Orbital Hall diffraction and its application for vortex measurement.

We observe significant orbital angular momentum (OAM)-helicity-dependent centroid shifts in the Fraunhofer patterns for the far-field diffraction of optical vortex beams passing through a thin single wire, thus suggesting the orbital Hall effect (OHE) of light in diffraction. Based on the OHE with a thin cross wire, we further experimentally develop a compact and robust alignment-free method to measure the OAM states of light. These findings indicate that not only does the OHE of light offer insights into vortex diffraction with broken rotational symmetry, it may also provide a reliable and efficient way to simplify the vortex measurement for waves of different natures.

Full-Scale Aggregated MobileUNet: An Improved U-Net Architecture for SAR Oil Spill Detection.

Oil spills are a major threat to marine and coastal environments. Their unique radar backscatter intensity can be captured by synthetic aperture radar (SAR), resulting in dark regions in the images. However, many marine phenomena can lead to erroneous detections of oil spills. In addition, SAR images of the ocean include multiple targets, such as sea surface, land, ships, and oil spills and their look-alikes. The training of a multi-category classifier will encounter significant challenges due to the inherent class imbalance. Addressing this issue requires extracting target features more effectively. In this study, a lightweight U-Net-based model, Full-Scale Aggregated MobileUNet (FA-MobileUNet), was proposed to improve the detection performance for oil spills using SAR images. First, a lightweight MobileNetv3 model was used as the backbone of the U-Net encoder for feature extraction. Next, atrous spatial pyramid pooling (ASPP) and a convolutional block attention module (CBAM) were used to improve the capacity of the network to extract multi-scale features and to increase the speed of module calculation. Finally, full-scale features from the encoder were aggregated to enhance the network's competence in extracting features. The proposed modified network enhanced the extraction and integration of features at different scales to improve the accuracy of detecting diverse marine targets. The experimental results showed that the mean intersection over union (mIoU) of the proposed model reached more than 80% for the detection of five types of marine targets including sea surface, land, ships, and oil spills and their look-alikes. In addition, the IoU of the proposed model reached 75.85 and 72.67% for oil spill and look-alike detection, which was 18.94% and 25.55% higher than that of the original U-Net model, respectively. Compared with other segmentation models, the proposed network can more accurately classify the black regions in SAR images into oil spills and their look-alikes. Furthermore, the detection performance and computational efficiency of the proposed model were also validated against other semantic segmentation models.

SpliceAPP: an interactive web server to predict splicing errors arising from human mutations.

BACKGROUND: Splicing variants are a major class of pathogenic mutations, with their severity equivalent to nonsense mutations. However, redundant and degenerate splicing signals hinder functional assessments of sequence variations within introns, particularly at branch sites. We have established a massively parallel splicing assay to assess the impact on splicing of 11,191 disease-relevant variants. Based on the experimental results, we then applied regression-based methods to identify factors determining splicing decisions and their respective weights. RESULTS: Our statistical modeling is highly sensitive, accurately annotating the splicing defects of near-exon intronic variants, outperforming state-of-the-art predictive tools. We have incorporated the algorithm and branchpoint information into a web-based tool, SpliceAPP, to provide an interactive application. This user-friendly website allows users to upload any genetic variants with genome coordinates (e.g., chr15 74,687,208 A G), and the tool will output predictions for splicing error scores and evaluate the impact on nearby splice sites. Additionally, users can query branch site information within the region of interest. CONCLUSIONS: In summary, SpliceAPP represents a pioneering approach to screening pathogenic intronic variants, contributing to the development of precision medicine. It also facilitates the annotation of splicing motifs. SpliceAPP is freely accessible using the link https://bc.imb.sinica.edu.tw/SpliceAPP . Source code can be downloaded at https://github.com/hsinnan75/SpliceAPP .

Biomimetic Integrated Nanozyme for Flare and Recurrence of Gouty Arthritis.

Flare and multiple recurrences pose significant challenges in gouty arthritis. Traditional treatments provide temporary relief from inflammation but fail to promptly alleviate patient pain or effectively prevent subsequent recurrences. It should also be noted that both anti-inflammation and metabolism of uric acid are necessary for gouty arthritis, calling for therapeutic systems to achieve these two goals simultaneously. In this study, we propose a biomimetic integrated nanozyme, HMPB-Pt@MM, comprising platinum nanozyme and hollow Prussian blue. It demonstrates anti-inflammatory properties by eliminating reactive oxygen species and reducing infiltration of inflammatory macrophages. Additionally, it rapidly targets inflamed ankles through the camouflage of macrophage membranes. Furthermore, HMPB-Pt@MM exhibits urate oxidase-like capabilities, continuously metabolizing locally elevated uric acid concentrations, ultimately inhibiting multiple recurrences of gouty arthritis. In summary, HMPB-Pt@MM integrates ROS clearance with uric acid metabolism, offering a promising platform for the treatment of gouty arthritis.

