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Objectives: To establish the epidemiology cut-off (ECOFF) values of eravacycline against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Acinetobacter baumannii and Staphylococcus aureus, from a multi-centre study in China., Methods: We collected 2500 clinical isolates from five hospitals in China from 2017 to 2020. The MICs of eravacycline were determined using broth microdilution. The ECOFF values of eravacycline against the five species commonly causing cIAIs were calculated using visual estimation and ECOFFinder following the EUCAST guideline., Results: The MICs of eravacycline against all the strains were in the range of 0.004-16 mg/L. The ECOFF values of eravacycline were 0.5 mg/L for E. coli, 2 mg/L for K. pneumonia and E. cloacae, and 0.25 mg/L for A. baumannii and S. aureus, consistent with the newest EUCAST publication of eravacycline ECOFF values for the populations. No discrepancy was found between the visually estimated and 99.00% ECOFF values calculated using ECOFFinder., Conclusions: The determined ECOFF values of eravacycline against the five species can assist in distinguishing wild-type from non-wild-type strains. Given its promising activity, eravacycline may represent a member of the tetracycline class in treating cIAIs caused by commonly encountered Gram-negative and Gram-positive pathogens., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Motivation: Mobile genetic elements (MGEs) are as ubiquitous in nature as they are varied in type, ranging from viral insertions to transposons to incorporated plasmids. Horizontal transfer of MGEs across bacterial species may also pose a significant threat to global health due to their capability to harbor antibiotic resistance genes. However, despite cheap and rapid whole-genome sequencing, the varied nature of MGEs makes it difficult to fully characterize them, and existing methods for detecting MGEs often do not agree on what should count. In this manuscript, we first define and argue in favor of a divergence-based characterization of mobile-genetic elements. Results: Using that paradigm, we present skandiver, a tool designed to efficiently detect MGEs from whole-genome assemblies without the need for gene annotation or markers. skandiver determines mobile elements via genome fragmentation, average nucleotide identity (ANI), and divergence time. By building on the scalable skani software for ANI computation, skandiver can query hundreds of complete assemblies against >65 000 representative genomes in a few minutes and 19 GB memory, providing scalable and efficient method for elucidating mobile element profiles in incomplete, uncharacterized genomic sequences. For isolated and integrated large plasmids (>10 kb), skandiver's recall was 48% and 47%, MobileElementFinder was 59% and 17%, and geNomad was 86% and 32%, respectively. For isolated large plasmids, skandiver's recall (48%) is lower than state-of-the-art reference-based methods geNomad (86%) and MobileElementFinder (59%). However, skandiver achieves higher recall on integrated plasmids and, unlike other methods, without comparing against a curated database, making skandiver suitable for discovery of novel MGEs., Availability and Implementation: https://github.com/YoukaiFromAccounting/skandiver., (© The Author(s) 2024. Published by Oxford University Press.)

The vaginal epithelium plays pivotal roles in host defense against pathogen invasion, contributing to the maintenance of an acidic microenvironment within the vaginal lumen through the activity of acid-base transport proteins. However, the precise defense mechanisms employed by the vaginal epithelium following bacterial infection remain incompletely understood. This study demonstrated that the bacterial lipopolysaccharide (LPS) potentiated net proton efflux by up-regulating the expression of Na + -H + exchanger 1 (NHE1), without affecting other acid-base transport proteins in vaginal epithelial cells. Pharmacological inhibition or genetic knockdown of Toll-like receptor-4 (TLR4) and the extracellular-signal-regulated protein kinase (ERK) signaling pathway effectively counteracted the up-regulation of NHE1 and the enhanced proton efflux triggered by LPS in vaginal epithelial cells. In vivo studies revealed that LPS administration led to luminal acidification through the up-regulation of NHE1 expression in the rat vagina. Moreover, inhibition of NHE exhibited impaired defense against acute bacterial infection in the rat vagina. These findings collectively indicated the active involvement of vaginal epithelial cells in facilitating luminal acidification during acute bacterial infection, offering potential insights into the treatment of bacterial vaginosis., (Copyright © 2024. Published by Elsevier Inc.)

Ethnopharmacological Relevance: Tubeimoside-I (TBM) promotes various cancer cell death by increasing the reactive oxygen species (ROS) production. However, the specific molecular mechanisms of TBM and its impact on oxaliplatin-mediated anti-CRC activity are not yet fully understood., Aim of the Study: To elucidate the therapeutic effect and underlying molecular mechanism of TBM on oxaliplatin-mediated anti-CRC activity., Materials and Methods: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, wound healing assays and flow cytometry were conducted to investigate the changes in cell phenotypes and ROS generation. Real-time quantitative PCR (qRT-PCR) and western blotting were performed to detect the expressions of related mRNA and proteins. Finally, mouse xenograft models demonstrated that synergistic anti-tumor effects of combined treatment with TBM and oxaliplatin., Results: The synergistic enhancement of the anti-tumor effects of oxaliplatin in colon cancer cells by TBM involved in the regulation of ROS-mediated endoplasmic reticulum (ER) stress, C-jun-amino-terminal kinase (JNK), and p38 MAPK signaling pathways. Mechanistically, TBM increased ROS generation in colon cancer cells by inhibiting heat shock protein 60 (HSPD1) expression. Knocking down HSPD1 increased TBM-induced antitumor activity and ROS generation in colon cancer cells. The mouse xenograft tumor models further validated that the combination therapy exhibited stronger anti-tumor effects than monotherapy alone., Conclusions: Combined therapy with TBM and oxaliplatin might be an effective therapeutic strategy for some CRC patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We report electrochemical measurements using in situ Raman spectroscopy at graphene/D 2 O interfaces under extremely low applied potentials. Here, the hydrophobic and catalytically inert nature of graphene and the insulating nature of the deionized (DI) water enables potentials as low as V applied = -7 V vs Ag/AgCl to be applied without exceeding 200 μA/cm 2 of current density. At higher currents, bubble formation (i.e., hydrogen evolution reaction) prohibits reliable spectra from being obtained from the electrode surface. Using CaF 2 as the supporting substrate enables significantly lower reducing potentials to be reached compared to glass substrates, likely due to trapped charge and impurities in the glass substrate. G band Raman spectra taken under various applied electrochemical potentials exhibit a linear relationship between the G band shift (Δω G ) and the applied potential, with blueshifts as high as Δω G = 18 cm -1 . These large Raman shifts indicate a large change in the Fermi level of Δ E F = -0.43 eV for graphene electrodes in contact with water, favoring reduction half-reactions. Based on the solution resistance measurement, there is a V IR = 3.1 V voltage drop across the solution for D 2 O (when the applied potential was V applied = -7 V vs Ag/AgCl) and the effective reducing potential on the working electrode is V effective = -3.9 V vs Ag/AgCl. We have also tested these graphene electrodes in ionic liquids [DEME][TFSI], which are limited to applied potentials above V applied = -2.7 V vs Ag/AgCl and a corresponding shift in the Fermi level Δ E F = -0.32 eV, indicating that pure water can provide a more robust electrolyte for reaching low reducing potentials than ionic liquids.

