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Chenhui Wang,1 Lei Han,2 Yuru Li,2 Xibin Mi,3 Mengwei Yan,4 Xinxiu Yu,2 Yu Lu,2 Meihong Shi,2 Pengfei Liu,2 Liang Han,2 Baoguo Wang1 1Department of Anesthesiology, Sanbo Brain Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Infirmary, Taikang Yanyuan Continuing Care Retirement Community, Beijing, People’s Republic of China; 3Department of Pain Management, Yanyuan Rehabilitation Hospital, Beijing, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Baoguo Wang, Department of Anesthesiology, Sanbo Brain Hospital, Capital Medical University, No. 50 Yikesong Street, Haidian District, Beijing, 100095, People’s Republic of China, Tel/Fax +86 10 6285 6766, Email wangbg@ccmu.edu.cnPurpose: To identify the prevalence of exacerbation of pre-existing chronic pain after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and investigate the impact of exacerbated previous chronic pain on quality of life, sleep quality, anxiety and depression levels and risk factors associated with exacerbated chronic pain among elderly coronavirus disease of 2019 (COVID-19) survivors.Patients and Methods: In this cross-sectional study, elderly COVID-19 survivors with chronic pain residing in Continuing Care Retirement Community (CCRC) were recruited from April 2023 to June 2023. Eligible individuals were divided into exacerbation and non-exacerbation groups based on the patient-reported worsening symptoms of previous chronic pain after SARS-CoV-2 infection. Baseline information, COVID-19 symptoms, laboratory parameters, characteristics of exacerbated chronic pain, quality of life, anxiety and depression levels were systematically collected.Results: Ninety-five (95/441, 21.5%) older adults suffered from exacerbated chronic pain with a median numerical rating scale (NRS) score of 6 (4– 7) on a median duration of 4.9 (4.3– 5.6) months after SARS-CoV-2 infection. More participants were not vaccinated against COVID-19 (46.5%, 40/86 vs 26.1%, 86/330, P < 0.001) in exacerbation group. Exacerbation group exhibited poor quality of life (EQ5D index: 0.734 [0.536– 0.862] vs 0.837 [0.716– 0.942], P < 0.001), more severe anxiety (GAD-7: 2 [0– 5] vs 0 [0– 3], P < 0.001) and depression (PHQ-9: 4 [2– 7] vs 2.5 [0– 5], P < 0.001) than non-exacerbation group. Risk factors significantly associated with exacerbation of pre-existing chronic pain were neuropathic pain (aOR 4.81, 95% CI 1.73– 13.32, P = 0.003), lymphocyte count (aOR 0.31, 95% CI 0.12– 0.78, P = 0.013) and D-dimer levels (aOR 6.46, 95% CI 1.92– 21.74, P = 0.003).Conclusion: Our study observed a prevalence of 21.5% exacerbation of pre-existing chronic pain after SARS-CoV-2 infection, with a consequence of poor quality of life, more severe anxiety and depression. Previous chronic neuropathic pain, lower lymphocyte count and higher D-dimer levels were risk factors associated with the development of exacerbated previous chronic pain.Keywords: post-COVID-19, older adults, chronic pain, exacerbated symptoms

The Zr37Hf16Ni12.5Cu12.5Al11Co6Nb5 bulk metallic glass (BMG) with strong glass-forming ability (GFA) and remarkable mechanical properties was designed, and its thermophysical properties were characterized simultaneously. The glass transition temperature reached up to 726 K, while the fragility index of 43 was derived by measuring alloy viscosity. The undercooled liquid of this BMG with such a low fragility index displayed a strong liquid behavior, corresponding to its small crystallization driving force and high GFA. The thermal expansion coefficient increased from 9.76 × 10−6 K−1 of glassy state to 2.71 × 10−5 K−1 of undercooled liquid, and the close-packed structure was evidenced by the low specific energy for free volume formation of 239.4 kJ/mol. Owing to its low free volume and high glass transition temperature, this BMG exhibited remarkable tensile and compressive yield strengths up to 1660.3 and 2042.3 MPa, respectively. [ABSTRACT FROM AUTHOR]

The occurrence of vegetation degradation may greatly affect the soil organic carbon (SOC) composition and carbon pool of wetland meadows in the Qinghai-Tibet Plateau (QTP). However, it is currently unclear how SOC will change under different degrees of degradation. Therefore, we studied the wetland meadows of Maqu, China on the eastern edge of the QPT with different degrees of vegetation degradation (undegraded (UD), light degraded (LD), moderately degraded (MD) and severely degraded (HD)), analyzed the impact of vegetation degradation on SOC composition, and calculated the carbon storage management index (CPMI). The results showed that the degradation of vegetation significantly reduces the SOC content of the Maqu wetland. With the aggravation of vegetation degradation, the proportion of SOCs in different fractions showed significant differences, especially in the topsoil layer. The mean CPMI value from 0-40 cm of LD, MD and HD has decreased by 47.29%, 41.64%, and 51.73% respectively compared to UD. It can be seen that vegetation degradation significantly increasing the carbon pool activity index (CAI) of Maqu. Our study suggested that vegetation degradation could considerably reduce the carbon pool index, which decrease the storage of wetland carbon, gradually undermine or even depleting the carbon sink capacity of QTP wetland system. [ABSTRACT FROM AUTHOR]

Engineered dissipative reservoirs have the potential to steer many-body quantum systems toward correlated steady states useful for quantum simulation of high-temperature superconductivity or quantum magnetism. Using up to 49 superconducting qubits, we prepared low-energy states of the transverse-field Ising model through coupling to dissipative auxiliary qubits. In one dimension, we observed long-range quantum correlations and a ground-state fidelity of 0.86 for 18 qubits at the critical point. In two dimensions, we found mutual information that extends beyond nearest neighbors. Lastly, by coupling the system to auxiliaries emulating reservoirs with different chemical potentials, we explored transport in the quantum Heisenberg model. Our results establish engineered dissipation as a scalable alternative to unitary evolution for preparing entangled many-body states on noisy quantum processors. [ABSTRACT FROM AUTHOR]

Weakly supervised semantic segmentation, based on image-level labels, abandons the pixel-level labels relied upon by traditional semantic segmentation algorithms. It only utilizes images as supervision information, thereby reducing the time cost and human resources required for marking pixel data. The prevailing approach in weakly supervised segmentation involves two-step method, introducing an additional network and numerous parameters, thereby complicating the model structure. Furthermore, image-level labels typically furnishes only category information for the entire image, lacking specific location details and accurate target boundaries during model training. We propose an innovative One-Step Triple Enhanced weakly supervised semantic segmentation network(OSTE). OSTE streamlines the model structure, which can accomplish both pseudo-labels generation and semantic segmentation tasks in just one step. Furthermore, we augment the weakly supervised semantic segmentation network in three key aspects based on the class activation map construction method, thereby enhancing segmentation accuracy: Firstly, by integrating local information from the activation map with the image, we can enhance the network's localization and expansion capabilities to obtain more accurate and rich location information. Then, we refine the seed areas of the class activation map by exploiting the correlation between multi-level feature. Finally, we incorporate conditional random field theory to generate pseudo-labels with higher confidence and richer boundary information. In comparison to the prevailing two-step weakly supervised semantic segmentation schemes, the segmentation network proposed in this paper achieves a more competitive mean Intersection over Union (mIoU) score of 58.47% on Pascal VOC. Additionally, it enhances the mIoU score by at least 5.03% when compared to existing end-to-end schemes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Quan 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.)

