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Objectives: To assess the feasibility of estimating an EQ-5D-5L value set using a small study design in cancer patients and to compare the EQ-5D-5L values based on the preferences of cancer patients with those of the general public., Methods: Patients with clinically diagnosed cancers were recruited from two hospitals in Shanghai, China. In face-to-face interviews using the EQ-PVT survey, health states were valued by cancer patients using both cTTO and DCE methods. cTTO data was modelled alone or jointly with DCE data. Forty-eight models using different model specifications (cross-attribute level effect [CALE] and additive models), random/fixed effects model assumptions, data heteroscedasticity and censoring were estimated. The best performed model was identified in terms of monotonicity of estimated model coefficients and out-of-sample prediction accuracy., Results: Data collected from 221 cancer patients who participated in the study were included. The hybrid CALE model using both TTO and DCE data performed best in terms of prediction accuracy (Lin's concordance coefficient = 0.989; root mean squared error = 0.058) and suggested that pain/discomfort and anxiety/depression were the most undesirable health problems. Compared to values based on general Chinese public's health preferences, the values based on cancer patients' preferences were much higher and lower for health states characterized by extreme mobility problems and severe/extreme pain or discomfort, respectively., Conclusion: This study demonstrated the feasibility of using a small design to develop EQ-5D-5L value sets based on cancer patients' health preferences. Since there were signs of differences between preferences of patients and general population, it may be valuable to develop patient-specific value sets and use them in clinical decision making and economic evaluations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Leaf shape is a vital agronomic trait that affects plant and canopy architecture, yield, and other production attributes of upland cotton. Compared with normal leaves, lobed leaves have potential advantages in improving canopy structure and increasing cotton yield. A chromosomal introgression segment from Gossypium barbadense L. conferring sub-okra leaf shape to Gossypium hirsutum L. was identified on chromosome D01. To determine the effects of this transferred sub-okra leaf shape on the leaf anatomical characteristics, photosynthesis-related traits, and yield of short-season cotton, we performed a field experiment with three sets of near-isogenic lines carrying okra, sub-okra, and normal leaf shape in Lu54 (L54) and Shizao 2 (SZ2) backgrounds. Compared with normal leaves, sub-okra leaves exhibited reduced leaf thickness and smaller leaf mass per area; moreover, the deeper lobes of sub-okra leaves improved the plant canopy structure by decreasing leaf area index by 11.24%-22.84%. Similarly, the intercepted PAR rate of lines with sub-okra leaf shape was also reduced. The chlorophyll content of sub-okra leaves was lower than that of okra and normal leaf shapes; however, the net photosynthetic rate of sub-okra leaves was 8.17%-29.81% higher than that of other leaf shapes at most growth stages. Although the biomass of lines with sub-okra leaf shape was less than that of lines with normal leaves, the average first harvest yield and total yield of lines with the sub-okra leaf shape increased by 6.36% and 5.72%, respectively, compared with those with normal leaves. Thus, improvements in the canopy structure and photosynthetic and physiological characteristics contributed to optimizing the light environment, thereby increasing the yield of lines with sub-okra leaf shape. Our results suggest that the sub-okra leaf trait from G. barbadense L. may have practical applications for cultivating short-season varieties with high photosynthetic efficiency, and improving yield, which will be advantageous for short-season varieties., 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 © 2024 Jiang, Ma, Shi, Gao, Zhang, Zhang, Chai, Wang, Wang, Wang, Chen, Zhang, Li, Zhao and Zhao.)

Background: Infectious meningitis/encephalitis (IM) is a severe neurological disease that can be caused by bacterial, viral, and fungal pathogens. IM suffers high morbidity, mortality, and sequelae in childhood. Metagenomic next-generation sequencing (mNGS) can potentially improve IM outcomes by sequencing both pathogen and host responses and increasing the diagnosis accuracy., Methods: Here we developed an optimized mNGS pipeline named comprehensive mNGS (c-mNGS) to monitor DNA/RNA pathogens and host responses simultaneously and applied it to 142 cerebrospinal fluid samples. According to retrospective diagnosis, these samples were classified into three categories: confirmed infectious meningitis/encephalitis (CIM), suspected infectious meningitis/encephalitis (SIM), and noninfectious controls (CTRL)., Results: Our pipeline outperformed conventional methods and identified RNA viruses such as Echovirus E30 and etiologic pathogens such as HHV-7, which would not be clinically identified via conventional methods. Based on the results of the c-mNGS pipeline, we successfully detected antibiotic resistance genes related to common antibiotics for treating Escherichia coli, Acinetobacter baumannii, and Group B Streptococcus. Further, we identified differentially expressed genes in hosts of bacterial meningitis (BM) and viral meningitis/encephalitis (VM). We used these genes to build a machine-learning model to pinpoint sample contaminations. Similarly, we also built a model to predict poor prognosis in BM., Conclusions: This study developed an mNGS-based pipeline for IM which measures both DNA/RNA pathogens and host gene expression in a single assay. The pipeline allows detecting more viruses, predicting antibiotic resistance, pinpointing contaminations, and evaluating prognosis. Given the comparable cost to conventional mNGS, our pipeline can become a routine test for IM., (© 2024. The Author(s).)

Periprosthetic osteolysis induced by the ultrahigh-molecular-weight polyethylene (UHMWPE) wear particles is a major complication associated with the sustained service of artificial joint prostheses and often necessitates revision surgery. Therefore, a smart implant with direct prevention and repair abilities is urgently developed to avoid painful revision surgery. Herein, we fabricate a phosphatidylserine- and polyethylenimine-engineered niobium carbide (Nb 2 C) MXenzyme-coated micro/nanostructured titanium implant (PPN@MNTi) that inhibits UHMWPE particle-induced periprosthetic osteolysis. The specific mechanism by which PPN@MNTi operates involves the bioresponsive release of nanosheets from the MNTi substrate within an osteolysis microenvironment, initiated by the cleavage of a thioketal-dopamine molecule sensitive to reactive oxygen species (ROS). Subsequently, functionalized Nb 2 C MXenzyme could target macrophages and escape from lysosomes, effectively scavenging intracellular ROS through its antioxidant nanozyme-mimicking activities. This further achieves the suppression of osteoclastogenesis by inhibiting NF-κB/MAPK and autophagy signaling pathways. Simultaneously, based on the synergistic effect of MXenzyme-integrated coatings and micro/nanostructured topography, the designed implant promotes the osteogenic differentiation of bone mesenchymal stem cells to regulate bone homeostasis, further achieving advanced osseointegration and alleviable periprosthetic osteolysis in vivo . This study provides a precise prevention and repair strategy of periprosthetic osteolysis, offering a paradigm for the development of smart orthopedic implants.

Mounting evidence suggests that intraplaque angiogenesis is associated with the progression of atherosclerotic plaques and the development of intraplaque hemorrhage. The specificity of intraplaque immune cell infiltration may be associated with abnormalities in the structure and function of the nascent capillaries. Here, we analyzed expression levels of angiogenesis-associated genes in early and advanced carotid atheromatous plaque tissues as well as in stable and intraplaque hemorrhage plaques. Expression profiles of advanced arterial plaques based on angiogenesis-associated genes were classified into subtypes by performing a consensus clustering analysis. The correlation between the immune microenvironment of plaques and expression of angiogenesis-associated genes was also explored using the single sample gene set enrichment analysis method and the CIBERSORT algorithm. We identified hub angiogenesis-associated genes showing similar expression patterns throughout plaque adverse progression, and constructed a prediction model using the random forest algorithm. Receiver operating curves were constructed to evaluate efficacy in identification of intraplaque hemorrhage in a plaque. Our results suggest that heterogeneity of angiogenesis-related genes may promote the malignant development of plaques and cause plaque rupture. In conclusion, we propose a model based on expression of angiogenesis-related genes to predict the risk of plaque rupture., 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., (© 2024 The Authors.)

