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Rationale and Objectives: To investigate the predictive value of a deep learning model based on multiparametric MRI (mpMRI) for tumor deposit (TD) in rectal cancer (RC) patients and to analyze their prognosis., Materials and Methods: Data from 529 RC patients who underwent radical surgery at two centers were retrospectively collected. 379 patients from center one were randomly divided into a training set (n = 265) and an internal validation (invad) set (n = 114) in a 7:3 ratio. 150 patients from center two were included in the external validation (exvad) set. Univariate and multivariate analyses were performed to identify independent clinical predictors and to construct a clinical model. Preoperative mpMRI images were utilized to extract deep features through the ResNet-101 model. Following feature selection, a deep learning model was developed. A nomogram was created by combining the clinical model with the deep learning model. The clinical applicability of each model was assessed using ROC curves, decision curve analysis (DCA), clinical impact curves (CIC), and deLong test. Kaplan-Meier survival analysis was conducted to evaluate prognostic outcome among patients., Results: Among the 529 patients, 142 (26.8%) were TD positive. In the training set, clinical model was constructed based on clinical independent predictors (cT and cN). 30 deep features were selected to calculate the deep learning radscore (DLRS) and develop the deep learning (DL) model. The AUC values for the clinical model were 0.724, 0.836, and 0.763 in the training set, invad set, and exvad set, respectively. The AUC values for the DL model were 0.903, 0.853, and 0.874, respectively. The nomogram achieved higher AUC values of 0.925, 0.919, and 0.9, respectively. The DeLong test indicated that the predictive performance of the nomogram was superior to both the DL model and the clinical model in training and invad sets. Kaplan-Meier survival analysis showed that both the DL model and the nomogram effectively stratified patients into high-risk and low-risk groups for 3-year DFS (p < 0.05)., Conclusion: The nomogram, which integrates mpMRI-based deep radiomic features and clinical characteristics, effectively predicts preoperative TD status in RC. Both the DL model and the nomogram can effectively stratify patients' 3-year DFS risk., 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 Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Autophagy-mediated chemoresistance is the core mechanism for therapeutic failure and poor prognosis in breast cancer. Breast cancer chemotherapy resistance is believed to be influenced by tumor-associated macrophages (TAMs), by which C-X-C motif chemokine ligand 1 (CXCL1) is the most abundant cytokine secreted. Yet, its role in mediating autophagy-related chemoresistance is still unknown. This study aimed to explore the molecular mechanisms by which TAMs/CXCL1 induced autophagy-mediated chemoresistance in breast cancer. It was found that TAMs/CXCL1 promoted chemoresistance of breast cancer cells through autophagy activation in vitro, and CXCL1 silence could enhance the chemosensitivity of paclitaxel-resistant breast cancer cells via autophagy inhibition. A high-throughput quantitative PCR chip and subsequent target validation showed that CXCL1 induced autophagy-mediated chemoresistance by inhibiting VHL-mediated IGF1R ubiquitination. The elevated IGF1R then promoted STAT3/HMGB1 signaling to facilitate autophagy. Additionally, TAMs/CXCL1 silence improved paclitaxel chemosensitivity by suppressing autophagy in breast cancer mice xenografts, and clinical studies further linked CXCL1 to IGF1R/HMGB1 signaling, as well as shorter free survival of recurrence. Taken together, these results not only uncover the crucial role of TAMs/CXCL1 signaling in mediating breast cancer chemoresistance through enhancing autophagy, but also shed novel light on the molecular mechanism of IGF1R/STAT3/HMGB1 pathway in regulating autophagy and its impact on cancer prognosis., (© 2024. The Author(s).)

Background: Triple-negative breast cancer (TNBC) is challenged by the low chemotherapy response and poor prognosis. Emerging evidence suggests that cytotoxic chemotherapy may lead to the pro-metastatic tumor microenvironment (TME) by eliciting pro-tumor extracellular vesicles (EVs) from cancer cells. However, the precise mechanisms and therapeutic approaches remain inadequately understood., Purpose: This study aims to determine whether XIAOPI formula (Chinese name XIAOPI San, XPS), a nationally sanctioned medication for mammary hyperplasia, can chemosensitize TNBC by remodeling the TME via modulating EV signaling, and exploring its underlying mechanisms., Methods: Multiple methodologies, such as EV isolation, transmission electron microscope, flow cytometry, dual-luciferase reporter assays, co-immunoprecipitation and in vivo breast cancer xenograft, were employed to elucidate the effect and molecular mechanisms of XPS on paclitaxel-induced EV signaling (EV-dead) of TNBC., Results: XPS, at non-toxic concentrations, synergized with PTX to inhibit the invasion and chemoresistance of TNBC cells co-cultured with macrophages. Compared to EV-dead, XPS co-treatment-elicited EVs (EV-dead XPS ) exhibited a decreased capacity to promote the invasion, chemoresistance and cancer stem cell subpopulation of the co-cultured TNBC cells. Mechanistically, XPS administration led to a reduction in CXCL1 cargo in EV-dead, and thereby attenuated its activation effect on macrophage polarization into M2 phenotype through the transcriptional downregulation of PD-L1 expression. Furthermore, XPS effectively reduced the number of EV-dead from TNBC cells by inhibiting CXCL1-mediated intraluminal vesicle (ILV) biogenesis in multivesicular bodies (MVBs). Moreover, molecular explorations revealed that XPS impaired ILV biogenesis by disrupting the RAB31/FLOT2 complex via suppressing the CXCL1/Myc signaling. Importantly, XPS significantly chemosensitized paclitaxel to inhibit TNBC growth and metastasis in vivo by suppressing EV-dead CXCL1 -induced PD-L1 activation and M2 polarization of macrophages., Conclusion: This pioneering study not only sheds novel light on EV-dead CXCL1 as a potential therapeutic target to suppress TNBC chemoresistance and metastasis, but also provides XPS as a promising adjuvant formula to chemosensitize TNBC by remodeling EV-dead CXCL1 -mediated immunosuppressive TME., 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 GmbH.)

Purpose: To explore the value of deep learning-based multi-parametric magnetic resonance imaging (mp-MRI) nomogram in predicting the Ki-67 expression in rectal cancer., Methods: The data of 491 patients with rectal cancer from two centers were retrospectively analyzed and divided into training, internal validation, and external validation sets. They were categorized into high- and low-expression group based on postoperative pathological Ki-67 expression. Each patient's mp-MRI data were analyzed to extract and select the most relevant features of deep learning, and a deep learning model was constructed. Independent predictive risk factors were identified and incorporated into a clinical model, and the clinical and deep learning models were combined to obtain a nomogram for the prediction of Ki-67 expression. The performance characteristics of the DL-model, clinical model, and nomogram were assessed using ROCs, calibration curve, decision curve, and clinical impact curve analysis., Results: The strongest deep learning features were extracted and screened from mp-MRI data. Two independent predictive factors, namely Magnetic Resonance Imaging T (mrT) staging and differentiation degree, were identified through clinical feature selection. Three models were constructed: a deep learning (DL)-model, a clinical model, and a nomogram. The AUCs of clinical model in the training, internal validation, and external validation set were 0.69, 0.78, and 0.67, respectively. The AUCs of the deep model and nomogram ranged from 0.88 to 0.98. The prediction performance of the deep learning model and nomogram was significantly better than the clinical model (P < 0.001)., Conclusion: The nomogram based on deep learning can help clinicians accurately and conveniently predict the expression status of Ki-67 in rectal cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Research on the microbiome and resistome in polar environments, such as the Arctic, is crucial for understanding the emergence and spread of antibiotic resistance genes (ARGs) in the environment. In this study, soil and reindeer faeces samples collected from Ny-Ålesund (Svalbard, High Arctic) were examined to analyze the microbiome, ARGs, and biocide/metal resistance genes (BMRGs). The dominant phyla in both soil and faeces were Pseudomonadota, Actinomycetota, and Bacteroidota. A total of 2618 predicted Open Reading Frames (ORFs) containing antibiotic resistance genes (ARGs) were detected. These ARGs belong to 162 different genes across 17 antibiotic classes, with rifamycin and multidrug resistance genes being the most prevalent. We focused on investigating antibiotic resistance mechanisms in the Ny-Ålesund environment by analyzing the resistance genes and their biological pathways. Procrustes analysis demonstrated a significant correlation between bacterial communities and ARG/BMRG profiles in soil and faeces samples. Correlation analysis revealed that Pseudomonadota contributed most to multidrug and triclosan resistance, while Actinomycetota were predominant contributors to rifamycin and aminoglycoside resistance. The geochemical factors, SiO 4 2- and NH 4 + , were found to significantly influence the microbial composition and ARG distribution in the soil samples. Analysis of ARGs, BMRGs, virulence factors (VFs), and pathogens identified potential health risks associated with certain bacteria, such as Cryobacterium and Pseudomonas, due to the presence of different genetic elements. This study provided valuable insights into the molecular mechanisms and geochemical factors contributing to antibiotic resistance and enhanced our understanding of the evolution of antibiotic resistance genes in the environment., 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.)

