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Introduction: Previous findings on the association between uric acid (UA) levels and cancer risk are conflicting. Moreover, the mechanisms underlying the interactions between UA levels, fatty acid traits, and cancer outcomes remain complex; it is still unclear whether elevated UA levels influence fatty acid traits and, thereby, contribute to an increased cancer risk. Therefore, we aimed to investigate the association between UA levels and cancer risk, with a specific focus on the potential mediating role of fatty acid traits., Methods: We employed a Mendelian randomization (MR) analysis utilizing genetic data from large-scale genome-wide association studies to assess the causal relationships among UA levels, fatty acid traits, and cancer risk. The primary method used was the inverse variance-weighted approach alongside Bayesian-weighted Mendelian randomization. Other MR models were also applied for comparison. Sensitivity analyses, based on various statistical assumptions, were also performed to evaluate the robustness of the findings. A two-step MR analysis was conducted to explore the mediating effects of fatty acid traits on the relationship between UA levels and cancer risk., Results and Discussion: Elevated UA levels were associated with an increased risk of in situ neoplasms, cervical cancer, and invasive mucinous ovarian cancer, while they were linked to a decreased risk of cancers of the eye and adnexa, small cell lung cancer, bronchus and lung cancer, respiratory system and intrathoracic organ cancers, as well as lung cancer. Mediation analysis revealed that fatty acid traits, particularly the docosahexaenoic acid/trans fatty acid ratio, mediated the relationship between UA levels and lung cancer risk. These findings underscore the potential of fatty acid traits to mediate the association between UA levels and cancer risk, offering new insights for targeted interventions and potentially improving clinical outcomes., 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 Li, Zhang, Fu, Wang, Cai, Xu, Xing and Tong.)

Carbon dots (CDs) have gained significant interest because of their potential in biomedical applications. Nevertheless, developing CDs with efficient photoinduced charge separation for tumor photodynamic therapy (PDT) remains a challenge. This study presents a novel class of supra-carbon-dots (supra-CDs) developed by fusing red emissive CDs with 2,3-dicyanohydroquinone (DCHQ) via post-solvothermal treatment. In supra-CDs, the core, acting as electron donors, is formed by assembled CDs with substantial sp 2 domains, the fused interface originating from DCHQ with electron-withdrawing groups functions as the electron acceptor. This configuration creates the unique donor-acceptor nanostructure. Upon white light irradiation, the excited electrons from the assembled CDs were transferred to the electron-withdrawing interface, whereas the photogenerated holes were retained within the assembled CDs as radicals, leading to effective photoinduced charge separation. The separated photogenerated electrons then react with oxygen to generate superoxide radicals. Simultaneously, the photogenerated holes undergo oxidation of crucial cellular substrates. This dual action underscores the exceptional cell-killing efficacy of supra-CDs. Moreover, the increased particle sizes (~20 nm) ensure supra-CDs to exhibit a notable capacity for tumor accumulation via the improved permeability and retention effect, thereby achieving satisfactory anti-tumor PDT efficacy in a mouse subcutaneous tumor model., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Transglutaminase (TGase)-mediated cross-linking has gained significant attention due to its potential to reduce the allergenicity of food proteins. This study investigates the effects of TGase cross-linking on allergenicity and conformational modifications in a dual-protein system comprising soy protein isolate (SPI) and β-lactoglobulin (β-LG). The results showed that TGase cross-linking effectively decreased the allergenic potential of both SPI and β-LG, with a more pronounced reduction observed in the allergenicity of soy protein in the dual-protein system. SDS-PAGE analysis revealed that the 7S and 11S subunits of soy protein were more easily cross-linked than β-LG. Secondary structure analysis indicated that TGase treatment disrupted β-sheet structures, increased the content of random coils, and enhanced protein flexibility. Ultraviolet absorption and intrinsic fluorescence analyses confirmed these structural alterations, with TGase treatment exposing additional aromatic amino acids. A reduction in free sulfhydryl groups and altered intermolecular forces further corroborated the occurrence of cross-linking. These findings suggest that TGase-mediated cross-linking effectively reduced the allergenicity of SPI and β-LG by modifying their conformations, offering potential strategies for the development of hypoallergenic dual-protein food products. PRACTICAL APPLICATION: This study has practical applications in the food industry to develop hypoallergenic food products, particularly those that combine soy and dairy proteins. By using TGase to cross-link these proteins, the allergenicity can be reduced, resulting in products that are safer for consumers with food allergies., (© 2024 Institute of Food Technologists.)

Objective: This study aims to comprehensively examine and assess the changes and significance of irisin levels in individuals with carotid atherosclerosis (CAS) who are concurrently dealing with obesity., Method: A total of 156 CAS patients admitted between March 2020 and March 2022 were categorized into CAS normal weight (C1), CAS overweight (C2), and CAS obesity (C3) groups based on BMI. Simultaneously, 80 healthy adults from the same period comprised the control group (C0). The study conducted a comparative analysis of biochemical indexes, serum irisin levels, and carotid artery ultrasounds across all groups. Correlation analyses and diagnostic assessments for serum irisin in obesity with carotid atherosclerosis were executed using ROC curves., Results: Statistically significant differences were observed in cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), serum homocysteine (Hcy), and irisin levels among all groups (P < .05). Obese CAS patients exhibited higher levels of TC, TG, LDL-C, and Hcy, with notably lower levels of HDL-C and irisin compared to other groups (P < .05). Significant variations in carotid artery ultrasound intima-media thickness (IMT) and Crouse scores were also evident among all groups (P < .05). Specifically, IMT and Crouse scores were higher in obese CAS patients compared to other groups (P < .05). Correlation analysis results indicated a significant negative correlation between irisin and TC, TG, LDL-C, Hcy, IMT, and Crouse score (P < .05). Conversely, irisin exhibited a significant positive correlation with HDL-C levels (P < .05). The ROC curve analysis for the diagnostic value of irisin in obesity with CAS revealed an area under the curve of 0.957., Conclusions: Serum irisin levels are significantly reduced in CAS patients, particularly those with overweight and obese. Additionally, irisin levels are closely associated with patients' blood lipids, homocysteine levels, and the severity of atherosclerosis.

Cell-type classification is a crucial step in single-cell sequencing analysis. Various methods have been proposed for transferring a cell-type label from an annotated reference atlas to unannotated query datasets. Existing methods for transferring cell-type labels lack proper uncertainty estimation for the resulting annotations, limiting interpretability and usefulness. To address this, we propose popular Vote (popV), an ensemble of prediction models with an ontology-based voting scheme. PopV achieves accurate cell-type labeling and provides uncertainty scores. In multiple case studies, popV confidently annotates the majority of cells while highlighting cell populations that are challenging to annotate by label transfer. This additional step helps to reduce the load of manual inspection, which is often a necessary component of the annotation process, and enables one to focus on the most problematic parts of the annotation, streamlining the overall annotation process., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Pitting corrosion caused by sulfate-reducing bacteria (SRB) significantly shortens the lifespan of metallic pipelines. Antibacterial coatings containing S 2- -responsive drug-loaded nanocontainers represent a promising method to mitigate SRB corrosion. However, the challenge of balancing rapid bactericide release with continuous antibacterial effect limits their practical application. In this study, a S 2- and pH dual-responsive periodic drug release system was developed based on raspberry-like mesoporous silica intelligent nanocontainers (BAC-RMSNs@Cu-BTA) loaded with bactericide benzalkonium chloride (BAC) and blocked by copper-benzotriazole nano valves (Cu-BTA). When S 2- concentration exceeded 0.5 mM or pH fell below 6.3, the intelligent nanocontainers accelerated drug release. Under simultaneous S 2- and pH stimulation, the drug release rate was increased by 91 %, compared to isolated S 2- stimulation. The sustained release duration exceeded 384 h, which was more than twice that of existing S 2- -responsive nanocontainers. The reversible dissociation-complexation transition of Cu-BTA nano valves and the adsorption effect of the raspberry structure facilitated an inhibition of drug release after the stimulation disappeared, thereby enabling cyclic drug release and extending the antibacterial duration. The epoxy coating embedded with BAC-RMSNs@Cu-BTA showed excellent repeatable sterilization, long-term antibacterial adhesion and corrosion medium barrier ability in the SRB environment. Based on active intelligent sterilization and passive physical barrier effects, the composite coating's resistance to SRB corrosion in the simulated internal environment of pipelines was 14.6 times that of coating containing BAC-RMSNs. This study aims to provide valuable insights for the design of innovative long-acting antibacterial coatings., 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 © 2025 Elsevier Inc. All rights reserved.)

