plate), and demographics and clinical characteristics of patients in different groups were compared. Results All 48 patients had functional outcome scores of the affected shoulder available at a mean of 23.8 ± 5.1 months, and there was a statistically significant improvement in the constant score, American shoulder and elbow surgeons (ASES) score, visual analogue scale (VAS) score at the end of follow-up (p

Abstract Pleural mesothelioma (PM) with pericardial involvement is extremely rare. We now report a rare case of malignant PM with constrictive pericarditis as the first presentation. A 59‐year‐old male diagnosed with constrictive pericarditis underwent pericardiectomy and pericardial pathology revealed mesothelial hyperplasia. Eight months after surgery, the patient was admitted to the hospital with chest tightness and wheezing for 5 days. Computed tomography scan of the chest showed a left lung expansion insufficiency, limited bilateral pleural thickening, pericardial thickening with a small amount of pericardial effusion, and multiple enlarged lymph nodes in the mediastinum, bilateral supraclavicular fossa, bilateral cervical roots, and right axilla. The pleural malignancy should be possibly considered. Pathology after pleural puncture showed malignant PM. Pathology after left supraclavicular lymph node puncture biopsy showed metastatic malignant mesothelioma. The diagnosis of this patient was clear. Although malignant PM rarely involves the pericardial constriction, we cannot ignore the fact that malignant PM involves the pericardium. The patient has been diagnosed with constrictive pericarditis, accompanied by pleural thickening and pleural effusion. Without other pathogenic factors, pleural biopsy should be aggressively performed in patients with constrictive pericarditis to determine the cause.

Abstract Background Osteosarcoma is the most common primary bone tumor in children and adolescents. However, some patients with osteosarcoma develop resistance to chemotherapy, leading to a poor clinical prognosis. Hence, effective therapeutic agents that can improve the response to chemotherapy drugs to improve the prognosis of patients with osteosarcoma are urgently needed. Cordycepin has recently emerged as a promising antitumor drug candidate. This study aims to explore the effect of cordycepin in suppressing osteosarcoma in vivo and in vitro and the synergistic effect of cordycepin combined with cisplatin and to demonstrate the underlying molecular mechanism. Methods CCK-8 assay was performed to investigate the inhibition effect of cordycepin combined with cisplatin in osteosarcoma cell lines. The colony formation and invasion abilities were measured by colony formation assay and Transwell assay. Osteosarcoma cells apoptosis was detected by flow cytometry. Western blot analysis were used to detect the expression of cell apoptosis-related proteins and AMPK and AKT/mTOR signaling pathway-related proteins. Finally, we performed the in vivo animal model to further explore whether cordycepin and cisplatin exert synergistic antitumor effects. Results Notably, we found that treatment with cordycepin inhibited cell proliferation, invasion, and induced apoptosis in osteosarcoma cells in vitro and in vivo. Moreover, the combination of cordycepin and cisplatin led to marked inhibition of osteosarcoma cell proliferation and invasion and promoted osteosarcoma cell apoptosis in vitro and in vivo. Mechanistically, we demonstrated that cordycepin enhanced the sensitivity of osteosarcoma cells to cisplatin by activating AMPK and inhibiting the AKT/mTOR signaling pathway. Conclusions In brief, this study provides comprehensive evidence that cordycepin inhibits osteosarcoma cell growth and invasion and induces osteosarcoma cell apoptosis by activating AMPK and inhibiting the AKT/mTOR signaling pathway and enhances the sensitivity of osteosarcoma cells to cisplatin, suggesting that cordycepin is a promising treatment for osteosarcoma.

Abstract Pancreatic cancer is an extremely malignant tumor with the lowest 5-year survival rate among all tumors. Pancreatic ductal adenocarcinoma (PDAC), as the most common pathological subtype of pancreatic cancer, usually has poor therapeutic results. Immune checkpoint inhibitors (ICIs) can relieve failure of the tumor-killing effect of immune effector cells caused by immune checkpoints. Therefore, they have been used as a novel treatment for many solid tumors. However, PDAC is not sensitive to monotherapy with ICIs, which might be related to the inhibitory immune microenvironment of pancreatic cancer. Therefore, the way to improve the microenvironment has raised a heated discussion in recent years. Here, we elaborate on the relationship between different immune cellular components in this environment, list some current preclinical or clinical attempts to enhance the efficacy of ICIs by targeting the inhibitory tumor microenvironment of PDAC or in combination with other therapies. Such information offers a better understanding of the sophisticated tumor-microenvironment interactions, also providing insights on therapeutic guidance of PDAC targeting. Video Abstract

