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Listeria monocytogenes, a zoonotic foodborne pathogen, presents a significant threat to global public health. Therefore, rapid and sensitive detection methods are crucial in mitigating the spread of L. monocytogenes induced diseases. This study introduced a loop-mediated isothermal amplification (LAMP) lyophilized powder detection reagent specifically designed for identifying Listeria monocytogenes. The reagent is user-friendly, quick, and can be easily transported and stored at room temperature. It exhibits no cross-reactivity with eight other types of bacteria and boasts a sensitivity of 101 CFU/mL. In a comparative study of 30 samples, the LAMP lyophilized powder detection reagent demonstrated higher sensitivity than the commercial Listeria monocytogenes qPCR detection kit. Additionally, the experimental time was reduced by approximately 30 min, making it highly suitable for rapid diagnosis. Preparation of lyophilized LAMP reagents may facilitate large-scale deployment, particularly in endemic areas or regions facing rapid outbreaks. This could greatly aid in controlling the transmission of pathogens, especially those transmitted through food. [ABSTRACT FROM AUTHOR]

We focused on the efflorescence induced microstructural evolution of ettringite-rich systems prepared with calcium aluminate cement (CAC) and anhydrite. The effects of anhydrite on the visible efflorescence, and the corresponding capillary absorption of CAC-anhydrite mortars were revealed. The composition and microstructure of efflorescence-causing substances were investigated by optical microscope, in-situ Raman spectroscopy, scanning electron microscope, energy dispersive spectrometer, thermogravimetric analysis, and differential scanning calorimetry, at multi-scales. Results indicate that, besides the calcium carbonate, ettringite is another main component of efflorescence-causing substances. Compared with the neat CAC mortars, the addition of anhydrite has a significant effect on the degree of efflorescence by acting on the composition of hydration products and pore structure. In addition, methods are proposed for the prevention of efflorescence of CAC-anhydrite binary system. [ABSTRACT FROM AUTHOR]

SMT-based model checkers, especially IC3-style ones, are currently the most effective techniques for verification of infinite state systems. They infer global inductive invariants via local reasoning about a single step of the transition relation of a system, while employing SMT-based procedures, such as interpolation, to mitigate the limitations of local reasoning and allow for better generalization. Unfortunately, these mitigations intertwine model checking with heuristics of the underlying SMT-solver, negatively affecting stability of model checking. In this paper, we propose to tackle the limitations of locality in a systematic manner. We introduce explicit global guidance into the local reasoning performed by IC3-style algorithms. To this end, we extend the SMT-IC3 paradigm with three novel rules, designed to mitigate fundamental sources of failure that stem from locality. We instantiate these rules for Linear Integer Arithmetic and Linear Rational Aritmetic and implement them on top of Spacer solver in Z3. Our empirical results show that GSpacer, Spacer extended with global guidance, is significantly more effective than both Spacer and sole global reasoning, and, furthermore, is insensitive to interpolation. [ABSTRACT FROM AUTHOR]

Obesity has become a global health problem. In recent years, the influence of dietary microbes in the obese population has attracted the attention of scholars. Our study aimed to investigate the link between live microbe intake and obesity in adults. Participants (aged over 20 years) for this study were from the 1999–2018 National Health and Nutrition Examination Survey (NHANES). Participants were categorised into low, medium and high dietary live microbe intake groups. Linear regression was used to analyse the link between live microbe intake and body mass index (BMI) and waist circumference (WC). Logistic regression was used to analyse the link between live microbe intake and obesity and abdominal obesity prevalence. Restricted cubic spline curves (RCS) were used to check whether there was a non-linear relationship between live microbe intake and obesity. A total of 42,749 participants were included in this study and the number of obese reached 15,463. We found that live microbe intake was negatively linked to BMI and WC. In models adjusted for all confounders, the high live microbe intake group had lower obesity (OR = 0.812, 95%CI: 0.754–0.873) and abdominal obesity prevalence (OR = 0.851, 95%CI: 0.785–0.923) than the lowest intake group. Upon further quantification of live microbe intake, we found similar results. RCS analyses showed that live microbe intake was nonlinearly negatively correlated with BMI, WC, obesity, and abdominal obesity prevalence (P for non-linearity < 0.05). This study preliminarily reveals a negative link between live microbe intake and obesity in adults. [ABSTRACT FROM AUTHOR]

In reality, people are often co-exposed to multiple heavy metals; however, current research has focused on the association between individual heavy metals and inflammation. Therefore, it is more relevant to explore the combined effects of multiple heavy metal exposure on inflammation. The study included data from the National Health and Nutrition Examination Survey (NHANES), 2011–2016. The systemic immune-inflammation index (SII) was used to reflect systemic immune-inflammation status. In this study, single variable models were used to assess the linear and non-linear relationships between single heavy metal exposures and SII. To analyze the combined effect of mixed heavy metals exposure on SII, we constructed three statistical models, including weighted quantile sum (WQS) regression, quantile-based g computation (qgcomp), and Bayesian kernel machine regression (BKMR). The single-exposure analysis found positive associations between multiple heavy metals and SII, while mercury in blood was negatively associated with SII, and U-shaped correlations were observed between blood lead, urine barium and strontium, and SII. In the WQS model, SII increased significantly with increasing concentrations of mixed heavy metals, while consistent results in the qgcomp model, but not statistically significant. In the BKMR model, exposure to heavy metal mixtures was positively associated with SII, with mercury, cadmium, and cobalt in urine contributing the most to the mixed exposure. In addition, synergistic and antagonistic effects between heavy metals on increasing SII were found in our study. In summary, our results reveal that combined exposure to multiple heavy metals is positively associated with SII in the US adults. [ABSTRACT FROM AUTHOR]

Myopia, a prevalent refractive error leading to visual impairment, presents a substantial global health challenge. Current preventive measures, including pharmaceutical interventions and optical corrections, require significant resources and a dedicated workforce. Digital healthcare technology, encompassing artificial intelligence (AI) and telemedicine, offers promising solutions by delivering scalable, portable, and dependable approaches. Inspired by the success of deep learning systems in ophthalmology, these digital health technologies can revolutionize myopia management, enhancing automation, scalability, and remote monitoring. In this comprehensive review, we explore the potential applications of digital healthcare technology in measuring, preventing, controlling, and managing myopia. We highlight specific focus areas, emphasize the advancements and benefits of digital healthcare, and discuss the challenges associated with the clinical implementation of digital devices and AI applications in myopia management. Realizing the full potential of digital technologies in myopia management necessitates addressing access barriers, seamless integration with digital healthcare systems, validation of their effectiveness, and fostering user engagement. While adoption challenges persist, harnessing digital healthcare solutions can lead to improved vision, reduced myopia-related difficulties, and overall enhanced eye health. As this field advances, it holds a promising future for individuals affected by myopia. [ABSTRACT FROM AUTHOR]

