Metabolic and protein expression responses of Shewanella baltica in golden pomfret broths to slightly acidic electrolysed water.

Shewanella baltica is a specific spoilage organism of golden pomfret. This study aims to explore the antibacterial mechanism of slightly acidic electrolysed water (SAEW) against S. baltica (strains ABa4, ABe2 and BBe1) in golden pomfret broths by metabolomics, proteomics and bioinformatics analyses. S. baltica was decreased by at least 3.94 log CFU/mL after SAEW treatment, and strain ABa4 had the highest resistance. Under SAEW stress, amino acids and organic acids in S. baltica decreased, and nucleotide related compounds degraded. Furthermore, 100 differentially expressed proteins (DEPs) were identified. Most DEPs of strains ABe2 and BBe1 were down-regulated, while some DEPs of strain ABa4 were up-regulated, especially those oxidative stress related proteins. These results suggest that the modes of SAEW against S. baltica can be traced to the inhibition of amino acid, carbon, nucleotide and sulphur metabolisms, and the loss of functional proteins for temperature regulation, translation, motility and protein folding.

Interleukin signaling in the regulation of natural killer cells biology in breast cancer.

In the field of breast cancer treatment, the immunotherapy involving natural killer (NK) cells is increasingly highlighting its distinct potential and significance. Members of the interleukin (IL) family play pivotal regulatory roles in the growth, differentiation, survival, and apoptosis of NK cells, and are central to their anti-tumor activity. These cytokines enhance the ability of NK cells to recognize and eliminate tumor cells by binding to specific receptors and activating downstream signaling pathways. Furthermore, interleukins do not function in isolation; the synergistic or antagonistic interactions between different interleukins can drive NK cells toward various functional pathways, ultimately leading to diverse outcomes for breast cancer patients. This paper reviews the intricate relationship between NK cells and interleukins, particularly within the breast cancer tumor microenvironment. Additionally, we summarize the latest clinical studies and advancements in NK cell therapy for breast cancer, along with the potential applications of interleukin signaling in these therapies. In conclusion, this article underscores the critical role of NK cells and interleukin signaling in breast cancer treatment, providing valuable insights and a significant reference for future research and clinical practice.

The High Estradiol Environment after IVF Causes the Increased Risk of Glucose Metabolic Dysfunction in Offspring.

CONTEXT: Assisted reproductive technology (ART) is associated with increased metabolic risks in offspring. The effect of high maternal estradiol (E2) levels during early pregnancy on the glucose metabolism of offspring remains unclear. OBJECTIVE: To evaluate glucose metabolism in in vitro fertilization (IVF)-conceived children and assess whether high E2 exposure during early pregnancy is associated with metabolic alterations. DESIGN/SETTING/PARTICIPANTS: This retrospective analysis included 500 singletons aged 3-10 years born after fresh embryo transfer (ET) (n=200), frozen ET (n=100), and natural conception (NC) (n=200) from a university hospital. METHODS: Children underwent anthropometric measurements and examinations for fasting glucose, insulin, and lipid levels. A mouse model of high E2 exposure during early pregnancy was established to study glucose and insulin tolerance, and insulin secretion. RESULTS: Compared with NC, children born after fresh ET showed higher fasting glucose/insulin levels, increased insulin resistance, and higher incidence of impaired fasting glucose, which might be associated with a higher maternal E2 levels. Frozen ET showed intermediate results. In mice, offspring exposed to high E2 levels during gestation exhibited impaired glucose/insulin tolerance and defects in insulin secretion. CONCLUSION: High maternal E2 levels in early pregnancy are associated with altered glucose metabolism and increased metabolic risks in IVF-conceived children. Further studies are needed to elucidate the underlying mechanisms.

Long-persistent luminescence by host-guest Förster resonance energy transfer.

