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Abstract Nontransformed cells form heterotypic cadherin junctions with adjacent transformed cells to inhibit tumor cell growth and motility. Transformed cells must override this form of growth control, called “contact normalization”, to invade and metastasize during cancer progression. Heterocellular cadherin junctions between transformed and nontransformed cells are needed for this process. However, specific mechanisms downstream of cadherin signaling have not been clearly elucidated. Here, we utilized a β-catenin reporter construct to determine if contact normalization affects Wnt signaling in transformed cells. β-catenin driven GFP expression in Src transformed mouse embryonic cells was decreased when cultured with cadherin competent nontransformed cells compared to transformed cells cultured with themselves, but not when cultured with cadherin deficient nontransformed cells. We also utilized a layered culture system to investigate the effects of oncogenic transformation and contact normalization on gene expression and oncogenic Src kinase mediated phosphorylation events. RNA-Seq analysis found that cadherin dependent contact normalization inhibited the expression of 22 transcripts that were induced by Src transformation, and increased the expression of 78 transcripts that were suppressed by Src transformation. Phosphoproteomic analysis of cells expressing a temperature sensitive Src kinase construct found that contact normalization decreased phosphorylation of 10 proteins on tyrosine residues that were phosphorylated within 1 h of Src kinase activation in transformed cells. Taken together, these results indicate that cadherin dependent contact normalization inhibits Wnt signaling to regulate oncogenic kinase activity and gene expression, particularly PDPN expression, in transformed cells in order to control tumor progression.

Abstract Luminescent materials that simultaneously embody bright singlet and triplet excitons hold great potential in optoelectronics, signage, and information encryption. However, achieving high-performance white-light emission is severely hampered by their inherent unbalanced contribution of fluorescence and phosphorescence. Herein, we address this challenge by pressure treatment engineering via the hydrogen bonding cooperativity effect to realize the mixture of n–π*/π–π* transitions, where the triplet state emission was boosted from 7% to 40% in isophthalic acid (IPA). A superior white-light emission based on hybrid fluorescence and phosphorescence was harvested in pressure-treated IPA, and the photoluminescence quantum yield was increased to 75% from the initial 19% (blue-light emission). In-situ high-pressure IR spectra, X-ray diffraction, and neutron diffraction reveal continuous strengthening of the hydrogen bonds with the increase of pressure. Furthermore, this enhanced hydrogen bond is retained down to the ambient conditions after pressure treatment, awarding the targeted IPA efficient intersystem crossing for balanced singlet/triplet excitons population and resulting in efficient white-light emission. This work not only proposes a route for brightening triplet states in organic small molecules, but also regulates the ratio of singlet and triplet excitons to construct high-performance white-light emission.

Abstract This study aims to illustrate epidemiology of comorbid CVD in the real-world clinical setting of patients with psoriasis in China. We used data of adult patients with psoriasis who were registered in the register of China National Clinical Center for Skin and Immune Diseases between August 2020 and September 2021. Psoriasis was clinically diagnosed following the national guidelines. Univariate and multivariate logistic regression models were used to examine the factors associated with comorbid CVD in patients with psoriasis. Of the 11,560 psoriasis patients (age ≥ 18 years, mean age 41.87 years, 64.88% males), 236 were ascertained with CVD, with the overall prevalence being 2.62%. Multivariate logistic regression analysis suggested that the odds ratio (95% confidence interval) of CVD in psoriasis patients was 2.27 (2.03–2.54) for older age (per 10-year increment), 0.65 (0.48–0.90) for female, 2.07 (1.39–3.06) for obesity (BMI ≥ 28 vs.

Abstract Objectives To investigate the effect of neutral 10-methacryloyloxydecyl dihydrogen phosphate salt (MDP-Na) on the dentin bond strength and remineralization potential of etch-&-rinse adhesive. Methods Two experimental etch-&-rinse adhesives were formulated by incorporating 0 wt% (E0) or 20 wt% (E20) neutral MDP-Na into a basic primer. A commercial adhesive, Adper Single Bond 2 (SB, 3 M ESPE), served as the control. Sixty prepared teeth were randomly allocated into three groups (n = 20) and bonded using either one of the experimental adhesives or SB. Following 24 h of water storage, the bonded specimens were sectioned into resin-dentin sticks, with four resin-dentin sticks obtained from each tooth for microtensile bond strength (MTBS) test. Half of the sticks from each group were immediately subjected to tensile loading using a microtensile tester at a crosshead speed of 1 mm/min, while the other half underwent tensile loading after 6-month incubation in artificial saliva (AS). The degree of conversion (DC) of both the control and experimental adhesives (n = 6 in each group) and the adsorption properties of MDP-Na on the dentin organic matrix (n = 5 in each group) were determined using Fourier-transform infrared spectrometry. Furthermore, the effectiveness of neutral MDP-Na in promoting the mineralization of two-dimensional collagen fibrils and the adhesive-dentin interface was explored using transmission electron microscopy and selected-area electron diffraction. Two- and one-way ANOVA was employed to assess the impact of adhesive type and water storage on dentin bond strength and the DC (α = 0.05). Results The addition of MDP-Na into the primer increased both the short- and long-term MTBS of the experimental adhesives (p = 0.00). No difference was noted in the DC between the control, E0 and E20 groups (p = 0.366). The MDP-Na remained absorbed on the demineralized dentin even after thorough rinsing. The intra- and extra-fibrillar mineralization of the two-dimensional collagen fibril and dentin bond hybrid layer was confirmed by transmission electron microscopy and selected-area electron diffraction when the primer was added with MDP-Na. Conclusions The use of neutral MDP-Na results in high-quality hybrid layer that increase the dentin bond strength of etch-&-rinse adhesive and provides the adhesive with remineralizing capability. This approach may represent a suitable bonding strategy for improving the dentin bond strength and durability of etch-&-rinse adhesive.

Background Vaccine hesitancy among young Chinese remains a challenge, contributing to low vaccination rates for the nonavalent Human Papillomavirus (HPV) vaccine. This study evaluated the knowledge and acceptance of this vaccine among students at a southern Chinese university and identified factors influencing these outcomes. Methods This cross-sectional, anonymous questionnaire survey was conducted from April to November 2023 at a multi-campus university in southern China. The questionnaire was comprised of three sections: the first collected demographic data; the second evaluated students’ knowledge of the nonavalent HPV vaccine on a scale from 0 to 15, with cut-off points at 5 and 10 delineating low, medium, and high knowledge levels, respectively; the third section assessed vaccine acceptance on a scale from 8 to 40, using scores above the 50th percentile as the benchmark for positive acceptance. Results Among the participants, 18% demonstrated low-level, 40.20% medium-level, and 41.70% high-level knowledge of the nonavalent HPV vaccine. Notably, 71.95% of respondents showed positive acceptance, whereas 28.05% expressed negative acceptance. Male students and those with lower economic conditions (monthly living expenses below 1000 RMB, P = 0.004; 1000-1499 RMB, P = 0.012) exhibited lower knowledge levels. As for acceptance, female students and those with higher monthly living expenses (1000-1499 RMB, P = 0.007; 1500-1999 RMB, P = 0.002; over 2000 RMB, P = 0.002) demonstrated greater vaccine acceptance. A positive correlation was noted between the level of knowledge and vaccine acceptance (r s = 0.256, P < 0.001). Conclusions Gender and economic status are significantly associated with nonavalent HPV vaccine knowledge and acceptance among university students. These findings highlight the potential impact of targeted educational initiatives, especially for economically disadvantaged male students, in enhancing vaccine uptake rates.

