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Shraddha S Kale,1,2 Rachel A Burga,1,3 Elizabeth E Sweeney,1 Zungho Zun,4–6 Raymond W Sze,1,4–6 Anthony Tuesca,7 J Anand Subramony,7 Rohan Fernandes1,3,5,61The Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National Health System, Washington, DC, USA; 2Department of Biomedical Engineering, George Washington University, Washington, DC, USA; 3The Institute for Biomedical Sciences, George Washington University, Washington, DC, USA; 4Division of Diagnostic Imaging and Radiology, Children’s National Health System, Washington, DC, USA; 5Department of Radiology, George Washington University, Washington, DC, USA; 6Department of Pediatrics, George Washington University, Washington, DC, USA; 7MedImmune LLC, Gaithersburg, MD, USA Abstract: Theranostic nanoparticles offer the potential for mixing and matching disparate diagnostic and therapeutic functionalities within a single nanoparticle for the personalized treatment of diseases. In this article, we present composite iron oxide-gadolinium-containing Prussian blue nanoparticles (Fe3O4@GdPB) as a novel theranostic agent for T1-weighted magnetic resonance imaging (MRI) and photothermal therapy (PTT) of tumors. These particles combine the well-described properties and safety profiles of the constituent Fe3O4 nanoparticles and gadolinium-containing Prussian blue nanoparticles. The Fe3O4@GdPB nanoparticles function both as effective MRI contrast agents and PTT agents as determined by characterizing studies performed in vitro and retain their properties in the presence of cells. Importantly, the Fe3O4@GdPB nanoparticles function as effective MRI contrast agents in vivo by increasing signal:noise ratios in T1-weighted scans of tumors and as effective PTT agents in vivo by decreasing tumor growth rates and increasing survival in an animal model of neuroblastoma. These findings demonstrate the potential of the Fe3O4@GdPB nanoparticles to function as effective theranostic agents.Keywords: theranostics, Prussian blue, iron oxide, MRI, photothermal therapy, cancer

Summary: Background: Infectious keratitis (IK) is the leading cause of corneal blindness globally. Deep learning (DL) is an emerging tool for medical diagnosis, though its value in IK is unclear. We aimed to assess the diagnostic accuracy of DL for IK and its comparative accuracy with ophthalmologists. Methods: In this systematic review and meta-analysis, we searched EMBASE, MEDLINE, and clinical registries for studies related to DL for IK published between 1974 and July 16, 2024. We performed meta-analyses using bivariate models to estimate summary sensitivities and specificities. This systematic review was registered with PROSPERO (CRD42022348596). Findings: Of 963 studies identified, 35 studies (136,401 corneal images from >56,011 patients) were included. Most studies had low risk of bias (68.6%) and low applicability concern (91.4%) in all domains of QUADAS-2, except the index test domain. Against the reference standard of expert consensus and/or microbiological results (seven external validation studies; 10,675 images), the summary estimates (95% CI) for sensitivity and specificity of DL for IK were 86.2% (71.6–93.9) and 96.3% (91.5–98.5). From 28 internal validation studies (16,059 images), summary estimates for sensitivity and specificity were 91.6% (86.8–94.8) and 90.7% (84.8–94.5). Based on seven studies (4007 images), DL and ophthalmologists had comparable summary sensitivity [89.2% (82.2–93.6) versus 82.2% (71.5–89.5); P = 0.20] and specificity [(93.2% (85.5–97.0) versus 89.6% (78.8–95.2); P = 0.45]. Interpretation: DL models may have good diagnostic accuracy for IK and comparable performance to ophthalmologists. These findings should be interpreted with caution due to the image-based analysis that did not account for potential correlation within individuals, relatively homogeneous population studies, lack of pre-specification of DL thresholds, and limited external validation. Future studies should improve their reporting, data diversity, external validation, transparency, and explainability to increase the reliability and generalisability of DL models for clinical deployment. Funding: NIH, Wellcome Trust, MRC, Fight for Sight, BHP, and ESCRS.

BackgroundTo compare the diagnostic performance of microbiological culture and 16S/18S rRNA gene polymerase chain reaction (PCR)-Sanger sequencing for infectious keratitis (IK) and to analyse the effect of clinical disease severity on test performance and inter-test concordance.MethodsThis was a three-arm, diagnostic cross-sectional study. We included all eligible patients who presented with presumed bacterial/fungal keratitis to the Queen's Medical Centre, Nottingham, UK, between June 2021 and September 2022. All patients underwent simultaneous culture (either direct or indirect culture, or both) and 16S (pan-bacterial)/18S (pan-fungal) ribosomal RNA (rRNA) PCR-Sanger sequencing. The bacterial/fungal genus and species identified on culture were confirmed using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. Relevant clinical data were also collected to analyze for any potential clinico-microbiological correlation. Main outcome measures included the diagnostic yield, test accuracy (including sensitivity and specificity), and inter-test agreement [including percent agreement and Cohen's kappa (k)].ResultsA total of 81 patients (86 episodes of IK) were included in this study. All organisms identified were of bacterial origin. Diagnostic yields were similar among direct culture (52.3%), indirect culture (50.8%), and PCR (43.1%; p = 0.13). The addition of PCR enabled a positive diagnostic yield in 3 (9.7%) direct culture-negative cases. Based on composite reference standard, direct culture had the highest sensitivity (87.5%; 95% CI, 72.4–95.3%), followed by indirect culture (85.4%; 95% CI, 71.6–93.5%) and PCR (73.5%; 95% CI, 59.0–84.6%), with 100% specificity noted in all tests. Pairwise comparisons showed substantial agreement among the three tests (percent agreement = 81.8–86.2%, Cohen's k = 0.67–0.72). Clinico-microbiological correlation demonstrated higher culture-PCR concordance in cases with greater infection severity.ConclusionsThis study highlights a similar diagnostic performance of direct culture, indirect culture and 16S rRNA PCR for bacterial keratitis, with substantial inter-test concordance. PCR serves as a useful diagnostic adjuvant to culture, particularly in culture-negative cases or those with lesser disease severity (where culture-PCR concordance is lower).

Objectives: Excessive reactive oxygen species (ROS) in diabetic wounds are major contributors to chronic wounds and impaired healing, posing significant challenges in regenerative medicine. Developing innovative drug delivery systems is crucial to address these issues by modifying the adverse microenvironment and promoting effective wound healing. Methods: Herein, we designed a novel drug delivery platform using manganese dioxide nanoflower hybridized gold nanoparticle composites (MnO2-Au) synthesized via a hydrothermal reaction, and investigated the potential of MnO2-Au nanoflowers to relieve the high oxidative stress microenvironment and regulate diabetic wound tissue healing. Results: This hybrid material demonstrated superior catalytic activity compared to MnO2 alone, enabling the rapid decomposition of hydrogen peroxide and a substantial reduction in ROS levels within dermal fibroblasts. The MnO2-Au nanoflowers also facilitated enhanced dermal fibroblast migration and Col-I expression, which are critical for tissue regeneration. Additionally, a hydrogel-based wound dressing incorporating MnO2-Au nanoflowers was developed, showing its potential as an intelligent drug delivery system. This dressing significantly reduced oxidative stress, accelerated wound closure, and improved the quality of neonatal epithelial tissue regeneration in a diabetic rat skin defect model. Conclusions: Our findings underscore the potential of MnO2-Au nanoflower-based drug delivery systems as a promising therapeutic approach for chronic wound healing, particularly in regenerative medicine.

The Barrel Toroid Magnet for the Magnet System of the ATLAs detector is described with a focus on the BO model coil.

