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Several microRNAs (miRNAs) and circular RNAs (circRNAs) were reported to be involved in the Docetaxel (DTX) chemoresistance of cancer treatment, but the underlying mechanisms remain to be explored. In this study, we established cellular and animal models respectively to study the effect and underlying molecular mechanisms of the dysregulation of circRNA_0006404 and circRNA_0000735 in tumor response to DTX treatment. Quantitative real-time PCR was performed to measure the expression of circRNA_0006404, miR-346, circRNA_0000735, miR-526b, Dickkopf-related protein 3 (DKK3), and Dickkopf-related protein 4 (DKK4) mRNA. The expression of circRNA_0006404 and circRNA_0000735 was remarkably suppressed and activated in DTX-treated SKOV3-R cell lines, respectively. As revealed by luciferase assays, circRNA_0006404 and circRNA_0000735 was found to be respectively targeted by miR-346 and miR-526b, while DKK3 and DKK4 were respectively targeted by miR-346 and miR-526b. Moreover, the expression of DKK3 and DKK4, which were targets of miR-346 and miR-526b, respectively, was significantly altered along with the expression of p-GP. Furthermore, circ_0006404 shRNA and circRNA_0000735 shRNA showed remarkable efficiency in stimulating the expression of circRNA_0006404, miR-346, DKK3, circRNA_0000735, miR-526b, DKK4, and p-GP in cellular and animal models. Accordingly, the cell apoptosis and proliferation were apparently changed by circ_0006404 shRNA and circRNA_0000735 shRNA in both cellular and animal models. In summary, our study found the involvement of the circRNA_0006404/miR-346/DKK3/p-GP and circRNA_0000735/miR-546b/DKK4/p-GP axis in the tumor response to DTX. Both the up-regulation of circRNA_0006404 and down-regulation of circRNA_0000735 could inhibit the expression of p-GP in vivo and ex vivo, leading to the suppressed tumor response to DTX treatment. [ABSTRACT FROM AUTHOR]

Radar imaging of typical planet landforms can be used for planetary exploration such as landform recognition and geometry measurement. This communication realizes high-resolution imaging simulations of typical planetary landforms, such as craters, hills, and volcanoes, by using parametric scattering center (SC) models. Based on the geometric models of these typical landforms, parametric SC models are constructed from scattered solutions of the physical optics (POs) method. Because the SC models take geometric parameters as model parameters, these models can simulate the scattered waves of landforms of different sizes. These SC models are validated by the PO results. In addition, the landform types can be recognized and their geometrical parameters are further extracted by SC model matching. The extracted geometric parameters show good agreement with real landforms, demonstrating that the SC models of typical planetary landforms have potential applications in planetary geomorphologic exploration. [ABSTRACT FROM AUTHOR]

Background. Golden plaster is the preferred and most commonly used in China for pain reduction in patients with knee osteoarthritis (OA). However, there was no evidence-based medical evidence about its effect in relieving pain of knee OA patients. Here, a multicenter randomized, double-blind, placebo-controlled trial was performed to evaluate the efficacy and safety of golden plaster for the improvement of pain relief and function's obstacle in patients with knee OA. Methods. 320 patients with knee OA were enrolled at four hospitals and randomly divided into the treatment group and the control group with 160 subjects in each group. Patients in treatment group were treated with golden plaster, and those in control group with placebo plaster. The study cycle in both groups was 21 days. Patient visits were documented before treatment and 7-, 14-, and 21-day follow-ups after treatment. The outcomes included VAS score, WOMAC score, and adverse events. Results. Compared to the control group, the VAS score in the treatment group was significantly decreased after treatment with golden plaster for 7 days, 14 days, and 21 days. Compared to the control group, the WOMAC score in the treatment group was significantly decreased 14 days and 21 days. The incidence rate of adverse events had no statistical difference between both the groups. Conclusions. In conclusion, our study, for the first time by carrying on the double-blind and placebo-controlled randomized trial, showed that golden plaster can effectively alleviate the pain of knee and improve the physical function in the patients with knee OA. This trial is registered with ChiCTR-TRC-13003418. [ABSTRACT FROM AUTHOR]

• CircCUL3 overexpression drives cervical cancer progression. • CircCUL3 acts as a sponge for miR-223-3p to upregulate ATG7 and activate autophagy. • Chloroquine reverses circCUL3-induced effects by restoring miR-223-3p expression. Circular RNA (circRNA) has emerged as a pivotal regulatory factor in cancer biology, yet its exact role in cervical cancer remains incompletely understood. In this study, we investigated the functional role of circCUL3 in cervical cancer and explored its potential as a therapeutic target. Functional gain and loss experiments were conducted in Hela and Siha cell lines to elucidate the biological functions of circCUL3 in cervical cancer. The results revealed that circCUL3 overexpression significantly enhanced cell viability, migration, and invasion while suppressing apoptosis, while circCUL3 knockout displayed the opposite effects. Mechanistically, we identified hsa-miR-223-3p as a target of circCUL3, with its expression being negatively regulated by circCUL3. Furthermore, we discovered that circCUL3 could sequester miR-223-3p, leading to the upregulation of ATG7 expression, and this was linked to the regulation of autophagy in cervical cancer cells. In vivo validation using a xenograft mouse model further supported our in vitro findings. Notably, we found that chloroquine (CQ), an autophagy inhibitor, restored miR-223-3p expression and counteracted the oncogenic effect of circCUL3 overexpression. In conclusion, circCUL3 potentially contributes to the malignant progression of cervical cancer by acting as a sponge for miR-223-3p, resulting in the upregulation of ATG7 and the activation of autophagy. [ABSTRACT FROM AUTHOR]

• Successfully designed and prepared a heterojunction VBiTNA. • VBiTNA exhibits excellent photocatalytic degradation of NOR. • Revealing the synergistic effect of oxygen vacancies and interfacial electric fields in VBiTNA. Fossil fuel consumption is a major source of greenhouse gas emissions. The Russia–Ukraine conflict has led to energy price volatility. Therefore, affordable energy poses a significant threat. The development of renewable energy to meet consumption demands has attracted researchers' attention in worldwide. In this study, a novel grey adaptive integrated model is proposed to balance the fitting and generalization abilities for renewable energy generation trends. First, feature selection was performed using the mutual information filter method for influencing factors and the wrapper method. Second, FGM(1,1) was used to mine the data features, and AGMC(1,n) was used to extract multivariate time-series relationships. Finally, an adaptive integrated model with a Gaussian kernel function was proposed in order to assign weights. It balances the results of the two forecasting models to avoid the underfitting/overfitting problem generated by excessive data volatility and the abrupt shift of the influencing factors. The study results have shown that the proposed integrated model solved the underfitting and overfitting problems to a certain degree. Its performance is better than single model. We analyze the forecasting results and propose corresponding suggestions for the government and enterprises separately. [ABSTRACT FROM AUTHOR]

Background: Collagen (COL) genes, play a key role in tumor invasion and metastasis, are involved in tumor extracellular matrix (ECM)-receptor interactions and focal adhesion pathways. However, studies focusing on the diagnostic value of the COL4 family in stomach adenocarcinoma (STAD) are currently lacking. Methods: The TCGA database was employed to retrieve the clinical features and RNA sequencing expression profiles of patients with STAD. We conducted an investigation to examine the expression disparities between STAD and adjacent normal tissues. Kaplan-Meier survival analysis was utilized to assess their prognostic significance, while Spearman correlation analysis was employed to determine their association with immune checkpoint genes and immunomodulatory molecules. Furthermore, GO and KEGG analyses were performed on the COL4s-related genes, revealing potential biological pathways through gene set enrichment analysis (GSEA). Subsequently, we explored the extent of immune infiltration of the COL4 family in STAD using the TIMER database. Lastly, the expression levels of the COL4 family in STAD were further validated through quantitative PCR (qPCR) and western blot techniques. Results: The expression levels of COL4A1/2 were significantly upregulated, while COL4A5/6 were conspicuously downregulated in STAD. The survival analysis revealed that the upregulated COL4s indicated poorer overall survival, first progression and post-progression survival outcomes. Additionally, our findings demonstrated a positive correlation between the expressions of COL4A1/2/3/4 and the infiltration of immune cells, including CD8 + T cells, dendritic cells, macrophages, neutrophils and CD4 + T cells. Further correlation analysis uncovered a favorable association between the expression of COL4A1/2/3/4 and various crucial immunomodulatory molecules, immunological checkpoint molecules, and chemokines. Quantitative PCR analysis confirmed that the expression patterns of COL4A1/3/4/6 genes aligned with the finding from the TCGA database. However, gastric cancer cells exhibited downregulation of COL4A2. Consistently, the protein level of COL4A1 was elevated, whereas the protein level of COL4A2 was reduced in the gastric cancer cell lines. Conclusion: COL4s could potentially serve as biomarkers for diagnosing and predicting the prognosis of STAD. [ABSTRACT FROM AUTHOR]

