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The fruit shape of cucumber is an important agronomic trait, and mining regulatory genes, especially dominant ones, is vital for cucumber breeding. In this study, we identified a short and fat fruit mutant, named sff, from an EMS mutagenized population. Compared to the CCMC (WT), sff (MT) exhibited reduced fruit length and increased dimeter. Segregation analysis revealed that the sff phenotype is controlled by a semi-dominant single gene with dosage effects. Through map-based cloning, the SFF locus was narrowed down to a 52.6 kb interval with two SNPs (G651A and C1072T) in the second and third exons of CsaV3_1G039870, which encodes an IQD family protein, CsSUN. The G651A within the IQ domain of CsSUN was identified as the unique SNP among 114 cucumber accessions, and it was the primary cause of the functional alteration in CsSUN. By generating CsSUN knockout lines in cucumber, we confirmed that CsSUN was responsible for sff mutant phenotype. The CsSUN is localized to the plasma membrane. CsSUN exhibited the highest expression in the fruit with lower expression in sff compared to WT. Histological observations suggest that the sff mutant phenotype is due to increased transverse cell division and inhibited longitudinal cell division. Transcriptome analysis revealed that CsSUN significantly affected the expression of genes related to cell division, expansion, and auxin signal transduction. This study unveils CsSUN's crucial role in shaping cucumber fruit and offers novel insights for cucumber breeding., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Currently, there are no effective therapeutic agents available to treat Alzheimer's disease (AD). However, edaravone dexborneol (EDB), a novel composite agent used to treat acute ischemic stroke, has recently been shown to exert efficacious neuroprotective effects. However, whether EDB can ameliorate cognitive deficits in AD currently remains unclear. To this end, we explored the effects of EDB on AD and its potential mechanisms using an AD animal model (male APP/PS1 mice) treated with EDB for 10 weeks starting at 6 months of age. Subsequent analyses revealed that EDB-treated APP/PS1 mice exhibited improved cognitive abilities compared to untreated APP/PS1 mice. Administration of EDB in APP/PS1 mice further alleviated neuropathological alterations of the hippocampus, including Aβ deposition, pyramidal cell karyopyknosis, and oxidative damage, and significantly decreased the levels of inflammatory cytokines (IL-1β, IL-6 and TNF-α) and COX-2 in the hippocampus of APP/PS1 mice. Transcriptome sequencing analysis demonstrated the critical role of the inflammatory reaction in EDB treatment in APP/PS1 mice, indicating that the alleviation of the inflammatory reaction by EDB in the hippocampus of APP/PS1 mice was linked to the action of the TREM2/TLR4/MAPK signaling pathway. Further in vitro investigations showed that EDB suppressed neuroinflammation in LPS-stimulated BV2 cells by inhibiting the TLR4/MAPK signaling pathway and upregulating TREM2 expression. Thus, the findings of the present study demonstrate that EDB is a promising therapeutic agent for AD-related cognitive dysfunction., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Polyetheretherketone (PEEK) implants have emerged as a clinically favored alternative to titanium alloy implants for cranial bone substitutes due to their excellent mechanical properties and biocompatibility. However, the biological inertness of PEEK has hindered its clinical application. To address this issue, we developed a dual-functional surface modification method aimed at enhancing both osteogenesis and antibacterial activity, which was achieved through the sustained release of chondroitin sulfate (CS) and levofloxacin (LVFX) from a biomimetic polydopamine (PDA) coating on the PEEK surface. CS was introduced to promote cell adhesion and osteogenic differentiation. Meanwhile, incorporation of antibiotic LVFX was essential to prevent infections, which are a critical concern in bone defect repairing. To our delight, experiment results demonstrated that the SPKD/CS-LVFX specimen exhibited enhanced hydrophilicity and sustained drug release profiles. Furthermore, in vitro experiments showed that cell growth and adhesion, cell viability, and osteogenic differentiation of mouse calvaria-derived osteoblast precursor (MC3T3-E1) cells were significantly improved on the SPKD/CS-LVFX coating. Antibacterial assays also confirmed that the SPKD/CS-LVFX specimen effectively inhibited the growth of Escherichia coli and Staphylococcus aureus , attributable to the antibiotic LVFX released from the PDA coating. To sum up, this dual-functional PEEK implant showed a promising potential for clinical application in bone defects repairing, providing excellent osteogenic and antibacterial properties through a synergistic approach.

Magnetic nanomaterials record information as fast as picoseconds in computer memories but retain it for millions of years in ancient rocks. This exceedingly broad range of times is covered by hopping over a potential energy barrier through temperature, ultrafast optical excitation, mechanical stress, or microwaves. As switching depends on nanoparticle size, shape, orientation, and material properties, only single-nanoparticle studies can eliminate the ensemble heterogeneity. Here, we push the sensitivity of photothermal magnetic circular dichroism down to individual 20 nm magnetite nanoparticles. Single-particle magnetization curves display superparamagnetic to ferromagnetic behaviors, depending on the size, shape, and orientation. Some nanoparticles undergo thermally activated switching on time scales of milliseconds to minutes. Surprisingly, the switching barrier varies with time, leading to dynamical heterogeneity, a phenomenon familiar in protein dynamics and supercooled liquids. Our observations will help to identify the external parameters influencing magnetization switching and, eventually, to control it, an important step for many applications.

In recent years, most studies on the gut microbiome have primarily focused on feces samples, leaving the microbial communities in the intestinal mucosa relatively unexplored. To address this gap, our study employed shotgun metagenomics to analyze the microbial compositions in normal rectal mucosa and matched feces from 20 patients with colonic polyps. Our findings revealed a pronounced distinction of the microbial communities between these two sample sets. Compared with feces, the mucosal microbiome contains fewer genera, with Burkholderia being the most discriminating genus between feces and mucosa, highlighting its significant influence on the mucosa. Furthermore, based on the microbial classification and KEGG Orthology (KO) annotation results, we explored the association between rectal mucosal microbiota and factors such as age, gender, BMI, and polyp risk level. Notably, we identified novel biomarkers for these phenotypes, such as Clostridium ramosum and Enterobacter cloacae in age. The mucosal microbiota showed an enrichment of KO pathways related to sugar transport and short chain fatty acid metabolism. Our comprehensive approach not only bridges the knowledge gap regarding the microbial community in the rectal mucosa but also underscores the complexity and specificity of microbial interactions within the human gut, particularly in the Chinese population., Importance: This study presents a system-level map of the differences between feces and rectal mucosal microbial communities in samples with colorectal cancer risk. It reveals the unique microecological characteristics of rectal mucosa and its potential influence on health. Additionally, it provides novel insights into the role of the gut microbiome in the pathogenesis of colorectal cancer and paves the way for the development of new prevention and treatment strategies., Competing Interests: The authors declare no conflict of interest.