PurposeThe purpose of this study was to assess the effectiveness of [99mTc]Tc-HYNIC-ALUG SPECT/CT in the initial staging of patients with newly diagnosed PCa.MethodsA retrospective analysis was conducted on 227 consecutive patients who underwent [99mTc]Tc-HYNIC-ALUG SPECT/CT imaging for the primary staging of newly diagnosed PCa. The presence and location of PSMA-positive lesions were determined, and the maximum standardized uptake values (SUVmax) of the primary prostate tumor were also measured. The metastatic findings and SUVmax were stratified according to International Society of Urological Pathology (ISUP) grade, prostate-specific antigen (PSA) levels, and D’Amico classification. Furthermore, the [99mTc]Tc-HYNIC-ALUG SPECT/CT findings were compared to the histopathological findings in patients who had undergone radical prostatectomy with pelvic lymph node dissection (PLND).ResultsOf the 227 patients, 92.1% (209/227) had positive [99mTc]Tc-HYNIC-ALUG SPECT/CT findings. Advanced disease was detected in 38.8% (88/227) of the patients and was positively correlated with increasing ISUP grade and PSA levels. Lymph node metastases (both pelvic and extrapelvic), bone metastases, and visceral metastases were detected in 30.0% (68/227), 25.6% (58/227), and 3.1% (7/227) of the patients, respectively. For the 129 patients who underwent radical prostatectomy with PLND, the sensitivity of [99mTc]Tc-HYNIC-ALUG SPECT/CT in the evaluation of PCa was 90.7% (117/129). The sensitivity, specificity, accuracy, and positive and negative predictive values for detecting pelvic lymph node metastases on [99mTc]Tc-HYNIC-ALUG SPECT/CT were 23.5% (12/51), 93.6% (73/78), 65.9% (85/129), 70.6% (12/17), and 65.2% (73/112), respectively. Among the 209 patients with PSMA-avid primary prostate disease, the SUVmax of the primary prostate tumor was significantly associated with ISUP grade (p19.8 ng/ml and SUVmax of the primary prostate tumor >7.4 had a sensitivity of 71.6% and 71.6% and specificity of 76.9% and 82.6%, respectively, for detecting metastatic disease.Conclusions[99mTc]Tc-HYNIC-ALUG SPECT/CT emerges as a valuable imaging tool for the initial staging of newly diagnosed PCa. The presence of advanced disease and the SUVmax of the primary prostate tumor were positively correlated with ISUP grade and PSA levels.

Background/objectivesPost-keratoplasty infectious keratitis (PKIK) is a unique sight-threatening clinical entity which often poses significant therapeutic challenges. This study aimed to examine the clinical presentation, risk factors, management, and clinical outcomes of PKIK.MethodsThis was a retrospective study of all patients who presented to the Queen’s Medical Centre, Nottingham, with PKIK between September 2015 and August 2022 (a 7-year period). Relevant data on types of keratoplasty, clinical presentations, causative microorganisms, management, and outcome were analyzed.ResultsForty-nine PKIK cases, including four cases of interface infectious keratitis, were identified during the study period. The most common graft indications for PKP, DALK and EK were failed grafts (9, 37.5%), keratoconus (6, 54.5%) and Fuchs endothelial corneal dystrophy (FECD; 8, 57.1%), respectively. Staphylococcus spp. were the most commonly identified organisms (15, 50.0%). Bullous keratopathy (18, 36.7%), ocular surface disease (18, 36.7%), and broken/loose sutures (15, 30.6%) were the most common risk factors. Concurrent use of topical steroids was identified in 25 (51.0%) cases. Of 31 functioning grafts at presentation, 12 (38.7%) grafts failed at final follow-up with 15 (48.4%) patients retaining a CDVA of ≥1.0 logMAR. The overall estimated 5-year survival rate post-PKIK was 55.9% (95% CI, 35.9%-75.9%), with DALK having the highest survival rate [63.6% (95% CI, 28.9%-98.3%)], followed by EK [57.1% (95% CI, 20.4%-93.8%)] and PKP [52.7% (95% CI, 25.1%-80.3%)], though no statistical difference was observed (p=0.48).ConclusionsPKIK represents an important cause of IK and graft failure. Bullous keratopathy, OSD and suture-related complications are the commonest risk factors, highlighting the potential benefit of prophylactic topical antibiotics (for unhealthy ocular surface) and early suture removal (where possible) in reducing the risk of PKIK. Graft survival may be higher in lamellar keratoplasty following PKIK but larger studies are required to elucidate this observation.

Keratoconus is the most common corneal ectatic disorder. It is characterized by progressive corneal thinning with resultant irregular astigmatism and myopia. Its prevalence has been estimated at 1:375 to 1:2,000 people globally, with a considerably higher rate in the younger populations. Over the past two decades, there was a paradigm shift in the management of keratoconus. The treatment has expanded significantly from conservative management (e.g., spectacles and contact lenses wear) and penetrating keratoplasty to many other therapeutic and refractive modalities, including corneal cross-linking (with various protocols/techniques), combined CXL-keratorefractive surgeries, intracorneal ring segments, anterior lamellar keratoplasty, and more recently, Bowman’s layer transplantation, stromal keratophakia, and stromal regeneration. Several recent large genome-wide association studies (GWAS) have identified important genetic mutations relevant to keratoconus, facilitating the development of potential gene therapy targeting keratoconus and halting the disease progression. In addition, attempts have been made to leverage the power of artificial intelligence-assisted algorithms in enabling earlier detection and progression prediction in keratoconus. In this review, we provide a comprehensive overview of the current and emerging treatment of keratoconus and propose a treatment algorithm for systematically guiding the management of this common clinical entity.

Introduction Infectious keratitis (IK) represents the fifth-leading cause of blindness worldwide. A delay in diagnosis is often a major factor in progression to irreversible visual impairment and/or blindness from IK. The diagnostic challenge is further compounded by low microbiological culture yield, long turnaround time, poorly differentiated clinical features and polymicrobial infections. In recent years, deep learning (DL), a subfield of artificial intelligence, has rapidly emerged as a promising tool in assisting automated medical diagnosis, clinical triage and decision-making, and improving workflow efficiency in healthcare services. Recent studies have demonstrated the potential of using DL in assisting the diagnosis of IK, though the accuracy remains to be elucidated. This systematic review and meta-analysis aims to critically examine and compare the performance of various DL models with clinical experts and/or microbiological results (the current ‘gold standard’) in diagnosing IK, with an aim to inform practice on the clinical applicability and deployment of DL-assisted diagnostic models.Methods and analysis This review will consider studies that included application of any DL models to diagnose patients with suspected IK, encompassing bacterial, fungal, protozoal and/or viral origins. We will search various electronic databases, including EMBASE and MEDLINE, and trial registries. There will be no restriction to the language and publication date. Two independent reviewers will assess the titles, abstracts and full-text articles. Extracted data will include details of each primary studies, including title, year of publication, authors, types of DL models used, populations, sample size, decision threshold and diagnostic performance. We will perform meta-analyses for the included primary studies when there are sufficient similarities in outcome reporting.Ethics and dissemination No ethical approval is required for this systematic review. We plan to disseminate our findings via presentation/publication in a peer-reviewed journal.PROSPERO registration number CRD42022348596.

A planar Langmuir probe, which can be used for both ion electric propulsion beam characteristics measurement and plasma diagnosis, was developed and applied to plume measurement and diagnosis experiments of an 8 cm Kaufman ion thruster to address the growing demand for miniaturized ion thruster plume measurement and diagnosis. The experimental results show that the plume area exhibits good symmetry along the central axis, and the beam dispersion angle of the 8 cm ion thruster is approximately 22.7°. The radial distributions of the floating potential, plasma space potential and ion density are similar, showing a high distribution in the middle and a relatively low distribution at the two ends. The miniaturized ion thruster plume measurement and diagnosis system is not only easy to manipulate, but also fast and efficient for plasma plume measurement and diagnosis, which provides more complete data support for analyzing the working state of the miniaturized ion thrusters and optimizing the design of the thruster structure.