Developing efficient pH-universal hydrogen evolution reaction (HER) catalysts is critical in the field of water electrolysis, however, which is severely hampered by the sluggish kinetics in alkaline media. Herein, a ruthenium (Ru) incorporation induced vacancy engineering strategy is firstly proposed to precisely construct oxygen vacancy (VO)-riched cobalt-ruthenium metaphosphate (CRPO) for high-efficiency pH-universal HER. The VO modifies the electronic structure, improves the superficial hydrophilic and gas spillover capacity, it also reduces the coordination number of Ru atoms and regulates the coordination environment. Theoretical calculations indicate that Ru tends to adsorb H2O and H*, whereas VO tends to adsorb OH−, which greatly promotes the H2O adsorption and the dissociation of HO–H bond. Ultimately, CRPO-2 exhibits remarkable HER performance, the mass activity is about 18.34, 21.73, and 38.07 times higher than that of Pt/C in acidic, neutral, and alkaline media, respectively, at the same time maintain excellent stability. Our findings may pave a new avenue for the rational design of electrocatalysts toward pH-universal water electrolysis. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy is a critical treatment modality for nasopharyngeal carcinoma (NPC). However, the mechanisms underlying radiation resistance and tumour recurrence in NPC remain incompletely understood. Methods: Oxidised lipids were assessed through targeted metabolomics. Ferroptosis levels were evaluated using cell viability, clonogenic survival, lipid peroxidation, and transmission electron microscopy. We investigated the biological functions of glutathione S-transferase mu 3 (GSTM3) in cell lines and xenograft tumours. Co-immunoprecipitation, mass spectrometry, and immunofluorescence were conducted to explore the molecular mechanisms involving GSTM3. Immunohistochemistry was performed to investigate the clinical characteristics of GSTM3. Results: Ionising radiation (IR) promoted lipid peroxidation and induced ferroptosis in NPC cells. GSTM3 was upregulated following IR exposure and correlated with IR-induced ferroptosis, enhancing NPC radiosensitivity in vitro and in vivo. Mechanistically, GSTM3 stabilised ubiquitin-specific peptidase 14 (USP14), thereby inhibiting the ubiquitination and subsequent degradation of fatty acid synthase (FASN). Additionally, GSTM3 interacted with glutathione peroxidase 4 (GPX4) and suppressed GPX4 expression. Combining IR treatment with ferroptosis inducers synergistically improved NPC radiosensitivity and suppressed tumour growth. Notably, a decrease in GSTM3 abundance predicted tumour relapse and poor prognosis. Conclusions: Our findings elucidate the pivotal role of GSTM3 in IR-induced ferroptosis, offering strategies for the treatment of radiation-resistant or recurrent NPC. [ABSTRACT FROM AUTHOR]

As the third generation of fuel cells, solid oxide fuel cell (SOFC) provides a clean and low-pollution technology. Electrolyte material, which often plays a vital role in SOFC, has always been the focus and difficulty of research. Y-doped barium cerate-based proton conductor electrolyte, BaCe1–xYxO3–δ (x = 0, 0.05, 0.1, 0.15), were prepared using the nitrate-citrate-glycine combustion method. A series of tests and characterizations were performed to examine the structural, morphological, and electrical properties. X-ray diffraction (XRD) analysis proved that the BCY powders with pure cubic perovskite structure were formed after calcined at 1100 °C. SEM results showed that the BCY ceramics sintered at 1350 °C were dense and well-developed grains. The electrochemical performance of BCY proton conductor electrolyte was determined using the electrochemical impedance spectroscopy in dry air and wet air atmosphere at 400–800 °C. Results showed that Y-doped BaCeO3-based material had superior conductivity in air and the conductivity of proton conductor was significantly improved under wet air environment. Furthermore, the electrical conductivity of BCY samples was related to the amount of Y3+ doping. The conductivity in a water vapor environment achieved a maximal value of 0.039 S cm−1 at 800 °C when x = 0.15. So BaCe1–xYxO3-based materials can be used as a proton conductor electrolyte for SOFC in the medium temperature range. [ABSTRACT FROM AUTHOR]

Background: Centrosome amplification is a well-recognized oncogenic driver of tumor initiation and progression across a variety of malignancies and has been linked with tumor aggressiveness, metastasis, and adverse prognosis. Nevertheless, the significance of centrosome amplification in HCC is not well understood. Methods: The TCGA dataset was downloaded for centrosome amplification-related signature construction using the LASSO-penalized Cox regression algorithm, while the ICGC dataset was obtained for signature validation. Single-cell RNA sequencing from GSE149614 was analyzed to profile gene expression and the liver tumor niche. Results: A total of 134 centrosome amplification-related prognostic genes in HCC were detected and 6 key prognostic genes (SSX2IP, SPAG4, SAC3D1, NPM1, CSNK1D, and CEP55) among them were screened out to construct a signature with both high sensitivity and specificity in diagnosis and prognosis of HCC patients. The signature, as an independent factor, was associated with frequent recurrences, high mortality rates, advanced clinicopathologic features, and high vascular invasions. Moreover, the signature was intimately associated with cell cycle-related pathways and TP53 mutation profile, suggesting its underlying role in accelerating cell cycle progression and leading to liver cancer development. Meanwhile, the signature was also closely correlated with immunosuppressive cell infiltration and immune checkpoint expression, making it a vital immunosuppressive factor in the tumor microenvironment. Upon single-cell RNA sequencing, SSX2IP and SAC3D1 were found to be specially expressed in liver cancer stem-like cells, where they promoted cell cycle progression and hypoxia. Conclusions: This study provided a direct molecular link of centrosome amplification with clinical characteristics, tumor microenvironment, and clinical drug-response, highlighting the critical role of centrosome amplification in liver cancer development and therapy resistance, thereby providing valuable insights into prognostic prediction and therapeutic response of HCC. [ABSTRACT FROM AUTHOR]

