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Supramolecular mechanophores typically exhibit much lower mechanical strengths than covalent counterparts, with strengths usually around 100 pN, which is significantly lower than the nN‐scale strength of covalent bonds. Inspired by the slow dissociation kinetics of the cucurbit[7]uril (CB[7])–hexanoate‐isoquinoline (HIQ) complex, we discovered that charge–dipole repulsion can be utilized to create strong supramolecular mechanophores. When activated at its −COO− state, the CB[7]−HIQ complex exhibits a high mechanical strength of ~700 pN, comparable to weak covalent bonds such as Au−S bonds or thiol–maleimide adducts. The strength of the CB[7]−HIQ complex can also be tuned with pH in a gradual manner, with a minimum value of ~150 pN at its −COOH state, similar to an ordinary supramolecular conjugate. This research may pave the way for the development of supramolecular architectures that combine the advantages of covalent and supramolecular systems. [ABSTRACT FROM AUTHOR]

Supramolecular mechanophores typically exhibit much lower mechanical strengths than covalent counterparts, with strengths usually around 100 pN, which is significantly lower than the nN‐scale strength of covalent bonds. Inspired by the slow dissociation kinetics of the cucurbit[7]uril (CB[7])–hexanoate‐isoquinoline (HIQ) complex, we discovered that charge–dipole repulsion can be utilized to create strong supramolecular mechanophores. When activated at its −COO− state, the CB[7]−HIQ complex exhibits a high mechanical strength of ~700 pN, comparable to weak covalent bonds such as Au−S bonds or thiol–maleimide adducts. The strength of the CB[7]−HIQ complex can also be tuned with pH in a gradual manner, with a minimum value of ~150 pN at its −COOH state, similar to an ordinary supramolecular conjugate. This research may pave the way for the development of supramolecular architectures that combine the advantages of covalent and supramolecular systems. [ABSTRACT FROM AUTHOR]

The inconsistency between mismatch repair (MMR) protein immunohistochemistry (IHC) and microsatellite instability PCR (MSI‐PCR) methods has been widely reported. We aim to investigate the prognosis and the effect of immunotherapy in dMMR by IHC but MSS by MSI‐PCR (dMMR&MSS) colorectal cancer (CRC) patients. A microsatellite instability (MSI) predicting model was established to help find dMMR&MSS patients. MMR and MSI states were detected by the IHC and MSI‐PCR in 1622 CRC patients (ZS6Y‐1 cohort). Logistic regression analysis was used to screen clinical features to construct an MSI‐predicting nomogram. We propose a new nomogram‐based assay to find patients with dMMR&MSS, in which the MSI‐PCR assay only detects dMMR patients with MSS predictive results. We applied the new strategy to a random cohort of 248 CRC patients (ZS6Y‐2 cohort). The consistency of MMR IHC and MSI‐PCR in the ZS6Y‐1 cohort was 95.7% (1553/1622). Both pMMR&MSS and dMMR&MSS groups experienced significantly shorter overall survival (OS) than those in dMMR by IHC and MSI‐H by MSI‐PCR (dMMR&MSI‐H) group (hazard ratio [HR] = 2.429, 95% confidence interval [CI]: 1.89–3.116, p <.01; HR = 21.96, 95% CI: 7.24–66.61, p <.01). The dMMR&MSS group experienced shorter OS than the pMMR&MSS group, but the difference did not reach significance (log rank test, p =.0686). In the immunotherapy group, the progression‐free survival of dMMR&MSS patients was significantly shorter than that of dMMR&MSI‐H patients (HR = 13.83, 95% CI: 1.508–126.8, p <.05). The ZS6Y‐MSI‐Pre nomogram (C‐index = 0.816, 95% CI: 0.792–0.841, already online) found 66% (2/3) dMMR&MSS patients in the ZS6Y‐2 cohort. There are significant differences in OS and immunotherapy effect between dMMR&MSI‐H and dMMR&MSS patients. Our prediction model provides an economical way to screen dMMR&MSS patients. [ABSTRACT FROM AUTHOR]

Appendicular osteosarcoma was diagnosed and treated in a pair of littermate Rottweiler dogs, resulting in distinctly different clinical outcomes despite similar therapy within the context of a prospective, randomized clinical trial (NCI-COTC021/022). Histopathology, immunohistochemistry, mRNA sequencing, and targeted DNA hotspot sequencing techniques were applied to both dogs' tumors to define factors that could underpin their differential response to treatment. We describe the comparison of their clinical, histologic and molecular characteristics, as well as those from a companion cohort of Rottweiler dogs. A pan-cancer genomic sequencing panel conducted in the sibling dogs demonstrated both shared and distinct alterations in several genes implicated in osteosarcoma, including CDKN2B, SETD2, MYC, and PDGFRA, while transcriptional profiling of primary tumor tissue indicated under-expression of key immunological response genes. This report provides new insight into molecular features and potential prognostic biomarkers for canine osteosarcoma. [ABSTRACT FROM AUTHOR]

Integrin β6 (ITGB6) is upregulated in multiple tumor types and elevated ITGB6 levels have been detected in patients with chronic pancreatitis. However, the role of ITGB6 in pancreatic fibrosis and cancer remains to be elucidated. In the present study, ITGB6 expression was assessed using western blotting and qRT-PCR. Besides, cell proliferation, cycling, migration, and invasion were evaluated using CCK-8, flow cytometry, wound healing, and transwell assays, respectively. The expression of fibrosis and JAK2/STAT3 signaling markers was detected by western blotting and immunofluorescence analysis. Moreover, nude mice were subcutaneously injected with co-cultured cell suspensions to establish an in vivo model. The results showed that ITGB6 was highly expressed in pancreatic cancer tissues and TGF-β-induced pancreatic stellate cells (PSCs). Inhibition of ITGB6 expression in PSCs resulted in clear inhibition of activated PSC proliferation, migration, and fibrogenesis. Additionally, reduced ITGB6 expression inhibits the JAK2/STAT3 signaling pathway. Interestingly, activators of the JAK2/STAT3 signaling pathway reversed the effects of ITGB6 disruption on PSCs. Activated PSCs notably promoted the proliferation, invasion, and migration of pancreatic cancer cells in a co-culture assay. In contrast, activated PSCs with low ITGB6 expression failed to significantly affect the malignancy of pancreatic cancer cells. Moreover, in vivo results showed that interference with ITGB6 inhibited the activation of PSCs and promoted the development of pancreatic cancer. Silencing ITGB6 inhibited the proliferation, migration, and fibrosis-like effects of activated PSCs and indirectly inhibited the metastasis and malignant process of pancreatic cancer by inhibiting the JAK2/STAT3 signaling pathway. Therefore, ITGB6 is a potential candidate target for pancreatic cancer prevention and treatment. [ABSTRACT FROM AUTHOR]