Withering is an important process for achieving high-quality flavor in tea. In this study, histological, metabolomics, transcriptomics, and biochemical analyses were combined to comprehensively explore the accumulation and molecular regulatory profiles of quality metabolites during tea withering. The results of tissue staining indicated that as the water content decreased, the vitality of the nucleus weakened, cytoplasmic content increased, flavone content decreased, and proteins degraded. Omics analysis showed that the total content of soluble sugars, free amino acids, and terpenoids increased, whereas that of catechins decreased significantly, although the caffeine content barely changed. Biochemical analysis revealed that the translated products of genes CSA010827 and CSA001819 catalyzed the biosynthesis of galactose and flavanol 3-O-glycosides, respectively, thereby increasing the content of soluble sugars and contributing to the astringent taste. Overall, by combining omics with histological and biochemical analyses, we revealed the metabolic profile and possible molecular mechanisms during the withering process of tea., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could influence the work reported in this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Rationale and Objectives: This study aimed to develop a deep learning (DL)-based model for detecting and diagnosing cerebral aneurysms in clinical settings, with and without human assistance., Materials and Methods: The DL model was trained using data from 3829 patients across 11 clinical centers and tested on 484 patients from three institutions. Image interpretations were conducted by 10 radiologists (four junior, six senior), the DL model alone, and a combination of radiologists with the DL model. Time spent on post-processing and reading was recorded. The analysis of the area under the curve (AUC), sensitivity, and specificity for the above-mentioned three reading modes was performed at both the lesion and patient levels., Results: Combining the DL model with radiologists reduced image interpretation time by 37.2% and post-processing time by 90.8%. With DL model assistance, the AUC increased from 0.842 to 0.881 (P = 0.008) for junior radiologists (JRs) and from 0.853 to 0.895 (P < 0.001) for senior radiologists (SRs). With DL model assistance, sensitivity significantly improved at both lesion (JR: 68.9% to 81.6%, P = 0.011; SR: 72.4% to 83.5%, P < 0.001) and patient levels (JR: 76.2% to 86.9%, P = 0.011; SR: 80.1% to 88.2%, P < 0.001). Specificity at the patient level showed improvement (JR: 82.6% to 82.7%, P = 0.005; SR: 82.6% to 86.1%, P = 0.021)., Conclusions: The DL model enhanced radiologists' diagnostic performance in detecting cerebral aneurysms, especially for JRs, and expedited the workflow., Competing Interests: Declaration of Competing Interest All the authors declare no relationships with any companies whose products or services may be related to the subject matter of the article., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

A novel thioxoimidazolidin-linked sialoside bovine serum albumin (WM-BSA) conjugate was synthesized and evaluated as an inhibitor of influenza virus hemagglutinin (HA) and neuraminidase (NA). The multivalent conjugate was prepared by the attachment of thioxoimidazolidin-sialoside monomer (WM) to BSA via adipate linker. Surface plasmon resonance analysis revealed that WM-BSA exhibited potent binding to recombinant influenza HA and NA proteins, with dissociation constants in the submicromolar range. WM-BSA also demonstrated inhibitory activities in the low micromolar range against HA and NA proteins from multiple influenza strains. Investigation of cytopathic effects in infected MDCK cells indicated that WM-BSA possessed antiviral activity with EC 50 values of 35-55 μM. The multivalent presentation of sialosides on the BSA scaffold significantly enhanced both the binding affinity and degree of inhibition compared to the monomeric compound WM. These results demonstrate the potential of multivalent sialoside-protein conjugate as a platform for developing novel anti-influenza agent., 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.)

Smart textiles with a high level of personal protection, health monitoring, physical comfort, and wearing durability are highly demanded in clothing for harsh application scenarios, such as modern sportswear. However, seamlessly integrating such a smart clothing system has been a long-sought but challenging goal. Herein, based on coaxial electrospinning techniques, a smart non-woven textile (Smart-NT) integrated with high impact resistance is developed, multisensory functions, and radiative cooling effects. This Smart-NT is comprised of core-shell nanofibers with an ionic conductive polymer sheath and an impact-stiffening polymer core. The soft smart textile, with a thickness of only 800 µm, can attenuate over 60% of impact force, sense pressure stimulus with sensitivity up to 201.5 kPa -1 , achieve temperature sensing resolution of 0.1 °C, and reduce skin temperature by ≈17 °C under a solar intensity of 1 kW m -2 . In addition, the stretchable Smart-NT is highly durable and robust, retaining its multifunction features over 10 000 bending and multiple washing cycles. Finally, application scenarios are demonstrated for real-time health monitoring, body protection, and physical comfort of smart sportswear based on Smart-NT for outdoor sports. The strategy opens a new avenue for seamless integration of smart clothing systems., (© 2024 Wiley‐VCH GmbH.)

Influenza remains a global public health threat, and the development of new antivirals is crucial to combat emerging drug-resistant influenza strains. In this study, we report the synthesis and evaluation of a sialyl lactosyl (TS)-bovine serum albumin (BSA) conjugate as a potential multivalent inhibitor of the influenza virus. The key trisaccharide component, TS, was efficiently prepared via a chemoenzymatic approach, followed by conjugation to dibenzocyclooctyne-modified BSA via a strain-promoted azide-alkyne cycloaddition reaction. Biophysical and biochemical assays, including surface plasmon resonance, isothermal titration calorimetry, hemagglutination inhibition, and neuraminidase inhibition, demonstrated the strong binding affinity of TS-BSA to the hemagglutinin (HA) and neuraminidase (NA) proteins of the influenza virus as well as intact virion particles. Notably, TS-BSA exhibited potent inhibitory activity against viral entry and release, preventing cytopathic effects in cell culture. This multivalent presentation strategy highlights the potential of glycocluster-based antivirals for combating influenza and other drug-resistant viral strains., 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 Masson SAS. All rights reserved.)

Introduction: Fast, accurate, and automatic analysis of histopathological images using digital image processing and deep learning technology is a necessary task. Conventional histopathological image analysis algorithms require the manual design of features, while deep learning methods can achieve fast prediction and accurate analysis, but rely on the drive of a large amount of labeled data., Methods: In this work, we introduce WSSS-CRAM a weakly-supervised semantic segmentation that can obtain detailed pixel-level labels from image-level annotated data. Specifically, we use a discriminative activation strategy to generate category-specific image activation maps via class labels. The category-specific activation maps are then post-processed using conditional random fields to obtain reliable regions that are directly used as ground-truth labels for the segmentation branch. Critically, the two steps of the pseudo-label acquisition and training segmentation model are integrated into an end-to-end model for joint training in this method., Results: Through quantitative evaluation and visualization results, we demonstrate that the framework can predict pixel-level labels from image-level labels, and also perform well when testing images without image-level annotations., Discussion: Future, we consider extending the algorithm to different pathological datasets and types of tissue images to validate its generalization capability., 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 Pan, Mi, Li, Ge, Sui and Jiang.)

