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Tricyclazole is commonly used to prevent rice blast to meet the carbohydrate intake needs of half of the global population, and a large number of toxicological reports indicate that monitoring of tricyclazole is necessary. Here, we analyzed the structure of tricyclazole and designed different hapten derivatization strategies to prepare a high-performance monoclonal antibody (half inhibition concentration of 1.61 ng/mL), and then a lateral flow immunochromatographic sensor based on gold nanoparticles for the detection of tricyclazole in rice, with a limit of detection of 6.74 μg/kg and 13.58 μg/kg in polished and brown rice, respectively. The recoveries in rice were in the range of 84.6-107.4%, no complex pretreatment was required for comparison with LC-MS/MS, and the comparative analysis demonstrated that our method had good accuracy and precision. Therefore, the developed lateral flow immunochromatographic analysis was a reliable and rapid means for the on-site analysis of tricyclazole in rice., 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.)

Dynamic therapy response is strongly associated with cancer outcomes. This study aimed to evaluate the significance of longitudinal Epstein-Barr virus (EBV) DNA and radiological tumor regression in risk stratification and response-adaptive treatment in locally-advanced nasopharyngeal carcinoma (LA-NPC). In total, 1312 patients from two centers were assigned to the training and validation cohorts. Based on the multipoint examination of EBV-DNA and tumor response, four post-induction chemotherapy, four mid-radiotherapy, and four post-radiotherapy subgroups were established. Then seven phenotypes were further generated according to different permutations and combinations. These phenotypes were subsequently congregated into four response clusters, which reflect distinct biological treatment responses. The four response clusters correlated with an evident 5-year progression-free survival in both the training and external validation cohorts (5-year: training cohort 91.1 %, 82.8 %, 30.6 %, and 10.0 %; external validation 94.4 %, 55.6 %, 40.0 %, and 12.7 %) had superior prognostic performance compared to TNM staging and nomogram model (concordance index: training cohort-0.825 vs. 0.603 vs. 0.756 and external validation-0.834 vs. 0.606 vs. 0.789). Importantly, the response clusters exhibited an excellent capability in selecting candidates who can benefit from adjuvant chemotherapy. In conclusion, risk stratification based on the dynamic assessment of both radiological and biological responses can significantly enhance prognostic insights and shed light on individualized treatment modifications in LA-NPCs., 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.)

Aims: This research sought to assess the efficacy of Bacillus subtilis (B. subtilis) R0179 and explore potential metabolites in mitigating experimental periodontitis in mice induced by Porphyromonas gingivalis (P. gingivalis) ATCC 33277., Methods: B. subtilis R0179 was administered to 8-week-old male C57BL/6J mice with periodontitis. Oral load of P. gingivalis ATCC 33277 and periodontal tissue loss were quantified. The cell-free supernatant (CFS) was separated to assess its anti-P. gingivalis effect. Proteomic and metabolomic analyses identified potential antibacterial components in the CFS, further evaluated for anti-P. gingivalis effects., Results: B. subtilis R0179 significantly reduced P. gingivalis ATCC 33277 levels and mitigated periodontal tissue loss in mice. The CFS, rather than inactivated B. subtilis R0179 cells, exhibited antibacterial activity. Proteomic and metabolomic analyses identified mesaconate and citraconate as key antibacterial agents. Disk diffusion assays confirmed the efficacy of mesaconate against P. gingivalis, while citraconate had no effect. Mesaconate showed a dose-dependent reduction in P. gingivalis ATCC 33277 population and periodontal tissue loss in mice., Conclusion: These findings highlight B. subtilis R0179 and its metabolite mesaconate as promising candidates for therapeutic development against periodontitis by inhibiting P. gingivalis ATCC 33277 effectively., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Light signaling plays a substantial role in regulating plant development, including the differentiation and elongation of single-celled tissue. However, the identity of the regulatory machine that affects light signaling on root hair cell (RHC) development remains unclear. Here, we investigated how darkness inhibits differentiation and elongation of RHC in Arabidopsis (Arabidopsis thaliana). We found that light promotes the growth and development of RHC. RNA-seq analysis showed that light signaling regulates the differentiation of RHC by promoting the expression of specific genes in the root epidermis associated with cell wall remodeling, JA, auxin, and ethylene signaling pathways. Together, these genes integrate light and phytohormone signals with root hair development. Our investigation also revealed that the core light signal factor ELONGATED HYPOCOTYL 5 (HY5) directly interacts with the key root hair development factor ROOT HAIR DEFECTIVE6 (RHD6), which promotes the transcription of RSL4. However, CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) repressed RHD6 function through the COP1-HY5 complex. Our genetic studies confirm associations between RHD6, HY5, and COP1, indicating that RHD6 largely depends on HY5 for root hair development. Ultimately, our work suggests a central COP1-HY5-RHD6 regulatory module that integrates light signaling and root hair development with several downstream pathways, offering perspectives to decipher single-celled root hair development., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Sodium sulfide (Na 2 S) as an initial cathode material in room-temperature sodium-sulfur batteries is conducive to get rid of the dependence on Na-metal anode. However, the micron-sized Na 2 S that accords with the practical requirements is obstructed due to poor kinetics and severe shuttle effect. Herein, a subtle strategy is proposed via regulating Na 2 S redeposition behaviours. By the synergistic effect from both conductive structure and cuprous sulfide (Cu 2 S) catalysis, the micron-sized Na 2 S particles are broken down and redeposited to nano-size during the initial cycle which can be fully utilized in subsequent cycles. Consequently, the Na 2 S/CPVP@Cu 2 S||Na cell delivers excellent cyclability (670 mAh g S -1 after 500 cycles) with a remarkable average Coulombic efficiency over 99.7% and rate capability (480 mAh g S -1 at 4 A g S -1 ). Besides, the Na-free anodes are used to prove the application prospects. This work provides an innovative idea for utilizing micron-sized Na 2 S and offers insights into its conversion pathway., Competing Interests: Competing interests The authors declare no competing interest., (© 2024. The Author(s).)

Background: The association of lipid-lowering drug targets and their gene variants with cardiovascular diseases has been previously clarified. However, the relationship between gene variants of lipid-lowering drug targets and the adverse prognosis of ischemic stroke patients remains unclear., Methods and Results: Multiple single-nucleotide polymorphisms associated with 6 lipid-lowering drug targets were genotyped for patients with ischemic stroke. The primary outcome was death or major disability within 2 years after ischemic stroke. Genetic risk score was constructed from significant single-nucleotide polymorphisms identified via additive models, which was calculated by multiplying the number of risk alleles at each locus by the corresponding beta coefficient and then summing the products. The rs2006760-C of the HMGCR , rs11206510-T of PCSK9 , and rs1864163-G and rs9929488-G of CETP were associated with increased odds of adverse outcomes within 2 years after ischemic stroke. Each additional risk allele was associated with higher odds of adverse outcomes. Genetic risk score was positively associated with the odds of primary outcome (odds ratio [OR], 1.48 [95% CI, 1.15-1.90]; P trend  = 0.001), major disability (OR, 1.56 [95% CI, 1.16-2.08]; P trend  = 0.002), death (hazard ratio [HR], 1.58 [95% CI, 1.12-2.25]; P trend  = 0.011), and the composite outcome of death or cardiovascular events (HR, 1.41 [95% CI, 1.08-1.85]; P trend  = 0.010) when 2 extreme quartiles were compared., Conclusions: rs2006760-C of HMGCR , rs11206510-T of PCSK9 , and rs1864163-G and rs9929488-G of CETP were associated with increased odds of adverse outcomes within 2 years after ischemic stroke. Furthermore, higher GRS was positively related to the odds of poor outcomes in patients with ischemic stroke. Registration: URL: https://www.clinicaltrials.gov; Identifier: NCT01840072.

Aluminum-based adjuvants have been indispensable to vaccine potency. However, their effectiveness is difficult to maintain after freeze-drying, which limits the storage and application of aluminum-adjuvanted vaccines. In this study, the impact of freeze-drying on aluminum oxyhydroxide nanorods (AlOOH NRs) was investigated. Freeze-drying led to aggregation and resulted in the loss of the surface hydroxyl content of aluminum adjuvants. To alleviate freeze-drying-induced damage, the potency of different alkyl glycosides as protectants was further evaluated. It was demonstrated that the structural balance of the head and tail of a glycoside was more conducive to protecting AlOOH NRs from aggregation and loss of surface hydroxyl groups. These results underline the proper selection of protectants to protect adjuvants against functional defects caused by freeze-drying, which is important for the stability and efficacy of vaccines and biopharmaceutical products.

Competing Interests: Declarations Conflict of interest The authors declare no competing interests. Ethical approval This article was approved by the ethics committee of Children’s Hospital, Zhejiang University School of Medicine (2023-IRB-0284-P-01). Informed consent Written informed consent was obtained from the parents of the patient for the publication of information and imaging findings.