Long noncoding RNA LINC00482 (LINC00482) is dysregulated in non-small cell lung cancer cells (NSCLC). Herein, this research examined the actions and specific mechanisms of LINC00482 in cisplatin (DDP) resistance in NSCLC. LINC00482 expression was assessed using RT-qPCR in clinical NSCLC tissues and cell lines. Knockdown and ectopic expression assays were conducted in A549 and HCC44 cells, followed by determination of cell proliferation with CCK-8 and clone formation assays, apoptosis with flow cytometry, and DDP sensitivity. The association between LINC00482, E2F1, and CLASRP was evaluated with dual-luciferase reporter, ChIP, and RIP assays. The role of LINC00482 in NSCLC was confirmed in nude mice. NSCLC tissues and cells had upregulated LINC00482 expression. LINC00482 was mainly localized in the cell nucleus, and LINC00482 recruited E2F1 to enhance CLASRP expression in NSCLC cells. LINC00482 knockdown enhanced the DDP sensitivity and apoptosis of NSCLC cells while reducing cell proliferation, which was negated by overexpressing CLASRP. LINC00482 knockdown restricted tumor growth and enhanced DDP sensitivity in NSCLC in vivo. LINC00482 silencing downregulated CLASRP through E2F1 to facilitate the sensitivity to DDP in NSCLC. [ABSTRACT FROM AUTHOR]

Shot peening is one of the most widely used surface strengthening processes. The shot peening process involves multiple process parameters, which have a complex and interdependent impact on the peening effects, including compressive residual stress distribution and surface roughness. Accurately predicting the influence of shot peening parameters on the shot peening effect is a tough challenge in the simulation. In this paper, a shot peening simulation model is developed to investigate the influence of peening process parameters. The model encompasses material, target surface, and shot stream modeling. A method is proposed to reconstruct target surface model based on real rough surface data obtained via confocal laser scanning microscope. Unlike similar surface models, such as the Gaussian model, the reconstructed surface model replicates the peaks and valleys of the target surface along with their exact locations. A random multiple-shot model incorporating the reconstructed surface with predefined target coverage is developed via Python in Abaqus. Experimental verification on TC4 titanium alloy targets validates the simulation accuracy. The effects of peening parameters (shot velocity, density, diameter, and initial surface roughness) on residual stress distribution and surface roughness are investigated via the established model. Results reveal the significant influence of shot velocity and the relatively minor impact of other parameters. Increasing the diameter, velocity, and density of the shots results in higher residual stress levels and surface roughness. Notably, excessive initial surface roughness leads to abnormal increases in surface compressive residual stress. [ABSTRACT FROM AUTHOR]

Assessing the effects of heavy metals (HMs) on kidney stone is often limited to analyzing individual metal exposures, with studies on the effects of exposure to mixtures of HMs being scarce. To comprehensively evaluate the relationship between exposure to mixed HMs and kidney stones, we analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2007–2016, which included 7809 adults. We used multiple statistical methods, including multiple logistic regression models, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp) and bayesian kernel machine regression (BKMR), to assess the association between single HM and mixed exposure to HMs and kidney stones. Firstly, in single exposure analysis, urinary cadmium (Cd) and cobalt (Co) demonstrated a positive association with the risk of kidney stones. Secondly, various other approaches consistently revealed that mixed exposure to HMs exhibited a positive association with kidney stone risk, primarily driven by Cd, Co, and barium (Ba) in urine, with these associations being particularly notable among the elderly population. Finally, both BKMR and survey-weighted generalized linear models consistently demonstrated a significant synergistic effect between urinary Co and urinary uranium (Ur) in elevating the risk of kidney stones. Overall, this study provides new epidemiological evidence that mixed exposure to HMs is associated with an increased risk of kidney stones. Further prospectively designed studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Melatonin is a functionally conserved broad-spectrum physiological regulator found in most biological organisms in nature. Enrichment of tomato fruit with melatonin not only enhances its agronomic traits but also provides extra health benefits. In this study, we elucidate the full melatonin biosynthesis pathway in tomato fruit by identifying biosynthesis-related genes that encode caffeic acid O-methyltransferase 2 (SlCOMT2) and N-acetyl-5-hydroxytryptamine-methyltransferases 5/7 (SlASMT5/7). We further reveal that red light supplementation significantly enhances the melatonin content in tomato fruit. This induction relies on the "serotonin—N-acetylserotonin—melatonin" biosynthesis route via the SlphyB2-SlPIF4-SlCOMT2 module. Based on the regulatory mechanism, we design a gene-editing strategy to target the binding motif of SlPIF4 in the promoter of SlCOMT2, which significantly enhances the production of melatonin in tomato fruit. Our study provides a good example of how the understanding of plant metabolic pathways responding to environmental factors can guide the engineering of health-promoting foods. Melatonin is a physiological regulator in many organisms including plants. Here, the authors demonstrate a molecular mechanism of red light-induced melatonin biosynthesis in tomato fruit which could guide the engineering of melatonin-enriched tomatoes. [ABSTRACT FROM AUTHOR]