Background: Studies have confirmed that epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)-like properties are conducive to cancer metastasis. In recent years, testes-specific protease 50 (TSP50) has been identified as a prognostic factor and is involved in tumorigenesis regulation. However, the role and molecular mechanisms of TSP50 in EMT and CSC-like properties maintenance remain unclear. Methods: The expression and prognostic value of TSP50 in breast cancer were excavated from public databases and explored using bioinformatics analysis. Then the expression of TSP50 and related genes was further validated by quantitative RT-PCR (qRT-PCR), Western blot, and immunohistochemistry (IHC). In order to investigate the function of TSP50 in breast cancer, loss- and gain-of-function experiments were conducted, both in vitro and in vivo. Furthermore, immunofluorescence (IF) and immunoprecipitation (IP) assays were performed to explore the potential molecular mechanisms of TSP50. Finally, the correlation between the expression of TSP50 and related genes in breast cancer tissue microarray and clinicopathological characteristics was analyzed by IHC. Results: TSP50 was negatively correlated with the prognosis of patients with breast cancer. TSP50 promoted CSC-like traits and EMT in both breast cancer cells and mouse xenograft tumor tissues. Additionally, inhibition of PI3K/AKT partly reversed TSP50-induced activation of CSC-like properties, EMT and tumorigenesis. Mechanistically, TSP50 and PI3K p85α regulatory subunit could competitively interact with the PI3K p110α catalytic subunit to promote p110α enzymatic activity, thereby activating the PI3K/AKT signaling pathway for CSC-like phenotypes maintenance and EMT promotion. Moreover, IHC analysis of human breast cancer specimens revealed that TSP50 expression was positively correlated with p-AKT and ALDH1 protein levels. Notably, breast cancer clinicopathological characteristics, such as patient survival time, tumor size, Ki67, pathologic stage, N stage, estrogen receptor (ER) and progesterone receptor (PR) levels, correlated well with TSP50/p-AKT/ALDH1 expression status. Conclusion: The effects of TSP50 on EMT and CSC-like properties promotion were verified to be dependent on PI3K p110α. Together, our study revealed a novel mechanism by which TSP50 facilitates the progression of breast cancer, which can provide new insights into TSP50-based breast cancer treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Social alienation refers to the state of feeling isolated, helpless, and unsatisfied due to maintaining distance from others or avoiding social interaction and activities. This phenomenon is caused by a lack of social skills, social anxiety, physical health problems, and other reasons. Older maintenance hemodialysis patients are exposed to a higher risk of social alienation. However, previous studies have been performed using the total score of the scale, which does not allow the identification of the characteristics of various patient groups with different levels of social alienation. In contrast, latent profile analysis can classify individuals into different categories based on continuous observational indicators, which improves accuracy and provides a more objective assessment by accounting for the uncertainty of variables. Given the concealed nature of social alienation and the differences in characteristics and treatment measures between different profiles, developing a predictive model for social alienation in older maintenance hemodialysis patients holds significance. Objective: To explore the latent profile analysis of social alienation in older maintenance hemodialysis patients and to develop and validate a predictive model for social alienation in this population. Methods: A total of 350 older maintenance hemodialysis patients were selected as the study subjects using convenience sampling. A cross-sectional survey was conducted using a general information questionnaire, the Generalized Alienation Scale, and the Self-Perceived Burden Scale. Based on the results of the Generalized Alienation Scale, a latent profile analysis was performed, followed by univariate analysis and multinomial logistic regression to develop a predictive model. The effectiveness of the predictive model was evaluated in terms of its authenticity, reliability, and predictive ability. Results: Three hundred nineteen valid questionnaires were collected. The social alienation of older maintenance hemodialysis patients based on latent profile analysis were divided into three profiles, which were named the low/medium/high-symptom groups, comprising 21%, 38.9%, and 40.1% of participants, respectively. Based on male, monthly social activity hours, Age-Adjusted Charlson Comorbidity Index, dialysis age, and Self-Perceived Burden Scale, a predictive model of social alienation for older maintenance hemodialysis patients was developed, and the Hosmer–Lemeshow tests showed no statistical significance (P > 0.05). The model has high predictive efficiency in authenticity, reliability and predictability. Conclusion: Older maintenance hemodialysis patients exhibited moderate to high levels of social alienation. The latent profile analysis based method was used to divide patients into low/medium/high-symptom profiles, and the predictive model demonstrates excellent authenticity, reliability, and predictability. [ABSTRACT FROM AUTHOR]

The submerged floating tunnel (SFT) is a novel form of transportation infrastructure for crossing deeper and wider seas. One of the primary challenges in designing SFTs is understanding their hydrodynamic response to complex environmental loads. In order to investigate the two-degree-of-freedom (2-DOF) flow-induced vibration (FIV) response of SFTs under current, a two-dimensional (2D) numerical model was developed using the Reynolds-averaged Navier–Stokes (RANS) method combined with the fourth-order Runge–Kutta method. The numerical results were validated by comparing them with the existing literature. The study then addressed the effects of coupled vibration and structural parameters, i.e., the mass ratio and natural frequency ratio, on the response and wake pattern of SFTs, numerically. The results indicated that coupled vibration had a significant impact on the SFT response at reduced velocities of Urwx ≥ 4.4. A decrease in mass ratio (m* < 1) notably amplified the 2-DOF vibration amplitudes of SFTs at Urwx ≥ 4.4, particularly for in-line vibration. Similarly, a decrease in natural frequency ratio (Rf < 1) significantly suppressed the in-line vibration of SFTs at Urwx ≥ 2.5. Therefore, for the design of SFTs, careful consideration should be given to the effect of mass ratio and natural frequency ratio on in-line vibration. [ABSTRACT FROM AUTHOR]

Objective: In this paper, a single-hand-operated hepatic pedicle clamp was introduced, and its application value in laparoscopic liver tumor resection was preliminarily discussed. Methods: The clinical data of 67 patients who underwent laparoscopic liver tumor resection at the First Affiliated Hospital of Wannan Medical College from March 2019 to October 2023 were retrospectively analyzed. The Pringle maneuver was performed with a hepatic pedicle clamp during the operation. The preoperative, intraoperative and postoperative clinical data were observed and recorded. Results: Sixty-seven patients had a median block number, block time, intraoperative blood loss, and postoperative length of hospital stay of 4, 55 min, 400 ml, and 7 days, respectively. The average operation time was 304.9±118.4 min, the time required for each block was 3.2±2.4 s, and the time required for each removed block was 2.6±0.7 s. None of the patients developed portal vein thrombosis or hepatic artery aneurysm formation. Conclusion: The hepatic pedicle clamping clamp is simple to use in laparoscopic hepatectomy, optimizes the operation process, and has a reliable blocking effect. It is recommended for clinical application. [ABSTRACT FROM AUTHOR]

The integrity of the intestinal mucosal barrier is crucial for protecting the intestinal epithelium against invasion by commensal bacteria and pathogens, thereby combating colitis. The investigation revealed that the absence of TSP50 compromised the integrity of the intestinal mucosal barrier in murine subjects. This disruption facilitated direct contact between intestinal bacteria and the intestinal epithelium, thereby increasing susceptibility to colitis. Mechanistic analysis indicated that TSP50 deficiency in intestinal stem cells (ISCs) triggered aberrant activation of the TGF‐β signaling pathway and impeded the differentiation of goblet cells in mice, leading to impairment of mucosal permeability. By inhibiting the TGF‐β pathway, the functionality of the intestinal mucosal barrier is successfully restored and mitigated colitis in TSP50‐deficient mice. In conclusion, TSP50 played a crucial role in maintaining the intestinal mucosal barrier function and exhibited the preventive effect against the development of colitis by regulating the TGF‐β signaling pathway. [ABSTRACT FROM AUTHOR]