The severity of soil molybdenum (Mo) pollution is increasing, and effective management of contaminated soil is essential for the sustainable development of soil. To investigate this, a pot experiment was carried out to assess the impact of different rates of humic acid (HA) and fulvic acid (FA) on the mobility of Mo in soil solution and its uptake by alfalfa, wheat and green bristlegrass. The concentration of Mo in Plants and soil was determined using an Atomic Absorption Spectrophotometer. The findings revealed that the application of HA led to an increase in Mo accumulation in the shoot and root of green bristlegrass and wheat, ranging from 10.56 % to 28.73 % and 62.15-115.79 % (shoot), and 17.52-46.53 % and 6.29-81.25 % (root), respectively. Nonetheless, the use of HA resulted in a slight inhibition of plant Mo uptake, leading to reduced Mo accumulation in alfalfa roots compared to the control treatment (from 3284.49 mg/kg to 2140.78-2813.54 mg/kg). On the other hand, the application of FA decreased Mo accumulation in the wheat shoot (from 909.92 mg/kg to 338.54-837.45 mg/kg). Furthermore, the bioavailability of green bristlegrass (with HA) and wheat (with FA) decreased, and the percentage of residual fraction of Mo increased (from 0.39 % to 0.78-0.96 %, from 3.95 % to 3.97∼ 4.34 %). This study aims to elucidate the ternary interaction among Mo, humic substances, and plants (alfalfa, wheat, and green bristlegrass), to enhance both the activation and hyperaccumulation of Mo simultaneously., 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.)

Gene-editing technology has become a transformative tool for the precise manipulation of biological genomes and holds great significance in the field of animal disease-resistant breeding. Mastitis, a prevalent disease in animal husbandry, imposes a substantial economic burden on the global dairy industry. In this study, a regulatory sequence gene editing breeding strategy for the successful creation of a gene-edited dairy (GED) goats with enhanced mastitis resistance using the ISDra2-TnpB system and dairy goats as the model animal is proposed. This included the targeted integration of an innate inflammatory regulatory sequence (IRS) into the promoter region of the lysozyme (LYZ) gene. Upon Escherichia Coli (E. coli) mammary gland infection, GED goats exhibited increased LYZ expression, showing robust anti-mastitis capabilities, mitigating PANoptosis activation, and alleviating blood-milk-barrier (BMB) damage. Notably, LYZ is highly expressed only in E. coli infection. This study marks the advent of anti-mastitis gene-edited animals with exogenous-free gene expression and demonstrates the feasibility of the gene-editing strategy proposed in this study. In addition, it provides a novel gene-editing blueprint for developing disease-resistant strains, focusing on disease specificity and biosafety while providing a research basis for the widespread application of the ISDra2-TnpB system., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Contrast-induced acute kidney injury (CI-AKI) is a prevalent cause of renal dysfunction among hospitalized patients, yet the precise pathogenesis and effective therapeutic strategies remain elusive. In this study, we investigated the role of tubular ferroptosis in both experimental CI-AKI models and in primary tubular epithelial cells (PTECs) treated with ioversol. Using whole exome sequencing, we identified metallothioneins (MTs) as being among the most significantly downregulated genes following ioversol exposure. Our findings reveal that overexpression of Mt1 mitigates, whereas suppression of Mt-1 exacerbates, ioversol-induced tubular ferroptosis. Interestingly, the level of MTF1 (metal regulatory transcription factor 1), a principal regulator of Mt1, was found to increase in response to ioversol treatment. We further elucidated that ioversol activates LATS1 (Large tumor suppressor homolog 1), a kinase that promotes the phosphorylation and nuclear translocation of MTF1, thereby inhibiting its transcriptional activity for Mt1. Both genetic and pharmacological inhibition of LATS1 reversed the ioversol-induced suppression of Mt-1. From a therapeutic perspective, the LATS1 inhibitor TDI-011536, in combination with zinc acetate, was administered to a rodent model of CI-AKI. Our data indicate that this combination synergistically upregulates Mt1 expression and provides protection against contrast media-induced tubular ferroptosis. In summary, our study demonstrates that the reduction of Mt-1 contributes to tubular ferroptosis associated with CI-AKI. We show that contrast media activate LATS1, which in turn suppresses the transcriptional activity of MTF1 for Mt1. Herein, the combination of zinc acetate and a LATS1 inhibitor emerges as a potential therapeutic approach for the treatment of CI-AKI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To synthesize the clinical experience of patients with COVID-19-associated acute respiratory distress syndrome (ARDS) or pulmonary fibrosis (PF) receiving lung transplantation (LTx) and compare the characteristics and outcomes of COVID-19 and non-COVID-19 LTx patients., Methods: A literature search of online databases (PubMed, Web of Science, Embase, the Cochrane Library, China Science and Technology Journal Database, and Wan Fang databases) was performed regarding LTx for COVID-19-associated ARDS or PF. This study was registered on PROSPERO (CRD2024507647)., Results: Eight eligible studies were included with 478 COVID-19 LTx patients and 163 non-COVID-19 LTx patients. In COVID-19 LTx patients, the pooled hospital mortality and follow-up survival rate was 0.00% (95% CI 0.00-0.03) and 87.40% (95% CI 0.76-0.96). Compared to non-COVID-19 LTx patients, COVID-19 LTx patients were associated with significantly higher rate of primary graft dysfunction (odds ratio [OR] 8.72, 95% CI 3.54-21.47, P < 0.001) but significantly higher follow-up survival rate (OR 2.48, 95% CI 1.02-6.01, P = 0.04), within an overall similar follow-up period., Conclusions: For patients with COVID-19-associated ARDS or PF, LTx offers acceptable short-term outcomes and is suggested as a viable lifesaving treatment., Competing Interests: Declarations 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 Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: This study aimed to establish a population pharmacokinetic (PK) model to evaluate the dynamic relationship between the concentrations of total and unbound paclitaxel, and the exposure-response analysis of albumin-bound paclitaxel (nab-paclitaxel) after pegylated recombinant human granulocyte colony-stimulating factor (PEG-G-CSF) administration in patients with metastatic breast cancer., Methods: A total of 653 concentrations corresponding to total paclitaxel and 334 concentrations corresponding to unbound paclitaxel were analyzed in 24 subjects who randomized received a single 260 mg/m 2 dose of two nab-paclitaxel formulations with a 21-35-day washout period. PEG-G-CSF was administered to all the patients in each cycle to prevent neutropenia. The exposure-response relationships were evaluated using the exposure to total, albumin-coated, and unbound paclitaxel, as well as the reduction in neutrophil count. The exposure data were analyzed using nonlinear mixed-effect modeling. A linear regression model was used to test the statistical significance of the correlation between percentage of reduction in neutrophil count and exposure., Results: The PK characteristics of total paclitaxel were described using a three-compartment model with first-order elimination, and a mechanism-based model incorporating linear release of nab-paclitaxel and the saturated binding of unbound paclitaxel to plasma components was established. The release ratio of paclitaxel from nab-paclitaxel was estimated to be 4.60% and the maximum unbound fraction (2.76%) was reached at the end of the infusion. The study found that a longer duration of total paclitaxel concentration > 0.19 µmol/L was significantly correlated with a reduction in neutrophil count (r 2  = 0.23, P = 0.00062). Specifically, a duration of > 8.6 h was a predictor of a decreased neutrophil count., Conclusion: The decrease in neutrophils induced by nab-paclitaxel was significantly correlated with the duration above a total paclitaxel concentration of 0.19 µmol/L despite the use of PEG-G-CSF., (© 2024. Crown.)