In this study, Förster resonance energy transfer (FRET) is harnessed to construct a novel stimulus-responsive long-persistent luminescence (LPL) system. Two organic molecules, DPSD and DPOD, were initially found to have no afterglow under ambient conditions, but exhibited prolonged afterglow upon friction with paper, showing a significantly promoted transition of triplet excited states. Substituting paper with α-cellulose (the main composition of paper) reveals a novel host-guest long afterglow system and allows for a deeper investigation of the above paper-promoted LPL phenomenon. The activation of the LPL effect was achieved by matrixing these components through a grinding process, capitalizing on the efficient FRET from the host to the guest owing to the appropriate energy level match, and the robust intersystem crossing (ISC) capability of the guest. This model presents a new matrix strategy to achieve efficient LPL by a facile, low cost and easy-to-handle process. Furthermore, we successfully implemented anti-counterfeiting, encryption and decryption, decoration, and water/heat stimulus-responsive applications of the obtained materials. These advancements bring LPL materials one step closer to practical commercialization.

Rapid preparation of anti-retrogradation starch by choline chloride based deep eutectic solvents: A comparative study.

Legumes are a widespread and cheap source of starch. However, legume starches are prone to retrogradation in applications. Therefore, enhancing the resistance to retrogradation is important to ensure the quality of starch products. In this study, the effects of amines, alcohols, and carboxylic acids deep eutectic solvents (DESs) on the retrogradation properties of pea starch (PS) were investigated. The results showed that the starches treated with carboxylic acid DESs for only 30 min exhibited low paste viscosity, high paste clarity and anti-retrogradation. The carboxylic acid DESs treatment resulted in holes or cracks appearing on the starch surface, a decrease in molecular ordering, relative crystallinity, and amylose content. The thermal enthalpy of starch as well as the pasting viscosity were substantially reduced after the treatment. The paste clarity and the resistance to retrogradation were significantly improved. Conversely, the structure, pasting and retrogradation properties of starch treated with amine and alcohol DESs exhibited only slight differences compared to PS. The carboxylic acid DESs took a short time for the starch modification, and the modified starch paste with low viscosity, high clarity, and resistance to retrogradation. The study could provide an environmentally-friendly and cost-effective method for the preparation of starch with well anti-retrogradation properties.

Short-term efficiency of plasma exchange in combination with immunosuppressants and/or biologics in the treatment of idiopathic inflammatory myopathy with rapidly progressive interstitial lung disease: a systematic review and meta-analysis.

OBJECTIVE: Rapidly progressive interstitial lung disease (RP-ILD) is a frequent and serious manifestation of idiopathic inflammatory myopathy (IIM) associated with poor outcomes. Plasma exchange (PE) can quickly remove pathogenic substances from the blood. Therefore, PE may be efficacious in IIM patients who have elevated levels of autoantibodies, cytokines and chemokines, fighting for time for immunosuppressive therapy. However, the value of adding PE to immunosuppressants remains unclear. The purpose of this study was to determine the short-term outcomes, including the survival rate at 6 months and change of the laboratory data, of PE in combination with immunosuppressants and/or biologics in the treatment of IIM-RP-ILD. METHODS: We searched PubMed, Embase and Cochrane Library to find reports of interest published from inception to March 4, 2024. STATA 15.1 was used for data analysis. A fixed or random-effects model with inverse-variance weighting was used to estimate the pooled risk ratio (RR) and 95% confidence interval (CI). RESULTS: Two hundred and thirty studies were identified. Eleven studies, including five retrospective cohort studies, four case-control studies and two case series, were included. PE was performed on 114 patients. The survival rate at 6 months was 80% (95%CI = 64%-92%), with moderate heterogeneity (I2=63.45%, p < 0.05). Moreover, the 6-month survival rate was significantly better in the PE group than in the non-PE group (RR, 1.34; 95% CI = 1.05-1.71, I2=30.7%; p = 0.194). ILD-related serum markers, including ferritin, KL-6 and anti-MDA-5 antibody titres, were significantly suppressed by a series of PE treatments (p < 0.05). CONCLUSION: The application of PE therapy plus treatment with corticosteroids, immunosuppressants and/or biologics was effective for patients with IIM-RP-ILD. PE may have additional supportive effect in intractable disease.

Systems biology approach for enhancing limonene yield by re-engineering Escherichia coli.

