Delivery of Synthetic Interleukin-22 mRNA to Hepatocytes via Lipid Nanoparticles Alleviates Liver Injury.

Hepatocellular injury, a pivotal contributor to liver diseases, particularly hepatitis, lacks effective pharmacological treatments. Interleukin-22 (IL-22), crucial for liver cell survival, shows potential in treating liver diseases by regulating repair and regeneration through signal transducer and activator of transcription 3 (STAT3) activation. However, the short half-life and off-target effects limit its clinical applications. To address these issues, lipid nanoparticles are employed to deliver synthetic IL-22 mRNA (IL-22/NP) for in situ IL-22 expression in hepatocytes. The study reveals that IL-22/NP exhibits liver-targeted IL-22 expression, with increased IL-22 levels detected in the liver as early as 3 h postintravenous injection, lasting up to 96 h. Furthermore, IL-22/NP activates STAT3 signaling in an autocrine or paracrine manner to upregulate downstream factors Bcl-xL and CyclinD1, inhibiting hepatocyte apoptosis and promoting cell proliferation. The therapeutic efficacy of IL-22/NP is demonstrated in both chronic and acute liver injury models, suggesting IL-22 mRNA delivery as a promising treatment strategy for hepatitis and liver diseases involving hepatocellular injury.

A systematic analysis of ARM genes revealed that GhARM144 regulates the resistance against Verticillium dahliae via interaction with GhOSM34.

Proteins of the armadillo repeat gene family play important roles in plant pathogen response. Here, 169 armadillo (ARM) genes were identified in upland cotton (Gossypium hirsutum). Phylogenetic analysis grouped these into 11 subfamilies, with conserved protein structures within each subfamily. The results signify that the expansion of the gene family occurred via whole genome duplication and dispersed duplication. Expression profiling and network analysis suggest that GhARM144 may regulate cotton resistance to Verticillium dahliae. GhARM144 was upregulated in roots by V. dahliae infection or salicylic acid treatment. This upregulation indicates a negative regulatory role of GhARM144' in the cotton immune responses, potentially by manipulating salicylic acid biosynthesis. Protein interaction studies found that GhARM144 associates with an osmotin-like protein, GhOSM34, at the plasma membrane. Silencing GhOSM34 reduced the resistance to V. dahliae, suggesting it may play a positive regulatory role. The results demonstrate that GhARM144 modulates cotton immunity through interaction with GhOSM34 and salicylic acid signalling. Further study of these proteins may yield insights into disease resistance mechanisms in cotton and other plants.

Seasonal modulation of the testis transcriptome reveals insights into hibernation and reproductive adaptation in Onychostoma macrolepis.

The Onychostoma macrolepis have a unique survival strategy, overwintering in caves and returning to the river for reproduction in summer. The current knowledge on the developmental status of its testes during winter and summer is still undiscovered. We performed RNA-seq analysis on O. macrolepis testes between January and June, using the published genome (NCBI, ASM1243209v1). Through KEGG and GO enrichment analysis, we were able to identify 2111 differentially expressed genes (DEGs) and demonstrate their functions in signaling networks associated with the development of organism. At the genomic level, we found that during the overwintering phase, genes associated with cell proliferation (ccnb1, spag5, hdac7) were downregulated while genes linked to testicular fat metabolism (slc27a2, scd, pltp) were upregulated. This indicates suppression of both mitosis and meiosis, thereby inhibiting energy expenditure through genetic regulation of testicular degeneration. Furthermore, in January, we observed the regulation of autophagy and apoptosis (becn1, casp13), which may have the function of protecting reproductive organs and ensuring their maturity for the breeding season. The results provide a basis for the development of specialized feed formulations to regulate the expression of specific genes, or editing of genes during the fish egg stage, to ensure that the testes of O. macrolepis can mature more efficiently after overwintering, thereby enhancing reproductive performance.

Zinc-Ion Anchor Induced Highly Reversible Zn Anodes for High Performance Zn-Ion Batteries.