TiO2-based catalysts with various surface heterostructures (0D, 1D, 2D, and 3D) have been widely researched owing to their cost-effectiveness, high stability, and environmentally friendly nature, and can be used for many applications in various fields, including hydrogen production and pollutant degradation. However, there are also many existing problems limiting their practical application, such as their large band gap and rapid electron–hole recombination rate. Owing to the abundance of recent achievements in materials science, we will summarize the recent structural engineering strategies which provide favorable photocatalytic activity enhancements, such as enhanced visible light absorption, stability, an increased charge–carrier separation rate and improved specific surface area. Among the various structural engineering methods in this review, we will introduce TiO2-based materials with different dimensional structures. Meanwhile, we also discuss recent achievements in synthesis methods and application of TiO2-based catalysts in various fields. We aim to display a comprehensive overview which can be a guide for the development of a new generation of TiO2-based catalysts according to their structural design for enhanced solar energy conversion. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common arrhythmia and its incidence increases with sepsis. However, data on new-onset AF during sepsis hospitalization remain limited in China. We aimed to evaluate the incidence, risk factors, and associated mortality of new-onset AF in sepsis patients in China. We conducted a retrospective study using the National Data Center for Medical Service system, from 1923 tertiary and 2363 secondary hospitals from 31 provinces in China from 2017 to 2019.In total we included 1,425,055 sepsis patients ≥ 18 years without prior AF. The incidence of new-onset AF was 1.49%. Older age, male sex, hypertension, heart failure, coronary disease, valvular disease, and mechanical ventilation were independent risk factor. New-onset AF was associated with a slight increased risk of mortality (adjusted RR 1.03, 95% CI 1.01–1.06). Population attributable fraction suggested AF accounted for 0.2% of sepsis deaths. In this large nationwide cohort, new-onset AF occurred in 1.49% of sepsis admissions and was associated with a small mortality increase. Further research should examine whether optimized AF management can improve sepsis outcomes in China. [ABSTRACT FROM AUTHOR]

An artificial neural network (ANN) algorithm, employing several Aqua MODerate-resolution Imaging Spectroradiometer (MODIS) channels, the retrieved cloud phase and total cloud visible optical depth, and temperature and humidity vertical profiles is trained to detect multilayer (ML) ice-over-water cloud systems identified by matched 2008 CloudSat and CALIPSO (CC) data. The trained multilayer cloud-detection ANN (MCANN) was applied to 2009 MODIS data resulting in combined ML and single layer detection accuracies of 87 % (89 %) and 86 % (89 %) for snow-free (snow-covered) regions during the day and night, respectively. Overall, it detects 55 % and ∼ 30 % of the CC ML clouds over snow-free and snow-covered surfaces, respectively, and has a relatively low false alarm rate. The net gain in accuracy, which is the difference between the true and false ML fractions, is 7.5 % and ∼ 2.0 % over snow-free and snow/ice-covered surfaces. Overall, the MCANN is more accurate than most currently available methods. When corrected for the viewing-zenith-angle dependence of each parameter, the ML fraction detected is relatively invariant across the swath. Compared to the CC ML variability, the MCANN is robust seasonally and interannually and produces similar distribution patterns over the globe, except in the polar regions. Additional research is needed to conclusively evaluate the viewing zenith angle (VZA) dependence and further improve the MCANN accuracy. This approach should greatly improve the monitoring of cloud vertical structure using operational passive sensors. [ABSTRACT FROM AUTHOR]

This paper reports a nanomixed valence FeWO 4 -coated 2D Ti 3 C 2 MXene (FW-MX) photocatalyst synthesised by a simple hydrothermal method. Ciprofloxacin, the main target pollutant, exhibited superior adsorption performance and high catalytic activity in the light-assisted Fenton system. In just 1 h, the removal rate of ciprofloxacin reached an impressive 76.89% using a minimal amount of FW-MX (10 mg). Meanwhile, the material exhibited good stability. Furthermore, the successful formation of mixed-valent FeWO 4 accelerated the rate-limiting step of Fe(III)/Fe(II) conversion, thereby enhancing the reactivity of the in situ photo-Fenton system. In the light-assisted Fenton system, FW-MX demonstrated greater potential compared to other common antibiotics, as FW-M100 exhibited superior photoreduction performance for heavy metal ions under the photo-Fenton oxidation system. This could further advance the practical application of AOPs technology in industrial wastewater treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

• Hybrid Ag-TiO 2 /water nanofluid in a copper porous nanochannel via MD. • Investigation of interaction energy, thermal conductivity, and heat flux values. • Effects of different atomic ratios of nanoparticles (1, 2, 3, 5 and 10%) were evaluated. Nanofluids have gained significant attention due to their improved heat transfer capability compared to traditional fluids, making them promising for various applications. Adding nanoparticles to the base fluid alters its thermophysical attributes, such as thermal conductivity, viscosity, and heat transfer characteristics. Understanding the thermal behavior of hybrid nanofluids in porous nanochannels is crucial for optimizing their performance in practical applications. Therefore, this research uses molecular dynamic simulation to evaluate the thermal performance of an Ag-TiO 2 /water hybrid nanofluid combined with a copper porous nanochannel. The changes in parameters such as interaction energy, thermal conductivity, and heat flux were evaluated with time. Also, the effects of different atomic ratios of nanoparticles (1, 2, 3, 5 and 10 %) on mentioned thermal parameters were evaluated. Based on the findings obtained from the molecular dynamics simulation, with the passage of 10 ns, the interaction energy, thermal conductivity, and heat flux values have converged to 1.356 kcal/mol.atom, 1.717 W/m.k and 114.09 W/m2, respectively. Also, by increasing the atomic ratio of added nanoparticles to 3 %, the thermal conductivity and heat flux values have increased to numerical values of 1.83 W/m.k and 126.84 W/m2. After that, by increasing the atomic ratio of nanoparticles to 10 %, the mentioned parameters reach numerical values of 1.79 W/m.k and 120.05 W/m2. [ABSTRACT FROM AUTHOR]

Large volume changes of lithium-ion batteries during battery operation affect battery lifetime and performance through mechanical degradation. Therefore, understanding the coupling between mechanics and electrochemistry in these systems is crucial. In this work, we use neutron diffraction to learn how commercial lithium-ion pouch cells are affected by stack pressure during charge and discharge. We find that a change in stack pressure affects the phase transitions in electrode materials, requiring more charge to reach higher state-of-charge phases which results in effective capacity loss for the battery. Also noteworthy is that the copper current collector experiences strain during charge and discharge due to the expansion of the graphite anode, something often overlooked in these systems. • Neutron diffraction reveals how stack pressure affects charging lithium-ion cells. • Lithium-ion pouch cells lose capacity when charged under applied stress. • Copper current collector experiences significant strain during charge cycling. • Electrode phase transitions require more charge under higher stack pressures. [ABSTRACT FROM AUTHOR]

This work proposes an effective design of bioactive 3D-printed Ti-6Al-4V scaffold with the CaO-MgO-SiO 2 glass-ceramic coating to realize a comparable elastic modulus of bone tissue and boost osteogenic differentiation. The improved elastic modulus and stiffness of Ti alloy were achieved via effectively increasing surface area of Ti alloy to reduce stress shielding effect. A hydrophilic surface and bioactive glass-ceramic coating were conducted via chemical etching and heat-treatment under argon atmosphere to enhance cells attachment and boost cell proliferation and osteogenic differentiation. The expression of osteogenic genes in bioactive CaO-MgO-SiO 2 glass-ceramic was evaluated through ALP, OPN, Runx2, and Col1A1 gene markers to explore the mechanism of superior osteogenic differentiation. Significant increase in OPN expression level confirmed the effect of CaO-MgO-SiO 2 coating for the enhancement of osteogenic bioactivity. This work provides a feasible approach through surface etching and bioactive CaO-MgO-SiO 2 glass-ceramic coating on the Ti alloy surface to enhance bioactivity and osteogenesis. [Display omitted] • A compatible bone tissue of 3D-printed Ti-6Al-4V scaffold with the novel bioactive CaO-MgO-SiO 2 glass-ceramic coating. • A superior surface modification to enhance cells attachment and boost cell proliferation and osteogenic differentiation. • This work provides a feasible approach on the Ti-alloy surface to enhance bioactivity and osteogenesis. [ABSTRACT FROM AUTHOR]