High-arsenic (As) geothermal water has been found over the world. However, the spatial distributions of As contents and genesis in geothermal systems remain to be fully understood due to the complexity of the sources and processes associated with As. In this study, the hydrochemical and isotopic methods and the self-organized mapping (SOM) were employed to investigate the spatial distributions and enrichment mechanism of As in hot springs in the Red River Fault Zone, southwest China. The results showed that arsenic concentration is low (less than 10 µg/L) in hot springs in the south part of the fault, while it is relatively high with a mean value of 212.73 µg/L in the north part of the fault. The distinct spatial differences in arsenic concentration of hot springs may be attributed to the heterogeneity of lithologies along the fault zone, with sedimentary rocks dominated in the northern and metamorphic rocks dominated in the southern section of the fault. Two sources of arsenic can be identified in the study area: 1) As is correlated with typical geothermal species such as Li and B, indicating that rock leaching from deep geothermal reservoirs can be a dominant source of As; 2) high level of HCO 3 - and weak alkalinity condition caused the desorption of arsenic from the sediment surface. In addition, the mixing with shallow groundwater also affects the As contents in hot springs. This study provides an insight into the formation and controls on high-arsenic geothermal water., 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.)

Rationale: We reported a rare case of recurrent cerebral infarction, intracerebral hemorrhage, and purulent meningitis, culminating in the diagnosis of a young patient with infective endocarditis who had been treated in 3 hospitals for a long course of illness for 8 months prior to diagnosis. It aims to enhance clinicians' understanding of the neurological complications caused by infective endocarditis., Patient Concerns: A 25-year-old male, student, was hospitalized for an 8-hour history of speech impairment and drooling with dysphagia. Magnetic resonance imaging (MRI) showed massive cerebral infarction in the right frontotemporal and insular lobes, and the first diagnosis was "cerebral infarction." Later, the patient developed recurrent cerebral infarction, intracerebral hemorrhage, and purulent meningitis., Diagnoses: Recurrent cerebral infarction, intracerebral hemorrhage, and purulent meningitis were confirmed to be caused by infective endocarditis., Interventions: The patient was treated with antiplatelet drugs such as aspirin and clopidogrel, mannitol to reduce intracranial pressure, and ceftriaxone and vancomycin to fight infection, and the patient's condition improved., Outcomes: The patient was diagnosed with infective endocarditis after 8 months without a clear diagnosis, and the patient was finally diagnosed with infective endocarditis during the final follow-up., Lessons: Febrile patients should be aware of infective endocarditis, particularly if the fever is persistent of unknown origin or structural changes in the heart with neurologic lesions. Cardiogenic neurological diseases are relatively more severe, have a worse prognosis, and have a higher recurrence rate than primary neurological diseases, so early diagnosis and treatment are more urgently needed., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rad51 filaments are Rad51-coated single-stranded DNA and essential in homologous recombination (HR). The yeast Shu complex (Shu) is a conserved regulator of homologous recombination, working through its modulation on Rad51 filaments to direct HR-associated DNA damage response. However, the biochemical properties of Shu remain unclear, which hinders molecular insights into Shu's role in HR and the DNA damage response. In this work, we biochemically characterized Shu and analyzed its molecular actions on single-stranded DNA and Rad51 filaments. First, we revealed that Shu preferentially binds fork-shaped DNA with 20nt ssDNA components. Then, we identified and validated, through site-specific mutagenesis, that Shu is an ATPase and hydrolyzes ATP in a DNA-dependent manner. Furthermore, we showed that Shu interacts with ssDNA and Rad51 filaments and alters the properties of ssDNA and the filaments with a 5'-3' polarity. The alterations depend on the ATP hydrolysis of Shu, suggesting that the ATPase activity of Shu is important in regulating its functions. The preference of Shu for acting on the 5' end of Rad51 filaments aligns with the observation that Shu promotes lesion bypass at the lagging strand of a replication fork. Our work on Shu, a prototype modulator of Rad51 filaments in eukaryotes, provides a general molecular mechanism for Rad51-mediated error-free DNA lesion bypass., Competing Interests: Declaration of Competing Interest No author has an actual or perceived conflict of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Tapering of chronic opioids has increased, with subsequent reports of exacerbated pain among patients who tapered. We aimed to evaluate the association between opioid dose tapering and subsequent pain-related healthcare utilization (ED visits, hospitalizations and primary care visits)., Design, Setting and Subjects: We conducted a retrospective cohort study from 2015-2019 using data from the Optum Labs Data Warehouse that contains de-identified retrospective administrative claims data for commercial and Medicare Advantage enrollees in the US. Adults aged ≥18 years who were prescribed stable doses of opioids, ≥50 morphine milligram equivalents (MME)/day, during a 12-month baseline period., Methods: Tapering was defined as ≥ 15% relative reduction in mean daily opioid dose during one of 6 overlapping 60-day periods. Tapered patient-periods were subclassified as tapered-and-continued (MME > 0) vs. tapered-and-discontinued (MME = 0). We modeled monthly counts of visits for pain diagnoses up to 12 months after cohort entry using negative binomial regression as a function of tapering, baseline utilization, and patient level-covariates., Results: Among 47,033 patients, 13,793 patients tapered. Compared to no taper, any taper was associated with more ED visits for pain (adjusted incidence rate ratio [aIRR] 1.21, 95% CI: 1.11-1.30), tapered then continued status was associated with more ED visits (aIRR 1.23, CI: 1.14-1.32) and hospitalizations (aIRR 1.14, CI: 1.03-1.27) for pain, and tapered-and-discontinued was associated with fewer primary care visits for pain (aIRR 0.68, CI: 0.61-0.76)., Conclusions: These associations suggest that opioid tapering may lead to increased emergency and hospital utilization for acute pain and possibly a decreased perceived need for primary care for those whose opioids were discontinued., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Zinc (Zn) deficiency is a global problem disorder affecting both crops and humans. Herein, modified functional carbon nanodots (MFCNs) with various structures and characteristics were developed to regulate tomato yields and Zn migration in plant-soil systems affected by Zn deficiency through structure-function relationships. Sulfur-doped FCNs (S-FCNs), nitrogen-doped FCNs (N-FCNs), and nitrogen‑sulfur co-doped FCNs (N,S-FCNs) were hydrothermally modified using FCNs as precursors. Their regulatory effects on tomatoes growing in Zn-deficient alkaline soils were studied in pot culture experiments. Specifically, 8 mg kg -1 of FCNs and S-FCNs improved tomato yields by 132 % and 108 %, respectively, compared with the control. However, N-FCNs and N,S-FCNs showed no significant effect on yield compared with the control (P < 0.05). Moreover, the application of FCNs or S-FCNs significantly improved fruit quality and nutritional value, including Zn content (by 26.3 % and 22.0 %, respectively) and naturally occurring antioxidants (by 3.37- and 2.08-fold for lycopene, 1.31- and 1.18-fold for flavonoids, and 2.28- and 1.89-fold for phenolics, respectively; P < 0.05). Although N-FCNs and N,S-FCNs increased Zn contents, they inhibited the synthesis of naturally occurring antioxidants in fruits. Zn bioaccessibility, uptake, and transportation in plant-soil systems were regulated by MFCNs through both direct and indirect mechanisms, including ionic reactions, plant physiology, and environmental effects. MFCNs regulated plant tolerance to Zn deficiency not only by affecting root activity, redox homeostasis, micronutrient balance, chelator synthesis, genetic expression, and plant photosynthesis but also by influencing rhizosphere soil properties and the microbial environment. Based on their dual role as "plant growth regulators" and "soil conditioners", MFCNs may have general applicability in agriculture. This study highlights the behavior of MFCNs in plant-soil systems, providing innovative nanotools for enhancing Zn availability, crop stress resistance and environmental preservation in sustainable agriculture., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Qiong Chen, Mei Yan reports financial support was provided by National Natural Science Foundation of China. Xiufeng Cao reports financial support was provided by National Natural Science Foundation of China. Qiong Chen, Mei Yan reports financial support was provided by Natural Science Foundation of Shandong Province. Qiong Chen reports financial support was provided by China Postdoctoral Science Foundation. Qiong Chen reports financial support was provided by Postdoctoral Research Startup Fund of University of Jinan. Mei Yan reports financial support was provided by Major Scientific and Technological Innovation Project of Shandong Province. Lijie Ci reports financial support was provided by School Research Startup Expenses of Harbin Institute of Technology (Shenzhen). If there are other authors, they 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.)

