Novel α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) potentiator LT-102: A promising therapeutic agent for treating cognitive impairment associated with schizophrenia.

AIMS: We aimed to evaluate the potential of a novel selective α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) potentiator, LT-102, in treating cognitive impairments associated with schizophrenia (CIAS) and elucidating its mechanism of action. METHODS: The activity of LT-102 was examined by Ca2+ influx assays and patch-clamp in rat primary hippocampal neurons. The structure of the complex was determined by X-ray crystallography. The selectivity of LT-102 was evaluated by hERG tail current recording and kinase-inhibition assays. The electrophysiological characterization of LT-102 was characterized by patch-clamp recording in mouse hippocampal slices. The expression and phosphorylation levels of proteins were examined by Western blotting. Cognitive function was assessed using the Morris water maze and novel object recognition tests. RESULTS: LT-102 is a novel and selective AMPAR potentiator with little agonistic effect, which binds to the allosteric site formed by the intradimer interface of AMPAR's GluA2 subunit. Treatment with LT-102 facilitated long-term potentiation in mouse hippocampal slices and reversed cognitive deficits in a phencyclidine-induced mouse model. Additionally, LT-102 treatment increased the protein level of brain-derived neurotrophic factor and the phosphorylation of GluA1 in primary neurons and hippocampal tissues. CONCLUSION: We conclude that LT-102 ameliorates cognitive impairments in a phencyclidine-induced model of schizophrenia by enhancing synaptic function, which could make it a potential therapeutic candidate for CIAS.

New role of platelets in schizophrenia: predicting drug response.

Background: Elevated platelet count (PLTc) is associated with first-episode schizophrenia and adverse outcomes in individuals with precursory psychosis. However, the impact of antipsychotic medications on PLTc and its association with symptom improvement remain unclear. Aims: We aimed to investigate changes in PLTc levels following antipsychotic treatment and assess whether PLTc can predict antipsychotic responses and metabolic changes after accounting for other related variables. Methods: A total of 2985 patients with schizophrenia were randomised into seven groups. Each group received one of seven antipsychotic treatments and was assessed at 2, 4 and 6 weeks. Clinical symptoms were evaluated using the positive and negative syndrome scale (PANSS). Additionally, we measured blood cell counts and metabolic parameters, such as blood lipids. Repeated measures analysis of variance was used to examine the effect of antipsychotics on PLTc changes, while structural equation modelling was used to assess the predictive value of PLTc on PANSS changes. Results: PLTc significantly increased in patients treated with aripiprazole (F=6.00, p=0.003), ziprasidone (F=7.10, p<0.001) and haloperidol (F=3.59, p=0.029). It exhibited a positive association with white blood cell count and metabolic indicators. Higher baseline PLTc was observed in non-responders, particularly in those defined by the PANSS-negative subscale. In the structural equation model, PLTc, white blood cell count and a latent metabolic variable predicted the rate of change in the PANSS-negative subscale scores. Moreover, higher baseline PLTc was observed in individuals with less metabolic change, although this association was no longer significant after accounting for baseline metabolic values. Conclusions: Platelet parameters, specifically PLTc, are influenced by antipsychotic treatment and could potentially elevate the risk of venous thromboembolism in patients with schizophrenia. Elevated PLTc levels and associated factors may impede symptom improvement by promoting inflammation. Given PLTc's easy measurement and clinical relevance, it warrants increased attention from psychiatrists. Trial registration number: ChiCTR-TRC-10000934.

Simplified S1 vertebral bone quality score independently predicts proximal junctional kyphosis after surgery for degenerative lumbar scoliosis.