Selective therapeutic efficacy of tyrosine kinase inhibitor sorafenib on the restoration of methylglyoxal-induced peritoneal fibrosis.

Peritoneal fibrosis, a common complication observed in long-term peritoneal dialysis patients, can gradually lead to ultrafiltration failure and the development of encapsulating peritoneal sclerosis. Although mechanisms of peritoneal fibrosis have been proposed, effective therapeutic options are unsatisfactory. Recently, several tyrosine kinase inhibitors have proven to be anti-fibrosis in rodent models. To assess the potential therapeutic effects of tyrosine kinase inhibitors on peritoneal fibrosis in the larger animal model, a novel porcine model of peritoneal fibrosis induced by 40 mM methylglyoxal in 2.5 % dialysate was established, and two different doses (20 mg/kg and 30 mg/kg) of sorafenib were given orally to evaluate their therapeutic efficacy in this study. Our results showed that sorafenib effectively reduced adhesions between peritoneal organs and significantly diminished the thickening of both the parietal and visceral peritoneum. Angiogenesis, vascular endothelial growth factor A production, myofibroblast infiltration, and decreased endothelial glycocalyx resulting from dialysate and methylglyoxal stimulations were also alleviated with sorafenib. However, therapeutic efficacy in ameliorating loss of mesothelial cells, restoring decreased ultrafiltration volume, and improving elevated small solutes transport rates was limited. In conclusion, this study demonstrated that sorafenib could potentially be used for peritoneal fibrosis treatment, but applying sorafenib alone might not be sufficient to fully rescue methylglyoxal-induced peritoneal defects.

Dome-type extracorporeal manual morcellation during laparoscopic uterine surgery: Two years' experience in a teaching hospital.

OBJECTIVE: This study aims to describe the dome-type manual morcellation technique, a modified form of C-type incision, its comparative advantages over existing morcellation methods, the perioperative outcomes of trainees with varying experience levels, and the variables influencing morcellation speed based on our two years of experience. METHODS: This retrospective cohort study included women who underwent laparoscopic myomectomy or hysterectomy using dome-type morcellation for tissue extraction at a tertiary teaching hospital between May 2020 and September 2022. Morcellation was performed by either a single surgeon or a trainee (resident). Basic patient characteristics, perioperative outcomes, and morcellation time and speed were compared between the surgeon and trainee group. Regression models were employed to analyze variables influencing morcellation speed. RESULTS: A total of 41 women were enrolled. Among them, 20 procedures were performed by a surgeon alone, while the remaining 21 procedures were completed by trainees under the surgeon's supervision. The median weight of the specimens was 378 g (range 91-1345 g), and the median time for morcellation was 10 min (range 1-55 min). The median morcellation speed of surgeon and trainees was 70.25 and 31.7 g/min, respectively. Trainees' level of experience was found to be associated with morcellation speed, particularly for soft specimens. Additionally, both incision size and specimen stiffness were significantly associated with morcellation speed. No morcellation-related complications or bag ruptures were observed. CONCLUSION: Dome-type manual morcellation is an intuitive, efficient and safe method for specimen removal and is easy to learn for beginners.

Sulfur vacancy-rich bismuth sulfide nanowire derived from CAU-17 for radioactive iodine capture in complex environments: Performance and intrinsic mechanisms.

Effective capture and immobilization of volatile radioiodine from the off-gas of post-treatment plants is crucial for nuclear safety and public health, considering its long half-life, high toxicity, and environmental mobility. Herein, sulfur vacancy-rich Vs-Bi2S3@C nanocomposites were systematically synthesized via a one-step solvothermal vulcanization of CAU-17 precursor. Batch adsorption experiments demonstrated that the as-synthesized materials exhibited superior iodine adsorption capacity (1505.8 mg g-1 at 200 °C), fast equilibrium time (60 min), and high chemisorption ratio (91.7%), which might benefit from the nanowire structure and abundant sulfur vacancies of Bi2S3. Furthermore, Vs-Bi2S3@C composites exhibited excellent iodine capture performance in complex environments (high temperatures, high humidity and radiation exposure). Mechanistic investigations revealed that the I2 capture by fabricated materials primarily involved the chemical adsorption between Bi2S3 and I2 to form BiI3, and the interaction of I2 with electrons provided by sulfur vacancies to form polyiodide anions (I3-). The post-adsorbed iodine samples were successfully immobilized into commercial glass fractions in a stable form (BixOyI), exhibiting a normalized iodine leaching rate of 3.81 × 10-5 g m-2 d-1. Overall, our work offers a novel strategy for the design of adsorbent materials tailed for efficient capture and immobilization of volatile radioiodine.