As a major human and animal pathogen, Staphylococcus aureus can attach to medical implants (abiotic surface) or host tissues (biotic surface), and further establish robust biofilms which enhances resistance and persistence to host immune system and antibiotics. Cell-wall-anchored proteins (CWAPs) covalently link to peptidoglycan, and largely facilitate the colonization of S. aureus on various surfaces (including adhesion and biofilm formation) and invasion into host cells (including adhesion, immune evasion, iron acquisition and biofilm formation). During biofilm formation, CWAPs function in adhesion, aggregation, collagen-like fiber network formation, and consortia formation. In this review, we firstly focus on the structural features of CWAPs, including their intracellular function and interactions with host cells, as well as the functions and ligand binding of CWAPs in different stages of S. aureus biofilm formation. Then, the roles of CWAPs in different biofilm processes with regards in development of therapeutic approaches are clarified, followed by the association between CWAPs genes and clonal lineages. By touching upon these aspects, we hope to provide comprehensive knowledge and clearer understanding on the CWAPs of S. aureus and their roles in biofilm formation, which may further aid in prevention and treatment infection and vaccine development., Competing Interests: Declaration of Competing Interest There are no conflicts to declare., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background and Objective: Our study aimed to evaluate the associations between platelet count (PC) and in-hospital outcomes for patients with stroke after rt-PA intravenous thrombolysis., Methods: We identified patients who had been hospitalized with a primary diagnosis of stroke and had received rt-PA intravenous thrombolysis from June 2015 to July 2019 at participating hospitals in the Chinese Stroke Center Alliance. PC measured before intravenous thrombolysis was categorized into the following four groups: severe thrombocytopenia (PC < 100 × 10 9 /L), mild thrombocytopenia (100 ≤ PC < 150 × 10 9 /L), normal PC (150 ≤ PC ≤ 450 × 10 9 /L), and thrombocythemia (PC > 450 × 10 9 /L). Outcomes were determined from clinical data collected during hospitalization. The primary clinical outcome was symptomatic intracranial hemorrhage (sICH). Secondary outcomes were mortality, bleeding events, gastrointestinal (GI) hemorrhage, and in-hospital stroke recurrence. We used multivariate logistic regression models to evaluate the associations between PC and outcomes., Results: We included 44,882 individuals with a median age of 66 years, of whom 34.7 % were female, 951 (2.1 %) had severe thrombocytopenia, 7218 (16.1 %) had mild thrombocytopenia, 36,522 (81.4 %) had a normal PC, and 191 (0.4 %) had thrombocythemia. Both severe and mild thrombocytopenia groups had higher risks of bleeding events (adjusted OR 1.30; 95 % CI,1.01-1.67; p = 0.045; adjusted OR 1.32; 95 % CI,1.19-1.46; p < 0.001) and sICH (adjusted OR 1.48;95 % CI,1.13-1.94; p = 0.005; adjusted OR 1.43;95 % CI,1.27-1.60; p < 0.001) than the normal PC group. Patients with 100 ≤ PC < 150 × 10 9 /L also had a higher risk of in-hospital stroke recurrence (adjusted OR 1.12; 95 % CI,1.02-1.22; p = 0.02)., Conclusions: Intravenous thrombolysis brings a high risk of sICH given PC < 150 × 10 9 /L, especially PC < 100 × 10 9 /L. It indicated that PC < 100 × 10 9 /L is a reasonable contraindication to thrombolysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Detecting temperature and concentration fields within engine combustors holds paramount significance in enhancing combustion efficiency and ensuring operational safety. Within the realm of engine combustors, the laminar absorption spectroscopy technique has garnered considerable attention. Particularly crucial is the optimization of the optical path configuration to enhance the efficacy of reconstruction. This study presents a flame parameter field reconstruction model founded on laminar absorption spectroscopy. Furthermore, an optimization approach for refining the optical path configuration is delineated. In addressing non-axisymmetric flames, the simulated annealing algorithm (SA) and Harris's Hawk algorithm (HHO) are employed to optimize the optical path layout across varying beam quantities. The findings underscore a marked reduction in imaging errors with the optimized optical path configuration compared to conventional setups, thereby elevating detection precision. Notably, the HHO algorithm demonstrates superior performance over the SA algorithm in terms of optimization outcomes and computational efficiency. Compared with the parallel optical path, the optimized optical path of the HHO algorithm reduces the temperature field error by 25.5% and the concentration field error by 26.5%.

Objective: To look into the effects of different anesthesia methods on the labor process and the expression of serum estrogen and progesterone in primiparas with painless labor., Methods: 60 primiparas receiving painless labor were selected as the research objects, and they were divided into either a Spinal & Continuous epidural anesthesia group (n = 30) or a continuous epidural anesthesia group (n = 30), anesthesia is administered using the corresponding anesthesia method. The authors compared serum estrogen and progesterone, inflammatory index expression, pain degree and neonatal health status in different periods., Results: At T2 and T3, serum P, LH, FSH and E2 levels in the Spinal & Continuous epidural anesthesia group were signally lower than those in the Spinal & Continuous epidural anesthesia group (p < 0.05). Spinal & Continuous epidural anesthesia group harbored faster onset and longer duration of sensory block and motor block than the Continuous epidural anesthesia group (p < 0.05). SAS and SDS scores of the Spinal & Continuous epidural anesthesia group were clearly lower than those of the Continuous epidural anesthesia group (p < 0.05). VAS score and serum TNF-α, IL-6 levels of pregnant women in the Spinal & Continuous epidural anesthesia group were memorably lower than those in the Continuous epidural anesthesia group at T2 and T3 (p < 0.05). The total incidence of postoperative complications in the Spinal & Continuous epidural anesthesia group was distinctively lower than that in the Continuous epidural anesthesia group (p < 0.05)., Conclusion: Spinal anesthesia combined with continuous epidural anesthesia has a better anesthesia effect in the painless labor of primiparas, which can effectually ameliorate the labor process and the expression of serum estrogen and progesterone., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Background: The complex etiology of Ischemia-Reperfusion Injury (IRI) induced by liver transplantation (LT) and the "one-target-focused" method limit the development of effective therapeutic interventions. We aimed to reveal the specific active ingredients and mechanisms involved in the Chinese herb Scutellaria baicalensis Georgi (SBG) in alleviating IRI in LT., Methods: The active ingredients and potential macromolecular targets of SBG were screened through related databases. The differentially expressed genes of LT were obtained from GSE151648. The protein-protein interaction network was constructed by the STRING database, and Cytoscape 3.7.1 was used to construct a compound-target-disease network. GO and KEGG enrichment analyses were performed on the DAVID database. Finally, the main active components of SBG and the corresponding mechanisms were verified in a donation after circulatory death (DCD) rat LT model., Results: Thirty-two active ingredients of SBG and their targets were identified, and a total of 38 intersection targets were obtained. GO function and KEGG pathway enrichment analyses demonstrated that the plasma membrane and its components play an important role. Molecular docking showed baicalein, the core component of SBG, had a strong binding ability to all hub targets. Next, in DCD rats, baicalein was proven to improve liver function, alleviate pathological injury and apoptosis, and increase the survival rate. Baicalein also significantly affected the expression of 7 hub genes. Furthermore, baicalein could inhibit ferroptosis by inhibiting phospholipid peroxidation., Conclusion: Baicalein, the main component of SBG, could alleviate IRI, affect the expression of hub genes, and inhibit ferroptosis in LT., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To investigate the prevalence and intensity of grasp reflexes and to examine changes in these reflexes after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH)., Methods: We enrolled 147 patients with probable iNPH. A standard procedure was used to determine the presence of grasp reflexes, and the intensity of these reflexes was assessed using a four-category classification. Clinical rating scales and their correlation with grasp reflexes were also evaluated. Grasp reflexes were reassessed in 72 patients 1 year after surgery., Results: We found that approximately 50.3% of patients with iNPH exhibited a positive grasp reflex. Among these patients, 69% exhibited bilateral positivity, while the remaining patients showed unilateral positivity. Furthermore, the intensity of the grasp reflex was significantly correlated with the severity of gait and with cognitive, urinary, motor, and behavioural symptoms. Surgical interventions led to a reduction (41.7%) or maintenance (30.6%) of the reflex intensity in 72.3% of iNPH patients. The changes in reflex intensity showed significant positive correlations with changes in the number of steps of the Timed Up and Go test and Trail Making Test-A scores but not with changes in total scores on the iNPH Grading Scale., Conclusion: This retrospective study identified grasp reflexes as a highly prevalent phenomenon in patients with iNPH. These reflexes can assist in evaluating the severity of various symptoms, including cognitive, gait, urinary, motor and emotional symptoms., (© 2024. The Author(s).)