Ferroptosis is a recently recognized form of regulated cell death, characterized by iron-dependent accumulation of lipid peroxidation. Ample evidence has depicted that ferroptosis plays an essential role in the cause or consequence of human diseases, including cancer, neurodegenerative disease and acute kidney injury. However, the exact role and underlying mechanism of ferroptosis in fibrotic kidney remain unknown. Acyl-CoA synthetase long-chain family member 4 (ACSL4) has been demonstrated as an essential component in ferroptosis execution by shaping lipid composition. In this study, we aim to discuss the potential role and underlying mechanism of ACSL4-mediated ferroptosis of tubular epithelial cells (TECs) during renal fibrosis. The unbiased gene expression studies showed that ACSL4 expression was tightly associated with decreased renal function and the progression of renal fibrosis. To explore the role of ACSL4 in fibrotic kidney, ACSL4 specific inhibitor rosiglitazone (ROSI) was used to disturb the high expression of ACSL4 in TECs induced by TGF-β, unilateral ureteral obstruction (UUO) and fatty acid (FA)-modeled mice in vivo, and ACSL4 siRNA was used to knockdown ACSL4 in TGF-β-induced HK2 cells in vitro. The results demonstrated that inhibition and knockdown of ACSL4 effectively attenuated the occurrence of ferroptosis in TECs and alleviated the interstitial fibrotic response. In addition, the expression of various profibrotic cytokines all decreased after ROSI-treated in vivo and in vitro. Further investigation showed that inhibition of ACSL4 obviously attenuates the progression of renal fibrosis by reducing the proferroptotic precursors arachidonic acid- and adrenic acid- containing phosphatidylethanolamine (AA-PE and AdA-PE). In conclusion, these results suggest ACSL4 is essential for tubular ferroptotic death during kidney fibrosis development and ACSL4 inhibition is a viable therapeutic approach to preventing fibrotic kidney diseases. Dai et al. identified that ACSL4 in kidney fibrosis increase ferroptotic precursors of tubular epithelial cells by modulating arachidonic acid (AA) and adrenic acid (AdA) of polyunsaturated fatty acids (PUFA). Inhibition of ferroptosis by targeting ACSL4 rescued tubular epithelial cells ferroptosis and alleviated kidney fibrosis, which provide more potential therapeutic approaches. [ABSTRACT FROM AUTHOR]

Carbamazepine (CBZ, an antiepileptic) is metabolized by multiple CYP enzymes to its epoxide and hydroxides; however, whether it is genotoxic remains unclear. In this study, molecular docking (CBZ to CYPs) and cytogenotoxic toxicity assays were employed to investigate the activation of CBZ for mutagenic effects, in various mammalian cell models. Docking results indicated that CBZ was valid as a substrate of human CYP2B6 and 2E1, while not for CYP1A1, 1A2, 1B1 or 3A4. In the Chinese hamster (V79) cell line and its derivatives genetically engineered for the expression of human CYP1A1, 1A2, 1B1, 2E1 or 3A4 CBZ (2.5 ~ 40 μM) did not induce micronucleus, while in human CYP2B6-expressing cells CBZ significantly induced micronucleus formation. In a human hepatoma C3A cell line, which endogenously expressed CYP2B6 twofold higher than in HepG2 cells, CBZ induced micronucleus potently, which was blocked by 1-aminobenzotriazole (inhibitor of CYPs) and ticlopidine (specific CYP2B6 inhibitor). In HepG2 cells CBZ did not induce micronucleus; however, pretreatment of the cells with CICTO (CYP2B6 inducer) led to micronucleus formation by CBZ, while rifampicin (CYP3A4 inducer) or PCB126 (CYP1A inducer) did not change the negative results. Immunofluorescent assay showed that CBZ selectively induced centromere-free micronucleus. Moreover, CBZ induced double-strand DNA breaks (γ-H2AX elevation, by Western blot) and PIG-A gene mutations (by flowcytometry) in C3A (threshold being 5 μM, lower than its therapeutic serum concentrations, 17 ~ 51 μM), with no effects in HepG2 cells. Clearly, CBZ may induce clastogenesis and gene mutations at its therapeutic concentrations, human CYP2B6 being a major activating enzyme. [ABSTRACT FROM AUTHOR]

Soil microbial community composition plays a key role in the decomposition of organic matter, while the quality of exogenous organic matter (EOM: rice straw, roots and pig manure) can influence soil chemical and biological properties. However, the evidences of the effect of combination of crop residues and pig manure on the changes in soil microbial community and enzymes activities are scarce. A greenhouse pot experiment was conducted to investigate the potential effect of EOM by analyzing soil properties, enzyme activities and microbial communities. The experiment consisted of eight treatments: CK (control), S (1% (w/w) rice straw), R (1% (w/w) rice root), SR (1% (w/w) rice straw + 1% (w/w) rice root), and added 1% (w/w) pig manure to CK, S, R and SR, respectively. Results showed that the straw treatment significantly increased the microbial biomass (carbon and nitrogen) and total carbon and nitrogen contents, cellulase and β-1,4-glucosidase activities, bacteria (i.e., gram-positive bacteria and gram-negative bacteria) PLFAs contents relative to CK regardless of whether pig manure was added. Moreover, the interaction between crop residues (e.g., straw and roots) and pig manure significantly influenced the contents of microbial biomass nitrogen and microbial biomass phosphorus, and the ratio of gram-positive bacteria to gram-negative bacteria. Redundance analysis confirmed that pH, nitrate nitrogen, ammonium nitrogen and dissolve organic carbon contents were significantly associated with soil microbial community under crop residues without pig manure addition. Furthermore, the experiment results showed that pig manure application not only provided more abundant nutrients (C, N and P) but also induced higher microbial and enzymatic activity compared with no pig manure addition. Our findings suggest that the combination of above-ground straw and pig manure is a better option for improving the functions of soil ecosystem. [ABSTRACT FROM AUTHOR]

Cytosine base editors (CBEs) efficiently generate precise C·G-to-T·A base conversions, but the activation-induced cytidine deaminase/apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (AID/APOBEC) protein family deaminase component induces considerable off-target effects and indels. To explore unnatural cytosine deaminases, we repurpose the adenine deaminase TadA-8e for cytosine conversion. The introduction of an N46L variant in TadA-8e eliminates its adenine deaminase activity and results in a TadA-8e-derived C-to-G base editor (Td-CGBE) capable of highly efficient and precise C·G-to-G·C editing. Through fusion with uracil glycosylase inhibitors and further introduction of additional variants, a series of Td-CBEs was obtained either with a high activity similar to that of BE4max or with higher precision compared to other reported accurate CBEs. Td-CGBE/Td-CBEs show very low indel effects and a background level of Cas9-dependent or Cas9-independent DNA/RNA off-target editing. Moreover, Td-CGBE/Td-CBEs are more efficient in generating accurate edits in homopolymeric cytosine sites in cells or mouse embryos, suggesting their accuracy and safety for gene therapy and other applications. Improved cytosine base editors are created by repurposing an adenine deaminase. [ABSTRACT FROM AUTHOR]