Prevalence, proportions of elevated liver enzyme levels, and long-term cardiometabolic mortality of patients with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIM: This study estimated the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) according to cardiometabolic risk factors. The long-term impacts of MASLD on all-cause and cardiometabolic-specific mortality were evaluated. METHODS: We enrolled 343 816 adults aged ≥30 years who participated in a health screening program from 1997 through 2013. MASLD was identified on the basis of abdominal ultrasonography and metabolic profiles. The participants were further categorized by liver enzyme elevation. Baseline cardiometabolic comorbidities were classified on the basis of self-reported medication use and clinical seromarkers. All-cause and cardiometabolic-specific deaths were determined through computerized data linkage with nationwide death certifications until December 31, 2020. RESULTS: The overall prevalence of MASLD was 36.4%. Among patients with MASLD, 35.9% had abnormal liver enzyme levels. Compared with patients without MASLD, abnormal liver enzymes were positively associated with cardiometabolic comorbidities in patients with MASLD (Pfor trend < 0.001). After follow-up, patients with MASLD had a 9%-29% higher risk of all-cause, cardiovascular-related, or diabetes-related mortality. In the groups with MASLD and elevated and normal liver enzyme levels, the multivariate-adjusted hazard ratios for cardiovascular deaths were 1.14 (1.05-1.25) and 1.10 (1.03-1.17), respectively, and those for diabetes deaths were 1.42 (1.05-1.93) and 1.24 (0.98-1.57), respectively, compared with those in the non-MASLD group (Pfor trend < 0.001). DISCUSSION: Individuals with MASLD and elevated liver enzyme levels exhibited significantly higher risks of all-cause and cardiometabolic deaths and should be monitored and given consultation on cardiometabolic modifications.

A combined nanotherapeutic approach targeting farnesoid X receptor, ferroptosis, and fibrosis for nonalcoholic steatohepatitis treatment.

Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist with favorable effects on fatty and glucose metabolism, has been considered the leading candidate drug for nonalcoholic steatohepatitis (NASH) treatment. However, its limited effectiveness in resolving liver fibrosis and lipotoxicity-induced cell death remains a major drawback. Ferroptosis, a newly recognized form of cell death characterized by uncontrolled lipid peroxidation, is involved in the progression of NASH. Nitric oxide (NO) is a versatile biological molecule that can degrade extracellular matrix. In this study, we developed a PEGylated thiolated hollow mesoporous silica nanoparticles (MSN) loaded with OCA, as well as a ferroptosis inhibitor liproxsatin-1 and a NO donor S-nitrosothiol (ONL@MSN). Biochemical analyses, histology, multiplexed flow cytometry, bulk-tissue RNA sequencing, and fecal 16S ribosomal RNA sequencing were utilized to evaluate the effects of the combined nanoparticle (ONL@MSN) in a mouse NASH model. Compared with the OCA-loaded nanoparticles (O@MSN), ONL@MSN not only protected against hepatic steatosis but also greatly ameliorated fibrosis and ferroptosis. ONL@MSN also displayed enhanced therapeutic actions on the maintenance of intrahepatic macrophages/monocytes homeostasis, inhibition of immune response/lipid peroxidation, and correction of microbiota dysbiosis. These findings present a promising synergistic nanotherapeutic strategy for the treatment of NASH by simultaneously targeting FXR, ferroptosis, and fibrosis.

Hyperthermia/glutathione-triggered ferritin nanoparticles amplify the ferroptosis for synergistic tumor therapy.