Objectives: To construct pressure injury risk prediction models for emergency patients based on different machine learning algorithms, to optimize the best model, and to provide a suitable assessment tool for preventing the occurrence of pressure injuries in emergency patients., Methods: A convenience sampling was used to select 312 patients admitted to the emergency department of a tertiary care hospital in Tianjin, China, from May 2022 to March 2023, and the patients were divided into a modeling group (n = 218) and a validation group (n = 94) in a 7:3 ratio. Based on the results of one-factor logistic regression analysis in the modeling group, three machine learning models, namely, logistic regression, decision tree, and neural network, were used to establish a prediction model for pressure injury in emergency patients and compare their prediction effects. The optimal model was selected for external validation of the model., Results: The incidence of pressure injuries in emergency patients was 8.97 %, 64.52 % of pressure injuries occurred in the sacrococcygeal region, and 64.52 % were staged as stage 1. Serum albumin level, incontinence, perception, and mobility were independent risk factors for pressure injuries in emergency patients (P < 0.05), and the area under the ROC curve of the three models was 0.944-0.959, sensitivity was 91.8-95.5 %, specificity was 72.2-90.9 %, and the Yoden index was 0.677-0.802; the decision tree was the best model that The area under the ROC curve for the validation group was 0.866 (95 % CI: 0.688-1.000), with a sensitivity of 89.8 %, a specificity of 83.3 %, and a Yoden index of 0.731., Conclusions: The decision tree model has the best predictive efficacy and is suitable for individualized risk prediction of pressure injuries in emergency medicine specialties, which provides a reference for the prevention and early intervention of pressure injuries in emergency patients., 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 Ltd.)

Metal-organic frameworks (MOFs) have gained significant prominence as sensing materials owing to their unique properties. However, understanding the correlation between the morphology, properties, and sensing performance in these MOF-based sensors remains a challenge, limiting their applications and potential for improvement. In this study, Zr-MOF was chosen as an ideal model to explore the impact of the MOF morphology on the sensing performance, given its remarkable stability and structural variability. Three luminescent MOFs (namely rod-like Zr-LMOF, prismoid-like Zr-LMOF, and ellipsoid-like Zr-LMOF) were synthesized by adjusting the quantities of the benzoic acid and the reaction time. More importantly, the sensing performance of these Zr-LMOFs in response to aflatoxin B1 (AFB1) was thoroughly examined. Notably, the ellipsoid-like Zr-LMOF exhibited significantly higher sensitivity compared to other Zr-LMOFs, attributed to its large specific surface area and pore volume. Additionally, an in-depth investigation into the detection mechanism of AFB1 by Zr-LMOFs was conducted. Building upon these insights, a ratiometric fluorescence sensor was developed by coordinating Eu 3+ with ellipsoid-like Zr-LMOF, achieving a remarkably lower detection limit of 2.82 nM for AFB1. This study contributes to an improved comprehension of the relationship between the MOF morphology and the sensing characteristics while presenting an effective approach for AFB1 detection.

Background: Balance plays a crucial role in the daily activities of older adults. Aquatic-based exercises (AE) are widely conducted as an alternative to land-based exercises (LE). Previous studies have compared AE and LE as effective ways to improve balance and have yielded inconsistent results. Therefore, this review aimed to compare the effects of AE and LE on balance function in older adults., Methods: Electronic databases, including PubMed, Web of Science, Scopus, and Embase, were searched. Randomized controlled trials published from January 2003 to June 2023 were included following predetermined criteria. Data extraction was carried out by two independent reviewers. Data synthesis was conducted using RevMan 5.3 software. The fixed-effect model or random-effect model was chosen based on the results of the heterogeneity test. Meta-analysis for the effect sizes of balance outcomes was calculated as standardized mean difference (SMD) with 95% confidence intervals (CI). The quality of the included studies was evaluated using the Physiotherapy Evidence Database (PEDro) scale. This review was registered at PROSPERO CRD42023429557., Results: A total of 29 studies involving 1486 older adults (with an average age of 66.2 years) were included. Meta-analysis results indicated that AE could improve balance ability based on two tests: the Berg balance scale (BBS: SMD = 1.13, 95% CI 0.25 to 2.00, p = 0.01, I 2  = 94%) and the 30-s chair stand test (30 CST: SMD = 2.02, 95% CI 0.50 to 3.54, p = 0.009, I 2  = 96%). However, there were no significant differences between the AE group and the LE group in terms of the 6-min walking test (6 MWT: SMD = 0.13, 95% CI -0.16 to 0.43, p = 0.38, I 2  = 62%) and time up to go test (TUGT: SMD = 0.44, 95% CI -0.44 to 0.91, p = 0.07, I 2  = 85%). Older adults with different health conditions have different gains in different balance measurements after AE intervention and LE intervention., Conclusions: Although this was influenced by participant health status, transfer effects, sample size, and other factors, AE offers better benefits than LE for improving balance function in older adults., (© 2024. The Author(s).)

The diagnosis of cardiomyopathy often relies on the subjective judgment of pathologists due to the variety of morphologic changes in the condition and its low specificity. This uncertainty can contribute to unexplained sudden cardiac deaths (USCD). To enhance the accuracy of hereditary cardiomyopathy diagnosis in forensic medicine, we proposed a combination of molecular autopsy and pathologic autopsy. By analyzing 16 deceased patients suspected of cardiomyopathy, using whole exome sequencing (WES) in molecular autopsy, and applying a combined diagnostic strategy, the study found pathogenic or likely pathogenic variants in 6 cases. Out of the 16 cases, cardiomyopathy was confirmed in 3, while 3 exhibited conditions consistent with it. Data for 4 cases was inconclusive, and cardiomyopathy was ruled out in 6. Notably, a novel variant of the TTN gene was identified. This research suggests that a grading diagnostic strategy, combining molecular and pathological evidence, can improve the accuracy of forensic cardiomyopathy diagnosis. This approach provides a practical model and strategy for precise forensic cause-of-death determination, addressing the limitations of relying solely on morphologic assessments in cardiomyopathy cases, and integrating genetic information for a more comprehensive diagnosis., 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 B.V. All rights reserved.)

Children's sharing behavior is profoundly shaped by social norms within their society, and they can learn these norms by directly observing how most others share in their immediate environment. Here we systematically investigated the impact of majority influence on the sharing behavior of young Chinese children through three studies (N = 336, 168 girls). Four- and 6-year-olds were allowed to choose 10 favorite stickers and had an opportunity to engage in anonymous sharing. Before making the sharing decision, children were assigned to one of two conditions: watching a video in which three peers all shared 8 out of 10 stickers (i.e., the majority sharing condition) or making their decisions without watching the video (i.e., the control condition). Results showed that both the 4- and 6-year-old children shared more stickers in the majority sharing condition than in the control condition (Studies 1 & 2). Moreover, the influence of the majority had a stronger effect compared to the influence of a single role model. Children shared more stickers after observing three peers sharing, compared to watching one peer sharing three times (Study 2). Furthermore, children were less likely to copy the majority's non-sharing behavior when it came to giving away stickers without prosocial outcomes, which was particularly evident among 4-year-olds (Study 3). The results reveal that majority influence uniquely shapes children's sharing behavior and that children selectively follow the majority based on whether the behavior exhibits prosocial attributes. A video abstract of this article can be viewed at https://youtu.be/8qNNhf9754I?si=7YfpaFpcD&#95;IjlXjJ RESEARCH HIGHLIGHTS: Observing a majority of three peers' unanimous generous sharing promoted sharing behavior in both 4- and 6-year-olds. The influence of three peers on children's sharing was stronger than that of one peer sharing three times. Four-year-olds, but not 6-year-olds, did not copy the non-sharing behavior of the majority as it did not lead to prosocial outcomes., (© 2024 John Wiley & Sons Ltd.)

To improve light harvest and plant structural support under low light intensity, it is useful to investigate the effects of different ratios of blue light on petiole and stem growth. Two true leaves of soybean seedlings were exposed to a total light intensity of 200μmolm-2 s-1 , presented as either white light or three levels of blue light (40μmolm-2 s-1 , 67μmolm-2 s-1 and 100μmolm-2 s-1 ) for 15days. Soybean petioles under the low blue light treatment upregulated expression of genes relating to lignin metabolism, enhancing lignin content compared with the white light treatment. The low blue light treatment had high petiole length, increased plant height and improved petiole strength arising from high lignin content, thus significantly increasing leaf dry weight relative to the white light treatment. Compared with white light, the treatment with the highest blue light ratio reduced plant height and enhanced plant support through increased cellulose and hemicellulose content in the stem. Under low light intensity, 20% blue light enhanced petiole length and strength to improve photosynthate biomass; whereas 50% blue light lowered plants' centre of gravity, preventing lodging and conserving carbohydrate allocation.