Objectives: Endovascular therapy (EVT) now penetrates the once obscure realm of large infarct core volume acute ischaemic stroke (LICV-AIS). This research aimed to investigate the potential correlation between different anaesthetic approaches and post-EVT outcomes in LICV-AIS patients., Methods: Between October 2020 and May 2022, the China ANGEL-Alberta Stroke Programme Early CT Score (ASPECT) trial studied patients with LICV-AIS, randomly assigning them to the best medical management (BMM) or BMM with EVT. This post hoc subgroup analysis categorised subjects receiving BMM with EVT into general anaesthesia (GA) and non-GA groups based on anaesthesia type. We applied multivariable logistic regression to evaluate the relationship between anaesthesia during EVT and patient functional outcomes, as measured by the modified Rankin scale (mRS), in addition to the occurrence of complications. Further adjustment for selection bias was achieved through propensity score matching (PSM)., Results: In total, 230 patients with LICV-AIS were enrolled (GA 84 vs Non-GA 146). No significant difference was observed between the two groups in terms of the proportion of patients who achieved an mRS score of 0-2 at 90 days (27.4% for the GA group vs 31.5% for the non-GA group, p=0.51). However, the GA group had significantly longer median surgical times (142 min vs 122 min, p=0.03). Furthermore, GA was associated with an increased risk of postoperative pneumonia (adjusted OR 2.03, 95% CI 1.04 to 3.98). The results of PSM analysis agreed with the results of the multivariate regression analysis. No significant difference in intracranial haemorrhage incidence or mortality rate was observed between the groups., Conclusion: This post hoc analysis of subgroups of the ANGEL-ASPECT trial suggested that there may be no significant association between the choice of anaesthesia and neurological outcomes in LICV-AIS patients. However, compared with non-GA, GA prolongs the duration of EVT and is associated with a greater postoperative pneumonia risk., Trial Registration Number: NCT04551664., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This letter discusses the publication by Feng et al . Iodine, selenium, and vitamin D are closely associated with thyroid hormone production in humans; however, the efficacy of selenium and vitamin D supplementation for type 2 diabetes mellitus (T2DM) patients with Hashimoto's thyroiditis (HT) remains controversial. In the retrospective study we discuss herein, the authors highlighted significant improvements in thyroid function, thyroid antibodies, blood glucose, and blood lipid in T2DM patients with HT following addition of vitamin D and selenium to their antidiabetic regimens, underscoring the value of these supplements. Our team is currently engaged in research exploring the relationship between micronutrients and HT, and we have obtained invaluable insights from the aforementioned study. Based on this research and current literature, we recommend a regimen of 4000 IU/day of vitamin D and 100-200 μg/day of selenium for over three months to six months for patients with HT, particularly for those with concurrent T2DM., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Artemisinin (ART) analogs, such as dihydroartemisinin, arteether, artemether, and artesunate, all featuring an endoperoxide bridge, have demonstrated efficacy against schistosomiasis. Artemisitene (ATT), which contains an additional α, β-unsaturated carbonyl structure, has shown enhanced biological activities. This study aims to evaluate the anti-schistosomaiasis japonica activity of ATT and compare it with ART., Methods: We assessed liver inflammation and fibrosis in mice using hematoxylin and eosin staining and Sirius red staining, respectively. RNA sequencing analyzed transcriptomics in female and male Schistosoma japonicum (S. japonicum) adult worms and mice livers, with cytokine profiling and flow cytometry to study immune responses under ART or ATT treatment., Results: ATT exhibits a marked reduction in female S. japonicum adult worms and egg numbers, damaging the adult worms' surface. It also influences the transcription of genes related to cellular anatomical structures. Notably, ATT treatment resulted in significant reductions in liver granuloma size and collagen area, alongside lowering serum levels of glutamic pyruvic and glutamic oxaloacetic transaminase more effectively than ART. Both ART and ATT markedly decreased neutrophil frequency in the liver and elevated eosinophil counts. However, only ATT treatment significantly reduced the M1/M2 and Th1/Th2 indices, indicating a pronounced shift in immune response profiles. ATT-affected host immunity correlated with the extent of liver fibrosis and the count of single males more strongly than ART., Conclusion: ATT, as a novel preventive strategy for schistosomiasis japonica in mice, significantly outperforms ART., (© 2024. The Author(s).)

Background: Metagenomic binning, the clustering of assembled contigs that belong to the same genome, is a crucial step for recovering metagenome-assembled genomes (MAGs). Contigs are linked by exploiting consistent signatures along a genome, such as read coverage patterns. Using coverage from multiple samples leads to higher-quality MAGs; however, standard pipelines require all-to-all read alignments for multiple samples to compute coverage, becoming a key computational bottleneck., Results: We present fairy ( https://github.com/bluenote-1577/fairy ), an approximate coverage calculation method for metagenomic binning. Fairy is a fast k-mer-based alignment-free method. For multi-sample binning, fairy can be > 250 × faster than read alignment and accurate enough for binning. Fairy is compatible with several existing binners on host and non-host-associated datasets. Using MetaBAT2, fairy recovers 98.5 % of MAGs with > 50 % completeness and < 5 % contamination relative to alignment with BWA. Notably, multi-sample binning with fairy is always better than single-sample binning using BWA ( > 1.5 × more > 50 % complete MAGs on average) while still being faster. For a public sediment metagenome project, we demonstrate that multi-sample binning recovers higher quality Asgard archaea MAGs than single-sample binning and that fairy's results are indistinguishable from read alignment., Conclusions: Fairy is a new tool for approximately and quickly calculating multi-sample coverage for binning, resolving a computational bottleneck for metagenomics. Video Abstract., (© 2024. The Author(s).)

Background: Nasopharyngeal carcinoma (NPC) is a malignant epithelial carcinoma arising from the nasopharyngeal mucosal lining. Diagnosis of NPC at early stage can improve the outcome of patients and facilitate reduction in cancer mortality. The most significant change between cancer cells and normal cells is the variation of cell nucleus. Therefore, accurately detecting the biochemical changes in nucleus between cancer cells and normal cells has great potential to explore diagnostic molecular markers for NPC. Highly sensitive surface-enhanced Raman scattering (SERS) could reflect the biochemical changes in the process of cell cancerization at the molecular level. However, rapid nuclear targeting SERS detection remains a challenge., Results: A novel and accurate nuclear-targeting SERS detection method based on electroporation was proposed. With the assistance of electric pulses, nuclear-targeting nanoprobes were rapidly introduced into different NPC cells (including CNE1, CNE2, C666 cell lines) and normal nasopharyngeal epithelial cells (NP69 cell line), respectively. Under the action of nuclear localization signaling peptides (NLS), the nanoprobes entering cells were located to the nucleus, providing high-quality nuclear SERS signals. Hematoxylin and eosin (H&E) staining and in situ cell SERS imaging confirmed the excellent nuclear targeting performance of the nanoprobes developed in this study. The comparison of SERS signals indicated that there were subtle differences in the biochemical components between NPC cells and normal nasopharyngeal cells. Furthermore, SERS spectra combined with principal component analysis (PCA) and linear discriminant analysis (LDA) were employed to diagnose and distinguish NPC cell samples, and high sensitivity, specificity, and accuracy were obtained in the screening of NPC cells from normal nasopharyngeal epithelial cells., Significance: To the best of our knowledge, this is the first study that employing nuclear-targeting SERS testing to screen nasopharyngeal carcinoma cells. Based on the electroporation technology, nanoprobes can be rapidly introduced into living cells for intracellular biochemical detection. Nuclear-targeting SERS detection can analyze the biochemical changes in the nucleus of cancer cells at the molecular level, which has great potential for early cancer screening and cytotoxicity analysis of anticancer drugs., 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: Gliomas are the most common primary brain tumours and constitute approximately half of all malignant glioblastomas. Unfortunately, patients diagnosed with malignant glioblastomas typically survive for less than a year. In light of this circumstance, genotyping is an effective means of categorising gliomas. The Ki67 proliferation index, a widely used marker of cellular proliferation in clinical contexts, has demonstrated potential for predicting tumour classification and prognosis. In particular, magnetic resonance imaging (MRI) plays a vital role in the diagnosis of brain tumours. Using MRI to extract glioma-related features and construct a machine learning model offers a viable avenue to classify and predict the level of Ki67 expression., Methods: This study retrospectively collected MRI data and postoperative immunohistochemical results from 613 glioma patients from the First Affliated Hospital of Nanjing Medical University. Subsequently, we performed registration and skull stripping on the four MRI modalities: T1-weighted (T1), T2-weighted (T2), T1-weighted with contrast enhancement (T1CE), and Fluid Attenuated Inversion Recovery (FLAIR). Each modality's segmentation yielded three distinct tumour regions. Following segmentation, a comprehensive set of features encompassing texture, first-order, and shape attributes were extracted from these delineated regions. Feature selection was conducted using the least absolute shrinkage and selection operator (LASSO) algorithm with subsequent sorting to identify the most important features. These selected features were further analysed using correlation analysis to finalise the selection for machine learning model development. Eight models: logistic regression (LR), naive bayes, decision tree, gradient boosting tree, and support vector classification (SVM), random forest (RF), XGBoost, and LightGBM were used to objectively classify Ki67 expression., Results: In total, 613 patients were enroled in the study, and 24,455 radiomic features were extracted from each patient's MRI. These features were eventually reduced to 36 after LASSO screening, RF importance ranking, and correlation analysis. Among all the tested machine learning models, LR and linear SVM exhibited superior performance. LR achieved the highest area under the curve score of 0.912 ± 0.036, while linear SVM obtained the top accuracy with a score of 0.884 ± 0.031., Conclusion: This study introduced a novel approach for classifying Ki67 expression levels using MRI, which has been proven to be highly effective. With the LR model at its core, our method demonstrated its potential in signalling a promising avenue for future research. This innovative approach of predicting Ki67 expression based on MRI features not only enhances our understanding of cell activity but also represents a significant leap forward in brain glioma research. This underscores the potential of integrating machine learning with medical imaging to aid in the diagnosis and prognosis of complex diseases., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yun Liu reports financial support was provided by The industry prospecting and common key technology key projects of Jiangsu Province Science and Technology Department., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