Reducing lead (Pb) exposure via oral ingestion of contaminated soils is highly relevant for child health. Elevating dietary micronutrient iron (Fe) intake can reduce Pb oral bioavailability while being beneficial for child nutritional health. However, the practical performance of various Fe compounds was not assessed. Here, based on mouse bioassays, ten Fe compounds applied to diets (100–800 mg Fe kg−1) reduced Pb oral relative bioavailability (RBA) in two soils variedly depending on Fe forms. EDTA-FeNa was most efficient, which reduced Pb-RBA in a soil from 79.5 ± 14.7 % to 23.1 ± 2.72 % (71 % lower) at 100 mg Fe kg−1 in diet, more effective than other 9 compounds at equivalent or higher doses (3.6–68 % lower). When EDTA-FeNa, ferrous gluconate, ferric citrate, and ferrous bisglycinate were supplemented, Fe-Pb co-precipitation was not observed in the intestinal tract. EDTA-FeNa, ferrous gluconate, ferric citrate, and ferrous sulfate suppressed duodenal divalent metal transporter 1 (DMT1)mRNA relative expression similarly (27–68 % lower). In comparison, among ten compounds, EDTA-FeNa elevated Fe concentrations in mouse liver, kidney, and blood (1.50–2.69-fold higher) most efficiently, suggesting the most efficient Fe absorption that competed with Pb. In addition, EDTA was unique from other organic ligands, ingestion of which caused 12.0-fold higher Pb urinary excretion, decreasing Pb concentrations in mouse liver, kidney, and blood by 68–88 %. The two processes (Fe-Pb absorption competition and Pb urinary excretion with EDTA) interacted synergistically, leading to the lowest Pb absorption with EDTA-FeNa. The results provide evidence of a better inhibition of Pb absorption by EDTA-FeNa, highlighting that EDTA-FeNa may be the most appropriate supplement for intervention on human Pb exposure. Future researches are needed to assess the effectiveness of EDTA-FeNa for intervention on human Pb exposure.

Abstract Background To assess the utility of routine postoperative laboratory tests for patients undergoing high tibial osteotomy (HTO) surgery. Methods The associations between clinical risk factors and postoperative clinical treatment were analyzed. Additionally, a logistic regression analysis was performed to detect independent risk factors for patients requiring postoperative clinical treatment. Results A total of 482 patients with symptomatic isolated medial compartment osteoarthritis from January 2015 to May 2020 were included in the present study and underwent examination by the full set of postoperative laboratory tests within 3 days after HTO surgery. However, only a small proportion of the patients with anemia (3.9 %), hypoalbuminemia (4.1 %), and abnormal serum potassium levels (3.5 %) required clinical intervention after surgery. Binary logistic regression analysis showed that the body mass index (BMI), preoperative hemoglobin level, estimated blood loss and operative duration were independent risk factors for postoperative blood transfusion in patients who underwent HTO surgery, and factors associated with albumin supplementation were female sex and preoperative albumin level. In addition, these results indicated that preoperative potassium was potential risk factor for patients who required potassium supplementation postoperatively. Conclusions Based on the analysis, we conclude that routinely ordering postoperative laboratory tests after HTO surgery is unnecessary. However, for patients with identified risk factors, routine postoperative laboratory tests are still needed.

Abstract In this paper we investigate the model of the anti-de Sitter gravity coupled to a Maxwell field and a free, complex scalar field, and construct a fully back-reacted holographic model of superconductor with excited states. With the fixed charge q, there exist a series of excited states of holographic superconductor with the corresponding critical chemical potentials. The condensates as functions of the temperature for the two operators $${\mathcal {O}}_1$$ O 1 and $${\mathcal {O}}_2$$ O 2 of excited states are also studied. For the optical conductivity in the excited states, we find that there exist the additional peaks in the imaginary and real parts of the conductivity. Moreover, the number of peaks corresponding to n-th excited state is equal to n.