The Japanese national guidelines recommend significantly lower doses of carvedilol for heart failure with reduced ejection fraction (HFrEF) management than the US guidelines. Using real-world data, we determined whether initial and target doses of carvedilol in Japanese patients (JPNs) differ from those in US patients (USPs), especially in Asian Americans (ASA) and Caucasians (CA), and investigated differences in outcomes. We collected data from the electronic medical records, including demographics, carvedilol dosing, tolerability, cardiac functional indicators like EF, cardiovascular events including all-cause deaths, and laboratory values from the University of California, San Diego Health and Osaka University. JPNs had significantly lower doses (mg/day) of carvedilol initiation (66 USPs composed of 38 CAs and 28 ASAs, 17.1±16.2; 93 JPNs, 4.3±4.2, p<0.001) and one year after initiation (33.0±21.8; 11.2±6.5, p<0.001), and a significantly lower relative rate (RR) of dose discontinuation and reduction than USPs (RR: 0.406, 95% confidence interval (CI): 0.181–0.911, p<0.05). CAs showed the highest reduction rate (0.184), and ASAs had the highest discontinuation rate (0.107). A slight mean difference with narrow 95% CI ranges straddling zero was observed between the two regions in the change from the baseline of each cardiac functional indicator (LVEF, -0.68 [−5.49–4.12]; LVDd, −0.55 [−3.24–2.15]; LVDd index, −0.25 [−1.92–1.43]; LVDs, −0.03 [−3.84–3.90]; LVDs index, −0.04 [−2.38–2.30]; heart rate, 1.62 [−3.07–6.32]). The event-free survival showed no difference (p = 0.172) among the races. Conclusively, despite JPNs exhibiting markedly lower carvedilol doses, their dose effectiveness has the potential to be non-inferior to that in USPs. Dose de-escalation, not discontinuation, could be an option in some Asian and ASA HFrEF patients intolerable to high doses of carvedilol. [ABSTRACT FROM AUTHOR]

Structural planes decrease the strength and stability of rock masses, severely affecting their mechanical properties and deformation and failure characteristics. Therefore, investigation and analysis of structural planes are crucial tasks in mining rock mechanics. The drilling camera obtains image information of deep structural planes of rock masses through high-definition camera methods, providing important data sources for the analysis of deep structural planes of rock masses. This paper addresses the problems of high workload, low efficiency, high subjectivity, and poor accuracy brought about by manual processing based on current borehole image analysis and conducts an intelligent segmentation study of borehole image structural planes based on the U2-Net network. By collecting data from 20 different borehole images in different lithological regions, a dataset consisting of 1,013 borehole images with structural plane type, lithology, and color was established. Data augmentation methods such as image flipping, color jittering, blurring, and mixup were applied to expand the dataset to 12,421 images, meeting the requirements for deep network training data. Based on the PyTorch deep learning framework, the initial U2-Net network weights were set, the learning rate was set to 0.001, the training batch was 4, and the Adam optimizer adaptively adjusted the learning rate during the training process. A dedicated network model for segmenting structural planes was obtained, and the model achieved a maximum F-measure value of 0.749 when the confidence threshold was set to 0.7, with an accuracy rate of up to 0.85 within the range of recall rate greater than 0.5. Overall, the model has high accuracy for segmenting structural planes and very low mean absolute error, indicating good segmentation accuracy and certain generalization of the network. The research method in this paper can serve as a reference for the study of intelligent identification of structural planes in borehole images. [ABSTRACT FROM AUTHOR]

Low temperatures largely determine the geographic limits of plant species by reducing survival and growth. Inter-specific differences in the geographic distribution of mangrove species have been associated with cold tolerance, with exclusively tropical species being highly cold-sensitive and subtropical species being relatively cold-tolerant. To identify species-specific adaptations to low temperatures, we compared the chilling stress response of two widespread Indo-West Pacific mangrove species from Rhizophoraceae with differing latitudinal range limits— Bruguiera gymnorhiza (L.) Lam. ex Savigny (subtropical range limit) and Rhizophora apiculata Blume (tropical range limit). For both species, we measured the maximum photochemical efficiency of photosystem II (F v/ F m) as a proxy for the physiological condition of the plants and examined gene expression profiles during chilling at 15 and 5 °C. At 15 °C, B. gymnorhiza maintained a significantly higher F v/ F m than R. apiculata. However, at 5 °C, both species displayed equivalent F v/ F m values. Thus, species-specific differences in chilling tolerance were only found at 15 °C, and both species were sensitive to chilling at 5 °C. At 15 °C, B. gymnorhiza downregulated genes related to the light reactions of photosynthesis and upregulated a gene involved in cyclic electron flow regulation, whereas R. apiculata downregulated more RuBisCo-related genes. At 5 °C, both species repressed genes related to CO2 assimilation. The downregulation of genes related to light absorption and upregulation of genes related to cyclic electron flow regulation are photoprotective mechanisms that likely contributed to the greater photosystem II photochemical efficiency of B. gymnorhiza at 15 °C. The results of this study provide evidence that the distributional range limits and potentially the expansion rates of plant species are associated with differences in the regulation of photosynthesis and photoprotective mechanisms under low temperatures. [ABSTRACT FROM AUTHOR]

Background and aims: Hakea prostrata (Proteaceae) is a highly phosphorus-use-efficient plant native to southwest Australia. It maintains a high photosynthetic rate at low leaf phosphorus (P) and exhibits delayed leaf greening, a convergent adaptation that increases nutrient-use efficiency. This study aimed to provide broad physiological and gene expression profiles across leaf development, uncovering pathways leading from young leaves as nutrient sinks to mature leaves as low-nutrient, energy-transducing sources. Methods: To explore gene expression underlying delayed greening, we analysed a de novo transcriptome for H. prostrata across five stages of leaf development. Photosynthesis and respiration rates, and foliar pigment, P and nitrogen (N) concentrations were determined, including the division of P into five biochemical fractions. Key results: Transcripts encoding functions associated with leaf structure generally decreased in abundance across leaf development, concomitant with decreases in foliar concentrations of 85% for anthocyanins, 90% for P and 70% for N. The expression of genes associated with photosynthetic function increased during or after leaf expansion, in parallel with increases in photosynthetic pigments and activity, much later in leaf development than in species that do not have delayed greening. As leaves developed, transcript abundance for cytosolic and mitochondrial ribosomal proteins generally declined, whilst transcripts for chloroplast ribosomal proteins increased. Conclusions: There was a much longer temporal separation of leaf cell growth from chloroplast development in H. prostrata than is found in species that lack delayed greening. Transcriptome-guided analysis of leaf development in H. prostrata provided insight into delayed greening as a nutrient-saving strategy in severely phosphorus-impoverished landscapes. [ABSTRACT FROM AUTHOR]

