The incidence and predictive factors of secondary epilepsy in patients with supratentorial brain metastases (st-BMs) after stereotactic radiosurgery: A multicenter retrospective study.

OBJECTIVE: To evaluate the incidence and the independent risk factors of SRS-related epilepsy in patients with supratentorial brain metastases (st-BMs), providing evidences for prevention or reduction secondary epilepsy after SRS. METHODS: Patients with st-BMs from four gamma knife centers who developed secondary epilepsy after SRS were retrospectively studied between January 1, 2017 and June 31, 2023. The incidence and clinical characteristics of the patients with secondary epilepsy were analyzed. The predictive role of baseline clinical-demographic variables was evaluated according to univariate and multivariate logistic regression model. The impact of secondary epilepsy on patients' OS was evaluated as well by log-rank test. RESULTS: 11.3 % (126/1120) of the patients with totally 158 st-BMs experienced secondary epilepsy after SRS in median 21 days. 61.9 % (78/126) of the patients experienced simple partial seizures. 91.3 % (115/126) patients achieved good seizure control after received 1-2 kinds of AEDs for median 90 days, while 7.1 % (9/126) of the patients suffered from refractory epilepsy. Patients had higher risk of secondary epilepsy if the tumor located in cortex and/or hippocampus, peri-tumor edema larger than 20.3 cm3 before SRS, had epilepsy history, and failed to receive bevacizumab prior to SRS. There was no difference in the OS of patients who experience secondary epilepsy or not after SRS. CONCLUSIONS: The incidence of SRS-related secondary epilepsy is 11.3 % in patients with st-BMs in this retrospective study. The risk of secondary epilepsy is higher in patients with st-BM located in cortex and/or hippocampus area, peri-tumor edema larger than 20.3 cm3 before SRS, and epilepsy history. Bevacizumab is suggested prior to SRS therapy, as it could be used for the control of peri-tumor edema and SRS-related damage, hence reduce the risk of secondary epilepsy. However, whether or not patients suffered from secondary epilepsy after SRS does not affect their OS.

HDL-cholesterol confers sensitivity of immunotherapy in nasopharyngeal carcinoma via remodeling tumor-associated macrophages towards the M1 phenotype.

BACKGROUND: The sustained effectiveness of anti-programmed cell death protein-1/programmed death-ligand 1 treatment is limited to a subgroup of patients with advanced nasopharyngeal carcinoma (NPC), and the specific biomarker determining the response to immunotherapy in NPC remains uncertain. METHODS: We assessed the associations between pre-immunotherapy and post-immunotherapy serum lipoproteins and survival in a training cohort (N=160) and corroborated these findings in a validation cohort (N=100). Animal studies were performed to explore the underlying mechanisms. Additionally, the relationship between high-density lipoprotein-cholesterol (HDL-C) levels and M1/M2-like macrophages, as well as activated CD8+T cells in tumor tissues from patients with NPC who received immunotherapy, was investigated. RESULTS: The lipoproteins cholesterol, HDL-C, low-density lipoprotein-cholesterol, triglycerides, apolipoprotein A-1 (ApoA1), and apolipoprotein B, were significantly altered after immunotherapy. Patients with higher baseline HDL-C or ApoA1, or those with increased HDL-C or ApoA1 after immunotherapy had longer progression-free survival, a finding verified in the validation cohort (p<0.05). Multivariate analysis revealed that baseline HDL-C and elevated HDL-C post-immunotherapy were independent predictors of superior PFS (p<0.05). Furthermore, we discovered that L-4F, an ApoA1 mimetic, could inhibit tumor growth in NPC xenografts. This effect was associated with L-4F's ability to polarize M2-like macrophages towards an M1-like phenotype via the activation of mitogen-activated protein kinase (MAPK) p38 and nuclear factor-κB (NF-κB) p65, thereby alleviating immunosuppression in the tumor microenvironment. Importantly, in patients with NPC with high plasma HDL-C levels, the number of M2-like macrophages was significantly decreased, while M1-like macrophages and activated CD8+T cells were notably increased in those with high HDL-C levels. CONCLUSION: Higher baseline HDL-C levels or an increase in HDL-C post-immunotherapy can enhance immunotherapeutic responses in patients with NPC by reprogramming M2-like macrophages towards the M1 phenotype. This suggests a potential role for prospectively exploring ApoA1 mimetics as adjuvant agents in combination with immunotherapy.

