Tumor microenvironment RNA test to predict immunotherapy outcomes in advanced gastric cancer: The TIMES001 trial.

BACKGROUND: Clinical trials support the efficacy of immune checkpoint blockades (ICBs) plus chemotherapy in a subset of patients with metastatic gastric cancer (mGC). To identify the determinants of response, we developed a TMEscore model to assess tumor microenvironment (TME), which was previously proven to be a biomarker for ICBs. METHODS: A reference database of TMEscore assays was established using PCR assay kits containing 30 TME genes. This multi-center prospective clinical trial (NCT#04850716) included patients with mGC who were administered ICB combined with chemotherapy as a first-line regimen. Eighty-six tumor samples extracted from five medical centers before treatment were used to estimate the TMEscore, PD-L1 (CPS), and mismatch repair deficiency. FINDINGS: The objective response rate (ORR) and median PFS of the cohort were 31.4% and six months. Enhanced ORR was observed in TMEscore-high mGC patients (ORR = 59%). The survival analysis demonstrated that high TMEscore was significantly associated with a more favorable PFS and OS. Moreover, TMEscore was found to be a predictive biomarker that surpassed MSI and CPS (AUC = 0.873, 0.511, and 0.524, respectively). By integrating the TMEscore and clinical variables, the fused model further enhances the predictive efficiency and translational application in a clinical setting. CONCLUSIONS: This prospective clinical study indicates that the TMEscore assay is a robust biomarker for screening patients with mGC who may derive survival benefits from ICB plus chemotherapy. FUNDING: Guangdong Basic and Applied Basic Research Foundation (2023A1515011214), Science and Technology Program of Guangzhou (202206080011), and Guangzhou Science and Technology Project (2023A03J0722 and 2023A04J2357).

Secondary Polycythemia May Be an Early Clinical Manifestation of Multiple Myeloma: A Case Report.

Multiple myeloma (MM) is a malignancy of plasma cells that can cause anemia due to renal failure and bone marrow failure. Secondary polycythemia (SE) is a clinically rare disease that involves the overproduction of red blood cells. To our knowledge, the association of multiple myeloma and polycythemia has been reported, but the association of SE and multiple myeloma is rare and has been infrequently reported in literature. In contrast to anemia, the presence of polycythemia in multiple myeloma patients is a rare finding. A patient of IgA-λ multiple myeloma with secondary erythrocytosis recently admitted to our department is now reported as follows and relevant literature is reviewed to improve clinicians' awareness of such rare comorbidities.

Deep cervical lymph nodes in Parkinson's disease and atypical Parkinson's disease: A potential ultrasound biomarker for differential diagnosis.

Background: Parkinson's disease (PD) is a common degenerative disease caused by abnormal accumulation of α-synuclein. The glymphatic pathway is essential for removing macromolecular proteins including α-synuclein from the brain, which flows into deep cervical lymph nodes (DCLNs) through meningeal lymphatics. As a terminal station for the cerebral lymphatic system drainage, DCLNs can be easily assessed clinically. Objectives: Although the drainage function of the cerebral lymphatic system is impaired in PD, the correlation between DCLNs and PD remains unknown. Design: Single-center retrospective cross-sectional study. Methods: The size of the DCLNs were measured using ultrasound. The Movement Disorder Society Sponsored Revision Unified Parkinson's Disease Rating Scale and other scales were used to assess PD motor and non-motor symptoms. Results: Compared with the healthy control (HC) and the atypical Parkinson's disease (AP) groups, the size of the second and third DCLNs in the Parkinson's disease (PD) group was significantly smaller (P < .05). The width diameter of the third DCLN (DCLN3(y)) was significantly smaller in the PD group than in the AP group (P = .014). DCLN3(y) combined with a variety of clinical features improved the sensitivity of AP identification (sensitivity = .813). Conclusion: DCLNs were able to distinguish HC, PD and AP and were mainly located in Robbins ΙΙA level. PD and AP were associated with different factors that influenced the size of the DCLNs. DCLN3(y) plays an important role in differentiating PD from AP, which, combined with other clinical features, has the ability to distinguish PD from AP; in particular, the sensitivity of AP diagnosis was improved.