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer. Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis (YTE-17), attributing these effects to the regulation of multiple signaling pathways. However, knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited. In this study, we conducted isobaric tags for relative and absolute quantification (iTRAQ) analysis on intestinal epithelial cells (IECs) exposed YTE-17, both in vitro and in vivo , revealing a significant inhibition of the Wnt family member 5a (Wnt5a)/c-Jun N-terminal kinase (JNK) signaling pathway. Subsequently, we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment (TME), specifically focusing on macrophage-mediated T helper 17 (Th17) cell induction in a colitis-associated cancer (CAC) model with Wnt5a deletion. Additionally, we performed the single-cell RNA sequencing (scRNA-seq) on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition, lineage, and functional status of immune mesenchymal cells during different stages of colorectal cancer (CRC) progression. Remarkably, our findings demonstrate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17, leading to the restoration of regulatory T (Treg)/Th17 cell balance in azoxymethane (AOM)/dextran sodium sulfate (DSS) model. Furthermore, we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages. Notably, our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical β-catenin oncogenic pathway in vivo . Specifically, we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with β-catenin activity within the TME, involving macrophages and T cells. In summary, our study undergoes the potential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment, thereby mitigating the risk of malignancies., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 Published by Elsevier B.V. on behalf of Xi’an Jiaotong University.)

Background: Encapsulation is commonly used to protect probiotics against harsh stresses. Thus, the fabrication of microcapsules with special structure is critical. In this work, microcapsules with the structure of S/O/W (solid-in-oil-in-water) emulsion were prepared for probiotics, with butterfat containing probiotics as the inner core and with whey protein isolate fibrils (WPIF) and antioxidants (epigallocatechin gallate, EGCG; glutathione, GSH) as the outer shell., Results: Based on the high viscosity and good emulsifying ability of WPIF, dry well-dispersed microcapsules were successfully prepared via the stabilization of the butterfat emulsion during freeze-drying with 30-50 g L -1 WPIF. WPIF, WPIF + EGCG, and WPIF + GSH microcapsules with 50 g L -1 WPIF protected probiotics very well against different stresses and exhibited similar inactivation results, indicating that EGCG and GSH exerted neither harm or protection on probiotics. This significantly reduced the harmful effects of antioxidants on probiotics. Almost all the probiotics survived after pasteurization, which was critical for the use of probiotics in other foods. The inactivation values of probiotics in microcapsules were around 1 log in simulated gastric juice (SGJ), about 0.5 log in simulated intestinal juice (SIJ), and around 1 log after 40 days of ambient storage., Conclusion: Dry S/O/W microcapsule, with butterfat containing probiotics as the inner core and WPIF as the outer shell, significantly increased the resistance of probiotics to harsh environments. This work proposed a preparation method of dry S/O/W microcapsule with core/shell structure, which could be used in the encapsulation of probiotics and other bioactive ingredients., (© 2023 Society of Chemical Industry.)

Papillary thyroid carcinoma (PTC), the most common endocrine tumor, often spreads to cervical lymph nodes metastasis (CLNM). Preoperative diagnosis of CLNM is important when selecting surgical strategies. Therefore, we aimed to explore the effectiveness of quantitative parameters of contrast-enhanced ultrasound (CEUS) in predicting CLNM in PTC. We retrospectively analyzed 193 patients with PTC undergoing conventional ultrasound (CUS) and CEUS. The CUS features and quantitative parameters of CEUS were evaluated according to PTC size ≤ 10 or > 10 mm, using pathology as the gold standard. For the PTC ≤ 10 mm, microcalcification and multifocality were significantly different between the CLNM (+) and CLNM (-) groups (both P < 0.05). For the PTC > 10 mm, statistical significance was noted between the two groups with respect to the margin, capsule contact, and multifocality (all P < 0.05). For PTC ≤ 10 mm, there was no significant difference between the CLNM (+) and CLNM (-) groups in all quantitative parameters of CEUS (all P > 0.05). However, for PTC > 10 mm, the peak intensity (PI), mean transit time, and slope were significantly associated with CLNM (all P < 0.05). Multivariate analysis showed that PI > 5.8 dB was an independent risk factor for predicting CLNM in patients with PTC > 10 mm (P < 0.05). The area under the curve of PI combined with CUS (0.831) was significantly higher than that of CUS (0.707) or PI (0.703) alone in the receiver operator characteristic curve analysis (P < 0.05). In conclusion, PI has significance in predicting CLNM for PTC > 10 mm; however, it is not helpful for PTC ≤ 10 mm.

Nitrated aromatic compounds (NACs) are key components of air pollution; however, due to the presence of complex mixtures of primary and secondary species, especially in urban environments, their atmospheric formation is poorly understood. Here we conducted a field campaign during a winter haze episode in urban Beijing, China to monitor gaseous and particulate NACs at 2-h time resolution. Through a standard-independent non-targeted approach, a total of 238 NACs were screened, of which 127 species were assigned chemical formula and 25 structures were confirmed. Four main classes were identified: nitrated aromatic hydrocarbons, nitrophenols, oxygenated nitrated aromatic compounds, and nitrated heterocyclic aromatic compounds. Hierarchical clustering analysis revealed disparate temporal variances of diurnal or nocturnal elevation, among which different nitration formations were captured, i.e., daytime photochemical oxidation and nighttime heterogeneous reactions. Isomeric information, particularly the substitution position of the nitro group on biphenyl, further demonstrated a potential heterogeneous mechanism of electrophilic nitration by NO 2 + . Assisted by source apportionment, we found that nighttime heterogeneous reactions significantly contributed to NAC formation, e.g., 31.3 % and 60.8 %, respectively, to 2-nitrofluoranthene and 2-nitropyrene, which were previously considered as classical daytime gas-phase products. This study provides comprehensive information on urban NAC species and highlights the importance of unheeded heterogeneous reactions in the atmosphere., 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.)

Drought has a severe impact on the quality and yield of cotton. Deciphering the key genes related to drought tolerance is important for understanding the regulation mechanism of drought stress and breeding drought-tolerant cotton cultivars. Several studies have demonstrated that NAC transcription factors are crucial in the regulation of drought stress, however, the related functional mechanisms are still largely unexplored. Here, we identified that NAC transcription factor GhNAC4 positively regulated drought stress tolerance in cotton. The expression of GhNAC4 was significantly induced by abiotic stress and plant hormones. Silencing of GhNAC4 distinctly impaired the resistance to drought stress and overexpressing GhNAC4 in cotton significantly enhanced the stress tolerance. RNA-seq analysis revealed that overexpression of GhNAC4 enriched the expression of genes associated with the biosynthesis of secondary cell walls and ribosomal proteins. We confirmed that GhNAC4 positively activated the expressions of GhNST1, a master regulator reported previously in secondary cell wall formation, and two ribosomal protein-encoding genes GhRPL12 and GhRPL18p, by directly binding to their promoter regions. Overexpression of GhNAC4 promoted the expression of downstream genes associated with the secondary wall biosynthesis, resulting in enhancing secondary wall deposition in the roots, and silencing of GhRPL12 and GhRPL18p significantly impaired the resistance to drought stress. Taken together, our study reveals a novel pathway mediated by GhNAC4 that promotes secondary cell wall biosynthesis to strengthen secondary wall development and regulates the expression of ribosomal protein-encoding genes to maintain translation stability, which ultimately enhances drought tolerance in cotton., (© 2023 Society for Experimental Biology and John Wiley & Sons Ltd.)

Since machine learning techniques for raindrop removal have not been capable of completely removing raindrops and have failed to take into account the constraints of edge devices with limited resources, a novel software-hardware co-designed method with a memristor for raindrop removal, named memristive attention recurrent residual generative adversarial network (MARR-GAN), is introduced in this research. A novel raindrop-removal network is specifically designed based on attention gate connections and recurrent residual convolutional blocks. By replacing the basic convolution unit with recurrent residual convolution unit, improved capturing of the changes in raindrop appearance over time is achieved, while preserving the position and shape information in the image. Additionally, an attention gate is utilized instead of the original skip connection to enhance the overall structural understanding and local detail preservation, facilitating a more comprehensive removal of raindrops across various areas of the image. Furthermore, a hardware implementation scheme for MARR-GAN is presented in this paper, where deep learning algorithms are seamlessly integrated with neuro inspired computing chips, utilizing memristor crossbar arrays for accelerated real-time image-data processing. Compelling evidence of the efficacy and superiority of MARR-GAN in raindrop removal and image restoration is provided by the results of the empirical study.