OBJECTIVE: Our study aimed to assess the effectiveness of the simplified S1 vertebral bone quality (VBQ) score in predicting the incidence of proximal junctional kyphosis (PJK) after surgery for degenerative lumbar scoliosis (DLS). METHODS: We reviewed 122 patients with DLS who underwent posterior lumbar decompression and long-segment fusion surgery in our hospital from January 2016 to December 2020. The patients were classified into PJK group and non-PJK group. S1 VBQ scores are determined by signal intensity measurements taken from the mid-sagittal plane of T1-weighted non-contrast MRI. Logistic regression analysis was used to identify factors associated with PJK. Receiver-operating characteristic curve (ROC) analysis was used to evaluate the value of S1 VBQ score in predicting pedicle PJK after DLS. RESULTS: 122 DLS patients (90 females and 32 males) met the inclusion criteria. In addition, 27 patients (22.13%) had PJK at the time of last follow-up. VBQ was higher in PJK patients than non-PJK patients (3.58 ± 0.67 vs. 3.08 ± 0.54, p < 0.001). Preoperatively, patients in the PJK group had a greater TLK than those in the non-PJK group (20.00 ± 6.22 vs. 16.86 ± 5.38, p = 0.011). After surgery, patients in the PJK group had greater TLK (p < 0.001) and PJA (p < 0.001) compared with the non-PJK group. At final FU, patients in the PJK group had greater TK (p = 0.002), TLK (p < 0.001), SVA (p < 0.001), and PJA (p < 0.001) than patients in the non-PJK group (Table 4). In multivariate logistic regression analysis, higher VBQ score (OR 4.565, 95% CI 1.43-14.568, p = 0.010), advanced age (OR 1.119, 95% CI 1.021-1.227, p = 0.016), and larger TLK (OR 1.191, 95% CI 1.041-1.362, p = 0.011) were significant predictors of postoperative PJK in patients with DLS (Table 6). A statistically significant positive correlation existed between VBQ score and PJA change (r = 0.370, p < 0.001). We created ROC curves for VBQ scores as predictors of PJK with a diagnostic accuracy of 72.1% (95% CI 60.15-82.9%.The ideal limit for the VBQ score was 3.205 (sensitivity: 77.8%, specificity: 81.4%). CONCLUSION: To the best of our knowledge, this is the first study to evaluate the effectiveness of the S1 VBQ score in predicting postoperative PJK in DLS. Our study included major risk factors and found that S1 VBQ score was a significant predictor of PJK in patients undergoing DLS surgery. The higher the S1 VBQ score, the higher the probability of PJK.

Histopathological staging and differential diagnosis of marginal zone lymphoma of gastric mucosa-associated lymphoid tissue.

The purpose of this study was to explore the histopathological staging and differential diagnosis of marginal zone lymphoma in gastric mucosa-associated lymphoid tissue (MALT lymphoma). We performed detailed histomorphology and immunohistochemistry investigations as well as genetic testing on endoscopic biopsy and endoscopic mucosal resection specimens from 18 patients with gastric MALT lymphoma. We found that gastric MALT lymphoma typically begins as a small, isolated area outside the lymphoid follicular mantle zone or proliferates in a multifocal, patchy manner, gradually spreads to the interfollicular zone, forming diffuse proliferation, invades the gastric mucosal glands, and infiltrates or proliferates into the center of peripheral reactive lymphoid follicles. Abnormally proliferating lymphocytes invade the surrounding lymphoid follicles, resulting in damage, atrophy, and disappearance of their normal follicles as well as of the gastric mucosa glands, forming diffuse proliferation. Redifferentiation and proliferation lead to the transformation of lymphocytes; that is, MALT transitions into highly invasive lymphoma. Based on our findings in this study, we propose the following five stages in the process of development and progression of gastric MALT lymphoma: the stage of cell proliferation outside the lymphoid follicular mantle zone; the stage of heterogeneous proliferative lymphoepithelial lesion; the stage of reactive lymphoid follicular implantation; the stage of lymphoid follicular clonal proliferation; and the stage of MALT transforming into highly invasive lymphoma. We examined the differential diagnosis of histopathological features at each stage. The clinicopathological staging of gastric MALT lymphoma can help clinicians provide accurate treatment and track malignant cell transformation, thus playing a significant role in controlling its development and progression.

Infection with SARS-CoV-2 can cause pancreatic impairment.

Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of diabetes. Herein, we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates (NHPs) models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 patients. Multi-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and humans. Minor and limited phenotypic and histopathological changes were observed in adult models. Systemic proteomics and metabolomics results indicated metabolic disorders, mainly enriched in insulin resistance pathways, in infected adult NHPs, along with elevated fasting C-peptide and C-peptide/glucose ratio levels. Furthermore, in elder COVID-19 NHPs, SARS-CoV-2 infection causes loss of beta (ß) cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis, activation of α-SMA and aggravated fibrosis consisting of lower collagen in serum, an increase of pancreatic inflammation and stress markers, ICAM-1 and G3BP1, along with more severe glycometabolic dysfunction. In contrast, vaccination maintained glucose homeostasis by activating insulin receptor α and insulin receptor ß. Overall, the cumulative risk of diabetes post-COVID-19 is closely tied to age, suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.

Phase II Trial of Cisplatin, Gemcitabine, and Intensity-Modulated Radiation Therapy for Locally Advanced Vulvar Squamous Cell Carcinoma: NRG Oncology/GOG Study 279.

PURPOSE: To assess efficacy and toxicity of cisplatin (C) and gemcitabine (G) with intensity-modulated radiation therapy (IMRT) in patients with locally advanced vulvar cancer not amenable to surgery. METHODS: Patients enrolled in a single-arm phase II study. Pretreatment inguinal-femoral nodal assessment was performed. Sixty-four Gy IMRT was prescribed to the vulva, with 50-64 Gy delivered to the groins/low pelvis. Radiation therapy (RT) plans were quality-reviewed pretreatment. C 40 mg/m2 and G 50 mg/m2 were administered once per week throughout IMRT. Complete pathologic response (CPR) was the primary end point. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and adverse events were assessed with Common Terminology Criteria for Adverse Events v 4.0. RESULTS: Fifty-seven patients enrolled, of which 52 were evaluable. The median age was 58 years (range, 25-58), and 94% were White. Forty (77%) had stage II or III disease, and all had squamous histology. A median of six chemotherapy cycles (range, 1-8) were received. Eighty-five percent of RT plans were quality-reviewed with 100% compliance to protocol. Seven patients came off trial because of toxicity or patient withdrawal. Of 52 patients available for pathologic assessment, 38 (73% [90% CI, 61 to 83]) achieved CPR. No pelvic exenterations were performed. With a median follow-up of 51 months, the 12-month PFS was 74% (90% CI, 62.2 to 82.7) and the 24-month OS was 70% (90% CI, 57 to 79). The most common grade 3 or 4 adverse events were hematologic toxicity and radiation dermatitis. There was one grade 5 event unlikely related to treatment. CONCLUSION: Weekly C and G concurrent with IMRT sufficiently improved CPR in women with locally advanced vulvar squamous cell carcinoma not amenable to surgical resection.

Exploring Control Authority Preferences in Robotic Arm Assistance for Power Wheelchair Users.

This paper uses mixed methods to explore the preliminary design of control authority preferences for an Assistive Robotic Manipulator (ARM). To familiarize users with an intelligent robotic arm, we perform two kitchen task iterations: one with user-initiated software autonomy (predefined autonomous actions) and one with manual control. Then, we introduce a third scenario, enabling users to choose between manual control and system delegation throughout the task. Results showed that, while manually switching modes and controlling the arm via joystick had a higher mental workload, participants still preferred full joystick control. Thematic analysis indicates manual control offered greater freedom and sense of accomplishment. Participants reacted positively to the idea of an interactive assistive system. Users did not want to ask the system to only assist, by taking over for certain actions, but also asked for situational feedback (e.g., 'How close am I (the gripper)?', 'Is the lid centered over the jug?'). This speaks to a future assistive system that ensures the user feels like they drive the system for the entirety of the task and provides action collaboration in addition to more granular situational awareness feedback.

Conditional survival and annual hazard of death in older patients with esophageal cancer receiving definitive chemoradiotherapy.