Orientational dynamics of the water layer adjacent to Au surface accelerated by polarization effect.

The orientation and rearrangement of water on a gold electrode significantly influences its physicochemical heterogeneous performance. Despite numerous experimental and theoretical studies aimed at uncovering the structural characteristics of interfacial water, the orientational behavior resulting from electrode-induced rearrangements remains a subject of ongoing debate. Here, we employed molecular dynamics simulations to investigate the adaptive structure and dynamics properties of interfacial water on Au(111) and Au(100) surfaces by considering a polarizable model for Au atoms in comparison with the non-polarizable model. Compared to the nonpolarizable systems, the polarization effect can enhance the interaction between water molecules and the gold surface. Unexpectedly, the rotational dynamics directly associated with the orientational behavior of water adjacent to the gold surface is accelerated, thereby reducing the hydrogen bond lifetime. The underlying mechanism for this anomalous phenomenon originates from the polarization effect, which induces the attraction of the positive hydrogen atoms to the surface by the negative image charge. This leads to a change in orientation that disrupts the hydrogen bonds in the first water layer and subsequently accelerates reorientation dynamics of water molecules adjacent to the gold surface. These results shed light on the intricate interplay between polarization effects and water molecule dynamics on metal surfaces, establishing the foundation for the rational regulation of the orientation of interfacial water.

Break down the decentralization-security-privacy trilemma in management of distributed energy systems.

Distributed energy systems encompass a diverse range of generation and storage solutions on the user side, where decentralized management schemes to maximize the overall social welfare are preferred considering their dispersed ownership. However, either security or privacy problems occur in recently proposed schemes. Here we report a decentralized framework leveraging the strengths of blockchain and parallelizable mathematical algorithms to overcome these potential drawbacks. The system owners bid cost functions and operating constraints through masked but coupled management subproblems, which are redistributed by the blockchain to be verifiably solved by competent peers. Such processes are iteratively executed as decisions and shadow prices are exchanged among participants, until an equilibrium is reached. The interactive framework ensures decentralized, privacy-preserving, and secure management of multiple energy sources, and reduces the total cost by 3.0 ~ 7.5% in the test system. Our results benefit the energy prosumers and promote a more active and competitive power grid.

The dual effects of dexmedetomidine on intestinal barrier and intestinal motility during sepsis.

BACKGROUND: Sepsis, characterized by dysregulated host responses to infection, remains a critical global health concern, with high morbidity and mortality rates. The gastrointestinal tract assumes a pivotal role in sepsis due to its dual functionality as a protective barrier against injurious agents and as a regulator of motility. Dexmedetomidine, an α2-adrenergic agonist commonly employed in critical care settings, exhibits promise in influencing the maintenance of intestinal barrier integrity during sepsis. However, its impact on intestinal motility, a crucial component of intestinal function, remains incompletely understood. METHODS: In this study, we investigated dexmedetomidine's multifaceted effects on intestinal barrier function and motility during sepsis using both in vitro and in vivo models. Sepsis was induced in Sprague-Dawley rats via cecal ligation and puncture. Rats were treated with dexmedetomidine post-cecal ligation and puncture, and various parameters were assessed to elucidate dexmedetomidine's impact. RESULTS: Our findings revealed a dichotomous influence of dexmedetomidine on intestinal physiology. In septic rats, dexmedetomidine administration resulted in improved intestinal barrier integrity, as evidenced by reduced mucosal hyper-permeability and morphological alterations. However, a contrasting effect was observed on intestinal motility, as dexmedetomidine treatment inhibited both the frequency and amplitude of contractions in isolated intestinal strips and decreased the distance of ink migration in vivo. Additionally, dexmedetomidine suppressed the secretion of pro-motility hormones while having no influence on hormones that inhibit intestinal peristalsis. CONCLUSION: The study revealed that during sepsis, dexmedetomidine exhibited protective effects on barrier integrity, although concurrently it hindered intestinal motility, partly attributed to its modulation of pro-motility hormone secretion. These findings underscore the necessity of a comprehensive understanding of dexmedetomidine's impact on multiple facets of gastrointestinal physiology in sepsis management, offering potential implications for therapeutic strategies and patient care.