Purpose: To examine whether and how carbohydrate response element-binding protein (ChREBP) plays a role in diabetic retinopathy., Methods: Western blotting was used to detect ChREBP expression and location following high glucose stimulation of Human Retinal Microvascular Endothelial Cells (HRMECs). Flow cytometry, TUNEL staining, and western blotting were used to evaluate apoptosis following ChREBP siRNA silencing. Cell scratch, transwell migration, and tube formation assays were used to determine cell migration and angiogenesis. Diabetic models for wild-type (WT) and ChREBP knockout (ChKO) mice were developed. Retinas of WT and ChKO animals were cultivated in vitro with vascular endothelial growth factor + high glucose to assess neovascular development., Results: ChREBP gene knockdown inhibited thioredoxin-interacting protein and NOD-like receptor family pyrin domain containing protein 3 expression in HRMECs, which was caused by high glucose stimulation, reduced apoptosis, hindered migration, and tube formation, and repressed AKT/mTOR signaling pathway activation. Compared with WT mice, ChKO mice showed suppressed high glucose-induced alterations in retinal structure, alleviated retinal vascular leakage, and reduced retinal neovascularization., Conclusions: ChREBP deficiency decreased high glucose-induced apoptosis, migration, and tube formation in HRMECs as well as structural and angiogenic responses in the mouse retina; thus, it is a potential therapeutic target for diabetic retinopathy., 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.)

Magnetorheological elastomer thin films (MREFs) exhibit remarkable deformability and an adjustable modulus under magnetic fields, rendering them promising in fields such as robotics, flexible sensors, and biomedical engineering. Here, we fabricated MREF by introducing magnetostrictive particles (MSPs) and evaluated the magneto-mechanical coupling effect on the enhancement of sensitivity. The saturation magnetization ( M s ) in a parallel anisotropic TbDyFe-PDMS MREF was 5.8 emu/g, and the initial tensile modulus was 55% greater than that of an Iso MREF. We propose a nonlinear magnetorheological formula on the magnetostriction effect, incorporating magnetic dipole interactions and the nonlinear prestress of magnetic particles. This formula highlights the complex nonlinear relationship between the external magnetic field ( H ) and the key parameters that affect the enhanced MR effect of MSPs-MREF, such as saturation magnetization, remanence ( M r ), magnetostriction constant ( λ s ) and stress deviator in ferromagnetic particles ( S ed ) in the magnetic chain structure. Furthermore, we validate the influence of the key parameters of the rectified magnetorheological formula on a nonlinear magneto-mechanical behavior of MSPs-MREF in PDMS-based MSPs-MREF models by using finite-element simulations. Finally, we developed a biosensor based on MSPs-MREF to detect human serum albumin at low concentrations in human urine samples. There is a 4-fold increase in sensitivity, a lower detection of limit (0.442 μg/mL), and a faster response time (15 min) than traditional biosensors, which in the future might provide an effective way of detecting biomolecules of low concentrations.

Sepsis, which is the most severe clinical manifestation of acute infection and has a mortality rate higher than that of cancer, represents a significant global public health burden. Persistent methicillin-resistant Staphylococcus aureus (MRSA) infection and further host immune paralysis are the leading causes of sepsis-associated death, but limited clinical interventions that target sepsis have failed to effectively restore immune homeostasis to enable complete eradication of MRSA. To restimulate anti-MRSA innate immunity, we developed CRV peptide-modified lipid nanoparticles (CRV/LNP-RNAs) for transient in situ programming of macrophages (MΦs). The CRV/LNP-RNAs enabled the delivery of MRSA-targeted chimeric antigen receptor (CAR) mRNA (SasA-CAR mRNA) and CASP11 (a key MRSA intracellular evasion target) siRNA to MΦs in situ , yielding CAR-MΦs with boosted bactericidal potency. Specifically, our results demonstrated that the engineered MΦs could efficiently phagocytose and digest MRSA intracellularly, preventing immune evasion by the "superbug" MRSA. Our findings highlight the potential of nanoparticle-enabled in vivo generation of CAR-MΦs as a therapeutic platform for multidrug-resistant (MDR) bacterial infections and should be confirmed in clinical trials.

Circular RNAs (circRNAs) have played an essential role in cancer development. This study aimed to illustrate the impact and potential mechanism of circRACGAP1 action in NSCLC development. The expression patterns of circRACGAP1, miR-1296, and CDK2 in NSCLC tissues and cell lines were analysed by RT-qPCR. The function of circRACGAP1 in NSCLC cell proliferation and apoptosis was investigated using the CCK-8 assay, flow cytometry, TUNEL staining, and Western blot. The interaction among circRACGAP1, miR-1296, and CDK2 was clarified by dual-luciferase reporter assay while the correlation was confirmed by the Pearson correlation coefficient. The expression of circRACGAP1 and CDK2 was up-regulated in NSCLC tissues, while the expression of miR-1296 was down-regulated. Cell function studies further revealed that circRACGAP1 could promote NSCLC cell proliferation, accelerate the cell cycle process, up-regulate B-cell lymphoma 2 (Bcl2) expression, and down-regulate Bcl2-associated X (Bax) expression. miR-1296 was identified as a downstream target to reverse circRACGAP1-mediated cell proliferation. miR-1296 directly targeted the 3'-UTR of CDK2 to regulate proliferation and apoptosis of NSCLC cells. Additionally, the dual-luciferase reporter assay and Pearson correlation coefficient analysis proved that circRACGAP1 acted in NSCLC cells by negatively regulating miR-1296 expression and positively regulating CDK2 expression. In summary, our study revealed that circRACGAP1 promoted NSCLC cell proliferation by regulating the miR-1296/CDK2 pathway, providing potential diagnostic and therapeutic targets for NSCLC.

The use of natural and safe ingredients in green food packaging material is a hot research topic. This study investigated the effect of different emulsifiers on starch film properties. Three types of emulsifiers, including Tween 80 as a small-molecule surfactant, sodium caseinate (CAS), whey protein isolate (WPI), and gelatin (GE) as macromolecule emulsifiers, whey protein isolate fibril (WPIF) as a particle emulsifier, were utilized to prepare Zanthoxylum bungeanum essential oil (ZBO) emulsions. The mechanical, physical, thermal, antibacterial properties, microstructure and essential oil release of starch films were investigated. CAS-ZBO nanoemulsion exhibited the smallest particle size of 198.6 ± 2.2 nm. The film properties changed with different emulsifiers. CAS-ZBO film showed the highest tensile strength value. CAS-ZBO and WPIF-ZBO films exhibited lower water vapor permeability than Tween-ZBO. CAS-ZBO film showed good dispersion of essential oil, the slowest release rate of essential oils in all food simulants, and the best antibacterial effect against Staphylococcus aureus and Listeria monocytogenes. The films composed of CAS-ZBO nanoemulsion, corn starch, and glycerol are considered more suitable for food packaging. This work indicated that natural macromolecule emulsifiers of CAS and WPIF are expected to be used in green food packaging material to offer better film properties., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Since the old industrial buildings bear many functions of industrial production and storage in the service stage, the dust generated by the regeneration construction is often accompanied by industrial pollutants, causing irreversible damage to the personal safety of construction workers. However, little consideration has been given to the uncertainty of dust emissions and the dynamics of construction personnel movement. Therefore, reducing the risk of dust hazards during the regeneration of old industrial buildings is imperative. This study draws on the trace intersecting theory to analyse the cause of the hazard risk associated with reconstruction dust and explore the impact of the spatiotemporal distribution characteristics of reconstruction dust and its coupling effect with construction on-site personnel activity trajectories and uses the risk matrix method to assess the dust hazard risk in the reconstruction of old industrial buildings. Finally, the renovation and reinforcement process of the first floor of a printing building in Xi'an was considered as an example for verification. The results indicate that the risk assessment model results were highly consistent with the actual situation and risk value for the entire area was 6.05, indicating a risk level of IV. Immediate measures should be implemented to reduce dust concentrations or the frequency of construction personnel activity, thereby minimising potential harm., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Liver fibrosis usually progresses to liver cirrhosis and even results in hepatocellular carcinoma, which accounts for one million deaths annually worldwide. To date, anti-liver fibrosis drugs for clinical treatment have not yet been approved. Nowadays, as a natural regulator, Relaxin (RLX) has received increased attention because the expression of RLX could deactivate the activation of hepatic stellate cells (aHSCs) and resolve liver fibrosis. However, its application in treatment is limited due to the short half-life in circulation and low accumulation within the target organ., Methods: To address these problems, a kind of polymeric metformin (PolyMet)-loaded relaxin plasmid (pRLX) core-membrane lipid nanoparticle (PolyMet-pRLX-LNPs, PRLNP) was prepared. Here, PolyMet was used as a carrier to replace the traditional polymer polyethylene diene (PEI), which is of higher toxicity, to prolong the circulation time of pRLX in vivo . Then, the antifibrotic ability of PRLNP to overcome liver fibrosis was carried out in C57BL/6 mice. It is worth mentioning that this is the first time to investigate the potential of PRLNP in carbon tetrachloride-induced liver fibrosis., Results: The results showed that PRLNP effectively downregulated fibrosis-related biomarkers such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Meanwhile, histopathological examinations also showed low collagen accumulation, revealing that PRLNP could histologically and functionally alleviate liver fibrosis. In addition, no significant difference in serum biochemical value between the PRLNP and the normal group, suggesting the safety profile of PRLNP., Conclusion: This research proposed a novel non-toxic treatment method for liver fibrosis with a nanosystem to effectively treat liver fibrosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Bioaerosols are a subset of important airborne particulates that present a substantial human health hazard due to their allergenicity and infectivity. Chemical reactions in atmospheric processes can significantly influence the health hazard presented by bioaerosols; however, few studies have summarized such alterations to bioaerosols and the mechanisms involved. In this paper, we systematically review the chemical modifications of bioaerosols and the impact on their health effects, mainly focusing on the exacerbation of allergic diseases such as asthma, rhinitis, and bronchitis. Oxidation, nitration, and oligomerization induced by hydroxyl radicals, ozone, and nitrogen dioxide are the major chemical modifications affecting bioaerosols, all of which can aggravate allergenicity mainly through immunoglobulin E pathways. Such processes can even interact with climate change including the greenhouse effect, suggesting the importance of bioaerosols in the future implementation of carbon neutralization strategies. In summary, the chemical modification of bioaerosols and the subsequent impact on health hazards indicate that the combined management of both chemical and biological components is required to mitigate the health hazards of particulate air pollution., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2023 The Authors.)

