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Bioelectrochemical systems (BESs) have shown great potential in enhancing sulfamethoxazole (SMX) removal. However, electroactive biofilms (EBs) constructed with single potentials struggle due to limited biocatalytic activity, hindering deep SMX degradation. Here, we constructed a double-working potential BES (BES-D) to investigate its ability to eliminate SMX and reduce the levels of corresponding antibiotic resistance genes (ARGs). The preferable electrochemical activity of EB in BES-D was confirmed by electrochemical characterization, EPS analysis, physical structure, viability of the biofilm, and cytochrome content. BES-D exhibited a notably greater SMX removal efficiency (94.2 %) than did the single-working potential BES (BES-S) and the open-circuit group (OC). Degradation pathway analysis revealed that the cooperative EB could accelerate the in-depth removal of SMX. Moreover, EB interaction in BES-D decreased the relative abundance of ARGs in biofilms compared to that in BES-S, although the absolute number of ARG copies increased in BES-D effluents. Compared to those in BES-S and OC, more complex cross-niche microbial associations in the EB of BES-D were observed by network analysis of the bacterial community and ARG hosts, enhancing the degradation efficiency of SMX. In conclusion, BES-D has significant potential for SMX removal and the enhancement of EB activity. Nonetheless, the risk of ARG dissemination in effluent remains a concern., 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: Transcatheter arterial chemoembolization (TACE) combined with targeted therapy and immunotherapy can significantly improve the prognosis of patients with hepatocellular carcinoma (HCC). T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) is a novel immunosuppressive molecule. This study aimed to analyze the clinical correlation between TIGIT expression on T cells and patients with HCC., Methods: Clinical data from 140 patients with HCC were retrospectively collected, and TIGIT expression on T cells was examined in each patient. Patients were subsequently divided into high- and low-expression groups, and their prognosis was analyzed., Results: Patients with a high TIGIT expression on their T cells at baseline had a larger tumor volume, later staging, higher proportion of regulatory T cells, higher blood concentrations of interleukin (IL)-6 and IL-10, and lower interferon-γ concentrations. Following TACE, CD155 concentration decreased; however, TACE did not affect TIGIT expression on T cells. Additionally, among patients receiving TACE combined with apatinib and camrelizumab treatment, patients with a high TIGIT expression on T cells had significantly shorter progression-free survival (PFS) and overall survival times than those of patients in the low-expression group. Patients receiving TACE combined with apatinib and camrelizumab treatment with higher TIGIT expression have shorter PFS time than those receiving TACE combined with apatinib treatment., Conclusions: Patients with HCC that have a high TIGIT expression on their T cells exhibited poorer baseline characteristics, immunosuppressive status, and prognosis after receiving TACE combined with apatinib and camrelizumab and maybe more suited to receive TACE combined with apatinib treatment instead., (© 2024. The Author(s).)

Copper ions, implicated in processes such as oxidative stress and inflammation, are believed to play a crucial role in cardiovascular disease, a prevalent and deadly disease. Despite this, current diagnostic methods fail to detect early stage cardiovascular disease or track copper ion accumulation, limiting our understanding of the disease's progression. Therefore, the development of noninvasive techniques to image copper ions in cardiovascular disease is urgently needed to enhance diagnostic precision and therapeutic strategies. In this study, we report the successful synthesis and application of a copper ion-activated photoacoustic probe, CS-Cu , which exhibits high sensitivity and selectivity toward copper ions both in vitro and in vivo. CS-Cu was able to noninvasively monitor the changes in copper ion levels and differentiate between different mice based on copper ions in urine. Furthermore, the probe demonstrated good photoacoustic stability and exhibited no significant toxicity in the mice. These findings suggest that CS-Cu could be a promising tool for early detection and monitoring of Cu 2+ levels in vivo and urine, providing a new perspective on the role of copper ions in cardiovascular disease.

Ferrous ions (Fe 2 ⁺) accumulation and abnormal alterations in lipid droplets (LDs) are closely associated with ferroptosis. In the liver, excessive iron accumulation promotes oxidative stress and exacerbates lipid droplet accumulation, while the disruption of iron homeostasis may also affect the formation and size of lipid droplets, their increased number and size can exacerbate the severity of disease under fatty liver conditions. The leads to hepatocyte damage, further triggering liver inflammation, fibrosis, and ultimately resulting in cirrhosis and hepatocellular carcinoma. Therefore, real-time monitoring of iron ion and lipid droplet changes is crucial for assessing the severity of liver disease, disease progression, and understanding the mechanisms of ferroptosis. We have developed a fluorescent probe, NRFep, for real-time monitoring of iron ion fluctuations and visualization of lipid droplet changes in ferroptosis and liver disease models. NRFep is specific and sensitive to iron ions and exhibits excellent stability in both cells and animal models. In addition, NRFep can be used to monitor changes in iron ions and lipid droplets in mouse liver injury and fatty liver models. Through fluorescence lifetime imaging technology, NRFep can also study the dynamic changes of intracellular iron ion content. NRFep provides a powerful tool for studying ferroptosis and related diseases, and its unique dual-monitoring function opens up new possibilities for developing new diagnostic and therapeutic strategies., 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.)

Microbial degradation plays a crucial role in removing sulfonamides from soil, enhancing sulfamethoxazole (SMX) remediation. To further augment SMX removal efficiency and mitigate the transmission risk associated with antibiotic resistance genes (ARGs), this study proposes a novel approach that integrates micro-animals, microorganisms, and microbial fuel cell (MFC) technology. The results showed that earthworm-MFC synergy substantially reduces SMX content and ARGs abundance in soil. The introduction of earthworms enhances humus content, facilitating electron transfer within MFC and consequently improving current generation. Furthermore, electrical stimulation applied to earthworms led to increased protein secretion and enhanced antioxidant system activity, thereby accelerating SMX degradation. Earthworms also foster MFC-associated bacterial growth and SMX-degrading bacteria proliferation, augmenting MFC treatment efficacy. This synergistic effect significantly augmented the overall efficacy of MFC treatment for antibiotics. Overall, integrating earthworm activity with MFC technology effectively optimizes electricity generation and enhances pollutant removal., 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.)

Background and Objectives: Transarterial chemoembolization (TACE) and 125 I seed implantation are methods used to treat hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), PVTT often associated with arterioportal shunts(APS), there are few reports on the combined use of TACE and 125 I seed implantation for such patients. This study aimed to evaluate the efficacy and safety of TACE combined with PVTT 125 I seed implantation in the treatment of HCC patients with APS., Methods: Forty-two patients diagnosed with HCC combined with PVTT and APS between January 2020 and December 2021 were included. Appropriate materials were selected to transarterial embolization of the APS, and 125 I seeds were implanted into the PVTT. The occlusion effect was observed and recorded after 3 months, the efficacy of intrahepatic lesions and PVTT was evaluated, and the patient survival, prognostic factors affecting APS recanalization were analyzed., Results: All 42 patients completed the follow-up three months after treatment. The immediate APS improvement rate was 100%, and the APS improvement rate at the three-month follow-up was 64.29%. The disease control rates of PVTT and intrahepatic lesions were 81.00% and 78.60%, respectively. The patients' 6-month and 12-month survival rates were 78.6% and 46.8%. The median OS for all patients was 11.90 months, and the median OS was 13.30 months in the APS effective treatment group and 8.30 months in the ineffective group. The PVTT type is the only independent factor affecting APS recanalization. ( P =0.02)., Conclusion: For HCC patients with PVTT and APS, TACE combine with 125 I seed implantation in PVTT is a potentially effective and safe method that contributes to prolonging patient survival., 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., (© 2024 Xia et al.)