Breast cancer is the most diagnosed malignancy in women globally, and drug resistance is among the major obstacles to effective breast cancer treatment. Emerging evidence indicates that photothermal therapy and ferroptosis are both promising therapeutic techniques for the treatment of drug-resistant breast tumors. In this study, we proposed a thermal/ferroptosis/magnetic resonance imaging (MRI) triple functional nanoparticle (I@P-ss-FRT) in which ferritin, an iron storage material with excellent cellular uptake capacity, was attached via disulfide bonds onto polydopamine coated iron oxide nanoparticle (I@P) as photothermal transduction agent and MRI probe. I@P-ss-FRT converted the near-infrared light (NIR) into localized heat which accelerated the release of ferrous ions from ferritin accomplished by glutathione reduction and subsequently induced ferroptosis. The drug-resistant cancer cell lines exhibited a more significant uptake of I@P-ss-FRT and sensitivity to PTT/ferroptosis compared with normal cancer cell lines. In vivo, I@P-ss-FRT plus NIR displayed the best tumor-killing potential with inhibitory rate of 83.46 %, along with a decline in GSH/GPX-4 content and an increase in lipid peroxides generation at tumor sites. Therefore, I@P-ss-FRT can be applied to combat drug-resistant breast cancer.

Assessing the response of marine fish communities to climate change and fishing.

Globally, marine fish communities are being altered by climate change and human disturbances. We examined data on global marine fish communities to assess changes in community-weighted mean temperature affinity (i.e., mean temperatures within geographic ranges), maximum length, and trophic levels, which, respectively, represent the physiological, morphological, and trophic characteristics of marine fish communities. Then, we explored the influence of climate change and fishing on these characteristics because of their long-term role in shaping fish communities, especially their interactive effects. We employed spatial linear mixed models to investigate their impacts on community-weighted mean trait values and on abundance of different fish lengths and trophic groups. Globally, we observed an initial increasing trend in the temperature affinity of marine fish communities, whereas the weighted mean length and trophic levels of fish communities showed a declining trend. However, these shift trends were not significant, likely due to the large variation in midlatitude communities. Fishing pressure increased fish communities' temperature affinity in regions experiencing climate warming. Furthermore, climate warming was associated with an increase in weighted mean length and trophic levels of fish communities. Low climate baseline temperature appeared to mitigate the effect of climate warming on temperature affinity and trophic levels. The effect of climate warming on the relative abundance of different trophic classes and size classes both exhibited a nonlinear pattern. The small and relatively large fish species may benefit from climate warming, whereas the medium and largest size groups may be disadvantaged. Our results highlight the urgency of establishing stepping-stone marine protected areas to facilitate the migration of fishes to habitats in a warming ocean. Moreover, reducing human disturbance is crucial to mitigate rapid tropicalization, particularly in vulnerable temperate regions.

Análisis de la respuesta de las comunidades de peces marinos ante el cambio climático y la pesca Resumen Las comunidades de peces marinos sufren alteraciones en todo el mundo causadas por el cambio climático y las perturbaciones humanas. Analizamos los datos sobre las comunidades de peces marinos de todo el mundo para valorar los cambios en la afinidad térmica media (es decir, la temperatura media dentro de las distribuciones geográficas), la longitud máxima y los niveles tróficos, todos con ponderación comunitaria, los cuales representan respectivamente las características fisiológicas, morfológicas y tróficas de las comunidades de peces marinos. Después exploramos la influencia del cambio climático y la pesca sobre estos rasgos, ya que desempeñan un papel a largo plazo en la formación de las comunidades de peces, especialmente sus efectos interactivos. Empleamos modelos espaciales lineales mixtos para investigar el impacto del cambio climático y la pesca sobre los valores promedio de los rasgos con ponderación comunitaria y sobre la abundancia de las diferentes longitudes de peces y grupos tróficos. Observamos una tendencia inicial en incremento en la afinidad térmica de las comunidades de peces marinos en todo el mundo, mientras que el promedio con ponderación comunitaria de la longitud y el nivel trófico mostró una tendencia en declinación. Sin embargo, estos cambios en las tendencias no fueron significativas, probablemente debido a la gran variación de las comunidades de latitud media. La presión de pesca incrementó la afinidad térmica de las comunidades de peces en las regiones que experimentan el calentamiento climático. Además, este calentamiento estuvo asociado con un incremento en el promedio con ponderación comunitaria de la longitud y el nivel trófico de las comunidades. La temperatura de referencia climática baja pareció mitigar el efecto del calentamiento climático sobre la afinidad térmica y los niveles tróficos. El efecto del calentamiento sobre la abundancia relativa de las diferentes clases tróficas y el tamaño de las clases exhibió un patrón no lineal. Las especies de peces pequeños y relativamente grandes podrían beneficiarse con el calentamiento climático, mientras que los grupos de mayor tamaño y tamaño mediano estarían en desventaja. Nuestros resultados resaltan la urgencia por establecer áreas marinas protegidas que faciliten la migración de peces hacia hábitats en un océano cada vez más caliente. Además, es crucial reducir la perturbación humana para mitigar la rápida tropicalización, particularmente en las regiones templadas vulnerables.