Engineered microorganisms have emerged as viable alternatives for limonene production. However, issues such as low enzyme abundance or activities, and regulatory feedback/forward inhibition may reduce yields. To understand the underlying metabolism, we adopted a systems biology approach for an engineered limonene-producing Escherichia coli strain K-12 MG1655. Firstly, we generated time-series metabolomics data and, secondly, developed a dynamic model based on enzyme dynamics to track the native metabolic networks and the engineered mevalonate pathway. After several iterations of model fitting with experimental profiles, which also included 13C-tracer studies, we performed in silico knockouts (KOs) of all enzymes to identify bottleneck(s) for optimal limonene yields. The simulations indicated that ALDH/ADH (aldehyde dehydrogenase/alcohol dehydrogenase) and LDH (lactate dehydrogenase) suppression, and HK (hexokinase) enhancement would increase limonene yields. Experimental confirmation was achieved, where ALDH-ADH and LDH KOs, and HK overexpression improved limonene yield by 8- to 11-fold. Our systems biology approach can guide microbial strain re-engineering for optimal target production.

Trajectories of perioperative nutritional status in patients with pancreatic tumor after surgery in six months.

PURPOSE: To characterize subgroups with similar nutritional status trajectories during the 6-month period after pancreatectomy and to identify demographic and clinical characteristics influencing changes in nutritional status in each subgroup. METHODS: This longitudinal prospective study recruited 112 patients with newly diagnosed pancreatic tumor from an outpatient pancreatic surgical department of a medical center in northern Taiwan between September 2016 and April 2019. Patients completed a demographic and clinical characteristics form, the Mini Nutritional Assessment scale, and the Symptom Severity Scale prior to surgery (T0), 3 months after surgery (T1), and 6 months after surgery (T2). Latent class growth analysis was used to investigate the trajectories of nutritional status. Generalized estimating equations were used to identify significant factors influencing each trajectory. RESULTS: Two latent groups of nutritional status trajectories were identified. Among 112 patients, 74.11% and 25.89% were classified as having high and low nutritional status trajectories, respectively. High nutritional status was significantly negatively correlated with changes in symptom severity. Low nutritional status was significantly negatively correlated with older age, surgical complications, and changes in symptom severity. CONCLUSIONS: Symptom severity has the most significant negative effect on perioperative nutritional status. Older age and surgical complications exert negative effects on perioperative nutritional status among patients with low nutritional status. These findings emphasize the need for nurses to identify at-risk individuals and provide individualized nutritional care to improve nutritional status in this population. CLINICAL TRIALS REGISTRATION: This study was registered on ClinicalTrials.gov (trial registration number: NCT02900677; approved date: September 14th, 2016). Link: https://clinicaltrials.gov/ct2/show/NCT02900677.

Recent advances in studies on FtsZ inhibitors.

With the abuse of antibiotics, multidrug resistant strains continue to emerge and spread rapidly. Therefore, there is an urgent need to develop new antimicrobial drugs. As a highly conserved cell division protein in bacteria, filamenting temperature-sensitive mutant Z (FtsZ) has been identified as a potential antimicrobial target. This paper reviews the structure, function, and action mechanism of FtsZ and a variety of natural and synthetic compounds targeting FtsZ, including 3-MBA derivatives, taxane derivatives, cinnamaldehyde, curcumin, quinoline and quinazoline derivatives, aromatic compounds, purpurin, and totarol. From these studies, FtsZ has a clear supporting role in the field of antimicrobial drug discovery. The urgent need and interest of antibacterial drugs will contribute to the discovery of new clinical drugs targeting FtsZ.

Burden of non-communicable diseases attributable to high temperature in a changing climate from 1990 to 2019: a global analysis.