In order to comprehensively understand the mechanical behavior of biological entities and aerospace applications subjected to hypergravity environments, we delve into the impact of hypergravity on the equivalent compliance of cubic lattice structures. Capitalizing on the periodic spatial distribution, we employ a unit cell methodology to deduce the homogenized stress-strain relationship for the lattice structures, subsequently obtaining the associated equivalent compliance. The equivalent compliance can be conveniently reduced to instances without hypergravity influence. Furthermore, numerical simulations are executed to validate the derivations and to illustrate that hypergravity indeed affects the mechanical properties of lattice structures. We introduce a non-dimensional hypergravity factor, which quantifies the impact of hypergravity magnitude relative to the Young’s modulus of the base material. Our findings reveal that the hypergravity factor influences perpendicular compliance quadratically and parallel compliance linearly. Simultaneously, the perpendicular shear compliance remains unaffected, whereas the parallel shear compliance experiences an inverse effect. Additionally, the lattice structure transforms into a gradient material oriented in the hypergravity direction, consequently generating a scale effect. [ABSTRACT FROM AUTHOR]

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Aims: To investigate the expression of polo-like kinase 1 protein (PLK1) and its phosphorylation level (p-PLK1) in extranodal NK/T cell lymphoma (NKTCL) and their correlation with clinical characteristics and prognosis. Methods: We collected 40 cases of NKTCL (referred to as the experimental group), which received diagnoses at the First Affiliated Hospital of Zhengzhou University between January 2018 and October 2022. Concurrently, we assembled a control group, including 20 cases afflicted with nasopharyngeal mucosal lymphoid hyperplasia diseases during the same timeframe. We utilized immunohistochemical techniques to evaluate the levels of PLK1 and p-PLK1 expression in both the experimental and control groups. Subsequently, we conducted an analysis to identify disparities in their expression and explore their relationships with clinical characteristics and patient prognosis. Results: Among the 40 NKTCL patients, there were 27 males and 11 females, with a median age of 51 years (range 12–80 years). Compared to the control group, the tissue samples of NKTCL patients exhibited significantly elevated expression levels and active phosphorylation levels of PLK1 (P < 0.05). Correlation analysis of the immunohistochemical H score and Ki-67 positive rate of PLK1 and p-PLK1, revealed a significant positive correlation for both (P < 0.0001, each). No statistically significant differences were observed in the distribution of PLK1 and p-PLK1 expression in NKTCL patients with respect to gender, age, Ann Arbor stage, PINK-E score, B-symptoms, lactate dehydrogenase, β2-microglobulin, blood EBV-DNA, bone marrow invasion, and lymph node metastasis (p > 0.05). Grouping based on PLK1 and p-PLK1 immunohistochemical H-scores revealed that the high expression of PLK1 and p-PLK1 was associated with poor prognosis. Conclusions: The expression levels and active phosphorylation levels of PLK1 were significantly increased in NK/T cell lymphoma, and patients with overexpression of PLK1 and p-PLK1 had a poorer prognosis. [ABSTRACT FROM AUTHOR]

Honeycomb materials frequently encounter hypergravity conditions in both aerospace and biological contexts during phases such as launch, reentry or under centrifugal motion. The significant body force engendered by hypergravity induces alterations in the microstructure of honeycomb materials, which in turn, influences their macroscopic mechanical behaviour. Leveraging the stiffness of the beam element as a pivotal variable, we successfully derived the equivalent moduli of the honeycomb material under hypergravity conditions. We further proposed the concept of a 'hypergravity factor', elucidating that the density of the base material, the dimensions of honeycomb cells and the magnitude of the hypergravity contribute to amplifying hypergravity effects. The results, numerically validated through finite-element simulations, could be reduced to the case that neglects body force. The critical buckling load of the honeycomb material under hypergravity can be assessed by setting the derived moduli to zero. In the presence of hypergravity, a honeycomb material undergoes a transition into a gradient material along the hypergravity direction, thereby exacerbating anisotropy. This phenomenon is theoretically expected to occur in virtually all porous materials. The analytical framework adopted, which employs beam stiffness as an intermediary variable, facilitates the extension of these results to honeycomb materials which encompass beam elements with functional gradients or varying cross-sectional morphologies. [ABSTRACT FROM AUTHOR]

The ongoing expansion of local government debt (LGD) in China constitutes a significant impediment to economic development, while the existing literature predominantly concentrates on macro-level investigations, neglecting the repercussions of government debt expansion on firms. Firms serve as fundamental constituents of the real economy, and the suitability of their investment structure is a pivotal determinant of their robust development. Therefore, it is of great significance to investigate whether the investment structure of non-financial firms will undergo deviations attributable to the expansion of local government debt. This paper uses a two-way fixed-effects model to examine the causal effect of local government debt on firms' investment structures. The quasi-natural experiment using the DID model with "Document 43" issued by China on local government debt governance as a policy shock can be a good endogeneity test. It is found that local government debt exacerbates the trend of "exit from real to virtual" of enterprises, leading to a bias towards financial investment in the investment structure of enterprises, and this result is still robust after a series of robustness tests. A heterogeneity analysis shows that the impact of LGD on the investment structure of firms mainly exists in non-state-owned firms, small-scale firms, and firms with high financing constraints. Overall, this study provides new evidence on how the government influences the investment structure of Chinese firms through the perspective of LGD, which helps firms to prevent and cope with the risks associated with LGD. Furthermore, it offers practical references and policy insights for government initiatives in the realm of local debt governance. [ABSTRACT FROM AUTHOR]

SUMMARY: Schrenkiella parvula, a leading extremophyte model in Brassicaceae, can grow and complete its lifecycle under multiple environmental stresses, including high salinity. Yet, the key physiological and structural traits underlying its stress‐adapted lifestyle are unknown along with trade‐offs when surviving salt stress at the expense of growth and reproduction. We aimed to identify the influential adaptive trait responses that lead to stress‐resilient and uncompromised growth across developmental stages when treated with salt at levels known to inhibit growth in Arabidopsis and most crops. Its resilient growth was promoted by traits that synergistically allowed primary root growth in seedlings, the expansion of xylem vessels across the root‐shoot continuum, and a high capacity to maintain tissue water levels by developing thicker succulent leaves while enabling photosynthesis during salt stress. A successful transition from vegetative to reproductive phase was initiated by salt‐induced early flowering, resulting in viable seeds. Self‐fertilization in salt‐induced early flowering was dependent upon filament elongation in flowers otherwise aborted in the absence of salt during comparable plant ages. The maintenance of leaf water status promoting growth, and early flowering to ensure reproductive success in a changing environment, were among the most influential traits that contributed to the extremophytic lifestyle of S. parvula. [ABSTRACT FROM AUTHOR]