BACKGROUND: Definitive chemoradiotherapy is one of the primary treatment modalities for older patients with esophageal cancer (EC). However, the evolution of prognosis over time and the factors affected non-EC deaths remain inadequately studied. We examined the conditional survival and annual hazard of death in older patients with EC after chemoradiotherapy. METHODS: We collected data from patients aged 65 or older with EC registered in the Surveillance, Epidemiology, and End Results database during 2000-2019. Conditional survival was defined as the probability of survival given a specific time survived. Annual hazard of death was defined the yearly event rate. Restricted cubic spline (RCS) analysis identified the association of age at diagnosis with mortality. RESULTS: Among 3739 patients, the 3-year conditional overall survival increased annually by 7-10%. Non-EC causes accounted for 18.8% of deaths, predominantly due to cardio-cerebrovascular diseases. The hazard of death decreased from 40 to 10% in the first 6 years and then gradually increased to 20% in the tenth year. Non-EC causes surpassed EC causes in hazard starting 5 years post-treatment. RCS indicated a consistent increase in death hazard with advancing age, following a linear relationship. The overall cohort was divided into two groups: 65-74 and ≥ 75 years old, with the ≥ 75-year-old group showing poorer survival and earlier onset of non-EC deaths (HR = 1.36, 95% CI: 1.15-1.62, P < 0.001). Patients with early-stage disease (I-II) had higher risks of death from non-EC causes (HR = 0.82, 95% CI: 0.68-0.98, P = 0.035). Tumor histology had no significant impact on non-EC death risk (HR = 1.17, 95% CI: 0.98-1.39, P = 0.081). CONCLUSIONS: Survival probability increases with time for older patients with EC treated with chemoradiotherapy. Clinicians and patients should prioritize managing and preventing age-related comorbidities, especially in older cohorts and those with early-stage disease.

Intercalated PtCo Electrocatalyst of Vanadium Metal Oxide Increases Charge Density to Facilitate Hydrogen Evolution.

Efforts to develop high-performance electrocatalysts for the hydrogen evolution reaction (HER) are of utmost importance in ensuring sustainable hydrogen production. The controllable fabrication of inexpensive, durable, and high-efficient HER catalysts still remains a great challenge. Herein, we introduce a universal strategy aiming to achieve rapid synthesis of highly active hydrogen evolution catalysts using a controllable hydrogen insertion method and solvothermal process. Hydrogen vanadium bronze HxV2O5 was obtained through controlling the ethanol reaction rate in the oxidization process of hydrogen peroxide. Subsequently, the intermetallic PtCoVO supported on two-dimensional graphitic carbon nitride (g-C3N4) nanosheets was prepared by a solvothermal method at the oil/water interface. In terms of HER performance, PtCoVO/g-C3N4 demonstrates superior characteristics compared to PtCo/g-C3N4 and PtCoV/g-C3N4. This superiority can be attributed to the notable influence of oxygen vacancies in HxV2O5 on the electrical properties of the catalyst. By adjusting the relative proportions of metal atoms in the PtCoVO/g-C3N4 nanomaterials, the PtCoVO/g-C3N4 nanocomposites show significant HER overpotential of η10 = 92 mV, a Tafel slope of 65.21 mV dec-1, and outstanding stability (a continuous test lasting 48 h). The nanoarchitecture of a g-C3N4-supported PtCoVO nanoalloy catalyst exhibits exceptional resistance to nanoparticle migration and corrosion, owing to the strong interaction between the metal nanoparticles and the g-C3N4 support. Pt, Co, and V simultaneous doping has been shown by Density Functional Theory (DFT) calculations to enhance the density of states (DOS) at the Fermi level. This augmentation leads to a higher charge density and a reduction in the adsorption energy of intermediates.

Molecular strategies of the pygmy grasshopper Eucriotettix oculatus adapting to long-term heavy metal pollution.