Current Environmental, Social, and Governance (ESG) rating systems encounter challenges due to their subjectivity, time lag, and inconsistent coverage, which present significant obstacles for investors in the stock market. In contrast, news reporting data, characterized by its objectivity, timeliness, publicity, and sociality, has been a crucial source of quality market information for investors. The potential of ESG-related news as a robust complement to the data sources used in existing ESG rating systems merits further exploration. This study investigates the impact of ESG-related news on the Chinese stock market, with the goal of providing compelling evidence for integrating news media into ESG assessments. By analyzing 32,296 ESG-related news articles covering 3643 companies in the Chinese market from 2015 to 2021, we utilize event study methodology to assess the market's abnormal returns in response to ESG-related news. Our findings suggest a significant market impact from ESG-related news, indicating that investors are increasingly attentive to information pertaining to ESG issues. The study also reveals that different attributes of ESG-related news have diverse effects on the market. Specifically, news with negative sentiments has the most significant impact, and investors demonstrate a stronger reaction to ESG-related news disseminated through unofficial media. Furthermore, the study highlights that enterprise heterogeneity affects the impact of ESG-related news, with companies in the secondary and tertiary industries showing higher sensitivity. Privately-owned enterprises are found to be more influenced by such news compared to state-owned enterprises. This study offers a novel perspective in evaluating corporate ESG performance using news media, proposing a more effective and objective method to assess and manage corporate sustainability in a dynamic market landscape. • Significant impact of ESG-related news on Chinese stock market returns. • Diverse market reactions to varying ESG-related news sentiments and sources. • Stock response differs by company industry and ownership type. • Provides a basis for ESG-related news as a complementary tool in ESG ratings. [ABSTRACT FROM AUTHOR]

The presence of short-lived shallow trapping states in semiconductor-based photocatalysts hinders efficient utilization of charge carrier, which compromises the solar-to-hydrogen efficiency. Here, we presented an engineered graphitic carbon nitride (g-CN) nanosheets with long-lived shallow trapping states achieved through an n-π * electronic transition. This transition induces a significant red-shifted absorption edge at 600 nm, effectively extending the range of light absorption compared to pristine g-CN. Moreover, the engineered g-CN nanosheets exhibit lower exciton binding energies (36 meV) compared to pristine counterparts (50.1 meV), as revealed by temperature-dependent photoluminescence (PL) spectra. Femtosecond transient absorption spectroscopy (fs-TAS) confirms the presence of long-lived shallow trapping states (lifetime: 565.8 ps) in the engineered g-CN nanosheets. These states enable a greater participation of photoinduced electrons in photocatalytic reactions, resulting in significantly enhanced photoactivity. Notably, the g-CN sample with the n-π * transition achieves a remarkable photocatalytic H 2 production rate of 61.8 µmol h−1, which is a fivefold enhancement over pristine g-CN nanosheets. These findings highlight the crucial role of the n-π * transition in g-CN for prolonging shallow electron trapping and ultimately leading to superior photocatalytic performance. [Display omitted] • The n-π* transition expands g-CN's absorption edge to 600 nm. • The n-π* transition creates long-lived shallow trapping states in g-CN. • Engineered g-CN achieves 5-fold higher photocatalytic H 2 generation. [ABSTRACT FROM AUTHOR]

[Display omitted] • 28 out of 57 target PFAS were detected in paper products from China. • 9 groups of PFAS with 1–3 confidence levels were identified by non-target analysis. • Ethanol in food simulants can increase the migration of PFAS. • Long-chain PFAS in popcorn bags can be degraded by microwave heating. • PFAS in some paper products exceeded the recommended daily intake values. The contamination characteristics, migration patterns and health risks of per- and polyfluoroalkyl substances (PFAS) were investigated in 66 Chinese paper products by using target and non-target screening methods. Among 57 target PFASs, 5 and 6 PFASs were found in the hygiene paper products (

• Oblique angle impact on fracture behaviors of nacre-like composites was emphasized. • Geometric and material impacts on crack paths in nacre-like composites were revealed. • Nacre-like composite fracture toughness was determined via PFM and compliance method. • Design criteria for improving overall mechanical properties were established. Nacre-inspired composites, composed of hard and soft phases, exhibit exceptional combinations of stiffness, strength, and fracture toughness. However, the fracture behaviors of these composites are significantly influenced by the geometric factors and material properties of their constituents. In this study, we systematically investigate the fracture behaviors of nacre-like composites by employing a phase-field fracture model considering the effects of oblique angle between loading and platelet directions, a critical factor often overlooked in previous studies, coupled with the effect of other geometric and material parameters, such as the aspect ratio, Young's modulus and fracture toughness ratio between hard and soft phase. Our findings highlight the significant influence of the oblique angle on the mechanical properties and fracture behaviors of these composites. Particularly, it is found the maximum Young's modulus and strength are obtained when the direction of hard platelet is aligned with the tension direction, while the maximum toughness is achieved at a moderate oblique angle, especially in cases of large aspect ratios, small Young's modulus and fracture toughness ratios between the hard and soft phases. Besides, the maximum fracture toughness is more likely to be obtained at a small aspect ratio and large Young's modulus ratio between hard and soft phases. The insights gained from our study would offer valuable guidance for the design and practical application of nacre-mimetic composites. [ABSTRACT FROM AUTHOR]

[Display omitted] • CsPbBr 3 with quantum-limited domain effects have reversible hydrochromic properties. • Different Organic solvents cause polarity-related discoloration of composites. • A detection model was developed for all-organic solvent polarity detection. Hydrochromic materials have received much attention in anticounterfeiting due to their reversible photoemission properties toward water. However, existing hydrochromic materials usually suffer from slow hydrochromic response and limited stability, repeatability, and color tunability. This paper found for the first time that CsPbBr 3 /Cs 4 PbBr 6 composites with quantum-limited domain effects had reversible hydrochromism. CsPbBr 3 /Cs 4 PbBr 6 composites were successfully synthesized in molecular sieve MCM-41 using an improved mechanochemical method. The composites underwent a reversible phase transition from Cs 4 PbBr 6 /CsPbBr 3 to CsPbBr 3 upon treatment with a trace amount of water, the photoluminescence colors underwent a change from blue to green, and reversion occurred due to heating. Mechanistic investigation revealed that quantum dots underwent soft agglomeration due to van der Waals forces in polar solvent environments, affecting the action of quantum domain-limiting effects. Therefore, organic solvents with different polarities can cause different degrees of reversible discoloration of the material. This study provides new ideas for understanding the phase transition and agglomeration of metal halide perovskite quantum dots in polar solvent environments. Additionally, it offered new options for aqueous color-changing materials and organic solvent polar detection materials. [ABSTRACT FROM AUTHOR]

Enhancing the green economy efficiency (GEE) is crucial for building a sustainable economy. How can the rapidly advancing digital transformation contribute to this process? The paper empirically examines the direct and spatial spillover effects of digital transformation on cities' GEE in China. This study utilizes the National E-commerce Pilot City (NEPC) policy as a quasi-natural experiment of regional digital transformation and employs the staggered difference-in-differences (DID) method with heterogeneous effects. The findings reveal that (i) implementing the NEPC policy significantly increases urban GEE by 2.6%, corresponding to a 16% increase in the mean of GEE. This effect is particularly pronounced in non-resource-based cities and cities with high Internet penetration. (ii) The mechanism test shows that the pilot policy positively affects GEE by promoting green structural transformation, enhancing green innovation, and strengthening public environmental concerns. (iii) The study highlights a positive spatial spillover effect of the NEPC policy on the GEE of nonpilot cities. (iv) The adoption of the NEPC plays a pivotal role in advancing energy use and carbon emission efficiency. This paper expands the existing knowledge on the green development effects of the digital economy while offering valuable policy insights for building an "Inclusive Green Economy". [Display omitted] • The staggered differences-in-differences method is employed to examine the direct and spatial spillover effects of NEPC on cities' GEE in China. • This paper uses NEPC as a quasi-experiment for digital transformation. • NEPC significantly improves green economic efficiency by 2.6%. • Green structural transformation, innovation, and environmental concerns are main channels. • Positive spillover effect of NEPC on green economy efficiency in non-pilot cities. [ABSTRACT FROM AUTHOR]

It is still a controversial issue that whether ductility of metals under high strain rates is varying or not. This paper presents results of a series of electromagnetic ring expansion experiments to study on this problem. Three types of probes were used to measure experimental signals. As a result, the strain at the fracture time can be acquired through in-situ diagnosis. It is found that for a typical metal material, i.e. Cu TU1 under strain rates between 1 × 1 0 3 and 9 × 1 0 3 s−1, the ductility is varying and the fracture strain increases monotonically. These results are new solid evidence of rate-dependent ductility of metals. • The strain at the fracture time can be acquired through in-situ diagnosis. • Through introducing B-dot probes, together with a Rogowski probe and PDV (photonic Doppler velocimetry) probes, more experiment data (current, voltage and velocity signals) is acquired. • Results in this paper offer solid evidence for rate-dependent ductility of the selected metal. [ABSTRACT FROM AUTHOR]