Piezoelectric materials, renowned for their ability to convert mechanical energy into electrical energy, have gained attention for their potential in biomedical applications. In particular, piezoelectric nanoparticles, such as barium titanate nanoparticles, hold great promise for treating neurologically related diseases. In this study, barium titanate piezoelectric nanoparticles are used as stimulators to directly treat epileptic neurons. After being modified by polyethylene glycol, barium titanate nanoparticles have shown excellent biocompatibility and dispersibility. Furthermore, such nanoparticles offer wireless piezoelectric stimulation to neurons in response to low-intensity pulsed ultrasound. More importantly, our experiments reveal that piezoelectric stimulation immediately reduces neuronal intracellular calcium concentration and restores cell viability. These effects are attributed to the opening of voltage-gated calcium channels and the release of active substances. These findings offer insights into the potential of piezoelectric stimulation as an approach for epilepsy treatment and enhance our understanding of the mechanisms underlying electrical stimulation in epileptic neurons.

Background: Cnidii Fructus (CF) is a herbal medicine with pharmacological activities such as antitumor, antiviral, antiallergic, antipruritic effects, and so on., Objective: In this study, an ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC- MS/MS) method was prepared and verified to measure the concentrations of seven analytes (bergapten, xanthotoxol, xanthotoxin, imperatorin, osthole, isopimpinellin, isoimperatorin) in HepG2 cells., Methods: The separation of seven analytes was performed on an ACQUITY UPLC® BEH C18 column (2.1×100 mm, 1.7 μm) with a gradient mobile phase system of 0.1% formic acid/water and acetonitrile., Results: The CV of analytes was within 7.77%, and the bias was in the range of -5.43%-3.84%. The matrix effects of analytes ranged from 92.95% to 104.58%, and the extraction recoveries ranged from 76.45% to 104.69%. The relative standard deviation of stability results was less than 8.21%, indicating that seven analytes were stable., Conclusion: The method was successfully applied to the determination of the content of seven analytes of CF extracts by UPLC-MS/MS, and the results will provide a reference for the cellular pharmacokinetics of CF., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: The precise segmentation of kidneys from a 2D ultrasound (US) image is crucial for diagnosing and monitoring kidney diseases. However, achieving detailed segmentation is difficult due to US images' low signal-to-noise ratio and low-contrast object boundaries., Methods: This paper presents an approach called deep supervised attention with multi-loss functions (MLAU-Net) for US segmentation. The MLAU-Net model combines the benefits of attention mechanisms and deep supervision to improve segmentation accuracy. The attention mechanism allows the model to selectively focus on relevant regions of the kidney and ignore irrelevant background information, while the deep supervision captures the high-dimensional structure of the kidney in US images., Results: We conducted experiments on two datasets to evaluate the MLAU-Net model's performance. The Wuerzburg Dynamic Kidney Ultrasound (WD-KUS) dataset with annotation contained kidney US images from 176 patients split into training and testing sets totaling 44,880. The Open Kidney Dataset's second dataset has over 500 B-mode abdominal US images. The proposed approach achieved the highest dice, accuracy, specificity, Hausdorff distance (HD95), recall, and Average Symmetric Surface Distance (ASSD) scores of 90.2%, 98.26%, 98.93%, 8.90 mm, 91.78%, and 2.87 mm, respectively, upon testing and comparison with state-of-the-art U-Net series segmentation frameworks, which demonstrates the potential clinical value of our work., Conclusion: The proposed MLAU-Net model has the potential to be applied to other medical image segmentation tasks that face similar challenges of low signal-to-noise ratios and low-contrast object boundaries., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The authors state that they have no known competing financial interests or close personal ties that could have influenced the research work presented in this paper., (© The Author(s) 2024.)

A quantitative structure-activity relationship (QSAR) study was conducted on 313 pesticides to predict their acute toxicity to Sheepshead minnow (Cyprinodon variegatus) by using DRAGON descriptors. Essentials accounting for a reliable model were all considered carefully, giving full consideration to the OECD (Organization for Economic Co-operation and Development) principles for QSAR acceptability in regulation during the model construction and assessment process. Nine variables were selected through the forward stepwise regression method and used as inputs to construct both linear and nonlinear models. The obtained models were validated internally and externally. Generally, machine learning-based methods, namely support vector machine (SVM), random forest (RF), and projection pursuit regression (PPR), perform better than the multiple linear regression (MLR) model. The statistical results (R 2  = 0.682-0.933, Q 2 LOO  = 0.604-0.659, Q 2 F1  = 0.740-0.796, CCC = 0.861-0.882) of the developed models show that they are robust, reliable, reproducible, accurate and predictive. Comparatively, the RF model performs best, giving predictive correlation coefficient Q 2 of 0.814, root mean squared error (RMSE) of 0.658 and mean absolute error (MAE) of 0.534 for the test set, respectively. The RF model (as well as SVM and PPR models) was visualized and explained by using the SHapley Additive explanation (SHAP) analysis to enhance its transparency and credibility. In addition, the applicability domain (AD) range of the RF model was characterized by the Williams plot and the tree manifold approximation and projection (TMAP) technology was utilized to illustrate similarity and diversity of the entire data space, to assist in the analysis of the outliers. Activity cliff detection was investigated by using Arithmetic Residuals in K-groups Analysis (ARKA) descriptors. It was found that none of the pesticides was identified as an activity cliff in the training set or a potential prediction cliff in the test set. Therefore, the RF model fulfills each OECD principle in regulation for QSAR models. The research in this work will aid in the in silico QSAR prediction of the acute toxicity to Sheepshead minnow (Cyprinodon variegatus) for untested and new toxic pesticides and can also be extended to other studies., 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.)

Objectives: Frailty is a heterogeneous syndrome with distinct patterns. This study aimed to identify frailty risk patterns and their predictive value for mortality in older adults., Design: Prospective longitudinal study., Setting and Participants: Data were obtained from a 2017 survey of 609 independently mobile adults aged 65 years and older in suburban Japan, focusing on those at risk for at least 1 frailty dimension., Methods: Frailty assessments were extracted from the Kihon checklist, and subgroups were identified using latent class analysis. Associations between frailty patterns and 3-year mortality were assessed using Kaplan-Meier survival analysis and Cox proportional hazards modeling., Results: Three frailty patterns were identified: "high risk of cognitive impairment" (76.0%), "moderate risk of cognitive, physical, and oral dysfunction" (14.3%), and "high risk of cognitive, physical, and functional decline" (9.7%). We recorded 52 deaths during a mean follow-up time of 25.7 months (standard deviation: 12.6) and a median follow-up time of 26.5 months. Kaplan-Meier analysis showed significant survival differences among the groups (log-rank: P < .001). Compared with the high risk of cognitive impairment group, the moderate risk of cognitive, physical, and oral dysfunction group had a 145% higher mortality risk (adjusted hazard ratio, 2.45; 95% confidence interval, 1.22-4.90), while the high risk of cognitive, physical, and functional decline group exhibited a 220% higher risk of mortality (adjusted hazard ratio, 3.20; 95% confidence interval, 1.53-6.70)., Conclusions and Implications: The findings reveal the heterogeneity of frailty among community-dwelling Japanese older adults, with a high prevalence of cognitive impairment risk. The subgroup with risk of cognitive, physical, and functional decline had the highest mortality risk, highlighting the need for multidimensional assessment and intervention., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: The high costs associated with biological agents often limit accessibility for many patients, whereas biosimilars allow the wider application of biological treatment. The objectives of this phase I clinical trial were to compare the pharmacokinetics, immunogenicity, and safety profiles of the biosimilar adalimumab-WIBP and the reference product Humira ® and to assess the precision of the bioequivalence evaluation., Methods: In this randomized, double-blind, parallel-group bioequivalence study, 164 healthy male Chinese participants were selected and randomly divided into two groups on a 1:1 ratio. The subjects were administered a single 40 mg subcutaneous dose of either adalimumab-WIBP or Humira ® . Blood samples extracted at multiple intervals after administration were analyzed to interpret pharmacokinetic parameters, and any adverse events were documented. Alongside ensuring safety measures, the subjects were monitored for immunogenicity., Results: The pharmacokinetic results demonstrated similar serum concentration-time curves in both groups. There were no significant differences in safety and no differences in immunogenicity profiles between the two groups. The bioequivalence was confirmed: the 90% confidence interval for the geometric mean ratio of the main pharmacokinetic parameters was within the range of 80-125%., Conclusion: The trial indicated the bioequivalence between adalimumab-WIBP and the reference product Humira ® based on pharmacokinetics, immunogenicity, and safety profile. These findings reinforce the use of the adalimumab-WIBP biosimilar as a possible therapeutic alternative to Humira ® ., Competing Interests: Declarations Conflict of interest Lu Yang, Xin Yue, Jiayou Zhang, Zejun Wang, and Yongbing Pan are employees of Wuhan Institute of Biological Products Co. Ltd., Wuhan, China. Funding This research was funded by the Wuhan Institute of Biological Products Co. Ltd., Wuhan, China. Human ethics approval declaration This study was conducted in line with the International Conference on Harmonization Standards for Good Clinical Practice, the Helsinki Declaration, and relevant national or international regulatory requirements. The study protocol was reviewed and approved by the hospital ethics committee (approval number: GCP-ICT-2019-28.01, approval date: May 13, 2019) and was registered at NMPA (CXSL1800014). Consent to participate Informed consent was obtained from all patients before undergoing any research procedures. Consent for publication Not applicable. Code availability Not applicable. Data availability Statement The datasets used in this study can be obtained from the corresponding author upon request. Author contributions All authors made a significant contribution to the work reported, whether that was in the conception, study design, execution, acquisition of data, analysis and interpretation or in all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agreed to be accountable for all aspects of the work., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The Pacific saury (Cololabis saira) is a pelagic fish commonly found in the North Pacific Ocean. Its population diversity and migratory lifestyle have long captured global attention. Despite the inherent complexity of the C. saira genome, characterized by extremely high heterozygosity, we successfully assembled a phased chromosome-level genome. The genome analysis revealed the expansion and natural selection of numerous functional genes, likely contributing to its enduring and extensive migratory lifestyle. Notably, gpr35 and igh genes showed significant expansion in the C. saira genome, potentially associated with regulating the immune response against environmental parasites and pathogens. Moreover, genes involved in DNA repair/replication and peroxisome function, including atm, ercc6, pex14, and pex16, displayed evidence of positive selection. Based on genome-sequencing of 80 individuals from eight sampling sites, we demonstrated that the genomic divergence among C. saira populations is relatively low. However, the sampling sites could be grouped into two distinct clusters, roughly corresponding to the migratory route of C. saira. This suggests a possible genome-wide divergence for C. saira within the open ocean region. Furthermore, the trmu gene, responsible for controlling otolith development and sharpness, exhibited differentiation between the two groups, consistent with previously reported differences in otolith morphology. This study has provided a reference genome and insights into the evolution, ecology, and conservation of Pacific saury and closely-related species., Competing Interests: Competing interests The authors declare no competing of interests, (© 2024. The Author(s).)