Background: Intervertebral degenerative disc (IDD) disease is one of the most common clinical conditions causing low back pain. The main objective of this study was to investigate the repair effect of platelet-rich plasma (PRP) and ferulic acid (FA) hydrogel compound on degenerative discs in rats in combination with bioengineering technology, which may provide a strong theoretical basis for the future treatment of IDD., Methods: Forty-five male Sprague-Dawley rats were randomly divided into groups A-F; MRI was performed in each group at 0, 4, and 8 weeks after injection; and disc tissues were obtained after executing the animals. The histomorphology, apoptosis, and protein synthesis of intervertebral discs in each group were observed by hematoxylin-eosin, Masson, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and Western blot., Results: The release concentration of all groups reached the peak at 12 hours, and the highest concentration was found in the hydrogel/PRP/FA group at the same time. The MTT assay showed that hydrogel/PRP/FA is well-cytocompatible. The results of animal experiments show that hydrogel/PRP/FA has a good effect on degenerative intervertebral disc in rats., Conclusion: PRP/FA-rich hydrogel compound plays an active role in promoting extracellular matrix synthesis, strengthening and repairing degenerated intervertebral discs in rats., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

With ever-growing demand for eco-friendly materials for wearable electronics, biopolymer-based hydrogels have drawn significant attention. As one of the most abundant and biodegradable biopolymers, starch-based hydrogels have a great potential for wearable electronics. However, mechanical fragility, low conductivity and subzero freeze restrict their applications. Here, a multifunctional hydrogel was facilely fabricated by integrating ionic liquid and graphene oxide into potato starch/polyvinyl alcohol skeleton via a green physical-crosslinking method. The abundant hydrogen-bond and electrostatic interactions endowed the hydrogel with excellent stretchability (657.5 %), strength (0.64 MPa), high conductivity (1.98 S·m -1 ) and good anti-freezing property (< -20 °C). Multiple characterizations and theoretical simulation (DFT) were combined to understand and confirm the interactions among different components. Taking advantage of these properties, multimodal wearable sensors were constructed for sensing tension (gauge factor: 6.04), compression (gauge factor: 3.27) and temperature (sensitivity: 0.71 %/°C), which are applied for monitoring human motion, daily-life pressure and body temperature. The sensor had a good anti-fatigue property with stable signals during 2000 cycles. Moreover, the sensor can effectively recognize handwriting and perform human-computer interaction. This work provides a promising route to develop sustainable and multifunctional biopolymer hydrogels for wearable sensors with versatile applications in human health, exercise monitors and soft robots., 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 Ltd. All rights reserved.)

Skeletal disorder is of concern to the poultry industry as it affects animal welfare and production performance. Traditional Chinese medicine could improve bone quality and reduce the incidence of bone disease, but the molecular regulation of Chinese medicine formula (CMF) on improving bone quality in broilers is still unclear. This study was performed to research the effects of CMF on skeletal performance of Cobb broilers and reveal the molecular regulation. A total of 120 one-day-old Cobb broilers were randomly allocated into 4 equal groups of 30 chickens, with 5 replicates and 6 chickens in each replicate. The control (CON) group was fed a diet without CMF, while the CMF1, CMF2, and CMF3 groups were supplemented with different CMF at 6,000 mg/kg diet, respectively. The broilers were raised to 60 d of age, then bone tissues were collected for biomechanical properties, micro-CT detection and transcriptomic sequencing analysis. The results showed that CMF3 improved the biomechanical properties of broiler tibia, via increasing the elastic modulus (P < 0.05), yield strength (P > 0.05), maximum stress (P < 0.05) and fracture stress (P < 0.05) of the tibia. Micro-CT analysis indicated that CMF3 increased the bone mineral density (BMD), bone volume/total volume (BV/TV), bone surface density (BS/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and decreased the trabecular separation (Tb.Sp) of femur cancellous bone (P < 0.05). RNA-seq analysis revealed 2,177 differentially expressed genes (DEGs) (|log 2 FoldChange| ≥ 1, FDR < 0.05) between the CMF3 group and CON group. Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis showed 13 pathways mostly associated with bone growth and development and bone metabolism, and we identified 39 bone-related DEGs. This study suggests that CMF3 could improve bone strength and bone microstructure of broilers, and showed a positive effect on bone performance. Our research could provide a theoretical reference for the development of pollution-free feed additives to improve the skeletal performance of broilers, which could help promote healthy farming of chickens., (Copyright © 2023. Published by Elsevier Inc.)

Introduction. Respiratory tract infection, which is associated with high morbidity and mortality, occurs frequently in children. At present, the main diagnostic method is culture. However, the low pathogen detection rate of the culture approach prevents timely and accurate diagnosis. Fortunately, next-generation sequencing (NGS) can compensate for the deficiency of culture, and its application in clinical diagnostics has become increasingly available. Gap Statement. Targeted NGS (tNGS) is a platform that can select and enrich specific regions before data enter the NGS pipeline. However, the performance of tNGS in the detection of respiratory pathogens and antimicrobial resistance genes (ARGs) in infections in children is unclear. Aim and methodology. In this study, we estimated the performance of tNGS in the detection of respiratory pathogens and ARGs in 47 bronchoalveolar lavage fluid (BALF) specimens from children using conventional culture and antimicrobial susceptibility testing (AST) as the gold standard. Results. RPIP (Respiratory Pathogen ID/AMR enrichment) sequencing generated almost 500 000 reads for each specimen. In the detection of pathogens, RPIP sequencing showed targeted superiority in detecting difficult-to-culture bacteria, including Mycoplasma pneumoniae . Compared with the results of culture, the sensitivity and specificity of RPIP were 84.4 % (confidence interval 70.5-93.5 %) and 97.7 % (95.9 -98.8%), respectively. Moreover, RPIP results showed that a single infection was detected in 10 of the 47 BALF specimens, and multiple infections were detected in 34, with the largest number of bacterial/viral coinfections. Nevertheless, there were also three specimens where no pathogen was detected. Furthermore, we analysed the drug resistance genes of specimens containing Streptococcus pneumoniae , which was detected in 25 out of 47 specimens in the study. A total of 58 ARGs associated with tetracycline, macrolide-lincosamide-streptogramin, beta-lactams, sulfonamide and aminoglycosides were identified by RPIP in 19 of 25 patients. Using the results of AST as a standard, the coincidence rates of erythromycin, tetracycline, penicillin and sulfonamides were 89.5, 79.0, 36.8 and 42.1 %, respectively. Conclusion. These results demonstrated the superiority of RPIP in pathogen detection, particularly for multiple and difficult-to-culture pathogens, as well as in predicting resistance to erythromycin and tetracycline, which has significance for the accurate diagnosis of pathogenic infection and in the guidance of clinical treatment.