Background: Knee osteoarthritis (KOA) is a common degenerative disease that causes pain, functional impairment, and reduced quality of life. Resistance training is considered as an effective approach to reduce the risk of muscle weakness in patients with KOA. Blood flow restriction (BFR) with low-load resistance training has better clinical outcomes than low-load resistance training alone. However, the degree of BFR which works more effectively with low-load resistance training has not been determined. The purpose of this study is to evaluate the effectiveness of different degrees of BFR with low-load resistance training in patients with KOA on pain, self-reported function, physical function performance, muscle strength, muscle thickness, and quality of life.Methods: This is a study protocol for a randomized, controlled trial with blinded participants. One hundred individuals will be indiscriminately assigned into the following groups: two training groups with a BFR at 40% and 80% limb occlusion pressure (LOP), a training group without BFR, and a health education group. The three intervention groups will perform strength training for the quadriceps muscles twice a week for 12 weeks, while the health education group will attend sessions once a week for 12 weeks. The primary outcome is pain. The secondary outcomes include self-reported function, physical function performance, muscle strength of the knee extensors, muscle mass of the quadriceps, quality of life, and adverse events. Intention-to-treat analysis will be conducted for individuals who withdraw during the trial.Discussion: Previous studies have shown that BFR with low-load resistance training is more effective than low-load resistance training alone; however, a high degree of BFR may cause discomfort during training. If a 40% LOP for BFR could produce similar clinical outcomes as an 80% LOP for BFR, resistance training with a low degree of BFR can be chosen for patients with KOA who are unbearable for a high degree of BFR.Trial Registration: Chinese Clinical Trial Registry ChiCTR2000037859 ( http://www.chictr.org.cn/edit.aspx?pid=59956&htm=4 ). Registered on 2 September 2020. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the genomic epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in China to identify predominant lineages and their associations with clinical data and antimicrobial resistance profiles. We performed a national prevalence study of patients with S. aureus infections in 22 tertiary hospitals in China from 2015 to 2017. Clinical data from patients and the antimicrobial phenotypes were collected for each isolate. Genome sequencing was performed on a proportion of isolates and a phylogenetic analysis was undertaken. Genotypic and phenotypic β-lactam susceptibilities were compared. A total of 1900 patients with S. aureus infections were included, of which 40% involved MRSA. Community-associated MRSA (CA-MRSA) infections were 24% of the total isolates. Genomic data showed that more than three-quarters of the MRSA were from three dominant lineages CC239 (25%, 116/471), CC5 (21%, 96/471) and CC59 (33%, 154/471) with CC59 accounting for more than half of the CA-MRSA isolates. Penicillin susceptibility genomic features were observed in 53% (251/470) of MRSA, including almost all of the CC59 (152/154) lineage, and 96% (242/251) of these isolates demonstrated in vitro susceptibility to penicillin or amoxicillin combined with clavulanic acid. Phylogenetic analysis indicated that the CC59 lineage can be divided into six lineages with all Asian CC59 isolates likely arising from an ancestral Mainland China lineage. This study showed a high prevalence of CA-MRSA in China, largely due to the widespread presence of CC59. As almost all isolates in this lineage possess genetic variants leading to increased β-lactam susceptibility, we suggest that to improve antibiotic stewardship combinations of penicillins and β-lactamase inhibitors should be included in the antibiotic susceptibility testing panels used to inform treatment decisions and research undertaken on this combination therapy. [ABSTRACT FROM AUTHOR]

Pectin degradation in the cell walls and middle lamella greatly affects the texture and the quality of the fruit including the taste and storage time. This directly affects its acceptability, supply to the consumer market, and economic benefits. It is therefore essential to establish the relationship between the chemical changes of pectin and the texture of the fruit to improve its preservation. This study was designed to evaluate the degradation of pectin in the peels of Tarocco blood orange and the textural changes during postharvest storage and further investigate their relationship over the study period. The texture of the fruit was characterized using the texture profile analyzer and the degradation of pectin was investigated by testing the content of the pectin, degree of esterification, and galacturonic acid content. The physicochemical properties, such as weight loss, moisture content, and anthocyanin content were also measured. Furthermore, the structural changes of the pectin were analyzed by molecular weight determination and FTIR test. The results showed that the Mw of pectin decreased from 568.05 kDa to 362.55 kDa, with a 42.1% decline in pectin content for storing for 63 d. The gradual solubilization, depolymerization, and de-esterification of the pectin consequently led to the decline in the textual properties of the fruit during postharvest storage. This can be applied and lead to improvements in quality control and process design in the food industry and the marketplace for the fruit during storage and preservation. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the relationship between kinesin-like family 6 (KIF6) polymorphisms and hypertension in a northeast Chinese cohort. In this study, two single nucleotide polymorphisms of KIF6 (rs20456 and rs6930913) and their haplotype were analyzed in 382 hypertension patients and 378 controls with SHEsis analysis platform, and the gene-environmental interactions were evaluated with logistic regression analysis. After adjusting for confounding factors, significantly lower risk of hypertension was observed in participants with genotype TC (0.416 (CI 0.299–0.578), p < 0.001) and CC (0.577 (0.389–0.857), p = 0.007) of rs20456 compared with TT. For rs6930913, allele T (0.522 (0.386–0.704), p < 0.001), genotype TT (0.325 (0.205–0.515), p < 0.001), and genotype CT (0.513 (0.379–0.693), p < 0.001) were significantly associated with lower risk of hypertension than allele C and CC genotype, respectively. Gene-environment analyses confirmed the significant influence on hypertension by the interactions between genotypes distribution in rs20456 (CT: p = 0.036 , TT: p = 0.022) and smoking status. No interactions were found between smoking and rs6930913, except those with dominant or recessive genetic models (both P s = 0.006). There were no interactions between KIF6 and overweight (all P s > 0.05). Haplotype analyses showed that CC (p = 0.005) and TC (p = 0.001) of rs20456 and rs6930913 were significantly associated with a statistically increased risk of hypertension. The false-positive report probability (FPRP) analysis was used to verify significant findings. In conclusions, KIF6 might affect the susceptibility of hypertension. The allele C (rs20456) and allele T (rs690913) were inclined to protect individuals from hypertension both in genotype and haplotype analyses. [ABSTRACT FROM AUTHOR]

[Display omitted] Alzheimer's disease (AD) is a progressive brain disorder, and one of the most common causes of dementia and amnesia. Due to the complex pathogenesis of AD, the underlying mechanisms remain unclear. Although scientists have made increasing efforts to develop drugs for AD, no effective therapeutic agents have been found. Natural products and their constituents have shown promise for treating neurodegenerative diseases, including AD. Thus, in-depth study of medical plants, and the main active ingredients thereof against AD, is necessary to devise therapeutic agents. In this study, N2a/APP cells and SAMP8 mice were employed as in vitro and in vivo models of AD. Multiple molecular biological methods were used to investigate the potential therapeutic actions of oxyphylla A, and the underlying mechanisms. Results showed that oxyphylla A, a novel compound extracted from Alpinia oxyphylla, could reduce the expression levels of amyloid precursor protein (APP) and amyloid beta (Aβ) proteins, and attenuate cognitive decline in SAMP8 mice. Further investigation of the underlying mechanisms showed that oxyphylla A exerted an antioxidative effect through the Akt-GSK3β and Nrf2-Keap1-HO-1 pathways. Conclusions. Taken together, our results suggest a new horizon for the discovery of therapeutic agents for AD. [ABSTRACT FROM AUTHOR]

Background: Canine distemper virus (CDV) infection of ferrets, dogs, and giant pandas causes an acute systemic disease involving multiple organ systems, including the respiratory tract, lymphoid system, and central nervous system. In this study, we tested a new candidate CDV vaccine-CDV nanoparticles-based on hemagglutinin protein. Methods: The nanoparticles were generated from conformation-stabilized CDV hemagglutinin tetramers. Immune responses against CDV were evaluated in mice. Immunization was initiated 6 weeks after birth and boosted two times with 4-week intervals. The blood and mucosal samples were collected 2 weeks after each immunization. Results: Vaccination with CDV nanoparticles elicited high levels of IgG antibody titers in mice (approximately sevenfold to eightfold higher than that obtained with soluble CDV H protein) and mucosal immune responses and developed increased CDV-specific neutralizing antibody. The mice that received nanoparticles showed significantly higher IFN-γ- and IL-4-secreting cell population in the spleen and lymph node compared with mice immunized with soluble H protein. The co-stimulatory molecular expression of CD80 and CD86 on the surface of DCs was also upregulated. Conclusion: The results demonstrate that self-assembly into nanoparticles can increase the immunogenicity of vaccine antigens, and nanoparticles assembled from conformation-stabilized CDV H protein can serve as a new CDV vaccine. [ABSTRACT FROM AUTHOR]