Unravelling the volcanic history of the enigmatic lunar farside is essential for understanding the hemispheric dichotomy of the Moon 1-3 . Cratering chronology established for the lunar nearside has been used to suggest long-lived volcanism on the farside of the Moon 3,4 , but without sample verification. Here we report two newly recognized episodes of basaltic volcanism with Pb-Pb dating for basalt fragments returned by the Chang'e-6 mission. One high-Al basalt fragment dated at 4,203 ± 4 million years ago (Ma) has a source 238 U/ 204 Pb ratio (µ value) of ~1,620, implying a KREEP-rich (K, rare earth elements, and P) source for this oldest-known occurrence of basaltic volcanism among returned samples. The main volcanic episode of the Chang'e-6 basalt documents a surprisingly young eruption age of 2,807 ± 3 Ma, which is not recognized from the nearside of the Moon. The initial Pb isotope compositions of these younger basalts indicate derivation from a source with a µ value of ~360, indicating a KREEP-poor mantle source. Mare volcanism on the lunar farside thus persisted for >1.4 billion years even with a shift to a source depleted in heat-producing elements. The consistency between the 2.8-billion-year basalt age and its crater-counting age indicates that the cratering chronology model established for the lunar nearside is also applicable to the farside of the Moon., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

An effective route to diameter-controlled single-walled carbon nanotubes (SWCNTs) remains elusive. The use of organic templates to precisely control the diameter of the resulting nanotubes holds great promise in this regard but has hitherto had very limited practical success. A main obstacle is the limited availability of suitable organic templates. Here, we report the diameter-controlled bottom-up synthesis of SWCNTs with elaborately designed [2 n ]collarenes, hydrocarbon belts consisting of alternating phenylene and 1,4-cyclohexadiene rings, as rigid organic templates. A new approach has been developed to construct these collarenes, which are then used as templates in the bottom-up growth of SWCNTs. The resulting SWCNTs exhibit narrow diameter distributions, matching the diameters of the employed collarene templates. This work greatly propels the synthesis of diameter-controlled SWCNTs.

Objectives: To investigate whether the signal intensity (SI) ratio of residual fibroid (RF) to myometrium using Contrast-Enhanced Magnetic Resonance Imaging (CE-MRI) could predict fibroid regrowth after high-intensity focused ultrasound (HIFU) treatment., Materials and Methods: A retrospective analysis was conducted among 164 patients with uterine fibroids who underwent HIFU. To predict the RF regrowth, the SI perfusion parameters were quantified using the RF-myometrium SI ratio on CE-MRI on day 1 post-HIFU and then compared with the fibroid-myometrium SI ratio on the T2-weighted image (T2WI) and Funaki classification 1 year later. Thirty cases from another center were used as an external validation set to evaluate the performance of RF-myometrium SI ratio., Results: The predictive performance of the RF-myometrium SI ratio on CE-MRI on day 1 post-HIFU (Area Under Curve, AUC: 0.869) was superior to that of the preoperative and postoperative fibroid-myometrium SI ratios on the T2WI (AUC: 0.724, 0.696) and Funaki classification (AUC: 0.663, 0.623). Multivariate analysis showed that the RF- myometrium SI ratio and RF thickness were independent factors. The RF-myometrium SI ratio reflects the long-term rate of re-intervention (r = 0.455, p < 0.001)., Conclusion: The RF-myometrium SI ratio on CE-MRI exhibits greater accuracy in predicting RF regrowth compared to the SI classification and the SI ratio on T2WI., Critical Relevance Statement: The ratio of residual uterine fibroid to myometrial signal intensity on contrast-enhanced (CE)-MRI can reflect residual blood supply, predict regrowth of fibroids, and thus reflect long-term re-intervention rate and recovery situation of clinical high-intensity focused ultrasound (HIFU) treatment., Key Points: Contrast-enhanced (CE)-MRI can indicate the blood supply of residual uterine fibroids after high-intensity focused ultrasound (HIFU) treatment. The predictive capability of CE-MRI ratio surpasses T2WI ratio and the Funaki. Residual fibroids can serve as a measure of the long-term efficacy of HIFU., Competing Interests: Declarations Ethics approval and consent to participate This study conformed to the Declaration of Helsinki on Human Research Ethics standards and was approved by the institutional review board of the Chongqing Haifu Hospital (HF2023-011). The need for written, informed consent was waived. Consent for publication All the authors consented to the publication of this article. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Thuggacin A ( 1 ) is a 17-membered-ring-polyketide antibiotic compound with excellent antituberculosis activity. The total synthesis of thuggacin A has not yet been reported so far. Herein, we disclose our efforts toward the convergent total synthesis of thuggacin A. The key synthetic features include our own one-pot cascade thiazole formation, Evans syn -aldol, Mukaiyama asymmetric aldol reaction, organosilicon-promoted selective alkyne reduction, Shiina macrolactonization, and a nucleophilic ring-opening of epoxide with alkyne to assemble the main framework of thuggacin A. The enantioselective synthesis of trimethylsilyl ethoxymethyl (SEM) derived thuggacin A analogue 2 was achieved in 18 longest linear steps with 2.0% overall yield, and the bioassay of 2 exhibited moderate antituberculosis activity with minimum inhibitory concentration (MIC) of 320 μg/mL.