Because of their high affinity, specificity, and environmental stability, nanobodies (Nbs) have continuously received attention from the field of biological research. However, it is tough work to obtain high-affinity Nbs using experimental methods. In the current study, 12 machine learning algorithms were compared in parallel to explore the potential patterns between Nb-ligand affinity and eight noncovalent interactions. After model comparison and optimization, four optimized models (SVMrB, RotFB, RFB, and C50B) and two stacked models (StackKNN and StackRF) based on nine uncorrelated (correlation coefficient <0.65) optimized models were selected. All the models showed an accuracy of around 0.70 and high specificity. Compared to the other models, RotFB and RFB were not capable of predicting nonaffinitive Nbs with lower precision (<0.44) but showed higher sensitivity at 0.6761 and 0.3521 and good model robustness (F1 score and MCC values). On the contrary, SVMrB, C50B, and StackKNN were able to effectively predict the future nonaffinitive Nbs (specificity >0.92) and reduce the number of true affinitive Nbs (precision >0.5). On the other hand, StackRF showed intermediate model performance. Furthermore, an in-depth feature analysis indicated that hydrogen bonding and aromatic-associated interactions were the key noncovalent interactions in determining Nb-ligand binding affinity. In summary, the current study provides, for the first time, a tool that can effectively predict whether there is an affinity between nanobodies and their intended ligands and explores the key factors that influence their affinity, which could improve the screening and design process of Nbs and accelerate the development of Nb drugs and applications., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Alphaviruses are important arthropod-transmitted pathogens of humans and livestock. Getah virus (GETV) is an arthritogenic alphavirus that causes disease in horses and piglets; it also poses a potential threat to humans. A live attenuated vaccine candidate named GETV-3ΔS2-CM1, harbouring a deletion in nonstructural protein 3 and substitutions in the capsid protein, is genetically stable and exhibits robust immunogenicity. It was shown to confer passive protection to piglets born to immunized sows. In mice, a single dose of GETV-3ΔS2-CM1 protected against infection with different strains of GETV, Semliki Forest virus, Ross River virus, o'nyong'nyong virus, chikungunya virus, and Barmah Forest virus. Chimaeras based on the GETV-3ΔS2-CM1 backbone maintained both the attenuated phenotype and high immunogenicity. The safety, efficacy, and ability to induce protection against multiple alphaviruses highlights the potential of GETV-3ΔS2-CM1 and chimaeras using this backbone as promising vaccine candidates. By contributing simultaneously to the wellbeing of animals and humans, our universal next generation vaccine strategy helps to achieve "One Health" goals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Frequency-modulated continuous-wave (FMCW) narrow linewidth lasers have served as the cornerstone behind applications such as autonomous driving, wearable technology, virtual reality, and remote sensing mapping. Strongly coherent lasers are typically used for these studies, with a clear demand for linear fast response and wide frequency tuning range. In this paper, profiting from the ultrahigh-quality factor of the crystalline whispering-gallery-mode resonator, by using a self-injection locking mechanism to suppress spontaneous emission noise and improve coherence, sub-kHz linewidth at 450 nm is obtained. Furthermore, based on the dispersive response principle, fast electrical tuning is realized by using the strain-influenced resonator, and the experimental test result reaches 81 pm/V. More importantly, we demonstrate the comprehensive performance of this type of FMCW laser in underwater detection, with a sensitivity of 319 MHz/m at a chirp frequency of 1 kHz.

Food security related to bacterial pathogens has seriously threatened human life and caused public health problems. Most of the reported methods are targeted at known major pathogens commonly found in food samples, but to some extent, they have the disadvantage of lacking simplicity, speed, high throughput, and high sensitivity. Microfluidics has become a promising tool for foodborne bacteria analysis and addresses the above limitations. In this perspective, we briefly discussed the ongoing research and development in this field. We outline the major types of microfluidics, the strategies of target biorecognition, and signal amplification technologies in the microfluidic system for the foodborne bacteria analysis. We also proposed the future directions of microfluidics for foodborne bacterial analysis, which aims to integrate multiple technologies toward intelligent analysis with high selectivity and sensitivity for unknown samples, multiple bacterial detection, and simultaneous detection of multiple food pollutants., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Importance: Acute back pain is a common reason for primary care visits and often results in low-value spinal imaging., Objective: To evaluate the effect of a standardized patient-delivered intervention on rates of low-value spinal imaging among primary care patients with acute low back pain., Design, Setting, and Participants: In this randomized clinical trial, physicians or advanced practice clinicians were recruited from March 22 to August 5, 2021, from 10 adult primary care or urgent care clinics in Sacramento, California. The intervention period was from May 1, 2021, to March 30, 2022, with follow-up from October 28, 2021, to June 30, 2023. Analyses were performed from April 1 to June 25, 2024., Intervention: Clinicians were randomized 1:1 to intervention or control. Intervention clinicians received 3 simulated office visits, each with a standardized patient instructor (SPI) portraying a patient with acute uncomplicated back pain. At each visit, SPIs provided clinician feedback guided by a 3-step model: (1) set the stage for deferred imaging by building trust, (2) convey empathy, and (3) communicate optimism while advocating watchful waiting without imaging. Control clinicians received no intervention., Main Outcomes and Measures: The primary outcome was lumbar spinal imaging completion within 90 days of acute low back pain visits, with study clinicians assessed up to 18 months of follow-up. Secondary outcomes were cervical spine imaging completion after acute neck pain visits, any imaging completion after an adult visit, patient experience ratings of clinicians (scale range, 0-100), and use of targeted communication skills during an audio-recorded standardized patient evaluation visit at median follow-up of 16.8 months (range, 14.1-18.0 months)., Results: The analysis included 53 clinicians; mean (SD) age was 46.7 (1.0) years, and 35 (66.0%) reported female gender. A total of 25 were in the intervention group and 28 in the control group. After adjustment for prerandomization rates, patients with acute low back pain who saw intervention and control clinicians during follow-up had similar rates of lumbar imaging (194 of 1234 clinic visits [15.7%] vs 226 of 1306 clinic visits [17.3%]; adjusted ratio of postintervention vs preintervention odds ratios [AORR], 1.00; 95% CI, 0.72-1.40). Adjusted follow-up rates of imaging for acute neck pain (AORR, 1.16; 95% CI, 0.83-1.63) and overall imaging (AORR, 1.07; 95% CI, 0.97-1.19) were not significantly different among patients of intervention and control clinicians. Intervention and control clinicians had similar mean (SD) patient experience ratings during follow-up (88.6 [28.7] vs 88.8 [28.3]; adjusted mean difference-in-differences, -1.0; 95% CI, -3.0 to 0.9). During audio-recorded standardized patient visits, intervention clinicians had significantly better ratings than controls on eliciting the patient's perspective (adjusted standardized difference [ASD], 0.62; 95% CI, 0.05-1.19) and conveying empathy (ASD, 1.16; 95% CI, 0.55-1.77)., Conclusions and Relevance: In this randomized clinical trial of an educational intervention using simulated office visits to encourage a watchful waiting approach for acute low back pain, the intervention had no significant effect on low-value spinal imaging rates or patient experience ratings., Trial Registration: ClinicalTrials.gov Identifier: NCT04255199.

Metal halide perovskites, a cost-effective class of semiconductos, hold great promise for display technologies that demand high-efficiency, color-pure light-emitting diodes (LEDs). Early research on three-dimensional (3D) perovskites showed low radiative efficiencies due to modest exciton binding energies. To inprove luminescence, reducing dimensionality or grain size has been a common approach. However, dividing the perovskite lattice into smaller units may hinder carrier transport, compromising electrical performance. Moreover, the increased surface area introduce additional surface trap states, leading to greater non-radiative recombination. Here, an ions-induced growth method is employed to assembe lattice-anchored perovskite nanocomposites for efficient LEDs with high color purity. This approach enables the nanocomposite thin films, composed of 3D CsPbBr 3 and its variant of zero-dimensional (0D) Cs 4 PbBr 6 , to feature significant low trap-assisted nonradiative recombination, enhanced light out-coupling with a corrugated surface, and well-balanced charge carrier transport. Based on the resultant 3D/0D perovskite nanocomposites, the perovskite LEDs (PeLEDs) achieving an remarkable external quantum efficiency of 31.0% at the emission peak of 521 nm with a narrow full width at half-maximum of only 18 nm. This sets a new benchmark for color purity in high performance PeLED research, highlighting the significant advantage of this approach., (© 2024 Wiley‐VCH GmbH.)