JOURNAL/nrgr/04.03/01300535-202410000-00030/figure1/v/2024-02-06T055622Z/r/image-tiff Photoreceptor cell degeneration leads to blindness, for which there is currently no effective treatment. Our previous studies have shown that Lycium barbarum (L. barbarum) polysaccharide (LBP) protects degenerated photoreceptors in rd1, a transgenic mouse model of retinitis pigmentosa. L. barbarum glycopeptide (LbGP) is an immunoreactive glycoprotein extracted from LBP. In this study, we investigated the potential protective effect of LbGP on a chemically induced photoreceptor-degenerative mouse model. Wild-type mice received the following: oral administration of LbGP as a protective pre-treatment on days 1-7; intraperitoneal administration of 40 mg/kg N-methyl-N-nitrosourea to induce photoreceptor injury on day 7; and continuation of orally administered LbGP on days 8-14. Treatment with LbGP increased photoreceptor survival and improved the structure of photoreceptors, retinal photoresponse, and visual behaviors of mice with photoreceptor degeneration. LbGP was also found to partially inhibit the activation of microglia in N-methyl-N-nitrosourea-injured retinas and significantly decreased the expression of two pro-inflammatory cytokines. In conclusion, LbGP effectively slowed the rate of photoreceptor degeneration in N-methyl-N-nitrosourea-injured mice, possibly through an anti-inflammatory mechanism, and has potential as a candidate drug for the clinical treatment of photoreceptor degeneration., (Copyright © 2024 Copyright: © 2024 Neural Regeneration Research.)

Chimeric antigen receptor (CAR) T-cell therapy has resulted in remarkable clinical success in the treatment of B-cell malignancies. However, its clinical efficacy in solid tumors is limited, primarily by target antigen heterogeneity. To overcome antigen heterogeneity, we developed CAR T cells that overexpress LIGHT, a ligand of both lymphotoxin-β receptor on cancer cells and herpes virus entry mediator on immune cells. LIGHT-expressing CAR T cells displayed both antigen-directed cytotoxicity mediated by the CAR and antigen-independent killing mediated through the interaction of LIGHT with lymphotoxin-β receptor on cancer cells. Moreover, CAR T cells expressing LIGHT had immunostimulatory properties that improved the cells' proliferation and cytolytic profile. These data indicate that LIGHT-expressing CAR T cells may provide a way to eliminate antigen-negative tumor cells to prevent antigen-negative disease relapse., (©2024 American Association for Cancer Research.)

Purpose: To evaluate temporal vascular arcade angle and its influencing factors in myopic children., Methods: It was a retrospective study, we reviewed the records of 119 patients aged 6-10 years with myopia (spherical equivalent refractive error (SER) ≤ -0.05D) in the third year of follow-up in Beijing Hyperopia Reserve Research. We measured temporal vascular arcade angles on the fundus photographs and measured 3-year rate of spherical equivalent(D/year) and axial length (AXL) changes(mm/year)., Results: Mean age at initial visit was 7.71±1.20 years and mean SER was -1.32±1.09D. Children were divided into two groups according to the refractive status of children at baseline: Myopia onset group (SER>-0.50D at baseline) (n = 107) and Myopia progression group (SER≤-0.50D at baseline) (n = 12). The mean SER in Myopia progression group was much smaller than Myopia onset group (P < 0.001) and mean AXL in Myopia progression group was much longer than Myopia onset group (P = 0.042). AXL (r=-0.320, P < 0.001), SER change rate (r=-0.209, P = 0.022) and AXL change rate (r=-0.232, P = 0.011) were associated with temporal vascular arcade angle in all participants. In Myopia onset group, AXL (r=-0.317, P < 0.001) and AXL change rate (r=-0.190, P = 0.05) were associated with temporal vascular arcade angle. There were no parameters were associated with temporal vascular arcade angle (all P > 0.05) in Myopia progression group. Only AXL (r=-0.306, P = 0.018) was associated with temporal vascular arcade angle in girls while AXL (r=-0.370, P = 0.004), SER change rate (r=-0.317, P = 0.013) and AXL change rate (r=-0.365, P = 0.004) were all associated with the Angle in boys., Conclusion: Temporal vascular arcade angle was associated with the rate of SER and AXL changes in myopia onset children, and showed gender differences. These may suggest that lamina cribrosa location has different influencing factors in different genders and different stages of myopia development. Due to the small number of people in Myopia progression group, large sample size studies are still needed in the future., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: To evaluate the occurrence and influencing factors of myopia occurrence in pre-myopia children aged 3-6 years., Methods: This study included 204 pre-myopia (-0.50D-0.50D). The length of macular BM was shorter in Myopia group than that in Non-myopia group (P < 0.001). Baseline SE and the length of macular BM were independent influencing factors which associated with myopia occurrence (OR, 0.031; 95 % CI, 0.008-0.117, P < 0.001 and OR, 0.204; 95 % CI, 0.055-0.763, P = 0.018, respectively) by multivariate binary logistic regression analysis. SE changing process represented the changes of SE, Myopia group had bigger SE changes (P < 0.001). And in the multivariate liner regression analysis, age was the common influencing factor of SE changing process in total participants, Non-myopia group and Myopia group (B = 0.234, P < 0.001; B = 0.078, P = 0.010; B = 0.161, P = 0.046, respectively) CONCLUSIONS: Initial SE and the length of macular BM in pre-myopia children aged 3-6 years were the independent factors of the occurrence of myopia. And initial age was the common factor that associated with SE changing process., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Morphological and structural remodeling of the heart, including cardiac hypertrophy and fibrosis, has been considered as a therapeutic target for heart failure for approximately three decades. Groundbreaking heart failure medications demonstrating reverse remodeling effects have contributed significantly to medical advancements. However, nearly 50% of heart failure patients still exhibit drug resistance, posing a challenge to the healthcare system. Recently, characteristics of heart failure resistant to ARBs and β-blockers have been defined, highlighting preserved systolic function despite impaired diastolic function, leading to the classification of heart failure with preserved ejection fraction (HFpEF). The pathogenesis and aetiology of HFpEF may be related to metabolic abnormalities, as evidenced by its mimicry through endothelial dysfunction and excessive intake of high-fat diets. Our recent findings indicate a significant involvement of mitochondrial hyper-fission in the progression of heart failure. This mitochondrial pathological remodeling is associated with redox imbalance, especially hydrogen sulphide accumulation due to abnormal electron leak in myocardium. In this review, we also introduce a novel therapeutic strategy for heart failure from the current perspective of mitochondrial redox-metabolic remodeling., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Here, we report an efficient transition-metal-free C(sp 2 )-C(sp 3 ) Suzuki-Miyaura-type cross-coupling between α-halo Weinreb-type amides and arylboronic acids. The reaction is carried out by capturing active aza-oxyallyl cation (AOAC) with arylboronic acid to form a boron "ate" complex, followed by 1,4-migration to give α-aryl amides with good yields.