Objective: To review research progress on the design, manufacturing, and clinical application of three-dimensional (3D) printed customized prosthesis in acetabular reconstruction of hip revision surgery., Methods: The related research literature on 3D printed customized prosthesis and its application in acetabular reconstruction of hip revision surgery was searched by key words of "3D printed customized prosthesis", "revision hip arthroplasty", "acetabular bone defect", and "acetabular reconstruction" between January 2013 and May 2024 in Chinese and English databases, such as CNKI, Wanfang database, PubMed, etc . A total of 34 271 articles were included. After reading the literature titles, abstracts, or full texts, the literature of unrelated, repetitive, low-quality, and low evidence level was screened out, and a total of 48 articles were finally included for analysis and summary., Results: The bone growth and mechanical properties of 3D printed customized prosthesis materials are better than those of non-3D printed customized prosthesis, which further solves the problem of elastic modulus mismatch between the implant and natural bone caused by "stress shielding"; the porous structure and antibacterial coating on the surface of 3D printed customized prosthesis have good anti-bacterial effect. 3D printed customized prosthesis can perfectly match the patient's individual acetabular anatomical characteristics and defect type, thus improving the accuracy of acetabular reconstruction and reducing the surgical time and trauma., Conclusion: 3D printed customized prosthesis can be used for precise and efficient individualized acetabular reconstruction in hip revision surgery with good early- and mid-term effectiveness. More optimized production technics and procedures need to be developed to improve the efficiency of clinical application and long-term effectiveness.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of preterm infants, with its incidence rising due to improved survival rates of these infants. BPD results from a combination of prenatal and postnatal factors, such as mechanical ventilation, oxygen toxicity, and infections, all of which significantly impact the prognosis and growth of affected infants. Current treatment options for BPD are largely supportive and do not address the underlying pathology. Exosomes are cell-derived bilayer-enclosed membrane structures enclosing proteins, lipids, RNAs, growth factors, cytokines and metabolites. They have become recognized as crucial regulators of intercellular communication in various physiological and pathological processes. Previous studies have revealed the therapeutic potential of human umbilical cord mesenchymal stem cells-derived exosomes (HUCMSCs-Exos) in promoting tissue repair and regeneration. Therefore, HUCMSCs-Exos maybe a promising and effective therapeutic modality for BPD. In this review, we firstly provide a comprehensive overview of BPD, including its etiology and the mechanisms of lung injury. Then we detail the isolation, characterization, and contents of HUCMSCs-Exos, and discuss their potential mechanisms of HUCMSCs-Exos in BPD treatment. Additionally, we summarize current clinical trials and discuss the challenges in translating these findings from bench to bedside. This review aims to lay the groundwork for future clinical applications of HUCMSCs-Exos in treating BPD., Competing Interests: Declaration of competing interest HL and XL are co-corresponding authors. The other authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Traditional fungi β-glucan commonly possesses high molecular weight with poor water solubility, which remains significant challenge in the drug development and medical application. Water-soluble β-glucan with high molecular weight (dHSCG) of 560 kDa, low molecular weight (dLSCG) of 60 kDa, and sulfated derivative (SCGS) with a molecular weight of 146 kDa and sulfate degree at 2.04 were obtained through well-controlled degradation and sulfated modification from Saccharomyces cerevisiae in this study. The structural characteristics were confirmed as β-1,3/6-glucan by FT-IR and NMR spectroscopy. Carbohydrate microarrays and surface plasmon resonance revealed distinct and contrasting binding affinities between the natural β-glucans and sulfated derivatives. SCGS exhibited strong binding to FGF and VEGF, while natural β-glucan showed no response, suggesting its potential as a novel antitumor agent. Moreover, SCGS significantly inhibited the migration rate of the highly metastatic melanoma (B16F10) cells. The lung metastasis mouse model also demonstrated that SCGS significantly reduced and eliminated the nodules, achieving an inhibition rate of 86.7% in vivo, with a dramatic improvement in IFN-α, TNF-α, and IL-1β levels. Through analysis of protein content and distribution in lung tissues, the anti-tumor and anti-metastasis mechanism of SCGS involves the regulation of degrading enzymes to protect extracellular matrix (ECM), as well as the reduction of angiogenic factor release. These findings provide a foundation for exploring the potential of SCGS in the development of new anti-tumor and anti-metastasis drugs and open up a new field in cancer research., 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.)

Background/aims: : The occurrence and development of circular RNAs in gastric cancer (GC) has attracted increasing attention. This study focused on investigating the biological role and molecular mechanism of circ&#95;0043947 in GC., Methods: : The expression levels of circ&#95;0043947, miR-384 and CAMP response element binding protein (CREB1) were determined by quantitative real-time polymerase chain reaction or Western blotting. Cell proliferation, migration, and invasion, the cell cycle and apoptosis were determined using a cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, colony formation assay, wound healing assay, transwell assay, and flow cytometry assay. The interaction between miR-384 and circ&#95;0043947 or CREB1 was verified by dual-luciferase reporter assay and RNA pull-down assay. The in vivo assay was conducted using a xenograft mouse model., Results: : Circ&#95;0043947 and CREB1 expression levels were significantly upregulated, whereas miR-384 expression levels were downregulated in GC tissues and cells. Functionally, knockdown of circ&#95;0043947 inhibited cell proliferation, migration and invasion and induced G0/G1 phase arrest and apoptosis in vitro . Circ&#95;0043947 could upregulate CREB1 expression by directly sponging miR-384. Rescue experiments showed that a miR-384 inhibitor significantly reversed the inhibitory effect of si-circ&#95;0043947 on GC progression, and CREB1 overexpression significantly reversed the inhibitory effect of miR-384 mimics on the progression of GC cells. Furthermore, silencing of circ&#95;0043947 inhibited tumor growth in vivo ., Conclusions: : Circ&#95;0043947 acted as an oncogenic factor in GC to mediate GC cell proliferation, migration, and invasion, the cell cycle and apoptosis by regulating the miR-384/CREB1 axis. Circ&#95;0043947 may be a potential target for GC diagnosis and therapy.

MAF bZIP transcription factor G (MAFG)-driven astrocytes have been reported to promote inflammation in the CNS. However, its function in depression, the primary cause of disability worldwide, has not been well characterized. This study investigated the possible perturbation of heme oxygenase 1 (HMOX1, also known as HO1) by the transcription factor MAFG as an underlying mechanism of the development of depression. The GSE98793 dataset was included for gene expression analysis of whole blood from donors with major depressive disorder and controls, and the target of MAFG was predicted by multiple database mining. Mouse and cellular models of depression were established by chronic unpredictable mild stress (CUMS) and lipopolysaccharide (LPS) treatment of astrocytes, which were treated with MAFG and HMOX1 knockdown plasmids. MAFG was highly expressed in the hippocampal tissues of CUMS-challenged mice and LPS-induced astrocytes. MAFG knockdown alleviated depression-like behaviors in mice. MAFG bound to the HMOX1 promoter and repressed its transcription. Knockdown of HMOX1 exacerbated neuroinflammation in astrocytes and accelerated depression-like behavior in mice. In conclusion, MAFG knockdown attenuated CUMS-stimulated depression-like behaviors in mice by astrocyte-mediated neuroinflammation via restoration of HMOX1., 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.)

Nitrogen (N) in the atmosphere frequently affects plant growth, ecological stoichiometric equilibrium, and homeostasis stability. However, the effect of N addition application on the growth of Hippophae rhamnoides seedlings remains ambiguous. We investigated the effects of N addition on the ecological stoichiometry and homeostatic characteristics of H. rhamnoides seedlings. Greenhouse cultivation experiments were conducted at five N application levels: 0 kg ha -1  yr -1 (CK), 100 kg ha -1  yr -1 (N10), 200 kg ha -1  yr -1 (N20), 400 kg ha -1  yr -1 (N40), 800 kg ha -1  yr -1 (N80). The results showed that pH and available phosphorus (AP) significantly decreased with increasing N, whereas soil C:P and N:P ratios significantly increased under the N40 and N80 treatments. The leaf C:N ratio significantly decreased with increasing N, whereas the N:P ratio increased. With N addition, the C:N ratio of plant stems and roots significantly decreased, whereas the C:P and N:P ratios significantly increased. N addition was significantly correlated with the ecological stoichiometry of plant leaves and soil properties (0.38 and 0.84, respectively). Homeostasis of the organs of H. rhamnoides seedlings exhibited an absolute steady state. The C, N, and C:P ratios of the roots exhibited insensitive states under the N40 treatment. N addition significantly modified both the soil ecological stoichiometry and the stoichiometry of H. rhamnoides seedlings. However, it did not demonstrate a pronounced negative effect on the homeostasis of H. rhamnoides seedlings. This study offers new insights into the ecological adaptation process of H. rhamnoides, particularly concerning its nutrient distribution, utilization strategies, and stability., 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.)

The application of manganese-oxidizing bacteria (MnOB) to produce manganese oxides (MnOx) has been widely studied, but often overlooking the concurrent formation of MnCO 3 . In this study, we found Ca 2+ plays a crucial role in controlling Mn(II) removal in the bacterium Aurantimonas sp. HBX-1. Under conditions with 6.8 mM Ca 2+ and without adding Ca 2+ , 100 μM Mn(II) was removed by 96.96 % and 38.28 % within 8 days, respectively. X-ray photoelectron spectroscopy (XPS) showed that adding Ca 2+ increased the average oxidation state (AOS) of the solid products from 2.05 to 2.37. X-ray absorption fine structure (XAFS) analysis revealed the product proportions as follows: under Ca 2+ -supplemented condition, the ratio of MnOx (1 < x ≤ 2) to MnCO₃ was 52 % to 28.1 %, while under Ca 2+ -free condition, the ratio shifted to 4.6 % for MnOx (1 < x ≤ 2) and 55.2 % for MnCO₃. Urease activity assay and proteomic analysis confirmed the expression of urease and carbonic anhydrase, leading to the formation of MnCO 3 . Additionally, animal heme peroxidase (AHP) in strain HBX-1 was found to be responsible for Mn(II) oxidation through superoxide production, with Ca 2+ addition promoting its expression level. Given the widespread presence of Ca 2+ in wastewater, its potential impact on the biogeochemical Mn(II) cycle driven by bacteria should be reconsidered., 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.)