A bimetallic steel bar (BSB) consisting of stainless-steel cladding and carbon steel substrate exhibits excellent corrosion resistance and good mechanical properties. The bimetallic structure of BSBs may affect their low-cycle fatigue performance, and current investigations on the above issue are limited. In this study, the low-cycle fatigue properties of bimetallic steel bars (BSBs) with inelastic buckling were investigated. Experiments and numerical studies were conducted to investigate the low-cycle fatigue capacity for BSBs, considering buckling. The buckling mode of BSBs is discussed. The hysteretic loops and energy properties of BSBs with various slenderness ratios ( L / D ) and fatigue strain amplitudes ( ε a ) are investigated. With increases in the L / D and ε a , the original symmetry for hysteresis loops disappears gradually, which is caused by the buckling. A predictive equation revealing the relation between the ε a and fatigue life is suggested, which considers the effects of the L / D . A numerical modelling method is suggested to predict the hysteretic curves of BSBs. The effect of buckling on the stress and energy properties of BSBs is discussed through the numerical analysis of 44 models including the effects of the L / D , ε a , and cladding ratios. The numerical analysis results illustrate that the hysteresis loops of BSBs with various ε a values exhibit similar shapes. The increase in the cladding ratio reduces the peak stress and the dissipated energy properties of BSBs. The hysteresis loop energy density decreases by about 3% with an increase of 0.1 in the cladding ratio. It is recommended that the proportion of stainless steel inBSBs should be minimized once the corrosion resistance requirements are met.

Optical tractor beams capable of pulling particles backward have garnered significant and increasing interest. Traditional optical tractor beams are limited to free space beams with small forward wavevectors, enabling them to pull selected particles. Here, we present a comprehensive theory for the optical force exerted by a surface wave using analytical and numerical calculations, revealing the relationship between the canonical momentum and optical forces. Based on this theory, we demonstrate a general purpose optical surface tractor beam that can pull any passive particle, regardless of size, composition, or geometry. The tractor beam utilizes a surface wave with negative canonical momentum characterized by a single well-defined negative Bloch k vector. The tractor beam relies on a mechanism where the negative incident force always surpasses the recoil force. As such, the tractor beam, when excited on the surface of a double-negative index metamaterial, can pull particles with different morphologies., (© 2024. The Author(s).)

The inhibition of autophagy is a potential therapeutic strategy to improve the chemosensitivity of triple-negative breast cancer (TNBC). In this study, we demonstrated that a natural terpenoid tanshinone I (TAN) enhanced the effectiveness of paclitaxel (PTX), at least in part, through an autophagy-dependent mechanism against TNBC. In vitro validation demonstrated that the combined therapy resulted in a synergistic decrease in the growth of TNBC cells. The chemosensitizing impact of TAN might be attributed to its inhibition of PTX-induced autophagy in the late phase by obstructing the fusion of autophagosomes and lysosomes, rather than by inhibiting lysosomal function. The findings from KEGG pathway analysis and molecular docking suggested that TAN might impact breast cancer chemoresistance primarily through the PI3K-Akt and MAPK signaling pathways. The non-canonical AKT/p38 MAPK signaling was further validated as the primary mechanism responsible for the inhibition of autophagy by TAN. In vivo study showed that the combined administration of TAN and PTX demonstrated a more significant suppression of tumor growth and autophagic activity compared to PTX monotherapy in the MDA-MB-231 xenograft nude mouse model. The safety evaluation of TAN in a zebrafish model, along with in vitro and in vivo validation, provided experimental and pre-clinical data supporting its potential as a natural adjunctive therapy in TNBC. Overall, this study suggests that the combination of TAN with PTX could provide an effective treatment option for advanced breast cancer, and targeting the AKT/p38 MAPK/late-autophagy signaling axis may be a promising approach for developing therapeutic interventions against TNBC., 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 Masson SAS.. All rights reserved.)

Objective: To investigate the changes in serum homeobox A9 ( HOXA9 ), soluble E-cadherin (SE-CAD) and type Ⅲ procollagen (PCⅢ) levels in acute myeloid leukemia (AML) patients after chemotherapy with DCAG regimen and their relationship with prognosis., Methods: The clinical data of 80 patients with relapsed/refractory AML diagnosed and treated in our hospital from March 2018 to December 2021 were retrospectively analyzed. According to different treatment regimen, the patients were divided into DCAG group ( n =40) and CAG group ( n =40). The clinical efficacy and changes of HOXA9 , SE-CAD and PCⅢ levels before and after treatment were compared. In addition, all patients were divided into remission group ( n =58) and non-remission group ( n =22) according to the clinical efficacy. Univariate and multivariate analyses were performed to analyze the risk factors affecting the prognosis of AML patients. The predictive efficacy of the three single indicators, HOXA9 , SE-CAD, and PC III, and their combination on prognosis was analyzed., Results: Compared with before treatment, the levels of HOXA9 , SE-CAD and PCⅢ in both the DCAG and CAG groups were decreased after treatment, and the improvement of each indicator and the clinical efficacy in the DCAG group were significantly better than those in the CAG group (all P < 0.05). Multivariate analysis showed that increased bone marrow blast count, HOXA9 mRNA, SE-CAD and PCⅢ levels were independent risk factors affecting the efficacy of chemotherapy in AML patients (all P < 0.05). ROC curves showed that the combination of HOXA9 mRNA, SE-CAD and PCIII could effectively predict the prognosis of AML patients, with a sensitivity of 84.80% and a specificity of 88.20%., Conclusion: DCAG regimen can significantly improve the levels of HOXA9 mRNA, SE-CAD and PCⅢ in AML patients, these three indicators are all independent risk factors affecting the prognosis of AML patients, and the combination of the three indicators can effectively predict the prognosis of the patients.