Introduction: Local exposure to ionizing radiation (IR) can induce changes in biological processes in distant tissues and organs. Exosomes are nanoscale vesicles that transport biomolecules, mediate communication between cells and tissues, and can affect the abscopal effects of radiotherapy., Methods: Mice were treated with 8.0 Gy doses of chest and abdomen IR, after which serum samples were taken 24 h after exposure. Their serum exosomes were then isolated via ultracentrifugation and the small RNA portions were extracted for sequencing and bioinformatic analysis. Exosomes were injected intravenously into the mice to assess their ability to cross the blood-brain barrier (BBB). Glioma cells and glioma stem cells (GSCs) were examined for malignant biological behaviors, stemness, and tumorigenic capacity after co-culturing with different groups of exosomes., Results: We found that serum exosomes crossed the BBB in mice after local IR exposure-which induced decreases in the expression of BBB tight-junction proteins and increased brain endothelial cell apoptosis. Exosomes from the exposed groups promoted malignant biological behaviors, stemness, and tumorigenic capacity in glioma cells and GSCs by upregulating the expression of SOS1. Phospho-MEK1/2 and Phospho-ERK1/2, of the MAPK signaling pathway, were found to be up-regulated in cells that were co-cultured with the exposing groups of the exosomes. Further analyses demonstrated that differentially expressed levels of miR-93-5p in mouse serum exosomes regulated the cellular expression of SOS1., Conclusion: Following local IR exposure, serum exosomes cross the BBB to promote the progression of distant gliomas. Exosomal microRNAs play an important role in this process., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Catkins, as a significant source of plant-caused pollution, disrupts daily human activities and industrial processes. Despite their impact, catkins have not been included in official environmental quality monitoring indicators, leading to a deficiency in scientifically rigorous collection and monitoring methodologies, as well as a lack of ecological prevention and management strategies. In this study, we introduced a fine-scale monitoring approach for catkins. Qualitative and quantitative relationships between catkin concentrations, plant community characteristics and microclimate factors were elucidated by analyzing on-site catkin concentration data from 33 representative plant communities in Beijing. Furthermore, we summarized the ecological strategies for the prevention and management of these catkins. The results indicated that (1) T S (three-dimensional green volume of trees in the catkin source layer), S B (three-dimensional green volume of shrubs in the catkin barrier layer), G B (three-dimensional green volume of ground cover plants in the catkin barrier layer), T (three-dimensional green volume of trees in the whole plant community), W (three-dimensional green volume of the whole plant community), species diversity, and relative air humidity were key plant community characteristics and microclimate factors influencing catkin concentration. Among these factors, T S , T, W, and relative air humidity showed a significant positive correlation with catkin concentration, while S B , G B , and species diversity exhibited a significant negative correlation with catkin concentration. (2) All seven key factors exhibited nonlinear relationships with catkin concentration. (3) T S served as the primary deciding factor for catkin concentration within the plant community. When T S  > 744.0755 m 3 , the secondary decision factor for catkin concentration was G B . Otherwise, the determinants were S B and species diversity. The results showed that enhancing tree species diversity, enhancing the three-dimensional green volume of shrubs and ground cover plants, and increasing air humidity were practical means to facilitate the sedimentation of catkins. The measures used to obstruct catkins vary depending on the T S . When catkin source plants are abundant within a plant community, it is advisable to prioritize increasing ground cover plants. Conversely, when fewer sources of such plants exist, emphasis can be placed on augmenting mid-layer shrubs and diversifying plant species. These findings provide a scientific foundation for the planting design and stock optimization of communities containing catkin source plants., (© 2024. The Author(s).)

In situ bioprinting enables precise 3D printing inside the human body using modified bioprinters with thermosensitive bioinks such as gelatin methacrylate (GelMA). However, these devices lack refined temperature-regulated mechanisms essential for ensuring bioink viscosity, as compared to traditional bio-3D printers. Addressing this challenge, this study presents a temperature-regulated printhead designed to improve the fabrication of thermosensitive bioink scaffolds in in situ bioprinting, integrated into a UR5 robotic arm. Featuring a closed-loop system, it achieves a temperature steady error of 1 °C and a response time of approximately 1 min. The effectiveness of the printer was validated by bioprinting multilayer lattice 3D bioscaffolds. Comparisons were made with or without temperature control using different concentrations of GelMA + LAP. The deformation of the bioscaffolds under both conditions was analyzed, and cell culture tests were conducted to verify viability. Additionally, the rheology and mechanical properties of GelMA were tested. A final preliminary in situ bioprinting experiment was conducted on a model of a damaged femur to demonstrate practical application. The fabrication of this printhead is entirely open source, facilitating easy modifications to accommodate various robotic arms. We encourage readers to advance this prototype for application in increasingly complex in situ bioprinting situations, especially those utilizing thermosensitive bioinks., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Objective: The aim of this study is to assess the use of machine learning methodologies in the diagnosis of endometriosis (EM)., Methods: This study included a total of 106 patients with EM and 203 patients with non-EM conditions (like simple cysts and simple uterine fibroids), all admitted to the Shunyi Women's and Children's Hospital of Beijing Children's Hospital between January 2017 and September 2022. All participants were free of comorbidities and their diagnoses were confirmed via postoperative pathology. Comparative analysis was conducted between the EM and non-EM groups. Baseline data were assessed, including white blood cell count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, mean platelet volume, hemoglobin, carbohydrate antigen 125 (CA125), carbohydrate antigen 199, coagulation parameters, and other serologic indicators. An optimal predictive model was developed using an artificial intelligence algorithm to determine the presence of EM. The objective is to provide new insights for the clinical diagnosis and treatment of EM., Results: The random forest algorithm demonstrated superior performance when compared to decision trees, LogitBoost, artificial neural networks, naïve Bayes, support vector machines, and linear regression in machine learning methods. Combining CA125 with the NLR yielded a better prediction of EM than using CA125 alone when applying the random forest algorithm. The accuracy of predicting EM with CA125 combined with NLR was 78.16%, with a sensitivity of 86.21% and an area under the curve (AUC) of 0.85 (P < 0.05). In contrast, using CA125 alone resulted in an EM prediction accuracy of 75.8%, with a sensitivity of 79.3% and an AUC of 0.82 (P < 0.05)., Conclusion: The diagnostic value of serum CA125 combined with the NLR for EM is higher than that of serum CA125 alone. This finding indicates that NLR could serve as a new supplementary biomarker along with serum CA125 in the diagnosis of EM., (© 2024. The Author(s).)

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with a ∼50% response rate to immune checkpoint blockade (ICB) therapy. To identify predictive biomarkers, we integrated bulk and single-cell RNA sequencing (RNA-seq) with spatial transcriptomics from a cohort of 186 samples from 116 patients, including bulk RNA-seq from 14 matched pairs pre- and post-ICB. In nonresponders, tumors show evidence of increased tumor proliferation, neuronal stem cell markers, and IL1. Responders have increased type I/II interferons and preexisting tissue resident (Trm) CD8 or Vδ1 γδ T cells that functionally converge with overlapping antigen-specific transcriptional programs and clonal expansion of public T-cell receptors. Spatial transcriptomics demonstrated colocalization of T cells with B and dendritic cells, which supply chemokines and costimulation. Lastly, ICB significantly increased clonal expansion or recruitment of Trm and Vδ1 cells in tumors specifically in responders, underscoring their therapeutic importance. These data identify potential clinically actionable biomarkers and therapeutic targets for MCC. Significance: MCC serves as a model of ICB response. We utilized the largest-to-date, multimodal MCC dataset (n = 116 patients) to uncover unique tumor-intrinsic properties and immune circuits that predict response. We identified CD8 Trm and Vδ1 T cells as clinically actionable mediators of ICB response in major histocompatibility complex-high and -low MCCs, respectively., (©2024 American Association for Cancer Research.)

The liquid state thermophysical properties and amorphous solidification kinetics of Fe&#95;{50-x}Co&#95;{x}Cr&#95;{14}Mo&#95;{14}C&#95;{9}B&#95;{8}Tm&#95;{5} (x=10, 15, 20, and 25) alloys were explored by electromagnetic and electrostatic levitation techniques. It was found that the surface tension of liquid alloys with Fe contents below 30 at. % had a strong temperature dependence. The high surface tension led to a sharp increase in the interfacial free-energy penalty. A high nucleation barrier was formed inside the melt, which greatly inhibited the nucleation rate. The liquid viscosity revealed the strong liquid feature of this alloy series, which became the dominant kinetic factor determining their solidification mechanisms. The high viscosity hindered atomic diffusion and delayed nucleation. The long crystallizing incubation time of Fe&#95;{30}Co&#95;{20}Cr&#95;{14}Mo&#95;{14}C&#95;{9}B&#95;{8}Tm&#95;{5} ensured a strong glass-forming ability and a low critical cooling rate of 2.11×10^{3}Ks^{-1}. As a result, a bulk metallic glass rod with an 8-mm diameter was successfully prepared by a convenient casting procedure. This rod could remain in a glassy state at a higher temperature and over a wider temperature range due to its high glass-transition temperature and large undercooled liquid region. The apparent activation energy for nucleation was derived as 463.8 kJmol^{-1} according to the nonisothermal crystallization kinetics, indicating that the bulk metallic glass had to absorb a large amount of energy to overcome the potential barriers before nucleation and thus exhibited excellent thermal stability.