Identifying small molecules that bind strongly to target proteins in rational molecular design is crucial. Machine learning techniques, such as generative adversarial networks (GAN), are now essential tools for generating such molecules. In this study, we present an enhanced method for molecule generation using objective-reinforced GANs. Specifically, we introduce BEGAN (Boltzmann-enhanced GAN), a novel approach that adjusts molecule occurrence frequencies during training based on the Boltzmann distribution exp(-Δ U /τ), where Δ U represents the estimated binding free energy derived from docking algorithms and τ is a temperature-related scaling hyperparameter. This Boltzmann reweighting process shifts the generation process toward molecules with higher binding affinities, allowing the GAN to explore molecular spaces with superior binding properties. The reweighting process can also be refined through multiple iterations without altering the overall distribution shape. To validate our approach, we apply it to the design of sex pheromone analogs targeting Spodoptera frugiperda pheromone receptor SfruOR16, illustrating that the Boltzmann reweighting significantly increases the likelihood of generating promising sex pheromone analogs with improved binding affinities to SfruOR16, further supported by atomistic molecular dynamics simulations. Furthermore, we conduct a comprehensive investigation into parameter dependencies and propose a reasonable range for the hyperparameter τ. Our method offers a promising approach for optimizing molecular generation for enhanced protein binding, potentially increasing the efficiency of molecular discovery pipelines.

Astrocytes, constituting the predominant glial cells in the brain, undergo significant morphological and functional transformations amidst the progression of Parkinson's disease (PD). A majority of these reactive astrocytes display a neurotoxic phenotype, intensifying inflammatory responses. Nonetheless, the molecular underpinnings steering neurotoxic astrocyte reactivity during PD progression remain mostly uncharted. Here, we uncover the unique role of cystathionine γ-lyase (CSE) in shaping astrocyte reactivity, primarily channeling astrocytes towards a neurotoxic phenotype, thereby escalating neuroinflammation in PD. Single-cell sequencing data drawn from PD patients coupled with RNA sequencing data from MPP + -treated astrocytes, highlighted a marked positive association between increased expression of Cth, the gene that encodes CSE, and neurotoxic astrocyte reactivity. Employing genetic manipulation of Cth in astrocytes, we evidenced that CSE instigates a transition to a neurotoxic state in PD-afflicted astrocytes under in vitro and in vivo settings. Moreover, we identified a CSE-Yes-associated protein (YAP) complex within astrocytes via label-free mass spectrometry. An increased formation of the CSE-YAP complex was found to facilitate the expression of gene patterns tied to neurotoxic astrocytes, driven by the transcription factor, forkhead box protein D3 (FOXD3). Consequently, our work unveils valuable insights into the cell type-specific function of CSE in the brain, and presents FOXD3 as a novel transcription factor influencing astrocyte phenotypes in PD. These findings lay the groundwork for the development of potential strategies intended to manage conditions associated with neuroinflammation., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Anthocyanins affect quality in fruits such as grape (Vitis vinifera). High temperatures reduce anthocyanin levels by suppressing the expression of anthocyanin biosynthesis genes and decreasing the biosynthetic rate. However, the regulatory mechanisms that coordinate these two processes remain largely unknown. In this study, we demonstrate that high-temperature-mediated inhibition of anthocyanin biosynthesis in grape berries depends on the auxin and endoplasmic reticulum (ER) stress pathways. Inactivation of these pathways restores anthocyanin accumulation under high temperatures. We identified and characterized FAR-RED ELONGATED HYPOCOTYL3 (FHY3), a high-temperature-modulated transcription factor that activates multiple anthocyanin biosynthesis genes by binding to their promoters. The auxin response factor VvARF3 interacts with VvFHY3 and represses its transactivation activity, antagonizing VvFHY3-induced anthocyanin biosynthesis. Additionally, we found that the ER stress sensor VvbZIP17 represses anthocyanin biosynthesis. VvFHY3 suppresses VvbZIP17 activity by directly binding to the VvbZIP17 promoter to repress its transcription and by physically interacting with VvbZIP17 to block its DNA binding ability. Furthermore, AUXIN RESPONSE FACTOR 3 (ARF3) interferes with the VvFHY3-VvbZIP17 interaction, releasing VvbZIP17 to activate the unfolded protein response and further suppress anthocyanin production. Our results unravel the VvARF3-VvFHY3-VvbZIP17 regulatory module, which links the auxin and ER stress pathways to coordinately repress anthocyanin structural gene expression and biosynthesis under high-temperature stress., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Several coastal regions require operational forecast systems for predicting the transport of pollutants released during marine accidents. In response to this need, surrogate models offer cost-effective solutions. Here, we propose a surrogate modeling method for predicting the residual transport of particle patches in coastal environments. These patches are collections of passive particles equivalent to Eulerian tracers but can be extended to other particulates. By only using relevant forcing, we train a deep learning model (DLM) to predict the displacement (advection) and spread (dispersion) of particle patches after one tidal period. These quantities are then coupled into a simplified Lagrangian model to obtain predictions for larger times. Predictions with our methodology, successfully applied in the Dutch Wadden Sea, are fast. The trained DLM provides predictions in a few seconds, and our simplified Lagrangian model is one to two orders of magnitude faster than a traditional Lagrangian model fed with currents., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Matias Duran-Matute reports financial support was provided by Dutch Research Council. Jeancarlo M. Fajardo-Urbina reports financial support was provided by Dutch Research Council. Theo Gerkema reports financial support was provided by Dutch Research Council. 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Obesity and adverse lipid profile leads to female infertility. The cardiometabolic index (CMI) is a promising indicator for predicting obesity-related diseases. The correlation between CMI and female infertility merits further investigation., Methods: The data for this study were acquired from the 2013-2020 National Health and Nutrition Examination Survey (NHANES), with 2333 women enrolled. The cardiometabolic index (CMI) of each participant was calculated as the ratio of triglycerides and high-density lipoprotein cholesterol multiplied by waist-to-height ratio. Weighted multivariate logistic regression models were used to assess the independent correlation between the log-transformed CMI and infertility. Subgroup analyses were carried out to assess the reliability of the findings. Interaction tests were employed to determine whether variables affected infertility by interacting with log CMI., Results: A total of 2333 participants aged 18-45 years were enrolled, 274 of whom were infertile. Log CMI of the infertility group was significantly higher than that of the non-infertility group (P < 0.001). After adjustment for potential confounders, women with higher CMI were at an increased risk of infertility (OR = 2.411, 95% CI: 1.416-4.112), and this correlation was still consistent in subgroups aged under 35 years (P < 0.001). Furthermore, restricted cubic spline analysis showed a positive non-linear relationship between log CMI and infertility., Conclusions: Cardiometabolic index levels are positively correlated with increased risk of infertility in American females. Our study demonstrates the predictive capacity of CMI for female infertility., Competing Interests: Declarations Consent for publication Not applicable. Competing interests The authors declare no competing interests. Ethics approval and consent to participate All data obtained from NHANES were reviewed and approved by National Center for Health Statistics (NCHS) Ethics Review Board and all participants agreed on the survey and signed written consent. The NHANES was conducted in compliance with local laws and institutional guidelines. Since NHANES is a publicly accessible database, no additional ethical approvals are required., (© 2024. The Author(s).)

Monitoring China's carbon dioxide (CO 2 ) concentration is essential for formulating effective carbon cycle policies to achieve carbon peaking and neutrality. Despite insufficient satellite observation coverage, this study utilizes high-resolution spatiotemporal data from the Orbiting Carbon Observatory 2 (OCO-2), supplemented with various auxiliary datasets, to estimate full-coverage, monthly, column-averaged carbon dioxide (XCO 2 ) values across China from 2015 to 2022 at a spatial resolution of 0.05° via the deep forest model. The 10-fold cross-validation results indicate a correlation coefficient (R) of 0.95 and a determination coefficient (R²) of 0.90. Validation against ground-based station data yielded R values of 0.93, and R² values reached 0.81. Further validation from the Greenhouse Gases Observing Satellite (GOSAT) and the Copernicus Atmosphere Monitoring Service Reanalysis dataset (CAMS) produced R² values of 0.87 and 0.80, respectively. During the study period, CO 2 concentrations in China were higher in spring and winter than in summer and autumn, indicating a clear annual increase. The estimates generated by this study could potentially support CO 2 monitoring in China., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

With the power conversion efficiency (PCE) of perovskite solar cells (PSCs) exceeding 26.7%, achieving further enhancements in device performance has become a key research focus. Here, we investigate the impact of electrical doping in the perovskite layer using the drift-diffusion equation-based device physics model, coupled with a self-developed equivalent circuit model. Our results demonstrate that electrical doping can increase the PCE from 24.78% to >28%. In-depth theoretical analysis reveals that these improvements in performance are driven by the modulation of carrier recombination processes through doping, leading to significant increases in the open-circuit voltage and fill factor. Additionally, we explore the influence of physical parameters on device performance. Our study identifies an optimal doping concentration range from 1.0 × 10 17 to 1.0 × 10 19 cm -3 and a transport layer mobility of >0.01 cm 2 V -1 s -1 . This work provides a theoretical foundation for the development of ultra-high-performance PSCs through targeted electrical doping strategies.