Deep cervical lymph nodes, a potential marker for the diagnosis of PD and AP. Deep cervical lymph nodes (DCLNs) were able to distinguish HC, PD and AP and were mainly located in Robbins ΙΙA level. PD and AP were associated with different factors that influenced the size of the DCLNs. DCLN3(y) plays an important role in differentiating PD from AP, which, combined with other clinical features, has the ability to distinguish PD from AP; in particular, the sensitivity of AP diagnosis was improved. DCLN has potential diagnostic value in differentiating PD from AP.

Oxaliplatin-associated shock in stage III colorectal cancer patients: real-world evidence in Taiwan.

Background: Oxaliplatin-associated shock (referred to as shock) is a rare but life-threatening adverse event. Objectives: This pioneering cohort study aimed to quantitatively investigate the association between oxaliplatin use and shock in patients with stage III colorectal cancer (CRC), identify potential independent risk factors for shock, and assess the cycle-to-shock during oxaliplatin treatment. Design: The study utilized a nested case-control (NCC) design to assess the association between oxaliplatin and shock and employed a case-crossover approach to address unmeasured confounders. Methods: All newly diagnosed stage III CRC patients were identified from the CRC Health Database (2012-2016). Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for oxaliplatin's link to shock incidence. Results: Among 6932 oxaliplatin recipients, 331 suffered shock. In all, 3309 controls were selected via risk-set sampling for the shock cases. Oxaliplatin use is associated with a doubled risk of shock (adjusted OR: 2.08, 95% CI: 1.23-3.52). Two independent risk factors were male sex (adjusted OR: 1.33, 95% CI: 1.05-1.69) and heart diseases (adjusted OR: 1.65, 95% CI: 1.17-2.32). The case-crossover analysis revealed a more than fourfold risk (OR: 4.4, 95% CI: 1.67-11.62). In total, 22 of 331 shock cases were exposed to oxaliplatin within 2 days of shock onset, with a median cycle-to-shock time at the seventh cycle. Conclusion: Oxaliplatin use significantly increased shock risk in stage III CRC patients. Male sex and heart disease are two independent risk factors.

This pioneering study identified potential independent risk factors and the cycle-to-shock of oxaliplatin-associated shock which is a rare but life-threatening adverse event Why was the study done? Oxaliplatin-induced anaphylactic shock (referred to as shock) is a rare but life-threatening adverse event which is a harmful and undesirable experience associated with medical care in a patient. What did the researchers do? This pioneering cohort study aimed to quantitatively investigate the association between oxaliplatin use and shock in patients with stage III colorectal cancer (CRC), identify potential independent risk factors for shock and assess the cycle-to-shock during oxaliplatin treatment. All newly diagnosed stage III CRC patients were identified from the CRC Health Database (2012­2016). The study utilized a nested case-control (NCC) design to assess the association between oxaliplatin and shock and employed a case-crossover approach to address unmeasured confounders. Conditional logistic regression was used to quantify the association between oxaliplatin and shock incidence. What did the researchers find? Among 6,932 oxaliplatin recipients, 331 suffered shock. 3,309 controls were selected via risk-set sampling for the shock cases. Oxaliplatin use is associated with a doubled risk of shock. Independent risk factors were male sex and heart diseases. The risk of shock was 33% higher for males and 65% higher for people with heart diseases compared to females and those without heart diseases. The case-crossover analysis revealed a more than four-fold risk of shock of oxaliplatin. Twenty-two of 331 shock cases were exposed to oxaliplatin within two days before the shock onset. The median cycle-to-shock time is at the seventh cycle. What do the findings mean? Oxaliplatin use significantly increased shock risk in stage III CRC patients. Male sex and having heart diseases are two independent risk factors.