Copolymers of Gelatin-graft-poly(3-hexylthiophene) for Transient Electronics.

As transient electronics continue to advance, the demand for new materials has given rise to the exploration of conducting polymer (CP)-based electronic materials. The big challenge lies in balancing conductivity while introducing controlled degradable properties into CP-based transient materials. In response to this, we present in this work a concept of using conducting polymers attached to an enzymatically biodegradable biopolymer to create transient polymer electronics materials. Specifically, poly(3-hexyl thiophene) (P3HT) is covalently grafted onto biopolymer gelatin, affording graft copolymer gelatin-graft-poly(3-hexyl thiophene) (termed Gel-g-P3HT). The thin films of Gel-g-P3HT that were produced by optimized processing solvent (THF/H2O cosolvent) showed enhanced π-π stacking domains of P3HT, resulting in semiconducting thin films with good electroactivity. Due to the presence of amide bonds in the gelatin backbone, Gel-g-P3HT underwent degradation over a period of 5 days, resulting in the formation of amphiphilic micellar nanoparticles that are biocompatible and nontoxic. The potential of these conductive and degradable graft copolymers was demonstrated in a pressure sensor. This research paves the way for developing biocompatible and enzymatically degradable polymer materials based on P3HT, enabling the next generation of transient polymer electronics for diverse applications, such as skin, implantable, and environmental electronics.

Outcomes of 2-SSRS plus bevacizumab therapy strategy for brainstem metastases (BSM) over 2 cm3: a multi-center study.

Despite 2-staged stereotactic radiosurgery (2-SSRS) has been reported to provide patients with improved survival and limited toxicity, 2-SSRS for brainstem metastases (BSM) larger than 2 cm3 remains challenging. We tried to find out the effectiveness and safety of 2-SSRS plus bevacizumab therapy for BSMs over 2 cm3 and prognostic factors that related to the tumor local control. Patients that received 2-SSRS plus bevacizumab therapy from four gamma knife center were retrospectively studied from Jan 2014 to December 2023. Patients' domestic characteristics and the tumor features were evaluated before and after the treatment. Cox regression model was used to find out prognostic factors for tumor local control. 53 patients with 63 lesions received the therapy. The median peri-tumor edema volume greatly reduced at the end of therapy (P < 0.01), the median tumor volume dramatically reduced (P < 0.01) and patients' KPS score improved significantly (P < 0.05) 3 months after the therapy. Patients' median OS was 12.8 months. The tumor local control rate at 3, 6, and 12 months was 98.4%, 93.4%, and 85.2%. The incidence side effects were mainly oral and nasal hemorrhage (5.7%, 3/53), and radiation necrosis (13.2%, 7/53). Patients with primary lung adenocarcinoma, therapeutic dose over 12 Gy at second-stage SRS, primary peri-tumor edema volume less than 2.3 cm³, primary tumor volume less than 3.7 cm³ would enjoy longer tumor local control. These results suggested that 2-SSRS plus bevacizumab therapy was effective and safe for BSMs over 2 cm3. However, it is important for patients with BSM to receive early diagnosis and treatment to achieve good tumor local control.