The advancement of cutting-edge energy conversion technologies offers significant potential for addressing environmental challenges, enhancing energy security, improving economic competitiveness, and promoting resource conservation. This progress necessitates the development of advanced electrocatalysts. WO x demonstrates high intrinsic catalytic activity, excellent conductivity, an abundance of active sites, and remarkable stability, positioning it as a promising candidate for electrocatalytic reactions. Recently, there has been swift advancement in the development of WO x -based catalysts for various energy-conversion reactions. This review provides a thorough summary of recent developments in WO x -based catalysts for electrocatalytic reactions, emphasizing their multifunctional roles as active species, electron-transfer carriers, hydrogen spillover carriers, and microenvironment regulators. Moreover, it highlights the applications of WO x -based catalysts across different electrocatalytic reactions, with particular focus on the structure-activity relationship. Finally, the review discusses the challenges and future directions of these technologies, as well as key research areas necessary for achieving large-scale applications.

Elucidating organismal developmental processes requires a comprehensive understanding of cellular lineages in the spatial, temporal, and molecular domains. In this study, we introduce Zebrahub, a dynamic atlas of zebrafish embryonic development that integrates single-cell sequencing time course data with lineage reconstructions facilitated by light-sheet microscopy. This atlas offers high-resolution and in-depth molecular insights into zebrafish development, achieved through the sequencing of individual embryos across ten developmental stages, complemented by reconstructions of cellular trajectories. Zebrahub also incorporates an interactive tool to navigate the complex cellular flows and lineages derived from light-sheet microscopy data, enabling in silico fate-mapping experiments. To demonstrate the versatility of our multimodal resource, we utilize Zebrahub to provide fresh insights into the pluripotency of neuro-mesodermal progenitors (NMPs) and the origins of a joint kidney-hemangioblast progenitor population., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The capability to spatially explore RNA biology in formalin-fixed paraffin-embedded (FFPE) tissues holds transformative potential for histopathology research. Here, we present pathology-compatible deterministic barcoding in tissue (Patho-DBiT) by combining in situ polyadenylation and computational innovation for spatial whole transcriptome sequencing, tailored to probe the diverse RNA species in clinically archived FFPE samples. It permits spatial co-profiling of gene expression and RNA processing, unveiling region-specific splicing isoforms, and high-sensitivity transcriptomic mapping of clinical tumor FFPE tissues stored for 5 years. Furthermore, genome-wide single-nucleotide RNA variants can be captured to distinguish malignant subclones from non-malignant cells in human lymphomas. Patho-DBiT also maps microRNA regulatory networks and RNA splicing dynamics, decoding their roles in spatial tumorigenesis. Single-cell level Patho-DBiT dissects the spatiotemporal cellular dynamics driving tumor clonal architecture and progression. Patho-DBiT stands poised as a valuable platform to unravel rich RNA biology in FFPE tissues to aid in clinical pathology evaluation., Competing Interests: Declaration of interests Z.B. and R.F. are inventors of a patent application related to this work. R.F. is scientific founder and adviser for IsoPlexis, Singleron Biotechnologies, and AtlasXomics. The interests of R.F. were reviewed and managed by Yale University Provost’s Office in accordance with the University’s conflict of interest policies. M.L.X. has served as consultant for Treeline Biosciences, Pure Marrow, and Seattle Genetics. Daiwei Zhang and M.L. are co-founders or OmicPath AI LLC. M.L. receives research funding from Biogen Inc. unrelated to the current manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Disentangling the mechanisms underlying community assembly is a central topic in community ecology and an important prerequisite for bioassessment. The relative importance of deterministic and stochastic processes is expected to change among organisms relying on different dispersal modes and may vary considerably through time. However, how seasonal change and dispersal modes will interplay to influence community assembly remains to be demonstrated. Here, we examined seasonal dynamics in the relative role of environmental filtering and potential dispersal pathways (overland vs. watercourse) on community assembly of aquatic macroinvertebrates in a Chinese river experiencing monsoon oscillations. We also investigated if and how community assembly processes are dependent on dispersal modes. To do this, we divided the entire metacommunity into three groups: strictly aquatic dispersers (G1), aquatic/aerial dispersers with weak dispersal ability (G2), aquatic/aerial dispersers with strong dispersal ability (G3). Our results showed strong changes in environmental conditions and community structure before, during and after the monsoon. Watercourse distances were more relevant for strictly aquatic dispersers (i.e., G1), whereas overland distances were more strongly related with taxa able to fly during their adult phase (i.e., G2 and G3). Environmental filtering was consistently predominant across seasons. Moreover, mechanisms underlying community assembly of strictly aquatic dispersers remained relatively stable among seasons. On the other hand, ecological correlates of aquatic/aerial dispersers exhibited pronounced seasonal dynamics, probably as a result of their changing dispersal abilities in the transition from larvae to adulthood. Overall, our findings suggest that the relative importance of environmental filtering and spatial processes are mediated by dispersal modes and the hydrological dynamics imposed by seasonal monsoons. Hence, we argue that incorporating the temporal aspect of intra-annual hydrological variation and considering multiple dispersal modes are crucial for unravelling the dynamic nature of community assembly and for improving river bioassessment and management., 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.)

Background and Objective: Long-term (LT) androgen deprivation therapy (ADT) has been found to be beneficial to patients with high-risk prostate cancer (PCa). However, administration of LT-ADT to all patients with high-risk PCa may lead to overtreatment. Enhanced risk stratification using genomic classifiers (such as the recently developed prostate subtyping classifier [PSC]) might be useful. This study aims to characterize the prognostic and predictive ability of the PSC in patients with high-risk PCa undergoing radiotherapy long-term (LT; 24-28 mo) versus short-term (ST; 4 mo) ADT., Methods: Biopsy samples from three randomized, phase 3 trials-NRG/RTOG 9202, 9413, and 9902-were classified as either PSC basal or luminal. The prognostic and predictive values of PSC for each oncologic endpoint (biochemical failure [BF], distant metastasis [DM], metastasis-free survival [MFS], PCa-specific mortality [PCSM], overall survival [OS]) and other cause-mortality (OCM) were assessed with Cox proportional hazards (MFS, OCM, and OS), Fine-Gray (BF, DM, and PCSM), and restricted mean survival time (RMST) models., Key Findings and Limitations: On a multivariable analysis, the basal subtype was found to have a worse prognosis for MFS (hazard ratio [HR] 1.8 [1.3-2.5], p < 0.001), PCSM (subdistribution HR 2.4 [95% confidence interval {CI} 1.4-4.1], p = 0.001), and OS (HR 1.8 [1.3-2.6], p < 0.001). Ten-year PCSM was 15% better for the luminal subtype than for the basal subtype (11% [95% CI 6-15%] vs 26% [95% CI 17-35%]). A significant interaction between ADT duration (LT vs ST) and PSC subtype (basal vs luminal) was observed for PCSM (p interaction  = 0.008), leading to the observation that 10-yr PCSM was improved with LT-ADT only in patients with basal-type tumors (5% [95% CI 0-11%] vs 42% [29-56%], p < 0.001). Improvements in 10-yr RMST with LT-ADT were greater for basal tumors for oncologic endpoints with the exception of OCM., Conclusions and Clinical Implications: PSC is both a prognostic and a predictive biomarker for patients who benefit from LT-ADT. PSC subtypes may be used to personalize ADT recommendations for patients with high-risk PCa, pending further validation in a prospective study., Patient Summary: In this study, we tried to understand the usefulness of a new genomic test in patients with high-risk, nonmetastatic prostate cancer who underwent radiation therapy and hormonal therapy (HT). We found that this test can help determine a patient's prognosis (eg, a patient's chance of having the cancer return) and, more importantly, personalize treatment decisions by understanding which patients may benefit from long-term HT. This has the potential to save many patients who may not benefit from prolonged HT from "overtreatment" or the unnecessary side effects of such treatment., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Although much progress has been made in chemotherapy or target therapy for advanced gastric cancer, the prognosis is still poor. It is necessary to screen biomarkers for early diagnosis and prognosis prediction. However, the prognostic value of LOX family in gastric cancer and the underlying molecular mechanisms for promoting the progression of gastric cancer remains unclear. Among five members of LOX family, LOXL1 was the unique independent prognostic risk factor. The nomogram established based on the expression of LOXL1 and other clinical parameters could predict the overall survival rate of gastric cancer. Knockdown (KD) of LOXL1 decreased cell proliferation and led to G1 phase arrest in gastric cells. According to GSEA analysis that LOXL1 was positively correlated with the WNT signaling pathway, in vitro experiment proved that LOXL1-KD reduced the phosphorylation level of β-catenin and the expression of the downstream G1 phase checkpoint CCND1.In Conclusion, LOXL1 has been identified as a potential risk prognostic biomarker for gastric cancer by promoting gastric cancer proliferation via WNT/β-catenin/cyclinD1 pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests or potential competing interests, and all authors should confirm its accuracy., (Copyright © 2024. Published by Elsevier Inc.)