Hypogonadism among HIV-positive men who have sex with men in Taiwan: Prevalence and associated factors.

BACKGROUND: Male hypogonadism is not uncommon in people with HIV (PWH), with estimated prevalence ranging from 9% to 16%. Existing data are limited on the serum testosterone levels in PWH in Asian populations. METHODS: We enrolled HIV-positive men who have sex with men (MSM) and had been on stable antiretroviral therapy and MSM without HIV between February 2021 and November 2022. Serum free testosterone levels, sex hormone-binding globulins and other associated hormones were measured. Multiple linear regression analysis was performed to assess the association between serum free testosterone levels and clinical variables collected. RESULTS: A total of 447 MSM with HIV and 124 MSM without HIV were enrolled. Compared with MSM without HIV, MSM with HIV had a higher age (median, 41 versus 29.5 years) and prevalence of symptomatic hypogonadism (8.3% versus 1.6%). Among MSM who were aged <35 years, there were no significant differences in the serum free testosterone levels and prevalences of hypogonadism between the two groups. In multiple linear regression analysis, serum free testosterone level significantly decreased with advanced age (a decrease of 1.14 pg/mL per 1-year increase) and a higher body-mass index (BMI) (a decrease of 1.07 pg/mL per 1-kg/m2 increase), but was not associated with HIV serostatus. CONCLUSION: We found that MSM with HIV had a higher prevalence of symptomatic hypogonadism than MSM without HIV in Taiwan, which could be attributed to age difference. Serum free testosterone levels were negatively correlated with age and BMI, but did not show a significant correlation with HIV serostatus.

N-ethyl-N-nitrosourea (ENU)-induced C-terminal truncation of Runx3 results in autoimmune colitis associated with Th17/Treg imbalance.

Inflammatory bowel disease (IBD) is a chronic and progressive inflammatory intestinal disease that affects people around the world. The primary cause of IBD is an imbalance in the host immune response to intestinal flora. Several human genes, including IL10, STAT3, IRGM, ATG16L1, NOD2 and RUNX3, are associated with inappropriate immune responses in IBD. It has been reported that homozygous Runx3-knockout (ko) mice spontaneously develop colitis. However, the high mortality rate in these mice within the first two weeks makes it challenging to study the role of Runx3 in colitis. To address this issue, a spontaneous colitis (SC) mouse model carrying a C-terminal truncated form of Runx3 with Tyr319stop point mutation has been generated. After weaning, SC mice developed spontaneous diarrhea and exhibited prominent enlargement of the colon, accompanied by severe inflammatory cell infiltration. Results of immunofluorescence staining showed massive CD4+ T cell infiltration in the inflammatory colon of SC mice. Colonic IL-17A mRNA expression and serum IL-17A level were increased in SC mice. CD4+ T cells from SC mice produced stronger IL-17A than those from wildtype mice in Th17-skewing conditions in vitro. In addition, the percentages of Foxp3+ Treg cells as well as the RORγt+Foxp3+ Treg subset, known for its role in suppressing Th17 response in the gut, were notably lower in colon lamina propria of SC mice than those in WT mice. Furthermore, transfer of total CD4+ T cells from SC mice, but not from wildtype mice, into Rag1-ko host mice resulted in severe autoimmune colitis. In conclusion, the C-terminal truncated Runx3 caused autoimmune colitis associated with Th17/Treg imbalance. The SC mouse model is a feasible approach to investigate the effect of immune response on spontaneous colitis.

Foldable paper-based photoelectrochemical biosensor based on etching reaction of CoOOH nanosheets-coated laser-induced PbS/CdS/graphene for sensitive detection of ampicillin.

Timely and rapid detection of antibiotic residues in the environment is conducive to safeguarding human health and promoting an ecological virtuous cycle. A foldable paper-based photoelectrochemical (PEC) sensor was successfully developed for the detection of ampicillin (AMP) based on glutathione/zirconium dioxide hollow nanorods/aptamer (GSH@ZrO2 HS@apt) modified cellulose paper as a reactive zone with laser direct-writing lead sulfide/cadmium sulfide/graphene (PbS/CdS/LIG) as photoelectrode and cobalt hydroxide (CoOOH) as a photoresist material. Initially, AMP was introduced into the paper-based reaction zone as a biogate aptamer, which specifically recognized the target and then left the ZrO2 HS surface, releasing glutathione (GSH) encapsulated inside. Subsequently, the introduction of GSH into the reaction region and etching of CoOOH nanosheets to expose the PbS/CdS/LIG photosensitive material increased photocurrent. Under optimal conditions, the paper-based PEC biosensor showed a linear response to AMP in the range of 5.0 - 2 × 104 pM with a detection limit of 1.36 pM (S/N = 3). In addition, the constructed PEC sensing platform has excellent selectivity, high stability and favorable reproducibility, and can be used to assess AMP residue levels in various real water samples (milk, tap water, river water), indicating its promising application in environmental antibiotic detection.