Renal interstitial fibrosis (RIF) is often associated with inflammatory cell infiltration and no effective therapy. Programmed death cell-1 (PD-1) and its ligand PD-L1 were playing critical roles in T cell coinhibition and exhaustion, but the role in RIF is unclear. Here the data analyses of serum from 122 IgA nephrology (IgAN) patients showed that high level of soluble PD-1(sPD-1) was an independent risk factor for RIF and renal function progression. PD-L1 was also overexpressed in renal interstitial tissues from both IgAN patients with high level of sPD-1 and the unilateral ureteral obstruction (UUO) mouse. PD-L1 was significantly overexpressed in HK-2 cells with upregulated collagen and α-SMA when stimulated by inflammation or hypoxia in vitro. Additionally, matrix metalloproteinases (MMP-2) could increase the level of sPD-1 in culture supernatant when added in co-culture system of HK-2 and jurkat cells, which implied serum sPD-1 of IgAN might be cleaved by MMP-2 from T cells infiltrated into the tubulointerstitial inflammatory microenvironment. Crucially, injection of PD-L1 fusion protein, the blocker of sPD-1, could ameliorate kidney fibrosis in UUO mice by increasing T cell coinhibition and exhaustion, suggesting the therapeutic potential of PD-L1 fusion targeting for renal fibrosis. Take together, it reveals a novel causal role of sPD-1 in serum and PD-L1 of renal interstitial tissues in the development of renal fibrosis of IgAN, and targeting sPD-1 in serum by PD-L1 fusion protein is a potential therapeutic approach to prevent renal fibrosis of IgAN., (Copyright © 2024. Published by Elsevier Inc.)

Objective: This study is aimed at investigating the pharmacokinetic (PK) characteristics of pegylated liposomal mitoxantrone (PLM) in patients with relapsed/refractory lymphoma or small cell lung cancer (SCLC) by constructing population pharmacokinetic (popPK) models for both liposome-encapsulated mitoxantrone and free mitoxantrone., Methods: A total of 23 patients with relapsed/refractory lymphoma and 42 patients with SCLC were included. A popPK model was simultaneously developed utilizing a non-linear mixed effects model (NONMEM) to explore the PK profiles of liposome-encapsulated mitoxantrone and free mitoxantrone. Clearance (CL) and distribution volume (V) were calculated, and covariate analysis was employed to evaluate the influence of patient disease type, demographic information, and biochemical indicators of liver and kidney function on PK parameters., Results: The concentration-time profiles for both liposome-encapsulated mitoxantrone and free mitoxantrone were described by a one-compartment model. The release (Rel) of liposome-encapsulated mitoxantrone to free mitoxantrone was determined to be 0.0191 L/h, and the V of liposome-encapsulated mitoxantrone was 2.32 L. The apparent CL of free mitoxantrone was estimated at 1.66 L/h. The apparent V of free mitoxantrone was 35.8 L in patients with relapsed/refractory lymphoma and 22.2 L for patients with SCLC. In patients with relapsed/refractory lymphoma, lower maximum concentration (C max ) and higher apparent V of free mitoxantrone were observed compared with patients with SCLC., Conclusion: The popPK characteristics of both liposome-encapsulated and free mitoxantrone in patients with relapsed/refractory lymphoma or SCLC were effectively described by a one-compartment model., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A pH/temperature bi-responsive gallic acid magnetic imprinted polymer (PTBG-MIP) was synthesized on a Fe 3 O 4 @SiO 2 @KH570 carrier using methacrylic acid (MAA), p-Vinylphenylboronic acid (p-VPBA), and N-isopropyl-acrylamide (NIPAAm) as complex functional monomers. The density functional theory (DFT) was employed to optimize the molar ratio of multi-functional monomers-template complex, which proved to be an effective tool for predicting complex configuration based on electrostatic potential (ESP) analysis and the lowest binding energy. DFT calculation and analysis determined the optimized molar ratio of 2:1:1:1 for GA-MAA-NIPAAm-p-VPBA, which showed good agreement with experimental results. The PTBG-MIP-4 obtained under the optimized conditions exhibited high pH- and temperature- dependence in rebinding the template, displaying a maximum adsorption capacity (Q e ) of 62.26 mg g -1 and a highest selection factor (α) of 5.217. Additionally, the PTBG-MIP-4 exhibited exceptional physicochemical properties encompassing magnetization characteristics, morphology, surface sites distribution, and adsorption performance. The application efficiency of this imprinted composite in the extraction and purification of gallic acid from Galla chinensis was remarkably demonstrated., Competing Interests: Declaration of competing interest My major investigation fields lie to two aspects: (1) molecularly imprinted polymer and (2) chromatographic separation and analysis. Recently, my interest aims at creating novel approach to perform solid phase extraction of bioactive compounds from some Traditional Chinese Medicine and at developing new molecularly imprinted polymers material as stationary phase in liquid phase and gas chromatography., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To compare anesthetic parameters using a novel prone single transverse chest roll technique (STR) to the standard thoraco-pelvic dual transverse roll technique (DTR)., Methods: A retrospective review of 441 patients who underwent PCNL between 2018 and 2022 was performed. A total of 4 surgeons were included-surgeon 1 utilized the STR technique while surgeons 2, 3, and 4 used the DTR technique. Anesthetic parameters including end-tidal CO 2 (ETCO 2 ), mean arterial pressure (MAP), peak airway pressure (P peak ), plateau airway pressure (P plat ), positive end-expiratory pressure (PEEP), oxygen saturation (SpO 2 ), and tidal volume (TV) were compared between both groups at 0 (supine), 15-, 30-, and 60-minute post-intubation intervals. Mixed effects regression models with interaction and pairwise comparisons were made between both groups (P <.05)., Results: A total of 581 PCNLs were performed with 199 using STR and 382 using DTR. Surgery duration, ASA class, and age were similar amongst the STR and DTR groups. Estimated blood loss (59cc vs 83cc, P = .007) and length of stay (77 hrs vs 163 hrs, P = <.001) was significantly lower in the STR group. There was a significantly lower P peak , P plat and TV in the STR compared to DTR group at 0, 15, 30, and 60 minutes (P <.001)., Conclusion: Usage of a single transverse chest roll during prone PCNL appears to be a safe positioning method. STR patients had lower P peak and P plat at all time points, which has been shown to be predictive of lower blood loss., Competing Interests: Declaration of Competing Interest Amy E. Krambeck Paid consultant for Ambu, Boston Scientific, Lumenis, Sonomotion, and Virtuoso Surgical. Board member of Sonomotion and Uriprene; Matthew S. Lee Paid consultant for Boston Scientific; the remaining authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Surface-enhanced Raman spectroscopy (SERS) is a powerful technique for discrimination of bimolecules in complex systems. However, its practical applications face challenges such as complicated manufacturing procedures and limited scalability of SERS substrates, as well as poor reproducibility during detection which compromises the reliability of SERS-based analysis. In this study, we developed a convenient method for simultaneous fabrication of massive SERS substrates with an internal standard to eliminate the substrate-to-substrate differences. We first synthesized Au@CN@Au nanoparticles (NPs) which contain embedded internal standard molecules with a single characteristic peak in the Raman-silent region, and then deposited the NPs on 6 mm glass wafers in a 96-well plate simply by centrifugation for 3 min. The one-time obtained 96 SERS substrates have excellent intrasubstrate uniformity and intersubstrate repeatability for SERS detection by using the internal standard (relative standard deviation = 10.47%), and were able to detect both charged and neutral molecules (crystal violet and triphenylphosphine) at a concentration of 10 -9 M. Importantly, cells can be directly cultured on glass wafers in the 96-well plate, enabling real time monitoring of the secretes and metabolism change in response to external stimulation. We found that the release of nucleic acids, amino acids and lipids by MDA-MB-231 cells significantly increased under hypoxic conditions. Overall, our approach enables fast and large-scale production of Au@CN@Au NPs-coated glass wafers as SERS substrates, which are homogeneous and highly sensitive for monitoring trace changes of biomolecules.