BACKGROUND: With global climate change, the health threats of ambient high temperature have received widespread attention. However, latest spatio-temporal patterns of the non-communicable diseases (NCDs) burden attributable to high temperature have not been systematically reported. We aimed to analyze vulnerable areas and populations based on a detailed profile for the NCDs burden attributable to high temperature globally. METHODS: We obtained data from the Global Burden of Diseases (GBD) Study (2019) to describe the temporal and spatial patterns of NCDs burden attributable to high temperature globally from 1990-2019. Then we analyzed the differences by region, sex, and socio-demographic index (SDI). Finally, the age­period­cohort (APC) model was utilized to explore the age, period, and cohort effects of NCDs mortality caused by high temperature. RESULTS: In 2019, the number of deaths and Disability-adjusted life years (DALYs) from high-temperature-related NCDs was about 150,000 and 3.4 million globally, of which about 70% were in South Asia and North Africa and Middle East, and the burden was higher in men. Among 204 countries and territories, the highest age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) were observed in Oman and United Arab Emirates, respectively. The global burden showed an upward trend from 1990 to 2019, with an EAPC of 3.66 (95%CI: 3.14-4.18) for ASMR and 3.68 (95%CI: 3.16-4.21) for ASDR. Cardiovascular diseases were the main contributors to the global burden of high-temperature-related NCDs in 2019. The age and period effect in APC model showed an increasing trend globally. There was a significant negative correlation between SDI and both ASMR (r = -0.17) and ASDR (r = -0.20) from 1990 to 2019. CONCLUSION: There was an increasing trend of the global burden of high-temperature-related NCDs. The burden was likely to be higher in males and the elderly, as well as in countries and regions with less economically and socially developed and in tropical climates. Surveillance and prevention measures should be implemented with a focus on these vulnerable areas and susceptible populations.

Acute necrotizing encephalopathy in adult patients with influenza: a case report and review of the literature.

The neurological complications of influenza affect mainly the pediatric Asian population. In the category of influenza-associated encephalopathy, acute necrotizing encephalopathy (ANE) is a rapidly progressive and fulminant brain disorder associated with significant neurological sequelae and mortality. To date, only a few adult cases of influenza-associated ANE have been reported. We describe a 44-year-old woman who presented with rapid progression of consciousness impairment and recurrent generalized convulsions. Influenza was diagnosed three days prior to presentation, and infection with influenza A (H3N2) pdm09 was subsequently confirmed. A diagnosis of ANE was made based on the presence of characteristic brain MRI findings, the exclusion of central nervous system infection, and an elevated serum interleukin-6 level. Pulse steroid therapy followed by tocilizumab was initiated, which led to clinical stabilization and improvement. Genetic testing revealed that the patient carried heterozygous human leukocyte antigen DQB1 03:03 and DRB1 09:01 genotypes. An analysis of the adult cases of influenza-associated ANE in the literature and the present case revealed a wide range of ages (22-71 years), a short interval (median 3 days) between the clinical onset of influenza and ANE, and a high overall mortality rate (32%). The thalamus was the most frequent (91%) location of the lesions. Our report highlights the importance of identifying this devastating but treatable neurological complication of influenza in adults, especially those of Asian descent. As a cytokine storm is the most accepted pathogenic mechanism for ANE, cytokine-directed therapies may be promising treatments for which further investigation is warranted.

Unipolar quantum optoelectronics for high speed direct modulation and transmission in 8-14 µm atmospheric window.

The large mid-infrared (MIR) spectral region, ranging from 2.5 µm to 25 µm, has remained under-exploited in the electromagnetic spectrum, primarily due to the absence of viable transceiver technologies. Notably, the 8-14 µm long-wave infrared (LWIR) atmospheric transmission window is particularly suitable for free-space optical (FSO) communication, owing to its combination of low atmospheric propagation loss and relatively high resilience to turbulence and other atmospheric disturbances. Here, we demonstrate a direct modulation and direct detection LWIR FSO communication system at 9.1 µm wavelength based on unipolar quantum optoelectronic devices with a unprecedented net bitrate exceeding 55 Gbit s-1. A directly modulated distributed feedback quantum cascade laser (DFB-QCL) with high modulation efficiency and improved RF-design was used as a transmitter while two high speed detectors utilizing meta-materials to enhance their responsivity are employed as receivers; a quantum cascade detector (QCD) and a quantum-well infrared photodetector (QWIP). We investigate system tradeoffs and constraints, and indicate pathways forward for this technology beyond 100 Gbit s-1 communication.

Gaps in the Global Regulatory Frameworks for the Use of Artificial Intelligence (AI) in the Healthcare Services Sector and Key Recommendations.