Chronic dermatitis is a disease with large unmet need for pharmacological improvement. Dermatitis conditions are maintained and exacerbated by various cytokine actions in the context of inflammation. Interleukin 6 signal transducer (Il6st), also known as glycoprotein 130 (Gp130), is a key component for surface reception of a multitude of cytokines and transduction and amplification of their pro-inflammatory signals. We hypothesized accordingly that pharmacological inhibition of Il6st can alter dermatitis pathology. Treatment with SC-144 and bazedoxifene, two representative small molecule Il6st inhibitors with different binding modes led to moderate but significant improvement of skin conditions in a 1-chloro-2,4-dinitrobenzene animal model. Part of cytokine expressions indicating the dermatological index were normalized particularly when treated with SC-144. Pruritic behaviors were blunted, also possibly giving limited contribution to disease improvement. In psoriatic skin and itch of an imiquimod animal model, those two treatments appeared to be relatively moderate. Collectively, pharmacological inhibition of Il6st seems to lessen pathological irritation. Inversely, this experimental attempt newly implies that Il6st participates in pathological mechanisms. In conclusion, we suggest Il6st as a novel target for improving dermatitis, and that agents with suitable efficacy and safety for its modulation are translatable.

In the present work, we evaluated the antifungal activities of two novel ebselen analogs, N-allyl-benzisoselenazol-3(2H)-one (N-allyl-bs) and N-3-methylbutylbenzisoselenazol-3(2H)-one (N-3mb-bs). Colorimetric and turbidity assays were performed to determine the minimum inhibitory concentration (MIC) of these compounds in S1 (fluconazole-sensitive) and S2 (fluconazole-resistant) strains of C. albicans. N-3mb-bs was more active than the N-allyl-bs compound. It is noteworthy that the concentration of N-3mb-bs observed to inhibit fungal growth by 50% (18.2 µM) was similar to the concentration observed to inhibit the activity of the yeast plasma membrane H+-ATPase (Pma1p) by 50% (19.6 µM). We next implemented a mouse model of vulvovaginal candidiasis (VVC) using the S1 strain and examined the mouse and yeast proteins present in the vaginal lavage fluid using proteomics. The yeast proteins detected were predominately glycolytic enzymes or virulence factors associated with C. albicans while the mouse proteins present in the lavage fluid included eosinophil peroxidase, desmocollin-1, and gasdermin-A. We then utilized the N-3mb-bs compound (12.5 mg/kg) in the mouse VVC model and observed that it significantly reduced the vaginal fungal burden, histopathological changes in vagina tissue, and expression of myeloperoxidase (MPO). All in all, the present work has identified a potentially promising drug candidate for VVC treatment.

Protective materials that can ensure the safety of personnel and equipment in extreme environments have a wide range of application prospects, such as outdoor protective clothing, fire-fighting clothing, etc. However, designing such highly functional materials is still considered a long-standing challenge. Herein, the superhydrophobic and oleophobic fibrous membranes (SOFM) prepared by electrospinning, heat treatment and spraying techniques, endowing the fibrous membranes with good thermal stability, air permeability and outstanding repellence to liquids such as water, oil and low surface energy solvents. The developed SOFM exhibits integrated properties with ethanol intrusion pressure of 0.75 KPa, excellent air permeability of 1.54 mm/s, water vapor transmission rate of 7.99 kg·m−2·d-1, high thermal decomposition temperature of 330 ℃, tensile strength of 9.2 MPa. Therefore, SOFM can effectively protect people and equipment in extreme environments. This work may contribute to the design of fiber materials with higher protection levels in the field of protective clothing.

The existing literature points towards the presence of robust mitochondrial mechanisms aimed at mitigating protein dyshomeostasis within the organelle. However, the precise molecular composition of these mechanisms remains unclear. Our data show that inorganic polyphosphate (polyP), a polymer well-conserved throughout evolution, is a component of these mechanisms. In mammals, mitochondria exhibit a significant abundance of polyP, and both our research and that of others have already highlighted its potent regulatory effect on bioenergetics. Given the intimate connection between energy metabolism and protein homeostasis, the involvement of polyP in proteostasis has also been demonstrated in several organisms. For example, polyP is a bacterial primordial chaperone, and its role in amyloidogenesis has already been established. Here, using mammalian models, our study reveals that the depletion of mitochondrial polyP leads to increased protein aggregation within the organelle, following stress exposure. Furthermore, mitochondrial polyP is able to bind to proteins, and these proteins differ under control and stress conditions. The depletion of mitochondrial polyP significantly affects the proteome under both control and stress conditions, while also exerting regulatory control over gene expression. Our findings suggest that mitochondrial polyP is a previously unrecognized, and potent component of mitochondrial proteostasis.

Abstract Purpose Since the unexplained in vitro fertilization failure occurs frequently, it is of great importance and clinical value to identify potential underlying predictors. This study aimed to explore whether the percentage of sperm with a small acrosome was correlated with unexplained in vitro fertilization failure. Methods A new acrosomal function evaluation index (the percentage of sperm with a small acrosome) was introduced into the analysis of sperm morphology. The association between the index and acrosome function by acrosin activity detection test and acrosome reaction test was investigated. In addition, the correlation with unexplained in vitro fertilization failure was further explored. Finally, the ROC curve was used to analyze the diagnostic efficacy on the failure of in vitro fertilization and the cutoff value was calculated. Results As the increasing of the percentage of sperm with a small acrosome, the value of acrosin activity, acrosome reaction rate, and in vitro fertilization rate were reduced, with a statistically significant difference (P

Abstract Background To demonstrate bioequivalence between two drug formulations, a pilot trial is often conducted prior to a pivotal trial to assess feasibility and gain preliminary information about the treatment effect. Due to the limited sample size, it is not recommended to perform significance tests at the conventional 5% level using pilot data to determine if a pivotal trial should take place. Whilst some authors suggest to relax the significance level, a Bayesian framework provides an alternative for informing the decision-making. Moreover, a Bayesian approach also readily permits possible incorporation of pilot data in priors for the parameters that underpin the pivotal trial. Methods We consider two-sequence, two-period crossover designs that compare test (T) and reference (R) treatments. We propose a robust Bayesian hierarchical model, embedded with a scaling factor, to elicit a Go/No-Go decision using predictive probabilities. Following a Go decision, the final analysis to formally establish bioequivalence can leverage both the pilot and pivotal trial data jointly. A simulation study is performed to evaluate trial operating characteristics. Results Compared with conventional procedures, our proposed method improves the decision-making to correctly allocate a Go decision in scenarios of bioequivalence. By choosing an appropriate threshold, the probability of correctly (incorrectly) making a No-Go (Go) decision can be ensured at a desired target level. Using both pilot and pivotal trial data in the final analysis can result in a higher chance of declaring bioequivalence. The false positive rate can be maintained in situations when T and R are not bioequivalent. Conclusions The proposed methodology is novel and effective in different stages of bioequivalence assessment. It can greatly enhance the decision-making process in bioequivalence trials, particularly in situations with a small sample size.

Solid-state batteries are rising rapidly in response to the fast-increasing energy demand. Metal-organic framework (MOF) loaded with ionic liquids has brought new opportunities for solid-state batteries owing to its good interfacial compatibility and high ionic conductivity. MOF-808 is selected to be filled with Li-contained ionic liquid for structure and ion dynamics investigation using nuclear magnetic resonance (NMR) and X-ray diffraction. This study finds that the introduced ionic liquid would partially soften the matrix of MOF-808 and thus yield amorphous phase. By selective isotope replacement under cycling symmetric 6Li metal cell, Li+ ion is observed to mainly go cross ionic liquid in the open channel of matrix under potential polarization.