Summary: Background: Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents. The molecular mechanism behind OS progression and metastasis remains poorly understood, which limits the effectiveness of current therapies. RNA N6-methyladenosine (m6A) modification plays a critical role in influencing RNA fate. However, the biological significance of m6A modification and its potential regulatory mechanisms in the development of OS remain unclear. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS), dot blotting, and colorimetric ELISA were used to detect m6A levels. Western blotting, quantitative real-time PCR (RT-qPCR) and immunohistochemistry (IHC) were used to investigate METTL14 expression levels. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptomic RNA sequencing (RNA-seq) were used to screen the target genes of METTL14. RNA pull-down and RNA immunoprecipitation (RIP) assays were conducted to explore the specific binding of target genes and relevant m6A “readers”. RNA stability and polysome analysis assays were used to detect the half-lives and translation efficiencies of the downstream genes of METTL14. IHC and clinical data were applied to explore the clinical correlations of METTL14 and its downstream target genes with the prognosis of OS. Findings: We observed the abundance of m6A modifications in OS and revealed that METTL14 plays an oncogenic role in facilitating OS progression. MeRIP-seq and RNA-seq revealed that MN1 is a downstream gene of METTL14. MN1 contributes to tumor progression and all-trans-retinoic acid (ATRA) chemotherapy resistance in OS. Mechanistically, MN1 is methylated by METTL14, specifically in the coding sequence (CDS) regions, and this modification is recognized by the specific m6A reader insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) to prevent MN1 mRNA degradation and promote it translation efficiency. IHC showed that MN1 expression was positively correlated with METTL14 and IGF2BP2 expression in OS tissues. The METTL14-IGF2BP2-MN1 panel demonstrated more promising prognostic value for OS patients than any of these molecules individually. Interpretation: Our study revealed that METTL14 contributes to OS progression and ATRA resistance as an m6A RNA methylase by regulating the stability and translation efficiency of MN1 and thus provides both an underlying biomarker panel for prognosis prediction in OS patients. Funding: This work was supported by the National Natural Science Foundation of China (Grants 81972510 and 81772864).

Abstract In this paper, we consider rotating multistate boson stars with quartic self-interactions. In contrast to the nodeless quartic-boson stars in [1], the self-interacting multistate boson stars (SIMBSs) have two types of nodes, including the 1 S 2 S and 1 S 2 P states. We show the mass M of SIMBSs as a function of the synchronized frequency ω, and the nonsynchronized frequency ω 2 for three different cases. Moreover, for the case of two coexisting states with self-interacting potential, we study the mass M of SIMBSs versus the angular momentum J for the synchronized frequency ω and the nonsynchronized frequency ω 2. Furthermore, for three different cases, we analyze the coexisting phase with both the ground and first excited states for SIMBSs. We also calculate the maximum value of coupling parameter Λ, and find the coupling parameter Λ exists the finite range.

Timely flowering is a determinative trait for many economically valuable species in the Dendrobium genus of the Orchidaceae family, some of which are used for ornamental and medicinal purposes. D. nobile, a representative species of nobile-type Dendrobium, normally flowers in spring after exposure to sufficient low temperatures in winter. However, flowering can be stopped or disrupted by the untimely application of high temperatures. Little is known about the regulation and the mechanisms behind this switch. In this study, we report two isoforms from the KFK09_017173 locus of the D. nobile genome, named DnFCAγ and DnFCAβ, respectively, that cooperatively regulate flowering in D. nobile. These two isoforms are generated by alternative 3′ polyadenylation of DnFCA (FLOWERING CONTROL LOCUS C in D. nobile) pre-mRNA and contain a distinct 3′-terminus. Both can partially rescue late flowering in the Arabidopsis fca-1 mutant, while in wild-type Arabidopsis, they tend to delay the flowering time. When introduced into the detached axillary buds or young seedlings of D. nobile, both were able to induce the transcription of DnAGL19 (AGAMOUS LIKE 19 in D. nobile) in seedlings, whereas only DnFCAγ was able to suppress the transcription of DnAPL1 (AP1-LIKE 1 in D. nobile) in axillary buds. Furthermore, the time-course change of DnFCAγ accumulation was opposite to that of DnAPL1 in axillary buds, which was remarkable under low temperatures and within a short time after the application of high temperatures, supporting the suggestion that the expression of DnAPL1 can be inhibited by a high accumulation of DnFCAγ in floral buds. In leaves, the accumulation of DnFCAβ was in accordance with that of DnAGL19 and DnFT (FLOWERING LOCUS T in D. nobile) to a large extent, suggesting the activation of the DnAGL19–DnFT pathway by DnFCAβ. Taken together, these results suggest that the DnFCAγ–DnAPL1 pathway in axillary buds and the DnFCAβ–DnAGL19 pathway in the leaves cooperatively promote flowering under low temperatures. The long-term and constant, or untimely, application of high temperatures leads to the constitutive suppression of DnAPL1 by a high level of DnFCAγ in axillary buds, which consequently delays floral development.