Artificial Intelligence (AI) has shown remarkable potential to revolutionise healthcare by enhancing diagnostics, improving treatment outcomes, and streamlining administrative processes. In the global regulatory landscape, several countries are working on regulating AI in healthcare. There are five key regulatory issues that need to be addressed: (i) data security and protection-measures to cover the "digital health footprints" left unknowingly by patients when they access AI in health services; (ii) data quality-availability of safe and secure data and more open database sources for AI, algorithms, and datasets to ensure equity and prevent demographic bias; (iii) validation of algorithms-mapping of the explainability and causability of the AI system; (iv) accountability-whether this lies with the healthcare professional, healthcare organisation, or the personified AI algorithm; (v) ethics and equitable access-whether fundamental rights of people are met in an ethical manner. Policymakers may need to consider the entire life cycle of AI in healthcare services and the databases that were used for the training of the AI system, along with requirements for their risk assessments to be publicly accessible for effective regulatory oversight. AI services that enhance their functionality over time need to undergo repeated algorithmic impact assessment and must also demonstrate real-time performance. Harmonising regulatory frameworks at the international level would help to resolve cross-border issues of AI in healthcare services.

The dynamic reconfiguration of the functional network during episodic memory task predicts the memory performance.

Episodic memory is essential for forming and retaining personal experiences, representing a fundamental aspect of human cognition. Traditional studies of episodic memory have typically used static analysis methods, viewing the brain as an unchanging entity and overlooking its dynamic properties over time. In this study, we utilized dynamic functional connectivity analysis on fMRI data from healthy adults performing an episodic memory task. We quantified integration and recruitment metrics and examined their correlation with memory performance using Pearson correlation. During encoding, integration across the entire brain, especially within the frontoparietal subnetwork, was significantly correlated with memory performance. During retrieval, recruitment becomes significantly associated with memory performance in visual subnetwork, somatomotor subnetwork, and ventral attention subnetwork. At the nodal level, a significant negative correlation was observed between memory scores and integration of the anterior cingulate gyrus, precentral gyrus, and inferior frontal gyrus within the frontoparietal network during encoding task. During retrieval task, a significant negative correlation was found between memory scores and recruitment in the left progranular cortex and right transverse gyral ventral, whereas positive correlations were seen in the right posterior inferior temporal, left middle temporal, right frontal operculum, and left operculum nodes. Moreover, the dynamic reconfiguration of the functional network was predictive of predict memory performance, as demonstrated by a significant correlation between actual and predicted memory scores. These findings advance our understanding network mechanisms underlying memory processes and developing intervention approaches for memory-related disorders as they shed light on critical factors involved in cognitive processes and provide a deeper understanding of the underlying mechanisms driving cognitive function.

Review of pharmacogenetics of antiseizure medications: focusing on genetic variants of mechanistic targets.

Antiseizure medications (ASMs) play a central role in seizure management, however, unpredictability in the response to treatment persists, even among patients with similar seizure manifestations and clinical backgrounds. An objective biomarker capable of reliably predicting the response to ASMs would profoundly impact epilepsy treatment. Presently, clinicians rely on a trial-and-error approach when selecting ASMs, a time-consuming process that can result in delays in receiving alternative non-pharmacological therapies such as a ketogenetic diet, epilepsy surgery, and neuromodulation therapies. Pharmacogenetic studies investigating the correlation between ASMs and genetic variants regarding their mechanistic targets offer promise in predicting the response to treatment. Sodium channel subunit genes have been extensively studied along with other ion channels and receptors as targets, however, the results have been conflicting, possibly due to methodological disparities including inconsistent definitions of drug response, variations in ASM combinations, and diversity of genetic variants/genes studied. Nonetheless, these studies underscore the potential effect of genetic variants on the mechanism of ASMs and consequently the prediction of treatment response. Recent advances in sequencing technology have led to the generation of large genetic datasets, which may be able to enhance the predictive accuracy of the response to ASMs.

Accurately identifying positive and negative regulation of apoptosis using fusion features and machine learning methods.

Apoptotic proteins play a crucial role in the apoptosis process, ensuring a balance between cell proliferation and death. Thus, further elucidating the regulatory mechanisms of apoptosis will enhance our understanding of their functions. However, the development of computational methods to accurately identify positive and negative regulation of apoptosis remains a significant challenge. This work proposes a machine learning model based on multi-feature fusion to effectively identify the roles of positive and negative regulation of apoptosis. Initially, we constructed a reliable benchmark dataset containing 200 positive regulation of apoptosis and 241 negative regulation of apoptosis proteins. Subsequently, we developed a classifier that combines the support vector machine (SVM) with pseudo composition of k-spaced amino acid pairs (PseCKSAAP), composition transition distribution (CTD), dipeptide deviation from expected mean (DDE), and PSSM-composition to identify these proteins. Analysis of variance (ANOVA) was employed to select optimized features that could yield the maximum prediction performance. Evaluating the proposed model on independent data revealed and achieved an accuracy of 0.781 with an AUROC of 0.837, demonstrating our model's potent capabilities.