The function of peripheral nociceptors, the neurons that relay pain signals to the brain, are frequently tuned by local and systemic modulator substances. In this context, neurohormonal effects are emerging as an important modulatory mechanism, but many aspects remain to be elucidated. Here we report that gonadotropin-releasing hormone (GnRH), a brain-specific neurohormone, can aggravate pain by acting on nociceptors in mice. GnRH and GnRHR, the receptor for GnRH, are expressed in a nociceptor subpopulation. Administration of GnRH and its analogue, localized for selectively affecting the peripheral neurons, deteriorated mechanical pain, which was reproducible in neuropathic conditions. Nociceptor function was promoted by GnRH treatment in vitro, which appears to involve specific sensory transient receptor potential ion channels. These data suggest that peripheral GnRH can positively modulate nociceptor activities in its receptor-specific manner, contributing to pain exacerbation. Our study indicates that GnRH plays an important role in neurohormonal pain modulation via a peripheral mechanism.

The uncontrolled bacterial infection-induced cytokine storm and sequential immunosuppression are commonly observed in septic patients, which indicates that the activation of phagocytic cells and the efficient and timely elimination of bacteria are crucial for combating bacterial infections. However, the role of dysregulated immune cells and their disrupted function in sepsis remains unclear. Here, we found that macrophages exhibited the impaired endocytosis capabilities in sepsis by Single-cell RNA sequencing and bulk RNA sequencing. Caveolae protein Caveolin-1 (Cav-1) of macrophages was inactivated by SHP2 rapidly during Escherichia coli (E.coli) infection. Allosteric inhibitor of SHP2 effectively maintains Cav-1 phosphorylation to enhance macrophage to endocytose and eliminate bacteria. Additionally, TLR4 endocytosis of macrophage was also enhanced upon E.coli infection by SHP099, inducing an increased and rapidly resolved inflammatory response. In vivo, pretreatment or posttreatment with inhibitor of SHP2 significantly reduced the bacterial burden in organs and mortality of mice subjected E.coli infection or CLP-induced sepsis. The cotreatment of inhibitor of SHP2 with an antibiotic conferred complete protection against mortality in mice. Our findings suggest that Cav-1-mediated endocytosis and bacterial elimination may play a critical role in the pathogenesis of sepsis, highlighting inhibitor of SHP2 as a potential therapeutic agent for sepsis.

Hepatocellular carcinoma (HCC) is one of the deadliest forms of cancer, but the drugs currently used for its treatment are less than ideal. Tilapia oligopeptides have a wide range of biological activities and are potential sources of new drugs. In this study, the role and mechanism of TBP-1 (Ser-Val-Val-Ala-Ile), an oligopeptide from tilapia, on inflammation and endothelial-mesenchymal transition (EMT) in HCC was investigated using the LPS-induced RAW264.7 inflammation model and the transforming growth factor (TGF)-β1-induced HCC EMT model. The results showed that TBP-1 could effectively inhibit inflammatory response. Moreover, in TGF-β1-induced human hepatocellular carcinoma (HepG2) cells, 100 μM TBP-1 significantly reduced the secretion of N-cadherin (54.2 ± 10.6 %), Vimentin (47.0 ± 9.4 %) and Snail (76.0 ± 9.0 %), increased the secretion of E-cadherin (56.0 ± 16.3 %), inhibited cell metastasis, and participated in the regulatory mechanisms of TGF-β/Smad and non-TGF-β/Smad mediated EMT. TBP-1 may be a potentially valuable inhibitor of HCC.

Croton oil is liquid at room temperature, with a pale-yellow color and spicy odor. It is commonly used in combination with phenol as a chemical peeling agent in dermatology, which reveals its caustic exfoliating effects. Topical use of croton oil at a high dose produces skin irritation, inflammation, swelling, pain, and even tumors. Therefore, croton oil has been widely used for inflammation, pain, and tumor related research, with different animal models having been established. However, mechanistic studies through which croton oil induces skin swelling, injury and activates tissue repair/regeneration are limited. The present study used croton oil to induce mouse ear edema and examined tissue responses 4 h after exposure. To this end, croton oil was applied to the ventral side of mouse ears, followed by tissue collection. Samples were analyzed by hematoxylin and eosin (H&E) staining, toluidine blue staining, and immunohistochemistry staining for myeloperoxidase (MPO) and matrix metalloproteinase-9 (MMP-9). Western blotting and ELISA were also carried out for MMP-9 together with unbiased proteomic analysis using mass-spectrometry. Results from our study demonstrated that as soon as 4 h of exposure to 2.5 % croton oil, the expression levels of MPO and MMP-9 in the dermis significantly increased compared to acetone-treated (vehicle) control ears, as did other inflammatory reactions such as swelling and neutrophil aggregation and infiltration. Subsequently, proteomic analysis confirmed that croton oil treatment resulted in significant upregulation of proteins such as myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9), and matrix metalloproteinase-8 (MMP-8) in the ear skin. Interestingly, mouse ears treated with acetone vehicle showed differential expression of 2,478 proteins relative to naïve tissues; among those differentially expressed in acetone-treated samples were members of the phosphatidylinositol-glycan biosynthesis class N, T and U proteins (PIGN, PIGT, and PIGU). Overall, this work confirms the presence of neutrophil-derived MPO and MMP-9 and extends the body of knowledge to show that MMP-8 is also present during croton oil-mediated skin inflammation in the mouse ear; moreover, we find that acetone vehicle is not inert and has effects on the skin that should be considered moving forward.

Abstract The incidence of lung cancer (LC) in chronic obstructive pulmonary disease (COPD) patients is dozens of times higher than that in patients without COPD. Elevated activity of nuclear factor-k-gene binding (NF-κB) was found in lung tissue of patients with COPD, and the continuous activation of NF-κB is observed in both malignant transformation and tumor progression of LC, suggesting that NF-κB and its regulators may play a key role in the progression of LC in COPD patients. Here, we report for the first time that a key long non-coding RNA (lncRNA)-ICL involved in the regulation of NF-κB activity in LC tissues of COPD patients. The analyses showed that the expression of ICL significantly decreased in LC tissues of LC patients with COPD than that in LC tissues of LC patients without COPD. Functional experiments in vitro showed that exogenous ICL only significantly inhibited the proliferation, invasion and migration in primary tumor cells of LC patients with COPD compared to LC patients without COPD. Mechanism studies have shown that ICL could suppress the activation of NF-κB by blocking the hsa-miR19-3p/NKRF/NF-κB pathway as a microRNA sponge. Furthermore, In vivo experiments showed that exogenous ICL effectively inhibited the growth of patient-derived subcutaneous tumor xenografts (PDX) of LC patients with COPD and significantly prolonged the survival time of tumor-bearing mice. In a word, our study shows that the decrease of ICL is associated with an increased risk of LC in patients with COPD, ICL is not only expected to be a new therapeutic target for LC in COPD patients, but also has great potential to be used as a new marker for evaluating the occurrence, severity stratification and prognosis of LC in patients with COPD.

Raw material with a high Al2O3 content has led to an increase in the Al2O3 content in blast furnace slag, which has affected the normal operation of a blast furnace. The exergy analysis method is an important method for studying the energy utilization of high-alumina blast furnace smelting. In this paper, to investigate the impact of slag composition on exergy efficiency and optimize exergy efficiency during the smelting process of high Al2O3 iron ore, a gray box exergy analysis model of blast furnace smelting and an objective function for minimizing the total exergy loss were developed. The results indicated that the blast furnace smelting process had an exergy efficiency (η) of 28.29% for hot metal and slag; the exergy efficiency of the blast furnace did not significantly increase with the increasing w(MgO)/w(Al2O3) and R (w(CaO)/w(SiO2)), but the exergy efficiency of the blast furnace declined with increasing w(Al2O3). The regional optimal solution for the objective function method was 7129.42 MJ with slag compositions of R = 1.295, w(MgO)/w(Al2O3) = 0.545, and w(Al2O3) = 15%.