Riboflavin deficiency (RD) induces liver damage, abnormal embryonic development, and high mortality. We hypothesized that the phenotype could be rescued by inhibiting ER stress. The objectives of the present study were to investigate the underlying molecular mechanisms of RD-induced embryonic defects using in vitro and in vivo models. Primary duck embryonic hepatocytes were treated with an ER stress inhibitor (4-PBA) or transfected with CHOP siRNA, and cultured in RD medium and riboflavin-sufficient (CON) medium for 8 days. Laying ducks (n = 20 cages/diet, 1 bird/cage) were fed an RD diet or CON diet for 14 wk, and the eggs were collected for hatching. At day 7 of incubation, the fertilized RD eggs were injected with or without 4-PBA into the yolk. RD decreased cell number and cell viability compared to the CON group, induced oxidative stress and apoptosis in primary duck embryonic hepatocytes. However, after being treated with an ER stress inhibitor (4-PBA) or transfected with CHOP siRNA, the apoptosis rate in RD hepatocytes decreased by 60.6 % and 86.1 %, respectively, being equal to the CON. These results indicated that RD-induced hepatocyte apoptosis is mediated by ER stress and the CHOP pathway. In vivo, RD embryos showed low hatchability, abnormal development, liver damage, ER stress, and apoptosis compared to the CON group. However, 4-PBA administration, as a model of ER stress inhibition, substantially restored embryonic development and alleviated liver damage in the RD group, including ER stress and apoptosis. Notably, hatchability in the RD group increased from 21.7 % to 72.7 % after 4-PBA treatment, though it remained less than the CON group (87.7 %). These results implicated ER stress-CHOP-apoptosis pathway as molecular mechanisms underlying RD-induced abnormal embryonic development and death, this target with potential for therapy or intervention., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Cholangiocarcinoma (CCA) is a hepatobiliary carcinoma with uncontrolled cell proliferation, poor prognosis, and high mortality. The ovarian tumor structural domain (OTU) containing protein 6B (OTUD6B) belongs to the OTU deubiquitin family and is vital in tumor development. However, its expression and biological function in CCA remain unknown. The expression of OTUD6B in CCA was analyzed using TIMER2.0, UALCAN, and GEO databases. MTT, clonal formation assay, immunofluorescence staining, immunohistochemistry staining, and flow cytometry examined the regulation of OTUD6B on cell proliferation, cycle, and apoptosis. The effects of OTUD6B on tumor volume and weight were assessed using the xenograft tumor model. The activities of PTK2 and STAT3 were detected by western blot and CO-IP. The biological database identified that OTUD6B was upregulated in CCA. In CCA cells, OTUD6B knockdown reduced CCA cell proliferation and promoted apoptosis. Cell cycle analysis indicated that the cycle stopped at the G0/G1 phase after OTU6B downregulation. Furthermore, OTUD6B knockdown resulted in a decrease in tumor volume and weight in xenograft tumor models. Mechanistically, OTUD6B is involved in the deubiquitination of PTK2. PTK2 further affected the phosphorylation of STAT3 thereby regulating the CCA process. Our study demonstrates that OTUD6B knockdown participates in the ubiquitination of PTK2 and phosphorylation of STAT3 to alleviate the process of CCA. These results suggest that OTUD6B may be a potential new strategy for CCA treatment., (© 2024 International Federation of Cell Biology.)

Carbon/Oxygen logging is an effective method to perform oil layer recognition and oil saturation calculation, which plays an important role in the evaluation of remaining oil after casing. At present, there are two main methods to calculate the ratio of carbon to oxygen (C/O). Compared with the energy window count method, the element yield method can avoid the influence of background count in the gamma spectrum and calculated carbon/oxygen value has the higher sensitivity and better accuracy, but it is still greatly affected by carbon and oxygen elements in the formation skeleton. Therefore, a new carbon/oxygen calculation method is proposed in this paper to overcome the influence of formation skeleton and improve the response sensitivity of Carbon/Oxygen logging. Based on Monte Carlo method, the inelastic gamma spectrum of pure sandstone and pure limestone skeletons are obtained. Based on spectrum analysis technology, the ratio relationship of carbon, oxygen yield and skeleton mark element (Si, Ca) yield in two skeletons are obtained. Using these ratio relationships, the carbon and oxygen yields from the sandstone and limestone reservoir skeletons are deducted from the total carbon and oxygen yield. A new carbon/oxygen parameter called the residual carbon/oxygen value (C/O) R is calculated to perform oil-water recognition and a set of oil saturation calculation model suitable for the residual carbon/oxygen value is proposed. The environment application of the residual carbon/oxygen value is also analyzed. The study shows that the residual carbon/oxygen value has higher sensitivity than original carbon/oxygen value in oil layer recognition and has a great accuracy in oil saturation calculation. In environment application aspect, the residual carbon/oxygen value is basically unaffected by formation water salinity and is affected by wellbore fluid and wellbore size obviously. This new carbon/oxygen value calculation method has an important significance to improve the application effect of Carbon/Oxygen logging., 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 Ltd. All rights reserved.)

Viruses employ various evasion strategies to establish prolonged infection, with evasion of innate immunity being particularly crucial. Porcine reproductive and respiratory syndrome virus (PRRSV) is a significant pathogen in swine industry, characterized by reproductive failures in sows and respiratory distress in pigs of all ages, leading to substantial economic losses globally. In this study, we found that the non-structural protein 5 (Nsp5) of PRRSV antagonizes innate immune responses via inhibiting the expression of type I interferon (IFN-I) and IFN-stimulated genes (ISGs), which is achieved by degrading multiple proteins of RIG-I-like receptor (RLR) signaling pathway (RIG-I, MDA5, MAVS, TBK1, IRF3, and IRF7). Furthermore, we showed that PRRSV Nsp5 is located in endoplasmic reticulum (ER), where it promotes accumulation of RLR signaling pathway proteins. Further data demonstrated that Nsp5 activates reticulophagy (ER-phagy), which is responsible for the degradation of RLR signaling pathway proteins and IFN-I production. Mechanistically, Nsp5 interacts with one of the ER-phagy receptor family with sequence similarity 134 member B (FAM134B), promoting the oligomerization of FAM134B. These findings elucidate a novel mechanism by which PRRSV utilizes FAM134B-mediated ER-phagy to elude host antiviral immunity.IMPORTANCEInnate immunity is the first line of host defense against viral infections. Therefore, viruses developed numerous mechanisms to evade the host innate immune responses for their own benefit. PRRSV, one of the most important endemic swine viruses, poses a significant threat to the swine industry worldwide. Here, we demonstrate for the first time that PRRSV utilizes its non-structural protein Nsp5 to degrade multiple proteins of RLR signaling pathways, which play important roles in IFN-I production. Moreover, FAM134B-mediated ER-phagy was further proved to be responsible for the protein's degradation. Our study highlights the critical role of ER-phagy in immune evasion of PRRSV to favor replication and provides new insights into the prevention and control of PRRSV., Competing Interests: The authors declare no conflict of interest.

Introduction: NAC (NAM, ATAF, and CUC) transcription factor family, one of the important switches of transcription networks in plants, functions in plant growth, development, and stress resistance. Night lily ( Hemerocallis citrina ) is an important horticultural perennial monocot plant that has edible, medicinal, and ornamental values. However, the NAC gene family of night lily has not yet been analyzed systematically to date., Methods: Therefore, we conducted a genome-wide study of the HcNAC gene family and identified a total of 113 HcNAC members from the Hemerocallis citrina genome., Results: We found that 113 HcNAC genes were unevenly distributed on 11 chromosomes. Phylogenetic analysis showed that they could be categorized into 16 instinct subgroups. Proteins clustering together exhibited similar conserved motifs and intron-exon structures. Collinearity analysis indicated that segmental and tandem duplication might contribute to the great expansion of the NAC gene family in night lily, whose relationship was closer with rice than Arabidopsis . Additionally, tissue-specific pattern analysis indicated that most HcNAC genes had relatively higher expression abundances in roots. RNA-Seq along with RT-qPCR results jointly showed HcNAC genes expressed differently under drought and salinity stresses. Interestingly, HcNAC35 was overexpressed in watermelon, and the stress resilience of transgenic lines was much higher than that of wild-type watermelon, which revealed its wide participation in abiotic stress response., Conclusion: In conclusion, our findings provide a new prospect for investigating the biological roles of NAC genes in night lily., 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 Cao, Wang, Ren, Jia, Liu, Yang, Yu, Guo, Hou, Xu, Li and Xing.)