Abstract Puerarin 6″‐O‐xyloside is a tumor suppressive derivate of Puerarin that is recently characterized as a lysine‐specific demethylase 6B inhibitor. Here we investigated the effects of Puerarin 6″‐O‐xyloside in hepatocellular carcinoma (HCC) cell lines SMMC‐7721 and HepG2. Cell viability, proliferation, stemness, protein expression, and autophagy were tested by CCK‐8, colony formation, sphere formation, western blotting, and LC3B GFP puncta per cell, respectively. Apoptosis, CD133‐positive cells, and JC‐1‐labeled mitochondrial membrane potential were measured by flow cytometry. The effects of Puerarin 6″‐O‐xyloside in vivo were explored in HepG2 xenograft mice. Puerarin 6″‐O‐xyloside inhibited cell viability, proliferation, and stemness, and promoted apoptosis in both SMMC‐7721 and HepG2 cells. Further experiments showed promoted autophagy and decreased mitochondrial membrane potential, and decreased expression of p‐PI3K, p‐AKT, and p‐mTOR in HepG2 cells. Co‐administration of 3‐MA with Puerarin 6″‐O‐xyloside obviously augmented these effects including inhibited protein expression of p‐PI3K, p‐AKT, and p‐mTOR, and inhibited proliferation, promoted apoptosis, and decreased stemness. In HepG2 xenograft mice, 100 mg/kg/d Puerarin 6″‐O‐xyloside significantly suppressed tumor growth, stemness, and apoptosis. In conclusion, our study indicated that Puerarin 6″‐O‐xyloside decreased cell viability, proliferation, and stemness, and promoted autophagy and mitochondria‐dependent apoptosis of HCC, at least partly through inhibiting PI3K/AKT/mTOR. These results highlighted Puerarin 6″‐O‐xyloside as a promising prodrug that could inhibit both PI3K/AKT/mTOR and epigenetic demethylation.

Abstract Motivated by the recent studies of the novel asymptotically global $$\hbox {AdS}_4$$ AdS4 black hole with deformed horizon, we consider the action of Einstein–Maxwell gravity in AdS spacetime and construct the charged deforming AdS black holes with differential boundary. In contrast to deforming black hole without charge, there exists at least one value of horizon for an arbitrary temperature. The extremum of temperature is determined by charge q and divides the range of temperature into several parts. Moreover, we use an isometric embedding in the three-dimensional space to investigate the horizon geometry. The entropy and quasinormal modes of deforming charged AdS black hole are also studied in this paper. Due to the existence of charge q, the phase diagram of entropy is more complicated. We consider two cases of solutions: (1) fixing the chemical potential $$\mu $$ μ ; (2) changing the value of $$\mu $$ μ according to the values of horizon radius and charge. In the first case, it is interesting to find there exist two families of black hole solutions with different horizon radii for a fixed temperature, but these two black holes have same horizon geometry and entropy. The second case ensures that deforming charged AdS black hole solutions can reduce to standard RN–AdS black holes.

Abstract We construct a class of counterexamples to cosmic censorship in four dimensional Einstein–Born–Infeld theory with asymptotically anti-de Sitter boundary conditions, and investigate the effect of the Born–Infeld parameter b in comparison with the counterpart of Einstein–Maxwell theory. When a charged massive scalar field is included into the action, we find that this class of counterexamples to cosmic censorship would be removed if the charge of scalar fields is above the bound of charge $$q_{w}$$ qw . In particular, the bound of charge required to preserve cosmic censorship increases with the increasing of Born–Infeld parameter. Meanwhile, we also show the lower bounds on charge-to-mass ratio with the different values of Born–Infeld parameter.