Targeting EFHD2 inhibits interferon-γ signaling and ameliorates non-alcoholic steatohepatitis.

BACKGROUND & AIMS: The precise pathomechanisms underlying the development of non-alcoholic steatohepatitis (NASH, also known as metabolic dysfunction-associated steatohepatitis [MASH]) remain incompletely understood. In this study, we investigated the potential role of EF-hand domain family member D2 (EFHD2), a novel molecule specific to immune cells, in the pathogenesis of NASH. METHODS: Hepatic EFHD2 expression was characterized in patients with NASH and two diet-induced NASH mouse models. Single-cell RNA sequencing (scRNA-seq) and double-immunohistochemistry were employed to explore EFHD2 expression patterns in NASH livers. The effects of global and myeloid-specific EFHD2 deletion on NASH and NASH-related hepatocellular carcinoma were assessed. Molecular mechanisms underlying EFHD2 function were investigated, while chemical and genetic investigations were performed to assess its potential as a therapeutic target. RESULTS: EFHD2 expression was significantly elevated in hepatic macrophages/monocytes in both patients with NASH and mice. Deletion of EFHD2, either globally or specifically in myeloid cells, improved hepatic steatosis, reduced immune cell infiltration, inhibited lipid peroxidation-induced ferroptosis, and attenuated fibrosis in NASH. Additionally, it hindered the development of NASH-related hepatocellular carcinoma. Specifically, deletion of myeloid EFHD2 prevented the replacement of TIM4+ resident Kupffer cells by infiltrated monocytes and reversed the decreases in patrolling monocytes and CD4+/CD8+ T cell ratio in NASH. Mechanistically, our investigation revealed that EFHD2 in myeloid cells interacts with cytosolic YWHAZ (14-3-3ζ), facilitating the translocation of IFNγR2 (interferon-γ receptor-2) onto the plasma membrane. This interaction mediates interferon-γ signaling, which triggers immune and inflammatory responses in macrophages during NASH. Finally, a novel stapled α-helical peptide targeting EFHD2 was shown to be effective in protecting against NASH pathology in mice. CONCLUSION: Our study reveals a pivotal immunomodulatory and inflammatory role of EFHD2 in NASH, underscoring EFHD2 as a promising druggable target for NASH treatment. IMPACT AND IMPLICATIONS: Non-alcoholic steatohepatitis (NASH) represents an advanced stage of non-alcoholic fatty liver disease (NAFLD); however, not all patients with NAFLD progress to NASH. A key challenge is identifying the factors that trigger inflammation, which propels the transition from simple fatty liver to NASH. Our research pinpointed EFHD2 as a pivotal driver of NASH, orchestrating the over-activation of interferon-γ signaling within the liver during NASH progression. A stapled peptide designed to target EFHD2 exhibited therapeutic promise in NASH mice. These findings support the potential of EFHD2 as a therapeutic target in NASH.

First Report of Kiwifruit Root Rot Caused by Globisporangium spinosum in China.