Herein, a direct in situ alkaline phosphatase (ALP)-labeled luminescent nanoimmunoassay platform was constructed using Mn 2+ -triggered aggregation-induced emission transformation of levodopa fluorescent copolymer (LFC) nanoparticles. Using cardiac troponin I (cTn I) as the model antigen, the proposed nanoimmunosensor has been applied to detect cTn I in clinical samples with satisfactory results.

Background: T cell receptor (TCR)-T cell therapy is an innovative form of cancer immunotherapy that genetically modifies patients' T cells to target and destroy cancer cells. However, the current status of clinical trials of TCR-T cell therapy for the treatment of cancer remains unclear. This study aimed to comprehensively analyze the registration trials related to TCR-T cell therapy for the treatment of cancer., Methods: A comprehensive search was conducted in the Trialtrove database for all clinical trials related to TCR-T cell therapy registered by August 1, 2024. Inclusion criteria focused on trials targeting TCR-T cell therapy for oncology, and excluded observational studies and incomplete data. Statistical analysis was performed on key trial characteristics, with between-group comparisons utilizing chi-square or Fisher's exact tests., Results: Analysis of 174 eligible clinical trials revealed that TCR-T cell therapy exhibits significant efficacy across various tumor types, particularly in refractory hematologic malignancies and certain solid tumors. Additionally, combining TCR-T cell therapy with other immunotherapies enhanced these anti-tumor effects., Conclusion: TCR-T cell therapy holds substantial promise for cancer treatment. Future research should focus on optimizing treatment protocols, enhancing efficacy, and minimizing prices to fully realize the potential of this therapy., 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 Li, Zhang, Fu, Xing, Cai, Li, Xu and Tong.)

Zero-dimensional (0D) structured lead-free metal halides have recently attracted widespread attention due to their high photoluminescence quantum yield (PLQY) and negligible self-absorption, showing enormous potential as optical waveguides towards miniaturized photonic devices. However, due to the great difficulty in growth of rod-like nano/micro-sized morphologies, such applications have been less explored. Herein, a new-type emissive organic-inorganic manganese (II) halide crystal (TPS 2 MnCl 4 , TPS=C 18 H 15 S, triphenylsulfonium) in the form of microrods is synthesized via a facile chloride ion (Cl - ) induced oriented growth method. Due to a combination of attractive features such as a high PLQY of 86 %, negligible self-absorption and smooth crystal surface, TPS 2 MnCl 4 microrods are well suited for use in optical waveguide with an ultra-low optical loss coefficient of 1.20 ⋅ 10 -4  dB μm -1 , superior to that of most organic-inorganic metal halide hybrids, organic materials, polymers and metal nanoclusters to the best of our knowledge. Importantly, TPS 2 MnCl 4 microrods can further work as dual-mode optical waveguides, combining active and passive light transmission functionalities in one single crystal. In addition, TPS 2 MnCl 4 microrods also display remarkable performance in lighting and anti-counterfeiting due to their distinct optical properties and commendable stability., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background: Food allergies are a growing concern worldwide, with soy proteins being important allergens that are widely used in various food products. This study investigated the potential of transglutaminase (TGase) and lactic acid bacteria (LAB) treatments to modify the allergenicity and structural properties of soy protein isolate (SPI), aiming to develop safer soy-based food products., Results: Treatment with TGase, LAB or their combination significantly reduced the antibody reactivity of β-conglycinin and the immunoglobulin E (IgE) binding capacity of soy protein, indicating a decrease in allergenicity. TGase treatment led to the formation of high-molecular-weight aggregates, suggesting protein crosslinking, while LAB treatment resulted in partial protein hydrolysis. These structural changes were confirmed by Fourier transform infrared spectroscopy, which showed a decrease in β-sheet content and an increase in random coil and β-turn contents. In addition, changes in intrinsic fluorescence and ultraviolet spectroscopy were also observed. The alterations in protein interaction and the reduction in free sulfhydryl groups highlighted the extensive structural modifications induced by these treatments., Conclusion: The synergistic application of TGase and LAB treatments effectively reduced the allergenicity of SPI through significant structural modifications. This approach not only diminished antibody reactivity of β-conglycinin and IgE binding capacity of soy protein but also altered the protein's primary, secondary and tertiary structures, suggesting a comprehensive alteration of SPI's allergenic potential. These findings provide a promising strategy for mitigating food allergy concerns and lay the foundation for future research on food-processing techniques aimed at allergen reduction. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: Clinical protocols in osteoporosis treatment could not meet the requirement of increasing local bone mineral density. A local delivery system was brought in to fix this dilemma. The high-energy extracorporeal shock wave (ESW) can travel into the deep tissues with little heat loss. Hence, ESW-driven nanoparticles could be used for local treatment of osteoporosis., Materials and Methods: An ESW-actuated nanomotor (NM) sealed into microneedles (MNs) (ESW-NM-MN) was constructed for localized osteoporosis protection. The NM was made of calcium phosphate nanoparticles with a high Young's modulus, which allows it to absorb ESW energy efficiently and convert it into kinetic energy for solid tissue penetration. Zoledronic (ZOL), as an alternative phosphorus source, forms the backbone of the NM (ZOL-NM), leading to bone targeting and ESW-mediated drug release., Results: After the ZOL-NM is sealed into hyaluronic acid (HA)-made microneedles, the soluble MN tips could break through the stratum corneum, injecting the ZOL-NM into the skin. As soon as the ESW was applied, the ZOL-NM would absorb the ESW energy to move from the outer layer of skin into the deep tissue and be fragmented to release ZOL and Ca 2+ for anti-osteoclastogenesis and pro-osteogenesis. In vivo , the ZOL-NM increases localized bone parameters and reduces fracture risk, indicating its potential value in osteoporotic healing and other biomedical fields., Conclusion: The ESW-mediated transdermal delivery platform (ESW-NM-MN) could be used as a new strategy to improve local bone mineral density and protect local prone-fracture areas., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To elucidate the characteristics of lymphocyte subsets in bronchopulmonary dysplasia (BPD) diagnosis following Jensen's criterion to understand the spectrum of lymphocytes in different degrees of BPD., Study Design: This single-center retrospective cohort study included 120 neonates admitted to the neonatal intensive care unit between 1 July 2014 and 30 June 2021, who had undergone peripheral blood lymphocyte subpopulation detection., Results: Thirty-one neonates were included in the control group, whereas 33 infants with BPD were included in the case group. In addition, we selected 56 infants with a gestational age (GA) <37 weeks without BPD who were receiving oxygen therapy. Among the three groups, the B cell and NK cell frequencies were significantly higher and the frequencies of T cells and CD4 + cells were significantly lower in the BPD group. In newborns without BPD, the distribution of T lymphocyte subsets was similar at different GAs. Comparing different degrees of BPD, the patients in the grades 2-3 BPD group had significantly lower percentages of T lymphocytes and CD4 + T cells than those in the other groups. Remarkably, the frequencies of NK cells were significantly higher in patients with grades 2-3 BPD, and the Treg cells slightly increased with BPD severity, although the differences were not significant., Conclusion: Healthy neonates had similar ratios of lymphocyte subsets among different GAs; although as the GAs increased, the percentage of lymphocytes increased slightly. Severe BPD was associated with lower CD4 + T cells and higher NK cells. However, whether such changes were the cause or the consequence of BPD has not been determined., (© 2024 Wiley Periodicals LLC.)

Narrow-bandgap (NBG) Pb-Sn perovskites are ideal candidates as rear subcell in all-perovskite tandem solar cells. Because Pb-Sn perovskites contain multiple components, the rational regulation of vertical structure and both interfaces of the film is primarily crucial to achieve high-performing NBG perovskite solar cells (PSCs). Herein, a molecule anchoring strategy is developed to in situ construct Cs 0.1 MA 0.3 FA 0.6 Pb 0.5 Sn 0.5 I 3 perovskite film with vertically aligned crystals and optimized interfaces. Specifically, l-alanine methyl ester is developed as an anchoring additive to induce the vertical crystal growth, while PEA 2 PbI 3 SCN film is introduced to promote the homogeneous crystallization at the buried interface via SCN- anchoring with cations. Further ethylenediamine dihalides (EDA(I/Cl) 2 ) post-treatment leads to the gradient energy level alignment on the film surface. Pb-Sn PSCs based on such film show efficient charge transport and extraction, producing a champion power conversion efficiency (PCE) of 22.3% with an impressive fill factor of 82.14%. Notably, combining with semitransparent 1.78 eV wide-bandgap PSCs, the four-terminal all-perovskite tandem device achieves a PCE of 27.1%. This work opens up a new pathway to boost the performance of Pb-Sn PSCs and their tandem devices., (© 2024 Wiley‐VCH GmbH.)