Effect of Regional Brain Activity Following Repeat Transcranial Magnetic Stimulation in SCA3: A Secondary Analysis of a Randomized Clinical Trial.

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuroregulatory technique used to treat neurodegenerative diseases, holds promise for spinocerebellar ataxia type 3 (SCA3) treatment, although its efficacy and mechanisms remain unclear. This study aims to observe the short-term impact of cerebellar rTMS on motor function in SCA3 patients and utilize resting-state functional magnetic resonance imaging (RS-fMRI) to assess potential therapeutic mechanisms. Twenty-two SCA3 patients were randomly assigned to receive actual rTMS (AC group, n = 11, three men and eight women; age 32-55 years) or sham rTMS (SH group, n = 11, three men and eight women; age 26-58 years). Both groups underwent cerebellar rTMS or sham rTMS daily for 15 days. The primary outcome measured was the ICARS scores and parameters for regional brain activity. Compared to baseline, ICARS scores decreased more significantly in the AC group than in the SH group after the 15-day intervention. Imaging indicators revealed increased Amplitude of Low Frequency Fluctuation (ALFF) values in the posterior cerebellar lobe and cerebellar tonsil following AC stimulation. This study suggests that rTMS enhances motor functions in SCA3 patients by modulating the excitability of specific brain regions and associated pathways, reinforcing the potential clinical utility of rTMS in SCA3 treatment. The Chinese Clinical Trial Registry identifier is ChiCTR1800020133.

Hemodynamics in nutcracker syndrome: implications for diagnosis.

BACKGROUND: Nutcracker syndrome is a disease characterized by complex symptoms, making its diagnosis challenging and often delayed, often resulting in a painful experience for the patients. OBJECTIVE: This study aimed to investigate the pathogenesis of nutcracker syndrome through the perspective of hemodynamics by simulating blood flow with varying compression degrees of the left renal vein. METHODS: 3D patient-specific vascular models of the abdominal aorta, superior mesenteric artery and left renal vein were constructed based on CT images of patients suspected of having nutcracker syndrome. A hemodynamic simulation was then conducted using computational fluid dynamics to identify the correlation between alterations in hemodynamic parameters and varying degrees of compression. RESULTS: The study indicated the presence of an evident gradient in velocity distribution over the left renal vein with relatively high degrees of stenosis (α ≤ 50°), with maximum velocity in the central region of the stenosis. Additionally, when the compression degree of the left renal vein increases, the pressure distribution of the left renal vein presents an increasing number of gradient layers. Furthermore, the wall shear stress shows a correlation with the variation of blood flow velocity, i.e., the increase of wall shear stress correlates with the acceleration of the blood flow velocity. CONCLUSIONS: Using computational fluid dynamics as a non-invasive instrument to obtain the hemodynamic characteristics of nutcracker syndrome is feasible and could provide insights into the pathological mechanisms of the nutcracker syndrome supporting clinicians in diagnosis.

Accurate diabatization based on combined-hyperbolic-inverse-power-representation: 1,2 2A' states of BeH2.

A diabatic potential energy matrix (DPEM) for the two lowest states of BeH2+ has been constructed using the combined-hyperbolic-inverse-power-representation (CHIPR) method. By imposing symmetry constraints on the coefficients of polynomials, the complete nuclear permutation inversion symmetry is correctly preserved in the CHIPR functional form. The symmetrized CHIPR functional form is then used in the diabatization by ansatz procedure. The ab initio energies are reproduced with satisfactory accuracy. In addition, the CHIPR-based DPEM also reproduces the local topology of a conical intersection. Future work will focus on a complete four-state diabatic representation with emphasis on the long-range interactions and spin-orbit couplings, which will enable accurate quantum scattering calculations for the Be+(2P) + H2 → BeH+(X1Σ+) + H(2S) reaction.

SPTLC3 Is Essential for Complex I Activity and Contributes to Ischemic Cardiomyopathy.