Topochemical reactions are a promising method to obtain crystalline polymeric materials with distance-determined regio- or stereoselectivity. It has been concluded on an empirical basis that the closest intermolecular C⋯C distance in crystals of alkynes, d(C⋯C)min, should reach a threshold of ∼3 Å for bonding to occur at room temperature. To understand this empirical threshold, we study here the polymerization of acetylene in the crystalline state under high pressure by calculating the structural geometry, vibrational modes, and reaction profile. We find d(C⋯C)min to be the sum of an intrinsic threshold of 2.3 Å and a thermal displacement of 0.8 Å (at room temperature). Molecules at the empirical threshold move via several phonon modes to reach the intrinsic threshold, at which the intermolecular electronic interaction is sharply enhanced and bonding commences. A distance–vibration-based reaction picture is thus demonstrated, which provides a basis for the prediction and design of topochemical reactions, as well as an enhanced understanding of the bonding process in solids.

As previously demonstrated, serum beta-human chorionic gonadotropin (β-hCG) is linked to identifying early gestational abnormalities. This research was aimed at investigating the correlation between serum β-hCG levels and thyroid metabolic function in pregnant women with hyperemesis gravidarum (HG). Ninety-one pregnant women with HG were selected as the study group and divided into early pregnancy (EP), mid-pregnancy (MP), and late pregnancy (LP) groups according to their gestational weeks, while 84 normal pregnant women were selected as the control group. Venous blood was collected from pregnant women in both groups and serum β-hCG levels were measured by chemiluminescent immunoassay. The levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), thyroid-stimulating hormone receptor antibody (TRAb), and thyroglobulin antibody (TgAb) were tested by chemiluminescent microparticle immunoassay. Visual analog scale (VAS) scores were utilized to assess the degree of HG. Pearson analysis was implemented to measure the correlations between serum β-hCG levels and serum FT3, FT4, TSH, TPOAb, TRAb, TgAb, as well as VAS scores and the correlations between β-hCG, FT3, FT4, TSH, TPOAb, TRAb, TgAb, as well as VAS scores and gestation period. The receiver operating characteristic (ROC) curve was plotted to analyze the diagnostic values of thyroid hormones, thyroid-related antibodies, and β-hCG levels for HG. Versus those in the control group, β-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores were higher and TSH levels were lower in the study group. Versus those in the EP group, β-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores of pregnant women in the MP and LP groups were decreased, and TSH levels were increased. Serum β-hCG levels of pregnant women with HG were positively correlated with FT3, FT4, TPOAb, TRAb, TgAb, and VAS scores and negatively correlated with TSH levels. Serum β-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores of pregnant women with HG had a negative correlation with the gestation period, while TSH levels had a positive correlation with the gestation period. The ROC curve analysis showed that β-hCG and thyroid function-related indicators were of high clinical values in the diagnosis of HG. Collectively, our article suggests that serum β-hCG expression of pregnant women with HG is abnormally elevated and closely related to the degree of HG and hyperthyroidism. In addition, β-hCG and thyroid function-related indicators have certain diagnostic efficacy for HG.

The develop of organic functional materials requires the exploration of the pressure dependent emissive mechanisms of molecular structures, conformations and stacking modes. Here, Tong et al propose a strategy for monitoring the pressure-induced fluorescence under multiple excitation channels.

Summary: Background: The paradigm of early phase dose-finding trials has evolved in recent years. Innovative dose-finding designs and protocols which combine phases I and II are becoming more popular in health research. However, the quality of these trial protocols is unknown due to a lack of specific reporting guidelines. Here, we evaluated the reporting quality of dose-finding trial protocols. Methods: We conducted a cross-sectional study of oncology and non-oncology early phase dose-finding trial protocols posted on ClinicalTrials.gov in 2017–2023. A checklist of items comprising: 1) the original 33-items from the SPIRIT 2013 Statement and 2) additional items unique to dose-finding trials were used to assess reporting quality. The primary endpoint was the overall proportion of adequately reported items. This study was registered with PROSPERO (no: CRD42022314572). Finding: A total of 106 trial protocols were included in the study with the rule-based 3 + 3 being the most used trial design (39.6%). Eleven model-based and model-assisted designs were identified in oncology trials only (11/58, 19.0%). The overall proportion of adequately reported items was 65.1% (95%CI: 63.9–66.3%). However, the reporting quality of each individual item varied substantially (range 9.4%–100%). Oncology study protocols showed lower reporting quality than non-oncology. In the multivariable analysis, trials with larger sample sizes and industry funding were associated with higher proportions of adequately reported items (all p-values

Ag and its alloys, when prepared by a selective laser melting (SLM) process, have a low density and poor overall performance due to their high reflectivity when the most commonly used laser (λ = 1060 nm) is used, and they have exorbitant thermal conductivity. These characteristics lead to the insufficient melting of the powders and severely limit the applications of additive manufactured silver alloys. To improve the absorption of the laser, as well as for better mechanical properties and higher resistance to sulfidation, Ag–Cu alloys with different La2O3 contents were prepared in this work using the SLM process, via the mechanical mixing of La2O3 nanoparticles with Ag–Cu alloy powders. A series of analyses and tests were conducted to study the effects of La2O3 in Ag–Cu alloys on their density, microstructure, mechanical properties, and corrosion resistance. The results revealed that the addition of La2O3 particles to Ag–Cu alloy powders improved the laser absorptivity and reduced defects during the SLM process, leading to a significant rise from 7.76 g/cm3 to 9.16 g/cm3 in the density of the Ag–Cu alloys. The phase composition of the Ag–Cu alloys prepared by SLM was Silver-3C. La2O3 addition had no influence on the phase composition, but refined the grains of the Ag–Cu alloys by inhibiting the growth of columnar grains during the SLM process. No remarkable preferred orientation existed in all the samples prepared with or without La2O3. An upwards trend was achieved in the hardness of the Ag–Cu alloy by increasing the contents of La2O3 from 0 to 1.2%, and the average hardness was enhanced significantly, from 0.97 GPa to 2.88 GPa when the alloy contained 1.2% La2O3 due to the reduced pore defects and the refined grains resulting from the effects of the La2O3. EIS and PD tests of the samples in 1% Na2S solution proved that La2O3 addition improved the corrosion resistance of the Ag–Cu alloys practically and efficaciously. The samples containing La2O3 exhibited higher impedance values and lower corrosion current densities.

IntroductionReading literacy is not only central to students’ academic success during their school years but also crucial to their personal development in their later life. The development of assessment instruments for reading literacy has been of interest to researchers, educators and educational administrators. The purpose of the present study was to construct and validate a comparable item bank for assessing fourth-grade students’ reading literacy.MethodsOne hundred fifteen reading comprehension items were developed and administered to 2,174 Grade 4 students to construct an item bank. Using the test equating technique and balanced incomplete block design, we divided participants into 10 subgroups, and the 115 items were further assigned into 10 test forms. Item response theory software was used to estimate discrimination, items’ threshold parameters, and students’ ability parameters. The criterion-related validity was also examined in 135 Grade 4 students who completed the reading literacy test and verbal self-description questionnaire.ResultsThe final item bank included 99 reading performance indicators to express high achievement. The correlation between the students’ reading literacy and the verbal self-description questionnaire was significant and demonstrated the item bank’s good criterion-related validity. The item bank developed in this study shows good psychometric characteristics and can be used to assess the reading literacy of fourth graders.