Oral bioavailability of arsenic (As) determines levels of As exposure via ingestion of As-contaminated soil, however, the role of gut microbiota in As bioavailability has not evaluated in vivo although some in vitro studies have investigated this. Here, we made a comparison in As relative bioavailability (RBA) estimates for a contaminated soil (3913 mg As kg−1) using a mouse model with and without penicillin perturbing gut microbiota and metabolites. Compared to soil exposure alone (2% w/w soil in diets), addition of penicillin (100 or 1000 mg kg−1) reduced probiotic Lactobacillus and sulfate-reducing bacteria Desulfovibrio, enriched penicillin-resistant Enterobacter and Bacteroides, and decreased amino acid concentrations in ileum. With perturbed gut microbiota and metabolic profile, penicillin and soil co-exposed mice accumulated 2.81–3.81-fold less As in kidneys, excreted 1.02–1.35-fold less As in urine, and showed lower As-RBA (25.7–29.0%) compared to mice receiving diets amended with soil alone (56 ± 9.63%). One mechanism accounted for this is the decreased concentrations of amino acids arising from the gut microbiota shift which resulted in elevated iron (Fe) and As co-precipitation, leading to reduced As solubilization in the intestine. Another mechanism was conversion of bioavailable inorganic As to less bioavailable monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV) by the antibiotic perturbed microflora. Based on in vivo mouse model, we demonstrated the important role of gut microbiota and gut metabolites in participating soil As solubilization and speciation transformation then affecting As oral bioavailability. Results are useful to better understand the role of gut bacteria in affecting As metabolism and the health risks of As-contaminated soils.

Abstract Motivated by the novel asymptotically global AdS4 solutions with deforming horizon in [21], we analyze the boundary metric with even multipolar differential rotation and numerically construct a family of deforming solutions with quadrupolar differential rotation boundary, including two classes of solutions: solitons and black holes. In contrast o solutions with dipolar differential rotation boundary, we find that even though the norm of Killing vector ∂ t becomes spacelike for certain regions of polar angle θ when ε > 2, solitons and black holes with quadrupolar differential rotation still exist and do not develop hair due to superradiance. Moreover, at the same temperature, the horizonal deformation of quadrupolar rotation is smaller than that of dipolar rotation. Furthermore, we also study the entropy and quasinormal modes of the solutions, which have the analogous properties to that of dipolar rotation.

Xinjiang brown cattle have better meat quality than Kazakh cattle. Circular RNAs (circRNAs) are a type of RNA that can participate in the regulation of gene transcription. Whether circRNAs are differentially expressed in the longissimus dorsi between these two types of cattle and whether differentially expressed circRNAs regulate muscle formation and differentiation are still unknown. In this study, we established two RNA-seq libraries, each of which consisted of three samples. A total of 5,177 circRNAs were identified in longissimus dorsi samples from Kazakh cattle and Xinjiang brown cattle using the Illumina platform, 46 of which were differentially expressed. Fifty-five Gene Ontology terms were significantly enriched, and 12 Kyoto Encyclopedia of Genes and Genomes pathways were identified for the differentially expressed genes. Muscle biological processes were associated with the origin genes of the differentially expressed circRNAs. In addition, we randomly selected six overexpressed circRNAs and compared their levels in longissimus dorsi tissue from Kazakh cattle and Xinjiang brown cattle using RT-qPCR. Furthermore, we predicted 66 interactions among 65 circRNAs and 14 miRNAs using miRanda and established a coexpression network. A few microRNAs known for their involvement in myoblast regulation, such as miR-133b and miR-664a, were identified in this network. Notably, bta_circ_03789_1 and bta_circ_05453_1 are potential miRNA sponges that may regulate insulin-like growth factor 1 receptor expression. These findings provide an important reference for prospective investigations of the role of circRNA in longissimus muscle growth and development. This study provides a theoretical basis for targeting circRNAs to improve beef quality and taste.