For the integrated design of composite material and structures, it is essential to have an effective micromechanical numerical tool to link macroscopic material properties to microstructural configurations. In this paper, 3D computational grains (CGs) with embedded fibers are proposed for the first time, for the direct micromechanical modeling of fiber composites. The microstructure of a unidirectional lamina with random fibers can be assembled by many CGs, and the stiffness matrix of each CG with an embedded fiber can be directly computed by combining two new algorithms. On one hand, a new kind of Trefftz trial displacement field based on scaled cylindrical harmonics is independently assumed, in addition to inter-elemental displacement interpolations with surface nodal degrees of freedom (DoFs). On the other hand, a new kind of multi-field boundary variational principle is proposed to relate independently assumed Trefftz fields to nodal DoFs and to derive the stiffness matrix. Numerical examples demonstrate that without the traditional fine meshing, accurate distribution of micro-stresses in a representative volume element (RVE) with thousands of fibers can be directly computed, and the equivalent orthotropic properties of fiber composites can be predicted. This is also the first time that a three-dimensional finite element with an embedded fiber is developed. [ABSTRACT FROM AUTHOR]

A multi-signal aptasensor for thrombin determination is proposed based on catalytically active gold nanoparticles (AuNPs) and fluorescent silicon quantum dots (SiQDs). Yellow 4-Nitrophenol (4-NP) could be converted to colorless 4-Aminophenol (4-AP) by catalytically active aptamer-modified AuNPs (S1-AuNPs). The SiQDs emitted strong blue fluorescence at 455 nm at the excitation wavelength of 367 nm. When thrombin was absent, S1-AuNPs could catalytically reduce yellow 4-NP to colorless 4-AP. When thrombin was added, the aptamer could be transformed into a G-quadruplex structure, which masked the surface-active catalytic sites of AuNPs and restrained the reduction of 4-NP. Thus, the fluorescence of SiQDs was greatly quenched by 4-NP through the inner filter effect (IFE), and the solution color remained yellow. As the concentration of thrombin increased, the catalytic activity of S1-AuNPs decreased. The concentration of 4-NP that was converted to 4-AP declined and the unconverted 4-NP increased. In this process, the absorption peak of 4-NP at 400 nm increased while the fluorescence emission of SiQDs at 455 nm decreased. The linear ranges of the fluorometric and colorimetric aptasensor were 0.5–30 nM and 0.3–30 nM, respectively. The limits of detection (LOD) for the two modes were 0.15 nM and 0.13 nM. Furthermore, a portable sensing platform was constructed by combining the smartphone-based device with the software ImageJ for the determination of thrombin. With the advantages of cost-effectiveness, simplicity of operation and broad applicability, this aptasensor provided a new perspective for on-site determination of thrombin in the clinical field. [ABSTRACT FROM AUTHOR]

The accrual of cancer mutation data and related functional and clinical associations have revolutionised human oncology, enabling the advancement of precision medicine and biomarker‐guided clinical management. The catalogue of cancer mutations is also growing in canine cancers. However, without direct high‐powered functional data in dogs, it remains challenging to interpret and utilise them in research and clinical settings. It is well‐recognised that canine and human cancers share genetic, molecular and phenotypic similarities. Therefore, leveraging the massive wealth of human mutation data may help advance canine oncology. Here, we present a structured analysis of sequence conservation and conversion of human mutations to the canine genome through a 'caninisation' process. We applied this analysis to COSMIC, the Catalogue of Somatic Mutations in Cancer, the most prominent human cancer mutation database. For the project's initial phase, we focused on the subset of the COSMIC data corresponding to Cancer Gene Census (CGC) genes. A total of 670 canine orthologs were found for 721 CGC genes. In these genes, 365 K unique mutations across 160 tumour types were converted successfully to canine coordinates. We identified shared putative cancer‐driving mutations, including pathogenic and hotspot mutations and mutations bearing similar biomarker associations with diagnostic, prognostic and therapeutic utility. Thus, this structured caninisation of human cancer mutations facilitates the interpretation and annotation of canine mutations and helps bridge the knowledge gap to enable canine precision medicine. [ABSTRACT FROM AUTHOR]

Given that the transition from ductal carcinoma in situ (DCIS) to invasive breast cancer (BC) is crucial during the BC progression, the mechanism involved in the invasion transition behind triple‐negative breast cancer (TNBC) and estrogen receptor‐positive (ER‐positive) subtype has remained elusive. This article detected distinct invasion patterns of BC cells between the ER‐positive and TNBC using intraductal murine models with intraductal administration of carbon nanoparticles (CNPs). First, the feasibility of the utility of CNPs as a tracer was proved. The area ratio of CNPs and tumor cells invading the stroma at the late stage was found significantly higher than that in the early stage in MNU‐induced ER‐positive BC. However, opposite results were obtained in the triple‐negative model. Consequently, we proposed that the ER‐positive phenotype cells behave differently between different stages during tumor progression while there is no such difference in the invasion process of TNBC cells. The analysis regarding the duct integrity along with immunohistochemical characteristics further explained the distinct invasion features between the ER‐positive and triple‐negative subtypes. Last, the relationship between the duct thickness and the duct integrity suggested that ER‐positive tumors gradually increased in size within the lumen before the invasion. Overall, this study suggested the different invasion characteristics of ER‐positive BC and TNBC in vivo. [ABSTRACT FROM AUTHOR]

In this study, the stage subsequent to filling mining is selected as the background, and the cemented tailings backfill serves as the research object. Given the effects of the layer effect, top load, lateral pressure coefficient, and so forth, a safety factor calculation model of cemented tailings backfill in large depth–width ratio stopes is developed in accordance with the Mohr–Coulomb failure criterion, which is compared with the models proposed by other scholars. Lastly, the characteristics of the effect exerted by a wide variety of factors are discussed. As indicated by the results, (1) there are three scenarios in the position of the sliding surface, located in the first layer, passing through two layers and passing through three layers, and mainly the first two. Compared with other models, the rationality and reliability of the model in this study are verified. Different models have different research backgrounds and different focuses, and certain differences exist in results. (2) The safety factor of cemented tailings backfills is reduced with the increase of the top load, the lateral pressure coefficient, and the bulk density, while it is increased with the increase of cohesion, internal friction angle, and bonding force ratio. Furthermore, a linear functional relationship exists between them. The safety factor has the maximum sensitivity to cohesion and the minimum sensitivity to top load. (3) Using Statistical Package for the Social Sciences (SPSS) software for regression analysis, a simplified multiple linear regression equation between the safety factor and the respective factor is built. The regression results achieve an error of 10%. As revealed by the result of this study, the simplified regression equation can be applied to the stability evaluation of the on-site cemented tailings backfill. [ABSTRACT FROM AUTHOR]

Over the past few months, the outbreak of Coronavirus disease (COVID-19) has been expanding over the world. A reliable and accurate dataset of the cases is vital for scientists to conduct related research and policy-makers to make better decisions. We collect the United States COVID-19 daily reported data from four open sources: the New York Times, the COVID-19 Data Repository by Johns Hopkins University, the COVID Tracking Project at the Atlantic, and the USAFacts, then compare the similarities and differences among them. To obtain reliable data for further analysis, we first examine the cyclical pattern and the following anomalies, which frequently occur in the reported cases: (1) the order dependencies violation, (2) the point or period anomalies, and (3) the issue of reporting delay. To address these detected issues, we propose the corresponding repairing methods and procedures if corrections are necessary. In addition, we integrate the COVID-19 reported cases with the county-level auxiliary information of the local features from official sources, such as health infrastructure, demographic, socioeconomic, and environmental information, which are also essential for understanding the spread of the virus. [ABSTRACT FROM AUTHOR]