In this study, a series of BiTeX (X = Cl, Br, I) photocatalysts were successfully synthesized via a simple hydrothermal method. The synthesis process involved dissolving BiX 3 and Te powder in toluene to identify the most efficient material for photocatalytic activity. The main objective of this approach is to facilitate the conversion of carbon dioxide into sustainable solar fuels, such as alcohols and hydrocarbons, offering an appealing solution to address environmental concerns and energy crises. The BiTeX photocatalysts demonstrated significant proficiency in converting CO 2 into CH 4 , particularly BiTeCl exhibited a notable photocatalytic conversion rate of up to 0.51 μmolg -1 h -1 . The optimized BiTeX photocatalysts displayed a gradual and selective transition from CO 2 to CH 4 , ultimately producing valuable hydrocarbons (C 2+ ). Furthermore, owing to their ability to reduce CO 2 , these photocatalysts show promise as materials for mitigating environmental pollution., 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: The benefits and risks of Xileisan (XLS) in the treatment of ulcerative colitis (UC) remain unclear., Aim: The present study aimed to evaluate the efficacy and safety of the combination of XLS and mesalazine when treating UC., Methods: We searched eight databases for clinical trials evaluating the combination of XLS and mesalazine in the treatment of UC, up to January 2024. Meta-analysis and trial sequential analysis (TSA) were performed using Revman 5.3 and TSA 0.9.5.10 beta, respectively., Results: The present study included 13 clinical studies involving 990 patients, of which 501 patients received XLS combined with mesalazine while 489 patients received mesalazine alone. The meta-analysis showed that, in terms of efficacy, the combination of XLS and mesalazine significantly improved the clinical efficacy rate by 22% [risk ratio (RR) = 1.22; 95%CI: 1.15-1.28; P < 0.00001] and mucosal improvement rate by 25% (RR = 1.25; 95%CI: 1.12-1.39; P = 0.0001), while significantly reducing the duration of abdominal pain by 2.25 days [mean difference (MD) = -2.25; 95%CI: -3.35 to -1.14; P < 0.0001], diarrhea by 2.06 days (MD = -2.06; 95%CI: -3.92 to -0.20; P = 0.03), hematochezia by 2.32 days (MD = -2.32; 95%CI: -4.02 to -0.62; P = 0.008), tumor necrosis factor alpha by 16.25 ng/mL (MD = -16.25; 95%CI: -20.48 to -12.01; P < 0.00001), and interleukin-6 by 14.14 ng/mL (MD = -14.14; 95%CI: -24.89 to -3.39; P = 0.01). The TSA indicated conclusiveness in the meta-analysis of the efficacy endpoints. In terms of safety, the meta-analysis revealed that the combination of XLS and mesalazine did not increase the occurrence of total and gastrointestinal adverse events, abdominal distension, and erythema ( P > 0.05). The TSA showed non conclusive findings in the meta-analysis of the safety endpoints. Harbord's test showed no publication bias ( P = 0.734)., Conclusion: Treatment with XLS alleviated the clinical symptoms, intestinal mucosal injury, and inflammatory response in patients with UC, while demonstrating good safety., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The aim of this study was to evaluate colloids and crystalloids used in perioperative fluid therapy for cardiac surgery patients to further investigate the optimal management strategies of different solutions., Method: RCTs about adult surgical patients allocated to receive perioperative fluid therapy for electronic databases, including Ovid MEDLINE, EMBase, and Cochrane Central Register of Controlled Trials, were searched up to February 15, 2023., Results: None of the results based on network comparisons, including mortality, transfuse PLA, postoperative chest tube output over the first 24 h following surgery, and length of hospital stay, were statistically significant. Due to the small number of included studies, the results, including acute kidney injury, serum creatinine, serum microglobulin, and blood urea nitrogen, are from the direct comparison. For transfusion of RBCs, significant differences were observed in the comparisons of 3% gelatine vs. 6% HES 200/0.5, 4% albumin vs. 5% albumin, 4% gelatine vs. 5% albumin, 5% albumin vs. 6% HES 200/0.5, and 6% HES 130/0.4 vs. 6% HES 200/0.5. In transfusion of FFP, significant differences were observed in comparisons of 3% gelatine vs. 4% gelatine, 3% gelatine vs. 6% HES 200/0.5, 5% albumin vs. 6% HES 200/0.5, 4% gelatine vs. 5% albumin, 4% gelatine vs. 6% HES 200/0.4, and 6% HES 130/0.4 vs. 6% HES 200/0.5. For urinary output at 24 h after surgery, the results are deposited in the main text., Conclusion: This study showed that 3% gelatin and 5% albumin can reduce the transfuse RBC and FFP. In addition, the use of hypertonic saline solution can increase urine output, and 5% albumin and 6% HES can shorten the length of ICU stay. However, none of the perioperative fluids showed an objective advantage in various outcomes, including mortality, transfuse PLA, postoperative chest tube output over the first 24 h following surgery, and length of hospital stay. The reliable and sufficient evidences on the injury of the kidney, including acute kidney injury, serum creatinine, serum microglobulin, and blood urea nitrogen, was still lacking. In general, perioperative fluids had advantages and disadvantages, and there were no evidences to support the recommendation of the optimal perioperative fluid for cardiac surgery., (© 2024. The Author(s).)

An influenza vaccine approach that overcomes the problem of viral sequence diversity and provides long-lived heterosubtypic protection is urgently needed to protect against pandemic influenza viruses. Here, to determine if lung-resident effector memory T cells induced by cytomegalovirus (CMV)-vectored vaccines expressing conserved internal influenza antigens could protect against lethal influenza challenge, we immunize Mauritian cynomolgus macaques (MCM) with cynomolgus CMV (CyCMV) vaccines expressing H1N1 1918 influenza M1, NP, and PB1 antigens (CyCMV/Flu), and challenge with heterologous, aerosolized avian H5N1 influenza. All six unvaccinated MCM died by seven days post infection with acute respiratory distress, while 54.5% (6/11) CyCMV/Flu-vaccinated MCM survived. Survival correlates with the magnitude of lung-resident influenza-specific CD4 + T cells prior to challenge. These data demonstrate that CD4 + T cells targeting conserved internal influenza proteins can protect against highly pathogenic heterologous influenza challenge and support further exploration of effector memory T cell-based vaccines for universal influenza vaccine development., (© 2024. The Author(s).)