Small heat shock proteins (sHsps) function in the response of insects to abiotic stress; however, their role in response to biotic stress has been under-investigated. Mythimna separata, the oriental armyworm, is polyphenetic and exhibits gregarious and solitary phases in response to high and low population density, respectively. In this study, three genes were identified encoding sHsps, namely MsHsp19.7, MsHsp19.8 and MsHsp21.4, and expression levels in solitary and gregarious M. separata were compared. The deduced protein sequences of the three MsHsps had molecular weights of 19.7, 19.8 and 21.4 kDa, respectively, and contained a conserved α-crystalline domain. Real-time PCR analyses revealed that the three sHsps were transcribed in all developmental stages and were dramatically up-regulated at the 6th larval stage in gregarious individuals. Expression of the three MsHsps was variable in different tissues of 6th instar larvae, but exhibited consistent up- and down-regulation in the hindgut and Malpighian tubules of gregarious individuals, respectively. In addition, MsHsp19.7 and MsHsp19.8 were significantly induced when solitary forms were subjected to crowding for 36 h, but all three MsHsps were down-regulated when gregarious forms were isolated. Our findings suggest that population density functions as a stress factor and impacts MsHsps expression in M. separata.

The robustness of in vitro bioaccessibility assays to predict oral relative bioavailability (RBA) of multiple metals in contaminated soils requires validation using additional soil samples. In this study, 11 contaminated soils from mining/smelting areas were analyzed for As-, Cd-, and Pb-RBA using a mouse bioassay and metal bioaccessibility via the UBM gastric phase assay. Metal-RBA varied considerably among soils, with As-RBA (2.5–23%, mean 12%) being generally lower than Cd-and Pb-RBA (3.4–88 and 3.3–59%, mean 42 and 28%), due to higher proportions of As in the residual fractions. Metal-RBA generally decreased with increasing metal concentrations probably due to reduced labile metal fractions. In addition, strong negative correlations were observed between total Fe with As-, Cd-, and Pb-RBA (R2 = 0.46–0.77), suggesting the role of Fe in controlling metal-RBA in soils. Like RBA, metal bioaccessibility by the UBM assay also varied among samples. However, strong in vivo-in vitro correlations (IVIVCs) were observed between metal-RBA and bioaccessibility (R2 = 0.52–0.81). Further, there were little differences when As-, Cd-, and Pb-IVIVCs established using soils from this study and soils pooled from literature were compared, suggesting the robustness of the UBM assay to predict metal-RBA in contaminated soils. Keywords: Heavy metals, Mouse model, Bioavailability, In vitro assay, Bioaccessibility

Antennas operating in the high-frequency (HF) bands are generally relatively large in size, which severely limits the application of the antennas. Therefore, miniaturisation of the antenna is necessary. Here, a dual-folded structure Yagi antenna is designed for HF surface wave radar (SWR). Genetic algorithm is employed to optimise and balance the antenna size and performance. At the same operating frequency, the optimised antenna size is much smaller than the traditional Yagi antenna size and can meet the performance requirements of HF surface wave radar transmitting antenna.

Assessment of variety distinctness is important for both the registration and the protection of particular variety. However, the current testing system, which assesses a range of morphological characters of each pair of varieties grown side-by-side, is time-consuming and is not suitable for the assessment of hundreds of samples. The objective of this study was to develop a procedure for the assessment of wheat variety distinctness using simple sequence repeat (SSR) markers. A comparison between the molecular and morphological profile of 797 varieties was made. On the basis of the comparison, pairs of varieties with a genetic similarity value (GSV) ≤90% were deemed to be distinct, accounting for ∼85% of varieties assessed in wheat regional trials. For the remaining ∼15% of varieties, GSVs between different varieties were >90%, among which ∼35% were not distinct and the other ∼65% were distinct. Therefore, if given a GSV>90%, the pairs of varieties should be morphologically assessed in the field. To avoid any errors in the assessments, we proposed the elimination of contaminant plants from the sample before comparing the varietal genotypes, scoring of the genotype at each locus with a pair of allele numbers when constructing a molecular profile, and faithfully recording two alleles at a non-homozygous locus. To reduce the workload and cost, a three-grade markers comparison among varieties is suggested. In addition, 80 SSR markers and a technical procedure for assessment of wheat variety distinctness have been proposed. Based on the procedure, the distinctness assessment of ∼85% of all wheat varieties is completed in our laboratory annually. Consequently, total field assessment has been reduced considerably.