Background: The tumor microenvironment plays a crucial role in the oncogenesis and treatment of diffuse large B-cell lymphoma (DLBCL). The H3K9me3-specific histone methyltransferase Suppressor of variegation 3-9 homolog 1 (SUV39H1) is a significant gene that promotes the progression of various malignancies. However, the specific expression of SUV39H1 in DLBCL remains unclear. Methods: By retrieving data from GEPIA, UCSC XENA and TCGA public databases, we observed the high expression of SUV39H1 in DLBCL. Combined with an immunohistochemical validation assay, we analyzed our hospital's clinical characteristics and prognosis of 67 DLBCL patients. The results showed that high SUV39H1 expression was closely associated with age over 50 years (P = 0.014) and low albumin levels (P = 0.023) of patients. Furthermore, the experiments in vitro were deployed to evaluate the regulation of SUV39H1 on the DLBCL immune microenvironment. Results: The results showed that high SUV39H1 expression was closely associated with age over 50 years (P = 0.014) and low albumin levels (P = 0.023) of patients. The prognostic analysis showed that the high SUV39H1 expression group had a lower disease-free survival (DFS) rate than the low SUV39H1 expression group (P < 0.05). We further discovered that SUV39H1 upregulated the expression of CD86+ and CD163+ tumor-associated macrophages by DLBCL patients' tissues and cell experiments in vitro (P < 0.05). And SUV39H1-associated T lymphocyte subsets and cytokines IL-6/CCL-2 were downregulated in DLBCL (P < 0.05). Conclusions: In summary, SUV39H1 might be not only a potential target for treating DLBCL but also a clinical indicator for doctors to evaluate the trend of disease development. [ABSTRACT FROM AUTHOR]

The variational principles and corresponding finite element formulations are developed in this work for the free vibration and buckling analysis of partial-interaction composite beams under complex engineering situations, such as axial loading conditions, non-uniform material distributions, multi-span boundaries. The composites structures consist of sub-components connected with shear connections of finite rigidities and thus suffer from the partial-interaction phenomenon, significantly affecting the structural performance. The macroscopic elements for dynamic and buckling behavior are explicitly derived by simultaneously considering the sub-elements' deformations and interlayer slips, avoiding the stress concentrations in the contact areas existing in the commercial packages. The generated frequencies and critical loads of several orders for the single- or two-span composite structures with different boundary conditions are then validated against the analytical and numerical results in the literature with well-matched agreement. The interfacial shear connections and structural parameters are also studied of their influences on the structural dynamic and buckling behavior. The present theory is finally implemented in the theoretical analysis of the steel box-girder viaduct with non-uniformly-distributed shear braces and multi-span continuous composite beams of Jiubao Bridge. The explicit expressions of the elements are provided and can be readily implemented into the commercial software with high computational efficiency. [ABSTRACT FROM AUTHOR]

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In this paper, the influence of the surface effect on wave propagation characteristics in functionally graded metal foam plates (FGMFPs) with nanopores is studied, where different porosity distribution patterns are taken in account. The surface effect between pore and matrix in FGMFP is considered by the Gurtin–Murdoch surface elasticity model. The plate is divided into finite thickness layers along the gradient, and each layer of porous material is homogenized using locally exact homogenization theory. On the basis of obtaining the effective modulus of each layer of porous material, the governing equations of the plates are obtained by Hamilton's principle and different plate theories, upon which wave dispersion and phase velocity curves of FGMFP are obtained. The developed method is verified by comparing the wave dispersion curves against existing literature. Finally, the effects of different plate theories, porosity distribution, unit cell array, surface effect, pore radius and its distribution pattern, and graphene platelet weight fraction on the wave dispersion and phase velocity curves are systematically investigated. The results in this paper may provide guidance for the design of FGMFPs with nanopores. [ABSTRACT FROM AUTHOR]

Fluoroelastomer has received increasing attention for energetic materials application due to its high fluorine contents. Different contents (0 wt%–30 wt%) of poly(VDF‐ter‐HFP‐ter‐TFE) terpolymer are added into Al/MnO2 nanothermite. The peak exothermic temperature of thermite reaction for Al/MnO2 system is about 554°C with 1070 Jg−1 heat release. After adding terpolymer, it mainly exists in the gap among Al nanoparticles and MnO2 nanorods, and react with Al and MnO2 at the range of 350 to 540°C before the occurrence of the thermite reaction. 10 wt% terpolymer has relatively little effect on the thermite reaction, but for the samples with higher terpolymer content, more nanothermite components react with terpolymer at an early stage. Ignition and combustion performance show terpolymer can reduce ignition current threshold by up to 9.82% and increase combustion duration time at least several times. The potential reasons for the above results are analyzed. This work can shed light on the application of fluoroelastomer in energetic‐materials. [ABSTRACT FROM AUTHOR]

Materials with tunable emission colors has attracted increasing interest in both fundamental research and applications. As a key member of light‐emitting materials family, lanthanide doped upconversion nanoparticles (UCNPs) have been intensively demonstrated to emit light in any color upon near‐infrared excitation. However, realizing the trichromatic emission in UCNPs with a fixed composition remains a great challenge. Here, without excitation pulsed modulation and three different near‐infrared pumping, we report an experimental design to fine‐control emission in the full color gamut from core–shell‐structured UCNPs by manipulating the energy migration through dual‐channel pump scheme. We also demonstrate their potential application in full‐color display. These findings may benefit the future development of convenient and versatile optical methos for multicolor tuning and open up the possibility of constructing full‐color volumetric display systems with high spatiotemporal resolution. [ABSTRACT FROM AUTHOR]

Materials with tunable emission colors has attracted increasing interest in both fundamental research and applications. As a key member of light‐emitting materials family, lanthanide doped upconversion nanoparticles (UCNPs) have been intensively demonstrated to emit light in any color upon near‐infrared excitation. However, realizing the trichromatic emission in UCNPs with a fixed composition remains a great challenge. Here, without excitation pulsed modulation and three different near‐infrared pumping, we report an experimental design to fine‐control emission in the full color gamut from core–shell‐structured UCNPs by manipulating the energy migration through dual‐channel pump scheme. We also demonstrate their potential application in full‐color display. These findings may benefit the future development of convenient and versatile optical methos for multicolor tuning and open up the possibility of constructing full‐color volumetric display systems with high spatiotemporal resolution. [ABSTRACT FROM AUTHOR]