Background: Observational studies have reported the association between tea consumption and the risk of lower respiratory tract infections (LRTIs). However, a consensus has yet to be reached, and whether the observed association is driven by confounding factors or reverse causality remains unclear. Method: A two-sample Mendelian randomization (MR) analysis was conducted to determine whether genetically predicted tea intake is causally associated with the risk of common LRTI subtypes. Genome-wide association study (GWAS) from UK Biobank was used to identify single-nucleotide polymorphisms (SNPs) associated with an extra cup of tea intake each day. The summary statistics for acute bronchitis, acute bronchiolitis, bronchiectasis, pneumonia, and influenza and pneumonia were derived from the FinnGen project. Results: We found that genetically predicted an extra daily cup of tea intake was causally associated with the decreased risk of bronchiectasis [odds ratio (OR) = 0.61, 95% confidence interval (CI) = 0.47–0.78, P < 0.001], pneumonia (OR = 0.90, 95% CI = 0.85–0.96, P = 0.002), influenza and pneumonia (OR = 0.91, 95% CI = 0.85–0.97, P = 0.002), but not with acute bronchitis (OR = 0.91, 95% CI = 0.82–1.01, P = 0.067) and acute bronchiolitis (OR = 0.79, 95% CI = 0.60–1.05, P = 0.100). Sensitivity analyses showed that no heterogeneity and pleiotropy could bias the results. Conclusions: Our findings provided new evidence that genetically predicted an extra daily cup of tea intake may causally associated with a decreased risk of bronchiectasis, pneumonia, and influenza and pneumonia. [ABSTRACT FROM AUTHOR]

Objective: A case–control study was utilized to investigate the relationship between genetic variation of JAK-STAT signaling pathway-related genes and the susceptibility to ankylosing spondylitis (AS). Methods: Fifteen SNPs in the JAK-STAT signaling pathway-related genes from 660 AS patients and 646 healthy controls were genotyped using iMLDR technology (JAK1: rs2230587, rs2230588, rs2780815, rs310241; JAK2: rs2274472, rs2230722, rs2230724, rs10758669; STAT1: rs10199181, rs1547550, rs2066802, rs45463799, rs6718902; STAT3: rs3744483; STAT5A: rs1135669). Results: Allele analysis revealed that the T allele of STAT1 rs6718902 was a protective agent for male AS patients (OR = 0.765, 95% CI = 0.644–0.909). Inheritance models showed that GG + CG as well as GG genotypes of STAT1 rs1547550 had a significant risk of developing AS in males (OR = 5.374, 95%CI = 2.505–11.526; OR = 5.186, 95%CI = 2.412–11.153). The TT + CT and TT genotypes at STAT1 rs6718902 were observed to be associated with a significantly decreased risk of AS compared to CC genotypes among male patients and male controls (OR = 0.637, 95%CI = 0.485–0.837; OR = 0.597, 95%CI = 0.422–0.845). Furthermore, the genotypes of JAK1 gene rs2230588, rs2780815, and rs310241 were correlated with the severity of clinical conditions in female AS patients, while the JAK2 rs2230724 genotypes may affect disease ability in male AS patients. Conclusion: These findings indicated that JAK-STAT signaling pathway-related gene single nucleotide polymorphisms may be associated with AS susceptibility in eastern Chinese Han population. Key Points • The T allele of rs6718902 on the STAT1 gene may be a protective agent for male AS patients. • STAT1 rs1547550 GG + CG and GG genotypes were observed to be connected with a risk of male AS patients. However, STAT1 rs6718902 TT + CT and TT genotypes reduced the susceptibility risk of male AS patients compared to wild-type CC. • The JAK1 genes rs2230588, rs2780815, and rs310241 may affect disease functional status in female AS patients, while the JAK2 rs2230724 genotype was related to disease activity in male AS patients. [ABSTRACT FROM AUTHOR]

The Hf0.5Zr0.5O2 (HZO)-based ferroelectric field-effect transistor (FeFET) synapse is a promising candidate for at-scale deep neural network (DNN) applications, because of its high symmetry, great accuracy and fast operation speed. However, the degradation of the remanent polarization (Pr) over time caused by the depolarization field has not been effectively resolved, greatly affecting the accuracy of the trained DNN. In this study, we demonstrate a ferroelectric (FE)-resistive switching (RS) switchable synapse using the FE mode for high-speed weight training and the RS mode for stable weight storage to overcome accuracy degradation. The FE-RS hybrid characteristic is accomplished by an HZO-based metal-ferroelectric-metal (MFM) capacitor with asymmetric electrodes, and the best FE endurance, as well as the most reliable RS behavior, is demonstrated by testing several electrodes materials. High memory windows are achieved in both FE and RS modes. Through this design, excellent accuracy is maintained over time, as verified by network simulation. [ABSTRACT FROM AUTHOR]

This paper describes a study on the corrosion behavior of steel reinforcement in CAC mortars via electrochemical methods including corrosion potential, electrochemical impedance, and linear polarization evaluation. Results indicate that there is a non-linear relationship between the corrosion degree of steel reinforcement in CAC mortar and the concentration of NaCl solution. The electrochemical parameters of specimens immersed in 3% NaCl solution suddenly drop at 40 days, earlier than 60 days of the reference. And the charge transfer resistivity of the specimen has decreased by 11 orders of magnitude at 40 days, showing an evident corrosion on steel reinforcement. However, it is interesting to notice that the corrosion is delayed by high external chloride concentration. The specimens immersed in 9% and 15% NaCl solutions remain in a relatively stable state within 120 days with slight pitting. The great corrosion protection of CAC concrete to embedded steel bars enables its wide application in marine. [ABSTRACT FROM AUTHOR]

As the climate continues to change, suicide is becoming more frequent. In this study, absolute humidity (AH) was included for the first time and Wuhu, a typical subtropical city along the Yangtze River, was taken as the research object to explore the impact of suicide death risk on meteorological factors. The daily meteorological factors and suicide mortality data of Wuhu city from 2014 to 2020 were collected. Guided by structural equation model (SEM), a time series analysis method combining distributed lag nonlinear model (DLNM) and generalized additive model (GAM) was adopted. To investigate the correlation among different populations, we stratified age and gender at different meteorological levels. A total of 1259 suicide deaths were collected in Wuhu. The results indicated that exceedingly low and low levels of AH short-term exposure increased suicide mortality, with the maximum effect occurring at lag 14 for both levels of exposure, when the relative risk (RR) was 1.131 (95% CI: 1.030, 1.242) and 1.065 (95% CI: 1.006, 1.127), respectively. Exposure to exceedingly high and exceedingly low levels of temperature mean (T mean) also increased suicide mortality, with maximum RR values of 1.132 (lag 14, 95% CI: 1.015, 1.263) and 1.203 (lag 0, 95% CI: 1.079, 1.340), sequentially. As for diurnal temperature range (DTR), low-level exposure decreased the risk of suicide, while high-level exposure increased this risk, with RR values of 0.955 (lag 0, 95% CI: 0.920, 0.991, minimum) and 1.060 (lag 0, 95% CI: 1.018, 1.104, maximum), sequentially. Stratified analysis showed that AH and DTR increased the suicide death risk in male and elderly people, while the risk effect of T mean have no effect on young people only. In summary, male and elderly people appear to be more vulnerable to adverse weather effects. [ABSTRACT FROM AUTHOR]