Background: The impact of type 1 diabetes (T1D) on inflammatory bowel disease (IBD) remains unclear., Aim: To analyze the causal relationship between T1D and IBD using Mendelian ran-domization (MR)., Methods: Single nucleotide polymorphisms were sourced from FinnGen for T1D, IBD, ulcerative colitis (UC) and Crohn's disease (CD). Inverse variance-weighted, MR-Egger, and weighted median tests were used to assess exposure-outcome causality. The MR-Egger intercept was used to assess horizontal pleiotropy. Co-chran's Q and leave-one-out method were used to analyze heterogeneity and sensitivity, respectively., Results: Our MR analysis indicated that T1D was associated with a reduced risk of IBD [odds ratio (OR): 0.959; 95% confidence interval (CI): 0.938-0.980; P < 0.001] and UC (OR: 0.960; 95%CI: 0.929-0.992; P = 0.015), with no significant association observed in terms of CD risk (OR: 0.966; 95%CI: 0.913-1.022; P = 0.227). The MR-Egger intercept showed no horizontal pleiotropy ( P > 0.05). Cochran's Q and leave-one-out sensitivity analyses showed that the results were not heterogeneous ( P > 0.05) and were robust., Conclusion: This MR analysis suggests that T1D serves as a potential protective factor against IBD and UC but is independent of CD., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The presence of an external magnetic field is found to affect the competition between the H 2 O and CO 2 reduction reactions by increasing mass transport via the Lorentz force. Increasing the magnetic field strength at the electrode surface from 0 to 325 mT increases the selectivity of CO over H 2 by 3×, while an increase in current density from 0.5 to 5 mA/cm 2 increases the selectivity of CO production by 5×. Cyclic voltammetry and finite-element simulations reveal that the origin of the enhanced CO selectivity is attributable to a magnetic field lowering the electrode-electrolyte interfacial pH. A drop in interfacial pH enables increased production of CO from CO 2 reduction due to a decrease in the activity of H 2 O reduction and increase in CO 2 solubility near the electrode surface. The insight provided in this study offers new opportunities to control reaction selectivity in electrocatalysis with magnetic field vectors.

Bacteria, especially drug-resistant strains, can quickly cause wound infections, leading to delayed healing and fatal risk in clinics. With the growing need for alternative antibacterial approaches that rely less on antibiotics or eliminate their use altogether, a novel antibacterial hydrogel named Ovtgel is developed. Ovtgel is formulated by chemically crosslinking thiol-modified ovotransferrin (Ovt), a member of the transferrin family found in egg white, with olefin-modified agarose through thiol-ene click chemistry. Ovt is designed to sequester ferric ions essential for bacterial survival and protect wound tissues from damages caused by the reactive oxygen species (ROS) generated in Fenton reactions. Experimental data have shown that Ovtgel significantly enhances wound healing by inhibiting bacterial growth and shielding tissues from ROS-induced harms. Unlike traditional antibiotics, Ovtgel targets essential trace elements required for bacterial survival in the host environment, preventing the development of drug resistance in pathogenic bacteria. Ovtgel exhibits excellent biocompatibility due to the homology of Ovt to mammalian transferrin. This hydrogel has the potential to serve as an effective antibiotic-free solution for combating bacterial infections., (© 2024 Wiley‐VCH GmbH.)

The anti-programmed death-ligand 1 (PD-L1) antibody is a standard therapy for advanced hepatocellular carcinoma (HCC). Tumor expression of PD-L1 can be induced upon stimulus. Because cyclin-dependent kinase 9 (CDK9) inhibition reduces the expression of inducible proteins, we explored the influence of CDK9 inhibition on PD-L1 expression in HCC cells. We found that PD-L1 expression was low in HCC cells; however, IFN-γ treatment increased this expression. CDK9 inhibitors AZD4573 and atuveciclib reduced the IFN-γ induced PD-L1 expression in a dose-dependent manner. CDK9 knockdown yielded similar results, but CDK9 overexpression reversed the influence of the CDK9 inhibitors. In the orthotopic mouse model, mice treated with a CDK9 inhibitor and an anti-PD-L1 antibody had significantly smaller tumors and exhibited longer survival than mice treated with either agent. In conclusion, CDK9 inhibition could reduce the expression of PD-L1 in HCC cells. Using both CDK9 inhibitors and anti-PD-L1 antibodies is more effective than using either agent alone., 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.)

Background: The literature lacks a consistent review of musculoskeletal symptoms in postmenopausal women., Aim: To identify features, measurements, determinants, treatments, and outcomes of musculoskeletal symptoms in postmenopausal women., Method: A scoping review was completed using six databases: Embase, Medline, Cochrane, CINAHL, Web of Science, and Scopus up to December 2022. Sixty-three articles were identified., Results: Musculoskeletal symptoms in postmenopausal women include somatic symptoms of non-specific origin, upper and lower limb symptoms, spinal pain, and decline in physical performance. Measurements were categorized into four groups: musculoskeletal symptoms for menopause, general musculoskeletal symptoms, menopause-specific quality of life, and general quality of life questionnaires. The determinants were grouped into four themes: demographics, physical determinants, psychosocial determinants, and lifestyle. Pharmacological interventions, supplementation options, and exercise regimens exist for postmenopausal women with musculoskeletal symptoms., Conclusion: A comprehensive policy is needed to address musculoskeletal symptoms in postmenopausal women, promoting diverse treatments for improved quality of life., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

2,2',6-Tribromobisphenol A (Tri-BBPA), the main debrominated congener of tetrabromobisphenol A (TBBPA), is ubiquitous in the environment and human body but with unknown toxicity. Tri-BBPA was synthesized and applied to investigate its sub-chronic exposure effects on 28 organ coefficients and clinical health indicators related to liver function, kidney function, and cardiovascular system function in female mice. Results showed that the liver was the targeted organ of Tri-BBPA exposure. Compared to the control group, the changes in liver coefficient, cholinesterase, total protein, albumin, γ-glutamyl transpeptidase, lactate dehydrogenase, and creatine kinase levels ranged from -61.2 % to 35.5 % in the high-exposed group. Creatine kinase was identified as a critical effect indicator of Tri-BBPA exposure. Using the Bayesian benchmark dose derivation method, a lower reference dose than TBBPA was established for Tri-BBPA (10.6 μg/kg-day). Serum metabolomics revealed that Tri-BBPA exposure may primarily damage the liver by disrupting tryptophan metabolism related to L-alanine, tryptamine, 5-hydroxyindoleacetic acid, and 5-methoxyindoleacetate in liver cells and leading to liver dysfunction. Notably, epilepsy, schizophrenia, early preeclampsia, and late-onset preeclampsia were the top six enriched diseases, suggesting that the nervous system may be particularly affected by Tri-BBPA exposure. Our findings hinted a non-negligible health risk of exposure to debrominated products of TBBPA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing commercial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6 J female mice were randomly allocated to three groups: the control group, F-53B 0.8 µg/kg/day group, and F-53B 8 µg/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5-14.5, the F-53B 8 µg/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8 µg/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1β, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Resident immune cells are at the forefront of sensory organ-specific signals, and changes in these cells are closely related to the aging process. The Sirt pathway can regulate NAD + metabolism during aging, thereby affecting the accumulation of ROS. However, the role of the Sirt pathway in resident immune cells in aged tissues is currently unclear., Methods: We investigated Sirt1 signalling in resident immune cells during chronic inflammation in an aged mouse model. Integrated single-cell RNA sequencing data from young and aged mice were used to refine the characterization of immune cells in aged tissues RESULTS: We found that C1q + macrophages could affect chronic inflammation during aging. C1q + macrophages acted in an opposing manner to Il1b + macrophages and were responsible for anti-inflammatory effects during aging. Sirt1 agonists inhibited the decrease in C1qb in macrophages during aging, and anti-aging drugs could affect the expression of C1qb in macrophages via the Sirt1 pathway., Conclusions: In this study, we first identified the relevance of C1q + macrophages in chronic inflammation during aging. The potential anti-aging effect of C1q + macrophages was mediated by the Sirt1 pathway, suggesting new strategies for aging immunotherapy., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

In this study, electroporation-surface-enhanced Raman scattering (SERS) was applied to rapidly measure intracellular pH. The generation of a sensitive SERS probe for measuring pH in the range of 6.0-8.0 was accomplished through the conjugation of the pH-sensitive molecule 4-mercaptobenzoic acid (4-MBA) to the surface of gold nanoparticles (Au NPs) through its thiol functional group. This bioprobe was then rapidly introduced into nasopharyngeal carcinoma CNE-1 cells by electroporation, followed by SERS scanning and the fitting of intensity ratios of each detection point's Raman peaks at 1423 cm -1 and 1072 cm -1 , to create the pH distribution map of CNE-1 cells. The electroporation-SERS assay introduces pH bioprobes into a living cell in a very short time and disperses the nanoprobe throughout the cytoplasm, ultimately enabling rapid and comprehensive pH analysis of the entire cell. Our work demonstrates the potential of electroporation-SERS for the biochemical analysis of live cells., 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.)