To clarify the regulating effect of vegetation and soil factors on microbial communities in the alpine steppe under degradation on the Qinghai-Xizang Plateau, the alpine steppe in the Sanjiangyuan area of the Qinghai-Tibet Plateau was chosen. We analyzed the differences in vegetation and soil factors in different stages of degradation （non-degradation, moderate degradation, and severe degradation） and detected the variations in microbial community characteristics in the alpine steppe under different degradation stages using high-throughput sequencing technology. Eventually, redundancy analysis （RDA） and multiple regression matrixes （MRM） based on the similarity or dissimilarity matrix were used to identify key environmental factors regulating microbial （bacterial and fungal） community changes under degradation. The results showed that the degradation of the alpine steppe significantly changed the community coverage, height, biomass, and important value of graminae； significantly reduced the contents of soil organic matter, total nitrogen, total phosphorus, and silt； and increased the soil bulk density and sand content. Degradation did not change the composition of bacteria and fungi, but their composition proportions changed and also resulted in the loss of microbial richness （Chao1 index and Richness index） but did not significantly change the microbial diversity （Shannon index）. With the occurrence of degradation, the vegetation characteristics, soil physicochemical properties, and microbial diversity showed a consistent change trend. Combined with the characteristics of the network topology changes （the number of nodes and clustering coefficient significantly decreased）, it was found that degradation of the alpine steppe led to the decline of interspecies interactions, decentralization of network, and homogenization of microorganisms, but the cooperation relations among the species were maintained （positive correlation connections accounted for more than 90% in all degradation stages）. Under the alpine steppe degradation, the vegetation-soil interaction had the greatest effect on soil bacterial community, whereas soil physicochemical properties had the greatest influence on soil fungal community. Specifically, vegetation community height, biomass, and soil bulk density were the mutual factors regulating soil microorganisms, whereas the vegetation Simpson index, important value of graminae, soil total phosphorus, total potassium, and silt content were the unique factors affecting the soil bacterial community, and soil pH and total nitrogen content were the particular factors affecting the soil fungal community.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and chemotherapy is the cornerstone treatment for TNBC. Regrettably, emerging findings suggest that chemotherapy facilitates pro-metastatic changes in the tumour microenvironment. Extracellular vesicles (EVs) have been highly implicated in cancer drug resistance and metastasis. However, the effects of the EVs released from dying cancer cells on TNBC prognosis and corresponding therapeutic strategies have been poorly investigated. This study demonstrated that paclitaxel chemotherapy elicited CXCL1-enriched EVs from apoptotic TNBC cells (EV-Apo). EV-Apo promoted the chemoresistance and invasion of co-cultured TNBC cells by polarizing M2 macrophages through activating PD-L1 signalling. However, baohuoside I (BHS) remarkably sensitized the co-cultured TNBC cells to paclitaxel chemotherapy via modulating EV-Apo signalling. Mechanistically, BHS remarkably decreased C-X-C motif chemokine ligand 1 (CXCL1) cargo within EV-Apo and therefore attenuated macrophage M2 polarization by suppressing PD-L1 activation. Additionally, BHS decreased EV-Apo release by diminishing the biogenesis of intraluminal vesicles (ILVs) within multivesicular bodies (MVBs) of TNBC cells. Furthermore, BHS bound to the LEU104 residue of flotillin 2 (FLOT2) and interrupted its interaction with RAS oncogene family member 31 (RAB31), leading to the blockage of RAB31-FLOT2 complex-driven ILV biogenesis. Importantly, BHS remarkably chemosensitised paclitaxel to inhibit TNBC metastasis in vivo by suppressing EV-Apo CXCL1 -induced PD-L1 activation and M2 polarization of tumour-associated macrophages (TAMs). This pioneering study sheds light on EV-Apo CXCL1 as a novel therapeutic target to chemosensitise TNBC, and presents BHS as a promising chemotherapy adjuvant to improve TNBC chemosensitivity and prognosis by disturbing EV-Apo CXCL1 biogenesis., (© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Prostate cancer (PCa) is the second most common malignancy among men globally. The Fu-Zheng-Yi-Liu (FZYL) Formula has been widely utilized in the treatment of PCa. This study investigates whether the FZYL Formula can inhibit PCa by targeting the TAMs/CCL5 pathway. We conducted in vitro co-cultures and in vivo co-injections of PCa cells and TAMs to mimic their interaction. Results showed that the FZYL Formula significantly reduced the proliferation, colony formation, subpopulations of PCSCs, and sphere-formation efficacy of PCa cells, even in the presence of TAM co-culture. Additionally, the Formula markedly decreased the migration, invasion, and epithelial-mesenchymal transition (EMT) of PCa cells induced by TAMs. The FZYL Formula also reversed M2 phenotype polarization in TAMs and dose-dependently reduced their CCL5 expression and secretion, with minimal cytotoxicity observed. Mechanistic studies confirmed that the TAMs/CCL5 axis is a critical target of the FZYL Formula, as the addition of exogenous CCL5 partially reversed the formula's inhibitory effects on PCSCs self-renewal in the co-culture system. Importantly, the Formula also significantly inhibited the growth of PCa xenografts, bone metastasis, and PCSCs activity in vivo by targeting the TAMs/CCL5 pathway. Overall, this study not only elucidates the immunomodulatory mechanism of the FZYL Formula in PCa therapy but also highlights the TAMs/CCL5 axis as a promising therapeutic target., (Copyright © 2024 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Background: Triple-negative breast cancer (TNBC) is the most aggressive malignancy. Psychological distress and elevated CXCL1 level have been reported to be closely associated with the poor prognosis and quality of life of patients with TNBC. In preclinical studies using xenograft mouse models, XIAOPI formula, a nationally approved drug prescribed to patients at high risk for breast cancer, inhibited CXCL1 expression and improved survival. Traditional Chinese medicine has unique advantages in improving patients' emotional disorders and quality of life. However, the impact of XIAOPI formula on the serum level of CXCL1, psychological distress, and quality of life among patients with TNBC is currently unknown., Methods: In this study, we designed a randomized, double-blind, placebo-controlled trial. Patients with TNBC were randomly assigned to receive either the XIAOPI formula or a placebo for three months. The primary outcomes include serum CXCL1 expression, Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS). Secondary outcomes included the Pittsburgh Sleep Quality Index (PSQI) and the Functional Assessment of Cancer Therapy-Breast (FACT-B)., Results: A total of 60 patients with TNBC were enrolled in the investigation. The results showed that the XIAOPI formula significantly decreased CXCL1 expression compared with the control group. Moreover, in comparison to the placebo, the XIAOPI formula increased FACT-B scores while decreasing SDS, SAS, and PSQI scores., Conclusion: In patients with TNBC, XIAOPI formula may be effective in reducing CXCL1 levels, enhancing psychological well-being, and quality of life. While our research offers a natural alternative therapy that may enhance the prognosis of TNBC, future validation of its therapeutic effects will require large-scale, long-term clinical trials., Clinical Registration Number: Registration website: www.chictr.org.cn, Registration date: 2018-1-19, Registration number: ChiCTR1800014535., Competing Interests: The authors declare no potential conflicts of interest in this work., (© 2024 Guo et al.)

Bioinspired skeleton transformation of a tricyclic lathyrane-type Euphorbia diterpene was conducted to efficiently construct a tetracyclic tigliane diterpene on a gram scale via a key aldol condensation. The tigliane diterpene was then respectively converted into naturally rare ingenane and rhamnofolane diterpenes through a semipinacol rearrangement and a visible-light-promoted regioselective cyclopropane ring-opening reaction. This work provides a concise strategy for high-efficiency access to diverse polycyclic Euphorbia diterpene skeletons from abundant lathyrane-type natural products and paves the way for biological activity investigation of naturally rare molecules.

Temporal modulations provide a new approach for realizing metamaterials. In this study, through the imposition of uniform temporal modulations, we achieve two types of reciprocal bi-anisotropic metamaterials. Notably, these achievements do not rely on any spatial modulation, preserving inversion symmetry at any instantaneous time. This stands in sharp contrast to the scenario of traditional bi-anisotropic metamaterials, where the disruption of inversion symmetry by spatial arrangements is necessary. Conditions for realizing nonzero bi-anisotropic coupling are discussed and verified through full-wave simulations. Our work will stimulate research in the field of temporal bi-anisotropic metamaterials, as well as the application of temporal modulations in manipulating photonic spin angular momentum.

Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and chemotherapy still serves as the cornerstone treatment functioning by inducing cytotoxic cell death. Notably, emerging evidence suggests that dying cell-released signals may induce cancer progression and metastasis by modulating the surrounding microenvironment. However, the underlying molecular mechanisms and targeting strategies are yet to be explored., Methods: Apoptotic TNBC cells induced by paclitaxel or adriamycin treatment were sorted and their released extracellular vesicles (EV-dead) were isolated from the cell supernatants. Chemokine array analysis was conducted to identify the crucial molecules in EV-dead. Zebrafish and mouse xenograft models were used to investigate the effect of EV-dead on TNBC progression in vivo., Results: It was demonstrated that EV-dead were phagocytized by macrophages and induced TNBC metastasis by promoting the infiltration of immunosuppressive PD-L1 + TAMs. Chemokine array identified CXCL1 as a crucial component in EV-dead to activate TAM/PD-L1 signaling. CXCL1 knockdown in EV-dead or macrophage depletion significantly inhibited EV-dead-induced TNBC growth and metastasis. Mechanistic investigations revealed that CXCL1 EV-dead enhanced TAM/PD-L1 signaling by transcriptionally activating EED-mediated PD-L1 promoter activity. More importantly, TPCA-1 (2-[(aminocarbonyl) amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide) was screened as a promising inhibitor targeting CXCL1 signals in EVs to enhance paclitaxel chemosensitivity and limit TNBC metastasis without noticeable toxicities., Conclusions: Our results highlight CXCL1 EV-dead as a novel dying cell-released signal and provide TPCA-1 as a targeting candidate to improve TNBC prognosis., (© 2024. The Author(s).)