The development of a portable smartphone-based electrochemical sensor for analyzing adrenaline levels in real samples can make a great contribution to the research community worldwide. In order to achieve this goal, the key challenge is to build sensing interfaces with excellent electrocatalytic properties. In this work, microspherical bimetallic metal-organic frameworks (CoNi-MOF) consisting of nanoclusters were first synthesized using a hydrothermal method. On this basis, the catalytic activity of pure chitosan-polyacrylamide hydrogel (CS-PAM) was modulated by adding different amounts of CoNi-MOF during the in-situ synthesis of CS-PAM. Finally, a portable electrochemical detection system based on CS-PAM was established for the detection of adrenaline. A series of resulting composite hydrogels with a large specific surface area, abundant active sites, and unique network structure facilitate the enrichment and catalysis of adrenaline molecules. Under optimal conditions, the analytical platform constructed by using CoNi-MOF-based CS-PAM has the advantages of a wide detection range (0.5-10 and 10-2500 μM), a low detection limit (0.167 μM), and high sensitivity (0.182 and 0.133 μA·μM·cm -2 ). In addition, the sensor maintains selective detection of the target in the presence of many different types of interferences, and the current response is not significantly reduced even after 60 cycles of testing. We strongly believe that the designed smart portable sensing can realize the accurate determination of adrenaline in complex systems, and this study can provide new ideas for the research of MOFs-based hydrogels in electrochemical analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Candida albicans ( C. albicans ) and Lactiplantibacillus plantarum subsp. plantarum ( L. plantarum ) are frequently identified in various niches, but their dual-species interaction, especially with C. albicans in yeast form, remains unclear. This study aimed to investigate the dual-species interaction of L. plantarum and C. albicans , including proliferation, morphology, and transcriptomes examined by selective agar plate counting, microscopy, and polymicrobial RNA-seq, respectively. Maintaining a stable and unchanged growth rate, L. plantarum inhibited C. albicans yeast cell proliferation but not hyphal growth. Combining optical microscopy and atomic force microscopy, cell-to-cell direct contact and co-aggregation with L. plantarum cells surrounding C. albicans yeast cells were observed during dual-species interaction. Reduced C. albicans yeast cell proliferation in mixed culture was partially due to L. plantarum cell-free culture supernatant but not the acidic environment. Upon polymicrobial transcriptomics analysis, interesting changes were identified in both L. plantarum and C. albicans gene expression. First, two L. plantarum quorum-sensing systems showed contrary changes, with the activation of lamBDCA and repression of luxS . Second, the upregulation of stress response-related genes and downregulation of cell cycle, cell survival, and cell integrity-related pathways were identified in C. albicans , possibly connected to the stress posed by L. plantarum and the reduced yeast cell proliferation. Third, a large scale of pathogenesis and virulence factors were downregulated in C. albicans , indicating the potential interruption of pathogenic activities by L. plantarum . Fourth, partial metabolism and transport pathways were changed in L. plantarum and C. albicans . The information in this study might aid in understanding the behavior of L. plantarum and C. albicans in dual-species interaction.IMPORTANCEThe anti- Candida albicans activity of Lactiplantibacillus plantarum has been explored in the past decades. However, the importance of C. albicans yeast form and the effect of C. albicans on L. plantarum had also been omitted. In this study, the dual-species interaction of L. plantarum and C. albicans was investigated with a focus on the transcriptomes. Cell-to-cell direct contact and co-aggregation with L. plantarum cells surrounding C. albicans yeast cells were observed. Upon polymicrobial transcriptomics analysis, interesting changes were identified, including contrary changes in two L. plantarum quorum-sensing systems and reduced cell survival-related pathways and pathogenesis determinants in C. albicans ., Competing Interests: The authors declare no conflict of interest.

In the realm of high-tech materials and energy applications, accurately measuring the transient heat flow at media boundaries and the internal thermal conductivity of materials in harsh heat exchange environments poses a significant challenge when using conventional direct measurement methods. Consequently, the study of photothermal parameter reconstruction in translucent media, which relies on indirect measurement techniques, has crucial practical value. Current research on reconstructing photothermal properties within participating media typically focuses on single-objective or time-invariant properties. There is a pressing need to develop effective methods for the simultaneous reconstruction of time-varying thermal flow fields and internal thermal conductivity at the boundaries of participating media. This paper introduces a computational model based on the numerical simulation theory of internal heat transfer systems in participating media, stochastic particle swarm optimization algorithms, and Kalman filter technology. The model aims to enable the simultaneous reconstruction of various thermal parameters within the target medium. Our results demonstrate that under varying levels of measurement noise, the inversion results for different target parameters exhibit slight oscillations around the true values, leading to a reduction in reconstruction accuracy. However, overall, the model demonstrates robustness and accuracy in ideal conditions, validating its effectiveness.

In the past two decades, photothermal microscopy (PTM) has achieved sensitivity at the level of a single particle or molecule and has found applications in the fields of material science and biology. PTM is a far-field imaging method; its resolution is restricted by the diffraction limits. In our previous work, the modulated difference PTM (MDPTM) was proposed to improve the lateral resolution, but its resolution improvement was seriously constrained by information loss and artifacts. In this Letter, a deep learning approach of the cycle generative adversarial network (Cycle GAN) is employed for further improving the resolution of PTM, called DMDPTM. The point spread functions (PSFs) of both PTM and MDPTM are optimized and act as the second generator of Cycle GAN. Besides, the relationship between the sample's volume and the photothermal signal is utilized during dataset construction. The images of both PTM and MDPTM are utilized as the inputs of the Cycle GAN to incorporate more information. In the simulation, DMDPTM quantitatively distinguishes a distance of 60 nm between two nanoparticles (each with a diameter of 60 nm), demonstrating a 4.4-fold resolution enhancement over the conventional PTM. Experimentally, the super-resolution capability of DMDPTM is verified by restored images of Au nanoparticles, achieving the resolution of 114 nm. Finally, the DMDPTM is successfully employed for the imaging of carbon nanotubes. Therefore, the DMDPTM will serve as a powerful tool to improve the lateral resolution of PTM.

Wastewater treatment plants (WWTPs) contribute significantly to the control of pollution in water. However, they are significant energy consumers. Identifying the factors influencing energy consumption is crucial for enhancing the energy efficiency of WWTPs. To address this, the unit energy consumption (UEC) of WWTPs was predicted using machine learning models. In order to accurately evaluate WWTPs' energy utilization efficiency, a comprehensive energy evaluation indicator, UEC (kWh/kg TOD removed ) was utilized in this study. Among the prediction models, the eXtreme Gradient Boosting (XGBoost) achieves the highest prediction accuracy. SHapley Additive exPlanations (SHAP) was adopted as the model explanation system, and the results revealed that UEC was negatively affected by TN concentration, which was the most influential factor. The stoichiometry-based model calculation result indicates that the nitrification consumes average 77 % of the overall oxygen demand. SHAP analysis illustrated that the UEC of main technologies decreases with increasing influential factors. Partial dependence plot (PDP) compared average UEC of these technologies and SBR consumed the least amount of energy. The research also indicated that low influent TN concentration is the main problem in China. Consequently, it is imperative to exert efforts in ensuring the influent TN concentration while simultaneously making appropriate adjustments to the treatment process. This study provides valuable implications and methods for retrofitting and upgrading WWTPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The remarkable efficacy of cancer immunotherapy has been established in several tumor types. Of the various immunotherapies, PD-1/PD-L1 inhibitors are most extensively used in the treatment of many cancers in clinics. These inhibitors restore the suppressed antitumor immune response and inhibit tumor progression by blocking the PD-1/PD-L1 signaling. However, the low response rate is a major limitation in the clinical application of PD-1/PD-L1 inhibitors. Therefore, combination strategies that enhance the response rate are the need of the hour. In this investigation, PT-100 (also referred to as Talabostat, Val-boroPro, and BXCL701), an orally administered and nonselective dipeptidyl peptidase inhibitor, not only augmented the effectiveness of anti-PD-1 therapy but also significantly improved T immune cell infiltration and reversed the immunosuppressive tumor microenvironment. The combination of PT-100 and anti-PD-1 antibody increased the number of CD4 + and CD8 + T cells. Moreover, the mRNA expression of T cell-associated molecules was elevated in the tumor microenvironment. The results further suggested that PT-100 dramatically reduced the ratio of tumor-associated macrophages. These findings provide a promising combination strategy for immunotherapy in lung cancer.