Summary: Shotgun metagenomics allows for direct analysis of microbial community genetics, but scalable computational methods for the recovery of bacterial strain genomes from microbiomes remains a key challenge. We introduce Floria, a novel method designed for rapid and accurate recovery of strain haplotypes from short and long-read metagenome sequencing data, based on minimum error correction (MEC) read clustering and a strain-preserving network flow model. Floria can function as a standalone haplotyping method, outputting alleles and reads that co-occur on the same strain, as well as an end-to-end read-to-assembly pipeline (Floria-PL) for strain-level assembly. Benchmarking evaluations on synthetic metagenomes show that Floria is  > 3× faster and recovers 21% more strain content than base-level assembly methods (Strainberry) while being over an order of magnitude faster when only phasing is required. Applying Floria to a set of 109 deeply sequenced nanopore metagenomes took <20 min on average per sample and identified several species that have consistent strain heterogeneity. Applying Floria's short-read haplotyping to a longitudinal gut metagenomics dataset revealed a dynamic multi-strain Anaerostipes hadrus community with frequent strain loss and emergence events over 636 days. With Floria, accurate haplotyping of metagenomic datasets takes mere minutes on standard workstations, paving the way for extensive strain-level metagenomic analyses., Availability and Implementation: Floria is available at https://github.com/bluenote-1577/floria, and the Floria-PL pipeline is available at https://github.com/jsgounot/Floria&#95;analysis&#95;workflow along with code for reproducing the benchmarks., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Hyperuricemia, as a very prevalent chronic metabolic disease with increasing prevalence year by year, poses a significant burden on individual patients as well as on the global health care and disease burden, and there is growing evidence that it is associated with other underlying diseases such as hypertension and cardiovascular disease. The association between hyperuricemia and dietary inflammatory index (DII) scores was investigated in this study., Methods: This study enrolled 13, 040 adult subjects (aged ≥ 20 years) from the US National Health and Nutrition Survey from 2003 to 2018. The inflammatory potential of the diet was assessed by the DII score, and logistic regression was performed to evaluate the relationship between the DII score and the development of hyperuricemia; subgroup analyses were used to discuss the influence of other factors on the relationship., Results: Participants in the other quartiles had an increased risk of hyperuricemia compared to those in the lowest quartile of DII scores. Stratification analyses stratified by body mass index (BMI), sex, hypertension, drinking, diabetes, education level and albumin-creatinine-ratio (ACR) revealed that the DII score was also associated with the risk of hyperuricemia (P<0.05). There was an interaction in subgroup analysis stratified by sex, age, and hypertension (P for interaction <0.05). The results showed a linear-like relationship between DII and hyperuricemia, with a relatively low risk of developing hyperuricemia at lower DII scores and an increased risk of developing hyperuricemia as DII scores increased., Conclusions: This study showed that the risk of hyperuricemia increased at slightly higher DII scores (i.e., with pro-inflammatory diets), but not significantly at lower levels (i.e., with anti-inflammatory diets). The contribution of the DII score to the development of hyperuricemia increased with higher scores. The relationship between inflammatory diets and hyperuricemia requires more research on inflammation, and this study alerts the public that pro-inflammatory diets may increase the risk of developing hyperuricemia., 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 Liu, Chen, Gao, Shi, Yin, Yu and Zhang.)

Motivation: Nonlinear low-dimensional embeddings allow humans to visualize high-dimensional data, as is often seen in bioinformatics, where datasets may have tens of thousands of dimensions. However, relating the axes of a nonlinear embedding to the original dimensions is a nontrivial problem. In particular, humans may identify patterns or interesting subsections in the embedding, but cannot easily identify what those patterns correspond to in the original data., Results: Thus, we present SlowMoMan (SLOW Motions on MANifolds), a web application which allows the user to draw a one-dimensional path onto a 2D embedding. Then, by back-projecting the manifold to the original, high-dimensional space, we sort the original features such that those most discriminative along the manifold are ranked highly. We show a number of pertinent use cases for our tool, including trajectory inference, spatial transcriptomics, and automatic cell classification., Availability and Implementation: Software: https://yunwilliamyu.github.io/SlowMoMan/; Code: https://github.com/yunwilliamyu/SlowMoMan., Competing Interests: No competing interest is declared., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Limited research has been conducted to quantitatively assess the impact of systemic inflammation in metabolic dysfunction-associated fatty liver disease (MAFLD) and sub-clinical carotid atherosclerosis (SCAS). The systemic immune-inflammation index (SII), which integrates inflammatory cells, has emerged as a reliable measure of local immune response and systemic inflammation Therefore, this study aims to assess the mediating role of SII in the association between MAFLD and SCAS in type 2 diabetes mellitus (T2DM)., Method: This study prospectively recruited 830 participants with T2DM from two centers. Unenhanced abdominal CT scans were conducted to evaluate MAFLD, while B-mode carotid ultrasonography was performed to assess SCAS. Weighted binomial logistic regression analysis and restricted cubic splines (RCS) analyses were employed to analyze the association between the SII and the risk of MAFLD and SCAS. Mediation analysis was further carried out to explore the potential mediating effect of the SII on the association between MAFLD and SCAS., Results: The prevalence of both MAFLD and SCAS significantly increased as the SII quartiles increased ( P< 0.05). MAFLD emerged as an independent factor for SCAS risk across three adjusted models, exhibiting odds ratios of 2.15 (95%CI: 1.31-3.53, P < 0.001). Additionally, increased SII quartiles and Ln (SII) displayed positive associations with the risk of MAFLD and SCAS ( P < 0.05). Furthermore, a significant dose-response relationship was observed ( P for trend <0.001). The RCS analyses revealed a linear correlation of Ln (SII) with SCAS and MAFLD risk ( P for nonlinearity < 0.05). Importantly, SII and ln (SII) acted as the mediators in the association between MAFLD and SCAS following adjustments for shared risk factors, demonstrating a proportion-mediated effect of 7.8% and 10.9%., Conclusion: SII was independently correlated with MAFLD and SCAS risk, while also acting as a mediator in the relationship between MAFLD and SCAS., 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 Wang, Guo, Qiu, Yu and Tu.)

Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87 μg/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30 μg/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There is growing interest in the joint effects of hazardous trace elements (HTEs) on lung function deficits, but the data are limited. This is a critical research gap given increased global industrialisation., Methods: A national cross-sectional study including spirometry was performed among 2112 adults across 11 provinces in China between 2020 and 2021. A total of 27 HTEs were quantified from urine samples. Generalised linear models and quantile-based g-computation were used to explore the individual and joint effects of urinary HTEs on lung function, respectively., Results: Overall, there were negative associations between forced expiratory volume in 1 s (FEV 1 ) and urinary arsenic (As) (z-score coefficient, -0.150; 95% CI, -0.262 to -0.038 per 1 ln-unit increase), barium (Ba) (-0.148, 95% CI: -0.258 to -0.039), cadmium (Cd) (-0.132, 95% CI: -0.236 to -0.028), thallium (Tl) (-0.137, 95% CI: -0.257 to -0.018), strontium (Sr) (-0.147, 95% CI: -0.273 to -0.022) and lead (Pb) (-0.121, 95% CI: -0.219 to -0.023). Similar results were observed for forced vital capacity (FVC) with urinary As, Ba and Pb and FEV 1 /FVC with titanium (Ti), As, Sr, Cd, Tl and Pb. We found borderline associations between the ln-quartile of joint HTEs and decreased FEV 1 (-20 mL, 95% CI: -48 to +8) and FVC (-14 mL, 95% CI: -49 to+2). Ba and Ti were assigned the largest negative weights for FEV 1 and FVC within the model, respectively., Conclusion: Our study investigating a wide range of HTEs in a highly polluted setting suggests that higher urinary HTE concentrations are associated with lower lung function, especially for emerging Ti and Ba, which need to be monitored or regulated to improve lung health., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

In this study, a 3 × 3 blue micro-LED array with a pixel size of 10 × 10 μm 2 and a pitch of 15 μm was fabricated on an epilayer grown on a sapphire substrate using metalorganic chemical vapor deposition technology. The fabrication process involved photolithography, wet and dry etching, E-beam evaporation, and ion implantation technology. Arsenic multi-energy implantation was utilized to replace the mesa etching for electrical isolation, where the implantation depth increased with the average energy. Different ion depth profiles had varying effects on electrical properties, such as forward current and leakage currents, potentially causing damage to the n-GaN layer and increasing the series resistance of the LEDs. As the implantation depth increased, the light output power and peak external quantum efficiency of the LEDs also increased, improving from 5.33 to 9.82%. However, the efficiency droop also increased from 46.3 to 48.6%., (© 2024. The Author(s).)