BACKGROUND: Dysregulated metabolism of bioactive sphingolipids, including ceramides and sphingosine-1-phosphate, has been implicated in cardiovascular disease, although the specific species, disease contexts, and cellular roles are not completely understood. Sphingolipids are produced by the serine palmitoyltransferase enzyme, canonically composed of 2 subunits, SPTLC1 (serine palmitoyltransferase long chain base subunit 1) and SPTLC2 (serine palmitoyltransferase long chain base subunit 2). Noncanonical sphingolipids are produced by a more recently described subunit, SPTLC3 (serine palmitoyltransferase long chain base subunit 3). METHODS: The noncanonical (d16) and canonical (d18) sphingolipidome profiles in cardiac tissues of patients with end-stage ischemic cardiomyopathy and in mice with ischemic cardiomyopathy were analyzed by targeted lipidomics. Regulation of SPTLC3 by HIF1α under ischemic conditions was determined with chromatin immunoprecipitation. Transcriptomics, lipidomics, metabolomics, echocardiography, mitochondrial electron transport chain, mitochondrial membrane fluidity, and mitochondrial membrane potential were assessed in the cSPTLC3KO transgenic mice we generated. Furthermore, morphological and functional studies were performed on cSPTLC3KO mice subjected to permanent nonreperfused myocardial infarction. RESULTS: Herein, we report that SPTLC3 is induced in both human and mouse models of ischemic cardiomyopathy and leads to production of atypical sphingolipids bearing 16-carbon sphingoid bases, resulting in broad changes in cell sphingolipid composition. This induction is in part attributable to transcriptional regulation by HIF1α under ischemic conditions. Furthermore, cardiomyocyte-specific depletion of SPTLC3 in mice attenuates oxidative stress, fibrosis, and hypertrophy in chronic ischemia, and mice demonstrate improved cardiac function and increased survival along with increased ketone and glucose substrate metabolism utilization. Depletion of SPTLC3 mechanistically alters the membrane environment and subunit composition of mitochondrial complex I of the electron transport chain, decreasing its activity. CONCLUSIONS: Our findings suggest a novel essential role for SPTLC3 in electron transport chain function and a contribution to ischemic injury by regulating complex I activity.

PQR309, a dual PI3K/mTOR inhibitor, synergizes with gemcitabine by impairing the GSK-3ß and STAT3/HSP60 signaling pathways to treat nasopharyngeal carcinoma.

End-stage nasopharyngeal carcinoma (NPC) has unsatisfactory survival. The limited benefit of chemotherapy and the scarcity of targeted drugs are major challenges in NPC. New approaches to treat late-stage NPC are urgently required. In this study, we explored whether the dual PI3K/mTOR inhibitor, PQR309, exerted a favorable antineoplastic effect and sensitized the response to gemcitabine in NPC. We observed that PI3K expression was positive and elevated in 14 NPC cell lines compared with that in normal nasopharygeal cell lines. Patients with NPC with higher PI3K levels displayed poorer prognosis. We subsequently showed that PQR309 alone effectively decreased the viability, invasiveness, and migratory capability of NPC cells and neoplasm development in mice xenograft models, and dose-dependently induced apoptosis. More importantly, PQR309 remarkably strengthened the anti-NPC function of gemcitabine both in vivo and in vitro. Mechanistically, PQR309 sensitized NPC to gemcitabine by increasing caspase pathway-dependent apoptosis, blocking GSK-3ß and STAT3/HSP60 signaling, and ablating epithelial-mesenchyme transition. Thus, targeting PI3K/mTOR using PQR309 might represent a treatment option to promote the response to gemcitabine in NPC, and provides a theoretical foundation for the study of targeted drugs combined with chemotherapy for NPC.

Ionic liquid post-modified carboxylate-rich MOFs for efficient catalytic CO2 cycloaddition under solvent-free conditions.