Background: Thyroid cancer (THCA) is the most common endocrine malignancy having a female predominance. The insulin-like growth factor (IGF) pathway contributed to the unregulated cell proliferation in multiple malignancies. We aimed to explore the IGF-related signature for THCA prognosis., Method: The TCGA-THCA dataset was collected from the Cancer Genome Atlas (TCGA) for screening of key prognostic genes. The limma R package was applied for differentially expressed genes (DEGs) and the clusterProfiler R package was used for the Gene Ontology (GO) and KEGG analysis of DEGs. Then, the un/multivariate and least absolute shrinkage and selection operator (Lasso) Cox regression analysis was used for the establishment of RiskScore model. Receiver Operating Characteristic (ROC) analysis was used to verify the model's predictive performance. CIBERSORT and MCP-counter algorithms were applied for immune infiltration analysis. Finally, we analyzed the mutation features and the correlation between the RiskScore and cancer hallmark pathway by using the GSEA., Result: We obtained 5 key RiskScore model genes for patient's risk stratification from the 721 DEGs. ROC analysis indicated that our model is an ideal classifier, the high-risk patients are associated with the poor prognosis, immune infiltration, high tumor mutation burden (TMB), stronger cancer stemness and stronger correlation with the typical cancer-activation pathways. A nomogram combined with multiple clinical features was developed and exhibited excellent performance upon long-term survival quantitative prediction., Conclusions: We constructed an excellent prognostic model RiskScore based on IGF-related signature and concluded that the IGF signal pathway may become a reliable prognostic phenotype in THCA intervention.

Promoting innate immunity through pyroptosis induction or the cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS-STING) pathway activation has emerged as a potent approach to counteract the immunosuppressive tumor microenvironment and elicit systemic antitumor immunity. However, current pyroptosis inducers and STING agonists often suffer from limitations including instability, unpredictable side effects, or inadequate intracellular expression of gasdermin and STING. Here, a tumor-specific nanotheranostic platform that combines photodynamic therapy (PDT) with epigenetic therapy to simultaneously activate pyroptosis and the cGAS-STING pathway in a light-controlled manner is constructed. This approach involves the development of oxidation-sensitive nanoparticles (NP1) loaded with the photosensitizer TBE, along with decitabine nanomicelles (NP2). NP2 enables the restoration of STING and gasdermin E (GSDME) expression, while NP1-mediated PDT facilitates the release of DNA fragments from damaged mitochondria to potentiate the cGAS-STING pathway, and promotes the activation of caspase-3 to cleave the upregulated GSDME into pore-forming GSDME-N terminal. Subsequently, the released inflammatory cytokines facilitate the maturation of antigen-presentation cells, triggering T cell-mediated antitumor immunity. Overall, this study presents an elaborate strategy for simultaneous photoactivation of pyroptosis and the cGAS-STING pathway, enabling targeted photoimmunotherapy in immunotolerant tumors. This innovative approach holds significant promise in overcoming the limitations associated with existing therapeutic modalities and represents a valuable avenue for future clinical applications., (© 2023 Wiley-VCH GmbH.)

Few studies have investigated the association between PM 2.5 and hypertension among floating populations. We therefore examined the relationship using binary logistic regression. Each grade of increment in the annual average PM 2.5 (grade one: ≤15 µg/m 3 ; grade two: 15-25 µg/m 3 ; grade three: 25-35 µg/m 3 [Excluding 25]; grade four: ≥35 µg/m 3 ) was associated with an increased risk of hypertension (odds ratio [OR] = 1.081, 95% confidence interval (CI): 1.034-1.129). Among the female floating population (OR = 1.114, 95% CI: 1.030-1.204), those with education level of primary school and below (OR = 1.140, 95% CI: 1.058-1.229), construction workers (OR = 1.228, 95% CI: 1.058-1.426), and those living in the eastern region of China (OR = 1.241, 95% CI: 1.145-1.346) were more vulnerable to PM 2.5 . These results indicate that PM 2.5 is positively associated with hypertension in floating populations. Floating populations who are female, less educated, construction workers, and living in the eastern region of China are more vulnerable to the adverse impacts of PM 2.5 .

There are limited studies investigating the association between short-term exposure to PM 2.5 and incident cardiovascular disease (CVD) cases in China. This study aims to examine the short-term effects of PM 2.5 on the incidence of cardiovascular diseases. A combination of Poisson-distribution generalized linear model and distributed lag non-linear model was used to examine the association between short-term exposure to PM 2.5 and incident cases of CVD. The results revealed that per 10 µg/m 3 increment of PM 2.5 would increase the incident CVD cases by 0.147% (Relative Risk: 1.00147, 95% Confidence Interval: 1.00008-1.00286) at a lag of 2 days. The stratified analyses showed higher effects risk in females, older residents (aged 60-75 years), and acute myocardial infarction group (p-value for difference <0.05). This study indicates that short-term exposure to PM 2.5 may increase the risk of CVD and highlights the necessity for a higher air quality standard in Yantai, China.

Multiple microenvironmental modulation of zeolite imidazole framework-8 (ZIF-8) is expected to solve the long-term intractable problem of low sensitivity in electrochemical sensing. Herein, the metal phthalocyanines with different central ions (PcM, M = Fe, Co, Ni and Cu) were introduced into ZIF-8 by in-situ synthesis method. Then, the hollow composite nanomaterials, HZIF-8/PcFe and HZIF-8@PcFe (HZIF-8, i.e., hollow ZIF-8) with different TA (tannic acid) coating thicknesses (∼11 nm and ∼33 nm) were successfully fabricated by carefully designed polyphenol-mediated modulation (PMM) strategy. Next, the HZIF-8@PcFe electrochemical sensor was constructed for selective and sensitive analysis by selecting dopamine (DA) as the analyte. The TA coating (superhydrophilic state), PcFe (redox properties) and hollow MOF cavity (faster mass transfer) was used as the triple microenvironment modulation of ZIF-8 to enhance the electrocatalytic performance. Under the optimum conditions (pH = 8.0), the linear correlations of 0.3 to 200 μmol/L was obtained for the peak current response, with a detection limit of 0.1 μmol/L (S/N = 3, i.e., Signal/Noise = 3). Meanwhile, the HZIF-8@PcFe electrochemical sensor exhibited excellent interference selectivity, reproducibility and stability, which enabled it to detect low abundance DA in real samples. And the F-test (homogeneity test of variance) and t-test (student's t test) statistical analyses were employed to enhance the accuracy of the actual samples' detection. This work will enlighten researchers working in the field of porous framework composites and open up new paths for the development of hollow MOFs hybrid materials in electrochemical sensing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Sensitive detection of cholesterol in animal-derived foods is crucial for maintaining human healthy diets. In this study, an elegant approach utilizing inorganic nanozyme-based magnetic mesoporous silica nanoparticles (MMSNs) for the highly sensitive detection of cholesterol in animal-derived food products was reported. The results revealed the fabricated MMSNs exhibited remarkably intrinsic peroxidase (POD)-like catalytic activities with improved affinity, and the catalytic behavior aligned well with Michaelis-Menten equation. In addition, the data indicated that the MMSNs enabled visual colorimetric detection of cholesterol with a remarkably low detection limit of 7.12 μM by combining catalytic oxidation with cholesterol oxidase (ChOx). Furthermore, the prepared MMSNs were successfully employed for assessing cholesterol content in milk and egg yolk samples, indicating potential applications for cholesterol detection in animal-derived foods in future., Competing Interests: Declaration of Competing Interest The work described has not been submitted elsewhere for publication, in whole or in part; and it has been read and approved by all the named authors. There are no known conflicts of interest associated with this publication., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Ischemic stroke is a major cause of disability and death worldwide. A narrow therapeutic window profoundly constrained the utilization of alteplase., Objectives: To investigate therapeutic effects and safety of intravenous recombinant human prourokinase (rhPro-UK) in patients with acute ischemic stroke (AIS) in the 4.5-6 h therapeutic time windows., Methods: We conducted a phase IIa, randomized, and open-label multicenter clinical trial. Between 4.5 and 6 h after the onset of AIS, patients were randomly administrated to receive intravenous rhPro-UK at a 50 mg or 35 mg dose. The primary endpoint was excellent functional outcome defined as modified Rankin scale (mRS) score of 1 or less at 90 days. The secondary outcome was the treatment response, which was based on an at least 4-point improvement from baseline National Institutes of Health stroke scale (NIHSS) score at 24 h after drug administration. Safety endpoints included death, symptomatic intracerebral hemorrhage (sICH), and other serious adverse events., Results: We enrolled 80 patients in the 4.5-6 h therapeutic time windows at 17 medical centers in China from December 2016 to November 2017. A total of 39 patients were treated with 50 mg rhPro-UK, and 39 were treated with 35 mg rhPro-UK. Compared with the baseline, the NIHSS score at 24 h and days 7, 14, 30, and 90 was decreased significantly among patients treated with either rhPro-UK 50 mg or 35 mg. The mean reduction in the NIHSS from baseline to 90 days after the onset was 3.56 and 5.79 in the rhPro-UK 50 mg group and the rhPro-UK 35 mg group, respectively. The rates of functional independence at 90 days of rhPro-UK 50 mg and 35 mg were 61.54% and 69.23%, respectively (P = 0.475), and the proportion of patients with functional response to treatment at 24 h were 28.21% and 33.33% (P = 0.624). No sICH occurred in the two groups, and death occurred in only one patient in the rhPro-UK 50 mg group. There was no significant difference in mortality at 90 days and the rate of other serious adverse events between two groups., Conclusion: In the 4.5-6 h time window, more than 60% of patients at either dose of rhPro-UK (50 mg or 35 mg) achieved functional independence at 90 days without increased mortality and sICH risk. Thus, intravenous rhPro-UK was effective and safe for patients with AIS within 4.5-6 h after stroke onset. While no significant differences were identified between different dosages of rhPro-UK regarding clinical outcomes, it is a logical step to further test the safety and efficacy of the low dose of rhPro-UK in a well-powered phase III study., Trial Registration: http://www.chictr.org.cn . Identifier: ChiCTR1800016519. Date of registration: 6 June 2018., (© 2023. The Author(s).)