Purpose: We investigated whether spleen volume (SV) changes were associated with treatment outcomes in advanced hepatocellular carcinoma (HCC) patients who received immunotherapy or first-line sorafenib., Patients and Methods: Patients with advanced HCC who underwent immunotherapy or first-line sorafenib at our institute were retrospectively analyzed. CT was used to measure SV before and within 3 months of treatment initiation. Tumor assessment followed Response Evaluation Criteria in Solid Tumors version 1.1. The association between SV change and tumor response or progression-free survival (PFS) was analyzed. The inverse probability of treatment weighting (IPTW) was used to adjust for differences in baseline characteristics., Results: The immunotherapy group comprised 143 patients (124 men, mean age, 59.8 years ± 11.2 [standard deviation]), while the sorafenib group had 57 (47 men, mean age, 59.6 years ± 9.9). SV increased in 108 (75.5%) immunotherapy and 21 (36.8%) sorafenib patients. In the immunotherapy group, patients with increased SV were more likely than those with decreased SV to have a higher disease control rate (76.9% vs 57.1%, p = 0.024) and durable clinical benefit (52.8% vs 25.7%, p = 0.005). It was also associated with extended PFS in the immunotherapy group in both the univariate ( p = 0.028) and multivariate ( p = 0.014) analysis. By contrast, in the sorafenib group, an increased in SV was not associated with treatment response but was presumably associated with reduced PFS ( p = 0.072) in the multivariate analysis. After IPTW adjustment, the increase in SV remained a significant predictor for DCB and PFS in the immunotherapy group., Conclusion: Most patients exhibited an increase in SV after the initiation of immunotherapy, which may be used to predict response and prognosis. However, this association was not observed in patients who received sorafenib., Competing Interests: Dr Chih-Hung Hsu reports grants from Roche, grants from AstraZeneca, grants from Eli Lilly, grants from Surface Oncology, personal fees from MSD, personal fees from Eisai, outside the submitted work. The authors report no other competing interests in this work., (© 2024 Chen et al.)

Purpose: A systematic review investigated the effectiveness of physical activity in alleviating lower limb lymphedema among patients with gynecological cancer after surgery., Methods: A systematic review of randomized controlled trials and quasi-experimental designs was conducted. Six databases, Cinahl, Cochrane, Embase, Medline, Scopus, and Web of Science, were searched for relevant publications from inception to October 2022 and updated in January 2024. RevMan software was used to perform meta-analysis using a random-effects model., Results: Seven studies (5 randomized controlled trials) containing 261 subjects were synthesized. The risk of bias was low in the included studies. The exercise interventions for lower limb lymphedema included active, aerobic, aquatic, and weight-lifting exercises. Meta-analyses showed that active exercise had no effect on lymphedema symptoms of limb volume, pain, and heaviness. However, the effectiveness of exercise on limb volume had subthreshold borderline significance in 2 studies (standardized mean difference = 0.43, 95% confidence interval - 0.01, 0.88; I 2  = 0%, p = 0.06). Three studies found that lymphedema symptoms were significantly improved after exercise interventions. The adherence rate of the exercise was 77-100%, with the only complication being cellulitis., Conclusions: Although the meta-analysis does not reveal a significant effect, the systematic review study demonstrated that exercise is feasible, safe, and has a clinical effect on alleviating lymphedema-related symptoms of women following gynecological cancer surgery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: This study aimed to investigate the prognostic value of alpha-fetoprotein (AFP) ratio in patients with AFP-negative hepatocellular carcinoma (HCC)., Patients and Methods: We retrospectively analyzed 600 AFP-negative HCC patients who underwent hepatectomy. The AFP ratio was calculated as the ratio of AFP level 1 week before surgery to the level 20-40 days after hepatectomy. Immunohistochemistry assay was used to assess protein expression in HCC tissue. The primary outcome measures were overall survival (OS) and disease-free survival (DFS)., Results: The study found that a cutoff value of 1.6 ng/ml for AFP ratio, determined using X-tile software, was optimal for predicting prognosis. Patients with a high AFP ratio had a worse prognosis compare to those with a low AFP ratio (DFS, P = .026; OS, P = .034). Patients with a high AFP ratio had a worse prognosis compared to those with a low AFP ratio. Multivariate analysis revealed that AFP ratio >1.6, negative HepPar-1 expression, and vascular invasion were independent predictors of both DFS and OS. Vascular invasion had a higher area under the curve (AUC) than AFP ratio and HepPar-1 expression in predicting recurrence and death. The combination of AFP ratio, HepPar-1 expression, and vascular invasion provided better predictive accuracy for DFS and OS., Conclusion: The AFP ratio is a potential prognostic marker for AFP-negative HCC patients after hepatectomy. Combining the analysis of AFP ratio with HepPar-1 expression and vascular invasion can enhance the accuracy of predicting prognosis in these patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: All methods in this research were carried out in accordance with relevant guidelines and regulations.

Background: The efficacy of high-flow nasal cannula (HFNC) in patients extubated after lung resection surgery remains inconclusive. Our objective was to execute a meticulous systematic meta-analysis to accurately assess the advantages of HFNC compared to conventional oxygen therapy (COT) for patients extubated after lung resection surgery, by examining postoperative hypoxemia and other patient-focused outcomes., Methods: We searched PubMed, Embase, the Cochrane Library, Web of Science and Scopus to identify randomized controlled trials (RCTs) from inception to July 2023. We employed the revised Cochrane risk of bias (RoB) tool (2.0) to evaluate the RoB of the included studies, and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method to ascertain the certainty of the pooled effect estimates. The primary outcome was the incidence of postoperative hypoxemia., Results: Five RCTs (n=564) were included in the ultimate analysis. Utilizing HFNC rather than COT did not reduce the risk of postoperative hypoxemia [relative risk (RR), 0.67; 95% confidence interval (CI): 0.30-1.49; low certainty]. Compared to COT, HFNC may significantly enhance oxygenation index within first 12 hours after extubation in patients with lung resection. There were no significant differences in reintubation rate (RR, 0.25; 95% CI: 0.04-1.54; high certainty), escalation of respiratory support (RR, 0.35; 95% CI: 0.11-1.08; high certainty), change in partial pressure of carbon dioxide (PaCO 2 ) within first 24 hours after extubation, hospital length of stay [mean difference (MD), -0.19; 95% CI: -0.44 to 0.06; moderate certainty], and intensive care unit (ICU) length of stay (MD, 0.02; 95% CI: -0.16 to 0.19; high certainty)., Conclusions: Our meta-analysis suggests that preemptive use of HFNC, instead of COT, in extubated patients following lung resection surgery may not significantly impact postoperative hypoxemia incidence, reintubation rate, escalation of respiratory support, postoperative PaCO 2 difference, hospital and ICU length of stay. However, HFNC may significantly enhance the oxygenation index within the first 12 hours post-extubation following lung resection surgery. To verify the effect of HFNC on this population, additional large-scale, multicenter studies are essential., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1758/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Background: Surface-enhanced Raman scattering (SERS) technology have unique advantages of rapid, simple, and highly sensitive in the detection of serum, it can be used for the detection of liver cancer. However, some protein biomarkers in body fluids are often present at ultra-low concentrations and severely interfered with by the high-abundance proteins (HAPs), which will affect the detection of specificity and accuracy in cancer screening based on the SERS immunoassay. Clearly, there is a need for an unlabeled SERS method based on low abundance proteins, which is rapid, noninvasive, and capable of high precision detection and screening of liver cancer., Results: Serum samples were collected from 60 patients with liver cancer (27 patients with stage T1 and T2 liver cancer, 33 patients with stage T3 and T4 liver cancer) and 40 healthy volunteers. Herein, immunoglobulin and albumin were separated by immune sorption and Cohn ethanol fractionation. Then, the low abundance protein (LAPs) was enriched, and high-quality SERS spectral signals were detected and obtained. Finally, combined with the principal component analysis-linear discriminant analysis (PCA-LDA) algorithm, the SERS spectrum of early liver cancer (T1-T2) and advanced liver cancer (T3-T4) could be well distinguished from normal people, and the accuracy rate was 98.5% and 100%, respectively. Moreover, SERS technology based on serum LAPs extraction combined with the partial least square-support vector machine (PLS-SVM) successfully realized the classification and prediction of normal volunteers and liver cancer patients with different tumor (T) stages, and the diagnostic accuracy of PLS-SVM reached 87.5% in the unknown testing set., Significance: The experimental results show that the serum LAPs SERS detection combined with multivariate statistical algorithms can be used for effectively distinguishing liver cancer patients from healthy volunteers, and even achieved the screening of early liver cancer with high accuracy (T1 and T2 stage). These results showed that serum LAPs SERS detection combined with a multivariate statistical diagnostic algorithm has certain application potential in early cancer screening., 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.)