Unstable Zn interface with serious detrimental parasitic side-reactions and uncontrollable Zn dendrites severely plagues the practical application of aqueous zinc-ion batteries. The interface stability was closely related to the electrolyte configuration and Zn2+ depositional behavior. In this work, a unique Zn-ion anchoring strategy is originally proposed to manipulate the coordination structure of solvated Zn-ions and guide the Zn-ion depositional behavior. Specifically, the amphoteric charged ion additives (denoted as DM), which act as zinc-ion anchors, can tightly absorb on the Zn surface to guide the uniform zinc-ion distribution by using its positively charged -NR4 + groups. While the negatively charged -SO3 - groups of DM on the other hand, reduces the active water molecules within solvation sheaths of Zn-ions. Benefiting from the special synergistic effect, Zn metal exhibits highly ordered and compact (002) Zn deposition and negligible side-reactions. As a result, the advanced Zn||Zn symmetric cell delivers extraordinarily 7000 hours long lifespan (0.25 mA cm-2, 0.25 mAh cm-2). Additionally, based on this strategy, the NH4V4O10||Zn pouch-cell with low negative/positive capacity ratio (N/P ratio=2.98) maintains 80.4 % capacity retention for 180 cycles. A more practical 4 cm*4 cm sized pouch-cell could be steadily cycled in a high output capacity of 37.0 mAh over 50 cycles.

Chelating Additive Regulating Zn-Ion Solvation Chemistry for Highly Efficient Aqueous Zinc-Metal Battery.

Aqueous zinc-metal batteries (AZMBs) usually suffered from poor reversibility and limited lifespan because of serious water induced side-reactions, hydrogen evolution reactions (HER) and rampant zinc (Zn) dendrite growth. Reducing the content of water molecules within Zn-ion solvation sheaths can effectively suppress those inherent defects of AZMBs. In this work, we originally discovered that the two carbonyl groups of N-Acetyl-ϵ-caprolactam (N-ac) chelating ligand can serve as dual solvation sites to coordinate with Zn2+, thereby minimizing water molecules within Zn-ion solvation sheaths, and greatly inhibit water-induced side-reactions and HER. Moreover, the N-ac chelating additive can form a unique physical barrier interface on Zn surface, preventing the harmful contacting with water. In addition, the preferential adsorption of N-ac on Zn (002) facets can promote highly reversible and dendrite-free Zn2+ deposition. As a result, Zn//Cu half-cell within N-ac added electrolyte delivered ultra-high 99.89 % Coulombic efficiency during 8000 cycles. Zn//Zn symmetric cells also demonstrated unprecedented long life of more than 9800 hours (over one year). Aqueous Zn//ZnV6O16 ⋅ 8H2O (Zn//ZVO) full-cell preserved 78 % capacity even after ultra-long 2000 cycles. A more practical pouch-cell was also obtained (90.2 % capacity after 100 cycles). This method offers a promising strategy for accelerating the development of highly efficient AZMBs.

Intrinsically Decoupled Coordination Chemistries Enable Quasi-Eutectic Electrolytes with Fast Kinetics toward Enhanced Zinc-Ion Capacitors.

Eutectic electrolytes show potential beyond conventional low-concentration electrolytes (LCEs) in zinc (Zn)-ion capacitors (ZICs) yet suffer from high viscosity and sluggish kinetics. Herein, we originally propose a universal theory of intrinsically decoupling to address these issues, producing a novel electrolyte termed "quasi-eutectic" electrolyte (quasi-EE). Joint experimental and theoretical analyses confirm its unique solution coordination structure doped with near-LCE domains. This enables the quasi-EE well inherit the advanced properties at deep-eutectic states while provide facilitated kinetics as well as lower energy barriers via a vehicle/hopping-hybridized charge transfer mechanism. Consequently, a homogeneous electroplating pattern with much enhanced Sand's time is achieved on the Zn surface, followed by a twofold prolonged service-life with drastically reduced concentration polarization. More encouragingly, the quasi-EE also delivers increased capacitance output in ZICs, which is elevated by 12.4 %-144.6 % compared to that before decoupling. Furthermore, the pouch cell with a cathodic mass loading of 36.6 mg cm-2 maintains competitive cycling performances over 600 cycles, far exceeding other Zn-based counterparts. This work offers fresh insights into eutectic decoupling and beyond.

Towards Understanding Neurodegenerative Diseases: Insights from Caenorhabditis elegans.