The synergistic armor-etching (SAE) approach was proposed using natural organic weak acid (tannic acid, i.e., TA) for the controllable assembly of hollow and interpenetrated HZIF-8@MWCNTs hybrid nanomaterial (ZIF-8, zeolitic imidazolate framework-8; MWCNTs, multi-walled carbon nanotubes), which exhibited highly ordered crystal structure and unique morphological characteristics. The SAE strategy not only can rapidly etch solid ZIF- material into a hollow structure (~ 10 min), but also form the TA shell (~ 33 nm) on its surface. Then, the HZIF-8@MWCNTs electrochemical sensor was constructed for selective and sensitive detection of the target molecule (dopamine, DA). A sequence of studies indicated that the fabricated TA coating was capable of promoting the spread of DA into the reactive centers of hollow MOF and MWCNTs, which exhibited outstanding electroanalytical characteristics through the synergistic effect. The DPV oxidation peak of DA was strongest at 50 mV vs. Ag/AgCl reference electrode. Under the optimal conditions, there are two linear dynamic ranges of current response of 0.01 ~ 10 and 10 ~ 550 µmol L - 1 with a detection limit of 0.003 µmol·L - 1 (S/N = 3). Simultaneously, the HZIF-8@MWCNTs electrochemical sensor could detect low levels of DA in real products. The recoveries of the actual sample tests were between 98.2% and 102%, and the relative standard deviation (R.S.D.) of all studies was less than 3.0%. The statistical analyses (F-test and t-test) were employed to demonstrate the accuracy of method developed. This work will enlighten researchers operating in the domain of MOFs composites, accelerating the advancement of electrochemical sensing on the basis of hollow MOFs materials., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Gait is a potential diagnostic tool for detecting mild cognitive impairment (MCI) and Alzheimer's disease (AD). Nevertheless, little attention has been paid to arm movements during walking, and there is currently no consensus on gait asymmetry. Therefore, in this study, we aimed to determine whether arm motion and gait asymmetry could be utilized for identifying MCI and AD., Methods: In total, 102 middle-aged and elderly individuals were included in the final analysis and were assigned to the following three groups: AD ( n = 27), MCI ( n = 35), and a normal control group ( n = 40). Gait and cognitive assessments were conducted for all participants. Gait detection included a single-task gait with free-speed walking and a dual-task gait with adding a cognitive task of successive minus seven to walking. Original gait parameters were collected using a wearable device featuring the MATRIX system 2.0. Gait parameters were shortened to several main gait domains through factor analysis using principal component extraction with varimax rotation. Subsequently, the extracted gait domains were used to differentiate the three groups, and the area under the receiver operating characteristic curve was calculated., Results: Factor analysis of single-task gait identified five independent gait domains: rhythm symmetry, rhythm, pace asymmetry, arm motion, and variability. Factor analysis of the dual-task gait identified four gait domains: rhythm, variability, symmetry, and arm motion. During single-task walking, pace asymmetry was negatively correlated with MoCA scores and could distinguish between the AD group and the other two groups. Arm motion was not associated with MoCA scores, and did not exhibit adequate discrimination in either task., Conclusion: Currently, there is no reliable evidence suggesting that arm motion can be used to recognize AD or MCI. Gait asymmetry can serve as a potential gait marker for the auxiliary diagnosis of AD but not for MCI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Zhu, Liu, Shi, Liu, Guo, Hu, Liu and Yang.)

Background: Hepatitis C threatens human health and brings a heavy economic burden. Shandong Province is the second most populous province in China and has uneven regional economic development. Therefore, we analyzed the incidence rate trend and regional differences of hepatitis C in Shandong Province from 2004 to 2021., Methods: The monthly and annual incidence rates of hepatitis C in Shandong Province from 2022 to 2030 were predicted by fitting Autoregressive Integrated Moving Average model (ARIMA), Long Short-Term Memory (LSTM) and ARIMA-LSTM combined model., Results: From 2004 to 2021, annual new cases of hepatitis C in Shandong Province increased from 635 to 5834, with a total of 61,707 cases. The incidence rate increased from 0.69/100 thousand in 2004 to 6.40/100 thousand in 2019, with a slight decrease in 2020 and 2021. The average annual incidence rate was 3.47/100 thousand. In terms of regional distribution, the hepatitis C incidence rate in Shandong Province was generally high in the west and low in the east. It is estimated that the hepatitis C incidence rate in Shandong Province will be 9.21 per 100 thousand in 2030., Conclusion: The hepatitis C incidence rate in Shandong Province showed an increasing trend from 2004 to 2019 and a decreasing trend in 2020 and 2021. Significant regional variations in incidence rate existed. An upward trend in incidence rate is predicted from 2022 to 2030. It is necessary to strengthen the prevention and control of hepatitis C to achieve the goal of eliminating viral hepatitis by 2030., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Male animals may adjust their resource allocations for reproduction and other fitness functions in response to cues from rivals. For instance, adult males increase their investment in sperm for a higher paternity share when they perceive sperm competition risk in their surroundings. In nature, both juveniles and adults may coexist spatially and temporally. Yet, it is not clear how juvenile males of different ages respond to cues from adult rivals and fine-tune their lifetime investment in sperm production and ejaculation in any insect. Here we used the Mediterranean flour moth, Ephestia kuehniella, which produces both fertile eupyrene and infertile apyrene sperm, to explore this question. We demonstrate that the late, but not early, instar larvae are sensitive to adult male cues. As a response, they produce more sperm before emergence and their resultant adults have shorter mating latency and ejaculate more sperm in the first few matings. When the juvenile stage produces more eupyrenes, the adult stops making these sperm, but regardless of the number of apyrenes produced during the juvenile stage, the adult continues to make them. These findings suggest that the number of spermatogonia for eupyrenes may be limited and that for apyrenes may be flexible. Our results show that the insect does not trade off survival, mating frequency, body size, or testis size for sperm production in response to adult males during the larval stage. Knowledge created in the present study offers insight into the stage-dependent sensitivity of juvenile males to cues from adult rivals and subsequent lifetime resource allocations., (© 2023 The Authors. Insect Science published by John Wiley & Sons Australia, Ltd on behalf of Institute of Zoology, Chinese Academy of Sciences.)