To study the heavy metal accumulation and its impact on insect exterior and chromosome morphology, and reveal the molecular mechanism of insects adapting to long-term heavy metal compound pollution habitats, this study, in the Diaojiang river basin, which has been polluted by heavy metals(HMs) for nearly a thousand years, two Eucriotettix oculatus populations was collected from mining and non-mining areas. It was found that the contents of 7 heavy metals (As, Cd, Pb, Zn, Cu, Sn, Sb) in E. oculatus of the mining area were higher than that in the non-mining 1-11 times. The analysis of morphology shows that the external morphology, the hind wing type and the chromosomal morphology of E. oculatus are significant differences between the two populations. Based on the heavy metal accumulation，morphological change, and stable population density, it is inferred that the mining area population has been affected by heavy metals and has adapted to the environment of heavy metals pollution. Then, by analyzing the transcriptome of the two populations, it was found that the digestion, immunity, excretion, endocrine, nerve, circulation, reproductive and other systems and lysosomes, endoplasmic reticulum and other cell structure-related gene expression were suppressed. This shows that the functions of the above-mentioned related systems of E. oculatus are inhibited by heavy metal stress. However, it has also been found that through the significant up-regulation of genes related to the above system, such as ATP2B, pepsin A, ubiquitin, AQP1, ACOX, ATPeV0A, SEC61A, CANX, ALDH7A1, DLD, aceE, Hsp40, and catalase, etc., and the down-regulation of MAPK signalling pathway genes, can enhanced nutrient absorption, improve energy metabolism, repair damaged cells and degrade abnormal proteins, maintain the stability of cells and systems, and resist heavy metal damage so that E. oculatus can adapt to the environment of heavy metal pollution for a long time.

Identify Potential Causal Relationships Between Cortical Thickness, Mismatch Negativity, Neurocognition, and Psychosocial Functioning in Drug-Naïve First-Episode Psychosis Patients.

BACKGROUND: Cortical thickness (CT) alterations, mismatch negativity (MMN) reductions, and cognitive deficits are robust findings in first-episode psychosis (FEP). However, most studies focused on medicated patients, leaving gaps in our understanding of the interrelationships between CT, MMN, neurocognition, and psychosocial functioning in unmedicated FEP. This study aimed to employ multiple mediation analysis to investigate potential pathways among these variables in unmedicated drug-naïve FEP. METHODS: We enrolled 28 drug-naïve FEP and 34 age and sex-matched healthy controls. Clinical symptoms, neurocognition, psychosocial functioning, auditory duration MMN, and T1 structural magnetic resonance imaging data were collected. We measured CT in the superior temporal gyrus (STG), a primary MMN-generating region. RESULTS: We found a significant negative correlation between MMN amplitude and bilateral CT of STG (CT_STG) in FEP (left: r = -.709, P < .001; right: r = -.612, P = .008). Multiple mediation models revealed that a thinner left STG cortex affected functioning through both direct (24.66%) and indirect effects (75.34%). In contrast, the effects of the right CT_STG on functioning were mainly mediated through MMN and neurocognitive pathways. CONCLUSIONS: Bilateral CT_STG showed significant association with MMN, and MMN plays a mediating role between CT and cognition. Both MMN alone and its interaction with cognition mediated the effects of structural alterations on psychosocial function. The decline in overall function in FEP may stem from decreased CT_STG, leading to subsequent MMN deficits and neurocognitive dysfunction. These findings underline the crucial role of MMN in elucidating how subtle structural alterations can impact neurocognition and psychosocial function in FEP.

Ferroptosis mechanisms and regulations in cardiovascular diseases in the past, present, and future.

Cardiovascular diseases (CVDs) are the main diseases that endanger human health, and their risk factors contribute to high morbidity and a high rate of hospitalization. Cell death is the most important pathophysiology in CVDs. As one of the cell death mechanisms, ferroptosis is a new form of regulated cell death (RCD) that broadly participates in CVDs (such as myocardial infarction, heart transplantation, atherosclerosis, heart failure, ischaemia/reperfusion (I/R) injury, atrial fibrillation, cardiomyopathy (radiation-induced cardiomyopathy, diabetes cardiomyopathy, sepsis-induced cardiac injury, doxorubicin-induced cardiac injury, iron overload cardiomyopathy, and hypertrophic cardiomyopathy), and pulmonary arterial hypertension), involving in iron regulation, metabolic mechanism and lipid peroxidation. This article reviews recent research on the mechanism and regulation of ferroptosis and its relationship with the occurrence and treatment of CVDs, aiming to provide new ideas and treatment targets for the clinical diagnosis and treatment of CVDs by clarifying the latest progress in CVDs research.