Effects of ankle Kinesio taping on knee and ankle joint biomechanics during unanticipated jumps in collegiate athletes.

OBJECTIVE: Most biomechanical research on the application of Kinesio taping (KT) to the ankle joint focused on testing anticipated movements. However, ankle sprains frequently occur in real life in unanticipated situations, where individuals are unprepared and face sudden external stimuli. This situation is completely different from the anticipated situation. The aim of the present study was to investigate the effects of ankle KT application on the kinematic and kinetic characteristics of the knee and ankle joints during unanticipated jump tasks in collegiate athletes. METHODS: Eighteen healthy collegiate athletes experienced three taping conditions in a randomized order: no taping (NT), placebo taping (PT), and KT, and performed unanticipated jump tasks. A 9-camera infrared high-speed motion capture system was employed to collect knee and ankle kinematic data, and a 3-dimensional force plate was utilized to collect knee and ankle kinetic data during the tasks. RESULTS: During the right jumps, KT significantly increased peak knee flexion angle (P = 0.031) compared to NT and significantly decreased peak vertical ground reaction force (P < 0.001, P = 0.001) compared to NT and PT. During the left jumps, KT significantly reduced peak ankle inversion angle (P = 0.022, P < 0.001) and peak ankle inversion moment (P = 0.002, P = 0.001) compared to NT and PT. CONCLUSION: During unanticipated jump maneuvers, KT reduced peak ankle inversion angle, peak vertical ground reaction force, and peak ankle inversion moment and increased peak knee flexion angle in collegiate athletes.

Olanzapine suppresses mPFC activity-norepinephrine releasing to alleviate CLOCK-enhanced cancer stemness under chronic stress.

BACKGROUND: Olanzapine (OLZ) reverses chronic stress-induced anxiety. Chronic stress promotes cancer development via abnormal neuro-endocrine activation. However, how intervention of brain-body interaction reverses chronic stress-induced tumorigenesis remains elusive. METHODS: KrasLSL-G12D/WT lung cancer model and LLC1 syngeneic tumor model were used to study the effect of OLZ on cancer stemness and anxiety-like behaviors. Cancer stemness was evaluated by qPCR, western-blotting, immunohistology staining and flow-cytometry analysis of stemness markers, and cancer stem-like function was assessed by serial dilution tumorigenesis in mice and extreme limiting dilution analysis in primary tumor cells. Anxiety-like behaviors in mice were detected by elevated plus maze and open field test. Depression-like behaviors in mice were detected by tail suspension test. Anxiety and depression states in human were assessed by Hospital Anxiety and Depression Scale (HADS). Chemo-sensitivity of lung cancer was assessed by in vivo syngeneic tumor model and in vitro CCK-8 assay in lung cancer cell lines. RESULTS: In this study, we found that OLZ reversed chronic stress-enhanced lung tumorigenesis in both KrasLSL-G12D/WT lung cancer model and LLC1 syngeneic tumor model. OLZ relieved anxiety and depression-like behaviors by suppressing neuro-activity in the mPFC and reducing norepinephrine (NE) releasing under chronic stress. NE activated ADRB2-cAMP-PKA-CREB pathway to promote CLOCK transcription, leading to cancer stem-like traits. As such, CLOCK-deficiency or OLZ reverses NE/chronic stress-induced gemcitabine (GEM) resistance in lung cancer. Of note, tumoral CLOCK expression is positively associated with stress status, serum NE level and poor prognosis in lung cancer patients. CONCLUSION: We identify a new mechanism by which OLZ ameliorates chronic stress-enhanced tumorigenesis and chemoresistance. OLZ suppresses mPFC-NE-CLOCK axis to reverse chronic stress-induced anxiety-like behaviors and lung cancer stemness. Decreased NE-releasing prevents activation of ADRB2-cAMP-PKA-CREB pathway to inhibit CLOCK transcription, thus reversing lung cancer stem-like traits and chemoresistance under chronic stress.