Dissolved organic matter (DOM) and recalcitrant dissolved organic matter (RDOM) play distinct roles in shaping microbial communities. However, characterizing these roles is difficult, especially in ecosystems subjected to varying degrees of anthropogenic influence. This study investigated the molecular compositions and ecological impacts of DOM and RDOM in the Fen River, Shanxi Taiyuan, comparing pristine upstream regions with highly urbanized downstream areas. Using 16S rRNA gene sequencing and LC-MS-based metabolomics, we observed significant shifts in microbial community composition, diversity, and metabolic functions. Upstream communities, characterized by higher diversity, were dominated by Bacteroidota, Proteobacteria, and Cyanobacteria, while downstream communities, influenced by pollution, exhibited increased expression of genes related to amino acid metabolism. Fluorescence spectroscopy and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) revealed that upstream DOM contained higher proportions of complex, high molecular weight compounds, including significant proportions of carboxyl-rich alicyclic molecules (CRAM) and island of stability (IOS) compounds, which play key roles in long-term carbon storage and microbial carbon sequestration. In contrast, downstream DOM was characterized as having lower aromaticity and more saturated compounds, with reduced proportions of CRAM and IOS, reflecting the impact of anthropogenic activities. These findings underscored the critical roles of CRAM and IOS in regulating DOM stability and microbial communities, further highlighting the need for targeted pollution control strategies to preserve ecosystem function in urbanized water bodies., 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.)

Background: The unilateral biportal endoscopic (UBE) technique has garnered significant attention for its little paraspinal iatrogenic damage, expedited recovery, and low complication rates. This method is also applicable to open transforaminal lumbar interbody fusion (TLIF). Therefore, this study aimed to conduct a comparative analysis of the outcomes associated with unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF), minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF), and TLIF for Meyerding grade I lumbar spondylolisthesis., Methods: The study examined the outcomes of 79 patients with Meyerding grade I lumbar spondylolisthesis who underwent single-level intervertebral fusion. Clinical assessments included the measurement of pain levels using the Visual Analogue Scale (VAS) for low back and leg pain, the Oswestry Disability Index (ODI), surgical data, and demographic information. Imaging techniques were utilized to evaluate the fusion rate., Results: The VAS-Back demonstrated a statistically significant improvement in Group UBE-TLIF compared to the other groups at the one-week postoperative evaluation (p < .05). Additionally, the UBE-TLIF group exhibited a significantly longer total operative time compared to the other groups (p < .05). However, it was noted that the Postop Hemovac drain were significantly greater in the MIS-TLIF and TLIF groups compared to the UBE-TLIF group (p < .05)., Conclusions: The present research demonstrated the effectiveness of UBE-TLIF, MIS-TLIF, and TLIF as surgical approaches for treating Meyerding grade I lumbar spondylolisthesis. Among these methods, UBE-TLIF demonstrated a reduction in Postop Hemovac drain, and an increase in operative duration., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the Institutional Ethics Committee of the Second Affiliated Hospital of Chongqing Medical University, and was conducted according to the ethical standards of Helsinki Declaration (1964) and its subsequent amendments. Informed consent was obtained from all subjects and/or their legal guardians. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Anticoagulation therapy in patients with atrial fibrillation (AF) and concomitant cancer can be challenging due to the significantly increased risk of both embolism and bleeding. Moreover, the benefits and risks of vitamin K antagonists (VKA, eg. warfarin) versus non-vitamin K antagonist oral anticoagulants (NOACs) in such patients are less well understood., Methods: From the prospective, global, multi-centered Global Registry on Long-Term Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), we characterized these patients according to their history of prior cancer when enrolled. All patients received anticoagulant therapy. The primary outcome was the composite of all-cause mortality, stroke, transient ischemic attack, systemic embolism. The secondary endpoints were all-cause mortality, cardiovascular death, stroke, major bleeding and thromboembolism during the 3 years follow-up period. Cox regression analyses were used to calculate the hazard ratio (HR) and confidence interval (CI) following propensity score matching (PSM)., Results: Overall, among 16,700 patients enrolled in Phase III in GLORIA-AF, 1725 (10%) patients had concomitant cancer(s) at enrolment. After PSM, the primary outcome occurred in 250 (14.8%) of patients with cancer(s) and 160 (9.3%) without cancer(s) (HR, 1.62 [95% CI, 1.33-1.97], p < .001) during the 3 years follow-up period. The risk of all-cause mortality was significantly higher in patients with cancer(s) versus non- cancer(s) (HR, 1.71 [95% CI, 1.37-2.12], p < .001). In patients with cancer(s), after PSM, the use of NOACs was associated with reduced risk of the primary outcome compared with that of VKA (HR, .69 [95% CI, .49-.99], p = .043), as well as a lower risk of thromboembolism (HR, .49 [95% CI, .24-1.00], p = .051), but the risk of major bleeding was not significantly different (HR, .87 [95% CI, .48-1.56], p = .635). Subgroup analysis in patients with cancers showed a reduced risk of major bleeding with NOACs compared with VKA (HR, .18 [95% CI, .04-.8], p = .024) in patients with coronary artery disease (CAD). For the main cancer subtypes (genitourinary, breast, gastrointestinal, haematological and skin), the trends for the risk of primary outcome were consistently favouring NOACs compared with VKA without any significant interaction among these five cancers., Conclusions: Cancer is a common comorbidity in patients with AF and is associated with increased risk of composite of all-cause mortality and thromboembolism. Compared with VKA, NOACs was associated with a lower risk of composite events and showed an advantage in lower risk of thromboembolism, as well as a reduced risk of major bleeding when CAD was also present., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background: We aimed to study the prognostic risk factors affecting patients with anaplastic thyroid carcinoma (ATC), develop a clinical prognostic model, and assess patient survival outcomes., Methods: Patients with anaplastic thyroid carcinoma from 2000 to 2019 were selected from the Surveillance, Epidemiology, and End Results (SEER) Program to extract the clinical variables used for analysis. The dataset was divided into training (70%) and validation (30%) sets based on a 7:3 ratio. Univariate and LASSO regression analyses were performed on clinical variables from the training set to identify independent prognostic factors. Independent prognostic factors were determined by Univariate and lasso regression according to the clinical variables of the training set, and a nomogram model was established to construct a prognostic model based on the contribution degree of the predictors. The prognostic model was evaluated and internally verified by C-index, ROC curve and calibration curve., Results: A total of 713 ATC patients were included in the SEER database. LASSO regression results indicated that age, marital status, race, tumor size, whether the primary lesion was limited to the thyroid gland, surgery, radiotherapy and chemotherapy, were associated with overall survival(OS) prognosis of ATC, and were used to construct nomograms. In the training cohort, the OS nomogram's C-index was 0.708 (95% CI 0.672-0.745); in the internal validation cohort, the C-index was 0.677 (95% CI 0.620-0.735). ROC curves demonstrated that the OS nomogram exhibits excellent predictive accuracy and discriminative ability. Calibration curves indicated strong consistency between the OS nomogram's predicted survival rates and actual survival rates., Conclusions: We established a survival prediction model for ATC, which can assist clinicians in assessing patient prognosis and making personalized treatment decisions., Competing Interests: Declarations Ethics approval and consent to participate All data used in this study came from publicly available databases, so this study received an exemption from the Ethics Committee of the Affiliated Mianyang Hospital of Chengdu University of Traditional Chinese Medicine. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Water-responsive polymers have received great attention in the field of smart actuators due to their mechanical response to humidity without energy consumption. Natural polymers-based actuators are competitive because of their green, sustainable, and biocompatible characteristics. In this paper, we report a natural twisting carboxymethyl cellulose (CMC) fiber-based actuator (TCFA) with remarkable performance under water and moist stimulation. The water-responsive CMC fibers were prepared using wet spinning and twisting. Owing to the helical structure, good water absorption, and swelling performance, the CMC fiber exhibits excellent rotational motion with a rotation speed of 4615 rpm and recovery speed of 1538.4 rpm under water stimulation. In addition, the actuator revolutions remained almost constant after more than 254 cycles, thus demonstrating the excellent cyclic stability of this untwisting recovery process. Moreover, the CMC fiber shows application in a smart rainy curtain, smart crane, and concentration detection for alcohol solution. We offer an easy and scalable method to obtain a CMC fiber-based actuator with low cost, sustainability as well as excellent driving performance. Our work inspires a new idea in the design of cellulose-derived actuators and their application in future intelligent systems., Competing Interests: Declaration of competing interest The authors declare that there are 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 B.V.)