Objective: Physical training (PT, e.g., Tai Chi and strength training) has been demonstrated to improve balance control and prevent falls. Recently, exergame intervention (EI) has emerged to prevent falls by enhancing both physical and cognitive functions in older adults. Therefore, we aim to quantitatively assess and compare the effects of PT and EI on the performance of balance control and fall prevention in healthy older adults via meta-analysis.Methods: A search strategy based on the PICOS principle was used to find the publication in the databases of PubMed, EMBASE, Web of Science, Cochrane Library, and MEDLINE. The quality and risk of bias in the studies were independently assessed by two researchers.Results: Twenty studies consisting of 845 participants were included. Results suggested that as compared to PT, EI induced greater improvement in postural control (sway path length, SMD = - 0.66, 95% CI - 0.91 to - 0.41, P < 0.001, I2 = 0%; sway speed, SMD = - 0.49, 95% CI - 0.71 to - 0.27, P < 0.001, I2 = 42%) and dynamic balance (SMD = - 0.19, 95% CI - 0.35 to - 0.03, P = 0.02, I2 = 0%) in healthy older adults. The EI with 90-119 min/week for more than 8-week significantly reduced falls. Subgroup analyses revealed that exergames, which were designed by the two principles of repeatedly performing diversified tasks and gradually increase the difficulty of the task, induced significant effects in improving balance control and falls prevention respectively (P = 0.03, P = 0.009). In addition, intervention that combines EI and PT induced significant improvement in postural control (P = 0.003).Conclusion: The exergame intervention, especially the combination of EI and PT, is a promising strategy to improve balance control and reduce falls in healthy older adults. Future studies with rigorous design, larger sample size, and follow-up assessments are needed to further assess the effectiveness of diverse exergame interventions in fall prevention and to quantify the "dose-effect" relationship, as well as the carry-over effect of such intervention, which will ultimately help optimize the rehabilitative strategies to improve balance control and prevent falls. [ABSTRACT FROM AUTHOR]

Background: Proteostasis unbalance and mitochondrial dysfunction are two hallmarks of aging. While the chaperone folds and activates its clients, it is the cochaperone that determines the specificity of the clients. Ids2 is an HSP90's cochaperone controlling mitochondrial functions, but no in vivo clients of Ids2 have been reported yet. Results: We performed a screen of the databases of HSP90 physical interactors, mitochondrial components, and mutants with respiratory defect, and identified Atp3, a subunit of the complex V ATP synthase, as a client of Ids2. Deletion of IDS2 destabilizes Atp3, and an α-helix at the middle region of Ids2 recruits Atp3 to the folding system. Shortage of Ids2 or Atp3 leads to the loss of mitochondrial DNA. The intermembrane space protease Yme1 is critical to maintaining the Atp3 protein level. Moreover, Ids2 is highly induced when cells carry out oxidative respiration. Conclusions: These findings discover a cochaperone essentially for maintaining the stability of mitochondrial DNA and the proteostasis of the electron transport chain—crosstalk between two hallmarks of aging. [ABSTRACT FROM AUTHOR]

Background: The nursing education system has evolved with an increased emphasis on student-centred education, such as implementing flipped classroom pedagogy. Given the promising positive educational outcomes, the trend of using flipped classroom pedagogy has become increasingly popular in undergraduate nursing education. However, little is known about how these flipped classroom methods impact on nursing educational practices in limited-resource settings situated in South Asia. Objective: To assess the feasibility of implementing flipped classroom pedagogy in undergraduate nursing education from the nursing students' perspective. Methods: This mixed-methods study employed a quantitative survey and six focus group discussions conducted in three state universities in Sri Lanka. The Nursing Students' Readiness for Flipped Classroom (NSR-FC) questionnaire was used to collect quantitative data. The semi-structured focus group discussions were conducted by using 18 reflective and open-ended questions. Descriptive statistics and multivariate analysis of variance methods were employed when analysing quantitative data. An inductive thematic analysis approach was used to summarize the focus group discussions. Results: The questionnaire survey revealed that nursing students reported high levels of personal, technical, and pedagogical readiness across all three universities, while environmental readiness was perceived as low. The inductive thematic analysis identified three themes, namely: enablers, challenges, and benefits. Specifically, nursing students valued the student-centred approach. They were ready to utilize their own devices to overcome limited technological provision; however, a short training session about how to engage in the flipped classroom was desirable. Also, their exposure to basic educational technology was perceived as adequate and they were aware of the positive outcomes of flipped classroom pedagogy. Conclusion: Nursing students were ready to enrol in a flipped classroom programme. The provision of technological resources in the education environment was identified as a great challenge for flipped classroom implementation. Overall, the findings indicate there are promising feasibilities for the flipped classroom implementation. [ABSTRACT FROM AUTHOR]

In this paper, we investigate widely-linear channel estimation and data detection for the uplink of the massive multiple-input multiple-output (MIMO) with in-phase or quadrature-phase imbalance (IQI). We firstly investigate widely-linear minimum mean square error (WL-MMSE) estimation for the effective channel which is the product of the IQI coefficients and the wireless channel. We reuse pilots among different user terminals (UTs) to reduce pilot overhead and derive a lower bound of the estimation MSE. Based on the optimal condition under which the lower bound is achieved, we show that if we assign the same pilot for the UTs of which the covariance matrices are orthogonal, the pilot interference does not affect the MSE performance. Then according to the obtained estimates of the effective channel, we further propose WL-MMSE data detection that is robust to the estimation error. The proposed widely-linear approach can cope with the IQI and multi-user interference jointly. With some results of operator-valued free probability theory, we derive an asymptotic deterministic equivalent for the ergodic achievable sum rate of the proposed robust WL-MMSE data detection. The performance of the proposed widely-linear processing approach is verified by the numerical results. [ABSTRACT FROM AUTHOR]

• The principle of difference information and the principle of minimum information are discussed. • The proposed method can deal with the environment problem in other regions. • The unequal adjacent accumulation multivariate grey model is used to forecast the public concern about air pollution. In grey theory, the principle of difference information holds that difference is information. To mine the difference information between data, the unequal accumulation is proposed in this paper. The unequal accumulation reduces the loss of difference information and improves the forecasting performance of the grey model. Based on the unequal accumulation, the unequal adjacent discrete multivariable grey model is proposed. According to the comparison with other models, the proposed model has good forecast performance and algorithm efficiency. To further prove the practical significance of the model, it is used to predict the public concern about air pollution in three cities of China. The results show that the public concern about air pollution in cities with different air pollution conditions is quite different. Environmental protection departments could pay attention to the public concern about air pollution to better control air pollution. [ABSTRACT FROM AUTHOR]