Breaking the Saturation of Sensitivity for Ultrawide Range Flexible Pressure Sensors by Soft-Strain Effect.

The flexible pressure sensors with a broad pressure range and unsaturated sensitivity are highly desired in practical applications. However, pressure sensors by piezoresistive effect are always limited by the compressibility of sensing layers, resulting in a theoretically decreasing sensitivity of less than 100%. Here, a unique strategy is proposed that utilizes the strain effect, simultaneously achieving a trade-off between a wider pressure detection range and unsaturated sensitivity. Ascribed to the strain effect of sensing layers induced by interlaced microdomes, the sensors possess an increased sensitivity (5.22-70 MPa-1) over an ultrawide pressure range (45 Pa-4.1 MPa), a high-pressure resolution (5 Pa), fast response/recovery time (30/45 ms), and a robust response under a high-pressure loading of 3.5 MPa for more than 5000 cycles. These superior sensing performances allow the sensor to monitor large pressure. The flexible pressure sensor array can assist doctors in restoring the neutral mechanical axis, tracking knee flexion angles, and extracting gait features. Moreover, the flexible sensing array can be integrated into the joint motion surveillance system to map the balance medial-lateral contact forces on the metal compartments in real time, demonstrating the potential for further development into precise medical human-machine interfaces during total knee replacement surgery.

Cation-Triggered Growth of Nanowires for Enhanced Oxygen Evolution Reaction.

The oxygen evolution reaction (OER), which occurs in a variety of energy-related devices, necessitates optimization of the reaction pathways for efficient and scalable deployment. Nevertheless, fully harnessing the advanced structure of synthetic electrocatalysts remains a significant challenge due to the inevitable surface reconstruction process during OER. Here we present an efficient and flexible method to control the surface reconstruction process by engineering an electrolyte containing trace Co2+ cation. This controllable reconstruction process enhances fast charge transfer, facilitates electroactive species transport, and exposes the inner active site, significantly improving the OER kinetics. An impressive 60% increase in current density at an applied potential of 2.2 V (vs RHE) confirms its remarkable contribution to the performance. The identification of cation-triggered reconstruction for the formation of a well-defined surface provides a novel insight into understanding electrolyte engineering and offers a viable pathway to address activity and stable concerns in electrocatalysts.

3MTox: A motif-level graph-based multi-view chemical language model for toxicity identification with deep interpretation.

Toxicity identification plays a key role in maintaining human health, as it can alert humans to the potential hazards caused by long-term exposure to a wide variety of chemical compounds. Experimental methods for determining toxicity are time-consuming, and costly, while computational methods offer an alternative for the early identification of toxicity. For example, some classical ML and DL methods, which demonstrate excellent performance in toxicity prediction. However, these methods also have some defects, such as over-reliance on artificial features and easy overfitting, etc. Proposing novel models with superior prediction performance is still an urgent task. In this study, we propose a motifs-level graph-based multi-view pretraining language model, called 3MTox, for toxicity identification. The 3MTox model uses Bidirectional Encoder Representations from Transformers (BERT) as the backbone framework, and a motif graph as input. The results of extensive experiments showed that our 3MTox model achieved state-of-the-art performance on toxicity benchmark datasets and outperformed the baseline models considered. In addition, the interpretability of the model ensures that the it can quickly and accurately identify toxicity sites in a given molecule, thereby contributing to the determination of the status of toxicity and associated analyses. We think that the 3MTox model is among the most promising tools that are currently available for toxicity identification.

Erdafitinib promotes ferroptosis in human uveal melanoma by inducing ferritinophagy and lysosome biogenesis via modulating the FGFR1/mTORC1/TFEB signaling axis.