Background: Osteosarcoma (OS) is a type of bone cancer most often affects pre-teens and teens, but it is still a rare disorder. Neuropilin and tolloid-like 2 (NETO2) has been reported to promote OS progression, but its upstream mechanism in OS cells remains obscure. Methods: Quantitative real-time PCR (RT-qPCR) and Western blot were conducted to examine RNA and protein levels, separately. Functional assays were performed to assess the impact of NETO2 on OS cell malignancy. Moreover, bioinformatics analyses and mechanism experiments were performed to identify the upstream mechanism of NETO2 in OS cells. Results: Functionally, NETO2 depletion repressed cell proliferation, migration and invasion as well as epithelial-mesenchymal transition (EMT) but triggered the apoptosis of OS cells. NETO2 is directly targeted and negatively regulated by microRNA-101-3p (miR-101-3p). Mechanically, miR-101-3p could combine with long noncoding RNA (lncRNA) TYMS opposite strand RNA (TYMSOS) in OS cells. In addition, our study proved that TYMSOS promotes the malignancy of OS via elevating NETO2 expression as miR-101-3p sponge. Conclusion: TYMSOS-miR-101-3p-NETO2 axis promotes the malignant behaviors of OS cells, which might offer a novel sight for OS treatment.

The tumor-adipose microenvironment (TAME) is a universal microecosystem, that is characterized by the dysfunction of lipid metabolism, such as excessive free fatty acids (FFAs). Macrophages are the most abundant immune cell type within TAME, although their diversity in the TAME is not clear. We first reveal that infiltration of M2-like macrophages in the TAME is associated with poor survival in breast cancer. To explore lipid-associated alterations in the TAME, we also detected the levels of FFAs transporters including fatty acid binding proteins (FABPs) and fatty acid transport protein 1 (FATP1). The results indicated that expression of fatty acid transporters in the TAME is tightly linked to the function of macrophages and predicts survival in breast cancer. To explore the impact of FFAs transporters on the function of macrophages, we performed single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics. Consequently, we identified a special subpopulation of macrophages defined as lipid-associated macrophages (LAMs), highly expressed macrophage markers (CD163, SPP1 and C1QC), genes involved in lipid metabolism (FABP3, FABP4, FABP5, LPL and LIPA) and some lipid receptors (LGALS3 and TREM2). Functionally, LAMs were characterized by a canonical functional signature of M2-like macrophages, lipid accumulation and enhancing phagocytosis, and they were mostly distributed in tumor-adipose junctional regions. Finally, the allograft cancer mouse models confirmed that LAMs depletion in the TAME synergizes the antitumorigenic effects of anti-PD1 therapy. In summary, we defined a novel subtype of macrophages in the TAME, that has unique features and clinical outcomes.

Artificial Intelligence (AI) has the power to improve our lives through a wide variety of applications, many of which fall into the healthcare space; however, a lack of diversity is contributing to limitations in how broadly AI can help people. The UCSF AI4ALL program was established in 2019 to address this issue by targeting high school students from underrepresented backgrounds in AI, giving them a chance to learn about AI with a focus on biomedicine, and promoting diversity and inclusion. In 2020, the UCSF AI4ALL three-week program was held entirely online due to the COVID-19 pandemic. Thus, students participated virtually to gain experience with AI, interact with diverse role models in AI, and learn about advancing health through AI. Specifically, they attended lectures in coding and AI, received an in-depth research experience through hands-on projects exploring COVID-19, and engaged in mentoring and personal development sessions with faculty, researchers, industry professionals, and undergraduate and graduate students, many of whom were women and from underrepresented racial and ethnic backgrounds. At the conclusion of the program, the students presented the results of their research projects at the final symposium. Comparison of pre- and post-program survey responses from students demonstrated that after the program, significantly more students were familiar with how to work with data and to evaluate and apply machine learning algorithms. There were also nominally significant increases in the students' knowing people in AI from historically underrepresented groups, feeling confident in discussing AI, and being aware of careers in AI. We found that we were able to engage young students in AI via our online training program and nurture greater diversity in AI. This work can guide AI training programs aspiring to engage and educate students entirely online, and motivate people in AI to strive towards increasing diversity and inclusion in this field.

Abstract Breast cancer is one of the most common malignant tumors among women worldwide. About 70‐75% of primary breast cancers belong to estrogen receptor (ER)‐positive breast cancer. In the development of ER‐positive breast cancer, abnormal activation of the ERα pathway plays an important role and is also a key point leading to the failure of clinical endocrine therapy. In this study, we found that the small molecule peptide chlorotoxin (CTX) can significantly inhibit the proliferation, migration and invasion of breast cancer cells. In in vitro study, CTX inhibits the expression of ERα in breast cancer cells. Further studies showed that CTX can directly bind to ERα and change the protein secondary structure of its LBD domain, thereby inhibiting the ERα signaling pathway. In addition, we also found that vasodilator stimulated phosphoprotein (VASP) is a target gene of ERα signaling pathway, and CTX can inhibit breast cancer cell proliferation, migration, and invasion through ERα/VASP signaling pathway. In in vivo study, CTX significantly inhibits growth of ER overexpressing breast tumor and, more importantly, based on the mechanism of CTX interacting with ERα, we found that CTX can target ER overexpressing breast tumors in vivo. Our study reveals a new mechanism of CTX anti‐ER‐positive breast cancer, which also provides an important reference for the study of CTX anti‐ER‐related tumors.

Power generation can be realized in space when current is induced on a bare electrodynamic tether system. The performance of power generation is discussed based on a debris mitigation mission by numerical simulation in the paper. A Li-ion battery subsystem is used to complete the energy conversion—harvest and supply the energy. The battery can provide 10–300 W average electric power continuously during several hundred hour mission time. The energy conversion efficiency ranges from 1% to a maximum value 30%. With constant power consumption on board, the battery operation generally experiences a discharging phase, a charging phase, and a stable phase. The first two phases determine the mission risk coefficient. The heating problem in the stable phase cannot be ignored. The optimization of battery design and tether design should be considered for each debris mitigation mission. An extra control circuit or small battery voltage with large capacity for battery design is suggested to eliminate the stable phase. Wide or long tether designs are more appropriate for mission with high or low power demands on board, respectively. The power generation is affected by the system mass and the mission orbit parameters.

Additive manufacturing is rapidly opening its way into many areas of the aerospace industry, where different 3D printing technologies are finding niche applications in which they do not only simplify the process and allow shorter lead times, but also the particularities of these new fabrication methods yield new material properties that enhance the component and can lead to higher performance and longer service life of an aerospace system. Although rapid manufacturing processes are being tested for in-space manufacturing and are commonly used to fabricate UAV parts and some spacecraft subsystems with 3D printed components have been tested in space, little research has been conducted on the potential application of these techniques to electric thrusters. This paper presents the study conducted on the application of selective laser melting, a powder bed fusion technology, to the fabrication of ion engine grids and the challenges faced during the process. The first proof of concept and its optimization are described. Later, the development of the selective laser melting process for molybdenum, the study of the 3D printed materials' properties, their direct application to ion extraction systems, and the tests of additively-manufactured ion optics are described. It was found that 3D printed grids can be accurately fabricated with titanium and molybdenum, that they perform similar to conventional optics in short tests, that the selective laser melting process allows certain control of the coefficient of thermal expansion of the output and that this fabrication method allows the reproduction of sputtering erosion patterns. Future research in this direction will cover sputtering tests of selectively-laser-melted samples and the additive manufacturing of carbon-carbon grids.

PURPOSE: Activation of Toll like receptors (TLRs) signaling has been implicated in promoting malignant cell invasion and metastatic potential. Previously we demonstrated that increased TLR-9 expression predicted poor survival in oral cancer patients. The objective of this study is to further investigate the roles and potential molecular mechanisms of TLR-9 signaling in human oral cancer cell invasion. METHODS: Cell migration, invasion and protein expression were detected by wound healing assay, Transwell chambers model and western blot. The secretion and activity levels of metalloproteinases-2/9 were quantified by ELISA and Gelatin zymography. EMSA and ChIP assays were employed to detect the activity of AP-1signal pathway. TLR-9 siRNA transfection was used to regulate the expression and activity of TLR-9 in oral cancer cell line HB cells. RESULT: The results of both wound healing assay and in vitro Transwell assay revealed that activation of TLR-9 induced dose- and time- dependent migration and invasion of HB cells. An increased expression, secretion and activity of MMP-2 were observed upon the treatment of CpG-ODN. The TLR-9 signaling-mediated MMP-2 expression appeared to be a consequence of AP-1 activation, because that their DNA binding activity was enhanced by CpG-ODN treatment. All these influences were efficiently repressed by the knockdown of TLR-9 through siRNA or pretreatment of an AP-1 inhibitor. CONCLUSION: Activation of TLR-9 signaling could promote human oral cancer HB cells invasion with the induction of MMP-2 presentation by attenuating AP-1 binding activity, suggesting a novel anti-metastatic application for TLR-9 targeted therapy in oral cancer in the future.