The elevated occurrence of debilitating neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD) and Machado-Joseph disease (MJD), demands urgent disease-modifying therapeutics. Owing to the evolutionarily conserved molecular signalling pathways with mammalian species and facile genetic manipulation, the nematode Caenorhabditis elegans (C. elegans) emerges as a powerful and manipulative model system for mechanistic insights into neurodegenerative diseases. Herein, we review several representative C. elegans models established for five common neurodegenerative diseases, which closely simulate disease phenotypes specifically in the gain-of-function aspect. We exemplify applications of high-throughput genetic and drug screenings to illustrate the potential of C. elegans to probe novel therapeutic targets. This review highlights the utility of C. elegans as a comprehensive and versatile platform for the dissection of neurodegenerative diseases at the molecular level.

Assessing ChatGPT as a Medical Consultation Assistant for Chronic Hepatitis B: Cross-Language Study of English and Chinese.

BACKGROUND: Chronic hepatitis B (CHB) imposes substantial economic and social burdens globally. The management of CHB involves intricate monitoring and adherence challenges, particularly in regions like China, where a high prevalence of CHB intersects with health care resource limitations. This study explores the potential of ChatGPT-3.5, an emerging artificial intelligence (AI) assistant, to address these complexities. With notable capabilities in medical education and practice, ChatGPT-3.5's role is examined in managing CHB, particularly in regions with distinct health care landscapes. OBJECTIVE: This study aimed to uncover insights into ChatGPT-3.5's potential and limitations in delivering personalized medical consultation assistance for CHB patients across diverse linguistic contexts. METHODS: Questions sourced from published guidelines, online CHB communities, and search engines in English and Chinese were refined, translated, and compiled into 96 inquiries. Subsequently, these questions were presented to both ChatGPT-3.5 and ChatGPT-4.0 in independent dialogues. The responses were then evaluated by senior physicians, focusing on informativeness, emotional management, consistency across repeated inquiries, and cautionary statements regarding medical advice. Additionally, a true-or-false questionnaire was employed to further discern the variance in information accuracy for closed questions between ChatGPT-3.5 and ChatGPT-4.0. RESULTS: Over half of the responses (228/370, 61.6%) from ChatGPT-3.5 were considered comprehensive. In contrast, ChatGPT-4.0 exhibited a higher percentage at 74.5% (172/222; P<.001). Notably, superior performance was evident in English, particularly in terms of informativeness and consistency across repeated queries. However, deficiencies were identified in emotional management guidance, with only 3.2% (6/186) in ChatGPT-3.5 and 8.1% (15/154) in ChatGPT-4.0 (P=.04). ChatGPT-3.5 included a disclaimer in 10.8% (24/222) of responses, while ChatGPT-4.0 included a disclaimer in 13.1% (29/222) of responses (P=.46). When responding to true-or-false questions, ChatGPT-4.0 achieved an accuracy rate of 93.3% (168/180), significantly surpassing ChatGPT-3.5's accuracy rate of 65.0% (117/180) (P<.001). CONCLUSIONS: In this study, ChatGPT demonstrated basic capabilities as a medical consultation assistant for CHB management. The choice of working language for ChatGPT-3.5 was considered a potential factor influencing its performance, particularly in the use of terminology and colloquial language, and this potentially affects its applicability within specific target populations. However, as an updated model, ChatGPT-4.0 exhibits improved information processing capabilities, overcoming the language impact on information accuracy. This suggests that the implications of model advancement on applications need to be considered when selecting large language models as medical consultation assistants. Given that both models performed inadequately in emotional guidance management, this study highlights the importance of providing specific language training and emotional management strategies when deploying ChatGPT for medical purposes. Furthermore, the tendency of these models to use disclaimers in conversations should be further investigated to understand the impact on patients' experiences in practical applications.

Duration of Remote Ischemic Conditioning and Outcome in Acute Ischemic Stroke.