This study investigated the relationship between children's mathematics performance and physical health using data from the Early Childhood Longitudinal Study Kindergarten Class of 2010–2011 (ECLS-K 2011). A two-level hierarchical growth curve model was used to explore the relationships between childhood mathematics performance and childhood health taking moderator effects into consideration. The study results indicate that higher body mass index relates to higher kindergarten mathematics performance, holding all else constant. The results of this study have implications for educators, parents, and health providers in understanding the relationship between mathematics performance and health indicators. [ABSTRACT FROM AUTHOR]

High mortality rate and poor survival in melanoma are associated with efficient metastatic colonization. The underlying mechanisms remain elusive. Elucidating the role of exosomes in mediating the interactions between cancer cells and the metastatic microenvironment has been focused on cancer cell derived exosomes in modulating the functions of stromal cells. Whether cancer stem cells (CSCs) can modify the metastatic properties of non-CSC cells, and whether exosomal crosstalk plays a role have not been demonstrated prior to this report. In this study, a paired M14 melanoma derivative cell line, i.e., melanoma parental cell (MPC) and its CSC derivative cell line melanoma stem cell (MSC) were employed. We demonstrated that exosomal crosstalk betwen MSCs and non-CSC MPCs is a new mechanism that underlies melanoma metastasis. Low metastatic melanoma cells (MPCs) can acquire the "metastatic power" from highly metastatic melanoma CSCs (MSCs). We illustrated an uncharacterized microRNA, miR-4535 in mediating such exosomal crosstalk. MSCs deliver its exosomal miR-4535 to the targeted MPCs. Upon entering MPCs, miR-4535 augments metastatic colonization of MPCs by inactivating the autophagy pathway. [ABSTRACT FROM AUTHOR]

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Whole-genome recoding has been shown to enable nonstandard amino acids, biocontainment and viral resistance in bacteria. Here we take the first steps to extend this to human cells demonstrating exceptional base editing to convert TAG to TAA for 33 essential genes via a single transfection, and examine base-editing genome-wide (observing ~40 C-to-T off-target events in essential gene exons). We also introduce GRIT, a computational tool for recoding. This demonstrates the feasibility of recoding, and highly multiplex editing in mammalian cells. Whole-genome recoding has been shown to enable nonstandard amino acids, biocontainment and viral resistance in bacteria. Here the authors extend this to human cells using base editing to convert TAG to TAA for 33 essential genes via a single transfection followed by examining base-editing genome-wide. [ABSTRACT FROM AUTHOR]

Objectives: COVID-19 pandemic has already had a tremendous impact on the process of human society; the survival of mankind and the healthy living environment deterioration with the influence will last for many years. This meta-analysis aims to assess the risk of COVID-19 in patients with rheumatic diseases. Methods: PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical Database (CBM) were systematically searched with no language restriction up to July 5, 2021. The pooled rates were synthesized by fixed effect model or random effect model depending on heterogeneity. Results: A total of 83 articles were included in this meta-analysis. The incidence of COVID-19 in patient with rheumatic diseases was 0.0190 (95% CI: 0.0136-0.0252), and the hospitalization rate, intensive care unit admission rate, mechanical ventilation rate, and case fatality rate of patients with rheumatic diseases infected with COVID-19 were 0.4396 (95% CI: 0.3899-0.4898), 0.0635 (95% CI: 0.0453-0.0836), 0.0461 (95% CI: 0.0330-0.0609), and 0.0346 (95% CI: 0.0218-0.0493), respectively. Conclusions: Our research shows that patients with rheumatic diseases have great risk of COVID-19. Differences in COVID-19 incidence, hospitalization rates, and mortality rates in regions were statistically significant. We still need to pay attention to the risk of COVID-19 in patients with rheumatic diseases. Key Points: • Although the risk of COVID-19 in patients with rheumatic diseases has been discussed in previous meta-analysis, their research directions were inconsistent, and few studies focus on prevalence or serious outcomes of COVID-19 in patient with rheumatic diseases, while the quality of these articles was variable. • The incidence of COVID-19 and serious clinical outcomes in patients with rheumatic diseases were still high along with differential risks in most regions. • The use of glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs did not affect the hospitalization rate and mortality in rheumatism patients with COVID-19. [ABSTRACT FROM AUTHOR]

Though the magnitude of any climate change is important, regions which have a larger signal of climate change relative to the background variations will potentially face greater risks than other regions, as they will see unusual or novel climate conditions more quickly as reported by Frame et al. (Nat Clim Chang 7(6):407–411, 2017). Providing more information about signal and noise on regional scales, and the associated attribution to particular causes, is therefore important for adaptation planning as discussed by Chen et al. (2021). However, whether a detectable signal in temperature extremes emerges in China at the local or regional level during 850–2005 has not been discussed. Based on six selected and bias-corrected global models under the Coupled Model Intercomparison Project Phase 5, relative to 1850–1900, we show that the temporal information of signal-to-noise ratio (S/N) in annual temperature extremes are consistent with annual mean temperature variations in China during 850–2005. Before 1850, absolute values of regional mean S/N in temperature extremes under cold climatic conditions are generally larger than those under warm climatic conditions. At the level of S/N > 1, local increasing signals of cold extremes emerge in the second half of thirteenth century and in the early nineteenth century after large volcanic eruptions in 1257 and 1815 in most part of China, especially in southern China and Tibet Plateau. Over the past 150 years under global warming, absolute values of regional mean S/N in temperature extremes have increasing trends. The regional mean increasing signals of warm extremes over China begin to exceed natural variability in 1963 at the level of S/N > 1, and local warm signals first occur in 1924 in Tibet Plateau. These warming signals are related to greenhouse gas forcing. [ABSTRACT FROM AUTHOR]