Abstract Demineralization of hard tooth tissues leads to dental caries, which cause health problems and economic burdens throughout the world. A biomimetic mineralization strategy is expected to reverse early dental caries. Commercially available anti-carious mineralizing products lead to inconclusive clinical results because they cannot continuously replenish the required calcium and phosphate resources. Herein, we prepared a mineralizing film consisting of hydroxypropylmethylcellulose (HPMC) and polyaspartic acid-stabilized amorphous calcium phosphate (PAsp-ACP) nanoparticles. HPMC which contains multiple hydroxyl groups is a film-forming material that can be desiccated to form a dry film. In a moist environment, this film gradually changes into a gel. HPMC was used as the carrier of PAsp-ACP nanoparticles to deliver biomimetic mineralization. Our results indicated that the hydroxyl and methoxyl groups of HPMC could assist the stability of PAsp-ACP nanoparticles and maintain their biomimetic mineralization activity. The results further demonstrated that the bioinspired mineralizing film induced the early mineralization of demineralized dentin after 24 h with increasing mineralization of the whole demineralized dentin (3–4 µm) after 72–96 h. Furthermore, these results were achieved without any cytotoxicity or mucosa irritation. Therefore, this mineralizing film shows promise for use in preventive dentistry due to its efficient mineralization capability. Graphical Abstract

The “Grain for Green” project (GGP) was launched in 1999 on China’s Loess Plateau to reduce soil erosion, which had far-reaching impacts on the local eco-hydrological processes. In this study, we use monthly runoff depth and precipitation datasets spanning 1961 to 2015 for 16 primary basins of the plateau to reveal changes in runoff generation capacity before and after the GGP. We use a Budyko-based elasticity method to calculate the runoff depth (R1) and runoff coefficient (C1) exclusively attributable to land use/cover change. Results indicate that the mean annual runoff coefficients (C0) decline by 26%–76% from the periods 1961–1999 to 2000–2015. The annual observed runoff depth (R0) and C0 for 75% of basins show significant downward trends during 1961–1999; after the implementation of the GGP, both annual R0 and annual C0 for over 50% of basins show upward trends. The study further finds that the increase of erosive rainfall during the period 2000–2015, whose mean increasing rate reaches 4.6 mm/year, is the main reason for the upward trends of R0 and C0. After removing the effect of precipitation variation during this period, we find that 11 out of 16 basins show decreased trends for C1, with the downward rate between 2.4% and 6.0% per year. The reduction rate in semi-arid areas is about four times the rate in semi-humid areas. The results remind us to consider the carrying capacity of local water resources when implementing soil and water conservation measures across the Loess Plateau.

BackgroundGlioma is an incurable malignant lesion with poor outcome characterized by easy recurrence after surgery with or without radiotherapy and chemotherapy. Studies have shown that COL6A2 is closely related to the tumorigenesis and development of a variety of tumors. However, the role of COL6A2 in glioma and the relationship between COL6A2 and tumor infiltrating immune cells remain unclear.MethodsWestern blot, real-time PCR, a tissue microarray and immunohistochemistry were applied to detect COL6A2 mRNA and protein amounts in glioma, and all experiments were repeated three times. A tissue microarray of glioma samples was used for prognostic analysis. Detection of COL6A2 co-expression with immune genes using immunohistochemical methods, and tumor modeling using nude mice for prevention and treatment studies. Based on the mRNA expression of COL6A2, patients with glioma in TCGA were divided into the low and high COL6A2 expression groups, and GO and KEGG pathway analyses were performed. A PPI network was constructed using STRING, and the associations of COL6A2 with tumor-infiltrating immune cells and immune genes were analyzed in the CIBERSORT and TISIDB databases. COL6A2 mRNA and protein amounts were increased in glioma.ResultsMultiple-database and tissue microarray analyses showed that COL6A2 expression in glioma was associated with poor prognosis, Tissue microarray showed that COL6A2 was the highest expressed in WHO IV and significantly higher in TCGA-GBM than in TCGA-LGG. Immunohistochemistry can well demonstrate the co-expression of COL6A2 with immune genes in a tumor model established in nude mice, showing that interference with COL6A2 expression may have an inhibitory effect on tumors. The mRNA expression of COL6A2 was involved in 22 KEGG pathways, and GSEA analysis showed that 28 and 57 gene sets were significantly enriched at nominal p values

Abstract Decomposing the uncertainty of global climate models is highly instructive in understanding climate change. However, it remains unclear whether sources of uncertainty have changed as the models have evolved and the extents to which uncertainty in temperature and precipitation are narrowed after bias correction (BC). We quantified uncertainty in temperature and precipitation projections over global land from three sources—model uncertainty, scenario uncertainty, and internal variability—and compared results from the models participating in the 5th and 6th phases of the Coupled Model Intercomparison Project (CMIP5 and CMIP6). In addition, we investigated the potential of four BC methods for narrowing uncertainty in temperature and precipitation over the globe and individual continents. Raw projections of temperature and precipitation have greater uncertainty and lower fractional uncertainty relative to their anomalies. The largest temperature uncertainties appear in high‐latitude and high‐altitude regions, and the largest precipitation uncertainties are in low‐latitude regions and mountainous and coastal areas. For uncertainties in CMIP6 temperatures, the contribution from model uncertainty decreases with time (from 99% to 39%), while the contribution from scenario uncertainty increases with time (from 0.01% to 61%). For precipitation projections, the contribution from model uncertainty predominates (98%), while the contributions from scenario uncertainty (1.8%) and internal variability (0.2%) are extremely low. Four BC methods have exhibited excellent ability to reduce uncertainty, and among them, BC and spatial disaggregation has the best performance. These findings can help us better understand the characteristics of the models, while also providing decision makers with more accurate information to address climate mitigation and adaptation measures.

BackgroundThe efficiencies that master protocol designs can bring to modern drug development have seen their increased utilization in oncology. Growing interest has also resulted in their consideration in non-oncology settings. Umbrella trials are one class of master protocol design that evaluates multiple targeted therapies in a single disease setting. Despite the existence of several reviews of master protocols, the statistical considerations of umbrella trials have received more limited attention.MethodsWe conduct a systematic review of the literature on umbrella trials, examining both the statistical methods that are available for their design and analysis, and also their use in practice. We pay particular attention to considerations for umbrella designs applied outside of oncology.FindingsWe identified 38 umbrella trials. To date, most umbrella trials have been conducted in early phase settings (73.7%, 28/38) and in oncology (92.1%, 35/38). The quality of statistical information available about conducted umbrella trials to date is poor; for example, it was impossible to ascertain how sample size was determined in the majority of trials (55.3%, 21/38). The literature on statistical methods for umbrella trials is currently sparse.ConclusionsUmbrella trials have potentially great utility to expedite drug development, including outside of oncology. However, to enable lessons to be effectively learned from early use of such designs, there is a need for higher-quality reporting of umbrella trials. Furthermore, if the potential of umbrella trials is to be realized, further methodological research is required.

Ferroptosis is an iron-dependent programmed cell death related to the biological process of many kinds of tumors. Long noncoding RNAs (LncRNA) have been found to play essential roles in the tumor, and their functions in the ferroptosis of tumor cells have been partially discovered. However, there is no summary of ferroptosis-related LncRNA and its functions in melanoma. In the present study, we aim to explore the expression profile of ferroptosis-related LncRNA genes and their value in melanoma prognosis by bioinformatics analysis. The expression of ferroptosis-related gene (FRG) from melanoma clinical data was extracted based on the Cancer Genome Atlas (TCGA) database. By screening the RNA expression data of 472 cases of melanoma and 810 cases of normal skin, eighteen ferroptosis-related differential genes were found to be related to the overall survival rate. Furthermore, 384 ferroptosis-related LncRNAs were discovered through constructing the mRNA-LncRNA co-expression network, and ten of them were found with prognostic significance in melanoma by multivariate Cox analysis. Risk assessment showed that the high expression of LncRNA00520 is associated with poor prognosis, while the increased expression of the other LncRNA is beneficial to the prognosis of patients with melanoma. From univariate and multivariate Cox regression analysis, there were ten ferroptosis-related LncRNA risk models towards to be significant independent prognostic factors for patients with melanoma and valuable predictive factors for overall survival (OS)(P

Background: Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma characterized by local invasion and recurrence. RNA sequencing (RNA-seq) allows the qualification of cellular RNA populations and provides information on the transcriptional state. However, few studies have comprehensively analyzed DFSP transcriptional data.Methods: Fourteen DFSP samples with paired non-neoplastic soft tissue from Chinese patients undergoing Mohs micrographic surgery were used for RNA-seq analysis. Differential expression analysis and enrichment analysis for RNA-seq data were performed to identify fusion genes, biomarkers, and microenvironment characteristics of DFSP.Results: This study systemically describes the transcriptomic characteristics of DFSP. First, we performed gene fusion analysis and identified a novel FBN1-CSAD fusion event in a DFSP patient with fibrosarcomatous transformation. Then, we identified TLK2 as a biomarker for DFSP based on functional enrichment analysis, and validated its accuracy for diagnosing DFSP by immunohistochemical staining and joint analysis with public data. Finally, microenvironment analysis described the infiltration characteristics of immune and stromal cells in DFSP.Conclusion: This study demonstrates that RNA-seq can serve as a promising strategy for exploring molecular mechanisms in DFSP. Our results provide new insights into accurate diagnosis and therapeutic targets of DFSP.