BACKGROUND: Remote ischemic conditioning has been found to be effective in improving functional outcomes in acute ischemic stroke. We conducted a post hoc analysis of the RICAMIS (Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke) trial to determine whether long-term remote ischemic conditioning duration after stroke onset is associated with better clinical outcomes in ischemic stroke. METHODS AND RESULTS: Patients from the full analysis set were included in this secondary analysis. The primary outcome was the proportion of patients with an excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. Among the 1776 patients, there were 55 patients in the 1 to 7 days remote ischemic conditioning group, 345 in the 8 to 10 days group, 412 in the 11 to 13 days group, 51 in the 14 to 16 days group, and 913 in the control group. Compared with the control group, a significantly higher proportion of excellent functional outcomes at 90 days was found in the 11 to 13 days remote ischemic conditioning group (adjusted absolute difference, 9.1% [95% CI, 3.7%-14.5%]; P =0.001), which was attenuated in the other groups (adjusted absolute difference in the 8-10 days group, 2.0% [95% CI, -4.0% to 8.0%]; P=0.51; adjusted absolute difference in the 14-16 days group, 7.4% [95% CI, -5.8% to 20.5%]; P=0.27), but compared to the control group, there was lower proportion of excellent functional outcomes in the 1 to 7 days group (adjusted absolute difference, -14.4% [95% CI, -27.8% to 0.0%]; P=0.05). CONCLUSIONS: Among patients with acute moderate ischemic stroke, a higher likelihood of excellent clinical outcome was found in patients with longer duration of remote ischemic conditioning.

Dexmedetomidine induces IL-10 secretion by B lymphocytes in the peripheral blood of patients with hepatocellular carcinoma.

BACKGROUND/AIM: To investigate the distribution of subpopulations of peripheral blood B lymphocytes in individuals with hepatocellular carcinoma (HCC), and to evaluate the effect of dexmedetomidine (DEX) on B lymphocyte differentiation in patients with HCC in vitro. METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from the HCC group and the healthy group, and the distribution of peripheral blood B-lymphocyte subpopulations in the two groups was examined by Flow Cytometry (FCM). B lymphocytes extracted from the peripheral blood of the HCC group were divided into D0, D1, D2 and D4 groups according to the different dose of DEX in the culture medium (0 µM, 1 µM, 2 µM and 4 µM). After 72 h of in vitro culture, FCM was used to detect differences in the percentage of apoptotic B lymphocytes and the percentage of B lymphocytes that can express interleukin 10(IL-10) and transforming growth factor-ß (TGF-ß) in each group. RESULTS: In contrast to the healthy group, the HCC group exhibited a statistically significant increase in the proportion of CD19 + CD73 + B lymphocyte subpopulation (P<0.05). In the in vitro culture experiment, the differences in apoptosis of B lymphocytes and the percentage of TGF-ß expression in each group were not statistically significant; When compared to the control group, there was a significant increase in the percentage of B lymphocytes expressing IL-10 across the D1, D2, and D4 groups (P<0.05). CONCLUSION: The peripheral blood of HCC patients is characterized by an elevated presence of CD19 + CD73 + B lymphocyte subpopulations; DEX may have an immunosuppressive effect by promoting IL-10 secretion from peripheral blood B lymphocytes of HCC patients.

Sulfur-bridged bonds enabled structure modulation and space confinement of MnS for superior sodium-ion capacitors.

Manganese sulfide (MnS) is a promising converion-type anode for sodium storage, owing to the virtues of high theoretical capacity, coupled with it crustal abundance and cost-effectiveness. Nevertheless, MnS suffers from inadequate electronic conductivity, sluggish Na+ reaction kinetics and considerable volume variation during discharge/charge process, thereby impeding its rate capability and capacity retention. Herein, a novel lamellar heterostructured composite of Fe-doped MnS nanoparticles/positively charged reduced graphene oxide (Fe-MnS/PG) was synthesized to overcome these issues. The Fe-doping can accelerate the ion/electron transfer, endowing fast electrochemical kinetics of MnS. Meanwhile, the graphene space confinement with strong MnSC bond interactions can facilite the interfacial electron transfer, hamper volume expansion and aggregation of MnS nanoparticles, stabilizing the structural integrity, thus improving the Na+ storage reversibility and cyclic stability. Combining the synergistic effect of Fe-doping and space confinement with strong MnSC bond interactions, the as-produced Fe-MnS/PG anode presents a remarkable capacity of 567 mAh/g at 0.1 A/g and outstanding rate performance (192 mAh/g at 10 A/g). Meanwhile, the as-assembled sodium-ion capacitor (SIC) can yield a high energy density of 119 Wh kg-1 and a maximum power density of 17500 W kg-1, with capacity retention of 77 % at 1 A/g after 5000 cycles. This work offers a promising strategy to develop MnS-based practical SICs with high energy and long lifespan, and paves the way for fabricating advanced anode materials.