Uveal melanoma (UM) is a rare yet lethal primary intraocular malignancy affecting adults. Analysis of data from The Cancer Genome Atlas (TCGA) database revealed that FGFR1 expression was increased in UM tumor tissues and was linked to aggressive behavior and a poor prognosis. This study assessed the anti-tumor effects of Erdafitinib, a selective pan-FGFR inhibitor, in both in vitro and in vivo UM models. Erdafitinib exhibited a robust anti-cancer activity in UM through inducing ferroptosis in the FGFR1-dependent manner. Transcriptomic data revealed that Erdafitinib mediated its anti-cancer effects via modulating the ferritinophagy/lysosome biogenesis. Subsequent research revealed that Erdafitinib exerted its effects by reducing the expression of FGFR1 and inhibiting the activity of mTORC1 in UM cells. Concurrently, it enhanced the dephosphorylation, nuclear translocation, and transcriptional activity of TFEB. The aggregation of TFEB in nucleus triggered FTH1-dependent ferritinophagy, leading to lysosomal activation and iron overload. Conversely, the overexpression of FGFR1 served to mitigate the effects of Erdafitinib on ferritinophagy, lysosome biogenesis, and the activation of the mTORC1/TFEB signaling pathway. In vivo experiments have convincingly shown that Erdafitinib markedly curtails tumor growth in an UM xenograft mouse model, an effect that is closely correlated with a decrease in FGFR1 expression levels. The present study is the first to demonstrate that Erdafitinib powerfully induces ferroptosis in UM by orchestrating the ferritinophagy and lysosome biogenesis via modulating the FGFR1/mTORC1/TFEB signaling. Consequently, Erdafitinib emerges as a strong candidate for clinical trial investigation, and FGFR1 emerges as a novel and promising therapeutic target in the treatment of UM.

Combination of microparticles vaccine with MSI-1436 exerts a strong immune response for hepatocellular carcinoma.

Although tumor cell-derived microparticles (MPs) vaccines have reportedly induced anti-tumor immune reactions for various cancers, the mechanism by which MPs derived from Hepa1-6 cells are taken up by dendritic cells (DCs) and provide the MPs antigens message to CD8+ T cells to exert their anti-hepatocellular carcinoma (HCC) effects remain unclear. Furthermore, the role of MPs in combination with the small-molecule drug MSI-1436, an inhibitor of protein tyrosine phosphatase 1B (PTP1B), in HCC has not yet been reported. In this study, protein mass spectrometry combined with cytology revealed that MPs are mainly taken up by DCs via the clathrin-mediated endocytosis and phagocytosis pathway and localized mainly in lysosomes. High concentration of tumor necrosis factor (TNF)-α and interferon (IFN)-γ were detected in CD8+ T cells stimulated with MPs-loaded DCs. Moreover, MPs combined with MSI-1436 further suppressed the proliferation of HCC cells in C57BL/6 tumor-bearing mice, which was closely correlated with CD4+/CD8+ T cells counts in peripheral blood, spleen, and the tumor microenvironment. Mechanistically, the combination of MPs and MSI-1436 exerts a more powerful anti-HCC effect, which may be related to the further inhibition of the expression of PTP1B. Overall, MPs combined with MSI-1436 exerted stronger anti-tumor effects than MPs or MSI-1436 alone. Therefore, the combination of MPs and MSI-1436 may be a promising means of treating HCC.

[Effect and mechanism of EtOAc extract of Draconis Sanguis onimproving atherosclerosis in ApoE~(-/-) mice].