Multitarget HDAC inhibitors capable of simultaneously blocking the BRD4-LIFR-JAK1-STAT3 signaling pathway hold great potential for the treatment of TNBC and other solid tumors. Herein, novel Fedratinib-based multitarget HDAC inhibitors were rationally designed, synthesized, and biologically evaluated, among which compound 25a p stood out as a potent HDAC/JAK/BRD4 triple inhibitor. Satisfyingly, compound 25a p led to concurrent inhibition of HDACs and the BRD4-LIFR-JAK1-STAT3 signaling pathway, which was validated by hyper-acetylation of histone and α-tubulin, hypo-phosphorylation of STAT3, downregulation of LIFR, MCL-1, and c-Myc in MDA-MB-231 cells. The multitarget effects of 25a p contributed to its robust antitumor response, including potent antiproliferative activity, remarkable apoptosis-inducing activity, and inhibition of colony formation. Notably, 25a p possessed an acceptable therapeutic window between normal and cancerous cells, desirable in vitro metabolic stability in mouse microsome, and sufficient in vivo exposure via intraperitoneal administration. Additionally, the in vivo antitumor potency of 25a p was demonstrated in an MDA-MB-231 xenograft model.

China is now confronting the intertwined challenges of air pollution and climate change. Given the high synergies between air pollution abatement and climate change mitigation, the Chinese government is actively promoting synergetic control of these two issues. The Synergetic Roadmap project was launched in 2021 to track and analyze the progress of synergetic control in China by developing and monitoring key indicators. The Synergetic Roadmap 2022 report is the first annual update, featuring 20 indicators across five aspects: synergetic governance system and practices, progress in structural transition, air pollution and associated weather-climate interactions, sources, sinks, and mitigation pathway of atmospheric composition, and health impacts and benefits of coordinated control. Compared to the comprehensive review presented in the 2021 report, the Synergetic Roadmap 2022 report places particular emphasis on progress in 2021 with highlights on actions in key sectors and the relevant milestones. These milestones include the proportion of non-fossil power generation capacity surpassing coal-fired capacity for the first time, a decline in the production of crude steel and cement after years of growth, and the surging penetration of electric vehicles. Additionally, in 2022, China issued the first national policy that synergizes abatements of pollution and carbon emissions, marking a new era for China's pollution-carbon co-control. These changes highlight China's efforts to reshape its energy, economic, and transportation structures to meet the demand for synergetic control and sustainable development. Consequently, the country has witnessed a slowdown in carbon emission growth, improved air quality, and increased health benefits in recent years., 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.)

Background: Previous studies examining trends in sleep loss among adolescents have mainly focused on single countriy and region. This study aims to analyze temporal trends in the prevalence of anxiety-induced sleep loss among adolescents from 29 countries in five regions., Methods: This study used data from the Global School-based Student Health Survey 2003-2018, which surveyed 215,380 adolescents from 29 countries with at least two cross-sectional surveys per country. The weighted country-specific prevalence of anxiety-induced sleep loss and trends across the survey years were evaluated. Random- or fixed-effects meta-analyses were used to calculate pooled prevalence and temporal trends across 29 countries., Results: Temporal variations in anxiety-induced sleep loss across countries were identified. Increasing (Suriname, Vanuatu, and Myanmar), decreasing (Namibia, Jamaica, the Philippines, Samoa, and Indonesia), and stable (all other countries) trends in anxiety-induced sleep loss were noted. The pooled weighted prevalence of anxiety-induced sleep loss was 11.35 and 10.67% in the first and last surveys, respectively. There was no meaningful change in the propensity to have anxiety-related sleep disorders over time, with the reduction and OR of these two surveys being 0.54 (-0.53-1.61) and 0.98 (0.88-1.10). For subgroup analyses, no significant differences in pooled anxiety-induced sleep loss trends were seen between the two surveys for different sexes, regions, incomes, survey years in the first wave, survey periods, or number of surveys., Conclusion: Trends in the prevalence of anxiety-induced sleep loss in adolescents varied significantly across different countries. Generally, a stable trend was observed in 21 of the 29 countries surveyed. Our study provides data that can aid policymakers in establishing country-specific strategies for reducing anxiety-induced sleep loss in adolescents., 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 Xu, Li, Yi, Li, Chai and Zhu.)

Irisin is a myogenic cytokine which plays an important role in the cardiovascular system. The aim of this study was to investigate the correlation between serum irisin levels and major adverse cardiovascular events (MACE) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). A total of 207 patients with AMI who underwent PCI were selected as research subjects. Serum irisin levels at admission were measured, and patients were stratified according to the receiver operating characteristic curve to assess differences in MACE within one year after PCI. After one year of follow-up, 207 patients were divided into two groups, 86 with MACE and 121 without MACE. There were significant differences in age, Killip grade, left ventricular ejection fraction, cardiac troponin I, creatine kinase-muscle/brain, and serum irisin between the two groups. Serum irisin level at admission in AMI patients significantly correlated with the occurrence of MACE after PCI, and could be used as an effective marker for predicting the occurrence of MACE in AMI patients after PCI.

Objective: To investigate the expression of lncRNA UCA1 in serum of patients with acute cerebral infarction (ACI) and its relationship with prognosis., Methods: The serum lncRNA UCA1 level in participants was detected, and the correlation between the neurological function score (NIHSS score) of ACI patients and lncRNA UCA1 expression was analyzed. Patients were followed up at 3 months after discharge and were divided into favorable and unfavorable prognostic groups according to the modified Rankin scale (mRs). The risk factors of ACI patients with poor prognosis were analyzed, and the predictive value of each index for ACI prognosis was evaluated by ROC curve., Results: The level of lncRNA UCA1 in ACI group was increased ( P <0.001). ROC analysis showed that high lncRNA UCA1 expression had clinical significance for the diagnosis of ACI. Spearman correlation analysis revealed that NIHSS score was positively correlated with lncRNA UCA1 expression level in ACI group (r=0.6537, P <0.001). Hcy level and NIHSS score in poor prognosis group (n=63) were higher than those in good prognosis group (n=84), and lncRNA UCA1 level in serum in poor prognosis group was increased in comparison to good prognosis group ( P <0.05). Logistic regression analysis investigated that admission NIHSS score, infarct size, and increased lncRNA UCA1 were the risk factors affecting the prognosis of ACI., Conclusion: Serum lncRNA UCA1 is abnormally elevated in ACI patients, and the elevated lncRNA UCA1 not only shows high accuracy in the diagnosis of ACI, but also has a certain predictive value for poor prognosis of ACI., (© 2023 by the Association of Clinical Scientists, Inc.)

In this work, an imidazolium-based poly (ionic liquid) (poly(1-octyl-3-vinyl- imidazolium naphthalene sulfonate)) functionalized silica (poly(C 8 VIm + NapSO 3 - ) @SiO 2 ) was successfully prepared for the determination of parabens in food samples. The prepared poly(C 8 VIm + NapSO 3 - )@SiO 2 was characterized by Fourier transform infrared spectrometry (FT-IR), X-ray photoelectron spectrogram (XPS) and Scanning electron microscopy (SEM). The simulation calculation results indicated that the suitable binding energies were between the polymeric ionic liquids and parabens, and the main interactions for extraction were hydrogen bonding, electrostatic and π-π stacking interactions. In addition, compared with commercial extraction materials, the prepared poly(C 8 VIm + NapSO 3 - )@SiO 2 sorbent showed comparable or even better extraction performance towards parabens. The effective parameters were optimized by a combination of the univariate method and Box-Behnken design (BBD). Under the optimum conditions, coupled with high performance liquid chromatography (HPLC), wide linear ranges (1.0-800 μg L -1 ), good linearity (R 2  ≥ 0.9997) and low limits of detection (0.1 μg L -1 ) were obtained. In addition, the intra-day and inter-day relative standard deviations (RSDs) were all lower than 6.3%. Moreover, the proposed method was successfully used for the determination of parabens in food samples and satisfactory recoveries in the range of 76.9-97.4% were obtained. The results indicated that the proposed method had good sensitivity, accuracy and precision for the detection of parabens in food samples., 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 B.V. All rights reserved.)