Perchlorate in foodstuffs from South China and its implication for human dietary exposure.

Perchlorate, an aqueous-soluble compound resistant to degradation, is mainly used in the synthesis of pyrotechnics, herbicides, and other products. It serves as a pivotal component in the production of fireworks, rocket fuel, and explosives. Perchlorate was recognized as a pollutant owing to the potential toxic risk to thyroid function, which could pose a potential threat to the nervous system of infants and pregnant women. Some study had found that perchlorate existed in food, water and air. This study aimed to investigate the levels of perchlorate in six types of foods (n = 570) from South China, and evaluate potential exposure risks for residents. Vegetables were found to have the highest median levels of foods, attributed to elevated water content in leafy vegetables and facile solubility of perchlorate in water. The relatively low levels of perchlorate in food compared to other studies could attribute to the fact that the period of food we purchased in this study was during the wet season while the contaminants, such as perchlorate, were diluted. The maximum hazard quotient (HQ) values for all residents consuming different foods and water were all higher than 1 This suggested that there is a potential health risk of perchlorate to residents in South China. Those may be attributed to the high levels of perchlorate in some individual samples of meat and eggs. However, the 95th percentile of HQ values in all residents was less than 1, indicating that there is no potential health risk of perchlorate to most residents in South China.

A Comprehensive Review on Synergy of Multi-Modal Data and AI Technologies in Medical Diagnosis.

Disease diagnosis represents a critical and arduous endeavor within the medical field. Artificial intelligence (AI) techniques, spanning from machine learning and deep learning to large model paradigms, stand poised to significantly augment physicians in rendering more evidence-based decisions, thus presenting a pioneering solution for clinical practice. Traditionally, the amalgamation of diverse medical data modalities (e.g., image, text, speech, genetic data, physiological signals) is imperative to facilitate a comprehensive disease analysis, a topic of burgeoning interest among both researchers and clinicians in recent times. Hence, there exists a pressing need to synthesize the latest strides in multi-modal data and AI technologies in the realm of medical diagnosis. In this paper, we narrow our focus to five specific disorders (Alzheimer's disease, breast cancer, depression, heart disease, epilepsy), elucidating advanced endeavors in their diagnosis and treatment through the lens of artificial intelligence. Our survey not only delineates detailed diagnostic methodologies across varying modalities but also underscores commonly utilized public datasets, the intricacies of feature engineering, prevalent classification models, and envisaged challenges for future endeavors. In essence, our research endeavors to contribute to the advancement of diagnostic methodologies, furnishing invaluable insights for clinical decision making.

Perspective insights into versatile hydrogels for stroke: From molecular mechanisms to functional applications.

As the leading killer of life and health, stroke leads to limb paralysis, speech disorder, dysphagia, cognitive impairment, mental depression and other symptoms, which entail a significant financial burden to society and families. At present, physiology, clinical medicine, engineering, and materials science, advanced biomaterials standing on the foothold of these interdisciplinary disciplines provide new opportunities and possibilities for the cure of stroke. Among them, hydrogels have been endowed with more possibilities. It is well-known that hydrogels can be employed as potential biosensors, medication delivery vectors, and cell transporters or matrices in tissue engineering in tissue engineering, and outperform many traditional therapeutic drugs, surgery, and materials. Therefore, hydrogels become a popular scaffolding treatment option for stroke. Diverse synthetic hydrogels were designed according to different pathophysiological mechanisms from the recently reported literature will be thoroughly explored. The biological uses of several types of hydrogels will be highlighted, including pro-angiogenesis, pro-neurogenesis, anti-oxidation, anti-inflammation and anti-apoptosis. Finally, considerations and challenges of using hydrogels in the treatment of stroke are summarized.

Chlorate and perchlorate in tea leaves from major producing regions in China and related human exposure risk.

Chlorate and perchlorate are emerging pollutants that may interfere with thyroid function. Since they are highly water soluble, chlorate and perchlorate in tea leaves cause health concerns but have scarcely been studied. In this study, chlorate and perchlorate concentrations in 216 tea samples from different regions of China were determined. Perchlorate was detected in all the samples with a median concentration of 44.1 µg kg-1, while the chlorate detection frequency was 15.7%. We observed regional differences in perchlorate contents in tea leaves, with the highest quantity found in the central region of China. Except for dark tea, the concentration of perchlorate in tea infusions decreased with the increased number of times the tea leaves were brewed. The hazard quotients (HQs) of chlorate and perchlorate in all the samples were less than 1, suggesting negligible health risks caused by these pollutants from tea consumption. To the best of our knowledge, this is the first study to investigate chlorate and perchlorate contamination in tea infusions by simulating brewing behavior.