Knowing the total number of species in a region has been a question of great interest motivated by the need to provide a reference point for current and future losses of biodiversity. Unfortunately, obtaining an accurate number is constrained by the fact that most species remain to be discovered, due to the imperfect detection of species in the field collection or because of temporal turnover in species composition. Here, to understand the inventory completeness at the local scale, we studied the temporal dynamics in the species richness and composition of bryophytes in Tianmushan National Nature Reserve. We used β-diversity to measure the temporal variation and analyzed the species attributes of newly discovered species collected this time. Furthermore, we evaluated our sampling strategy to measure sampling effect and estimated the species that remain to be discovered. We found that total β-diversity was largely driven by turnover. The analysis of species attributes showed that epiphytic species dominate the newly recorded species in both the narrow and wide elevational range species. Further, if only one of the methods was adopted, 26%-29% of the newly discovered species would be missed, and we inferred that there are likely are 185 bryophytes yet to be discovered. Our results indicate that when the same effort was made, an appropriate sampling methodology is crucial to accelerate newly recorded species discovery. Further, the results of our study highlight that species temporal turnover should be considered when assessing the completeness of species inventories at the local scale., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Biomolecular dynamics simulation is a fundamental technology for life sciences research, and its usefulness depends on its accuracy and efficiency 1-3 . Classical molecular dynamics simulation is fast but lacks chemical accuracy 4,5 . Quantum chemistry methods such as density functional theory can reach chemical accuracy but cannot scale to support large biomolecules 6 . Here we introduce an artificial intelligence-based ab initio biomolecular dynamics system (AI 2 BMD) that can efficiently simulate full-atom large biomolecules with ab initio accuracy. AI 2 BMD uses a protein fragmentation scheme and a machine learning force field 7 to achieve generalizable ab initio accuracy for energy and force calculations for various proteins comprising more than 10,000 atoms. Compared to density functional theory, it reduces the computational time by several orders of magnitude. With several hundred nanoseconds of dynamics simulations, AI 2 BMD demonstrated its ability to efficiently explore the conformational space of peptides and proteins, deriving accurate 3 J couplings that match nuclear magnetic resonance experiments, and showing protein folding and unfolding processes. Furthermore, AI 2 BMD enables precise free-energy calculations for protein folding, and the estimated thermodynamic properties are well aligned with experiments. AI 2 BMD could potentially complement wet-lab experiments, detect the dynamic processes of bioactivities and enable biomedical research that is impossible to conduct at present., (© 2024. The Author(s).)

Our ability to pinpoint causal variants using GWAS is dependent on understanding the dynamic epigenomic and epistatic context of each associated locus. Being the best studied skeletal locus, GDF5 associates with many diseases and has a complex cis-regulatory architecture. We interrogate GDF5 regulatory interactions and model disease variants in vitro and in vivo . For all regulatory regions we see that local epigenetic activation/repression impacts patterns of joint-specific expression and disease risk. By modeling the most cited risk variant in mice we found that it had no impact on expression, joint morphology, or disease. Yet, we identified significant epistatic expression interactions between this risk variant and others lying within regulatory regions subject to repression or activation. These findings are important lessons on how regulatory interactions and local epistasis work in the etiology of disease risk, and that assessment of individual variants of high GWAS significance need not alone be considered causal., Competing Interests: Competing Interests The following individuals have competing interests: Dr. Hao Chen (Genentech); Dr. Ata Kiapour (MIACH orthopedics), Dr. Pushpanathan Muthuirulan (23&Me); Dr. Zun Liu (Sanofi); Dr. Vicki Rosen (Incyte Pharmaceuticals; Lightning Pharmaceuticals). All other authors do not have competing interests.

The fusion of low-resolution hyperspectral images (LR-HSI) with high-resolution multispectral images (HR-MSI) provides a cost-effective approach to obtaining high-resolution hyperspectral images (HR-HSI). Existing methods primarily based on convolutional neural networks (CNNs) struggle to capture global features and do not adequately address the significant scale and spectral resolution differences between LR-HSI and HR-MSI. To tackle these challenges, our novel FCSwinU network leverages the spectral fast Fourier convolution (SFFC) module for spectral feature extraction and utilizes the Swin Transformer's self-attention mechanism for multi-scale global feature fusion. FCSwinU employs a UNet-like encoder-decoder framework to effectively merge spatiospectral features. The encoder integrates the Swin Transformer feature abstraction module (SwinTFAM) to encode pixel correlations and perform multi-scale transformations, facilitating the adaptive fusion of hyperspectral and multispectral data. The decoder then employs the Swin Transformer feature reconstruction module (SwinTFRM) to reconstruct the fused features, restoring the original image dimensions and ensuring the precise recovery of spatial and spectral details. Experimental results from three benchmark datasets and a real-world dataset robustly validate the superior performance of our method in both visual representation and quantitative assessment compared to existing fusion methods.

Background: Unfavorable social determinants of health (SDoH) are associated with depression. Both depression and SDoH are associated with increased risks of mortality, but their joint impacts on mortality risks remain unclear. This study aims to investigate the joint effects of depression and SDoH on mortality risk., Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018, 24,727 adults aged ≥ 20 were included. SDoH was assessed based on the 5 domains outlined in the U.S. Healthy People 2030 initiative. The cumulative number of unfavorable SDoH was calculated and categorized into low and high burden levels. The definition of depression was based on the Patient Health Questionnaire-9 (PHQ-9) scores ≥ 10. The joint associations of depression and SDoH with all-cause, cardiovascular disease (CVD), and cancer mortality were examined using Cox proportional hazard models., Results: We identified 2,377 (6.84%) all-cause deaths (CVD, 717; cancer, 606) during a median follow-up of 7.0 years. Depression was associated with increased mortality risks, and SDoH could explain 32.4% and 28.3% of the associations between depression and all-cause and CVD mortality, respectively. No significant interactions were observed between depression and SDoH on mortality. However, a low burden of unfavorable SDoH reduced the risk of all-cause mortality in depressed patients (hazard ratio [HR], 0.58; 95% confidence interval [CI]: 0.36-0.92). In the joint analysis, individuals with both depression and a high burden of unfavorable SDoH had the highest risks of all-cause and CVD mortality. Specifically, compared with individuals with no depression and a low burden of unfavorable SDoH, those with depression and a high burden of unfavorable SDoH had higher risks of all-cause (HR, 2.52; 95% CI: 2.01-3.18) and CVD mortality (HR, 2.79; 95% CI: 1.95-3.99)., Conclusion: Adults with both depression and a high burden of unfavorable SDoH had the highest risks of all-cause mortality and CVD mortality. The result suggests considering depression and SDoH jointly in developing targeted intervention strategies to improve survival outcomes and calls for larger cohort studies and clinical trials to validate our findings., (© 2024. The Author(s).)