Association between dietary inflammatory index and cognitive impairment among American elderly: a cross-sectional study.

Background: It has been shown that inflammation may be associated with cognitive impairment (CI). Diet modulates inflammation. However, there is currently a scarcity of epidemiological studies exploring the connection between the inflammatory potential of diet and CI. The objective was to investigate the correlation between the dietary inflammatory index (DII) and cognitive impairment in older adults in the United States. Methods: The present investigation utilized a cross-sectional dataset obtained from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. Dietary intake data was used to calculate DII scores, which were then used to categorize participants into quartiles. Participants' cognitive function was assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Individuals who scored in the lowest quartile on any of these tests were classified as exhibiting low cognitive performance. The association between DII and cognitive impairment was investigated by multivariate logistic regression, smooth curve fitting, and subgroup analysis. Results: A total of 947 older adults were enrolled in the study. Following the adjustment of confounding variables, DII scores exhibited a significant and positive correlation with low cognitive performance, as measured by AFT (OR 1.15, 95% CI 1.02-1.28, p = 0.02) and the DSST (OR 1.38, 95% CI 1.13-1.68, p = 0.004). Compared with the lowest quartile of DII, the highest weighted odds ratio of cognitive impairment based on AFT was observed in the fourth quartile group (OR 1.89, 95% CI 1.05-3.38, p = 0.03). Similarly, a comparable pattern was evident in DSST (OR 4.30, 95% CI 1.85-9.98, p = 0.003). Additionally, the smooth curve fitting results showed a nonlinear relationship between DII and cognitive decline evaluated by DSST (p for nonlinearity = 0.016). No interaction effects between cognitive impairment and age or gender were observed in relation to all cognitive test scores. Conclusion: This research reveals a positive link between diet with higher inflammatory potential and cognitive decline among elderly individuals in America. However, additional studies on dietary interventions are necessary to explore the cause-and-effect relationship.

Hydrogen-Bond-Network Breakdown Boosts Selective CO2 Photoreduction by Suppressing H2 Evolution.

Conventional strategies for highly efficient and selective CO2 photoreduction focus on the design of catalysts and cocatalysts. In this study, we discover that hydrogen bond network breakdown in reaction system can suppress H2 evolution, thereby improving CO2 photoreduction performance. Photosensitive poly(ionic liquid)s are designed as photocatalysts owing to their strong hydrogen bonding with solvents. The hydrogen bond strength is tuned by solvent composition, thereby effectively regulating H2 evolution (from 0 to 12.6 mmol g-1 h-1). No H2 is detected after hydrogen bond network breakdown with trichloromethane or tetrachloromethane as additives. CO production rate and selectivity increase to 35.4 mmol g-1 h-1 and 98.9 % with trichloromethane, compared with 0.6 mmol g-1 h-1 and 26.2 %, respectively, without trichloromethane. Raman spectroscopy and theoretical calculations confirm that trichloromethane broke the systemic hydrogen bond network and subsequently suppressed H2 evolution. This hydrogen bond network breakdown strategy may be extended to other catalytic reactions involving H2 evolution.

Evaluation of the ecological status of shallow-water coral reefs in China using a novel method and identification of environmental factors for coral decline.

Coral reefs worldwide have faced extensive damage due to natural catastrophes and anthropogenic disturbances.The decline can cause their widespread collapse and an inability to recover from natural disturbances, highlighting the urgent need for their protection. This study conducted an extensive ecological condition assessment of seven coral reef regions in China's offshore. Our findings revealed the presence of 204 species of scleractinian corals belonging to 16 families. Massive corals were the predominant reef-building corals in all regions. The degradation of coral reef ecosystems was apparent in the present compared to historical reef conditions. The ecosystem suffered varying degrees of damage in surveyed regions according to a novel assessment approach, impling more effective measures should be taken to mitigate the local pressures. Our research establishes a baseline for understanding the status of coral reefs that can be used in future and provides a crucial foundation to designate protective zones for their conservation.