Many patients who underwent hepatic percutaneous microwave ablation (MWA) reported experiencing pain during the procedure. This study utilized a well-designed multicentral, randomized, and placebo-controlled format to investigate the effects of Butorphanol. Patients who underwent MWA were randomly assigned to either Butorphanol or normal saline group. The primary outcomes of the study were assessed by measuring the patients' intraoperative pain levels using a 10-point visual analog scale (VAS). Secondary outcomes included measuring postoperative pain levels at the 6-h mark (VAS) and evaluating comprehensive pain assessment outcomes. A total of 300 patients were divided between the control group (n = 100) and the experimental group (n = 200). Butorphanol showed statistically significant reductions in intraoperative pain levels compared to the placebo during surgery (5.00 ± 1.46 vs. 3.54 ± 1.67, P < 0.001). Significant differences were observed in postoperative pain levels at the 6-h mark and in the overall assessment of pain (1.39 + 1.21 vs. 0.65 + 0.81, P < 0.001). Butorphanol had a significant impact on reducing the heart rate of patients. The empirical evidence supports the effectiveness of Butorphanol in reducing the occurrence of visceral postoperative pain in patients undergoing microwave ablation for hepatic tumor. Furthermore, the study found no noticeable impact on circulatory and respiratory dynamics., (© 2024. The Author(s).)

Endocrine therapy is standard for hormone receptor-positive (HR + ) breast cancer treatment. However, current strategies targeting estrogen signaling pay little attention to estradiol metabolism in the liver and is usually challenged by treatment failure. In a previous study, we demonstrated that the natural compound naringenin (NAR) inhibited HR + breast cancer growth by activating estrogen sulfotransferase (EST) expression in the liver. Nevertheless, the poor water solubility, low bio-barrier permeability, and non-specific distribution limited its clinical application, particularly for oral administration. Here, a novel nano endocrine drug NAR-cell penetrating peptide-galactose nanoparticles (NCG) is reported. We demonstrated that NCG presented specific liver targeting and increased intestinal barrier permeability in both cell and zebrafish xenotransplantation models. Furthermore, NCG showed liver targeting and enterohepatic circulation in mouse breast cancer xenografts following oral administration. Notably, the cancer inhibition efficacy of NCG was superior to that of both NAR and the positive control tamoxifen, and was accompanied by increased hepatic EST expression and reduced estradiol levels in the liver, blood, and tumor tissue. Moreover, few side effects were observed after NCG treatment. Our findings reveal NCG as a promising candidate for endocrine therapy and highlight hepatic EST targeting as a novel therapeutic strategy for HR + breast cancer., (© 2024. The Author(s).)

To construct a stochastic version of [R. J. Barro, J. Polit. Econ. 87 , 940-971 (1979)] normative model of tax rates and debt/GDP dynamics, we add risks and markets for trading them along lines suggested by [K. J. Arrow, Rev. Econ. Stud. 31 , 91-96 (1964)] and [R. J. Shiller, Creating Institutions for Managing Society's Largest Economic Risks (OUP, Oxford, 1994)]. These modifications preserve Barro's prescriptions that a government should keep its debt-gross domestic product (GDP) ratio and tax rate constant over time and also prescribe that the government insure its primary surplus risk by selling or buying the same number of shares of a Shiller macro security each period., Competing Interests: Competing interests statement:The authors declare no competing interest.

Objectives: To assess when and whether clamping the double-lumen endobronchial tube (DLT) limb of the non-ventilated lung is more conducive to a rapid and effective lung deflation than simply allowing the open limb of the DLT to communicate with the atmosphere., Design: This was a single-center, single-blind, randomized, controlled trial., Setting: The trial was performed in a single institutional setting., Participants: The participants were 60 patients undergoing elective video-assisted thoracoscopic surgery., Interventions: Patients were randomized to the open-clamp airway technique (OCAT group) or control group. Patients in the control group had one-lung ventilation initiated upon being placed in the lateral decubitus position. The OCAT group had two-lung ventilation maintained until the pleural cavity was opened with the introduction of a planned thoracoscopic access port to allow the operated lung to fall away from the chest wall. Thereafter, ventilation was suspended (temporarily ceased) for 1 minute before the DLT lumen of the isolated lung was clamped. The primary outcome of the trial was the time to complete lung collapse scored as determined from video clips taken during surgery. The secondary outcomes were (1) lung collapse score at 30 minutes after pleural incision, (2) surgeon satisfaction with surgery, and (3) intraoperative hypoxemia., Measurements and Main Results: The median time to reach complete lung collapse in the OCAT group was 10 minutes (odds ratio 10.0, 95% CI 6.3-13.7), which was much shorter than that of the control group (25 minutes [odds ratio 25.0, 95% CI 13.6-36.4]). The difference in complete lung collapse at 30 minutes between the 2 groups was significant (p < 0.001). The surgeon's satisfaction with surgery was higher in the OCAT group than in the control group (8.5 ± 0.2 vs 6.8 ± 0.2; p < 0.001). There was no difference regarding intraoperative hypoxemia., Conclusions: Suspending ventilation of both DLT limbs for 1 minute after pleural cavity opening and then clamping the DLT lumen of the isolated lung resulted in a more rapid deflation of the surgical lung. This open-clamp airway technique is an effective technique for rapid surgical lung collapse during thoracoscopic surgery., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Future renewable energy supply and green, sustainable environmental development rely on various types of catalytic reactions. Copper single-atom catalysts (Cu SACs) are attractive due to their distinctive electronic structure (3d orbitals are not filled with valence electrons), high atomic utilization, and excellent catalytic performance and selectivity. Despite numerous optimization studies are conducted on Cu SACs in terms of energy conversion and environmental purification, the coupling among Cu atoms-support interactions, active sites, and catalytic performance remains unclear, and a systematic review of Cu SACs is lacking. To this end, this work summarizes the recent advances of Cu SACs. The synthesis strategies of Cu SACs, metal-support interactions between Cu single atoms and different supports, modification methods including modification for carriers, coordination environment regulating, site distance effect utilizing, and dual metal active center catalysts constructing, as well as their applications in energy conversion and environmental purification are emphatically introduced. Finally, the opportunities and challenges for the future Cu SACs development are discussed. This review aims to provide insight into Cu SACs and a reference for their optimal design and wide application., (© 2023 Wiley-VCH GmbH.)

Background: Sarcopenia is associated with poor outcomes in many malignancies. However, the relationship between sarcopenia and the prognosis of pancreatic cancer has not been well understood. The aim of this meta-analysis was to identify the prognostic value of preoperative sarcopenia in patients with pancreatic cancer after curative-intent surgery., Methods: Database from PubMed, Embase, and Web of Science were searched from its inception to July 2023. The primary outcomes were overall survival (OS), progression-free survival (PFS), and the incidence of major complications. The hazard ratio (HR), odds ratio (OR), and 95% confidence intervals (CIs) were used to assess the relationship between preoperative sarcopenia and the prognosis of patients with pancreatic cancer. All statistical analyses were conducted by Review Manager 5.3 and STATA 17.0 software., Results: A total of 23 retrospective studies involving 5888 patients were included in this meta-analysis. The pooled results demonstrated that sarcopenia was significantly associated with worse OS (HR = 1.53, P < 0.00001) and PFS (HR = 1.55, P < 0.00001). However, this association was not obvious in regard to the incidence of major complications (OR = 1.33, P = 0.11)., Conclusion: Preoperative sarcopenia was preliminarily proved to be associated with the terrible prognosis of pancreatic cancer after surgery. However, this relationship needs to be further validated in more prospective studies., (© 2024. The Author(s).)

Background: Detecting pathogens in pediatric central nervous system infection (CNSI) is still a major challenge in medicine. In addition to conventional diagnostic patterns, metagenomic next-generation sequencing (mNGS) shows great potential in pathogen detection. Therefore, we systematically evaluated the diagnostic performance of mNGS in cerebrospinal fluid (CSF) in pediatric patients with CNSI., Methods: Related literature was searched in the Web of Science, PubMed, Embase, and Cochrane Library. We screened the literature and extracted the data according to the selection criteria. The quality of included studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool and the certainty of the evidence was measured by the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) score system. Then, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odd's ratio (DOR), and area under the curve (AUC) of the summary receiver operating characteristic curve (sROC) were estimated in Stata Software and MetaDisc. Subgroup analyses were performed to investigate the potential factors that influence the diagnostic performance., Results: A total of 10 studies were included in the meta-analysis. The combined sensitivity was 0.68 (95% confidence interval [CI]: 0.59 to 0.76, I 2  = 66.77%, p < 0.001), and the combined specificity was 0.89 (95% CI: 0.80 to 0.95, I 2  = 83.37%, p < 0.001). The AUC of sROC was 0.85 (95% CI, 0.81 to 0.87). The quality level of evidence elevated by the GRADE score system was low., Conclusions: Current evidence shows that mNGS presents a good diagnostic performance in pediatric CNSI. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusion., (© 2024. The Author(s).)