Absent epilepsy is a kind of refractory epilepsy, which is characterized by 2–4 Hz spike and wave discharges (SWDs) in electroencephalogram. Open-loop deep brain stimulation (DBS) targeting the thalamic reticular nucleus (TRN) is an effective method to treat absent epilepsy by eliminating SWDs in the brain. Compared with open-loop DBS, closed-loop DBS has been recognized by researchers for its advantages of significantly inhibiting seizures and having fewer side effects. Since traditional trial-and-error methods for adjusting closed-loop controller parameters are too dependent on the experience of doctors, in this paper we designed two proportional integral (PI) controllers based on the basal ganglia-cortical-thalamic model, whose PI parameters are calculated from the stability of the system. The two PI controllers can automatically adjust the frequency and amplitude of DBS respectively according to the change of the firing rate detected by substantia nigra pars reticulata (SNr). The parameters of the PI controller are calculated based on the Routh-Hurwitz stability criterion of a linear system which transformed by the original system using controlled auto-regressive (CAR) model and recursive least squares (RLS) method. Numerical simulation results show that both PI controllers significantly destroy the SWDs of the cerebral cortex and restore it to the other two normal discharge modes according to the different target firing rate, which supplies a promising brain stimulation strategy. [ABSTRACT FROM AUTHOR]

Hafnia-based ferroelectrics have greatly revived the field of ferroelectric memory (FeRAM), but certain reliability issues must be satisfactorily resolved before they can be widely applied in commercial memories. In particular, the imprint phenomenon severely jeopardizes the read-out reliability in hafnia-based ferroelectric capacitors, but its origin remains unclear, which hinders the development of its recovery schemes. In this work, we have systematically investigated the imprint mechanism in TiN/Hf0.5Zr0.5O2 (HZO)/TiN ferroelectric capacitors using experiments and first-principles calculations. It is shown that carrier injection-induced charged oxygen vacancies are at the heart of imprint in HZO, where other mechanisms such as domain pinning and dead layer are less important. An imprint model based on electron de-trapping from oxygen vacancy sites has been proposed that can satisfactorily explain several experimental facts such as the strong asymmetric imprint, leakage current variation, and so forth. Based on this model, an effective imprint recovery method has been proposed, which utilizes unipolar rather than bipolar voltage inputs. The remarkable recovery performances demonstrate the prospect of improved device reliability in hafnia-based FeRAM devices. [ABSTRACT FROM AUTHOR]

Flexible memory devices are promising for information storage and data processing applications in portable, wearable, and smart electronics operating under curved conditions. In this work, we realized high-performance flexible ferroelectric capacitors based on Hf0.5Zr0.5O2 (HZO) thin film by depositing a buffer layer of Al2O3 on polyimide (PI) substrates using atomic layer deposition (ALD). The flexible ferroelectric HZO films exhibit high remnant polarization (Pr) of 21 µC/cm2. Furthermore, deterioration of polarization, retention, and endurance performance was not observed even at a bending radius of 2 mm after 5,000 bending cycles. This work marks a critical step in the development of high-performance flexible HfO2-based ferroelectric memories for next-generation wearable electronic devices. [ABSTRACT FROM AUTHOR]

Objectives: The association of interleukin-6 (IL-6) -174G/C (rs1800795) and IL-6 -572G/C (rs1800796) single-nucleotide polymorphism (SNP) with the risk of acquiring rheumatoid arthritis (RA) was inconsistent among previous studies. This paper aims to investigate the association between IL-6 promoter polymorphism with RA in different ethnics. Methods: Relevant studies were searched using Medline and Google Search engines; STATA software was used to perform the meta-analysis. Pooled odds ratios (OR) were calculated to estimate the potential genetic associations. Subgroup analysis and sensitivity analysis were applied to explore the sources of heterogeneity. Lastly, we used TSA (trial sequential analysis) software to verify the reliability of meta-analysis results. Results: A total of 18 studies were included, involving 8116 subjects (3820 RA patients and 4296 controls). We found a tendency to associate RA with the IL-6 -174G/C allele in Asians (C vs G: OR = 4.56, 95% CI = 1.85–11.23; P < 0.001); with IL-6 -572G/C genotype or allele frequencies, there was no statistical differences between RA patients and controls (P > 0.05). TSA results indicate that the current meta-analysis can draw conclusions. Conclusions: IL-6-174G/C gene polymorphism were associated with increased risk of RA in Asians, but not in Caucasians. There was no association between IL-6 -572G/C gene polymorphism and the risk of RA. Key Points • Although the association between interleukin-6 (IL-6) promoter polymorphism and rheumatic arthritis (RA) has been discussed in the previous meta-analysis, their conclusions are inconsistent. • In this study, trial sequential analysis (TSA) was introduced into the meta-analysis, and the following two important conclusions were confirmed: (1) IL-6-174G/C gene polymorphism was associated with increased risk of RA in Asians, but not in Caucasians. (2) There was no association between IL-6 -572G/C gene polymorphism and the risk of RA. [ABSTRACT FROM AUTHOR]

Resistance to small-molecule drugs is the main cause of the failure of therapeutic drugs in clinical practice. Missense mutations altering the binding of ligands to proteins are one of the critical mechanisms that result in genetic disease and drug resistance. Computational methods have made a lot of progress for predicting binding affinity changes and identifying resistance mutations, but their prediction accuracy and speed are still not satisfied and need to be further improved. To address these issues, we introduce a structure-based machine learning method for quantitatively estimating the effects of single mutations on ligand binding affinity changes (named as PremPLI). A comprehensive comparison of the predictive performance of PremPLI with other available methods on two benchmark datasets confirms that our approach performs robustly and presents similar or even higher predictive accuracy than the approaches relying on first-principle statistical mechanics and mixed physics- and knowledge-based potentials while requires much less computational resources. PremPLI can be used for guiding the design of ligand-binding proteins, identifying and understanding disease driver mutations, and finding potential resistance mutations for different drugs. PremPLI is freely available at https://lilab.jysw.suda.edu.cn/research/PremPLI/ and allows to do large-scale mutational scanning. Sun et al. present PremPLI, a machine learning approach and web tool to predict how missense mutations in a drug's target protein will affect the drug's binding affinity. PremPLI can be applied to identify drug resistance mechanisms in cancer cells and microorganisms and develop drugs to combat drug resistance. [ABSTRACT FROM AUTHOR]