Kiwifruit is widely cultivated for its high vitamin C content and nutritional value. In January 2022, root rot symptoms were found in about 30% of Actinidia chinensis cv. Jinyan plants grafted on A. deliciosa rootstocks in an orchard located in Sanming (26.32°N, 117.23°E), Fujian Province of China. The affected plants appeared stunted, with brown and decaying roots, some of which were covered with white hyphae. To isolate the pathogen, the surfaces of typical symptomatic roots were sterilized for 30 s using 75% ethanol, followed by four rinses in sterile water, placing on potato dextrose agar (PDA), and incubating away from light at 25°C for 7 days. 16 Globisporangium-like isolates were obtained through hyphal tip isolation, displaying a milky-white appearance with irregular protuberances on the surface, and yellow-white backs with radial fold lines. The isolates were then cultured on corn meal agar for 5 days at 25°C in dark for morphological characteristics. Under microscope, the hyphae appeared as long strips without septa and 4.1 to 8.2 µm wide (average 6.7 µm), containing irregularly sized spherical droplets. Both terminal and intercalary hyphae swellings were observed; these appeared either spherical or subspherical, with some having projections. Their dimensions were 12.3 to 27.6 µm (average 17.3 µm). The oospores were mostly spherical, either plerotic or aplerotic, 11.8 to 22.3 µm wide (average 18.9 µm), with occasional projections. The antheridia were rod-shaped and curved, with one end attached to the oogonia. Amplification of the sequences of internal transcribed spacer (ITS) regions and cytochrome c oxidase subunit I (COI) were conducted using the primers ITS1/ITS4 (White et al. 1990) and OomCoxI-Levlo/OomCoxI-Levup (Robideau et al. 2011), respectively. The sequencing results revealed identical ITS and COI sequences in all 16 isolates. BLASTn analysis of the 969-bp ITS sequence ON202808 showed 99.38-99.59% similarity (965/971bp, 967/971bp) with the KJ162353 and AY598701 sequences from Globisporangium spinosum isolates, while the 700-bp COI sequence ON075783 showed 100% and 99.41% identity (680/680bp, 676/680bp) with the GenBank sequences HQ708835 and HQ708832, respectively, from G. spinosum. Phylogenetic analysis also showed that the obtained isolate (termed MA16) clustered with isolates from G. spinosum on the same evolutionary branch. For pathogenicity testing, four-month-old healthy Jinyan (A. chinensis) plants grown in sterilized media were transferred to sterile petri dishes covered with wet filter paper, and their roots were inoculated with a 5-mm-wide disk of MA16 when cultivated on PDA medium for 5 days. Miliang-1 (A. deliciosa) and Hongyang (A. chinensis) plants were treated similarly. The control groups each included three plants that were inoculated with non-colonized PDA. The plants were kept at 25 °C with a 12-/12-h light/dark cycle for 10 days when the inoculated plants exhibited root rot symptoms similar to those seen in the field, together with rotting and browning of the leaves. The control plants appeared healthy with no symptoms. After re-isolated from infected tissues, the pathogen was verified to be G. spinosum according to its ITS sequence, thus fulfilling the Koch's postulates. Recently, Pythium spinosum has been classified as G. spinosum according to whole-genome sequencing and phylogenomic analysis (Nguyen et al. 2022). Based on the morphological features and pathogenicity results, MA16 was identified as G. spinosum (van der Plaats-Niterink 1981; Huo et al. 2023). This report appears to be the first description of kiwifruit root rots caused by G. spinosum in China, and its identification will assist the development of strategies to counteract the disease.

Causal association between thyroid dysfunction and sepsis: a two-sample mendelian randomization study.

Background: The causal association between thyroid dysfunction (including hyperthyroidism and hypothyroidism) and sepsis is controversial in previous studies. Therefore, we used Mendelian randomization (MR) to explore the causal association between hyperthyroidism or hypothyroidism and the susceptibility to four distinct subtypes of sepsis (streptococcal sepsis, puerperal sepsis, asthma-associated pneumonia or sepsis, and other sepsis). Methods: In our research, we conducted two-sample Mendelian randomization (MR) analyses utilizing publicly available genome-wide association studies (GWAS) data from Sakaue et al. and the Finnish database to investigate the potential causal associations between hyperthyroidism, hypothyroidism, and each of the four distinct subtypes of sepsis, in addition to reverse MR analyses of the positive results to examine the existence of reverse causality. Results: Genetic hypothyroidism was causally related to the development of asthma-associated pneumonia or sepsis (ORIVW: 1.097, 95% CI: 1.024 to 1.174, P = 0.008); hypothyroidism was significantly associated with the development of other sepsis (ORIVW: 1.070, 95% CI: 1.028 to 1.115, P < 0.001). In addition, sensitivity analysis substantiated the robustness of these two MR findings, with no evidence of horizontal pleiotropy observed (P > 0.05). MR Egger regression analysis demonstrated no heterogeneity between instrumental variables (IVs). Inverse MR results confirmed no reverse causality between hypothyroidism and asthma-associated pneumonia or sepsis, or between hypothyroidism and other sepsis. The findings of this study also unveiled that there is no evidence of a causal link between hypothyroidism and the development of streptococcal sepsis or puerperal sepsis. Additionally, the research provided evidence indicating the absence of a causal relationship between hyperthyroidism and streptococcal sepsis, puerperal sepsis, asthma-associated pneumonia or sepsis, and other sepsis. Conclusions: This study identified a causal link between hypothyroidism and the occurrence of asthma-associated pneumonia or sepsis, and other sepsis, but not with the development of streptococcal sepsis and puerperal sepsis. Moreover, our findings did not reveal any causal association between hyperthyroidism and streptococcal sepsis, puerperal sepsis, asthma-associated pneumonia or sepsis, and other sepsis.