Rationale & Objective: Light and heavy chain deposition disease (LHCDD) is a rare form of monoclonal immunoglobulin (Ig) deposition disease, and limited clinical data are available characterizing this condition. Here we describe the clinicopathological characteristics and outcomes of LHCDD., Study Design: Case series., Setting & Participants: 13 patients with biopsy-proven LHCDD diagnosed between January 2008 and December 2022 at one of 2 Chinese medical centers., Findings: Among the 13 patients described, 6 were men and 7 were women, with a mean age of 52.6±8.0 years. Patients presented with hypertension (76.9%), anemia (84.6%), increased serum creatinine concentrations (84.6%; median, 1.7mg/dL), proteinuria (100%; average urine protein, 3.0g/24h), nephrotic syndrome (30.8%), and microscopic hematuria (76.9%). Serum immunofixation electrophoresis showed monoclonal Ig for 11 patients (84.6%). Serum free light chain ratios were abnormal in 11 patients (84.6%), and heavy/light chain ratios were abnormal in 9 of 10 patients (90%) with available data. Five patients were diagnosed with multiple myeloma. A histological diagnosis of nodular mesangial sclerosis was made in 10 patients (76.9%). Immunofluorescence demonstrated deposits of IgG subclass in 7 patients (γ-κ, n=4; γ-λ, n=3) and IgA in 5 patients (α-κ, n=2; α-λ, n=3). Six patients underwent IgG subclass staining (γ1, n=3; γ2, n=2; γ3, n=1). The deposits of IgD-κ were confirmed by mass spectrometry in 1 patient. Among 12 patients for whom data were available during a median of 26.5 months, 11 received chemotherapy and 1 received conservative treatment. One patient died, and disease progressed to kidney failure in 3 (25%). Among the 9 patients evaluable for hematological and kidney disease progression, 5 (56%) had a hematologic response and 1 (11%) exhibited improvement in kidney disease., Limitations: Retrospective descriptive study, limited number of patients, urine protein electrophoresis or immunofixation electrophoresis test results missing for most patients., Conclusions: In this case series of LHCDD, light and heavy chain deposition in kidney tissues were most frequent with monoclonal IgG1-κ. Among patients with evaluable data, more than half had a hematologic response, but a kidney response was uncommon., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The soybean hawkmoth Clanis bilineata tsingtauica Mell (Lepidoptera, Sphingidae; CBT), as one of the main leaf-chewing pests of soybeans, has gained popularity as an edible insect in China recently due to its high nutritional value. However, high-quality genome of CBT remains unclear, which greatly limits further research. In the present study, we assembled a high-quality chromosome-level genome of CBT using PacBio HiFi reads and Hi-C technologies for the first time. The size of the assembled genome is 477.45 Mb with a contig N50 length of 17.43 Mb. After Hi-C scaffolding, the contigs were anchored to 29 chromosomes with a mapping rate of 99.61%. Benchmarking Universal Single-Copy Orthologues (BUSCO) completeness value is 99.49%. The genome contains 252.16 Mb of repeat elements and 14,214 protein-coding genes. In addition, chromosomal synteny analysis showed that the genome of CBT has a strong synteny with that of Manduca sexta. In conclusion, this high-quality genome provides an important resource for future studies of CBT and contributes to the development of integrated pest management strategies., (© 2024. The Author(s).)

The stabilization of the formamidinium lead iodide (FAPbI 3 ) structure is pivotal for the development of efficient photovoltaic devices. Employing two-dimensional (2D) layers to passivate the three-dimensional (3D) perovskite is essential for maintaining the α-phase of FAPbI 3 and enhancing the power conversion efficiency (PCE) of perovskite solar cells (PSCs). However, the role of bulky ligands in the phase management of 2D perovskites, crucial for the stabilization of FAPbI 3 , has not yet been elucidated. In this study, we synthesized nanoscale 2D perovskite capping crusts with  = 1 and 2 Ruddlesden-Popper (RP) perovskite layers, respectively, which form a type-II 2D/3D heterostructure. This heterostructure stabilizes the α-phase of FAPbI 3 , and facilitates ultrafast carrier extraction from the 3D perovskite network to transport contact layer. We introduced tri-fluorinated ligands to mitigate defects caused by the halide vacancies and uncoordinated Pb 2+ ions, thereby reducing nonradiative carrier recombination and extending carrier lifetime. The films produced were incorporated into PSCs that not only achieved a PCE of 25.39% but also maintained 95% of their initial efficiency after 2000 h of continuous light exposure without encapsulation. These findings underscore the effectiveness of a phase-pure 2D/3D heterostructure-terminated film in inhibiting phase transitions passivating the iodide anion vacancy defects, facilitating the charge carrier extraction, and boosting the performance of optoelectronic devices., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)

Uneven Zn deposition and unfavorable side reactions have prevented the reversibility of the Zn anode. Herein, we design a rearranged (002) textured Zn anode inspired by a traditional curvature-enhanced adsorbate coverage (CEAC) process to realize the highly reversible Zn anode. The rearranged (002) textured structure directs superconformal Zn deposition by controlling the spatial deposition rate of the rearranged crystal planes, thereby promoting bottom-up "superfilling" of the 3D Zn skeletons. Meanwhile, our designed anode also induces the epitaxial Zn deposition, alleviating the parasitic reactions owing to the lowest surface energy of the (002) plane. Attributed to these superiorities, uniform and oriented Zn deposition can be obtained, exhibiting an ultra-long lifespan over 479 hrs at an ultrahigh depth of discharge (DOD) of 82.12 %. The Zn|Na 2 V 6 O 16  ⋅ 3H 2 O battery delivers an improved cycling performance, even at a high area capacity of 5.15 mAh/cm 2 with a low negative/positive (N/P) capacity ratio of 1.63. The superconformal deposition approach for Zn anodes paves the way for the practical application of high-performance zinc-ion batteries., (© 2024 Wiley-VCH GmbH.)

Background: Fowl adenovirus serotype 4 (FAdV-4) is the main pathogen of hepatitis-hydropericardium syndrome (HHS), which brings huge economic losses to the poultry industry worldwide. Fiber-1 protein plays an important role in viral infection and pathogenesis by binding directly to cellular receptors of FAdV-4. In particular, the knob domain of fiber-1 protein has been reported to induce the production of neutralizing antibodies and arouse protection against the lethal challenge of chickens with FAdV-4., Methods: The fiber-1 knob (F1K) protein was expressed in a prokaryotic expression system and purified using Ni-NTA affinity chromatography. Monoclonal antibodies (mAbs) against FAdV-4 were generated by immunizing BALB/c mice with the purified F1K protein and screened using a series of immunoassays. Potential B cell epitopes on the knob domain of fiber-1 protein were mapped using enzyme-linked immunosorbent assay (ELISA) and dot-blot. Precious location and crucial amino acids of the identified epitopes were determined using peptide array scanning, truncations and alanine-scanning mutagenesis. The epitopes were analyzed and visualized on the knob trimer of FAdV-4 fiber-1 protein using the PyMOL software., Results: Water-soluble recombinant fiber-1 knob (F1K) protein was obtained with the assistance of chaperone. Four monoclonal antibodies (5C10, 6F8, 8D8, and 8E8) against FAdV-4 were generated and characterized using indirect ELISA, Western blot, dot-blot, and immunological fluorescence assay (IFA). The mAbs were demonstrated to be from different hybridoma cell lines based on the sequences of the variable regions. Meanwhile, three distinct novel linear B-cell epitopes ( 319 SDVGYLGLPPH 329 , 328 PHTRDNWYV 336 , and 407 VTTGPIPFSYQ 417 ) on the knob domain of fiber-1 protein were identified and the key amino acid residues in the epitopes were determined. Structural analysis showed that the two adjacent epitopes 319 SDVGYLGLPPH 329 and 328 PHTRDNWYV 336 were exposed on the surface of the fiber-1 knob trimer, whereas the epitope 407 VTTGPIPFSYQ 417 was located inside of the spatial structure., Conclusion: This was the first identification of B-cell epitopes on the knob domain of fiber-1 protein and these findings provided a sound basis for the development of subunit vaccines, therapeutics, and diagnostic methods to control FAdV infections., 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 Chai, Jin, Zhu, Guo, Lu, Chai, Xing, Han, Xing and Zhang.)