This study aims to investigate the effect and mechanism of the EtO Ac extract of Draconis Sanguis(DSE) on improving athero sclerosis in ApoE gene knockout(ApoE~(-/-)) mice. The ApoE~(-/-) mice were randomly divided into five groups: control group, mo delgroup, positive group treated with ezetimibe of 5 mg·kg~(-1)(EG), and low(100 mg·kg~(-1)) and high dose(200 mg·kg~(-1)) groups ofDSE. xcept for the control group, all other groups were fed a high-fat diet and administered drugs for 16 successive weeks. After 16 weeks of Eadministration, the body weight, liver, and epididymal fat mass of the mice were measured; the level of blood lipid and the plaquearea of the aortic outflow tract were detected to evaluate the efficacy of DSE in vivo. In addition, in vitro cultures of human umbilical v ein endothelial cell(HUVEC) were conducted. Oxidative stress of endothelial cells was induced by oxidized low-density lipoprot ein(ox-LDL), and the effects of DSE on oxidative stress-related proteins in endothelial cells were examined. The results sho wedthat both doses of DSE significantly improved the epididymal fat mass and index of ApoE~(-/-) mice with atherosclerosis, lowered thelevels of plasma cholesterol, triglyceride, and non-high density lipoprotein cholesterol, and reduced the plaque area of the aortic ou tflow tract. totIn alvitro experiments confirmed that ox-LDL significantly increased the level of lipid peroxidation marker 4-HNE in HUVECcells, confirming that DSE improved the degree of atherosclerotic lesions in ApoE~(-/-) mice by inhibiting ox-LDL-induced oxidative stress in vascular endothelial cells.

The Role of Serine Protease 8 in Mediating Gefitinib Resistance in Non-small Cell Lung Cancer.

OBJECTIVE: This investigation aims to explore the expression levels of serine protease 8 (PRSS8) in gefitinib-resistant Non-Small Cell Lung Cancer (NSCLC) cell lines (PC9/GR) and elucidate its mechanism of action. METHODOLOGY: We measured PRSS8 expression in gefitinib-resistant (PC9/GR) and sensitive (PC9) NSCLC cell lines using Western blot analysis. PRSS8-specific small interfering RNA (PRSS8-siRNA), a recombinant plasmid, and a corresponding blank control were transfected into PC9/GR cells. Subsequently, Western blot analyses were conducted to assess the expression levels of PRSS8, phosphorylated AKT (p-AKT), AKT, phosphorylated mTOR (p-mTOR), mTOR, and various apoptosis-related proteins within each group. Additionally, a cell proliferation assay utilizing Cell Counting Kit-8 (CCK8) was performed on each group treated with gefitinib. RESULT: PRSS8 expression was markedly higher in PC9/GR cells compared to PC9 cells (p < 0.05). The group treated with PRSS8-siRNA exhibited significantly reduced protein expression levels of PRSS8, p-AKT, p-mTOR, ß-catenin, and BCL-2 compared to the control siRNA (Con-siRNA) group, whereas expressions of Caspase9 and Bax were significantly increased. In the untransfected PC9/GR cells, protein expressions of PRSS8, p-AKT, pmTOR, and BCL-2 were significantly elevated when compared with the plasmid-transfected group, which also showed a significant reduction in Bax expression. The proliferative activity of the PRSS8-siRNA group postgefitinib treatment was significantly diminished at 24, 48, and 72 hours in comparison to the Con-siRNA group. CONCLUSION: The findings indicate that PRSS8 contributes to the acquisition of resistance to gefitinib in NSCLC, potentially through regulation of the AKT/mTOR signaling pathway.

A novel prognostic index for extranodal natural killer/T-cell lymphoma in the era of pegaspargase/L-asparaginase.

Aim: This multicenter retrospective study aimed to develop a novel prognostic system for extranodal natural killer/T-cell lymphoma (ENKTL) patients in the era of pegaspargase/L-asparaginase. Materials & methods: A total of 844 newly diagnosed ENKTL patients were included. Results: Multivariable analysis confirmed that Eastern Cooperative Oncology Group performance status, lactate dehydrogenase, Chinese Southwest Oncology Group and Asia Lymphoma Study Group ENKTL (CA) system, and albumin were independent prognostic factors. By rounding up the hazard ratios from four significant variables, a maximum of 7 points were assigned. The model of Huaihai Lymphoma Working Group-Natural killer/T-cell Lymphoma prognostic index (NPI) was identified with four risk groups and the 5-year overall survival was 88.2, 66.7, 54.3 and 30.5%, respectively. Conclusion: Huaihai Lymphoma Working Group-NPI provides a feasible stratification system for patients with ENKTL in the era of pegaspargase/L-asparaginase.