The oriental armyworm, Mythimna separata, is a major insect pest in China and other Asian countries. Unfortunately, suitable reference genes for quantitative real-time PCR (qRT-PCR) have not been previously identified in M. separata for normalizing target gene expression. In this study, we evaluated the expression stability of eight candidate genes (18S, ACT, EF1-α, GAPDH, RPS7, RPS13, RPL32 and TUB) in M. separata using the comparative ΔCt method, BestKeeper, Normfinder geNorm and ReFinder, a comprehensive software platform. The results indicated that the appropriate reference gene varied depending on the experimental conditions. We found that ACTIN, EF1-α and TUB were optimal for different developmental stages; TUB, RPS13 and EF1-α showed the most stable expresssion in different tissues; RPS13 and 18S were the best reference genes for monitoring expression under high temperature conditions; TUB, RPS13 and RPS7 exhibited the most stable expression under larval-crowding conditions; RPS7, EF1-α, RPL32 and GAPDH were the best for pesticide exposure experiments. This study provides tools for reliable normalization of qRT-PCR data and forms a foundation for functional studies of target gene expression in M. separata.

In this study, we examined the role of mRNAs and miRNAs in variations in intramuscular fat content in the longissimus dorsi muscle in Xinjiang brown cattle. Two groups of Xinjiang brown cattle with extremely different intramuscular fat content in the longissimus dorsi were selected for combined of miRNA and mRNA analysis using an RNA-Seq. In total, 296 mRNAs and 362 miRNAs were significantly differentially expressed, including 155 newly predicted miRNAs, 275 significantly upregulated genes, 252 significantly upregulated miRNAs, 21 significantly downregulated genes and 110 significantly downregulated miRNAs. The combined miRNA and mRNA analysis identified 96 differentially expressed miRNAs and 27 differentially expressed mRNAs. In all, 47 upregulated miRNAs had a regulatory effect on 14 differentially downregulated target genes, and 49 downregulated miRNAs had a regulatory effect on 13 upregulated target genes. To verify the sequencing results, 10 differentially expressed genes (DEGs) and 10 differentially expressed miRNAs were selected for qRT-PCR. The qRT-PCR results confirmed the sequencing results. The results of this study shed light on the molecular regulation of bovine adipose tissue, which might help with the development of new strategies for improving meat quality and animal productivity in beef cattle to provide healthier meat products for consumers.

Quantitative real time PCR (qRT-PCR) has emerged as a reliable and reproducible technique for studying gene expression analysis. For accurate results, the normalization of data with reference genes is particularly essential. Once the transcriptome sequencing of Frankliniella occidentalis was completed, numerous unigenes were identified and annotated. Unfortunately, there are no studies on the stability of reference genes used in F. occidentalis. In this work, seven candidate reference genes, including actin, 18S rRNA, H3, tubulin, GAPDH, EF-1 and RPL32, were evaluated for their suitability as normalization genes under different experimental conditions using the statistical software programs BestKeeper, geNorm, Normfinder and the comparative ΔCt method. Because the rankings of the reference genes provided by each of the four programs were different, we chose a user-friendly web-based comprehensive tool RefFinder to get the final ranking. The result demonstrated that EF-1 and RPL32 displayed the most stable expression in different developmental stages; RPL32 and GAPDH showed the most stable expression at high temperatures, while 18S and EF-1 exhibited the most stable expression at low temperatures. In this study, we validated the suitable reference genes in F. occidentalis for gene expression profiling under different experimental conditions. The choice of internal standard is very important in the normalization of the target gene expression levels, thus validating and selecting the best genes will help improve the quality of gene expression data of F. occidentalis. What is more, these validated reference genes could serve as the basis for the selection of candidate reference genes in other insects.