Purpose: The aim of this study was to evaluate the inter- and intrafractional organs motions and dosimetric advantages of MRI guided online adaptive radiotherapy for cervical cancer., Methods: A total of 150 fractions treated on the 1.5 T Unity MR-Linac were included in this study. Each fraction, pre-treatment, position validation and post-treatment MRI scans were obtained. Structures including CTV, rectum and bladder were delineated by the same radiation oncologists on each MRI. The inter- and intrafractional changes of contours were assessed by Hausdorff distance (HD), dice similarity coefficient (DSC), relative volume difference (ΔV) and the relative positions of the geometric center. The non-ART plans and online adaptive plans were obtained by recalculating or re-optimizing from reference plans on daily MRI, respectively. CTV coverage and OARs constraints were evaluated between ART and non-ART plans., Results: For each fraction, the interfractional changes of HD, ΔV and DSC for CTV, bladder and rectum were significant. Our study also examined the relationship of bladder and rectum filling on CTV position. For 150 non-ART plans, CTV coverage constraints (D 98%  ≥ 45 Gy) were not met by 45 %, while 15 % were not covered by more than 5 % of the prescribed dose. Compared to the non-ART plans, the ART plans had higher CTV coverage and lower dose to the bladder and rectum (P < 0.05). During the treatment, the intrafractional changes of bladder, rectum and CTV may affect actual dose delivery. And we observed an intrafractional time trend in the motion of the CTV. There were 15 % fractions failing the CTV coverage constraints in post-MRI due to intrafractional motion. The adaptive plans optimized with 3 mm margin could cover CTV of post-MRI in 98 % fractions., Conclusions: Considerable inter- and intrafractional CTV and OARs changes were observed in cervical cancer patients treated on MR-Linac. MRI guided online ART has significant dosimetric advantages in cervical cancer and is an ideal approach for achieving individualized and precise radiotherapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Background: Genetic factors, including the Hedgehog Interacting Protein (HHIP) gene, play a crucial role in Chronic Obstructive Pulmonary Disease (COPD) susceptibility. This study examines the association between HHIP gene polymorphisms and COPD susceptibility, phenotypes, and serum IL-17 and IL-18 levels in a Han Chinese population., Methods: A case-control study was conducted with 300 COPD patients and 300 healthy controls in Chinese Han population. Participants underwent genotyping for HHIP gene polymorphisms, pulmonary function tests, and quantitative CT scans. DNA samples were sequenced using a custom chip targeting the HHIP gene. Serum IL-17 and IL-18 levels were measured by enzyme-linked immunosorbent assay. Associations between SNPs, COPD susceptibility, and phenotypes were analyzed using logistic and multiple linear regression models, adjusting for confounders., Results: Our study identified the rs11100865 polymorphism in the HHIP gene as significantly associated with COPD susceptibility (OR 2.479, 95% CI 1.527-4.024, P = 2.39E-04) after screening 114 SNPs through rigorous quality control. Stratified analyses further indicated this association was particularly in individuals aged 60 or older. Serum levels of IL-17 and IL-18 were significantly elevated in COPD patients compared to controls, with rs11100865 showing a notable association with IL-18 levels (B = 49.654, SE = 19.627, P = 0.012). However, no significant associations were observed between rs11100865 and serum IL-17 levels, COPD-related imaging parameters, or clinical phenotypes., Conclusion: This study identified a significant association between HHIP gene polymorphisms and COPD susceptibility in a Han Chinese population, with connections to inflammation, but found no significant associations between this SNP and COPD-related imaging or clinical phenotypes., Trial Registration: www.chictr.org.cn ID: ChiCTR2300071579 2023-05-18., (© 2024. The Author(s).)

Articular cartilage has limited self-healing ability, resulting in injuries often evolving into osteoarthritis (OA), which poses a significant challenge in the medical field. Although some treatments exist to reduce pain and damage, there is a lack of effective means to promote cartilage regeneration. Reactive Oxygen Species (ROS) have been found to increase significantly in the OA micro-environment. They play a key role in biological systems by participating in cell signaling and maintaining cellular homeostasis. Abnormal ROS expression, caused by internal and external stimuli and tissue damage, leads to elevated levels of oxidative stress, inflammatory responses, cell damage, and impaired tissue repair. To prevent excessive ROS accumulation at injury sites, biological materials can be engineered to respond to the damaged microenvironment, release active components in an orderly manner, regulate ROS levels, reduce oxidative stress, and promote tissue regeneration. Hydrogels have garnered significant attention due to their excellent biocompatibility, tunable physicochemical properties, and drug delivery capabilities. Numerous antioxidant hydrogels have been developed and proven effective in alleviating oxidative stress. This paper discusses a comprehensive treatment strategy that combines antioxidant hydrogels with existing treatments for OA and explores the potential applications of antioxidant hydrogels in cartilage tissue engineering., 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 He, Wu, He, Han, Chen and Huang.)

Background: Hydrocephalus ranks among the most prevalent neurosurgical conditions worldwide, with a growing body of literature suggesting a potential association with inflammation. Employing bibliometric methods, this research visually analyzes the scholarly output on inflammation in hydrocephalus over the past 2 decades and provides a scientific framework for delineating research pathways and addressing key issues in this field., Methods: Publications sourced from the Web of Science Core Collection as of July 18, 2024 encompassed articles and reviews in English spanning from January 1, 2000, to December 31, 2024. Statistical analyses of countries, institutions, authors, references, and keywords were conducted utilizing VOSviewer1.6.20 and CiteSpace6.3. R1., Results: A total of 424 reviews and articles were included in the analysis, showcasing a rising trajectory in publications concerning inflammation and hydrocephalus over time. The United States emerged as the leading contributor in terms of publication output, with Harvard Medical School topping the list of institutions. Notably, World Neurosurgery and Journal of Neurosurgery emerged as the most prolific journals and the most frequently cited, respectively. Authors Keep, Richard F., and Xi, Guo Hua, demonstrated the highest productivity, while Karimy, J.K., emerged as the author with the highest co-citation count. Following thorough analysis, the predominant keywords identified include mechanisms, management, inflammation, posthemorrhagic hydrocephalus, cerebrospinal fluid, surgery, microglia, risk factors, and choroid plexus, reflecting current research hotspots likely to persist., Conclusions: This study will help researchers determine the mainstream research directions and latest hotspots of inflammation in hydrocephalus and provide a reference for revealing the molecular mechanism of hydrocephalus., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The association among coronary heart disease, ischemic stroke, and hydrocephalus remains ambiguous., Objectives: There is a need for a Mendelian randomization study to evaluate the underlying causality between coronary heart disease, ischemic stroke, and hydrocephalus., Methods: The data source utilized genome-wide association studies, employing a threshold of p < 5 × 10 -8 to identify single nucleotide polymorphisms strongly linked to ischemic stroke and coronary heart disease as instrumental variables (IVs). Five methods-inverse variance weighted (IVW), Mendelian randomization (MR) Egger, Weighted Median, Weighted mode, and Simple mode-utilized the selected IVs to estimate the causality between ischemic stroke, coronary heart disease, and hydrocephalus., Results: The IVW demonstrated that ischemic stroke and coronary heart disease serve as risk factors for hydrocephalus (odds ratio [OR] = 1.650, 95% CI: 1.066-2.554, p = 0.025; OR = 1.307, 95% CI: 1.023-1.668, p = 0.032). Both the MR-Egger intercept test and Cochran's Q test affirmed the relative reliability of the IVW analysis results. However, no evidence of a reverse causation was observed between hydrocephalus and coronary heart disease or ischemic stroke., Conclusions: Coronary heart disease and Ischemic stroke may increase the risk of hydrocephalus., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Purpose: To achieve high-resolution fetal brain anatomical imaging without introducing image artifacts by reducing the FOV, and to demonstrate improved image quality compared to conventional full-FOV fetal brain imaging., Methods: Reduced FOV was achieved by applying outer volume suppression (OVS) pulses immediately prior to standard single-shot fast spin echo (SSFSE) imaging. In the OVS preparation, a saturation RF pulse followed by a gradient spoiler was repeated three times with optimized flip-angle weightings and a variable spoiler scheme to enhance signal suppression. Simulations and phantom and in-vivo experiments were performed to evaluate OVS performance. In-vivo high-resolution SSFSE images acquired using the proposed approach were compared with conventional and high-resolution SSFSE images with a full FOV, using image quality scores assessed by neuroradiologists and calculated image metrics., Results: Excellent signal suppression in the saturation bands was confirmed in phantom and in-vivo experiments. High-resolution SSFSE images with a reduced FOV acquired using OVS demonstrated the improved depiction of brain structures without significant motion and blurring artifacts. The proposed method showed the highest image quality scores in the criteria of sharpness, contrast, and artifact and was selected as the best method based on overall image quality. The calculated image sharpness and tissue contrast ratio were also the highest with the proposed method., Conclusion: High-resolution fetal brain anatomical images acquired using a reduced FOV with OVS demonstrated improved image quality both qualitatively and quantitatively, suggesting the potential for enhanced diagnostic accuracy in detecting fetal brain abnormalities in utero., (© 2024 International Society for Magnetic Resonance in Medicine.)