Pyroptosis is a proinflammatory form of programmed cell death featured with membrane pore formation that causes cellular swelling and allows the release of intracellular inflammatory mediators. This cell death process is elicited by the activation of the pore-forming proteins named gasdermins, and is intricately orchestrated by diverse regulatory factors in mammalian hosts to exert a prompt immune response against infections. However, growing evidence suggests that bacterial pathogens have evolved to regulate host pyroptosis for evading immune clearance and establishing progressive infection. In this review, we highlight current understandings of the functional role and regulatory network of pyroptosis in host antibacterial immunity. Thereafter, we further discuss the latest advances elucidating the mechanisms by which bacterial pathogens modulate pyroptosis through adopting their effector proteins to drive infections. A better understanding of regulatory mechanisms underlying pyroptosis at the interface of host-bacterial interactions will shed new light on the pathogenesis of infectious diseases and contribute to the development of promising therapeutic strategies against bacterial pathogens., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Elucidating the cellular organization of the cerebral cortex is critical for understanding brain structure and function. Using large-scale single-nucleus RNA sequencing and spatial transcriptomic analysis of 143 macaque cortical regions, we obtained a comprehensive atlas of 264 transcriptome-defined cortical cell types and mapped their spatial distribution across the entire cortex. We characterized the cortical layer and region preferences of glutamatergic, GABAergic, and non-neuronal cell types, as well as regional differences in cell-type composition and neighborhood complexity. Notably, we discovered a relationship between the regional distribution of various cell types and the region's hierarchical level in the visual and somatosensory systems. Cross-species comparison of transcriptomic data from human, macaque, and mouse cortices further revealed primate-specific cell types that are enriched in layer 4, with their marker genes expressed in a region-dependent manner. Our data provide a cellular and molecular basis for understanding the evolution, development, aging, and pathogenesis of the primate brain., Competing Interests: Declaration of interests Stereo-seq is covered in pending patents. BGI employees hold company stock., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The current diagnostic biomarkers of acute myocardial infarction (AMI), troponins, lack specificity and exist as false positives in other non-cardiac diseases. Previous studies revealed that cuproptosis, ferroptosis, and immune infiltration are all involved in the development of AMI. We hypothesize that combining the analysis of cuproptosis, ferroptosis, and immune infiltration in AMI will help identify more precise diagnostic biomarkers. The results showed that a total of 19 cuproptosis- and ferroptosis-related genes (CFRGs) were differentially expressed between the healthy and AMI groups. Functional enrichment analysis showed that the differential CFRGs were mostly enriched in biological processes related to oxidative stress and the inflammatory response. The immune infiltration status analyzed by ssGSEA found elevated levels of macrophages, neutrophils, and CCR in AMI. Then, we screened 6 immune-related CFRGs (CXCL2, DDIT3, DUSP1, CDKN1A, TLR4, STAT3) to construct a nomogram for predicting AMI and validated it in the GSE109048 dataset. Moreover, we also identified 5 pivotal miRNAs and 10 candidate drugs that target the 6 feature genes. Finally, RT-qPCR analysis verified that all 6 feature genes were upregulated in both animals and patients. In conclusion, our study reveals the significance of immune-related CFRGs in AMI and provides new insights for AMI diagnosis and treatment., (© 2023. The Author(s).)

In our previous research, a series of phenylsulfonylfuroxan-based hydroxamates were developed, among which compound 1 exhibited remarkable in vitro and in vivo antitumor potency due to its histone deacetylase (HDAC) inhibitory and nitric oxide (NO)-donating activities. Herein, the in-depth study of compound 1 revealed that this HDAC inhibitor-NO donor hybrid could enduringly increase the intracellular levels of acetyl histones and acetyl α-tubulin, which could be ascribed to its irreversible inhibition toward class I HDACs and HDAC6. Structural modification of compound 1 led to a novel phenylsulfonylfuroxan-based hydroxamate 4 , which exhibited considerable HDAC6 inhibitory activity and selectivity. Furthermore, compound 4 could inhibit intracellular HDAC6 both selectively and irreversibly. To the best of our knowledge, this is the first research reporting the irreversible inhibition of HDAC6. It was also demonstrated that compared with ACY-241 (a reversible HDAC6 inhibitor in clinical trials), the irreversible HDAC6 selective inhibitor 4 exhibited not only superior anti-multiple myeloma activity but also improved therapeutic index.

Indoor localization has broad application prospects, but accurately obtaining the location of test points (TPs) in narrow indoor spaces is a challenge. The weighted K-nearest neighbor algorithm (WKNN) is a powerful localization algorithm that can improve the localization accuracy of TPs. In recent years, with the rapid development of metaheuristic algorithms, it has shown efficiency in solving complex optimization problems. The main research purpose of this article is to study how to use metaheuristic algorithms to improve indoor positioning accuracy and verify the effectiveness of heuristic algorithms in indoor positioning. This paper presents a new algorithm called compact snake optimization (cSO). The novel algorithm introduces a compact strategy to the snake optimization (SO) algorithm, which ensures optimal performance in situations with limited computing and memory resources. The performance of cSO is evaluated on 28 test functions of CEC2013 and compared with several intelligent computing algorithms. The results demonstrate that cSO outperforms these algorithms. Furthermore, we combine the cSO algorithm with WKNN fingerprint positioning and RSSI positioning. The simulation experiments demonstrate that the cSO algorithm can effectively reduce positioning errors.

Background: Mild cognitive impairment (MCI) is the predementia phase of Alzheimer's disease (AD). The intestinal microbiome is altered in MCI and AD, and apolipoprotein E (ApoE) ε4 gene polymorphism is a risk factor for the progression of MCI to AD. This study aims to investigate the improvement in cognitive function of MCI patients with and without ApoE ε4 due to acupuncture and the changes in gut microbiota community composition and abundance in MCI., Methods: This randomized assessor-blind controlled study will enrol MCI patients with and without the ApoE ε4 gene (n = 60/60). Sixty subjects with the ApoE ε4 gene and 60 subjects without the ApoE ε4 gene will be randomly allocated into treatment and control groups in a 1:1 ratio. Intestinal microbiome profiles will be evaluated by 16 S rRNA sequencing of faecal samples and compared between the groups., Results/conclusions: Acupuncture is an effective method to improve cognitive function in MCI. This study will provide data on the relationship between the gut microbiota and the effectiveness of acupuncture in patients with MCI from a new angle. This study will also provide data on the relationship between the gut microbiota and an AD susceptibility gene by integrating microbiologic and molecular approaches., Trial Registration: www.chictr.org.cn , ID: ChiCTR2100043017, recorded on 4 February 2021., (© 2023. The Author(s).)

The regulation of antiviral immunity is crucial in maintaining host immune homeostasis, a process that involves dynamic modulations of host organelles. The Golgi apparatus is increasingly perceived as a host organelle functioning as a critical platform for innate immunity, but the detailed mechanism by which it regulates antiviral immunity remains elusive. Here, we identify the Golgi-localized G protein-coupled receptor 108 (GPR108) as a regulator of type Ι interferon responses by targeting interferon regulatory factor 3 (IRF3). Mechanistically, GPR108 enhances the ubiquitin ligase Smad ubiquitylation regulatory factor 1 (Smurf1)-mediated K63-linked polyubiquitination of phosphorylated IRF3 for nuclear dot 10 protein 52 (NDP52)-dependent autophagic degradation, leading to suppression of antiviral immune responses against DNA or RNA viruses. Taken together, our study provides insight into the crosstalk between the Golgi apparatus and antiviral immunity via a dynamic and spatiotemporal regulation of GPR108-Smurf1 axis, thereby indicating a potential target for treating viral infection., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Cost-utility analysis (CUA) is the preferred form of economic evaluation in many countries. As one of the key data inputs in cost-utility models, health state utility (HSU) has a crucial impact on CUA results. In the past decades, health technology assessment has been expanding rapidly in Asia, yet research examining the methodology and process used to generate cost-effectiveness evidence is scarce. The aim of this study was to examine the reporting of the characteristics of HSU data used in CUAs in Asia and how the characteristics have changed over time., Methods: A systematic literature search was performed to identify published CUA studies targeting Asian populations. Information was extracted for both the general characteristics of selected studies and the characteristics of reported HSU data. For each HSU value identified, we extracted data for four key characteristics, including 1) estimation method; 2) source of health-related quality of life (HRQoL) data; 3) source of preference data; and 4) sample size. The percentage of nonreporting was calculated and compared over two time periods (1990-2010 vs 2011-2020)., Results: A total of 789 studies were included and 4,052 HSUs were identified. Of these HSUs, 3,351 (82.7%) were from published literature and 656 (16.2%) were from unpublished empirical data. Overall, the characteristics of HSU data were not reported in more than 80% of the studies. Of HSUs whose characteristics were reported, most of them were estimated using the EQ-5D (55.7%), Asian HRQoL data (91.9%), and Asian health preferences (87.7%); 45.7% of the HSUs was estimated with a sample of 100 or more individuals. All four characteristics showed improvements after 2010., Conclusion: Over the past two decades, there has been a significant increase in CUA studies targeting Asian populations. However, HSU's characteristics were not reported in most of the CUA studies, making it difficult to evaluate the quality and appropriateness of the HSUs used in those cost-effectiveness studies., (© 2023. The Author(s).)