Drug resistance is a major hurdle for the effectiveness of tamoxifen (TAM) to provide clinical benefit. Therefore, it is essential to identify a sensitizer that could be used to improve TAM efficacy in treating TAM‐resistant breast cancer. Here, we investigated the ability of baicalein to reverse TAM resistance. We found that baicalein increased the efficacy of TAM in inhibiting proliferation and inducing apoptosis of TAM‐resistant cells. It also enhanced the TAM‐induced growth reduction of resistant cells from NOD/SCID mouse mammary fat pads, without causing obvious systemic toxicity. Analyses using the CellMiner tool and the Kaplan–Meier plotter database showed that HIF‐1α expression was inversely correlated with TAM therapeutic response in NCI‐60 cancer cells and breast cancer patients. HIF‐1α expression was increased in TAM‐resistant cells due to an increase in mRNA levels and reduced ubiquitin‐mediated degradation. Baicalein reduced HIF‐1α expression by promoting its interaction with PHD2 and pVHL, thus facilitating ubiquitin ligase‐mediated proteasomal degradation and thereby suppressing the nuclear translocation, binding to the hypoxia‐response element, and transcriptional activity of HIF‐1α. As a result, baicalein downregulated aerobic glycolysis by restricting glucose uptake, lactate production, ATP generation, lactate/pyruvate ratio and expression of HIF‐1α‐targeted glycolytic genes, thereby enhancing the antiproliferative efficacy of TAM. Furthermore, baicalein interfered with HIF‐1α inhibition of mitochondrial biosynthesis, which increased mitochondrial DNA content and mitochondrial numbers, restored the generation of reactive oxygen species in mitochondria, and thus enhanced the TAM‐induced mitochondrial apoptotic pathway. The HIF‐1α stabilizer dimethyloxallyl glycine prevented the baicalein‐induced downregulation of glycolysis and mitochondrial biosynthesis and reduced the effects of baicalein on reversing TAM resistance. Our results indicate that baicalein is a promising candidate to help overcome TAM resistance by sensitizing resistant cells to TAM‐induced growth inhibition and apoptosis. The mechanism underlying the effects of baicalein consists of inhibition of HIF‐1α–mediated aerobic glycolysis and mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Background: Low back pain during pregnancy affects the normal daily activities of pregnant women to a certain extent. Current studies have shown that Kinesio Taping (KT) may be a treatment for low back pain during pregnancy, but there is still a lack of key evidence. The purpose of this study is to evaluate the efficacy and safety of KT in the treatment of low back pain during pregnancy.Methods: PubMed, Web of Science, The Cochrane Library, Scopus, Embase, Wanfang Data, CNKI, and VIP databases were searched to collect randomized controlled trials (RCTs) of the efficacy of KT intervention on low back pain in women during pregnancy. The retrieval time limit is from the establishment of the database to April 2021. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias in the included studies. Meta-analysis was performed using RevMan5.3 software.Results: A total of 7 RCTs were included, including 444 patients. Meta-analysis results showed that: Compared with the control group, KT intervention could significantly improve low back pain and dysfunction, VAS score (- 1.62, 95%CI - 2.08 to - 1.16, P < 0.00001, I2 = 77%), RMDQ score (- 1.00, 95%CI - 1.54 to - 0.46, P = 0.0003, I2 = 80%); The results of the meta-analysis of the subgroup showed that compared with the control group, the KT intervention was less than or equal to 1 week, and the waist pain and dysfunction were improved, with statistically significant differences. The difference in the improvement of low back pain was statistically significant after KT intervention for more than 1 week, but there was no statistically significant difference in RMDQ score (- 1.25, 95%CI - 2.66 to 0.15, P = 0.08, I2 =77%). Compared with the control group, KT intervention improved low back pain in the second and third trimesters, and the difference was statistically significant.Conclusion: KT has a positive effect on the improvement of low back pain during pregnancy, KT intervention can significantly improve pregnant women's low back pain and dysfunction problems, improve the quality of life. It is suggested that future research should focus on the prevention and treatment of low back pain during pregnancy to provide more research data for improving women's health. [ABSTRACT FROM AUTHOR]

In low-frequency vibration-assisted drilling (LFVAD) of CFRP/Ti6Al4V stacks, owing to the different mechanical and thermal performances of the involved carbon fiber–reinforced plastic (CFRP) composite and Ti6Al4V alloy, the short tool life of commonly used carbide (WC) tools and rapidly deteriorated machining quality are the major problems. This paper aims to explore whether the polycrystalline diamond (PCD) tool can achieve a competitive effect on drilling CFRP/Ti6Al4V stacks compared with previous CFRP drilling studies. To avoid the frequent occurrence of chisel edge fracture in LFVAD of Ti6Al4V alloy, a model of plowing behavior is established and parametric experiments based on it are performed with both PCD and WC drills. It is found that the periodically dynamic force is the major factor causing the chisel edge fracture of the PCD drill, which can be alleviated by reducing the feed rate. Besides, by using PCD drills instead of WC drills in Ti6Al4V drilling, the exit burr height, drilling diameter deviation, and surface roughness value are reduced under each given parameter. Finally, PCD and WC drill bits are used to perform a wear test on the CFRP/Ti6Al4Vstacks under optimized parameters. The PCD drill achieves superior performance, including lower wear rate, better hole quality, and higher consistency. The experiments discussed in this paper provide some suggestions for selecting tools and cutting parameters when drilling CFRP/Ti6Al4V stacks. [ABSTRACT FROM AUTHOR]

Objective. This study tends to assess the dose-dependent effects of spironolactone on TGF-β1 expression, atrial fibrosis, and the vulnerability to atrial fibrillation in spontaneously hypertensive rats (SHRs) and tries to clarify the association of atrial fibrosis with the vulnerability to atrial fibrillation. Methods. Forty 20-week-old male SHRs were randomly divided into 4 groups (10 rats per group): 3 spironolactone groups were lower-dose group (10 mg·kg−1·d−1, dissolved in 2 ml saline solution, group SL), medium-dose group (40 mg·kg−1·d−1, dissolved in 2 ml saline solution, group SM), higher-dose group (80 mg·kg−1·d−1, dissolved in 2 ml saline solution, group SH) and one hypertension group (2 ml saline solution for stomach gavage, group H). Ten matched homologous WKY rats were set as the control group (group C). After 7 weeks of gavage, a multiple electroconductive physiological recorder was used to detect atrial electrical parameters, including P-wave duration, PR interval, and atrial effective refractory period (AERP), the inducibility, and duration of atrial fibrillation. HE staining was used to determine myocardial cell size. Masson staining was used to detect the deposition of the interstitial collagen fibers in atrial muscle. The expression of TGF-β1 was detected by immunohistochemistry and western blot. Results. Compared with group C, the myocardial cell size, atrial fibrosis, TGF-β1 expression, P-wave duration, PR interval, AERP, inducibility, and duration of atrial fibrillation in group H were conspicuously increased (p < 0.05); compared with group H, there was no significant difference in the myocardial cell size, atrial fibrosis, TGF-β1 expression, and electrophysiological indexes in group SH upon spironolactone intervention (p > 0.05); compared with group H, the myocardial cell size, atrial fibrosis, the expression of TGF-β1, P-wave duration, PR interval, the inducibility, and duration of atrial fibrillation in the group SL and group SM were all decreased (p < 0.05); compared with group SM, the effect in the group SL was more prominent (p < 0.01). Conclusion. Hypertension can lead to cardiomyocyte hypertrophy, deposition of interstitial fibrosis in myocardial tissue, and an increase in the vulnerability to atrial fibrillation. Spironolactone showed a certain dose-dependent effect in SHRs. Lower-dose spironolactone was superior to higher-dose spironolactone in the aspect of reducing hypertensive atrial fibrosis and TGF-β1 expression, as well as preventing the occurrence of atrial fibrillation. [ABSTRACT FROM AUTHOR]

Background: Since interferon regulatory factor (IRF) family functions in immune response to viral infection, its role in colorectal cancer (CRC) has not been inspected before. This study tries to investigate members of IRF family using bioinformatics approaches in aspect of differential expressions, biological function, tumor immune infiltration and clinical prognostic value for patients with CRC.Methods: Transcriptome profiles data, somatic mutations and clinical information of CRC were obtained from COAD/READ dataset of The Cancer Genome Atlas (TCGA) as a training set. Gene expression data (GSE17536 and GSE39582) were downloaded from the Gene Expression Omnibus as a validating set. A random forest algorithm was used to score the risk for every case. Analyzing gene and function enrichment, constructing protein-protein interaction and noncoding RNA network, identifying hub-gene, characterizing tumor immune infiltration, evaluating differences in tumor mutational burden (TMB) and sensitivity to chemotherapeutics or immunotherapy were performed by a series of online tools and R packages. Immunohistochemical (IHC) examinations were carried out validation in tissue samples.Results: Principal-component analysis (PCA) suggested that the transcript expression levels of nine members of IRF family differed between normal colorectum and CRC. The risk score constructed by IRF family not only acted as an independent factor for predicting survival in CRC patients with different biological processes, signaling pathways and TMB, but also indicated different immunotherapy response with diverse immune and stromal cells infiltration. IRF3 and IRF7 were upregulated in CRC and suggested a shorter survival time in patients with CRC. Differentially expressed members of IRF family exhibited varying degrees of immune cell infiltration. IHC analysis showed a positive association between IRF3 and IRF7 expression and tumor-infiltrating immune cells, including CD4+ T cell and CD68+ macrophages.Conclusions: On account of differential expression, IRF family members can help to predict both response to immunotherapy and clinical prognosis of patients with CRC. Our bioinformatic investigation not only gives a preliminary picture of the genetic features as well as tumor microenvironment, but it may provide a clue for further experimental exploration and verification on IRF family members in CRC. [ABSTRACT FROM AUTHOR]

For POL-EDM tumors, leukocyte infiltration was comparable to that in POL-WT tumors, whereas CD8+ T-cell infiltration was significantly higher than that in POL-WT tumors. After excluding hypermutant tumors, leukocyte infiltration and CD8+ T-cell infiltration in POL-non-EDM tumors (but not POL-EDM tumors, probably due to the limited sample size) remained higher than those in POL-WT tumors (Figure 4E,F). To the Editor: With the development of immunotherapy, cancer treatment has stepped into a new era.1 Though POLE/POLD1 mutation (POL-MUT) have been proven to be a promising marker in ICI treatment,2-5 the predictive value of different types of POL-MUTs has yet to be fully investigated. Despite the higher neoantigen burden in POL-EDM tumors, neither leukocyte infiltration nor CD8+ T-cell infiltration was found to be different between POL-EDM tumors and POL-non-EDM tumors (Figure 4C,D). [Extracted from the article]