Asymmetric synthesis of 3-(3-indolomethyl)oxindoles through the addition of indole-substituted enolized ketoesters to 3-bromo-3-substituted oxindoles has been achieved using a N , N '-dioxide/Ho(III) complex. A number of 3-(3-indolomethyl)oxindoles, which may possess biological activity, were obtained in good yields with high diastereo- and enantioselectivities (up to 97% yield, >19 : 1 dr, 98% ee). Furthermore, time-dependent reversal of diastereoselectivity enabled access to optically active diastereomers. The product followed by facile transformations gave a new route into trigolute analogs.

Objectives: Excessive reactive oxygen species (ROS) in diabetic wounds are major contributors to chronic wounds and impaired healing, posing significant challenges in regenerative medicine. Developing innovative drug delivery systems is crucial to address these issues by modifying the adverse microenvironment and promoting effective wound healing. Methods: Herein, we designed a novel drug delivery platform using manganese dioxide nanoflower hybridized gold nanoparticle composites (MnO 2 -Au) synthesized via a hydrothermal reaction, and investigated the potential of MnO 2 -Au nanoflowers to relieve the high oxidative stress microenvironment and regulate diabetic wound tissue healing. Results: This hybrid material demonstrated superior catalytic activity compared to MnO 2 alone, enabling the rapid decomposition of hydrogen peroxide and a substantial reduction in ROS levels within dermal fibroblasts. The MnO 2 -Au nanoflowers also facilitated enhanced dermal fibroblast migration and Col-I expression, which are critical for tissue regeneration. Additionally, a hydrogel-based wound dressing incorporating MnO 2 -Au nanoflowers was developed, showing its potential as an intelligent drug delivery system. This dressing significantly reduced oxidative stress, accelerated wound closure, and improved the quality of neonatal epithelial tissue regeneration in a diabetic rat skin defect model. Conclusions: Our findings underscore the potential of MnO 2 -Au nanoflower-based drug delivery systems as a promising therapeutic approach for chronic wound healing, particularly in regenerative medicine.

Background and Purpose: Quantitative susceptibility mapping is an emerging method for characterizing tissue composition and studying myelination and iron deposition. However, accurate assessment of myelin and iron content in the newborn brain using this method is challenging because these two susceptibility sources of opposite signs (myelin, negative; iron, positive) occupy the same voxel, with minimal and comparable content in both sources. In this study, susceptibilities were measured in the normal newborn brain using susceptibility source separation., Materials and Methods: Sixty-nine healthy newborns without clinical indications were prospectively recruited for MRI. All newborns underwent gradient echo imaging for quantitative susceptibility mapping. Positive (paramagnetic) and negative (diamagnetic) susceptibility sources were separated using additional information from R2* with linear modeling performed for the newborn brain. Average susceptibility maps were generated by normalizing all susceptibility maps to an atlas space. Mean regional susceptibility measurements were obtained in the cortical GM, WM, deep GM, caudate nucleus, putamen, globus pallidus, thalamus, and the four brain lobes., Results: A total of sixty-five healthy newborns (mean postmenstrual age, 42.8 ± 2.3 weeks; 34 females) were studied. The negative susceptibility maps visually demonstrated high signals in the thalamus, brainstem and potentially myelinated WM regions, whereas the positive susceptibility maps depicted high signals in the GM compared to all WM regions, including both myelinated and unmyelinated WM. The WM exhibited significantly lower mean positive susceptibility and significantly higher mean negative susceptibility than cortical GM and deep GM. Within the deep GM, the thalamus showed a significantly lower mean negative susceptibility than the other nuclei, and the putamen and globus pallidus showed significant associations with newborn age in positive and/or negative susceptibility. Among the four brain lobes, the occipital lobe showed a significantly higher mean positive susceptibility and a significantly lower mean negative susceptibility than the frontal lobe., Conclusions: This study demonstrates regional variations and temporal changes in positive and negative susceptibilities of the newborn brain, potentially associated with myelination and iron deposition patterns in normal brain development. It suggests that quantitative susceptibility mapping with source separation may be used for early identification of delayed myelination or iron deficiency., Abbreviations: CGM = cortical gray matter; DGM = deep gray matter; PMA = postmenstrual age; QSM = quantitative susceptibility mapping., Competing Interests: The authors declare no conflicts of interest related to the content of this article., (© 2024 by American Journal of Neuroradiology.)

Osteoarthritis is a highly prevalent progressive joint disease that still requires an optimal therapeutic approach. Intermittent fasting is an attractive dieting strategy for improving health. Here this study shows that intermittent fasting potently relieves medial meniscus (DMM)- or natural aging-induced osteoarthritic phenotypes. Osteocytes, the most abundant bone cells, secrete excess neuropeptide Y (NPY) during osteoarthritis, and this alteration can be altered by intermittent fasting. Both NPY and the NPY-abundant culture medium of osteocytes (OCY-CM) from osteoarthritic mice possess pro-inflammatory, pro-osteoclastic, and pro-neurite outgrowth effects, while OCY-CM from the intermittent fasting-treated osteoarthritic mice fails to induce significant stimulatory effects on inflammation, osteoclast formation, and neurite outgrowth. Depletion of osteocyte NPY significantly attenuates DMM-induced osteoarthritis and abolishes the benefits of intermittent fasting on osteoarthritis. This study suggests that osteocyte NPY is a key contributing factor in the pathogenesis of osteoarthritis and intermittent fasting represents a promising nonpharmacological antiosteoarthritis method by targeting osteocyte NPY., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Spinal cord injury (SCI) is a serious trauma of the central nervous system. The clearance of myelin debris is a critical step in the functional recovery following spinal cord injury (SCI). Recent studies have begun to reveal critical roles for professional phagocytes in the central nervous system, microglia, and their receptors in the control of myelin debris in neurodegenerative disease. Repeated trans-spinal magnetic stimulation (rTSMS) has been demonstrated as a noninvasive SCI treatment that enhances tissue repair and functional recovery. In this study, we investigated the role and molecular mechanism of rTSMS on microglial phagocytosis of myelin debris in a rat SCI model. In our studies, we found that rTSMS significantly promoted the motor function recovery of SCI rats associated with the inhibition the neuroinflammation and glia scar formation. Immunofluorescence results further showed that the rTSMS promotes the clearance of myelin debris by microglia in vivo and in vitro. Additionally, receptor-associated protein (RAP), a Low-density lipoprotein receptor-related protein-1 (LRP-1) inhibitor, could cancel the accelerated microglial phagocytosis of myelin debris after rTSMS in vitro experiments. Simultaneously, Elisa's results and western blotting respectively showed that rTSMS significantly decreased the levels of soluble LRP-1(sLRP-1) and the LRP-1 splicing enzyme of ADAM17. In conclusion, rTSMS could promote the clearance of myelin debris by microglia through LRP-1 to improve the functional recovery of SCI rats., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The activation and polarization of astrocytes are involved in neuroinflammation and brain functional rehabilitation after ischemic stroke. Our previous studies display the neuroprotective effect of genistein-3'-sodium sulfonate (GSS) in the acute phase of cerebral ischemia-reperfusion injury (CI/RI). This study aimed to investigate the brain function improvement of GSS during the recovery period after CI/RI in rats and to explore the potential mechanism from the perspective of astrocyte activation and polarization. The transient middle cerebral artery occlusion (tMCAO) rats were treated with GSS (1 mg/kg) continuously for 28 days. The behavior tests were measured to assess neurological function. The mRNA and protein expression in affected cerebral cortex were detected on day 29 after tMCAO. Our results demonstrated that GSS treatment significantly improved the spatial and temporal gait parameters in the Catwalk gait test, prolonged the time on the stick and increased the rotation speed in the rotarod test, and decreased the time to find the hidden platform and increased the time in the target quadrant in the Morris water maze test. In addition, GFAP, GBP2, C3, IL-1β protein expressions and Nos2A mRNA level were decreased, while Nrf2, BDNF, IL-10 protein expressions and Sphk1 and Nef2l2 mRNA levels increased after GSS treatment. Interestingly, GSS presented a strong binding affinity to TLR4 and suppressed the activation of NF-κB signaling. In conclusion, GSS can promote brain function recovery by inhibiting astrocyte activation and polarization to A1 phenotype, and enhancing astrocyte polarization to A2 phenotype via inactivating TLR4/NF-κB signaling, which provide a candidate compound for clinical rehabilitation therapy in the recovery period after ischemic stroke., 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 B.V. All rights reserved.)