[Box: see text].

Tracking cognitive trajectories in older survivors of COVID-19 up to 2.5 years post-infection.

Emerging evidence suggests that neurological and other post-acute sequelae of COVID-19 can persist beyond or develop following SARS-CoV-2 infection. However, the long-term trajectories of cognitive change after a COVID-19 infection remain unclear. Here we investigated cognitive changes over a period of 2.5 years among 1,245 individuals aged 60 years or older who survived infection with the original SARS-CoV-2 strain in Wuhan, China, and 358 uninfected spouses. We show that the overall incidence of cognitive impairment among older COVID-19 survivors was 19.1% at 2.5 years after infection and hospitalization, evaluated using the Telephone Interview for Cognitive Status-40. Cognitive decline primarily manifested in individuals with severe COVID-19 during the initial year of infection, after which the rate of decline decelerated. Severe COVID-19, cognitive impairment at 6 months and hypertension were associated with long-term cognitive decline. These findings reveal the long-term cognitive trajectory of the disease and underscore the importance of post-infection cognitive care for COVID-19 survivors.

Vanadium Redox Flow Battery: Review and Perspective of 3D Electrodes.

Vanadium redox flow battery (VRFB) has garnered significant attention due to its potential for facilitating the cost-effective utilization of renewable energy and large-scale power storage. However, the limited electrochemical activity of the electrode in vanadium redox reactions poses a challenge in achieving a high-performance VRFB. Consequently, there is a pressing need to assess advancements in electrodes to inspire innovative approaches for enhancing electrode structure and composition. This work categorizes three-dimensional (3D) electrodes derived from materials such as foam, biomass, and electrospun fibers. By employing a flexible electrode design and compositional functionalization, high-speed mass transfer channels and abundant active sites for vanadium redox reactions can be created. Furthermore, the incorporation of 3D electrocatalysts into the electrodes is discussed, including metal-based, carbon-based, and composite materials. The strong interaction and ordered arrangement of these nanocomposites have an influence on the uniformity and stability of the surface charge distribution, thereby enhancing the electrochemical performance of the composite electrodes. Finally, the challenges and perspectives of VRFB are explored through advancements in 3D electrodes, 3D electrocatalysts, and mechanisms. It is hoped that this review will inspire the development of methodology and concept of 3D electrodes in VRFB, so as to promote the future development of scientific energy storage and conversion technology.

Relationship between stress hyperglycemia ratio and prognosis in patients with aneurysmal subarachnoid hemorrhage: a two-center retrospective study.

Previous research have demonstrated that the stress hyperglycemia ratio (SHR) accurately reflects acute hyperglycemic states and correlates with adverse outcomes. This study aims to explore the relationship between SHR and the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH). Patients with aSAH were categorized into four groups based on SHR tertiles. Functional outcomes were evaluated at 12 months using the modified Rankin Scale (mRS), with scores ranging from 0 to 2 indicating a good outcome and 3-6 indicating a poor outcome. The associations between SHR and functional outcomes were analyzed using logistic regression models and restricted cubic spline analysis. A total of 127 patients exhibited poor functional outcomes. Following comprehensive adjustments, those in the highest SHR tertile had a significantly increased risk of poor prognosis compared to those in the lowest tertile (odds ratio [OR], 4.12; 95% confidence interval [CI]: 1.87-9.06). Moreover, each unit increase in SHR was associated with a 7.51-fold increase in the risk of poor prognosis (OR, 7.51; 95% CI: 3.19-17.70). Further analysis using restricted cubic spline confirmed a linear correlation between SHR and poor prognosis (P for nonlinearity = 0.609). Similar patterns were observed across all studied subgroups. Elevated SHR significantly correlates with poor functional prognosis at one year in patients with aSAH, independent of their diabetes status.