Hypomethylation-enhanced CRTC2 expression drives malignant phenotypes and primary resistance to immunotherapy in hepatocellular carcinoma.

The cyclic AMP-responsive element-binding protein (CREB)-regulated transcription coactivator 2 (CRTC2) is a crucial regulator of hepatic lipid metabolism and gluconeogenesis and correlates with tumorigenesis. However, the mechanism through which CRTC2 regulates hepatocellular carcinoma (HCC) progression is largely unknown. Here, we found that increased CRTC2 expression predicted advanced tumor grade and stage, as well as worse prognosis in patients with HCC. DNA promoter hypomethylation led to higher CRTC2 expression in HCC. Functionally, CRTC2 contributed to HCC malignant phenotypes through the activated Wnt/ß-catenin pathway, which could be abrogated by the small-molecular inhibitor XAV-939. Moreover, Crtc2 facilitated tumor growth while concurrently downregulating the PD-L1/PD-1 axis, resulting in primary resistance to immunotherapy. In immunocompetent mice models of HCC, targeting Crtc2 in combination with anti-PD-1 therapy prominently suppressed tumor growth by synergistically enhancing responsiveness to immunotherapy. Collectively, targeting CRTC2 might be a promising therapeutic strategy to sensitize immunotherapy in HCC.

Association Between Family History and Early-Onset Atrial Flutter Across Racial and Ethnic Groups.

BACKGROUND: Genetic and familial contributions to early-onset atrial fibrillation are described primarily in individuals of European ancestry. However, the role of racial and familial contributions in the pathogenesis of early-onset atrial flutter (EOAFL) is unclear. METHODS AND RESULTS: In this cross-sectional study, participants were enrolled prospectively from 2015 to 2021 in multiple academic centers with a diagnosis of atrial flutter (AFL) confirmed by ECG. EOAFL was defined as a diagnosis of AFL before age 66 years with no concomitant or previous diagnosis of atrial tachyarrhythmias. Family history was adjudicated through baseline questionnaires and direct family interviews about the diagnosis of atrial tachyarrhythmias, stroke, and cardiomyopathy. The primary exposure was a positive family history in first-degree relatives, and the primary outcome was the odds of EOAFL versus late-onset AFL. A total of 909 patients were enrolled. Participants with a positive family history of atrial tachyarrhythmias were younger, less likely to be of Black race, and more likely to have EOAFL. The adjusted odds ratio (OR) for EOAFL in those with a positive family history was 1.8 (95% CI, 1.1-3.0). There was an increased odds of EOAFL in those of Black race (OR, 2.1 [95% CI, 1.4-3.2]), alcohol use (OR, 1.6 [95% CI, 1.0-2.6]), and obstructive sleep apnea (OR, 1.9 [95% CI, 1.0-3.4]). Use of cardioselective ß blockers or calcium channel blockers before the diagnosis of AFL were associated with a lower odds of EOAFL (OR, 0.5 [95% CI, 0.2-0.9]). CONCLUSIONS: These findings suggest a potentially hereditary predisposition to EOAFL across race and ethnicity, warranting further study of the genetic contributions to AFL.

Identifying spatiotemporal trends of SARS-CoV-2 RNA in wastewater: from the perspective of upstream and downstream wastewater-based epidemiology (WBE).