By employing non-equilibrium molecular dynamics (NEMD) simulations and time-dependent Ginzburg-Landau (TDGL) theory for solidification kinetics [Cryst. Growth Des. 20, 7862 (2020)], we predict the kinetic coefficients of FCC(100) crystal-melt interface (CMI) of soft-spheres modeled with an inverse-sixth-power repulsive potential. The collective dynamics of the local interfacial liquid phase at the equilibrium FCC(100) CMIs are calculated based on a recently proposed algorithm [J. Chem. Phys. 157, 084 709 (2022)] and are employed as the resulting parameter that eliminates the discrepancy between the predictions of the kinetic coefficient using the NEMD simulations and the TDGL solidification theory. A speedup of the two modes of the interfacial liquid collective dynamics (at wavenumbers equal to the principal and the secondary reciprocal lattice vector of the grown crystal) is observed. With the insights provided by the quantitative predictive theory, the variation of the solidification kinetic coefficient along the crystal-melt coexistence boundary is discussed. The combined methodology (simulation and theory) presented in this study could be further applied to investigate the role of the inter-atomic potential (e.g., softness parameter s = 1/n of the inverse-power repulsive potential) in the kinetic coefficient., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background and Aims: Latitudinal diversity gradients have been intimately linked to the tropical niche conservatism hypothesis, which posits that there has been a strong filter due to the challenges faced by ancestral tropical lineages to adapt to low temperatures and colonize extra-tropical regions. In liverworts, species richness is higher towards the tropics, but the centres of diversity of the basal lineages are distributed across extra-tropical regions, pointing to the colonization of tropical regions by phylogenetically clustered assemblages of species of temperate origin. Here, we test this hypothesis through analyses of the relationship between macroclimatic variation and phylogenetic diversity in Chinese liverworts., Methods: Phylogenetic diversity metrics and their standardized effect sizes for liverworts in each of the 28 regional floras at the province level in China were related to latitude and six climate variables using regression analysis. We conducted variation partitioning analyses to determine the relative importance of each group of climatic variables., Key Results: We find that the number of species decreases with latitude, whereas phylogenetic diversity shows the reverse pattern, and that phylogenetic diversity is more strongly correlated with temperature-related variables compared with precipitation-related variables., Conclusions: We interpret the opposite patterns observed in phylogenetic diversity and species richness in terms of a more recent origin of tropical diversity coupled with higher extinctions in temperate regions., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Annals of Botany Company. 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.)

Objective: To observe the effects of thunder-fire moxibustion on the balance function and musculoskeletal metabolism in female patients of primary osteoporosis (POP) with low muscle mass., Methods: Sixty female patients of POP with low muscle mass were randomly divided into an observation group (30 cases, 5 cases dropped out) and a control group (30 cases, 2 cases dropped out). The patients in the control group were treated with oral administration of Caltrate D (1.5 g calcium carbonate + 125 IU vitamin D3), one tablet per day for 12 weeks. In addition to the control treatment, the patients in the observation group were treated with thunder-fire moxibustion at Mingmen (GV 4), Yaoyangguan (GV 3), bilateral Ganshu (BL 18), Shenshu (BL 23), and Dachangshu (BL 25), 30 min per acupoint, once every other day, three times a week, for 12 weeks. Balance function indexes (95% confidence ellipse area of the center of pressure [COP], total displacement, average speed), lumbar pain visual analogue scale (VAS), serum muscle metabolism factors (myostatin [MSTN], peroxisome proliferator-activated receptor γ coactivator-1α [PGC-1α]) and bone metabolism factors (aminoterminal propeptide typeⅠ procollagen [PINP], C-terminal telopeptide of typeⅠcollagen [CTX-Ⅰ]) were compared before and after treatment in both groups., Results: Compared before treatment, the 95% confidence ellipse area of COP, total displacement, and average speed in the observation group were decreased after treatment ( P <0.01), and the above indexes in the observation group were lower than those in the control group ( P <0.05). Compared before treatment, the VAS scores in both groups were decreased after treatment ( P <0.01), the score in the observation group was lower than that in the control group ( P <0.01). Compared before treatment, the serum levels of MSTN, PINP and CTX-Ⅰ in the observation group were reduced after treatment ( P <0.01), while the serum level of PGC-1α was increased ( P <0.01). The control group showed a decrease in serum level of MSTN ( P <0.05). The observation group had lower serum levels of MSTN and PINP ( P <0.05) and higher serum level of PGC-1α ( P <0.01) compared to the control group., Conclusion: The thunder-fire moxibustion can effectively relieve lumbar pain, improve balance function, and regulate musculoskeletal metabolism in female patients of POP with low muscle mass.

Accurate prediction of drug-target binding affinity (DTA) plays a pivotal role in drug discovery and repositioning. Although deep learning methods are widely used in DTA prediction, two significant challenges persist: (i) how to effectively represent the complex structural information of proteins and drugs; (ii) how to precisely model the mutual interactions between protein binding sites and key drug substructures. To address these challenges, we propose a MSFFDTA (Multi-scale feature fusion for predicting drug target affinity) model, in which multi-scale encoders effectively capture multi-level structural information of drugs and proteins are designed. And then a Selective Cross Attention (SCA) mechanism is developed to filter out the trivial interactions between drug-protein substructure pairs and retain the important ones, which will make the proposed model better focusing on these key interactions and offering insights into their underlying mechanism. Experimental results on two benchmark datasets demonstrate that MSFFDTA is superior to several state-of-the-art methods across almost all comparison metrics. Finally, we provide the ablation and case studies with visualizations to verify the effectiveness and the interpretability of MSFFDTA. The source code is freely available at https://github.com/whitehat32/MSFF-DTA/., 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.)

Human activities have caused an imbalance in the input nitrogen and phosphorus (N/P) in the biosphere. The imbalance of N/P is one of the characteristics of water eutrophication, which is the fundamental factor responsible for the blooms. The effects of the N/P imbalance on diatom and phycospheric bacteria in blooms are poorly understood. In this study, the N/P molar ratio in real water (14:1) and the predicted N/P molar ratio in future water (65:1) were simulated to analyze the response of Cyclotella sp. and phycospheric bacteria to the N/P imbalance. The results showed that the N/P imbalance inhibited the growth of Cyclotella sp., but prolonged diatom bloom duration. The resistance of Cyclotella sp. to the N/P imbalance is related to phycospheric bacteria, and there are dynamic regulatory mechanisms within the phycospheric bacteria community to resist the N/P imbalance: (1) the increase of HNA bacterial density, the decrease of LNA bacterial density, (2) the increase of phycospheric bacterial diversity and eutrophic bacteria abundance, and the change of denitrifying bacteria abundance, (3) the activity of nitrogen and phosphorus metabolism of HNA bacteria enhanced, while that of LNA bacteria decreased. And the gene hosts of nitrogen and phosphorus metabolism were most enriched in Proteobacteria, indicating that Proteobacteria played an important role in maintaining the stability of phycospheric bacteria and was the dominant phylum resistant to the N/P imbalance. This study clarified that the algal-bacteria system was resistant to the N/P imbalance and implied that the N/P imbalance had little effect on the occurrence of diatom bloom events due to the presence of phycospheric bacteria., 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.)