Purpose: This study aimed to evaluate the effectiveness and safety of iodine-125 brachytherapy as a treatment for right lower paratracheal lymph node metastasis following unsuccessful prior therapies., Methods: A retrospective review of patients who underwent iodine-125 brachytherapy for right lower paratracheal lymph node metastasis was conducted. The study included 24 patients who met the predefined criteria. Iodine-125 seeds were implanted under CT guidance, and treatment planning was performed using a treatment planning system. The primary endpoint was the objective response rate (ORR), while overall survival (OS) and complications were secondary endpoints., Results: The ORR was 87.5%, with 4 patients achieving complete response (CR) and 17 patients achieving partial response (PR). The mean diameter of metastatic lymph nodes significantly reduced from 40.21 ± 6.66 mm before treatment to 12.25 ± 9.27 mm at the last follow-up (p < 0.001). The median OS was 14.70 months, with 1-year and 2-year survival rates of 78.9% and 20.9%, respectively. Clinical symptoms significantly improved, as indicated by increased Karnofsky Performance Score (KPS) scores. Complications were manageable, with no procedure-related deaths., Conclusion: Iodine-125 brachytherapy demonstrated promising efficacy and safety as an alternative treatment for right lower paratracheal lymph node metastasis after unsuccessful prior therapies., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Apoptosis, as type I cell death, is an active death process strictly controlled by multiple genes, and plays a significant role in regulating various activities. Mounting research indicates that the unique modality of cell apoptosis is directly or indirectly related to different diseases including cancer, autoimmune diseases, viral diseases, neurodegenerative diseases, etc. However, the underlying mechanisms of cell apoptosis are complicated and not fully clarified yet, possibly due to the lack of effective chemical tools for the nondestructive and real-time visualization of apoptosis in complex biological systems. In the past 15 years, various small-molecule fluorescent probes (SMFPs) for imaging apoptosis in vitro and in vivo have attracted broad interest in related disease diagnostics and therapeutics. In this review, we aim to highlight the recent developments of SMFPs based on enzyme activity, plasma membranes, reactive oxygen species, reactive sulfur species, microenvironments and others during cell apoptosis. In particular, we generalize the mechanisms commonly used to design SMFPs for studying apoptosis. In addition, we discuss the limitations of reported probes, and emphasize the potential challenges and prospects in the future. We believe that this review will provide a comprehensive summary and challenging direction for the development of SMFPs in apoptosis related fields.

Introduction: The apolipoprotein E (APOE) ε4 allele exerts a significant influence on peripheral inflammation and neuroinflammation, yet the underlying mechanisms remain elusive., Methods: The present study enrolled 54 patients diagnosed with late-onset Alzheimer's disease (AD; including 28 APOE ε4 carriers and 26 non-carriers). Plasma inflammatory cytokine concentration was assessed, alongside bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs)., Results: Plasma tumor necrosis factor α, interferon γ, and interleukin (IL)-33 levels increased in the APOE ε4 carriers but IL-7 expression notably decreased. A negative correlation was observed between plasma IL-7 level and the hippocampal atrophy degree. Additionally, the expression of IL-7R and CD28 also decreased in PBMCs of APOE ε4 carriers. ScRNA-seq data results indicated that the changes were mainly related to the CD4+ Tem (effector memory) and CD8+ Tem T cells., Discussion: These findings shed light on the role of the downregulated IL-7/IL-7R pathway associated with the APOE ε4 allele in modulating neuroinflammation and hippocampal atrophy., Highlights: The apolipoprotein E (APOE) ε4 allele decreases plasma interleukin (IL)-7 and aggravates hippocampal atrophy in Alzheimer's disease. Plasma IL-7 level is negatively associated with the degree of hippocampal atrophy. The expression of IL-7R signaling decreased in peripheral blood mononuclear cells of APOE ε4 carriers Dysregulation of the IL-7/IL-7R signal pathways enriches T cells., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Calycosin (Caly), a flavonoid compound, demonstrates a variety of beneficial properties. However, the specific mechanisms behind Caly's anticancer effects remain largely unexplored. Network pharmacology was used to explore the potential targets of Caly in renal cancer. Additionally, RNA-seq sequencing was used to detect changes in genes in renal cancer cells after Caly treatment. Validation was carried out through quantitative reverse transcription-PCR and Western blot analysis. The luciferase reporter assay was applied to pinpoint the interaction site between MAZ and HAS2. Furthermore, the immunoprecipitation assay was utilized to examine the ubiquitination and degradation of MAZ. In vivo experiments using cell line-derived xenograft mouse models were performed to assess Calycosin's impact on cancer growth. Network pharmacology research suggests Caly plays a role in promoting apoptosis and inhibiting cell adhesion in renal cancer. In vitro, Caly has been observed to suppress proliferation, colony formation, and metastasis of renal cancer cells while also triggering apoptosis. Additionally, it appears to diminish hyaluronic acid synthesis by downregulating HAS2 expression. MAZ is identified as a transcriptional regulator of HAS2 expression. Calycosin further facilitates the degradation of MAZ via the ubiquitin-proteasome pathway. Notably, Caly demonstrates efficacy in reducing the growth of renal cell carcinoma xenograft tumors in vivo. Our findings indicate that Caly suppresses the proliferation, metastasis, and progression of renal cell carcinoma through its action on the MAZ/HAS2 signaling pathway. Thus, Caly represents a promising therapeutic candidate for the treatment of renal cell carcinoma., (© 2024 John Wiley & Sons, Ltd.)

This article discusses the importance of early tumor detection, particularly in liver cancer, and the role of leucine aminopeptidase (LAP) as a potential marker for liver cancer diagnosis and prognosis assessment. The article highlights the limitations of current tumor markers and the need for new markers and multi-marker approaches to improve accuracy. The authors introduce a novel near-infrared fluorescent probe, NTAP, designed for LAP detection. They describe the synthesis of the probe and evaluate its spectral properties, including the LOD was 0.0038 U/mL, and QY was 0.32 %. The kinetic properties of NTAP, such as the relationship between LAP concentration (0-0.08 U/mL), reaction time (3 min), and fluorescence excitation spectra (475 nm) and emission spectra (715 nm) are investigated. The article also discusses the stability and selectivity of the probe and its ability to detect LAP in complex samples. Cellular imaging experiments demonstrate the NATP specificity and selectivity in detecting LAP activity and its inhibition. Animal models of liver and lung metastasis are used to evaluate the probe's imaging capabilities, showing its ability to accurately locate and detect metastatic lesions. The article concludes by emphasizing the potential applications of the NTAP probe in early tumor diagnosis, treatment monitoring, and the study of tumor metastasis mechanisms., Competing Interests: Declaration of competing interest This work is financially supported by grants of the Postdoctoral Science Foundation of China (No. 2019M651781 and 2019TQ0142). There have no other business or economic disputes., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Focal adhesion kinase (FAK) is a cytoplasmic non-receptor tyrosine kinase over-expressed in various malignancies which is related to various cellular functions such as adhesion, metastasis and proliferation., Areas Covered: There is growing evidence that FAK is a promising therapeutic target for designing inhibitors by regulating the downstream pathways of FAK. Some potential FAK inhibitors have entered clinical phase research., Expert Opinion: FAK could be an effective target in medicinal chemistry research and there were a variety of FAKIs have been patented recently. Here, we updated an overview of design, synthesis and structure-activity relationship of chemotherapeutic FAK inhibitors (FAKIs) from 2017 until now based on our previous work. We hope our efforts can broaden the understanding of FAKIs and provide new ideas and insights for future cancer treatment from medicinal chemistry point of view.