We reported herein a visible light mediated de Mayo-type reaction between 1,3-diketones and BCB. The reaction proceeds through a [2π+2σ] cycloaddition and retro-aldol sequence, producing cis-difunctionalized cyclobutanes in high yields with good regio- and diastereoselectivity., (© 2024 Wiley-VCH GmbH.)

Background: To evaluate contemporary preoperative risk factors and subsequent postoperative management of incidental prostate cancer (iPCa) and incidental clinically significant prostate cancer (icsPCa, Grade Group [GG] ≥ 2 PCa)., Methods: A retrospective cohort of 811 men undergoing Holmium enucleation of the prostate (HoLEP) (January 2021-July 2022) were identified. Advanced preoperative testing was defined as prostate health index (PHI), prostate MRI, and/or negative preoperative biopsy. Descriptive statistics (Whitney-Mann U test, Chi-squared test) and multivariable logistic regression were performed., Results: iPCa and icsPCa detection rates were 12.8% (104/811) and 4.4% (36/811), respectively. Advanced preoperative testing (406/811, 50%) was associated with younger age and higher (prostate specific antigen) PSA, prostate volume, and PSA density. On multivariable analysis, PHI ≥ 55 was associated with iPCa (OR 6.91, 95% CI 1.85-26.3, p = 0.004), and % free PSA (%fPSA) was associated with icsPCa (OR 0.83, 95% CI 0.67, 0.94, p = 0.01). GG1 disease comprised the majority of iPCa (65%, 68/104) with median 1% involvement. iPCa patients were followed with active surveillance (median follow up 9.3 months), with higher risk patients receiving prostate MRI and confirmatory biopsy. Three patients proceeded to radical prostatectomy or radiation., Conclusions: In the era of MRI and advanced biomarkers, the majority of iPCa following HoLEP is low volume GG1 suitable for active surveillance. A tentative follow-up strategy is proposed. Patients with PHI ≥ 55 or low %fPSA, even with negative prostate MRI, can consider preoperative prostate biopsy before HoLEP., (© 2024 The Author(s). The Prostate published by Wiley Periodicals LLC.)

Surface modification of graphene-based nanomaterials (GBNs) may occur in aquatic environment and during intentional preparation. However, the influence of the surface groups on the developmental toxicity of GBNs has not been determined. In this study, we evaluated the developmental toxicity of three GBNs including GO (graphene oxide), RGO (reduced GO) and RGO-N (aminated RGO) by employing zebrafish embryos at environmentally relevant concentrations (1-100 μg/L), and the underlying metabolic mechanisms were explored. The results showed that both GO and RGO-N disturbed the development of zebrafish embryos, and the adverse effect of GO was greater than that of RGO-N. Furthermore, the oxygen-containing groups of GBNs play a more important role in inducing developmental toxicity compared to size, defects and nitrogen-containing groups. Specifically, the epoxide and hydroxyl groups of GBNs increased their intrinsic oxidative potential, promoted the generation of ROS, and caused lipid peroxidation. Moreover, a significant decrease in guanosine and abnormal metabolism of multiple glycerophospholipids were observed in all three GBN-treated groups. Nevertheless, GO exposure triggered more metabolic activities related to lipid peroxidation than RGO or RGO-N exposure, and the disturbance intensity of the same metabolite was greater than that of the other two agents. These findings reveal underlying metabolic mechanisms of GBN-induced developmental toxicity., 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.)

Device-to-device (D2D) is a pivotal technology in the next generation of communication, allowing for direct task offloading between mobile devices (MDs) to improve the efficient utilization of idle resources. This paper proposes a novel algorithm for dynamic task offloading between the active MDs and the idle MDs in a D2D-MEC (mobile edge computing) system by deploying multi-agent deep reinforcement learning (DRL) to minimize the long-term average delay of delay-sensitive tasks under deadline constraints. Our core innovation is a dynamic partitioning scheme for idle and active devices in the D2D-MEC system, accounting for stochastic task arrivals and multi-time-slot task execution, which has been insufficiently explored in the existing literature. We adopt a queue-based system to formulate a dynamic task offloading optimization problem. To address the challenges of large action space and the coupling of actions across time slots, we model the problem as a Markov decision process (MDP) and perform multi-agent DRL through multi-agent proximal policy optimization (MAPPO). We employ a centralized training with decentralized execution (CTDE) framework to enable each MD to make offloading decisions solely based on its local system state. Extensive simulations demonstrate the efficiency and fast convergence of our algorithm. In comparison to the existing sub-optimal results deploying single-agent DRL, our algorithm reduces the average task completion delay by 11.0% and the ratio of dropped tasks by 17.0%. Our proposed algorithm is particularly pertinent to sensor networks, where mobile devices equipped with sensors generate a substantial volume of data that requires timely processing to ensure quality of experience (QoE) and meet the service-level agreements (SLAs) of delay-sensitive applications.

The atrophic myocardium resulting from mechanical unloading and nutritional deprivation is considered crucial as maladaptive remodeling directly associated with heart failure, as well as interstitial fibrosis. Conversely, myocardial hypertrophy resulting from hemodynamic loading is perceived as compensatory stress adaptation. We previously reported the abundant presence of highly redox-active polysulfide molecules, termed supersulfide, with two or more sulfur atoms catenated in normal hearts, and the supersulfide catabolism in pathologic hearts after myocardial infarction correlated with worsened prognosis of heart failure. However, the impact of supersulfide on myocardial remodeling remains unclear. Here, we investigated the involvement of supersulfide metabolism in cardiomyocyte remodeling, using a model of adenosine 5'-triphosphate (ATP) receptor-stimulated atrophy and endothelin-1 receptor-stimulated hypertrophy in neonatal rat cardiomyocytes. Results revealed contrasting changes in intracellular supersulfide and its catabolite, hydrogen sulfide (H 2 S), between cardiomyocyte atrophy and hypertrophy. Stimulation of cardiomyocytes with ATP decreased supersulfide activity, while H 2 S accumulation itself did not affect cardiomyocyte atrophy. This supersulfide catabolism was also involved in myofibroblast formation of neonatal rat cardiac fibroblasts. Thus, unraveling supersulfide metabolism during myocardial remodeling may lead to the development of novel therapeutic strategies to improve heart failure., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2024 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Influenza viruses contribute significantly to the global health burden, necessitating the development of strategies against transmission as well as effective antiviral treatments. The present study reports a biomimetic strategy inspired by the natural antiviral properties of mucins. A bovine serum albumin (BSA) conjugate decorated with the multivalent neuraminidase inhibitor Zanamivir (ZA-BSA) was synthesized using copper-free click chemistry. This synthetic pseudo-mucin exhibited potent neuraminidase inhibitory activity against several influenza strains. Virus capture and growth inhibition assays demonstrated its effective absorption of virion particles and ability to prevent viral infection in nanomolar concentrations. Investigation of the underlying antiviral mechanism of ZA-BSA revealed a dual mode of action, involving disruption of the initial stages of host-cell binding and fusion by inducing viral aggregation, followed by blocking the release of newly assembled virions by targeting neuraminidase activity. Notably, the conjugate also exhibited potent inhibitory activity against Oseltamivir-resistant neuraminidase variant comparable to the monomeric Zanamivir. These findings highlight the application of multivalent drug presentation on protein scaffold to mimic mucin adsorption of viruses, together with counteracting drug resistance. This innovative approach has potential for the creation of antiviral agents against influenza and other viral infections., 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.)