Purpose: To observe the effect of demodex infection on the ocular surface changes of patients with meibomian gland dysfunction (MGD) and analyze the correlation between the number of demodex and the changes of the ocular surface.Methods: Hundred patients with MGD aged 18-70 years who visited the dry eye center of Shanghai Aier Eye Hospital were recruited. All patients were examined with in vivo confocal microscopy to quantify the demodex and divided them into two groups (demodex negative group and demodex positive group) according to the number of demodex mites. The subjects underwent questionnaires of ocular surface disease index (OSDI) and a series of examinations. Parameters including the OSDI score, fluorescein tear film break-up time (FBUT), meibum quality, meibum gland expressibility, meibomian gland dropout (MG dropout), and ocular redness were recorded and compared between the two groups. The correlation between the number of demodex and the ocular surface changes was further analyzed.Results: Among 100 patients, 51 were positive for demodex. The demodex-positive group showed significantly increased scores of OSDI (24.41 ± 3.43 vs 20.98 ± 2.31, P = 0.00), ocular redness score (1.38 ± 0.46 vs 1.00 ± 0.30, P = 0.00), and MG dropout (3.00 ± 1.13 vs 2.18 ± 0.64, P = 0.00) and decreased FBUT (6.40 ± 1.63 vs 6.54 ± 1.83, P = 0.00), compared to the demodex-negative group. A significant correlation was noted between the number of demodex and OSDI, ocular redness, and FBUT.Conclusion: : Ocular demodex infestation might play a role in the ocular surface discomfort, inflammation, and meibomian gland dropout in MGD patients. It is necessary to pay attention to the examination and treatment of demodex mite in patients with MGD. [ABSTRACT FROM AUTHOR]

Introduction: Patients with knee osteoarthritis (KOA) often complain about clinical symptoms affected by weather-related factors. The purpose of the present study was to use cross-sectional analysis to determine whether weather sensitivity was associated with clinical symptoms, as well as structure abnormalities, in KOA patients. Methods: Data from 80 participants were obtained from the Feng Hans Shi Effects on OA (FHS) study, an OA cohort study initiated in China in 2015. The weather sensitivity of each participant was determined by a self-reported questionnaire. The following measurements were used to assess clinical outcomes: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for symptoms, and semi-quantitative Whole-Organ Magnetic Resonance Imaging Score (WORMS) for cartilage defects and marrow abnormalities of magnetic resonance imaging (MRI). Chi-square with Cochran–Armitage test for trend and regression analysis were used to evaluate the associations between weather sensitivity and WOMAC and WORMS of KOA patients. Results: Most of the KOA participants (57.5%) perceived the weather as affecting their knee-joint clinical symptoms. After adjusting for age, gender, and body mass index (BMI), weather sensitivity was not only associated with knee pain [OR = 3.3 (95% CI 1.1, 9.9), P = 0.032], dysfunction [OR = 5.5 (95% CI 1.8, 16.8), P = 0.003], and overall clinical symptoms [OR = 3.3 (95% CI 1.1, 10.2), P = 0.034], but also associated with cartilage defect [OR = 3.1 (95% CI 1.1, 8.5), P = 0.027] and marrow abnormality [OR = 3.0 (95% CI 1.1, 8.1), P = 0.029]. Conclusions: In KOA patients, weather sensitivity was associated with clinical symptoms and structural abnormalities. Future longitudinal study is warranted for the causal relationship. Infographic: [ABSTRACT FROM AUTHOR]

Background: Hypoxic tumor microenvironment (TME) promotes tumor metastasis and drug resistance, leading to low efficiency of cancer chemotherapy. The development of targeted agents or multi-target therapies regulating hypoxic microenvironment is an important approach to overcome drug resistance and metastasis. Methods: In this study, chitosan oligosaccharide (COS)-coated and sialic acid (SA) receptor-targeted nano-micelles were prepared using film dispersion method to co-deliver cisplatin (CDDP) and nitric oxide (NO) (denoted as CTP/CDDP). In addition, we explored the mechanisms by which NO reversed CDDP resistance as well as enhanced anti-metastatic efficacy in hypoxic cancer cells. Results: Because of the different affinities of COS and SA to phenylboronic acid (PBA) under different pH regimes, CTP/CDDP micelles with intelligent targeting property increased cellular uptake of CDDP and enhanced cytotoxicity to tumors, but reduced systemic toxicity to normal organs or tissues. In addition, CTP/CDDP showed stimulus-responsive release in TME. In terms of anti-tumor mechanism, CTP/CDDP reduced CDDP efflux and inhibited epithelial-mesenchymal transition (EMT) process of tumor by down-regulating hypoxia-inducible factor-1α (HIF-1α), glutathione (GSH), multidrug resistance-associated protein 2 (MRP2) and matrix metalloproteinase 9 (MMP9) expression, thus reversing drug resistance and metastasis of hypoxic tumor cells. Conclusions: The designed micelles significantly enhanced anti-tumor effects both in vitro and in vivo. These results suggested that CTP/CDDP represented a promising strategy to treat resistance and metastatic tumors. [ABSTRACT FROM AUTHOR]

The growth and evolvement features of crack are of great significance to study the failure mechanism of rock mass and valuate the stability of the cavity. In this study, in order to obtain the mechanics parameters and external macroscopic crack propagation characteristics of red sandstone, triaxial compression tests were carried out. Based on the experimental results, a numerical model was established through the reasonable parameter calibration by the PFC3D software. The internal and external crack propagation processes of red sandstone under triaxial compression were simulated. Moreover, to verify the simulation results, the CT scanning and three-dimensional reconstruction technologies were used to observe the internal crack state of the specimens. The results showed that the internal crack failures occurred first at the end of the rock specimen. Then, the microcracks continued to accumulate and expand under the combined action of axial stress and confining pressure. The accumulated microcracks finally converged to form a macroscopic oblique shear failure. Based on the homogenizing treatment and reasonable parameter calibration, the internal and external crack expansion and evolution processes of the rock were simulated by the PFC3D model and the simulation results are consistent with the results obtained from the triaxial compression test and the CT scanning. The macro- and microfailure mode of crack propagation of the specimen deepens the understanding of rock failure mechanism. The PFC3D homogenization simulation method provides a new feasible method to study the macro- and microfailure mode of internal and external crack propagation of rock under compression. [ABSTRACT FROM AUTHOR]

Surface air temperature (Ta), as an important climate variable, has been used in a wide range of fields such as ecology, hydrology, climatology, epidemiology, and environmental science. However, ground measurements are limited by poor spatial representation and inconsistency, and reanalysis and meteorological forcing datasets suffer from coarse spatial resolution and inaccuracy. Previous studies using satellite data have mainly estimated Ta under clear-sky conditions or with limited temporal and spatial coverage. In this study, an all-sky daily mean land Ta product at a 1 km spatial resolution over mainland China for 2003–2019 has been generated mainly from the Moderate Resolution Imaging Spectroradiometer (MODIS) products and the Global Land Data Assimilation System (GLDAS) dataset. Three Ta estimation models based on random forest were trained using ground measurements from 2384 stations for three different clear-sky and cloudy-sky conditions. The random sample validation results showed that the R2 and root-mean-square error (RMSE) values of the three models ranged from 0.984 to 0.986 and from 1.342 to 1.440 K, respectively. We examined the spatiotemporal patterns and land cover type dependences of model accuracy. Two cross-validation (CV) strategies of leave-time-out (LTO) CV and leave-location-out (LLO) CV were also used to evaluate the models. Finally, we developed the all-sky Ta dataset from 2003 to 2009 and compared it with the China Land Data Assimilation System (CLDAS) dataset at a 0.0625 ∘ spatial resolution, the China Meteorological Forcing Data (CMFD) dataset at a 0.1 ∘ spatial resolution, and the GLDAS dataset at a 0.25 ∘ spatial resolution. Validation accuracy of our product in 2010 was significantly better than other datasets, with R2 and RMSE values of 0.992 and 1.010 K, respectively. In summary, the developed all-sky daily mean land Ta dataset has achieved satisfactory accuracy and high spatial resolution simultaneously, which fills the current dataset gap in this field and plays an important role in the studies of climate change and the hydrological cycle. This dataset is currently freely available at 10.5281/zenodo.4399453 (Chen et al., 2021b) and the University of Maryland (http://glass.umd.edu/Ta%5fChina/ , last access: 24 August 2021). A sub-dataset that covers Beijing generated from this dataset is also publicly available at 10.5281/zenodo.4405123 (Chen et al., 2021a). [ABSTRACT FROM AUTHOR]