The synthesis of cyclic carbonates through cycloaddition reactions between epoxides and carbon dioxide (CO2) is an important industrial process. Metal-Organic Frameworks (MOFs) have functional and ordered pore structures, making them attractive catalysts for converting gas molecules into valuable products. One approach to enhance the catalytic activity of MOFs in CO2 cycloaddition reactions is to create open metal sites within MOFs. In this study, the amino-functionalized rare earth Gd-MOF (Gd-TPTC-NH2) and its ionic liquid composite catalysts (Gd-TPTC-NH-[BMIM]Br) were synthesized using 2'-amino-[1,1':4',1''-terphenyl]-3,3'',5,5''-tetracarboxylic acid (H4TPTC-NH2) as the ligand. The catalytic performance of these two catalysts was observed in the cycloaddition reaction of CO2 and epoxides. Under the optimized reaction conditions, Gd-TPTC-NH-[BMIM]Br can effectively catalyze the cycloaddition reaction of a variety of epoxide substrates with good to excellent yields of cyclic carbonate products. Comparatively, epichlorohydrin and epibromohydrin, which possess halogen substituents, promote higher yields of cyclic carbonates due to the electron-withdrawing nature of Cl and Br substituents. Additionally, the Gd-TPTC-NH-[BMIM]Br catalyst demonstrated good recyclability and reproducibility, maintaining its catalytic activity without any changes in its structure or properties after five reuse cycles.

Dynamics of the soil microbial community associated with Morchella cultivation: diversity, assembly mechanism and yield prediction.

Introduction: The artificial cultivation of morels has been a global research focus owing to production variability. Understanding the microbial ecology in cultivated soil is essential to increase morel yield and alleviate pathogen harm. Methods: A total of nine Morchella cultivation experiments in four soil field types, forest, paddy, greenhouse, and orchard in Shanghai city were performed to determine the potential ecological relationship between Morchella growth and soil microbial ecology. Results: Generally, significant variation was observed in the soil microbial diversity and composition between the different experimental field types. The niche width analysis indicated that the bacterial habitat niche breadth was significantly greater than the fungal community width, which was further confirmed by a null model that revealed that homogeneous selection could explain 46.26 and 53.64% of the variance in the bacterial and fungal assemblies, respectively. Moreover, the neutral community model revealed that stochastic processes dominate the bacterial community in forests and paddies and both the bacterial and fungal communities in orchard crops, whereas deterministic processes mostly govern the fungal community in forests and paddies and both the bacterial and the fungal communities in greenhouses. Furthermore, co-occurrence patterns were constructed, and the results demonstrated that the dynamics of the soil microbial community are related to fluctuations in soil physicochemical characteristics, especially soil potassium. Importantly, structural equation modeling further demonstrated that the experimental soil type significantly affects the potassium content of the soil, which can directly or indirectly promote Morchella yield by inhibiting soil fungal richness. Discussion: This was the first study to predict morel yield through soil potassium fertilizer and soil fungal community richness, which provides new insights into deciphering the importance of microbial ecology in morel agroecosystems.

The circRNA hsa-circ-0013561 regulates head and neck squamous cell carcinoma development via the miR-7-5p/PDK3 axis.

BACKGROUND: Circular RNAs (circRNAs) belong to a class of covalently closed single stranded RNAs that have been implicated in cancer progression. Former investigations showed that hsa-circ-0013561 is abnormally expressed in head and neck squamous cell carcinoma (HNSCC). Nevertheless, the role of hsa-circ-0013561 during the progress of HNSCC still unclear. METHODS: Present study applied FISH and qRT-PCR to examine hsa-circ-0013561 expression in HNSCC cells and tissue samples. Dual-luciferase reporter assay was employed to identify downstream targets of hsa-circ-0013561. Transwell migration, 5-ethynyl-2'-deoxyuridine incorporation, CCK8 and colony formation assays were utilized to test cell migration and proliferation. A mouse tumor xenograft model was utilized to determine the hsa-circ-0013561 roles in HNSCC progression and metastasis in vivo. RESULTS: We found that hsa-circ-0013561 was upregulated in HNSCC tissue samples. hsa-circ-0013561 downregulation inhibited HNSCC cell proliferation and migration to promote apoptosis and G1 cell cycle arrest. The dual-luciferase reporter assay revealed that miR-7-5p and PDK3 are hsa-circ-0013561 downstream targets. PDK3 overexpression or miR-7-5p suppression reversed the hsa-circ-0013561-induced silencing effects on HNSCC cell proliferation and migration. PDK3 overexpression reversed miR-7-5p-induced effects on HNSCC cell proliferation and migration. CONCLUSION: The findings suggest that hsa-circ-0013561 downregulation inhibits HNSCC metastasis and progression through PDK3 expression and miR-7-5p binding modulation.