Background: Osteoarthritis (OA) is an age-related disease characterised by the accumulation of senescent chondrocytes, which drives its pathogenesis and progression. Senescent cells exhibit distinct features, including mitochondrial dysfunction and the excessive accumulation and release of reactive oxygen species (ROS), which are highly correlated and lead to a vicious cycle of increasing senescent cells. Stem cell therapy has proven effective in addressing cellular senescence, however, it still has issues such as immune rejection and ethical concerns. Microvesicles (MVs) constitute the primary mechanism through which stem cell therapy exerts its effects, offering a cell-free approach that circumvents these risks and has excellent anti-ageing potential. Nonetheless, MVs have a short in vivo half-life, and their secretion composition varies considerably under diverse conditions. This study aims to address these issues by constructing a ROS-responsive hydrogel loaded with pre-stimulant MVs. Through responding to ROS levels this hydrogel intelligently releases MVs, and enhancing mitochondrial function in chondrocytes to improving cellular senescence., Result: We employed Interferon-gamma (IFN-γ) as a stem cell-specific stimulus to generate IFN-γ-microvesicles (iMVs) with enhanced anti-ageing effects. Simultaneously, we developed a ROS-responsive carrier utilising 3-aminophenylboronic acid (APBA)-modified silk fibroin (SF) and polyvinyl alcohol (PVA). This carrier served to protect MVs, prolong longevity, and facilitate intelligent release. In vitro experiments demonstrated that the Hydrogel@iMVs effectively mitigated cell senescence, improved mitochondrial function, and enhanced cellular antioxidant capacity. In vivo experiments further substantiated the anti-ageing capabilities of the Hydrogel@iMVs., Conclusion: The effect of MVs can be significantly enhanced by appropriate pre-stimulation and constructing a suitable carrier. Therefore, we have developed a ROS-responsive hydrogel containing IFN-γ pre-stimulated iMVs to target the characteristics of ageing chondrocytes in OA for therapeutic purposes. Overall, this novel approach effectively improving mitochondrial dysfunction by regulating the balance between mitochondrial fission and fusion, and the accumulation of reactive oxygen species was reduced, finally, alleviates cellular senescence, offering a promising therapeutic strategy for OA., (© 2023. The Author(s).)

The response rate of cancer immune checkpoint inhibitors (ICI) varies among patients, making it challenging to pre-determine whether a particular patient will respond to immunotherapy. While gene mutation is critical to the treatment outcome, a framework capable of explicitly incorporating biology knowledge has yet to be established. Here we aim to propose and validate a mutation-based deep learning model for survival analysis on 1571 patients treated with ICI. Our model achieves an average concordance index of 0.59 ± 0.13 across nine types of cancer, compared to the gold standard Cox-PH model (0.52 ± 0.10). The "black box" nature of deep learning is a major concern in healthcare field. This model's interpretability, which results from incorporating the gene pathways and protein interaction (i.e., biology-aware) rather than relying on a 'black box' approach, helps patient stratification and provides insight into novel gene biomarkers, advancing our understanding of ICI treatment., (© 2023. The Author(s).)

For the first time, organic light-emitting diodes (OLEDs) based on bis(8-hydroxyquinoline) zinc with a styryl group (ZnStq) dispersed in poly(N-vinylcarbazole) matrix (ZnStq&#95;R:PVK, where R = H, Cl, OCH 3 ) were fabricated. The ZnStq&#95;R:PVK films made via the spin-coating method were used as the active layer in these devices. The produced OLEDs showed strong electroluminescence with yellow emissions at 590, 587 and 578 nm for the ZnStq&#95;H:PVK, ZnStq&#95;Cl:PVK and ZnStq&#95;OCH 3 :PVK, respectively. For all the studied thin films, the main photoluminescence emission bands were observed between 565 and 571 nm. The OLED with the ZnStq&#95;OCH 3 :PVK layer with a narrow electroluminescence spectrum was found to have sufficient color purity to produce ultra-high-resolution displays with reduced power consumption (full width at half maximum of 59 nm, maximum brightness of 2244 cd/m 2 and maximum current efficiency of 1.24 cd/A, with a turn-on voltage of 6.94 V and a threshold voltage of 7.35 V). To characterize the photophysical properties of the active layer, the ZnStq&#95;R:PVK layers samples were additionally deposited on glass and silicon substrates. We found that the obtained results predestine ZnStq&#95;R:PVK layers for use in the lighting industry in the future.

Background: Recurrent vulvovaginal candidiasis (RVVC) is a recalcitrant medical condition that affects many women of reproductive age. The importance of biofilm formation by Candida in RVVC has been recently questioned. This study aimed to elucidate the fundamental growth modes of Candida in the vagina of patients with RVVC or sporadic vulvovaginal candidiasis (VVC) and to assess their roles in the persistence of RVVC., Methods: Vaginal tissues were sampled from twelve patients clinically and microbiologically diagnosed as RVVC or VVC at a post-antifungal-treatment and asymptomatic period. High-resolution scanning electron microscopy, fluorescence in situ hybridization in combination with Candida -specific 18S rRNA probes and viable fungal burden were used to qualitatively and quantitatively evaluate Candida growth in the human vagina. The presence of Candida biofilm extracellular polymeric substances was examined using confocal laser scanning microscopy and biopsy sections pre-stained with Concanavalin A. Histopathological analysis was carried out on infected vaginal tissues stained with hematoxylin and eosin. Lastly, the susceptibility of epithelium-associated Candida biofilms to fluconazole at the peak serum concentration was evaluated., Results: Candida species grew on the vaginal epithelium of RVVC patients as morphologically disparate biofilms including monolayers, microcolonies, and macro-colonies, in addition to sporadic adherent cells. Candida biofilm growth on the vaginal epithelium was associated with mild lymphocytic infiltration of the vaginal mucosa. These epithelium-based Candida biofilms presented an important characteristic contributing to the persistence of RVVC that is the high tolerance to fluconazole., Conclusions: In summary, our study provides direct evidence to support the presence of Candida biofilms in RVVC and an important role of biofilm formation in disease persistence., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Yue Qu reports financial support was provided by The Alfred Research Trusts. Yihong Pan reports financial support was provided by Zhejiang Province Natural Science Foundation. Zhenbo Xu reports financial support was provided by South China University of Technology., (© 2023 The Authors.)

As a unique microbial response to adverse circumstances, the viable but nonculturable (VBNC) state is characterized by the loss of culturability of microbial cells on/in nutrient media that normally support their growth, while maintaining metabolic activity. These cells can resuscitate to a culturable state under suitable conditions. Given the intrinsic importance of the VBNC state and recent debates surrounding it, there is a need to redefine and standardize the term, and to address essential questions such as 'How to differentiate VBNC from other similar terms?' and 'How can VBNC cells be standardly and accurately determined?'. This opinion piece aims at contributing to an improved understanding of the VBNC state and promoting its proper handling as an underestimated and controversial microbial survival strategy., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Staphylococcus aureus is a major human pathogen, a potential "Super-bug" and a typical biofilm forming bacteria. With usage of large amount of antibiotics, the residual antibiotics in clinical settings further complicate the colonization, pathogenesis and resistance of S. aureus . This study aimed at investigating the phenotypical and global gene expression changes on biofilm formation of a clinical S. aureus isolate treated under different types of antibiotics. Firstly, an isolate Guangzhou-SAU749 was selected from a large sale of previously identified S. aureus isolates, which exhibited weak biofilm formation in terms of biomass and viability. Secondly, 9 commonly prescribed antibiotics for S. aureus infections treatment, together with 10 concentrations ranging from 1/128 to 4 minimum inhibitory concentration (MIC) with 2-fold serial dilution, were used as different antibiotic stress conditions. Then, biofilm formation of S. aureus Guangzhou-SAU749 at different stages including 8 h, 16 h, 24 h, and 48 h, was tested by crystal violet and MTS assays. Thirdly, the whole genome of S. aureus Guangzhou-SAU749 was investigated by genome sequencing on PacBio platform. Fourthly, since enhancement of biofilm formation occurred when treated with 1/2 MIC tetracycline (TCY) and 1/4 MIC streptomycin (STR) since 5 h, the relevant biofilm samples were selected and subjected to RNA-seq and bioinformatics analysis. Last, expression of two component system (TCS) and biofilm associated genes in 4 h, 8 h, 16 h, 24 h, and 48 h sub-MIC TCY and STR treated biofilm samples were performed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Although most antibiotics lowered the biomass and cell viability of Guangzhou-SAU749 biofilm at concentrations higher than MIC, certain antibiotics including TCY and STR promoted biofilm formation at sub-MICs. Additionally, upon genome sequencing, RNA-seq and RT-qPCR on biofilm samples treated with sub-MIC of TCY and STR at key time points, genes lytR , arlR , hssR , tagA , clfB , atlA and cidA related to TCS and biofilm formation were identified to contribute to the enhanced biofilm formation, providing a theoretical basis for further controlling on S. aureus biofilm formation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier B.V.)