The expression of metabotropic glutamate receptor 5 (mGluR5) is subject to developmental regulation and undergoes significant changes in neuropsychiatric disorders and diseases. Visualizing mGluR5 by fluorescence imaging is a highly desired innovative technology for biomedical applications. Nevertheless, there are substantial problems with the chemical probes that are presently accessible. In this study, we have successfully developed a two-photon fluorogenic probe, mGlu-5-TP, based on the structure of mGluR5 antagonist 6-methyl-2-(phenylethynyl)pyridine (MPEP). Due to this antagonist-based probe selectively recognizes mGluR5, high expression of mGluR5 on living SH-SY5Y human neuroblastoma cells has been detected during intracellular inflammation triggered by lipopolysaccharides (LPS). Of particular significance, the probe can be employed along with two-photon fluorescence microscopy to enable real-time visualization of the mGluR5 in Aβ fiber-treated neuronal cells, thereby establishing a connection to the progression of Alzheimer's disease (AD). These results revealed that the probe can be a valuable imaging tool for studying mGluR5-related diseases in the nervous system., 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.)

Cryptosporidium spp., Enterocytozoon bieneusi, and Giardia duodenalis are common intestinal pathogens that infect humans and animals. To date, research regarding these three protozoa in the Ningxia Hui Autonomous Region (Ningxia) has mostly been limited to a single pathogen, and comprehensive data on mixed infections are unavailable. This study aimed to evaluate the zoonotic potential of these three protozoa. In this study, small subunit ribosomal RNA (SSU rRNA) and 60 kDa glycoprotein (gp60) genes of Cryptosporidium; internal transcribed spacer (ITS) gene of E. bieneusi; and SSU rRNA, glutamate dehydrogenase (gdh), triosephosphate isomerase (tpi), and beta-giardin (bg) genes of G. duodenalis were examined. DNA extraction, polymerase chain reaction, and sequence analysis were performed on fecal samples collected from 320 dairy cattle at three intensive dairy farms in Ningxia in 2021 to determine the prevalence and genetic characteristics of these three protozoa. The findings revealed that 61.56% (197/320) of the samples were infected with at least one protozoan. The overall prevalence of Cryptosporidium was 19.38% (62/320), E. bieneusi was 41.56% (133/320), and G. duodenalis was 29.38% (94/320). This study identified four Cryptosporidium species (C. bovis, C. andersoni, C. ryanae, and C. parvum) and the presence of mixed infections with two or three Cryptosporidium species. C. bovis was the dominant species in this study, while the dominant C. parvum subtypes were IIdA15G1 and IIdA20G1. The genotypes of E. bieneusis were J, BEB4, and I alongside the novel genotypes NX1-NX8, all belonging to group 2, with genotype J being dominant. G. duodenalis assemblages were identified as assemblages E, A, and B, and a mixed infection involving assemblages A + E was identified, with assemblage E being the dominant one. Concurrently, 11 isolates formed 10 different assemblage E multilocus genotypes (MLGs) and 1 assemblage A MLG and assemblage E MLGs formed 5 subgroups. To the best of our knowledge, this is the first report on mixed infection with two or three Cryptosporidium species in cattle in Ningxia and on the presence of the C. parvum subtype IIdA20G1 in this part of China. This study also discovered nine genotypes of E. bieneusis and novel features of G. duodenalis assemblages in Ningxia. This study indicates that dairy cattle in this region may play a significant role in the zoonotic transmission of Cryptosporidium spp., E. bieneusi, and G. duodenalis., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Integrated MFC-MBR systems effectively remove antibiotics and control the release of antibiotic resistance genes (ARGs). However, the fouling layers on membranes can potentially act as reservoirs for ARGs. This study aims to elucidate the roles of membrane fouling layers and levels in influencing sulfamethoxazole (SMX) removal and ARGs control within an MFC-MBR system. Our findings demonstrate that low-intensity bioelectricity (400-500 mV) mitigates membrane fouling rates. The membrane fouling layer significantly contributes (39%-47%) to SMX removal compared to the cathode/anode zones. Higher extracellular polymeric substance (EPS) content and a lower protein/polysaccharide (PN/PS) ratio favor SMX removal by the membrane fouling layer. Across different levels of membrane fouling, the PN/PS ratio rather than EPS concentration plays a crucial role in SMX removal efficiency. The MFC-MBR with low fouling achieved superior SMX removal (69.1%) compared to medium (54.3%) and high fouling conditions (46.8%). The presence of ARGs in the membrane fouling layer increases with fouling formation, with intrinsic ARGs prevailing. Dense membrane fouling layers effectively retain ARGs, thereby reducing the risk of extracellular ARGs (eARGs) diffusion in effluents. These results provide insights into controlling ARGs in MFC-MBR systems and underscore the significant role of membrane fouling layers in antibiotics and ARGs removal., 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.)

Endocrine-resistant ER+HER2- breast cancer (BC) is particularly aggressive and leads to poor clinical outcomes. Effective therapeutic strategies against endocrine-resistant BC remain elusive. Here, analysis of the RNA-sequencing data from ER+HER2- BC patients receiving neoadjuvant endocrine therapy and spatial transcriptomics analysis both show the downregulation of innate immune signaling sensing cytosolic DNA, which primarily occurs in endocrine-resistant BC cells, not immune cells. Indeed, compared with endocrine-sensitive BC cells, the activity of sensing cytosolic DNA through the cGAS-STING pathway is attenuated in endocrine-resistant BC cells. Screening of kinase inhibitor library show that this effect is mainly mediated by hyperactivation of AKT1 kinase, which binds to kinase domain of TBK1, preventing the formation of a trimeric complex TBK1/STING/IRF3. Notably, inactivation of cGAS-STING signaling forms a positive feedback loop with hyperactivated AKT1 to promote endocrine resistance, which is physiologically important and clinically relevant in patients with ER+HER2- BC. Blocking the positive feedback loop using the combination of an AKT1 inhibitor with a STING agonist results in the engagement of innate and adaptive immune signaling and impairs the growth of endocrine-resistant tumors in humanized mice models, providing a potential strategy for treating patients with endocrine-resistant BC., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: The combination of transcatheter arterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs) has shown broad prospects in prolonging the survival of patients with hepatocellular carcinoma (HCC). TACE and TKIs can affect the immune microenvironment in patients with HCC., Aim: To determine the overall effects and differences between TACE and different TKIs combinations on the immune microenvironment., Methods: Data and immune cell profile test results from 213 HCC patients treated with TACE combined with apatinib, lenvatinib, sorafenib, or donafenib before and after 3 wk of treatment were collected. Monocytes were co-cultured with LM3 liver cancer cells, and their ability to inhibit cancer cell growth was analyzed using the MTT method and a nude mouse subcutaneous tumorigenesis experiment. Simulated combined therapy was done using an in situ liver cancer C57BL/6 male mouse model, and the immune response of tumor tissues was analyzed using immunohistochemistry., Results: Compared to before combination therapy, the proportion of programmed cell death protein 1 (PD-1)+ mononuclear cells and the number of CD4+ T cells decreased in the TACE + apatinib group, while the number of absolute count of CD4+ and CD8+ T cells increased in the TACE + lenvatinib group. Furthermore, the number of regulatory cells decreased in the TACE + donafenib group, whereas the number of CD8+ T and natural killer cells increased. Additionally, monocytes in the TACE combined with donafenib or lenvatinib groups had a stronger ability to inhibit cancer cell growth than those in the other groups. Combining TACE with donafenib or lenvatinib increased CD8+ T cell infiltration into the tumor tissue. In addition, the proportion of PD-1+ in CD8+ cells, absolute CD8+ T lymphocyte count, and regulatory T cells proportion were independent prognostic factors affecting the survival time of patients with HCC., Conclusion: TACE, in combination with different TKIs, produces different immune responses. Specifically, TACE combined with donafenib or lenvatinib may induce strong anti-tumor immune responses., 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 incidence of pneumothorax is higher in patients with emphysema who undergo percutaneous lung biopsy. Needle embolization has been shown to reduce the incidence of pneumothorax in patients with emphysema. Existing studies have reported small sample sizes of patients with emphysema, or the degree of emphysema has not been graded. Therefore, the efficacy of biopsy embolization in the prevention of pneumothorax induced by percutaneous pulmonary biopsy in patients with emphysema remains to be determined., Methods: In this retrospective, controlled study, patients with emphysema who underwent CT-guided PTLB were divided into two groups: group A (n = 523), without tract embolization, and Group B (n = 504), with tract embolization. Clinical and imaging features were collected from electronic medical records and Picture Archiving and Communication Systems. Univariate and multivariate analyses were performed to identify risk factors for pneumothorax and chest tube placement., Results: The two groups did not differ significantly in terms of demographic characteristics and complications other than pneumothorax. The incidence of pneumothorax and chest tube placement in group B was significantly lower than in group A (20.36% vs. 46.12%, p < 0.001; 3.95% vs. 9.18%, p < 0.001, respectively). In logistic regression analyses, variables affecting the incidence of pneumothorax and chest tube placement were the length of puncture of the lung parenchyma (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.07-1.30, p = 0.001; OR = 1.55, 95% CI: 1.30-1.85, p < 0.001, respectively), tract embolization (OR = 0.31, 95% CI: 0.24-0.41, p < 0.001; OR = 0.39, 95% CI: 0.22-0.69, p = 0.001, respectively), and grade of emphysema., Conclusions: Tract embolization with gelatin sponge particles after CT-guided PTLB significantly reduced the incidence of pneumothorax and chest tube placement in patients with emphysema. Tract embolization, length of puncture of the lung parenchyma, and grade of emphysema were independent risk factors for pneumothorax and chest tube placement., Trial Registration: Retrospectively registered., (© 2024. The Author(s).)