Abstract Background Despite progress that has been made in the treatment of many immune-mediated inflammatory diseases (IMIDs), there remains a need for improved treatments. Randomised controlled trials (RCTs) provide the highest form of evidence on the effectiveness of a potential new treatment regimen, but they are extremely expensive and time consuming to conduct. Consequently, much focus has been given in recent years to innovative design and analysis methods that could improve the efficiency of RCTs. In this article, we review the current use and future potential of these methods within the context of IMID trials. Methods We provide a review of several innovative methods that would provide utility in IMID research. These include novel study designs (adaptive trials, Sequential Multi-Assignment Randomised Trials, basket, and umbrella trials) and data analysis methodologies (augmented analyses of composite responder endpoints, using high-dimensional biomarker information to stratify patients, and emulation of RCTs from routinely collected data). IMID trials are now well-placed to embrace innovative methods. For example, well-developed statistical frameworks for adaptive trial design are ready for implementation, whilst the growing availability of historical datasets makes the use of Bayesian methods particularly applicable. To assess whether and how these innovative methods have been used in practice, we conducted a review via PubMed of clinical trials pertaining to any of 51 IMIDs that were published between 2018 and 20 in five high impact factor clinical journals. Results Amongst 97 articles included in the review, 19 (19.6%) used an innovative design method, but most of these were relatively straightforward examples of innovative approaches. Only two (2.1%) reported the use of evidence from routinely collected data, cohorts, or biobanks. Eight (9.2%) collected high-dimensional data. Conclusions Application of innovative statistical methodology to IMID trials has the potential to greatly improve efficiency, to generalise and extrapolate trial results, and to further personalise treatment strategies. Currently, such methods are infrequently utilised in practice. New research is required to ensure that IMID trials can benefit from the most suitable methods.

Penoscrotum extramammary Paget disease (pEMPD) is a rare cutaneous carcinoma with an unknown cell origin. pEMPD always presents as a tumor in situ with an indolent process, whereas some progress into invasive forms with more aggressive behavior. The in situ and invasive cases display different morphologies and biological behavior, and thus far, a relationship between these two components has not been demonstrated. Immunohistochemistry was used to disclose the immunotype of pEMPD, and the results revealed that invasive/in situ pEMPD possessed with some identical immunophenotypes such as CK7, P63, and CK10, which inferred the clonal relatedness. The variable expressions of GCDFP-15 and carcino embryonic antigen hinted that tumor cell origin might be an epidermal sweat gland in epiderma. In our cohort, invasive pEMPD presented increased expression of androgen receptor and decreased MUC5CA expression, and these two changes might bring to the shift of invasive phenotype. To better understanding the relationship between these distinct tumor forms, we performed whole exome sequencing testing to evaluate overlapping genomic alterations of six paired invasive/in situ pEMPDs. The results showed that missense mutation was the predominant mutation type, and C>T transition accounted for 65.1% in all SNP mutation. Among the top 20 differential genes obtained from the six paired invasive/in situ pEMPD analysis, MUC4 (one missense, one in frame del, and one multi-hit), AHNAK2 (two missense and one multi-hit), DOT1L (two missense and one multi-hit), and FRG1 (two missense and one-multi hit) mutations were most enriched in invasive pEMPDs, which postulated that these genes may play roles in the disease progression.

BackgroundA-kinase interacting protein 1 (AKIP1) promotes tumor progression and chemoresistance in several malignancies; meanwhile, it is related to higher tumor size and recurrence risk of papillary thyroid carcinoma, while the role of AKIP1 in anaplastic thyroid carcinoma (ATC) is unclear. The aim of this study is to explore the effect of AKIP1 knockdown on cell malignant behaviors and doxorubicin resistance in ATC.MethodsAKIP1 knockdown was conducted in ATC cell lines (8505C and CAL-62 cells) by siRNA; then, cell viability, apoptosis, invasion, PI3K/AKT and β-catenin pathways, and doxorubicin sensitivity were detected. Subsequently, doxorubicin-resistant 8505C cells (8505C/Dox) were established. Additionally, AKIP1 was modified in 8505C and 8505C/Dox cells that underwent doxorubicin treatment by siRNA or overexpression plasmid, followed by cellular function and pathway detection.ResultsAKIP1 was elevated in FRO, 8505C, CAL-62, and KHM-5M cells compared to control cells (all p < 0.05). Subsequently, AKIP1 knockdown elevated apoptosis, inhibited viability and invasion, and inactivated PI3K/AKT and β-catenin pathways in 8505C and CAL-62 cells (all p < 0.05). AKIP1 knockdown decreased relative cell viability in doxorubicin-treated 8505C and CAL-62 cells; then, AKIP1 was elevated in 8505C/Dox cells compared to 8505C cells (all p < 0.05). Furthermore, AKIP1 knockdown restored doxorubicin sensitivity (reflected by decreased cell viability and invasion, and increased apoptosis), but inactivated PI3K/AKT and β-catenin pathways in doxorubicin-treated 8505C/Dox cells. However, AKIP1 overexpression presented an opposite effect on these functions and pathways in doxorubicin-treated 8505C cells.ConclusionAKIP1 knockdown decreases cell survival and invasion while promoting sensitivity to doxorubicin via inactivating PI3K/AKT and β-catenin pathways in ATC.

BackgroundMost of data available in the literature reported the sperm retrieval rate and limited intracytoplasmic sperm injection (ICSI) results of microdissection testicular sperm extraction (micro-TESE) in non-obstructive azoospermia (NOA) patients with different etiologies. Unfortunately, there is currently a lack of comprehensive data to guide clinicians in conducting comprehensive consultations with NOA patients.ObjectivesTo obtain more comprehensive evidence-based data and clinical outcomes for better consultation of NOA patients who opted to undergo micro-TESE combined with ICSI-IVFMethodsIt was a retrospective study involved 968 NOA patients underwent micro-TESE during January 2015 to December 2019. Embryological, clinical, and live birth outcomes were demonstrated comprehensively and three kinds of stratification analyses were performed based on ICSI-IVF cycles using frozen and fresh sperm, different etiologies of NOA and various amounts of sperm retrieved.ResultsThe sperm retrieval rate was 44.6%, and ICSI was performed in 299 couples leading to 150 clinical pregnancies and 140 live-birth deliveries. The clinical pregnancy rate (CPR) was 50.17%, and the cumulative live birth rate (LBR) was 46.82%, and the low birth defects rate was 1.43%. No significant difference was observed about cumulative LBR in frozen sperm group and fresh sperm group (47.5% vs 42.9%, P>0.05). NOA patients with AZFc microdeletions had the lowest rate of a high-score embryo on day 3 (4.4%, P