Chromatin interactions create spatial proximity between distal regulatory elements and target genes in the genome, which has an important impact on gene expression, transcriptional regulation, and phenotypic traits. To date, several methods have been developed for predicting gene expression. However, existing methods do not take into consideration the effect of chromatin interactions on target gene expression, thus potentially reducing the accuracy of gene expression prediction and mining of important regulatory elements. In this study, we developed a highly accurate deep learning-based gene expression prediction model (DeepCBA) based on maize chromatin interaction data. Compared with existing models, DeepCBA exhibits higher accuracy in expression classification and expression value prediction. The average Pearson correlation coefficients (PCCs) for predicting gene expression using gene promoter proximal interactions, proximal-distal interactions, and both proximal and distal interactions were 0.818, 0.625, and 0.929, respectively, representing an increase of 0.357, 0.16, and 0.469 over the PCCs obtained with traditional methods that use only gene proximal sequences. Some important motifs were identified through DeepCBA; they were enriched in open chromatin regions and expression quantitative trait loci and showed clear tissue specificity. Importantly, experimental results for the maize flowering-related gene ZmRap2.7 and the tillering-related gene ZmTb1 demonstrated the feasibility of DeepCBA for exploration of regulatory elements that affect gene expression. Moreover, promoter editing and verification of two reported genes (ZmCLE7 and ZmVTE4) demonstrated the utility of DeepCBA for the precise design of gene expression and even for future intelligent breeding. DeepCBA is available at http://www.deepcba.com/ or http://124.220.197.196/., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In the quest for durable photovoltaic devices, 2D halide perovskites have emerged as a focus of extensive research. However, the reduced dimension in structure is accompanied by inferior optical-electrical properties, such as widened band gap, enhanced exciton binding energy, and obstructed charge transport. As a result, the efficiency of 2D perovskite solar cells (PSCs) lags significantly behind their 3D counterparts. To overcome these constraints, extensive investigations into materials and processing techniques are pursued rigorously to augment the efficiency of 2D PSCs. Herein, The cutting-edge delve into developments in 2D PSCs, with a focus on chemical and material engineering, as well as their structure and photovoltaic properties. The review starts with an introduction of the crystal structure, followed by the key evaluation criteria of 2D PSCs. Then, the strategies around solution chemical engineering, processing technique, and interface optimization, to simultaneously boost efficiency and stability are systematically discussed. Finally, the challenges and perspectives associated with 2D perovskites to provide insights into potential improvements in photovoltaic performance will be outlined., (© 2024 Wiley‐VCH GmbH.)

Radiated tumor cell-derived extracellular vesicles (RT-EVs) encapsulate abundant DNA fragments from irradiated tumor cells, in addition to acting as integrators of multiple tumor antigens. Accumulating evidence indicates these DNA fragments from damaged cells are involved in downstream immune responses, but most of them are degraded in cells before incorporation into derived RT-EVs, thus the low abundance of DNA fragments limits immune responses of RT-EVs. Here, this study found that different radiations affected fates of DNA fragments in RT-EVs. Boron neutron capture therapy (BNCT) induced DNA accumulation in RT-EVs (BEVs) by causing more DNA breaks and DNA oxidation resisting nuclease degradation. This is attributed to the high-linear energy transfer (LET) properties of alpha particles from the neutron capture reaction of 10 B. When being internalized by dendritic cells (DCs), BEVs activated the DNA sensing pathway, resulting in functional enhancements including antigen presentation, migration capacity, and cytokine secretion. After vaccination of the BEVs-educated DCs (BEV@BMDCs), the effector T cells significantly expanded and infiltrated into tumors, suggesting robust anti-tumor immune activation. BEV@BMDCs not only effectively inhibited the primary tumor growth and metastasis formation but also elicited long-term immune memory. In conclusion, a successful DC vaccine is provided as a promising candidate for tumor vaccine., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Although nanozymes sensor arrays have the potential to recognize multiple target substances simultaneously, they currently rarely identify phenolic acids in food due to limited catalytic performance and complex preparation conditions of nanozymes. Here, inspired by the structure of polyphenol oxidase, we have successfully prepared a novel gallic acid-Cu (GA-Cu) nanozyme with laccase-like activity. Due to the different catalytic efficiency of GA-Cu nanozymes towards six common phenolic acids, a three-channel colorimetric sensor array was constructed using reaction kinetics as the sensing unit to achieve high-throughput detection and identification of six phenolic acids within a concentration range from 1 to 100 μM. This method avoids the creation of numerous sensing units. Notably, the successful discrimination of six phenolic acids in samples of juice, beer, and wine has been achieved by the sensor array. Finally, aided by smartphones, a portable technique has been devised for the detection of phenolic acids., 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.)

Matrix protein 2 (M2) and matrix protein 1 (M1) of the influenza B virus are two important proteins, and the interactions between BM2 and BM1 play an important role in the process of virus assembly and replication. However, the interaction details between BM2 and BM1 are still unclear at the atomic level. Here, we constructed the BM2 - BM1 complex system using homology modelling and molecular docking methods. Molecular dynamics (MD) simulations were used to illustrate the binding mechanism between BM2 and BM1. The results identify that the eight polar residues (E88 B , E89 B , H119 BM1 , E94 B , R101 BM1 , K102 BM1 , R105 BM1 , and E104 B ) play an important role in stabilizing the binding through the formation of hydrogen bond networks and salt-bridge interactions at the binding interface. Furthermore, based on the simulation results and the experimental facts, the mutation experiments were designed to verify the influence of the mutation of residues both within and outside the effector domain. The mutations directly or indirectly disrupt interactions between polar residues, thus affecting viral assembly and replication. The results could help us understand the details of the interactions between BM2 and BM1 and provide useful information for the anti-influenza drug design.

Background: In the recent decade, there has been substantial progress in the technologies and philosophies associated with diagnosing and treating anterior cruciate ligament (ACL) injuries in China. The therapeutic efficacy of ACL reconstruction in re-establishing the stability of the knee joint has garnered widespread acknowledgment. However, the path toward standardizing diagnostic and treatment protocols remains to be further developed and refined., Objective: In this context, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) collaboratively developed an expert consensus on diagnosing and treating ACL injury, aiming to enhance medical quality through refining professional standards., Methods: The consensus drafting team invited experts across the Greater China region, including the mainland, Hong Kong, Macau, and Taiwan, to formulate and review the consensus using a modified Delphi method as a standardization approach. As members of the CSSM Lower Limb Study Group and the CAOS Arthroscopy and Sports Medicine Study Group, invited experts concentrated on two pivotal issues: "Graft Selection" and "Clinical Outcome Evaluation" during the second part of the consensus development., Results: This focused discussion ultimately led to a strong consensus on nine specific consensus terms., Conclusion: The consensus clearly states that ACL reconstruction has no definitive "gold standard" graft choice. Autografts have advantages in healing capability but are limited in availability and have potential donor site morbidities; allografts reduce surgical trauma but incur additional costs, and there are concerns about slow healing, quality control issues, and a higher failure rate in young athletes; synthetic ligaments allow for early rehabilitation and fast return to sport, but the surgery is technically demanding and incurs additional costs. When choosing a graft, one should comprehensively consider the graft's characteristics, the doctor's technical ability, and the patient's needs. When evaluating clinical outcomes, it is essential to ensure an adequate sample size and follow-up rate, and the research should include patient subjective scoring, joint function and stability, complications, surgical failure, and the return to sport results. Medium and long-term follow-ups should not overlook the assessment of knee osteoarthritis., Competing Interests: We, the undersigned, declare that for the manuscript entitled Diagnosis and Treatment of Anterior Cruciate Ligament Injuries: Consensus of Chinese Experts Part II: Graft Selection and Clinical Outcome Evaluation, the following is a true and accurate statement of all our potential conflicts of interest, financial or otherwise, that might influence the work or its interpretation., (© 2024 Published by Elsevier B.V. on behalf of Chinese Speaking Orthopaedic Society.)