Identifying lithology from well logs is an important step in deep prospecting and resource estimation. Various machine learning algorithms have been adopted to identify lithology in oil and gas fields. Such algorithms, however, are rarely used for mineral deposits because of their complex geological conditions. In this paper, we propose an application framework using the gradient boosting decision tree (GBDT) algorithm to identify lithology from well logs in a mineral deposit. The GBDT classifier was built via the procedure of grid search and cross-validation to optimize the hyperparameters. In the Zhaoxian gold deposit, as the study area, an optimized GBDT classifier was built to fit the association between a set of well logs and ten lithological classes. The results demonstrate that the GBDT classifier has good classification performance in lithology identification, with a precision of 93.55%, a recall of 93.49% and an F1-score of 93.27%. The GBDT classification results also indicate that the major features contributing to the lithology classification are resistivity, followed by spontaneous potential and natural gamma according to the model interpretation of feature importance and partial dependence plots. The study demonstrates that the GBDT model can enhance our understanding of lithology identification from well logs in mineral deposits, which provides significant implications for further exploration targeting the deep-seated parts of mineral deposits. [ABSTRACT FROM AUTHOR]

Ternary polyamide (tPA) copolymer is susceptible to degradation when it is irradiated by electron beam (e-beam), and effective methods to avoid degradation and increase gel content are highly desirable for crosslinking. Carboxylated multiwall carbon nanotube (MWCNT) is modified by hydroxyethyl acrylate (HEA) in this paper and used as a co-agent for the e-beam irradiation crosslinking of tPA copolymer. HEA modified MWCNT can function as an effective co-agent for the e-beam irradiation crosslinking of tPA copolymer to increase the gel content and improve the mechanical properties of tPA copolymer. Under an irradiation of 160 kGy, addition of 2 parts per hundred (phr) HEA modified MWCNT into tPA copolymer can increase the gel content of tPA copolymer from about 20% to 40% (mass ratio) and increase the tensile strength from 45 to 59MPa. The irradiation also affects the glass transition temperature of tPA copolymer by increasing the gel content. The results show that HEA modified MWCNT can act as a nucleating agent to increase the crystallization temperature, melting temperature and crystallinity of tPA copolymer. [ABSTRACT FROM AUTHOR]

Model checking is a formal verification technique. It takes an exhaustively strategy to check hardware circuits and network protocols against desired properties. Having been developed for more than three decades, model checking is now playing an important role in software engineering for verifying rather complicated software artifacts.This paper surveys the role of model checking in software engineering. In particular, we searched for the related literatures published at reputed conferences, symposiums, workshops, and journals, and took a survey of (1) various model checking techniques that can be adapted to software development and their implementations, and (2) the use of model checking at different stages of a software development life cycle. We observed that model checking is useful for software debugging, constraint solving, and malware detection, and it can help verify different types of software systems, such as object- and aspect-oriented systems, service-oriented applications, web-based applications, and GUI applications including safety- and mission-critical systems.The survey is expected to help human engineers understand the role of model checking in software engineering, and as well decide which model checking technique(s) and/or tool(s) are applicable for developing, analyzing and verifying a practical software system. For researchers, the survey also points out how model checking has been adapted to their research topics on software engineering and its challenges. [ABSTRACT FROM AUTHOR]

Purpose: Given the critical role of parental care for pediatric cancer patients, this pilot study evaluated the feasibility and effectiveness of a hospital-based solution-focused brief therapy (SFBT) intervention for reducing psychological distress among parents of pediatric cancer patients in China. Differences between treatment and active control (AC) groups were assessed on dimensions of psychological distress. Parents' level of hope was also assessed.Methods: Participants (N = 44) were randomly assigned to SFBT or AC. Parents received four sessions of SFBT twice a week delivered by graduate-level hospital social workers. Pre- and post-intervention assessments measured change in distress (depression, anxiety, and somatization symptoms) of parents as well as their level of hope.Results: Analysis of covariance (ANCOVA) indicated the SFBT group had better outcomes than the AC group on overall distress of somatic, anxiety, depression symptoms and level of hope. Within- and between-group treatment effects reported significantly greater effect of the SFBT group than of the AC group.Conclusions: Considering the inherent limits of a pilot feasibility study, results suggest that SFBT is a feasible, culturally compatible, and promising intervention for alleviating distress among Chinese parents of children with cancer. Additional comprehensive trials are needed to draw more definitive conclusions.Relevance: SFBT may be beneficial for improving the critical support systems of parents of pediatric cancer patients. Thus, SFBT may have the potential to enhance children's well-being during cancer treatment and recovery. [ABSTRACT FROM AUTHOR]

The ecotoxicity of α-FeO nanoparticles (NPs) and its interaction with a typical natural organic matter (NOM), fulvic acid (FA) on the physiological responses of Synechococcus sp. PCC7942 was studied. α-FeO NPs inhibited the algae growth at concentration higher than 10 mg L and induced oxidative stress, indicated by enhanced antioxidant enzymes activities, elevated protein and sugar content. FA could efficiently recover cell growth and reduce antioxidant enzyme activities which induced by α-FeO NPs, indicating the toxicity of NPs was alleviated in the presence of FA. α-FeO NPs could form large aggregates coating on cell surface and inhibit cell growth. FTIR spectra verified FA interacted with α-FeO NPs through carboxyl groups, partly replaced the binding sites of α-FeO NPs on algal cell walls, thus reduced NPs aggregates coating on cell surface. This favors reducing the oxidative stress caused by direct contact and increasing light availability, thus mitigate NPs toxicity. [ABSTRACT FROM AUTHOR]

In this paper, a subspace three-term conjugate gradient method is proposed. The search directions in the method are generated by minimizing a quadratic approximation of the objective function on a subspace. And they satisfy the descent condition and Dai-Liao conjugacy condition. At each iteration, the subspace is spanned by the current negative gradient and the latest two search directions. Thereby, the dimension of the subspace should be 2 or 3. Under some appropriate assumptions, the global convergence result of the proposed method is established. Numerical experiments show the proposed method is competitive for a set of 80 unconstrained optimization test problems. [ABSTRACT FROM AUTHOR]