Recently, many efforts have been made to address the rapid spread of newly identified COVID-19 virus variants. Wastewater-based epidemiology (WBE) is considered a potential early warning tool for identifying the rapid spread of this virus. This study investigated the occurrence of SARS-CoV-2 in eight wastewater treatment plants (WWTPs) and their sewerage systems which serve most of the population in Taoyuan City, Taiwan. Across the entire study period, the wastewater viral concentrations were correlated with the number of COVID-19 cases in each WWTP (Spearman's r = 0.23-0.76). In addition, it is confirmed that several treatment technologies could effectively eliminate the virus RNA from WWTP influent (> 90%). On the other hand, further results revealed that an inverse distance weighted (IDW) interpolation and hotspot model combined with the geographic information system (GIS) method could be applied to analyze the spatiotemporal variations of SARS-CoV-2 in wastewater from the sewer system. In addition, socio-economic factors, namely, population density, land use, and income tax were successfully identified as the potential drivers which substantially affected the onset of the COVID-19 outbreak in Taiwan. Finally, the data obtained from this study can provide a powerful tool in public health decision-making not only in response to the current epidemic situation but also to other epidemic issues in the future.

Systematic pan-cancer analysis of RNF186 with potential implications in progression and prognosis in human cancer.

AIMS: Cancer remains a significant global public health issue. There is growing proof that Ring Finger Protein 186 (RNF186) may play a function in pan-cancer, however, this has not yet been thoroughly determined. This study aims to analyze RNF186 with potential implications in progression and prognosis in human cancer. MATERIALS AND METHODS: A comprehensive bioinformatics approaches combined with experimental verification were used across 33 types of cancers in this study to conduct a pan-cancer investigation of RNF186 from the perspectives of gene expression, prognosis, genomic alterations, immunological markers, gene set, and function. KEY FINDINGS: RNF186 is a valuable prognostic biomarker in several cancer types, especially breast invasive carcinoma (BRCA) and uterine corpus endometrial carcinoma (UCEC). The levels of RNF186 promoter methylation and genetic alterations may be responsible for some cancers' abnormal expression. Furthermore, RNF186 expression was determined to be associated with immune checkpoint genes. Analysis of RNF186-related genes revealed that proteasome and PI3K-AKT signaling pathway were primarily involved in the cellular function of RNF186. Additionally, our research first confirmed that RNF186 may function as an oncogene and contribute to cancer proliferation, migration and invasion in UCEC. In contrast, RNF186 may play an inhibitory role in BRCA progression. This function depends on the ligase activity of RNF186. SIGNIFICANCE: This study suggests that RNF186 is a novel critical target for tumor progression in BRCA and UCEC. It reveals that RNF186 may be associated with tumor immunotherapy, which may provide an effective predictive evaluation of the prognosis of immunotherapy.

Prospects for daily online adaptive radiotherapy for cervical cancer: Auto-contouring evaluation and dosimetric outcomes.

BACKGROUND: Training senior radiation therapists as "adapters" to manage influencers and target editing is critical in daily online adaptive radiotherapy (oART) for cervical cancer. The purpose of this study was to evaluate the accuracy and dosimetric outcomes of automatic contouring and identify the key areas for modification. METHODS: A total of 125 oART fractions from five postoperative cervical cancer patients and 140 oART fractions from five uterine cervical cancer patients treated with daily iCBCT-guided oART were enrolled in this prospective study. The same adaptive treatments were replanned using the Ethos automatic contours workflow without manual contouring edits. The clinical target volume (CTV) was subdivided into several separate regions, and the average surface distance dice (ASD), centroid deviation, dice similarity coefficient (DSC), and 95% Hausdorff distance (95% HD) were used to evaluate contouring for the above portions. Dosimetric results from automatic oART plans were compared to supervised oART plans to evaluate target volumes and organs at risk (OARs) dose changes. RESULTS: Overall, the paired CTV had high overlap rates, with an average DSC value greater than 0.75. The uterus had the largest consistency differences, with ASD, centroid deviation, and 95% HD being 2.67 ± 1.79 mm, 17.17 ± 12 mm, and 10.45 ± 5.68 mm, respectively. The consistency differences of the lower nodal CTVleft and nodal CTVright were relatively large, with ASD, centroid deviation, and 95% HD being 0.59 ± 0.53 mm, 3.6 ± 2.67 mm, and 5.41 ± 4.08 mm, and 0.59 ± 0.51 mm, 3.6 ± 2.54 mm, and 4.7 ± 1.57 mm, respectively. The automatic online-adapted plan met the clinical requirements of dosimetric coverage for the target volume and improved the OAR dosimetry. CONCLUSIONS: The accuracy of automatic contouring from the Ethos adaptive platform is considered clinically acceptable for cervical cancer, and the uterus, upper vaginal cuff, and lower nodal CTV are the areas that need to be focused on in training.