Advancing electrochemical nitrogen reduction: Efficacy of two-dimensional SiP layered structures with single-atom transition metal catalysts.

Researchers are interested in single-atom catalysts with atomically scattered metals relishing the enhanced electrocatalytic activity for nitrogen reduction and 100 % metal atom utilization. In this paper, we investigated 18 transition metals (TM) spanning 3d to 5d series as efficient nitrogen reduction reaction (NRR) catalysts on defective 2D SiPV layered structures through first-principles calculation. A systematic screening identified Mo@SiPV, Nb@SiPV, Ta@SiPV and W@SiPV as superior, demonstrating enhanced ammonia synthesis with significantly lower limiting potentials (-0.25, -0.45, -0.49 and -0.15 V, respectively), compared to the benchmark -0.87 eV for the defective SiP. In addition, the descriptor ΔG*N was introduced to establish the relationship between the different NRR intermediates, and the volcano plot of the limiting potentials were determined for their potential-determining steps (PDS). Remarkably, the limiting voltage of the NRR possesses a good linear relationship with the active center TM atom Ɛd, which is a reliable descriptor for predicting the limiting voltage. Furthermore, we verified the stability (using Ab Initio Molecular Dynamics - AIMD) and high selectivity (UL(NRR)-UL(HER) > -0.5 V) of these four catalysts in vacuum and solvent environments. This study systematically demonstrates the strong catalytic potential of 2D TM@SiPV(TM = Mo, Nb, Ta, W) single-atom catalysts for nitrogen reduction electrocatalysis.

Spatially controlled diffusion range of tumor-associated angiogenic factors to develop a tumor model using a microfluidic resistive circuit.

Developing a tumor model with vessels has been a challenge in microfluidics. This difficulty is because cancer cells can overgrow in a co-culture system. The up-regulation of anti-angiogenic factors during the initial tumor development can hinder neovascularization. The standard method is to develop a quiescent vessel network before loading a tumor construct in an adjacent chamber, which simulates the interaction between a tumor and its surrounding vessels. Here, we present a new method that allows a vessel network and a tumor to develop simultaneously in two linked chambers. The physiological environment of these two chambers is controlled by a microfluidic resistive circuit using two symmetric long microchannels. Applying the resistive circuit, a diffusion-dominated environment with a small 2-D pressure gradient is created across the two chambers with velocity <10.9 nm s-1 and Péclet number <6.3 × 10-5. This 2-D pressure gradient creates a V-shaped velocity clamp to confine the tumor-associated angiogenic factors at pores between the two chambers, and it has two functions. At the early stage, vasculogenesis is stimulated to grow a vessel network in the vessel chamber with minimal influence from the tumor that is still developed in the adjacent chamber. At the post-tumor-development stage, the induced steep concentration gradient at pores mimics vessel-tumor interactions to stimulate angiogenesis to grow vessels toward the tumor. Applying this method, we demonstrate that vasculogenic vessels can grow first, followed by stimulating angiogenesis. Angiogenic vessels can grow into stroma tissue up to 1.3 mm long, and vessels can also grow into or wrap around a 625 µm tumor spheroid or a tumor tissue developed from a cell suspension. In summary, our study suggests that the interactions between a developing vasculature and a growing tumor must be controlled differently throughout the tissue development process, including at the early stage when vessels are still forming and at the later stage when the tumor needs to interact with the vessels.

Identification of Endothelial Cell Protein C Receptor by Urinary Proteomics as Novel Prognostic Marker in Non-Recovery Kidney Injury.

Acute kidney injury is a common and complex complication that has high morality and the risk for chronic kidney disease among survivors. The accuracy of current AKI biomarkers can be affected by water retention and diuretics. Therefore, we aimed to identify a urinary non-recovery marker of acute kidney injury in patients with acute decompensated heart failure. We used the isobaric tag for relative and absolute quantification technology to find a relevant marker protein that could divide patients into control, acute kidney injury with recovery, and acute kidney injury without recovery groups. An enzyme-linked immunosorbent assay of the endothelial cell protein C receptor (EPCR) was used to verify the results. We found that the EPCR was a usable marker for non-recovery renal failure in our setting with the area under the receiver operating characteristics 0.776 ± 0.065; 95%CI: 0.648-0.905, (p < 0.001). Further validation is needed to explore this possibility in different situations.