Background: Glycemic control for patients with diabetes in the surgical department is often unsatisfactory. Compounding this issue is the fact that conventional glucose management models are often inefficient and difficult to monitor over time., Objective: To investigate the impact of inpatient glucose team-based management on glycemic control and hospital days in surgical patients with diabetes., Methods: A retrospective analysis was conducted on 4156 patients with diabetes in the surgical department who received inpatient management of diabetes at a tertiary medical center from June 2020 to May 2022. Based on whether they received inpatient glucose team-based management, the surgical patients with diabetes were divided into two groups: the inpatient glucose team-based management (GM group, consisting of 1698 participants) and the conventional blood glucose management group (control group, consisting of 2458 participants). We compared the two groups in terms of glycemic control, hospital days, and health-care costs. Multiple logistic regression analysis was performed to build the hospital days prediction model and nomogram. Finally, the performance of the model was evaluated., Results: The rate of glucose detection was higher in the GM group at 2 h postprandial (P < 0.01). The incidence of hypoglycemia and severe hyperglycemia, blood glucose attainment time, pre-operative preparation days, hospital days, and health-care costs were lower in the GM group than in the control group (P < 0.01). The linear regression model revealed that blood glucose attainment time, incidence of hypoglycemia (< 3.9mmol/L), preoperative preparation days, perioperative complications, and health-care costs were the factors influencing the hospital days (Total Point 83.4 points, mean hospital days 9.37 days). Receiver operating characteristic (ROC) curve analysis demonstrated that the nomogram had good accuracy for predicting hospital days (area under the ROC curve 0.83, 95% confidence interval [CI], 0.74 to 0.92)., Conclusion: Inpatient glucose team-based management demonstrated significant improvements in glycemic control among surgical patients with diabetes, resulting in reduced hospital days and associated costs. The developed nomogram also exhibited promising potential in predicting hospital days, offering valuable clinical applications., (© 2023. The Author(s).)

Background: Endothelial barrier dysfunction is critical for the pathogenesis of sepsis-induced acute lung injury (ALI). Lipopolysaccharide (LPS)-stimulated human pulmonary microvascular endothelial cells (HPMECs) are widely used as the cell model of sepsis-associated ALI for exploration of endothelial barrier dysfunction. Dickkopf (DKK) family proteins were reported to mediate endothelial functions in various diseases. The present study explored the effect of Dickkopf-3 (DKK3) on endothelial barrier permeability, angiogenesis, and tight junctions in LPS-stimulated HPMECs., Methods: RT-qPCR was required for detecting DKK3 and miR-98-3p expression. The angiogenesis of HPMECs was evaluated by tube formation assays. Monolayer permeability of HPMECs was examined by Transwell rhodamine assays. The protein expression of DKK3 and tight junctions in HPMECs was measured via western blotting. Luciferase reporter assay was used to verify the interaction between miR-98-3p and DKK3., Results: LPS treatment inhibited angiogenetic ability while increasing the permeability of HPMECs. DKK3 expression was upregulated while miR-98-3p level was reduced in LPS-treated HPMECs. DKK3 knockdown alleviated HPMEC injury triggered by LPS stimulation. MiR-98-3p targeted DKK3 in HPMECs. Overexpression of miR-98-3p protects HPMECs from the LPS-induced endothelial barrier dysfunction, and the protective effect was reversed by DKK3 overexpression., Conclusions: MiR-98-3p ameliorates LPS-evoked pulmonary microvascular endothelial barrier dysfunction in sepsis-associated ALI by targeting DKK3.

Due to the widespread commercial production and use of brominated flame retardants (BFRs) in China, their potential impact on human health development should not be underestimated. This review searched the literature on Polybrominated diphenyl ethers and Novel brominated flame retardant (PBDEs and NBFRs) (broad BFRs) in the aquatic environment (including surface water and sediment) in China over the last decade. It was found that PBDEs and NBFRs entered the aquatic environment through four main pathways, atmospheric deposition, surface runoff, sewage effluent and microplastic decomposition. The distribution of PBDEs and NBFRs in the aquatic environment was highly correlated with the local economic structure and population density. In addition, a preliminary risk assessment of existing PBDEs and PBDEs in sediments showed that areas with high-risk quotient values were always located in coastal areas with e-waste dismantling sites, which was mainly attributed to the historical legacy of electronic waste. This research provides help for the human health development and regional risk planning management posed by PBDEs and NBFRs., Competing Interests: Declaration of competing interest The authors declared that there were no conflicts of interest regarding the publication of this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We have developed a nonlocal effective medium theory (EMT) for phononic temporal metamaterials using the multiscale technique. Our EMT yields closed-form expressions for effective constitutive parameters and reveals these materials as reciprocal media with symmetric band dispersion. Even without spatial symmetry breaking, nonzero Willis coupling coefficients emerge with time modulation and broken time-reversal symmetry, when the nonlocal effect is taken into account. Compared to the local EMT, our nonlocal version is more accurate for calculating the bulk band at high wavenumbers and essential for understanding nonlocal effects at temporal boundaries. This nonlocal EMT can be a valuable tool for studying and designing phononic temporal metamaterials beyond the long-wavelength limit., (Creative Commons Attribution license.)

Competing Interests: The authors declare that they have no conflict of interest.

Context: Guilu-Erxian-Glue (GLEXG) is a traditional Chinese formula used to improve male reproductive dysfunction., Objective: To investigate the ferroptosis resistance of GLEXG in the improvement of semen quality in the oligoasthenospermia (OAS) rat model., Materials and Methods: Male Sprague-Dawley (SD) rats were administered Tripterygium wilfordii polyglycoside, a compound extracted from Tripterygium wilfordii Hook F. (Celastraceae), at a dose of 40 mg/kg/day, to establish an OAS model. Fifty-four SD rats were randomly divided into six groups: sham, model, low-dose GLEXG (GLEXGL, 0.25 g/kg/day), moderate-dose GLEXG (GLEXGM, 0.50 g/kg/day), high-dose GLEXG (GLEXGH, 1.00 g/kg/day) and vitamin E (0.01 g/kg/day) group. The semen quality, structure and function of sperm mitochondria, histopathology, levels of oxidative stress and iron, and mRNA levels and protein expression in the Keap1/Nrf2/GPX4 pathway, were analyzed., Results: Compared with the model group, GLEXGH significantly improved sperm concentration (35.73 ± 15.42 vs. 17.40 ± 4.12, p  < 0.05) and motility (58.59 ± 11.06 vs. 28.59 ± 9.42, p  < 0.001), and mitigated testicular histopathology. Moreover, GLEXGH markedly reduced the ROS level (5684.28 ± 1345.47 vs. 15500.44 ± 2307.39, p  < 0.001) and increased the GPX4 level (48.53 ± 10.78 vs. 23.14 ± 11.04, p  < 0.01), decreased the ferrous iron level (36.31 ± 3.66 vs. 48.64 ± 7.74, p  < 0.05), and rescued sperm mitochondrial morphology and potential via activating the Keap1/Nrf2/GPX4 pathway., Discussion and Conclusions: Ferroptosis resistance from GLEXG might be driven by activation of the Keap1/Nrf2/GPX4 pathway. Targeting ferroptosis is a novel approach for OAS therapy.

Lipid-structured vesicles have been applied for drug delivery system for over 50 years. Based on their origin, lipid-structured vesicles are divided into two main categories, namely synthetic lipid vesicles (SLNVEs) and vesicles of mammalian origin (MDVEs). Although SLNVEs can stably transport anti-cancer drugs, their biocompatibility is poor and degradation of exogenous substances is a potential risk. Unlike SLNVEs, MDVEs have excellent biocompatibility but are limited by a lack of stability and a risk of contamination by dangerous pathogens from donor cells. Since the first discovery of plant-derived vesicles (PDVEs) in carrot cell supernatants in 1967, emerging evidence has shown that PDVEs integrate the advantages of both SLNVEs and MDVEs. Notably, 55 years of dedicated research has indicated that PDVEs are an ideal candidate vesicle for drug preparation, transport, and disease treatment. The current review systematically focuses on the role of PDVEs in cancer therapy and in particular compares the properties of PDVEs with those of conventional lipid vesicles, summarizes the preparation methods and quality control of PDVEs, and discusses the application of PDVEs in delivering anti-cancer drugs and their underlying molecular mechanisms for cancer therapy. Finally, the challenges and future perspectives of PDVEs for the development of novel therapeutic strategies against cancer are discussed., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Zhao et al.)