The achievement of covalent organic frameworks (COFs) with high stability and exceptional proton conductivity is of tremendous practical importance and challenge. Given this, we hope to prepare the highly stable COFs carrying CN connectors and enhance their proton conductivity via a post-modification approach. Herein, one COF, TpTta, was successfully synthesized by employing 1,3,5-triformylphloroglucinol (Tp) and 4,4',4″-(1,3,5-triazine-2,4,6-triyl)-trianiline (Tta) as starting materials, which has a β-ketoenamine structure bearing a large amount of -NH groups and intramolecular H-bonds. TpTta was then post-modified by inserting imidazole (Im) and histamine (His) molecules, yielding the corresponding COFs, Im@TpTta and His@TpTta, respectively. As a result, their proton conductivities were surveyed under changeable temperatures (30-100 °C) and relative humidities (68-98 %), revealing a degree of temperature and humidity dependence. Impressively, under identical conditions, the optimum proton conductivities of the two post-modified COFs are 1.14 × 10 -2 (Im@TpTta) and 3.45 × 10 -3 S/cm (His@TpTta), which are significantly greater than that of the pristine COF, TpTta (2.57 × 10 -5 S/cm). Finally, their proton conduction mechanisms were hypothesized based on the computed activation energy values, water vapor adsorption values, and structural properties of these COFs. Additionally, the excellent electrochemical stability of the produced COFs was expressed, as well as the prospective application value., 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.)

Acute lung injury (ALI) is a serious pulmonary inflammatory disease resulting from excessive reactive oxygen species (ROS) which could cause the damage of the alveolar epithelial cells and capillary endothelial cells. Peroxynitrite, as one of short-lived reactive oxygen species, is closely related to the process of ALI. Thus, it is important to monitor the fluctuation of peroxynitrite in living system for understanding the process of ALI. Herein, the novel mitochondria-targeted fluorescent probe BHMT was designed to respond to peroxynitrite and pH with distinct fluorescence properties respectively. The absorption spectrum of the probe BHMT exhibited a notable red shift as the pH value declined from 8.8 to 2.6. Upon reaction with peroxynitrite, BHMT had a significant increase of fluorescence intensity (63-fold) with maintaining a detection limit of only 43.7 nM. Furthermore, BHMT could detect the levels of endogenous peroxynitrite and image the intracellular pH in ratiometric channels utilizing cell imaging. In addition, BHMT was successfully applied to revealing the relationship between the peroxynitrite and the extent of ALI. Thus, these results indicated the probe BHMT could be a potential tool for diagnosing the early stage of ALI and revealed the peroxynitrite was likely to be a crucial therapeutic target in ALI treatment., 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.)

γ-Glutamyltranspeptidase (γ-GGT), as a key enzyme, exhibits markedly higher expression levels in tumor cells compared to normal cells. Under normal conditions, γ-GGT activity on the cell membrane is relatively low, but it undergoes a significant upregulation in cancer cells, making it a potential cancer biomarker. Particularly in A549 cells, a prominent cancer cell line, the pronounced upregulation of γ-GGT expression emphasizes its potential as a unique recognition target and a robust marker for A549 cells. This study successfully synthesized a highly selective γ-GGT fluorescent probe, the exhibits commendable sensitivity (LOD = 0.0021U/mL) and selectivity, achieving efficient detection at the cellular level and providing accurate insights into differential expression between normal and cancer cells. The alterations in fluorescence lifetime observed before and after the probe's reaction with γ-GGT serve as a crucial foundation for fluorescence lifetime imaging on living cells. The probe has become a powerful tool for precise localization of tumor cells, particularly demonstrating its capability for specific recognition in A549 cells. Overall, this research highlights the potential of γ-GGT as a target for fluorescent probes, emphasizing its prospects in specific recognition, particularly in A549 cells, with profound implications for advancing early cancer diagnosis and treatment methods., 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.)

This study investigated the effects of different external circuit loading mode on pollutants removal and power generation in microbial fuel cells (MFC). The results indicated that MFC exhibited distinct characteristics of higher maximum power density (P max ) (named MFC-HP) and lower P max (named MFC-LP). And the capacitive properties of bioanodes may affect anodic electrochemistry. Reducing external load to align with the internal resistance increased P max of MFC-LP by 54.47 %, without no obvious effect on MFC-HP. However, intermittent external resistance loading (IER) mitigated the biotoxic effects of sulfamethoxazole (SMX) (a persistent organic pollutant) on chemical oxygen demand (COD) and NH 4 + -N removal and maintained high P max (424.33 mW/m 2 ) in MFC-HP. Meanwhile, IER mode enriched electrochemically active bacteria (EAB) and environmental adaptive bacteria Advenella, which may reduce antibiotic resistance genes (ARGs) accumulation. This study suggested that the external circuit control can be effective means to regulate electrochemical characteristics and pollutants removal performance of MFC., 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.)