Measurement of thermal properties of thin films is challenging. In particular, thermal characterization is very difficult in semi-transparent samples. Here, we use two photothermal methods to obtain information about the thermal diffusivity as well as thermal conductivity of azoheteroarene functionalized polymer thin layers. The photothermal beam deflection (PBD) method is employed to gather data directly on thermal conductivity and thermal diffusivity, while the thermal lens (TL) method is employed to measure the effective thermal diffusivity. Consequently, the thermal diffusivity of the layers is indirectly estimated from the effective thermal diffusivity using a well-established theoretical relationship. Despite the utilization of distinct methods, our study reveals a remarkable consistency in the highly accurate results obtained from both approaches. This remarkable agreement reaffirms the reliability and mutual compatibility of the employed methods, highlighting their shared ability to provide accurate and congruent outcomes.

Objective. Ultra-high-dose-rate radiotherapy, referred to as FLASH therapy, has been demonstrated to reduce the damage of normal tissue as well as inhibiting tumor growth compared with conventional dose-rate radiotherapy. The transient hypoxia may be a vital explanation for sparing the normal tissue. The heterogeneity of oxygen distribution for different doses and dose rates in the different radiotherapy schemes are analyzed. With these results, the influence of doses and dose rates on cell survival are evaluated in this work. Approach. The two-dimensional reaction-diffusion equations are used to describe the heterogeneity of the oxygen distribution in capillaries and tissue. A modified linear quadratic model is employed to characterize the surviving fraction at different doses and dose rates. Main results. The reduction of the damage to the normal tissue can be observed if the doses exceeds a minimum dose threshold under the ultra-high-dose-rate radiation. Also, the surviving fraction exhibits the 'plateau effect' under the ultra-high dose rates radiation, which signifies that within a specific range of doses, the surviving fraction either exhibits minimal variation or increases with the dose. For a given dose, the surviving fraction increases with the dose rate until tending to a stable value, which means that the protection in normal tissue reaches saturation. Significance. The emergence of the 'plateau effect' allows delivering the higher doses while minimizing damage to normal tissue. It is necessary to develop appropriate program of doses and dose rates for different irradiated tissue to achieve more efficient protection., (© 2023 Institute of Physics and Engineering in Medicine.)

A novel recursive cascaded full-resolution residual network (RCFRR-Net) for abdominal four-dimensional computed tomography (4D-CT) image registration was proposed. The entire network was end-to-end and trained in the unsupervised approach, which meant that the deformation vector field, which presented the ground truth, was not needed during training. The network was designed by cascading three full-resolution residual subnetworks with different architectures. The training loss consisted of the image similarity loss and the deformation vector field regularization loss, which were calculated based on the final warped image and the fixed image, allowing all cascades to be trained jointly and perform the progressive registration cooperatively. Extensive network testing was conducted using diverse datasets, including an internal 4D-CT dataset, a public DIRLAB 4D-CT dataset, and a 4D cone-beam CT (4D-CBCT) dataset. Compared with the iteration-based demon method and two deep learning-based methods (VoxelMorph and recursive cascaded network), the RCFRR-Net achieved consistent and significant gains, which demonstrated that the proposed method had superior performance and generalization capability in medical image registration. The proposed RCFRR-Net was a promising tool for various clinical applications., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of The American Institute of Chemical Engineers.)

Salvigenin is a Trimethoxylated Flavone enriched in Scutellariae Barbatae Herba and Scutellariae Radix and is demonstrated to have anti-tumor properties in colon cancer. Notwithstanding, the function and mechanism of Salvigenin in hepatocellular carcinoma (HCC) are less well studied. Different doses of Salvigenin were taken to treat HCC cells. Cell viability, colony formation ability, cell migration, invasion, apoptosis, glucose uptake, and lactate production levels were detected. As shown by the data, Salvigenin concentration dependently dampened HCC cell proliferation, migration, and invasion, weakened glycolysis by abating glucose uptake and lactate generation, and suppressed the profiles of glycolytic enzymes. Moreover, Salvigenin strengthened HCC cells' sensitivity to 5-fluorouracil (5-FU) and attenuated HCC 5-FU-resistant cells' resistance to 5-FU. Through network pharmacological analysis, we found Salvigenin potentially regulates PI3K/AKT pathway. As shown by the data, Salvigenin repressed the phosphorylated levels of PI3K, AKT, and GSK-3β. The PI3K activator 740Y-P induced PI3K/AKT/GSK-3β pathway activation and promotive effects in HCC cells. However, Salvigenin substantially weakened 740Y-P-mediated effects. In-vivo assay revealed that Salvigenin hampered the growth and promoted apoptosis of HCC cells in nude mice. Collectively, Salvigenin impedes the aerobic glycolysis and 5-FU chemoresistance of HCC cells by dampening the PI3K/AKT/GSK-3β pathway., (© 2023. The Author(s).)