Effect of salinity on the toxicokinetics, oxidative stress, and metallothionein gene expression in Meretrix meretrix exposed to cadmium.

To understand the effect of salinity on the toxicokinetics, oxidative stress, and detoxification of cadmium-exposed Meretrix meretrix, M. meretrix were acclimatized to different salinities (8, 14, 20, 26, and 32 ppt) for 14 d, exposed to 10 µg/L Cd for 7 d, followed by a 28-day depuration period. The internal Cd concentration was determined, and the activities of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and glutathione-S-transferase (GST)), and the malondialdehyde (MDA) content were measured. The mRNA expression levels of antioxidant enzyme (Cu/Zn SOD, CAT) and detoxification-related genes metallothionein (MT) were analyzed. The mean concentrations of Cd in M. meretrix tissues were in the order gill > digestive gland > mantle > axe foot. The Cd uptake rate in the four tissues decreased with increasing salinity (range: 14-26 ppt). The Cd elimination half-lives were the highest at 8 ppt and 14 ppt salinity. Cadmium activated the four oxidative stress-related related enzymes in the gills. At the end of accumulation period, Cd exposure at 20 ppt salinity significantly increased the expression of Cu/Zn SOD. CAT expression was significantly inhibited at 20 ppt salinity, but was induced at 32 ppt. MT mRNA expression was only induced under Cd at 20 ppt salinity. At the end of depuration period, Cu/Zn SOD expression was inhibited at salinities of 8, 14, and 26 ppt. The results indicated that SOD, CAT, GST, MDA, Cu/Zn SOD, CAT, and MT were sensitive to cadmium in a water environment, and can be used as indicators of marine heavy metal pollution.

Peptidase inhibitor 16 promotes proliferation of pancreatic ductal adenocarcinoma cells through OASL signaling.

Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive cancer with a poor prognosis and a 5-year survival rate of less than 11%. As a member of the CAP superfamily of proteins, the role of peptidase inhibitor 16 (Pi16) in tumor progression is still unclear. Immunohistochemistry and quantitative RT-PCR methods were used to detect the expression levels of Pi16 protein and mRNA in PDAC patients. CRISPR/Cas9 technology was used to knock out the expression of Pi16 in PDAC cell lines. In vivo and in vitro experiments were used to verify the effect of Pi16 on PDAC proliferation ability. By RNA sequencing, we found that oligoadenylate synthetase L (OASL) can serve as a potential downstream target of Pi16. The expression of Pi16 was higher in PDAC tissues than in matched adjacent tissues. High expression of Pi16 was associated with PDAC progression and poor prognosis. Overexpression of Pi16 could promote the proliferation of PDAC cells in vitro and in vivo. Bioinformatics analysis and coimmunoprecipitation assays showed that Pi16 could bind to OASL. Moreover, the functional recovery test confirmed that Pi16 could promote the proliferation of PDAC via OASL. Our present study demonstrates that Pi16 might participate in the occurrence and development of PDAC by regulating cell proliferation by binding to OASL, indicating that Pi16 might be a promising novel therapeutic target for PDAC.

Biological functions and clinical significance of tRNA-derived small fragment (tsRNA) in tumors: Current state and future perspectives.