Background: Oral nucleoside (acid) analogues (NAs) are recommended for patients with acute-on-chronic liver failure (ACLF) associated with hepatitis B virus (HBV-ACLF). The efficacy and safety of tenofovir (TDF) and entecavir (ETV) in these patients remain unclear., Methods: A comprehensive literature search in PubMed, Web of Science, The Cochrane Library, and Embase database was conducted to select studies published before December 2022 on TDF or ETV for HBV-ACLF. The primary outcomes were survival rates at 4, 12, and 48 weeks. Secondary outcomes were virologic and biochemical responses, serum antigen conversion, liver function score, and safety., Results: Four prospective and one retrospective cohort studies were selected. The overall analysis showed comparable survival rates at 4, 12, and 48 weeks for all patients receiving TDF or ETV (4-week: RR = 1.17, 95% CI: 0.90-1.51, p = 0.24; 12-week: RR = 1.00, 95% CI: 0.88-1.13, p = 0.94; 48-week: RR = 0.96, 95% CI: 0.58-1.57, p = 0.86). Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease (MELD) score at 12 weeks were comparable in both groups but lower than baseline (CTP: SMD = -0.75, 95% CI:-2.81-1.30, p = 0.47; MELD: SMD = -1.10, 95% CI:-2.29-0.08, p = 0.07). At 48 weeks, estimated glomerular filtration rate (eGFR) levels were found to decrease to different degrees from baseline in both the TDF and ETV groups, and the decrease was greater in the TDF group than in the ETV group. No significant differences were found in biochemical, virologic response, and serum antigen conversion between the two groups during the observation period., Conclusion: TDF treatment of HBV-ACLF is similar to ETV in improving survival, liver function, and virologic response but the effects on renal function in two groups in the long term remain unclear. More and larger long-term clinical trials are required to confirm these findings., (© 2023. The Author(s).)

Background: Bone metastasis occurs in nearly 70% of patients with metastatic prostate cancer (PCa), and represents the leading cause of death in patients with PCa. Emerging evidence has demonstrated the potential activities of icariin in modulating bone metabolism and remodelling the tumor microenvironment (TME). However, whether icariin could inhibit PCa bone metastasis and destruction by modulating the TME as well as the underlying mechanisms remains unclear., Purpose: This study investigated whether icariin could inhibit PCa bone metastasis and destruction by modulating the bone TME as well as the underlying mechanisms., Methods: Osteoclasts were induced from mouse bone marrow-derived macrophages (BMMs) or Raw264.7 cells. PCa cells were cultured in the conditional medium (CM) of macrophages in vitro or co-injected with macrophages in vivo to simulate their coexistence in the TME. Multiple molecular biology experiments and the mouse RM1-Luc PCa bone metastasis model were used to explore the inhibitory activity and mechanism of icariin on PCa metastasis and bone destruction., Results: Icariin treatment significantly suppressed PCa growth, bone metastasis and destruction as well as osteoclastogenesis in vivo. Furthermore, icariin remarkably inhibited osteoclast differentiation, even in the presence of the CM of tumor-associated macrophages (TAMs), while exhibiting no obvious effect on osteoblasts. Moreover, icariin suppressed the M2 phenotype polarization of Raw264.7-derived TAMs and transcriptionally attenuated their CC motif chemokine ligand 5 (CCL5) expression and secretion via inhibiting SPI1. Additionally, CCL5 induced the differentiation and chemotaxis of osteoclast precursor cells by binding with its receptor CCR5. The clinicopathological analysis further verified the positive correlation between the TAM/CCL5/CCR5 axis and osteoclastogenesis within the TME of PCa patients. More importantly, icariin remarkably suppressed PCa metastasis-induced bone destruction in vivo by inhibiting osteoclastogenesis via downregulating the TAM/CCL5 pathway., Conclusion: Altogether, these results not only implicate icariin as a promising candidate immunomodulator for PCa bone metastasis and destruction but also shed novel insight into targeting TAM/CCL5-mediated osteoclastogenesis as a potential treatment strategy for osteolytic bone metastasis. This study helps to advance the understanding of the crosstalk between bone TME and bone homeostasis., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Background: The identification of vanishing bile duct syndrome (VBDS) is still challenging before liver biopsy. This study tried to explore non-invasive biomarkers for identification of VBDS among children with acute cholestatic hepatitis., Methods: Between January 2017 and December 2021, 192 children underwent native-liver biopsy for acute cholestatic hepatitis with onset after 6 months of age. VBDS was diagnosed by liver biopsy. Differences of liver biochemical indices were compared between children with and without VBDS. Diagnostic performances for VBDS were tested by receiver operating characteristic (ROC) curve analyses., Results: Among the 192 patients, 24 (12.5%) were diagnosed with VBDS based on liver biopsy. At biopsy, their levels of total bilirubin (TB), direct bilirubin (DB), γ-glutamyl transpeptidase (GGT), total bile acid, triglyceride, and total cholesterol (TCH) were higher than patients without VBDS (all P<0.05). However, only GGT and TCH could distinguish patients with VBDS from patients without VBDS with an area under ROC curve (AUC) >0.850. Using GGT >446 U/L as a cut-off value, the sensitivity was 87.5%, the specificity was 91.6%, and the AUC was 0.948 (P<0.001). Using TCH >6.4 mmol/L as a cut-off value, the sensitivity was 100.0%, the specificity was 89.8%, and the AUC was 0.983 (P<0.001). A total of 28 patients had both GGT >446 U/L and TCH >6.4 mmol/L, including 21 patients with VBDS and 7 without VBDS (21/28 vs . 3/143, P<0.0001). Three patients with VBDS would be missed for GGT <446 U/L., Conclusions: Both GGT and TCH can be used as non-invasive biomarkers for identification of VBDS among children with acute cholestatic hepatitis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-23-305/coif). The authors have no conflicts of interest to declare., (2023 Translational Pediatrics. All rights reserved.)

The naturally scarce eupholathone-type euphornin E (1) was efficiently prepared from abundant lathyrane-type Euphorbia factor L 1 via a visible-light-induced Sc(OTf) 3 -catalyzed tandem process. Eupholathones 2 and 3 were also smoothly obtained by changing the reaction solvent. This route provides a convenient method for easily constructing scarce eupholathone- from lathyrane-type Euphorbia diterpenes, and confirms the biogenetic relationship between them from a chemical standpoint. Notably, compound 1 exhibited good anti-HIV activity.

Background: Depression increases the risk of breast cancer recurrence and metastasis. However, there lacks potential biomarkers for predicting prognosis in breast cancer. 5-hydroxytryptamine (5-HT) plays a key role in the pathogenesis and treatment of depression. In this study, we developed a prognostic signature based on 5-HT receptors (5-HTRs) and elucidated its potential immune regulatory mechanisms for breast cancer prognosis., Methods: Oncomine, GEPIA, UALCAN, cBioPortal, Kaplan-Meier plotter, and TIMER were used to analyze differential expression, prognostic value, genetic alteration, and immune cell infiltration of HTRs in breast cancer patients. The model training and validation assays were based on the analyses of GSE1456 and GSE86166. A risk signature was established by univariate and multivariate Cox regression analyses. The transwell assay was utilized to verify the effect of the 5-HTRs expression on breast cancer invasion. Effects of HTR2A/2B inhibitor on CD8 + T cell proliferation and infiltration as well as apoptosis of 4T1 cells in the tumor microenvironment were detected by flow cytometry and TUNEL assay. Zebrafish and mouse breast cancer xenografts were used to determine the effect of HTR2A/2B inhibitor on breast cancer metastasis., Results: The expression levels of HTR1A, HTR1B, HTR2A, HTR2B, HTR2C, HTR4, and HTR7 were significantly downregulated in highly malignant breast cancer types. 5-HTRs were significantly associated with recurrence-free survival (RFS) in breast cancer patients. The genetic alteration of HTR1D, HTR3A, HTR3B, and HTR6 in breast cancer patients was significantly associated with shorter overall survival (OS). Finally, HTR2A and HTR2B were determined to construct the risk signature. The expression of HTR2A/2B was positively correlated with the infiltration of immune cells such as CD8 + T cells and macrophages. Furthermore, inhibition of HTR2A expression could suppress CD8 + T cell proliferation and enhance invasion and metastasis of breast cancer cells in both zebrafish and mice model., Conclusions: The HTR2A/2B risk signature not only highlights the significance of HTRs in breast cancer prognosis by modulating cancer immune microenvironment, but also provides a novel gene-testing tool for early prevention of depression in breast cancer patients and lead to an improved prognosis and quality of life., 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 © 2023 Zhan, Wang, Zheng, Wang, Yang, Pan, Wang and Wang.)