Objective: The mechanism of left ventricular outflow tract obstruction (LVOTO) is complex in hypertrophic cardiomyopathy (HCM). We aimed to evaluate the impact of mitral valve geometry on LVOTO by echocardiography., Materials and Methods: The study population comprised 177 consecutive patients with HCM. Morphological findings of left ventricular hypertrophy and LVOTO-related abnormalities were assessed by comprehensive transthoracic echocardiography. Aortomitral angle, mitral leaflet length, and coaptation height were measured and analyzed at rest. Multivariable stepwise forward logistic regression analysis was performed to identify geometric predictors of LVOTO., Results: One hundred thirty-seven patients had an LVOT gradient ≥30 mm Hg. Multivariable logistic regression showed that aortomitral angle (odds ratio [OR], 0.89; 95% CI, 0.83-0.95, P < .001), coaptation height (OR, 1.96; 95% CI, 1.41-2.72, P < .001), and accessory mitral valve chordae tendineae (OR, 13.1; 95% CI, 4.32-39.95; P < .001) were independently associated with LVOTO. Receiver operating characteristic analysis showed that the area under the curve of mitral coaptation height was higher (area under the curve = 0.815) than the other 2 indicators (P < .05)., Conclusion: Mitral coaptation height, aortomitral angle, and accessory mitral valve chordae tendineae were important predictors of SAM and LVOTO in HCM independent of septal hypertrophy., Competing Interests: Disclosures None., (Copyright © 2024 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Mitogen-activated protein kinase (MAPK) cascade is the center of plant signal transduction system that amplify immune signals into cellular responses by phosphorylating diverse substrates. The MAPK cascade consisting of MAPK kinase kinases (MAPKKKs), MAPK kinases (MAPKKs), and MAPKs is well characterized in plants, in which Raf-like kinases are generally regarded as MAPKKKs. However, it is rarely reported that Raf-like MAPKKKs function as middle regulators to link MAPK and its downstream transcription factors in plant immunity. Verticillium wilt, caused by the soil-borne vascular fungus Verticillium dahliae, is a serious disease in many plants, including cotton. The previous studies showed that GhMPK9 (a MAPK) is involved in the response to Verticillium wilt. Here, the Raf-like kinase GhRAF39&#95;1 is reported as helper regulates the phosphorylation of WRKY transcription factor GhWRKY40a by GhMPK9. The phosphorylated GhWRKY40a can further activate the transcription of GhERF1b to up-regulate defense-related genes while inhibit the transcription of GhABF2 to regulate the stomatal opening, thus improving the resistance to Verticillium wilt in cotton. This study reveals a new signaling module of GhMPK9-GhRAF39&#95;1-GhWRKY40a to regulate GhERF1b- and GhABF2-mediated defense responses, which triggers plant defense against Verticillium wilt., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Engineering a catalytic membrane capable of efficiently removing emerging organic microcontaminants under ultrahigh flux conditions is of significance for water purification. Herein, drawing inspiration from the functional attributes of lymphatic vessels involved in immunosurveillance and fluid transport with minimal energy consumption, a novel hierarchical porous catalytic membrane is engineered. This membrane, based on an innovative nitrogen-rich conjugated microporous polymer (polytripheneamine, PTPA), is synthesized using an electrospinning coupled in situ polymerization approach. The resulting bioinspired membrane with hierarchical channels comprises a thin layer (≈1.7 µm) of crosslinked PTPA nanoparticles covering the interconnected electrospun nanofibers. This unique design creates an intrinsic microporous angstrom-confined system capable of activating peroxymonosulfate (PMS) to generate 98.7% singlet oxygen ( 1 O 2 ), enabling durable and highly efficient degradation of microcontaminants. Additionally, the presence of a thin layer of mesoporous structure between PTPA nanoparticles and macroporous channels within the interwoven nanofibers enhances mass transfer efficiency and facilitates high flux rates. Notably, the prepared hierarchical porous organic catalytic membrane demonstrates enduring high-efficiency degradation performance with a superior permeance (>95% and >2500 L m -2 h -1 bar -1 ) sustained over 100 h. This work introduces an innovative pathway for the design of high-performance catalytic membranes for the removal of emerging organic microcontaminants., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Aims: Atrial fibrillation (AF) is the most common arrhythmia. Heart failure (HF) is a disease caused by heart dysfunction. The prevalence of AF and HF were progressively increasing over time. The co-existence of AF and HF presents a significant therapeutic challenge. In order to provide new ideas for the diagnosis of AF and HF, it is necessary to carry out biomarker related studies., Methods and Results: The training set and validation set data of AF and HF patient samples were downloaded from the GEO database, 'limma' was used to compare the differences in gene expression levels between the disease group and the normal group to screen for differentially expressed genes (DEGs). Weighted correlation network analysis (WGCNA) identified the modules with the highest positive correlation with AF and HF. Functional enrichment and PPI network construction of key genes were carried out. Biomarkers were screened by machine learning. The infiltration of immune cells in AF and HF groups was evaluated by R-packet 'CIBERSORT'. The miRNA network was constructed and potential therapeutic agents for biomarker genes were predicted through the drugbank database. Through WGCNA analysis, it was found that the modules most positively correlated with AF and HF were MEturquoise (r = 0.21, P value = 0.09) and MEbrown (r = 0.62, P value = 8e-12), respectively. We screened 25 genes that were highly correlated with both AF and HF. Lasso regression analysis results showed 7 and 20 core genes in AF and HF groups, respectively. The top 20 important genes in AF and HF groups were obtained as core genes by RF model analysis. Four biomarkers were obtained after the intersection of core genes in four groups, namely, GLUL, NCF2, S100A12, and SRGN. The diagnostic efficacy of four genes in AF validation sets was good (AUC: GLUL 0.76, NCF2 0.64, S100A12 0.68, and SRGN 0.76), as well as in the HF validation set (AUC: GLUL 0.76, NCF2 0.84, S100A12 0.92, and SRGN 0.68). The highest correlation with neutrophils was observed for GLUL, NCF2, and S100A12, while SRGN exhibited the strongest correlation with T cells CD4 memory resting in the AF group. GLUL, NCF2, S100A12, and SRGN were most associated with neutrophils in the HF group. A total of 101 miRNAs were predicted by four genes, and GLUL, NCF2, and S100A12 predicted a total of 10 potential therapeutic agents., Conclusions: We identified four biological markers that are highly correlated with AF and HF, namely, GLUL, NCF2, S100A12, and SRGN. Our findings provide theoretical basis for the clinical diagnosis and treatment of AF and HF., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)