BackgroundA series of full-endoscopic lumbar interbody fusions have been reported, but special fusion cages or operating instruments are often needed, and there are many complications in the operation and the learning curve is long. We have used a single portal endoscopic system for lumbar interbody fusion in a novel posterolateral transarticular approach, which will take advantage of the incision for pedicle screw insertion and avoid nerve root damage by using a transparent plastic working tube. The purpose of this study was to present the surgical technique of full endoscopic posterolateral transarticular lumbar interbody fusion (FE-PTLIF) and to analyze the preliminary clinical results.MethodsA total of 39 patients (17 men and 22 women; mean age [x̅ ± s] 55.2 ± 12.2 years) have been enrolled in this retrospective study between March 2019 and January 2021 in the Second Affiliated Hospital of Chongqing Medical University. All patients were treated with full endoscopic lumbar interbody fusion via posterolateral transarticular approach with a transparent plastic working tube. Demographic characteristics, diagnosis, operative time, and estimated blood loss were evaluated. Intraoperative photo and perioperative imaging were recorded. The preoperative and postoperative clinical data were collected for statistical analysis.ResultsThe preliminary clinical follow-up data achieved good results. No patients had serious postoperative complications and none of these patients required revision surgery during the perioperative or follow-up period. We compared the visual analogue scale and Oswestry disability index scores before and after surgery. The differences were statistically significant (P

Slag compositions are significant for the viscosity of blast furnace slag. An improved Urbain model (IUM) was proposed by introducing R5 ((X(CaO) + X(MgO) + 2X(TiO2))/(2X(SiO2) + 3X(Al2O3))) and N (X(MgO)/3X(Al2O3)) as the model parameters. By comparing IUM with other models, the model parameters of R5 and N are more reasonable and suitable for TiO2-bearing blast furnace slag, and IUM for predicting viscosity has a higher precision, and its relative error is only 10%. The viscosity isolines of the CaO–SiO2–15%Al2O3–MgO–2.5% TiO2 system were plotted, and the results show that the viscosity center of the slag is between Rw2 (w(CaO)/w(SiO2)) = 0.77–1.39 and Nw (w(MgO)/w(Al2O3)) = 0–1.37, the value of the viscosity center is 0.3 Pa·s, the viscosity increases gradually from the center to the outside, and the viscosity of the slag gradually decreases with the increase in Nw and Rw2. Furthermore, FTIR (Fourier Transform Infrared Spectroscopy) analysis was carried out in order to understand the mechanism between the slag structure and viscosity. With the increase in Nw and Rw2, the peak values of the symmetrical stretching vibration of non-bridging oxygen in the Si–O tetrahedral structure of slag decrease, and the slag structures depolymerize, which leads to the decrease in the viscosity of the slag.

Abstract Mechanical cues are widely used for regulating cell behavior because of their overarching, extensive, and non‐invasive advantages. However, unlike chemical cues, mechanical cues are not efficient enough to determine cell fate independently and improving the mechanosensitivity of cells is rather challenging. In this study, the combined effect of chemical and mechanical cues on the osteogenic differentiation of human mesenchymal stem cells is examined. These results show that chemical cues such as the presence of an osteogenic medium, induce cells to secrete more collagen, and induce integrin for recruiting focal adhesion proteins that mature and cascade a series of events with the help of the mechanical force of the scaffold material. High‐resolution, highly ordered hollow‐micro‐frustum‐arrays using double‐layer lithography, combined with modified methacrylate gelatin loaded with pre‐defined soluble chemicals to provide both chemical and mechanical cues to cells. This approach ultimately facilitates the achievement of cellular osteodifferentiation and enhances bone repair efficiency in a model of femoral fracture in vivo in mice. Moreover, the results also reveal these pivotal roles of Integrin α2/Focal adhesion kinase/Ras homolog gene family member A/Large Tumor Suppressor 1/Yes‐associated protein in human mesenchymal stem cells osteogenic differentiation both in vitro and in vivo. Overall, these results show that chemical cues enhance the microtopographical sensitivity of cells.

Abstract Documenting the spatiotemporal changes in vegetation cover and hydrological cycle of the Earth system and understanding how they interact are important especially under climate warming. In this research, we quantified the changes in vegetation and evapotranspiration (E) across China during 1982–2015 and then revealed the complex relationships in climate–vegetation–evapotranspiration system. Results show that the upward trend in vegetation leaf area index (LAI) during 2000–2015 (an increase of 0.95% per year) was almost 8 times the trend during 1982–1999. The zones of the Loess Plateau and the Three‐North Shelter Forest Program are the most notable areas for LAI increases between these two periods, with increases of 11.65% and 2.87%, respectively. Increased LAI, along with the warming climate, has accelerated E across China in the past several decades, and the annual increase in the E rate was 0.34% (1.34 mm year−1) during 1982–1999 and 0.40% (1.62 mm year−1) during 2000–2015. The zones of the Loess Plateau and the karst landform are the most notable areas for transpiration increases, with individual increases of 10% and 5%, respectively. In general, the dominant causes for evaporation changes across all of China are temperature and precipitation, while the main reasons for transpiration changes include temperature, LAI, and sunshine duration. This study improves our understanding of the relationships within the climate–vegetation–evapotranspiration system and provides important support for future ecological policies across China.

The protein arginine methyl transferase PRMT5 is an enzyme expressed in oligodendrocyte lineage cells and responsible for the symmetric methylation of arginine residues on histone tails. Previous work from our laboratory identified PRMT5 as critical for myelination, due to its transcriptional regulation of genes involved in survival and early stages of differentiation. However, besides its nuclear localization, PRMT5 is found at high levels in the cytoplasm of several cell types, including oligodendrocyte progenitor cells (OPCs) and yet, its interacting partners in this lineage, remain elusive. By using mass spectrometry on protein eluates from extracts generated from primary oligodendrocyte lineage cells and immunoprecipitated with PRMT5 antibodies, we identified 1196 proteins as PRMT5 interacting partners. These proteins were related to molecular functions such as RNA binding, ribosomal structure, cadherin and actin binding, nucleotide and protein binding, and GTP and GTPase activity. We then investigated PRMT5 substrates using iTRAQ-based proteomics on cytosolic and nuclear protein extracts from CRISPR-PRMT5 knockdown immortalized oligodendrocyte progenitors compared to CRISPR-EGFP controls. This analysis identified a similar number of peptides in the two subcellular fractions and a total number of 57 proteins with statistically decreased symmetric methylation of arginine residues in the CRISPR-PRMT5 knockdown compared to control. Several PRMT5 substrates were in common with cancer cell lines and related to RNA processing, splicing and transcription. In addition, we detected ten oligodendrocyte lineage specific substrates, corresponding to proteins with high expression levels in neural tissue. They included: PRC2C, a proline-rich protein involved in methyl-RNA binding, HNRPD an RNA binding protein involved in regulation of RNA stability, nuclear proteins involved in transcription and other proteins related to migration and actin cytoskeleton. Together, these results highlight a cell-specific role of PRMT5 in OPC in regulating several other cellular processes, besides RNA splicing and metabolism.

Abstract Background Controlled ovarian stimulation (COS) has a negative effect on the endometrial receptivity compared with natural menstrual cycle. Whether it’s necessary to postpone the first frozen embryo transfer (FET) following a freeze-all strategy in order to avoid any residual effect on endometrial receptivity consequent to COS was inconclusive. Objective The purpose of this retrospective study was to explore whether the delayed FET improve the live birth rate and neonatal outcomes stratified by COS protocols after a freeze-all strategy. Methods A total of 4404 patients who underwent the first FET cycle were enrolled in this study between April 2014 to December 2017, and were divided into immediate (within the first menstrual cycle following withdrawal bleeding) or delayed FET (waiting for at least one menstrual cycle and the transferred embryos were cryopreserved for less than 6 months). Furthermore, each group was further divided into two subgroups according to COS protocols, and the pregnancy and neonatal outcomes were analyzed between the immediate and delayed FET following the same COS protocol. Results When FET cycles following the same COS protocol, there was no significant difference regarding the rates of live birth, implantation, clinical pregnancy, multiple pregnancy, early miscarriage, premature birth and stillbirth between immediate and delayed FET groups. Similarly, no significant differences were found for the mean gestational age, the mean birth weight, and rates of low birth weight and very low birth weight between the immediate and delayed FET groups. The sex ratio (male/female) and the congenital anomalies rate also did not differ significantly between the two FET groups stratified by COS protocols. Conclusion Regardless of COS protocols, FET could be performed immediately after a freeze-all strategy for delaying FET failed to improve reproductive and neonatal outcomes.