Breaking spatial and temporal homogeneities simultaneously incurs the combination of wavenumber and frequency translations. In this work, broadband frequency translations with both redshifts and blueshifts triggered by a single photonic space-time interface (PSTI) with weak temporal change of permittivity across which a homogeneous medium suddenly becomes a one-dimensional photonic crystal is proposed. Mode conversions induced by the PSTI are analyzed, according to which the frequency translation amplitudes are independent of the change of permittivity and the initial frequency but are given by the product of the phase speed of the homogeneous medium and the spatial modulation frequency of the photonic crystal. Hence, a static field can be partially converted into dynamic fields by imposing the PSTI. Our findings pave the way for the study of PSTIs and provide a new scheme to realize broadband frequency translations.

Background: Red cell distribution width (RDW) may be related to the prognosis of hip fractures. The purpose of this study was to evaluate the association between (RDW) and all-cause mortality in elderly hip fractures., Materials and Methods: Elderly patients aged ≥65 years who had a hip fracture were screened between January 1, 2015, and September 30, 2019. The age, gender of patients and other demographics, as well as history of allergy, injury mechanism, underlying illnesses at the time of admission, fracture classification, time from admission to operation, RDW, operation time, blood loss, infusion, transfusion, treatment strategy, and length in hospital stay and follow-up and other clinical characteristics were collected. Linear and nonlinear multivariate Cox regression models were used to identify the association between RDW and mortality in these patients. Analyses were performed using EmpowerStats and the R software., Results: A total of 2587 patients were included in this retrospective cohort study. The mean follow-up period was 38.92 months. A total of 873 (33.75%) patients died due to all-cause mortality. The RDW was linearly associated with mortality in elderly patients with hip fractures. Linear multivariate Cox regression models showed that RDW was associated with mortality (hazard ratio [HR]=1.03, 95% confidence interval [CI]:1.02-1.05, P < 0.0001) after adjusting for confounding factors. The mortality risk increased by 3% when RDW increased by 1 fL., Conclusion: RDW is associated with mortality in elderly patients with hip fractures, and RDW could be considered a predictor of mortality risk., Registration: ChiCTR2200057323., Competing Interests: The authors declare that they have no competing interests for this work., (© 2023 Wang et al.)

As the temporal counterparts of traditional antireflection coatings, antireflection temporal coatings (ATCs) provide a novel approach to eliminate reflections by employing two-step temporal modulations. The interval between these two temporal modulation steps is called the time duration of the ATC. In this Letter, we explore ATCs utilizing Lorentzian dispersive media through an extended temporal transfer matrix method, and we discover that they exhibit diverse time durations and offer the potential for enhanced transmission. On one hand, the Lorentzian dispersive ATC can function as a temporal quarter-wave impedance transformer, similar to nondispersive ATCs. In this scenario, the time durations are consistently shorter than those of nondispersive ATCs, gradually converging to a constant value as the dielectric constant of the output layer approaches infinity. On the other hand, by finely tuning the parameters of the Lorentzian dispersive temporal coating, reflections can also be accidentally eliminated, which is not achievable with nondispersive temporal coatings. Consequently, Lorentzian dispersive ATCs offer additional time durations compared with nondispersive ATCs. Furthermore, Lorentzian dispersive ATCs with different time durations lead to distinct transmission characteristics. In certain cases, they can even enhance transmissions, a feat unattainable for nondispersive ATCs. These Lorentzian dispersive ATCs are feasible in the gigahertz and even terahertz regimes.

Background: Infectious disease is a large burden on public health globally. Metagenomic next-generation sequencing (mNGS) has become popular as a new tool for pathogen diagnosis with numerous advantages compared to conventional methods. Recently, research on mNGS increases yearly. However, no bibliometric analysis has systematically presented the full spectrum of this research field. Therefore, we reviewed all the publications associated with this topic and performed this study to analyze the comprehensive status and future hotspots of mNGS for infectious disease diagnosis., Methods: The literature was searched in the Web of Science Core Collection and screened without year or language restrictions, and the characteristics of the studies were also identified. The outcomes included publication years, study types, journals, countries, authorship, institutions, frontiers, and hotspots with trends. Statistical analysis and visualization were conducted using VOSviewer (version 1.6.16) and CiteSpace (version 6.1. R3)., Results: In total, 325 studies were included in the analysis after screening. Studies were published between 2009 and 2022 with a significantly increasing number from 1 to 118. Most of the studies were original articles and case reports. Frontiers in Cellular and Infection Microbiology and Clinical Infectious Disease were the most commonly cited and co-cited journals. Institutions and researchers from China contributed the most to this field, followed by those from the USA. The hotspots and frontiers of these studies are pneumonia, tuberculosis, and central nervous system infections., Conclusion: This study determined that mNGS is a hot topic in the diagnosis of infectious diseases with development trends and provides insights into researchers, institutions, hotspots and frontiers in mNGS, which can offer references to related researchers and future research., 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 © 2023 He, Wei, Feng, Liu, Wang, Chen and Xiong.)

Background: Systemic inflammation is associated with the development and progression of hepatitis B-associated acute-on-chronic liver failure (HBV-ACLF). The neutrophil-to-lymphocyte ratio (NLR) has been reported to be a prognostic biomarker in patients with HBV-ACLF. However, the role of the monocyte-to-lymphocyte ratio (MLR) as a prognostic inflammatory biomarker in multiple diseases is rarely mentioned in HBV-ACLF., Methods: We included a total of 347 patients with HBV-ACLF who met the definition of the Chinese Guidelines for the Diagnosis and Treatment of Liver Failure (2018 edition). Among them, 275 cases were included retrospectively, and 72 cases were collected prospectively. Clinical characteristics and laboratory examination data were collected from medical records within 24 h after diagnosis to calculate MLR and NLR levels, and lymphocyte subpopulation counts were collected in prospectively included patients., Results: Of the 347 patients with HBV-ACLF, 128 patients in the non-surviving group had a mean age of 48.87 ± 12.89 years; 219 patients in the survival group had a mean age of 44.80 ± 11.80 years and a combined 90-day mortality rate of 36.9%. The median MLR was higher in the non-survivors than in the survivors (0.690 vs 0.497, P < 0.001). MLR values were significantly associated with 90-day mortality in HBV-ACLF (OR 6.738; 95% CI 3.188-14.240, P < 0.001). The AUC for the predictive power of the combined MLR and NLR analysis for HBV-ACLF was 0.694, and the calculated MLR threshold was 4.495. In addition, in the analysis of peripheral blood lymphocyte subsets in HBV-ACLF, a significant decrease in the number of circulating lymphocytes was found in HBV-ACLF patients in the non-surviving group (P < 0.001), with a predominant decrease in the number of CD8 + T cells and no significant difference in the number of CD4 + T cells, B cells or NK cells., Conclusion: Increased MLR values are associated with 90-day mortality in patients with HBV-ACLF, and the MLR may serve as a potential prognostic indicator for patients with HBV-ACLF. Decreased CD8 + T-cell counts may be associated with poor survival in patients with HBV-ACLF., 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 © 2023 Elsevier B.V. All rights reserved.)