Soybean seeds are susceptible to damage from the Riptortus pedestris, which is a significant factor affecting the quality of soybean seeds. Currently, manual screening methods for soybean seeds are limited to visual inspection, making it difficult to identify seeds that are phenotypically defect-free but have been punctured by stink bugs on the sub-surface. To facilitate the convenient and efficient identification of healthy soybean seeds, this paper proposes a soybean seed pest detection method based on spatial frequency domain imaging combined with RL-SVM. Firstly, soybean optical data is obtained using single integration sphere technique, and the vigor index of soybean seeds is obtained through germination experiments. Then, based on the above two data items using feature extraction algorithms (the successive projections algorithm and the competitive adaptive reweighted sampling algorithm), the characteristic wavelengths of soybeans are identified. Subsequently, the spatial frequency domain imaging technique is used to obtain the sub-surface images of soybean seeds in a forward manner, and the optical coefficients such as the reduced scattering coefficient μ ' s and absorption coefficient μ a of soybean seeds are inverted. Finally, RL-MLR, RL-GRNN, and RL-SVM prediction models are established based on the ratio of the area of insect-damaged sub-surface to the entire seed, soybean varieties, and μ a at three wavelengths (502 nm, 813 nm, and 712 nm) for predicting and identifying soybean the stinging and sucking pest damage levels of soybean seeds. The experimental results show that the spatial frequency domain imaging technique yields small errors in the optical coefficients of soybean seeds, with errors of less than 15% for μ a and less than 10% for μ ' s . After parameter adjustment through reinforcement learning, the Macro-Recall metrics of each model have improved by 10%-15%, and the RL-SVM model achieves a high Macro-Recall value of 0.9635 for classifying the pest damage levels of soybean seeds., (© 2024. The Author(s).)

Background: The selection of appropriate second-line therapy for liver cancer after first-line treatment failure poses a significant clinical challenge due to the lack of direct comparative studies and standard treatment protocols. A network meta-analysis (NMA) provides a robust method to systematically evaluate the clinical outcomes and adverse effects of various second-line treatments for hepatocellular carcinoma (HCC)., Methods: We systematically searched PubMed, Embase, Web of Science and the Cochrane Library to identify phase III/IV randomized controlled trials (RCTs) published up to March 11, 2024. The outcomes extracted were median overall survival (OS), median progression-free survival (PFS), time to disease progression (TTP), disease control rate (DCR), objective response rate (ORR), and adverse reactions. This study was registered in the Prospective Register of Systematic Reviews (CRD42023427843) to ensure transparency, novelty, and reliability., Results: We included 16 RCTs involving 7,005 patients and 10 second-line treatments. For advanced HCC patients, regorafenib (HR = 0.62, 95%CI: 0.53-0.73) and cabozantinib (HR = 0.74, 95%CI: 0.63-0.85) provided the best OS benefits compared to placebo. Cabozantinib (HR = 0.42, 95%CI: 0.32-0.55) and regorafenib (HR = 0.46, 95% CI: 0.31-0.68) also offered the most significant PFS benefits. For TTP, apatinib (HR = 0.43, 95% CI: 0.33-0.57), ramucirumab (HR = 0.44, 95% CI: 0.34-0.57), and regorafenib (HR = 0.44, 95% CI: 0.38-0.51) showed significant benefits over placebo. Regarding ORR, ramucirumab (OR = 9.90, 95% CI: 3.40-42.98) and S-1 (OR = 8.68, 95% CI: 1.4-154.68) showed the most significant increases over placebo. Apatinib (OR = 3.88, 95% CI: 2.48-6.10) and cabozantinib (OR = 3.53, 95% CI: 2.54-4.90) provided the best DCR benefits compared to placebo. Tivantinib showed the most significant advantages in terms of three different safety outcome measures., Conclusions: Our findings suggest that, in terms of overall efficacy and safety, regorafenib and cabozantinib are the optimal second-line treatment options for patients with advanced HCC., (© 2024. The Author(s).)

With the advantages of high-throughput manufacturing and customizability, on-microsphere construction of in vitro multicellular analytical systems has garnered significant attention. However, achieving a precise, biocompatible cell arrangement and spatial signal analysis in hydrogel microspheres remains challenging. In this work, a microfluidic method is reported for the biocompatible generation of addressable supersegmented multicompartmental microspheres. Additionally, these microspheres are developed as novel label-free multicellular systems. In the microfluidic approach, controllable microfluidics is used to finely tune the internal microstructure of the microspheres, and the gas ejector ensures the biocompatibility of the preparation process. As a proof of concept, six- and twenty-compartment microspheres were obtained without the addition of any biohazardous reagents. For microsphere decoding, the visualization of two basic compartments can provide clues for identifying label-free cells due to the structural regularity of the microspheres. Finally, by encapsulating cells of different types, these microspheres as multicellular systems were successfully used for cell coculture and drug testing. These biocompatible, scalable, and analyzable microspheres will open up new prospects for biomedical analysis.

Glassy hybrid metal halides have emerged as promising materials in recent years due to their high structural adjustability and low melting points, offering unique merits that overcome the limitations of their crystalline and polycrystalline counterparts as well as other conventional amorphous semiconductors. This review article comprehensively explores the structural characteristics, electronic properties, and chemical coordination of hybrid metal halides, emphasizing their role in the glass transition from the crystalline phase to the amorphous phase. We examine the intrinsic disorder within the amorphous phase that facilitates light transmission and discuss recent advances in device architecture and interface engineering by optimizing the charge transport of glassy hybrid metal halides for high-quality applications. With full theoretical understanding and rational structural design, potential applications in displays, information storage, X-ray imaging, and sensing are highlighted, underscoring the transformative impact of glassy hybrid metal halides in the fields of materials science and information science.

The upper reaches of the Yellow River are critical ecological barriers within the Yellow River Basin (YRB) that are crucial for source conservation. However, environmental challenges in this area, from Longyangxia to Lijiaxia, have emerged in recent years. To assess the ecological environment quality (EEQ) evolution from 1991 to 2021, we utilized remote sensing ecological indices (RSEIs) on the Google Earth Engine (GEE) platform. Spatial autocorrelation and heterogeneity impacting EEQ changes were examined. The results of this study show that the mean value of the RSEIs fluctuated over time (1991: 0.70, 1996: 0.77, 2001: 0.67, 2006: 0.71, 2011: 0.68, 2016: 0.65, and 2021: 0.66) showing an upward, downward, and then upward trend. The mean values of the overall RSEI are all at 0.65 and above. Most regions showed no significant EEQ change during 1991-2021 (68.59%, 59.23%, and 55.78%, respectively). Global Moran's I values (1991-2021) ranged from 0.627 to 0.412, indicating significant positive correlation between EEQ and spatial clustering, and the LISA clustering map (1991-2021) shows that the area near Longyangxia Reservoir shows a pattern of aggregation, dispersion, and then aggregation again. The factor detection results showed that heat was the most influential factor, and the interaction detection results showed that greenness and heat had a significant effect on regional ecosystem distribution. Our study integrates spatial autocorrelation and spatial heterogeneity and combines them with reality to provide an in-depth discussion and analysis of the Longyangxia to Lijiaxia Basin. These findings offer guidance for ecological governance, vegetation restoration, monitoring, and safeguarding the upper Yellow River's ecological integrity.

Intracerebral hemorrhage (ICH) is a significant public health matter that has no effective treatment. ICH-induced destruction of the blood-brain barrier (BBB) leads to neurological deterioration. Astrocytic sonic hedgehog (SHH) alleviates brain injury by maintaining the integrity of the BBB after ICH. Silent information regulator 1 (SIRT1) is neuroprotective in several central nervous system diseases via BBB regulation. It is also a possible influential factor of the SHH signaling pathway. Nevertheless, the role of SIRT1 on BBB and the underlying pathological process associated with the SHH signaling pathway after ICH remain unclear. We established an intracerebral hemorrhagic mouse model by collagenase injection. SRT1720 (a selective agonist of SIRT1) was used to evaluate the effect of SIRT1 on BBB integrity after ICH. SIRT1 expression was reduced in the mouse brain after ICH. SRT1720 attenuated neurobehavioral impairments and brain edema of ICH mouse. After ICH induction, SRT1720 improved BBB integrity and tight junction expressions in the mouse brain. The SHH signaling pathway-related factors smoothened and glioma-associated oncogene homolog-1 were increased with the intervention of SRT1720, while cyclopamine (a specific inhibitor of the SHH signaling pathway) reversed these effects. These findings suggest that SIRT1 protects from ICH by altering BBB permeability and tight junction expression levels. This process is associated with the SHH signaling pathway, suggesting that SIRT1 may be a potential therapeutic target for ICH., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)