Hepatocellular carcinoma (HCC) seriously threatens the human health. Previous investigations revealed that γ-glutamyltranspeptidase (GGT) was tightly associated with the chronic injury, hepatic fibrosis, and the development of HCC, therefore might act as a potential indicator for monitoring the HCC-related processes. Herein, with the contribution of a structurally optimized probe ETYZE-GGT, the bimodal imaging in both far red fluorescence (FL) and photoacoustic (PA) modes has been achieved in multiple HCC-related models. To our knowledge, this work covered the most comprehensive models including the fibrosis and developed HCC processes as well as the premonitory induction stages (autoimmune hepatitis, drug-induced liver injury, non-alcoholic fatty liver disease). ETYZE-GGT exhibited steady and practical monitoring performances on reporting the HCC stages via visualizing the GGT dynamics. The two modes exhibited working consistency and complementarity with high spatial resolution, precise apparatus and desirable biocompatibility. In cooperation with the existing techniques including testing serum indexes and conducting pathological staining, ETYZE-GGT basically realized the universal application for the accurate pre-clinical diagnosis of as many HCC stages as possible. By deeply exploring the mechanically correlation between GGT and the HCC process, especially during the premonitory induction stages, we may further raise the efficacy for the early diagnosis and treatment of HCC., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Acral persistent papular mucinosis (APPM) is a rare idiopathic subtype of localized lichen myxedematosus. To date, there have been less than 41 APPM cases reported worldwide, however, almost all patients were older than 18 years of age. A 7-year-old child was first reported in this paper., Case Description: A 7-year-old boy was admitted to our hospital with a solitary skin-colored papule on the radial side of the middle segment of his right index finger. The patient wanted to know the exact diagnosis and remove it because the flexion movement of the middle segment had been affected. Thus, a surgery was performed. Histopathological examination of a biopsy specimen obtained from the papule on the radial side of the middle segment of his right index finger showed a focal and well-circumscribed deposit of mucin in the papillary and middermis. The deposit never extended deeply into the reticular dermis. Mucin spared a subepidermal area in the papillary dermis. Alcian blue stains can highlight the mucin. The papule was histologically diagnosed as an APPM and excised surgically. The wound gradually healed after the operation, and no obvious recurrence, scar or other discomfort was observed during follow-up so far., Conclusions: To the best of our knowledge, this is the rare case of a child APPM presenting as a solitary papule affecting the flexion movement of the middle segment. Since it is a rare disease, we report this case to contribute to future research on the diagnosis and pathogenesis of APPM., 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-23-607/coif). The authors have no conflicts of interest to declare., (2024 Translational Pediatrics. All rights reserved.)

Targeting ferroptosis for cancer therapy has slowed because of an incomplete understanding of ferroptosis mechanisms under specific pathological contexts such as tumorigenesis and cancer treatment. Here, we identify TRPML1-mediated lysosomal exocytosis as a potential anti-ferroptotic process through genome-wide CRISPR-Cas9 activation and kinase inhibitor library screening. AKT directly phosphorylated TRPML1 at Ser 343 and inhibited K552 ubiquitination and proteasome degradation of TRPML1, thereby promoting TRPML1 binding to ARL8B to trigger lysosomal exocytosis. This boosted ferroptosis defense of AKT-hyperactivated cancer cells by reducing intracellular ferrous iron and enhancing membrane repair. Correlation analysis and functional analysis revealed that TRPML1-mediated ferroptosis resistance is a previously unrecognized feature of AKT-hyperactivated cancers and is necessary for AKT-driven tumorigenesis and cancer therapeutic resistance. TRPML1 inactivation or blockade of the interaction between TRPML1 and ARL8B inhibited AKT-driven tumorigenesis and cancer therapeutic resistance in vitro and in vivo by promoting ferroptosis. A synthetic peptide targeting TRPML1 inhibited AKT-driven tumorigenesis and enhanced the sensitivity of AKT-hyperactivated tumors to ferroptosis inducers, radiotherapy, and immunotherapy by boosting ferroptosis in vivo. Together, our findings identified TRPML1 as a therapeutic target in AKT-hyperactivated cancer.

To date, developing crystalline proton-conductive metal-organic frameworks (MOFs) with an inherent excellent proton-conducting ability and structural stability has been a critical priority in addressing the technologies required for sustainable development and energy storage. Bearing this in mind, a multifunctional organic ligand, 3,4-dimethylthiophene[2,3- b ]thiophene-2,5-dicarboxylic acid (H 2 DTD), was employed to generate two exceptionally stable three-dimensional porous Zr/Hf MOFs, [Zr 6 O 4 (OH) 4 (DTD) 6 ]·5DMF·H 2 O ( Zr-DTD ) and [Hf 6 O 4 (OH) 4 (DTD) 6 ]·4DMF·H 2 O (Hf-DTD ), using solvothermal means. The presence of Zr 6 or Hf 6 nodes, strong Zr/Hf-O bonds, the electrical influence of the methyl group, and the steric effect of the thiophene unit all contribute to their structural stability throughout a wide pH range as well as in water. Their proton conductivity was fully examined at various relative humidities (RHs) and temperatures. Creating intricate and rich H-bonded networks between the guest water molecules, coordination solvent molecules, thiophene-S, -COOH, and -OH units within the framework assisted proton transfer. As a result, both MOFs manifest the maximum proton conductivity of 0.67 × 10 -2 and 4.85 × 10 -3 S·cm -1 under 98% RH/100 °C, making them the top-performing proton-conductive Zr/Hf-MOFs. Finally, by combining structural characteristics and activation energies, potential proton conduction pathways for the two MOFs were identified.

Antibiotic resistance genes (ARGs) have been steadily increasing due to the extensive overuse of antibiotics in the marine environment. Currently, the research considering ARGs distribution in marine ecosystems gains more interest. As the coastal sea has been regarded as one of the most polluted areas by antibiotic contaminants in China. However, no comprehensive review of the spatial distribution of ARGs in marine environment surrounding China. The main objective of this review is to investigate the level, characteristic, and spatial distribution of ARGs in the marine environment (seawater and sediments) surrounding China. Key sea areas, such as Bohai Sea, Yellow Sea, East China Sea, and South China Sea were selected in this review. The marine environment was the reservoir of ARGs, and ARGs in seawater were generally 1 to 2 orders of magnitude higher than that in sediments. Total ARGs were more abundant in the Yellow Sea, followed by the Bohai Sea, the East China Sea, and the South China Sea. This study raises questions regarding the spread and distribution for antibiotic resistance in marine environments., Competing Interests: Declaration of competing interest The authors declare that they have no competing., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Glioblastoma is the most fatal and insidious malignancy, due to the existence of the blood-brain barrier (BBB) and the high invasiveness of tumor cells. Abnormal mitochondrial viscosity has been identified as a key feature of malignancies. Therefore, this study reports on a novel fluorescent probe for mitochondrial viscosity, called ZVGQ, which is based on the twisted intramolecular charge transfer (TICT) effect. The probe uses 3-dicyanomethyl-1,5,5-trimethylcyclohexene as an electron donor moiety and molecular rotor, and triphenylphosphine (TPP) cation as an electron acceptor and mitochondrial targeting group. ZVGQ is highly selective, pH and time stable, and exhibits rapid viscosity responsiveness. In vitro experiments showed that ZVGQ could rapidly recognize to detect the changes in mitochondrial viscosity induced by nystatin and rotenone in U87MG cells and enable long-term imaging for up to 12 h in live U87MG cells. Additionally, in vitro 3D tumor spheres and in vivo orthotopic tumor-bearing models demonstrated that the probe ZVGQ exhibited exceptional tissue penetration depth and the ability to penetrate the BBB. The probe ZVGQ not only successfully visualizes abnormal mitochondrial viscosity changes, but also provides a practical and feasible tool for real-time imaging and clinical diagnosis of glioblastoma.

Hydrogen sulfide (H 2 S), a critical gas signaling molecule, and N -acetyltransferase 2 (NAT2), a key enzyme in drug metabolism, are both known active biomarkers for liver function. However, the interactions and effects of H 2 S and NAT2 in living cells or lesion sites remain unknown due to the lack of imaging tools to achieve simultaneous detection of these two substances, making it challenging to implement real-time imaging and precise tracking. Herein, we report an activity-based two-photon fluorescent probe, TPSP-1 , for the cascade detection of H 2 S and NAT2 in living liver cells. Continuous conversion from TPSP-1 to TPSP-3 was achieved in liver cells and tissues. Significantly, leveraging the outstanding optical properties of this two-photon fluorescent probe, TPSP-1 , has been effectively used to identify pathological tissue samples directly from clinical liver cancer patients. This work provides us with this novel sensing and two-photon imaging probe, which can be used as a powerful tool to study the physiological functions of H 2 S and NAT2 and will help facilitate rapid and accurate diagnosis and therapeutic evaluation of hepatocellular carcinoma.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC., Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821., Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group., Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile., Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project., Competing Interests: We declare no competing interests., (© 2024 Published by Elsevier Ltd.)