We analyze crude oil's dependence and the risk spillover effect on the Chinese stock market and the gold market. We compare both static and dynamic copula functions and calculate the average upward and downward spillover effect using the time-varying Copula model and the conditional value-at-risk approach. By utilizing daily data on crude oil prices, China's stock market, and the gold market, we observe an asymmetric spillover effect: the downside spillover effects from crude oil prices on the Chinese stock market and gold market are larger than the upside spillover effect. We then identify changes in the structure of the sample periods and calculate the dynamic conditional correlation between them. In addition, we explore the optimal weight and hedge ratios in diversified portfolios to mitigate potential risks. Our results suggest that investors and portfolio managers should frequently adjust their portfolio strategies, particularly during extreme events like COVID-19, when financial assets become more volatile. Furthermore, crude oil can help reduce the risk in the Chinese stock market and gold market to some extent during different sub-periods. [ABSTRACT FROM AUTHOR]

There are only six isolated living giant panda populations, and a comprehensive understanding of their genetic health status is crucial for the conservation of this vulnerable species. Liangshan Mountains is one of the main distribution areas of living giant pandas and is outside the newly established Giant panda national park. In this study, 971 giant panda fecal samples were collected in the heartland of Liangshan Mountains (Mabian Dafengding Nature Reserve: MB; Meigu Dafengding Nature Reserve: MG; and Heizhugou Nature Reserve: HZG). Microsatellite markers and mitochondrial D‐loop sequences were used to estimate population size and genetic diversity. We identified 92 individuals (MB: 27, MG: 22, HZG: 43) from the three reserves. Our results showed that: (1) genetic diversity of three giant panda populations was moderate; (2) several loci deviated significantly from the Hardy–Weinberg equilibrium and almost all these deviated loci showed significant heterozygote deficiencies and inbreeding; (3) three giant panda populations have substantial genetic differentiation with the most differentiation between MB and the two other populations; and (4) a large amount of giant panda feces outside the three reserves were found, implying the existence of protection gap. These results indicated that under stochastic events, the giant panda populations in Liangshan Mountains are at risk of genetic decline or extinction and urgent need of human management. This study revealed that high attention should be paid to the protection of these giant panda populations outside the Giant panda national park, to ensure their survival in their distribution areas. [ABSTRACT FROM AUTHOR]

This paper examines the dynamic relationships and the volatility spillover effects among crude oil, gold, and Chinese electricity companies' stock prices, from 2 December 2008 to 25 July 2022. By estimating the dynamic conditional correlation (DCC) model, we identify the time-varying correlation between crude oil, gold, and Chinese electricity stocks. Then, we use the time-varying parameter VAR model (TVP-VAR) to analyze the total and net volatility spillover effects. In addition, we compare the hedge ratio strategy and the portfolio weights strategy, as well as the corresponding hedging effectiveness among the crude oil, gold, and Chinese electricity companies. Considering the impact of the extreme events, we also extend the examination to the special period analysis of two crises, the Chinese stock market crash in 2015 and the COVID-19 pandemic in 2020. The results indicate that significant volatility spillover effects exist among crude oil, gold, and Chinese electricity companies' stock volatility, and the total spillover effects show a sharp increase under the impact of the crisis. On average, gold is a much cheaper hedging tool than crude oil, whereas these two commodity assets remain net volatility receivers during the whole period and the crisis. However, it is worth noting that for specific assets, the impact of the crisis on spillover effects depends on the characteristics of crisis events and the assets analyzed. Additionally, most optimal weight strategies provide better hedging effectiveness than hedging strategies from the perspective of hedging effectiveness. [ABSTRACT FROM AUTHOR]

As one of the critical phenomena during the firing of guns, propellant combustion creates an expanding gas plume with smoke containing the combustion residues. This paper aims to clarify the influence of gunshot residue particles on muzzle flow. Firstly, a two‐dimensional gas‐solid two‐phase model is established to describe the muzzle flow with gunshot residue for a small caliber rarefaction wave gun. And a discrete phase model is used to track particle trajectories for the dilute gas‐solid flow. Then the different development processes are discussed between the pure‐gas and the gas‐solid flow. Finally, the particle diameter and the mass fraction of particles are investigated to show the effects on the development process of the muzzle flow with gunshot resides. The results show that particles greatly influence the main flow parameters in the muzzle flow with gunshot residue. The gas velocity decreases due to the interaction between the particles and the gas. This paper provides a valuable reference for the study of muzzle flow. [ABSTRACT FROM AUTHOR]

Cortical bone is a complex hierarchical structure consisting of biological fiber composites with transversely isotropic constituents, whose microstructures deserve extensive study to understand the mechanism of living organisms and explore development of biomimetic materials. Based on this, we establish a three-level hierarchical structure from microscale to macroscale and propose a multiscale micromechanics model of cortical bone, which considers Haversian canal, osteonal lamellae, cement line and interstitial lamellae. In order to study the microstructural effect on the elastic behavior of hierarchical structures, the Mori–Tanaka model and locally exact homogenization theory are introduced for the homogenization of heterogeneous materials of microstructure at each level. Within sub-microscale, Haversian canal and Osteonal lamella are treated as fiber and matrix, whose homogenization is surrounded with cement line matrix in microstructure (or what we called "osteon") for the second homogenization; finally, osteon and interstitial lamella establish the meso-structure for the third homogenization, predicting the effective moduli of cortical bone. The correctness of the model in this paper is verified against the data in literature with good agreement. Finally, the dynamic viscoelastic response of cortical bones is investigated from a multiscale perspective, where the measured data are substituted into the present models to study the hydration and aging effect on bones' stiffness and viscoelasticity. It is demonstrated that the hydration is much more influential in affecting the storage and loss moduli of cortical bone than the aging effect. We also present a few numerical investigations on microstructural material and geometric parameters on the overall mechanical properties of cortical bone. [ABSTRACT FROM AUTHOR]

Summary: Plant adaptation to a desert environment and its endemic heat stress is poorly understood at the molecular level. The naturally heat‐tolerant Brassicaceae species Anastatica hierochuntica is an ideal extremophyte model to identify genetic adaptations that have evolved to allow plants to tolerate heat stress and thrive in deserts.We generated an A. hierochuntica reference transcriptome and identified extremophyte adaptations by comparing Arabidopsis thaliana and A. hierochuntica transcriptome responses to heat, and detecting positively selected genes in A. hierochuntica.The two species exhibit similar transcriptome adjustment in response to heat and the A. hierochuntica transcriptome does not exist in a constitutive heat 'stress‐ready' state. Furthermore, the A. hierochuntica global transcriptome as well as heat‐responsive orthologs, display a lower basal and higher heat‐induced expression than in A. thaliana. Genes positively selected in multiple extremophytes are associated with stomatal opening, nutrient acquisition, and UV‐B induced DNA repair while those unique to A. hierochuntica are consistent with its photoperiod‐insensitive, early‐flowering phenotype.We suggest that evolution of a flexible transcriptome confers the ability to quickly react to extreme diurnal temperature fluctuations characteristic of a desert environment while positive selection of genes involved in stress tolerance and early flowering could facilitate an opportunistic desert lifestyle. [ABSTRACT FROM AUTHOR]