DNBSEQ employs a patterned array to facilitate massively parallel sequencing of DNA nanoballs (DNBs), leading to a considerable boost in throughput. By employing the ultra-high-density (UHD) array with an increased density of DNB binding sites, the throughput of DNBSEQ can be further expanded. However, the typical imaging system of the DNBSEQ sequencer is unable to resolve adjacent DNBs spaced smaller than the resolution limit, resulting in poor base-calling performance of the UHD array and hindering its practical application. In this study, we propose a deep-learning-based DNB image super-resolution network named DNBSRN to address this problem. DNBSRN has a specifically designed structure for DNB images and employs a histogram-matching-based preprocessing approach. For the eight DNB image datasets generated from the DNBSEQ sequencer using UHD arrays with 360 nm pitch, the base-calling performances are significantly improved after super-resolution reconstruction by DNBSRN and reached a comparable level to those of the regular density array. In terms of reconstruction speed, DNBSRN takes only 7.61 ms for an input image with 500 × 500 pixels, which minimizes its influence on throughput. Furthermore, compared with state-of-the-art super-resolution networks, DNBSRN demonstrates superior performance in terms of both the quality and speed of DNB image reconstruction. DNBSRN successfully addresses the DNB image super-resolution task. Integrating DNBSRN into the image analysis workflow of DNBSEQ will allow for the application of UHD array, hence enabling a considerable improvement in throughput as well as tremendous savings in unit reagent cost., Competing Interests: Competing interests DNBSRN is covered by a pending patent. Zhiwei Zhai, Hao Zhang, Zeyu Su, Yang Liu, Hongmin Chen, Yuxiang Li, and Mengzhe Shen are employees of BGI Research, a subsidiary of BGI Group. Junfeng Li declare no competing interests., (© 2024. The Author(s).)

Nitrogen is often a limiting nutrient for microbial communities and plants in glacier forefields. Nitrogen-fixing microorganisms (diazotrophs) play an important role in providing bioavailable nitrogen, with their composition determining the nitrogen-fixating capacities. This study investigates the spatial and temporal dynamics of diazotrophs in the forefields of three Tibetan glaciers: Qiangyong, Kuoqionggangri, and Longxiazailongba. We collected soil samples from recently deglaciated barren grounds, and also along an ecosystem succession transect at Kuoqionggangri glacier, encompassing barren ground, herb steppe, legume steppe, and alpine meadow ecosystems. Our finding revealed abundant and diverse diazotrophs in the recently deglaciated barren ground. They are taxonomically affiliated with anaerobic Bradyrhizobium, Desulfobulbus, and Pelobacter, which may be relics from subglacial sediments. The vegetated soils (herb steppe, legume steppe, and alpine meadow) were dominated by phototrophic Nostoc and Anabaena, as well as symbiotic Sinorhizobium. Soil physicochemical parameters, such as soil organic carbon, pH, and nitrate ion, significantly influenced diazotroph community structure. This study highlights the critical role of diazotrophs in mitigating nitrogen limitation during early ecosystem development in glacier forefields. Understanding the distribution and ecological drivers of diazotrophs in these rapidly changing environments provides insights into biogeochemical cycling and ecosystem resilience under climate change., Competing Interests: Declarations Conflict of Interest The authors declare no competing interests., (© 2024. The Author(s).)

True random numbers are crucial for various research and engineering problems. Their generation depends upon a robust physical entropy noise. Here, we present true random number generation from the conductance noise probed in structurally metastable 1T' molybdenum ditelluride (MoTe 2 ). The noise, fitting a Poisson process, is proved to be a robust physical entropy noise at low and even cryogenic temperatures. Noise characteristic analyses suggest the noise may originate from the polarization variations of the underlying ferroelectric dipoles in 1T' MoTe 2 . We demonstrate the noise allows for true random number generation, and this facilitates their use as the seed for generating high-throughput secure random numbers exceeding 1 Mbit/s, appealing for practical applications in, for instance, cryptography where data security is now critical. As an example, we show biometric information safeguarding in neural networks by using the random numbers as the mask, proving a promising data security measure in big data and artificial intelligence.

β-Fluoromethyl (CH 2 F, CHF 2 , and CF 3 )-substituted chiral ketones are essential moieties and are vital building blocks in pharmaceutical and agrochemistry. However, general and convenient methods for enantio-diverse access to diverse β-fluoromethylated ketones are lacking, hindering the further development of these functional moieties. In this study, we developed an ene-reductase-based photobiocatalytic platform for efficient synthesis of enantio-divergent β-fluoromethylated chiral ketones. Our method highlights substrate-type diversity, excellent enantioselectivity, enzymatic enantio-divergent synthesis, as well as a dicyanopyrazine (DPZ)-type photosensitizer for biocompatible olefin E / Z isomerization in enzymatic stereoconvergent olefin asymmetric reduction, thereby providing a general photobiocatalytic solution to diverse β-fluoromethylated chiral ketones.

Zearalenone (ZEA) is a widely distributed mycotoxin that presents a substantial worldwide health risk to animals. Several natural compounds have shown promise in mitigating the detrimental impacts of ZEA. This study examined the detoxification potential of previously identified compounds by utilizing zebrafish embryos as a model organism. Hydroxytyrosol stands out among these natural compounds. Our findings indicate that hydroxytyrosol effectively mitigated mortality, hatching delay, and phenotypic abnormalities induced by ZEA in the assessed embryos. Furthermore, hydroxytyrosol restored the frequency and intensity of tail coiling (TC) while decreasing the expression of heat shock proteins (HSPs) in the zebrafish embryos. Extended incubation with hydroxytyrosol demonstrated protective effects on zebrafish growth and morphology, muscle birefringence, and touch-evoked escape behavior. Subsequent investigations indicated that hydroxytyrosol reversed the expression of proapoptotic targets (e.g., bax and caspase 8) and cell cycle regulators (e.g., p 21, gadd 45 a , and rbl 2), thereby mitigating apoptosis and G2 cell cycle arrest induced by ZEA in zebrafish embryos. Additionally, hydroxytyrosol decreased staining for senescence associated-β-galactosidase (SA-β-Gal). Notably, p53/FoxO pathway plays an important role in detoxification mechanisms. Overall, these novel findings highlight the potential of hydroxytyrosol to reverse ZEA-induced toxicity in multiple aspects. The mitigating effect of hydroxytyrosol on ZEA toxicity may have been underestimated.

Daratumumab and bortezomib, the first-line drugs for AL amyloidosis, typically yield a complete hematologic response (CHR) rate of nearly 60% when used in combinations. An early achievement of CHR is crucial in amyloidosis. We retrospectively evaluated the relationship between dFLC (the difference between free light chain) reduction by Day 7 in Cycle 1 (C1D7) and CHR, organ response, and survival in 48 newly diagnosed AL amyloidosis patients receiving daratumumab, bortezomib, and dexamethasone. The CHR rate within six months was 66.7%. Using Receiver Operating Characteristic Curve curve analysis, we predicted CHR based on a dFLC reduction in C1D7 (67.0% change, optimal sensitivity 87.5%, specificity 81.3%). We introduce the novel concept of "rapid hematologic dFLC response", defined as a reduction in dFLC levels ≥ 67% in C1D7. The CHR rate in rapid responders' groups was higher than that in slow responders' group (90.3% vs. 23.5%, P<0.01). After a median follow-up of 19 months (range: 0.3-57), the renal response rate in rapid responders was higher than that in slow responders (72.0% vs. 27.5%, P = 0.025). The median major organ deterioration event-free survival in the rapid responders' group (not reached) was significantly superior to that in the slow responders' group (19 m, 95% CI: 1.79-23.14 m, P = 0.048). In conclusion, early dFLC reduction in C1D7 indicates a high possibility of CHR and organ response and may allow for early modification of therapy in selected patients., Competing Interests: Declarations Conflict of interest All authors declare no potential conflict of interest. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)