Erectile dysfunction (ED) is a major health problem affecting a large proportion of the general population. Testosterone also plays a key role in sexual dysfunction. In this study, we found that testosterone can inhibit cavernous fibrosis by affecting the expression of miR-22-3p, providing a new basis for research and treatment of ED. Old and young rats were used to study the effects of testosterone on cavernous fibrosis. Hematoxylin and eosin (HE) and Masson's staining were used to observe the cavernous tissue. A luciferase assay was used to analyze the relationship between the miR-22-3p, TGFβR1, and Galectin-1 signaling pathways. CCK-8 and flow cytometry were used to detect the proliferation and apoptosis rates of cavernosum smooth muscle cells (CSMCs) following testosterone intervention. Immunohistochemical analysis was performed to examine the positive rate of caspase 3 and Ki67. IF was used to analyze the expression of collagen IV, MMP2, and α-SMA. The levels of GnRH, tT, LH, and F-TESTO in old rats increased after testosterone intervention. miR-22-3p inhibits the expression of TGFβR1 and Galectin-1. The protein expression of TGFβR1, Galectin-1, SMAD2, and p-SMAD2 was reduced by testosterone. The expression levels of α-SMA, collagen I, collagen IV, FN, and MMP2 in the cavernous tissues of old rats treated with testosterone were significantly reduced. The levels of caspase 3 and collagen IV decreased, and the levels of MMP2, Ki67, and α-SMA increased. Testosterone and miR-22-3p inhibit CSMC apoptosis and promote cell proliferation. Testosterone promoted the expression of miR-22-3p to interfere with the expression of the cavernous TGFβR1 and Galectin-1 signaling pathways. Testosterone can reduce cavernous fibrosis during the treatment of functional ED., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Metasurfaces that can operate without a strictly periodic arrangement of meta-atoms are highly desirable for practical optical micro-nano devices. In this paper, we propose two kinds of Kerker-type metasurfaces that exhibit immunity to positional disorder. These metasurfaces consist of two distinct core-shell cylinders that satisfy the first and second Kerker conditions, respectively. Despite significant positional disorder perturbations of the meta-atoms, the metasurfaces can maintain excellent performance comparable to periodic ones, including total transmission and magnetic mirror responses. This positional disorder immunity arises from the unidirectional forward or backward scattering of a single core-shell cylinder, which results in minimal lateral scattering coupling between neighboring cylinders, thereby having little impact on multiple scattering in either the forward or backward direction. In contrast, the response of positional disorder non-Kerker-type metasurfaces decreases significantly. Our findings present a new approach for designing robust metasurfaces and expanding the applications of metasurfaces in sensing and communications within complex practical scenarios.

Background: Emerging studies have identified chronic psychological stress as an independent risk factor influencing breast cancer growth and metastasis. However, the effects of chronic psychological stress on pre-metastatic niche (PMN) formation and the underlying immunological mechanisms remain largely unknown., Methods: The effects and molecular mechanisms of chronic unpredictable mild stress (CUMS) on modulating tumor-associated macrophages (TAMs) and PMN formation were clarified by multiplex immunofluorescence technique, cytokine array, chromatin immunoprecipitation, the dual-luciferase reporter assay, and breast cancer xenografts. Transwell and CD8 + T cytotoxicity detection were used to analyze the mobilization and function of myeloid-derived suppressor cells (MDSCs). mCherry-labeled tracing strategy and bone marrow transplantation were applied to explore the crucial role of splenic CXCR2 +/+ MDSCs facilitating PMN formation under CUMS., Results: CUMS significantly promoted breast cancer growth and metastasis, accompanied by TAMs accumulation in the microenvironment. CXCL1 was identified as a crucial chemokine in TAMs facilitating PMN formation in a glucocorticoid receptor (GR)-dependent manner. Interestingly, the spleen index was significantly reduced under CUMS, and splenic MDSCs were validated as a key factor mediating CXCL1-induced PMN formation. The molecular mechanism study revealed that TAM-derived CXCL1 enhanced the proliferation, migration, and anti-CD8 + T cell functions of MDSCs via CXCR2. Moreover, CXCR2 knockout and CXCR2 -/- MDSCs transplantation significantly impaired CUMS-mediated MDSC elevation, PMN formation, and breast cancer metastasis., Conclusion: Our findings shed new light on the association between chronic psychological stress and splenic MDSC mobilization, and suggest that stress-related glucocorticoid elevation can enhance TAM/CXCL1 signaling and subsequently recruit splenic MDSCs to promote PMN formation via CXCR2., (© 2023. The Author(s).)

Introduction: Chronic psychological stress is a well-established risk factor for breast cancer development. Si-Ni-San (SNS) is a classical traditional Chinese medicine formula prescribed to psychological disorder patients. However, its action effects, molecular mechanisms, and bioactive phytochemicals against breast cancer are not yet clear., Objectives: This study aimed to explore the modulatory mechanism and bioactive compound of SNS in regulating estrogen metabolism during breast cancer development induced by chronic psychological stress., Methods: Mouse breast cancer xenograft was used to determine the effect of SNS on breast cancer growth and metastasis. Metabolomics analysis was conducted to discover the impact of SNS on metabolic profile changes in vivo. Multiple molecular biology experiments and breast cancer xenografts were applied to verify the anti-metastatic potentials of the screened bioactive compound., Results: SNS remarkably inhibited chronic psychological stress-induced breast cancer growth and metastasis in the mouse breast cancer xenograft. Meanwhile, chronic psychological stress increased the level of cholic acid, accompanied by the elevation of estradiol. Mechanistic investigation demonstrated that cholic acid activated farnesoid X receptor (FXR) expression, which inhibited hepatocyte nuclear factor 4α (HNF4α)-mediated estrogen sulfotransferase (EST) transcription in hepatocytes, and finally resulting in estradiol elevation. Notably, SNS inhibited breast cancer growth by suppressing estradiol level via modulating FXR/EST signaling. Furthermore, luciferase-reporting gene assay screened naringenin as the most bioactive compound in SNS for triggering EST activity in hepatocytes. Interestingly, pharmacokinetic study revealed that naringenin had the highest absorption in the liver tissue. Following in vivo and in vitro studies demonstrated that naringenin inhibited stress-induced breast cancer growth and metastasis by promoting estradiol metabolism via FXR/EST signaling., Conclusion: This study not only highlights FXR/EST signaling as a crucial target in mediating stress-induced breast cancer development, but also provides naringenin as a potential candidate for breast cancer endocrine therapy via promoting estradiol metabolism., 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 © 2023. Production and hosting by Elsevier B.V.)

In a wireless sensor network (WSN), geocasting is a location-based routing protocol used for data collection or information delivery. In geocasting, a target region usually contains many sensor nodes with limited battery capacity, and sensor nodes in multiple target regions need to transmit data to the sink. Therefore, how to use location information to construct an energy efficient geocasting path is a very important issue. FERMA is a geocasting scheme for WSNs based on Fermat points. In this paper, an efficient grid-based geocasting scheme for WSNs, which is called GB-FERMA, is proposed. The scheme uses the Fermat point theorem to search for the specific nodes as Fermat points in a grid-based WSN, and it selects the optimal relay nodes (gateways) in the grid structure to realize energy-aware forwarding. In the simulations, when the initial power 0.25 J, the average energy consumption of GB-FERMA is about 53% of FERMA-QL, 37% of FERMA, and 23% of GEAR; however, when with the initial power 0.5 J, the average energy consumption of GB-FERMA is about 77% of FERMA-QL, 65% of FERMA, and 43% of GEAR. The proposed GB-FERMA can effectively reduce the energy consumption and thus prolong the lifetime of the WSN.

The effect of pH is a key factor in biomineralization mediated by Acidithiobacillus ferrooxidans to promote the transformation of Fe into secondary iron minerals. This study aimed to investigate the effects of initial pH and carbonate rock dosage on bio-oxidation and secondary iron mineral synthesis. Variations in pH and the concentrations of Ca 2+ , Fe 2+ , and total Fe (TFe) in the growth medium of A. ferrooxidans were examined in the laboratory to determine how they affect the bio-oxidation process and secondary iron mineral synthesis. The results showed that in systems with an initial pH of 1.8, 2.3, and 2.8, the optimum dosages of carbonate rock were 30, 10, and 10 g, respectively, which significantly improved the removal rate of TFe and the amount of sediments. At an initial pH of 1.8 and a carbonate rock dosage of 30 g, the final removal rate of TFe reached 67.37%, which was 28.03% higher than that of the system without the addition of carbonate rock, and 36.9 g·L -1 of sediments were generated, which was higher than that of the system without the addition of carbonate rock (6.6 g·L -1 ). Meanwhile, the number of sediments generated by adding carbonate rock were significantly higher than those without the addition of carbonate rock. The secondary minerals were characterized by a progressive transition from low crystalline assemblages composed of calcium sulfate and subordinated jarosite, to well crystal-line assemblages composed of jarosite, calcium sulfate, and goethite. These results have important implications for comprehensively understanding the dosage of carbonate rock in mineral formation under different pH conditions. The findings help reveal the growth of secondary minerals during the treatment of AMD using carbonate rocks under low-pH conditions, which offers valuable information for combining the carbonate rocks with secondary minerals to treat AMD.