Collagen-type I alpha 1 chain (COL1A1) and COL1A2 are abnormally expressed in intracranial aneurysm (IA), but their mechanism of action remains unclear. This study was performed to investigate the mechanism of COL1A1 and COL1A2 affecting the occurrence and rupture of IA. Quantitative real-time polymerase chain reaction was used to measure the expression of hsa-miR-513b-5p, COL1A1, COL1A2, TNF-α, IL-6, MMP2, MMP3, MMP9 and TIMP4 in patients with ruptured IA (RA) (n = 100), patients with un-ruptured IA (UA) (n = 100), and controls (n = 100). Then, human vascular smooth muscle cells (HASMCs) were cultured, and dual luciferase reporter assay was performed to analyse the targeting relationship between miR-513b-5p and COL1A1 or COL1A2. The effects of the miR-513b-5p mimic and inhibitor on the proliferation, apoptosis, and death of HASMC and the RIP1-RIP3-MLKL and matrix metalloproteinase pathways were also explored. The effect of silencing and over-expression of COL1A1 and COL1A2 on the role of miR-513b-5p were also evaluated. Finally, the effects of TNF-α on miR-513b-5p targeting COL1A1 and COL1A2 were tested. Compared with those in the control group, the serum mRNA levels of miR-513b-5p, IL-6 and TIMP4 were significantly decreased in the RA and UA groups, but COL1A1, COL1A2, TNF-α, IL-1β, MMP2, MMP3 and MMP9 were significantly increased (p < 0.05). Compared with those in the UA group, the expression of COL1A1, COL1A2, TNF-α, IL-1β and MMP9 was significantly up-regulated in the RA group (p < 0.05). Results from the luciferase reporter assay showed that COL1A1 and COL1A were the direct targets of miR-513b-5p. Further studies demonstrated that miR-513b-5p targeted COL1A1/2 to regulate the RIP1-RIP3-MLKL and MMP pathways, thereby enhancing cell death and apoptosis. Over-expression of COL1A1 or COL1A2, rather than silencing COL1A1/2, could improve the inhibitory effect of miR-513b-5p on cell activity by regulating the RIP1-RIP3-MLKL and MMP pathways. Furthermore, over-expression of miR-513b-5p and/or silencing COL1A1/2 inhibited the TNF-α-induced cell proliferation and enhanced the TNF-α-induced cell death and apoptosis. The mechanism may be related to the inhibition of collagen I and TIMP4 expression and promotion of the expression of RIP1, p-RIP1, p-RIP3, p-MLKL, MMP2 and MMP9. MiR-513b-5p targeted the inhibition of COL1A1/2 expression and affected HASMC viability and extracellular mechanism remodelling by regulating the RIP1-RIP3-MLKL and MMP pathways. This process might be involved in the formation and rupture of IA. [ABSTRACT FROM AUTHOR]

Background: We investigated the therapeutic effect of targeting extracellular vesicles (EVs) loaded with indocyanine green (ICG) and paclitaxel (PTX) on glioma. Methods: Raw264.7 cells were harvested to extract EVs for the preparation of ICG/PTX@RGE-EV by electroporation and click chemistry. We evaluated the success of modifying Neuropilin-1 targeting peptide (RGE) on the EV membrane of ICG/PTX@RGE-EV using super-resolution fluorescence microscopy and flow cytometry. Spectrophotometry and high performance liquid chromatography (HPLC) were implemented for qualitative and quantitative analysis of the ICG and PTX loaded in EVs. Photothermal properties of the vesicles were evaluated by exposing to 808-nm laser light. Western blot analysis, cell counting kit 8 (CCK-8), Calcein Acetoxymethyl Ester/propidium iodide (Calcein-AM/PI) staining, and flow cytometry were utilized for assessing effects of vesicle treatment on cellular behaviors. A nude mouse model bearing glioma was established to test the targeting ability and anti-tumor action of ICG/PTX@RGE-EV in vivo. Results: Under exposure to 808-nm laser light, ICG/PTX@RGE-EV showed good photothermal properties and promotion of PTX release from EVs. ICG/PTX@RGE-EV effectively targeted U251 cells, with activation of the Caspase-3 pathway and elevated apoptosis in U251 cells through chemotherapy combined with hyperthermia. The anti-tumor function of ICG/PTX@RGE-EV was confirmed in the glioma mice via increased accumulation of PTX in the ICG/PTX@RGE-EV group and an increased median survival of 48 days in the ICG/PTX@RGE-EV group as compared to 25 days in the PBS group. Conclusion: ICG/PTX@RGE-EV might actively target glioma to repress tumor growth by accelerating glioma cell apoptosis through combined chemotherapy-hyperthermia. [ABSTRACT FROM AUTHOR]

Noise overexposure leads to hair cell loss, synaptic ribbon reduction, and auditory nerve deterioration, resulting in transient or permanent hearing loss depending on the exposure severity. Oxidative stress, inflammation, calcium overload, glutamate excitotoxicity, and energy metabolism disturbance are the main contributors to noise-induced hearing loss (NIHL) up to now. Gene variations are also identified as NIHL related. Glucocorticoid is the only approved medication for NIHL treatment. New pharmaceuticals targeting oxidative stress, inflammation, or noise-induced neuropathy are emerging, highlighted by the nanoparticle-based drug delivery system. Given the complexity of the pathogenesis behind NIHL, deeper and more comprehensive studies still need to be fulfilled. [ABSTRACT FROM AUTHOR]

Background The secretion of organic solutes by the proximal tubules is an essential intrinsic kidney function. The degree to which secretory solute clearance corresponds with the glomerular filtration rate (GFR) and potential metabolic implications of net secretory clearance are largely unknown. Methods We evaluated 1240 participants with chronic kidney disease (CKD) from the multicenter Chronic Renal Insufficiency Cohort (CRIC) Study. We used targeted mass-spectrometry to quantify candidate secretory solutes in paired 24-h urine and plasma samples. CRIC study personnel measured GFR using 125I-iothalamate clearance (iGFR). We used correlation and linear regression to determine cross-sectional associations of secretory clearances with iGFR and common metabolic complications of CKD. Results Correlations between iGFR and secretory solute clearances ranged from ρ  = +0.30 for hippurate to ρ  = +0.58 for kynurenic acid. Lower net clearances of most secretory solutes were associated with higher serum concentrations of parathyroid hormone (PTH), triglycerides and uric acid. Each 50% lower kynurenic acid clearance was associated with a 21% higher serum PTH concentration [95% confidence interval (CI) 15–26%] and a 10% higher serum triglyceride concentration (95% CI 5–16%) after adjustment for iGFR, albuminuria and other potential confounders. Secretory solute clearances were not associated with statistically or clinically meaningful differences in serum calcium, phosphate, hemoglobin or bicarbonate concentrations. Conclusions Tubular secretory clearances are modestly correlated with measured GFR among adult patients with CKD. Lower net secretory clearances are associated with selected metabolic complications independent of GFR and albuminuria, suggesting potential clinical and biological relevance. [ABSTRACT FROM AUTHOR]

Background: Online health communities (OHCs), with a wealth of multi-source information exchange, have provided a convenient way for people with diabetes to actively participate in their self-management and have been widely used. Information exchange assists people with diabetes with health-related decisions to actively engage in their care, and reduce the occurrence of potential complications of diabetes. However, there has been relatively little research on the information exchange behaviors and their effect on health in professional online medical platforms-OHCs.Objective: Using a social exchange theory, this study focuses on two sources of information (doctors and people with diabetes) to investigate information exchange behaviors and consequences. Moreover, we also examine moderating effects of information price as patients need to pay prices for consulting with doctors to obtain medical information on OHCs.Methods: By using the Python program, a rich dataset contained 22,746 doctor-patient dialogues from December 2017 to December 2018 is collected from the biggest OHC in China. Then the logistic and ordinal regression models are used to get empirical results.Results: We found that first information sharing from doctors and other people with diabetes can promote their information sharing behavior. Second, the moderating effects of information price are heterogeneous and change with the exchange participants. Third, rich information exchange supports self-management of people with diabetes and improves their health status.Conclusion: This study is among the first that tests the information exchange behavior and consequence for diabetes in OHCs and examines the moderating effects of the information price. The present study produces several insights, which have implications for social exchange, patient behavior, online health communities, and information technology in diabetes self-management literature. [ABSTRACT FROM AUTHOR]