Plant protein-based foods have become dietary preferences worldwide, and the quality of this food group is highly associated with the ingredients used. This study investigated the effects of incorporating caramel, tomato powder, and carrot powder on the product quality of soy protein-based meat patties (SPMPs). The color, total phenolic content (TPC), antioxidant activity, lipid oxidation, and texture profile of uncooked and cooked soy protein meat patties were analyzed. Among the cooked SPMPs, caramel SPMPs exhibited the lowest color difference (ΔE) values, and the ΔE value of tomato SPMPs was lower than that of carrot SPMPs, indicating that caramel has the best color stability, and the tomato experienced less color change than the carrot during cooking. Notably, carrot SPMPs exhibited lower color stability during refrigeration storage than the others. Both carrot and tomato powders increased the total phenolic content (TPC) and antioxidant stability and inhibited lipid oxidation in SPMPs during cooking. However, tomato SPMPs exhibited higher TPC values and greater antioxidant stability compared to carrot SPMPs. The addition of caramel and carrot powders decreased the hardness of raw SPMPs, but tomato powder increased the hardness. The texture profile of tomato SPMPs was more affected by the cooking process compared to caramel and carrot SPMPs. This study showed that incorporating both carrot and tomato powders positively influenced the quality characteristics of SPMPs compared to caramel powder, however, tomato powder exhibited superior efficacy.

Multiple odour nuisance in livestock farming is a notorious problem that has a significant impact on the living environment of surrounding communities. Adsorbents based on metal-organic framework (MOF) materials show great promise for controlling odour pollution, as they offer a high specific surface area, a controllable structure and an abundance of active sites. However, the MOF formation process is prone to problems such as pore clogging or collapse and reduced porosity, which limits its further application. In this study, a series of odour adsorbents were prepared by in situ growth of NH 2 -UiO-66 on tea stem biochar (TSBC) using a hydrothermal method and named UiO (Zr)-TSBC x . The physical and chemical properties and composition of UiO (Zr)-TSBC x have been systematically characterized using SEM, TEM, XRD, FT-IR, N 2 adsorption-desorption and XPS. The release of odours from the pig farm effluent was monitored using in-situ continuous Proton-Transfer-Reaction Mass Spectrometry (PTR-MS), and the obtained primary compositions were tested for further adsorption. In dynamic adsorption experiments focused on butyric acid, UiO (Zr)-TSBC 2 showed a high adsorption capacity of 3.99 × 10 5  μg/g and exceptional structural stability. UiO (Zr)-TSBC 2 showed variable adsorption efficiencies for different odorous gases, with the best performance for the removal of ammonia, toluene and butyric acid. It also demonstrated the ability to rapidly mitigate instantaneous high concentrations of hydrogen sulfide (H 2 S), methanethiol and toluene resulting from agitation. Additionally, based on the relationship between the adsorption amount and the structural characteristics of the adsorbent as well as the nature of the odours, a possible adsorption mechanism of UiO (Zr)-TSBC 2 for a variety of odours released from pig farm effluent was proposed. This work demonstrates a novel approach to promote deodorization applications in livestock and poultry farming environments by the in-situ growth of NH 2 -UiO-66 on biochar prepared from tea stem., 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.)

Idiopathic pulmonary fibrosis treatments are limited, often with severe side effects, highlighting the need for novel options. Taraxerone has diverse biomedical properties, but its mechanism remains unclear. This study investigates taraxerone's impact and the mechanisms involved in bleomycin-induced pulmonary fibrosis in mice. After establishing a pulmonary fibrosis mouse model, taraxerone was intraperitoneally injected continuously for 14-28 days. The in vivo antifibrotic and antioxidative stress effects of taraxerone were assessed. In vitro, the influence of taraxerone on transforming growth factor-β1-induced myofibroblast transformation and oxidative stress was investigated. Subsequently, quantitative polymerase chain reaction screened the histone deacetylase and Sirtuin family, and taraxerone's effects on SIRT1 were assessed. After SIRT1 siRNA treatment, changes in myofibroblast transformation and antioxidant capacity in response to taraxerone were observed. Acetylation and phosphorylation levels of Smad3 were evaluated. We also examined the binding levels of SIRT1 with Pho-Smad3 and Smad3, as well as the nuclear localization of Smad2/3. EX527 confirmed SIRT1's in vivo action in response to taraxerone. In vitro experiments suggested that taraxerone inhibited myofibroblast differentiation by activating SIRT1 and reducing oxidative stress. We also observed a new interaction between SIRT1 and the Smad complex. Taraxerone activates SIRT1, enabling it to bind directly to Smad3. This leads to reduced Smad complex phosphorylation and limited nuclear translocation. As a result, the transcription of fibrotic factors is reduced. In vivo validation confirms taraxerone's SIRT1-mediated antifibrotic effectiveness. This suggests that targeting SIRT1-mediated inhibition of myofibroblast differentiation could be a key strategy in taraxerone-based therapy for pulmonary fibrosis., (© 2024 John Wiley & Sons Ltd.)

Background and Aims: The mitotic catastrophe (MC) pathway plays an important role in hepatocellular carcinoma (HCC) progression and tumor microenvironment (TME) regulation. However, the mechanisms linking MC heterogeneity to immune evasion and treatment response remain unclear., Methods: Based on 94 previously published highly correlated genes for MC, HCC patients' data from the Cancer Genome Atlas (TCGA) and changes in immune signatures and prognostic stratification were studied. Time and spatial-specific differences for MCGs were assessed by single-cell RNA sequencing and spatial transcriptome (ST) analysis. Multiple external databases (GEO, ICGC) were employed to construct an MC-related riskscore model., Results: Identification of two MC-related subtypes in HCC patients from TCGA, with clear differences in immune signatures and prognostic risk stratification. Spatial mapping further associates low MC tumor regions with significant immune escape-related signaling. Nomogram combining MC riskscore and traditional indicators was validated great effect for early prediction of HCC patient outcomes., Conclusion: MC heterogeneity enables immune escape and therapy resistance in HCC. The MC gene signature serves as a reliable prognostic indicator for liver cancer. By revealing clear immune and spatial heterogeneity of HCC, our integrated approach provides contextual therapeutic strategies for optimal clinical decision-making., 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 Mao, Gao, Long, Guo, Chen, Huan and Yin.)

Anthracycline drugs mainly include doxorubicin, epirubicin, pirarubicin, and aclamycin, which are widely used to treat a variety of malignant tumors, such as breast cancer, gastrointestinal tumors, lymphoma, etc. With the accumulation of anthracycline drugs in the body, they can induce serious heart damage, limiting their clinical application. The mechanism by which anthracycline drugs cause cardiotoxicity is not yet clear. This review provides an overview of the different types of cardiac damage induced by anthracycline-class drugs and delves into the molecular mechanisms behind these injuries. Cardiac damage primarily involves alterations in myocardial cell function and pathological cell death, encompassing mitochondrial dysfunction, topoisomerase inhibition, disruptions in iron ion metabolism, myofibril degradation, and oxidative stress. Mechanisms of uptake and transport in anthracycline-induced cardiotoxicity are emphasized, as well as the role and breakthroughs of iPSC in cardiotoxicity studies. Selected novel cardioprotective therapies and mechanisms are updated. Mechanisms and protective strategies associated with anthracycline cardiotoxicity in animal experiments are examined, and the definition of drug damage in humans and animal models is discussed. Understanding these molecular mechanisms is of paramount importance in mitigating anthracycline-induced cardiac toxicity and guiding the development of safer approaches in cancer treatment., 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 Xie, Sun, Zhao, Xiao, Zhou, Lin, Wang, Lin, Wang, Fang, Wang and Zhang.)