Alkaline phosphatase (ALP) is a crucial marker for the clinical analysis and detection of many diseases. In this study, an accurate signal amplification strategy was proposed for the sensing and quantification of alkaline phosphatase using poly (3, 4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), gold nanoparticles (AuNPs), and Ag+. Signal amplification was achieved by the modification of PEDOT:PSS and AuNPs on glassy carbon electrodes. Atomic force microscopy was performed to characterize the morphology of the modified nanomaterials. To detect ALP, 1-naphthyl phosphate (1-NP) was used as the substrate, and alkaline phosphatase catalyzed 1-NP into 1-naphthol (1-N), which resulted in the reduction of Ag+ to Ag0 on the surface of the modified electrode (AuNPs/PEDOT:PSS/GCE). The deposition of Ag drastically enhanced the detection signal. Differential pulse voltammograms of 1-N, which is the enzymatic product from the ALP reaction with 1-NP, were recorded. In the linear range of 0.1–120 U L−1, a quantitative analysis of alkaline phosphatase was achieved, with high sensitivity and a low detection limit of 0.03 U L−1. Stable, selective, and reproducible electrochemical sensors were designed. Moreover, the proposed electrochemical sensor exhibited a prominent sensing performance in the spiked diluted human serum. Thus, the sensor can be used in numerous applications in alkaline phosphatase or other analyte detection. [ABSTRACT FROM AUTHOR]

Epidemic modelling is an essential tool to understand the spread of the novel coronavirus and ultimately assist in disease prevention, policymaking, and resource allocation. In this article, we establish a state-of-the-art interface between classic mathematical and statistical models and propose a novel space-time epidemic modelling framework to study the spatial-temporal pattern in the spread of infectious diseases. We propose a quasi-likelihood approach via the penalised spline approximation and alternatively reweighted least-squares technique to estimate the model. The proposed estimators are consistent, and the asymptotic normality is established for the constant coefficients. Utilizing spatiotemporal analysis, our proposed model enhances the dynamics of the epidemiological mechanism and dissects the spatiotemporal structure of the spreading disease. We evaluate the numerical performance of the proposed method through a simulation example. Finally, we apply the proposed method in the study of the devastating COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Coxiella burnetii is the etiological agent of the zoonotic disease Q fever, which is featured by its ability to replicate in acid vacuoles resembling the lysosomal network. One key virulence determinant of C. burnetii is the Dot/Icm system that transfers more than 150 effector proteins into host cells. These effectors function to construct the lysosome-like compartment permissive for bacterial replication, but the functions of most of these effectors remain elusive. In this study, we used an affinity tag purification mass spectrometry (AP-MS) approach to generate a C. burnetii-human protein-protein interaction (PPI) map involving 53 C. burnetii effectors and 3480 host proteins. This PPI map revealed that the C. burnetii effector CBU0425 (designated CirB) interacts with most subunits of the 20S core proteasome. We found that ectopically expressed CirB inhibits hydrolytic activity of the proteasome. In addition, overexpression of CirB in C. burnetii caused dramatic inhibition of proteasome activity in host cells, while knocking down CirB expression alleviated such inhibitory effects. Moreover, we showed that a region of CirB that spans residues 91–120 binds to the proteasome subunit PSMB5 (beta 5). Finally, PSMB5 knockdown promotes C. burnetii virulence, highlighting the importance of proteasome activity modulation during the course of C. burnetii infection. Author summary: As the causative agent of Q fever, C. burnetii colonizes host cells by transferring effector proteins into the host cytoplasm through its Dot/Icm secretion system to construct a replicative vacuole. The function of effectors remains largely unknown. Here, we performed a large-scale AP-MS screen to analyze the interactions among C. burnetii effectors and human proteins. These analyses found that CirB functions as an inhibitor of host proteasome activity, revealing that proteasome activity is important for intracellular survival of C. burnetii. Our data have laid the foundation for future exploring the molecular mechanisms underlying the roles of C. burnetii effectors in its virulence and for the identification of novel potential drug targets for the development of novel therapeutic treatment for C. burnetii infection. [ABSTRACT FROM AUTHOR]

Our previous study identified annexin A2 (ANXA2) as a Gaq‐interacting partner in natural killer/T cell lymphoma (NKTCL) cells transfected with the GNAQ T96S mutation vector by immunoprecipitation and mass spectrometry; however, the detailed molecular mechanisms by which GNAQ T96S might regulate ANXA2 remain to be defined in NKTCL. Herein, we found that the GNAQ T96S mutation significantly promotes the phosphorylation of ANXA2 at the Y24 site, whereas phosphorylation of ANXA2 abolishes the ability of WT GNAQ to trigger cell apoptosis. Further investigation revealed that a GNAQ T96S peptide inhibitor induced apoptosis by competing with ANXA2 binding to GNAQ T96S in NKTCL cells. In vivo animal experiments showed that a GNAQ T96S peptide inhibitor suppresses the growth of NKTCL cells carrying the GNAQ T96S mutation. Our current data suggest a role for GNAQ T96S/Src/ANXA2 in mediating the apoptosis of NKTCL cells, and the GNAQ T96S peptide could be a promising agent for therapy in NKTCL patients. [ABSTRACT FROM AUTHOR]

Zinc–air battery-based desalination (ZABD) is a potential solution to effectively desalinate brackish water and supply energy simultaneously, which requires catalysts with high and durable electrocatalytic activity for the oxygen reduction reaction (ORR) on the cathode of zinc–air batteries. Herein, a N-doped hierarchically porous carbon material encapsulating Co/Fe3O4 nanoparticles was successfully prepared using zeolitic imidazolate framework-8 (ZIF-8) as the precursor. Due to the integration of large specific surface area, hierarchically porous structure, and Co/Fe3O4 nanoparticles, the Co/Fe3O4@ZIF-8C catalyst exhibits a limiting current density of 5.93 mA cm−2 and a half-wave potential of 0.83 V, which is comparable to that of commercial platinum/carbon (Pt/C). It also presents outstanding durability and methanol endurance, superior to the Pt/C catalyst. More importantly, Co/Fe3O4@ZIF-8C achieved the dual functions of a fast salt removal rate (32.9 μg cm−2 min−1) and high energy output (91.6 KJ mol−1) when employed as the cathode catalyst of ZABD, which can process brine of 3000 ppm to a drinking water level of 128 ppm. The employment of Co/Fe3O4@ZIF-8C enables ZABD to possess stable batch cyclability and durable desalination performance. This is the first time that a non-noble metal catalyst has been applied in ZABD, realizing an outstanding desalination performance comparable to that of commercial Pt/C. Accordingly, the high-efficiency and low-cost ORR catalytic material provided by this work has significant application prospects in seawater desalination and metal–air discharge batteries. [ABSTRACT FROM AUTHOR]

A novel and simple HCl-mediated, photocatalytic method for quinoxaline(on)es C3-H arylation with arylhydrazine under transition metal catalyst- and oxidant-free conditions is presented. Various quinoxaline(on)es underwent this transformation smoothly, demonstrating a broad substrate tolerance and providing the corresponding aryl products in moderate to excellent yields. Mechanistic studies indicated that a radical pathway may be involved in this transformation. [ABSTRACT FROM AUTHOR]