Tracking and eradicating Staphylococcus aureus in the periprosthetic microenvironment are critical for preventing periprosthetic joint infection (PJI), yet effective strategies remain elusive. Here, we report an implant nanoparticle coating that locoregionally yields bactericidal super chimeric antigen receptor macrophages (CAR-MΦs) to prevent PJI. We demonstrate that the plasmid-laden nanoparticle from the coating can introduce S. aureus -targeted CAR genes and caspase-11 short hairpin RNA (CASP11 shRNA) into macrophage nuclei to generate super CAR-MΦs in mouse models. CASP11 shRNA allowed mitochondria to be recruited around phagosomes containing phagocytosed bacteria to deliver mitochondria-generated bactericidal reactive oxygen species. These super CAR-MΦs targeted and eradicated S. aureus and conferred robust bactericidal immunologic activity at the bone-implant interface. Furthermore, the coating biodegradability precisely matched the bone regeneration process, achieving satisfactory osteogenesis. Overall, our work establishes a locoregional treatment strategy for priming macrophage-specific bactericidal immunity with broad application in patients suffering from multidrug-resistant bacterial infection.

Target identification by modification-free proteomic approaches can potentially reveal the pharmacological mechanism of small molecular compounds. By combining the recent solvent-induced protein precipitation (SIP) method with TMT-labeling quantitative proteomics, we propose solvent-induced proteome profiling (SIPP) approach to identify small molecule-protein interactions. The SIPP approach enables to depict denaturation curves of the target protein by varying concentrations of organic solvents to induce unfolding and precipitation of the cellular proteome. By using this approach, we have successfully identified the known targets of market drugs and natural products and extended the proteome information of SIP for target identification., (© 2023 Wiley-VCH GmbH.)

Objective: To probe the effect of trehalose on myocardial hypertrophy and its specific molecular mechanism., Methods: C57BL/6J male mice were divided into four subgroups: Sham operation subgroup (Sham), negative sham subgroup (Sham+Trehalose), transverse aortic constriction (TAC), and trehalose treatment subgroup (TAC+Trehalose). Immediately after the TAC operation, trehalose at a dose of 10 mg/kg was given daily via gavage. After four weeks, changes in cardiac function were evaluated using ultrasound to measure EF (ejection fraction), FS (fractional shortening), IVRT (isovolumic relaxation time), MPI (myocardial performance index), Tau (isovolumic relaxation time constant), LVESP (left ventricular end-systolic pressure), and EDPVR (end-diastolic pressure-volume relationship). The profiles of autophagy-associated proteins (p62, LC3II/I, and Beclin-1) and GATA4 protein in mice myocardial tissues were assessed by Western blotting (WB). Myocardial cells were classified from TAC mice into five groups: Control, Trehalose, Phenylephrine (PE), PE+Trehalose, and PE+Trehalose+autophagy inhibitor chloroquine groups. In the PE group, cardiomyocytes were treated with 50 μmol/L PE. Then, the cells were treated with trehalose (100 μmol/L), trehalose (100 μmol/L)+autophagy (20 μmol/L) for 24 hours respectively. The Control group was treated with the same amount of normal saline. Flow cytometry was utilized to detect myocardial cell apoptosis in each subgroup. The alterations in apoptosis and autophagy-correlated proteins (p62, LC3II/I, and Beclin-1) were assessed by WB. Additionally, the level of GATA4 protein upstream of autophagy was estimated. Furthermore, the expression levels of pro-apoptotic proteins Bad, BAX, Cleaved-caspase-3, and anti-apoptotic protein Bcl-2 were examined by WB., Results: The TAC operation significantly augmented myocardial hypertrophy, heart weight-to-body weight ratio, and myocardial cell apoptosis in mice ( p < 0.05). Trehalose significantly improved cardiac hypertrophy, cardiomyocyte apoptosis, and cardiac function decline in mice. Additionally, it also significantly enhanced autophagy in mouse cardiac tissues ( p < 0.05). At the cellular level, trehalose significantly decreased PE-elicited apoptosis and promoted the protein expressions of Beclin-1 and LC3 II/I in cardiomyocytes while significantly dampening the profiles of p62 and GATA4 in cells. The effect of trehalose and chloroquine treatment was significantly greater than that of the trehalose group., Conclusions: Trehalose significantly abates myocardial hypertrophy and pressure overload-induced cardiomyocyte apoptosis in mice. The cardioprotective effect of trehalose on enhanced autophagy is attributed, at least in part, to the promotion of autophagic degradation of GATA4., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by Discovery Medicine.)

DNA self-assembly has been developed as a kind of robust signal amplification strategy, but most of reported assembly pathways are programmed to amplify signal in one direction. Herein, based on mutual-activated cascade cycle of hybridization chain reaction (HCR) and catalytic hairpin assembly (CHA), a closed cycle circuit (CCC) based DNA machine is developed for sensitive logic operation and molecular recognition. Benefiting from the synergistically accelerated signal amplification, the closed cyclic DNA machine enabled the logic computing with strong and significant output signals even at weak input signals. The typical logic operations such as OR, YES, AND, INHIBIT, NOR, and NAND gate, are conveniently and clearly executed with this DNA machine through rational design of the input and computing elements. Moreover, by integrating the target recognition module with the CCC module, the proposed DNA machine is further employed in the homogeneous detection of apurinic/apyrimidinic endonuclease 1 (APE1). The precise recognition and exponential signal amplification facilitated the highly selective and sensitive detection of APE1 with limit of detection (LOD) of 7.8 × 10 -5 U mL -1 . Besides, the normal cells and tumor cells are distinguished unambiguously by this method according to the detected concentration difference of cellular APE1, which indicates the robustness and practicability of this method., (© 2023 Wiley-VCH GmbH.)

Authenticity verification is a very important aspect of medical device registration quality management system verification of medical device. How to verify the authenticity of samples is a problem worth discussing. This study analyzes the methods of authenticity verification from the aspects of product retention sample, registration inspection report, traceability of records, hardware facilities and equipment. In order to provide reference for relevant supervisors and inspectors in the verification of registration quality management system.

Background: Pancreatic cancer (PAC), a malignancy that is fatal and commonly diagnosed at a late stage. Despite considerable advancements in cancer treatment, the survival rate of PAC remains largely consistent for the past 60 years. The traditional Chinese medicine formula Pulsatilla Decoction (PD) has been clinically used to treat inflammatory diseases for millennia and recently as a supplementary anti-cancer treatment in China. However, the bioactive ingredients and mechanisms underlying its anti-cancer effect remains unclear., Methods: The composition and quality control of PD were verified through analysis by high performance liquid chromatography. Cell viability was determined using Cell Counting Kit-8 assay. The cell cycle distribution was analyzed through PI staining and flow cytometry analysis, while apoptotic cells were measured by double staining with Annexin V-FITC and PI. We used immunoblotting to examine protein expressions. The in vivo effects of β-peltatin and podophyllotoxin were evaluated on a subcutaneously-xenografted BxPC-3 cell nude mice model., Results: The current study demonstrated that PD markedly inhibited PAC cell proliferation and triggered their apoptosis. Four herbal PD formula was then disassembled into 15 combinations of herbal ingredients and a cytotoxicity assay showed that the Pulsatillae chinensis exerted the predominant anti-PAC effect. Further investigation indicated that β-peltatin was potently cytotoxic with IC 50 of ~ 2 nM. β-peltatin initially arrested PAC cells at G2/M phase, followed by apoptosis induction. Animal study confirmed that β-peltatin significantly suppressed the growth of subcutaneously-implanted BxPC-3 cell xenografts. Importantly, compared to podophyllotoxin that is the parental isomer of β-peltatin but clinically obsoleted due to its severe toxicity, β-peltatin exhibited stronger anti-PAC effect and lower toxicity in mice., Conclusions: Our results demonstrate that Pulsatillae chinensis and particularly its bioactive ingredient β-peltatin suppress PAC by triggering cell cycle arrest at G2/M phase and apoptosis., (© 2023. The Author(s).)