Breast cancer lung metastases (BCLM) are a major cause of high mortality in patients. The shortage of therapeutic targets and rapid drug screening tools for BCLM is a major challenge at present. Mitochondrial autophagy, which involves the degradation of proteins associated with cancer cell aggressiveness, represents a possible therapeutic approach for the treatment of BCLM. Herein, four fluorescent biosensors with different alkyl chains were designed and synthesized to monitor mitochondrial autophagy. Among them, PMV-12 demonstrated the highest sensitivity to viscosity variance, the least impact on polarity, and the longest imaging time. The introduction of the C 12 -chain made PMV-12 anchored in the mitochondrial membrane without being disturbed by changes of the mitochondrial membrane potential (MMP), thereby achieving the long-term monitor in situ for mitochondrial autophagy. Mitochondria stained with PMV-12 induced swelling and viscosity increase after treating with apigenin, which indicated that apigenin is a potential mitochondrial autophagy inducer. Apigenin was subsequently verified to inhibit cancer cell invasion by 92%. Furthermore, PMV-12 could monitor the process of BCLM in vivo and evaluate the therapeutic effects of apigenin. This work provides a fluorescent tool for elucidating the role of mitochondrial autophagy in the BCLM process and for anti-metastatic drug development., 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.)

A brand-new procedure for the synthesis of 3-alkynylated 3,3-disubstituted isoindolinones has been disclosed via a HOTf or Fe(OTf) 3 -catalyzed dehydrative alkynylation of 3-hydroxyisoindolinones with terminal alkynes. Aryl, alkenyl and alkyl terminal alkynes are suitable to couple with a broad range of 3-hydroxyisoindolinones to afford the desired products in moderate to good yields. This protocol features the use of an inexpensive catalyst, mild reaction conditions, broad substrate scope and easy elaboration of the products.

Hypoxia, a significant feature of the tumor microenvironment, is closely associated with tumor growth, metastasis, and drug resistance. In the field of tumor microenvironment analysis, accurately imaging and quantifying hypoxia - a critical factor associated with tumor progression, metastasis, and resistance to therapy - remains a significant challenge. Herein, a hypoxia-activated red-emission fluorescent probe, ODP, for in vivo imaging of hypoxia in the tumor microenvironment is presented. Among various imaging methods, optical imaging is particularly convenient due to its rapid response and high sensitivity. The ODP probe specifically targets nitroreductase (AzoR), an enzyme highly expressed in hypoxic cells, playing a vital role by catalyzing the cleavage of azo bonds. The optical properties of ODP exhibited excellent performance in terms of fluorescence enhancement, fluorescence lifetime (0.81 ns), and detection limit (0.86 µM) in response to SDT. Cell imaging experiments showed that ODP could effectively detect and image intracellular hypoxia and the imaging capability of ODP was studied under various conditions including cell migration, antioxidant treatment, and different incubation times. Through comprehensive in vitro and in vivo experiments, including cellular imaging and mouse tumor models, this work demonstrates the efficacy of ODP in accurately detecting and imaging hypoxia. Moreover, ODP's potential in inducing apoptosis in cancer cells offers a promising avenue for integrating diagnostic and therapeutic strategies in cancer treatment. This innovative approach not only contributes to the understanding and assessment of tumor hypoxia but also opens new possibilities for targeted cancer therapy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Urease is the main virulence factor of infectious gastritis and gastric ulcers. Urease inhibitors are regarded as the first choice for the treatment of such diseases. Based on the triazolone/oxadiazolone skeleton, a urea-like fragment being able to specifically bind the urease activity pocket and prevent urea from hydrolysis, we designed and synthesized 45 triazolones/oxadiazolones as urease inhibitors. Eight compounds were proved to show excellent inhibitory activity against Helicobacter pylori urease, being more potency than the clinically used urease inhibitor acetohydroxamic acid. The most active inhibitor with IC 50 value of 1.2 μM was over 20-fold higher potent than the positive control. Enzymatic kinetic assays showed that these novel inhibitors reversibly inhibited urease with a mixed competitive mechanism. Molecular dockings provided evidence for the observations in enzyme assays. Furthermore, these novel inhibitors were proved as drug-like compounds with very low cytotoxicity to mammalian cells and favorable water solubility. These results suggested that triazolone and oxadiazolone were promising scaffolds for the design and discovery of novel urease inhibitors, and were expected as good candidates for further drug development., 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.)

In this work, we reported a fluorescent probe Fur-SH, a derivative of benzofuranone, which was used to detect H 2 S in living cells and zebrafish. Based on the three structural characteristics of the probe, the effects of different structural modifications on the optical properties of the fluorophore were compared. Then, the fluorophore Fur-OH was synthesized by modifying diethylamino group with benzofuranone as the main skeleton. With 2,4-dinitrofluorobenzene as the recognition group and diethylamino as the electron donor, the push-pull electron effect occurred with nitro group, which led to fluorescence quenching, and an openable fluorescent probe Fur-SH was formed. The probe Fur-SH (λ ex  = 510 nm; λ em  = 570 nm) had the advantages of smaller full width at half maxima, rapid response (5 min) and wide pH window. The quantitative properties of the probe were excellent, reaching saturation at 50 equivalents of substrate. The probe Fur-SH showed high sensitivity to H 2 S, with LOD of 48.9 nM and LOQ of 50 nM. At present, the probe Fur-SH had been applied to fluorescence imaging of MCF-7 cells and zebrafish. By comparing the effects of different structures on the optical properties of fluorophores, this work was expected to be helpful to the development of fluorescent probes in the future., 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. Published by Elsevier B.V.)

Indium-based metal-organic frameworks (In-MOFs) have now become an attractive class of porous solids in materials science and electrochemistry due to their diverse structures and promising applications. In the field of proton conduction, to find more crystalline MOFs with splendid proton-conductive properties, herein, five three-dimensional isostructural In-MOFs, MIL-68-In or MIL-68-In-X (X = NH 2 , OH, Br, or NO 2 ) using terephthalic acid (H 2 BDC) or functionalized terephthalic acids (H 2 BDC-X) as multifunctional linkages were efficiently fabricated. First, the outstanding structural stability of the five MOFs, including thermal and water stability, was verified by thermal analysis and powder X-ray diffraction. Subsequently, the H 2 O-mediated proton conductivities (σ) were fully assessed and compared. Notably, their σ evinced a significant positive correlation between the temperature or relative humidity (RH) and varied with the functional groups on the organic ligands. Impressively, their highest σ values are up to 10 -3 -10 -4 S/cm (100 °C/98% RH) and change in this order: MIL-68-In-OH (1.72 × 10 -3 S/cm) > MIL-68-In-NH 2 (1.70 × 10 -3 S/cm) > MIL-68-In-NO 2 (4.47 × 10 -4 S/cm) > MIL-68-In-Br (4.11 × 10 -4 S/cm) > MIL-68-In (2.37 × 10 -4 S/cm). Finally, the computed activation energy values under 98 or 68% RHs are assessed, and the related proton conduction mechanisms are speculated. Moreover, after electrochemical testing, these MOFs illustrate remarkable structural rigidity, laying a meritorious material foundation for future applications.