[Global quantification of the spatial variability and temporal stability of throughfall]. / æž—å† ç©¿é€é›¨ç©ºé—´å¼‚è´¨æ€§åŠå ¶æ—¶é—´ç¨³å®šæ€§ç‰¹å¾çš„å ¨çƒé‡åŒ–.

Spatial variability of throughfall (i.e. the non-uniform characteristics of throughfall at different canopy positions) and its temporal persistence (i.e. time stability) are related to the quantity and efficiency of soil moisture replenishment, and affect plant competition and community succession dynamics by affecting resource availability. We carried out a meta-analysis with 554 papers (from 2000 to 2022) retrieved from Web of Science and China National Knowledge Infrastructure (CNKI) based on keyword search, quantified and compared the amount, spatial heterogeneity, and temporal stability characteristics of penetrating rain in different climate zones and plant functional types. Our results that throughfall proportion was lower in arid regions (72.0%±13.6%) than humid (75.1%±9.3%) and semi-humid areas (79.9%±10.4%). Cold climates had lower values (74.1%±14.6%) than temperate (74.2%±7.5%) and tropical climates (80.9%±14.6%). Shrubs (68.9%±14.9%) generally had lower throughfall proportion than trees (76.7%±9.1%). Broad-leaved trees (75.2%±11.1%) and conifers (75.1%±9.9%) showed similar throughfall proportions, as did evergreen (76.7%±10.0%) and deciduous species (74.7%±11.9%). Additionally, spatial variability (coefficient of variation) did not significantly differ across rainfall zones, temperature zones, or vegetation types. The spatial distribution of throughfall was relatively stable. Canopy structure was the dominant factor affecting temporal stability of throughfall. However, there was a lack of comparison between typical geographic units (i.e. spatial units with basically consistent geographical environmental conditions) at various temporal scales. Future research should expand upwards to the summary of global spatial scale rules and downwards to the analysis of process based temporal scale mechanisms, to depict the dynamic distribution of penetrating rain and unify observation standards to enhance comparability of different studies, in order to efficiently promote research on canopy penetrating rain and provide ecological and hydrological basis for protecting nature, managing artificial activities, and restoring degraded ecosystems.

Efficacy and safety of pralsetinib in patients with RET fusion positive non-small cell lung cancer: An observational real world study.

BACKGROUND: Pralsetinib, a selective RET targeted tyrosine kinase inhibitor (TKI), has been approved for treating locally advanced or metastatic RET fusion-positive NSCLC in adults who have previously received platinum-based chemotherapy in China. METHODS: In this retrospective analysis conducted at Hunan Cancer Hospital in China, we examined 36 patients with advanced NSCLC with RET fusion, who were treated with pralsetinib between January 2021 and December 2023. The study focused on assessing the efficacy (Progression-free survival (PFS) and overall survival (OS)) and safety profile of pralsetinib in these patients. Statistical analyses were conducted using SPSS version 20.0, with a significance level set at p < 0.05. RESULTS: The results revealed that pralsetinib exhibited significant activity in this patient cohort. Kaplan-Meier survival analysis indicated a median PFS of 10.7 months and a median OS of 21.2 months. The overall response rate(ORR) and disease control rate (DCR) was 55.6 % and 72.2 %, respectively. Pralsetinib was generally well tolerated, with most adverse events being mild to moderate (grades 1-2). The most common serious adverse events (≥grade 3) observed were lymphopenia (13.9 %), hypertension (11.1 %), leukopenia (8.3 %), neutropenia (8.3 %), and creatine kinase elevation (8.3 %). CONCLUSION: Pralsetinib demonstrated promising activity in patients with advanced NSCLC harboring RET fusion with a favorable safety profile.