Description. Cutaneous melanoma (SKCM) is one of the most common skin malignancies. miR-100-5 has been found to highly express microRNAs in a variety of cancers. This is a novel biomarker to inhibit the proliferation, migration, and invasion of cutaneous melanoma. However, its function and potential mechanisms in SKCM remain unknown. Objective. To better understand the role and underlying mechanisms of SKCM, we conducted bioinformatics analysis and in vivo experiments. Results. We found its role as a tumor suppressor gene in SKCM and its effect on prognosis. In addition, this study found that miR-100-5p had a bidirectional effect on SKCM microenvironment. After exploring the relationship between the two, it was found that tumors with intermediate miR-100-5p expression had the highest level of immune cell infiltration. In addition, the value of miR-100-5p was assessed by survival analysis, univariate Cox regression analysis, and nomogram prognostic prediction. Finally, we constructed a regulatory network to illustrate the regulatory relationship of miR-100-5p. Conclusions. In conclusion, the antitumor effect of miR-100-5p is revealed, and the present study is followed by a discussion of its molecular regulatory network, followed by novel insights into SKCM therapy.

Epi-aszonalenin A (EAA) is an alkaloid that is isolated and purified from the secondary metabolites of coral symbiotic fungi and has been shown to have good atherosclerotic intervention activity and anti-angiogenic activity in our previous studies. In the present study, antiangiogenic activity was used as a basis of an intensive study of its mechanism of action against tumor metastasis and invasion. Invasive metastatic pairs are a hallmark of malignancy, and the dissemination of tumor cells is the most dangerous process in the development of tumors. The results of cell wound healing and the Transwell chamber assay showed that EAA interfered well with PMA-induced migration and invasion of HT1080 cells. Western blot and the ELISA assay showed that EAA decreased MMPs and vascular endothelial growth factor (VEGF) activity and inhibited the expression of N-cadherin and hypoxia-inducible factor-1α (HIF-1α) by regulating the phosphorylation of downstream mitogen-activated protein kinase (MAPK), PI3K/AKT, and NF-κB pathways. Simultaneous molecular docking results revealed that the mimic coupling between the EAA and MMP-2/-9 molecules formed a stable interaction. The results of this study provide a research basis for the inhibition of tumor metastasis by EAA, and together with previous studies, confirm the potential pharmacology and drug potential for this class of compound for application in angiogenesis-related diseases and further improve the availability of coral symbiotic fungi.

Due to the high randomness and volatility of renewable energy sources such as wind energy, the traditional thermal unit commitment (UC) model is no longer applicable. In this paper, in order to reduce the possible negative effects of an inaccurate wind energy forecast, the chance-constrained programming (CCP) method is used to study the UC problem with uncertainty wind power generation, and chance constraints such as power balance and spinning reserve are satisfied with a predetermined probability. In order to effectively solve the CCP problem, first, we used the sample average approximation (SAA) method to transform the chance constraints into deterministic constraints and to obtain a mixed-integer quadratic programming (MIQP) model. Then, the quadratic terms were incorporated into the constraints by introducing some auxiliary variables, and some second-order cone constraints were formed by combining them with the output characteristics of thermal unit; therefore, a tighter mixed-integer second-order cone programming (MISOCP) formulation was obtained. Finally, we applied this method to some systems including 10 to 100 thermal units and 1 to 2 wind units, and we invoked MOSEK in MATLAB to solve the MISOCP formulation. The numerical results obtained within 24 h confirm that not only is the MISOCP formulation a successful reformulation that can achieve better suboptimal solutions, but it is also a suitable method for solving the large-scale uncertain UC problem. In addition, for systems of up to 40 units within 24 h that do not consider wind power and pollution emissions, the numerical results were compared with those of previously published methods, showing that the MISOCP formulation is very promising, given its excellent performance.

Abstract The Hippo pathway effector TAZ promotes cellular growth, survival, and stemness through regulating gene transcription. Recent studies suggest that TAZ liquid–liquid phase separation (LLPS) compartmentalizes key cofactors to activate transcription. However, how TAZ LLPS is achieved remains unknown. Here, it is shown that the paraspeckle protein NONO is required for TAZ LLPS and activation in the nucleus. NONO is a TAZ‐binding protein. Their interaction shows temporal regulation parallel to the interaction between TAZ and TEAD as well as to the expression of TAZ target genes. NONO depletion reduces nuclear TAZ LLPS, while ectopic NONO expression promotes the LLPS. Accordingly, NONO depletion reduces TAZ interactions with TEAD, Rpb1, and enhancers. In glioblastoma, expressions of NONO and TAZ are both upregulated and predict poor prognosis. Silencing NONO expression in an orthotopic glioblastoma mouse model inhibits TAZ‐driven tumorigenesis. Together, this study suggests that NONO is a nuclear factor that promotes TAZ LLPS and TAZ‐driven oncogenic transcriptional program.

The fuel segregation distribution sintering process, with a high fuel dosage in upper layer and a low fuel dosage in bottom layer of the sintering bed, was studied to handle uneven heat distribution problems in the conventional iron ore sintering process. A mathematical simulation method was adopted to contrastively study the fuel segregation distribution sintering process and the conventional iron ore sintering process. The accuracy of the model was verified through the sintering experiments. In addition, different heights of the upper and bottom sintering beds were discussed to assess the fuel segregation distribution sintering technology. In contrast to the conventional iron ore sintering process, the temperature evolution in the sintering bed using the fuel segregation distribution sintering technology tended to be more reasonable and the heat accumulation in the upper bed increased, which meant that the melt quantity index increased from 2178 to 2387 K·min−1, and cooling rate decreased from 360 to 199 K·min−1. The drawbacks of the conventional iron ore sintering process, such as the heat shortage in upper bed and excess heat in lower bed, were therefore improved, which was also proven to promote the sinter quality.

Cardiac complications are common in antiretroviral therapy-treated (ART-treated) acquired immune deficiency syndrome (AIDS) patients, and the incidence increases with age. Myocardial injury in ART-treated AIDS patients with a relatively longer disease duration has been evaluated. However, there is no relevant study on whether patients with a short AIDS duration have cardiac dysfunction. Thirty-seven ART-treated males with AIDS and eighteen healthy controls (HCs) were prospectively included for CMR scanning. Clinical data and laboratory examination results were collected. The ART-treated males with AIDS did not have significantly reduced biventricular ejection fraction, myocardial edema, or late gadolinium enhancement. Compared with the HCs, the biventricular volume parameters and left ventricle myocardial strain indices in ART-treated males with AIDS were not significantly reduced (all p > 0.05). ART-treated males with AIDS were divided into subgroups according to their CD4+ T-cell counts (p > 0.05). In Pearson correlation analysis, CD4+ T-cell counts were not significantly correlated with biventricular volume parameters or left ventricular myocardial strain indices. In conclusion, ART-treated males with AIDS receiving ART therapy with a short disease duration (less than 3 years) might not develop obvious cardiac dysfunction as evaluated by routine CMR, so it is reasonable to appropriately extend the interval between cardiovascular follow-ups to more than 3 years.