Background: Traditional Chinese medicine (TCM) has been used to prevent and treat type 2 diabetes (T2DM) for thousands of years. The holistic view of TCM and the "multitarget" characteristics of Chinese medicine have unique advantages in the prevention and treatment of T2DM. TCM syndrome differentiation and treatment are effective for T2DM; however, currently, the therapeutic effect of TCM is generally evaluated by asking for patients' subjective feelings, or by checking the changes in relevant indicators. The main problems are that the patient's descriptions are unclear and subjective, and although the self-reported symptoms may have improved significantly, the relevant indicators are sometimes not obvious, which cannot truly reflect the therapeutic effect of TCM. Therefore, it is urgent to develop a novel, sensitive, and noninvasive method to quantitatively evaluate the therapeutic effect of TCM., Methods: In this study, ultra-weak photon emission (UPE) was measured at four sites of hands of T2DM patients with Qi-Yin deficiency before treatment and after 1 and 2 weeks of treatment with TCM. The UPE intensity and spectral distribution were calculated and analyzed using the results measured at these four sites. Spearman's correlation coefficient was used to quantify the correlation between the UPE parameters and the syndrome scores of TCM., Results: The UPE intensity of T2DM patients with Qi-Yin deficiency decreased gradually with the course of the treatment and was significantly lower than that before the treatment. The ratio of photon counts between the wavelength ranges of 495-550 nm and 550-610 nm after the treatment was higher than that before the treatment and negatively correlated with the corresponding syndrome scores so that the degree of symptoms improvement could be characterized by the ratio (495-550 nm/550-610 nm)., Conclusions: The therapeutic effect of TCM in T2DM patients with Qi-Yin deficiency can be shown at the level of UPE. UPE is a potential and noninvasive tool for evaluating the therapeutic effect of TCM in patients with T2DM., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Total antioxidant capacity (TAC) is currently considered as a vital indicator of food quality in antioxidant ability and attracts much attention for human healthcare. It is thus of great significance to realize the accurate and rapid detection of TAC in foods. Herein, we have constructed a preferable hybrid nanozyme based on the mesoporous silica-stabilized CuO composited Fe 3 O 4 nanoparticles (Fe 3 O 4 @MSNs@CuO, FMC NPs), which possess the enhanced peroxidase (POD)-like activity via cascade response for specific and sensitive determination of TAC in fruit foods. The results showed the hybrid nanozyme displayed a remarkable POD-like activity, excellent selectivity and sensitivity, and the limit of detection (LOD) of the colorimetric sensor was 6.13 mM with the concentration range from 10 to 45 mM. Therefore, the fabricated hybrid nanozyme can be regarded as an effective biosensor for the evaluation of antioxidant quality in fruit foods in future. KEY POINTS: • The stabilized bimetallic nanozyme was constructed for TAC analysis in fruits. • The hybrid nanozyme possessed the enhanced POD-like activity by cascading effects. • The nanozyme was an effective biosensor for antioxidant quality evaluation in fruits., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: As a novel energy homeostasis regulator, Adropin not only plays a vital part in meditating energy metabolism, but also has a certain correlation with atherosclerotic diseases. The purpose of this study was to evaluate the effect of Adropin on the long-term prognosis of patients with acute myocardial infarction (AMI)., Methods: 162 recruited patients with AMI were divided into low Adropin group (Adropin<166.3 pg/mL, n = 82) and high Adropin group (Adropin≥166.3 pg/mL, n = 80), according to the mean value of serum Adropin level. Patients were followed up and major adverse cardiac events (MACEs) were recorded. The Kaplan-Meier method and Cox regression model were used to evaluate the survival of patients and the related factors of cardiac events., Results: Diabetes was more common in low Adropin group than that in high Adropin group (P < 0.05). Patients were followed up for an average of 50.3 ± 19.2 months. MACEs occurred in 37 patients (22.8%), including 6 cardiac deaths (3.7%), 14 recurrent myocardial infarction (8.6%) and 17 rehospitalization of heart failure (10.5%). The incidence of recurrent myocardial infarction in low Adropin group was higher than that in high Adropin group (13.4% vs 3.8%, P < 0.05). There was no significant difference in the overall incidence of MACE, cardiac death and rehospitalization of heart failure between the two groups. Kaplan-Meier method (log rank test) analysis results showed that patients with low Adropin had lower survival rate without recurrent myocardial infarction (log rank P = 0.035)., Conclusion: Low Adropin level was associated with an increased risk of long-term recurrent myocardial infarction in patients with AMI., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Azoospermia is a significant cause of male infertility, with non-obstructive azoospermia (NOA) being the most severe type of spermatogenic failure. NOA is mostly caused by congenital factors, but our understanding of its genetic causes is very limited. Here, we identified a frameshift variant (c.201&#95;202insAC, p.Tyr68Thrfs∗17) and two nonsense variants (c.1897C>T, p.Gln633∗; c.2005C>T, p.Gln669∗) in KCTD19 (potassium channel tetramerization domain containing 19) from two unrelated infertile Chinese men and a consanguineous Pakistani family with three infertile brothers. Testicular histological analyses revealed meiotic metaphase I (MMI) arrest in the affected individuals. Mice modeling KCTD19 variants recapitulated the same MMI arrest phenotype due to severe disrupted individualization of MMI chromosomes. Further analysis showed a complete loss of KCTD19 protein in both Kctd19 mutant mouse testes and affected individual testes. Collectively, our findings demonstrate the pathogenicity of the identified KCTD19 variants and highlight an essential role of KCTD19 in MMI chromosome individualization., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Glucose plays a central role in tumor metabolism and development and is a target for novel therapeutics. To characterize the response of cancer cells to blockade of glucose uptake, we collected time-resolved microscopy data to track the growth of MDA-MB-231 breast cancer cells. We then developed a mechanism-based, mathematical model to predict how a glucose transporter (GLUT1) inhibitor (Cytochalasin B) influences the growth of the MDA-MB-231 cells by limiting access to glucose. The model includes a parameter describing dose dependent inhibition to quantify both the total glucose level in the system and the glucose level accessible to the tumor cells. Four common machine learning models were also used to predict tumor cell growth. Both the mechanism-based and machine learning models were trained and validated, and the prediction error was evaluated by the coefficient of determination (R 2 ). The random forest model provided the highest accuracy predicting cell dynamics (R 2  = 0.92), followed by the decision tree (R 2  = 0.89), k-nearest-neighbor regression (R 2  = 0.84), mechanism-based (R 2  = 0.77), and linear regression model (R 2  = 0.69). Thus, the mechanism-based model has a predictive capability comparable to machine learning models with the added benefit of elucidating biological mechanisms., (© 2023. The Author(s).)

Limited studies examined the interaction effects between exposure to ambient PM 2.5 and economic development on the settlement intention of floating population. We used binary logistic model to examine the association of PM 2.5 , per capita GDP (PGDP), PM 2.5 [Formula: see text] PGDP on the settlement intention. Additive interaction term of PM 2.5 and PGDP level was used to investigate their interactive effects. Overall, each one grade increment in annual average PM 2.5 was associated with decreased probability of settlement intention (OR = 0.847, 95%CI: 0.811-0.885). The interaction effect between PM 2.5 and PGDP on settlement intention was significant (OR = 1.168, 95%CI: 1.142-1.194). The stratified analysis showed PM 2.5 exhibits lower settlement intention in the aged 55 years or above, engaged in low-skilled works, and living in the western China. This study indicates that PM 2.5 -exposed will decrease the settlement intention of floating population. High economic development level can weaken the relationship between PM 2.5 and settlement intention. Policymakers should balance the socio-economic development and environmental health and focus on vulnerable population., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

There are limited studies investigating the relationship between exposure to PM 2.5 and the health status among the mobile population. A cross-sectional analysis was performed in a nationally representative sample (2017 China Migrants Dynamic Survey data) consisting of 169,469 mobile population. The ordered logistic regression model was used to examine the association between PM 2.5 and the health status in mobile population. Stratified analyses were performed to identify whether the association varied across gender, age group, and regions in China. Overall, every 10 μg/m 3 increment in annual average PM 2.5 was associated with increased risk of poor self-reported health (OR = 1.021, 95% CI: 1.012-1.030). Mobile population aged 31-49 years and living in the central region suffers the highest PM 2.5 -associated health risk (OR = 1.030, 95% CI: 1.019-1.042; OR = 1.095, 95% CI: 1.075-1.116). Our study suggests that PM 2.5 exposure was associated with an increased risk of poor self-reported health in mobile population, particularly among the population aged 31-49 years and people living in the central region of China. Policymakers should pay more attention to the vulnerable mobile population to tackle the health burden of ambient air pollution., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Unsupervised dimension reduction and clustering are frequently used as two separate steps to conduct clustering tasks in subspace. However, the two-step clustering methods may not necessarily reflect the cluster structure in the subspace. In addition, the existing subspace clustering methods do not consider the relationship between the low-dimensional representation and local structure in the input space. To address the above issues, we propose a robust discriminant subspace (RDS) clustering model with adaptive local structure embedding. Specifically, unlike the existing methods which incorporate dimension reduction and clustering via regularizer, thereby introducing extra parameters, RDS first integrates them into a unified matrix factorization (MF) model through theoretical proof. Furthermore, a similarity graph is constructed to learn the local structure. A constraint is imposed on the graph to guarantee that it has the same connected components with low-dimensional representation. In this spirit, the similarity graph serves as a tradeoff that adaptively balances the learning process between the low-dimensional space and the original space. Finally, RDS adopts the l 2,1 -norm to measure the residual error, which enhances the robustness to noise. Using the property of the l 2,1 -norm, RDS can be optimized efficiently without introducing more penalty terms. Experimental results on real-world benchmark datasets show that RDS can provide more interpretable clustering results and also outperform other state-of-the-art alternatives.

Photothermal microscopy (PTM) was developed to image non-fluorescent objects. In the past two decades, PTM has reached single-particle and single-molecule sensitivity and has been used in the fields of material science and biology. However, PTM is a far-field imaging method whose resolution is restricted by the diffraction limits. This Letter reports a resolution improvement approach for photothermal microscopy called modulated difference PTM (MD-PTM), which utilizes Gaussian and doughnut formalism heating beams that are modulated at the same frequency but are of opposite phase to generate the photothermal signal. Furthermore, the opposite phase characteristics of the photothermal signals are applied to determine the objective profile from the PTM magnitude, and this helps to improve the lateral resolution of PTM. The lateral resolution is related to the difference coefficient between the Gaussian and doughnut heating beams; an increase in the difference coefficient causes a larger sidelobe of the MD-PTM amplitude, which readily forms an artifact. A pulse-coupled neural network (PCNN) is employed for phase image segmentations of MD-PTM. We experimentally study the micro-imaging of gold nanoclusters and crossed nanotubes using MD-PTM, and the results indicate that MD-PTM has merit in terms of improving the lateral resolution.