Purpose: While the role of drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) is established, questions regarding appropriate bead size for use in patients remain. This trial evaluated the effectiveness and safety of DEB-TACE using small-size (≤ 100 μm) microspheres loaded with epirubicin., Materials and Methods: This prospective, single-arm, multicenter study enrolled patients diagnosed with HCC who underwent DEB-TACE using 40 (range, 30-50), 75 (range, 60-90), or 100 (range, 75-125) μm epirubicin-loaded microspheres (TANDEM microspheres, Varian Medical). Bead size was at the discretion of treating physicians and based on tumor size and/or vascular structure. The primary outcome measure was 6-month objective response rate (ORR). Secondary outcome measures were 30-day and 3-month ORR, time to tumor progression and extrahepatic spread, proportion of progression-free survival and overall survival (OS) at one year, and incidence of treatment-associated adverse events., Results: Data from 108 patients from ten centers was analyzed. Six-month ORR was 73.3 and 71.3% based on European association for the study of the liver (EASL) and modified response evaluation criteria in solid tumors (mRECIST) criteria, respectively. Thirty-day ORR was 79.6% for both EASL and mRECIST criteria with 3-month ORR being 80.0 and 81.0%, respectively, for each criteria. One-year PPF and OS rate were 60.3 and 94.3%. There was a total of 30 SAEs reported to be likely to definitely associated with microsphere (n = 9), epirubicin (n = 9), or procedure (n = 12) with none resulting in death., Conclusion: DEB-TACE using epirubicin-loaded small-sized (≤ 100 μm) microspheres demonstrates promising local tumor control and acceptable safety in patients with HCC., Trial Registration: Clinicaltrials.gov NCT03113955; registered April 14, 2017. Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017., Level of Evidence: 2, Prospective, Non-randomized, Single-arm, study., (© 2024. The Author(s).)

Background: Human herpesvirus-6 is a rare infection in an immunocompetent adult. In existing literature, there is a dearth of knowledge that mainly exists as case reports and case series., Case Presentation: In this case report, we described a 29-year-old female of Myanmarese descent patient from Myanmar who presented with altered mental status and non-specific respiratory and gastrointestinal symptoms. She was initially treated for pneumonia and discharged well. However, she re-presented to the hospital and was subsequently treated for severe central nervous system infection. Cerebrospinal fluid studies detected human herpesvirus-6 polymerase chain reaction with associated high serum human herpesvirus-6 concentration. This infection also triggered hemophagocytic lymphohistiocytosis. Treatment was initiated against both human herpesvirus-6 infection and hemophagocytic lymphohistiocytosis, and she responded to antiviral treatment and steroids, respectively., Conclusion: This case study highlights the need for prompt diagnosis and treatment of this severe disease and the dangerous complications. Additionally, the authors share insights on the diagnostic challenges faced in the treatment of this patient., (© 2024. The Author(s).)

Objective: Surface-guided radiation therapy (SGRT, AlignRT) was used to analyze motion during stereotactic body radiotherapy (SBRT) in lung cancer patients and to explore the margin of the planning target volume (PTV)., Methods: The residual errors of the AlignRT were evaluated based on grayscale cone-beam computed tomography registration results before each treatment. AlignRT log file was used to analyze the correlation between the frequency and longest duration of errors larger than 2 mm and lasting longer than 2 s and maximum error with age and treatment duration. The displacement value at the end of treatment, the average displacement value, and the 95% probability density displacement interval were defined as intrafraction errors, and PTV1, PTV2, PTV3 were calculated by Van Herk formula or Z score analysis. Organ dosimetric differences were compared after the experience-based margin was replaced with PTV3., Results: The interfraction residual errors were Vrt 0 , 0.06 ± 0.18 cm; Lng 0 , -0.03 ± 0.19 cm; Lat 0 , 0.02 ± 0.15 cm; Pitch 0 , 0.23 ± 0.7°; Roll 0 , 0.1 ± 0.69°; Rtn 0 , -0.02 ± 0.79°. The frequency, longest duration and maximum error in vertical direction were correlated with treatment duration (r = 0.404, 0.353, 0.283, p < 0.05, respectively). In the longitudinal direction, the frequency was correlated with age and treatment duration (r = 0.376, 0.283, p < 0.05, respectively), maximum error was correlated with age (r = 0.4, P < 0.05). Vertical, longitudinal, lateral margins of PTV1, PTV2, PTV3 were 2 mm, 4 mm, 2 mm; 2 mm, 2 mm, 2 mm, 3 mm, 5 mm, 3 mm, respectively. After replacing the original PTV, mean lung dose (MLD), 2-cm 3 chest wall dose (CD), lung V 20 decreased by 0.2 Gy, 2.1 Gy, 0.5%, respectively (p < 0.05)., Conclusion: AlignRT can be used for interfraction setup and monitoring intrafraction motion. It is more reasonable to use upper and lower limits of the 95% probability density interval as an intrafraction error., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Biochar is a carbon-neutral tool for combating climate change. Artificial intelligence applications to estimate the biochar mitigation effect on greenhouse gases (GHGs) can assist scientists in making more informed solutions. However, there is also evidence indicating that biochar promotes, rather than reduces, N 2 O emissions. Thus, the effect of biochar on N 2 O remains uncertain in constructed wetlands (CWs), and there is not a characterization metric for this effect, which increases the difficulty and inaccuracy of biochar-driven alleviation effect projections. Here, we provide new insight by utilizing machine learning-based, tree-structured Parzen Estimator (TPE) optimization assisted by a meta-analysis to estimate the potency of biochar-driven N 2 O mitigation. We first synthesized datasets that contained 80 studies on global biochar-amended CWs. The mitigation effect size was then calculated and further introduced as a new metric. TPE optimization was then applied to automatically tune the hyperparameters of the built extreme gradient boosting (XGBoost) and random forest (RF), and the optimum TPE-XGBoost obtained adequately achieved a satisfactory prediction accuracy for N 2 O flux (R 2  = 91.90%, RPD = 3.57) and the effect size (R 2  = 92.61%, RPD = 3.59). Results indicated that a high influent chemical oxygen demand/total nitrogen (COD/TN) ratio and the COD removal efficiency interpreted by the Shapley value significantly enhanced the effect size contribution. COD/TN ratio made the most and the second greatest positive contributions among 22 input variables to N 2 O flux and to the effect size that were up to 18% and 14%, respectively. By combining with a structural equation model analysis, NH 4 + -N removal rate had significant negative direct effects on the N 2 O flux. This study implied that the application of granulated biochar derived from C-rich feedstocks would maximize the net climate benefit of N 2 O mitigation driven by biochar for future biochar-based CWs., 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.)

The semipinacol rearrangement is a powerful and versatile method for constructing all-carbon quaternary stereocenters. The development of catalytic asymmetric semipinacol rearrangements using multifunctionalizable electrophiles remains highly sought-after in organic synthesis. In this study, a catalytic enantioselective allylic cation-induced semipinacol rearrangement reaction was presented that enables the simultaneous construction of two skipped chiral carbon centers. Chiral Ir(I)-(P,olefin) and Sc(OTf) 3 catalysts cooperatively initiate the asymmetric allylic alkylation of alkenyl cyclobutanols with allylic alcohols, triggering ring expansion of the cyclobutanol moiety through a stereoselective 1,2-alkyl migration. The reaction afforded a range of cyclopentanones bearing an α-quaternary carbon that is adjacent to a chiral allyl scaffold. The products were applied to synthesize enantioenriched fused tricyclopentanoids bearing four stereogenic carbon centers.