Purpose: Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies., Materials and Methods: In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing., Results: By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor β diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores., Conclusion: Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.

Introduction: Corneal endothelial dysfunction results in cornea opacity, damaging sightedness, and affecting quality of life. A corneal transplant is the current effective intervention. Due to the scarcity of donated cornea, such an unmet medical need requires a novel therapeutic modality., Objectives: Customizing patients' corneal endothelial progenitor cells with proliferative activity and lineage restriction properties shall offer sufficient therapeutic cells for corneal endothelial dystrophy., Methods: The customized induced human corneal endothelial progenitor-like cell (iHCEPLC) was obtained through cell fate conversions starting from PBMC (peripheral blood mononuclear cell), hiPSC (human induced pluripotent stem cell), and hNCC (human neural crest cell), while it finally reached the iHCEPLC state via a series of induction. Several molecular diagnoses were applied to depict its progenitor state, including RNAseq, FlowCytometer, immunostainings, and rtPCR. Significantly, it can be induced to gain differentiation maturity through contact inhibition. In addition, a BAK-mediated rabbit model of corneal endothelial dystrophy was established in the present study to test the therapeutic effectiveness of the iHCEPLC., Results: After inducing cell fate conversion, the specific HCEC markers were detected by rtPCR and immunostaining in iHCEPLC. Further, RNAseq was applied to distinguish its progenitor-like cell fate from primary human corneal endothelial cells (HECE). FlowCytometry profiled the heterogeneity subpopulation, consistently displaying a subtle difference from primary HCEC. A terminal differentiation can be induced in iHCEPLC, addressing its progenitor-like fate. iHCEPLC can restore the BAK-based rabbit model of corneal endothelial dystrophy. Immunohistochemistry verified that such acuity restoration of the BAK-treated cornea is due to the introduced iHCEPLC, and such therapeutic effectiveness is observed in the long term., Conclusion: Here, we demonstrated that customized iHCEPLC has long-term therapeutic efficacy. As a progenitor cell, our iHCEPLC has a restricted cell lineage nature and can proliferate in vitro, supporting sufficient therapeutic candidate cells. Due to the immune-privileged nature of the cornea, our iHCEPLC proves the principle of therapeutical feasibility in both autogenic and allogeneic modalities., 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. Production and hosting by Elsevier B.V.)

Organic crystal materials with metal-free feature and intrinsically low molecular mass are highly desirable for applications in flexible smart devices. Here, we reported a plastic crystal, tris(hydroxymethyl)aminomethane perchlorate (Tris-HClO 4 ), which crystallizes in the R 3̄ space group at room temperature and undergoes plastic phase transition at 369 K, showing a large entropy gain of 70.5 J mol -1 K -1 , much higher than its fusion entropy gain (12.9 J mol -1 K -1 ). PXRD measurement indicates that it has cubic lattice symmetry in the high-temperature phase. Moreover, it exhibits excellent dielectric permittivity switching properties and robust cyclic stability. This work could be the pathway for chemical designing multifunctional switchable materials with the motive of combining the idea of symmetry breaking and plastic phase transition.

Background: The specific benefits of Yangxinshi tablet (YXST) in the treating chronic heart failure (CHF) remain uncertain., Aim: To systematically evaluate the efficacy and safety of YXST in the treatment of CHF., Methods: Randomized controlled trials (RCTs) investigating YXST for CHF treatment were retrieved from eight public databases up to November 2023. Meta-analyses of the included clinical studies were conducted using Review Manager 5.3., Results: Twenty RCTs and 1845 patients were included. The meta-analysis results showed that the YXST combination group, compared to the conventional drug group, significantly increased the clinical efficacy rate by 23% [relative risk (RR) = 1.23, 95%CI: 1.17-1.29], P < 0.00001), left ventricular ejection fraction by 6.69% [mean difference (MD) = 6.69, 95%CI: 4.42-8.95, P < 0.00001] and 6-min walk test by 49.82 m (MD = 49.82, 95%C: 38.84-60.80, P < 0.00001), and reduced N-terminal pro-B-type natriuretic peptide by 1.03 ng/L [standardized MD (SMD) = -1.03, 95%CI: -1.32 to -0.74, P < 0.00001], brain natriuretic peptide by 80.95 ng/L (MD = -80.95, 95%CI: -143.31 to -18.59, P = 0.01), left ventricular end-diastolic diameter by 3.92 mm (MD = -3.92, 95%CI: -5.06 to -2.78, P < 0.00001), and left ventricular end-systolic diameter by 4.34 mm (MD = -4.34, 95%CI: -6.22 to -2.47, P < 0.00001). Regarding safety, neither group reported any serious adverse events during treatment (RR = 0.54, 95%CI: 0.15-1.90, P = 0.33). In addition, Egger's test results indicated no significant publication bias ( P = 0.557)., Conclusion: YXST effectively improves clinical symptoms and cardiac function in patients with CHF while maintaining a favorable safety profile, suggesting its potential as a therapeutic strategy for CHF., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Minimizers and convolutional neural networks (CNNs) are two quite distinct popular techniques that have both been employed to analyze categorical biological sequences. At face value, the methods seem entirely dissimilar. Minimizers use min-wise hashing on a rolling window to extract a single important k-mer feature per window. CNNs start with a wide array of randomly initialized convolutional filters, paired with a pooling operation, and then multiple additional neural layers to learn both the filters themselves and how they can be used to classify the sequence. In this study, our main result is a careful mathematical analysis of hash function properties showing that for sequences over a categorical alphabet, random Gaussian initialization of convolutional filters with max-pooling is equivalent to choosing a minimizer ordering such that selected k-mers are (in Hamming distance) far from the k-mers within the sequence but close to other minimizers. In empirical experiments, we find that this property manifests as decreased density in repetitive regions, both in simulation and on real human telomeres. We additionally train from scratch a CNN embedding of synthetic short-reads from the SARS-CoV-2 genome into 3D Euclidean space that locally recapitulates the linear sequence distance of the read origins, a modest step toward building a deep learning assembler, although it is at present too slow to be practical. In total, this article provides a partial explanation for the effectiveness of CNNs in categorical sequence analysis.