Improved effectiveness of X-PDT against human triple-negative breast cancer cells through the use of liposomes co-loaded with protoporphyrin IX and perfluorooctyl bromide.

In this study, we utilized X-ray-induced photodynamic therapy (X-PDT) against triple-negative breast cancer (TNBC) cells. To achieve this, we developed a liposome delivery system that co-loaded protoporphyrin IX (PPIX) and perfluorooctyl bromide (PFOB) in a rational manner. Low-dose X-ray at 2 Gy was employed to activate PPIX for the generation of reactive oxygen species (ROS), and the co-loading of PFOB provided additional oxygen to enhance ROS production. The resulting highly toxic ROS effectively induced cell death in TNBC. In vitro X-PDT effects, including intracellular ROS generation, cell viability, and apoptosis/necrosis assays in TNBC cells, were thoroughly investigated. Our results indicate that the nanocarriers effectively induced X-PDT effects with very low-dose radiation, making it feasible to damage cancer cells. This suggests the potential for the effective utilization of X-PDT in treating hypoxic cancers, including TNBC, with only a fraction of conventional radiotherapy.

A Fully Integrated Handheld Electrochemical Sensing Platform for Point-of-Care Testing of Escherichia coli O157:H7.

Fully integrated devices that enable full functioning execution without or with minimum external accessories or equipment are deemed to be one of the most desirable and ultimate objectives for modern device design and construction. Escherichia coli O157:H7 (E. coli O157:H7) is often linked to outbreaks caused by contaminated water and food. However, the sensors that are currently used for point-of-care E. coli O157:H7 (E. coli O157:H7) detection are often large and cumbersome. Herein, we demonstrate the first example of a handheld and pump-free fully integrated electrochemical sensing platform with the capability to point-of-care test E. coli O157:H7 in the actual samples of E. coli O157:H7-spiked tap water and E. coli O157:H7-spiked watermelon juice. This platform was made possible by overcoming major engineering challenges in the seamless integration of a microfluidic module for pump-free liquid sample collection and transportation, a sensing module for efficient E. coli O157:H7 testing, and an electronic module for automatically converting and wirelessly transmitting signals into a single and compact electrochemical sensing platform that retains its inimitable stand-alone, handheld, pump-free, and cost-effective feature. Although our primary emphasis in this study is on detecting E. coli O157:H7, this pump-free fully integrated handheld electrochemical sensing platform may also be used to monitor other pathogens in food and water by including specific antipathogen antibodies.

The volume of gray matter mediates the relationship between glucolipid metabolism and neurocognition in first-episode, drug-naïve patients with schizophrenia.

We aimed to examine the hypotheses that glucolipid metabolism is linked to neurocognition and gray matter volume (GMV) and that GMV mediates the association of glucolipid metabolism with neurocognition in first-episode, drug-naïve (FEDN) patients with schizophrenia. Parameters of glucolipid metabolism, neurocognition, and magnetic resonance imaging were assessed in 63 patients and 31 controls. Compared to controls, patients exhibited higher levels of fasting glucose, triglyceride, and insulin resistance index, lower levels of cholesterol and high-density lipoprotein cholesterol, poorer neurocognitive functions, and decreased GMV in the bilateral insula, left middle occipital gyrus, and left postcentral gyrus. In the patient group, triglyceride levels and the insulin resistance index exhibited a negative correlation with Rapid Visual Information Processing (RVP) mean latency, a measure of attention within the Cambridge Neurocognitive Test Automated Battery (CANTAB), while showing a positive association with GMV in the right insula. The mediation model revealed that triglyceride and insulin resistance index had a significant positive indirect (mediated) influence on RVP mean latency through GMV in the right insula. Glucolipid metabolism was linked to both neurocognitive functions and GMV in FEDN patients with schizophrenia, with the effect pattern differing from that observed in chronic schizophrenia or schizophrenia comorbid with metabolic syndrome. Moreover, glucolipid metabolism might indirectly contribute to neurocognitive deficits through the mediating role of GMV in these patients.