Purpose: The incidence of gastroparesis is higher in individuals diagnosed with type 2 diabetes mellitus (T2DM) compared to the healthy individuals. Our study aimed to explore the risk factors for gastroparesis in T2DM and to establish a clinical prediction model (nomogram)., Methods: Our study enlisted 694 patients with T2DM from two medical centers over a period of time. From January 2020 to December 2022, 347 and 149 patients were recruited from the Beilun branch of Zhejiang University's First Affiliated Hospital in the training and internal validation cohorts, respectively. The external validation cohort consisted of 198 patients who were enrolled at Nanchang University's First Affiliated Hospital from October 2020 to September 2021. We conducted univariate and multivariate logistic regression analyses to select the risk factors for gastroparesis in patients with T2DM; subsequently,we developed a nomogram model. The performance of the nomogram was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), calibration curve, and decision curve analysis(DCA)., Results: Four clinical variables, including age, regular exercise, glycated hemoglobin level(HbA1c), and Helicobacter pylori ( H. pylori ) infection, were identified and included in the model. The model demonstrated excellent discrimination, with an AUC of 0.951 (95% CI = 0.925-0.978) in the training group, and 0.910 (95% CI = 0.859-0.961) and 0.875 (95% CI = 0.813-0.937) in the internal and external validation groups, respectively. The calibration curve showed good consistency between prediction of the model and observed gastroparesis. The DCA also demonstrated good clinical efficacy., Conclusion: The nomogram model developed in this study showed good performance in predicting gastroparesis in patients with T2DM., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

In this work, a fluorescent probe, TPABF-HS, was developed for detecting hydrogen sulfide (H 2 S) using a human serum albumin (HSA)-binding-based approach for amplifying the fluorescence signal and extending the linear correlation range. Compared to the most recent probes for H 2 S, the most interesting feature of the detection system developed herein was the especially wide linear range (0-1000 μM (0-100 eq.)), which covered the physiological and pathological levels of H 2 S. TPABF-HS could be used in applications high sensitivity and selectivity with an LOD value of 0.42 μM. Further, site-competition experiments and molecular docking simulation experiments indicated that signal amplification was realized by the binding of the TPABF fluorophore to the naproxen-binding site of HSA. Moreover, the extension of the measurement span could allow for applications in living cells and Caenorhabditis elegans for imaging both exogenous and endogenous H 2 S. This work brings new information to the strategy of signal processing by exploiting fluorescent probes.

Lipid metabolism diseases have become a tremendous risk worldwide, along with the development of productivity and particular attention to public health. It has been an urgent necessity to exploit reliable imaging strategies for lipids and thus to monitor fatty liver diseases. Herein, by converting the NIR-I signal to the NIR-II signal with IR1061 for the monitoring of lipid, the in vivo imaging of fatty liver disease was promoted on the contrast and visual effect. The main advantages of the imaging promotion in this work included a long emission wavelength, rapid response, and high signal-background-ratio (SBR) value. After promoting the NIR-I signal to NIR-II signal, IR1061 achieved higher SBR value and exhibited a dose-dependent fluorescence intensity at 1100 nm along with the increase of the EtOH proportion as well as steady and selective optical responses toward liposomes. IR1061 was further applied in the in vivo imaging of lipid in fatty liver diseases. In spite of the differences in body weight gain and TC level between healthy mice and fatty liver diseases two models, IR1061 achieved high-resolution imaging in the liver region to monitor the fatty liver disease status. This work might be informatic for the clinical diagnosis and therapeutical treatments of fatty liver diseases.

Objectives: The aims of the study are to systematically evaluate the effect of body weight support training on lower extremity motor function(s) in patients with spinal cord injury and to compare the effect differences among three body weight support training methods., Design: PubMed, Web of Science, Cochrane Library, Embase, CNKI, CBM, China Scientific Journal, and Wan Fang databases were searched until December 31, 2022. Meta-analysis and network meta-analysis were conducted using RevMan 5.4 and ADDIS 1.16.8., Results: Nineteen randomized controlled trials involving 864 patients were included. The meta-analysis showed that body weight support training could improve lower extremity motor scores according to the International Standards for Neurological Classification of Spinal Cord Injury standard (mean difference = 6.38, 95% confidence interval = 3.96-8.80, P < 0.05), walking speed (standard mean difference = 0.77, 95% confidence interval = 0.52-1.02, P < 0.05), and modified Barthel Index scores (mean difference = 9.85, 95% confidence interval = 8.39-11.30, P < 0.05). The network meta-analysis showed no significant difference among the three body weight support training methods for improving lower extremity motor scores in patients with spinal cord injury. The best probability ranking of the body weight support training methods for improving lower extremity motor scores in patients with spinal cord injury was robot-assisted gait training ( P = 0.60), followed by aquatic exercise ( P = 0.21) and body weight support training ( P = 0.19)., Conclusions: Body weight support training can improve lower extremity motor score in patients with spinal cord injury. No significant difference was observed among the three body weight support training methods, but robot-assisted gait training may produce the best effect., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management., (© 2023. Asian Pacific Association for the Study of the Liver.)

Ethnopharmacological Relevance: Aspirin, as a first-line drug for the treatment of cardiovascular diseases, currently has high clinical usage. However, reports of aspirin-induced gastric mucosal injury are increasing. Xiaojianzhong decoction (XJZD), a classic traditional Chinese medicine formula, has been shown to alleviate gastric mucosal injury, although its potential mechanism of action requires further study., Aim of the Study: This study aimed to explore the effect and mechanism of XJZD in preventing aspirin-induced gastric mucosal injury., Materials and Methods: Aspirin was used to induce damage in the morning, while XJZD was applied as an intervention in the afternoon. The compounds in the XJZD were analyzed by means of both high-performance liquid chromatography and ultra-performance liquid chromatography-tandem mass spectrometry. The overall condition of the aspirin-related gastric mucosal injury was evaluated. The expressions of inflammatory factors and tight-junction-related proteins and apoptosis were observed via immunohistochemistry and immunofluorescence. The expression levels of the apoptosis-related proteins were detected using Western blot. Transcriptomics was used to perform the integrative analysis of gastric tissues, which was then validated. Molecular dynamics was used to explore the interaction of key compounds within the XJZD with relevant targets. Finally, non-targeted metabolomics was used to observe any metabolic changes and construct a network between the differentially expressed genes and the differential metabolites to elucidate their potential relationship., Results: XJZD can alleviate inflammation response, maintain the gastric mucosal barrier's integrity, reduce apoptosis and necroptosis levels, and promote the proliferation and repair of gastric mucosal tissues. Its mechanism of action may be related to the regulation of TNF-α signaling. Furthermore, molecular docking showed that the cinnamaldehyde within XJZD played an important role in its effects. In addition, XJZD can correct metabolic disorders, mainly regulating amino acid metabolism pathways. Moreover, six differential genes (Cyp1a2, Cyp1a1, Pla2g4c, etc.) were determined to alleviate both gastric mucosal injury and inflammation by regulating arachidonic acid metabolism, Tryptophan metabolism, etc. CONCLUSIONS: This study is the first to report that XJZD can inhibit necroptosis and gastric mucosal injury induced by aspirin, thereby revealing the complex mechanism of XJZD in relation to alleviating gastric mucosal injury from multiple levels and perspectives., 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. Published by Elsevier B.V.)

T helper (Th) cells are central members of adaptive immunity and comprise the last line of defense against pathogen infection and malignant cell invasion by secreting specific cytokines. These cytokines then attract or induce the activation and differentiation of other immune cells, including antibody-producing B cells and cytotoxic CD8 + T cells. Therefore, the bidirectional communication between Th cells and tumor cells and their positioning within the tumor microenvironment (TME), especially the tumor immune microenvironment (TIME), sculpt the tumor immune landscape, which affects disease initiation and progression. The type, number, and condition of Th cells in the TME and TIME strongly affect tumor immunity, which is precisely regulated by key effectors, such as granzymes, perforins, cytokines, and chemokines. Moreover, microRNAs (miRNAs) have emerged as important regulators of Th cells. In this review, we discuss the role of miRNAs in regulating Th cell mediated adaptive immunity, focusing on the development, activation, fate decisions, and tumor immunity., 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 Xu, Chen, Chang and Li.)