Temporary alleviation of MAPK by arbutin alleviates oxidative damage in the retina and ARPE-19 cells.

Dry age-related macular degeneration (AMD) is one of the main diseases that causes blindness in humans, and the number of cases is increasing yearly. However, effective treatments are unavailable, and arbutin (ARB) has been reported to have antioxidant, anti-inflammatory, and anti-aging effects in other age-related diseases. However, whether ARB can be used to treat dry AMD remains unknown. To explore the therapeutic potential and molecular mechanism of arbutin in the treatment of dry AMD. MTT assays, reactive oxygen species (ROS) production assays, flow cytometry assays, qPCR and western blotting were used to assess the impact of ARB on human RPECs induced by H2O2. A transcriptome sequencing assay was used to further explore how ARB acts on human RPECs treated with H2O2. Hematoxylin and eosin (H&E) staining and total antioxidant capacity (T-AOC) assays were used to observe the impact of ARB on mouse retina induced by sodium iodate. ARB counteracted the H2O2-induced reduction in human RPECs viability, ARB reversed H2O2-induced cellular ROS production by increasing the expression of antioxidant-related genes and proteins, ARB also reversed H2O2-induced cell apoptosis by altering the expression of apoptosis-related genes and proteins. Transcriptome sequencing and western blotting showed that ARB reduced ERK1/2 and P-38 phosphorylation to prevent H2O2-induced oxidation damage. The in vivo experiments demonstrated that ARB protected against retinal morphology injury in mice, increased serum T-AOC levels and increased antioxidant oxidase gene expression levels in the mouse retina induced by sodium iodate. We concluded that ARB reversed the H2O2-induced decrease in human RPECs viability through the inhibition of ROS production and apoptosis. The ERK1/2 and P38 MAPK signaling pathways may mediate this process. ARB maintained retinal morphology, increased serum T-AOC level and improved the expression of antioxidant oxidase genes in mice.

A novel frequency 32-tupling ROF system without bit walk-off effect based on MZM with inserting pilot.

A novel scheme for a frequency 32-tupling millimeter wave (MMW) radio over fiber(ROF) system without the bit walk-off effect is proposed. The operation principle and feasibility of our proposed scheme are theoretically analyzed and verified with simulation experiments. The main part of our scheme is a ±16th order sidebands generator (SG) which is constructed by eight Mach-Zehnder modulators (MZM) connected in parallel. In the back-to-back(BTB) transmission case, by properly adjusting the voltage and initial phase of the radio frequency (RF) drive signals of the MZMs, ±16th order sidebands are generated by the SG. In the data transmission case, the data signal is split into two beams first, one of which modulates the RF drive signal with an electrical phase modulator (PM), and the other is amplified by an electrical gainer (EG), and then the two beams are combined into one and used as the RF drive signal of the MZMs. By adjusting the modulation index of the PM and the gain of the EG, the data signal can be modulated only to the +16th order sideband of the output of the SG. The optical carrier from the CW laser is split into two paths, one is sent into the SG, and the other is used as a pilot. The output signal of SG is combined with the pilot signal and is transmitted to the base station(BS) via optical fiber. In BS, the pilot signal is filtered out by an FBG and used as the carrier for uplink for carrier reuse. After filtering out the pilot, the signal from the FBG which is ±16th order sidebands is injected into the photodetector, and a frequency 32-tupling MMW with downlink data is generated. The influence on the bit error rate (BER) and Q factor by the key parameters in the system is also analyzed. Our scheme can not only effectively overcome the bit walk-off effect caused by optical fiber chromatic dispersion, greatly increase the fiber transmission distance, but also effectively improve the performance of the downlink, it has important application prospects in ROF systems.