Hirudo nipponia, a blood-sucking leech native to East Asia, possesses a rich repertoire of active ingredients in its saliva, showcasing significant medical potential due to its anticoagulant, anti-inflammatory, and antibacterial effects against human diseases. Despite previous studies on the transcriptomic and proteomic characteristics of leech saliva, which have identified medicinal compounds, our knowledge of tissue-specific transcriptomes and their spatial expression patterns remains incomplete. In this study, we conducted an extensive transcriptomic profiling of the salivary gland tissue in H. nipponia based on de novo assemblies of tissue-specific transcriptomes from the salivary gland, teeth, and general head region. Through gene ontology (GO) analysis and hierarchical clustering, we discovered a novel set of anti-coagulant factors-i.e., Hni-Antistasin, Hni-Ghilanten, Hni-Bdellin, Hni-Hirudin-as well as a previously unrecognized immune-related gene, Hni-GLIPR1 and uncharacterized salivary gland specific transcripts. By employing in situ hybridization, we provided the first visualization of gene expression sites within the salivary gland of H. nipponia. Our findings expand on our understanding of transcripts specifically expressed in the salivary gland of blood-sucking leeches, offering valuable resources for the exploration of previously unidentified substances with medicinal applications., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Carcinosarcoma (CS) is an aggressive form of gynecologic malignancy that accounts for ~5% of carcinomas in the endometrium and ovaries. There has been no significant improvement in survival over the last decades despite additional treatment options. PReferentially Expressed Antigen in MElanoma (PRAME) is an immunotherapy target used for the treatment of several solid tumors. We explored the PRAME protein expression levels in ovarian and uterine CS (n = 29). The expression levels were recorded by H-score (percentage of positively stained cells multiplied by staining intensity) in carcinomatous and sarcomatous components separately and compared by paired t-test. The marker expression levels of ovarian and uterine CS were tested against each other in the CS group. Sarcoma-predominant samples (>50% of the sampled tissue) were compared with samples without predominant sarcomatous components by a 2-sample pooled t-test. In addition, high-grade carcinomatous components of CS samples were tested against low-grade endometrioid carcinoma (International Federation of Gynecology and Obstetrics grades 1 and 2; n = 13), and sarcomatous components against uterine leiomyosarcoma (n = 14). There was no significant difference between any subgroups except for sarcomatous elements of CS and leiomyosarcoma ( P < 0.001). A weak positive correlation was found between H-scores of carcinomatous and sarcomatous components ( P = 0.062, r = 0.36). In the ovarian CS group, there was a moderate inverse correlation between age and the mean H-score of the carcinomatous component ( r = -0.683, P = 0.02). Our results further support PRAME overexpression in gynecologic cancers, including CS with similar expression levels in epithelial and mesenchymal components. PRAME might have a role in epithelial-mesenchymal transition in this group of cancers., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 by the International Society of Gynecological Pathologists.)

Background: Urosepsis is a common disease in urology, which is characterized by high treatment costs and high mortality. In the treatment of sepsis, anti-infection therapy is the most important means. However, the effect of empirical anti-infection therapy is often not ideal. Therefore, it is necessary to continuously monitor the prevalence of bacterial isolates in the blood culture of patients with urinary sepsis and their sensitivity to antibacterial drugs. This is of great significance to improve the efficacy of empirical antibiotic therapy for urosepsis., Objective: To elucidate the landscape of prevailing bacterial profiles and their antimicrobial susceptibilities in urosepsis cases, and to furnish robust clinical evidence to underpin the timely initiation of empirical antibiotic treatment., Methods: Collect the basic information and blood culture results of patients with urosepsis hospitalized from 2017 to 2020. Retrospective analysis of bacterial species and antimicrobial susceptibility in urosepsis and changes over 4 years., Results: Gram-negative bacteria (178 isolates, 75.11%) constituted the main pathogens causing urosepsis, followed by Gram-positive bacteria (46 isolates, 19.41%) and fungus (13 isolates, 5.48%). The sensitivity of ertapenem, meropenem, amikacin, and imipenem to Gram-negative bacteria all exceeded 85%. The sensitivity rates of levofloxacin, gentamicin, and ciprofloxacin are decreasing every year ( p  < 0.05). Tigecycline, vancomycin, and linezolid exhibited excellent sensitivity against Gram-positive bacteria. Among fungi, fluconazole demonstrated universal sensitivity, while itraconazole-resistant isolates have been found, and amphotericin B is still effective., Conclusion: Analysis of blood culture results of patients more accurately reflected the etiology of urosepsis, mainly Escherichia coli , Enterococcus , and Klebsiella pneumoniae . If there are no definitive blood culture results, empiric treatment of urosepsis should not include fluoroquinolone antibiotics. Cefepime, cefoxitin, and ceftazidime are the most sensitive antibiotics to Gram-negative bacteria besides carbapenem antibiotics. In addition, the current situation regarding extended-spectrum β-lactamase-producing bacteria and carbapenem-resistant Enterobacteriaceae bacteria resistance is extremely concerning with limited therapeutic options available. Strengthening antibiotic management practices and exploring novel antibacterial agents can help mitigate this issue., (© The Author(s), 2024.)

Background: Taxonomic classification of reads obtained by metagenomic sequencing is often a first step for understanding a microbial community, but correctly assigning sequencing reads to the strain or sub-species level has remained a challenging computational problem., Results: We introduce Mora, a MetagenOmic read Re-Assignment algorithm capable of assigning short and long metagenomic reads with high precision, even at the strain level. Mora is able to accurately re-assign reads by first estimating abundances through an expectation-maximization algorithm and then utilizing abundance information to re-assign query reads. The key idea behind Mora is to maximize read re-assignment qualities while simultaneously minimizing the difference from estimated abundance levels, allowing Mora to avoid over assigning reads to the same genomes. On simulated diverse reads, this allows Mora to achieve F1 scores comparable to other algorithms while having less runtime. However, Mora significantly outshines other algorithms on very similar reads. We show that the high penalty of over assigning reads to a common reference genome allows Mora to accurately infer correct strains for real data in the form of E. coli reads., Conclusions: Mora is a fast and accurate read re-assignment algorithm that is modularized, allowing it to be incorporated into general metagenomics and genomics workflows. It is freely available at https://github.com/AfZheng126/MORA ., (© 2024. The Author(s).)

We report the electrochemical potential dependence of photocatalysis produced by hot electrons in plasmon-resonant grating structures. Here, corrugated metal surfaces with a period of 520 nm are illuminated with 785 nm wavelength laser light swept as a function of incident angle. At incident angles corresponding to plasmon-resonant excitation, we observe sharp peaks in the electrochemical photocurrent and dips in the photoreflectance consistent with the conditions under which there is wavevector matching between the incident light and the spacing between the lines in the grating. In addition to the bare plasmonic metal surface (i.e., Au), which is catalytically inert, we have measured grating structures with a thin layer of Pt, Ru, and Ni catalyst coatings. For the bare Au grating, we observe that the plasmon-resonant photocurrent remains relatively featureless over the applied potential range from -0.8 to +1.2 V vs NHE. For the Pt-coated grating, we observe a sharp peak around -0.3 V vs NHE, three times larger than the bare Au grating, and near complete suppression of the oxidation half-reaction, reflecting the reducing nature of Pt as a good hydrogen evolution reaction catalyst. The photocurrent associated with the Pt-coated grating is less noisy and produces higher photocurrents than the bare Au grating due to the faster kinetics (i.e., charge transfer) associated with the Pt-coated surface. The plasmon-resonant grating structures enable us to compare plasmon-resonant excitation with that of bulk metal interband absorption simply by rotating the polarization of the light while leaving all other parameters of the experiment fixed (i.e., wavelength, potential, electrochemical solution, sample surface, etc.). A 64X plasmon-resonant enhancement (i.e., p-to-s polarized photocurrent ratio) is observed for the Pt-coated grating compared to 28X for the bare grating. The nickel-coated grating shows an increase in the hot-electron photocurrent enhancement in both oxidation and reduction half-reactions. Similarly, Ru-coated gratings show an increase in hot-electron photocurrents in the oxidation half-reaction compared to the bare Au grating. Plasmon-resonant enhancement factors of 36X and 15X are observed in the p-to-s polarized photocurrent ratio for the Ni and Ru gratings, respectively.