BACKGROUND:Accurate prognostication of locally advanced nasopharyngeal carcinoma (NPC) will benefit patients for tailored therapy. Here, we addressed this issue by developing a mathematical algorithm based on support vector machine (SVM) through integrating the expression levels of multi-biomarkers. METHODOLOGY/PRINCIPAL FINDINGS:Ninety-seven locally advanced NPC patients in a randomized controlled trial (RCT), consisting of 48 cases serving as training set and 49 cases as testing set of SVM models, with 5-year follow-up were studied. We designed SVM models by selecting the variables from 38 tissue molecular biomarkers, which represent 6 tumorigenesis signaling pathways, and 3 EBV-related serological biomarkers. We designed 3 SVM models to refine prognosis of NPC with 5-year follow-up. The SVM1 displayed highly predictive sensitivity (sensitivity, specificity were 88.0% and 81.9%, respectively) by integrating the expression of 7 molecular biomarkers. The SVM2 model showed highly predictive specificity (sensitivity, specificity were 84.0% and 94.5%, respectively) by grouping the expression level of 12 molecular biomarkers and 3 EBV-related serological biomarkers. The SVM3 model, constructed by combination SVM1 with SVM2, displayed a high predictive capacity (sensitivity, specificity were 88.0% and 90.3%, respectively). We found that 3 SVM models had strong power in classification of prognosis. Moreover, Cox multivariate regression analysis confirmed these 3 SVM models were all the significant independent prognostic model for overall survival in testing set and overall patients. CONCLUSIONS/SIGNIFICANCE:Our SVM prognostic models designed in the RCT displayed strong power in refining patient prognosis for locally advanced NPC, potentially directing future target therapy against the related signaling pathways.

BACKGROUND: Microbubbles (MBs) can serve as an ultrasound contrast agent, and has the potential for magnetic resonance imaging (MRI). Due to the relatively low effect of MBs on MRI, it is necessary to develop new MBs that are more suitable for MRI. In this study, we evaluate the properties of SonoVue® and custom-made Fe(3)O(4)-nanoparticle-embedded microbubbles (Fe(3)O(4)-MBs) in terms of contrast agents for ultrsonography (US) and MRI. METHODOLOGY/PRINCIPAL FINDINGS: A total of 20 HepG2 subcutaneous-tumor-bearing nude mice were randomly assigned to 2 groups (i.e., n = 10 mice each group), one for US test and the other for MRI test. Within each group, two tests were performed for each mouse. The contrast agent for the first test is SonoVue®, and the second is Fe(3)O(4)-MBs. US was performed using a Technos(MPX) US system (Esaote, Italy) with a contrast-tuned imaging (CnTI™) mode. MRI was performed using a 7.0T Micro-MRI (PharmaScan, Bruker Biospin GmbH, Germany) with an EPI-T(2)* sequence. The data of signal-to-noise ratio (SNR) from the region-of-interest of each US and MR image was calculated by ImageJ (National Institute of Health, USA). In group 1, enhancement of SonoVue® was significantly higher than Fe(3)O(4)-MBs on US (P0.05). The SNR analysis of the enhancement process reveals a strong negative correlation in both cases (i.e., SonoVue® r = -0.733, Fe(3)O(4)-MBs r = -0.903, with P

Background: Mesenchymal stem cells (MSCs) are considered a promising therapeutic strategy for rheumatoid arthritis (RA), but the current clinical results are varied. This study is to analyze the therapeutic effect of cell-based strategies on RA. Materials and Methods: The searches were performed with public databases from inception to June 17, 2021. Randomized controlled trials researching cell-based therapies in RA patients were included. Results: Eight studies, including 480 patients, were included in the analysis. The results showed that compared to the control, MSC treatment significantly reduced the disease activity score (DAS) at the second standardized mean difference (SMD): -0.70; 95% confidence interval (CI): -1.25, -0.15; P = 0.01) and 3rd month (SMD: -1.47; 95% CI: -2.77, -0.18; P < 0.01) and significantly reduced the rheumatoid factor (RF) level at the first (SMD: -0.38; 95% CI: -0.72, -0.05; P = 0.03) and 6th months (SMD: -0.81; 95% CI: -1.32, -0.31; P < 0.01). In the network meta-analysis, MSCs combined with interferon-γ (MSC_IFN) had a significant effect on increasing the American college of rheumatology criteria (ACR) 20, ACR50, and DAS <3.2 populations, had a significant effect on reducing the DAS, and decreased the RF level for a long period. Conclusion: MSCs could relieve the DAS of RA patients in the short term and reduce the level of RF. MSC_IFN showed a more obvious effect, which could significantly improve the results of ACR20, ACR50, and DAS <3.2 and reduce the DAS and RF levels. [ABSTRACT FROM AUTHOR]