A new class of noncoding RNAs, tsRNAs are not only abundant in humans but also have high tissue specificity. Recently, an increasing number of studies have explored the correlations between tsRNAs and tumors, showing that tsRNAs can affect biological behaviors of tumor cells, such as proliferation, apoptosis and metastasis, by modulating protein translation, RNA transcription or posttranscriptional regulation. In addition, tsRNAs are widely distributed and stably expressed, which endows them with broad application prospects in diagnosing and predicting the prognosis of tumors, and they are expected to become new biomarkers. However, notably, the current research on tsRNAs still faces problems that need to be solved. In this review, we describe the characteristics of tsRNAs as well as their unique features and functions in tumors. Moreover, we also discuss the potential opportunities and challenges in clinical applications and research of tsRNAs.

Excessive fluoride induces ovarian function impairment by regulating levels of ferroptosis in fluorosis women and ovarian granulosa cells.

The aim of this study was to investigate the role of ferroptosis in fluorosis women and the in vitro molecular mechanisms leading to ovarian dysfunction and abnormal hormone secretion by sodium fluoride (NaF) treatment of KGN cells. Fifty women with fluorosis as Fluorosis group and fifty healthy women as Control group were included in this study. The levels of lipid peroxidation and activities of antioxidant enzyme were assessed by photometric methods. The content of iron and glutathione (GSH) in serum was measured by microplate method. KGN cells were treated by different concentration of NaF (0, 1, 2, 4 and 8 ×10-3 M) for 24 h. The mRNA and protein expression levels of ferroptosis-related molecules, including glutathione peroxidase 4 (GPX4), solute carrier family 7 member (SLC7A11), nuclear factor erythroid 2-related factor 2 (Nrf2), ferritin heavy chain 1 (FTH1) and p53, were assessed by qRT-PCR and western blot analysis. Fluorosis group women had a significant higher levels of iron, Malondialdehyde (MDA), FSH and LH, and a lower levels of E2 and antioxidant enzyme in serum than that in the control group. The representative molecular changes of ferroptosis, such as the decrease in GPX4, Nrf2 and SLC7A11 expression (mRNA and protein expression), the increase in protein expression of p53, and a reduced level of E2 were observed in KGN cells treated by excessive NaF.It is concluded therefore that NaF increases the expression of p53 and inhibits ovarian granulosa cell ferroptosis preventive protein expression, resulting in abnormal hormone secretion and the ovarian dysfunction.

FeN3 S1 ─OH Single-Atom Sites Anchored on Hollow Porous Carbon for Highly Efficient pH-Universal Oxygen Reduction Reaction.

Regulating the asymmetric active center of a single-atom catalyst to optimize the binding energy is critical but challenging to improve the overall efficiency of the electrocatalysts. Herein, an effective strategy is developed by introducing an axial hydroxyl (OH) group to the Fe─N4 center, simultaneously assisting with the further construction of asymmetric configurations by replacing one N atom with one S atom, forming FeN3 S1 ─OH configuration. This novel structure can optimize the electronic structure and d-band center shift to reduce the reaction energy barrier, thereby promoting oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) catalytic activities. The optimal catalyst, FeSA -S/N-C (FeN3 S1 ─OH anchored on hollow porous carbon) displays remarkable ORR performance with a half-wave potential of 0.92, 0.78, and 0.64 V versus RHE in 0.1 m KOH, 0.5 m H2 SO4 , and 0.1 m PBS, respectively. The rechargeable liquid Zn-air batteries (LZABs) equipped with FeSA -S/N-C display a higher power density of 128.35 mW cm-2 , long-term operational stability of over 500 h, and outstanding reversibility. More importantly, the corresponding flexible solid-state ZABs (FSZABs@FeSA -S/N-C) display negligible voltage changes at different bending angles during the charging and discharging processes. This work provides a new perspective for the design and optimization of asymmetric configuration for single-atom catalysts applied to the area of energy conversion and storage.